tbuckley/cabot-search huggingface dataset:
Early tumor shrinkage (ETS) and deepness of response (DoR) to predict progression-free, postprogression, and overall survival: Results from the phase III TRIBE trial.
Authors: Chiara Cremolini, Fotios Loupakis, Sara Lonardi, Patrizia Trenta, Carlotta Antoniotti, Gianluca Masi, Gianluca Tomasello, Monica Ronzoni, Libero Ciuffreda, Alberto Zaniboni, Chiara Carlomagno, Corrado Boni, Francesca Negri, Carlo Barone, Stefano Vitello, Nicola Giuntini, Andrea Bonetti, Mauro D'Amico, Luca Boni, Alfredo Falcone
Journal: Journal of Clinical Oncology (2014)

521 Background: The TRIBE trial demonstrated that first-line FOLFOXIRI plus bevacizumab (bev) improves PFS, response rate (RECIST), and OS in comparison to FOLFIRI plus bev (ASCO Annual Meeting 2013). Recent experiences evidenced that both ETS and DoR may implement the assessment of response and correlate with survival in metastatic colorectal cancer (mCRC). Methods: ETS was defined as the relative change in the sum of longest diameters of RECIST target lesions at week 8 compared to baseline. A 20% decrease was adopted as cut-off value to discriminate early responders and non-responders. DoR was defined as the relative change in the sum of longest diameters of RECIST target lesions at the nadir in the absence of new lesions or progression of non-target lesions compared to baseline. The median value was used as cut-off. Results: Out of 508 randomized patients, 443 and 484 patients were evaluable for ETS and DoR, respectively. Early responders achieved longer PFS (median PFS: 12.7 vs 10.0 mos, HR: 0.66 [0.52-0.79], p&lt;0.0001), post-progression survival (median PPS: 17.1 vs 10.7 mos, HR: 0.64 [0.47-0.81], p=0.0005) and OS (median OS: 35.8 vs 22.4 mos, HR: 0.54 [0.39-0.67], p&lt;0.0001). Patients achieving a DoR higher than the median reported longer PFS (median PFS: 13.1 vs 9.3 mos, HR: 0.61 [0.49-0.73], p&lt;0.0001), PPS (median PPS: 18.4 vs 10.5 mos, HR: 0.58 [0.44-0.73], p&lt;0.0001) and OS (median OS: 36.8 vs 21.3 mos, HR: 0.47 [0.35-0.58], p&lt;0.0001). A significant correlation of DoR as a continuous variable with PFS (HR: 0.983 [0.979-0.986], p&lt;0.0001), PPS (HR: 0.987 [0.984-0.991], p&lt;0.0001) and OS (HR: 0.979 [0.975-0.983], p&lt;0.0001) was observed. No differences across arms were reported. Conclusions: ETS and DoR predict PFS, PPS and OS. These findings support the hypothesis that the adoption of active upfront regimens, able to induce a rapid and deep tumor shrinkage, may positively affect the subsequent disease history, thus translating into an advantage in survival. Clinical trial information: NCT00719797.
Assessment of bone metastases in patients (pts) with urothelial carcinoma using <sup>18</sup>F-sodium fluoride PET/CT (<sup>18</sup>F-NaF) versus <sup>18</sup>F-fluorodeoxyglucose PET/CT (<sup>18</sup>F-FDG).
