tbuckley/cabot-search huggingface dataset:
Long-term response to sunitinib treatment in metastatic renal cell carcinoma (mRCC).
Authors: Nizar M. Tannir, Robert A. Figlin, Martin Eric Gore, Dror Michaelson, Robert J. Motzer, Camillo Porta, Brian I. Rini, Caroline J. Hoang, Xun Lin, Bernard Escudier
Journal: Journal of Clinical Oncology (2016)

598 Background: A subset of patients (pts) with mRCC treated with sunitinib achieves a long-term response. This study aimed to characterize the duration of treatment and clinical outcomes of pts with mRCC who were long-term responders (LTRs), defined as pts who had progression-free survival (PFS) &gt; 2 years, while on sunitinib therapy. Methods: A retrospective analysis of data from 5714 pts with mRCC treated with sunitinib in 8 phase II or III clinical trials and pts treated in the expanded access program (EAP). Data on treatment duration and response to treatment were compared between LTRs and pts who had PFS ≤ 2 years (others). Results: A total of 529 (9.3%) pts achieved a long-term response, 5162 (90.3%) achieved other response, and data were missing for 23 (0.4%) pts. Overall, 309 (5.4%) pts achieved PFS between &gt;2 and ≤3 years, 125 (2.2%) pts achieved PFS between &gt;3 and ≤4 years, 62 (1.1%) pts achieved PFS between &gt;4 and ≤5 years, and 33 (0.6%) pts achieved PFS between &gt;5 and ≤6 years. The median (range) duration of sunitinib treatment was 36.7 (23.4–71.7) months for LTRs versus 6.5 (0–69.8) months for others. Response rates comparing LTRs versus others are presented in Table. Conclusions: With over 500 pts with mRCC achieving PFS &gt;2 years and 33 achieving PFS &gt;5 years, this analysis of sunitinib LTRs is the largest published to date. Additional analyses are being conducted to describe the clinical characteristics of these LTRs and identify risk factors that may predict long-term response. [Table: see text]
Phase III study of addition of docetaxel (D) to hormonal therapy (HT) versus HT alone in nonmetastatic high-risk prostate cancer (PC) patients (pts): Final results on PSA progression-free survival
Authors: S. Oudard, I. Latorzeff, P. Beuzeboc, E. Banu, A. Caty, E. Sevin, R. Delva, F. Rolland, F. Priou, R. Elaidi, S. Culine
Journal: Journal of Clinical Oncology (2011)

4523 Background: Around 75% of nonmetastatic high risk PC pts undergo PSA recurrence within 2 years after local therapy. Activity of D in addition to HT was investigated in this population. Methods: A multicenter, randomized phase III study was designed to compare A: HT+D (70 mg/m2 Q3W, 6 cycles) and B: HT (triptorelin, every 3 months (m) for 1 year in non-metastatic PC pts at high-risk of recurrence after radical prostatectomy (RP) and/or radiotherapy (RT). Stratification factors (SF): RP vs RT and PSA-DT < or > 6m. Inclusion criteria were at least 1 of: Gleason > 8, PSA-DT < 6m, positive surgical margins, PSA velocity > 0.75ng/mL/year, pathological pelvic lymph nodes, time from RP/RT to inclusion < 12m. Within 90 days before inclusion, at least 3 consecutive progressive PSA > 0.2ng/mL (RP) or > 1ng/mL (RT). Primary endpoint was PSA PFS; secondary endpoints were PSA response, time to metastasis, overall survival, QoL and safety (NCI-CTC 2.0). Progression definition: not-responding pts, 25% PSA increase above baseline; responding pts, PSA increase > 25% above nadir (3 values) above 0.1ng/mL with absolute increase (AI); no definition of AI is available for PSA progression in this setting, therefore AI was incremented from 0.2 to 2.0ng/mL by 0.1 step. We also investigated a definition with 50% PSA increase. Multivariate analysis: Cox regression model adjusted on SF. Results: Included =254, ITT=251. Arm A (125) vs B (126): median age(y) 64 vs 66, time(m) initial diagnosis to inclusion 35 vs 34, ECOG=0 96% vs 93%, Gleason score (%) > 8 32 vs 27, RP (%) 69.6 vs 71.4, RT (%) 37.6 vs 38.1, PSA-DT (%) < 6m 53.6 vs 53.2, respectively. PSA response (%pts) in A vs B was: CR=74 vs 64, PR=21 vs 32, SD=4 vs 3. Toxicity was reported at ASCO 2010 (Abstract 4685). Upon variation of AI, Hazard Ratio A vs B spread between 0.74 and 0.91 (p<0.05 for AI=0.8-0.9ng/mL). Therefore, whatever the AI, a risk reduction was observed in arm A vs B. Results were identical at 25% or 50% increase above nadir. Conclusions: Addition of docetaxel to hormonotherapy at an early stage in nonmetastatic high-risk PC patients reduces risk of PSA relapse by 9-26%. Clinical PFS monitoring is ongoing.
Quality improvement research in oncology: A bibliometric analysis.
Authors: Samir Mohamed Haq, Knox H. Todd
Journal: Journal of Clinical Oncology (2012)

