tbuckley/cabot-search huggingface dataset:
Treatment of cancer-associated thrombosis after craniotomy.
Authors: Oksana V. Katelnitskaya, Oleg I. Kit, Eduard Evgenevich Rostorguev, Natalya S. Kuznetsova, David H. Porksheyan, Dmitriy P. Atmachidi, Sergey E. Kavitskiy, Nailya K. Guskova, Viktoria R. Zakharchenko, Anastasia S. Nozdricheva, Svetlana V. Abakumova, Olesya N. Selyutina, Irina V. Tselishcheva, Svetlana V. Belgova
Journal: Journal of Clinical Oncology (2019)

e13510 Background: The high rates of mortality from venous thromboembolism (VTE) in neurooncological patients determine the relevance of the topic. The risk of VTE in patients with glioma reaches 36% during the treatment period, 16.1% during the first 6 months and increases by 3 times after tumor biopsy. The aim of this study was to evaluate the efficacy and safety of VTE treatment with fondaparinux after surgical interventions for brain tumors. Methods: The study included 32 cancer patients aged from 27 to 76 years (mean 56.5 years) in the acute period of VTE, the first month after craniotomy. Creatinine clearance below 30 ml/min, active bleeding, thrombocytopenia below 50x109/l were exclusion criteria. Glioma was diagnosed in 15 patients (46.9%), metastasis - 9 (28.1%), and meningioma - 8 patients (25%). Radical interventions were performed in 12 (37.5%) cases, palliative - 20 (62.5%). In 81.2% of cases (26 patients) deep vein thrombosis of lower extremities (DVT) was detected, 3 patients (9.4%) had combination with pulmonary embolism. VTE developed in the postoperative period with radiotherapy in 9 cases (32%), dexamethasone - 13 (40.6%). Surgical treatment of DVT was performed in 8 patients (thrombectomy, plication of the femoral vein). Segmental deep vein thrombosis of the lower leg was detected in 14 (43.8%) cases. Results: The efficiency of anticoagulant therapy was assessed by a decrease of thrombinemia markers (fibrinogen, SFMC and D-dimer). After a week of anticoagulant therapy, a significant reduction in the level of D-dimer was observed. However, the decline in fibrinogen and SFMC was statistically insignificant. VTE therapy was performed with fondaparinux in a therapeutic dose from 10 days to 1 month, followed by a transition to oral anticoagulants. There was no hospital mortality. Hematuria developed in one case (3.1%), and was managed conservatively. There were no hemorrhagic complications in the operative intervention zone. Two patients (6.25%) had a recurrence of VTE during the period of radiation therapy. Conclusions: An integrated approach to the treatment of VTE in patients undergoing craniotomy provides a low incidence of recurrent VTE and major bleeding.
Patient attendance at molecular tumor board: A new means of shared decision making?
Authors: Timothy Lewis Cannon, Donald L. Trump, Laura Knopp, Hongkun Wang, Tiffani DeMarco, John Milburn Jessup
Journal: Journal of Clinical Oncology (2019)

e18001 Background: Patient engagement in medical decision-making improves patient related outcomes through compliance and patient satisfaction. The Inova Schar Cancer Institute (ISCI) has a weekly molecular tumor board (MTB) to match comprehensive genomic sequencing results with targeted therapies for patients. The ISCI MTB invites patients to attend and engage in the MTB discussion. We performed a pilot study to investigate the feasibility and satisfaction in patients who attended MTB. Methods: During the time of this study, August 2017 through October 2018, 139 patients were presented and all 20 who were able to attend MTB completed pre-and post- MTB surveys. Patients who did not attend were either not invited by their primary oncologist, unable to attend, or chose not to attend. The survey included six questions related to comprehension, engagement, and satisfaction with the treatment team. Results: There was a statistically significant change for the question “I am satisfied with how well informed I am about targeted therapy” with p = 0.016. All 20 patients answered positively that it was beneficial for them to attend. Many patients expressed concerns about their difficulty understanding the technical aspects of the meeting. Conclusions: Patients who attended MTB reported a higher level of satisfaction after MTB attendance as compared to before MTB. This may reflect a sense of engagement in shared decision making rather than comprehension of genomic information. A more holistic method of studying this practice would include sampling a larger patient population and a formal evaluation of the physicians’ experience with patients attending. Supported by philanthropic funds from the Inova Schar Cancer Institute.
Case 16-1964
Authors: Thornton Brown, Walter G. J. Putschar
Journal: New England Journal of Medicine (1964)

