tbuckley/cabot-search huggingface dataset:
Long-term outcome and success for new risk models of pleurodesis in metastatic breast cancer: An analysis of 75 cases.
Authors: N. Matsubara, K. Ito, S. Nagai, H. Mukai
Journal: Journal of Clinical Oncology (2011)

e11033 Background: Malignant pleural effusions are a common and devastating complication of metastatic breast cancer. This occurs in about 30% of patients with metastatic breast cancer during the clinical course and chemical pleurodesis is sometimes performed for relieving dyspnea. However, long term outcome of pleurodesis in breast cancer and factors affecting control of pleurodesis were not clarified. The aim of this analysis is to evaluate the long term outcome of pleurodesis and to create risk factors associated with failure. Methods: The data of 75 patents, received chemical pleurodesis by OK-432 for pleural effusion due to metastatic breast cancer were reviewed retrospectively. The primary outcome is success rate and pleural progression free survival (PPFS) rate. Success of pleurodesis is defined as no observation of pleural fluid re-accumulation. PPFS is defined as the day from chest tube insertion to the first time observation of pleural fluid re-accumulation or last follow up. Results: The median duration of follow up was 134 days (range: 8-975 days). During follow up period, 22 patients were observed pleural fluid re-accumulation. Overall success rate was 70.5% (53/75). The 4-weeks, 8-weeks and 12-weeks PPFS rate were 88.0%, 84.0% and 78.7% respectively. Multivariate analysis identified ER negative, 24-hours drainage volume more than 100mL before extubation and NSAIDS using as the factors independently associated with the pleurodesis failure. The overall PPFS rate was 94.1% in low risk group (n=17, no unfavorable factor), 83.3% in intermediate risk group (n=30, 1 or 2 unfavorable factors) and 42.9% in high risk group (n=28, 3 unfavorable factors) respectively. The PPFS curves according to these risk groups are statistically significant (p=0.001, by fivefold cross-validation). Conclusions: Pleurodesis for metastatic breast cancer was efficacious for controlling malignant pleural effusion. New risk group model based on these risk factors seems to be simple and may be useful.
Comparative effectiveness of CSFs for hospitalization risk in real-world oncology practice.
Authors: H. Tan, J. Yu, M. Ahmed, A. Inamoto, S. Yager, R. G. Deeter
Journal: Journal of Clinical Oncology (2011)

e16531 Background: Limited published data exist on how the granulocyte-macrophage colony-stimulating factor (CSF) affects risk of hospitalizations. This study compares the effectiveness of prophylaxis with G-CSFs filgrastim (FIL) and pegfilgrastim (PEG), and GM-CSF sargramostim (SAR). Methods: A retrospective analysis of administrative claims from US commercial health plans identified adult patients with NHL, breast, lung, colorectal, or ovarian cancer treated with myelosuppressive chemotherapy between July 2004 and April 2010. For these patients, the first course of chemotherapy and each cycle with use of CSFs (FIL, PEG, or SAR) was identified as prophylaxis if used within the first 5 days of each cycle and prior to neutropenia-related hospitalization. The risk of neutropenia-related (neutropenia, fever, or infection) and all-cause hospitalization was then evaluated on a cycle basis. A generalized estimating equation (GEE) was used to adjust for baseline patient demographics and clinical characteristics. Results: Among 30,264 prophylactic CSF patient-cycles, 5.5% used FIL, 93.1% PEG, and 1.3% SAR. The neutropenia-related hospitalization rates were 3.6% (n=60) for FIL, 2.1% (n=588) for PEG, and 6.9% (n=28) for SAR. Correspondingly, all-cause hospitalization rates were 6.2% (n=103), 4.1% (n=1150), and 8.6% (n=35). Unadjusted and adjusted odds of hospitalization were consistently higher for FIL (by 55%-78%) and SAR (by 118%-248%) versus PEG (Table). Conclusions: Among prophylactic CSF use in clinical practice, PEG was associated with significant lower risk of neutropenia-related and all-cause hospitalization compared to FIL and SAR. Unadjusted and adjusted odds ratio (OR) for hospitalizations. Unadjusted Adjusted* OR 95% CI P value OR 95% CI P value Neutropenia-related FIL vs. PEG 1.75 1.34-2.29 <0.001 1.78 1.28-2.48 0.001 SAR vs. PEG 3.48 2.35-5.15 <0.001 3.48 2.11-5.74 <0.001 All-cause FIL vs. PEG 1.55 1.26-1.90 <0.001 1.57 1.25-1.97 <0.001 SAR vs. PEG 2.22 1.56-3.15 <0.001 2.18 1.41-3.36 <0.001 * Adjusted for age, gender, region, plan type, tumor type, cycle number, previous neutropenia event, metastases, myelosuppresive regimen, comorbid conditions, and baseline health care utilization.
A phase II study of cisplatin plus S-1 in patients with carcinomas of unknown primary site.
Authors: T. Kurata, A. Tsuya, A. Tamiya, I. Okamoto, S. Ueda, N. Sugimoto, K. Matsumoto, I. Goto, M. Fukuoka, K. Nakagawa
Journal: Journal of Clinical Oncology (2011)

