tbuckley/cabot-search huggingface dataset:
Phase I dose escalation trial using stereotactic body radiation therapy (SBRT) for partial breast irradiation (PBI).
Authors: Asal Shoushtari Rahimi, Ann Spangler, Dan Patrick Garwood, A. Marilyn Leitch, Roshni Rao, Stephen Seiler, Rachel D. Wooldridge, Aeisha Rivers, Stella Stevenson, Sally Goudreau, Barbara B. Haley, Ying Dong, David Euhus, Kevin V. Albuquerque, Micheal Folkert, John Henry Heinzerling, Chuxiong Ding, Chul Ahn, Hak Choy, Robert D. Timmerman
Journal: Journal of Clinical Oncology (2015)

1057 Background: To evaluate tolerability of escalating doses of 5 fraction SBRT PBI in treating early stage breast cancer after partial mastectomy on a phase I dose escalation trial. The primary objective was to escalate the PBI dose utilizing a robotic stereotactic radiation system treating the lumpectomy cavity without exceeding the maximum tolerated dose (MTD). Methods: Eligible patients included DCIS or invasive ductal histologies, AJCC stage 0-II with tumor size < 3cm, and margins ≥ 2mm. Prior to simulation 3-4 four gold fiducials were placed around the lumpectomy cavity for real-time respiratory tracking. Dose limiting toxicity (DLT) equaled grade ≥ 3 toxicity by CTCAE deemed definitely related to treatment for: skin, bone (fracture), pulmonary, neurological (intercostal or brachial plexus nerves) or any grade 4/ 5 toxicity definitely attributed to therapy. Both patients and physicians completed baseline and subsequent cosmesis questionnaires using a four point scale – excellent, good, fair, poor. Starting dose was 30 Gy in 5 fractions. Dose was escalated by 2.5 Gy total, provided 4 or fewer of 15 patients experienced a DLT within 90 days of treatment within each dose group. If more patients had DLT in a given dose cohort, the MTD would be exceeded. Results: 68 patients (15 per dose cohort (cohort 5 -8 patients)) enrolled with median age 62 years. Median follow-up for cohorts 1,2,3,4, and 5 were - 36.3, 26.4, 16, 8.8, and 2.3 months. The first 3 dose cohorts completed 90 day follow-up without DLTs. There was 1 focal grade 3 dermatitis DLT at 37.5 Gy. DLT follow-up is still ongoing in cohort 5. There were 72 grade 1 toxicity events, 2 grade 2 toxicities (rib fracture and breast pain), and 2 grade 3 radiation dermatitis toxicities. Physicians scored cosmesis as excellent or good in 94.9%, 100%, 97.7%, and 100% respectively (p = 0.28), at baseline, 6, 12, and 24 months post SBRT, while patients scored the same periods 82.7%, 96.2%, 95.4%, and 92.8% (p = 0.04). Conclusions: Dose is escalated to 37.5 Gy in 5 fractions without MTD thus far. Soon we are completing dose escalation for 40Gy in 5 fractions PBI, hoping to increase the likelihood of long term tumor control while evaluating toxicity and cosmesis of this innovative therapy. Clinical trial information: NCT01162200.
Impact of circulating members of the insulin-like growth factor receptor (IGF-1R) axis on outcomes in acute myeloid leukemia.
