tbuckley/cabot-search huggingface dataset:
Application of ALBI and PALBI score as prognostic variables in hepatocellular carcinoma patients treated with transarterial-chemoembolization.
Authors: Preetha Aravind, Kiruthikah Thillai, Abid Suddle, Nigel Heaton, John Karani, Pauline Kane, Praveen Peddu, Dylan Lewis, Debashis Sarker, Paul J. Ross
Journal: Journal of Clinical Oncology (2017)

241 Background: Albumin-Bilirubin Score(ALBI) is simple prognostic tool to stratify HCC patients on liver function. It is proposed as more accurate predicting score of hepatic dysfunction compared with Child-Pugh (CP) grading. Platelet-Albumin-Bilirubin Score (PALBI) incorporating platelet count may offer further prognostic sensitivity. We sought to correlate ALBI, PALBI and CP grade with overall survival in HCC patients who underwent transarterial-chemoembolization (TACE). Methods: 431 HCC patients who received TACE between 2006 and 2012 at a Liver Centre, UK was included. Serum albumin, bilirubin and platelet were used to calculate ALBI and PALBI scores. Patients were classified into three groups using previously described formulas. Survival outcomes (Median OS) were measured using Kaplan-Meier method. Results: Median age of study population was 62 years. Patients classified by ALBI score, Group 1 was 208 patients (48%), 2 was 196 (45.4%) and 3 was 27 (6.3%). Median OS for Group 1 was 26.1 months (m) (95% CI 19.5-32.6), 2 was 18.6m (95% CI 14.9-21.5) and 3 was 11.7m (95% CI 6.1-17.3) (p &lt; 0.001). PALBI Group 1 was 179 (41.5%), 2 was 150 (34.8%) and 3 was102 (23.7%). PALBI group 1 had median OS 25.5m (95% CI 17.9-33.1), 2 had 22.3m (95% CI 18.3-26.3), 3 had 10m (95% CI 5.9-14.3) (p &lt; 0.001). Majority were class CP-A. (A = 365, B = 63, C = 2). CP-A patients were re-stratified on ALBI and PALBI status. ALBI Group 1 (N = 204) OS 26.0m (95% CI 19.5-32.6), 2 (N = 151) OS 19.1m (95% CI 14.7-23.5), 3 (N = 7) OS 7.6m (95% CI2.27-12.9) (p = 0.04). Survival of CP-A patients by PALBI was significantly different - Group1 (N = 175) OS 28.8m (95%CI 20.79-36.74), 2 (N = 140) OS 22.6m (95%CI 18.89-26.25) and 3 (N = 50) OS 8.9m (95%CI 6.25-11.5) (p &lt; 0.001). Conclusions: Significant comparable survival difference was seen in ALBI and PALBI groups. CP-A patients with group 3 ALBI or PALBI had significantly poorer survival than groups 1 and 2 suggesting increased sensitivity determining hepatic dysfunction compared with CP status. Our results suggest ALBI and PALBI scores likely more accurate stratifying method for mild liver disease and guide treatment. Further prospective studies using both scores are warranted.
The CHAPPP study: Changing care with PSMA-PET for prostate cancer—A retrospective study of the role of PSMA imaging in altering treatment pathways.
Authors: Andrew Schmidt, Jeffrey C. Goh, Manoj Bhatt, Paul Thomas, Aneta Suder
Journal: Journal of Clinical Oncology (2017)

