tbuckley/cabot-search huggingface dataset:
Two-stage hepatectomy for colorectal metastases: Association of pathologic response to intensified preoperative chemotherapy with second stage completion and longer survival.
Authors: Frederic Bibeau, Marie-Hélène Pissas, Hugo Gil, Lise Roca, Sebastien Carrere, Mathias Aline, Philippe Rouanet, Helene de Forges, Bernard Saint-Aubert, Fabienne Portales, Olivia Sgarbura, Marc Ychou, Emmanuelle Samalin, Lakhdar Khellaf, Francois Quenet
Journal: Journal of Clinical Oncology (2016)

3549 Background: The two-stage surgical resection (TSR) of bilobar colorectal liver metastases (CRLM) is widely used and has shown encouraging survival results. The risk of drop-out after the first-stage hepatectomy remains high and associated with poor survival rates. Our objective was to evaluate the predictive factors of long-term survival, based on the pathologic response to an intensified systemic chemotherapy administered preoperatively. Methods: Data from 899 patients treated for CRLM in our institution were collected prospectively between January 2003 and August 2013. We evaluated the pathologic response to preoperative chemotherapy, and its impact on the second-stage completion and on survival. The Tumour Regression Grade (TRG), the Blazer grade, and the modified-TRG were used to classify patients as responders (TRG and mTRG 1-3, Blazer 0-1) or non-responders (TRG and mTRG 4-5, Blazer 2) after the first stage Results: Sixty-seven patients were eligible for the TSR first stage. All patients underwent an intensified chemotherapy in combination with a biotherapy (Bevacizumab or Cetuximab) in 38cases. Responders in the three classifications (TRG: p = 0.033; mTRG: p = 0.03, Blazer: p = 0.005), and initial metastases number (p = 0.001) were independent predictive factors for the second-stage completion. Triple chemotherapy was significantly associated with responders in the three classifications (TRG and mTRG: 73.7% versus 26.3% p < 0.0001 ; Blazer : 84.2% versus 15.8% p = 0.001). Median overall survival (OS) of patients who completed TSR was significantly different (44, 84 versus 18,39 months; p < 0.0001). Conclusions: A good pathologic response to intensified preoperative chemotherapy is associated with completion of the second stage of TSR, and thus with a longer survival. Knowing this response before the first-stage resection may allow avoiding useless resections for patients who will not benefit from this strategy. Updated relapse-free survival and OS and particular patterns of pathologic response will be presented for this meeting.
Plasminogen regulators could be markers of malignancy for brain tumors.
Authors: Eduard Evgenevich Rostorguev, Oleg I. Kit, Elena M. Frantsiyants, Larisa S. Kozlova, Yulia A. Pogorelova, Dmitriy P. Atmachidi, Natalya S. Kuznetsova, David H. Porksheyan, Sergey E. Kavitskiy, Marina I. Vereskunova, Vladimir E. Rostorguev, Islam U. Cherkiev
Journal: Journal of Clinical Oncology (2018)

