tbuckley/cabot-search huggingface dataset:
The efficacy of pemetrexed and bevacizumab intrapleural injection for malignant pleural mesothelioma-mediated malignant pleural effusion.
Authors: Nan Du, Dianjun Chen
Journal: Journal of Clinical Oncology (2015)

e18545 Background: To evaluate the efficacy of pemetrexed chemotherapy combined with intrapleural injection of pemetrexed and bevacizumab in the treatment of malignant pleural mesothelioma(MPM)-mediated malignant pleural effusion, and analyze the objective response rate (ORR), the median progression free survival (PFS) and the median overall survival (OS). Methods: We analyzed the clinical data of 23 MPM patients with pleural effusion who was treated with a combination chemotherapy of pemetrexed at 500mg/m2, on day 1 plus cisplatin (DDP) at 20mg/m2 on day 1-5 of each 21 day cycle, and concurrently, intrapleural injection of pemetrexed 0.5g and bevacizumab 300mg was administered on day 3 or day 4 after complete effusion drainage. ELISA test was applied to detect the vascular endothelial growth factor (VEGF) level in the pleural effusion and serum, and assess the objective response rate and survival. Results: In the 23 evaluable patients, the VEGF level in the pleural effusion and serum was significantly decreased, P < 0.01, pleural effusion of 20 patients (86.96%) was controlled effectively. There were 8 complete responses, 7 partial responses, 5 stable disease and 3 progressive disease, the ORR was 65.21%, the DCR was 86.96%, the median PFS was 6 months, the median OS was 14.5 months, and the one-year survival rate was 41.22%. Toxicities were generally mild and manageable, the major toxicities included myelosuppression, fatigue and anemia, mainly were grade 1-2 which could be managed by symptomatic treatments. Conclusions: The combination of pemetrexed chemotherapy with intrapleural injection of pemetrexed and bevacizumab is efficacious and safe for MPM pleural effusion, and results of the present study demonstrate some improvement in the PFS and OS. The expression of VEGF in the pleural effusion and serum plays a guiding role in monitoring the efficacy of bevacizumab in the treatment of malignant pleural effusion.
Standardization for lymphatic mapping in breast, melanoma, and GI cancers: An international survey.
Authors: Mohammed Nawaf Kanaan, Yuko Kitagawa, Markus Zuber, Madhavi Manyam, Philip Gafford, David Wiese, Thomas Beutler, Madan L. Arora, Hiroya Takeuchi, Sukamal Saha
Journal: Journal of Clinical Oncology (2012)

e14045 Background: The technique of SLNM varies between surgeons, hospitals, and countries in terms of type and amount of dye, pathologic examination of SLN, technical issues of dye injection. The purpose of this study is to evaluate the methods of lymphatic mapping in solid tumors around the world to create a form of international reference for all surgeons to use in patients with breast, melanoma, and GI cancers. Methods: A web-based survey form was created with 12 questions in regards to various aspects of SLNM, for melanoma, breast, esophagus, stomach, colon and rectal cancers. This questionnaire was distributed to 425 centers in the U.S, 60 in Europe, and 60 in Japan. Results: Of the 545 centers surveyed, 122 centers (22.4 %) responded. Of these, 47 were from U.S, 60 from Japan, and 15 from Europe. The order of frequency of the organ sites for lymphatic mapping were: Breast, melanoma, stomach, colon, esophagus, and rectum. There were 56 centers that perform SLNM in one organ site (most common breast), 39 on 2 organ sites, and 14 centers on 3 organ sites. Radiocolloid was the most common mapping agent used 80%. Most common blue dyes were Lymphazurin/Isosulfan in U.S, Patent Blue in Europe and Indocyanine Green in Japan. For breast , the most common site of injection was subareolar, while in upper GI submucosal, and in lower G.I it was subserosal. Overall the average volume of injection for mapping was 1-2 ml (range 0.4-5 ml). Pathological intraoperative interpretation varied from 74% in breast, 38% in melanoma, and 42% in upper G.I and 26% in lower G.I. Conclusions: Although a pattern of continuity emerged through this survey in regards to mapping techniques, there were significant variances between centers and organ sites.Thus, the need for standardization in lymphatic mapping for solid tumors to act as a reference point for future oncologists to follow. [Table: see text]
Proton beam therapy combined with selective intra-arterial infusion chemotherapy for locally advanced tongue cancer.
