Survival In Advanced Cancer Research Articles

Predicting survival in advanced cancers by applying machine learning to clinical narratives.

32 Background: We previously showed that a text mining approach can identify clinical prognostic factors from electronic medical records (EMR) in patients with advanced cancers (1). Here we further examine whether clinical narratives can be exploited to build prognostic tools by applying a machine-learning (ML) approach. Methods: A retrospective study of all patients with stage IV tumors was conducted at a single tertiary cancer centre. The text corpus was formed by extracting narratives from initial consultation letters authored by oncologists, and a feature learning pipeline (2) was then used to extract text features correlating to survival. Five classes of ML algorithms was then applied for survival prediction. Classification performance was assessed by stratified cross-validation and compared with Eastern Cooperative Oncology Group (ECOG) performance scores. Results: EMR were available for analysis in 4791 of 7043 patients from 2001-2017, and in 2211 of these cases ECOG performance scores were available. By applying ML on features extracted from EMR text, survival of patients at 2, 6, 12, 26, 52, and 80 weeks was predicted, with areas under the receiver operating characteristic (ROC) curve of 0.82, 0.80, 0.77, 0.72, 0.72, and 0.76 respectively. ML outperformed ECOG score in predicting patient prognosis between 12-16 weeks ( p < 0.05) and after 52 weeks ( p < 0.05), and was non-inferior at all other time points. Random forest was the best algorithm for the prognostic classification task. Feature filtering threshold was important to classification accuracy ( p < 0.001). Conclusions: In patients with advanced cancers, ML analysis of clinical narratives can be used to automate prognostication with greater accuracy than is currently obtainable from ECOG status.

Association of Patient Sex With Efficacy of Immune Checkpoint Inhibitors and Overall Survival in Advanced Cancers

Sex-associated differences in immune response are known, but a meta-analysis suggested men, compared with women, derive greater value from immunotherapy for advanced solid-organ malignant neoplasms. However, methodologic concerns and subsequent trials have placed these results in doubt. To perform an updated, comprehensive meta-analysis that assesses the efficacy of immunotherapy in advanced cancers according to patient sex. A systematic review of studies (n = 23) indexed in MEDLINE (PubMed), Embase, and Scopus from inception of these databases to October 2, 2018, was conducted. Randomized clinical trials that compared immunotherapy with standard of care in the treatment of advanced solid-organ malignant neoplasms were included if overall survival was reported as an outcome and if data stratified by patient sex were available. Observational studies, editorials, commentaries, review articles, non-peer-reviewed publications, studies that compared various immunotherapy regimens, studies that reported other measures of oncologic response, and studies that reported subgroup analyses for 1 sex only were excluded. Overall survival, with a test for heterogeneity between women and men, to assess the null hypothesis that no difference in the survival advantage of immunotherapy exists by patient sex. This meta-analysis included 23 randomized clinical trials that reported on 9322 men (67.9%) and 4399 women (32.1%); the age of most patients was in the 70s. An overall survival benefit of immunotherapy was found for both men (hazard ratio [HR], 0.75; 95% CI, 0.69-0.81; P < .001) and women (HR, 0.77; 95% CI, 0.67-0.88; P = .002). Random-effects meta-analysis of study-level differences in response to immunotherapy demonstrated no statistically significant difference between the sexes (I2 = 38%; P = .60). Subgroup analyses according to disease site, line of therapy, class of immunotherapy, study methodology, and representation of women recapitulated these findings. Stratified analyses demonstrated no statistically significant association of patient sex with the efficacy of immunotherapy in the treatment of advanced cancers using overall survival as the outcome.

The prognostic value of hypoxia-inducible factor-1α in advanced cancer survivors: a meta-analysis with trial sequential analysis.

