tbuckley/cabot-search huggingface dataset:
Outcomes of early stage lung cancer treatments in older patients: A SEER database analysis.
Authors: Alissa S. Marr, Valerie Shostrom, K. M Islam, Apar Kishor Ganti
Journal: Journal of Clinical Oncology (2013)

7571 Background: Although the majority of lung cancer patients are over the age of 65, there are limited data on outcomes of treatment options for early stage lung cancer in older patients. Methods: Treatment and outcome data of stage I and II non-small cell lung cancer (NSCLC) patients were obtained from the Surveillance, Epidemiology and End Results (SEER) database. Treatment modalities included no treatment, surgery, radiation, and a combination of surgery and radiation. Patients were divided based on age groups into &lt;65, 65-75, and &gt;75 years old. Multivariate logistic regression was used to compare the likelihood of survival in the three age groups while controlling for gender and race. Results: A total of 10,763 patients diagnosed with stage I and II NSCLC between 1988 and 2007 within the SEER database were analyzed. The age distribution was as follows: &lt;65 (n=3558), 65-75 years (n= 4454), &gt;75 years (n=2751). Patients &lt;65 years of age were more likely than those &gt;75 years of age to be treated with surgery (72.5% vs. 53.5%, respectively; p = &lt;0.0001). Patients &gt;75 years of age were more often treated with radiation alone (23%) or no treatment (18.2%) as compared to those patients &lt;65 (9% and 4.9%, respectively; p = &lt;0.0001). Patients &lt;65 years of age with stage I lung cancer had a statistically significant improved lung cancer-specific 5-year survival with surgery alone as compared to those 65-75 years and &gt;75 years. Lung cancer specific mortality at 5 years was 19%, 26% and 30%, respectively; p= &lt;0.0001. Similar results were seen in stage II patients. When stage I patients received radiation therapy, lung cancer-specific deaths at 5 years were not different between the three groups (66% vs. 63% vs. 66%, respectively; p=0.1263). The 5-year lung cancer- related mortality was lower in younger patients who received no treatment (51% in &lt;65, 56% in 65-75, and 57% in &gt;75 years old; p=0.006). Conclusions: Older patients treated surgically for stages I and II NSCLC have a lower lung cancer-specific survival when compared to younger patients. In contrast, there is no difference in lung cancer-specific survival for patients treated with radiation therapy. Hence, careful selection of older patients for surgical therapy of early stage NSCLC is warranted.
Erratum: Corrigendum: Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus
Authors: Patrick Tarpey, Shery Thomas, Nagini Sarvananthan, Uma Mallya, Steven Lisgo, Chris J Talbot, Eryl O Roberts, Musarat Awan, Mylvaganam Surendran, Rebecca J McLean, Robert D Reinecke, Andrea Langmann, Susanne Lindner, Martina Koch, Sunila Jain, Geoffrey Woodruff, Richard P Gale, Chris Degg, Konstantinos Droutsas, Ioannis Asproudis, Alina A Zubcov, Christina Pieh, Colin D Veal, Rajiv D Machado, Oliver C Backhouse, Laura Baumber, Cris S Constantinescu, Michael C Brodsky, David G Hunter, Richard W Hertle, Randy J Read, Sarah Edkins, Sarah O'Meara, Adrian Parker, Claire Stevens, Jon Teague, Richard Wooster, P Andrew Futreal, Richard C Trembath, Michael R Stratton, F Lucy Raymond, Irene Gottlob
Journal: Nature Genetics (2011)
A pilot study on the clinical value of <sup>18</sup>F-sodium fluoride PET/CT in advanced prostate cancer.
Authors: Joseph W. Kim, Maria Liza Lindenberg, William L. Dahut, James L. Gulley, Ravi A. Madan, Lauren V. Wood, Yolanda McKinney, Peter L. Choyke, Karen A Kurdziel, Andrea Borghese Apolo
Journal: Journal of Clinical Oncology (2012)

