Molecular Profiling in Daily Clinical Practice: Practicalities in Advanced Cholangiocarcinoma and Other Biliary Tract Cancers

Background: Molecular profiling is becoming increasingly relevant in the management of patients with advanced cancer; to identify targetable aberrations and prognostic markers to enable a precision medicine strategy. Methods: Eligible patients were those diagnosed with advanced biliary tract cancer (BTC) including intrahepatic (iCCA) and extrahepatic cholangiocarcinoma (eCCA), gallbladder cancer (GBC), and ampullary carcinoma (Amp) who underwent molecular profiling between April 2017 and June 2020 based on analysis of either tumour samples (FoundationOne CDx®/Oncomine® platforms) or ctDNA (FoundationOne Liquid® platform (Foundation Medicine, Cambridge, MA, USA)). Baseline patient characteristics and molecular profiling outcomes were extracted. The primary aim was to describe sample failure rate. Secondary aims included description of reason for sample failure, summary of findings derived from molecular profiling, and assessment of concordance between paired tissue and ctDNA samples. Results: A total of 149 samples from 104 individual patients diagnosed with advanced BTC were identified and eligible for this analysis: 68.2% iCCA, 100% advanced stage; 94.2% received palliative therapy. The rate of sample failure was 26.8% for tissue and 15.4% for ctDNA; p-value 0.220, predominantly due to insufficient (defined as <20%) tumour content in the sample (the reason for 91.2% of tissue sample failure). Of the 112 samples successfully analysed, pathological molecular findings were identified in the majority of samples (88.4%) and identification of pathological findings using ctDNA, was possible regardless of whether the patient was on active treatment at time of blood acquisition or not (p-value 1.0). The rate of targetable alterations identified was 40.2% across all successfully-analysed samples (39 iCCA; 6 non-iCCA): IDH1 mutations (19.1% of individual patients), FGFR2 alterations (10.1% and 5.6% of individual patients had FGFR2 fusions and mutations, respectively); 10.6% of all patients (12.4% of patients with successfully analysed samples) entered trials with matched targeted therapies as a consequence. Concordance of findings for paired tissue and paired tissue-ctDNA was high (3/3; 100% and 6/6; 100%, respectively). Twelve ctDNA samples were taken prior to palliative treatment initiation, median maximum mutant allele frequency (MAF) was 0.47 (range 0.21–19.8); no significant association between reported maximum MAF and progression-free survival (PFS) or overall survival (OS) (all Cox regression p-values > 0.273). A total of 15 patients (16.6%) harboured alterations in DNA damage repair (DDR) genes; when treated with platinum-based chemotherapy, there was a trend towards increased partial response rate (21.4% vs. 15.9%; p-value 0.653), radiological benefit rate (64.3% vs. 36.2%; p-value 0.071), and longer OS (median OS 20.4 months (95% CI 7.9–26.7) vs. 13.3 (95 CI 11.0–16.4); Cox Regression HR 0.79 (95% CI 0.39–1.61), p-value 0.527). Conclusions: Molecular profiling is of use for identification of novel therapeutic strategies for patients with advanced BTC (mainly iCCA). One in four archived tissue samples may have insufficient tumour content for molecular profiling; ctDNA-based approaches may overcome these obstacles.

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Molecular profiling of advanced pancreatic ductal adenocarcinoma (PDAC): Role of ctDNA.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.425 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 425-425

Author(s):

Angela Lamarca ◽

Mairead Geraldine McNamara ◽

Richard Hubner ◽

Juan W. Valle

Keyword(s):