e14074 Background: Tumor progression and neovascularization are associated with plasminogen activators and the PAI-1 inhibitor; however, their role and interaction in various brain tumors are poorly studied. Our purpose was to compare plasminogen regulators in meningiomas without perifocal edema (M), primary glioblastomas (G) and metastases from breast cancer (BC mts) in brain tissues. Methods: Tumors (T) and their perifocal tissues (PT) were studied by ELISA in 86 patients aged 36-72 years: 29 BC mts, 34 G and 23 M. Results: M had no perifocal edema, so we studied histologically unchanged brain tissue around M as their PT and considered it as intact (N). Levels of pro-uPA and uPA in M exceeded N by 1.7 and 2.1 times; pro-tPA and tPA were lower than N by 3.9 and 1.8 times. Pro-uPA and uPA in G were increased by 3.3 and 1.4 times; pro-tPA in G was similar to N, and tPA was 4.3 times lower. Pro-uPA and uPA in BC mts exceeded N by 1.7 and 3.6 times, and pro-tPA and tPA were decreased by 3.3 and 19.7 times, compared to N. Pro-uPA in G PT was increased by 2.9 times, and uPA was 1.5 times decreased, compared to N; pro-tPA and tPA were decreased by 1.3 and 3.7 times. In BC mts PT, pro-uPA was 1.2 times increased (p < 0.05), uPA was lower than N by 2.1 times, and pro-tPA and tPA were decreased by 16.7 and 13.0 times, compared to N. Pro-PAI-1 in M was 2.5 times lower than N, and PAI-1 was 1.2 times higher (p < 0.05). In G, pro-PAI-1 exceeded N by 10.6 times, while PAI-1 was 3.5 times higher. In BC mts, pro-PAI-1 exceeded N by 17.1 times, and PAI-1 exceeded N by 2.7 times. Pro-PAI-1 in G PT was higher than N by 4.8 times, and PAI-1 was increased by 1.5 times. In PT of BC mts, pro-PAI-1 was increased by 11.2 times, and PAI-1 – by 2.7 times. Conclusions: uPA and PAI-1 were confirmed to be involved in the metabolism of G and brain mts from BC; tPA protected M, and its activation in G and BC mts was inhibited. Increased uPA and PAI-1 in all T, as well as significant differences between levels of uPA, tPA and PAI-1 in G, BC mts and M, correspond to the published results for other tumors. Levels of uPA in malignant primary G were 1.6 times lower than in M, and the levels in BC mts were 1.7 times higher. Highly increased levels of pro-PAI-1 and PAI-1 in G, BC mts and their PTs (prevailing in T) indicated the presence of tumor-associated PAI-1 in G and BC mts.
Outcomes of six-dose high-dose cytarabine (HiDAC-6) as a salvage regimen for patients with relapsed/refractory acute myeloid leukemia (RR-AML).
Authors: Lauren Westfall Veltri, Brandi Anders, Abraham Sebastian Kanate, Alexandra Shillingburg, Michael D. Craig, Aaron Cumpston
Journal: Journal of Clinical Oncology (2016)

e18508 Background: RR-AML is associated with a poor prognosis and long-term survival requires allogeneic hematopoietic cell transplantation (AHCT). There are limited regimens available to obtain remission prior to AHCT. Single agent high-dose cytarabine has been used as induction therapy, but has only been reported with a 10 to 12 dose regimen. HiDAC-6 is commonly used as a consolidation regimen; but has never been evaluated as an induction therapy. Methods: We present a retrospective review of 26 patients with RR-AML receiving single-agent cytarabine 3g/m2intravenously every 12 hours on days 1, 3 and 5 for a total of six doses (HiDAC-6) from June 2001- July 2015. All patients received prophylactic antimicrobials and G-CSF post-chemotherapy. Results: Patient characteristics are shown in Table 1. Median follow-up for surviving patients was 10.4 months (range 1.6-112.2 months). The complete response rate was 62% (54% CR and 8% CRi). The median overall survival (OS) was 9.6 months (range 1-112 months) and the median relapse-free survival (RFS) was 22.3 months (range 0.7-112.2 months). Thirty-five percent of patients were able to subsequently proceed to AHCT. Treatment-related toxicities included neutropenic fever (38%), infection (35%), neurotoxicity (8%) and skin toxicity (8%). Conclusions: This is the first study to demonstrate HiDAC-6 as an active treatment option for patients with RR-AML which can effectively serve as a bridge to AHCT without significant toxicity. Patient characteristics. Patient Characteristics N = 26 Median age, years (range) 46 (20-58) Male gender, n (%) 16 (62%) AML Diagnosis, n (%) --- De novo 23 (88%) Treatment-related 3 (12%) Prior MDS, n (%) 3 (12%) ECOG Performance Status, median (range) 1 (0-2) Disease Status, n (%) --- Primary Refractory 18 (69%) Relapsed 8 (31%) Prior Therapies, median (range) 1 (1-4) Prior Treatments --- 7+3 23 (88%) HiDAC 8 (31%) Etoposide/Mitoxantrone 2 (8%) Genetic Risk Group, n (%) --- Favorable 5 (19%) Intermediate I 10 (39%) Intermediate II 6 (23%) Poor risk 5 (19%)
Inbreeding of house dust mites, a tool for genomic studies and allergy‐related applications
Authors: José Cristian Vidal‐Quist, Matías García, Félix Ortego, Pedro Castañera, Pedro Hernández‐Crespo
Journal: Allergy (2018)

