Search

Abstract Introduction There have been no reports about predicting survival of patients with advanced cancer constructed entirely with objective variables. We aimed to develop a prognostic model based on laboratory findings and vital signs using a fractional polynomial (FP) model. Methods A multicentre prospective cohort study was conducted at 58 specialist palliative care services in Japan from September 2012 to April 2014. Eligible patients were older than 20 years and had advanced cancer. We developed models for predicting 7-day, 14-day, 30-day, 56-day and 90-day survival by using the FP modelling method. Results Data from 1039 patients were analysed to develop each prognostic model (Objective Prognostic Index for advanced cancer [OPI-AC]). All models included the heart rate, urea and albumin, while some models included the respiratory rate, creatinine, C-reactive protein, lymphocyte count, neutrophil count, total bilirubin, lactate dehydrogenase and platelet/lymphocyte ratio. The area under the curve was 0.77, 0.81, 0.90, 0.90 and 0.92 for the 7-day, 14-day, 30-day, 56-day and 90-day model, respectively. The accuracy of the OPI-AC predicting 30-day, 56-day and 90-day survival was significantly higher than that of the Palliative Prognostic Score or the Prognosis in Palliative Care Study model, which are based on a combination of symptoms and physician estimation. Conclusion We developed highly accurate prognostic indexes for predicting the survival of patients with advanced cancer from objective variables alone, which may be useful for end-of-life management. The FP modelling method could be promising for developing other prognostic models in future research. Highlights • We developed a prognostic index that required only laboratory data and vital signs. • Survival of advanced cancer patients can be predicted without a physician's assessments. • Our prognostic index was more accurate than existing predictive tools. • Our prognostic index could minimize attrition rates of clinical trials. • Fractional polynomials model is a promising way to develop prognostic indexes. [ABSTRACT FROM AUTHOR]

Background Adolescent and young adult (AYA) patients with advanced solid tumours are often considered for phase I clinical trials with novel agents. The outcome of AYAs in these trials have not been described before. Aim To study the outcome of AYA patients in phase I clinical trials. Methods Clinical trial data of AYAs (defined as aged 15–39 years at diagnosis) treated at the Drug Development Unit, Royal Marsden Hospital, between 2002 and 2016, were analysed. Results From a prospectively maintained database of 2631 patients treated in phase I trials, 219 AYA patients (8%) were identified. Major tumour types included gynaecological cancer (25%) and sarcoma (18%). Twenty-five (11%) had a known hereditary cancer syndrome (most commonly BRCA). Molecular characterisation of tumours (n = 45) identified mutations most commonly in TP53 (33%), PI3KCA (18%) and KRAS (9%). Therapeutic targets of trials included DNA damage repair (16%), phosphoinositide 3-kinase (PI3K) (16%) and angiogenesis (16%). Grade 3/4 toxicities were experienced in 26% of patients. Of the 214 evaluable patients, objective response rate was 12%, with clinical benefit rate at 6 months of 22%. Median overall survival (OS) was 7.5 months (95% confidence interval: 6.3–9.5), and 2-year OS was 11%. Of patients with responses, 36% were matched to phase I trials based on germline or somatic genetic aberrations. Conclusion We describe the outcome of the largest cohort of AYA patients treated in phase I trials. A subgroup of these patients demonstrates benefit, with several durable responses beyond 2 years. A sizeable proportion of AYA patients have cancer syndromes, significant family history or somatic molecular aberrancies which may influence novel therapeutic treatment options. [ABSTRACT FROM AUTHOR]