13 Background: The low sensitivity of standard imaging (SI) techniques in detecting metastases (Ms) may lead to unnecessary local treatment for patients (Pts) with newly diagnosed or recurrent prostate cancer (PC). Ga-68-PSMA (Prostate Specific Membrane Antigen)-PET-CT is a novel imaging technique with increased sensitivity in detection of PC especially at low PSA values and may change the decision to pursue primary local or salvage treatment. This study quantified changes in definitive local treatment secondary to occult Ms detected on Ga-68-PSMA not visualized on SI. Methods: A retrospective study was performed of 509 consecutive PSMA scans (and 481 Pts) at our tertiary cancer centre, the Royal Brisbane and Women’s Hospital between Sept 2014 and Dec 2015. PSMA imaging was compared with a CT scan and bone scan to determine whether PSMA results altered the decision to pursue local treatment. Results: 81 (16%) Pts had PSMA-PET-CT scan and no Ms on SI, 40 prior to definitive local treatment and 41 as work up for recurrence. 9/40 Pts (23%) undergoing primary work-up had PSMA-identified Ms not visible on SI and altered these patients treatment pathway (mean PSA 20.5 ng/mL). Because of PSMA-diagnosed Ms, 3 did not receive local treatment. 4 had pelvic nodal involvement and received definitive radiotherapy (RT) including nodal fields. 2 Pts proceeded to radical prostatectomy with the addition of lymph node dissection. 41 Pts investigated for recurrence following local treatment had SI for comparison, (mean PSA 4.7, range 0.11 – 35 ng/mL). 11/41 (27%) were found to have distant or nodal Ms not visualized on SI. 7/11 with prior surgery did not proceed to salvage RT and the remaining Pts who had Ms were referred for an earlier medical oncology opinion. In total 20/81 (25%) of Pts had a direct change in treatment due to the additional information conferred by PSMA imaging. Conclusions: PSMA is more sensitive in the detection of prostate cancer Ms for patients being evaluated for primary treatment or looking for recurrence following local treatment. These results show clinically meaningful changes in management with avoidance of local treatment because of enhanced detection of metastases.
EGFR-Dependent Regulated Intramembrane Proteolysis of EpCAM—Letter
Authors: Olivier Gires
Journal: Cancer Research (2017)

Hsu and colleagues reported on EGF/EGFR–triggered activation of regulated intramembrane proteolysis (RIP) of EpCAM that induces an EMT phenotype (1). This finding is of utmost interest, as it might explain contradicting effects of EpCAM on adhesion, proliferation, and invasion and shed light on EpCAM-based plasticity in cancer progression.EGF treatment of one endometrial carcinoma line induced a loss of the extracellular domain of EpCAM (EpEX) at the membrane. Treatment of cells with EGFR inhibitor Iressa suggested a dependency of the observed phenotype on EGFR signaling, which however was not further explored. Parallel treatment of cells with γ-secretase inhibitor DAPT counteracted effects of EGF and restored EpEX expression at the membrane of EGFR-positive cells (Fig. 1A; ref. 1).Classically, RIP depends on initial shedding of the substrate's ectodomain by α- (e.g., ADAMs) and/or β-proteases (e.g., BACE1). Ectodomain shedding is a commonly accepted prerequisite for subsequent intramembrane cleavage of the resulting C-terminal fragments (CTF) through the action of the γ-secretase complex (see Fig. 1 for schematic representation).In contrast to the authors' assumption, "stabilization of EpCAM by the inhibition of EpICD cleavage" through γ-secretase inhibitor DAPT should not impact on EpEX shedding, because aforesaid shedding must have preceded EpICD release. Evidence therefore was reported by Maetzel and colleagues in the initial description of EpCAM cleavage (Fig. 2A and B in ref. 2). DAPT treatment inhibited EpICD formation and resulted in the accumulation of EpCAM-CTFs (Fig. 2A), whereas pharmacologic and genetic inhibition of ADAM17 resulted in EpEX, EpCAM-CTF, and EpICD reduction or loss (Figs. 2B and 3). These results have been repeatedly confirmed, for example, by Lin and colleagues, who unquestionably demonstrated a lack of effect of DAPT on EpEX formation (Fig. 4E in ref. 3), Schnell and colleagues (Fig. 5C in ref. 4), and Tsaktanis and colleagues (Fig. 1A in ref. 5).In conclusion, it appears hardly conceivable that inhibition of γ-secretase has any direct effect on EGF/EGFR–mediated shedding of EpEX. Inhibition of ADAMs and BACE1 with small-molecule inhibitors such as TAPI and C3 would have been more informative to address this central mechanistic question of the article, which remains open and further challenged by conflicting reports on enhanced signaling of EGFR in presenilin-deficient cells (6).See the Response, p. 1777No potential conflicts of interest were disclosed.
Understanding the experience of living with non-small cell lung cancer (NSCLC): A qualitative study.
Authors: Joanne S. Buzaglo, Christopher Gayer, Rajiv Mallick, Ellyn Micco, Anne Morris, Andrea Stern Ferris, Mitch Golant, Corey J. Langer, C. Daniel Mullins, David Cella
Journal: Journal of Clinical Oncology (2013)

