tbuckley/cabot-search huggingface dataset:
Effect of estrogens on growth factors in melanoma and nevi.
Authors: Valeria A. Bandovkina, Oleg Ivanovich Kit, Elena M. Frantsiyants, Vyacheslav A. Sustretov, Olga V. Mkhitaryan, Marina I. Vereskunova, Irina V. Kaplieva, Lidia K. Trepitaki, Irina Stasio Tavaryan
Journal: Journal of Clinical Oncology (2018)

e21628 Background: Melanoma pathogenesis is still poorly studied. In more than 70% of cases, melanoma arises from a nevus. Gender differences in the rates and course of melanoma indicate the role of a hormonal factor in the disease pathogenesis. The purpose of the study was the search of correlations between the hormonal status and some neoangiogenesis factors in nevi and cutaneous melanoma. Methods: Levels of estrone (E1), estriol (E3), total (T) and free testosterone (fT), prolactin (PRL), progesterone (P4), VEGF-A, EGF, IGF-I, IGF-II, TGFβ and FGF were studied by RIA and ELISA in tissues of cutaneous melanoma (n = 40) (pT1-3N0-1M0) and pigmented nevi (n = 30) of men and women. Intact skin obtained during surgery from patients without cancer was used as a control (n = 20). Correlations were analyzed using the Pearson correlation coefficient (r). Results: Melanoma tissues showed increased levels of PRL, E1, VEGF, EGF, IGF-I, IGF-II, TGFβ and FGF, while T, E3 and P4 were decreased. A strong negative correlation between PRL and P4 (r = –0.95, р < 0.05) was observed in melanoma patients, as well as positive correlations between PRL and E1 (r = 0.99, р < 0.05), E1 and VEGF, IGF-I and TGF (r1= 0.95, r2= 0.99, r3= 0.98, р1,2,3< 0.05). E1 levels in nevi were similar to the levels in intact skin, while E3 was increased by 1.6 times, T – by 1.4 times, and fT – by 8.7 times. High T levels in nevi resulted in the shift of steroid balance towards androgens, and not estrogens, as in melanoma. Correlations between E1 and VEGF-A in nevi were not found. High levels of EGF, IGF-II and FGF in nevi could indicate a high proliferative activity in the tissues. Conclusions: The shift of steroid balance towards estrogens in melanoma correlates with neoangiogenesis factors which could be a pathognomonic factor.
High baseline lymphocyte count is a predictive biomarker of prolonged time to progression in patients with advanced solid tumors receiving checkpoint inhibitors.
Authors: Mariangela Maltese, Stefano Panni, Silvia Lazzarelli, Matteo Brighenti, Federica Negri, Margherita Ratti, Maria Olga Giganti, Rodolfo Passalacqua
Journal: Journal of Clinical Oncology (2017)

e14532 Background: Biomarkers predicting response to checkpoint inhibitor are needed to better select patients most likely to benefit from treatment. We observed that baseline absolute lymphocyte count (ALC) can predict durable responses to anti-PD-1 antibodies in various malignancies. Methods: This is a retrospective analysis of patients with advanced solid tumors treated with anti-PD-1 antibodies. Pembrolizumab was given at 2 mg/kg every 3 weeks, Nivolumab at 3 mg/kg every 2 weeks. Peripheral ALC and absolute neutrophil count (ANC) from routine safety labs were collected at baseline, cycle 4 and cycle 8. Evaluation of response was based on irRECIST. Neutrophil lymphocyte ratio [NLR = ANC/ALC] was stratified by ≤4 or &gt; 4. The lymphocyte count cutoff was 1000/mm3. Time to progression (TTP) and overall survival (OS) were estimated with the Kaplan-Meier method. Differences between groups were estimated with the log rank test. Results: We have retrospectively evaluated 40 patients with unresectable stage III/IV Non Small Cell Lung Cancer (squamous n. 17; 42.5%, adenocarcinoma n. 7; 17.5%), Malignant Melanoma (n.11; 27.5%), Renal Cell Carcinoma (n.5; 12.5%) treated with anti-PD-1 antibodies. 6 pts (15%) received treatment as 1 st line, 14 pts (35%) as 2 nd line, 20 pts (15%) as ≥ 3 rd line. We observed a 29% partial response (PR), 31% stable disease (SD) and 40% progressive disease (PD). The overall response rate (ORR) was 29% [I.C. 95% 13-42]. Median TTP was 5.5 months [IC 95% 3.3-NR]. Median OS was not reached. Pts with baseline ALC ≥1000/mm3 had significantly longer TTP (median value not reached), compared with those who had ALC &lt; 1000/mm3 (median TTP 2.8 months), p = 0.01. There was also a trend for longer TTP in patients with NLR &lt; 4 vs ≥4 (4.9 vs 10.5 months, p 0.44). Conclusions: In our observation baseline ALC ≥1000/mm3 is a predictive biomarker of prolonged TTP in patients treated with anti-PD-1 antibodies. The potential predictive value of this test should be prospectively validated.
