tbuckley/cabot-search huggingface dataset:
A phase I study of adoptive T-cell therapy with or without dendritic cell vaccination in patients with metastatic melanoma.
Authors: Roger Tell, Jonas Mattson, Lars Adamson, Isabel Poschke, Mats Engström, Tanja Lövgren, Johan Hansson, Giuseppe V. Masucci, Andreas Lundqvist, Rolf Kiessling
Journal: Journal of Clinical Oncology (2014)

TPS3118 Background: The addition of autologous dendritic cell vaccine (DCV) to adoptive T-cell therapy (ACT) may enhance the anti-tumor immune responses in melanoma. Methods: Study Population - Patients with advanced malignant melanoma who have tumor that is accessible for core biopsy or is resectable; confirmed progressing metastatic disease; refractory to standard therapy; not having had prior systemic cancer therapy within the past four weeks at the time of the start of the lymphodepletion regimen. Sample Size - 10 patients will be evaluated, 5 patients in each group. Study Desig - A phase I, nonrandomized, multicohort trial will be conducted to enroll patients at a single institution in a modified 5+5 design. Five patients will be assigned to each cohort (A or B) and receive adoptive transfer of in vitro expanded autologous tumor infiltrating lymphocytes (TIL) without (A) or with (B) autologous tumor lysate loaded DCV administered i.d. 3-5 times with weekly intervals. Prior to TIL transfer all patients will be pre-treated with a preconditioning regimen consisting of cyclophosphamide (60 mg/kg per day for 2 days) followed by fludarabine (25 mg/m(2) per day for 5 days). Administration of TIL will be followed by IL-2 administration (100,000 IU/kg intravenously three times a day to a maximum of 14 doses). All subjects will be monitored for 17 weeks. Outcome Measures - (1) The primary objective of the study is to investigate the safety of the T-cell therapy, with and without DCV, as evaluated according to the NCI CTCAE scale version 4.0. (2) The secondary objective is to measure time to disease progression according to RECIST 1.1. (3) TIL will be analyzed for anti-tumor reactivity as a possible predictive biomarker using an autologous melanoma cell line generated from the patient (when possible), or semi-allogeneic melanoma cell line that has at least one matched HLA-A allele, as targets. (4) In order to assess if the addition of DCV post TIL transfer has influenced TIL persistence, TIL and PBMC will be analysed by TCR sequencing. Clinical trial information: NCT01946373.
Molecular signatures of multiple myeloma progression through single cell RNA-Seq
Authors: Jin Sung Jang, Ying Li, Amit Kumar Mitra, Lintao Bi, Alexej Abyzov, Andre J. van Wijnen, Linda B. Baughn, Brian Van Ness, Vincent Rajkumar, Shaji Kumar, Jin Jen
Journal: Blood Cancer Journal (2019)

Abstract We used single cell RNA-Seq to examine molecular heterogeneity in multiple myeloma (MM) in 597 CD138 positive cells from bone marrow aspirates of 15 patients at different stages of disease progression. 790 genes were selected by coefficient of variation (CV) method and organized cells into four groups (L1–L4) using unsupervised clustering. Plasma cells from each patient clustered into at least two groups based on gene expression signature. The L1 group contained cells from all MGUS patients having the lowest expression of genes involved in the oxidative phosphorylation, Myc targets, and mTORC1 signaling pathways ( p &lt; 1.2 × 10 −14 ). In contrast, the expression level of these pathway genes increased progressively and were the highest in L4 group containing only cells from MM patients with t (4;14) translocations. A 44 genes signature of consistently overexpressed genes among the four groups was associated with poorer overall survival in MM patients (APEX trial, p &lt; 0.0001; HR, 1.83; 95% CI, 1.33–2.52), particularly those treated with bortezomib ( p &lt; 0.0001; HR, 2.00; 95% CI, 1.39–2.89). Our study, using single cell RNA-Seq, identified the most significantly affected molecular pathways during MM progression and provided a novel signature predictive of patient prognosis and treatment stratification.
Weekly administration of bevacizumab, eribulin, and oxalilplatin in patients with platinum-resistant and refractory ovarian carcinomas: A phase II study.
