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1.
Christina Fotopoulou Andrea Rockall Haonan Lu Philippa Lee Giacomo Avesani Luca Russo Federica Petta Beyhan Ataseven Kai-Uwe Waltering Jens Albrecht Koch William R. Crum Paula Cunnea Florian Heitz Philipp Harter Eric O. Aboagye Andreas du Bois Sonia Prader 《British journal of cancer》2022,126(7):1047
Background Predictive models based on radiomics features are novel, highly promising approaches for gynaecological oncology. Here, we wish to assess the prognostic value of the newly discovered Radiomic Prognostic Vector (RPV) in an independent cohort of high-grade serous ovarian cancer (HGSOC) patients, treated within a Centre of Excellence, thus avoiding any bias in treatment quality.Methods RPV was calculated using standardised algorithms following segmentation of routine preoperative imaging of patients (n = 323) who underwent upfront debulking surgery (01/2011-07/2018). RPV was correlated with operability, survival and adjusted for well-established prognostic factors (age, postoperative residual disease, stage), and compared to previous validation models.Results The distribution of low, medium and high RPV scores was 54.2% (n = 175), 33.4% (n = 108) and 12.4% (n = 40) across the cohort, respectively. High RPV scores independently associated with significantly worse progression-free survival (PFS) (HR = 1.69; 95% CI:1.06–2.71; P = 0.038), even after adjusting for stage, age, performance status and residual disease. Moreover, lower RPV was significantly associated with total macroscopic tumour clearance (OR = 2.02; 95% CI:1.56–2.62; P = 0.00647).Conclusions RPV was validated to independently identify those HGSOC patients who will not be operated tumour-free in an optimal setting, and those who will relapse early despite complete tumour clearance upfront. Further prospective, multicentre trials with a translational aspect are warranted for the incorporation of this radiomics approach into clinical routine.Subject terms: Prognostic markers, Cancer imaging 相似文献
2.
Xinwei Hua Mario Kratz Rachel C. Malen James Y. Dai Sara Lindstrm Yingye Zheng Polly A. Newcomb 《British journal of cancer》2021,125(6):806
Background Biomarker studies on colorectal cancer (CRC) prognosis are limited to pre-diagnostic or pre-operative measures. Post-treatment biomarkers are not well understood for their associations with CRC survival.Methods We included 306 eligible incident stage II–III CRC cases from the population-based Seattle Colon Cancer Family Registry. Concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), adiponectin, and leptin were measured using post-treatment plasma samples. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and CRC-specific mortality were calculated using Cox proportional hazard models.Results Elevated levels of CRP, IL-6, MCP-1, and adiponectin were significantly associated with a higher risk of all-cause mortality within 10 years post blood draw with HRs (95% CI) of 1.32 (1.10–2.59), 2.72 (2.07–3.56), 1.97 (1.18–3.28) and 1.71 (1.14–2.58), respectively. IL-6 and adiponectin had a dose–response effect (Ptrend < 0.0001). For CRC-specific mortality, we observed positive associations for CRP (HR = 1.75, 95% CI: 1.2–2.56), IL-6 (HR = 5.02, 95% CI: 2.92–8.59), MCP-1 (HR = 3.78, 95% CI: 1.41–10.08), and adiponectin (HR = 3.16, 95% CI: 1.27–7.86), and inverse association for leptin (HR = 0.44, 95% CI: 0.29–0.68) within the first year of blood draw, whereas the association for IL-6 remained statistically significant over 10 years.Conclusion Our results support the role of chronic inflammation in CRC progression and suggested several post-treatment inflammatory biomarkers, particularly IL-6, are promising prognostic markers for stage II–III CRC patients.Subject terms: Prognostic markers, Colorectal cancer, Epidemiology 相似文献
3.
D. Gareth Evans Kelly-Anne Phillips Roger L. Milne Robert Fruscio Cezary Cybulski Jacek Gronwald Jan Lubinski Tomasz Huzarski Zerin Hyder Claire Forde Kelly Metcalfe Leigha Senter Jeffrey Weitzel Nadine Tung Dana Zakalik Maria Ekholm Ping Sun Steven A. Narod kConFab Investigators Polish Hereditary
Breast Cancer Consortium Hereditary Breast Cancer Clinical Study Group 《British journal of cancer》2021,124(9):1524
Background The impact of various breast-cancer treatments on patients with a BRCA2 mutation has not been studied. We sought to estimate the impact of bilateral oophorectomy and other treatments on breast cancer-specific survival among patients with a germline BRCA2 mutation.Methods We identified 664 women with stage I–III breast cancer and a BRCA2 mutation by combining five different datasets (retrospective and prospective). Subjects were followed for 7.2 years from diagnosis to death from breast cancer. Tumour characteristics and cancer treatments were patient-reported and derived from medical records. Predictors of survival were determined using Cox proportional hazard models, adjusted for other treatments and for prognostic features.Results The 10-year breast-cancer survival for ER-positive patients was 78.9% and for ER-negative patients was 82.3% (adjusted HR = 1.23 (95% CI, 0.62–2.45, p = 0.55)). The 10-year breast-cancer survival for women who had a bilateral oophorectomy was 89.1% and for women who did not have an oophorectomy was 59.0% (adjusted HR = 0.45; 95% CI, 0.28–0.72, p = 0.001). The adjusted hazard ratio for chemotherapy was 0.83 (95% CI, 0.65–1.53: p = 0.56).Conclusions For women with breast cancer and a germline BRCA2 mutation, positive ER status does not predict superior survival. Oophorectomy is associated with a reduced risk of death from breast cancer and should be considered in the treatment plan.Subject terms: Targeted therapies, Breast cancer 相似文献
4.