Authors: Kanako Takayama, Tatsuya Nakamura, Akinori Takada, Chiyoko Makita, Motohisa Suzuki, Youjirou Ishikawa, Yusuke Azami, Yasuhiro Kikuchi, Iwao Tsukiyama, Takahiro Kato, Iwai Tohnai, Nobukazu Fuwa
Journal: Journal of Clinical Oncology (2013)

6086 Background: The standard treatment for locally advanced tongue cancer is surgery. However, the patient’s quality of life is lost. As a newly non-operative treatment, we report the efficacy and toxicity of proton beam therapy combined with selective intra-arterial infusion chemotherapy (PBT-IACT) for locally advanced tongue cancer. Methods: Between February 2009 and August 2012, 45 cases of stage III-IV(M0) squamous cell carcinoma of the tongue (28 men and 17 women) were treated by PBT-IACT at Southern TOHOKU Proton Therapy Center. Median age was 58 years (range:24-83 years), and clinical stage III/IVA/IVB were 11/32/2 respectively. In case of surgery, the patients required subtotal or total resection of the tongue. Initially, 2 courses of systemic chemotherapy and prophyractic whole neck irradiation (36Gy/20fr.) were performed. Subsequently, for gross tumor targets, PBT (33Gy/15fr.) and IACT were administered via the superficial temporal artery by continuous infusion of cisplatin with sodium thiosulphate. For PBT, 1 or 2 portals of 210 MeV proton beam were arranged in optimal angles to avoid overdosing the risk organ. Systemic chemotherapy was performed only for age of 70 years or younger. Results: The median follow-up was 27 months (range:8-48 months). Over all survival (OS), disease-free survival (DFS), and local control (LC) rates at 2 years were 88%,78%, 80%, respectively. LC of cervical lymph node metastases at 2 years was 86%. As the early toxic event, grade 3 mucositis (32/45) and blood/bone marrow toxicity (22/45) were observed. Within 6 months after this therapy, mandibular osteomyelitis occurred in 1 case. Conclusions: PBT-IACT appeared to be safe and has a good LC rate for locally advanced tongue cancer. Furthermore, it is not inferior to surgery and can be one of the new effective treatment options for locally advanced tongue cancer.
Polymorphisms of the androgen transporting gene <i>SLCO2B1</i> and response to abiraterone acetate in mCRPC patients.
Authors: Silvana Giacinti, Maria Bassanelli, Michela Roberto, Lidia Strigari, Cosimo De Nunzio, Anna Maria Aschelter, Paolo Marchetti
Journal: Journal of Clinical Oncology (2017)

174 Background: Abiraterone Acetate (AA), an effective treatment for metastatic castration resistant prostate cancer (mCRPC), is highly variable in its effectiveness and it is well known that form of primary and acquired resistance to this agent, exist. This resistance may partly depend on the increased capacity of CRPC cells to synthesize testosterone and dihydrotestosterone from weak adrenal androgens (i.e. DHEA, DHEA-S) or de novo from cholesterol, in response to a chronic exposition to a low-testosterone environment. The organic anion-transporting polypeptides (OATPs) encoded by SLCO genes, mediate the cellular uptake of many compounds, including adrenal androgens. We hypothesized that germ-line variants of the androgen transporter gene SLCO2B1 (solute carrier organic anion transporter family member 2B1), altering the ability of the prostate cancer cell to stock adrenal precursors, may influence the response to AA of mCRPC patients. Methods: Three single nucleotide polymorphisms (SNPs), exonic SNP rs12422149 and intronic SNPs rs1789693 and rs1077858, were genotyped in a cohort of 21 consecutive patients with mCRPC who were treated with AA at the Sant’Andrea Hospital of Rome, Italy. The SNPs were detected in blood samples using pyrosequencing technique. The median TTBP (Time to Biochemical Progression), PFS (Progression Free Survival) and OS (Overall Survival) was estimated using the Kaplan-Meier method, with 95% CI. To test the association between SNPs and TTBP, PFS and OS the log-rank test was used. Results: The intronic polymorphism of SLCO2B1 rs1077858A &gt; G was associated with TTBP (p = 0.03) and PFS (p = 0.04) of mCRPC patients on AA therapy. Patients carrying the SLCO2B1 rs1077858 risk genotype (GG) exhibited a TTBP that was 8 months shorter than that of patients with the major allele of SNP rs1077858 (AA or GA) (TTBP: A/A+G/A = 12 (95% CI: 12-NA) vs G/G = 4 (95% CI: NA) months). Patients carrying genotype GG of SNP rs1077858 also showed an 11 months shorter PFS on AA therapy than patients with AA or GA genotype (PFS: GG = 5.1 (95% CI:NA) vs AA+GA = 16.7 (95%CI:14.9-NA) months). Conclusions: Genetic variants of SLCO2B1 may function as pharmacogenomic determinants of resistance to AA in mCRPC.