10589 Background: We evaluated the clinical utility of 18 F-sodium fluoride PET/CT bone scan ( 18 F-NaF) in the detection of bone metastases in patients (pts) with prostate cancer in comparison with Technetium-99m MDP bone scan (TcBS). Methods: In a prospective study, from October 2010-December 2011, 30 prostate cancer pts (ages 51-79), 21 with known bone metastases and 9 without known bone metastases, had 18 F-NaF and a TcBS performed. Abnormal foci of uptake on both TcBS and 18 F-NaFwere classified as benign, malignant or indeterminate. Benign lesions included uptake in the joints and linear uptake at the endplates of the vertebral bodies consistent with degenerative changes. Malignant uptake on 18 F-NaF scans was confirmed by characteristic osteoblastic features on CT. All TcBS and 18 F-NaF were reviewed by an experienced nuclear medicine physician. For the patient-based analysis, scan results were categorized as positive (POS) = any malignant lesion; indeterminate (IND) = not distinctly malignant or benign; negative (NEG) = benign lesions only. Results: In the lesion-based analysis, 21 of 30 (70%) pts had more malignant lesions identified on 18 F-NaF than on TcBS. The mean number of additional malignant lesions per patient on 18 F-NaF vs TcBS was 4. Eight of the 30 pts had same number of malignant lesions identified in both studies. One of 30 pts had one less malignant lesion identified on 18 F-NaF than on TcBS. CT correlation by 18 F-NaF PET/CT of this particular lesion did not confirm osteoblastic feature. Malignant lesion distribution on 18 F-NaF included: spine (28%), thorax (26%), pelvis (24%), long bones (13%) and skull (10%). In the patient-based analysis, 24 pts (80%) were POS by 18 F-NaF, of whom 14 pts were POS, 8 were IND, and 2 were NEG by corresponding TcBS; in the 4 pts with NEG 18 F-NaF, zero were POS, 2 were IND and 2 were NEG by corresponding TcBS. Conclusions: 18 F-NaF identified more malignant lesions than TcBS. 18 F-NaF may also add useful information in the management of advanced prostate cancer pts with and without known bone metastases.
NHS will publish national list of “low value” drugs to curb GPs’ prescribing costs
Authors: Gareth Iacobucci
Journal: BMJ (2017)

NHS England is to publish a national list of “low value” drugs as part of a new drive to reduce GPs’ prescribing costs.

The proposals were unveiled just a week after The BMJ reported that locally driven plans from clinical commissioning groups (CCGs) to limit GPs’ prescribing of over-the-counter medicines had sparked debate among GPs and had prompted calls for national guidance.1

Announcing its plans on Tuesday 28 March,2 NHS England said that it would now issue national guidance to CCGs from April 2017 to ensure consistency in how policies are applied. It said that the changes could save the NHS £400m (€462m; $496m) a year that could be reinvested to benefit patients better.

The review will initially focus on 10 treatments that NHS Clinical Commissioners—the body that represents CCGs—estimates could save £128m a year.3 These products, which include lidocaine plasters for treatment of post-herpetic …
Mobilized circulating endothelial progenitor cells after the first cycle of chemotherapy with prophylactic G-CSF can be used as a predictive biomarker and patient selection marker for anti-angiogenesis combination treatment
Authors: S. Shin, H. Jeung, J. Ahn, H. Choi, B. Cho, S. Rha, N. Yoo, J. Roh, H. Chung, H. Chung
Journal: Journal of Clinical Oncology (2007)