Authors: Yuji Ikeda, Masashi Takano, Hiroko Kouta, Naoki Sasaki, Sayaka Ikeda, Kazuya Kudoh, Tsunekazu Kita, Ryoko Kikuchi, Tomoko Goto, Kenichi Furuya, Yoshihiro Kikuchi
Journal: Journal of Clinical Oncology (2014)

5566 Background: Eribulin, inhibiting a protein component of tubulin, is a candidate for paclitaxel-refractory breast cancers, and Bevacizumab (B) is known to enhance efficacy of anti-cancer agents in ovarian cancers. A phase II study to evaluate weekly administration of B with eribulin and oxaliplatin (EriOX) in patients with platinum-resistant and refractory ovarian carcinomas (PR-ROC) was performed. Methods: Simon's two-stage design was used. In the first stage, 15 patients were accrued. If there were no responder in these patients, the study would be stopped. Otherwise, eight additional patients will be accrued for a total of 23. If three or more responder were observed in 23 patients, this design yields a type I error rate of 0.03 and power of 0.80 when the true response rate were 18%. Patients with PR-ROC were treated with weekly-B-EriOX consisting of B (2mg/kg), eribulin (1mg/m2) and oxaliplatin (30mg/m2). Results: Among 15 patients in the first stage, four responses were observed, and a total of 23 patients were analyzed in this study. There were no cases that discontinued the therapy due to toxicities. Median age of the patient was 58 years (range:38-71). Median number of previous regimen was 4 (range:2-8). Two patients (9%) had a complete response (CR), 3 patients (13%) had a partial remission (PR) and 9 patients (39%) had a stable disease (SD). The response rate and clinical benefit rate (CR+PR+SD) were 17% and 56%, respectively. Median progression-free survival was 3 months (range: 1-8+). Hematological adverse effects (AE) with grade 3/4 were observed in 4 patients (17%). Hypo albuminemia and edema with grade 3 were in 1 patient (8%), respectively. However, all AE were manageable and tolerable. Conclusions: Weekly B and EriOX administration had significant activity with mild AE in patients with PR-ROC. These results warrant further prospective study.
Abstract 21167: Impact of Sex-Mismatch on Heart Transplantation: A Meta-Analysis and Systematic Review
Authors: Vanessa Blumer, Luis Arcay, Mehdi Khalafi, Rodrigo Mendirichaga, Gerardo Zablah, Gabriel A Hernandez, Conrad Macon, Sandra Chaparro
Journal: Circulation (2017)

Introduction: Limited research has explored heart transplantation (HT) outcomes in patients with sex-mismatched organ donors and recipients. Findings on which type of sex-mismatch has worse post-transplant outcomes have been contradictory. Methods: We searched Medline, Embase, Scopus and Cochrane for publications reporting HT outcomes according to donor/recipient sex mismatch through May 2017. Sex mismatched HT male recipients were compared to non-mismatched male recipients, and sex mismatched HT female recipients were compared to non-mismatched female recipients. Outcomes were compared under the random-effects model and heterogeneity examined via Chi 2 and I 2 statistics. Sensitivity analyses were performed. Results: A total of 8 studies including 110211 patients were included in the analysis. Of these, 80% were male recipients and 29% had sex-mismatched transplants. In male recipients, sex mismatch was associated with a higher rate of rejection (OR 1.25; 95% CI 1.19-1.32; p&lt;0.00001). In female recipients, sex mismatch was associated with less rejection (OR 0.72; 95% CI 0.53-0.97; p=0.03). Sex mismatch was not associated with early mortality in either sex. Mortality at 10 years had a tendency of being greater in both male and female mismatched patients; however, the heterogeneity was high and it did not achieve statistical significance (Figure 1). Conclusions: Our analysis suggests that sex-mismatch in HT may affect the incidence of rejection without necessarily having clear impact on mortality. Sex-mismatch in HT remains an area in need of investigation and further studies are needed to determine if sex-mismatch truly influences HT outcomes.
Microsatellite instability as a predictive marker for response to neoadjuvant chemoradiation in locally advanced rectal cancer.