Phase I lead-in to a 2x2x2 factorial trial of dose-dense temozolomide, memantine, mefloquine, and metformin as postradiation adjuvant therapy of glioblastoma (GBM).
Authors: Marta Penas-Prado, Morris D. Groves, Aaron G. Mammoser, Isaac Melguizo, John Frederick De Groot, Charles A. Conrad, Ivo Tremont-Lukats, Monica Elena Loghin, Vinay K. Puduvalli, Erik P. Sulman, Kenneth R. Hess, Kenneth D. Aldape, Mark R. Gilbert, W. K. Alfred Yung
Journal: Journal of Clinical Oncology (2013)

TPS2106 Background: Treatment for GBM is an area of unmet need. Despite optimal therapy, survival is poor and 2nd line therapies are scarce. There is an urgent need to find better treatments for recurrence, but also more effective 1st line therapies. Dose-dense temozolomide (ddTMZ) using the 7/14-day regimen has shown promising preliminary results in combination with cytostatic agents. Memantine (MEM) is a glutamate receptor (NMDA) blocker with antiproliferation properties and possibly neuroprotective effect. Mefloquine (MFQ) induces autophagy and apoptosis. Metformin (MFM) has mTOR inhibitor properties. Methods: Trial Design: Phase I/II trial to evaluate adjuvant ddTMZ with MEM MFQ and MFM. Primary objective Phase I: MTDs of ddTMZ with MEM/MFQ/MFM, 3+3 design. MTDs will be the recommended Phase II doses for a subsequent randomized factorial Phase II trial (ddTMZ alone and single, double and triple combinations). Accrual of about 55 eligible patients was calculated for Phase I (48-144). Clinical trial registry number is NCT01430351. Treatment planned: Patients accrued sequentially to ddTMZ with 1, 2, or 3 drugs. Arm 1 (ddTMZ alone) will be enrolled in Phase II only. Patients were first accrued to 1-drug Arms 2-4. Once MTDs were determined, accrual started to 2-drug Arms 5-7. Once completed, accrual to Arm 8 will start. Arms 2-4 were started at a predetermined target dose, and deescalated if excessive toxicity. Treatment in Arms 5-8 will be escalated for each drug to reach MTDs of Arms 2-4. Major eligibility criteria: Adults (≥ 18) with supratentorial GBM, KPS ≥60, adequate bone marrow and organ function. Post chemoradiation MRI ≤14 days before enrollment on stable/decreasing steroids and no progression; registration ≤5 weeks of chemoradiation. Patients on MFQ: no EIAED, EKG without prolonged QTc or arrhythmia. Pregnancy not allowed; adequate contraception required. Informed consent in keeping with IRB policies. Current enrollment: To date, 49 patients started treatment and 18 are still active. Enrollment to Arms 2-4 and 6 is completed and MTDs determined. Accrual is ongoing in Arms 5 and 7, and pending in Arm 8. Clinical trial information: NCT01430351.
