Outcome In Advanced Cancer Patients Research Articles

Immortal time bias in the association between toxicity and response for immune checkpoint inhibitors: A systematic review and meta-analysis.

e15080 Background: A number of studies have addressed the association between Immune related Adverse Events (IrAE) and outcome in patients treated with Immune Checkpoint Inhibitors (ICI). Only a minority of them considered the effect of immortal time bias (ITB), and results of these papers are conflicting. The aim of our meta-analysis was to assess the relationship between IrAE and outcomes for patients treated with ICIs, with a focus on ITB in weighing the role of this association. Methods: PubMed, Embase (Ovid), and Scopus were searched through January 2, 2020. Studies reporting the prognostic impact of IrAE development on outcome in advanced cancer patients treated with anti PD-1 or PD-L1.Two investigators independently extracted data from each study following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guideline. Author name, cancer type, PD-1 and PD-L1 inhibitor used, number of patients, number and type of all adverse events, presence of a landmark analysis, median OS and PFS and difference between patient with or without IrAE in terms of OS and PFS (Hazard Ratio) and ORR (Odds Ratio) were extracted. Data were pooled using a random-effects model. Main outcome were Overall Survival (OS), Progression Free Survival (PFS) and Overall Response Rate (ORR). Analysis was performed with dedicated software (R studio version 1.2.1335, metafor package). Results: A total of 29 articles comprising 7430 patients were included. 7 papers published the results of survival analysis according to landmark analysis, 2 papers published only the naïve analysis while stating that a landmark analysis resulted non significant, and the others did not perform a landmark analysis. IrAEs were associated with improved outcomes with high heterogeneity ( I2 70.8%, p < 0.001 for OS; 65.7%, p 0.002 for PFS; 62.1%, p 0.001 for ORR). When subgroup analysis was performed according to the adoption of a landmark approach, the association between IrAE and outcome remains significant for OS, PFS and ORR but the effect size was smaller ( HR 0.61 vs 0.41 for OS, ANOVA Q-test for difference between subgroup p = 0.015; HR 0.66 vs 0.47 for PFS, ANOVA Q-test p 0.029; OR 2.59 vs 6.77 for ORR, ANOVA Q-test p < 0.001) while heterogeneity was substantially reduced (I2 for papers using LM 43% for OS, p 0.115; 9.7% for PFS, p 0.355; 0.0% for ORR, p 0.556). Conclusions: Our analysis suggests a significant confounding effect of ITB as well as a real effect of IrAE development on outcome.

Mathematical prediction of clinical outcomes in advanced cancer patients treated with checkpoint inhibitor immunotherapy.

We present a mechanistic mathematical model of immune checkpoint inhibitor therapy to address the oncological need for early, broadly applicable readouts (biomarkers) of patient response to immunotherapy. The model is built upon the complex biological and physical interactions between the immune system and cancer, and is informed using only standard-of-care CT. We have retrospectively applied the model to 245 patients from multiple clinical trials treated with anti-CTLA-4 or anti-PD-1/PD-L1 antibodies. We found that model parameters distinctly identified patients with common (n = 18) and rare (n = 10) malignancy types who benefited and did not benefit from these monotherapies with accuracy as high as 88% at first restaging (median 53 days). Further, the parameters successfully differentiated pseudo-progression from true progression, providing previously unidentified insights into the unique biophysical characteristics of pseudo-progression. Our mathematical model offers a clinically relevant tool for personalized oncology and for engineering immunotherapy regimens.

A comparison of treatment preferences, decision making, and psychosocial outcomes in advanced cancer patients with and without minor children: A matched cohort study.

