tbuckley/cabot-search huggingface dataset:
Evaluation of the MPM2 score versus clinical predictions of mortality in a tertiary cancer center.
Authors: Alison Wiesenthal, Vinnidhy Dave, Howard T. Thaler, Paul A. Glare
Journal: Journal of Clinical Oncology (2015)

9547 Background: Prognostication is an essential yet challenging clinical skill for oncologists, even as patients approach death. Goals-of-care discussions may be improved by giving patients and families objective reference for likelihood of mortality, but tools are needed to assist clinicians in identifying which patients are at the highest risk of dying in hospital. The aim of this study was to evaluate the transferability of the ICU-derived Mortality Probability Models Version 2 (MPM2) score to the general wards at a comprehensive cancer center, and to compare it to clinical predictions of dying in hospital (CPDH). Methods: Prospective case series of inpatients receiving palliative medicine consultations over a 3 month period. Prior to calculating MPM2 score, the CPDH was estimated in categories: unlikely (<10%), less likely (25%), possible (50%), probable (75%), consistent with (>90%). Overall survival was determined 6 months after end of enrollment. Calibration of MPM2 in these patients was evaluated by logistic regression. For survival analysis, MPM2 scores were grouped as <10%, 10-50%, >50%. Results: Of 79 patients consecutively evaluated, 18 (22%) died in hospital. Another 41 (52%) died after discharge. MPM2 score and CPDH were each significantly predictive of dying in hospital (p<0.001). Agreement between CPDH categories and corresponding MPM2 categories was fair (weighted kappa 0.37), CPDH being more pessimistic overall and avoiding use of the middle category (see Table). Overall survival was significantly different between the three MPM2 groups (median 131.5, 36 and 6 days respectively; log rank test df 2, χ2=42.6 , p<0.001). Conclusions: The MPM2 score shows promise as a clinical tool for determining in-hospital mortality outside of the ICU. It was most helpful for identifying and correctly classifying patients with intermediate likelihoods of surviving. Larger studies in this and other settings are needed. CPDH category n Died in hospital n (%) Categorized MPM2 score n Died in hospital n (%) Unlikely 36 3 (8) 0-10% 49 6 (12) Less likely 20 1 (5) 10.1-25% 13 2 (15) Possible 0 -- 25.1-74.9% 11 5 (45) Probable 15 7 (47) 75-90% 3 3 (100) Consistent with 8 7 (88) >90% 3 2 (67)
A phase II clinical trial on combined axitinib and transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC): Final results and evaluation of clinical predictor for response.
Authors: Stephen Lam Chan, Winnie Yeo, Frankie Mo, Leung Li, Kit Fai Lee, Anthony WH Chan, Edwin Pun Hui, Paul B. S. Lai, Tony Mok, Anthony T. C. Chan, Simon Yu
Journal: Journal of Clinical Oncology (2015)

4073 Background: Axitinib is a potent and specific inhibitor of VEGFRs. Elevation of VEGF level in plasma and tumor is frequently observed after TACE treatment for HCC. We hypothesize that combining axitinib and TACE has synergism by inhibiting the VEGF surge after TACE. We conducted a phase II clinical trial to study the combination for treatment of inoperable HCC. Methods: This is an investigator-initiated, single-arm, phase II study. Key eligibility criteria include: diagnosis of inoperable HCC; Child’s A function; without main portal vein thrombosis/distant metastases. Patients (pts) were started axitinib 5mg bid followed by TACE at 5thweek. Assessment of further TACE is conducted every 2 months (m). TACE is given if there is viable HCC and pts are suitable for TACE. Axitinib is withheld 24 hours before and resumed 24 hours after TACE. CT Imaging is arranged every 8 weeks (mRECIST). The primary endpoint is 2-year survival rate. Secondary endpoints include determination of response, toxicity and clinical predictors of outcome. The sample size is 50. Results: From May 11 to Apr 14, 50 pts have been recruited. Data cut-off date was 31 Dec 14. The median follow-up is 21.6m. Median age: 61.8 years; median tumor diameter: 6.8cm. BCLC Stage B/C: 38/12. Median cycle of TACE given is 2. The median OS is 15.9m (95% CI 13.7-31.9m) with 2-year OS rate of 41.9%. The median time-to-progression is 10.4m. Amongst 45 evaluable pts, 30 (68.2%) have partial or complete response. Total 6 pts underwent surgical resection after downstaging of HCC with 5 of the specimens showing complete tumor necrosis. Common ≥ grade 3 toxicities include: ALT elevation (40%), hypertension (24%) and hand-foot skin reaction (12%). The median dose density of axitinib is 90.6%. Development of hypertension (any grade) during the treatment course is associated with better OS (25.0 vs. 13.7m; p = 0.03). Conclusions: The combination of axitinib and TACE is efficacious with high response rate. The regimen is well tolerated without significant safety concern. Selected pts could be converted to operable state after downstaging. Further clinical development is indicated. (NCT01352728) Clinical trial information: NCT01352728.