e13620 Background: Carcinomas of unknown primary site (CUP) represent a group of heterogeneous tumors and accounts for about 5% of all cancer patients (pts). The prognosis of CUP is generally poor with a median overall survival time (OS) of 4 to 6 months, and no standard chemotherapy has been established. S-1 is a new oral fluoropyrimidine and shows broad efficacy for many carcinomas. Therefore, we conducted a phase II study of novel combination chemotherapy using cisplatin (CDDP) plus S-1 in pts with CUP to evaluate the efficacy and safety. Methods: The treatment schedule included CDDP given intravenously on day 8, and S-1 given orally twice a day on days 1-21, every 5 weeks. The primary endpoint was objective response rate, and secondary endpoints included safety, OS, and 1-year survival rate. Results: A total of 46 chemotherapy naïve pts were enrolled. Median age of pts was 63 years (range 31-84). There were twenty-five male. Twenty-three pts had adenocarcinoma, fourteen had squamous cell carcinoma, three had poorly differentiated carcinoma, and three had poorly differentiated adenocarcinoma. Eighteen pts presented with nodal metastasis only, and twenty-two with nodal and multiple organ metastasis. The median number of courses was four. The overall response rate and the disease control rate were 41.3% and 80.4%, respectively. (CR/PR/SD/PD/NE; 2/17/18/7/2) The median progression-free survival time and the overall survival time were 7.5 months and 17.4 months, respectively. The most common grade 3 or worse adverse events were hematologic and non-hematologic toxicities were generally mild. Neutropenia, thrombocytopenia, and febrile neutropenia occurred in 28.3%, 13%, and 2.2%, respectively. Conclusions: This study demonstrates the activity of CDDP plus S-1 combination chemotherapy in patients with CUP. Updated response rate, safety data, and OS data will be presented.
Acupuncture for chemotherapy-induced fatigue: A randomized controlled trial.
Authors: G. E. Deng, Y. Chan, K. S. Yeung, A. J. Vickers, B. R. Cassileth
Journal: Journal of Clinical Oncology (2011)

9029 Background: Many cancer patients continue to experience chronic fatigue after the completion of chemotherapy even when no medical etiology can be identified. Currently there is no reliable treatment for chemotherapy induced chronic fatigue. In a previous single armed study, acupuncture appeared to reduce fatigue in this population of patients.The primary objective of this trial is to determine whether acupuncture reduces chronic fatigue after chemotherapy more effectively than placebo. Methods: A randomized sham-controlled trial comparing true acupuncture with sham acupuncture. Treatment regimen is once weekly for six weeks. Brief Fatigue Inventory (BFI), Hospital Anxiety and Depression Scale and Functional Assessment of Cancer Treatment Scale were evaluated before, during and after the treatment period. Results: A total of 97 patients received either true or sham acupuncture treatment. Seventy four patients (40 in the sham group and 34 in the acupuncture group) were evaluable for the primary endpoint. In both groups, BFI scores fell by about 1 point between baseline and follow-up, with no statistically significant differences between groups. The upper bound of the 95% confidence interval for acupuncture effect is 0.7 points. As such, we can rule out acupuncture having an effect much above placebo for the treatment of chronic post-chemotherapy fatigue. Conclusions: Acupuncture treatment regimen used in this trial does not reduce post-chemotherapy chronic fatigue more than sham acupuncture.
Prognostic factors for progression-free survival (PFS) in patients with metastatic renal cell carcinoma (mRCC): Results from the French randomized phase II study TORAVA.
Authors: B. J. Escudier, S. Negrier, D. Perol, G. Gravis, R. Delva, J. Bay, L. Geoffrois, E. Legouffe, S. Metzger, C. Ferlay
Journal: Journal of Clinical Oncology (2011)

