tbuckley/cabot-search huggingface dataset:
NGR-hTNF and doxorubicin in relapsed ovarian cancer (OC).
Authors: Domenica Lorusso, Giovanni Scambia, Giulia Amadio, Alessia di Legge, Antonella Pietragalla, Rosa De Vincenzo, Valeria Masciullo, Mirella Di Stefano, Giorgia Mangili, Antonio Lambiase, Claudio Bordignon
Journal: Journal of Clinical Oncology (2012)

5059 Background: NGR-hTNF (asparagine-glycine-arginine human tumor necrosis factor) is able to promote antitumor immune responses and to improve the intratumoral doxorubicin (D) uptake by selectively damaging tumor vessels. Methods: OC patients (pts) with progressive disease (PD) after ≥ 1 platinum/taxane regimen and with a platinum free interval lower than 6 months (PFI &lt;6) or ranging from 6 to 12 months (PFI 6-12) received NGR-hTNF (N) 0.8 µg/m 2 and D 60 mg/m 2 on day 1 every 3 weeks. Primary endpoint of this phase 2 trial was response rate by RECIST criteria with a target of ≥ 6/37 responding pts. Secondary aims were progression free survival (PFS) and overall survival (OS). Results: 37 pts (median age 57 years; PS 0/1 32/5; PFI &lt; 6/6-12 25/12; prior regimens 1-5) were enrolled. Median baseline peripheral blood lymphocyte count (PBLC) was 1.6/mL (interquartile range 1.2-2.1). In all, 177 cycles were given, with 18 pts (49%) receiving ≥ 6 cycles and 12 pts (32%) 8 cycles. Neither grade 3/4 adverse events (AEs) related to N nor increase of D-related AEs were noted. Common grade 1/2 AEs included chills (65%). Eight pts (23%; 95% CI 12-39) had partial response (PR; 2 with PFI &lt; 6 and 6 with PFI 6-12; median duration: 8.2 months). Fifteen pts had stable disease (SD, 43%; 10 with PFI &lt; 6 and 5 with PFI 6-12; median duration: 4.9 months) for an overall disease control (DC, PR+SD) rate of 66%. Mean changes from baseline in target tumor size after 2, 4, 6, and 8 cycles were 2%, -54%, -69%, and -77%, respectively. Median PFS was 5.0 months (95% CI 3.1-6.9) and median OS was 17.0 months (10.4-23.6). In pts with PFI &lt; 6 or 6-12, median PFS were 3.8 and 7.8 months (p=.03) and median OS were 14.3 and 20.1 months (p=.14), respectively. Pts with DC had longer median OS than those with early PD (24.0 and 4.9 months, respectively, p=.02). Longer PFI (p=.03) and higher PBLC (p=.01) were associated with better PFS, while OS correlated only with PBLC (p=.001). In the subset with PFI &lt; 6, pts with PBLC ≥ or &lt; 1.2/mL (1st quartile) had median PFS of 4.9 and 2.6 months (p=.02) and median OS of 15.8 and 4.3 months (p=.0001), respectivel Conclusions: A randomized phase II trial is currently testing D ± NGR-hTNF in pts with PFI &lt; 6 (refractory/resistant). The role of PBLC as blood-based biomarker deserves further investigation.
Evaluation of chemokine-ligand pathways in pretreatment tumor biopsies as predictive biomarker of response to adoptive therapy in metastatic melanoma patients.