Palliative Therapy ◽

Progression Free Survival ◽

Patient Characteristics ◽

Molecular Profiling ◽

Ductal Adenocarcinoma ◽

P Value ◽

Ctdna Analysis ◽

Chemotherapy Initiation ◽

The Impact

425 Background: Molecular profiling of tumour samples and circulating tumour DNA (ctDNA) may inform treatment of advanced cancer; the role of ctDNA to predict progression-free-survival (PFS) and overall survival (OS) in advanced PDAC is not fully understood. Methods: Eligible patients: those diagnosed with advanced PDAC undergoing molecular profiling [tumour (Foundation Medicine CDx/Caris) or ctDNA (FoundationMedicine Liquid (72 cancer-related genes))]. Baseline patient characteristics and molecular profiling outcomes, including mutant allele frequency (MAF) for pathological alterations were extracted. The primary aim was to assess the impact of presence of ctDNA at time of systemic chemotherapy initiation on PFS and OS. Results: Total of 26 samples (ctDNA 18 samples and 8 tumour samples) from 25 patients diagnosed with advanced PDAC underwent molecular profiling. When the whole population was analysed, the rate of sample analysis failure seemed to be higher when tumour tissue was tested (37.5%) compared to ctDNA (5.56%); p-value 0.072. The overall rate of identification of pathological findings was 72.73%, with 18.18% of patients having targetable findings [EGFRmut (1 patient), KRAS G12C mut (1 patient), FGFR2 fusion (1 patient), RNF43 mut (1 patient)]; these findings impacted treatment management in one patient only (RNF43 mutation; Wnt inhibitor). Variants of unknown significance were identified in 63.64% of samples. Patients with ctDNA analysis at time of palliative chemotherapy initiation (16 samples; 15 patients) were analysed [6 female (40.00%), median age 69.57 years (range 51.61-81.49), metastatic disease (66.67%), 80% first-line (80%), 20% second-line]. Pathological mutations were identified in 9/15 (60.00%) of these patients (KRAS mutation identified in 6/9). After median follow-up of 8.33 months from sample acquisition, 80% and 53.33% of patients had progressed and died, respectively. Median estimated PFS and OS were 5.65 months (95% CI 1.59-8.17) and 7.80 months (95% CI 4.13-not reached). Presence (vs absence) of pathological alterations in ctDNA showed a trend towards shorter PFS (2.91 vs 6.51 months; HR 1.38 (95% CI 0.40-4.77)) and OS (6.12 vs 9.72 months; HR 2.03 (95% CI 0.60-6.82)). Conclusions: This pilot study demonstrates the feasibility of ctDNA analysis in patients with advanced PDAC prior to initiation of palliative therapy. The presence of pathological alterations in ctDNA may prognosticate for worse PFS and OS. Larger studies are required to confirm these findings.

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Downregulation and Prognostic Performance of MicroRNA 224 Expression in Prostate Cancer

Clinical Chemistry ◽

10.1373/clinchem.2012.191502 ◽

2013 ◽

Vol 59 (1) ◽

pp. 261-269 ◽

Cited By ~ 44

Author(s):

Konstantinos Mavridis ◽

Konstantinos Stravodimos ◽

Andreas Scorilas

Keyword(s):

Prostate Cancer ◽

Cox Regression ◽

Specific Antigen ◽

Progression Free Survival ◽

Prognostic Indicator ◽

Disease Stage ◽

Clinical Value ◽

Prostate Tumors ◽

Tissue Samples ◽

Total Rna

INTRODUCTION The extensive use of prostate-specific antigen as a general prostate cancer biomarker has introduced the hazards of overdiagnosis and overtreatment. Recent studies have revealed the immense biomarker capacity of microRNAs (miRNAs) in prostate cancer. The aim of this study was to analyze the expression pattern of miR-224, a cancer-related miRNA, in prostate tumors and investigate its clinical utility. METHODS Total RNA was isolated from 139 prostate tissue samples. After the polyadenylation of total RNA by poly(A) polymerase, cDNA was synthesized with a suitable poly(T) adapter. miR-224 expression was assessed by quantitative real-time PCR and analyzed with the comparative quantification cycle method, Cq(2−ΔΔCq). We performed comprehensive biostatistical analyses to explore the clinical value of miR-224 in prostate cancer. RESULTS miR-224 expression was significantly downregulated in malignant samples compared with benign samples (P < 0.001). Higher miR-224 expression levels were found in prostate tumors that were less aggressive (P = 0.017) and in an earlier disease stage (P = 0.018). Patients with prostate cancer who were positive for miR-224 had significantly enhanced progression-free survival intervals compared with miR-224–negative patients (P = 0.021). Univariate bootstrap Cox regression confirmed that miR-224 was associated with favorable prognosis (hazard ratio 0.314, P = 0.013); nonetheless, multivariate analysis, adjusted for conventional markers, did not identify miR-224 as an independent prognostic indicator. CONCLUSIONS miR-224 is aberrantly expressed in prostate cancer. Its assessment by cost-effective quantitative molecular methodologies could provide a useful biomarker for prostate cancer.

