Efficacy of Oral SERDs in the treatment of ER+, HER2 - metastatic breast cancer, a stratified analysis of the ESR1 wild type and mutant subgroups.

BACKGROUND: Oral SERDs are a novel drug class that have been developed to counteract resistance due to ESR1 mutations. Several SERDs have emerged from phase 2 and 3 trials, with the FDA limiting approval for Elacestrant to patients with ESR1mt tumours despite PFS benefit in the overall population. However, questions remain on whether patients with ESR1wt tumours stand to benefit from oral SERDs. PATIENTS AND METHODS: Manuscripts and conference presentations of Randomised Controlled Trials were extracted after a systematic search of Embase, PubMed and Cochrane from inception until January 21,2023. RCTs investigating the efficacy of oral SERDs versus endocrine therapy for ER positive, HER2 negative advanced breast cancer, and which reported the Kaplan Meier (KM) curves of PFS in the overall and ESR1 mutant (ESR1mt) population were selected. A graphical reconstructive algorithm was applied to estimate time-to-event outcomes from reported KM curves in all overall and ESR1mt cohorts. A bipartite matching algorithm, KMSubtraction, was used to derive survival data for unreported (ESR1wt) subgroups. An individual patient data (IPD) meta-analysis was then pursued, pooling data by ESR1 mutation status in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane Guidelines for IPD. RESULTS: The randomized clinical trials ACELERA, AMEERA-3, EMERALD and SERENA-2 were included, totalling 1290 patients. In the pooled analysis of the overall cohort, PFS benefit was observed with oral SERDs when compared with treatment of physicians choice (TPC) (HR 0.783, 95%CI 0.681-0.900, p<0.001). In the ESR1mt subgroup, oral SERDs demonstrated improved PFS (HR 0.557, 95%CI 0.440-0.705, p<0.001) compared to TPC. In the ESR1wt subgroup, oral SERDs demonstrated no significant PFS benefit (HR 0.944, 95%CI 0.783-1.138, p=0.543) when compared to TPC. CONCLUSIONS: The results of this IPD meta-analysis suggests that PFS benefit in the overall population is mainly driven by the ESR1mt subgroup.

Interobserver variation in the classification of tumor deposits in rectal cancer-is the use of histopathological characteristics the way to go?

The focus on lymph node metastases (LNM) as the most important prognostic marker in colorectal cancer (CRC) has been challenged by the finding that other types of locoregional spread, including tumor deposits (TDs), extramural venous invasion (EMVI), and perineural invasion (PNI), also have significant impact. However, there are concerns about interobserver variation when differentiating between these features. Therefore, this study analyzed interobserver agreement between pathologists when assessing routine tumor nodules based on TNM 8. Electronic slides of 50 tumor nodules that were not treated with neoadjuvant therapy were reviewed by 8 gastrointestinal pathologists. They were asked to classify each nodule as TD, LNM, EMVI, or PNI, and to list which histological discriminatory features were present. There was overall agreement of 73.5% (κ 0.38, 95%-CI 0.33-0.43) if a nodal versus non-nodal classification was used, and 52.2% (κ 0.27, 95%-CI 0.23-0.31) if EMVI and PNI were classified separately. The interobserver agreement varied significantly between discriminatory features from κ 0.64 (95%-CI 0.58-0.70) for roundness to κ 0.26 (95%-CI 0.12-0.41) for a lone arteriole sign, and the presence of discriminatory features did not always correlate with the final classification. Since extranodal pathways of spread are prognostically relevant, classification of tumor nodules is important. There is currently no evidence for the prognostic relevance of the origin of TD, and although some histopathological characteristics showed good interobserver agreement, these are often non-specific. To optimize interobserver agreement, we recommend a binary classification of nodal versus extranodal tumor nodules which is based on prognostic evidence and yields good overall agreement.

Timing of arthrocentesis in the management of temporomandibular disorders: an integrative review and meta-analysis.