159 Background: As part of the Affordable Care Act of 2010, the U.S. government has established a “National Strategy for Quality Improvement in Health Care,” with the goal of implementing evidence-based research into practice. The quantity of oncology research devoted to quality improvement is uncertain. We use the percentage of quality improvement articles in the oncology literature as a proxy metric to gauge the importance given to quality improvement in oncology. Methods: A MEDLINE literature search was performed on July 14, 2012. We approximated the number of articles published in the field of oncology using a PubMed search with the MeSH (Medical Subject Headings) term “neoplasm” or keywords “neoplasm,” “cancer,” or “oncology.” Results were limited to English language and publication dates between July 2010 and June 2012. From this data, the number of articles concerning quality improvement was approximated using the MeSH term “quality improvement” or keywords “quality improvement.” Results: Of approximately 246,000 English language, oncology-related articles published in the last two years, 314 focused on “quality improvement.” The topic of quality improvement comprised only 0.1% of the oncology literature over this period. Conclusions: Using bibliometric analysis, it appears that research on quality improvement in oncology is infrequent. Quality improvement research has been found effective in other fields and requires increased emphasis by the oncology research community. To improve the quality of care in oncology, evidence-based research in the field of quality improvement should increase.
Implementation of clinical practice guidelines in a multicenter radiation oncology department.
Authors: Sewit Teckie, Lucille Lee, Henry Chou, Petrina Zuvic, Louis Potters
Journal: Journal of Clinical Oncology (2014)

117 Background: Recent reports suggest that less than 20% of cancer care is based upon level I evidence. As a result, the majority of cancer care tends to be ad-hoc. Furthermore, deviations from established standards-of-care are associated with worse clinical outcomes. Systematic and evidence-based approaches to cancer care are widely regarded as an effective way of improving quality and value in oncology, yet their implementation remains broadly circumspect. In our multicenter radiation medicine department, we developed clinical practice guidelines (CPGs) that encourage consistent care in order to minimize variations in patient treatment, outcome, and experience. We hypothesized that CPGs would also improve efficiency, performance, and cost. Methods: We developed a system for prioritizing value in radiation oncology (Smarter Radiation Oncology) comprising three pillars – quality, evidence-based care, and patient experience. We created 87 unique, evidence-based and consensus-driven electronic CPGs that apply to the majority of patients undergoing radiation therapy in our department. Each CPG delineates an evidence-based treatment approach for a specific cancer site and stage, as well as many technical components such as simulation, treatment planning, quality assurance, clinical care requirements and survivorship. Results: Overall compliance to CPGs was &gt;88%. Six-sigma Z-scores indicated improvement in efficiency and compliance. Treatment delays decreased and patients reported more favorable ratings on a variety of measures, including likelihood to recommend, wait times, understanding of treatment, and physician sensitivity. For breast and prostate cancer, adherence to CPG treatment resulted in 20% and 15% average lower costs than standard, non-CPG treatment. Conclusions: We demonstrate that consensus- and evidence-based CPGs can be successfully implemented in a multicenter department, with high adherence rates. CPGs improve safety and reduce costs by minimizing variation and deviations from standards-of-care. In an era of rising cancer spending, CPGs can be expanded beyond radiation oncology to the entire oncologic care process, thereby improving value for all cancer patients.
Prognostic values of microRNAs in phase III clinical trial gastric cancer patients treated with S-1/oxaliplatin or doxifluridine/oxaliplatin.
Authors: J. Jiang, C. Wu, X. Zheng, Q. Zhou, X. Zhang, X. Xu, B. Lu, J. Ju
Journal: Journal of Clinical Oncology (2011)

