tbuckley/cabot-search huggingface dataset:
A phase II study of neoadjuvant erlotinib in patients with muscle-invasive bladder cancer undergoing radical cystectomy: Preliminary results
Authors: W. Y. Kim, G. I. Grigson, E. M. Wallen, R. S. Pruthi
Journal: Journal of Clinical Oncology (2008)

11076 Background: Despite surgical therapy, only 50% of patients undergoing radical cystectomy for transitional cell carcinoma (TCC) of the bladder will experience long-term disease-free survival. Effective adjuvant therapies that have low-moderate toxicity and that are easily administered would represent a significant advancement in this disease. The epidermal growth factor receptor (EGFR) family (ErbB family) has been implicated in TCC development and progression. This study seeks to evaluate the clinicopathological efficacy of neoadjuvant erlotinib, an EGFR inhibitor, for invasive TCC in patients undergoing radical cystectomy. Methods: This phase II trial aims to determine the effect of neoadjuvant erlotinib (150 mg qd × 4 weeks) before radical cystectomy on the pathological complete response rate (P0 rate) in cystectomy specimens. In addition, the safety of therapy with erlotinib was also evaluated. Enrollment criteria include histologically- confirmed muscle invasive TCC (clinical stage T2) who have undergone initial TURBT. Results: 12 patients have undergone neoadjuvant erlotinib therapy followed by radical cystectomy. On surgical pathology, 3 patients (25%) were pT0, 1 patient pTis, 4 patients pT2, and 4 patients pT3/4. The overall pT0 rate was 25%, organ-confined rate 66%, and LN-positive rate 0%. At a median follow up of 12 months, 2 patients have recurred and 1 patient has died of other causes (MI). Erlotinib was tolerated in all patients with 6 patients having a drug rash (2 grade 3), and 1 patient with diarrhea. Interestingly all pT0 and pTis patients had a rash and 5 of 6 patients with a rash had organ-confined disease. (Erlotinib- associated rash has been associated with better disease specific survival in lung cancer patients.) Conclusions: The EGFR-inhibitor, erlotinib, when given neoadjuvantly, may have beneficial effects on operative pathology and short-term outcomes in patients undergoing radical cystectomy for invasive TCC. Analysis is underway to examine the molecular impact of neoadjuvant therapy in these patients. Longer follow- up with a larger cohort will be necessary to better evaluate the true clinical effects of EGFR inhibition in TCC and this study is currently underway. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration OSI Oncology
Sharing experiences and building collective projects in quality management: The strength of UNICANCER group.
Authors: Gregory Sieradzki, Helene Esperou, Anne De Jesus
Journal: Journal of Clinical Oncology (2014)

226 Background: UNICANCER is a hospital group entirely devoted to fighting cancer. UNICANCER groups together 20 French Comprehensive Cancer Centers (FCCC), which are private, non-profit establishments with a threefold mission of patient care, research and oncology teaching. They share the same organizational model to take care the patients and they have organized an informal network of quality and risk management In 2005, the FCCC federation (former Unicancer group) was created a Quality department in order to build a common approach to improve the quality of care and patient management in Cancer Centers. One the most important tools to set up this shared works were comparative analysis and feedback system. Methods: Every year, the quality department of Unicancer group coordinated the results of several indicators recorded by each centers. These results were summarized in the benchmarks dashboards to identify the priority actions for the group. Results: Between 2006 and 2014, some collaborative projects have been carried out in various fields: (1) development of the culture of continuous improvement, (2) involvement to the national implementationof hospital quality and safety indicators in France, (3) development of specific indicators of cancer care, (4) implementation of questionnaire survey to assess the in- or outpatient satisfaction. As far as concerned the different results of external assessment (1) the values of quality and safety indicators are above the national average, (2) the Cancer Centers have the best level of “certification” for the French National Authority for Health. Conclusions: The teamwork and benchmarking is an innovative way of working. The level of quality of care and patient management increases steadily in Cancer Centers in France. The next step consists of developing a common standard to keep competitive edge. [Table: see text]
Putting pediatric palliative care in prime time.
Authors: Rebecca A Kirch, Christina K Ullrich
Journal: Journal of Clinical Oncology (2014)