Authors: Reem Karmali, Jeffrey Allen Borgia, Melissa L. Larson, Jamile M. Shammo, Sanjib Basu, Parameswaran Venugopal
Journal: Journal of Clinical Oncology (2014)

7069 Background: AML is a disease with conservative response rates to standard therapy in the adult population. Dysregulations in insulin-like growth factor receptor-1 (IGF-1R) signaling is implicated in leukemogenesis and chemo-resistant disease, but remains poorly elucidated. We explore associations of circulating levels of the IGF-1R axis, consisting of IGF binding proteins 1-7, IGF-1, and c-peptide as a control, with clinical outcomes of patients with aggressive AML. Methods: Peripheral blood samples in newly diagnosed non-M3 AML patients (n=30) were collected prospectively under IRB consent. Relevant clinical parameters (cytogenetics, molecular data, treatment response) were annotated for each patient. Circulating levels of the IGF-1R axis were established using Luminex-based assays and analyzed using independent t-tests, ANOVA, and log-rank in SPSS v15.0 and R statistical software. Results: The median age was 56. Using the ELN cytogenetic/molecular risk model, patients were stratified as either adverse risk (47% of patients; FLT-3 positive/NMP negative CN AML, c-kit positive CBF AML, MLL gene rearrangement (11q23), chromosome 5 and/or 7 abnormalities, or complex karyotype), good risk (13% of patients; CBF AML without c-kit positivity and FLT-3 negative/NPM mutated CN AML), or intermediate risk (40%; all others). Increased IGFBP-4 correlated with therapy response (p <0.05) using independent t-tests. Median overall survival (OS) in the cohort was 5.2 months. Differences in progression-free survival (PFS) and OS between groups with "low" and "high" protein expression were determined using optimal discovery threshold with log-rank. Increased expression of IGFBP-1 and -6 correlated with improved PFS (p < 0.03 and 0.01, respectively) while increased IGFBP-1, -2, -6 and -7 were associated with improved OS (p < 0.001, 0.009, 0.003 and 0.001, respectively). A trend for decreased IGFBP-3 in adverse risk patients was noted. Conclusions: The IGF-1R axis appears to be relevant in disease refractory AML. IGFBP signatures are predictive tools in AML with applications in remission surveillance, early detection of relapse and the development of IGFBP-directed biologic therapy.
High-dose chemotherapy and autologous peripheral blood stem cell rescue (Auto-SCT) in multiple myeloma (MM) patients: Busulfan + melphalan-140 (BuMel) versus (vs) melphalan-200 (Mel-200) as conditioning regimens
Authors: R. Carrion Galindo, D. Serrano, A. Perez-Corral, P. Balsalobre, I. Buno, J. Anguita, A. Gomez-Pineda, M. Mayayo, J. Diez-Martin
Journal: Journal of Clinical Oncology (2006)

7612 Background: Auto-SCT is the preferred treatment modality for MM. From the results of IFM 9502 (Moreau et al. Blood, 2002) melphalan 200 mg/m 2 was considered the new standard as conditioning regimen due to its lower toxicity. However, many chemotherapy regimens have been tested. We present our results with two cohorts of consecutive patients (pts) diagnosed of MM and treated with Auto-SCT between 1996 and 2005 in our BMT Unit. Methods: Following induction chemotherapy (median of 6 courses) 20 pts were conditioning with busulfan 16 mg/kg + melphalan 140 mg/m 2 (BuMel) and 23 (since September-2002) with melphalan 200 mg/m 2 (Mel-200). Clinical features: median age (BuMel vs Mel-200) 55 vs 58 (p=0.5); female sex 10 vs 10; Bence-Jones MM 5 vs 5; renal failure (B) 2/20 (10%) vs 7/23 (30%)(p=0.48); previous treatment with local irradiation 6/20 vs 3/23; status previous Auto-SCT (complete remission, CR) 7/20 (35%) vs 6/23 (26%), p=0.5. A median of 4.8 vs 4.4 x 10e6/kg CD34+ cells were infused, respectively (p=0.15). Results: Four toxic deaths: 2 pts by hemorrhagic cystitis-enterocolitis (at day +84 and +96), 1 pt with disseminated candidiasis (day +7), and 1 pt by pulmonary fibrosis (day +452). At 3 months following Auto-SCT, 13/19 (68%) treated with BuMel and 12/23 (52%) of those treated with Mel-200 achieved CR (p=0.28). At 24 months, probability of remaining disease free was 87% for BuMel group and 55% for Mel-200 (p=0.08). Conclusions: 1) Conditioning regimen BuMel was associated with a higher toxicity than Mel-200, as well as a higher mortality treatment related. 2) However, a trend for higher CR rates and probability of disease free progression were shown in BuMel group without statistical significance [Table: see text] No significant financial relationships to disclose.
