tbuckley/cabot-search huggingface dataset:
Extending the patient navigator research program from Harlem to the nation
Authors: R. Garcia, K. M. Freund, D. Dudley, K. Fiscella, J. D. Jones, S. R. Patierno, P. C. Raich, R. G. Roetzheim, E. Paskett, C. L. Bennett
Journal: Journal of Clinical Oncology (2006)

6096 Background: Low-income persons face barriers when attempting to seek cancer diagnostics tests and treatment. In 1990, Harold Freeman implemented a novel patient navigator program for women with abnormal mammograms, resulting in earlier presentations and better survival. Identified barriers included lack of insurance, poor social support, coping styles, health beliefs such as fatalism, and poor health literacy skills. Single-site navigator programs have been subsequently implemented. Building on these experiences, the National Cancer Institute is supporting navigator programs at 9 sites. Methods: At 9 sites, the skill set of the navigators, community partnerships, target patient populations were reviewed for information regarding cancer type, number of patients seen, and navigator type. Common data elements include time to diagnosis and time to initiation of treatment, navigation costs, cost-effectiveness of the intervention (in order to address sustainability), and navigation satisfaction. Results: See Table . Conclusions: While programs such as the Breast and Cervical Cancer Treatment Act, the Department of Veterans Affairs, and the Indian Health Board provide financial support to pay for diagnostic/treatment services, the Patient Navigator Research Program will provide medical, social, and psychosocial services for 5,295 patients with positive breast cancer screens, 3,528 patients with positive cervical cancer screens, 5,507 patients with colorectal cancer screens, and 1,167 patients with prostate cancer screens. Diversity of sites, navigator skill sets, patient eligibility, sociodemographics, and study design in conjunction with common data elements, outcomes, and analytic plans will allow us to assess the efficacy and costs of a range of navigation programs. [Table: see text] No significant financial relationships to disclose.
Frequency and clinical implications of pathologic complete response (pCR) at cystectomy for muscle-invasive bladder cancer (MIBC) with or without neoadjuvant chemotherapy (NAC).
Authors: Matt D. Galsky, Kristian Stensland, John Sfakianos, Russell Bailey McBride, Reza Mehrazin, Che-Kai Tsao, Paolo Boffetta, William K. Oh
Journal: Journal of Clinical Oncology (2016)

383 Background: Subsets of patients (pts) with MIBC, with or without NAC, have no pathologic evidence of disease at cystectomy. The frequency and implications of pCR in “real world” pts has not been well characterized. Methods: Using the National Cancer Database, pts with cT2-4aN0M0 bladder cancer who underwent cystectomy alone (CYS) or with NAC from 2003-2011 were identified. pCR was defined as pT0N0M0. In the CYS and NAC cohorts, the association between pCR and overall survival was analyzed using Cox proportional hazard methods. Results: 12,245 pts met eligibility (CYS: 10,940; NAC: 1,305). The pCR rate with CYS was 4.8% (95% CI 4.4-5.3%) and with NAC was 21.6% (95% CI 19.4-24.0%). In both cohorts, logistic regression revealed lower cT stage and higher cystectomy volume were associated with increased pCR. pCR was associated with a significant improvement in survival in both cohorts (Table). Conclusions: The frequency of pCR in real world pts was substantially lower than reported in clinical trials; however, pCR was associated with markedly improved survival in both CYS and NAC groups. Molecular predictors of pCR in both groups warrant evaluation. Whether the survival benefit associated with pCR in the CYS cohort simply reflects the “smallest/best” tumors or whether there is a role, and mechanistic rationale, for surgical approaches to increase pCR (i.e., re-TURBT in MIBC) warrants study. Finally, our findings lend further support for use of pCR as an endpoint in NAC clinical trials. [Table: see text]
A comparative assessment of the incidence of steatohepatitis seen with modern chemotherapy agents
Authors: G. D. Leonard, S. D. Curran, N. E. Kemeny, L. H. Schwartz, Y. Fong
Journal: Journal of Clinical Oncology (2005)