68 Background: For patients and families at any age and stage, treating the symptoms and stress of cancer is as important as treating the disease. Palliative care has hit its stride as one of the nation’s fastest growing health care trends, with a robust evidence base, new quality standards, increasing awareness and understanding, and a related public policy agenda. This momentum positions pediatric palliative care as an essential aspect of advancing childhood cancer survivorship with high quality of life – particularly important for children given the documented symptoms, late effects and disabling conditions they experience into adulthood and across their lifetime. This oral presentation will describe pediatric palliative care’s prominent role in addressing the challenges of childhood cancer and survivorship across the continuum, providing practical clinical case study context and highlights of consumer research findings and an advocacy agenda helping address palliative care’s “identity problem” that affects access to quality care. Methods: This presentation provides practical information for integrating palliative care to benefit children and families, including lessons learned through implementation of early pediatric palliative care alongside disease-directed treatment under the Concurrent Care for Children Requirement and other initiatives. It will also identify available resources for communicating about palliative care based on consumer research from the American Cancer Society and Center to Advance Palliative Care. Results: This presentation will inform and inspire person-centered and family-focused activities to advance early integration of palliative care in research and clinical practice. It will also highlight opportunities for active involvement in the QOL national movement to improve quality cancer care. Conclusions: Audience will understand benefits of pediatric palliative care and strategies supporting its delivery through the pediatric concurrent care experience in oncology. They will also gain improved proficiency in communicating about palliative care, and will be well-positioned to engage in the QOL legislative campaign to bring palliative care everywhere as an essential element of quality care.
Opportunities for precision medicine: Factors associated with participation in genetic research among breast cancer survivors.
Authors: Vanessa Sheppard, Ling Zheng, Kristi D Graves, Alejandra Hurtado-de-Mendoza, Mahlet Tadasse
Journal: Journal of Clinical Oncology (2016)

94 Background: Finding unique cancer therapies based on the specific genomic profiles of a person’s tumor is a national priority. Precision medicine can reduce disparate outcomes – particularly among Black breast cancer survivors who have higher mortality rates. Black women tend to be underrepresented in genomic research. Methods: Hormone receptive positive breast cancer survivors (Whites = 334, Blacks = 124, Other = 23) were recruited via hospitals and outreach. Data were collected via telephone interviews to assess sociocultural and health care processes; clinical data were abstracted from charts. Cell pellets were harvested from mouthwashes by centrifugation, followed by washing with PBS solution twice. After the baseline, women had a brief telephone information session. Low literacy materials explaining biospecimen collection were mailed. The primary outcome was receipt of the biospecimen sample in three months. Logistic regression assessed factors associated with biospecimens receipt. Results: Most (69%) survivors provided biospecimens. Most (92.8%) samples had good size cell pellets. Most (93%) of the mouth wash samples will have sufficient DNA for genotyping assays. In bivariate analysis, race, education, and mistrust were not associated with biospecimen receipt (p&gt; .05). Survivors more likely to provide biospecimens had higher ratings of: confidence in physicians’ technical skills, communication with providers, satisfaction with time with providers, and overall satisfaction with care (p&lt; .05). Health literacy and functional well-being were also associated with biospecimen receipt. In multivariate models, only survivor’s ratings of their level of confidence in her oncologists’ technical skills remained significant (OR: 1.6 per 1 point increase; CI: 1.1, 2.5). Conclusions: Regardless of race, most breast cancer survivors are willing to provide biospecimens for genomics research. Brief informational sessions and simple low-literacy materials may enhance participation. Relationships with oncologists are salient to promoting survivors participation in genomics research.
The effect of neoadjuvant chemotherapy (NACT) on lymph node retrieval in gastroesophageal carcinoma: A comparison of two cohorts treated at a single institution.
Authors: Tiago Cordeiro Felismino, Milton Jose De Barros E. Silva, Marcello Ferretti Fanelli, Wilson Luiz da Costa, Felipe José Fernandez Coimbra, Celso Lopes Mello
Journal: Journal of Clinical Oncology (2015)

