tbuckley/cabot-search huggingface dataset:
Clinical efficacy and safety of apatinib in treatment of alpha fetoprotein-positive advanced gastric cancer.
Authors: Jia Chen, Lingxiang Chen, Li Yang, Chunrong Zhu, Chaoying Liu
Journal: Journal of Clinical Oncology (2017)

e15513 Background: Alpha fetoprotein (AFP)-producing gastric cancer (APGC) is a minor subtype of gastric cancer (GC) with high malignancy, rapid progress, high metastatic rate and poor prognosis. Treatment of AFP-positive GC is not different from that of AFP-negative GC, but the efficacy can not match for the latter. Apatinib, a novel inhibitor of VEGFR-2, has achieved survival improvement in advanced GC patients. We aimed to evaluate the efficacy and safety of apatinib in AFP-positive advanced gastric cancer patients. Methods: This was a single-arm, open-label, exploratory study design. Eligibility criteria included histologically proven GC; patient age 18-75 years; AFP-positive; clinical stage III or IV; and ECOG performance status of 1 or 2. A history of receiving previous treatment was not required. All the patients were orally given apatinib at an initial dose of 500 mg (qd) until disease progression or death. Dose reduction to 250 mg was allowed. Results: A total of 16 pts including 15 males and 1 female were eligible. The median age was 62.5 years (range 26-74 years). Poorly differentiated adenocarcinoma was the main histological type, and the main metastatic sites were liver (12/16) and abdominal (2/16). Ten pts received gastric surgery and 13 had previous chemotherapy prior to apatinib, and 10 patients received chemotherapy along with apatinib. Among the 16 pts, 14 were available for the efficacy evaluation. Two pts achieved partial response (PR), 10 had stable disease (SD), and 2 had progressive disease (PD). The objective response rate (ORR) and the disease control rate (DCR) were 14.3% (2/14) and 85.7% (12/14), respectively. All pts were included for safety analysis. The incidence of adverse events (AEs) was 87.5%. Main AEs were bone marrow suppression (43.75%), hypertension (50%), and abdominal pain (31.25%). Conclusions: Administration of apatinib make clinical benefit to AFP positive advanced gastric cancer with a comparable disease control and tolerable adverse reactions. Clinical trial information: ChiCTR-OPC-16008295. Clinical trial information: ChiCTR-OPC-16008295.
Prognosis of desmoid tumors (DT): A prospective nationwide survey of 771 patients (pts).
Authors: Thomas Ryckewaert, Axel Le Cesne, Sylvie Bonvalot, Jean-Yves Blay, Antoine Giraud, Emmanuelle Bompas, Maria Rios, S Bastien Salas, Nicolas Isambert, Pascaline Boudou-Rouquette, Charles Honoré, Antoine Italiano, Isabelle Laure Ray-Coquard, Sophie Piperno-Neumann, Francois Gouin, Francois Bertucci, Francoise Ducimetiere, Jean-Michel Coindre, Nicolas Penel
Journal: Journal of Clinical Oncology (2017)

11047 Background: Prognostic factors and optimal management of DT are not yet established. Methods: We analyzed the outcome of 771 consecutive DT pts treated between 01/2010 and 12/2016 in France. We have calculated event-free survival (EFS) defined as local relapse after surgery, progressive disease during non surgical approach or change in treatment strategy (e.g. from wait and see to systemic treatment or local treatment). Results: The sex ratio M/F was 219/552, the median age was 39 (2-90), and the median size 57 mm (4-700). 596 DT are found CTNNB1-mutated (71%). The 1st treatment was wait and see (369, 48%), surgery (343, 44%), systemic treatment (25, 3%), or radiotherapy (3, 0%). The median follow-up was 32 mo. 230 events occurred (including 1 death). The median EFS was 27 mo. After initial wait and see, pts required systemic treatment in 61 cases (15%), radiotherapy (4; 1%), cryotherapy (3; 1%), surgery (2; 0%) and radiofrequency (1, 0%). After initial surgery, DT pts required wait and see for relapse in 88 cases (25%), systemic treatment in 17 cases (5%), radiotherapy (6; 2%), cryotherapy (2; 0%) and surgery (1, 0%). Univariate analysis identified 3 factors associated with EFS: favorable locations (median not reached (NR) vs. 21 mo; p = 0.0001), nature of sampling (core needle biopsy: 31 mo; resection 26 mo and open biopsy 15 mo, p = 0.046) and superficial DT (NR vs. 28 mo, p = 0.00001). Favorable locations included: abdominal wall (236 pts), intra-abdominal (78 pts), breast (27 pts) and digestive viscera (42 pts). Chest wall (209 pts), head and neck (28 pts), lower limb (90 pts), upper limb (25 pts) and pelvis (18 pts) were all associated with poor EFS. Multivariate analysis identified only 1 prognostic factor for EFS: favorable location HR = 0.52 [0.39-0.69]. Compared to surgery, wait and see as 1st treatment was associated with better EFS in unfavorable DT locations (HR = 0.74 [0.74-0.56]; p = 0.001) but not associated with EFS in favorable locations (HR = 0.89 [0.69-1.13]; p = 0.420). Conclusions: Since primary location of DT is the major determinant of DT outcome, stratified approach according to location has to be prospectively assessed. Correlative biology analyses are warranted to better understand these findings.