4638 Background: We investigated whether the level of circulating endothelial progenitor cells (CEPs) and endothelial cells (CECs) could be used as surrogate predictors of clinical outcome in patients receiving taxotere-based chemotherapy for advanced gastric cancer. Methods: Peripheral blood mononuclear cells were obtained in 49 gastric cancer patients who received taxotere combined with 5-FU and leucovorine (FLT regimen) after chemotherapy and prophylactic G-CSF treatment. To categorize the endothelial cells, immunofluorescent staining for specific endothelial cell markers (CD34, vWF, P1H12, CD31) was used. The changes of CEPs and CECs and their clinical significance on the response prediction and prognosis were analyzed. Results: After the first cycle of chemotherapy, the numbers of CD34 + /vWF + , CD34 + , vWF + , P1H12 + and CD31 + cells of 49 patients were 19.5 (2.7% of PBMCs), 20.1 (2.7%), 30.0 (4.8%), 12.9 (2.7%) and 214.3 (26.5%) cells/ml, respectively. The number of CD34 + /vWF + and CD34 + cells after the first and second cycle of chemotherapy were found to be higher in non-responders than responders (the first cycle: P=.012 and P=.008, the second cycle: P=.027 and P=.013, respectively). Moreover, the level of CD31 + cells after the second cycle of chemotherapy were significantly decreased compared with the first cycle in the patients who showed response (P=.026). In non-responders, however, the level of CD34 + cells was significantly increased after the second cycle of chemotherapy (P=.034). The level of CD34 + cells significantly related to the median time to progression (TTP) (6.1 and 4.0 months in CD34 low and CD34 high , respectively, cutoff level: 5.8, P=.046). Conclusion: CD34 + /vWF + and CD34 + cells can be used as a biomarker for prediction and prognosis in taxotere-based chemotherapy. CEP after the first cycle of chemotherapy can be a selection marker for addition of anti-angiogenic treatment after chemotherapy. No significant financial relationships to disclose.
Gemcitabine and S-1 as first-line chemotherapy in patients with metastatic or advanced pancreatic cancer.
Authors: Weijia Fang, Peng Zhao, Yi Zheng, Weiqin Jiang
Journal: Journal of Clinical Oncology (2017)

492 Background: Gemcitabine and S-1 are both effective antitumor chemotherapeutic agents for pancreatic cancer. We evaluate the efficacy and safety of the combination of gemcitabine (GEM) and S-1 (GS) as first-line chemotherapy in Chinese patients with metastatic or advanced pancreatic cancer. Methods: Patients with previously untreated metastatic or advanced pancreatic cancer who had measurable lesion(s) were enrolled. Gemcitabine was administered intravenously at a dose of 1,000 mg/m (2) during 30 min on days 1 and 8 and oral S-1 was given twice daily (BSA &lt; 1.25 m(2), 80 mg/day; 1.25 ≤ BSA &lt; 1.50 m(2), 100 mg/day; 1.50 m(2) ≤ BSA, 120 mg/day) on days 1-14 followed by a drug-free interval of 1 week every 21-day cycle. Results: Twenty-five patients were enrolled between 2012 and 2014. The assessed overall response rate was 24 % partial response in 6 patients, 56 % stable disease in 14 patients, and 20 % progressive disease in 5 patients. Sixteen patients (64 %) received second-line chemotherapy. The estimated median progression-free survival and median overall survival times were, respectively, 5.6 months (95 % CI 4.1-6.7 months) and 10.2 months (95 % CI 6.5-14.2 months). The major hematological toxicities were included grade 3/4 leucocytopenia in 8 patients (32 %), grade 3/4 neutropenia in 13 patients (52 %), and one patients (4 %) suffered grade 1 febrile neutropenia. The common grade 3/4 non-hematological toxicity was Anorexia, rash and fatigue, held the proportion of 12%, 16% and 12%, respectively. Conclusions: Gemcitabine and S-1 (GS) combination therapy showed promising activity with acceptable toxicities as first-line chemotherapy in Chinese patients with metastatic or advanced pancreatic cancer.
Health-Related Quality of Life (HRQoL) Measurements in Multiple Myeloma Patients Obtained By EORTC QLQ-C30; A Critical Review of Interpreting HRQoL Data in Longitudinal Studies
Authors: Lene Kongsgaard Nielsen, Mary Jarden, Christen Lykkegaard Andersen, Henrik Frederiksen, Niels Abildgaard
Journal: Blood (2016)
Use of high-intensity surveillance in patients following a diagnosis of stage I-II non-small cell lung cancer.
Authors: Jason Dennis Wright, Alfred I. Neugut, Zainab Siddiq, Sherry A. Glied, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2013)