182 Background: Surgery for gastric cancer (GC) has evolved over time. D2-lymphademectomy with a minimum of 16 nodes is the current approach in many countries. In locally advanced GC, surgery alone has high rates of recurrence. Hence, adjuvant therapies are needed. Adjuvant chemoradiotherapy (CRT) and perioperative chemotherapy (PCT) are standard. The effect of PCT causing histological changes and tumor regression is clear. However it is unknown if PCT could change the number of dissected nodes due to tumor response and histological modification. Our aim is to evaluate patients treated with gastrectomy followed by CRT or PCT and surgery and define the impact of PCT in the number of nodes dissected. Methods: We retrospectively analyzed two historical cohorts treated at our institution. Cohort 1 (C1) underwent upfront gastrectomy and CRT. Cohort 2 (C2) underwent PCT and gastrectomy. Results: C1 had 51 patients. Median age was 54y. 60.8% male and 39.2% female. There were 88% primary gastric and 12% esophagastric junction (EGJ). Pathologic stages II or III were described in 92.2%. Median follow-up was 65 m. C2 had 66 patients. Median age was 58y. 70.1% male and 29.9% female. There were 71.6% primary gastric and 28.4% EGJ. cT3 was described in 82% and cN+ in 77.4%. Main chemotherapy regimens were DCF in 35.8%, EOX in 23.9% and CF in 13.4%. At surgery, 67.1% had stages II or III. Six patients had pathologic complete response. Three patients died due to toxicity. Median follow-up time was 34 m. Median number of dissected nodes was 35 in C1 and 31 in C2 (p=0.08). 90.2% in C1 and 91% in C2 had more then 16 nodes dissected. Median number of positive nodes was four in C1 and one in C2 (p=0.01). Regarding chemotherapy, DCF or a non-taxane regimen had the same median of 31 nodes dissected. 3-year recurrence free survival was 78.3% for C1 and 66% for C2 (p=0.21). 28.3% of patients recurred in C1 and 35% in C2, mainly in distant sites. Only two patients in each group had local failure. Conclusions: Although NACT induces histological changes, it does not reduce the number of retrieved lymph nodes at surgery. Moreover, PCT is associated with a lower median number of positive nodes, related to tumor downstaging.
Enabling quality improvement in systemic cancer treatment through a collaborative approach.
Authors: Vicky Simanovski, Sherrie Hertz, Esther Green, Elaine Meertens, Leonard Kaizer, Monika K. Krzyzanowska, Judy Burns, Kelly Woltman
Journal: Journal of Clinical Oncology (2012)

88 Background: The Regional Systemic Treatment Program at Cancer Care Ontario (CCO) aims to ensure the highest quality of systemic treatment is available to Ontarians, as close to home as possible. CCO initiated a provincial collaborative with the aim of improving the safe delivery of parenteral chemotherapy from orders through preparation, to administration, for patients, and providers. Methods: From April 2011 to March 2012, interdisciplinary hospital teams across Ontario followed multiple Plan, Do, Study, Act cycles to perform QI projects focusing on safe delivery of systemic treatment. Over this period, three in-person sessions educating participants on improvement methodology were held. Monthly teleconferences and an electronic discussion forum encouraged a culture of knowledge sharing and collaboration. Results: 113 participants from 26 teams participated in a total of 81 improvement initiatives. 96% of participants surveyed indicated that the collaborative provided a valuable opportunity to network with peers, share ideas, and discuss lessons learned. During the collaborative, teams reported their progress on a scale of 1-5. At May 2011, teams averaged a self-assessment score of 1, indicating no progress had been made. By February 2012, this increased to an average score of 4, indicating significant progress and achievement of at least one improvement objective/goal. CCO has leveraged the foundations built by the collaborative to develop a Regional Quality and Safety Network. This network provides a regular forum for health care providers and administrators to share knowledge and collaborate on strategies for improving quality and safety in the delivery of systemic treatment. Conclusions: The collaborative demonstrated that the use of a formal quality improvement model is a successful mechanism for regional engagement; that provides the foundation necessary for building a provincial network with common goals and understanding regarding quality improvement. By educating participants, supporting local efforts and enabling knowledge transfer and exchange, the collaborative showed that shared ideas and even small changes can lead to large-scale improvements for patients and providers.
Differential induction of antibody-dependent cellular cytotoxicity (ADCC) against human EGFR-expressing NSCLC cell lines by necitumumab, cetuximab, and panitumumab.
Authors: D. Patel, B. Saxena, Q. Zhou, W. Walton, R. Srikakulum, R. Manteiga, J. Haurum, J. R. Tonra, X. Kang
Journal: Journal of Clinical Oncology (2011)