Background:Expression of hypoxia-inducible factors (HIFs) has been observed, but their prognostic role in advanced cancers remains uncertain. We conducted a meta-analysis to establish the prognostic effect of HIFs and to better guide treatment planning for advanced cancers.Methods:Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Trial sequential analysis (TSA) was also performed. The clinical outcomes included overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), cancer-specific survival (CSS), relapse/recurrence-free survival (RFS), and metastasis-free survival (MFS) in patients with advanced tumors according to multivariate analysis.Results:A total of 31 studies including 3453 cases who received chemotherapy, radiotherapy, or chemoradiotherapy were identified. Pooled analyses revealed that HIF-1α expression was correlated with worse OS (HR = 1.61, p < 0.001), DFS (HR = 1.61, p < 0.001), PFS (HR = 1.49, p = 0.01), CSS (HR = 1.65, p = 0.056), RFS (HR = 2.10, p = 0.015), or MFS (HR = 2.36, p = 0.002) in advanced cancers. HIF-1α expression was linked to shorter OS in the digestive tract, epithelial ovarian, breast, non-small cell lung, and clear cell renal cell carcinomas. Subgroup analysis by study region showed that HIF-1α expression was correlated with poor OS in Europeans and Asians, while an analysis by histologic subtypes found that HIF-1α expression was not associated with OS in squamous cell carcinoma. No relationship was found between HIF-2α expression and OS, DFS, PFS, or CSS.Conclusions:Targeting HIF-1α may be a useful therapeutic approach to improve survival for advanced cancer patients. Based on TSA, more randomized controlled trials are strongly suggested.

Palliative Care Clinician Overestimation of Survival in Advanced Cancer: Disparities and Association With End-of-Life Care

ContextClinicians frequently overestimate survival time in serious illness. ObjectiveThe objective of this study was to understand the frequency of overestimation in palliative care (PC) and the relation with end-of-life (EOL) treatment. MethodsThis is a multisite cohort study of 230 hospitalized patients with advanced cancer who consulted with PC between 2013 and 2016. We asked the consulting PC clinician to make their “best guess” about the patients' “most likely survival time, assuming that their illnesses are allowed to take their natural course” (<24 hours; 24 hours to less than two weeks; two weeks to less than three months; three months to less than six months; six months or longer). We followed patients for up to six month for mortality and EOL treatment utilization. Patients completed a brief interviewer-facilitated questionnaire at study enrollment. ResultsMedian survival was 37 days (interquartile range: 12 days, 97 days) and 186/230 (81%) died during the follow-up period. Forty-one percent of clinicians' predictions were accurate. Among inaccurate prognoses, 85% were overestimates. Among those who died, overestimates were substantially associated with less hospice use (ORadj: 0.40; 95% CI: 0.16–0.99) and later hospice enrollment (within 72 hours of death ORadj: 0.33; 95% CI: 0.15–0.74). PC clinicians were substantially more likely to overestimate survival for patients who identified as Black or Latino compared to others (ORadj: 3.89; 95% CI: 1.64–9.22). EOL treatment preferences did not explain either of these findings. ConclusionOverestimation is common in PC, associated with lower hospice use and a potentially mutable source of racial/ethnic disparity in EOL care.

Effect of chemotherapy combined with bioimmune therapy on clinical efficacy and survival of advanced prostate cancer

Objective To investigate the effect of chemotherapy combined with biological immunotherapy on clinical efficacy and survival of advanced prostate cancer. Methods Ninety-six patients with advanced prostate cancer who were treated from September 2013 to March 2016 in our hospital were randomly divided into two groups. The control group was given chemotherapy alone, the observation group was given chemotherapy combined with biological immunity for treatment. The clinical efficacy and immunohistochemical response of patients with advanced prostate cancer were compared and analyzed. After 4 months of treatment, the patients were followed up for 1 year. The mortality, survival and time to disease progression (TTP) as well as the occurrence of adverse reactions of the two groups were observed. Results After treatment, the total effective rate of the observation group was 87.5% (42/48), which was significantly higher than that of the control group [68.8%(33/48]. There was significant difference between the two groups (P<0.05). The numbers of Tlymphocytes, T helper cells, Tsuppressor cells, natural killer cells and naturak killer T were significantly higher than that in the control group in the external T lymph. There was a significant difference between the two groups (P <0.05). After 1 year of follow-up, the mortality rate of the observation group was lower than that of the control group, and the survival time (36.6 ± 5.4) months was higher than that of the control group (20.7 ± 7.2) months, TTP of the observation group was higher than that of the control group [(29.8 ± 5.7) months vs.(19.7±9.3)months] (P<0.05). The adverse reaction rate (22.9%) in the observation group was significantly lower than that in the observation group (43.8%), and the difference between the two groups was statistically significant (P<0.05) . Conclusions Chemotherapy combined with biological immunotherapy is effective in advanced prostate cancer, which can effectively enhance the activity of immune function cells, prolong survival time, TTP, reduce mortality, reduce the incidence of adverse reactions and improve the quality of life after treatment. Key words: Prostatic Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Immunotherapy

Chinese and South Asian ethnicity, immigration status, and clinical cancer outcomes in the Ontario Cancer System.