Effect of chemotherapy in patients with early stage synovial sarcoma on disease-free survival or overall survival.
Authors: Minggui Pan, Maqdooda Merchant, Laurel A. Habel
Journal: Journal of Clinical Oncology (2016)

e22550 Background: The benefit of adjuvant chemotherapy for soft tissue sarcoma is controversial. Methods: We retrosectivly analyzed the database of Northern California Kaiser Permanente from 1981 to 2014. Results: We identified 153 cases with synovial sarcoma. Both male to female and white to non-white ratio was approximately 3:2. Median age was 38 years old. Thirty-seven percent of cases presented with tumor size < 5.0 cm, 56% > 5.0 cm and the rest unclear. Age older than 40 years was significantly associated with higher percentage of tumor size > 5.0 cm. Tumor size > 5.0 cm was significantly associated with higher percentage of stage IV disease. Histologically, 52.2% were monophasic, 36% biphasic, 6.5 poorly differentiated and 5.3% unknown. Histologic subtype was not associated with differential outcome. Patients whose tumor size > 5.0 cm (n = 85), or age > 40 years (n = 70) or presented with unusual primary site (oropharynx, mediastinum, lung, or retroperitoneum) (n = 10) had significantly worse DFS and overall survival (OS). Forty of the 130 cases (31%) with early stage disease were treated with pre-operative (n = 22) or adjuvant chemotherapy (n = 15) or both (n = 3). Chemotherapy regimens included adriamycin plus ifosfomide (82.5%), cyclophosphamide plus adriamycin (12.5%), adriamycin alone (2.5%) and dactinomycin plus vincristine (2.5%). There was no significant difference between the chemotherapy and no-chemotherapy group on the distribution of age, sex, tumor size, race or histologic subtypes. DFS was 50.4 months for no-chemotherapy group and 44.1 months for chemotherapy group (p = 0.79). OS was 92 months for no-chemotherapy group and 99 months for chemotherapy group (p = 0.87). Patients who received chemotherapy either in pre-operative or adjuvant setting or both did not derive benefit from DFS or OS. Similar results were found when the analysis was limited to the extremity primary only (n = 97). Conclusions: Our analysis suggested that chemotherapy did not improve DFS and OS and that tumor size > 5.0 cm, unusual primary site and age > 40 years old were associated with poorer outcome.
Rationale and design of the ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload) trial
Authors: Wilfried Mullens, Frederik H. Verbrugge, Petra Nijst, Pieter Martens, Katrien Tartaglia, Evi Theunissen, Liesbeth Bruckers, Walter Droogne, Pierre Troisfontaines, Kevin Damman, Johan Lassus, Alexandre Mebazaa, Gerasimos Filippatos, Frank Ruschitzka, Matthias Dupont
Journal: European Journal of Heart Failure (2018)
Apatinib for advanced osteosarcoma after failure of standard multimodal therapy: An open label phase 2 clinical trial.