Gemcitabine (G), capecitabine (C) and bevacizumab (BV) in patients with advanced biliary cancers (ABC): final results of a multicenter phase II study.
Authors: Renuka V. Iyer, Adrienne Groman, Wen Wee Ma, Usha Malhotra, Dan Iancu, Catherine Grande, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2015)

4078 Background: Role of antiangiogenic therapy is still undefined in ABC. We examined BV combined with G + C, a standard chemotherapy for ABC when the study began. Methods: Pts with ABC (inoperable stage III or IV), ECOG PS 0-1, normal organ and marrow function. Schema: BV 15 mg/ kg q 21 days; C 650 mg/m2 bid x 14 days, both starting day 1; G 1000 mg/m2 days 1 & 8; cycles repeated q 21 days. Primary objective was progression free survival (PFS), secondary objectives were overall survival (OS) toxicity, quality of life (QOL) using the FACT HEP tool and circulating tumor cell (CTC) number. Results: Fifty pts enrolled at 2 sites; 11(22%) gall bladder (GB), 29(58%) intrahepatic cholangiocarcinoma (IHC) and 10(20%) extrahepatic cholangiocarcinoma (EHC). Median age 63 (range 25- 84 years), 52% male, inoperable 16% and metastatic 84%. Cycles: median 8 cycles/patient (range 1- 33), median time on treatment was 5.8 months. Responses (RECIST): PR 12(24%), SD 24 (48%), PD 6(12%) and 8 (16%) 2 too early/6 clinical progression (nonevaluable). Clinical benefit rate (PR + SD) = 72 %. Median PFS: 8.1months (95% CI:5.3, 9.9). Median OS: 11.3 months (95% CI:8.1, 13.1). One year survival rate was 0.47 (95%CI: 0.32-0.60). Grade 3/4 toxicities ( > 5%): hematologic 28(58%), GI 18 (36%), infections 14 (28%) and thromboembolic events 6 (12%). Treatment discontinuation for toxicity (10%), progression (64%), death (4%), or other reasons (22%). Median OS in 21 (46%) pts with detectable CTCs was 9.4 months compared to 13.7 months in the 25(54%) pts without detectable CTCs at baseline.Patients with QOL scores after one and two cycles of therapy that were above median score at baseline for the whole group had higher OS of 13 months compared to 11.3 months. Conclusions: PFS and OS in ABC with the combination of gemcitabine, capecitabine and bevacizumab is relatively comparable to that reported with gemcitabine and cisplatin with acceptable toxicity. Lack of detectable CTCs and higher than median QOL score after one/two cycles of therapy may serve as biomarkers to predict improved outcome. Acknowledgement: Study is supported by a grant from Genentech. Clinical trial information: NCT01007552.
Providing cancer survivorship care plans for Spanish language speakers: Overall use and satisfaction patterns.