In the United States, certain minority groups have been shown to have inferior cancer outcomes compared with the white majority population. However, to the authors' knowledge, the majority of research has not separated ethnicity from immigration status. The objective of the current study was to determine the impact of ethnicity, independent of immigration status, on cancer outcomes in Chinese and South Asian populations in Ontario, Canada. The authors conducted a population-based retrospective cohort study using administrative databases in Ontario, Canada. Incident cancer cases were captured in Canadian-born Chinese and South Asian individuals, Chinese and South Asian immigrants, and the general Ontario reference population (non-Chinese/non-South Asian and non-immigrant) between 2000 and 2012. Subjects were followed until death (all-cause and cancer-specific), and Cox proportional hazard models were used to estimate the impact of Chinese and South Asian ethnicity on cancer outcomes after adjusting for explanatory variables. A total of 423,678 cancer cases were identified; at total of 6631 cases were identified in Canadian-born Chinese individuals and 2752 cases in Canadian-born South Asian individuals. After adjustment, the rate of all-cause mortality was lower for Canadian-born Chinese (hazard ratio [HR], 0.829; 95% confidence interval [95% CI], 0.795-0.865), Canadian-born South Asian (HR, 0.856; 95% CI, 0.797-0.919), and Chinese immigrant (recent immigrant: HR, 0.661 [95% CI, 0.610-0.716] and non-recent immigrant: HR, 0.853 [95% CI, 0.803-0.906]) populations compared with the general Ontario population. A similar effect was found for cancer-specific mortality. Chinese and South Asian ethnic groups appear to have lower cancer mortalities compared with the general Ontario population. After removing the well-documented protective effect of immigration, Chinese and South Asian ethnicities were found to be associated with a cancer survival advantage in Ontario, Canada. Cancer 2018;124:1473-82. © 2018 American Cancer Society.

Wide Under- and Over-Estimation by PCPs Regarding Bleeding and Perforation Rates of Screening Colonoscopy

Introduction: Only about 62% of patients 50 years or older get Screening for Colorectal Cancer (SCRC). We surveyed Primary Care Physicians (PCPs) who are medical school faculty to find if they know how useful or harmful colonoscopy is, the estimates of survival they give to patients if colorectal cancer is found without screening, and what they think of newer Stool Based Methods (SBMs) for SCRC. Methods: An online anonymous Google survey was sent by email to PCPs at Family Medicine (FM) and Internal Medicine residency programs at Baylor College of Medicine and to a FM residency program at Eastern Virginia Medical School. Results: Of the 42 responses received, 60% were from FM; the setting was academic in 68%; 63% had been PCPs for over 10 years; and 65% estimated that their rate of SCRC was at national average. Their most common estimates respectively for annual Fecal Occult Blood Testing (FOBT), annual Fecal Immunnochemical Test (FIT), Cologuard every 3 years and colonoscopy every 10 years were 50-75%, 75-90%, 75-90% and >90% for sensitivity for SCRC, <50%, 50-75%, 75-90%, and >90% for sensitivity for screening for advanced adenomas, and 50-75%, 50-75%, 75-90% and >90% for specificity for SCRC. Although 44% of PCPs correctly estimated that rates of perforation and bleeding in screening colonoscopy are 4 in 10,000 and 8 in 10,000, 21% PCPs estimated them to be 4 in 1000 and 8 in 1000 and 30% PCPs estimated them to be 20 in 10,000 and 40 in 10,000 respectively. Although 56% of PCPs correctly estimated 5-year survival to be 90%, 70% and 10% respectively for screen-detected (stages 1 and 2), regional (stage 3) and distant (stage 4) cancer, 37% PCPs estimated this to be 90%, 50% and 5%. 38% PCPs thought colonoscopy was the same or only slightly better than SBMs, only 52% agreed that SBM should only be done if patients decline colonoscopy, and 19% did not prefer colonoscopy for SCRC. Conclusion: The estimates of PCPs regarding sensitivity and specificity of SCRC methods were similar to data reported by the US Preventive Task Force in 2016 except that PCPs under-estimated specificity of FOBT and FIT for SCRC and over-estimated specificity of Cologuard for screening of advanced adenomas. 37% PCPs under-estimated survival in advanced cancer. Although colonoscopy is recommended as the preferred modality of screening, 19% of PCPs did not prefer it. The most significant finding was that 21% PCPs underestimated perforation and bleeding rates during screening colonoscopy by 5 times, and 31% overestimated the rates by 5 times.