Authors: Lu Xie, Jie Xu, Xin Sun, Xiaodong Tang, Taiqiang Yan, Rongli Yang, Wei Guo
Journal: Journal of Clinical Oncology (2018)

11520 Background: Anti-angiogenesis Tyrosine kinase inhibitors (TKIs) have been proved to show promising effects on prolonging progression-free survival (PFS) for advanced steosarcoma after failure of standard multimodal Therapy. Methylsulfonic apatinib is one of those TKIs which specifically inhibits VEGFR-2. We aimed to assess the activity of apatinib in patients with locally advanced or multiple metastatic high-grade osteosarcoma progressing after standard treatment. Methods: This non-randomised phase 2 trial was done in Peking University People's Hospital. We enrolled participants (≥16 years) with relapsed or unresectable osteosarcoma progressing after standard treatment (methotrexate, cisplatin, doxorubicin, and ifosfamide). Participants received 750 mg or 500mg apatinib according to body surface area (BSA) once daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (CR+PR at least 3 months according to RECIST 1.1) and PFS at 4 months. All analyses were intention-to-treat. Results: 37 participant were enrolled between March 17th, 2016 and June 9th, 2017. Until final follow-up, the objective response rate (CR+PR at least 3 m) was 56.76% (21/37). And the 4-m PFS rate was 52% (95% CI 32%–68%). However 9/37 (24.32%) patients was progression free at 6 months. Median PFS and OS were 4.44 (95% CI 3.12–7.08) and 8.77 (95% CI 6.73–16.70) months, respectively. Toxic effects led to dose reductions, or interruptions in a total of 25/37 (67.57%) patients. The most common grade 3–4 adverse events were pneumothorax in 5 (13.51%) patients, wound dehiscence in 4 (10.81%), abdominal cramps in 3 (8.11%), hypokalemia in 2 (5.41%) and bilirubin increase, proteinuria, hypertriglyceridaemia, hand–foot skin reaction and anemia each in one (2.70%). No other serious adverse events were reported during the trial. There were no treatment-related deaths. Conclusions: Apatinib was a sensitive drug for advanced osteosarcoma with high response rate after failure of chemotherapy, with almost the same duration of response comparing to other TKIs. Clinical trial information: NCT02711007.
Overall survival (OS) and transplantation (ASCT) utilization in real-world patients with relapsed/refractory diffuse large B-cell lymphoma (RR-DLBCL).
Authors: Chadi Nabhan, Andrew Klink, Choo Hyung Lee, Jalyna R. Laney, Yin Yang, Anna G. Purdum
Journal: Journal of Clinical Oncology (2018)

7545 Background: Many patients (pts) with RR-DLBCL treated in the real-world are not offered ASCT despite its curative potential. Understanding the impact of ASCT on OS in the real world is critical to better position novel therapies as an alternative to ASCT. Methods: We retrospectively analyzed real-world pts with RR-DLBCL treated between 1/1/10-12/31/16 in 126 community-based hematology/oncology practices across the US. Pts treated with first line (1L) R-CHOP or DA-EPOCH-R were grouped into 2 categories: early relapse (progressive disease [PD] on treatment within 365 days from completing last cycle) and late relapse (any 2L treatment 366-730 days from last cycle of 1L). Pts were stratified whether ASCT was performed after 2L. Pts receiving rituximab monotherapy in 2L or later were excluded from analysis. A period of ≥6 months of clinical inactivity at end of follow-up served as a proxy for death. Median (95% CI) OS were estimated by Kaplan-Meier method, and adjusted hazard ratios (HR) were estimated by Cox proportional hazard models to adjust for differences in pt characteristics (sex, age at DLBCL diagnosis, time to relapse (2L), 1L R-CHOP, and comorbidities). Results: For the 430 pts, median age was 65 (range 18-84) years and 61% were male. Following 1L, over 86% (n = 371) had early relapse, and 14% (n = 59) had late relapse. Across all lines, 33% (n = 144) pts received a salvage regimen intended for transplant, with 38% (n = 55) of these pts proceeding to ASCT. For all pts at first relapse, median OS was 13.8 mo. from initiation of 2L. Median OS was significantly longer among those who underwent ASCT compared to those who did not (21.4 mo. vs 10.5 mo.; adjusted P< 0.01); HR = 0.51 (95% CI 0.32-0.81). Median OS shortened with each subsequent line of therapy—more so for non-ASCT group with a median OS at 2L of 10.5 mo., 3L of 9.4 mo., and 4L+ of 3.9 mo. for non-ASCT. Conclusions: Although 33% of real-world pts with RR-DLBCL received salvage regimens intended for ASCT, only 13% of all evaluable pts eventually underwent ASCT. The low utility of ASCT and the poor OS rates in non-ASCT pts in this real-world population demonstrate an unmet need for novel therapies in this setting.