Evaluation of thymidylate synthase and ERCC1 mRNA levels as predictive markers in colorectal cancer patients treated with S-1 and oxaliplatin
Authors: H. Kuramochi, K. Hayashi, G. Nakajima, H. Kamikozuru, M. Yamamoto
Journal: Journal of Clinical Oncology (2009)

e15071 Background: Oxaliplatin has been widely used for the treatment of colorectal cancer. The mechanism of action of platinum compounds such as oxaliplatin is to bind to a DNA molecule in the form of a platinum-DNA-adduct. Excision repair cross complementation group 1 (ERCC1), which plays a major role in the nucleotide excision pathway, has a polymorphism in codon 118, and is reported to be associated with a resistance to platinum-based therapy. Thymidylate synthase (TS) and dehydropyrimidine dehydrogenase (DPD) are key enzymes of 5-FU metabolism and are well known to be associated with a response to 5-FU-based therapy. Methods: Twenty-one colorectal cancer patients (male:female = 7:14; median age, 65) treated with a combination of oxaliplatin and S-1 as a first-line therapy were analyzed for ERCC1 codon 118 polymorphism and the mRNA expression levels of TS, ERCC1, and DPD. Formalin-fixed paraffin- embedded surgical specimens were used and t-RNA and DNA were extracted. The mRNA expression levels were measured using real-time RT-PCR, and the polymorphism was analyzed using the allelic discrimination method together with real-time PCR. Results: No correlation was observed between ERCC1 codon118 polymorphism and any response to the chemotherapy. ERCC1 mRNA levels tended to be higher in the patients with wild-type homozygous alleles in codon 118 than in those with at least one mutant allele(1.19 vs.0.68: p= 0.15). Patients with both high TS and ERCC1 mRNA levels showed a significantly lower response rate than the others (25% vs. 67%, p=0.02). No relationship was seen between DPD mRNA expression levels and the response. Conclusions: The mRNA expression levels of TS and ERCC1 appear to be useful markers for the treatment of S-1 and oxaliplatin. No particular usefulness of ERCC1 codon 118 polymorphism was verified. No significant financial relationships to disclose.
Pulmonary function in adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort Study (SJLIFE).