e21075 Background: Necitumumab, cetuximab and panitumumab are monoclonal antibodies specific for human epidermal growth factor receptor (EGFR). They act as functional antagonists by blocking ligand binding (EGF and TGFa) to EGFR and inhibit EGFR activation and downstream signaling in tumor cells. Necitumumab and cetuximab are IgG1 molecules and panitumumab is an IgG2 molecule. Methods: In the present study, we analyzed the binding of all three antibodies to EGFR, human Fc receptors and C1q. We also examined the ability to elicit antibody-dependent cellular cytotoxicity (ADCC) in vitro using non-small cell lung cancer (NSCLC) cells expressing various levels of EGFR. Fc-receptor and C1q binding activity was evaluated by ELISA. ADCC was evaluated with a reporter gene based assay using Jurkat cells or human peripheral blood mononuclear cells (PBMC) from normal donors as effector cells. Results: Necitumumab and cetuximab exhibited similar binding to FcgRIa, FcgRIIa, FcgRIIIa and C1q, whereas no binding activity was observed for panitumumab. Necitumumab and cetuximab induced potent ADCC against NSCLC tumor cells at a concentration as low as 1.0 nM. Interestingly, the extent of ADCC induced by cetuximab and necitumumab correlated with the level of EGFR expression on the cell surface. Panitumumab did not elicit ADCC against EGFR expressing tumor cells, even though panitumumab binding to EGFR was similar to that of necitumumab and cetuximab. Conclusions: Both necitumumab and cetuximab, but not panitumumab, target effector cells to EGFR-expressing NSCLC cells to elicit ADCC, with a magnitude that correlates with EGFR expression level. C1q binding studies suggest the relative abilities of EGFR antibodies to fix complement will parallel results with ADCC.
Correlation of the clinical frailty scale with long-term survival after radical cystectomy.
Authors: Mario W. Kramer, Martin JP Hennig, Christoph A. J. von Klot, Gerd Wegener, Annika Heinisch, Inga Peters, Thomas R. W. Herrmann, Markus A. Kuczyk, Hossein Tezval, Axel S. Merseburger
Journal: Journal of Clinical Oncology (2015)