6505 Background: The incidence of stage I and II lung cancer has been increasing due to the reported benefits of CT screening in high risk individuals. Guidelines suggest continued surveillance following diagnosis, however the extent to which this is done is unclear. We examined the patterns and predictors of surveillance imaging in patients following a diagnosis of stage I-II non-small cell lung cancer (NSCLC). Methods: The SEER-Medicare database was used to identify patients with stage I-II, NSCLC who underwent curative intent surgical resection from 2000-2006.Three surveillance periods (6-18, 18-30, 30-42 months) after diagnosis were identified. Use of imaging was quantified for each period and logistic regression models developed to examine predictors of thoracic imaging during all 3 surveillance periods. Results: Between 2000-2006 5269 patients were identified. During the first year of surveillance use of chest CT (48% in 2000 to 78% in 2006) and PET (2% to 23%) increased while use of bone scan (12% to 6%) and chest radiography (87% to 71%) decreased over time. Similar trends were noted for surveillance periods 2 and 3. During the study, surveillance imaging was performed in all 3 surveillance periods in 38% of the cohort. Yearly surveillance imaging increased with time; 21% of patients diagnosed in 2000 vs. 78% diagnosed in 2006 underwent testing in the first 3 years of follow-up (P&lt;0.0001). In a multivariable model, in addition to year of diagnosis, patients with high socioeconomic status (OR=1.96; 95% CI, 1.51-2.55 compared to low SES) were more likely to undergo yearly surveillance imaging, while Hispanics (OR=0.42; 95% CI, 0.21-0.85) and older patients (OR=0.52; 95% CI, 0.43-0.63) were less likely to undergo testing. Conclusions: The use of costly diagnostic imaging of uncertain value is increasing rapidly for patients with localized NSCLC. Non-clinical factors including high socioeconomic status and white race are among the strongest predictors of use of high intensity surveillance.
NOTCH1-mutated chronic lymphocytic leukemia cells are characterized by a MYC-related overexpression of nucleophosmin 1 and ribosome-associated components
Authors: F Pozzo, T Bittolo, E Vendramini, R Bomben, P Bulian, F M Rossi, A Zucchetto, E Tissino, M Degan, G D’Arena, F Di Raimondo, F Zaja, G Pozzato, D Rossi, G Gaidano, G Del Poeta, V Gattei, M Dal Bo
Journal: Leukemia (2017)
Prognosis of renal cell carcinoma with bone metastases: Experience in 300 consecutive patients.
Authors: Fiorella Ruatta, Lisa Derosa, Laurence Albiges, Christophe Massard, Yohann Loriot, Karim Fizazi, Bernard Escudier
Journal: Journal of Clinical Oncology (2017)

463 Background: Bone metastases (BMs) are associated with significant morbidity and shorter survival in metastatic renal cell carcinoma (mRCC). Our purpose was to identify prognostic factors for mRCC patients (pts) with BMs. Methods: Data from mRCC pts with BMs, treated at Gustave Roussy between April 1992 and March 2016, were retrospectively collected. Age, sex, ECOG-Performance Status (PS), Memorial Sloan-Kettering Cancer Center (MSKCC) score, histology, number and site of BMs, concomitant metastases (presence and sites), therapy for BMs (radical resection or palliative surgery, radiotherapy, other local and systemic treatments), time to BMs, and outcome were analyzed. Synchronous solitary bone metastasis (SSBM) was defined as a single bone metastasis without concomitant visceral lesions at the initial diagnosis of RCC. Overall survival (OS) was calculated from the date of BMs diagnosis to death or last follow-up using Kaplan-Maier method and modelled with Cox-regression analysis. Results: Three hundred pts were identified. Median time to BMs was 32.4 months (range 0–324 months). In 64 pts (21%), bone was the only metastatic site and 22 of them (7%) had a SSBM; 236 pts (79%) had concomitant metastases in other sites. Median OS was 23.22 months. SSBM pts had better OS then those with concomitant metastases (40 vs. 20 months; p&lt;0.001). At univariate analysis, number of BMs (p&lt;0.0001), spinal column as site of BMs (p&lt;0.005), concomitant metastases (p&lt;0.0001), Fuhrman grade (p&lt;0.001), non-clear cell histology (p&lt;0.003), and MSKCC score (p&lt;0.001) were significantly associated with poor prognosis. At multivariate analysis, concomitant metastases remained predictor of poor prognosis while good MSKCC, radical resection, and SSBM were predictors of better OS. Conclusions: To our knowledge,this is the largest single-institution experience evaluating prognosis in pts with BMs from RCC. This study suggests that MSKCC score, number of BMs (1 vs. &gt;1) and radical resection are prognostic factors. Additionally, in presence of solitary bone metastasis without other concomitant metastases at the initial diagnosis of RCC, bone surgery should be considered to achieve local tumor control and increase survival.
The impact of docetaxel-related toxicities on health-related quality of life in patients with metastatic cancer (The QoLiTax-Trial of the Arbeitsgemeinschaft Internistische Onkologie, AIO).
Authors: Claudia Pauligk, Wael Hozaeel, Ralf Hofheinz, Axel Hinke, Christiane Windemuth-Kieselbach, Felix Karl Tauchert, Andreas Hübner, Martin Burmester, Michael Koenigsmann, Jörg Wiegand, Jochen Eggert, Manfred Welslau, Rosemarie Kuhl, Salah-Eddin Al-Batran
Journal: Journal of Clinical Oncology (2014)