4073 Background: Translational control mediated by microRNAs plays a key role in chemoresistance. The goal of this study is to evaluate the effectiveness of S-1/oxaliplatin (28 patients) vs. doxifluridine/oxaliplatin (27 patients) regimen and to identify miRNAs as potential prognostic biomarkers from archival FFPE clinical samples of phase III clinical trial patients. In this study, the expression of candidate miRNAs (e.g. let-7g, miR-200c, miR-140, miR-21, miR-192, miR-181b) was quantified from stage III and IV gastric cancer FFPE specimens with clinical follow up information. Methods: Gastric cancer patients with KPS > 70 were recruited for the phase III trial. Control group was treated with 400 mg/twice/day doxifluridine plus iv. with Oxaliplatin at 130 mg/m2/first day/4 week cycle. Testing group was treated with S-1 at 40 mg/twice/day/4 week cycle plus iv. with oxaliplatin at 130 mg/m2/first day/4 week cycle. Total RNAs were extracted from normal and gastric FFPE tumor specimens using Trizol based approach. The levels of miRNAs were quantified using real time qRT-PCR expression analysis. Results: The overall objective response rate (CR+PR) of patients treated with S-1/oxaliplatin was 33.3% (CR+PR) vs. 17.6% (CR+PR) with doxifluridine/oxaliplatin for stage III and IV gastric cancer patients. The average overall survival for patients treated with S-1/oxaliplatin was 7.25 month vs. 7.01 month with patients treated with doxifluridine/oxaliplatin. The expression of miR-181b (p=0.0028) and miR-21 (p=0.0001) was significantly overexpressed in gastric tumors compared to normal gastric tissues. Kaplan-Meier survival analysis by Cox regression revealed that low levels of miR-21 expression (Log rank test, hazard ratio: 0.17, CI= 0.06-0.45; p=0.0004) and miR-181b (Log rank test, hazard ratio: 0.37, CI= 0.16-0.87; p=0.018) are closely associated with better patient’s overall survival for both S-1 and Doxifluridine based regimens. Conclusions: Patients treated with S-1/oxaliplatin had a better response than doxifluridine/oxaliplatin. miR-21 and miR-181b hold great potential as prognostic biomarkers in late stage gastric cancer.
An improved classification of thin stage I melanomas using AJCC prognostic factors
Authors: P. Gimotty, J. Botbyl, L. Kruper, D. Guerry
Journal: Journal of Clinical Oncology (2005)

7512 Background: Thin stage I cutaneous melanomas (≤ 1 mm, T1a and T1b) make up the majority of melanomas in SEER, and were under-represented in the cohort used by the American Joint Cancer Committee (AJCC) to develop the 2001 staging system. We examined prognostic factors to develop a classification for prognosis that could better discriminate among patients than the current AJCC dichotomous classification with 10 year survival of ∼88% for T1a and ∼83% for T1b. Methods: This study includes 27,963 patients diagnosed with thin melanomas between 1988 and 2001 from SEER, a population-based registry including 11 sites together representative of the United States population. A classification tree was developed to identify factors that identified patients at varying risk of melanoma-specific death. Multivariate Cox proportional hazard models were used to identify independent prognostic factors. Results: The overall ten year survival rate was 94.2%. The classification tree analysis identified two factors associated with survival, Clark level and ulceration (see rates in table below). As in the current AJCC staging system, the survival rates for patients with ulcerated melanomas were worse than, or similar to, the rates for non-ulcerated lesions at the next higher stage. In the multivariate survival analysis thickness, level, ulceration, age, sex, and anatomic site were significant independent prognostic factors. Nevertheless, the risk ratios for level and ulceration were significantly higher than those for the other factors. Conclusion: Prognosis differs among patients with thin melanomas and can be better specified than in the current AJCC staging system by using the full range of levels plus ulceration. No significant financial relationships to disclose.
Optimization of an imaging protocol for stage I seminoma surveillance based on variations in relapse location over time.
Authors: Andrew McPartlin, Ali Hosni, Philippe L. Bedard, Aaron Richard Hansen, Michael A.S. Jewett, Robert James Hamilton, Martin O'Malley, Joan Sweet, Padraig Richard Warde, Peter W. M. Chung
Journal: Journal of Clinical Oncology (2016)

