tbuckley/cabot-search huggingface dataset:
Obesity and the odds of weight gain following androgen deprivation therapy for prostate cancer: Toward a risk adapted approach for ADT use.
Authors: Lior Zvi Braunstein, Ming-Hui Chen, Marian J. Loffredo, Philip W. Kantoff, Anthony Victor D'Amico
Journal: Journal of Clinical Oncology (2014)

5045 Background: Increasing BMI is associated with an increased risk of mortality; however, quantifying weight gain in men undergoing ADT for prostate cancer (PC) as stratified by baseline BMI remains unexplored and was the subject of the current study. Methods: Between 1995 and 2001, 206 men with unfavorable-risk prostate cancer were enrolled on a randomized trial evaluating the impact on survival of adding 6-months of ADT to radiotherapy (RT). BMI, both at baseline and after therapy, was available in 171 men who formed the study cohort. The primary endpoint was weight gain of ≥10 lbs by the 6-month follow-up. Logistic regression multivariable analysis was performed to assess whether baseline BMI or treatment-received was associated with this endpoint adjusting for comorbidity and known PC prognostic factors. Results: By the 6 month follow-up, 12 men were observed to have gained ≥10 lbs of which 10 (83%) were treated with RT and ADT and, of these, 7 (70%) were obese at randomization. As shown in the table, men treated with RT as compared to RT and ADT were significantly less likely to experience a weight gain of ≥ 10 pounds (adjusted odds ratio (AOR): 0.18 [95% confidence interval (CI) 0.04 - 0.89]; p = 0.04); whereas this risk was significantly increased with increasing BMI (AOR: 1.15 [ 95% CI 1.01 – 1.31]; p = 0.04). Moreover, weight gain persisted at 2 years for the obese men who gained ≥ 10 lbs after treatment with RT and ADT (median: 13.0 lbs; range: 9.0 to 21.0). Conclusions: Consideration should be given to avoiding ADT use in obese men with low or favorable-intermediate risk PC where improved cancer control has not been observed, but a shortened life expectancy from weight gain is expected. Clinical trial information: NCT00116220. Clinical factor No. of men No. of men who gained ≥ 10 lbs by EOT Multivariable analysis AOR (95% CI) P value RT 85 2 0.18 (0.04, 0.89) 0.04 RT + AST 86 10 1 (Ref) - BMI increase per kg/m2 171 12 1.15 (1.01, 1.31) 0.04 PSA increase per ng/mL 171 12 0.97 (0.87, 1.08) 0.57 Age 171 12 0.95 (0.85, 1.06) 0.38 Gleason score 8 to 10 26 3 1.17 (0.17, 7.93) 0..87 7 94 6 0.55 (0.10, 3.06) 0.49 6 or less 51 3 1 (Ref) - T2 88 8 1.99 (0.49, 7.99) 0.33 T1 83 4 1 (ref) - Mod to sev comorbidity 41 5 2.11 (0.54, 8.26) 0.28 No or min comorbidity 130 7 1 -
Validation of the numerical rating scale versions of the Edmonton Symptom Assessment Aystem (ESAS) and ESAS-r among outpatients with advanced cancer.