9621 Background: Docetaxel is a widely used cytotoxic agent. It causes a number of side effects, most frequently leukopenia and neutropenia, alopecia, nausea, diarrhea, and fatigue. This study evaluates the impact of docetaxel toxicities on patient’s health-related Quality of life (QoL). Methods: We conducted a multicenter, prospective, non-interventional trial, in which the QoL was assessed using the EORTC QLQ-C30 questionnaire at baseline and every 4 weeks up to 40 weeks in patients receiving a docetaxel-based chemotherapy for metastatic disease. The primary endpoint was the 4-months ≥5% deterioration rate of the global health status/QoL scale in patients with vs. those without grade 3/4 leukopenia or neutropenia. Secondary endpoints were the effect of other treatment-related adverse events on QoL. Uni- and multivariate analyses were applied. Results: From January 2008 to June 2011 a total of 2,659 patients were included. The majority of patients (48.1%) had prostate cancer, followed by breast (17.1%) and non-small-cell-lung cancer (15.8%). Patients received a median of 5 docetaxel cycles with median dose of 75 mg/m². The 4 months ≥5% deterioration rate of the global health status/QoL was similar between patients with and without grade 3 or 4 leukopenia/neutropenia (adjusted odds ratio 1.024, p=.4). Among other treatment-related toxicities, the presence of grade 3/4 diarrhea showed the strongest effect on global health status/QoL average scores (50.91 vs. 33.06), followed by vomiting (50.91 vs. 35.17), dyspnea (50.94 vs. 35.81), stomatitis (50.88 vs. 36.41), nausea (50.91 vs. 36.68), infection (50.90 vs. 37.14), fatigue (50.90 vs. 43.82) and anemia (50.91 vs. 41.03), p<0.05 for all comparisons. Grade 3/4 leukopenia/neutropenia, alopecia, constipation, neuro- and nail toxicity had no significant impact on the global health status/QoL or other items. Conclusions: Docetaxel associated non-hematological toxicity, but not isolated leukopenia strongly impact patient’s QoL. This has to be considered by clinicians while making therapeutic decisions.
Evaluation of the psychosocial needs of cancer survivors.
Authors: Smitha Pabbathi, Ariana Abid, Kanan Mehta, Dinorah Tyson Martinez, Carrie Hall, Susan McMillan
Journal: Journal of Clinical Oncology (2017)