The aim of this study was to assess the best timing to perform arthrocentesis in the management of temporomandibular disorders with regard to conservative treatment. A systematic search based on PRISMA guidelines, including a computer search with specific keywords, reference list search, and manual search was performed. Relevant articles were selected after three search rounds for final review based on six predefined inclusion criteria, followed by a round of critical appraisal. Eleven publications, including eight randomized controlled trials and three prospective clinical studies, were included in the review. The studies were divided into three groups based on the timing of arthrocentesis: (1) arthrocentesis as the initial treatment; (2) early arthrocentesis; and (3) late arthrocentesis. Meta-analysis was carried out to compare the efficacy of improvement in mouth opening and pain reduction in the three groups. All three groups showed improvement in mouth opening and pain reduction, with forest plots suggesting that arthrocentesis performed within 3 months of conservative treatment might produce beneficial results. We conclude that there is a knowledge gap in the current literature regarding the preferable timing to perform arthrocentesis in the management of temporomandibular disorders, and more high-quality randomized controlled trials are required to shed light on this subject.

Women with advanced pelvic organ prolapse and levator ani muscle avulsion would significantly benefit from mesh repair surgery.

OBJECTIVES: Mesh repair surgery for pelvic organ prolapse (POP) has been suspended in some countries owing to concerns about its associated complications. However, mesh repair has been shown to reduce the risk of prolapse recurrence after surgery. In view of this controversy, our aim was to assess the incidence of subjective and objective recurrence of POP following mesh repair surgery vs native-tissue repair in women with Stage-III or Stage-IV POP. METHODS: This was a prospective observational study of women who presented with Stage-III or Stage-IV POP and received primary prolapse surgery between 2013 and 2018. Transperineal ultrasound was performed before the operation and volumes were analyzed offline to assess the presence of levator ani muscle (LAM) avulsion. All women were counseled on either mesh repair or native-tissue reconstruction. The mesh-repair group was followed up for up to 5 years and the native-tissue-repair group for up to 2 years after the operation. Prolapse symptoms and POP quantification (POP-Q) staging were assessed at follow-up. Subjective recurrence of POP was defined as symptoms of prolapse (vaginal bulge sensation or dragging sensation) reported by the patient. Objective recurrence was defined as POP-Q ≥ Stage II. The subjective and objective recurrences of prolapse were compared between women with and those without mesh use. Multivariate regression analysis was used to identify risk factors for the recurrence of POP. RESULTS: A total of 154 Chinese women with Stage-III or Stage-IV prolapse were recruited. Of these, 104 (67.5%) underwent mesh repair (transabdominal in 57 women and transvaginal in 47 women) and 50 (32.5%) had native-tissue repair surgery. Ninety-five (61.7%) women had LAM avulsion. Both the subjective POP recurrence rate (4.8% vs 20.0%; P = 0.003) and the objective recurrence rate (20.2% vs 46.0%; P = 0.001) were significantly lower in the mesh-repair group than in the native-tissue-repair group. On multivariate logistic regression analysis, mesh repair was associated significantly with a reduced risk of subjective recurrence (odds ratio (OR), 0.20 (95% CI, 0.07-0.63)) and of objective recurrence (OR, 0.16 (95% CI, 0.07-0.55)) of prolapse. On subgroup analysis of women with LAM avulsion, mesh repair significantly reduced the risk of subjective recurrence (OR, 0.24 (95% CI, 0.07-0.87)) and objective recurrence (OR, 0.23 (95% CI, 0.09-0.57)) of POP. The incidence of mesh-related complications was low, and mesh exposure could be treated conservatively or by minor surgery. CONCLUSIONS: Mesh repair surgery, compared with native-tissue repair, was associated with a 5-fold reduction in the risk of subjective recurrence and a 6-fold reduction in the risk of objective recurrence of prolapse in women with Stage-III or Stage-IV POP. In women with concomitant LAM avulsion, mesh repair surgery was associated with a 4-fold reduction in both objective and subjective recurrence of POP. The rate of mesh-related complications was low, and mesh exposure could be treated conservatively or by minor surgery. The benefit of mesh surgery for these high-risk women appears to outweigh the risks of mesh complications, and it could be a treatment option for this group of women. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Is there a difference between the thicknesses of the rami in mandibular asymmetry?