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Prospective observational study of prevalence, assessment and treatment of pancreatic exocrine insufficiency (PEI) in patients with advanced pancreatic cancer (aPC): PanDA.

Journal of Clinical Oncology ◽

10.1200/jco.2020.39.28_suppl.196 ◽

2021 ◽

Vol 39 (28_suppl) ◽

pp. 196-196

Author(s):

Angela Lamarca ◽

Lindsay Carnie ◽

Dinakshi Shah ◽

Kate Vaughan ◽

Zainul Abedin Kapacee ◽

...

Keyword(s):

Pancreatic Cancer ◽

High Risk ◽

Observational Study ◽

Breath Test ◽

Cox Regression ◽

Pancreatic Enzyme ◽

Palliative Therapy ◽

Advanced Pancreatic Cancer ◽

P Value ◽

Screening Methods

196 Background: PEI in patients with advanced pancreatic cancer is well documented, but there is a lack of consensus regarding optimal screening. Methods: Eligible patients for this observational study (NCT03616431) were those diagnosed with aPC referred for consideration of palliative therapy who consented to evaluation by a research dietitian. In addition to symptom and full dietetic assessment (including Mid-Upper Arm Circumference (MUAC), handgrip and stair climb test), full nutritional blood panel, faecal elastase (FE) and 13C mixed triglyceride breath test (for diagnostic cohort (DiC)) were performed. Primary objectives: prospective assessment of PEI prevalence (dietitian-assessed; demographic cohort (DeC)), and to design (using breath test as gold standard; DiC) and validate (follow-up cohort (FuC)) the most suitable screening tool for PEI in patients with aPC. Logistic and Cox regression were used for statistical analysis (Stat v.12). Results: Between 1st July 2018 and 30th October 2020, 112 eligible patients [50 (DeC), 25 (DiC), 37 (FuC)]. Prevalence of PEI in the DeC was 64.0% (PEI-related symptoms were flatus (84.0%), weight loss (84.0%), abdominal discomfort (50.0%) and steatorrhea (48.0%)); 70.0% of patients required pancreatic enzyme replacement therapy and 74.0% had anorexia (low appetite); 44.0% and 18.0% had low vitamin D and vitamin A levels, respectively. Designed PEI screening panel (DiC; 19 patients with breath test completed) included FE [normal/missing (0 points); low (1 point)] and MUAC [normal/missing ( > percentile 25 for age/gender) (0 points); low (2 points)] and identified patients at high-risk (2-3 total points) of PEI [vs. low-medium risk (0-1 total points)]. When patients from DeC and DiC) were analysed together, those classified as “high-risk of PEI” according to the screening panel had shorter overall survival (multivariable Hazard Ratio (mHR) 1.86 (95% CI 1.03-3.36); p-value 0.040) when adjusted for other prognostic factors, including presence of PEI symptoms (mHR 2.28 (95% CI 1.19-4.35); p-value 0.013). The screening panel was tested in the FuC; 78.38% were classified as patients at “high-risk of PEI”; of these, 89.6% were confirmed to have PEI by the dietitian. The panel was feasible for use in clinical practice, (64.8% of patients completed fully the assessments required) and acceptability was high (87.5% of patients would do it again). The majority of patients (91.3%) recommended that all future patients with aPC should have dietitian input. Conclusions: PEI is present in the majority of patients with aPC, and early dietetic input is important to provide a holistic nutritional overview, including, but not limited to, PEI. This proposed screening panel could be used to prioritise patients at higher risk of PEI requiring urgent dietitian input. Its prognostic role needs further validation. Clinical trial information: NCT03616431.