Targeting Autophagy in Cancer: Update on Clinical Trials and Novel Inhibitors.

Eukaryotes use autophagy as a mechanism for maintaining cellular homeostasis by degrading and recycling organelles and proteins. This process assists in the proliferation and survival of advanced cancers. There is mounting preclinical evidence that targeting autophagy can enhance the efficacy of many cancer therapies. Hydroxychloroquine (HCQ) is the only clinically-approved autophagy inhibitor, and this systematic review focuses on HCQ use in cancer clinical trials. Preclinical trials have shown that HCQ alone and in combination therapy leads to enhancement of tumor shrinkage. This has provided the base for multiple ongoing clinical trials involving HCQ alone and in combination with other treatments. However, due to its potency, there is still a need for more potent and specific autophagy inhibitors. There are multiple autophagy inhibitors in the pre-clinical stage at various stages of development. Additional studies on the mechanism of HCQ and other autophagy inhibitors are still required to answer questions surrounding how these agents will eventually be used in the clinic.

Prevalence of sarcopenia and predictors of body composition among women with early-stage breast cancer.

160 Background: Body mass index (BMI) does not accurately reflect body composition, particularly among cancer survivors. Sarcopenia (low skeletal muscle mass) and low muscle radio-density (MD; suggesting fat infiltration into muscle, compromising function) increase risk of surgical complications and chemotherapy toxicity and are associated with worse survival in advanced cancer. Little is known about the prevalence or predictors of sarcopenia and low MD in early-stage breast cancer. Methods: We studied 2,914 Kaiser Permanente members diagnosed with Stage I-III breast cancer from 2005-2013. Using computed tomography (CT) scans of the third lumbar vertebra from clinical care, we determined sarcopenia (skeletal muscle index &lt; 41 muscle [cm2]/height [m2]) and low MD ( &lt; 25-Hounsfield Units for non-obese; &lt; 33 for obese) using published cut points. We assessed associations with characteristics including age, race, BMI, age, stage, lifestyle and co-morbidities with logistic regression. We also examined moderate/vigorous physical activity among a subset of 672 women with activity questionnaires. Results: At diagnosis, mean age was 56 years and time to CT was 1 month. Both sarcopenia and low MD were common among early-stage breast cancer survivors (40% and 38% respectively). In multivariate analyses, the odds of sarcopenia and low MD increased with age (per 5 years, Odds Ratio [OR] 95% Confidence Interval [CI] of OR = 1.33; 95%CI: 1.27, 1.39 and OR = 1.41; 95%CI: 1.35, 1.47 respectively). The odds of sarcopenia decreased with greater BMI (OR = 0.80; 95%CI: 0.78, 0.82 per kg/m2), while the odds of low MD increased (OR = 1.03; 95%CI: 1.01, 1.04 per kg/m2). Black race was associated with lower odds of sarcopenia and low MD, while physical activity levels were associated with lower odds of sarcopenia and more favorable MD. Conclusions: Sarcopenia and low MD are highly prevalent among breast cancer survivors. While older age is strongly associated with these conditions, they occur across ages and stages. Differences in body composition by race and age may underlie differences in the association of BMI with cancer outcomes; understanding these may help guide clinical interventions.

The Association of Hydration Status with Physical Signs, Symptoms and Survival in Advanced Cancer-The Use of Bioelectrical Impedance Vector Analysis (BIVA) Technology to Evaluate Fluid Volume in Palliative Care: An Observational Study.