Authors: Rebecca Maria Shulman, Vladimir Avkshtol, Lyudmila DeMora, Nestor F. Esnaola, Michael J. Hall, Elizabeth Handorf, Joshua E. Meyer
Journal: Journal of Clinical Oncology (2018)

806 Background: Microsatellite instability (MSI) is a marker for hypermutability due to impaired DNA mismatch repair and has been shown to be a favorable prognostic marker in colon cancer. We examined the role of MSI in locally advanced rectal cancer (LARC) as a predictive marker for response to neoadjuvant chemoradiation (CRT). Methods: We identified T3-T4 or ≥ N1 rectal cancer with reported MSI status in the National Cancer Data Base from 2007 – 2012. Patients were eligible if they were treated with CRT followed by surgical resection. Squamous cell and carcinoid histologies were excluded. The primary outcome was neoadjuvant rectal (NAR) score, categorized as low ( &lt; 8), intermediate (8-16), and high ( &gt; 16), representing a good, intermediate, and poor response to CRT, respectively. The secondary outcomes were complete pathologic response (ypCR) rate and overall survival (OS). Chi-square, Fisher’s exact, and independent sample t-tests were used to compare MSI status. Multivariable logistic regression models were used to examine factors associated with increasing level of NAR score and ypCR. OS was examined using multivariable Cox proportional hazards models. Results: A total of 1849 patients were eligible for the study and were classified as MSI-high (n = 52) or MSI-low/stable (n = 1797). Patients in the MSI-high group were younger (median age 50.5 vs 57.0, p = 0.005) and had higher rates of mucinous and signet ring histology (p &lt; 0.001), clinical T4 disease (p = 0.001), and clinically positive lymph nodes (p = 0.049). The two groups did not differ in gender, race, grade, or resection margin status. While clinical T and N stage, histology, LVI, tumor grade, and PNI were correlated with the NAR score groups, MSI-high status was not significantly associated with a higher NAR score group on multivariable analysis (OR 1.168, 95% CI 0.673 – 2.028). The MSI-high group also did not differ significantly from MSI-low/stable group in ypCR rate (OR 0.748, 95% CI 0.179 – 3.115) or OS (HR 1.727, 95% CI 0.864 – 3.453) on multivariable analysis. Conclusions: MSI status in LARC was not associated with NAR score, ypCR rate, or OS. Our results do not support the use of MSI status as a predictive marker for response to CRT in LARC.
Correlation of molecular subtypes with survival in AVAglio (bevacizumab [Bv] and radiotherapy [RT] and temozolomide [T] for newly diagnosed glioblastoma [GB]).
Authors: Heidi Phillips, Thomas Sandmann, Congfen Li, Timothy Francis Cloughesy, Olivier L. Chinot, Wolfgang Wick, Ryo Nishikawa, Warren P. Mason, Roger Henriksson, Frank Saran, Albert Lai, Nicola Moore, Priti S. Hegde, Lauren E. Abrey, Richard Bourgon, Josep Garcia, Carlos Bais
Journal: Journal of Clinical Oncology (2014)

2001^ Background: Factors that correlate the extent of clinical benefit with anti-VEGF therapy are poorly understood. Two phase 3 trials in newly diagnosed GB (AVAglio and RTOG-0825) reported that Bv+RT/T prolonged PFS but not OS v placebo (P)+RT/T. Specific GB pt subgroups may derive OS benefit from 1st-line Bv; tumor profiling has uncovered intrinsic and prognostic GB molecular subtypes. Bv efficacy in molecular subtypes was evaluated as an exploratory objective in AVAglio. Methods: An 800 gene platform capable of reliable gene expression (GE) measurement in formalin-fixed, paraffin-embedded samples was developed/validated. In AVAglio, randomizedpts (n=921) received: RT/T+Bv or P, 6 wks; 28-day break; maintenance T+Bv or P (x6); Bv or P until PD/unacceptable toxicity. Samples from 342 AVAglio pts (Bv/P; biomarker evaluable population) were profiled and classified into known GB molecular subtypes (pre-defined hypothesis); assigned subtypes were correlated with OS. An exploratory outcome-driven analysis to discover novel predictor subtypes more directly associated with OS benefit from Bv was then performed. Results: Per recent data from The Cancer Genome Atlas (TCGA), pts with proneural tumors with wild-type isocitrate dehydrogenase 1 (IDH1) had the worst prognosis among all GB subtypes (defined by TCGA [Verhaak, Cancer Cell 2010]/Phillips, Cancer Cell 2006). Importantly, this analysis uncovered a relationship between molecular subtype and extent of OS benefit in Bv-treated pts. Exploratory outcome-driven GE analyses identified novel gene clusters associated with prolonged OS with Bv v P. Pt groups predicted to derive Bv benefit in the outcome-driven method overlapped with, but were not identical to, groups defined by known GB subtypes; thus, novel OS-associated candidate predictors may more precisely identify pts likely to derive benefit from Bv. Conclusions: Candidate molecular predictors were identified in AVAglio, suggesting that a subgroup of newly diagnosed GB pts may derive OS benefit from Bv; these data could impact pt stratification and therapy and give insights into Bv mode of action, and warrant further validation in other datasets. Clinical trial information: NCT00943826.