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Efficacy and Safety of FLOT regimen vs. DCF, FOLFOX, and ECF regimens as Perioperative Chemotherapy Treatments for Resectable Gastric Cancer Patients

10.1101/2021.01.26.21250550 ◽

2021 ◽

Author(s):

Pegah Farrokhi ◽

Alireza Sadeghi ◽

Mehran sharifi ◽

Payam Dadvand ◽

Rachel Riechelmann ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Cox Regression ◽

Progression Free Survival ◽

R0 Resection ◽

P Value ◽

Perioperative Chemotherapy ◽

Resectable Gastric Cancer ◽

Gastric Cancer Patients

AbstractAimThis study aimed to evaluate and compare the efficacy and toxicity of common regimens used as perioperative chemotherapy including ECF, DCF, FOLFOX, and FLOT to identify the most effective chemotherapy regimen with less toxicity.Material and MethodsThis retrospective cohort study was based on 152 eligible gastric cancer patients recruited in a tertiary oncology hospital in Isfahan, Iran (2014-2019). All resectable gastric cancer patients who had received one of the four chemotherapy regimens including ECF, DCF, FOLFOX, or FLOT, and followed for at least one year (up to five years) were included. The primary endpoint of this study was Overall Survival (OS), Progression-Free Survival (PFS), Overall Response Rate (ORR), and R0 resection. We also considered toxicity according to CTCAE (v.4.0) criteria as a secondary endpoint. Cox -regression models were used applied to estimate OS and PFS time, controlled for relevant covariates.ResultsOf included patients, 32(21%), 51(33.7%), 37(24.3%), and 32(21%) had received ECF, DCF, FOLFOX and FLOT, respectively. After the median 25 months follow-up, overall survival was higher with the FLOT regimen in comparison with other regimens (hazard ratio [HR] = 0. 052). The median OS of the FLOT regimen was not reachable in Kaplan-Meier analysis and the median OS was 28, 26, and 23 months for DCF, FOLOFX, and ECF regimens, respectively. On the other hand, a median PFS of 25, 17, 15, and 14 months was observed for FLOT, DCF, FOLFOX, and ECF regimens, respectively (Log-rank = 0. 021). FLOT regimen showed 84. 4% ORR which was notably higher than other groups (p-value<0. 01).ConclusionsFor resectable gastric cancer patients, the perioperative FLOT regimen seemed to lead to a significant improvement in patients’ OS and PFS in comparison with ECF, DCF, and FOLFOX regimens. As such, the FLOT regimen could be considered as the optimal option for managing resectable gastric cancer patients.

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Role of ctDNA to predict risk of recurrence following potentially curative resection of biliary tract and pancreatic malignancies.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.336 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 336-336

Author(s):

Angela Lamarca ◽

Mairead Geraldine McNamara ◽

Richard Hubner ◽

Juan W. Valle

Keyword(s):