Amina Amadou Heinz Freisling Mazda Jenab Konstantinos K. Tsilidis Antonia Trichopoulou Paolo Boffetta Bethany Van Guelpen Olatz Mokoroa Tom Wilsgaard Frank Kee Ben Schttker Jos M. Ordez-Mena Satu Mnnist Stefan Sderberg Roel C. H. Vermeulen J. Ramn Quirs Linda M. Liao Rashmi Sinha Kari Kuulasmaa Hermann Brenner Isabelle Romieu 《British journal of cancer》2021,124(11):1882
Background We investigated whether associations between prevalent diabetes and cancer risk are pertinent to older adults and whether associations differ across subgroups of age, body weight status or levels of physical activity.Methods We harmonised data from seven prospective cohort studies of older individuals in Europe and the United States participating in the CHANCES consortium. Cox proportional hazard regression was used to estimate the associations of prevalent diabetes with cancer risk (all cancers combined, and for colorectum, prostate and breast). We calculated summary risk estimates across cohorts using pooled analysis and random-effects meta-analysis.Results A total of 667,916 individuals were included with an overall median (P25–P75) age at recruitment of 62.3 (57–67) years. During a median follow-up time of 10.5 years, 114,404 total cancer cases were ascertained. Diabetes was not associated with the risk of all cancers combined (hazard ratio (HR) = 0.94; 95% confidence interval (CI): 0.86–1.04; I2 = 63.3%). Diabetes was positively associated with colorectal cancer risk in men (HR = 1.17; 95% CI: 1.08–1.26; I2 = 0%) and a similar HR in women (1.13; 95% CI: 0.82–1.56; I2 = 46%), but with a confidence interval including the null. Diabetes was inversely associated with prostate cancer risk (HR = 0.81; 95% CI: 0.77–0.85; I2 = 0%), but not with postmenopausal breast cancer (HR = 0.96; 95% CI: 0.89–1.03; I2 = 0%). In exploratory subgroup analyses, diabetes was inversely associated with prostate cancer risk only in men with overweight or obesity.Conclusions Prevalent diabetes was positively associated with colorectal cancer risk and inversely associated with prostate cancer risk in older Europeans and Americans.Subject terms: Risk factors, Cancer epidemiology 相似文献
5.
Geffen Kleinstern Dirk R. Larson Cristine Allmer Aaron D. Norman Grace Muntifering Jason Sinnwell Alissa Visram Vincent Rajkumar Angela Dispenzieri Robert A. Kyle Susan L. Slager Shaji Kumar Celine M. Vachon 《Blood cancer journal》2022,12(4)
Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant clonal disorder that progresses to multiple myeloma (MM), or other plasma-cell or lymphoid disorders at a rate of 1%/year. We evaluate the contribution of body mass index (BMI) to MGUS progression beyond established clinical factors in a population-based study. We identified 594 MGUS through a population-based screening study in Olmsted County, Minnesota, between 1995 and 2003. Follow-up time was calculated from the date of MGUS to last follow-up, death, or progression to MM/another plasma-cell/lymphoid disorder. BMI (kg/m2 < 25/≥25) was measured close to screening date. We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of BMI ≥ 25 versus BMI < 25 with MGUS progression and also evaluated the corresponding c-statistic and 95% CI to describe discrimination of the model for MGUS progression. Median follow-up was 10.5 years (range:0–25), while 465 patients died and 57 progressed and developed MM (N = 39), AL amyloidosis (N = 8), lymphoma (N = 5), or Waldenstrom-macroglobulinemia (N = 5). In univariate analyses, BMI ≥ 25 (HR = 2.14,CI:1.05–4.36, P = 0.04), non-IgG (HR = 2.84, CI:1.68–4.80, P = 0.0001), high monoclonal (M) protein (HR = 2.57, CI:1.50–4.42, P = 0.001), and abnormal free light chain ratio (FLCr) (HR = 3.39, CI:1.98–5.82, P < 0.0001) were associated with increased risk of MGUS progression, and were independently associated in a multivariable model (c-statistic = 0.75, CI:0.68–0.82). The BMI association was stronger among females (HR = 3.55, CI:1.06–11.9, P = 0.04) vs. males (HR = 1.39, CI:0.57–3.36, P = 0.47), although the interaction between BMI and sex was not significant (P = 0.15). In conclusion, high BMI is a prognostic factor for MGUS progression, independent of isotype, M protein, and FLCr. This association may be stronger among females.Subject terms: Risk factors, Cancer 相似文献
6.