Real-world clinical characteristics and treatment of advanced non-small cell lung cancer (NSCLC) patients in China.
Authors: Yuankai Shi, Xin Zhang, Gang Wu, Jianping Xu, Yong He, Dong Wang, Cheng Huang, Mingwei Chen, Ping Yu, Yan Yu, Wei Li, Qi Li, Xiao-hua Hu, Guofang Sun, Yulin Li, Lilian Bu
Journal: Journal of Clinical Oncology (2018)

e21187 Background: Lung cancer is the leading cause of cancer related mortality worldwide. Approximately 85% of lung cancer is Non-Small Cell Lung Cancer (NSCLC). The clinical profiles and routine practice of advanced NSCLC in China have yet to be described. Methods: This is a multicenter, prospective non-interventional study enrolling and following adult patients who were newly diagnosed with unresectable Stage IIIB or IV NSCLC and received first-line systemic therapy between June, 2015 and October, 2017 in multiple regions in China, to describe the patient journey in terms of diagnosis, treatment, and clinical outcomes. Patient and disease characteristics were analyzed, treatment distribution and duration was evaluated. If in time, survival data will be presented. Results: Overall 1324 patients met the eligibility criteria and were included in the analysis. Median age was 60 years; 65.1% were male; 44.0% were non-smokers; 74.0% were adenocarcinoma, 21.5% were squamous cell carcinoma. The epidermal growth factor receptor (EGFR) mutation testing rate was 44.3% (587/1324). Among patients tested for EGFR, EGFR mutation (EGFRmut) rate was 48.7% (286/587) and among those mutations 87.4%(250/286) were del 19 or exon 21 mutations. Patients with EGFRmut NSCLC were more likely to be female, non-smoker, with stage IV non-squamous tumors. A total of 1101 (83.2%) patients received first line chemotherapy, and 402 (30.4%) patients received first line targeted therapy. Among 286 patients with EGFRmut NSCLC, majority (67.1%) patients received an EGFR tyrosine kinase inhibitor (TKI), with a longer median treatment duration (11.8 months) compared to those receiving chemotherapy (3.7 months) in the first line setting. Conclusions: Our data show that the characteristics of Chinese advanced NSCLC patients, including their EGFR testing and mutation rates, were generally consistent with previous reports. Majority EGFRmut advanced NSCLC patients received an EGFR TKI, and the duration of first line EGFR TKI was longer than that of chemotherapy for EGFRmut patients in this study. Clinical trial information: NCT02458651.
Initial results of a dose escalation study of a selective and structurally differentiated PI3Kδ inhibitor, ME-401, in relapsed/refractory (R/R) follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).
Authors: Jacob Drobnyk Soumerai, John M. Pagel, Deepa Jagadeesh, Huda S. Salman, Vaishalee Padgaonkar Kenkre, Adam Steven Asch, Anastasios Stathis, Nishitha M. Reddy, Alexia Iasonos, Richard Ghalie, Andrew David Zelenetz
Journal: Journal of Clinical Oncology (2018)

7519 Background: ME-401, an oral tyrosine kinase inhibitor highly selective for PI3Kδ was studied in a phase 1b trial for patients (pts) with R/R FL or CLL/SLL. The starting dose was based on pharmacokinetic and pharmacodynamic data from a study in healthy volunteers. Methods: Eligible adult pts had ECOG ≤2, no prior PI3K therapy, and no prior progression of disease (POD) on BTK therapy. ME-401 was given once daily on days 1-28 of 28-day cycle until POD or unacceptable toxicity. All pts received PJP prophylaxis and CMV monitoring was mandatory. At least 6 evaluable pts were treated at each dose level, with option to expand to 12 pts for efficacy assessment. Dose limiting toxicities (DLT) were assessed up to Day 56. Response was assessed after Cycles 2 and 6. Results: 31 pts (21 FL, 10 CLL/SLL) received ME-401 and 30 were evaluable for DLT: 12 at 60 mg, 12 at 120 mg, and 6 at 180 mg. Median age was 65 (range: 47-79), 14/30 (47%) pts received ≥2 prior therapies, and 9/21 (43%) pts with FL had POD < 24 months after initial chemoimmunotherapy (POD24). Of 29 pts evaluable for response, the overall objective response rate was 83% (24/29), with 75% (15/20) in FL, including 9/9 (100%) with POD24, and 100% (9/9) in CLL/SLL, occurring by Cycle 2 in 20/24 responders. No DLTs were reported and escalation above 180 mg was closed given frequent responses across lower dose levels. With a median follow-up of 20 weeks (range: 2-53 weeks) 3 pts had POD at 8, 14 and 17 weeks after starting therapy. Five pts discontinued MEI-401 due to adverse events (AEs): rash (n = 3), colitis (n = 1), and cardiomyopathy (n = 1), and 2 pts discontinued for personal reasons. Most common AEs (all grades/grade ≥3) were diarrhea (32%/16%), fatigue (29%/0%), cough (29%/0%), rash (29%/10%), and nasal congestion (26%/0%). All grade ≥3 AEs were reported in Cycle 3 or later. Conclusions: ME-401 was well tolerated with high early response rates among R/R FL and CLL/SLL pts. No DLTs were reported. An alternative dosing (ME-401 days 1-7 of 28-day cycle starting with Cycle 3) is being evaluated, including dosing ME-401 at 45 mg and at 60 mg in combination with rituximab. Clinical trial information: NCT02914938.
