tbuckley/cabot-search huggingface dataset:
Optimization of the size variation threshold for imaging evaluation of response in patients with platinum-refractory advanced transitional cell carcinoma of the urothelium treated with vinflunine.
Authors: K. M. Krajewski, R. Fougeray, T. K. Choueiri, F. Pons, F. A. B. Schutz, J. E. Rosenberg, Y. Salhi, J. Bellmunt
Journal: Journal of Clinical Oncology (2011)

4570 Background: Vinflunine (VFL) has been approved in the European Union for second-line treatment of advanced transitional cell carcinoma of the urothelial tract (TCCU) in patients who progress after a platinum-based regimen. In the phase III trial comparing VFL and best supportive care (BSC) with BSC alone, patients receiving VFL+BSC demonstrated a survival advantage, however, very few patients achieved criteria for response by RECIST. Therefore, another “response” threshold may be more useful than RECIST 1.0 in this setting. Methods: 179 patients with advanced TCCU treated with second-line VFL therapy had chest CT scans and abdominal/pelvic CT or MRI performed at baseline and at first follow-up after therapy initiation. Tumor measurements and response by RECIST 1.0 were correlated with overall survival (OS). Kaplan-Meier and receiver operating characteristic (ROC) analysis were then used to determine if there was an optimal size threshold to define “responders” and “non-responders”. The impact of known adverse prognostic factors including ECOG PS >0, Hb <10g/dL, and liver metastases were adjusted for. Results: Tumor response included 13 partial response (PR) by RECIST 1.0 and 51 patients with >10% decrease in the sum of longest diameters (SLD). Responders by RECIST 1.0 did not have a statistically significant improvement in OS compared to non-responders. On the other hand, the threshold of 10% decrease in the SLD correlated with OS and showed optimum sensitivity and specificity among the thresholds. Patients with SLD reduction of >10% had a longer OS than those with SLD reduction of <10%: 11.3 versus 6.9 months (logrank p=0.02). ROC analysis yielded 10% decrease in SLD as the optimal size change that correlates with OS. These results persisted on multivariate analysis. Conclusions: A reduction of 10% in the SLD on the first follow-up imaging study is a better early predictor of disease outcome than response criteria using RECIST in patients with advanced TCCU receiving second-line VFL therapy.
An umbrella protocol for histology-independent, phase I modular study based on EGFR mutation status: Using erlotinib alone or in combination with cetuximab, bortezomib, or dasatinib to overcome resistance.
Authors: J. Fok, R. Kurzrock, A. M. Tsimberidou, S. Wen, A. Naing, D. S. Hong, F. Janku, G. S. Falchook, S. A. Piha-Paul, R. Katz, S. Fu, S. L. Moulder, J. J. Wheler
Journal: Journal of Clinical Oncology (2011)

2536 Background: Combinations of EGFR inhibitors and other targeted agents in patients whose tumors have EGFR mutations and/or have previously responded to EGFR inhibitors but then progressed may provide synergy and help overcome resistance. Methods: Patients with advanced cancers received daily erlotinib at an oral dose of 150 mg or daily erlotinib at an oral dose of 100-150 mg with either bortezomib 1mg/m2 – 1.3mg/m2 IV days 1,4,8 and 11, or cetuximab 125mg/m2 – 250mg/m2 IV weekly, or oral dasatinib 50-70mg bid. An umbrella Phase I 3+3 trial was designed to determine MTD. At MTD, additional patients with EGFR mutations and/or prior response to EGFR inhibitors were treated in the expansion cohorts. Results: Sixty-nine patients have been enrolled to date. In the erlotinib/bortezomib arm, no significant toxicities have been observed. MTD is erlotinib 150mg PO qd/bortezomib 1.3mg/m2 IV d1,4,8 and 11). In the erlotinib/cetuximab arm, 1 DLT was observed (grade 3 rash). MTD is erlotinib 150mg PO qd/cetuximab 250mg/m2 IV weekly. In the erlotinib/dasatinib arm, 2 patients experienced DLTs (grade 3 rash; grade 3 diarrhea). MTD is erlotinib 75mg PO qd/dasatinib 70mg PO qd). 7 patients with EGFR mutations have been evaluated. 2 of these patients received prior EGFR therapy with PD. 3/7 EGFR+ patients (43%) had SD > 5 mos or PR: a patient with EGFR+ NSCLC (no prior EGFR inhibitor exposure) treated with erlotinib/cetuximab (PR; 9+ mos); a patient with EGFR+ NSCLC (previously failed an EGFR inhibitor) on erlotinib/bortezomib (SD, 7 mos); and, a patient with EGFR+ parathyroid cancer (no prior EGFR inhibitor exposure) treated with erlotinib (SD, 5 mos). Of 48 patients without an EGFR mutation, 6 patients (11%) had SD for > 4 months. Conclusions: Treatment with erlotinib combined with bortezomib, cetuximab or dasatinib has demonstrated safety and is a feasible approach.
Assessing the quality of breast cancer care in cancer center hospitals in Japan.
Authors: T. Higashi, F. Nakamura, H. Mukai, T. Sobue, E. Mekata, M. Ohtani, S. Higashide, T. Shinkai, T. Okamura
Journal: Journal of Clinical Oncology (2011)