Angelika M. Starzer Ariane Steindl Maximilian J. Mair Carola Deischinger Anika Simonovska Georg Widhalm Brigitte Gatterbauer Karin Dieckmann Gerwin Heller Matthias Preusser Anna S. Berghoff 《British journal of cancer》2021,124(7):1294
Background Systemic inflammation measured by the neutrophil-to-lymphocyte ratio (NLR), leucocyte-to-lymphocyte ratio (LLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and CRP/albumin ratio (CRP/Alb) was shown to impact the survival prognosis in patients with extracranial solid cancer.Methods One thousand two hundred and fifty patients with newly diagnosed brain metastases (BM) were identified from the Vienna Brain Metastasis Registry.Results PLR and CRP/Alb were higher in patients with progressive extracranial disease and lower in patients with no evidence of extracranial disease. Lower NLR (cut-off = 5.07; 9.3 vs. 5.0 months), LLR (cut-off = 5.76; 10.0 vs. 5.3 months), PLR (cut-off = 335; 8.0 vs. 3.8 months), MLR (cut-off = 0.53; 6.0 vs. 3.5 months) and CRP/Alb (cut-off = 2.93; 8.5 vs. 3.7 months; padj < 0.05) were associated with longer overall survival (OS). In multivariate analysis with graded prognostic assessment (hazard ratio (HR) 1.45; 95% confidence interval (CI): 1.32–1.59; padj = 1.62e − 13), NLR (HR 1.55; 95% CI: 1.38–1.75; padj = 1.92e − 11), LLR (HR 1.57; 95% CI: 1.39–1.77; padj = 1.96e − 11), PLR (HR 1.60; 95% CI: 1.39–1.85; padj = 2.87955e − 9), MLR (HR 1.41; 95% CI: 1.14–1.75; padj = 0.027) and CRP/Alb (HR 1.83; 95% CI: 1.54–2.18; padj = 2.73e − 10) remained independent factors associated with OS at BM diagnosis.Conclusions Systemic inflammation, measured by NLR, LLR, PLR, MLR and CRP/Alb, was associated with OS in patients with BM. Further exploration of immune modulating therapies is warranted in the setting of BM.Subject terms: CNS cancer, Prognostic markers, Outcomes research 相似文献
7.
Peter G. Alexander Antonia K. Roseweir Kathryn A. F. Pennel Hester C. van Wyk Arfon G. M. T. Powell Donald C. McMillan Paul G. Horgan Caroline Kelly Jennifer Hay Owen Sansom Andrea Harkin Campbell S. D. Roxburgh Janet Graham David N. Church Ian Tomlinson Mark Saunders Tim J. Iveson Joanne Edwards James H. Park 《British journal of cancer》2021,124(4):786
Background The Glasgow Microenvironment Score (GMS) combines peritumoural inflammation and tumour stroma percentage to assess interactions between tumour and microenvironment. This was previously demonstrated to associate with colorectal cancer (CRC) prognosis, and now requires validation and assessment of interactions with adjuvant therapy.Methods Two cohorts were utilised; 862 TNM I–III CRC validation cohort, and 2912 TNM II–III CRC adjuvant chemotherapy cohort (TransSCOT). Primary endpoints were disease-free survival (DFS) and relapse-free survival (RFS). Exploratory endpoint was adjuvant chemotherapy interaction.Results GMS independently associated with DFS (p = 0.001) and RFS (p < 0.001). GMS significantly stratified RFS for both low risk (GMS 0 v GMS 2: HR 3.24 95% CI 1.85–5.68, p < 0.001) and high-risk disease (GMS 0 v GMS 2: HR 2.18 95% CI 1.39–3.41, p = 0.001). In TransSCOT, chemotherapy type (pinteraction = 0.013), but not duration (p = 0.64) was dependent on GMS. Furthermore, GMS 0 significantly associated with improved DFS in patients receiving FOLFOX compared with CAPOX (HR 2.23 95% CI 1.19–4.16, p = 0.012).Conclusions This study validates the GMS as a prognostic tool for patients with stage I–III colorectal cancer, independent of TNM, with the ability to stratify both low- and high-risk disease. Furthermore, GMS 0 could be employed to identify a subset of patients that benefit from FOLFOX over CAPOX.Subject terms: Prognostic markers, Predictive markers, Outcomes research, Surgical oncology 相似文献
8.