Nonmetastatic inflammatory breast cancer: Evolution of invasive disease-free (IDFS) and overall survival (OS) over a 21-year period.
Authors: Mahmoud Fekih, Stefan Michiels, Chafika Mazouni, Mahasti Saghatchian, Sofia Rivera, Marie-Christine Mathieu, Fabrice Andre, Suzette Delaloge
Journal: Journal of Clinical Oncology (2014)

1082 Background: Inflammatory breast cancer (IBC) is a very aggressive type of locally advanced BC with a poor prognosis. Its management incorporating preoperative chemotherapy (CT), surgery, radiotherapy (RT), and hormone therapy (HT), when indicated, has become standard in the late 80s. Little is known regarding the evolution of its prognosis throughout the past 20 yrs. The objective of this single center study was to evaluate the evolution of IDFS and OS among patients (pts) with newly diagnosed, localized IBC. Methods: We retrospectively reviewed the records of all pts treated at Gustave Roussy for localized IBC between 01/01/1988 and 31/12/2008. 280 pts were eligible for the study. Pts were subdivided in 4 time groups: 1988 to 1992, 1993 to 1997, 1998 to 2002 and 2003 to 2008. We estimated IDFS and OS from the time of diagnosis using the Kaplan-Meier method. Log-rank tests were used to compare survival curves. Results: Median age was 51 yrs (22-91). 52 % of 231 cases tested for ER were positive and 33% of 78 cases tested for Her2 were positive. Pts received CT (98 %), surgery (55 %), RT (96 %) and HT (61%). Pts characteristics, median IDFS and OS across to 4 periods are all reported in Table 1. While IDFS and OS were mostly stable between 1988 and 2002, a significant improvement was noted thereafter (logrank p-value comparing 4thperiod with the 3 other is 0.046 for IDFS and 0.056 for OS). During the 2 last time periods, median IDFS was 38 mo in Her2+ pts vs 46 mo in Her2- pts (p=0.27), while median OS was 96 mo in Her2+ vs 74 mo in Her2- pts (p=0.33). Conclusions: This study demonstrated a significant improvement in DFS and OS of IBC over the past two decades, especially since 2003. 1988-92 1993-97 1998-02 2003-08 p n 117 47 53 63 - Median age (yrs) 52 50 52 52 P=0.74 ER + (%) 37 45 42 54 P=0.39 HER-2+ (% of tested) NA NA 11 32 - Surgery (%) 21 40 93 97 P<0.001 Chimiotherapy (%) 95 89 98 95 P=0.81 Median nb of CT cycles 8 7 6 9 P=0.001 RT (%) 97 98 93 97 P=0.38 Median IDFS (mo) 32 30 39 63 - Median OS (m) 53 66 63 91 - 5-years IDFS (%) 39 36 45 56 - 5-years OS (%) 48 55 55 71 -
Variable Clinical Presentation of Congenital Thrombotic Thrombocytopenic Purpura in a Large Cohort of Patients Carrying a New Mutation in the CUB1 Domain of ADAMTS13 Gene
Authors: Oleg Pikovsky, Maram Arafat, Hilla Ovadia, Yoav Sharoni, Kayed Al-Athamen, Bibi Kanengisser-Pines, Anat Keren-Politansky, Itai Levi, Ruti Parvari, Anat Rabinovich
Journal: Blood (2018)
Impact of a novel inflammation-based prognostic system on patients undergoing surgery for colorectal cancer: A retrospective study of 480 Japanese patients.