Authors: Daniel M. Green, Liang Zhu, Matthew J. Krasin, Saumini Srinivasan, Dennis C Stokes, Deo Kumar Srivastava, Kirsten K. Ness, Beth McCarville, Daniel A. Mulrooney, Gregory T. Armstrong, Ching-Hon Pui, Sheri L. Spunt, Monika Metzger, Fariba Navid, Andrew M. Davidoff, Bhaskar N. Rao, Leslie L. Robison, Melissa M. Hudson
Journal: Journal of Clinical Oncology (2015)

10018 Background: The relationship between treatment exposures and long-term pulmonary function of childhood cancer survivors (CCS) treated with pulmonary toxic therapies has not been well studied. Methods: 606 of 989 SJLIFE CCS treated with pulmonary toxic therapy underwent assessment of forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), single breath diffusion capacity for carbon monoxide corrected for hemoglobin (DLCOcorr) and total lung capacity (TLC) according to American Thoracic Society standards. Results were expressed as percent of race-, age-, and sex predicted values. Lung radiation dose was estimated using the patients’ actual treatment ports and a CT dosimetry phantom. Associations were assessed using logistic regression. Variables significant at p < 0.1 on univariate analysis were entered into the multivariable models. Results: Median age at evaluation was 34.2 years [interquartile range (IQR), 28.7 to 40.1] and median time from diagnosis 21.9 years (IQR 16.6 to 27.8). Among survivors, 50.7% had FEV1 < 80% of predicted, 47.2% FVC < 80%, 31.2% TLC < 75%, and 44.6% DLCOcorr < 75%. Only 0.8% of survivors had obstructive (FEV1/FVC < 0.7), but 31.2% had restrictive (TLC < 75%) lung defects. Risk factors are shown in the Table. Conclusions: These risk factors identified CCS who may benefit from interventions to improve pulmonary function. Risk factor Odds Ratio (95% Confidence Interval) DLCO corr < 75% predicted FEV1 < 80% predicted TLC < 75% predicted Age at diagnosis (years) 5 – 9 0.81 (0.44, 1.50) 0.41 (0.21, 0.81) 0.71 (0.38, 1.35) 10 – 14 0.55 (0.31, 1.00) 0.53 (0.28, 0.99) 0.32 (0.17, 0.60) 15 – 22 0.39 (0.21, 0.71) 0.38 (0.20, 0.72) 0.25 (0.13, 0.47) Elapsed time after diagnosis 1.04 (1.01, 1.06) 1.08 (1.05, 1.11) 1.08 (1.05, 1.11) Lobectomy, metastectomy, wedge resection * 2.18 (1.30, 3.63) 2.35 (1.36, 4.05) Other chest surgery * 4.95 (1.30, 18.92) * Current smoker * * 0.56 (0.34, 0.93) Bleomycin (per 40 mg/m2) 0.93 (0.75, 1.16) * 0.93 (0.72, 1.20) Cyclophosphamide (per 1000 mg/m2) 1.04 (1.01, 1.08) 1.03 (0.99, 1.07) 1.02 (0.98, 1.06) V10 (per 10% increase) 1.14 (1.08, 1.21) 1.18 (1.11, 1.25) 1.19 (1.11, 1.27) *-Did not satisfy criterion for inclusion in multivariable model.
Effect of nanosomal docetaxel lipid suspension (NDLS) on response rate compared to docetaxel: A randomized phase II study in patients with locally advanced or metastatic breast cancer.
Authors: Ateeq Ahmad, Saifuddin Sheikh, Rakesh Taran, Shanti P Srivastav, Krishna Prasad, Senthill J Rajappa, Vijay Kumar, Gopichand M, Mahesh Paithankar, Manish Sharma, R. C. Rane, Imran Ahmad
Journal: Journal of Clinical Oncology (2013)

577 Background: Docetaxel formulated inpolysorbate 80 and ethanol (Docetaxel) is among the most active agents in the treatment of breast cancer. The primary rationale for developing nanosomal docetaxel lipid suspension (NDLS) is to improve the drug’s safety profile by eliminating polysorbate 80 and ethanol from docetaxel formulation. Previously, we conducted a clinical study comparing pharmacokinetic parameters of NDLS and docetaxel at 75 mg/m 2 . The log transformed NDLS/docetaxel ratio for C max and AUC 0-t was 149.3% and 119.3% respectively. The higher systemic availability of NDLS prompted us to conduct current efficacy study. Methods: 72 locally advanced or metastatic breast cancer patients were enrolled into the study after failure of prior chemotherapy. The mean age for the enrolled patients was 47 years and the racial make-up of the study was 100% Asian. Patients were administered NDLS or docetaxel at 75 mg/m 2 as per randomization schedule, by IV infusion for one hour in each cycle of 21 days. Each patient received maximum of 6 cycles of NDLS or docetaxel. No premedication was given to the patients in NDLS treatment group. Results: Safety - The total number of post-dose AEs observed in the study was 510. The breakdown by treatment groups is as follows: AEs were reported in 91.30% and 93.88% patients who received the docetaxel and NDLS respectively. There were 34 SAEs in the study, out of which 04 SAEs resulted in death of the patients (3 in docetaxel and 1 in NDLS). Efficacy - The results showed that 4.2% patients had complete response (CR) in NDLS treatment group while there was no CR in docetaxel treatment group. Further, 31.3% partial response rate (PR) was observed in NDLS treatment group and 26.3% in docetaxel treatment group. Overall response (CR+PR) rate was 35.4% in NDLS treatment group and 26.3% in docetaxel treatment group. Stable disease (SD) was observed in 45.8% patients in NDLS group and 63.2% patients in docetaxel group. Conclusions: Overall, the NDLS was well tolerated in the multiple doses of 75 mg/m 2 and found to increase response rate compared to docetaxel in breast cancer patients. Clinical trial information: CTRI/2010/091/000610.