Authors: Davide Bedognetti, Sara Tomei, Tara L Spivey, Valeria De Giorgi, Maria Libera Ascierto, Ena Wang, Mark E. Dudley, Lorenzo Uccellini, Mario Roberto Sertoli, Francesco Marincola, Steven A. Rosenberg
Journal: Journal of Clinical Oncology (2012)

8576 Background: Adoptive therapy with tumor infiltrating lymphocytes (TILs) induces objective responses (OR) in approximately 50% of patients with metastatic melanoma. The recruitment of TILs through CXCR3/CCR5-ligand chemokines is believed critical for immune-mediated rejection. Here, we investigated the predictive role of a gene-signature based on CXCR3/CCR5-ligand chemokine transcripts in pre-treatment melanoma biopsies, its biological role and its relation with CCR5-Δ32 polymorphism, which encodes a protein not expressed on cell surface. Methods: Expression of CXCR3/CXCR3-ligand transcripts (i.e CXCL9, 10, 11) and CCR5/CCR5-ligand transcripts (i.e. CCL3, 4, 5) were assessed in 113 pre-treatment tumor biopsies from patients enrolled in adoptive therapy trials: 24 patients achieved a complete remission (CR), 34 a partial remission (PR), and 55 did not respond (NR). Copy number variation and gene expression profile of these target genes were assessed in 15 biopsy-derived cell lines. CCR5-Δ32 was assessed by sequencing germinal DNA. Results: CXCL9, 10 and 11 and CCL5 clustered together and were selected for hierarchical clustering analysis based on the mean-centered gene expression values. A signature characterized by the over-expression of these genes was associated with the likelihood to achieve a clinical response (OR rate: PR+CR: 65% vs 38%, High vs Low, respectively, P=0.015). Neither correlation between the copy number variation and the gene-expression of the corresponding genes, nor correlation between the transcripts of the investigated genes between tumor biopsies and the matched cell lines was detected. Transcript expression of the target genes did not differ between CCR5-Δ32 (n =20) and wild type patients (n=93). Conclusions: Coordinate over-expression of CXCR3/CCR5 ligands in pre-treatment tumor samples was associated with responsiveness to treatment. However, the lack of correlation between in vivo and ex vivo data suggest the inflammatory status characterized by the up-regulation of these inflammatory chemokine genes is an in vivo multifactorial phenomenon.
Everolimus for Korean patients with metastatic renal cell carcinoma who have failed initial treatment of a vascular endothelial growth factor (VEGF): Tyrosine kinase inhibitor (TKI).
Authors: Kwonoh Park, Jin-Hee Ahn, Cheryn Song, Jun Hyuk Hong, Choung-Soo Kim, Hanjong Ahn, Jae-Lyun Lee
Journal: Journal of Clinical Oncology (2013)

e15516 Background: To assess the efficacy, prognostic factor, and safety of everolimus for Korean patients with metastatic renal cell carcinoma (mRCC) who have failed treatment with vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI). Correlation between everolimus associated adeverse events (AEs) and clinical outcome was also analyzed. Methods: Clinical data was collected from all patients with mRCC treated with second-line or more everolimus, patients who has not underwent follow up evaluation after 2 weeks without evidence of disease progression were excluded due to lack of safety evaluation. Results: Totally 100 patients met the inclusion criteria, the median follow-up duration from the time of everolimus initiation was 10.2 months (range, 0.9 – 30.9). The median progression free survival (PFS) of everolimus was 4.4 months, and the overall survival (OS) was 9.1 months. Heng’s criteria was an independent prognostic factor for OS. [Hazzard ratio (HR) (favouralbe risk group vs. poor risk group) = 0.12, P=0.014; HR (intermediate vs. poor) = 0.40, P=0.005] Response to initial VEGF-TKI was also independent prognostic factor for both PFS and OS. [PFS : HR (progression group vs. disease control group) = 3.17, P=0.002; and OS : HR =4.75, P&lt;0.001] Grade 3 or more AEs with everolimus were anemia (15%), hyperglycemia (8%), pneumonitis (7%), and stomatitis (6%). Of note, incidence of pneumonitis was similar (28 cases, 29%) to that of western, 12 patients permanently discontinued. Existence of hyperglycemia and anemia independently correlated with favorable PFS, [HR (Hyperglycemia group vs. non-hyperglycemia group) = 0.58, P =0.056; HR (Anemia group vs. non-anemia group) = 0.51, P=0.021]. Conclusions: Our results suggest that everolimus was effective also in Korean patients. Types and incidences of AEs after everolimus in Korean were mostly similar to western, while they were more severe and permanent discontinuation occurred, especially in pneurmonitis. Thus, Korean mRCC patients who were treated with everolimus should be carefully assessed for AEs to achieve uninterrupted full-dose therapy.
