tbuckley/cabot-search huggingface dataset:
Analysis of patterns of care and benefit of thoracic radiotherapy for patients with stage IV NSCLC in the immunotherapy-era from a national hospital-based registry.
Authors: Michael Kharouta, Andrew Jonathan Gross, Kevin Kelley, Serah Choi, Tithi Biswas
Journal: Journal of Clinical Oncology (2021)

9123 Background: Metastatic non-small cell lung cancer (mNSCLC) has classically been treated with platinum-doublet chemotherapy. Recent studies have established immunotherapy as an integral part of therapy for mNSCLC without targetable mutations. There are limited data on the role of consolidative thoracic radiotherapy (TRT) for patients with mNSCLC in the immunotherapy-era. A secondary analysis of KEYNOTE-001 showed significant improvement in overall survival in patients who received radiotherapy with pembrolizumab compared to patients not previously receiving radiotherapy. Methods: We queried the National Cancer Database (NCDB) for patients with metastatic presentation, stage IVA/IVB non-small cell lung cancer between the ages of 18-90 years treated between 2012-2017 with a combination of chemotherapy, immunotherapy, and thoracic radiotherapy. Patients with unknown treatment status, follow up time, or vital status were excluded. Overall survival (OS) was estimated using the Kaplan-Meier method and compared between treatment groups utilizing log-rank testing. A 3:1 nearest-neighbor propensity-score matching was performed utilizing clinical and demographic covariates to reduce the impact of potential confounders of overall survival on the probability of receipt of TRT. Cox proportional hazards regression was used to identify predictors of overall survival. Results: A total of 81,382 patients were identified that met inclusion criteria. The median age was 68 (18-90) years. The majority of patients (n = 51,681, 64%) had chemotherapy, while 7,929 (10%) patients received immunotherapy, and 15,984 (20%) received TRT. The median follow-up was 6.18 (range 0-76.9) months. For the entire cohort of patients receiving immunotherapy, 2 year OS was 29.4% with TRT compared to 32.7% without. Following propensity matching by age, sex, race, and comorbidity score, a total number of 4,264 patients receiving immunotherapy were matched. The 2 year OS was 27.7% in patients receiving TRT and immunotherapy vs. 22.2% in patients with immunotherapy alone (p = 0.004). On multivariable analysis receipt of TRT was a significant predictor of OS after adjustment for age, race, comorbidity score, sex, and median income (p = 0.0003, HR 0.87, 95% CI 0.80 - 0.94). For patients receiving BED10 &gt; 39 Gy (equivalent to 30 Gy in 10 fractions), 2 year OS was significantly improved at 37.0% vs 18.1% (p &lt; 0.0001). Conclusions: In patients with mNSCLC, the addition of TRT to immunotherapy is associated with improved overall survival at 2 years. Receipt of a higher BED10 is associated with further improved survival. Selection of mNSCLC patients receiving immunotherapy for TRT approaching definitive doses warrants further investigation. Data from prospective, randomized trials may better elucidate this benefit and identify a potential mechanism.
A retrospective study to evaluate the safety and efficacy of anlotinib plus camrelizumab in management of advanced retroperitoneal sarcoma.
Authors: Jianhui WU, Hui Qiu, Ang Lv, Bonan Liu, Qiao Liu, Chengpeng Li, Daoning LIU, Zhen Wang, Xiuyun Tian, Chunyi Hao
Journal: Journal of Clinical Oncology (2021)