Aim The aim of this study is to firmly delineate temporal and age trends regarding sex discrepancies in cancer risk and survival as well as quantifying the potential gain achieved by eliminating this inequality. Methods We performed a population-based cohort study using data on all adult incident cancer cases (n = 872,397) recorded in the Swedish Cancer Register in 1970–2014. To assess the associations between sex and cancer risk and sex and survival, male-to-female incidence rate ratios (IRRs) and excess mortality ratios (EMRs) adjusted for age and year of diagnosis were estimated using Poisson regression. Results Men were at increased risk for 34 of 39 and had poorer prognosis for 27 of 39 cancers. Women were at increased risk for 5 of 39 and had significantly poorer survival for 2 of 39 cancers. IRRs among male predominant sites ranged from 1.05; 95% confidence interval (CI), 1.03–-1.1 (lung adenocarcinoma) to 8.0; 95% CI, 7.5–8.5 (larynx). EMRs among sites with male survival disadvantage ranged from 1.1; 95% CI, 1.03–1.1 (colon) to 2.1; 95% CI, 1.5–-2.8 (well-differentiated thyroid). Conclusion Male sex is associated with increased risk and poorer survival for most cancer sites. Identifying and eliminating factors driving the observed sex differences may reduce the global cancer burden. [ABSTRACT FROM AUTHOR]

Introduction A number of phase I immunotherapy trials for cancer patients incorporate the absolute lymphocyte count (ALC) as an inclusion criteria. This study aims to assess whether ALC is associated with a lack of response to anti-PD-1/PD-L1 in early clinical trials. Methods All consecutive patients treated with anti-PD-1/PD-L1 monotherapy in phase I trials in our institution between December 2011 and January 2014 were reviewed. Baseline ALC, neutrophil-to-lymphocyte ratio (NLR), Royal-Marsden Hospital (RMH) prognostic score, objective response rate (ORR) and disease control rate (DCR = SD + PR + CR, stable disease (SD), partial response (PR), complete response (CR)) defined by Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 were retrieved. Results Out of a total of 167 patients, 48 (28.7%) and 8 patients (4.8%) had baseline ALCs of <1 G/l and <0.5 G/l, respectively. The RECIST change (%) was not correlated with ALC (G/l) (Spearman's rho = −0.06, P = 0.43). We did not observe any difference in terms of ORR (8.3% versus 15.1%, P = 0.32) or of DCR (58.3% versus 61.3%, P = 0.73) between patients with ALC <1 G/l versus >1 G/l. When using 0.5 G/l as ALC threshold, we did not find any difference either in ORR or in DCR. In a multivariate Cox regression analysis, baseline ALC was not associated with overall survival, whereas the RMH and the number of previous lines of treatment remained independent prognostic factors. Conclusions Baseline ALC was not associated with response to anti-PD-1/PD-L1 in cancer patients enrolled in phase I trials. Patients should not be excluded from early phase clinical trials testing immune checkpoints blockers because of ALC. [ABSTRACT FROM AUTHOR]

Introduction Life expectancy evaluation is crucial when selecting patients who may benefit from phase I studies. The Royal Marsden Hospital (RMH) prognostic score, based on three objective variables (number of metastatic sites, lactate dehydrogenase (LDH) and serum albumin) was validated in patients treated with cytotoxics and targeted therapies. We aimed to determine if those factors were applicable to immune-checkpoint therapies (ICTs) in phase I trials and to evaluate new variables that may preclude a better prognosis in patients receiving ICT. Patients and methods We conducted a retrospective analysis of survival risk factors in a discovery cohort of 155 patients enrolled into ICT phase I trials at our institution. We computed univariate analysis and multivariate analysis (MVA) of demographics, clinical and biological data to assess their prognostic value for overall survival (OS). MVA results were used to build a prognostic score for OS. A validation cohort of 113 patients enrolled in phase I ICT trials was used to prospectively validate this score. Results A total of 155 patients (M/F: 83/72; median age 59) receiving an experimental ICT between March 2012 and January 2016 were included in the discovery cohort. An MVA assessing the RMH score variables showed that low albumin (hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.05–2.86) and LDH > upper limit normal (ULN) (HR 1.88, 95% CI 1.12–3.15) were independent negative prognostic factors for OS. Interestingly, neutrophil-to-lymphocyte ratio (NLR) > 6 (HR 1.75, 95% CI 1.04–2.95) was associated with a decrease in OS. The number of metastases was not associated with a poorer outcome for this ICT cohort (HR 0.83, 95% CI 0.51–1.35). A risk score based on the results of the MVA (NLR > 6 = 1; LDH > ULN = 1; albumin < 35 g/l = 1) showed that patients presenting a high score (>1) had a significantly shorter OS (20.4 weeks; 95% CI 5.7–35.2) compared to those with a low score (0 or 1) (68.9 weeks; 95% CI 50–83.7) (HR 2.9, 95% CI 1.87–4.64). In the validation cohort of 113 patients, again the patients presenting a high score showed an inferior OS (HR 6.3, 95% CI 2.7–14.8). Conclusion In ICT phase I trials, traditional prognostic variables included in the RMH score may be suboptimal to determine patient's prognosis. In this context, the NLR is a significant prognostic variable. The Gustave Roussy Immune Score, based on albumin, LDH and NLR, allows a better selection of patients for ICT phase I trials. [ABSTRACT FROM AUTHOR]