8051 Background: Steatohepatits, otherwise known as fatty liver, has been associated with a number of chemotherapy agents, in particular the fluoropyrimidines. Chemotherapy Associated Steatohepatitis (CASH) can cause a number of clinical problems including misinterpretation of fatty liver for tumor progression and increased morbidity and mortality post liver resection (Kooby et al J Gastrointest Surg 2003). There has been no formal evaluation of the relative incidence of CASH with modern chemotherapy agents although a recent report suggests that oxaliplatin may be associated with hepatic sinusoidal obstruction (Rubbia-Brandt et al Ann Oncol 2004). Methods: We randomly identified 75 chemonaive patients from our institution that were treated with at least 2 months of either 5-fluorouracil and leucovorin (FU/LV) (n=25), irinotecan + FU/LV (n=25), or oxaliplatin + FU/LV (n=25) for advanced colorectal carcinoma (CRC). A quantitative assessment of CASH was performed by measuring Hounsfield units in 3 separate areas on the liver, spleen and paraspinal muscles respectively on pre and post chemotherapy computed tomography (CT) scans in each patient. Results: Attenuation measurements were performed on all 75 patients at a number of levels in the right lobe of the liver and at the closest corresponding levels of the spleen and muscle, immediately prior to and after administration of chemotherapy. Mean liver-spleen attenuation difference values were compared and those values which reduced by more than a predefined threshold value post chemotherapy were considered fatty. The results show 6 of 25 (24%) of the 5FU group, 12 of 25 (48%) of the CPT11 group, and 7 of 25 (28%) of the FOLFOX treated group showed attenuation differences consistent with interval development of diffuse fatty change in the liver. Conclusions: CASH can occur with modern chemotherapy agents. Verification of these results are necessary using more accurate measures of steatohepatitis such as non-contrast CT scans. With the increasing utilization of these agents for neoadjuvant therapy for advanced CRC, clinicopatholoigical studies are required to further characterize CASH and its potential complications. No significant financial relationships to disclose.
Smoking-related and non-smoking-related carcinogensis in adenocarcinoma of the lung
Authors: T. Mitsudomi, R. Onozato, T. Kosaka, Y. Yatabe
Journal: Journal of Clinical Oncology (2008)

22001 Background: Recently, female, never-smoking patients with adenocarcinoma of the lung appear to increase worldwide. However, molecular basis of these lung cancers is not well understood. Methods: We sequenced EGFR, HER2, KRAS gene and transmembrare region of the MET in a cohort of 211 lung adenocarcinoma. In addition, we searched for mutation of the TP53, LKB1 and PIK3CA gene in 195, 71 and 68 adenocarcinomas, respectively. Results: EGFR, HER2, KRAS and MET mutations were found in 103 (49%), 5 (2%), 29 (14%) and 7 (3%), respectively. These four mutations had a strict mutual exclusionary relationship. All the 7 MET mutations deleted exon 14 that contained a putative binding site for c-cbl that degraded MET. In 4 of 7 tumors, we found different intronic mutations resulting in disruption of splicing consensus. There was a striking difference among these patients in terms of incidence of never-smokers and other features (Table). Never-smokers were frequent in patients with EGFR or HER2 tumors but rare in KRAS tumors. In contrast, incidence of the TP53 mutation was not significantly different by the mutated oncogenes. However, G to T transversion of the TP53 gene, a hallmark of tobacco-related carcinogenesis, was almost absent in EGFR tumors. LKB1 mutations were found in 3 of 71 (4%), all of which were in male smokers and each of them either had EGFR, TP53 or KRAS mutation. Two identical PIK3CA mutations (E545K) were found in 68 adenocarcinomas (3%). These two patients were female, never smokers and they both had EGFR L858R mutation. Conclusions: There appeared to exist two classes of cancer genes in lung adenocarcinomas. EGFR, HER2, PIK3CA gene mutations were associated with non-smoking-related carcinonogenesis, while KRAS, G to T TP53, LKB1 gene mutation were associated with smoking-related one. Also these cancer genes could be divided into two categories. One included genes whose mutations occur in mutually exclusionary fashion and the other includes genes without such relationship. Results of Mutation Analysis Oncogenes Number mutated (%) Never-smoker (%) Female (%) Poorly diff. (%) TP53 mutation (%) G to T TP53 mutation (%) EGFR 103 49 68 65 19 34 1 HER2 5 2 60 80 20 40 20 KRAS 29 14 24 24 38 45 17 MET 7 3 43 43 29 14 14 None of above 67 32 33 42 49 40 22 No significant financial relationships to disclose.
Re-engineered RNA-Guided FokI-Nucleases for Improved Genome Editing in Human Cells
Authors: Steven Havlicek, Yang Shen, Yunus Alpagu, Michaela B. Bruntraeger, Nurdiana B.M. Zufir, Zhi Yi Phuah, Zhiyan Fu, Norris R. Dunn, Lawrence W. Stanton
Journal: Molecular Therapy (2017)

Clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 enables us to generate targeted sequence changes in the genomes of cells and organisms. However, off-target effects have been a persistent problem hampering the development of therapeutics based on CRISPR/Cas9 and potentially confounding research results. Efforts to improve Cas9 specificity, like the development of RNA-guided FokI-nucleases (RFNs), usually come at the cost of editing efficiency and/or genome targetability. To overcome these limitations, we engineered improved chimeras of RFNs that enable higher cleavage efficiency and provide broader genome targetability, while retaining high fidelity for genome editing in human cells. Furthermore, we developed a new RFN ortholog derived from Staphylococcus aureus Cas9 and characterize its utility for efficient genome engineering. Finally, we demonstrate the feasibility of RFN orthologs to functionally hetero-dimerize to modify endogenous genes, unveiling a new dimension of RFN target design opportunities. Clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 enables us to generate targeted sequence changes in the genomes of cells and organisms. However, off-target effects have been a persistent problem hampering the development of therapeutics based on CRISPR/Cas9 and potentially confounding research results. Efforts to improve Cas9 specificity, like the development of RNA-guided FokI-nucleases (RFNs), usually come at the cost of editing efficiency and/or genome targetability. To overcome these limitations, we engineered improved chimeras of RFNs that enable higher cleavage efficiency and provide broader genome targetability, while retaining high fidelity for genome editing in human cells. Furthermore, we developed a new RFN ortholog derived from Staphylococcus aureus Cas9 and characterize its utility for efficient genome engineering. Finally, we demonstrate the feasibility of RFN orthologs to functionally hetero-dimerize to modify endogenous genes, unveiling a new dimension of RFN target design opportunities.
Thomas Laurence Moody
Authors: Caroline Moody
Journal: BMJ (2017)

Thomas Laurence Moody (“Tom”) was born in Coleraine, Northern Ireland. After the war, his family moved to Stockton on Tees, County Durham, where his father was a general practitioner for many years. Tom attended Pocklington School and then studied medicine at the University of Newcastle upon Tyne, then known as King’s College, one of the colleges of Durham University. There he met his future wife, Eileen Elizabeth, in November 1963. In 1967 they both graduated, Tom in medicine and Eileen in French. They married in June 1969.

While at university, Tom joined the Royal Navy and in 1967 started working as a medical officer. After working briefly on HMS Ganges , …
Neoadjuvant chemotherapy &amp; low dose extracorporeal irradiation for treatment of osteosarcoma
Authors: G. F. El-Wahidi, I. Eldesoky, S. Kotb, I. Awad, M. Thabet, Y. Thaleh
Journal: Journal of Clinical Oncology (2005)

9074 Background:Excision with bone cement followed by prosthetic replacement is the best line of treatment of osteosarcoma. A better substitute to higher costs of prosthesis is to give extracorporeal irradiation of resected specimen to be reimplanted again to assist stability of the bone matrix. Methods: 53 patients with osteosarcoma were selected for study.16 cases undergone excision+bone cement before prosthetic implant while 37 cases received ECI, 12 of which received low dose ECI (50 Gy) & 25 cases received high dose ECI(300 Gy). All cases received 3 cycles of neoadjuvant chemotherapy (CAP)* protocol. Results: Table 1: Recurrence rate after ECI was lower than excision+bone cement with prosthetic replacement neverseless metastases free survival and OAS were nearly identical. This difference didn’t reach statistical significance (P ≥ 0.203) Table 2: showed similar local tumor response with no significant difference (P ≥ 0.304). Table 3: Functional outcome with results nearly identical in subgroups Conclusions: ECI is considered a reasonable substitute to excision+prosthetic replacement for treatment of osteosarcoma with equivalent results as regard recurrence, MFS & OAS. More over the endpoint to this treatment with local control & functional outcome is nearly identical if we used low dose ECI & high dose ECI even low dose is beneficial for functional integrity & mechanical stability of bone. * cyclophosphamide, Adriablastin, Cisplatin No significant financial relationships to disclose.
Survival among cancer patients undergoing opioid rotation to methadone as compared to other opioids.
Authors: Akhila Sunkepally Reddy, Sriram Yennu, Ulrich S. Schuler, Maxine Grace De la Cruz, Jimin Wu, Diane D Liu, Eduardo Bruera
Journal: Journal of Clinical Oncology (2015)