e23545 Background: Several studies have demonstrated the antitumor activity of single-agent anlotinib in the treatment of soft tissue sarcoma (STS). However, the most effective results were from cases of alveolar soft part sarcoma (ASPS), which was a rare subtype in retroperitoneal sarcoma (RPS). The therapy of RPS is still dismal. Thus, we evaluated the effectiveness and safety of anlotinib plus camrelizumab for the treatment of RPS. Methods: We retrospectively reviewed the data of 36 patients with advanced/metastatic RPS in Sarcoma Centre of Peking University Cancer Hospital from July 2019 to February 2021. Anlotinib was given 12mg Qd 2 weeks on and 1 week off, and camrelizumab was transfused 200mg at Q3w. Patients that underwent at least 4 cycles of therapy were enrolled in this study. The primary endpoint is objective response rate (ORR) and evaluated according to the irRECIST 1.1 criteria. Results: The pathologic subtypes of enrolled cases include liposarcoma (LP) (n = 16), leiomyosarcoma (LMP) (n = 5), uncertain differentiation sarcoma (n = 7), fibroblastic and myofibroblastic tumours (n = 4), rhabdomyosarcoma (n = 2) and malignant peripheral nerve sheath tumour (MPNST) (n = 2). Two patients (5.6%) achieved CR and 9 patients (25.0%) achieved PR, with an ORR of 30.6%. Eighteen patients (50.0%) achieved SD and 7 patients (19.4%) were evaluated as PD, with the disease control rate (DCR) of 80.6%. The progression-free rate (PFR) at six months was 60.0%. Five patients underwent further radical surgical resection. The two CR cases were diagnosed as dedifferentiated liposarcoma (DDLP) and MDM2 amplified MPNST respectively, and both patients have been under CR status for over 12 months until now. The only grade 3 or higher treatment related adverse event was hypertension (22.2%). Camrelizumab related reactive cutaneous capillary endothelial proliferation (RCCEP) was not observed in this group of patients. Conclusions: The combination of anlotinib and camrelizumab demonstrated encouraging efficacy and safety in the treatment of RPS. A further clinical study with biomarker exploration should be performed in the future.
How did the COVID crisis affect use of neoadjuvant therapy for patients with breast cancer?
Authors: Anees B. Chagpar, Donald R. Lannin, Sarah Schellhorn Mougalian, Elizabeth Rapp Berger, Cary Philip Gross, Nina Ruth Horowitz, Tara B. Sanft, Michael DiGiovanna, Mehra Golshan, Lajos Pusztai
Journal: Journal of Clinical Oncology (2021)

e18708 Background: The COVID-19 pandemic has caused shifts in terms of cancer management, but the impact of this has not been well-elucidated in a contemporary cohort of patients in clinical practice in the US. We hypothesized that closure of operating rooms would increase the use of neoadjuvant therapy (NT) during the early pandemic period. Methods: The nationwide Flatiron Health database is a longitudinal electronic health record (EHR)-derived database, comprising de-identified, patient-level structured and unstructured data, curated via technology-enabled abstraction. These data originated from approximately 280 cancer clinics. We compared patients diagnosed with non-metastatic breast cancer during the early pandemic period (March 1 – June 30, 2020; group 1) with those diagnosed in the four month period prior (November 1, 2019 – February 29, 2020; group 2) and those diagnosed during the same period one year earlier (March 1 – June 30, 2019; group 3). Results: There were 174 patients in group 1, 277 in group 2, and 348 in group 3. Overall, 591 (74.1%) were ER/PR+HER2-, 100 (12.6%) were HER2+, and 106 (13.3%) were triple negative (TN). Patients in the three groups were equally likely to be ER/PR+HER2- (75.3% vs. 72.2% vs. 74.9%, p = 0.68), HER2+ (12.1% vs. 14.9% vs. 11%, p = 0.33), TN (12.6% vs. 12.7% vs. 14.2%, p = 0.83) and to be high risk by genomic testing (either Oncotype Dx or Mammaprint; p = 0.72). While there was no difference in the clinical stage (p = 0.36) nor patient age at diagnosis (p = 0.76) across the three groups, patients diagnosed during the early pandemic (group 1) were more likely to receive NT compared to those diagnosed one year earlier (group 3); 28.7% vs 16.4%, p &lt; 0.01 (see table). The use of NT differed between the three groups in the ER/PR+her2- (p &lt; 0.01) and her2+ patients (p = 0.05), but not in the TN patients (p = 0.61). There was no difference in the use of NT overall during the pandemic by geographic state (p = 0.32) nor practice setting (p = 0.23); NT was also similar by geographic state and practice setting when considering the ER/PR+HER2-, HER2+, and TNBC subsets. Conclusions: Despite similar clinicopathologic features as earlier time periods, there was an increased use of NT during the early pandemic when compared to the same period in the prior year. This was seen particularly in the ER/PR+HER2- group, suggesting an increased use of neoadjuvant endocrine therapy.[Table: see text]
Practice transformation at scale through a microsystems quality improvement (QI) approach.
Authors: Lucio N. Gordan, Basit Iqbal Chaudhry, Maen A. Hussein, Nora Connor, Andrew Yue, Michael Diaz, T. R. Strickland, Lisa Tran, Nathan Walcker
Journal: Journal of Clinical Oncology (2021)