The impact of novel induction regimens on transplant outcome in newly diagnosed multiple myeloma after controlling for high-risk FISH cytogenetics.
Authors: Rajshekhar Chakraborty, Eli Muchtar, Shaji Kumar, Francis Buadi, David Dingli, Angela Dispenzieri, Suzanne R. Hayman, William J. Hogan, Prashant Kapoor, Martha Lacy, Nelson Leung, Morie A. Gertz
Journal: Journal of Clinical Oncology (2016)

8033 Background: Induction therapy with novel agents followed by autologous stem cell transplant (ASCT) is standard of care for eligible patients with newly diagnosed multiple myeloma (MM). The primary objective of our retrospective study was to compare overall survival (OS) in 1086 patients receiving frequently used novel agent–based induction regimens followed by early ASCT, after controlling for presence of high-risk cytogenetics by fluorescence in situ hybridization (FISH) at diagnosis. Methods: Study patients included those who had first transplant within 12 months of diagnosis, did not receive > 1 induction regimen, did not relapse prior to transplant and did not receive treatment for smoldering MM. Factors included in multivariate analysis were presence of high-risk FISH cytogenetics, induction-regimen group and use of maintenance or consolidation therapy post-transplant. Results: Major subgroups by induction therapy included cyclophosphamide-bortezomib-dexamethasone (CyBorD; n = 193), bortezomib-lenalidomide-dexamethasone (VRd; n = 126), lenalidomide-dexamethasone (Rd; n = 251), thalidomide-dexamethasone (Td; n = 155), and bortezomib-dexamethasone (Vd; n = 64); vincristine-doxorubicin-dexamethasone or dexamethasone alone (VAD/Dex; n = 228) was used as the reference group. Median age at diagnosis was 60.3 (interquartile range 53.9-65.9) years and median follow-up was 66.7 (95% CI 60.4-74.7) months. FISH cytogenetics at diagnosis was available for 466 patients. Using Kaplan-Meier analysis, 5-year OS rates (with 95% CI) for CyBorD, VRd, Vd, Rd, Td and VAD/Dex were 79.2 (65.3-88.5), 79.0 (65.7-88.1), 72.3 (58.5-82.9), 79.2 (72.9-84.4), 57.4 (49.5-65.0) and 63.2 (57.0-69.4) % respectively. Multivariate analysis showed VRd to have superior OS compared to CyBorD (HR 0.35; 95% CI, 0.11-0.93; P = .0353) and Vd (HR, 0.20; 95% CI, 0.06-0.66; P = .0077) irrespective of high-risk FISH cytogenetics at diagnosis. Conclusions: In conclusion, our study showed that among patients completing induction therapy and having an early ASCT, use of VRd induction led to superior OS compared to CyBorD and Vd in those with or without high-risk FISH cytogenetics.
Clinical benefit among lenalidomide (LEN)-treated patients (pts) with RBC transfusion-dependent (RBC-TD) low-/int-1-risk myelodysplastic syndromes (MDS) without del(5q).