Intratumoral vaccination with activated allogeneic dendritic cells in patients with newly diganosed metastatic renal cell carcinoma (mRCC).
Authors: Anders Magnusson, Anna Laurell, Maria Lonnemark, Einar Brekkan, Lars Adamson, Anna Tolf, Bengt Andersson, AnnaCarin Wallgren, Rolf Kiessling, Alex Karlsson-Parra
Journal: Journal of Clinical Oncology (2014)

3085 Background: Accumulating data indicate that the efficient induction of antigen-specific CTLs characterizing viral infections is caused by cross-priming where infected DCs produce an unique set of inflammatory factors that recruit and activate non-infected ”bystander” DCs. Accordingly, we have developed a cellular adjuvant consisting of activated DCs producing high levels of DC-recruiting and DC-maturating factors in a sustained fashion. This concept doesn´t require MHC-compatibility between injected cells and the patient and therefore introduces the possibility of using pre-produced and freeze-stored DCs from healthy blood donors as an ”off-the-shelf” anti-tumor vaccine when injected intratumorally. Methods: 12 patients with newly diagnosed mRCC (5 with poor prognosis according to Heng criteria) where included in a clinical phase I/II study. Vaccine cells (50 doses) were produced from a leukapheresis-product from one healthy blood donor and subsequently deep-frozen. 5-20 x 10(6) vaccine cells were injected intratumorally twice with 2 weeks interval before nephrectomy. Results: No vaccine-related severe adverse events were observed. 9 out of 11 evaluated patients exhibited an increase in circulating tumor-specific lymphocytes (IFN-gamma ELISPOT) after vaccination. A strong infiltration of CD8+ T cells was found in 7 out of 12 removed kidney tumors, of which 5 tumors, to the best of our knowledge, exhibit the most intensive and general infiltration of CD8+ T cells ever reported in any human solid tumor. Median overall survival (mOS) in the poor prognosis (PP) group is still not reached but has already passed (without addition of targeted therapy) the expected mOS in poor prognosis patients on targeted therapy (9.8 vs 7.8 months). 40% of the patients in the PP-group have to date (Jan 2014) survived for more than 17 months (without addition of targeted therapy) compared to an expected 17 months-survival of 20% in PP patient groups on targeted therapy. Conclusions: Our findings indicate that intratumoral injections of pre-activated allogeneic DCs is safe and induce a systemic CTL-mediated anti-tumor response that may prolong survival in mRCC patients. Clinical trial information: NCT01525017.
Is there a gender effect in bladder cancer?: A population-based study of practice and outcomes.