The purpose of this retrospective study was to investigate whether the thicknesses of the two rami differ in patients with mandibular asymmetry. Preoperative cone beam computed tomography scans of 78 patients with mandibular asymmetry were assessed for ramus thickness, mandibular length, and mandibular shift. The results showed that the ramus was thinner on the longer side than on the shorter side in 85.9% of the patients. On average, the longer side of the mandible was 2.74mm longer (range 0.07-9.90mm, standard deviation 1.92mm) and 0.55mm thinner (range -0.61 to 2.02mm, standard deviation 0.59mm) than the shorter side (both P<0.001). This study indicates a trend in the discrepancy in ramus thickness between the longer and shorter side of about 8% of the mean thickness of the ramus. Regression analysis showed that for every 1-mm increase in the length of the mandible, the thickness of the superior aspect of the ramus was reduced by 0.041 mm (P=0.009) and the anterior aspect by 0.125 mm (P=0.001). Age and sex did not have a significant influence on the thickness of the mandible. It is concluded that the longer side of the mandible tends to be thinner at the ramus than the shorter side in patients with mandibular asymmetry. The implication of this finding could be important in relation to the sagittal split ramus osteotomy.

Surgical morbidities of sagittal split ramus osteotomy versus intraoral vertical ramus osteotomy for the correction of mandibular prognathism: a randomized clinical trial.

The sagittal split ramus osteotomy (SSRO) and intraoral vertical ramus osteotomy (IVRO) are two common orthognathic procedures for the treatment of mandibular prognathism. This randomized clinical trial compared the surgical morbidities between SSRO and IVRO for patients with mandibular prognathism over the first 2 years postoperative. Ninety-eight patients (40 male, 58 female) with a mean age of 24.4±3.5 years underwent bilateral SSRO (98 sides) or IVRO (98 sides) as part or all of their orthognathic surgery. IVRO presented less short-term and long-term surgical morbidity in general. The SSRO group had a greater incidence of inferior alveolar nerve deficit at all follow-up time points (P< 0.01). There was more TMJ pain at 6 weeks (P= 0.047) and 3 months (P= 0.001) postoperative in the SSRO group. The SSRO group also presented more minor complications, which were related to titanium plate exposure and infection. There were no major complications for either technique in this study. Despite the need for intermaxillary fixation, IVRO appears to be associated with less surgical morbidity than SSRO when performed as a mandibular setback procedure to treat mandibular prognathism.

Comparison of colonic stents, stomas and resection for obstructive left colon cancer: a meta-analysis.

BACKGROUND: Emergency surgery (ES) is the standard-of-care for left-sided obstructing colon cancer, with self-expanding metallic stents (SEMSs) and diverting colostomies (DCs) being alternative approaches. The aim of this study was to review the short- and long-term outcomes of SEMS versus ES or DC. METHODS: Embase and Medline were searched for articles comparing SEMS versus ES or DC. Primary outcomes were survival and recurrence rates. Secondary outcomes were peri- and postoperative outcomes. SEMS-specific outcomes include success and complication rates. Pooled odds ratio and 95% confidence interval were estimated with DerSimonian and Laird random effects used to account for heterogeneity. RESULTS: Thirty-three studies were included, involving 15,224 patients in 8 randomized controlled trials and 25 observational studies. There were high technical and clinical success rates for SEMS, with low rates of complications. Our meta-analysis revealed increased odds of laparoscopic surgery and anastomosis, and decreased stoma creation with SEMS compared to ES. SEMS led to fewer complications, including anastomotic leak, wound infection, ileus, myocardial infarction, and improved 90-day in-hospital mortality. There were no significant differences in 3- and 5-year overall, cancer-specific and disease-free survival. SEMS, compared to DC, led to decreased rates of stoma creation, higher rates of ileus and reoperation, and led to longer hospital stay. CONCLUSIONS: SEMS leads to better short-term outcomes but confers no survival advantage over ES. It is unclear whether SEMS has better short-term outcomes compared to DC. There is a lack of randomized trials with long-term outcomes for SEMS versus DC, hence results should be interpreted with caution.

Bone regeneration at the distal aspect of the adjacent second molar after lower third molar coronectomy: a long-term analysis.

A residual bone defect at the distal aspect of the adjacent second molar may occur after total removal of the lower third molar. Lower third molar coronectomy has been proved to be a safe alternative to total removal, but the extent of bone regeneration at the adjacent tooth after coronectomy is not well reported. The aim of this prospective study was to investigate the long-term bone regeneration at the distal aspect of the adjacent second molar after lower third molar coronectomy. Preoperative and postoperative cone beam computed tomography scans were measured to assess bone regeneration at the distobuccal (DB), mid-distal (MD), and distolingual (DL) aspects of the lower second molar. Forty-eight coronectomies in 37 patients (23 female) with a mean±standard deviation age of 29.1±7.2 years were assessed. The mean follow-up was 93.2±8.7 months. The mean bone level increase at DB, MD, and DL aspects was 3.2±1.6mm, 3.5±1.5mm, and 3.2±1.6mm, respectively; the bone levels were significantly higher than the preoperative measurements (P<0.001). Age and impaction patterns were not factors affecting bone regeneration. Based on this study, it appears that coronectomy of the lower third molar brings favourable bone regeneration at the distal aspect of the adjacent second molar.