e18667 Background: How oncology providers should implement practice transformation for value-based care is unclear, particularly at scale. Organizational size enables efficient “top down” approaches, but also presents challenges such as physician engagement. Dis-economies of scale can be acute in oncology due to physician autonomy and coordination costs. We hypothesized that organizational change based in sense-making models that enhance physician engagement and use a decentralized, iterative microsystems approach will enable practice transformation to scale. Methods: Florida Cancer Specialists &amp; Research Institute (FCS) is a physician led 250-oncologist statewide practice, with regional variation in disease state/mix, patient cohort, etc., making a purely top-down approach to organizational change infeasible. FCS prototyped a transformation strategy starting in June 2017 based on sharing interpreted data with physician and executive leadership. Later implementation directly engaged physicians in a microsystems quality QI strategy focused on regional performance. Interventions targeted disease, health service utilization, location, and individual physicians. Performance was evaluated using data from Medicare’s Oncology Care Model (OCM) and assessed using the one-sided risk target (4% below benchmark). We analyzed 70,239 performance period (PP) episodes at FCS across 35,116 patients. Results: In the pre- intervention period (90% of PP1 episodes, completed by June 2017), FCS was 5.8% above target. Performance was 10.9% above target for the remainder of PP1 (10% of PP1 episodes), then improved to 0.3% above target in PP2 and PP3, and below target by 0.9%, 0.8%, and 0.75% in PP4, PP5, and PP6. Early QI efforts focused on performance in lung cancer, which was 2.5% over target in PP1; it improved to 2.1% under target in PP6. Later regional QI sessions targeted cancer, utilization and providers. Pre-intervention, all 18 regions were above target; by PP6, 11 out of 19 regions were below target. Relative to the pre-intervention period, per-episode inpatient costs increased by 12.1% for the remainder of PP1 and increased by 4.3% and 1.3% in PP2 and PP6; inpatient costs decreased in PP3, PP4, and PP5 by 3.8%, 2.4% and 4.8%. Conclusions: Practice transformation in oncology can achieve scale through models of organizational change that foster physician engagement. Data, when clinically contextualized, is a foundational tool in the sense-making process. Scale can develop through an additive microsystems approach in which QI units are de-centralized, accountability is defined, and iteration becomes part of organizational culture. [Table: see text]
RNA expression profiles and splicing alterations in grade 1/2 neuroendocrine neoplasms from small intestine origin (siNENs). Final results of the GETNE-NETSEQ study
Authors: J. Capdevila, J.P. Castaño, F.M. Mancuso, S. Pedraza-Arevalo, I. Matos, H.G. Palmer, F. Salva, S. Landolfi, P. Jimenez-Fonseca, R. Garcia-Carbonero, C. Lopez, Z. Ogbah, P.G. Nuciforo, A. Casteras, D. Acosta, M. Diez, J. Hernando, R.M. Luque, A. Vivancos
Journal: Annals of Oncology (2019)
EPCT-20. TECHNICAL FEASIBILITY SODIUM (23NA) MRI OF PEDIATRIC GLIOMAS
Authors: Aashim Bhatia
Journal: Neuro-Oncology (2021)