Sweet Ping Ng Houda Bahig Amit Jethanandani Erich M. Sturgis Faye M. Johnson Baher Elgohari G. Brandon Gunn Renata Ferrarotto Jack Phan David I. Rosenthal Steven J. Frank Clifton D. Fuller Adam S. Garden 《British journal of cancer》2021,124(3):628
Background This study aimed to evaluate the prognostic value of pre-treatment NLR in patients with oropharyngeal cancer.Methods Patients who completed definitive radiotherapy (RT) for oropharyngeal cancer and had blood counts taken pre-RT from 2002 to 2013 were included. NLR was calculated as total neutrophil/lymphocytes. Survival rates were estimated using the Kaplan–Meier method. Univariable and multivariable analyses were conducted with linear and Cox regression methods. NLR was analysed posteriori and dichotomised on the discovered median.Results Eight hundred and forty-eight patients were analysed. The median pre-RT NLR was 3. Patients with NLR of <3 had improved overall survival (OS) than those with NLR ≥ 3 (5-year OS 85 vs 74%, p < 0.0001). OS differences remained significant when stratified according to HPV status (HPV-positive p = 0.011; HPV-negative p = 0.003). Freedom from any recurrence (FFR), locoregional control (LRC) and freedom of distant recurrence (FDR) were better in those with NLR < 3. The negative impact of elevated pre-RT NLR on OS (HR = 1.64, p = 0.001), FFR (HR = 1.6, p = 0.006) and LRC (HR = 1.8, p = 0.005) remained significant on multivariable analysis.Conclusions Pre-RT NLR is an independent prognostic factor in patients with oropharyngeal cancer regardless of HPV status. Patients with lower NLR had more favourable OS and disease control.Subject terms: Prognostic markers, Head and neck cancer 相似文献
9.
10.
Jin-Hyoung Kang Ki-Hyeong Lee Dong-Wan Kim Sang-We Kim Hye Ryun Kim Joo-Hang Kim Jin-Hyuk Choi Ho Jung An Jin-Soo Kim Joung-Soon Jang Bong-Seog Kim Heung Tae Kim 《British journal of cancer》2021,124(4):713
Background This study compared the efficacy/safety of the camptothecin analogues belotecan and topotecan for sensitive-relapsed small-cell lung cancer (SCLC).Methods One-hundred-and-sixty-four patients were randomised (1:1) to receive five consecutive daily intravenous infusions of topotecan (1.5 mg/m2) or belotecan (0.5 mg/m2), every 3 weeks, for six cycles. Main outcomes were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), tolerability and toxicity. The study statistical plan was non-inferiority design with ORR as the endpoint.Results In the belotecan vs. topotecan groups, ORR (primary endpoint) was 33% vs. 21% (p = 0.09) and DCR was 85% vs. 70% (p = 0.030). PFS was not different between groups. Median OS was significantly longer with belotecan than with topotecan (13.2 vs. 8.2 months, HR = 0.69, 95% CI: 0.48–0.99), particularly in patients aged <65 years, with more advanced disease (i.e., extensive-stage disease, time to relapse: 3–6 months), or Eastern Cooperative Oncology Group performance status 1 or 2. More belotecan recipients completed all treatment cycles (53% vs. 35%; p = 0.022).Conclusions The efficacy/safety of belotecan warrants further evaluation in Phase 3 trials. Belotecan potentially offers an alternative to topotecan for sensitive-relapsed SCLC, particularly in patients aged <65 years, with more advanced disease, or poor performance.Subject terms: Small-cell lung cancer, Lung cancer 相似文献
11.
Usha Patel Manish Pandey Sadhana Kannan Tanuja A. Samant Poonam Gera Neha Mittal Swapnil Rane Asawari Patil Vanita Noronha Amit Joshi Vijay M. Patil Kumar Prabhash Manoj B. Mahimkar 《British journal of cancer》2020,123(12):1757
Background Anti-EGFR-based therapies have limited success in HNSCC patients. Predictive biomarkers are greatly needed to identify the patients likely to be benefited from these targeted therapies. Here, we present the prognostic and predictive association of biomarkers in HPV-negative locally advanced (LA) HNSCC patients.Methods Treatment-naive tumour tissue samples of 404 patients, a subset of randomised Phase 3 trial comparing cisplatin radiation (CRT) versus nimotuzumab plus cisplatin radiation (NCRT) were analysed to evaluate the expression of HIF1α, EGFR and pEGFR by immunohistochemistry and EGFR gene copy change by FISH. Progression-free survival (PFS), locoregional control (LRC) and overall survival (OS) were estimated by Kaplan–Meier method. Hazard ratios were estimated by Cox proportional hazard models.Results Baseline characteristics of the patients were balanced between two treatment groups (CRT vs NCRT) and were representative of the trial cohort. The median follow-up was of 39.13 months. Low HIF1α was associated with better PFS [HR (95% CI) = 0.62 (0.42–0.93)], LRC [HR (95% CI) = 0.56 (0.37–0.86)] and OS [HR (95% CI) = 0.63 (0.43–0.93)] in the CRT group. Multivariable analysis revealed HIF1α as an independent negative prognostic biomarker. For patients with high HIF1α, NCRT significantly improved the outcomes [PFS:HR (95% CI) = 0.55 (0.37–0.82), LRC:HR (95% CI) = 0.55 (0.36–0.85) and OS:HR (95% CI) = 0.54 (0.36–0.81)] compared to CRT. While in patients with low HIF1α, no difference in the clinical outcomes was observed between treatments. Interaction test suggested a predictive value of HIF1α for OS (P = 0.008).Conclusions High HIF1α expression is a predictor of poor clinical response to CRT in HPV-negative LA-HNSCC patients. These patients with high HIF1α significantly benefited with the addition of nimotuzumab to CRT.Clinical trial registration Registered with the Clinical Trial Registry of India (Trial registration identifier—CTRI/2014/09/004980).Subject terms: Tumour biomarkers, Head and neck cancer, Tumour biomarkers, Head and neck cancer, Predictive markers 相似文献
12.