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Waiting time to diagnosis and treatment of the head and neck cancer in four institutions in Portugal in 2012.
Authors: Ana Filipa Martins Ferreira Castro, Joana Febra, Andreia Machado Coelho, Mariana Rocha, Silvia Lopes, Ana Joaquim, Helena Gouveia, Francisco Monteiro, Teresa Mota, Antonio M.F. Araujo
Journal: Journal of Clinical Oncology (2016)

e17524 Background: Reducing waiting time for the treatment of the head and neck cancer and a better evaluation of the initial symptoms are key points for a better control of the tumor and survival rates. The present study evaluates the waiting time since diagnosis and the respective treatments. Methods: A retrospective study was developed based on data collection from the clinical files of four institutions of the North of Portugal. A total of patients (n = 179) diagnosed with head and neck cancer between January 2012 and December 2012 in these institutions were evaluated. Results: In the study group, the median age at diagnosis was 60 years (rang: 17-93) and 70.4% of patients had an age below 65 years. The most common stage at diagnosis was stage IVa (36%). The median time from diagnosis to first treatment was 40.5 days (range:0-170). The most common treatment was surgery (45.09%) followed by radiotherapy (23.7%). The waiting time until the first treatment was lower in patients undergoing surgery (median days 27, range: 0-150) followed by chemotherapy group (days 48, range: 5-60), while radiotherapy had the highest waiting time (62, range: 4-170). The median time to the first treatment was lower in the less advanced stages (stage ≤ III: 37 days, range: 0-170) when compared to advanced stages (45 days, range: 0-157). The estimated overall survival was 36.44 months (30.1% of events). Conclusions: In 2012 the waiting time to the initial treatment of the head and neck cancer was above the standard values suggested by the General Health Direction in Portugal. Patients with more advanced stages, usually undergo chemo and radiotherapy, so, its time to the initial treatment is superior to patients undergoing surgery. Delays in radio and chemotherapy may be related to the placement of venous central catheter and dental treatments that patients are subjected before start treatment. These delays are an important issue because in patients with advanced stages the risk of dissemination of the tumor is higher to the more localized stages. As the best of our knowledge this is the first study regarding the waiting time. The authors intend to compare these data with the year of 2015, since it was implemented a new national guidance.
To censor or not to censor? Impact on real-world treatment duration.
Authors: Sarika Ogale, Erru Yang, Ning Wu, Lisa Carman, Daniel Sheinson
Journal: Journal of Clinical Oncology (2018)

e21111 Background: Payers and pathways are providing evidence on the value of treatment options to help physicians make informed treatment decisions. A recent study of 1L non-small cell lung cancer (NSCLC) regimens by Newcomer et al.1, reported real-world treatment durations (a proxy for effectiveness) that were substantially lower than those seen in clinical trials. However, the analyses excluded patients who were still on treatment as of the study end date (censored patients). The objective of our study was to assess the potential impact of excluding censored patients on treatment durations. 1Newcomer et al. JCO 35. no 15 suppl (May 2017) 9046 Methods: Patients initiating 1L NSCLC treatment between June 2015-May 2016 (the same study period used in the previous study1) were identified from the Truven MarketScan commercial claims database and were classified as ‘completers’ or ‘censored’ based on whether they had completed treatment as of the study end date. Treatment durations were compared between the two groups. Results: Of the 844 1L NSCLC patients assessed, 63% were classified as censored and 37% completers. A greater proportion of the censored patients (33.6%) vs. completers (3.5%) had longer treatment durations (6-12 months). Conclusions: In this analysis, we found that the majority of patients were censored and these patients had longer treatment durations. Thus, an analysis excluding these censored patients is likely to underestimate the true treatment duration, and hence the treatment effectiveness. While this bias may be mitigated for older treatments by accumulation of data over time, it will disproportionately impact newly launched treatments, and treatments on which patients stay longer due to better safety and/or efficacy. Payers and pathways, seeking to inform provider decisions, should adjust for censoring using Kaplan-Meier estimates, when the amount of censoring is moderate. For analyses where a large proportion of patients are censored (as is the case in this study), longer follow-up should be required before generating estimates of treatment duration. Treatment Duration Censored (N = 529) Completers (N = 315) N % N % < 1 mo 56 10.6% 24 7.6% 1-2 mo 62 11.7% 65 20.6% 2-4 mo 131 24.8% 168 53.3% 4-6 mo 102 19.3% 47 14.9% 6-12 mo 178 33.6% 11 3.5%
Venous thromboembolism (VTE) in multiple myeloma (MM) patients undergoing autologous hematopoietic cell transplantation (HCT).
Authors: Fahrettin Covut, Raisa Pinto, Michelle Park, Ehsan Malek, Hillard Lazarus, Paolo Fabrizio Caimi, Ben Kent Tomlinson, Leland L. Metheny, Marcos J.G. De Lima, Brenda W. Cooper
Journal: Journal of Clinical Oncology (2017)