Presentation of CaseA twenty-four-year-old man entered the hospital because of pain in the neck.Three years previously he had sustained a blow to the back of the neck; x-ray films were interpreted as normal, and he was placed in cervical traction for five days. He resumed full activity but continued to experience pain in the neck and right shoulder in association with change in the weather. Five months before admission the pain became more severe, and he remained in bed for a week. The pain was increased by coughing and sneezing but did not radiate to the arms, back . . .
Local experience with ipilimumab and nivolumab in treatment of metastatic melanoma: From world standards to individualized approaches in real clinical practice.
Authors: Georgy M. Manikhas, Rashida Orlova, Natalia V. Zhukova, Nina Antimonik, Svetlana I. Kutukova, Natalia P. Beliak, Natalia V. Popova
Journal: Journal of Clinical Oncology (2019)

e21023 Background: Ipilimumab (Ipi) is the first agent in metastatic melanoma treatment that achieved long-term efficacy in selected patients. Nivolumab (Nivo) is one of agents, PD-1 inhibitors, that change treatment paradigm of advanced melanoma due to improving OS for lots of patients. There is still needed to evaluate efficacy of this drugs in regular medical settings. Methods: 43 patients with advanced melanoma were treated in SPb Clinical Oncology Dispensary from 2014 till now: 16 male and 27 female, median age is 58y.o. (from 39 to 84). 31 patients received Ipi, 12 patients received Nivo. Almost of patients are progressed after 1-4 lines of previous systemic therapy before starting treatment with Ipi or Nivo. Initial performance status (PS) assessed by ECOG scale was following; 1 patient had PS = 0 by ECOG, 37 patients – PS = 1 by ECOG and 5 patients had PS = 2 status by ECOG. Adverse events (AEs) are collected according to CTC AE v4.03. Results: At the time of analysis median FU is 25.75 month (95% CI: 6,6-35.9). The most frequently reported AEs are: pruritis 20%, fatigue 10%, diarrhea 7%, hepatitis 4%. 6% of AEs are grade 3/4. There are no any infusion reactions to Ipi and Nivo. Ipilimumab: median PFS is 6.0 month (95% CI: 4.9;7.1), 19% of patients (n = 6) have no PD at the moment. Median OS is 12.0 months (95% CI: 9.7;14.3), 29% of patients are still alive (n = 9). 6-months OS is 81%, 1-year OS is 35%. Nivolumab: Only 3 from 12 patients have PD after Nivo on the time of analysis. Median PFS and OS is not reached: 10 patients are still alive. 1-year OS is 83,33%. 52% of patients have reported AEs. Conclusions: Efficacy and tolerability of Ipi and Nivo in our clinical practice is similar to data from international clinical studies. The treatment with Ipi and Nivo is not associated with drug related infusion reactions and immediate AEs and doesn’t require supervision of patients at in-patient departments.Ipi and Nivo treatment is safe, could be used on out patients’ basis in regular medical settings.
First-line treatment for patients with advanced non-small cell lung carcinoma and high PD-L1 expression: pembrolizumab or pembrolizumab plus chemotherapy
Authors: Yixin Zhou, Zuan Lin, Xuanye Zhang, Chen Chen, Hongyun Zhao, Shaodong Hong, Li Zhang
Journal: Journal for ImmunoTherapy of Cancer (2019)

Pembrolizumab monotherapy has become the preferred treatment for patients with advanced non-small cell lung carcinoma (NSCLC) and a programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS) of at least 50%. However, little is known about the value of adding chemotherapy to pembrolizumab in this setting. Therefore, we performed an indirect comparison for pembrolizumab plus chemotherapy versus pembrolizumab, using the frequentist methods. The primary outcomes were overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). Data were retrieved from randomized trials comparing pembrolizumab plus chemotherapy or pembrolizumab monotherapy against chemotherapy. Five trials involving 1289 patients were included. Direct meta-analysis showed that both pembrolizumab plus chemotherapy (ORR: relative risk (RR) 2.16; PFS: hazard ratio (HR) 0.36; OS: HR 0.51) and pembrolizumab alone (ORR: RR 1.33; PFS: HR, 0.65; OS: HR 0.67) improved clinical outcomes compared with chemotherapy. Indirect comparison showed that pembrolizumab plus chemotherapy was superior to pembrolizumab alone, in terms of ORR (RR 1.62, 1.18–2.23) and PFS (HR 0.55, 0.32–0.97). A trend towards improved OS was also observed (HR 0.76, 0.51–1.14). In conclusion, the addition of chemotherapy to pembrolizumab further improves the outcomes of patients with advanced NSCLC and a PD-L1 TPS of at least 50%.
Determining the biomarker landscape and its impact on outcomes in HPV+ head and neck cancer after primary resection.
Authors: Suchin Rajeev Khanna, Trisha Michel Wise-Draper
Journal: Journal of Clinical Oncology (2019)