Authors: Breffni Hannon, Martin Dyck, Ashley Pope, Nadia Swami, Christopher Lo, Lisa Le, Camilla Zimmermann
Journal: Journal of Clinical Oncology (2014)

e20638 Background: The ESAS is usually presented as a numerical rating scale (NRS); but has been validated for outpatients with cancer only as a visual analogue scale. We aimed to validate the NRS versions of ESAS and ESAS-r, and to assess patient preference for either version. Methods: Patients with advanced cancer (N=202) attending ambulatory palliative care clinics at the Princess Margaret Cancer Centre, Toronto, between February 2012 and January 2013, completed both the conventional ESAS, with an added time window of “past 24 hours”, and the ESAS-r, which includes a time window of ”now” and symptom definitions. Participants completed the Memorial Symptom Assessment Scale (MSAS) and a patient-rated version of the Eastern Cooperative Oncology Group (ECOG) performance status measure. Physicians rated the ECOG independently. At 24 hours, 26 patients completed a test-retest study. Results: ESAS and ESAS-r total distress scores both correlated well with total MSAS scores (Spearman’s rho: 0.62 and 0.64, respectively). Correlation of individual ESAS symptoms with MSAS symptoms are shown in the Table, as are correlations of the overall ESAS scores with physician and patient-rated ECOG. Participants preferred the ESAS-r (42.8% versus 18.6%), finding the definitions helpful (87.1%), but preferred the time window of “past 24 hours” (52.8%) over “now” (21.3%). The 24 hour test-retest evaluation of the ESAS showed good correlation (ICC = 0.74). Conclusions: The ESAS and ESAS-r NRS versions are valid and reliable for outpatients with advanced cancer. The 24 hour time window was preferred and may best capture fluctuating symptoms (e.g. nausea, shortness of breath) in this population. Correlations of ESAS scores/subscores with validation measures. Measure ESAS score/subscore ESAS ESAS-r Patient completed ECOG, N (r) EDS 193 (0.40) 192 (0.33) Physician completed ECOG, N (r) EDS 173 (0.35) 172 (0.24) MSAS Pain * 0.68 0.66 Lack of energy Tiredness 0.58 0.52 Nervous Anxiety 0.57 0.59 Nausea * 0.72 0.64 Drowsiness * 0.66 0.61 Shortness of breath * 0.80 0.74 Sad Depression 0.66 0.64 Worry Anxiety 0.64 0.65 Appetite * 0.63 0.73 *same item name for ESAS; EDS, ESAS distress score.
In hindsight if treatment had begun early: A study to determine the OS and PFS in patients with stage III lung carcinoma based on the time elapsed from the diagnosis to start of treatment.
Authors: Jyothirmai Seepana, Abdo S. Haddad, Suryanarayan Mohapatra, Sidra Khalid, Subanandhini Subramaniam, Xuefei Jia
Journal: Journal of Clinical Oncology (2017)

230 Background: Stage III non-small cell lung cancer (NSCLC) is defined as loco-regionally advanced disease due to primary tumor extension into the extra-pulmonary structures (T3 or T4) or mediastinal lymph node involvement (N2 or N3) without evidence of distant metastasis. Patients are concerned about beginning treatment early after diagnosis. The role of the study is to determine the outcome if treatment is started within 8 weeks or after 8 weeks. In a retrospective study, the Cleveland Clinic’s database was used to identify patients treated through 2003 – 2014. Methods: Stage III NSCLC was ascertained as per the pathological or clinical stage. Kaplan-Meier estimate was used to determine the survival of patients. Results: Of the 561 patients patients with stage III NSCLC, 408 had treatment within 8 weeks and 153 after 8 weeks. See table. Treatment within 8 weeks of diagnosis: In total, 105 patients were recorded as having died, the median survival was 55.1 months (95% CI: 48.2, 62.5). The 2-year survival rate was 98% ± 0.9%, and the 5-year survival rate was 44.5% ± 4.7%. The median PFS was 15.3 months (95%Ci 12.0, 23.1). The 2-year PFS was 43% ± 0.28%, and the 5-year PFS was 14.5% ± 2.1%. Treatment after 8 weeks of diagnosis: In total, 34 patients were recorded as having died, the median survival was 60.6 months (95% CI: 50.3, 73.8). The 2-year survival rate was 97.5% ± 1.4%, and the 5-year survival rate was 53.2% ± 8.3%. The median PFS was 12.1 months (95%Ci 9.5, 15.3). The 2-year PFS was 32.8% ± 4.4%, and the 5-year PFS was 12.8% ± 3.2%. Among the following sub-groups: &lt; 65 years, 65-75 years and &gt; 75 years, there was no observable difference whether treatment was begun within eight weeks or after eight weeks. Conclusions: In the combined group and within subgroups, OS and PFS were not significantly different between patients who received treatment within 8 weeks and those who received treatment after 8 weeks. [Table: see text]
Decision support networks of women newly diagnosed with breast cancer.