Authors: Mitsuru Ishizuka
Journal: Journal of Clinical Oncology (2014)

e14596 Background: Recent studies have demonstrated that the systemic inflammatory response (SIR), including reactive thrombocytosis and neutrophil to lymphocyte ratio (NLR), is associated with the postoperative survival of patients with several types of cancer. The aim of this study isto estimate the usefulness of a novel inflammation-based prognostic system, named combination of platelet count and neutrophil to lymphocyte ratio (COP-NLR), for predicting the postoperative survival of patients with colorectal cancer (CRC). Methods: The COP-NLR was calculated on the basis of data obtained on the day of admission as follows: patients with both an elevated platelet count (>30 x 104/mm3) and an elevated NLR (>3) were allocated a score of two, and patients showing one or neither were allocated a score of one or zero, respectively. Results: Four hundred eighty patients were enrolled. Multivariate analysis of clinical characteristics selected by univariate analysis such as the maximum tumor diameter (<40/>40, mm), serum levels of C-reactive protein (CRP), albumin, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), the Glasgow Prognostic Score (GPS) and COP-NLR showed that the COP-NLR (0/1, 2) (odds ratio, 1.970; 95% C.I., 1.006 - 3.859; P = 0.048) had an association with cancer-specific survival, along with CEA (odds ratio, 1.004; 95% C.I., 1.001-1.008; P = 0.009) and CA19-9 (odds ratio, 1.001; 95% C.I., 1.000-1.001; P = 0.040). Kaplan-Meier analysis revealed that the COP-NLR was able to divide such patients into three independent groups (P < 0.001). Conclusions: The COP-NLR is considered to be a useful predictor of postoperative survival in patients with CRC.
Imapct of Clonal Hematopoiesis of Indeterminate Potential (CHIP) Associated Mutations and Risk of Comorbidities in Patients with Myelodysplastic Syndrome
Authors: Kiran Naqvi, Koji Sasaki, Guillermo Montalban-Bravo, Ana Alfonso, Musa Yilmaz, Nicholas J Short, Rita Assi, Elias J. Jabbour, Farhad Ravandi, Tapan M. Kadia, Sherry A. Pierce, Koichi Takahashi, Graciela M. Nogueras González, Rashmi Kanagal-Shamanna, Keyur P. Patel, Hagop M. Kantarjian, Guillermo Garcia-Manero
Journal: Blood (2018)
Metastases resection after FOLFIRI-aflibercept (FA) in oxaliplatin-refractory colorectal cancer patients (ORF-CRC).