e15118 Background: The aim of this work was to investigate factors predicting PFS of patients (pts) with mRCC, randomly assigned to: Temsirolimus + bevacizumab (T+B) combination, or sunitinib (S), or B + Interferon (B+I) combination. Methods: From 03/2008 to 05/2009, TORAVA trial included 171 pts. Demographic characteristics, clinical and blood parameters of the 88, 42 and 41 patients treated with T+B, S and B+I, respectively were tested in a univariate step. Variables statistically significant at 0.15 a-level were included in a multivariate Cox model. A backward stepwise procedure was used to identify independent prognostic factors for PFS. To validate the final multivariate models, a bootstrap resampling technique was used according to the two-step method of Chen and George, generalized by Sauerbei and Schumacher. One hundred bootstrap samples were created in the first step and 200 in the second. Results: For the whole cohort, the median PFS was 8.6 months (95% CI, 8.0 to 10.9). In univariate analysis, pretreatment features associated with a shorter PFS were: low Karnofsky performance status (< 80%), no prior nephrectomy, stage III/IV of Fürhman grade, time from diagnosis to treatment of less than 1 year, hemoglobin less than the lower limit of normal (LLN), neutrophils count greater than the upper limit of normal (ULN), platelets count greater than the ULN, and elevated serum LDH level (i.e. > 1.5 ULN). The first step of bootstrap allowed to keep only 3 parameters selected more than a half time over the 100 samples: the Fürhman grade, the LDH and hemoglobin levels. Multivariate analysis, followed by bootstrap validation, identified only two MSKCC factors with independent prognostic value for PFS: low hemoglobin (HR 2.04, 95% CI, 1.32-3.17, p < 0.01) and elevated LDH (HR 3.91, 95% CI, 1.84-8.32, p < 0.001). The results were not substantially modified after adjustment on the treatment. Conclusions: This analysis identified 2 risk criteria of the MSKCC model (low hemoglobin and elevated LDH levels) as prognostic factors for PFS in mRCC patients treated with targeted therapy.
Phase I study of the HSP90 inhibitor AUY922 in combination with capecitabine as treatment for patients with advanced solid tumors.
Authors: Shubham Pant, Lowell L. Hart, Johanna C. Bendell, Jeffrey R. Infante, Suzanne Fields Jones, Adil Mohyuddin, Patrick Murphy, Jeffrey Patton, William Charles Penley, Dana Shelton Thompson, Howard A. Burris
Journal: Journal of Clinical Oncology (2013)

3564 Background: Heat shock protein 90 (HSP90) is a molecular chaperone involved in the maintenance and function of client proteins, many of which are integral to key oncogenic processes. AUY922 is a competitive inhibitor of HSP90. Preclinical evidence suggests potential synergy between HSP90 inhibition and fluorouracil. This phase I study was designed to determine the maximum tolerated dose (MTD) of AUY922 in combination with standard dose of capecitabine as treatment for patients with advanced solid tumors. Methods: Pts with refractory solid tumors received AUY922 with capecitabine in a standard 3+3 dose escalation. Dose levels were capecitabine 1000mg/m 2 PO BID d 1-14 of 21-day cycles, with escalating doses of AUY922 IV days 1, 8, and 15; the 6th dose level combined the MTD of AUY922 with capecitabine 1250mg/m 2 . Dose-limiting toxicities (DLTs), safety, and efficacy were evaluated. Results: 23 pts were treated at 6 dose levels: 22mg/m 2 (n = 3); 28mg/m 2 (n = 3); 40mg/m 2 (n = 3); 55mg/m 2 (n = 5); 70mg/m 2 (n = 3); 70mg/m 2 with capecitabine 1250mg/m 2 (n= 6). No DLTs were observed until the 6th dose level (grade 3 diarrhea). Related adverse events (% grade 1/2; % grade 3/4) included: diarrhea (43%; 17%), fatigue (30%; 13%), nausea (39%; 0), hand-foot skin reaction (30%; 5%), anorexia (30%; 4%), vomiting (30%; 0), and darkening vision (26%; 0). Vision darkening, a class effect of HSP90 inhibitors, was reversible with drug hold and retreatment was possible. Two pts (9%) had hematologic G 3/4 events of neutropenia. Of the 19 pts evaluable for response, partial response was noted in 4 patients (colorectal, 2; breast, 1; stomach, 1); 2 had progressed on prior fluorouracil, and remained on treatment for 13-35 wks. Stable disease was noted in 8 pts (35% [colorectal, 5; pancreas, 2; breast, 1]) with a median duration of 25.5 wks (range: 11-44+). All 5 colorectal pts were refractory to 5-FU. Conclusions: The addition of AUY922 to standard dose capecitabine was well-tolerated at doses of up to 70mg/m 2 . Preliminary efficacy is encouraging, particularly as seen in pts previously resistant to fluorouracil, and warrants further investigation of this regimen. Clinical trial information: NCT01226732.
Management of thymic epithelial tumors (TETs) at the National Cancer Institute (NCI).
Authors: A. Rajan, R. J. Kelly, A. Lopez-Chavez, C. A. Carter, E. Szabo, B. Scepura, M. J. (. Manu, A. W. Berman, G. Giaccone
Journal: Journal of Clinical Oncology (2011)