BackgroundHydration in advanced cancer is a controversial area; however, current hydration assessments methods are poorly developed. Bioelectrical impedance vector analysis (BIVA) is an accurate hydration tool; however its application in advanced cancer has not been explored. This study used BIVA to evaluate hydration status in advanced cancer to examine the association of fluid status with symptoms, physical signs, renal biochemical measures and survival.Materials and methodsAn observational study of 90 adults with advanced cancer receiving care in a UK specialist palliative care inpatient unit was conducted. Hydration status was assessed using BIVA in addition to assessments of symptoms, physical signs, performance status, renal biochemical measures, oral fluid intake and medications. The association of clinical variables with hydration was evaluated using regression analysis. A survival analysis was conducted to examine the influence of hydration status and renal failure.ResultsThe hydration status of participants was normal in 43 (47.8%), 'more hydrated' in 37 (41.1%) and 'less hydrated' in 10 (11.1%). Lower hydration was associated with increased symptom intensity (Beta = -0.29, p = 0.04) and higher scores for physical signs associated with dehydration (Beta = 10.94, p = 0.02). Higher hydration was associated with oedema (Beta = 2.55, p<0.001). Median survival was statistically significantly shorter in 'less hydrated' patients (44 vs. 68 days; p = 0.049) and in pre-renal failure (44 vs. 100 days; p = 0.003).ConclusionsIn advanced cancer, hydration status was associated with clinical signs and symptoms. Hydration status and pre-renal failure were independent predictors of survival. Further studies can establish the utility of BIVA as a standardised hydration assessment tool and explore its potential research application, in order to inform the clinical management of fluid balance in patients with advanced cancer.

SUN-P086: Weight Loss and Survival in Advanced Cancer in Relation to Inadequate Energy Intake

SUN-P086: Weight Loss and Survival in Advanced Cancer in Relation to Inadequate Energy Intake

Combined splenectomy does not improve survival in radical total gastrectomy for advanced gastric cardia cancer.

Splenectomy is the most common combined organ resection in the surgical management for gastric cardia cancer. The role of combined splenectomy is still controversial. From January 1998 to December 2006, a total of 174 patients received radical total gastrectomy for advanced adenocarcinoma of cardia. Patients with previous gastric surgery or tumor invasion of pancreas or spleen were excluded. Among them, 115 patients were enrolled in this study. Patients were divided into group 1 (splenectomy, n=47) and group 2 (spleen preservation, n=68). Their clinicopathological characteristics were compared. Multivariate analysis showed that only tumor size and lymphovascular invasion were two independent indicators of survival. The surgically-related morbidity and mortality rates were similar between the two groups. Among the 3 patients with splenic hilar lymph nodes metastasis, all of them had large tumor size (=4cm), advanced stage (stage III and IV) and tumor center located at the posterior wall of stomach. The 5-year overall survival for advanced cancer was similar (57.1% vs. 60.2%, p=0.681). Splenectomy does not improve overall survival in the management of advanced gastric cardia cancer. Splenectomy has limited clinical benefits except for large advanced tumors located at the posterior wall of stomach.

Cancer cachexia, sarcopenia and biochemical markers in patients with advanced non-small cell lung cancer-chemotherapy toxicity and prognostic value.

Cancer cachexia and sarcopenia are frequently observed in cancer patients and associated with poor survival. The majority of studies of cancer cachexia and sarcopenia have been done in patients with solid tumors of different origins, and there are currently no good predictors of the benefit of chemotherapy or factors that predict survival in advanced cancer. The purpose of our prospective study was to evaluate prevalence of cachexia and sarcopenia using international consensus definition and criteria for diagnosis in patients with diagnosed advanced non-small cell lung cancer (NSCLC) stage IIIB and IV and their relation to chemotherapy toxicity and survival prediction. A secondary aim was to compare several biochemical markers (CRP, IL-6, protein, and albumin) with time to tumor progression in order to assess prognostic value or to guide a treatment. Between December 2013 and April 2015, the prospective cohort study of 100 Caucasian patients with advanced NSCLC stage IIIB or IV, who were referred consecutively to Department for Respiratory Diseases "Jordanovac," was evaluated. Anthropometric measurements and biochemical data (CRP, albumin, protein, IL-6, haemoglobin) together with body composition measurements (total muscle cross-sectional area, lumbar skeletal muscle index) were obtained for each patient before starting with platinum-doublet therapy. Skeletal muscle cross-sectional area at the third lumbar vertebra was measured by computerized tomography, and sarcopenia was defined using a previously published cutoff point. Toxicity was assessed after cycle 1 of treatment and time-to-tumor progression was determined prospectively. One hundred patients with advanced lung cancer were recruited: 67 were male and median age was 64years. The median time to disease progression was 187days. The prevalence of cachexia and sarcopenia in study cohort was 69 and 47%, respectively. CRP, IL-6, and albumin concentration in cachectic compared to non-cachectic patients demonstrated statistically significant difference (p = 0.020, p = 0.040, p = 0.003). Cachexia and sarcopenia were not found to be predictors of chemotoxicity nor was time to tumor progression. On the contrary, albumin concentration with established cutoff point of 37.5g/L was clearly proved as the predictive factor of both chemotoxicity (OR (95% CI) = 0.85; p < 0.001) and survival (HR (95% CI) = 0.55). Albumin level has been shown to be more important predictive marker of chemotherapy toxicity and survival than cachexia and sarcopenia are. This approach in clinical settings can be used to guide the choice of oncologic treatment.