Abstract Pediatric glioma response to novel targeted therapy can be heterogeneous on conventional proton (1H) MRI. Sodium concentration, as measured with 23Na MRI in adult brain tumors can provide complementary assessment of tumor proliferation to conventional MRI. However, 23Na MRI pediatric brain tumor studies are lacking. Determine the technical feasibility of performing sodium23Na MRI on pediatric glioma patients. Prospective study of an immunotherapy trial for newly diagnosed and recurrent gliomas (high-grade gliomas, low-grade gliomas, brainstem gliomas) in which participants were imaged with 23Na MRI at 3.0 Tesla. The participants (n=26, 14 males) with median age of 11 years (range = 4–23 years of age) were prospectively evaluated with sodium. 23Na MRI is technically feasible in the pediatric population and can distinguish different types of pediatric gliomas at baseline.
Abstract 12001: Left Ventricular Wall Stress as Predictor of Myocardial Functional Recovery in Patients With Severe Aortic Stenosis and Systolic Dysfunction Undergoing TAVI
Authors: Simone Calcagno, Fabio Infusino, Massimo Mancone, Carlotta De Carlo, Chiara Loffredo, Mariateresa Pucci, Paolo Severino, Viviana Maestrini, Natale Marco Martello, Riccardo Di Pietro, Gennaro Sardella, Francesco Fedele
Journal: Circulation (2018)

Introduction: The prognosis of severe and symptomatic aortic stenosis (AS) is poor, especially in the ‘Low-flow/Low-Gradient’ subgroup. TAVI is a therapeutic alternative for many patients, but ther...
A phase II study of vorolanib in combination with toripalimab in patients with non-small cell lung cancer.
Authors: Jun Zhao, Jianjie Li, Hanxiao Chen, Xue Yang, Jia Zhong, Minglei Zhuo, Bo Jia, Tongtong An, Meina Wu, Ziping Wang, Lieming Ding, Li Mao
Journal: Journal of Clinical Oncology (2021)

e21053 Background: VEGF promotes an immunosuppressive microenvironment and contributes to resistance of immune checkpoint inhibitors in cancer treatment. VEGF inhibitors have been shown to enhance efficacy of checkpoint inhibitors in clinical studies. Vorolanib (CM082) is a multi-target tyrosine kinase inhibitor including VEGF, PDGF, c-kit, and Flt-3. Toripalimab (JS001) is a humanized IgG4 mAb against programmed death-1 (PD-1). This phase II study aims to evaluate efficacy and safety of the combination of vorolanib and JS001 in non-small cell lung cancer (NSCLC) patients who progressed with prior first-line standard therapy. Methods: This single-arm, single-center, phase II study (NCT03848611) enrolls NSCLC patients with measurable disease (RECIST 1.1) and Eastern Cooperative Oncology Group performance status ≤ 1, regardless of PD-L1 status. 15 patients received 150 mg oral CM082 daily plus 240 mg intravenous JS001 every 3 weeks while 3 patients received 100 mg oral CM082 daily plus 240 mg intravenous JS001 every 3 weeks until disease progression or intolerable toxicity. The primary endpoint is objective response rate (ORR). Results: Between April 2019 and July 2020, 18 patients were enrolled. Median age was 64 years. 9 of 18 patients (50%) were adenocarcinoma and 9 of 18 patients (50%) were squamous. Males account for 83% (15/18) with 4 non-smokers among the male patients. At the data cutoff (January 11, 2021), we observed 2 (11%) confirmed and 1 (6%) unconfirmed partial response (PR), 6 (33%) stable disease (SD) and 9 (50%, including 2 PR of the target lesions) progression disease (PD). Tumor shrinkage was seen in 6 (33%) of the 18 patients. Two (11%) patients were still on the study drugs. Interestingly, all the patients with confirmed PR or PR of the target lesions were squamous histology. The most common treatment-related adverse events were proteinuria (67%), elevated ALT (60%), elevated AST (53%), hypertension (40%), and increased bilirubin (40%). Grade 3 adverse events include elevated ALT (20%), elevated AST (20%), liver function damage (13%), elevated GGT (7%), fatigue (7%), bellyache (7%), ruptured and infected tumor (7%), and dysphagia (7%). One Grade 4 adverse event was pulmonary embolism. Conclusions: Vorolanib with toripalimab showed a promising antitumor activity with acceptable safety profiles for patients with NSCLC. We hypothesized that the potential benefits of combination therapy for patients with squamous cell carcinoma may be better than those for patients with adenocarcinoma, and the study is ongoing. Clinical trial information: NCT03848611.
The fear of cancer progression and recurrence in patients with pancreatic cancer.
Authors: Esther N. Pijnappel, Willemieke P.M. Dijksterhuis, Mirjam A.G. Sprangers, Simone Augustinus, Lonneke V van de Poll-Franse, Judith de Vos-Geelen, Hjalmar van Santvoort, Ignace H.J.T. de Hingh, I. Quintus Molenaar, Olivier R.C. Busch, Marc G.H. Besselink, Johanna Wilmink, Hanneke W.M. Van Laarhoven
Journal: Journal of Clinical Oncology (2021)