Alicia F. C. Okines Emma Kipps Tazia Irfan Maria Coakley Vaselios Angelis Bernice Asare Kabir Mohammed Geraldine Walsh Alistair Ring Stephen R. D. Johnston Marina Parton Nicholas C. Turner Ian E. Smith 《British journal of cancer》2021,125(2):299
Background The optimal time to deliver adjuvant chemotherapy has not been defined.Methods A retrospective study of consecutive patients receiving adjuvant anthracycline and/or taxane 1993–2010. Primary endpoint included 5-year disease-free survival (DFS) in patients commencing chemotherapy <31 versus ≥31 days after surgery. Secondary endpoints included 5-year overall survival (OS) and sub-group analysis by receptor status.Results We identified 2003 eligible patients: 1102 commenced chemotherapy <31 days and 901 ≥31 days after surgery. After a median follow-up of 115 months, there was no difference in 5-year DFS rate with chemotherapy <31 compared to ≥31 days after surgery in the overall population (81 versus 82% hazard ratio (HR) 1.15, 95% confidence interval (95% CI) 0.92–1.43, p = 0.230). The 5-year OS rate was similar in patients who received chemotherapy <31 or ≥31 days after surgery (90 versus 91%, (HR 1.21, 95% CI 0.89–1.64, p = 0.228). For 250 patients with triple-negative breast cancer OS was significantly worse in patients who received chemotherapy ≥31 versus <31 days (HR = 2.18, 95% CI 1.11–4.30, p = 0.02).Discussion Although adjuvant chemotherapy ≥31 days after surgery did not affect DFS or OS in the whole study population, in TN patients, chemotherapy ≥31 days after surgery significantly reduced 5-year OS; therefore, delays beyond 30 days in this sub-group should be avoided.Subject terms: Chemotherapy, Breast cancer 相似文献
13.
Maryam S. Farvid Nicholas D. Spence Bernard A. Rosner Walter C. Willett A. Heather Eliassen Michelle D. Holmes 《British journal of cancer》2021,124(11):1873
Background We examined the role of post-diagnostic coffee and tea consumption in relation to breast cancer-specific and all-cause mortality among women with breast cancer in prospective cohort studies.Methods We identified 8900 women with stage I–III breast cancer from 1980 through 2010 in the Nurses’ Health Study (NHS) and from 1991 through 2011 in the NHSII. Post-diagnostic coffee and tea consumption was assessed by a validated food frequency questionnaire every 4 years after diagnosis.Results During up to 30 years of follow-up, we documented 1054 breast cancer-specific deaths and 2501 total deaths. Higher post-diagnostic coffee consumption was associated with a lower breast cancer-specific mortality: compared with non-drinkers, >3 cups/day of coffee was associated with a 25% lower risk (hazard ratio (HR) = 0.75, 95% confidence interval (CI) = 0.59–0.96; Ptrend = 0.002). We also observed a lower all-cause mortality with coffee consumption: compared with non-drinkers, >2 to 3 cups/day was associated with a 24% lower risk (HR = 0.76, 95% CI = 0.66–0.87) and >3 cups/day was associated with a 26% lower risk (HR = 0.74, 95% CI = 0.63–0.87, Ptrend < 0.0001). Post-diagnostic tea consumption was associated with a lower all-cause mortality: compared with non-drinkers, >3 cups/day was associated with a 26% lower risk (HR = 0.74, 95% CI = 0.58–0.95; Ptrend = 0.04).Conclusions Among breast cancer survivors, higher post-diagnostic coffee consumption was associated with better breast cancer and overall survival. Higher post-diagnostic tea consumption may be related to better overall survival.Subject terms: Breast cancer, Outcomes research 相似文献
14.