The accuracy of clinicians' predictions of survival in advanced cancer: a review.

The process of formulating an accurate survival prediction is often difficult but important, as it influences the decisions of clinicians, patients, and their families. The current article aims to review the accuracy of clinicians' predictions of survival (CPS) in advanced cancer patients. A literature search of Cochrane CENTRAL, EMBASE, and MEDLINE was conducted to identify studies that reported clinicians' prediction of survival in advanced cancer patients. Studies were included if the subjects consisted of advanced cancer patients and the data reported on the ability of clinicians to predict survival, with both estimated and observed survival data present. Studies reporting on the ability of biological and molecular markers to predict survival were excluded. Fifteen studies that met the inclusion and exclusion criteria were identified. Clinicians in five studies underestimated patients' survival (estimated to observed survival ratio between 0.5 and 0.92). In contrast, 12 studies reported clinicians' overestimation of survival (ratio between 1.06 and 6). CPS in advanced cancer patients is often inaccurate and overestimated. Given these findings, clinicians should be aware of their tendency to be overoptimistic. Further investigation of predictive patient and clinician characteristics is warranted to improve clinicians' ability to predict survival.

Progression-free survival as a surrogate for overall survival in advanced cancer.

e17765 Background: Progression-free survival (PFS) is sometimes being used instead of overall survival (OS) as a primary end-point in clinical trials of advanced cancer patients (ACP). We examine t...

Thoughts of self-harm and depression as prognostic factors in palliative care patients

BackgroundThis study explored whether scores indicating depression on Patient Health Questionnaire 9 and patient reports of thoughts of self-harm were prognostic factors for survival in advanced cancer. MethodPatients with advanced cancer were recruited into the study from palliative care day units and invited to complete measures for depression which included Patient Health Questionnaire 9, and Edinburgh Depression Scale at recruitment, and at 8, 16 and 24 weeks. Results629 patients were recruited into the study; 139 (22%) died during 6 months follow up and 235 patients (37.4%) died during the study period. The age range of patients recruited was 21–94 years—mean age 66 years and 67% of patients recruited were female. The overall median survival of patients recruited was 37.1 weeks (95% CI 36.0, 39.9 weeks) (range 0–116 weeks). The estimated median survival time of patients whose baseline PHQ9≥9 was 36 weeks with 95% confidence interval of (31, 39) and for patients whose baseline PHQ9<9 was 39 weeks (95% CI 37, 45)—baseline PHQ9 alone was predictive of death. The median survival times were 37.9 weeks for patients who did not indicate thoughts of self-harm and 34.7 weeks for patients who reported thoughts of self-harm at baseline suggesting that risk of death was 1.4 times higher among patients who reported thoughts of self-harm. LimitationsPatients were recruited only from within palliative day care units and assessments were made only by validated tools and not by clinical interviews. ConclusionsIn this large longitudinal study, moderate to severe depression as measured by PHQ9 and patient reports of thoughts of self-harm were associated with earlier mortality. This paper supports the need for supporting patients psychologically at the end of life and specifically in treating depression in this patient group.

Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: american society of clinical oncology clinical practice guideline focused update.

To update the ASCO clinical practice guideline on adjuvant endocrine therapy on the basis of emerging data on the optimal duration of treatment, particularly adjuvant tamoxifen. ASCO convened the Update Committee and conducted a systematic review of randomized clinical trials from January 2009 to June 2013 and analyzed three historical trials. Guideline recommendations were based on the Update Committee's review of the evidence. Outcomes of interest included survival, disease recurrence, and adverse events. This guideline update reflects emerging data on duration of tamoxifen treatment. There have been five studies of tamoxifen treatment beyond 5 years of therapy. The two largest studies with longest reported follow-up show a breast cancer survival advantage with 10-year durations of tamoxifen use. In addition to modest gains in survival, extended therapy with tamoxifen for 10 years compared with 5 years was associated with lower risks of breast cancer recurrence and contralateral breast cancer. Previous ASCO guidelines recommended treatment of women who have hormone receptor-positive breast cancer and are premenopausal with 5 years of tamoxifen, and those who are postmenopausal a minimum of 5 years of adjuvant therapy with an aromatase inhibitor or tamoxifen followed by an aromatase inhibitor (in sequence). If women are pre- or perimenopausal and have received 5 years of adjuvant tamoxifen, they should be offered 10 years total duration of tamoxifen. If women are postmenopausal and have received 5 years of adjuvant tamoxifen, they should be offered the choice of continuing tamoxifen or switching to an aromatase inhibitor for 10 years total adjuvant endocrine therapy.