Early tumor shrinkage (ETS) and depth of response (DpR) in wild-type (WT) RAS tumors from the phase III trial of panitumumab (pmab) plus best supportive care (BSC) versus BSC in chemorefractory metastatic colorectal cancer (mCRC).
Authors: Tae Won Kim, Anneli Elme, Joon Ho Park, Anghel Adrian Udrea, Nebojsa S. Manojlovic, Xuesong Guan, A. Scott Jung, Eduard Vrdoljak
Journal: Journal of Clinical Oncology (2017)

3561 Background: Activating RAS mutation is a negative predictor of anti-EGFR therapy. In the final analysis of 20100007, the first phase 3 study to prospectively evaluate efficacy and safety of WT RAS ( KRAS and NRAS exons 2, 3, 4 ) mCRC, pmab + BSC continued to show improved survival (OS and PFS) and ORR. Recent data suggest that tumor burden reduction and ETS may contribute to improved OS. Previous studies have shown that pmab plus chemotherapy results in ETS, which correlates with OS benefit (Douillard et al, EJC, 2015; Rivera et al, JCO, 2015; Mansmann et al, JCO 2013). Here we report analyses of ETS and DpR and the effect on OS in patients (pts) with WT RAS mCRC treated with pmab monotherapy in the ‘0007 trial. Methods: Anti-EGFR naïve pts with WT KRAS exon 2 mCRC were randomized 1:1 to pmab + BSC or BSC. Pt tumors were further evaluated for RAS status, and DpR (percent tumor shrinkage at nadir or progression) and ETS (≥/&lt; 0% or ≥/&lt; 20% by week 8) were analyzed in WT RAS pts. OS and PFS were compared for each ETS group. Results: Of 377 pts with WT KRAS exon 2 mCRC, 270 were WT RAS (142 pmab + BSC, 128 BSC alone). In the pmab + BSC arm, 69.5% and 38.2% of pts had ≥0% and ≥20% ETS, respectively, and median (Q1, Q3) DpR was 16.9% (0%, 37.5%). OS was improved in pts with higher ETS (≥0% or ≥20%) compared with lower ETS (&lt;0% or &lt;20%; Table). Conclusions: In this post-hoc analysis, pmab monotherapy provided any ETS benefit (≥0%) in 69.5% of WT RAS mCRC pts, and ETS was associated with improved PFS and OS. Pmab should be considered both in combination and as monotherapy for its significant impact on OS and also for its ability for substantial ETS in pts with WT RAS mCRC. Validation is necessary to investigate the value and cutoff of ETS in a prospective study. Clinical trial information: NCT01412957. [Table: see text]
Maintainence chemotherapy in metastatic gastro-esophogeal junction and gastric tumors.