4132 Background: Patients with pancreatic cancer run a considerable risk of disease progression or, after resection, disease recurrence, ultimately leading to death. Therefore, it is plausible that pancreatic cancer patients experience fear of cancer recurrence or progression (FOP). The aim of this study was to compare FOP in patients with pancreatic cancer treated with surgery, palliative systemic treatment or best supportive care (BSC), and examine the association between quality of life (QoL) and FOP and between FOP and overall survival (OS), respectively. Methods: This prospective multicenter cohort study included patients diagnosed with pancreatic cancer between 2015 and 2018, who participated in the Dutch Pancreatic Cancer Project (PACAP). Data on FOP (worry of cancer progression scale [WOPS]) and QoL (EORTC QLQ-C30 summary scale score), were obtained from the PACAP database. Data regarding patient and tumor characteristics were derived from the nationwide Netherlands Cancer Registry. The association between QoL and WOPS was assessed with logistic regression analysis. OS was evaluated using Kaplan Meier curves with log-rank test and multivariable Cox proportional hazard analyses. Results: In total, 315 patients were included, of whom 111 patients underwent surgery, 138 received palliative systemic treatment, and 66 BSC. WOPS scores tended to decrease and stabilize over time in all subgroups. Patients who underwent surgery had significantly lower WOPS scores (i.e. less FOP) at initial diagnosis compared to patients in the palliative systemic treatment and BSC group (p = 0.004). Higher QoL scores were independently associated with a lower probability of high WOPS scores in patients receiving BSC only (OR 0.95, P = 0.006). Baseline WOPS score was not independently associated with OS. Conclusions: Pancreatic cancer patients reported FOP at diagnosis, which decreased and stabilized over time. Given the distress that FOP evokes, FOP should be explicitly addressed by health care providers when guiding pancreatic cancer patients through their treatment trajectory, especially those receiving palliative treatment or BSC.
What is the optimal target for a T2T approach in axial spondyloarthritis?
Authors: Joachim Sieper, Denis Poddubnyy
Journal: Annals of the Rheumatic Diseases (2021)

An international expert group had formulated and recently updated a set of recommendations for treatment targets (treat to target—T2T) in axial spondyloarthritis (axSpA).1 According to these recommendations, the treatment target should be clinical remission/inactive disease defined as the absence of clinical and laboratory evidence of significant disease activity, which is currently best defined by reaching an Ankylosing Disease Activity Score (ASDAS) <1.3, termed ASDAS inactive disease.2 In some mostly older studies, information is only available for another remission outcome, Assessment of Spondyloarthritis International Society (ASAS) partial remission.3 Only if it is not possible to achieve remission a low disease activity, which is defined as ASDAS <2.1, can be taken as an alternative target. Indeed, in observational axSpA cohorts, patients with an ASDAS <1.3 showed less spinal radiographic progression compared with patients with a higher ASDAS4 5 and patients treated with tumour necrosis factor (TNF) blockers also showed less radiographic progression if the ASDAS was reduced to values <1.3.6 In addition, disease activity should be measured and treatment should be adjusted frequently (tight control) in order to reach an optimal control of disease activity.