207 Background: Even after enduring successful treatment of their cancer, the late physical and psychosocial effects of treatment often continue to haunt as many as 50% of survivors. Furthermore, the needs of cancer survivors differ from those undergoing active treatment. However, there is a lack of comprehensive assessment for providers caring for survivors. Therefore, there is a need for one tool to assess the physical and psychosocial needs as well as evaluate their severity when initially establishing care in general survivorship clinic. In this study, we determine the most commonly identified of these needs as well as the degree to which they impact overall health of this population. Methods: A retrospective chart review of 220 patient records from the past six years in General Survivorship Clinic using Moffitt Cancer Center’s EHR was performed. All patients (ages 18-85 years) diagnosed with cancer without evidence of current disease and who had complete Clinical Needs Assessment Tool for Cancer Survivors (CNAT-CS) were eligible for inclusion. The CNAT- CS is a questionnaire of 36 items on which survivors identify as “not a concern”, “is a concern but I am managing”, or “I need help”. Results: A majority (65.5%) was female and white (81.3%); African Americans made up 11.4%. The mean age was 57.6 (SD = 11.3). Subjects had survived a variety of types of cancer with more than half (57%) having breast cancer. Their mean distress score was 2.75 (SD = 2.86). Fear of recurrence was the concern most often identified (56%), followed by feeling of high stress (50%), sleep disturbances (49%) and memory/ attention difficulties (40%). Highest scores were found on items about fear of the cancer returning (Mean = 0.71; SD = .55), information needed for follow-up care (mean = .64; SD = .59), stress in my life (mean = .60; SD = .65) and trouble with my memory/attention (mean = 0.52; SD = .69). Conclusions: These results indicate a relatively low mean distress score from the distress thermometer. Areas identified most frequently as a concern also tended to be the areas with the highest mean scores. Although almost 20% of survivors were in minority groups, ethnic minorities were underrepresented in this sample. Thus, future studies should focus on increasing the representativeness of the sample.
Validation of the predictive value of modeled HCG residual production “P” in low-risk gestational trophoblastic neoplasia (GTN) patients treated in GOG-174 phase III trial.
Authors: Benoit You, Wei Deng, Amit M. Oza, Raymond Osborne
Journal: Journal of Clinical Oncology (2012)

5110 Background: In low-risk GTN, chemotherapy is changed according to serum hCG levels. We previously showed mathematical modeling of hCG kinetics provides a parameter production “P”, a useful early predictor of methotrexate (MTX) resistance (You et al; Ann Oncol 2010; ASCO and ISSTD 2011). We applied this approach to patient cohort of GOG-174 trial, in which weekly MTX (Arm 1) was compared to dactinomycin (Arm 2). Methods: Database (210 patients, including 78 with resistance) was split into 2 sets. A 126 patient Model Set was initially used to adjust model parameters. Patient hCG kinetics from day7 to day50 were fit with NONMEM™ program to: “[hCG(time)] = hCG0 i * exp(–k*time) + P”; where P is residual hCG tumor production, hCG0 i is the initial hCG level, and k is the rate constant. Three putative P-based classifiers of resistance were assessed using ROC analyses. Then an 84 patient Test Set with blinded-resistance status was used to assess the validity of predictions. The primary endpoint was treatment resistance defined as relapse and/or lack of hCG normalization. Results: Due to initial surge in 14% patients, hCG kinetic modeling was started on day7. Individual hCG decline profiles of Model Set patients were modeled. There was no impact of treatment arm on variability of kinetic parameter estimates. The best P cut-offs to discriminate resistant vs. sensitive patients were 7.7 in Arm 1 and 74.0 in Arm 2. They were combined to define 2 predictive groups with low vs. high risks of resistance (ROC AUC = 0.82; Se = 93.8%; Sp = 70.5%). The model was then applied to Test Set patient cohort. The predictive value of P-based predictive groups regarding resistance was reproducible (ROC AUC = 0.81; Se = 88.9% (95% CI: 70.8%-97.7%); Sp = 73.1% (95% CI: 60.0%-84.4%)). Both P and treatment arm were associated with resistance using multivariate logistic regression tests. Predictive value of P was less accurate in dactinomycin arm. Conclusions: The early predictive value of the modeled kinetic parameter P regarding resistance appears promising in GOG-174 study, especially in MTX arm. This is the second positive evaluation of this procedure study. Prospective validation is warranted.