e16566 Background: Breast cancer is the most frequently occurring cancer among women in Japan and in many parts of the world. Advances in breast cancer care are expected to reduce the burden of the disease. To do so, however, the currently available knowledge must be applied to patients by their primary providers. We aimed to examine the current status of the quality of breast cancer care in community cancer center hospitals in Japan. Methods: A panel of multidisciplinary experts developed 43 process-of-care quality indicators based on clinical practice guidelines and the medical literature. Each quality indicator described target patients and the standards of care these patients should receive. We applied these quality indicators to the care provided to a cohort of patients diagnosed with breast cancer at the 17 participating cancer care hospitals in 2008 using medical record abstraction. Results: The care provided to a total of 1,051 breast cancer patients was examined. Overall, 76% of care processes were provided as indicated. Although many quality indicators appeared reasonably satisfied (e.g., trastuzumab for lymph node-positive patients, 96%, and hormone receptor test, 97%), we identified significant room for improvement in some areas of care. Patient explanation generally appeared insufficient; 37% of mastectomy patients received information on reconstruction surgery, and 54% of surgical patients were informed of both sentinel lymph node biopsy and lymph node dissection. Among patients with “2+” results in the HER-2 immunohistochemistry test, 64% were evaluated using fluorescence in situ hybridization. Patients who underwent breast-conserving surgery received radiation therapy 70% of the time. Type three 5-hydroxytryptamine (5-HT3) receptor antagonists were prescribed along with a highly emetic regimen 96% of the time, whereas steroids were prescribed 79% of the time. We also revealed a variation in quality across hospitals. Conclusions: There is room for improvement in the quality of breast cancer care provided in community cancer center hospitals. Systematic efforts to continuously monitor quality focusing on the identified gaps in care are necessary to improve breast cancer care in Japan.
The Risk of Central Nervous System (CNS) Relapses in Patients with Peripheral T-Cell Lymphoma
Authors: Dai Chihara, Michelle A Fanale, Roberto N. Miranda, Mansoor Noorani, Jason R. Westin, Loretta J. Nastoupil, Fredrick B. Hagemeister, Luis E. Fayad, Jorge E. Romaguera, Felipe Samaniego, Francesco Turturro, Hun Ju Lee, Sattva S. Neelapu, Alma Rodriguez, Michael Wang, Nathan Fowler, L. Jeffrey Medeiros, Richard Eric Davis, Yasuhiro Oki
Journal: Blood (2016)
Delirium assessment in patients with advanced cancer presenting to the emergency department of a comprehensive cancer center.
Authors: Ahmed F. Elsayem, Alan D. Valentine, Carla L. Warneke, Valda D Page, Eduardo Bruera, Sai-ching J. Yeung, Patricia A Brock, Julio Silvestre, Holly Michelle Holmes, Knox H Todd
Journal: Journal of Clinical Oncology (2015)