On this background, a clinical trial investigating the concept of T2T in axSpA (1) has to define a treatment target to be reached, (2) has to define the frequency of the control measurements (tight control), (3) has to outline the treatment escalation in case the target is not reached and, finally, (4) an adequate control group has to be selected. To a further extent, it is desirable to demonstrate short-term and also long-term benefits of the T2T approach including inhibition of structural damage progression. Potential benefits should be carefully weighed against potential risks, for example, risks associated with an intensified treatment in the T2T arm.

The study on T2T in axSpA published …
Safety, pharmacokinetics, pharmacodynamics profiles and preliminary antitumor activity of phase 1b/2a study of NT-I7, a long-acting interleukin-7, plus pembrolizumab in patients with advanced solid tumors: The phase 1b data report.
Authors: Aung Naing, Jean Fan, Byung Ha Lee, Debashree Basudhar, Shubham Pant, Marya F. Chaney, Cristina Laviada, Cynthia Rajan, Ngocdiep T. Le, Minal A. Barve
Journal: Journal of Clinical Oncology (2021)

2594 Background: NT-I7 (efineptakin alfa) is the first-in-class long-acting IL-7 which can increase the number and functionality of T cells in the peripheral blood (PB) of patients (pts). The combination of NT-I7 and pembrolizumab (pembro), a PD-1 Checkpoint Inhibitor (CPI), may augment and broaden the efficacy of CPIs. Methods: This is an open-label, phase 1b/2a study in pts with relapsed/refractory (R/R) advanced solid tumors. In the phase 1b (Dose Escalation), which followed the 3+3 design, pts received NT-I7 intramuscularly (IM) at 3 dose levels (DLs): 480, 960, and 1200 µg/kg every 6 weeks (Q6W) plus pembro 200 mg intravenously (IV) Q3W. The objectives of the phase 1b were to evaluate Dose Limiting Toxicity (DLT), determine the Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RP2D), and assess pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity. Results: As of 12 January 2021, 12 pts were enrolled in the phase 1b: DL1 (n=3), DL2 (n=3) and DL3 (n=6). Median age 58.0 years [43-77], ECOG PS 0 (50%), PS 1 (50%), median number of prior therapies 4 [1-8]. MTD was not reached. One DLT (Grade [G] 3 ALT increased) was reported in DL3. Treatment-related adverse events (AEs) occurred in 11 (91.7%) pts, 11 (91.7%) G1-2 and 4 (33.3%) G3; no G4 or G5 AEs reported. Common treatment-emergent AEs were injection site reaction (n=8, 66.7%), chills (n=7, 58.3%), nausea (n=6, 50%) and pyrexia (n=6, 50%). Preliminary PK analysis showed T max = 24 hours and T 1/2 = 123 hours for NT-I7 at DL3. NT-I7 + pembro induced dose-dependent lymphocyte proliferation in the PB, with ̃ 3-fold increase at DL3, and a corresponding decrease in neutrophil to lymphocyte ratio at 14 days after the 1 st treatment. Importantly, increased number of T cells in the tumor microenvironment (TME) was also observed (Table). One pt with metastatic mucosal melanoma who had not responded to prior combination of nivolumab and ipilimumab had a rapid, confirmed partial response with 46% tumor reduction. Patient follow-up continues and updated data will be presented. The combination of NT-I7 1200 µg/kg IM Q6W + pembro 200 mg IV Q3W has been selected as the RP2D. Conclusions: The combination of NT-I7 + pembro was well tolerated in pts with R/R advanced solid tumors. NT-I7 + pembro significantly increased T cell numbers in both the TME and the PB, and there was encouraging antitumor activity with the combination in this pt population. These results support continued evaluation of NT-I7 in combination with pembro in pts with R/R advanced solid tumors. The phase 2a of the study is enrolling pts with either CPI-pretreated or CPI-naïve solid tumors (NCT04332653). Clinical trial information: NCT04332653. [Table: see text]