Dana M. Roque Eric R. Siegel Natalia Buza Stefania Bellone Dan-Arin Silasi Gloria S. Huang Vaagn Andikyan Mitchell Clark Masoud Azodi Peter E. Schwartz Gautam G. Rao Jocelyn C. Reader Pei Hui Joan R. Tymon-Rosario Justin Harold Dennis Mauricio Burak Zeybek Gulden Menderes Gary Altwerger Elena Ratner Alessandro D. Santin 《British journal of cancer》2022,126(12):1695
Background This multi-center RP2 study assessed activity/safety of ixabepilone + bevacizumab compared to ixabepilone in platinum-resistant/refractory ovarian/fallopian tube/primary peritoneal cancer. Additional objectives were to examine the role of prior bevacizumab and taxanes, and explore class III-ß-tubulin (TUBB3) as a predictive biomarker.Methods Participants were randomised to receive ixabepilone 20 mg/m2 days 1, 8, 15 with (IXA + BEV) or without (IXA) bevacizumab 10 mg/kg days 1, 15 every 28 days. Patients were stratified by prior BEV. The primary endpoint was PFS. OS, safety, and ORR served as secondary endpoints.Results Among 76 evaluable patients who received IXA + BEV (n = 39) compared to IXA (n = 37), the ORR was 33% (n = 13) versus 8% (n = 3)(P = 0.004), durable at 6 months in 37% (n = 14) and 3% (n = 1) (P < 0.001). BEV significantly improved PFS (median:5.5 vs 2.2 months, HR = 0.33, 95%CI 0.19–0.55, P < 0.001) and OS (median:10.0 vs 6.0 months, HR = 0.52, 95%CI 0.31–0.87, P = 0.006). Both regimens were well-tolerated. TUBB3 expression did not predict response. Subgroup analyses revealed minimal effect of prior BEV or taxane resistant/refractory status on response to IXA + BEV.Conclusions IXA + BEV is a well-tolerated, effective combination for platinum/taxane-resistant ovarian cancer that extends PFS and likely OS relative to IXA monotherapy. Prior receipt of BEV should not preclude the use of IXA + BEV. TUBB3 is not a predictive biomarker.Clinical trial registration NCT3093155.Subject terms: Translational research, Phase II trials 相似文献
15.
Frances Willenbrock Catrin M. Cox Eileen E. Parkes Charlotte S. Wilhelm-Benartzi Aswin G. Abraham Robert Owens Ahmad Sabbagh Christopher M. Jones Daniel L. I. Hughes Tim Maughan Christopher N. Hurt Eric E. ONeill Somnath Mukherjee 《British journal of cancer》2021,124(3):581
Background The Phase 2 SCALOP trial compared gemcitabine with capecitabine-based consolidation chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC).Methods Thirty-five systematically identified circulating biomarkers were analysed in plasma samples from 60 patients enroled in SCALOP. Each was measured in triplicate at baseline (prior to three cycles of gemcitabine-capecitabine induction chemotherapy) and, for a subset, prior to CRT. Association with overall survival (OS) was determined using univariable Cox regression and optimal thresholds delineating low to high values identified using time-dependent ROC curves. Independence from known prognostic factors was assessed using Spearman correlation and the Wilcoxon rank sum test prior to multivariable Cox regression modelling including independent biomarkers and known prognostic factors.Results Baseline circulating levels of C-C motif chemokine ligand 5 (CCL5) were significantly associated with OS, independent of other clinicopathological characteristics. Patients with low circulating CCL5 (CCL5low) had a median OS of 18.5 (95% CI 11.76–21.32) months compared to 11.3 (95% CI 9.86–15.51) months in CCL5high; hazard ratio 1.95 (95% CI 1.04–8.65; p = 0.037).Conclusions CCL5 is an independent prognostic biomarker in LAPC. Given the known role of CCL5 in tumour invasion, metastasis and the induction of an immunosuppressive micro-environment, targeting of CCL5-mediated pathways may offer therapeutic potential in pancreatic cancer.Clinical trial registration The SCALOP trial was registered with ISRCTN, number 96169987 (registered 29 May 2008).Subject terms: Pancreatic cancer, Tumour biomarkers 相似文献
16.