217 Background: The exact frequency of delirium among patients with advanced cancer presenting to emergency departments (EDs) is unknown. The purpose of this study is to determine the prevalence of delirium among patients with advanced cancer who present to the ED at MD Anderson Cancer Center. Methods: The exact frequency of delirium among patients with advanced cancer presenting to emergency departments (EDs) is unknown. The purpose of this study is to determine the prevalence of delirium among patients with advanced cancer who present to the ED at MD Anderson Cancer Center. Results: A total of 624 patients were screen for this study, and 243 patients were enrolled. The main reasons for exclusion were: 1) cancer was not advanced, 2) the patient had been in the ED for over 12 hours and 3) the patient was non-English speaking. The median age for all patients enrolled was 62 years (range 19 – 89 years), 167 (69%) were white, and 120(49.4) were female. CAM was positive in 22(9%) of patients. The median MDAS score of CAM positive patients was 14 (range 9 – 22 out of 30). Ten (10%)of 99 patients aged 65 and older were delirious as compared to 12 (8%) of 144 patients younger than 65 years (p = 0.6). Physician correctly predicted delirium in 13 patients (59%). Among the patients who were CAM positive 18 (82%) were admitted to the hospital as compared to 115 (52%) of patients without delirium (p = 0.012). Patients with delirium had higher hospital, and six months mortality rate. Conclusions: Delirium was identified in 9% of patients with advanced cancer visiting an ED, and is associated with more hospitalization and poor survival.
Understanding the comorbidome and its effect on survival in colorectal cancer.
Authors: Erin Elizabeth Hahn, Ernest Shen, Janet S. Lee, Corrine E. Munoz-Plaza, Carly Parry, Michael K Gould
Journal: Journal of Clinical Oncology (2016)

210 Background: Effectively managing comorbidities is an essential component of high-quality cancer care. Evidence suggests colorectal cancer (CRC) patients with multiple comorbid conditions are less likely to complete standard treatments and can have lower rates of survival. In order to provide personalized care, it is critical to understand how comorbid conditions cluster within CRC patients. Methods: We identified Kaiser Permanente Southern California CRC patients diagnosed with first malignancy between 01/01/2008 - 12/31/2013. We used latent class analysis to identify clinically useful phenotypes defined by combinations of comorbidities at diagnosis, and compared survival using the Kaplan-Meier method. Results: The cohort included 7803 patients: 52% male; average age at diagnosis 66 years (SD: 13); 22% Hispanic, 15% Black, 9% Asian, 52% White; 42% Stage I, 22% Stage II, 22% Stage III, and 14% Stage IV. One-fifth of patients had a Charlson comorbidity index score of ≥ 4. We found 4 distinct classes (Lo-Mendell-Rubin p&lt;0.001). Class 1 was relatively healthy with few comorbidities (Table). Class 2 included individuals with cardiovascular diseases; those in Class 3 had complicated diabetes. Class 4 members had multiple chronic conditions, including diabetes with micro- and macrovascular complications. Kaplan-Meier estimates revealed a statistically significant difference in overall survival by class (log rank p&lt;0.001). Conclusions: We identified 4 clinically distinct classes of comorbid conditions in CRC patients. These data can be used to inform personalized care for CRC patients throughout the cancer care continuum. [Table: see text]
The effect of blocking the prosurvival AKT/P13K/mTOR and mutant KRAS–signaling pathways on chemotherapy resistance of pancreatic cancer.
Authors: C. Cong, S. Lu, D. Shrayer, H. J. Wanebo, Y. Wan, W. Bowen
Journal: Journal of Clinical Oncology (2011)