91 Background: Patients with advanced cancer who have minor children face unique challenges when coping with their life-limiting illness and the impact of their illness on their families. The goal of this study was to examine whether psychosocial functioning, treatment preferences, and treatment decisions in advanced cancer differ by parental status. Methods: A cohort of 60 parents with metastatic solid tumors age-matched with 60 non-parents (N = 120) participated in three structured interviews assessing treatment preferences and decisions over six months with complementary medical record review. Participants also completed validated measures of psychosocial functioning. Results: Seventy percent (n = 85) of the sample completed all study assessments. Mean age (45 years, SD 8), mean performance status score (ECOG = 1.2, SD 0.9), median duration of metastatic illness (19 months, range 1-115), gender ratio (66% female), and dropout rates were similar between groups. Parents and non-parents reported similar overall health-related quality of life, but parents were more likely to report poorer emotional well-being (p = 0.006) and more symptoms of depression (p = 0.04) and anxiety (p = 0.04) than non-parents. Parents and non-parents were equally likely to describe life-extension as their primary goal of anti-neoplastic treatment. Parents reported greater willingness to live in pain (48% “very willing” vs 27%, p = 0.007) and accept intubation/ventilation (40% vs 20%, p = 0.01) for life-extension. Compared to non-parents, parents were more likely to report their family members as the most influential factor in their decision-making (44% vs 12%) and less likely to cite their oncologist’s recommendation (25% vs 41%). There were no significant differences between groups for completion of a health care power of attorney or living will. Conclusions: Compared to similarly aged adults with metastatic cancer, parents experience greater psychological distress, are more willing to live in pain for life extension, and place greater importance on family-related factors in their cancer treatment decision-making.

VENOUS ACCESS DEVICE RELATED COMPLICATIONS IN ONCOLOGIC PATIENTS ENROLLED ON HOME PARENTERAL NUTRITION

Oncologic patients with important anorexia or alterated digestive tract function, for obstruction or malabsorption, may benefit by Home Parenteral Nutrition. Aim: to evaluate the incidence of venous access related complications in cancer patients undergoing HPN. We included 195 patients enrolled on HPNon the basis of ESPEN guidelines, in 2015- 2016. Incidence of complications were expressed as events per 1000 HPN days, calculated from the HPN start date until the discontinuation of home infusions or the removal of the VAD or the death of the patient. The VADs used were peripherally inserted central catheters (PICCs), subcutaneous implanted port, tunneled central catheters (TCCs) or non tunneled central catheters (NTCCs). 111 males, 84 females; median age 65 years(27-94). Median HPN duration was 106 days. A total of 208 VADs were studied: 67% PICCs, 21% ports, 9% TCCs and 3% NTCCs. Both thrombosis and tip migrations occurred only in PICCs, while infections happened in PICCs, ports and TCCs. The overall incidence of VAD related complications per 1000 HPN days was 0,73(0,27 in TCCs, 0,70 in PICCs, 1,25 in ports and null in NTCCs). HPN results to be a supportive therapy with low rate of VADs related complications. Infections are the most frequent complication and may occur in all kind of devices. Cotogni P. Catheter-related complications in cancer patients on home parenteral nutrition: a prospective study of over 51,000 catheter days. JPEN J Parenter Enteral Nutr. 2013;37(3):375-83 Vashi PG. A longitudinal study investigating quality of life and nutritional outcomes in advanced cancer patients receiving home parenteral nutrition.BMC Cancer.2014;14:593

Abstract 1597: Real-world large-scale study kinase domain duplications across diverse tumor types in Chinese populations