Authors: Guillermo Garcia-Manero, Antonio Medina Almeida, Pierre Fenaux, Norbert Gattermann, Aristoteles Giagounidis, Stuart Goldberg, Keiya Ozawa, Jerry Weaver, Mary M. Sugrue, Valeria Santini
Journal: Journal of Clinical Oncology (2016)

7014 Background: In the phase III MDS-005 study of LEN in RBC-TD lower-risk (LR) non-del(5q) MDS pts ineligible for/refractory to erythropoiesis-stimulating agents (ESAs), a statistically significant and clinically relevant higher proportion of LEN-treated pts achieved RBC transfusion independence (RBC-TI) ≥ 8 wks vs placebo (PBO) (P < 0.001); other measures of efficacy collected included erythroid improvement and cytogenetic response (CyR). This analysis evaluates the relationship between LEN and clinically meaningful measures of response in pts from MDS-005. Methods: Pts were randomized 2:1 to LEN 10 mg/day (n = 160) or PBO (n = 79) once daily. Clinical benefit ≥ 8 wks was defined as the composite endpoint of RBC-TI ≥ 8 wks, or transfusion reduction of ≥ 4 units packed RBCs (pRBCs) ≥ 8 wks, or hemoglobin (Hb) increase ≥ 1.5 g/dL at 8 wks (IWG 2006), or CyR. The rate of transfusion reduction was calculated using data collected during a 112-day assessment period to account for on-study differences in transfusion burden. CyR was also evaluated separately. Results: Clinical benefit was higher in pts treated with LEN vs PBO (Table). In evaluable pts with ≥ 1 follow-up assessment (n = 43), CyR with LEN was reported in 9 (33.3%) pts (major: n = 5; minor: n = 4). No CyR occurred in the PBO group. Among pts with CyR, 5 (55.6%) also achieved RBC-TI ≥ 8 wks. Conclusions: In RBC-TD pts with LR non-del(5q) MDS ineligible for or refractory to ESAs, LEN was associated with significantly greater clinical benefit, as measured by this newly defined composite endpoint, vs PBO. This analysis provides evidence that other measures of response in addition to RBC-TI may be valuable in the management of LR non-del(5q) MDS. Clinically meaningful responses to LEN in non-del(5q) pts include CyR, decrease in transfusions, and increased Hb, in addition to RBC-TI. Clinical trial information: NCT01029262.Response, n (%) LEN (n = 160) PBO (n = 79) OR (95% CI) Clinical benefit 51 (31.9) 3 (3.8) 11.85 (3.57–39.38) RBC-TI ≥ 8 wks 43 (26.9) 2 (2.5) Transfusion reduction ≥ 4 pRBC units ≥ 8 wks1 34 (21.3) 0 Hb increase ≥ 1.5 g/dL (IWG 2006) 31 (19.4) 2 (2.5) CyR 9 (5.6) 0 1 Data normalized to 8 wks using data from a 112-day assessment period divided by 2.
CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature
Authors: Antoine Louveau, Jasmin Herz, Maria Nordheim Alme, Andrea Francesca Salvador, Michael Q. Dong, Kenneth E. Viar, S. Grace Herod, James Knopp, Joshua C. Setliff, Alexander L. Lupi, Sandro Da Mesquita, Elizabeth L. Frost, Alban Gaultier, Tajie H. Harris, Rui Cao, Song Hu, John R. Lukens, Igor Smirnov, Christopher C. Overall, Guillermo Oliver, Jonathan Kipnis
Journal: Nature Neuroscience (2018)
Outcomes of patients with melanoma who discontinue immunotherapy.