e13514 Background: Pancreatic adenocarcinoma continues to be a highly lethal malignancy (5 yr survival 5%) is poorly responsive to all chemotherapy and has only modest sensitivity to the current best. C6 ceramide demonstrates chemo enhancement of gemcitabine, cetuximab and other agents in vitro. Exploration of the C6 mechanism suggests reversal of chemo resistance pathways – pro-survival and mutant KRAS-signaling in pancreatic cancer cells. Methods: In vivo: 2-3 month SCID male mice with pancreatic (pan) tumor implants (2 x 106 L3.6 cells) received intraperitoneal (I.P.) injections (3x/wk) of paclitaxel (Pax) (3.0mg/gm), gemcitabine (Gem, 10mg/gm) with/without C6 ceramide (10mg/mL) and were observed 6 weeks and tumor response/survival recorded. In vitro: drug dose Pax 3ug/mL, Gem 3 ug/mL, C6 ceramide 10 ug/mL. The MTT anti tumor response was measured in 3 pancreatic lines L3.6, PANC-1, and MIA (Kras mutated). Signaling activation by Western blot utilized antibodies: LY294002, and Wortmannin to block PI3K/AKT pathway, U0126 and PD 98059 to block ERK pathway and rapamycin to block mTORC1 pathway. Results: Administration of Gem or Pax with C6 ceramide induced a significant increase in cell death and apoptosis in pancreatic cancer cells (L3.6, PANC-1 and MIA PaCa-2) which were associated with inhibiting perturbations of cell signaling pathways including pro-survival PI3K/Akt/mTOR, and ERK/MAPK, Ras signaling pathways. Pharmacological inhibition with specific signaling pathway inhibitors enhanced cytotoxicity by Gem or Pax, suggesting that survival pathway inhibition might be the key mechanism contributing to C6 ceramide inhibition synergism of Pax or Gem antitumor effects. Conclusions: C6 Ceramide an apoptosis signal potentiates the anti tumor effects of chemo agents Gem and Pac and the biologic EGFR inhibitor cetuximab against 3 aggressive pancreatic cancer cell lines by apparent inhibition of the pro-survival PI3K/AKT/mTOR pathways and the Kras mutated ERK/MAPK pathway.
Postchemotherapy neutropenia: Should National Cancer Institute (NCI) grade 4 (G4) be further subclassified? Experience from Nairobi.
Authors: N. A. Othieno-Abinya, S. A. Mwanzi, G. O. Yonga, S. Das
Journal: Journal of Clinical Oncology (2011)

e13009 Background: Neutropenia is the single most important dose-limiting toxicity in cancer chemotherapy, commonly graded according to World Health Organization (WHO)/NCI criteria. In a study we conducted in 2007, grade 4 neutropenia complicated 25.7% of non-leukaemia chemotherapy administrations, and 27.6% of patients hospitalised with febrile neutropenia died. Methods: A prospective study on neutrophil dynamics postchemotherapy between August 2009 and December 2010 inclusive. Prechemotherapy neutrophil counts were recorded, and also expected nadir counts according to the treatment protocol, or earlier in high risk patients who could not afford to have colony-stimulating factors. Chemotherapy protocols frequently administered were: doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 (AC) without or with 5-fluorouracil 600mg/m2 (CAF) for breast cancer; cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) without or with rituximab (R-CHOP) for non-Hodgkin’s lymphomas; or paclitaxel 175 mg/m2 with carboplatin (AUC6)(C/P) for epithelial ovarian cancer. Results: Seventy patients were included, with the most common diagnoses being - 34 (48.6%) with breast cancer, 11 (15.7%) with poor prognostic phenotype non-Hodgkin’s lymphomas and 6 (8.6%) epithelial ovarian cancer. A total of 282 treatment cycles were analysed. G4 neutropenia was registered following 34 treatments (12%) with nadir neutrophil counts as follows: < 50 neutrophils/ml (9); 50-99 (3); 100-199 (5); 200-499 (16). Time to G4 neutropenia varied narrowly according to chemotherapy protocol (Table). Three deaths were recorded, all in treatments in which neutrophil counts were below 200/ml at admission. Conclusions: Despite small numbers in, it is apparent that the outcome of severe neutropenia has greatly improved compared with the previous study, though neutrophil counts below 200 cells/ml remain problematic. The current improvements in supportive care may require further subclassification of G4 neutropenia. Time from treatment to grade 4 neutropenia (days) according to treatment protocol. Protocol Median Range Mean AC 12.5 8-16 11.5 CAF 15 14-16 14.7 CHOP 11 8-14 10.3 C/P 14 10-15 13
SBRT as an alternative to RFA for the treatment of primary and metastatic liver tumors.
Authors: Erqi Liu, Matthew H. Stenmark, Oliver E Lee, Matthew J Schipper, Elaine M Caoili, Edgar Ben-Josef, Theodore Steven Lawrence, Mary Uan-Sian Feng
Journal: Journal of Clinical Oncology (2012)