Authors: Lauren P. Wallner, Yun Li, Chandler McLeod, Ann S. Hamilton, Kevin C. Ward, Lawrence C. An, Nancy K. Janz, Steven J. Katz, Sarah T. Hawley
Journal: Journal of Clinical Oncology (2017)

157 Background: Prior studies suggest that women often involve a network of family and friends in their cancer treatment decision making, yet very little is known about the size and characteristics of these decision support networks and whether their involvement leads to high-quality breast cancer treatment decisions. Methods: A weighted random sample of patients newly diagnosed with breast cancer in 2014-15 as reported to the Georgia and Los Angeles SEER registries were surveyed approximately 6 months after diagnosis (N = 2,502, 70% response rate). Network size was estimated by asking women to list up to 3 of the most important decision support people (DSP) who helped them make their locoregional therapy decisions. Decision deliberation was measured using 4-items assessing degree to which patients thought through the decision, with higher scores reflecting more deliberative breast cancer treatment decisions. We compared the size of the network (0-3+ people) across patient-level characteristics and estimated the adjusted mean deliberation scores across levels of network size using multivariable linear regression. Results: Of the 2,502 women included in this analysis, 51% reported having at least 3 DSPs, 20% reported 2, 18% reported 1, and 10% reported not having any DSPs. Among women who were not partnered (N = 961), 51% had 3 DSPs, 18% had 2, 16% had 1 and 16% had 0 DSPs. Of the DSPs that the respondents identified, the majority were children (30%), followed by partners/spouses (23%), friends (15%), siblings (10%), other family members (6%), and parents (5%). Married/partnered women (p &lt; 0.001), those younger than 45 years old (p &lt; 0.001), those with more than 1 comorbidity (p &lt; 0.001), and black women (p = 0.02) were all more likely to report larger networks on average. Larger support networks were associated with more deliberative surgical decisions (p &lt; 0.001). Conclusions: In this population-based sample, the majority of women engaged DSPs in their treatment decision making and for non-partnered patients, DSPs still played a key role in decision making. Larger size decision support networks were associated with higher quality decisions, underscoring the importance of efforts to identify and engage DSPs in the breast cancer decision making process.
Distant metastasis in head and neck cancer: Baseline factors.
Authors: Rahul Krishnatry, Tejpal Gupta, Vedang Murthy, Sudhir Vasudevan Nair, Deepa Nair, Pankaj Chaturvedi, A. K. Dcruz, Kumar Prabhash, Sarbani Laskar Ghosh, Ashwini Narsingrao Budrukkar, Jaiprakash Agarwal
Journal: Journal of Clinical Oncology (2012)

e16021 Background: Loco-regional relapse is predominant pattern of failure in locally advanced head &amp; neck squamous cell cancer (HNSCC). Distant metastasis (DM) is increasingly detected on follow-up. this study attempts to identify baseline patient, tumor &amp; treatment characteristics which determine poor survival in radically treated HNSCC patients developing DM. Methods: Clinical outcome audit of HNSCC receiving radical treatment from 1990-2010 in a single HNCC radiotherapy (RT) clinic who developed DM, using electronic search of a prospectively maintained database. The Disease free survival (DFS) &amp; overall survival (OS) were calculated using Kaplan Meier method. The Log rank test &amp; Cox regression (p&lt; 0.05 significant) were used for univariate &amp; multivariate analysis respectively. Results: 104 HNC patients developed DM, baseline characteristics are shown in table 1. DM was detected at a median of 7(IQR 3-14) months from treatment completion &amp; median survival after diagnosis of DM was 2.6 (0-6) months. The median DFS &amp; OS were 19(13-26), 21.5(16-29) months respectively. On univariate analysis, factors affecting DFS &amp; OS were advanced tumor and nodal stage, perinodal extension &amp; treatment factors (surgery &amp; RT gap &gt;30 days). On multivariate analysis stage and PNE remained significant for DFS while only stage showed significance for OS. Conclusions: Locally advanced stage of presentation (stage IV, T4, N2+) is the most important baseline factor determining poor outcome in HNC patients developing DM. Trials for aggressive primary systemic treatment (chemotherapy, targeted agents) are needed. [Table: see text]
Phase I study of gemcitabine (GEM) and premetrexed (ptx) in the treatment of advanced solid tumors