Authors: Christine Hill-Kayser, Carolyn Vachani, Margaret K. Hampshire, Gloria A. Di Lullo, James M. Metz
Journal: Journal of Clinical Oncology (2013)

e20671 Background: Cancer survivorship care plans may be communication aides to assist healthcare providers and empower survivors. A paucity of information exists regarding the provision of survivorship care plans to the Spanish speaking population. Methods: The LIVESTRONG Care Plan is an Internet-based tool for creation of survivorship care plans, originally launched in 5/07. It is available at www.livestrongcareplan.org, and via OncoLink, a cancer information website based at the University of Pennsylvania, serving over 3.9 million pages/ month to 185,000 unique IP addresses. A direct link on the homepage directs users to the Spanish version. All information is provided and translated by oncology nurses and physicians. Results: Since launch of the tool, 293 Spanish care plans have been created (1% of total care plans). Care plans in Spanish have been created by survivors in 78% of cases, and healthcare providers in 22%. This differs from the entire user population, in which use by HCP approaches 50% (p=&lt; 0.001). Spanish-speaking users are 52% female, and 82% Latino/a, and less likely from the US (60% vs 87% , p=0.02), also being from Mexico (15%), Spain (10%), Chile (9%), Puerto Rico (5%) and Venezuela (3%). Spanish users were most often survivors of breast (20%) GU (33%) and GI (20%) cancers (vs general population 50%, p = 0.03; 10%, p = 0.04; 11%, p = 0.03, respectively). Only 8% of Spanish-speaking users report having received previous survivorship information vs 13% in the overall group (p=0.07). All users (100%) of the Spanish version rate experience and satisfaction with the care plan as “very good” or “excellent.” Average time for completion of Spanish plans was 9:28 min. Conclusions: Most users of the Spanish plan are survivors who have not received this information before, from the US and several Central/South American countries. They are highly satisfied with the information provided. Healthcare providers are proportionally less likely to use the Spanish version of the plan than survivors are.
Sulfasalazine inhibits growth of mantle cell lymphoma cell cultures via cyst ine starvation and delays tumour growth in a newly developed murine MCL model
Authors: G. Bebb, D. W. Doxsee, C. Tucker, D. N. Waterhouse, M. E. Williams, D. Masin, R. D. Gascoyne, Y. Wang, P. W. Gout
Journal: Blood (2003)
Phase II study of dalantercept, a novel inhibitor of ALK1-mediated angiogenesis, in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.
Authors: Antonio Jimeno, Lori J. Wirth, Marshall R. Posner, Roger B. Cohen, Jared Weiss, Elizabeta C. Popa, Nabil F. Saba, Kenneth F. Grossmann, Ammar Sukari, Ezra E.W. Cohen, Athanassios Argiris, Carolyn H Condon, Dawn Wilson, Ty McClure, Marat Alimzhanov, Scott Pearsall, Kenneth M. Attie, Matthew L. Sherman, Shuchi Sumant Pandya
Journal: Journal of Clinical Oncology (2013)

TPS6098 Background: Despite advances in the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN), the prognosis remains poor with a need to develop novel therapeutic strategies. Targeting angiogenesis in SCCHN is an active area of clinical research. Activin receptor-like kinase 1 (ALK1) is a type 1 receptor in the TGF-ß superfamily which is selectively expressed on activated endothelial cells. ALK1 binds bone morphogenetic proteins (BMP) 9 and 10 (ligands for ALK1) and is primarily involved in the maturation stage of angiogenesis. Dalantercept is a human ALK1-Fc receptor fusion protein that binds BMP9/10 and acts as a ligand trap. In preclinical tumor models, dalantercept demonstrated a decrease in tumor vascularization and delayed tumor growth. In a completed phase I study, dalantercept demonstrated anti-tumor activity in patients with advanced solid tumors including SCCHN. Methods: An open label, multi-center, multiple dose, phase II study to evaluate dalantercept in patients with advanced SCCHN is ongoing. Dalantercept is being administered every three weeks via SC injection in a total of 45 patients to assess safety, tolerability, and efficacy. 13 patients were enrolled at the 0.6 mg/kg dose level. To date, 6 out of 30 planned patients have received dalantercept at the 1.2 mg/kg dose level. Key inclusion criteria are tumors arising from the oral cavity, oropharynx, hypopharynx, or larynx, at least one prior platinum-containing regimen, ECOG performance status &lt;/= 1, and measurable disease. Exclusion criteria include prior anti-angiogenesis therapy, significant pulmonary, cardiovascular, or bleeding risk. The primary efficacy endpoint is RR. Secondary endpoints include PFS, OS, TTP, DOR, DCR, and PD biomarkers on tumor and serum specimens including BMP9/10 and ALK1 expression. Clinical trial information: NCT01458392.