158 Background: Radiofrequency ablation (RFA) is a widely used local therapy for small, unresectable liver tumors (LT). Stereotactic body radiotherapy (SBRT) has been used for similar patients, and has the advantage that it can be used when lesions are adjacent to blood vessels, are difficult to reach and cannot be imaged on ultrasound. We examined RFA and SBRT outcomes for treating primary and metastatic LT at our institution and identified predictive factors for local control. Methods: This study included 62 patients (pts) with 106 LT (69 metastatic, 37 primary) treated with SBRT and 127 pts with 206 LT (80 metastatic, 126 primary) treated with RFA from 2000 to 2010. 42 lesions were ablated intra-operatively while 164 were ablated percutaneously. Mean tumor size by maximum diameter was 2.2 cm (0.4-11) and 2.3 cm (0.6-6.2) for RFA- and SBRT-treated LT, respectively. Freedom from local progression (FFLP) for SBRT was defined as absence of progressive LT within or at the PTV margin while FFLP for RFA was defined as recurrence within or immediately adjacent to the ablation zone. Results: With a median follow-up of 29.4 months (0.46 to 120.8), 1- and 2-yr FFLP rates for all SBRT- vs RFA-treated LT were 93% and 84% vs 86% and 83%. There were 14 cases of residual LT after RFA, 6 of which were re-ablated; these were not counted as RFA failures. Significantly more pts in the SBRT group had received prior systemic therapy (54% vs 31%, p=0.0001) and had active extrahepatic disease at treatment start (36% vs 23%, p=0.01). For SBRT, neither LT size nor dose predicted for FFLP. For RFA, tumor size ≥3 cm had worse FFLP (HR: 5.3, p&lt;0.0001) but an intraoperative approach had better FFLP (HR: −2.2, p=0.01). For tumors &gt;3cm, SBRT had significantly better FFLP than percutaneous RFA (HR: 0.32, p=0.018). In the RFA group, there were 9 complications, including pneumothorax, hemothorax, and small bowel injury, 2 of which resulted in death. In the SBRT group, there was 1 case of radiation-induced liver disease in a Child-Pugh Class B pt but no other significant toxicities. Conclusions: SBRT is a safe alternative to RFA, can be used in a wider variety of patients, and may be more effective than percutaneous RFA at locally controlling larger liver tumors.
NHS 111 sends more and more callers to emergency departments, analysis shows
Authors: Gareth Iacobucci
Journal: BMJ (2017)

The NHS 111 telephone advice service in England is sending an ever greater number and proportion of callers to emergency departments, an analysis by the healthcare think tank the Nuffield Trust has found.1

The analysis, based on monthly NHS figures and data from NHS England’s weekly winter operational updates published from 1 December to the end of February each year, showed that the number of people calling 111 who were either sent an ambulance or advised to go to their local emergency unit increased from around 150 000 a month to over 200 000 a month in …
“First chemotherapy” or “first local” approach for liver-only synchronic metastasis rectal cancer? A single institution experience.
Authors: Ismael Ghanem, Oliver Higuera Gomez, Alberto Mata, Jose Reyes, Nuria Rodriguez, Jose Castell, Ana B. Custodio, Virginia Martinez, Laura Guerra Pastrian, Jaime Feliu
Journal: Journal of Clinical Oncology (2015)