Authors: A. Kalykaki, S. Agelaki, K. Kalbakis, A. Kotsakis, N. Kentepozidis, C. Christophyllakis, S. Giassas, L. Vamvakas, N. Vardakis, D. Mavroudis
Journal: Journal of Clinical Oncology (2006)

12025 Background: GEM has activity against a wide range of tumors and ptx is a multitargeted antifolate agent with activity in mesothelioma and non small lung cancer (NSCLC). A phase I study of a combination of GEM plus ptx for advanced malignancies was conducted. Methods: Patients with advanced malignancies were enrolled in this accelerated dose escalation trial. Both patients with or without prior chemotherapy were also eligible. They were treated with Gem followed by ptx on days 1 and 15 every 4 weeks. The starting dose was GEM 1250 mg/m 2 and ptx 300 mg/m 2 . The dose of each drug was escalated alternately by 250 mg for GEM and 50 mg for ptx at each dose level. Results: A total of 41 patients (9 female/32 males) with median age of 60 years were enrolled at 6 dose levels. A total of 93 cycles were conducted with a median number of 2 cycles/pt. 35 patients were assessable for efficacy and all courses were assessable for toxicity. Grade 3/4 neutropenia was observed in 8 cycles whereas grade 3 /4 anemia and grade 3/4 thrombocytopenia in 3 and 2 cycles respectively. Grade 3 febrile neutropenia occurred in 1 cycle. Other ≥ grade 3 non-hematological toxicities were observed in only 3 cycles [grade 3/4 asthenia: in 2 cy; grade 3 edema: in 1 cy). The MTD was 1750 mg/m 2 for GEM and 450 mg/m 2 for ptx. Dose limiting toxicities were grade IV neutropenia, grade III thrombocytopenia and febrile neutropenia. Two partial responses (1 patient with ovarian cancer and 1 with NSCLC) were observed and stable disease in 4. Conclusions: The recommended doses for further phase II studies are GEM (1750 mg/m 2 ) followed by ptx (450 mg/m 2 ) biweekly. No significant financial relationships to disclose.
Mass Cytometry As a Modality to Identify Candidates for Immune Checkpoint Inhibitor Therapy within Acute Myeloid Leukemia
Authors: Adam Lamble, Yoko Kosaka, Fei Huang, A Kate Sasser, Homer Adams, Cristina E. Tognon, Ted Laderas, Shannon K. McWeeney, Marc M. Loriaux, Jeffrey W. Tyner, Brian J. Druker, Evan F. Lind
Journal: Blood (2016)
The international rare cancers initiative.
Authors: Nicola Jane Keat, Kate Law, Andrea McConnell, Fabien M. Calvo, Anastassia Negrouk, Denis A. Lacombe, Jack Welch, Edward Lloyd Trimble, Thomas Gross, Gaetan De Schaetzen, Jeanne-Marie Brechot, Iris Pauporte, Maura O'Riordan, Matthew T. Seymour
Journal: Journal of Clinical Oncology (2014)

e17504 Background: Together, rare cancers account for more than 20% of all cancer diagnoses. Patients with rare cancers face particular challenges, including late or incorrect diagnosis and difficulties accessing clinical expertise and appropriate treatments. Furthermore, undertaking clinical studies is challenging because of the small number of patients. Unfortunately, the average outcome for patients with a rare cancer is therefore worse than that of patients with more common cancers. In an attempt to address these issues, the International Rare Cancers Initiative (IRCI) was established in 2011. Methods: IRCI is a joint initiative between the National Institute for Health Research Cancer Research Network (NCRN), Cancer Research UK (CRUK), the National Cancer Institute (NCI) the European Organisation for Research and Treatment of Cancer (EORTC) and the Institut National du Cancer (INCa). IRCI organises meetings to facilitate the development of international clinical trials for patients with rare cancers (an incidence of <2 per 100,000). IRCI encourages the use of innovative methodologies to maximise the potential for answering research questions and to identify and overcome barriers to running international trials. Results: 9 rare cancers currently form the core activities of IRCI; Salivary gland cancer, Small bowel adenocarcinoma, Gynaecological sarcoma, Penile cancer, Thymoma, Ocular melanoma, Relapsed/metastatic anal cancer, Rare brain tumours and Desmoplastic Small Round Cell Tumours.11 clinical trials are in development, with 3 clinical trials now open to recruitment. Conclusions: IRCI will boost the progress of new treatments for rare cancer patients by aiding its existing groups, working through the issues of international trial setup and taking on further rare cancer types. Additionally, IRCI will endeavour to expand to involve other interested organisations and to develop relationships with industry.