475 Background: Surveillance is recommended for patients with stage I seminoma post orchidectomy but CT imaging involves ionising radiation, with risk of associated secondary malignancies. We assessed site of disease relapse during surveillance to guide development of a risk adapted imaging protocol. Methods: Data was obtained from a prospectively maintained database of patients with stage I seminoma on surveillance after orchidectomy from 1981-2011. Relapse was determined by clinical and/or radiographic finding with or without pathological confirmation or tumour marker elevation. Results: 753 patients were identified. The median age at orchidectomy was 33.7 years. With a median follow up of 10.5 years, range 1.1-30.1, 115 (15.3%) patients relapsed. Relapse was detected radiologically in 114 (99.1%), with 9 (7.8%) having simultaneously elevated tumour markers. A clinical diagnosis of relapse was made in 1 case (inguinal node – 0.9%). The location and time to relapse are shown in table. Conclusions: In stage I seminoma surveillance, pelvic nodal relapse was restricted to the early period of follow up. Excluding the pelvis during CT imaging after the third year of surveillance may optimise the detection of relapse whilst minimising total radiation exposure. This has now been adopted at our centre since 2011 without any subsequent late pelvic relapses. [Table: see text]
TLR4/MD2 specific peptides stalled in vivo LPS-induced immune exacerbation
Authors: Seolhee Park, Hyeon-Jun Shin, Masaud Shah, Hey-Young Cho, Muhammad Ayaz Anwar, Asma Achek, Hyuk-Kwon Kwon, Byugsung Lee, Tae Hyeon Yoo, Sangdun Choi
Journal: Biomaterials (2017)
The prognostic role of protumoral macrophages in AJCC stage I/II melanoma
Authors: T. O. Jensen, M. Hoyer, H. Schmidt, H. J. Moller, T. Steiniche
Journal: Journal of Clinical Oncology (2008)

9017 Background: Depending on the micro-environmental signals in solid tumors, macrophages have pivotal functions: Anti- tumoral, killing tumor cells or pro-tumoral mediating tumor cell growth and invasion. The scavenger receptor CD163 is associated with pro-tumoral macrophages and it is shed from their surface (soluble CD163), in response to inflammatory stimuli. We studied CD163 expression in blood and primary melanomas from patients with stage I/II disease. Methods: 2,200 serum samples from 227 patients with stage I/II melanoma were collected during a 5-year follow-up period at the Plastic Surgery Department, Aarhus University Hospital in 1997 to 2002. In 190 of these patients paraffin embedded primary melanomas were available for examination.Tumor macrophage infiltration was studied by immunohistochemistry (anti-CD163) and estimated semi-quantitatively (5 categorical values) in three tumor compartments: tumor islets, stroma surrounding tumor islets, and at the invasive front of the tumor. Soluble CD163 in patients’ serum were analyzed with ELISA technique. The endpoints of this retrospective study were: Overall survival (OS) and progression-free survival (PS). Results: During a follow-up period of 61 months (range, 1 to 114 months), 44 relapses and 41 deaths were observed. CD163+ cell infiltration in stroma and tumor islets was analyzed with ulceration and thickness in a Multivariate Cox proportional hazard model. A high stromal infiltration of CD163+ macrophages was an independent prognostic factor of poor OS (hazard ratio [HR] = 3.7; 95% CI, 1.1–12.5; p=0.03) and of short PS ([HR] = 3.4; 95% CI, 1.0–11.5; p=0.05) together with thickness. Soluble CD163 treated as an updated continuous covariate as well as the baseline value was analyzed in a Cox proportional hazard model. There was no correlation to survival. Conclusions: High infiltration of CD163+ macrophages in stroma of primary melanoma was an independent prognostic factor of relapse and death in stage I/II melanoma. Results must be confirmed in an independent study. No significant financial relationships to disclose.
Does progesterone receptor status matter in endocrine-responsive breast cancer?
Authors: J. M. Coll, N. Healy, J. Coyne, C. Malone, R. McLaughlin, M. M. Keane, K. J. Sweeney, M. J. Kerin
Journal: Journal of Clinical Oncology (2011)