A cross-sectional analysis of factors associated with detection of oncogenic human papillomavirus in human immunodeficiency virus-infected and uninfected Kenyan women.

BACKGROUND: Cervical cancer is caused by oncogenic human papillomaviruses (HPV) and is one of the most common malignancies in women living in sub-Saharan Africa. Women infected with the human immunodeficiency virus (HIV) have a higher incidence of cervical cancer, but the full impact on HPV detection is not well understood, and associations of biological and behavioral factors with oncogenic HPV detection have not been fully examined. Therefore, a study was initiated to investigate factors that are associated with oncogenic HPV detection in Kenyan women. METHODS: Women without cervical dysplasia were enrolled in a longitudinal study. Data from enrollment are presented as a cross-sectional analysis. Demographic and behavioral data was collected, and HPV typing was performed on cervical swabs. HIV-uninfected women (n = 105) and HIV-infected women (n = 115) were compared for demographic and behavioral characteristics using t-tests, Chi-square tests, Wilcoxon sum rank tests or Fisher's exact tests, and for HPV detection using logistic regression or negative binomial models adjusted for demographic and behavioral characteristics using SAS 9.4 software. RESULTS: Compared to HIV-uninfected women, HIV-infected women were older, had more lifetime sexual partners, were less likely to be married, were more likely to regularly use condoms, and were more likely to have detection of HPV 16, other oncogenic HPV types, and multiple oncogenic types. In addition to HIV, more lifetime sexual partners was associated with a higher number of oncogenic HPV types (aIRR 1.007, 95% CI 1.007-1.012). Greater travel distance to the clinic was associated with increased HPV detection (aOR for detection of ≥ 2 HPV types: 3.212, 95% CI 1.206-8.552). Older age (aOR for HPV 16 detection: 0.871, 95% CI 0.764-0.993) and more lifetime pregnancies (aOR for detection of oncogenic HPV types: 0.706, 95% CI, 0.565-0.883) were associated with reduced detection. CONCLUSION: HIV infection, more lifetime sexual partners, and greater distance to health-care were associated with a higher risk of oncogenic HPV detection, in spite of ART use in those who were HIV-infected. Counseling of women about sexual practices, improved access to health-care facilities, and vaccination against HPV are all potentially important in reducing oncogenic HPV infections.

Spinal anesthesia performed for cesarean delivery after external ventricular drain placement in a parturient with symptomatology from an intracranial mass.

We describe a case in which spinal anesthesia was undertaken in a pregnant patient with a space-occupying tumor and significant symptomatology. The collaborative efforts of all medical disciplines involved and the willingness of the neurosurgeon to discuss and help determine the safety of neuraxial anesthesia, culminated in placing an external ventricular drain to help monitor and manage intracranial pressure, so that we could proceed with spinal anesthesia and more easily monitor neurologic status.

Open ureteroureterostomy for repair of upper-pole ectopic ureters in children with duplex systems: is stenting really necessary?

BACKGROUND: Ectopic upper-pole (UP) ureters in duplex kidneys can be managed surgically by ipsilateral distal ureteroureterostomy (U-U) with or without ureteric stenting. Evidence to support routine stenting during this procedure is lacking. OBJECTIVE: The authors present their outcomes of children with ectopic UP ureters who underwent ipsilateral distal U-U. They also compared outcomes of those who underwent routine ureteric stenting to those who did not. STUDY DESIGN: Between 2009 and 2015, the authors performed a prospective analysis on consecutive patients with duplex collecting systems who underwent distal U-U via an inguinal incision for ectopic UP ureters by one of two pediatric urologists. The demographic information, operative factors, and any postoperative complications on follow-up were recorded. RESULTS: The study included 47 patients (28 female) who underwent distal U-U with a mean age of 9.8 months. There were 30 patients who were routinely stented, and 17 who were not based on the routine practices of the operating surgeons without any selection bias. The mean operative time was 90 min, and the mean hospital stay was 0.9 days. No major complications were observed in this series, with 96% of patients showing resolution of hydronephrosis. There were no statistical differences between the stented and stentless U-U groups in terms of operative time, hospital stay, hydronephrosis resolution, time to resolution of hydronephrosis, and major complications. Only stented patients were found to have minor complications (2-urinary tract infection, 2-dysuria, and 2-stent displacement). All patients who underwent routine stent placement required a secondary planned procedure under general anesthesia for the cystoscopic removal of stent. CONCLUSION: Stenting was associated with a higher number of minor complications compared to the stentless group and thus, may not be routinely necessary when performing distal U-U for management of UP ectopic ureters associated with duplicated collecting systems.