e19503 Background: HCT is commonly used for consolidation for MM patients (pts). These pts have a significant risk of VTE and may potentially be candidates for prophylactic anticoagulation. However, incidence and outcomes of VTE in peri-transplant period remain unclear for MM pts. Methods: Between 2006 and 2016, 160 MM pts underwent autologous HCT at our institution. Peri-transplant period was defined as between initiation of stem cell collection (SCC) and 30 days after discharge from HCT hospitalization. No pts received routine VTE prophylaxis. Clinically significant bleeding was defined as a bleeding event that led to a specific clinical intervention, such as transfusion. We used Cox regression to assess risk factors for peri-transplant VTE. We compared overall survival (OS) using log-rank test. Results: In peri-transplant period, 18 symptomatic VTE occurred in 17 pts (10.6%; 95% CI 7 - 17). Twelve (7.5%) were catheter-related, 4 (2.5%) were non-catheter-related deep venous thrombosis, and 2 (1.3%) were pulmonary emboli. Seven VTE occurred between SCC and HCT. Importantly, among 11 VTE after HCT, only 1 VTE occurred before neutrophil engraftment and only 2 VTE occurred at a platelet count less than 50 x 10 9 /L (median: 138, range: 30 - 464). Clinically significant bleeding occurred in 9 (5.6%) pts during peri-transplant period, without any fatal bleeding. Multivariate analysis was performed including; treatment with immunomodulatory drugs (p = 0.008), HCT comorbidity index ≥ 2 (p = 0.036), age &gt; 60 (p = 0.07), smoking at any time (p = 0.07), BMI &gt; 30 at HCT (p = 0.19), partial remission at HCT (p = 0.20), ISS stage 3 at diagnosis (p = 0.37). At median follow-up of 31 months since HCT, 3-year OS for pts with and without peri-transplant VTE was 58.8% (CI 38% - 91%) and 77.6% (CI 70% - 86%), respectively (p = 0.11). Conclusions: Peri-transplant symptomatic VTE was highly prevalent in our cohort of pts with MM and vast majority of VTE events occurred either between SCC and HCT or after neutrophil engraftment. Our findings indicate that routine VTE prophylaxis in peri-transplant period should be considered for MM pts and timing of VTE prophylaxis can be tailored to optimize balance between safety and efficacy.
Guideline for the Management of <i>Clostridium Difficile</i> Infection in Children and Adolescents With Cancer and Pediatric Hematopoietic Stem-Cell Transplantation Recipients
Authors: Caroline Diorio, Paula D. Robinson, Roland A. Ammann, Elio Castagnola, Kelley Erickson, Adam Esbenshade, Brian T. Fisher, Gabrielle M. Haeusler, Susan Kuczynski, Thomas Lehrnbecher, Robert Phillips, Sandra Cabral, L. Lee Dupuis, Lillian Sung
Journal: Journal of Clinical Oncology (2018)

The aim of this work was to develop a clinical practice guideline for the prevention and treatment of Clostridium difficile infection (CDI) in children and adolescents with cancer and pediatric hematopoietic stem-cell transplantation (HSCT) patients.An international multidisciplinary panel of experts in pediatric oncology and infectious diseases with patient advocate representation was convened. We performed systematic reviews of randomized controlled trials for the prevention or treatment of CDI in any population and considered the directness of the evidence to children with cancer and pediatric HSCT patients. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to generate recommendations.The panel made strong recommendations to administer either oral metronidazole or oral vancomycin for the initial treatment of nonsevere CDI and oral vancomycin for the initial treatment of severe CDI. Fidaxomicin may be considered in the setting of recurrent CDI. The panel suggested that probiotics not be routinely used for the prevention of CDI, and that monoclonal antibodies and probiotics not be routinely used for the treatment of CDI. A strong recommendation to not use fecal microbiota transplantation was made in this population. We identified key knowledge gaps and suggested directions for future research.We present a guideline for the prevention and treatment of CDI in children and adolescents with cancer and pediatric HSCT patients. Future research should include randomized controlled trials that involve children with cancer and pediatric HSCT patients to improve the management of CDI in this population.
Primary analysis of phase 2 results for cemiplimab, a human monoclonal anti-PD-1, in patients with metastatic cutaneous squamous cell carcinoma (mCSCC).
Authors: Danny Rischin, Michael Robert Migden, Anne Chang, Christine H. Chung, Lara Dunn, Alexander Guminski, Axel Hauschild, Leonel Hernandez-Aya, Brett Gordon Maxwell Hughes, Karl D. Lewis, Annette May Ling Lim, Badri Modi, Dirk Schadendorf, Chrysalyne Schmults, Jocelyn Booth, Siyu Li, Kosalai Kal Mohan, Elizabeth Stankevich, Israel Lowy, Matthew G. Fury
Journal: Journal of Clinical Oncology (2018)