Relapse Rate ◽

Curative Resection ◽

Cox Regression ◽

Statistical Significance ◽

Molecular Profiling ◽

P Value ◽

Relapse Risk ◽

Baseline Characteristics

336 Background: The potential role of ctDNA to identify residual disease after potentially curative resection has been suggested in some malignancies; its role in resected pancreatico(P)-biliary(B) malignancies is unknown. Methods: Patients diagnosed with PB malignancies underwent molecular profiling (ctDNA) using FoundationMedicine Liquid (72 cancer-related genes) following potentially curative resection. Baseline patient characteristics and molecular profiling outcomes, including mutant allele frequency (MAF) for pathological alterations were extracted. Primary objective: prevalence of ctDNA identification and its correlation with recurrence (relapse-free survival (RFS) and relapse rate). Results: Total of 11 individuals had ctDNA analysed following potentially curative resection for PB malignancies: 8 B (4 extra-hepatic cholangiocarcinoma (eCCA), 2 ampulla, 1 intrahepatic cholangiocarcinoma (iCCA), 1 gallbladder cancer (GBC)) and 3 P. Baseline characteristics: 6 female (54.55%), median age 71.59 years (range 39.98-81.19). Most were pT2 (45.45%), pN0 (54.55%) and R0 (63.64%). Following surgery, 6 patients were started on adjuvant chemotherapy; at the end of follow-up (data cut-off 25/6/2020; median follow-up 11.15 months (range 5.45-13.52); 5 relapsed (45.45%) and 2 died (18.18%). Estimated median RFS was 11.43 months (95% CI 2.28-not reached); median overall survival was not reached. No sample failed ctDNA analysis; presence of ctDNA was identified in 3/11 (27.27%) of the samples; 2 and 1 samples had 2 and 1 pathological alterations identified, respectively: ALK fusion (1 sample; GBC), TP53 mutation (2 samples; eCCA and GBC), CHEK2 mutation (1 sample; pancreas), IDH2 mutation (1 sample; eCCA). Mean maximum MAF was 1.47 (2 in biliary; 0.43 in pancreas). Variants of unknown significance were identified in 72.73% of the samples (87.5% in B; 33.33% in P; p-value 0.152). None of the baseline characteristics explored correlated with presence of ctDNA. There was a trend towards increased relapse risk in the patients with ctDNA present following potentially curative surgery; Cox regression for RFS [HR 2.64 (95% CI 0.36-19.31); median RFS 11.44 months (95% CI 2.28-not reached) vs 10.87 (95% CI 2.21-not reached)]; relapse rate 37.5% (ctDNA absent) vs 66.67% (ctDNA present); statistical significance was not reached (p-value 0.340 and p-value 0.545, respectively). Conclusions: This pilot study demonstrates the feasibility of testing for ctDNA following potentially curative resection in PB malignancies. Presence of ctDNA may be associated with increased relapse risk; further studies are required to increase sample size and assess clinical implications.

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Efficacy and Safety of Pembrolizumab for Gemcitabine/Cisplatin-Refractory Biliary Tract Cancer: A Multicenter Retrospective Study

Journal of Clinical Medicine ◽

10.3390/jcm9061769 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1769 ◽

Cited By ~ 1

Author(s):

Sang Hoon Lee ◽

Hee Seung Lee ◽

Sang Hyub Lee ◽

Sang Myung Woo ◽

Dong Uk Kim ◽

...

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Biliary Tract ◽

Biliary Tract Cancer ◽

Progression Free Survival ◽

Cancer Type ◽

Extrahepatic Cholangiocarcinoma ◽

Tract Cancer ◽

Tertiary Hospitals ◽

Melanoma Treatment

Pembrolizumab, an anti-programmed cell death (PD)-1 monoclonal antibody, is an anticancer agent showing substantial benefit in lung cancer and melanoma treatment. Biliary tract cancer (BTC) has been shown to respond to pembrolizumab; however, no credible data of such treatment outcomes exist. Therefore, we assessed the clinical outcomes and safety of pembrolizumab in patients with gemcitabine/cisplatin-refractory BTC. In this multicenter study, we retrospectively analyzed 51 patients with programmed cell death 1-ligand 1 (PD-L1)-positive gemcitabine/cisplatin-refractory BTC treated with pembrolizumab in four tertiary hospitals in Korea. PD-L1 positivity was defined as the expression of PD-L1 in ≥1% of tumor cells based on immunohistochemical staining (22C3, SP263, and E1L3N assays). The median age of the patients was 66 (range, 43–83) years and 29 (56.9%) were male. Extrahepatic cholangiocarcinoma was the most common cancer type (n = 30, 58.8%). Partial response and stable disease were achieved in 5 (9.8%) and 13 (25.5%) patients, respectively. Median progression-free survival and overall survival were 2.1 (95% CI, 1.7–2.4) and 6.9 (95% CI, 5.4–8.3) months, respectively. Overall, 30 (58.8%) patients experienced treatment-related adverse events (AEs). Only four (7.8%) patients experienced grades 3 and 4 AEs. In PD-L1-positive gemcitabine/cisplatin-refractory BTC, pembrolizumab presented durable efficacy, with a 9.8% response rate and manageable toxicity.