Authors: Samuel Rosner, Kita Bogatch, Michael Andrew Postow
Journal: Journal of Clinical Oncology (2017)

9548 Background: The question of when to discontinue (d/c) anti-program death-1 (PD-1) monotherapy (mono) or nivolumab in combination with ipilimumab (combo) immunotherapy (IT) is unknown. Methods: After IRB approval, a single center (Memorial Sloan Kettering Cancer Center), retrospective study was performed of 162 pts with unresectable stage III or IV melanoma treated with either mono (n = 106) or combo (n = 56) IT. Objective response rate (ORR), progression free survival (PFS), and overall survival (OS) were calculated for all pts from the 1 st dose of IT. For pts (n = 40; mono and n = 40; combo) who d/c IT due to reasons (Table) other than progression or death, starting from the last date of IT, we then reported PFS, time to treatment failure (TTF) defined as any subsequent surgery/radiation/systemic therapy, and OS. Results: For pts that were alive at time of analysis, the median follow up was 28 mos. For all 162 pts (demographics in Table), ORR was 38.7% (mono) and 60.7% (combo); median PFS and OS were 12 months (mos) and 25 mos for mono; 34 mos and not reached (NR) for combo, respectively. From the last dose of IT, the PFS, TTF, and OS for 40 mono pts and 40 combo pts who d/c IT for reasons other than progression/death are shown in Table. Reasons included CR, toxicity, or other (most commonly protocol completion or prolonged PR). Conclusions: Outcomes in this cohort of pts with long follow-up treated with mono or combo IT are similar to results from other clinical trials. Pts who d/c IT for reasons other than progression/death were a highly selected group. Nonetheless, favorable PFS, TTF, and OS were seen after IT d/c, even in pts who did not obtain a CR. [Table: see text]
Better survival with fludarabine and timed sequential busulfan regimen in older patients with AML/MDS.
Authors: Uday R. Popat, Rima Saliba, Betul Oran, Sairah Ahmed, Amin Majid Alousi, Qaiser Bashir, Stefan O. Ciurea, Chitra Hosing, Partow Kebriaei, Issa F. Khouri, David Marin, Yago Nieto, Amanda Leigh Olson, Muzaffar H. Qazilbash, Katayoun Rezvani, Ben Valdez, Roy B. Jones, Elizabeth J. Shpall, Borje Andersson, Richard E. Champlin
Journal: Journal of Clinical Oncology (2017)

7046 Background: We previously reported 6% 100 day NRM with a MA fludarabine (Flu) and busulfan (Bu) in older patients with a median age of 60 years. MA dose of Bu in this timed sequential (TS) regimen was administered over a longer period of time. To assess its impact on survival, we compared the outcomes of older patients treated with the TS Bu (TS cohort) or the RIC Flu/Bu regimen, which is used as standard (ST) for older patients at our center (ST cohort). Methods: Patients in the TS cohort received IV Bu 80 mg/m 2 /d on day -13 and -12 and Flu 40 mg/m 2 /d followed by IV Bu on day -6 to -3, dose adjusted to achieve a total Bu course AUC of 20,000 μmol-min based on PK studies. Patients in the ST cohort received Flu 40 mg/m 2 day followed by IV Bu daily for 4 days (day -6 to -3) dosed to achieve AUC of 16,000 μmol-min. Patients with AML or MDS were eligible for the study if they had adequate organ function, had matched related or unrelated donor and were treated between Jan 2012 and Sept 2016. Results: 162 patients, 50 with MDS and 112 with AML, were included in this study. Patient characteristics including age, sex, disease status, cytogenetic risk group, donor type, graft source CMV status and comorbidity were well balanced and without any significant difference in the two cohorts. Median age was 66 and 65 years in ST and TS cohorts, respectively. Overall survival (OS) and progression free survival (PFS) were significantly better in the TS cohort (see Table). This was due to a reduction in the disease progression without any increase in the non-relapse mortality (NRM). After adjusting for other covariates, the multivariate analysis for PFS confirmed longer PFS with TS Bu regimen (HR: 0.36; P=0.003). The benefit was mainly seen in patients with a comorbidity score ≤ 3. Conclusions: The myeloablative timed sequential Bu regimen improves survival and appears promising in older patients with AML/MDS. Clinical trial information: NCT01572662. [Table: see text]
TCT-339 Paclitaxel-Eluting Balloon vs. Everolimus-Eluting Stent in Patients with Diabetes Mellitus and In-Stent Restenosis: Insights from the Randomized DARE Trial
Authors: Bimmer Claessen, Jose PS. Henriques, Rene van der Schaaf, Kirsten Boerlage-Van Dijk, Jeroen Vendrik, Martijn Meuwissen, Niels van Royen, Marcel Gosselink, Marleen van Wely, Karin Arkenbout, Jan Piek, Jan Baan
Journal: Journal of the American College of Cardiology (2018)
The influence of age on treatment compliance and outcome in patients with stage IV head and neck cancer treated with radiotherapy and concurrent cisplatin or cetuximab.