Authors: Kamyar Nader, Peter T. Georges, Kumar Rajagopalan, Krystal Hunter, Polina Khrizman, Kimberly Krieger, Alexandre Hageboutros
Journal: Journal of Clinical Oncology (2016)

e15576 Background: Maintenance therapy is an evolving field in medical oncology. The role of maintenance therapy in gastroesophogeal junction (GEJ) and gastric cancers remains elusive. The purpose of this study is to evaluate the role of maintenance capecitabine and 5-fluorouracil (5FU) in metastatic GEJ and gastric adenocarcinomas. Methods: 51 patients with metastatic GEJ and gastric adenocarcinomas who presented from 1/1/2011 to 12/31/14 to Cooper University Hospital were reviewed. Twenty-four with ECOG performance status of ≤ 2 who had received some form of initial chemotherapy were selected. The primary end-point was to assess after initial chemotherapy, whether the overall survival (OS) of patients who received maintenance with either 5FU or capecitabine chemotherapy regimens (M) arm was different from patients who did not receive such therapy (NM) arm. Secondary end-pointsincluded any significant difference of OS in the first 12 months between m and NM arms, time-to-first-progression (TFP) between m vs NM arms, whether Her2-neu disease status affected OS in m vs NM arms and whether any difference of grade 2 or higher toxicity existed between m and NM arms. Results: Average age was 52.8 years. 71.4% of patients in m arm and 41.2% of patients in NM arm received 2nd line chemotherapy. 57.1% of patients in m and 17.6% of patients in NM arm were HER2-neu positive. Average maintenance chemotherapy was about 5.7 months. Over 38.5 month period, the OS in m arm compared to NM arm was statistically significant (24 months vs 18 months; p < 0.074). There was also a statistical difference of OS at 12 months between m and NM groups (p < 0.074). There was no difference between TFP in m and NM arms (10 months vs 11 months; p = 0.736). There was no difference between m and NM in regard to HER2-neu status (p = 0.732) and grade 2 or higher toxicity (p = 0.305). Conclusions: Although a small and retrospective study, it brings insight of the possible role of maintenance therapy in patients with metastatic GEJ and gastric adenocarcinomas with a good performance status. Limitation of this study is heterogeneous initial and 2nd line chemotherapy regimens that could have affected the results. Further prospective studies and clinical trials are needed to validate this study.
Lack of cardiac toxicity in patients treated with aldoxrubicin with doxorubicin equivalent doses beyond 1000mg/m2.
Authors: Kamalesh Kumar Sankhala, Robin Lewis Jones, Victoria S. Chua, Katherine Kim, Shiva Sreenath Andrali, Doris V. Quon, Steven G. Wong, John H. Lee, Shahrooz Rabizadeh, Esha Sachdev, Sant P. Chawla
Journal: Journal of Clinical Oncology (2018)

11585 Background: Aldoxrubicin is classical Doxorubicin with a linker which rapidly binds to albumin on IV administration. Doxorubicin, either alone or in combination with ifosfamide, is still considered standard therapy for sarcomas. Aldoxorubicin alone or in combination with ifosfamide have been shown to improve antitumor activity and lack of cardiac toxicity. The allowable maximum cumulative lifetime dose of doxorubicin is 550 mg/m2. We report on the evaluation of cardiac function in patients who received aldoxorubicin with Doxorubicin equivalent at doses beyond 1000 mg/m2. Methods: Fifty-two patients enrolled in a Phase 1/2 study of aldoxorubicin and ifosfamide/mesna and a Phase 3 study using aldoxorubicin alone were treated for at least 6 cycles of aldoxorubicin at either 250 mg/m2 or 350 mg/m2 per dose i.v. every 3 weeks. Cardiac function using 2D echocardiogram was evaluated at regular intervals every two cycles of aldoxorubicin until end of treatment and every six months after completion of the treatment. Results: In eleven patients, the median cumulative doxorubicin dose prior to aldoxorubicin treatment was 158 (range: 64-360) mg/m2. The cumulative aldoxorubicin dose ranged from 1000 to 7500 mg/m2. No patient developed any sign or symptom of clinical congestive heart failure. Ventricular ejection fractions ranged from 45-74% baseline, and 50-77% at end of treatment, median being 60% both at the beginning and end of treatment. Conclusions: Aldoxorubicin lacks cardiotoxicity in these patients treated with aldoxorubicin alone or in combination with ifosfamide/mesna. We did not find any evidence of cardiac toxicity of aldoxorubicin up to doxorubicin equivalent dose of 7500mg/m2. Clinical trial information: NCT# 02235701.