Authors: Benjamin Adam Weinberg, Maria Liza Lindenberg, Karen A. Kurdziel, Seth M. Steinberg, David J. Liewehr, Kattie Khadar, Yolanda McKinney, Peter L. Choyke, Andrea Borghese Apolo
Journal: Journal of Clinical Oncology (2014)

329 Background: 18 F-NaF has shown improved sensitivity for bone imaging when compared to conventional planar imaging or SPECT/CT using 99m Tc-MDP. We compared the number of bone lesions detected on 18 F-NaF versus 18 F-FDG in urothelial cancer pts with known bone metastases undergoing treatment. Methods: Pts enrolled in a prospective single-arm phase II study of cabozantinib underwent 18 F-NaF and 18 F-FDG scans at baseline and at 8 weeks of therapy. In a lesion-based analysis independently confirmed by a nuclear medicine physician, abnormal foci of radiotracer uptake were categorized by location (skull, spine, pelvis, thorax, or long bones) and by disease state (benign, malignant, or indeterminate). A patient-based analysis was performed to determine if findings indicated disease progression, stable disease, or improvement of disease, based on the number of lesions and standardized uptake values (SUVs). Results: 294 total bone lesions were identified at baseline in 10 pts (8 male and 2 female, ages 44-73). 18 F-NaF identified more lesions than 18 F-FDG at baseline, 294 vs. 119. In a paired analysis, the median difference was 11.5 more lesions detected per patient on 18 F-NaF vs. 18 F-FDG (by Wilcoxon signed-rank test, p = 0.023). More total thoracic bone lesions at baseline, 100 vs. 23, were also detected on 18 F-NaF vs. 18 F-FDG, median 6.5 vs. 1.0 with a median difference of 6 more lesions per patient on 18 F-NaF (p = 0.016). 18 F-NaF also detected more skull lesions at baseline, 19 vs. 1, which was clinically but not statistically significant (p = 0.250). There was general concordance in the patient-based analysis; only 1 18 F-NaF scan demonstrated progressive disease while its corresponding 18 F-FDG scan showed stable disease. Conclusions: 18 F-NaF identified more lesions than 18 F-FDG at baseline, making it a good staging exam. However, there was agreement between 18 F-NaF and 18 F-FDG in terms of tumor response in almost all the follow-up scans. Therefore, although a greater number of bone lesions are seen in 18 F-NaF compared with 18 F-FDG, the clinical significance in assessing treatment response remains to be determined. Clinical trial information: NCT01688999.
Hyperphosphorylation of auto-antigen targets of paraproteins in MGUS, multiple myeloma (MM), and Waldentrom macroglobulinemia (WM) is a consistent finding and suggests chronic antigenic stimulation by post-translationally modified auto-antigens as a common mechanism playing a role in the pathogenesis of MGUS/MM/WM.
Authors: S. Grass, K. Preuss, N. Fadle, E. Regitz, M. Pfreundschuh
Journal: Journal of Clinical Oncology (2011)

e18573 Background: Paratarg-7 (P-7) is a frequent target of paraproteins from patients with MGUS, multiple myeloma (MM) and Waldenstroem's macroglobulinemia (WM). Patients with paratarg-7 specific paraproteins are carriers of a hyperphosphorylated paratarg-7 (pP-7). pP-7 carrier state is inherited in an autosomal-dominant fashion, explaining cases of familial MGUS/MM/WM. The aim of this study was to determine whether other auto-antigenic targets of human paraproteins are also hyperphosphorylated. Methods: Moleculary defined auto-antigenic targets of paraproteins were subjected to DNA sequencing, gel electrophoresis and isoelectric focussing. Results: Of 11 molecularly defined antigenic targets of paraproteins, 9 were auto-antigens. Of these 9 cases, autologous tissues from the patients whose paraprotein targeted the respective auto-antigen were available from 8 patients. These autoantigens were: paratarg-2= TTP2, paratarg-5 = microtubulus-associated protein, paratarg-6 = LAPTM5, paratarg-7 = SLP-2, paratarg 8 = ATG-13, paratarg 9 = RSP16, paratarg-10 = SPAG7 and paratarg 11 = SIVA. SNPS or mutations in the autologous patient were excluded by sequencing the genes coding for the respective auto-antigens in the patients and in healthy controls. However, isoelectric focussing before and after phosphatase treatment revealed that all autoantigens tested were hyperphosphorylated in the respective patients compared to healthy controls. For two antigenic targets (paratarg-7 and paratarg-8) an autosomal-dominant inheritance could be shown. Conclusions: The consistent finding of hyperphosphorylated autoantigens suggests that these posttranslationally modified autoantigens entertain a chronic auto-immune response. Hyperphosphorylation of antigenic targets of paraproteins represents a common underlying mechanism associated with the pathogenesis of MGUS/MM, the elucidation of which can now be addressed using specific molecular tools.