e20618 Background: As non-small cell lung cancer (NSCLC) treatments improve and patients live longer, it is increasingly important to develop interventions to help patients live fuller lives. We sought to identify key components of quality of life (QOL) and social support in determining therapeutic decision-making and overall value of life-extension, in patients with NSCLC. Methods: Three semi-structured focus groups (n=16) and telephone interviews (n=15) were conducted and recorded with NSCLC patients (N=31), to explore the full range of symptoms that patients considered important to QOL. A tradeoff format assessed the value of life-extension relative to QOL. Patients were asked to consider a hypothetical treatment option that offered on average a 3 month life extension. Results: Mean age was 61.6 years, 67.6% were female, 77.4% white, 61.3% were not employed/retired, 58.1% were living with a spouse/other, 93.5% had health insurance, and 48.4% were Stage III/IV. Sixty-Eight percent of patients conceptualized emotions and attitudinal orientation as symptoms of NSCLC. Key symptoms/concerns changed over time – 74% of patients reported shock and fear at diagnosis, 55% felt fear or loneliness during the beginning of therapy, 52% successfully connected with other NSCLC patients (peers) and support groups, and reported a positive shift in feelings with social/emotional support from all social networks. 26% of patients reported confusion and isolation during treatment due to education gaps. Financially, 23% of patients reported being adversely impacted by co-pays, 36% by unexpected gaps in coverage, 39% by other bills, and 52% accepted help from any/all sources. The most important factor driving treatment-decision making about life-extending therapy was the somatic (i.e., physical symptom) dimension (84% cited as important), followed by functional (32%), relational (23%), and emotional (10%) factors. Conclusions: Patients with advanced NSCLC tend to conflate emotional well-being post diagnosis with symptoms of their cancer and treatment toxicities. However, somatic QOL concerns, ahead of functional, emotional and relational QOL, emerge as the dominant driver of therapeutic decision-making.
A Phase 1 Study of Denintuzumab Mafodotin (SGN-CD19A) in Relapsed/Refactory B-Lineage Non-Hodgkin Lymphoma
Authors: Craig H Moskowitz, Michelle A Fanale, Bijal D Shah, Ranjana H Advani, Robert Chen, Stella Kim, Ana Kostic, Tina Liu, Joanna Peng, Andres Forero-Torres
Journal: Blood (2015)
A retrospective study of inflammatory breast cancer patients from seven hospitals in the United Kingdom.
Authors: Saeed Rafii, Christopher John Poole, Adele Francis, Shalini Chaudhri, Daniel Rea
Journal: Journal of Clinical Oncology (2012)