Phase I trial to determine the safety and tolerability of GW572016 in combination with oxaliplatin (OX)/5-fluorouracil (5-FU)/leucovorin (LV) [FOLFOX4] in patients with solid tumors
Authors: W. S. Lakhai, J. H. Beijnen, S. S. Den Boer, A. M. Westermann, M. Versola, K. Koch, P. Ho, L. Pandite, D. J. Richel, J. Schellens
Journal: Journal of Clinical Oncology (2004)

2044 Background: EGFR and erbB2 receptor expression in tumors predicts a poor outcome. GW572016 (GW) is a potent EGFR/erbB2 RTK inhibitor. The FOLFOX4 is an effective therapy in colorectal cancer. It is hypothesized that inhibition of kinase activation by GW will contribute to the cytotoxicity of FOLFOX4. This phase I trial aimed to determine the safety and optimally tolerated regimen (OTR) of FOLFOX4 with daily oral GW in patients (pts) with solid tumors. Methods: Pts were sequentially enrolled into 3 cohorts: cohort 1 - GW 1250 mg/day + FOLFOX4 at –20% of the standard dose; cohort 2 –GW 1250 mg/day + FOLFOX4 at standard dose; cohort 3 –GW 1500 mg/day + FOLFOX4 at standard dose. OTR was the dose level at which ≤ 1/6 pts experiences a DLT. DLT was based on hematological and non-hematological toxicity in cycle 1. Assessments of anti-tumor activity and left ventricular ejection fraction (LVEF) were performed every 4 cycles. Results: 13 pts were treated (cohort 1 - 3; cohort 2 - 3; cohort 3 - 7). Median age was 57 years (39–70). Histology: 2 colon, 1 ovary, 3 rectum, 2 cholangio, 2 cervix, 2 pancreas, and 1 esophagus. Total of 57 cycles were delivered: median 4 (2–9). Main toxicities are summarized in the table. 2 Pts had grade ≥ 3 hematological toxicities, which resolved after delay of the next cycle. No DLTs have been reported. LVEF values were relatively unchanged compared to pre-study values. 7 pts are evaluable for response. 2 PR, 2 SD and 3 PD. Conclusion: Standard dose FOLFOX4 in combination with GW 1500 mg/day is well tolerated. Enrollment continues at this dose level including pharmacokinetic assessments. No significant financial relationships to disclose.
Palliation of relapsed aggressive histology NHL with high-dose celecoxib and 'metronomic' low-dose cyclophosphamide
Authors: R. Buckstein, M. Crump, Y. Shaked, C. Foden, R. Nayar, D. Taylor, F. Bertolini, S. Baruchel, S. Man, R. Kerbel
Journal: Journal of Clinical Oncology (2004)

3016 Background: Relapsed aggressive Non-Hodgkin's Lymphoma (NHL) has a poor prognosis; and new treatments are needed. Angiogenesis is increased in aggressive NHL, and may be a target in these diseases. Low dose chronic chemotherapy (metronomic chemotherapy, MC) inhibits angiogenesis in vitro. Since COX-2 may promote neoplasia and tumour angiogenesis, selective COX-2 inhibitors may have anti-tumour effects in NHL.We assessed response to MC and COX-2 inhibition and toxicity in patients (pts) with relapsed aggressive NHL following anthracycline based chemotherapy. Methods: Pts with measureable disease and normal renal function received cyclophosphamide 50 mg po qd + celecoxib 400 mg po bid. Pts were assessed clinically monthly x 6 then q 2 mos; CT scans q 3 mos, serial plasma VEGF and TSP-1 levels. Pharmacokinetics (PK)and serial LN biopsies for COX-2 IHC were performed in selected pts. Serial circulating endothelial cells (CEC) and their precursors (CEP) were measured by flow cytometry. Results: To date 21 of a planned 32 pts have been treated; 17 are evaluable for response. Median age 65 y (range 46–81). Histology: 17 DLBCL, 2 MCL, 2 transformed (CLL+FL). Median 3.3 yrs from diagnosis (range 0.9 to 9.5); 5 in 1st relapse, 4 in 