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Phase III Study of VCAP-AMP-VECP vs. Biweekly CHOP in Aggressive Adult T-Cell Leukemia-Lymphoma (ATLL): Japan Clinical Oncology Group Study, JCOG9801.

Blood ◽

10.1182/blood.v106.11.812.812 ◽

2005 ◽

Vol 106 (11) ◽

pp. 812-812 ◽

Cited By ~ 1

Author(s):

Kunihiro Tsukasaki ◽

Takuya Fukushima ◽

Atae Utsunomiya ◽

Syuichi Ikeda ◽

Masato Masuda ◽

...

Keyword(s):

Cox Regression ◽

Performance Status ◽

Progression Free Survival ◽

Complete Response ◽

Phase Iii ◽

Rank Test ◽

P Value ◽

Minimization Method ◽

Adult T Cell Leukemia ◽

Non Hodgkin Lymphoma

Abstract Background: In our study for non-Hodgkin lymphoma (NHL) in 1980’s (JCOG8701), human T-lymphotropic virus type-1- associated ATLL was the poorest prognostic subtype in NHL. The complete response (CR) rate was 42%, the median survival time (MST) was 8 months, and the 4-yr overall survival (OS) was 12% (Proc ASCO13:378, 1994). Our previous phase II study (JCOG9303) of G-CSF-supported, dose-intensified multi-agent chemotherapy with VCAP (vincristine, cyclophosphamide, doxorubicin, prednisolone), AMP (doxorubicin, ranimustine, prednisolone) and VECP (vindesine, etoposide, carboplatin, prednisolone) with intrathecal prophylaxis for aggressive ATLL, showed promising results with response rate (RR) of 81% and MST of 13 months (Br J Haematol113:375,2001). To test the superiority of this VCAP-AMP-VECP regimen over biweekly-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone), we conducted a phase III trial. Methods: Previously untreated patients (pts) with aggressive ATLL, acute-, lymphoma- or unfavorable chronic-type, were randomized either to receive 6 courses of VCAP-AMP-VECP every 4 weeks (arm A) or 8 courses of biweekly-CHOP (arm B) with minimization method balancing performance status and institution. Both regimens were supported with G-CSF and intrathecal prophylaxis using cytarabine, methotrexate and prednisolone. Eligibility included preserved organ functions and aged 15–69 years. Primary endpoint was OS to be compared by log-rank test. Assuming 60 eligible pts in each arm, the study had 0.8 power to detect a 15% difference in 3-year OS at 0.05 one-sided alpha. Results: 118 pts (57 in arm A, 61 in arm B) were randomized between 07/98 and 10/03. Median follow-up time in all randomized pts was 11.0 months at 12/04. 72 % of the pts responded, with 23 pts achieving CR (40%) and 18 achieving partial response (PR; 32%) in arm A. The RR was 66%, with 15 pts achieving CR (25%) and 25 achieving PR (41%) in arm B. The median progression-free survival (PFS) time and PFS at one-year in arm A were 7.0 months and 28.1%, respectively, whereas 5.4 months and 16.2% in arm B. The MST and OS at 3 years in arm A were 12.7 months and 23.6%, respectively, whereas 10.9 months and 12.7% in arm B. Log-rank p-value for primary end point, OS, was 0.085. After adjustment of patients’ characteristics at registration by Cox regression, the p value became 0.029 because of unbalanced prognostic factors such as bulky lesion. In arm A vs. arm B, %G4 neutropenia, %G4 thrombocytopenia and %G4 infection were 98% vs. 83%, 74% vs. 17% and 7% vs. 3%, respectively. Three toxic deaths were reported in arm A. Conclusions: These results demonstrate that VCAP-AMP-VECP yields longer OS time than biweekly-CHOP but with higher toxicity profiles that are acceptable, and suggest that the former regimen should be the standard therapy for aggressive ATLL.