780 Background: Approximately 10% of patients (p) with rectal cancer have synchronic liver-only metastasis (RCSLM). Although local and systemic therapies are required for this setting, there is not a well defined sequence of treatments. We analyze both, the initial systemic and local approaches at a single institution. Methods: We retrospectively reviewed the medical records of RCSLM p between Jan 2006 and Dec 2013. The “first chemotherapy” (Ch) approach and the “first local” (Lo) approach (surgery or radiotherapy) were reviewed in terms of patient characteristics, tumour features and survival. Results: Forty-five p (26 men) with a median age of 65 years old (35-88) and ECOG 0-1 (91%) were analyzed. Most (84%) of the 32 p with known K-Ras status had wild-type. Twenty-five p (56%) had bilobar liver metastasis (LM) with a median number LM of 3 and a median size of 2.6 cm for the largest lesion. Thirty-four p (75%) were treated with curative intention and, liver and rectal resections (LRR) were performed for 24 p (53%). Bilobar LM (p=0.029), basal CEA&gt;60 (p=0.014), non-LRR (p=0.001) and non-R0 resection of LM (p=0.004) were found to be predictor of poor overall survival (OS). Twenty-five p were treated with Ch and 9 p with Lo approach”. Table 1 shows the characteristics of both groups of p. After a median follow up of 28 months there were 12 events (35%) with a median OS of 55m vs. not reached (p=0.72) for Ch and Lo respectively. Conclusions: Bilobar LM, basal CEA&gt;60, non-LRR and non-R0 resection of LM were predictors of poor OS. The Ch approach was chosen for patients with worse prognostic. However, there were no significant differences in OS between Ch and Lo approaches. Clinical trials are needed to evaluate the best therapy strategy at this setting. [Table: see text]
Three-Dimensional Eye Shape, Myopic Maculopathy, and Visual Acuity: The Zhongshan Ophthalmic Center–Brien Holden Vision Institute High Myopia Cohort Study
Authors: Xinxing Guo, Ou Xiao, Yanxian Chen, Huawang Wu, Linxing Chen, Ian G. Morgan, Mingguang He
Journal: Ophthalmology (2017)
Validation of a plasma-based miRNA PCR test for early detection of colorectal cancer.
Authors: Søren Jensby Nielsen, Hanni Willenbrock, Jacob Fog, Jan Stenvang, Thorarinn Blondal, Torben Orntoft, Nils Brünner, Claus Lindbjerg Andersen, Hans J. Nielsen, Adam Baker
Journal: Journal of Clinical Oncology (2012)

424 Background: Colorectal cancer (CRC) is a major cause of mortality in the western world. Early detection of CRC improves survival and screening for CRC has been clinically proven to lower CRC-related mortality in the screening population. However, although population screening programs have been implemented in a number of countries, screening rates among the 50-75 year olds are unsatisfactory. There is therefore a clear unmet need for a quick, sensitive, specific, and minimally invasive screening assay to select at risk individuals for definitive diagnosis by colonoscopy. Methods: In order to detect microRNA (miRNA) biomarkers for CRC in blood plasma, we developed an LNA-enhanced miRNA RT-qPCR platform with high sensitivity and linearity for optimal quantitation of miRNAs from limited plasma samples. A clinical reference- lab compatible workflow that allows for the entire procedure from sample preparation through data acquisition and QC to test result to be completed within one working day was established. A reference melting curve database has been implemented to ensure the integrity of each data point, and appropriate controls monitor plate-to-plate and day-to-day variation. State-of-the-art normalization protocols have been evaluated to ensure optimal normalization of datasets prior to data analysis. Results: We previously determined a miRNA signature in a multi hospital discovery cohort that is differentially expressed between healthy individuals and stage II CRC patients. Here we report on the validation of this miRNA signature in an independent set of plasma samples from CRC patients and healthy volunteers. We have counter-screened the miRNA signature in a set of patients with other prevalent diseases, including hypertension, diabetes, diverticulitis, and others. Conclusions: A plasma miRNA signature for early detection of CRC from patient plasma was developed and validated in an independent clinical sample set. The signature was specific with respect to other diseases prevalent in the screening population. A second large-scale validation project is on-going. We conclude that plasma miRNA biomarkers can constitute an effective minimally invasive approach to population-wide CRC screening.