Authors: Francis Patafio, William J. Mackillop, D. Robert Siemens, Xuejiao Wei, Christopher M. Booth
Journal: Journal of Clinical Oncology (2015)

e15541 Background: It is well known that the incidence of bladder cancer varies by gender. Whether differences exist between women and men in extent of disease, treatment, and outcome is not well described. Here we evaluate gender differences in muscle-invasive bladder cancer using a population-based cohort. Methods: Electronic records were linked to the population-based Ontario Cancer Registry to identify all patients with bladder cancer treated with cystectomy or radiotherapy (RT) in Ontario 1994-2008. Pathology reports were reviewed for all cystectomy cases. In this study we compare extent of disease, treatment, and outcomes between women and men. Logistic regression was used to analyze factors associated with treatment choice. Cox models were used to explore the association between gender and survival. Results: 5259 patients with bladder cancer were treated with cystectomy or radical RT; 25% (1296/5259) were women. There was no gender difference in the proportion of patients treated with cystectomy [75% of women (974/1296), 73% of men (2905/3963), p = 0.189]. Among those patients treated with cystectomy, there was no difference in rates of pre-operative referral to radiation oncology [10% women (100/974), 9% men (270/2905), p = 0.371]. Among the cystectomy cohort, women were slightly more likely to have muscle-invasive disease at the time of surgery [86% (835/974) vs 80% (2335/2905), p < 0.001] but less likely to have lymph nodes dissected [68% (664/974) vs 76% (2210/2905), p < 0.001]. Five year cancer-specific survival (CSS) and overall survival (OS) did not differ between women and men (38% vs 39%, p = 0.522; 33% vs 33% p = 0.795). Among the 2944 patients with muscle-invasive urothelial carcinoma treated with cystectomy, use of chemotherapy and outcomes did not differ significantly between genders. Conclusions: Despite the greater incidence of bladder cancer among men, this population-based cohort did not demonstrate any differences in extent of disease, treatment, or outcome between genders. Pre-op MO NACT Post-op MO ACT 5 yr CSS 5 yr OS Women 17% 5% 38% 18% 35% 29% Men 18% 4% 39% 20% 36% 30% P 0.70 0.42 0.76 0.19 0.51 0.94 MO = medical oncology referral; NACT = neoadjuvant chemotherapy; ACT = adjuvant chemotherapy
Central nervous system lymphoma: Prognostic factors.
Authors: Miriam Huelves, Isabel Millán, Blanca Cantos, Bernard Gaston Doger de Speville, Patricia Ibeas, Ana Lopez-Gonzalez, Miriam Mendez, Antonio Sánchez, Constanza Maximiano, Mariano Provencio
Journal: Journal of Clinical Oncology (2012)

e18521 Background: CNSL constitute less than 2% of all the NHL and 3% of the tumors of the CNS. We studied the prognostic factors of these patients. Methods: This is a retrospective study, we analyzed data from 21 patients, diagnosed on the last 20 years. We used the test of Chi-square corrected by Yachts and Fisher's exact test for qualitative variables and the contrast t of Student and the contrast not parametric U of Mann-Whitney for quantitative variables. The curves of survival were estimated by Kaplan-Meier's method. Results: 62% were males, with a median age of 53.4 years (range 31-72), and the 90.5% were HIV negative. The most frequent histological type (52.4 %) was the Diffuse Large B-cells Lymphoma. Most of them, 75%, were treated with High dose-Metotrexate (HD-MTX). Patients treated with other schedules obtained less disease free survival (DFS) and overall survival (OS). Many prognostic factors were analyzed, but only high LDH values at diagnosis was associated to worse prognostic (p=0.021). The OS and DFS at the first year were 88.2 % and 67.7 % respectively. Conclusions: The best results were obtained in patients treated with HD–MTX. Because of difficult management of these patients, we believe they must be treated in reference centers.
Prognosis value of HER2 in osteosarcomas: A systematic review with meta-analysis.
Authors: Flavio Mavignier Carcano, Lucas Vieira dos Santos, Daniel Onofre Vidal, Luiz Fernando Lopes, Joao Paulo da Silveira Nogueira Lima
Journal: Journal of Clinical Oncology (2015)

e21504 Background: Osteosarcoma is a genetic complex disease and little is known about the molecular mechanisms that lead to its aggressiveness. HER2 overexpression as a prognostic marker has been assessed, but the results are conflicting. This systematic review evaluates the role of HER2 overexpression in osteosarcomas. Methods: Reports assessing HER2 overexpression and outcomes of osteosarcoma were retrieved from MEDLINE, EMBASE, LILACS, CENTRAL databases and main meeting websites. Meta-analyses of overall survival (OS) and event-free survival (EFS) were performed and estimates were expressed as hazard ratios (HR) with confidence intervals (CI) and heterogeneity between studies (I²). Subgroup analysis according to metastatic status (M0, M1) was conducted and interaction test was applied. Results: Twenty studies were included and eight of them (405 patients) had extractable data. Cytoplasmic staining was the most frequent pattern and the meta-analysis suggests that HER2 overexpression is related to poor prognosis: EFS in M0 patients (263 patients; HR 1.91; 95% CI 1.11 to 3.31; p = 0.02; I² = 0) and OS in all patients (280 patients; HR 2.51; 95% CI 1.55 to 4.07; p = 0.0002; I² = 0; interaction between metastatic status p = 0.57). Conclusions: HER2 overexpression seems to be a prognostic marker in osteosarcomas, although a deeper comprehensive analysis is necessary to elucidate its role in clinical outcomes.