Introduction Performance status (PS) is an established prognostic factor in patients with advanced cancer and is usually scored by the treating physician. The EORTC QLQ-C30 questionnaire as reported by cancer patients is a validated tool to assess quality of life (QoL). Subjectivity plays a role in both assessments, and data on a direct comparison are scarce. Methods We compared the prognostic value for overall survival (OS) of the WHO PS to the baseline physical function scale of the EORTC QLQ-C30 (QLQ-C30 PF) in a prospective randomised phase 3 trial in advanced colorectal cancer (ACC), the CAIRO study. Patients were divided into two groups based on the baseline QLQ-C30 PF. QLQ-C30 PF was considered ‘good’ if the score was more than 66.7% and ‘poor’ if 66.7% or less. Results were validated in a subsequent phase 3 study in ACC, the CAIRO2 study. Results The median OS for patients with a ‘good’ QLQ-C30 PF and a ‘poor’ PF in patients with WHO PS 0 was 20.3 months (n = 300) and 10.4 months (n = 44), in patients with WHO PS 1 16.8 months (n = 125) and 10.1 months (n = 63), and in patients with WHO PS 2 16.2 months (n = 11) and 9.9 months (n = 12), respectively. In a Cox regression model which included other prognostic factors, ‘good’ versus ‘poor’ QLQ-C30 PF was significantly prognostic for OS (0.57 95% confidence interval: 0.46–0.72), but not WHO PS. These results were confirmed in the CAIRO2 study. Conclusions We demonstrate in ACC patients that PF, as assessed by patients using the EORTC QLQ-C30, is superior in terms of prognostic value to WHO PS as scored by physicians. Our data support to include the results of baseline EORTC QLQ-C30 PF instead of WHO PS as a stratification parameter in oncology trials. [ABSTRACT FROM AUTHOR]

Current staging classifications in colorectal cancer are not able to accurately predict patient outcome, and the need for novel prognostic markers is evident. S100A4 is a Ca2+-binding protein which promotes metastasis in several tumour types, and the aim of the present study was to investigate the prognostic impact of S100A4 expression in colorectal cancer. Two hundred and forty two patients with curatively resected adenocarcinoma of the colon or rectum were prospectively included in the study at the time of surgery. S100A4 expression was analysed by immunohistochemistry, and associations with clinicopathological variables and patient outcome were investigated. Nuclear expression of S100A4 was observed in 29% and cytoplasmic expression was observed in 64% of the tumours. In univariate analysis, nuclear S100A4 was a negative predictor of metastasis-free (P =0.006) and overall survival (P =0.01), whereas cytoplasmic S100A4 was not associated with patient outcome. In multivariate analysis, nuclear localisation was inversely associated with metastasis-free (P =0.03) and overall survival (P =0.02). Interestingly, the prognostic impact was largely confined to TNM stage II, and stage II patients with tumours expressing nuclear S100A4 had a similar prognosis as stage III patients. In conclusion, nuclear expression of S100A4 is a novel prognostic marker in colorectal cancer, and the prognostic value in TNM stage II suggests that nuclear S100A4 could be used in the stratification of stage II patients for adjuvant treatment. [Copyright &y& Elsevier]