2nd, 4 in 3rd, 4 in 4th and 2 with PD. Median # of previous chemotherapy regimens: 3 (range 1–6); prior ASCT: 7. Median time to death or last follow-up: 8.5 mos (range 1.8–17); 6/17 pts responded (1 CRu, 5 PR,ORR 35%) at a median time of 4.6 mos, and 4 remain in PR at 18, 14, 12 and 3 mos. Two pts have SD and 10 have progressed at a median time of 1.9 mos (range <1–9); 7 have died of NHL. Median OS and PFS are 8.5 and 3.9 mos, respectively. Adverse events(# pts): grade 3–4 ANC (2), grade 3 plt (3), grade 3 hypertension(1), grade 3 headache(1) and grade 3 drug rash(1). This regimen has been well tolerated with minimal GI toxicity. Lab correlates (COX-2 IHC, PK, serum VEGF, TSP-1 and blood CEC and CEP levels will be presented. Conclusions: MC with high-dose celecoxib and low dose cyclophosphamide is well tolerated and active in heavily treated relapsed aggressive NHL. The anti-angiogenic activity of this regimen is still being determined. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration CIHR Pfizer Inc.
Blinatumomab exposure and pharmacodynamic response in patients with non-Hodgkin lymphoma (NHL).
Authors: Youssef Hijazi, Matthias Klinger, Andrea Schub, Benjamin Wu, Min Zhu, Peter Kufer, Andreas Wolf, Dirk Nagorsen
Journal: Journal of Clinical Oncology (2013)

3051 Background: Blinatumomab (AMG 103) is an investigational, bispecific, T cell engaging (BiTE) antibody targeting CD19-expressing B cells. We describe the exposure-pharmacodynamic (PD) response of blinatumomab in patients with NHL, using a quantitative pharmacology approach. Methods: In a phase 1 study, 76 patients with NHL received blinatumomab by continuous intravenous infusion (cIV) at doses of 0.5 to 90 μg/m 2 /d in 4- or 8-week cycles. Pharmacokinetics (PK) was determined. PD responses evaluated included lymphocytes and cytokines measured during treatment, and sum of the products of the greatest diameters of tumor size in lymph nodes (SPD) at the end of treatment. Blinatumomab concentration at steady state (C ss ) and the cumulative area under the concentration (AUC cum )–time curve over the period before the evaluation of SPD were used to evaluate the exposure-SPD relationship. Results: Blinatumomab showed linear PK. Early PD responses were characterized by B cell depletion, T cell redistribution, and transient cytokine release. Following cIV at doses from 0.5 to 90 μg/m 2 /d, B cells declined at a first-order rate with a dose-dependent rate constant, ranging from 0.16 to 1.0 h -1 . Complete B cell depletion was achieved within 48 hours at doses ≥5 μg/m 2 /d. A dose-independent decrease in T cell counts was observed within 24 hours after dosing, and T cells returned to baseline within 2 weeks of treatment. Cytokine elevation occurred in some patients and was dose-dependent. Blinatumomab exposure-SPD relationship was best described by an inhibitory E max model (E = E 0 -(I max *C)/(IC 50 +C)). According to the model estimation, a 50% reduction in SPD would be achieved when C ss is 2141 pg/mL and AUC cum is 1381 h*μg/L, equivalent to a blinatumomab dose of 54 µg/m 2 /d given over 27 days. Conclusions: B lymphocytes were completely depleted from the circulation at blinatumomab doses ≥5 μg/m 2 /d. Depletion was faster at higher doses. Higher blinatumomab C ss and AUC cum were associated with better tumor reduction. Tissue accessibility may explain the higher dose requirement for SPD reduction versus peripheral B cell depletion. The PK/PD model has utility for the design of future studies of blinatumomab in NHL. Clinical trial information: NCT00274742.