Phase II study of dichloroacetate (DCA) in combination with chemoradiation (CRT) for unresected, locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN).
Authors: Steven Francis Powell, William Charles Spanos, Lora Jane Black, Christie Ellison, W. Keith Miskimins, Susan E Puumala, John H. Lee, Mark M. Gitau
Journal: Journal of Clinical Oncology (2015)

e17089 Background: DCA is a metabolic inhibitor that blocks pyruvate dehydrogenase kinase (PDK), which reduces tumor lactate production and may facilitate immune clearance. In vivo SCCHN mouse model data demonstrates improved treatment response with DCA in combination with cisplatin-based CRT. We performed a randomized phase II study to evaluate the safety and efficacy of this approach in patients (pts) with LA-SCCHN. Methods: Pts with previously untreated stage III-IVB SCCHN of the hypopharynx (HP), oropharynx (OP), oral cavity (OC), and larynx (L) were included. Pts were randomized 1:1 to receive DCA 12.5mg/kg or placebo (P) PO or per G-tube twice a day during CRT. CRT consisted of cisplatin 100 mg/m2 (days 1, 22, and 43) given in with radiotherapy (70 Gy/35 fractions/7 weeks). The primary outcome was safety, defined as the group difference between grade 3 and higher adverse events (AEs) based on CTCAE version 4.0. Efficacy was evaluated by overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: 50 pts were enrolled. Tumor sites included 58% OP, 26% L, 12% OC, and 2% HP. There were no significant differences in HPV status, tumor site, or stage between groups. Safety analysis revealed no significant difference in overall grade 3/4 AEs (96% DCA vs 96% P; p = 0.99). The DCA group did have a higher rate of grade 4 AEs (40% DCA vs 19% P; p = 0.02). Grade 4 events in the DCA group included lymphocytopenia (n = 6), neutropenia (n = 2), leukopenia (n = 2), respiratory failure (n = 1), laryngeal edema (n = 1), vomiting (n = 1), and sepsis (n = 1). Treatment delays (36% DCA vs 24% P; p = 0.35) and discontinuations (16% DCA vs 4% P; p = 0.35) were not significantly different. Of the 35 pts (16 DCA, 19 P) evaluable for response at 3 months, ORRs did not significantly differ between groups (94% DCA vs 84% P; p = 0.61). 1-year PFS and OS data will be presented at the meeting. Conclusions: While adding DCA to definitive CRT did not show a significant difference in overall grade 3/4 AEs, grade 4 events were higher. These events were predominantly due to myelosuppression and did not lead to significant treatment delays. Further evaluation of this approach is needed. Clinical trial information: NCT01386632.
Application of the ASCO framework for assessing value in metastatic colorectal cancer clinical trials.