183 Background: Recent studies have reported that methadone has antineoplastic activity. Other studies have associated methadone with lower overall survival in patients with chronic pain. Methadone is the most frequent opioid chosen for purpose of opioid rotation (OR) in cancer patients experiencing refractory pain or opioid induced neurotoxicity. There is no data available on the association of methadone with overall survival in cancer patients. Our aim was to compare the characteristics and overall survival in cancer patients in methadone group with other strong opioid group. Methods: In this ad hoc analysis, we reviewed 2471 consecutive patient visits to the supportive care center of a tertiary cancer center in 2008 for ORs from strong opioids to methadone or other strong opioids with a follow-up visit within 6 weeks. Information regarding demographics, Edmonton Symptom Assessment Scale (ESAS), and morphine equivalent daily dose (MEDD) were collected. Successful pain response was defined as 2-point or 30% reduction in pain score. Kaplan-Meier curves were used to evaluate survival. Results: Of the 102 eligible patients, 54 underwent OR to methadone and 48 to other strong opioids. The median age was 56 years, 56% were male, and 81% had advanced cancer. There were no significant differences between the methadone group and the other opioid group in patient characteristics, performance status, MEDD, and ESAS scores. Although both the groups showed significant pain response, methadone group (72%) had a significantly higher pain response as compared to the other opioid group (65%; P = 0.04). The Kaplan-Meier curves revealed no significant difference in overall survival (OS) between the methadone group and the other opioid group [median OS: 5.2 months (95% CI 3.64-7.41) vs. 5.9 months (95% CI 2.6-9.2); P = 0.89]. Conclusions: We observed no significant difference in overall survival in cancer patients in methadone group as compared to other opioids. Further validation studies in a larger sample are warranted.
Characteristics and clinical outcomes of patients with renal cell carcinoma with sarcomatoid dedifferentiation (sRCC).
Authors: Megan M. Merrill, Christopher G. Wood, Nizar M. Tannir, Rebecca Slack, Kara Babaian, Eric Jonasch, Lance C. Pagliaro, Zachary Compton, Pheroze Tamboli, Kanishka Sircar, Louis L. Pisters, Surena F. Matin, Jose A. Karam
Journal: Journal of Clinical Oncology (2013)

401 Background: sRCC is an aggressive subset of renal cell carcinomas that is associated with poor prognosis. We describe clinical and pathological characteristics and outcomes of the largest single-institutional cohort of patients with sRCC who underwent nephrectomy. Methods: Data were collected from 1986 to 2011 for patients identified as having sRCC. 221 patients with complete data who underwent a radical or partial nephrectomy and had a sarcomatoid component in the primary kidney tumor were included in the analysis. Clinical and pathologic variables were reviewed and Kaplan-Meier curves were used to compare differences in overall survival. Results: Mean age at diagnosis was 57 years and median tumor size was 11 cm (range 1.5-27.0 cm). 93% of patients were symptomatic at presentation and 96% had an ECOG performance status of 0 or 1. 12 patients had a preoperative biopsy that showed sRCC. 75% of patients were pT3 or higher at time of nephrectomy and 69% presented with metastatic disease. Of these, 11.8% had radiographic evidence of regional nodal involvement alone and 88.2% had distant metastatic disease. The associated epithelial component was clear cell in 72% of the patients, papillary in 12.7% and chromophobe in 3.1%. 29 patients received presurgical systemic therapy, while 161 patients received postoperative systemic therapy. During a median follow-up of 20.5 months, 187 patients (84%) died. Overall survival for the entire cohort at 1 year was 48%. Overall 1-, 2-, and 3-year survival rates for patients with metastatic disease at presentation versus no metastatic disease were 36, 20, and 16% versus 74, 51, and 44% respectively (p &lt; 0.001). Patients with clear cell RCC epithelial component had a survival advantage over those with non-clear cell components with 1-, 2-, and 3-year survival rates of 52, 34, and 31% versus 38, 19, and 12% (p = 0.0057). Conclusions: The majority of patients with sRCC who underwent nephrectomy present with metastatic disease and outcomes are dismal despite surgical intervention and multimodal therapy. Overall survival is better for patients who present without metastatic disease and have clear cell histology at time of nephrectomy.
Evaluating utilization characteristics for the Onco<i>type</i> DX recurrence score in early-stage breast cancer.
Authors: C. Chen, D. A. Patt, D. R. Kazzaz, J. Shankleton, M. T. Forsyth, R. Ganesh
Journal: Journal of Clinical Oncology (2011)