An open-label, single-group, multicenter phase II study of lanreotide autogel (LAN) in Japanese patients (pts) with neuroendocrine tumors (NET).
Authors: Tetsuhide Ito, Seiichi Hisamatsu, Akihiro Nakajima, Akira Shimatsu
Journal: Journal of Clinical Oncology (2017)

471 Background: LAN is a long-acting somatostatin analog indicated in EU for the treatment of carcinoid syndrome and in the US and EU as antiproliferative treatment in pts with gastroenteropancreatic (GEP) -NET. The antitumor efficacy of LAN in pts with GEP-NET was evaluated in the phase III CLARINET study. No study to date has reported the antitumor effects of somatostatin analog in Japanese pts with NET. Methods: In this open-label, single-arm study, Japanese pts with Grade 1 or 2 unresectable metastatic or locally advanced NET received 120 mg once every 4 weeks for 48 weeks. Pts who completed the study were subsequently enrolled in the long-term extension study. The primary endpoint was the clinical benefit rate (CBR: the ratio of pts with a complete response, a partial response (PR), or stable disease over 24 weeks). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR) (RECIST 1.1, central review), serum chromogranin A (CgA) level and quality of life using the EORTC QLQ-C30. The results of the CLARINET study cohort were compared with those from a matched population. Results: 32 pts were recruited in 10 sites. Mean age was 61.7 years. 67.9% were male. The primary tumor sites were pancreas (n = 14), foregut (2), midgut (2), hindgut (8), and unknown (6). Four pts had gastrinoma, and 3 of them had multiple endocrine neoplasia type 1. In the Full Analysis Set (n = 28), 39.3% of pts had progressive disease at baseline according to RECIST criteria. The CBR at 24 weeks was 64.3% (18 of 28 pts) and the median PFS was 36.3 weeks. A PR was confirmed in 1 patient during the 60 weeks of the extension study (ORR: 3.6%). For PFS, the subgroup analysis showed that the results of pts with no progressive disease at baseline or prior treatments for NET were similar to the results of pts in the CLARINET study. LAN decreased serum CgA by at least 50% in 15 of 17 pts (88.2%) who had elevated CgA levels at baseline. Frequent adverse reactions included injection site induration (28.1%), pale stools (18.8%), flatulence (12.5%), and diabetes (12.5%). Conclusions: The efficacy and safety of LAN in this study clearly show that LAN will be a useful treatment option for Japanese pts with NET. Clinical trial information: 132375,142698.
Diagnostic and prognostic significance of circulating endothelial cell in advanced non-small cell lung cancer.