e11062 Background: Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast cancer characterised by rapidly progressive breast erythema, pain and tenderness, oedema and paeu d’orange. It is estimated that between 1-4 % of all newly diagnosed breast cancer patients in the United Kingdom have IBC. Methods: We retrospectively identified 51 patients who were treated for IBC at 7 hospitals in the West midlands area of the United Kingdom between 1997 and 2011. Data including patients’ demographics, clinical, radiological and histopathological characteristics were collected from electronic clinical records. The test for HER-2 over-expression was not carried out routinely before 2002, therefore HER-2 status of such patients were assessed retrospectively on the archived tissues. A cox regression analysis was used for statistical assessment of survival and prognostic factors. Results: Median age at diagnosis was 55 years (range 34-83 yrs). Median overall (OS) and progression free survival (PFS) were 32 months (range 7-97 months) and 27 months (range 2-53 months) respectively. The 3–year survival rate for the entire cohort was 32%. Majority of patients were ER and HER-2 positive (49% and 52% respectively). The rate of complete pathological response (pCR) after neoadjuvant chemotherapy was 14%. All cases who had achieved pCR were HER-2 positive who had received anti HER-2 treatment during the neoadjuvant chemotherapy. The OS for the HER-2 positive patients with pCR was not statistically different from the whole cohort (49 vs 32 months, p=0.09) or from the patients with residual disease (49 vs 26 months, p=0.13). Although the triple negative IBC patients consisted 20% of the cohort, no patients in this group had achieved pCR. The OS and PFS for the triple negative patients were 20 and 14 months respectively. Although the rate of pCR was higher in patients treated with taxane compared to those treated with anthracycline containing chemotherapy (35% vs 7%), there was no significant difference in OS between either of these regimens (29 vs 27 months). Conclusions: HER-2 positive IBC patients had higher rate of achieving pCR after neo-adjuvant anti HER-2 therapy. However higher rate of pCR did not improve the OS.
MERiDiAN: A phase III, randomized, double-blind study of the efficacy, safety, and associated biomarkers of bevacizumab plus paclitaxel compared with paclitaxel plus placebo, as first-line treatment of patients with HER2-negative metastatic breast cancer.
Authors: David Miles, Leonardo Faoro, Yan V. Wang, Joyce O'Shaughnessy
Journal: Journal of Clinical Oncology (2013)

TPS1142^ Background: Bevacizumab (BV), a humanized monoclonal antibody targeting the angiogenic VEGF, has demonstrated activity in patients with metastatic breast cancer (MBC). Plasma VEGF-A levels ([VEGF-A] p ) appear to positively correlate with the effect of BV on progression-free survival (PFS) in MBC, metastatic pancreatic, and advanced gastric cancers. The MERiDiAN study will prospectively investigate (1) whether baseline [VEGF-A] p predict treatment benefit with BV, (2) efficacy of BV with weekly paclitaxel (P), based on previously observed differences in the magnitude of benefit compared with BV + non-P chemotherapies. Methods: MERiDiAN is a global, randomized, double-blind, phase III study enrolling patients with HER2-negative MBC (first patient was enrolled in August 2012). The co-primary endpoints are PFS by investigator assessment in the intent-to-treat (ITT) population, and PFS in the subgroup with high baseline [VEGF-A] p . Secondary endpoints are overall survival (OS), 1-year survival, objective response rate and duration, and safety. Exploratory objectives include assessing the predictive or prognostic potential of blood, DNA and tumor tissue markers, and genetic variants involved in angiogenesis and tumorigenesis, with regard to BV efficacy and safety.Patients will be randomized 1:1 to either P 90 mg/m 2 IV weekly (qw) for 3 weeks followed by a 1-week rest and BV 10 mg/kg every 2 weeks (q2w) until disease progression (PD); or P 90 mg/m 2 IV qw for 3 weeks followed by a 1-week rest and placebo 10 mg/kg q2w until PD. An interim analysis of OS will be performed at the time of the primary PFS analysis. Clinical Trial Registry Number NCT01663727. Clinical trial information: NCT01663727.
Impact of response to prior chemotherapy (RTPC) on outcomes in second-line therapy for advanced urothelial carcinoma (UC): Implications for trial design.
Authors: Gregory Russell Pond, Joaquim Bellmunt, Ronan Fougeray, Toni K. Choueiri, Angela Q. Qu, Yacine Salhi, Guenter Niegisch, Peter Albers, Giuseppe Di Lorenzo, Matt D. Galsky, Andrea Necchi, Guru Sonpavde
Journal: Journal of Clinical Oncology (2013)