Relapse impact on overall survival in trastuzumab-treated women with HER2+ early-stage breast cancer.
Authors: Christopher M. Gallagher, Kenneth More, Anthony Masaquel, Tripthi Kamath, Annie Guérin, Raluca Ionescu-Ittu, Marjolaine Gauthier-Loiselle, Roy Nitulescu, Eric Qiong Wu, Nicholas Sicignano, Elizabeth Butts, Brian Barnett
Journal: Journal of Clinical Oncology (2014)

e11601 Background: Adjuvant trastuzumab (T) reduces the risk of relapse in women with HER2+ early stage breast cancer (EBC). This study assessed the impact of relapse on overall survival (OS) in women with HER2+ EBC. Methods: Adult women initiating adjuvant T for HER2+ EBC were selected from the US Department of Defense (DOD) health claims database (2003-2012). An algorithm based on secondary neoplasm ICD9 codes and treatment gaps was used to identify relapses, which were grouped as occurring within 1 year, 1-3 years and >3 years of T initiation. Each relapse cohort was compared to a relapse-free cohort in the same time period. OS was compared between the relapse and relapse-free cohorts from each period's start until death or study end using Kaplan-Meier analyses and multivariable Cox regressions. Results: Of 3,188 women in the sample, 564 (18%) had a relapse. Survival rates were significantly lower in relapsers vs. non-relapsers, regardless of the period of comparison. After adjustment for potential confounders, relapsers continued to be significantly associated with higher hazards of death (Table). Conclusions: To our knowledge, this is one of few studies on T treatment and the impact of relapse on OS in community settings. The findings of this study suggest that the prevention of relapses with T would significantly increase the OS of patients with HER2+ EBC. Patients who relapsed >3 years of T initiation had a higher 5-year survival than those who relapsed within 3 years. Disclaimer: The views expressed in this abstract are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, DOD, or the US Government. Relapse within 1-year of T initiation Relapse 1-3 years of T initiation Relapse >3 years of T initiation Yes No Yes No Yes No N 216 2,972 279 2,252 69 1,366 Crude survival rates (95% CIs) 1-year 92% (88 - 95) 99% (99 - 99) 100%† 100%† 3-years 70% (63 - 76) 95% (94 - 96) 81% (75 - 85) 98% (97 - 99) 100%† 5-years 62% (54 - 69) 91% (89 - 92) 58% (50 - 64) 96% (95 - 97) 87% (75 - 93) 99% (98 - 99) Adjusted‡ effect of relapse vs. no relapse on OS Hazard ratio (95% CIs) 4.9 (3.7 - 6.5) 11.8 (8.5 - 16.3) 12.9 (6.2 - 27.0) † By design; ‡Age, Charlson comorbidity, radiotherapy, surgery type, receipt of T neoadjuvant.
Comparison of <sup>18</sup>F-FDG-PET-CT and bone scintigraphy for evaluation of osseous metastases in newly diagnosed and recurrent osteosarcoma.