Authors: Dongmei Yuan, Yanling Lv, Xingqun Ma, Hongbing Liu, Yi Shi, Yong Song
Journal: Journal of Clinical Oncology (2012)

e18116 Background: The aim of this study was to evaluate the diagnostic and prognostic value of circulating endothelial cells (CECs) during first-line therapy in patients with advanced non-small cell lung cancer (NSCLC). Methods: 102 newly diagnosed advanced NSCLC patients were enrolled in this study. The amount of CECs (CD45- CD31+ CD146+) was enumerated by flow cytometry at baseline and after two cycles of treatment. We correlated CEC counts and the reduction of CECs with objective response rate (ORR) and progression-free survival (PFS). Results: The CECs level was significantly higher in advanced NSCLC patients, ranging from 57 to 1300 cells/10 5 cells (n=102, mean±SD=299±221 cells/10 5 cells), than patients with benign lesions (n=35, 205±97 cells/10 5 cells), and healthy volunteers (n=34, 117±33 cells/10 5 cells). When the cut off value of CEC counts was 210 cells/10 5 cells, there was no significant association between CEC counts and OR/PFS of the enrolled patients. However, patients with CECs response after chemotherapy has more chances to achieve OR (P&lt;0.001), and such patients showed longer PFS than those without CECs response (P = 0.041). In the multivariate analysis, the independent prognostic roles of performance status (HR: 3.245, 95% CI: 1.189-8.854), brain metastasis (HR: 3.673, 95% CI: 1.062-12.704), and CECs response (HR: 0.046, 95% CI: 0.188-0.984) were found. Conclusions: The CEC counts could be considered as the diagnostic biomarker for advanced NSCLC patients. And the reduction of CECs after treatment might be more ideal than the CEC counts as a predictive or prognostic factor in patients treated with platinum-based chemotherapy.
Phase II study of volociximab (M200), an α5β1 anti-integrin antibody in refractory metastatic clear cell renal cell cancer (RCC)
Authors: R. A. Figlin, G. V. Kondagunta, S. Yazji, R. J. Motzer, R. M. Bukowski
Journal: Journal of Clinical Oncology (2006)

4535 Background: Blocking angiogenesis has been shown to be an effective strategy for controlling tumor growth in RCC. Tumor angiogenesis occurs when pro-angiogenic growth factors are released, stimulating endothelial cell proliferation and migration to form neovessels. M200 is an IgG4 chimeric monoclonal antibody that targets α5β1, thereby inducing apoptosis of proliferating endothelial cells. M200 activity is independent of growth factor stimulus, suggesting that binding of fibronectin to α5β1 occurs downstream of growth factor signalling, and is possibly a final common pathway for the development of neovasculature. Methods: This is a multicenter, open label, single cohort pilot phase II study of 40 patients (pts) with RCC. Pts received no more than 2 prior regimens. Pts received M200 10 mg/kg IV every 2 weeks until disease progression. Pts were evaluated for efficacy every 8 weeks by objective response using RECIST criteria. An independent data safety monitoring board was utilized to review safety data. Results: A total of 40 pts were enrolled. All pts were evaluable for safety and 37 pts for objective response (to date). Median age was 62.8 years. ECOG score was 0 in 27 (67.5%) and 1 in 13 (32.5%) pts. Prior nephrectomy occured in 39 (97%) pts. Other prior treatment included IL-2 in 15 (37.5%), interferon alpha in 6 (15%), IL-2 + interferon in 2 (5%) pts. Most frequent side effects were fatigue 37.5%, nausea 15% and hypertension 7.5%. Five pts died in the study, four with progressive disease (PD) and 1 with arrhythmia (unrelated to M200). SD was observed in 32/37 (87%) of pts. No changes in hematological, renal and hepatic parameters were noted. Median time to progression was 113+ days. The average peak and trough concentrations of circulating M200 following 6 weeks of treatment were 390 μg/mL and 140 μg/mL, respectively. There were no detectable immune responses to M200. Conclusions: M200 is well tolerated at 10 mg/kg Q2W. Stable disease is noted in 87% of pts. Follow-up continues. A higher dose level is being evaluated. [Table: see text]
Future considerations for clinical dermatology in the setting of 21st century American policy reform: The Medicare Access and Children's Health Insurance Program Reauthorization Act and Alternative Payment Models in dermatology
Authors: John S. Barbieri, Jeffrey J. Miller, Harrison P. Nguyen, Howard P. Forman, Jean L. Bolognia, Marta J. VanBeek
Journal: Journal of the American Academy of Dermatology (2017)
Pre-treatment PSA- progression as a negative prognostic factor in patients using 5-alpha-reductase inhibitors prior to radiotherapy for prostate cancer.