A Prospective, Multi Center Phase II Study Evaluating Predictive Factors for Lenalidomide Treatment in Relapse or Refractory Chronic Lymphocytic Leukemia Patients (LE.P.RE.): Preliminary Results about the First 20 Enrolled Patients
Authors: Rossana Maffei, Silvia Martinelli, Giulia Debbia, Gian Matteo Rigolin, Lara Rizzotto, Ilaria Castelli, Goretta Bonacorsi, Jenny Bulgarelli, Stefania Fiorcari, Patrizia Zucchini, Rita Santachiara, Francesco Forconi, Davide Rossi, Luca Laurenti, Giuseppe A Palumbo, Daniele Vallisa, Antonio Cuneo, Gianluca Gaidano, Mario Luppi, Roberto Marasca
Journal: Blood (2011)
Efficacy and safety of FOLFIRI regimen in elderly versus nonelderly patients with advanced colorectal and gastric cancer.
Authors: Jin Won Kim, Kyu-Pyo Kim, Ju Hyun Lee, Yong Sang Hong, Sun Young Kim, Sook Ryun Park, Byung-Ho Nam, Keun-Wook Lee, Ik-Joo Chung, Young Suk Park, Jee Hyun Kim, Tae Won Kim
Journal: Journal of Clinical Oncology (2016)

701 Background: Irinotecan-based chemotherapy is a standard backbone in patients (pts) with advanced colorectal (CRC) or gastric cancer (GC). However, there is still a paucity of information concerning the efficacy and safety of irinotecan-based regimen in elderly pts. Methods: Using pt cohort (N = 1,545) of the UGT1A1 genotype study (Kim KP, et al. J Clin Oncol 33, 2015 (suppl; abstr 3600)), we performed subgroup analysis comparing the efficacy and safety between elderly (age ≥ 70 years, median 73 years, N = 245) and non-elderly ( &lt; 70 years, median 57 years, N = 1,300) pts with advanced CRC or GC who received first- or second-line FOLFIRI chemotherapy. Results: In both CRC (N = 934) and GC cohorts (N = 611), elderly pts received significantly lower dose of irinotecan (CRC: mean 74.8% vs. 80.9%, P &lt; 0.001; GC: 72.4% vs. 76.2%, P = 0.018) and infusional 5-fluorouracil (CRC: 61.6% vs. 71.8%, P &lt; 0.001; GC: 47.1% vs. 55.8%, P = 0.004). However, the response rate was similar between elderly and non-elderly pts in both CRC (28.7% vs. 32.9%, P = 0.347) and GC cohorts (22.9% vs. 18.3%; P = 0.369). The progression-free survival was also similar between the two age groups in both CRC (median 27.9 vs. 29.1 weeks, P = 0.202) and GC cohorts (20.1 vs. 17.0 weeks, P = 0.407). In addition, the overall survival was comparable between the two age groups in both CRC (81.9 vs. 91.8 weeks, P = 0.965) and GC cohorts (33.6 vs. 49.3 weeks, P = 0.085). In both cohorts, asthenia was significantly more frequent in elderly pts, while nausea and vomiting were significantly more frequent in non-elderly pts. In CRC cohort, grade 3-4 toxicities that were significantly more frequent in elderly pts were asthenia (1.3% vs. 0.2% per cycle, P &lt; 0.001), mucositis (0.4% vs. 0.1%, P = 0.021), and anorexia (0.8% vs. 0.2%, P = 0.005) in CRC cohort. However, in GC cohort, grade 3-4 toxicities were not significantly different between the two age groups. Conclusions: Despite relatively lower dose intensity in elderly pts, efficacy of FOLFIRI regimen in this subset was comparable to that of non-elderly pts. FOLFIRI regimen was relatively well tolerated in elderly pts. Taken together, FOLFIRI is a considerable standard backbone in elderly pts with advanced CRC or GC.
Allogeneic transplantation for patients with high-risk or refractory neuroblastoma.