Authors: Caitlin Hurley, Beth McCarville, Barry L. Shulkin, Shenghua Mao, Jianrong Wu, Fariba Navid, Najat C. Daw, Alberto S. Pappo, Michael William Bishop
Journal: Journal of Clinical Oncology (2015)

10047 Background: Bone scintigraphy (BS) is routinely used to detect osseous metastases in osteosarcoma. The use of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET-CT) to assess tumor extent in pediatric sarcomas has increased recently. We compared the sensitivity, specificity, and diagnostic accuracy of PET-CT and BS for detection of osseous metastases in osteosarcoma. Methods: We retrospectively reviewed 39 patients with osteosarcoma who underwent paired PET-CT and BS at diagnosis and/or first recurrence between 2003 and 2012. PET-CT and BS studies were independently reviewed by 2 pediatric imaging specialists who were blinded to results of the opposing modality and reference standard. Reviewers categorized lesions as benign, malignant or indeterminate. Reference standard for lesion histology was biopsy or clinical follow-up. Diagnostic performance of PET-CT, BS, and combined modalities were determined. Results: Forty-two examinations from 39 patients were reviewed and 123 bone lesions were evaluated. Median age was 11 years (range 5-19 years). Four patients had 13 osseous metastases at diagnosis (3 biopsied, 10 clinically), and 3 had 9 osseous metastases at recurrence (2 biopsied, 7 clinically). For all sites combined, sensitivity, specificity and diagnostic accuracy were 92%, 76%, and 84% respectively for PET-CT, 77%, 94%, and 85% for BS, and 98%, 69%, and 84% for PET-CT and BS combined. For metastatic sites alone, sensitivity, specificity and diagnostic accuracy were 77%, 76% and 76% for PET-CT, 41%, 94% and 80% for BS, and 96%, 69% and 76% for combined modalities. Improved sensitivity of PET-CT for metastatic sites compared to BS was borderline significant (p = 0.077). PET-CT and BS combined did not improve sensitivity over PET-CT alone (p = 0.125), but was significantly higher than BS alone (p < 0.001). BS specificity was superior to both PET-CT (p = 0.02) and combined imaging (p < 0.001). Conclusions: 18F-FDG-PET-CT is at least as sensitive as BS in detecting osseous metastases in osteosarcoma; combined use with BS further increases sensitivity. Our findings support the use of both 18F-FDG-PET-CT and BS for staging of osteosarcoma.
Response to neoadjuvant chemotherapy and outcome based on breast cancer subtype
Authors: A. Guerrero-Zotano, J. Gavila, M. A. Climent, M. J. Juan, V. Guillem, A. Ruiz
Journal: Journal of Clinical Oncology (2009)

e11516 Background: Gene expression profiling identifies several breast cancer subtypes with different chemosensitivity and outcome. We used immunohistochemistry surrogate markers to classify tumors according to known breast cancer subtypes and examined the relationship between neoadjuvant chemotherapy (NAC) response and long-term end points, including distant disease-free survival (DDFS) and overall survival (OS). Methods: Review of clinical and pathological data from 271 breast cancer patients treated in our institution with NAC between 1991–2008. Breast cancer subtypes were defined as follows: Luminal A: Estrogen receptor positive (ER+) and/or progesterone peceptor positive (PR+), human epidermal growth factor receptor 2-positive (Her-2+); Luminal B: ER+ and/or PR+,Her-2+; Basal: ER-,PR-,Her-2-;HER2: ER-,PR-,Her-2 +. ER and PR positive scored as positive if tumor cell nuclear staining was at least 2+. Her-2 scored as positive if test DAKO scored 3+ or FISH ratio Her-2/CEP-17&gt;2.2. Results: 121 (45.8%) patients were classifed as Luminal A; 22 (8.1%) as Luminal B; 75 (27.7%) as Basal, and 50 (18.5%) as HER2. Most patients (63%) received NAC based on anthracyclines and taxanes. 36% Her-2+ patients were treated with NAC based on trastuzumab, and 43% received trastuzumab as adjuvant treatment. Response and outcome results are shown below (Table). Independently from subtype, only four patients out of 58 with pCR relapsed. Among patients who didn´t achieved pathologic complete response (pCR), basal and HER2 subtypes have the worst outcome (4 years SG 80% and 72% respectevely) compared with Luminal A (4 years SG: 94.7%), (log-rank p=0.009). Conclusions: Basal and HER2 tumor despite high chemosensitivity have worst long term outcome, particularly if pCR is not achieved after NAC. [Table: see text] No significant financial relationships to disclose.
Exercise, metabolic syndrome, and cardiovascular fitness in breast cancer survivors.