4539 Background: Performance status (PS), hemoglobin (Hb), liver metastasis (LM), and time from prior chemotherapy (TFPC) are significant prognostic factors in second-line therapy for advanced UC. Setting of prior chemotherapy, i.e., metastatic or perioperative, has not appeared significant. However, the impact of prior chemosensitivity is unclear, which may confound trial interpretation. Hence, we examined the prognostic impact of RTPC, when prior therapy was given for metastatic disease. Methods: Six phase II trials evaluating second-line chemotherapy and/or biologics (n=504) were pooled. Patients who received prior therapy for metastatic disease were eligible for analysis if data regarding Hb, LM, PS, and TFPC were available. Response by RECIST to first-line therapy was recorded. Progression-Free Survival (PFS) and overall survival (OS) were calculated from the date of registration using the Kaplan-Meier method. Results: 275 pts were evaluable for analysis. Patients received gemcitabine-paclitaxel, cyclophosphamide-paclitaxel, pazopanib, docetaxel plus vandetanib/placebo or vinflunine (2 trials). Those with prior response (n=111) had a median (95% CI) OS of 8.0 (6.8-9.4) months (mo) and PFS of 3.0 (2.6-4.0), compared with OS and PFS of 5.9 (5.0-6.6) mo and 2.6 (2.0-2.8) for those without prior response (n=164). Multivariable analysis did not reveal an independent impact of RTPC on PFS or OS (Table). Conclusions: RTPC in patients receiving prior chemotherapy for metastatic disease did not confer an independent prognostic impact with second-line therapy for advanced UC. Patients who received prior chemotherapy in peri-operative or metastatic settings may be enrolled in the same second-line trial stratified for PS, anemia, LM and TFPC. [Table: see text]
Leading anaesthetist praises NHS response to Westminster attacks
Authors: Anne Gulland
Journal: BMJ (2017)

A consultant anaesthetist at one of the trauma centres that received casualties after this week’s attacks in Westminster has praised his colleagues for their “fantastic response.”

Helgi Johannsson, clinical director of anaesthesia at Imperial College Healthcare NHS Trust, which received eight casualties, said that the trust had taken part in a pan-London simulation exercise in the past year, which simulated a major train accident. He said that the training kicked in once the Westminster incident was declared at 15.55 on Wednesday.

“I couldn’t fault our teams, they did an absolutely fantastic job. The whole …
ANGIOTAX-PLUS trial: A randomized phase II trial assessing the activity of weekly paclitaxel (WP) plus or minus bevacizumab (B) in advanced angiosarcoma (AS).
Authors: Nicolas Penel, Jean-Yves Blay, Olivier Mir, Emmanuelle Tresch, Emmanuelle Bompas, Julien Domont, Philippe Alexandre Cassier, Frederic Rolland, Sophie Piperno-Neumann, Antoine Italiano, Christine Chevreau, Didier Cupissol, Jacques-Olivier Bay, Olivier Collard, Esma Saada, François Bertucci, Nicolas Isambert, Corinne Delcambre, Stephanie Clisant, Isabelle Laure Ray-Coquard
Journal: Journal of Clinical Oncology (2014)