Authors: T. A. Driscoll, P. L. Martin, J. Moffet, M. Daniel, K. Page, S. Parikh, V. Prasad, P. Szabolcs, J. Kurtzberg
Journal: Journal of Clinical Oncology (2011)

9552 Background: While the survival of high-risk neuroblastoma patients has improved with myeloablative chemotherapy (MAC) and 13-cis retinoic acid, 60% of children fail this approach, thus other strategies are needed. As a potential platform for future immunologic-based therapies, we report a retrospective, single-center experience using allogeneic hematopoietic stem cell transplantation (allo-HSCT) following MAC for high risk or recurrent neuroblastoma (NB). Methods: Between June 1994 and November 2007, 17 pediatric patients with high risk or recurrent NB underwent allo-HSCT: allograft sources were related bone marrow (MRD) in 10 patients (pts) and unrelated umbilical cord blood (UCB) in 7 pts. At initial diagnosis the median age was 3.5 years, 16 pts had stage 4 and 1 patient had stage 3 disease. N-myc was amplified in 4 of the 12 pts with available N-myc status. Prior to allo-HSCT, 4 pts were in CR and 7 pts had failed autologous HSCT. Median time from NB diagnosis to allo-HSCT was 14.9 months. Regarding MAC, 7 pts received total body irradiation (TBI)-based regimens: (5 TBI/melphalan (Mel) and 2 TBI/thiotepa), 6 pts received cyclophosphamide (Cy)-based regimens (5 Cy/Mel and 1 Cy-thiotepa), 1 received carboplatin /etoposide/melphalan (CEM), and 3 pts received therapeutic I-131MIBG based regimens (MIBG /CEM in 1, MIBG /campath /Mel in 1, and MIBG/TBI/Mel in 1). Results: The median day to neutrophil engraftment (ANC > 500) was 10.5 days for MRD BMT and 22 days for UCBT. The median day to platelet engraftment (plt >20k) for MRD BMT was 29.5 days and for UCBT was 62 days. Acute GVHD (grades I-IV) was seen in 6 patients: 3 grade-I skin, 1 grade-II skin, and 2 grade-III involving both skin and gut. Eleven pts (65%) died at a median of 377 days post-allo-HSCT: 2 infections (PCP pneumonia, Pseudomonal sepsis), 2 MSOF, 1 leukemic relapse (child with recurrent NB and secondary AML) and 6 NB progression. Six patients (5 MRD, 1 UCB) are long-term survivors with overall survival of 35% at 10 years. Conclusions: Allo-HSCT provided durable remission in a very high risk group of NB patients. Therefore a strategy that incorporates early allografting with targeted immunologic therapy should be investigated for refractory or ultra-high risk NB patients.
First-line treatment patterns for recurrent and/or metastatic head and neck cancer (R/M HNC) in Europe.
Authors: M. C. Merlano, J. B. Vermorken, H. Wilke, J. Bourhis, R. Mesia, J. Guigay, U. Keilholz, M. Hartmann, J. Lefebvre
Journal: Journal of Clinical Oncology (2010)

e16016 Background: The first-line treatment of R/M HNC has evolved in recent years with the introduction of many new therapies. The objective of the current patient record-based survey was to investigate the different treatment modalities and combinations used for R/M HNC in Europe. Methods: Between 9/10/09 and 7/12/09, ear, nose and throat, and radiation and medical oncology specialists from France, Germany, Italy and Spain were asked to provide completed record forms for the last 7-10 HNC patients they treated with chemotherapy (CT), a targeted therapy and/or radiotherapy (RT). Raw data were weighted and analyzed using the “Ethnos” reporting system. First-line treatment patterns for R/M disease are reported here, and data for 2009 were compared with data from a similar survey conducted in 2008. Results: 256 physicians provided 2065 patient records. 845 records were for patients with R/M disease, of whom 747 (88%) were given first-line treatment. Of these patients, 557 (75%) received a systemic treatment only, 22% received systemic treatment plus RT and 3% received RT alone. 403/557 (72%) patients treated with first-line systemic treatment received combination therapy. The most common combination was CT and the epidermal growth factor receptor-targeted monoclonal antibody cetuximab (65%), with the main combination used being cetuximab + platinum + 5-FU (41%). The remaining 35% of patients received platinum-based combination CT. Among the 154 patients receiving single-agent therapy, the most commonly used agent was cetuximab (51%), followed by a taxane (29%), a platinum compound (9%), methotrexate and other drugs (6% each). Between 2008 and 2009, there was a doubling of the use of the systemic combination of platinum-based CT plus cetuximab first-line (27.5% vs 56%), which is replacing the use of platinum-based combination CT only (65% vs 35%). Conclusions: This analysis of current clinical practice in 4 large European countries shows that after many years without a substantial change in management strategies for first-line R/M HNC, treatment has evolved, with the combination of platinum-based CT and cetuximab replacing the sole use of platinum-based combination CT as the standard approach. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Institut Gustave Roussy, Merck KGaA Merck Serono, sanofi-aventis Amgen, Bristol-Myers Squibb, Merck Serono, Pfizer, Roche, sanofi-aventis Merck Serono
Prognostic biomarker exploration for patients with metastatic renal cell carcinoma receiving VEGFR TKI.