Authors: Vittoria G. Espeli, Francesco Martucci, Simona Cima, Antonella Richetti, Michele E. G. Ghielmini, Marco Siano
Journal: Journal of Clinical Oncology (2018)

e18065 Background: Previous studies suggested that cisplatin and cetuximab administered concurrently to radiotherapy (RT) improve only marginally the outcome of patients older than 65 years. Methods: Forty-two patients with HNC were treated with curative Intensity-modulated or Volumetric Arc RT concurrent with cisplatin or cetuximab from September 2005 to September 2014 at our center. Three-weekly cisplatin and weekly cetuximab were considered standard treatments. Weekly cisplatin and no systemic treatment were considered non-standard treatments. We evaluate the 3-year-progression free survival (3y PFS) and the 3-years-overall survival (3y OS) of patients 65 years or older versus their younger counterparts. Results: Median age was 65 years (range 45-86). Twenty-one patients (50%) were younger than 65 years. All patients were able to receive the prescribed RT dose. Standard treatment was proposed to 27 (64%) patients and it was completed in 13 (31%). When divided by age, 17/21 patients younger than 65 years (81%) were proposed standard treatment, which was completed by 9 (53%). For patients older than 65 years, standard treatment was proposed to 10/21 (47%) and completed by 4 (40%). Accordingly, 29 patients (69%) were not able to receive the intended systemic treatment: 57% of patients < 65 years and 81% of ≥65 years. There was no significant difference in 3y PFS or 3y OS in patients younger versus older than 65 years nor in patients treated with standard treatment versus non-standard treatment (Table). Conclusions: In clinical practice, standard treatment is often not proposed because more difficult to perform in elderly patients with advanced HNC. Despite of this, our single center retrospective analysis could not see a different outcome for elderly HNC patients ( > 65y) compared to younger patients. All patients (n = 42) < 65 years (n = 21) ≥ 65 years (n = 21) Standard treatment 27 (81%) 17 (81%) 10 (47%) Non-standard treatment 15 (19%) 4 (19%) 11 (53%) Standard treatment completed 13 (31%) 9 (53%) 4 (40%) 3 y PFS 72% 75% 76% p = 0.83 3 y OS 78% 81% 75% p = 0.62 3 y PFS standard treatment under-treatment 69% 73% p = 0.98 3 y OS standard treatment under-treatment 84% 75% p = 0.50
Lenalidomide as treatment for relapsed or refractory primary CNS lymphoma: A single institutional experience.
Authors: Donna M Molaie, Jethro Lisien Hu, Jeremy David Rudnick
Journal: Journal of Clinical Oncology (2018)

e14036 Background: Primary CNS Lymphoma (PCNSL) is an aggressive form of diffuse large B-cell lymphoma (DLBCL). Lenalidomide is an immunomodulatory agent which has shown activity in R/R non-CNS DLBCL non-germinal center subtype (GCB) and R/R CNS DLBCL (primary and secondary). The ideal dosing, timing of lenalidomide as consolidation therapy, and it’s role in maintenance therapy remain unclear. Methods: Here we describe three elderly patients with R/R PCNSL who were treated with lenalidomide. All patients had a pathological diagnosis of PCNSL (subtypes: 2 GCB, 1 non-GCB), immunocompetent status, R/R status despite at least 2 previous therapies including intravenous methotrexate and rituximab. One of the patients had also failed autologous stem cell transplant (ASCT). Lenalidomide was administered orally, 25mg/day on days 1-21 of a 28-day cycle. Results: Median age was 68 (range 65-71). Median KPS was 70 (range 60-70). Patient 1 achieved complete response (CR) after cycle 4, 2 additional maintenance cycles (20mg; reduced for Grade 3-4 Thrombocytopenia), and is in remission after 9 months. Patient 2 achieved partial response (PR) after cycle 1, CR after cycle 8, and 2 additional maintenance cycles; dose reduced at cycle 6 (20mg) for Grade 3-4 Neutropenia, and is in remission after 12 months. Patient 3 achieved PR after cycle 1, mixed response after cycle 2, and died 15 weeks after start of treatment; of note, patient was also on rituximab. Molecular and immunologic correlates are pending and will be presented with the abstract. Conclusions: This case series shows lenalidomide has single agent activity in heavily pre-treated R/R PCNSL. All three patients had clinical and radiographic response to treatment, and two patients remain progression-free at 9 and 12 month follow-up. Hematologic toxicities occurred at the higher dose, however even at reduced dose, lenalidomide was effective in maintaining remission. In elderly patients, using lenalidomide at relapse and deferring neurotoxic treatment options may have a role in preserving good performance status. Further prospective studies are warranted to determine the efficacy and optimal dose of lenalidomide in patients with newly diagnosed and R/R PCNSL.