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Analysis of everolimus starting dose as prognostic marker in HR+ mBC patients treated with everolimus (EVE) + exemestane (EXE): Results of the 3rd interim analysis of the non-interventional trial BRAWO.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.1061 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 1061-1061 ◽

Cited By ~ 2

Author(s):

Peter A. Fasching ◽

Eva-Maria Grischke ◽

Florian Schuetz ◽

Thomas Decker ◽

Christoph Uleer ◽

...

Keyword(s):

Interim Analysis ◽

Cox Regression ◽

Eastern Cooperative Oncology Group ◽

Progression Free Survival ◽

Analysis Data ◽

P Value ◽

Hormone Receptor Positive ◽

Starting Dose ◽

Practice Methods ◽

The Impact

1061 Background: BRAWO is a German non-interventional study, which enrolled more than 2400 patients (pts) with advanced/metastatic, hormone-receptor-positive and HER2-negative breast cancer treated with EVE and EXE. Main objectives are a) the impact of physical activity on efficacy and quality of life, b) prophylaxis and management of stomatitis in clinical routine, and c) the sequence of therapy when EVE is used in daily clinical practice. Methods: In this update on the results of the 3rd interim analysis (data cut-off 18-Oct-2016) we analyzed under real world conditions the first 1.078 patients followed up until disease progression for their progression-free survival (PFS) events. A two-stage process based on a Cox regression model was used to check the relevance of the start dose on PFS. In the first step potentially relevant covariates defined by medical experts were evaluated for relevance. In the second step start dose and all covariates showing a p-value of at most 0.1 in first step including all two-interaction of start dose with these parameters were included into the model. Results: Our multivariate analysis support the evidence that predictive factors, such as body mass index (BMI, p-value: < 0.001), therapeutic line (1st vs. 2nd+3rd vs. ≥4th; p-value: 0.013), presence of visceral metastases (p-value: < 0.001) and ECOG (Eastern Cooperative Oncology Group, p-value: < 0.001) status at the beginning of the therapy correlated significantly with the PFS. 283 patients started with 5mg and 795 Patients started with 10 mg. Starting dose had no significant impact on the PFS (neither as main effect nor within interactions, p-value: 0.44-0.88). Conclusions: Even though the approved and recommended starting dose for treatment with EVE is 10 mg, physicians sometimes start EVE-treatment with a lower starting dose, trying subsequently to increase the dose to the recommended dose of 10mg to allow the patient’s organism to adapt to the therapeutic. As the study was not powered to detect possible differences in PFS by starting dose, the result of showing no detrimental effect of a lower start dose may be the result of limited power. Clinical trial information: EUPAS9462.

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Carboxypeptidase N1 is anticipated to be a synergy metrics for chemotherapy effectiveness and prognostic significance in invasive breast cancer

Cancer Cell International ◽

10.1186/s12935-021-02256-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ranliang Cui ◽

Chaomin Wang ◽

Tiantian Li ◽

Jialei Hua ◽

Ting Zhao ◽

...