10501 Background: Paclitaxel is an active agent in advanced AS. The objective of this study was to explore the activity and safety of adding B to WP in treatment of AS. Methods: We conducted a multicenter randomized (1/1) phase II trial for assessing both regimens. WP: 90 mg/m² d1,8 and 15 in 4-wks cycle for 6 cycles, +/- B 10 mg/kg d1,8 and 15 followed by maintenance therapy 15 mg/kg/3 wks until intolerance/progression. Stratification factors were: superficial vs visceral AS, de novo vs radiation-induced (RI) AS. Primary endpoint was 6-month progression-free rate (RECIST 1.1). Statistical assumptions were: P0=20%; P1=40%, α=10% and β=20%. Results: From 09/2010 to 09/2013, 50 pts (26 in WP and 26 in WP-B arm) have been enrolled in 14 centers. There were 12 men and 38 women (median age 66, 24-82). Most common primaries were: breast (24, 49%) and skin (6, 12%). There was 17 (34%) visceral and 24 (49%) RI AS. PS was 0 in 24 (50%) and 1 in 23 (48%). 16 pts have previously received anthracyclines (32%); 32 pts (64%) were chemo-naive. 8/24 (33%) pts enrolled in WP-B arm have received B as maintenance therapy. Median follow-up was 14.5 months. Both regimens were considered active with a 6-mPFR of 57% (15/26) in WP arm and 57% (14/24) in WP+B arm. Median PFS was 6.8 vs 6.9 months. 1-year OS was 55 vs 58%. 4 pts experienced Gr5-AE: 1 in WP arm (hemorrhage) and 3 in WP-B arm (suicide, intestinal occlusion, general condition deterioration). We had observed arterial hypertension in both arms: WP (1 Gr2) and WP-B (1 Gr2/1 Gr3), hemorrhage in both arms: WP (2 Gr1/1 Gr5) and WP-B (2 Gr1/1 Gr2), thrombosis in both arms: WP (1 Gr1) and WP-B (1 Gr2/ 1 Gr4) and 1 case of Gr1 proteinuria in WP-B arm. There was no reported wound dehiscence and gastro-intestinal perforation. Hematological toxicity profile was similar in both arms. Conclusions: WP and WP-B are both active regimens of AS. B did not improve the outcome of AS pts. This study illustrates the importance of randomization in phase II trial. In the present trial, WP provides PFS (6.8 vs 4.0 months) and OS (>12 vs 8 months) significantly higher than previously reported in the AngioTax Study (Penel JCO 2008). Clinical trial information: 2009-017020-59.
DNA repair gene promoter methylation in non-small cell lung cancer (NSCLC) patients treated with DNA damaging agents.
Authors: Lela Buckingham, Gregory Pelkey, Mary J. Fidler, Philip D. Bonomi
Journal: Journal of Clinical Oncology (2013)

e22130 Background: Approximately 75% of NSCLC patients are advanced at time of diagnosis. Treatments include regimens of DNA-damaging and alkylating agents. Previous in vitro studies have shown that loss of BRCA1 and BRCA2 function through promoter methylation increases sensitivity to sapacitabine, suggesting that tumor cells may be protected by repair systems including BRCA-RAD50 and MGMT pathways induced by DNA damage. The purpose of this study is to investigate the effect of DNA repair gene promoter methylation on outcome of NSCLC patients treated with DNA damaging agents. DNA repair gene promoter hypermethylation may sensitize tumor cells to DNA damaging agents. Methods: The patient group of 240 patients included 135 early stage and 105 late stage (III/IV) cases. Chemotherapy regimens of late stage patients included carboplatin, cisplatin and gemcitabine, as well as other non-DNA damaging agents. Mean overall survival (OS) was 43.7 months. DNA was extracted from micro-dissected primary tumor, bisulfite converted and assessed by pyrosequencing to quantify methylation of cytosine nucleotides along the MGMT, BRCA1 and BRCA2 promoters. Results: Overall average methylation values were 8.4%, 7.3% and 8.3% for MGMT, BRCA1, BRCA2 respectively (compared to 3.2%, 3.6% and 7.3%, respectively, in nonmalignant lung tissue). Percent promoter methylation levels were not significantly correlated with age, gender, smoking status nor histology, with the exception of higher MGMT promoter methylation in smokers. Hypermethylation (greater than 10%) of BRCA1 and BRCA2 promoter was not significantly associated with survival in late stage patients (6.6 mos vs 6.8 mos; p=0.533) in this patient group, however, superior survival was observed with BRCA2 promoter hypermethylation when early stage patients were included (29.3 mos vs median not reached; p=0.045). Promoter hypermethylation of MGMTwas significantly associated with lower five-year survival rate in early stage patients (p=0.022). Conclusions: These data suggest epigenetic control of DNA repair gene expression can affect response to therapy. Further studies on specific treatment regimens will be required to definitively assess these effects.