Three-dimensional radiographic evaluation of root migration patterns 4-8.5 years after lower third molar coronectomy: a cone beam computed tomography study.

This prospective study in patients with a follow-up of 4-8.5years aimed to describe the long-term, three-dimensional changes of coronectomized lower third molar roots. Pre- and postoperative cone beam computed tomography (CBCT) scans were compared. The distance of root migration, the direction of root translation and rotation, and the amount of bone regeneration at the adjacent second molar and superficially to the third molar root were recorded. Age, gender, time elapsed following surgery, the status of the retained root including, impaction pattern and depth of impaction were tested to check if they were influencing factors for the above outcomes. A total of 57 coronectomized third molars from 44 patients were included. The distance of the mean root migration was 2.82mm, and they predominantly translated mesially (76.8%). Age negatively correlated with the distance of migration. Root remnants with a soft tissue coverage had less bone regenerated at the adjacent second molar (1.27mm vs. 2.95mm) in comparison to their impacted counterparts. Based on the present radiographic results and the absence of any pathological findings, coronectomy can be recommended for selected cases of third molar removal as a safe procedure with favourable long-term outcomes.

No evidence of excessive cancer screening in female noncarriers from BRCA1/2 mutation-positive families.

BACKGROUND: In families with a proven BRCA1/2 mutation, women not carrying the familial mutation should follow the cancer screening recommendations applying to women in the general population. In the present study, we evaluated the cancer screening practices of unaffected noncarriers from families with a proven BRCA mutation, and we assessed the role of family history in their screening practices. METHODS: Self-report data were provided retrospectively by 220 unaffected female noncarriers for periods of up to 10 years (mean: 4.3 years) since disclosure of their BRCA1/2 genetic test result. A ratio for the annual frequency of breast and ovarian cancer screening exams (mammography, breast ultrasonography, breast magnetic resonance imaging, transvaginal or pelvic ultrasound, cancer antigen 125 testing) was calculated as number of screening exams divided by the number of years in the individual observation period. RESULTS: The annual average for mammography exams was 0.15, 0.4, 0.56, and 0.71 in women 30-39, 40-49, 50-59, and 60-69 years of age respectively. The uptake of other breast and ovarian cancer screening exams was very low. Mammography and breast ultrasonography and magnetic resonance imaging were generally more frequent among participants with at least 1 first-degree relative affected by breast cancer. CONCLUSIONS: In most noncarriers, screening practices are consistent with the guidelines concerning women in the general population. When noncarriers adopt screening behaviours that are different from those that would be expected for average-risk women, those behaviours are influenced by their familial cancer history. IMPACT: Decision tools might help female noncarriers to be involved in their follow-up in accordance with their genetic status and their family history, while taking into account the benefits and disadvantages of cancer screening.

Pharmacogenetics of ABCB5, ABCC5 and RLIP76 and doxorubicin pharmacokinetics in Asian breast cancer patients.

This study investigated the impact of ABCB5, ABCC5 and RLIP76 polymorphisms on doxorubicin pharmacokinetics in Asian breast cancer patients (N=62). Direct sequencing was performed to screen for previously identified ABCC5 polymorphisms as well as polymorphisms in the exons and exon-intron boundaries of ABCB5 and RLIP76 genes. Genotype-phenotype correlations were analyzed using Mann-Whitney U-test. The homozygous variant allele at the ABCC5 g.+7161G>A (rs1533682) locus was significantly associated with higher doxorubicin clearance (g.+7161AA vs g.+7161GG, CL/BSA (Lh-1m-2): 30.34 (25.41-33.60) vs 22.46 (15.04-49.4), P=0.04). Homozygosity for the reference allele at the ABCC5 g.-1679T>A locus was associated with significantly higher doxorubicinol exposure (g.-1679TT vs g.-1679TA, AUC0-∞/dose/BSA (hm-5): 15.48 (6.18-67.17) vs 8.88 (3.68-21.71), P=0.0001). No significant influence of the three newly identified ABCB5 polymorphisms (c.2T>C, c.343A>G and c.1573G>A) on doxorubicin pharmacokinetics was observed. No polymorphisms were identified in the RLIP76 gene. These findings suggest that ABCC5 polymorphisms may explain partially the interpatient variability in doxorubicin disposition.