Joshua Bauml Lu Chen Jinbo Chen Jean Boyer Michael Kalos Susan Q. Li Angela DeMichele Jun J. Mao 《Breast cancer research : BCR》2015,17(1)
Introduction
Arthralgia is a common toxicity among women taking aromatase inhibitors (AIs) and can lead to premature discontinuation of therapy. We evaluated the association between arthralgia, co-morbid fatigue and/or insomnia, and inflammatory biomarkers among women taking AIs.Methods
Women taking AIs for early-stage breast cancer completed a modified version of the Brief Pain Inventory, the Brief Fatigue Inventory, and the Insomnia Severity Index and provided blood samples for simultaneous assessment of 34 inflammatory biomarkers with a Luminex kit. Two-sided t tests were used to compare inflammatory biomarker concentrations for patients with or without moderate to severe arthralgia. Multivariate linear regression analyses were performed to evaluate the relationship between comorbid arthralgia, fatigue, and insomnia with identified biomarker concentrations.Results
Among 203 participants, the severity of arthralgia, fatigue, and insomnia were significantly correlated with each other (p < 0.001 for all comparisons). After controlling for race, chemotherapy history, non-steroidal anti-inflammatory drug use, age, and body mass index, the coexistence of arthralgia, fatigue, and insomnia was associated with elevated C-reactive protein (CRP) (β = 93.1; 95 % confidence interval (CI): 25.1–161.1; p = 0.008), eotaxin (β = 79.9; 95 % CI: 32.5–127.2; p = 0.001), monocyte chemoattractant protein (MCP)-1 (β = 151.2; 95 % CI: 32.7–269.8; p = 0.013), and vitamin D–binding protein (VDBP) (β = 19,422; 95 % CI: 5500.5–33,344; p = 0.006).Conclusions
Among women taking AIs, the coexistence of arthralgia, fatigue, and insomnia was associated with increased levels of inflammatory biomarkers (elevated CRP, eotaxin, MCP-1, and VDBP). These findings suggest a possible shared inflammatory mechanism underlying these common symptoms.Electronic supplementary material
The online version of this article (doi:10.1186/s13058-015-0599-7) contains supplementary material, which is available to authorized users. 相似文献17.
Daniel Martin Klotz Theresa Link Pauline Wimberger Jan Dominik Kuhlmann 《Molecular oncology》2021,15(12):3626
The pleiotropic protein hepatocyte growth factor (HGF) is the only known ligand of the tyrosine kinase mesenchymal–epithelial transition (cMET) receptor. The HGF/cMET pathway mediates invasion and migration of ovarian cancer cells, and upregulation of HGF/cMET pathway components has been associated with poor prognosis. This study investigated the clinical relevance of circulating HGF in serum of patients with ovarian cancer. Serum HGF (sHGF) was determined by enzyme‐linked immunosorbent assay in a total of 471 serum samples from 82 healthy controls and 113 patients with ovarian cancer (88.5% with ≥ FIGO III). Patient samples were collected at primary diagnosis and at four follow‐up time points throughout treatment and at disease recurrence. Patients with ovarian cancer showed elevated median sHGF levels at primary diagnosis, and sHGF levels transiently increased after surgery and normalized in the course of chemotherapy, even dropping below initial baseline. Higher levels of sHGF were an independent predictor for shorter overall survival (OS) (a) at primary diagnosis (HR = 0.41, 95% CI: 0.22–0.78, P = 0.006), (b) at longitudinal follow‐up time points (after surgery and before/during/after chemotherapy), (c) along the patients’ individual dynamics (HR = 0.21, 95% CI: 0.07–0.63, P = 0.005), and (d) among a subgroup analysis of patients with BRCA1/2 wild‐type ovarian cancer. This is the first study proposing sHGF as an independent prognostic biomarker for ovarian cancer at primary diagnosis and in the course of platinum‐based chemotherapy, irrespective of the postoperative residual disease after surgical debulking. sHGF could be implemented into clinical diagnostics as a CA125 auxiliary tumor marker for individualized prognosis stratification and sHGF‐guided therapy monitoring. 相似文献
18.
Bella Pajares Marina Pollán Miguel Martín John R Mackey Ana Lluch Joaquín Gavila Charles Vogel Manuel Ruiz-Borrego Lourdes Calvo Tadeusz Pienkowski álvaro Rodríguez-Lescure Miguel Angel Seguí Olivier Tredan Antonio Antón Manuel Ramos María del Carmen Cámara César Rodríguez-Martín Eva Carrasco Emilio Alba 《Breast cancer research : BCR》2013,15(6):R105
Introduction
Obesity is an unfavorable prognostic factor in breast cancer (BC) patients regardless of menopausal status and treatment received. However, the association between obesity and survival outcome by pathological subtype requires further clarification.Methods
We performed a retrospective analysis including 5,683 operable BC patients enrolled in four randomized clinical trials (GEICAM/9906, GEICAM/9805, GEICAM/2003–02, and BCIRG 001) evaluating anthracyclines and taxanes as adjuvant treatments. Our primary aim was to assess the prognostic effect of body mass index (BMI) on disease recurrence, breast cancer mortality (BCM), and overall mortality (OM). A secondary aim was to detect differences of such prognostic effects by subtype.Results
Multivariate survival analyses adjusting for age, tumor size, nodal status, menopausal status, surgery type, histological grade, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, chemotherapy regimen, and under-treatment showed that obese patients (BMI 30.0 to 34.9) had similar prognoses to that of patients with a BMI < 25 (reference group) in terms of recurrence (Hazard Ratio [HR] = 1.08, 95% Confidence Interval [CI] = 0.90 to 1.30), BCM (HR = 1.02, 0.81 to 1.29), and OM (HR = 0.97, 0.78 to 1.19). Patients with severe obesity (BMI ≥ 35) had a significantly increased risk of recurrence (HR = 1.26, 1.00 to 1.59, P = 0.048), BCM (HR = 1.32, 1.00 to 1.74, P = 0.050), and OM (HR = 1.35, 1.06 to 1.71, P = 0.016) compared to our reference group. The prognostic effect of severe obesity did not vary by subtype.Conclusions
Severely obese patients treated with anthracyclines and taxanes present a worse prognosis regarding recurrence, BCM, and OM than patients with BMI < 25. The magnitude of the harmful effect of BMI on survival-related outcomes was similar across subtypes. 相似文献19.