Authors: M. Tish Knobf, Albert Sinusas, Margaret Holland, Sangchoon Jeon
Journal: Journal of Clinical Oncology (2017)

165 Background: Metabolic syndrome (MetS) has been reported higher in breast cancer survivors (BCS) compared to age-matched postmenopausal women. The risk for cardiovascular disease and diabetes is significantly increased in women with MetS. Lifestyle behaviors are recommended first line interventions to reduce risk for MetS. Methods: From a 12 month randomized controlled trial (RCT) of a fitness center exercise intervention compared to a home physical activity group, the criteria for MetS (3 of 5 components: waist circumference [WC] ≥ 80cm, triglycerides ≥ 150mg/dL, HDL cholesterol &lt; 40 mg/dL, blood pressure [BP] ≥ 130/85 mmHg, fasting blood sugar [FBS] &gt; 100mg/dL) were used to identify BCS with MetS. General estimating equation was employed for longitudinal changes. Heart rate recovery (reduction in heart rate from peak heart rate at one minute after exercise stress test) was used as a measure of cardiovascular fitness. Pearson correlation coefficients assessed associations between heart rate recovery and metabolic outcomes. Results: Of 148 subjects in the RCT, 21.6% (N = 32) met the criteria for MetS, with a higher baseline incidence in the home (30.1%) versus fitness center (13.3%) groups (p = 0.01). Of subjects on Tamoxifen, 30.9% had MetS, compared to 17.1% on an aromatase inhibitor and 20.7% not on endocrine therapy; these were not significantly different (p = .28). Among those with MetS at baseline, we observed a significant decrease in MetS (p &lt; .01) with significant changes in HDL (p = 0.02) and FBS (p = .01) after the 12 month intervention. The fitness center and home physical activity groups both resulted in fewer subjects meeting MetS criteria at 12 months, but only the home group had a significant change over time (OR = 0.66 (0.44, 0.98) p = .04). Heart recovery rate at 6 months was significantly associated with all 5 MetS components: WC (-0.28 p &lt; .01), triglycerides (-0.32 p &lt; .01), HDL (0.20 p = .04), systolic BP (-0.38 p &lt; .01), diastolic BP (-0.27 p &lt; .01) and FBS (-0.35 p &lt; .01). Conclusions: All-cause mortality now exceeds breast cancer specific mortality. MetS identifies a unique vulnerable population of BCS at high risk for cardiovascular disease. Lifestyle behaviors represent critical risk reduction strategies.
Blocking MIR155HG/miR-155 axis inhibits mesenchymal transition in glioma
Authors: Xuechao Wu, Yingyi Wang, Tianfu Yu, Er Nie, Qi Hu, Weining Wu, Tongle Zhi, Kuan Jiang, Xiefeng Wang, Xiaojie Lu, Hailin Li, Ning Liu, Junxia Zhang, Yongping You
Journal: Neuro-Oncology (2017)

MIR155 host gene (MIR155HG) is a long noncoding RNA that has been considered as the primary micro (mi)RNA of miR-155. MIR155HG plays an essential role in hematopoiesis, inflammation, and tumorigenesis. Our study investigated the clinical significance, biological function, mechanisms, and small-molecule inhibitors of the MIR155HG/miR-155 axis in glioma. We analyzed the expression of the MIR155HG/miR-155 axis and the correlation with glioma grade and patient survival using 2 different glioma gene expression datasets. Biological significance was elucidated through a series of in vitro and in vivo experiments. Furthermore, we conducted a high-throughput screening for small molecules to identify a potential inhibitor of the MIR155HG/miR-155 axis. Increased MIR155HG was associated with glioma grade, mesenchymal transition, and poor prognosis. Functionally, MIR155HG reduction by small interfering RNA inhibited cell proliferation, migration, invasion, and orthotopic glioma growth by repressing the generation of its derivatives miR-155-5p and miR-155-3p. Bioinformatics and luciferase reporter assays revealed that protocadherin 9 and protocadherin 7, which act as tumor suppressors by inhibiting the Wnt/β-catenin pathway, were direct targets of miR-155-5p and miR-155-3p, respectively. Finally, we identified NSC141562 as a potent small-molecule inhibitor of the MIR155HG/miR-155 axis. Our results demonstrate that the MIR155HG/miR-155 axis plays a critical role in facilitating glioma progression and serves as a prognostic factor for patient survival in glioblastoma. High-throughput screening indicated that the MIR155HG/miR-155 axis inhibitor NSC141562 may be a useful candidate anti-glioma drug.