TCT-93 The Physiological Pattern of Disease Assessed by Pressure Wire Pullback has an Influence on Fractional Flow Reserve/Instantaneous Wave-Free Ratio Discordance: Insight From Multicenter AJIP Registry
Authors: Takayuki Warisawa, Christopher Cook, James Howard, Yousif Ahmad, Shunichi Doi, Masafumi Nakayama, Sonoka Goto, Yohei Yakuta, Kenichi Karube, Matthew Shun-Shin, Ricardo Petraco, Sayan Sen, Sukhjinder Nijjer, Rasha Al-Lamee, Manabu Takai, Yuki Ishibashi, Hisao Matsuda, Javier Escaned, Carlo Di Mario, Darrel Francis, Yoshihiro Akashi, Justin Davies
Journal: Journal of the American College of Cardiology (2018)
Phase Ib study of neoadjuvant chemoradiation (CRT) with midostaurin, 5-fluorouracil (5-FU) and radiation (XRT) for locally advanced rectal cancer: Sensitization of RAS mutant tumors.
Authors: Theodore S. Hong, Jennifer Yon-Li Wo, David P. Ryan, Hui Zheng, Darrell R Borger, Eunice Lee Kwak, Jill N. Allen, David L. Berger, David W Rattner, James C. Cusack, Angelo J Gemma, Harvey J. Mamon, Christine E Eyler, Paul C. Shellito, Andrew X. Zhu, Lipika Goyal, Jeffrey W. Clark, Henning Willers, Kevin M. Haigis
Journal: Journal of Clinical Oncology (2018)

e15674 Background: RAS mutations confer radiation resistance in rectal cancer, with very low pCR rates, below 5%. Midostaurin is an oral, multi-target TKI, FDA-approved for FLT3 mutated leukemia, that sensitizes colorectal tumors to radiation, and more pronounced in RAS mutant tumors through inhibition of PKCα. The purpose of this study is to establish the MTD of midostaurin with 5-FU-based CRT for locally advanced rectal cancer and explore the efficacy based on genotype. Methods: Patients with MRI or ultrasound defined T3 or T4 or node+ adenocarcinoma of the rectum and without evidence of metastatic disease were enrolled an IRB-approved protocol (NCT01282502). Patients received infusional 5-FU 225 mg/M2/day continuously. Standard radiotherapy was administered to 50.4 Gy in 28 fractions. Midostaurin was given on days of radiation twice daily. Dose was escalated in a 3+3 design: dose level 1 was 50 mg BID, dose level 2 was 75 mg BID. TME was performed 6-9 weeks following the completion of chemoradiation. Genotyping was performed using whole exome sequencing, with either blood or adjacent normal tissue normal control. Results: 19 patients were enrolled from October 2011 through November 2016. 3/19 patients were female; median age was 53 years. Clinical stage: 5/19 stage II, 14/19 stage III. The MTD was declared at 75 mg BID. All 19 patients completed therapy and underwent resection. At least one grade 3-4 toxicity occurred in 9/19 of patients. The most common Gr 3+ toxicity was lymphopenia (5/19) and rash (3/19) The pathologic complete response (pCR) for all patients completing study therapy was 3/19. R0 resection was achieved in all 19 patients. With a median follow up of 3.0 years, two patients had recurrence- both had synchronous local and distant. DFS at 3 years is 89.5% (CI 75.7-100%), and OS-3 was 87.7% (CI 71.6-100%). 16/19 tumors have been sequenced: KRAS mutant 2/16, NRAS 3/16, BRAF 3/16. Genotype of pCR patients: 2/3 RAS mutant, 1/3 not sequenced yet. Conclusions: Midostaurin combined with chemoradiation is well tolerated. Final genotyping results and correlation of RAS status and pCR will be presented at the meeting. Clinical trial information: NCT01282502.