e17520 Background: Human Papillomavirus (HPV) has emerged as a risk factor for oropharyngeal squamous cell carcinoma (OPSCC). Despite the better prognosis, HPV OPSCC is managed the same as HPV-negative cancer with toxic multimodality therapy. Numerous clinical trials are ongoing in an attempt at de-escalation treatment strategies in this population. However, the population is heterogenous in that 25% of patients still do poorly despite aggressive therapy. Tools to accurately separate this subset with poorer prognosis remain elusive. Finding the molecular means of prognosticating and risk-stratifying HPV OPSCC patients is an area of emerging interest to help better identify suitable candidates for de-escalation. We conducted an exploratory analysis of biomarkers with this goal in mind, specifically looking at HPV OPSCC patients that underwent definitive resection as their primary treatment. Methods: Tumor specimens from 26 patients with HPV OPSCC that underwent primary definitive resection were clinically annotated with variables of interest including patient demographics, presence of adverse pathological features, and recurrence and survival outcomes. A tissue microarray (TMA) was generated and tissue was stained by immunohistochemistry (IHC) with highly specific antibodies for molecular markers with known involvement in the pathogenesis of OPSCC. Pathologists reviewed the slides and assessed both the percentage of positive cells and the intensity of immunoreactivity. Scores were given based on these values. Results: Decreased pAMPk IHC expression portended better progression free survival (PFS), with hazard ratio (HR) of 0.004 with p = 0.09 trending towards statistical significance. The HR for biomarker expression and outcomes for ERCC1, p4EBP1, pMTOR, PI3K, PTEN, pAkt, pS6 did not achieve statistical significance. Conclusions: Decreased expression of pAMPk appeared to signify better PFS with a trend towards statistical significance. This was an exploratory analysis and was not powered to detect a difference in expression in any particularly studied biomarker, and the sample size was a limitation. Further studies should be powered to specifically detect a meaningful difference of pAMPk expression as it relates to outcomes.
Predictors of early immunotherapy response in head and neck cancer: Per lesion analysis of a prospective randomized trial with nivolumab.
Authors: Yao Yu, Linda Chen, Nadeem Riaz, Jung Kang, C. Jillian Tsai, Eric Jeffrey Sherman, Nancy Y. Lee, Sean Matthew McBride
Journal: Journal of Clinical Oncology (2019)

6041 Background: The capacity for radiation and checkpoint inhibitors to elicit clinical responses is impacted by tumor immunogenicity and the immune microenvironment. We sought to determine whether head and neck primary site and metastatic tumor location was associated with initial response in non-irradiated lesions. Methods: We evaluated response in 144 non-irradiated lesions from 59 patients with metastatic head and neck cancer enrolled on a phase II randomized controlled trial of nivolumab with stereotactic body radiotherapy (n=30) vs. nivolumab alone (n=29). Nivolumab was administered 3 mg/kg intravenously every 2 weeks. Radiated lesions were treated with 27 Gy / 3 fractions to a single lesion within 14 days of the first dose of nivolumab. Non-target lesion progression was defined ≥30% increase in the greatest axial diameter 8 weeks after enrollment. Fisher’s exact test with nested bootstrap resampling was used for univariate analysis. Logistic regression with a mixed random effects term was used for multivariate analysis. Results: Primary tumor site, metastatic tumor organ sites, and the unadjusted likelihood of progressive disease by site are listed in the table. On multivariate logistic regression controlling for PD-L1 status (p=0.66) and viral status (p=0.29), lymph node metastases (OR 0.79, p=0.0064) were associated with decreased risk of progression, while liver metastases (OR 1.39, p=0.014) and oral cavity primaries (OR 1.56, p=0.018) were associated with increased risk of progression at 8 weeks, using lung metastases and larynx/hypopharynx primaries as reference. Conclusions: Primary tumor subsite and metastasis location were predictors of response or stable disease following treatment with nivolumab. Metastases from oral cavity primaries and metastases to the liver were at increased risk of early progression. Clinical trial information: NCT02684253. [Table: see text]
Association of STK11/LKB1 genomic alterations with lack of benefit from the addition of pembrolizumab to platinum doublet chemotherapy in non-squamous non-small cell lung cancer.
Authors: Ferdinandos Skoulidis, Kathryn Cecilia Arbour, Matthew David Hellmann, Pradnya Dinkar Patil, Melina Elpi Marmarelis, Mark M. Awad, Joseph Christopher Murray, Jessica Hellyer, Justin F. Gainor, Anastasios Dimou, Christine M. Bestvina, Catherine A. Shu, Jonathan W. Riess, Collin Michael Blakely, Chad Victor Pecot, Laura Mezquita, Fabrizio Tabbò, Matthias Scheffler, Vassiliki Papadimitrakopoulou, John Heymach
Journal: Journal of Clinical Oncology (2019)