LUX-Lung 6: Patient-reported outcomes (PROs) from a randomized open-label, phase III study in first-line advanced NSCLC patients (pts) harboring epidermal growth factor receptor (EGFR) mutations.
Authors: Sarayut Lucien Geater, Caicun Zhou, Cheng-Ping Hu, Ji Feng Feng, Shun Lu, Yunchao Huang, Wei Li, Mei Hou, Jian Hua Shi, Kye Young Lee, Dan Massey, Juliane Lungershausen, Yang Shi, Victoria Zazulina, Yi Long Wu
Journal: Journal of Clinical Oncology (2013)

8061 Background: Afatinib (A) is an oral, irreversible, ErbB Family Blocker, blocking signaling from EGFR (ErbB1), human epidermal growth factor receptor 2 (HER2; ErbB2) and ErbB4. In LUX-Lung 6, A was significantly better than gemcitabine/cisplatin (GC) in terms of progression free survival (PFS) and tumor response, with a more favorable safety profile. Here, we report the PRO results. Methods: 364 pts were randomized (2:1) to receive A or GC. PROs were measured using EORTC questionnaires QLQ-C30/LC13 at baseline and q3w until progression. Changes of ≥10 points (scale 0–100) were considered clinically significant. Analyses of cough, dyspnea and pain were prespecified. Time to deterioration (1st 10-point worsening from baseline) was analyzed using a stratified log-rank test. Percentage improved/worsened by ≥10 points or stable was determined. Mean scores over time were estimated using longitudinal (mixed-effects growth curve) models. Results: Compliance on treatment with questionnaires was &gt;90%. Baseline symptom burden was low (cough: 35; dyspnea: 25; pain: 24). Compared with GC, therapy with A significantly delayed time to deterioration for cough (HR=0.45; p=0.0001), dyspnea (HR=0.54; p&lt;0.0001) and pain (HR=0.70; p=0.03). A higher proportion of A-treated pts had ≥10-point improvements in cough (76% vs 55%; p=0.0003), dyspnea (71% vs 48%; p&lt;0.0001) and pain (64% vs 47%; p=0.003) compared with GC, particularly among pts with baseline symptoms. Mean scores over time for cough, dyspnea and pain also significantly favored A. Consistent with their safety profiles, a significantly higher proportion of A-treated pts had worsening of diarrhea, sore mouth and dysphagia, while fatigue, nausea, and vomiting were significantly worse with GC. Overall, therapy with A significantly improved global health-related quality of life (HRQoL; p&lt;0.0001), physical (p&lt;0.0001), role (p=0.01) and social (p&lt;0.001) functioning compared with GC. Conclusions: In LUX-Lung 6, prolongation of PFS with A was associated with significantly better HRQoL and significantly longer control of lung cancer-related symptoms compared with GC. Clinical trial information: NCT01121393.
Bevacizumab (BEV) use in disseminated choroid plexus papilloma (DCCP).