Authors: Daniel Taussky, Julie Piotte, Kevin Zorn, Marc Zanaty, Vimal Krishnan, Jean-Paul Bahary, Marie-Claude Beauchemin, Maroie Barkati, Cynthia Menard, Guila Delouya, Carole Lambert
Journal: Journal of Clinical Oncology (2017)

96 Background: To investigate the impact of 5-alpha-reductase inhibitors (5-ARIs) usage on radiotherapy outcomes for localized prostate cancer. Methods: From our institutional database of over 2500 patients, we identified 203 patients on a 5-ARI. They were all treated with either external beam radiotherapy (EBRT) or brachytherapy for localized prostate cancer. Patients receiving a 5-ARI were analyzed according to the following prostate cancer progression criteria: a) progression of Gleason score or increase in cancer volume on the biopsy, b) first biopsy positive for cancer after being treated for urinary symptoms with a 5-ARI, and c) prostate-specific antigen (PSA) progression with or without a previous cancer diagnosis. Biochemical failure (BF) was defined by the Phoenix definition. Log-rank test was used for survival analysis. Results: At a median follow-up of 36 months (interquartile range [IQR] 22-52 months), 10 (4.9%) patients experienced BF. 52% of men demonstrated none of the progression criteria, 37% showed only one prostate cancer progression criteria and 11% showed two. Using a univariate analysis, PSA progression (p = 0.004) and appearance of a positive biopsy (p &lt; 0.001) but not Gleason progression (p = 0.3) were a significant predictive factor of BF. With separate multivariate analysis adjusted for the CAPRA score (HR 1.7, 95% CI 1.2-2.3, p = 0.003), a rising PSA (HR 5.7, 95% CI 1.1-28.8, p = 0.04) and the number of cancer progression factors (HR 2.9, 95%CI 1.2-7.0, p = 0.02) remained adverse risk factors. Both Gleason score progression (p = 0.4) and first biopsy positive for cancer (p = 0.13) failed to remain significant. Age and obesity were not significant factors in univariate or multivariate analysis. Conclusions: A PSA progression experienced while under 5-ARI treatment before EBRT or brachytherapy is predictive of worse biochemical outcome. Such details should be considered when counseling men prior to radiation therapy.
Overall and cancer-specific survival of breast, colon, and lung cancer in patients with and without chronic lymphocytic leukemia: A SEER population-based study of over 1 million patients.
Authors: Benjamin Maurice Solomon, Kari G. Rabe, Susan L Slager, Jerry D Brewer, James R. Cerhan, Tait D. Shanafelt
Journal: Journal of Clinical Oncology (2012)

6571 Background: Chronic lymphocytic leukemia (CLL) is associated with an increased risk of developing second cancers. However, it is unknown whether CLL alters the natural history of these cancers once they occur. Methods: All patients with breast (n=583,838), colon (n=412,932), prostate (n=632,922), lung (n=489,290), kidney (n=95,902), pancreas (n=82,121) and ovarian (n=61,958) cancer reported to the Surveillance, Epidemiology, and End Results (SEER) Program from 1990 to 2007 were identified. Overall survival (OS; death due to any cause) and cancer-specific survival (death due to cancer site of interest) were examined, comparing patients with or without pre-existing CLL. Age- and sex-adjusted hazard ratios (HRs) were calculated. Results: OS for patients with pre-existing CLL was inferior for patients with breast (HR=1.61; p&lt;0.001), colon (HR=1.65; p&lt;0.001), kidney (HR=1.41; p&lt;0.001), prostate (HR=1.75; p&lt;0.001), and lung (HR=1.22; p&lt;0.001) cancer after adjusting for age and sex. After excluding CLL-related deaths, OS remained shorter among patients with breast (p&lt;0.001), colon (p&lt;0.001), kidney (p=0.03), prostate (p&lt;0.001), and lung (p&lt;0.001) cancer. Cancer-specific survival was inferior for patients with breast (HR=1.29; p=0.03), colon (HR=1.75; p&lt;0.001), and lung cancer (HR=1.17; p&lt;0.001) who had pre-existing CLL after adjusting for age and sex. Conclusions: Several common cancers, including breast, colon, and lung, have inferior overall and cancer-specific survival when there is coexistent CLL. [Table: see text]