Keyword(s):

Breast Cancer ◽

Invasive Breast Cancer ◽

Cox Regression ◽

Prognostic Significance ◽

Progression Free Survival ◽

Poor Overall Survival ◽

Tissue Samples ◽

Cox Regression Analysis ◽

Potential Biomarker ◽

Incidence And Mortality

Abstract Background The incidence and mortality of invasive breast cancer (IBC) are increasing annually. Hence, it is urgently needed to determine reliable biomarkers for not only monitoring curative effects, but evaluating prognosis. In present study, we aim to determine the potential role of Carboxypeptidase N1 (CPN1) in IBC tissues on chemotherapeutic efficacy and poor prognosis. Methods The expression level of CPN1 in IBC tissue samples (n = 123) was quantified by tissue microarray technique and immunohistochemical staining. Moreover, sera of IBC patients (n = 34) that underwent three to five consecutive chemotherapy sessions were collected. The patients were randomly stratified into a training (n = 15) as well as a validation group (n = 19). The expression of serum CA153 and CPN1 was quantified by electrochemiluminescence and ELISA assay, respectively. Results By univariate and multivariate Cox regression analysis, we show that CPN1 expression in IBC tissues, as an independent risk factor, is related to a poor overall survival (OS) and progression-free survival (PFS) (P < 0.05). Analysis of the data revealed that CPN1 over-expression could be consistently linked to adverse clinicopathological features such as lymph node metastasis and the pathological stage (pTNM) (P < 0.05). The serum CPN1 level trajectory of individual patients generally decreased during chemotherapy. In line with these findings were changes in the follow-up ultrasonography and a consistent decrease in serum CPN1 levels. The comparison of the area under the receiver operating curves (ROC) revealed that CPN1 has a better surveillance value than CA153 in the training (AUCCPN1 = 0.834 vs. AUCCA153 = 0.724) as well as the validation set (AUCCPN1 = 0.860 vs. AUCCA153 = 0.720) when comparing cycle2 versus cycle3. Conclusions CPN1 is a suitable potential biomarker for chemotherapeutic surveillance purposes as well as being an appropriate prognostic indicator which would support an improved chemotherapy regimen.

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Evaluation of the Agreement Between the Tissue Sample and Bronchoalveolar Lavage (BAL) Fluid in the Diagnosis of Tuberculosis in Patients with Anthracosis

Current Respiratory Medicine Reviews ◽

10.2174/1573398x15666190719162914 ◽

2020 ◽

Vol 15 (4) ◽

pp. 266-271

Author(s):

Mohammad Samet ◽

Masoud Rahimian ◽

Samaneh Meshkat ◽

Sanaz Zand

Keyword(s):

Bronchoalveolar Lavage ◽

Tissue Sample ◽

Good Alternative ◽

Diagnostic Methods ◽

P Value ◽

Cross Sectional ◽

Tissue Samples ◽

Tissue Biopsy ◽

Significant Difference ◽

Bronchial Tissue

Background: Black dust deposited in the lungs is called anthracosis. By damaging bronchial mucosa, anthracosis can affect the mucociliary cleaning function. Initial reports indicate that there is a relationship between anthracosis and pulmonary tuberculosis. Due to obstructive effects of anthracosis on distal airways and disruption in a proper sampling of bronchoalveolar lavage (BAL), other diagnostic methods are necessary for estimating the tuberculosis prevalence in these patients. The aims of this study was to evaluate tissue samples adjacent to an anthracotic plaque for acid-fast bacilli smear and culture. Methods: his is a cross-sectional analysis study on 100 patients referred to Shahid Sadoughi Hospital who required bronchoscopy and anthracotic plaque based on bronchoscopy results. Bronchial fluid lavage, two biopsy samples for culture, and a smear of Mycobacterium tuberculosis from the surrounding of these plaques were prepared. Data analyses were carried out using SPSS (version 18). Results: One-hundred patients og the age range 46-91years were studied. The patients with tuberculosis diagnosis based on the smear of BAL and bronchial tissue samples and culture of BAL and bronchial tissue samples were 7%, 13%, 6% and 8% respectively. The presence of granuloma in histopathology was seen in 15 patients infected with tuberculosis. (κ > 0.04, p-value <0.05). In patients with positive tuberculosis, culture of bronchoalveolar lavage was superior to other methods. Conclusions: Diagnostic value of BAL method and tissue biopsy in anthracosis patients with tuberculosis did not show a statistically significant difference. As compared with other methods, BAL culture was more positive. Therefore, tissue biopsy is not a good alternative to BAL.

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