9519 Background: CSCC is rivaled only by basal cell carcinoma as the most common cancer in the US. There is no standard of care for patients with mCSCC; hence there is a significant unmet need in these patients. Cemiplimab (REGN2810) treatment at 3 mg/kg Q2W demonstrated encouraging preliminary activity in CSCC in a phase 1 study (ASCO 2017, #9503). We present the primary analysis of the mCSCC cohort from the pivotal phase 2 study (NCT02760498; data cutoff date Oct 27, 2017). Methods: Patients with mCSCC (defined as nodal and/or distant) received cemiplimab 3 mg/kg by intravenous infusion over 30 minutes every 2 weeks (Q2W). Tumor measurements were performed every 8 weeks. The primary objective was to evaluate overall response rate (ORR; complete response [CR] + partial response [PR]) according to independent central review (per RECIST 1.1 for scans; modified WHO criteria for photos). Duration of response (DOR) was a key secondary endpoint. Durable disease control rate (DDCR) was defined as stable disease or response for ≥16 weeks. Results: 59 patients were enrolled (54 M/ 5 F; median age: 71.0 years [range: 38–93]; ECOG performance status: 0 and 1 in 23 and 36 patients, respectively). 33 patients (55.9%) had received prior systemic therapy and 50 (84.7%) had received prior radiotherapy. Median duration of follow-up was 7.9 months (range: 1.1–15.6). ORR by central review was 47.5% (95% CI: 34.3–60.9; 4 CRs and 24 PRs). Responses were observed irrespective of prior systemic therapy. Median DOR has not been reached. Only 3 responding patients had subsequent disease progression at the time of data cut-off. DDCR was 61% (95% CI: 47.4–73.5). Median time to response was 1.9 months (range: 1.7–6.0). The most common adverse events (AEs) regardless of attribution (all grades, ≥Grade 3) were diarrhea (27.1%, 1.7%), fatigue (23.7%, 1.7%), and nausea (16.9%, 0.0%). Immune-related AEs ≥Grade 3 (per investigator assessment) occurred in 10.2% of patients. Conclusions: In the largest prospective study reported in patients with mCSCC, cemiplimab 3 mg/kg Q2W showed substantial activity and durable responses with an acceptable safety profile. Clinical trial information: NCT02760498.
Response to: Electronic cigarette vapour enhances pneumococcal adherence to airway epithelial cells under abnormal conditions of exposure
Authors: Jonathan Grigg
Journal: European Respiratory Journal (2018)

M. Caruso and co-workers raise several points related to our electronic cigarette (EC) study [1]. First, they suggest that we generated EC vapour (ECV) under "extreme" experimental conditions, which could lead to overheating and thermal decomposition of E-liquids around a heated coil [2]. However, we minimised the potential effect of coil overheating by ensuring that the EC reservoir was always more than three quarters full, and by using a low power second generation EC device (3.7 V), instead of a later generation 8 V device, which would have an increased potential for substantially higher coil temperatures and under-dry conditions [2]. In addition, our use of a 4-s puff duration and 8-s interpuff interval cannot be regarded as extreme, since a recent long-term study of young vaping adults found that one inhalation pattern is multiple rapid puffs taken over very short time periods [3]. Furthermore, the production of toxins under extreme conditions in vitro does not explain why we found that a "normal" vaping session increased nasal platelet-activating factor receptor (PAFR) expression in adult volunteers. Studies using cultures of human airway cells provide important insights into the toxicity of vaping <http://ow.ly/Pj7X30kM9h3>