e17511 Background: TETs are very rare anterior mediastinal tumors. Methods: We performed a retrospective review of patients (pts.) with TETs presenting to the NCI for enrollment in ongoing clinical trials, standard-of-care therapy or a second opinion. Results: Seventy-three pts. were seen between 12/2007 and 12/2010; 43 males (41%), median age at diagnosis: 48 years (range, 17 – 81). Fifty-four pts. were Caucasian (74%), 7 (10%) African-American, 8 (11%) Asian and 4 (6%) Hispanic. Histology: B1 5 (7%), B2 13 (18%), B2/B3 1 (1%), B3 9 (12%), thymic carcinoma (TC) 35 (48%), atypical carcinoid 2 (3%) and unclassified thymoma 8 (11%). Fifty pts. were enrolled in clinical trials: 28 on a phase II study of the HDAC inhibitor, belinostat (B), 27 on a phase II study of the IGF -1R inhibitor cixutumumab (C) (including 10 previously on B), 3 on a phase I study of chemotherapy (PAC) plus B and 2 on a phase II study of the cyclin-dependant kinase inhibitor PHA-848125AC. Median number of previous systemic therapy regimen that had been administered was 2 (range, 0-10). Forty-three pts. (59%) had extra-thoracic metastases; liver, bone and lymph nodes were the most common sites. Fourteen pts. (19%) had at least one autoimmune disease; myasthenia gravis (10%) was the most common. Three out of six pts. with TC with neuroendocrine features had Cushing’s syndrome. Eleven pts. (15%) had opportunistic infections including shingles (8%) and candidiasis (4%). Forty-eight pts. on clinical trials were evaluable for response: B: 2PR, 18SD, 8PD; C: 1PR, 16SD, 8PD; PAC-B: 1PR, 2SD; PHA: 2SD. Median survival for all pts. was 117 months (T – not reached; TC – 56 months). Among 28 pts. enrolled on B, the only clinical predictor of response and survival was presence of intra-thoracic disease only. Of 12 tumors (B1-1, B2-2, B3-1, C-7, atypical carcinoid-1) evaluated for overexpression of HER2 by IHC, none was positive. One patient with TC had a c-KIT mutation in exon 11. Conclusions: Histologic diagnosis of thymoma and the presence of intra-thoracic disease only predicts for longer survival in pts. with TETs. Targeted drugs can induce prolonged disease stabilization and few responses in heavily pretreated patients. Molecular profiling of tumors will be necessary in order to advance the field.
Treatment patterns and outcomes of acneiform skin eruptions from anti-epidermal growth factor receptor (EGFR) therapies for metastatic colorectal cancer (mCRC).
Authors: Bogdan Dascalu, Hagen F. Kennecke, Howard John Lim, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2012)

e19547 Background: Use of anti-EGFR therapies, such as cetuximab (Cmab) and panitumumab (Pmab), is associated with acneiform eruptions. Because research suggests a correlation between rash severity and outcomes in unselected patients, concerns remain that prophylactic treatment of rash may interfere with anti-tumor activities of these drugs. Our aims were to 1) characterize the treatment patterns for rash due to Cmab and Pmab and 2) evaluate if a prophylactic vs reactive approach to rash management modifies outcomes. Methods: All patients diagnosed with wild-type K-ras mCRC from July 2009 to June 2011 in British Columbia, Canada and prescribed either Cmab or Pmab were reviewed to describe patterns of prophylactic (before rash) and reactive (after rash) use of antibiotics and steroid creams. Using Cox regression, the relationship between rash management and overall survival was characterized. Results: In total, 119 patients were analyzed: median age at diagnosis was 63 years, 61% were men, 34% received Cmab and 66% Pmab, and median number of anti-EGFR treatment was 9 cycles. Rash occurred in over 90% of patients. Among them, reactive was favored over prophylactic treatment (66 vs 34%). Older patients (60+ years) and those with ECOG 0/1 were more likely to receive prophylactic creams (44 vs 20%, p=0.01) and antibiotics (62 vs 12%, p=0.01), respectively. There were no further differences in rash management based on other patient or tumor characteristics (all p&gt;0.05). Median OS was 7.0 months. The number of treatment cycles and overall survival were similar in both prophylactic and reactive groups (both p&gt;0.05). In Cox regression, ECOG 2+ correlated with worse survival than ECOG 0/1 (HR for death 5.25 95% CI 2.01- 9.23, p&lt;0.01). However, survival outcomes were statistically similar between patients prescribed antibiotics prophylactically vs. reactively (HR=1.10, 95% CI 0.43-2.80, p=0.85) and between patients given steroid creams prophylactically vs. reactively (HR=2.00, 95% CI 0.58-6.92, p=0.27). Conclusions: Prophylactic treatment of anti-EGFR related rash is associated with similar outcomes as compared to reactive rash treatment in mCRC patients.
The PEARL score predicts 90-day readmission or death after hospitalisation for acute exacerbation of COPD
Authors: C Echevarria, J Steer, K Heslop-Marshall, S C Stenton, P M Hickey, R Hughes, M Wijesinghe, R N Harrison, N Steen, A J Simpson, G J Gibson, S C Bourke
Journal: Thorax (2017)