625 Background: The Oncotype DX Recurrence Score is a clinically validated molecular test that can be used to predict the risk of distant recurrence and the likelihood of chemotherapy benefit among patients with newly diagnosed ER+ early stage breast cancer. By avoiding unnecessary chemotherapy use in patients with low Recurrence Score disease, toxicity and cost could be reduced. By giving chemotherapy to patients with high Recurrence Score disease, recurrences could be reduced. The objective of this investigation was to determine if patient or practice characteristics drive utilization. Methods: Early stage breast cancer patients who were diagnosed between January 2008 and June 2009 with ER+, LN-, HER2 non-amplified tumors, who were evaluated within the USON, and who were registered within the EMR were included. Patients enrolled on clinical trial or treated for another cancer during the study period were excluded. The oncology specific electronic medical record (EMR) system software iKnowMed is used within 80% of the US Oncology Network. Percent utilization was evaluated by patient characteristics including age, ECOG PS, tumor size, and tumor grade. Practice characteristics were evaluated by region of the country and practice size. Statistical significance of observed associations was evaluated using the Chi-squared, CMH, and Cochran-Armitage trend tests. Homogeneity of association across risk groups were evaluated using the Breslow-Day test. Results: 5,644 patients were included. Recurrence Scores were obtained for 1,543 (27%) of these patients. Utilization was 33.5% in patients 45 yrs or less, 35% in patients 46-55, 32% in patients 56-65, 24% in patients 66-75, and 6% in patients 76 and older (p<0.0001). Utilization was 31%, 23%, 9%, and 7% in patients with ECOG PS 0, 1, 2, and 3, respectively (p<0.0001). Utilization was 6%, 8%, 24%, 36%, 26%, and 8% in T1mic, T1a, T1b, T1c, T2, and T3 tumors respectively (p<0.0001). Conclusions: Younger patients were more likely to receive the test as were patients who had better performance status and higher grade tumors. Utilization did not vary greatly among regions or practice size.
Is survivorship care plan discussion important to patients?
Authors: Amy Eiko Leatherwood, Charles R. Thomas, Sara J Walker, Susan Hedlund
Journal: Journal of Clinical Oncology (2017)

49 Background: The 2015 Commission on Cancer standard requires that cancer survivors receive a personalized survivorship care plan (SCP). There exists a gap in consistency of how and when this plan is delivered. There is a need to evaluate patient satisfaction with personalized care along with direct education regarding the SCP and follow up. The aim of the current study was to determine the 1) rate at which cancer survivors find in-person discussion of SCP helpful, and 2) the rate at which they find the in-person discussion more helpful than the alternatives. Methods: An anonymous questionnaire was routinely administered, for quality assurance purposes, to cancer patients who completed treatment in a radiation oncology setting at a NCI-Designated Cancer Center. The population consisted of survivors of breast, prostate, colon, anal, pancreatic, lung, and liver cancers. Patients were given the questionnaire at the conclusion of a survivorship visit with a nurse practitioner devoted to survivorship care. During the visit they received a SCP with full discussion and explanation of the content. The questionnaire asks two Yes/No questions: 1) Did you find the survivorship visit helpful and/or educational? 2) Was it more helpful to have the survivorship summary explained to you in person? Results: 71 survivorship visit patients were offered a questionnaire to complete at the end of their visit. 71 completed questionnaires were received from patients. Of these 71 questionnaires, 69/71 or 97% of responses were “yes” for question 1. For question 2, 68/71, or 96% of responses were “yes.” Conclusions: Our data show that the majority of patients are finding survivorship summaries to be a positive aspect of the care continuum. In addition, patients are also indicating that visits “in person,” with face-to-face explanation of survivorship summaries, are more helpful than receiving a summary without verbal involvement or explanation. These findings suggest that such in-person discussions could be considered important in quality cancer care. Future directions include investigating the effect of other individual, disease, or treatment characteristics on an individual’s preference for SCP delivery.