Authors: Inkeun Park, Yong Mee Cho, Jae-Lyun Lee, Jin-Hee Ahn, Dae Ho Lee, Dalsan You, In Gab Jeong, Cheryn Song, Bum-Sik Hong, Jun Hyuck Hong, Hanjong Ahn
Journal: Journal of Clinical Oncology (2015)

491 Background: To verify the prognostic importance of selected tumor tissue biomarkers in metastatic renal cell carcinoma (mRCC) patients (pts), we performed immunohistochemical (IHC) staining in tumor sample and statistical analyses. Methods: The clinicopathological features, treatment, and outcome of mRCC pts treated with vascular endothelial growth factor tyrosine kinase inhibitor (VEGFR TKI) between July 2006 and March 2011 at our center were reviewed. IHC staining for FGF base, FGFR1, 2, 3, and 4, HGF, PTEN, CAIX, pS6, HIF-1a, HIF-2a, IL-8, mTOR was done, and each specimen was scored based on the staining intensity and the percentage of positive cells. We performed univariate and multivariable analyses to verify prognostic factors for overall survival (OS). Results: We found 123 pts who met inclusion criteria. Most pts had clear cell carcinoma (107 pts, 87.0%). Fuhrman’s nuclear grade (NG) was 2 in 21 (17.1%), 3 in 49 (39.8%), and 4 in 52 (42.3%), respectively. Sarcomatoid change and coagulative necrosis were found in 51 pts and 58 pts. Using Heng’s criteria, 20 pts (16.3%), 87 (70.7%), and 16 (13.0%) belonged to favorable, intermediate, and poor risk group, respectively. First-line VEGFR TKIs prescribed were sunitinib (97 pts, 78.9%), sorafenib (23 pts, 18.7%), and pazopanib (3 pts, 2.4%). In univariate analysis, CAIX (less than 47.5% vs 47.5% or more, p=0.001), mTOR (20% or less vs more than 20%, p=0.0032), Heng risk group (good vs intermediate vs poor, p&lt;0.001), sarcomatoid change (40% or less vs more than 40%, p&lt;0.001), coagulative necrosis (20% or less vs more than 20%, p&lt;0.001), Furhman NG (2 vs 3 vs 4, p=0.037) were statistically significant. In multivariable analysis, CAIX, Heng risk group, sarcomatoid change, and hyaline necrosis were identified as independent prognostic factors (Table). Conclusions: All investigated biomarkers but CAIX did not show prognostic importance for mRCC pts receiving VEGFR TKI. [Table: see text]
Clinical improvement and rapid radiographic regression induced by a MET inhibitor in a patient with MET-amplified glioblastoma.