Recommendations on breast cancer screening and prevention in the context of implementing risk stratification: impending changes to current policies.

In recent years, risk stratification has sparked interest as an innovative approach to disease screening and prevention. The approach effectively personalizes individual risk, opening the way to screening and prevention interventions that are adapted to subpopulations. The international perspective project, which is developing risk stratification for breast cancer, aims to support the integration of its screening approach into clinical practice through comprehensive tool-building. Policies and guidelines for risk stratification-unlike those for population screening programs, which are currently well regulated-are still under development. Indeed, the development of guidelines for risk stratification reflects the translational aspects of perspective. Here, we describe the risk stratification process that was devised in the context of perspective, and we then explain the consensus-based method used to develop recommendations for breast cancer screening and prevention in a risk-stratification approach. Lastly, we discuss how the recommendations might affect current screening policies.

The metabolic syndrome and diabetes mellitus as predictors of thoracic aortic calcification as detected by non-contrast computed tomography in the Multi-Ethnic Study of Atherosclerosis.

AIMS: The metabolic syndrome (MetS) is a clustering of low levels of HDL cholesterol, hyperglycaemia, high waist circumference, hypertension and elevated triglycerides, and is associated with cardiovascular disease. Calcified atherosclerotic plaque in the thoracic aorta (TAC), measured by non-contrast cardiac computed tomography (CT) scans, is a marker for atherosclerosis and relates to mortality. We sought to evaluate the independent association of MetS and TAC on cardiac CT scans. METHODS: We examined the relation of the MetS, and each of its components, to the prevalence of TAC, measured from 2000 to 2002 in 6778 white, Chinese, African-American and Hispanic participants in the Multi-Ethnic Study of Atherosclerosis (MESA). RESULTS: Adjusting for age, gender, race, smoking, LDL cholesterol and lipid-lowering medications, relative risks and 95% confidence intervals (CI) for a TAC score > 0 were: 1.19 (95% CI 1.11 to 1.28) for participants with MetS, 1.34 (95% CI 1.21 to 1.49) for those with diabetes and MetS, and 1.33 (95% CI 1.11, 1.58) for those with diabetes and no MetS compared with participants who were free of the MetS and diabetes. Associations were found for most of the components of the MetS with TAC. CONCLUSIONS: We conclude that in adults without known heart disease, the MetS, most of its components and diabetes are associated with a higher prevalence of calcified atherosclerotic plaque in the thoracic arteries in a multi-ethnic population of men and women.

Hope, optimism and survival in a randomised trial of chemotherapy for metastatic colorectal cancer.

PURPOSE: Psychological responses to cancer are widely believed to affect survival. We investigated associations between hope, optimism, anxiety, depression, health utility and survival in patients starting first-line chemotherapy for metastatic colorectal cancer. METHODS: Four hundred twenty-nine subjects with metastatic colorectal cancer in a randomised controlled trial of chemotherapy completed baseline questionnaires assessing the following: hopefulness, optimism, anxiety and depression and health utility. Hazard ratios (HRs) and P values were calculated with Cox models for overall survival (OS) and progression-free survival (PFS) in univariable and multivariable analyses. RESULTS: Median follow-up was 31 months. Univariable analyses showed that OS was associated negatively with depression (HR 2.04, P < 0.001) and positively with health utility (HR 0.56, P < 0.001) and hopefulness (HR 0.75, P = 0.013). In multivariable analysis, OS was also associated negatively with depression (HR 1.72, P < 0.001) and positively with health utility (HR 0.73, P = 0.014), but not with optimism, anxiety or hopefulness. PFS was not associated with hope, optimism, anxiety or depression in any analyses. CONCLUSIONS: Depression and health utility, but not optimism, hope or anxiety, were associated with survival after controlling for known prognostic factors in patients with advanced colorectal cancer. Further research is required to understand the nature of the relationship between depression and survival. If a causal mechanism is identified, this may lead to interventional possibilities.