Authors: Mark Daniel Anderson, Brett James Theeler, Morris D. Groves, Marta Penas-Prado, W. K. Alfred Yung
Journal: Journal of Clinical Oncology (2013)

e13039 Background: Choroid plexus papilloma (CCP) is a rare primary neuro-ectodermal tumor of the choroid plexus, representing less than 1% of intracranial tumors in adults. The most common location in adults is the 4 th ventricle and treatment is gross total resection (GTR). Leptomeningeal disease (LMD) can rarely occur, even when the tumor retains benign histology. Because of the rarity of DCCP, there is no standard treatment, with less than 20 published cases. There have no previous descriptions of the use of BEV therapy in DCCP. Methods: We present 2 patients (pts) with DCCP, who received gross total resection, radiation and chemotherapy with continued progression, who received treatment with BEV therapy. Results: Pt 1 presented with a 4 th ventricular mass and evidence of LMD. GTR of the posterior fossa lesion revealed an atypical CCP. The pt received craniospinal radiation with concurrent temozolomide (TMZ) therapy. After 4 years, there was leptomeningeal disease progression and the pt developed progressive radicular pain and weakness, unresponsive to typical treatments. He was initiated on TMZ and BEV therapy, but the TMZ was discontinued due to thrombocytopenia and the pt was continued on BEV alone. While the MRI showed stable disease at, the pt had complete remission of pain and some improvement of ataxia. When BEV was held due to toxicity, the pain returned until BEV was restarted. Carboplatin was added to BEV with progression of LMD at 21 months. Pt 2 is a 58-year-old man who present with a 4 th ventricular mass, shown to be CCP after gross total resection. The pt received radiotherapy for diffuse sacral recurrence. After three years of surveillance, the pt received lomustine and 6-thioguanine for disease progression, limited to 5 cycles by thrombocytopenia. After 5 years, the pt noted continued progressive radicular pain in his lower extremities. The pt completed a planned course of 10 doses of bevacizumab and had improvement in pain control and stable imaging at 11 months. Conclusions: While bevacizumab resulted in stable imaging when used in DCCP, there was significant improvement in debilitating radicular symptoms. The complications of BEV therapy must be considered with the potential benefit of symptomatic relief. Prospective studies are needed.
A first-in-human study of pegylated recombinant human IL-10 (AM0010), daily administered for four months in selected advanced solid tumors.
Authors: Todd Michael Bauer, Kyriakos P. Papadopoulos, Karen A. Autio, Patrick Alexander Ott, Melinda Whiteside, Martin Oft, Jeffrey R. Infante, F. Stephen Hodi, Jedd D. Wolchok
Journal: Journal of Clinical Oncology (2014)

TPS3126 Background: Cancer immunotherapy targets the activation of tumor infiltrating CD8 T cells. Tumor associated inflammation on the other hand is thought to both promote tumor growth and to inhibit the CD8 mediated immune responses. IL-10 directly induces Interferon gamma in tumor resident CD8+ T cells, stimulates the cytotoxic activity of CD8+ T cells, increases the immunoglobulin production of B cells and has strong anti-inflammatory activity. In preclinical studies, PEGylated IL-10 (PEG-IL-10) but not non-PEGylated-IL-10 induces the rejection of large syngeneic tumors and the development of immunological memory against the tumor cells. Maximal antitumor efficacy required daily subcutaneous injections of PEG-IL-10 for 2-4 weeks indicating the need for prolonged stimulation of the immune system. rHuIL-10 was used in previous clinical trials in inflammatory diseases but its short T1/2 prevented a meaningful clinical benefit. AM0010, a PEGylated human IL-10, is safe in preclinical species and a first in human study was started November 2013. Methods: This study will be performed in two parts and will enroll approximately 28 patients with advanced solid tumors in the escalation phase, followed by at least one expansion cohort of 15 patients. Patients with melanoma, non-small cell lung cancer, renal cell cancer, colorectal cancer, castrate resistant prostate cancer, ovarian cancer and pancreatic cancer will be enrolled during the dose escalation phase, followed by at least one disease specific expansion cohort. Patients will daily self-administrate subcutaneous doses of AM0010 for four cycles of 1 month without dosing holidays. The primary objectives are to establish the safety and tolerability, dose limiting toxicities, and MTD of AM0010. Secondary objectives are to assess preliminary anti-tumor activity, pharmacokinetics, and immunogenicity of AM0010. The pharmacodynamic effects of AM0010 on innate and adaptive immunity will be evaluated using serum cytokine measurements, immunohistochemistry of tumor infiltrating T cells and humoral and cellular tumor antigen specific responses in the blood of patients. Clinical trial information: NCT02009449.