e11085 Background: The significance of the progesterone receptor (PR) as a predictor of response to endocrine therapy in invasive breast cancer is controversial and no consensus exists as to its role. The objective of this study is to compare tumour-specific features and survival rates of breast cancer tumours depending on their oestrogen and progesterone receptor status. Methods: Patients diagnosed with breast cancer in the west of Ireland between 1995 and 2005 were selected from a prospectively maintained database. ER and HER2/neu status, age, grade, stage of disease were recorded. During this period ER and PR status was determined using immunohistochemistry. Disease free and overall survival was determined for each of the patients. Statistical analysis was performed using SPSS. Results: 1,190 patients were diagnosed with breast cancer between 1995 and 2005. Of these 851 had both oestrogen receptor (ER) and PR assessed. 468 (55%) patients were designated ER+/PR+, 119 (14%) ER+/PR-, 77(9%) ER-/PR+ and 187(22%) ER-/PR-. Those patients in the ER+/PR- group were older than patients in the other groups with a mean age of 63.75 (p<0.001). Patients designated ER- were more likely to have a higher grade of disease (p<0.001). ER+/PR+ tumours had a higher proportion of HER2/neu negative tumours than the other 3 groups (p<0.001). Patients in the ER-/PR+ group were identified to have a distinct survival advantage at 5 years follow-up. This was significantly better than those with the ER-/PR- phenotype and similar to those who had ER+ but PR- disease. Conclusions: This study indicates that PR status is an independent predictor of response to endocrine therapy. It highlights the importance of measuring PR in invasive breast cancer, as otherwise 10% of endocrine responsive patients would be denied valuable adjuvant therapy. ER+/PR+ ER+/PR- ER-/PR+ ER-/PR- P value n (%) n (%) n (%) n (%) Total 468 (55) 119 (14) 77 (9) 187 (22) Age Mean ± SD 57 ± 13 64 ± 14 53 ± 12 56 ± P < 0.001 Grade Grade 1 50 (17) 10 (14) 11 (29) 10 (15) Grade 2 144 (48) 42 (59) 9 (20) 24 (17) Grade 3 107 (35) 19 (27) 26 (56) 94 (68) P < 0.001 Her2/neu Positive 49 (19) 20 (31) 15 (32) 50 (31) Status Negative 213 (81) 45 (69) 32 (68) 57 (69) P < 0.001
Quality-adjusted survival in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) receiving first-line therapy with panitumumab plus FOLFOX versus FOLFOX alone in the PRIME trial.
Authors: Jianmin Wang, Jun Dong, Patrick Johnson, Gregory A. Maglinte, Alan Rong, Beth L. Barber, Jean-Yves Douillard
Journal: Journal of Clinical Oncology (2015)

537 Background: The pivotal phase III PRIME trial demonstrated that, compared with FOLFOX alone, panitumumab plus FOLFOX prolongs overall survival and progression-free survival in patients with RASWT mCRC without having a detrimental effect on overall quality of life. The objective of this analysis was to use the quality-adjusted time without symptoms of disease or toxicity of treatment (Q-TWiST) method to compare quality-adjusted survival between the treatment arms of PRIME. Methods: Patients with RASWT mCRC from each treatment arm of PRIME were included in this analysis, and the area under the survival curve (AUSC) was estimated using the nonparametric Kaplan-Meier method (48 months follow-up). The AUSC was partitioned into three health states: toxicity (TOX), time without symptoms of disease progression or toxicity (TWiST, i.e., PFS minus TOX), and relapse (REL, i.e., OS minus PFS). The durations of the health states were then adjusted using utility weights derived from patient-reported EuroQoL 5 measures. The null hypothesis of no difference between treatment arms was tested based on the normal approximation, with standard errors calculated by the bootstrap method. In the primary analysis, TOX consisted of grade 3 and 4 adverse events. A sensitivity analysis, with grade 2, 3, and 4 adverse events classified as TOX, was performed. Results: Of 1,183 patients with mCRC who were randomized, 512 patients had RAS WT tumors (panitumumab plus FOLFOX, n=259; FOLFOX alone, n=253) and were included in this analysis. Patients receiving panitumumab plus FOLFOX had a significantly longer Q-TWiST (20.5 months) than patients receiving FOLFOX alone (18.2 months) resulting in 2.3 ± 1.0 (SE) additional quality-adjusted months (p&lt;0.03). The sensitivity analysis yielded similar results, indicating that the analysis was robust. Conclusions: This Q-TWiST analysis showed that in a previously untreated RAS WT mCRC population, patients treated with panitumumab plus FOLFOX had a significantly improved duration of quality-adjusted survival compared with patients treated with FOLFOX alone. Clinical trial information: NCT00364013.
Identification of Specific Transcriptional Patterns Associated with Hyperdiploidy in Multiple Myeloma.
Authors: Antonino Neri, Katia Todoerti, Luca Agnelli, Sonia Fabris, Silvio Bicciato, Laura Mosca, Lucia Nobili, Donata Verdelli, Domenica Ronchetti, Daniela Intini, Marta Lionetti, Giorgio Lambertenghi Deliliers, Luigia Lombardi
Journal: Blood (2006)
Blocking Specific CD44 Splicing Variant Isoform Inhibits the Differentiation of Th-2 Cells through Interfering with IL-4/IL-4R Signaling Pathway
Authors: Chun Yang, Jianhong Lin, Hongyan Liang, Ariel Kwart, Meng Jiang, Jianjun Zhao, Xiaofeng Jiang, Nikhil C. Munshi
Journal: Blood (2015)