Authors: Andres J. Muñoz Martín, Silvia Garcia Adrian, Carles Pericay, Ana Ruíz, Patricia Ibeas, Rosana Grandez, Elena Diaz Pena, Ana Maria Lopez, Juez MARTEL Ignacio, Irene Gonzalez Cebrian, Sara Encinas García, Julia Alcaide, Ana Fernandez Fernandez Montes, Carmen Soriano, Teresa Mercade Macarulla, Beatriz García-Paredes, Gema Pulido, Jose M. Mazo, Nuria Rodriguez Salas, Pilar Garcia Alfonso
Journal: Journal of Clinical Oncology (2018)

862 Background: Recent data suggest resection of colorectal metastases after second-line chemotherapy offers similar overall survival (OS) benefit compared to what described in first-line. The improvement in response rate with FA in second-line may increase the number of patients eventually undergo metastases resection. Methods: We performed a retrospective analysis of 32 patients from 26 Spanish hospitals who underwent surgical resection after FA in ORF-CRC in real-life setting. Our aim was to analyze the impact of metastases resection in different organs (liver, lung, etc.) in terms of OS and progression-free survival (PFS) and post-surgical mortality and morbidity. Results: Clinical characteristics: Median age: 65 years (43-83). Sex: 78.1% male, 21.9% female. ECOG 0/1 53.1/46.9%. Ras: wild-type/mutated 25/75%. Type of tumor: colon 75.0%, rectal 25.0%. Location: right 28.1%, transverse 9.4%, and left-side 62.5%. Previous treatment: oxaliplatin combinations (100%), bevacizumab 37.5%, cetuximab 21.97%. Ras wild-type patients received previous anti-EGFR therapy. FA in second-line 93.7% and beyond second-line 6.3%. Median FA cycles before surgery: 6.5 (range 3-44). Type of surgery: liver metastases 46.9%, lung metastases 25.0%, cytoreductive surgery for peritoneal carcinomatosis 15.6%, supraadrenalectomy 3.1%, simultaneous liver and peritoneal carcinomatosis 9.4%. Better tumor response with FA (RECIST1.1): partial response 56.3%, complete response 3.1%, stable disease 40.6%. Median follow-up: 20.9 months [m] (range 3.8-57.3 m). Median PFS from surgery: 8.0 m (confidence interval [CI] 95% 2.5-13.5 m). Median OS from surgery: 37.3 m (CI 95% 23.3-51.4 m). No significant difference between right and left-side tumors in OS or PFS were observed. 90-day postoperative mortality/morbidity: 18.8/0% Reoperation rate: 9.4%. Resection rates: R0 75.0%, R1 15.6%, R2 9.4%. Aflibercept after surgery: 22% patients. Conclusions: Metastases resection following FA in ORF-CRC offers encouraging OS with favorable surgical mortality and morbidity. Salvage surgery should be considered in highly selected patients in second-line setting with oligometastatic disease.
Trends and safety of image-guided percutaneous pleural biopsies in cancer patients.
Authors: Melissa Kate Accordino, Jason Dennis Wright, Jin Joo Shim, Alfred I. Neugut, Grace Hillyer, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2014)

6608 Background: Image-guided percutaneous pleural needle biopsy (IGPPB) is an important tool in the diagnosis and management of cancer patients. Complications of IGPPB include pneumothorax and chest tube placement. Small, single institution studies report rates of pneumothorax between 8-60% and subsequent chest tube in 6-53%. We performed a population-based analysis to evaluate patterns of use, complication rates, and cost associated with IGPPB. Methods: The Premier Perspective database was used to identify cancer patients with at least 1 claim for IGPPB from 2006-2012. Perspective is a fee-supported database created to measure resource utilization and quality from >600 US hospitals. Patients with a pneumothorax were defined by claims within 1 month of IGPPB; rates of hospitalization, chest tube placement and hospital length of stay (LOS) after pneumothorax were analyzed. Multivariable analysis was performed to further examine patient, insurance and hospital characteristics associated with biopsy setting (outpatient vs. inpatient). Pleural biopsy volume and procedure-associated costs over time were evaluated. Results: We identified 59,796 cancer patients who received ≥1 IGPPB, 32,474 (54.3%) in outpatients and 27,322 (45.7%) in inpatients. Characteristics associated with outpatient IGPPB included: younger age, white race, less comorbidity, tumor type, commercial insurance and larger hospitals (p<0.01). Of patients who received outpatient IGPPB, 3,835 (11.8%) developed a pneumothorax, 749 (19.5%, 2.3% of total) were hospitalized and 140 (3.7%, 0.4% of total) required chest tube. Among patients who received IGPPB as an inpatient, 5,638 (20.6%) developed a pneumothorax and, of those, 2,321 (41.2%, 20.4% total) required chest tube. LOS was similar for patients hospitalized after outpatient IGPPB (median 6, mean 7.9) compared to inpatient IGPPB (median 6, mean 8.7). Over time, IGPPB volume increased by 33%, patient costs rose by 53% and outpatient costs rose by 16%. Conclusions: We have shown that in a large population-based sample the use of IGPPB has increased substantially. While pneumothorax was frequent in outpatients, the rate of hospitalization and chest tube placement was small.