102 Background: Addition of pembrolizumab (P) to platinum-doublet chemotherapy [carboplatin (or cisplatin) and pemetrexed (CP)] prolongs overall survival and is a standard of care (SOC) for the 1 st line treatment of metastatic EGFR/ALK wild-type (wt) non-squamous non-small cell lung cancer (mnsNSCLC). Despite widespread adoption of the CPP regimen, molecular determinants of clinical benefit from the addition of P to CP remain poorly defined. We previously identified genomic alterations in STK11/LKB1 as a major driver of primary resistance to PD-1/PD-L1 blockade in mnsNSCLC. Here, we examine the impact of STK11/LKB1 alterations on clinical outcomes with CPP chemo-immunotherapy. Methods: 497 pts with mnsNSCLC and tumor genomic profiling encompassing STK11/LKB1 from 17 academic institutions in the US and Europe were included in this study. Clinical outcomes were collected for two distinct patient cohorts: a) 377 pts treated with first-line CPP (or &gt; 1 st line following FDA-approved TKIs) that were alive for 14 days thereafter and b) 120 STK11/LKB1-mt pts that received CP prior to regulatory approval of CPP. Results: Among 377 CPP-treated pts, STK11/LKB1 genomic alterations (N = 102) were associated with significantly shorter PFS (mPFS 4.8m vs 7.2m, HR 1.5, 95% CI 1.1 to 2.0; P = 0.0063) and shorter OS (mOS 10.6m vs 16.7m, HR 1.58, 95% CI 1.09 to 2.27; P = 0.0083) compared with STK11/LKB1-wt tumors (N = 275). ORR also differed significantly between the two groups (32.6% vs 44.7%, P = 0.049). Similar results were obtained when limiting the analysis to EGFR and ALK-wt tumors (N = 333). Importantly, in pts with STK11/LKB1-mt mnsNSCLC, addition of pembrolizumab to CP did not improve PFS (mPFS 4.8m vs 4.3m, HR 1.13, 95% CI 0.83 to 1.54, P = 0.75) or OS (mOS 10.6m vs 10.3m, HR 1.03, 95% CI 0.71 to 1.49, P = 0.79) compared to CP alone. Conclusions: In mnsNSCLC, STK11/LKB1 alterations define a subgroup of pts with inferior clinical outcomes with CPP and lack of benefit from the addition of pembrolizumab to CP chemotherapy. Novel therapeutic strategies are required to establish effective antitumor immunity in STK11/LKB1-mutant NSCLC.
Angiotensin-converting enzyme inhibitor prescription is associated with decreased progression-free survival (PFS) and overall survival (OS) in patients with lung cancers treated with PD-1/PD-L1 immune checkpoint blockers.
Authors: Soleine Medjebar, Corentin Richard, Jean-David Fumet, Julie Malo, Arielle Elkrief, Normand Blais, Mustapha Tehfe, Marie Florescu, Romain Boidot, Caroline Truntzer, Bertrand Routy, François Ghiringhelli
Journal: Journal of Clinical Oncology (2019)