<h3>Background</h3> One in three patients hospitalised due to acute exacerbation of COPD (AECOPD) is readmitted within 90 days. No tool has been developed specifically in this population to predict readmission or death. Clinicians are unable to identify patients at particular risk, yet resources to prevent readmission are allocated based on clinical judgement. <h3>Methods</h3> In participating hospitals, consecutive admissions of patients with AECOPD were identified by screening wards and reviewing coding records. A tool to predict 90-day readmission or death without readmission was developed in two hospitals (the derivation cohort) and validated in: (a) the same hospitals at a later timeframe (internal validation cohort) and (b) four further UK hospitals (external validation cohort). Performance was compared with ADO, BODEX, CODEX, DOSE and LACE scores. <h3>Results</h3> Of 2417 patients, 936 were readmitted or died within 90 days of discharge. The five independent variables in the final model were: Previous admissions, eMRCD score, Age, Right-sided heart failure and Left-sided heart failure (PEARL). The PEARL score was consistently discriminative and accurate with a c-statistic of 0.73, 0.68 and 0.70 in the derivation, internal validation and external validation cohorts. Higher PEARL scores were associated with a shorter time to readmission. <h3>Conclusions</h3> The PEARL score is a simple tool that can effectively stratify patients9 risk of 90-day readmission or death, which could help guide readmission avoidance strategies within the clinical and research setting. It is superior to other scores that have been used in this population. <h3>Trial registration number</h3> UKCRN ID 14214.
A phase II study of the combination of endocrine treatment and bortezomib in patients with endocrine-resistant metastatic breast cancer.
Authors: X. B. Trinh, L. Sas, S. J. Van Laere, A. Prove, I. Deleu, M. A. Rasschaert, H. Van De Velde, P. Vinken, P. B. Vermeulen, P. A. van Dam, A. Wojtasik, P. De Mesmaeker, W. A. Tjalma, L. Y. Dirix
Journal: Journal of Clinical Oncology (2011)

e11072 Background: The majority of patients with hormone receptor-positive metastatic breast cancer die from disease progression despite different types of anti-hormonal treatments. Preclinical studies have indicated that resistance to anti-hormonal therapies may be the result of an activated NF-κB signalling pathway in breast cancer. Bortezomib is a proteasome inhibitor that blocks the NF-κB pathway. Recent pharmacodynamic and pharmacokinetic xenograft studies have shown that drug exposure may be a crucial factor for the efficacy of bortezomib in solid tumours. Methods: The aim was to investigate whether the addition of bortezomib to anti-hormonal therapy would result in antitumour activity in patients with both progressive and measurable disease on the identical endocrine agent. Clinical benefit was defined as patients obtaining SD, PR or CR after 2 cycles, lasting for at least another five weeks. Bortezomib was administered on days 1, 8, 15, 22 of a 5 week regimen (1.6 mg/sqm). Results: Eight patients received an aromatase inhibitor and bortezomib, while one received tamoxifen and bortezomib. There were 3 grade III gastro-intestinal toxicities. Median time to treatment failure was 69 days [35-140]. Two out of the 9 patients had stable disease for more than 10 weeks. Despite an effective target inhibition, suggested in peripheral blood mononuclear cells and available tumour samples, no objective antitumour responses were observed. Conclusions: Addition of a proteasome inhibitor to anti-hormonal therapy resulted in a clinical benefit rate of 22% in a limited number of patients with endocrine resistant and progressive metastatic breast cancer. The demonstrated proteasome inhibition in tumour tissue provides evidence that the lack of clinical responses is not attributed to deficient drug exposure. Eudract-N°2006-004144-23.