KNOWLEDGE AND PRACTICE OF PALLIATIVE CARE PROFESSIONALS IN PREVENTION OF PATHOLOGICAL FRACTURE

BackgroundMetastatic bone disease (MBD) has a damaging effect on quality of life and pathological fracture can impact on survival in advanced cancer. Patients with breast and prostatic cancer in particular...

The Association between Phase Angle of Bioelectrical Impedance Analysis and Survival Time in Advanced Cancer Patients: Preliminary Study.

BackgroundA frequent manifestation of advanced cancer patients is malnutrition, which is correlated with poor prognosis and high mortality. Bioelectrical impedance analysis (BIA) is an easy-to-use and non-invasive technique to evaluate changes in body composition and nutritional status. We investigated BIA-derived phase angle as a prognostic indicator for survival in advanced cancer patients.MethodsTwenty-eight patients treated at the hospice center of Seoul St. Mary's Hospital underwent BIA measurements from January, 2013 to May, 2013. We also evaluated palliative prognostic index (PPI) and palliative performance scale to compare with the prognostic value of phase angle. Cox's proportional hazard models were constructed to evaluate the prognostic effect of phase angle. The Kaplan Meier method was used to calculate survival.ResultsUsing univariate Cox analysis, phase angle (hazard ratio [HR], 0.61/per degree increase; 95% confidence interval [CI], 0.42 to 0.89; P = 0.010), PPI (HR, 1.21; 95% CI, 1.00 to 1.47; P = 0.048) were found to be significantly associated with survival. Adjusting age, PPI, body mass index, phase angle significantly showed association with survival in multivariate analysis (HR, 0.64/per degree increase; 95% CI, 0.42 to 0.95; P = 0.028). Survival time of patients with phase angle ≥ 4.4° was longer than patients with phase angle < 4.4° (log rank, 6.208; P-value = 0.013).ConclusionOur data suggest BIA-derived phase angle may serve as an independent prognostic indicator in advanced cancer patients.

Prognostic Factors in Patients with Advanced Cancer: A Comparison of Clinicopathological Factors and the Development of an Inflammation-Based Prognostic System

In advanced cancer, oncological treatment is influenced by performance status (PS); however, this has limitations. Biomarkers of systemic inflammation may have prognostic value in advanced cancer. The study compares key factors in prognosis (performance status, patient-reported outcomes; PRO) with an inflammation-based score (Glasgow Prognostic Score, mGPS). A new method of prognosis in advanced cancer (combining performance status and mGPS) is tested and then validated. Two international biobanks of patients with advanced cancer were analyzed. Key prognostic factors [performance status, PROs (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C-30), and mGPS (using C-reactive protein and albumin concentrations)] were examined. The relationship between these and survival was examined using Kaplan-Meier and Cox regression methods, in a test sample before independent validation. Data were available on 1,825 patients (test) and 631 patients (validation). Median survival ranged from 3.2 months (test) to 7.03 months (validation). On multivariate analysis, performance status (HR 1.62-2.77) and mGPS (HR 1.51-2.27) were independently associated with, and were the strongest predictors of survival (P < 0.01). Survival at 3 months varied from 82% (mGPS 0) to 39% (mGPS 2) and from 75% (performance status 0-1) to 14% (performance status 4). When used together, survival ranged from 88% (mGPS 0, PS 0-1) to 10% (mGPS 2, performance status 4), P < 0.001. A systemic inflammation-based score, mGPS, and performance status predict survival in advanced cancer. The mGPS is similar to performance status in terms of prognostic power. Used together, performance status and mGPS act synergistically improving prognostic accuracy. This new method may be of considerable value in the management of patients with advanced cancer.