Meike Kohlruss Marie Krenauer Bianca Grosser Nicole Pfarr Moritz Jesinghaus Julia Slotta-Huspenina Alexander Novotny Alexander Hapfelmeier Thomas Schmidt Katja Steiger Matthias M. Gaida Magdalena Reiche Lukas Bauer Katja Ott Wilko Weichert Gisela Keller 《British journal of cancer》2021,125(12):1621
Background The Cancer Genome Atlas (TCGA) consortium described EBV positivity(+), high microsatellite instability (MSI-H), genomic stability (GS) and chromosomal instability (CIN) as molecular subtypes in gastric carcinomas (GC). We investigated the predictive and prognostic value of these subtypes with emphasis on CIN in the context of neoadjuvant chemotherapy (CTx) in GC.Methods TCGA subgroups were determined for 612 resected adenocarcinomas of the stomach and gastro-oesophageal junction (291 without, 321 with CTx) and 143 biopsies before CTx.EBV and MSI-H were analysed by standard assays. CIN was detected by multiplex PCRs analysing 22 microsatellite markers. Besides the TCGA classification, CIN was divided into four CIN-subgroups: low, moderate, substantial, high. Mutation profiling was performed for 52 tumours by next-generation sequencing.Results EBV(+) (HR, 0.48; 95% CI, 0.23–1.02), MSI-H (HR, 0.56; 95% CI, 0.35–0.89) and GS (HR, 0.72; 95% CI, 0.45–1.13) were associated with increased survival compared to CIN in the resected tumours. Considering the extended CIN-classification, CIN-substantial was a negative prognostic factor in uni- and multivariable analysis in resected tumours with CTx (each p < 0.05). In biopsies before CTx, CIN-high predicted tumour regression (p = 0.026), but was not prognostically relevant.Conclusion A refined CIN classification reveals tumours with different biological characteristics and potential clinical implications.Subject terms: Gastric cancer, Surgical oncology, Prognostic markers, Predictive markers 相似文献
20.
《Journal of thoracic oncology》2017,12(12):1779-1787
IntroductionKilovoltge cone beam computed tomography (kV-CBCT) allows for tumor localization and response assessment during definitive chemoradiotherapy for locally advanced NSCLC. We hypothesize that significant tumor volume loss occurs early during radiotherapy and that the extent of volume loss correlates with clinical outcomes.MethodsA total of 52 patients with locally advanced NSCLC treated with definitive chemoradiotherapy were reviewed. kV-CBCT images were used to contour primary gross tumor volumes at four time points during treatment. Patients were dichotomized according to absolute and relative volume changes at each time point. Statistical analyses were performed to evaluate correlations between volume changes and clinical outcomes.ResultsThe median gross tumor volumes were 77.1, 48.3, 42.5, and 29.9 cm3 for fractions 1, 11, 21, and final, respectively. Greater relative volume loss between fractions 1 and 21 correlated with improved distant control (hazard ratio [HR] = 0.35, 95% confidence interval [CI]: 0.13–0.94, p = 0.038) and overall survival (HR = 0.40, 95% CI: 0.16–0.98, p = 0.046). Greater relative volume loss between fractions 11 and 21 correlated with improved progression-free survival (HR = 0.39, 95% CI: 0.17–0.88, p = 0.02) and trended toward improved overall survival (HR = 0.43, 95% CI: 0.17–1.06, p = 0.07). On multivariate analysis, greater relative volume loss between fractions 11 and 21 correlated with improved progression-free survival (HR = 0.39, 95% CI: 0.16–0.97, p = 0.041) and overall survival (HR = 0.31, 95% CI: 0.11–0.88, p = 0.027).ConclusionsSignificant primary tumor volume loss occurs early during radiotherapy for locally advanced NSCLC. Greater relative tumor volume loss during treatment correlates with improved disease control and overall survival. Thus, kV-CBCT has potential to be used as a practical prognostic imaging marker. 相似文献