314 Background: Demographic changes account for an increasingly large proportion of elderly patients with urothelial carcinoma of the bladder. It remains under debate to which extent a patient might benefit from major surgery such as the radical cystectomy. Current tools for preoperative assessment of biological age might be of limited significance. The frailty concept, which refers to a biological syndrome of decreased reserve to stressors and resistance to stressors, has gained recent recognition for measuring patient’s physiological reserve and has been linked to adverse outcomes after surgery. Methods: Clinical, surgical and pathological data of patients undergoing radical cystectomy and lymph node dissection at Hannover Medical School with a minimum age of 60 years were retrospectively collected from 2000 to 2010. Frailty was assessed using the clinical frailty scale by Rockwood et al. derived from the Canadian Study of Health and Aging (CSHA). The relationship between frailty and various risk assessment tools such as the ASA-score, Charlson Comorbidity Index (CCI) and Karnofsky score (KS) in regard of long-term follow-up data was analyzed. Results: Our cohort included 255 patients (male 197, female 58). Mean age was 70 years (SD ±6.14). Patients were categorized into “not frail” (n=53, 21%), “vulnerable and mildly frail” (n=156, 61%), and “moderately/severely frail” (n=46, 18%). Higher CSHA was associated with increased CCI and higher rate of perioperative complications (each p&lt;0.001). 179 (70%) patients had died during follow-up (mean follow-up, 61 months). Median survival differed significantly between groups (68 vs. 29 vs. 12 months, p&lt;0.0001). In univariate analyses ASA, CCI, KI, and CSHA correlated with long-term survival (each p&lt;0.001). In multivariate analysis only CSHA remained predictor of survival besides age, lymph node involvement, resection margins, and T-stage. Conclusions: The clinical frailty scale is an easy to use tool. It correlates with survival and perioperative complications after radical cystectomy. This study warrants further assessment of the frailty concept; however, it still has to be determined whether the clinical frailty scale is superior to other frailty assessment schemes.
Clinical Relevance of Circulating Poly-Ubiquitin as a Prognostic Indicator in Chronic Lymphocytic Leukemia.
Authors: Wanlong Ma, Hagop M. Kantarjian, Xiuqiang Wang, Susan O'Brien, Chen-Hsiung Yeh, XI Zhang, Zeev Estrov, Anthony Sferruzza, William Weirda, Michael Keating, Maher Albitar
Journal: Blood (2009)
FDG-PET in the staging and prognosis of T-cell lymphoma.
Authors: C. Casulo, J. Maragulia, A. D. Zelenetz, H. Schöder, J. Feeney, S. M. Horwitz
Journal: Journal of Clinical Oncology (2011)

e18502 Background: We have previously reported that fluoro-deoxy-glucose positron emission tomography scan (FDG-PET) is almost universally positive in patients (pts) with T-cell lymphoma (Feeney, Amer J Roentgenol, 2010 195: 333). In the current analysis we examined the role of FDG-PET in initial staging and at interim (int) evaluation as a prognostic factor for pts with peripheral T-cell lymphoma (PTCL). Methods: We reviewed the PTCL database at Memorial Sloan-Kettering Cancer Center to identify pts with mature T or NK lymphomas with PET scans as part of initial staging or relapse (N=91), and a subset of pts with repeat PET for int restaging while treated with curative intent (N=50). Results: The frequency of specific T-cell histologies included in this analysis were: PTCL-NOS (N=35); angioimmunoblastic T-cell lymphoma (N=17); anaplastic large cell lymphoma, ALK-1+ (N=10) and ALK-1- (N=11); HTLV-1 associated lymphoma (N=7); NK/T cell lymphoma (N=5); other (N=6). Seventy three pts were newly diagnosed, 18 had relapsed disease. FDG-PET during pre-treatment staging was positive in 97% of pts. Compared to CT-based evaluation, stage, if PET-based, would be altered in staging 10 pts (11%): 3 pts were upstaged and 7 pts downstaged. PET-based staging did not alter treatment for any pt. PET identified new disease sites in 46 pts (50%). Most frequently identified additional sites were: other nodal (N=24); bone (N=8); skin (N=7); nasopharynx (N=3); spleen (N=3); and lung (N=2). After a median of 4 cycles of chemotherapy, 50 pts underwent int PET. Treatment regimens included CHOP (N=19); CHOP/ICE (N=24); other (N=7). At median follow up of 2.2 years, pts with negative int PET had superior OS and PFS compared to pts with positive int PET. Eighty five percent of pts with negative int PET were alive at median follow up vs. 44% with positive int PET, and 73% of pts with negative int PET were progression free vs. 24.3% with positive int PET. Conclusions: In this data set, PET was positive at initial staging in most pts with PTCL. Additional disease sites were found by PET in 50% of pts but stage was impacted on in only 11% of pts, with no alteration in treatment. Int FDG-PET predicted for both OS and PFS. Achieving a negative int PET seems to be an important predictor of outcome in pts with PTCL.