Authors: A. S. Chi, E. L. Kwak, J. W. Clark, D. L. Wang, D. N. Louis, A. J. Iafrate, T. Batchelor
Journal: Journal of Clinical Oncology (2011)

2072 Background: The MET tyrosine kinase receptor gene is amplified in 5% of glioblastoma (GBM). We prospectively screen GBM patients for MET amplification by fluorescence in situ hybridization as a part of comprehensive molecular profiling offered to all glioma patients. We identified a recurrent GBM patient with MET amplification and enrolled her onto a phase I trial of crizotinib (PF-02341066), an oral small molecule dual MET/ALK inhibitor, for solid tumors with MET amplification or ALK translocation. Methods: A 62 year old woman with dizziness was found to have a 2.2 cm enhancing lesion within the genu of the corpus callosum on a cranial MRI. Stereotactic biopsy established a diagnosis of GBM, and molecular profiling of her tumor revealed MET amplification. She was enrolled onto a phase II trial of cediranib, an oral pan-VEGF receptor inhibitor, with concurrent radiation and temozolomide followed by monthly temozolomide and cediranib. After 5 post-radiation cycles of temozolomide and cediranib, she developed disorientation and a MRI demonstrated progressive disease. She was started on dexamethasone 2 mg BID and enrolled onto a phase I trial of crizotinib monotherapy. Results: After 2 monthly cycles of crizotinib, a MRI demonstrated 40% reduction of the contrast-enhancing lesion with decrease in the surrounding T2/FLAIR abnormality. Disorientation improved and she was otherwise neurologically unchanged. Two weeks after starting crizotinib, dexamethasone was tapered off. During the 1st crizotinib cycle she developed grade 1 fatigue. After the 2nd cycle she developed left popliteal venous thrombosis, thought unrelated to crizotinib, and was started on enoxaparin. She currently remains neurologically and radiographically stable after 4.5 months on crizotinib. Conclusions: We report clinical improvement and rapid radiographic regression in a MET-amplified GBM patient treated with crizotinib, a dual MET/ALK inhibitor. This case suggests MET may be a rational target in GBM, even for patients who progress on anti-angiogenic therapy. In addition, comprehensive prospective molecular profiling of clinical specimens enabled rational selection of a targeted agent clinical trial.
Postmortem evaluation of end-organ toxicity in patients with glioblastoma (GBM) treated with temozolomide (TMZ) and bevacizumab (BEV).
Authors: J. Zhu, X. J. Tian, N. Linendoll, R. Pfannl, M. Pilichowska
Journal: Journal of Clinical Oncology (2011)

e19579 Background: BEV and TMZ are the main chemotherapy options for GBM. BEV containing regimens are also used for metastatic systemic cancers. There are concerns of end-organ damage from long term use of BEV containing regimens. However, post-mortem examination result has not been reported. Methods: Postmortem organ specific morphologic studies including electron microscopy (EM) and immunofluorescence (IF) were performed in 7 cases of GBM who were on palliative care prior to their death. Six male and 1 female subjects were included with age ranging from 52 to 77 years old (median 57 years old). All patients received standard treatment for GBM with subsequent monthly TMZ. After GBM progression they received BEV with TMZ or irinotecan (5-49 treatments, median 17 treatments). Medical records of all subjects were reviewed. Clinical toxicities and laboratory abnormalities were documented and correlated with autopsy results. Consent for autopsy exams were obtained from the next of kin. Results: Clinically, 5 subjects developed proteinuria (trace to 3+) and 2 subjects had hypertension. At autopsy, there was no significant morphologic evidence of TMZ/BEV-related injury in heart, liver, adrenal glands, thyroid, pancreas, spleen, or bone marrow. In all cases the glomeruli revealed variable degree of glomerular basement membrane thickening with segmental to global double contours and without proliferative lesions. EM examination of kidney showed homogenized substructure and subendothelial rarefaction with wrinkling of the glomerular basement membrane. The vasculature showed variable mural thickening as observed in hypertensive changes. IF examination showed no immune complex deposition. The cause of death in most patients was bronchopneumonia (6/7). Pulmonary embolism was found in 3 cases with 1 case showing additional alveolar hemorrhage. One case had peritonitis with diverticular perforation during BEV therapy. Conclusions: With exception of the kidneys there is no significant end-organ damage associated with TMZ and BEV therapies. In the kidney the toxicity is mild to moderate endothelial damage which corresponds to the proteinuria and hypertension seen clinically.