e20512 Background: Angiotensin converting enzyme (ACE) inhibitors are used to treat hyperblood pressure and congestive heart failure. Preclinical evidence show that ACE has a role in both innate and adaptive responses thus suggesting a capacity of ACE to promote antitumor immunity. Interaction between ACE inhibitors and Immune checkpoint blockers (ICB) has not been investigated in cancer patients (pts). Our study evaluated the effect of ACE inhibitors in Non Small cell lung cancer (NSCLC) pts treated with PD-1/PD-L1 inhibitors. Methods: We conducted a retrospective multicohort retrospective analysis of pts treated with PD-1/PD-L1 inhibitors for NSCLC at Dijon Cancer Center, and at the University of Montreal Hospital. ACE inhibitors groups were defined as pts treated with ACE inhibitors given during the treatment with ICB. PFS and OS were compared between both groups among all pts. Statistical analyses were performed using the Kaplan-Meier method and Cox univariate analysis. Multivariate Cox regression analyses was used to adjust for classical prognostic factors. Tumor RNA sequencing were performed and CIBERSORT was used to estimate immune cell infiltration in ACE inhibitors group and None ACE inhibitors group. Results: Among 283 pts included (177 pts from Dijon, and 106 pts from Montreal), 27 (10%) received ACE inhibitors. ACE inhibitors group did not differ from None ACE inhibitors group for main clinical prognostic characteristics. However, ACE inhibitors group are more frequently treated with statin, beta blocker and metformin. ACE inhibitors group had shorter median PFS compared to None ACE inhibitors group : 2.5 vs. 3.8 months, p = 0.02 (HR = 1.7 IC95% 1.1-2.5 p = 0.02 Cox Univariate). The negative impact of ACE inhibitors group was maintained after multivariate analyses adjusting for risk factors (HR = 1.9 IC95% 1.1-3.5 p = 0.02 for PFS and HR = 2.3 IC95% 1.2-4.4 p = 0.01 for OS). RNA sequencing and CIBERSORT analysis underlines that ACE inhibitors group has lower M1 macrophage, activated Mast cells, NK cells and memory activated T cells thus suggesting an immunosuppressive state. Conclusions: ACE inhibitors prescription concomitant to the PD-1/PD-L1 inhibitors treatment impairs the outcome in patients with advanced NSCLC pts. This reduction is independent of classical prognostic factors. Biological date underlines an immunosuppressive state in ACE inhibitors group. These data should be validated in larger cohort.
Primary prevention and smoking habit among <i>BRCA1/2</i> mutation carriers.
Authors: Patricia Cordeiro, Rocio Lesta, Igor Gómez-Randulfe, Cristina Reboredo Rendo, Aurea Molina Díaz, Maria Quindós Varela, Silvia Antolín Novoa, María Eva Pérez López, Lourdes Calvo Martínez, Belen Lopez Cortabitarte, Javier Prato, Vanessa Suárez, Joaquín Mosquera Martínez, Berta Rodríguez Sánchez, Montserrat Rodríguez Pedreira, Carlota Czestokowa, Alberto Bouzón, Luis Albaina Latorre, Carmen Cereijo Garea, Begoña Graña-Suárez
Journal: Journal of Clinical Oncology (2019)

e13061 Background: Smoking is the leading cause of avoidable death in the world. Although controversial for years, current prospective studies suggest that smoking increases the risk of cancer in women with a deleterious BRCA1/2 mutation. Actually, we have very limited information about tobacco habit among BRCA1/2 carriers. Methods: We report an observational retrospective study of a consecutive sample of 198 BRCA1/2 carriers studied between April 2014 and March 2018 at the Family Cancer Clinic of the University Hospital of Coruña (NW-Spain). The main objective of the study is to know the prevalence of smoking in BRCA1/2 women, and to determine if carriers undergoing risk-reducing surgeries (RRS) abandon their tobacco habit as part of the primary prevention strategy. Results: The sample includes 136 patients affected by cancer (84% breast, 19% ovary) and 62 healthy women. During their follow-up [Median = 22, (1-43) months], 85 carriers underwent RRS (29% mammary, 54% prophylactic salpingo-oophorectomy, 16% both). At first visit, 46 were active smokers, 47 ex-smokers, 77 non-smokers and 28 did not specify their habit. The percentage of smokers and never smokers is similar between sick and healthy BRCA1/2 carriers, presenting a greater proportion of former smokers among those affected of cancer (30% vs. 23%), and of active smokers among healthy women (35% vs. 23%) [p &gt; 0.5)]. Moreover, 23% of BRCA1/2 carriers are active smokers despite a previous diagnosis of cancer. RRS are not associated to a greater tobacco cessation, persisting in the habit 18% of the women that underwent any preventive surgery (p &gt; 0.5). Conclusions: Smoking habit is high (55%) among BRCA1/2 carriers followed at our family cancer clinic. At least 23% of our BRCA1/2 positive women are active smokers despite a previous diagnosis of cancer.The performance of aggressive RRS is not associated with greater abandonment of tobacco in carriers, persisting in the smoking habit 18% of operated women.It is essential to improve anti-tobacco strategies in family cancer consultations if we want to be efficient in the management of high-risk cancer individuals.