Authors: Doreen Anuli Ezeife, Sunil Parimi, Ellen R. Cusano, Matthew K Smith, Tony H. Truong, Soundouss Raissouni, Yongtao Lin, Jose Gerard Monzon, Haocheng Li, Vincent C. Tam, Patricia A. Tang
Journal: Journal of Clinical Oncology (2017)

687 Background: Phase III trials (P3T) in metastatic colorectal cancer (mCRC) have collectively led to incredible advancements in patient outcomes over the past thirty years. It is unknown how many of these trials have led to clinically relevant improvements based on clinical benefit, toxicity and cost. Our objective was to characterize the evolution of mCRC P3T with the ASCO Value Framework. Methods: P3T of systemic therapy for mCRC published between 1980 and 2015 were identified. Data regarding the trial sample size, journal year of publication, statistical significance, journal impact factor, and citation by the 2015 mCRC National Comprehensive Cancer Network (NCCN) guidelines were extracted. For each trial, the Net Health Benefit (NHB) score was calculated using the June 2015 (original) and May 2016 (revised) ASCO Value Advanced Disease Frameworks. Data were analyzed to identify associations using the Chi-square, Kruskal-Wallis, and t-tests. Results: There were 108 mCRC P3T eligible for calculation of the original and revised NHB score. Median NHB score was 4.1, range -30 to 43.5, using the revised framework. Only 13% of trials received at least 10 bonus points for palliation, quality of life, or tail of the curve. The revised framework demonstrated moderate correlation with the original framework (Pearson correlation coefficient = 0.63, p&lt;0.0001). NHB scores were normally distributed with the revised framework, unlike the original framework. Trials with significant results had significantly higher revised NHB scores (median NHB score 23.1 vs 2.5, p &lt; 0.0001). Clinical trials cited in NCCN had higher revised NHB scores than those not cited (median NHB score 7.6 vs 0, p = 0.03). In multivariate linear regression analysis, the only significant predictor of a high revised NHB score was a statistically significant improvement in the primary outcome. Conclusions: Median revised NHB score for mCRC P3T was 4.1. Higher NHB scores were associated with significant studies and citation by NCCN guidelines, a surrogate for practice-changing trials. The revised ASCO Value Framework can be a useful tool to assess the value of new mCRC treatments.
Pattern and predictors of relapse among early breast cancer patients as seen in a low-income setting: Experience from Nairobi.
Authors: Nicolas Anthony Othieno-Abinya, Peter Bird, Richard Barasa, Henry Otieno Abwao, Catherine Nyongesa, Ahmed Kalebi
Journal: Journal of Clinical Oncology (2015)

e11531 Background: Relapse-free survival (RFS) in early breast cancer depends largely on stage, histology, grade, hormone receptor status, Her2/Neu expression, and treatment, and in screen-detected small tumours, tumour biology plays a vital role. Methods: One thousand and seventeen resectable breast cancer patients seen at Hurlingham Oncology between 1998 and 2014 are included. Adjuvant chemotherapy was mainly doxorubicin/cyclophosphamide ± a taxane. Study variables included age, histology, stage, grade, treatment, ER/PR and Her2/Neu status; also relapse timing, site and outcome. Results: Only 105 patients received treatment. Men were 2 (1.9%), median age was 49.5 years, range 25-82. Ductal carcinoma constituted 81 of 88 cases (92%), lobular carcinoma 6 (6.8%). Sixty-eight were evaluable for stage based on AJCC criteria. Two (2.9 %) were stage 1, 43 (63.2%) stage II, 23 (33.8 %) stage III. Tumour grades I occurred in 7 out of 97 cases (7.1 %), II in 19 (19.2 %), III in 24 (24.2 %), and II/III in 2 (2.9%). It was not established in 47 (47.5 %). Both ER and PR were expressed in 46 out of 86 (53.5 %), ER only in 6 (7 %), PR only in 10 (11.6%), and 40 (46.5 %) were negative for both. Her2/Neu was overexpressed in 17 out of 69 (24.6 %), 44 (63.8%) did not, 8 (%) were equivocal. Of 61 evaluable 8 (13.1%) expressed both hormone receptors and Her2/Neu, 22 (36.1%) expressed none.Initial sites of relapse were local/regional in 9 out of 22 (40.9%), lungs and pleura in 6 (27.3%), bone in 4 (18.2%). At a median follow-up of 48 months, RFS ranged between 5-180 months, 29 out of 55 (49%) had RFS of ≥ 60 months. Seven of 31 patients in stage II (22.6 %) and 13 of 21 in stage III (61.9% %) relapsed, being statistically significant (p < 0.01). Hormone receptors and her2/Neu status did not correlate with risk of relapse. Conclusions: Loco-regional relapses were commonest, and stage was the key RFS determinant.