Abstract Background: Recently, kinase domain duplications (KDD) in BRAF, EGFR, MET and FGFR1 were reported, along with responses to tyrosine kinase inhibitors (TKI). However, its frequency and clinical outcomes in advanced cancer patients are larglely uncertain. We assessed the frequency of KDD across 14, 491 advanced cancers to reveal the landscape in a wide variety of subtypes. Methods: A multicenter study in China was initiated from July 2013, and advanced cancer patients have been enrolled as of September 2018. We analyzed data from 14, 491 clinical advanced cancer cases, each of which had results from next-generation sequencing (NGS)-based 381 genes panel assay, analogous to the index patient. Results: Of this entire cohort [6837 lung cancer (47.18%), 1894 breast cancer (13.07%), 1325 colorectal cancer (9.14%), 710 urinary system tumor (4.90%), 536 gynecological tumor (3.70%), 592 hepatobiliary cancer (4.09%), 221 gastric cancer (1.53%), 312 soft tissue sarcoma (2.15%), 260 head and neck cancer (1.79%) and 1804 others (12.45%)], 71 patients were identified with KDD, including EGFR (16), BRAF (12), MET (11), FGFR3 (8), RET (3), PDGFRA (3), ROS1 (3), FGFR1 (2), ERBB2 (2), SOX17 (2), ALK (2), KIT (1), NTRK1 (1), BAP1 (1), TMPRSS2 (1), ERBB4 (1), VHL (1), NTRK3 (1). KDD were seen in 0.39% (27/6837) of lung cancer [EGFR(9), BRAF (2), MET (6), FGFR3 (2), RET (1), PDGFRA (1), ROS1 (2), ERBB2 (1), ALK (1), NTRK1 (1), and ERBB4 (1)]; 0.21%(4/1894) of breast cancer [BRAF (1), FGFR3 (2), FGFR1 (1)]; 0.60%(8/1325) of colorectal cancer [EGFR (1), BRAF (3), FGFR3 (2), RET (1), ROS1 (1)]; 0.28%(2/710) of urinary system tumor [TMPRSS2(1), VHL (1)]; 0.19%(1/536) of gynecological tumor [SOX17 (1)]; 0.17%(1/592) of hepatobiliary cancer [EGFR (1)]; 0.45%(1/221) of gastric cancer [ERBB2 (1)]; 0.96%(3/312) of soft tissue sarcoma [EGFR (1), FGFR3 (1), PDGFRA (1)]; 0.77%(2/260) of head and neck cancer [BRAF (2)]; and 1.22%(22/1804) of others [EGFR (4), BRAF (4), MET (5), FGFR3 (1), RET (1), PDGFRA (1), FGFR1 (1), SOX17 (1), ALK (1), KIT (1), BAP1 (1), and NTRK3 (1)]; KDD possibly related to target resistance were seen in ERBB2 amplification gastric cancer and ALK-related NSCLC. Conclusion: Diverse KDD are found across diverse tumor types and may underlie acquired resistance, and can benefit from matched targeted treatment. In addition, for short- or long-term responses to targeted treatment, we can use the NGS assay to explore differential gene alter in the future. Citation Format: Chun-wei Xu, Wen-xian Wang, Xiao-jia Wang, You-cai Zhu, Qu-xia Zhang, Yong Fang, Xiu-yu Cai, Yu Chen, Li Lin, Hong Wang, Mei-yu Fang, Yin-bin Zhang, Shi-jie Lan, Xin Liu, Xing-xiang Pu, Zong-yang Yu, Bing Wan, Jian-ying Li, Xian-bin Liang, Li-ping Wang, Wu Zhuang, Ling Lin, Gang Chen, Tang-feng Lv, Yong Song. Real-world large-scale study kinase domain duplications across diverse tumor types in Chinese populations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1597.

Prognostic value of ALDH1 and Nestin in advanced cancer: a systematic meta-analysis with trial sequential analysis.

Background:Novel prognostic markers and therapeutic targets for advanced cancer are urgently needed. This report with trial sequential analysis (TSA) was first conducted to provide robust estimates of the correlation between aldehyde dehydrogenase 1 (ALDH1) and Nestin and clinical outcomes of advanced cancer patients.Methods:Hazard ratios (HRs) with 95% confidence intervals (CIs) were summarized for 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) from multivariable analysis. TSA was performed to control for random errors.Results:A total of 20 studies with 2050 patients (ALDH1: 15 studies with 1557 patients and Nestin: 5 studies with 493 patients) were identified. ALDH1 (HR = 2.28, p < 0.001) and Nestin (HR = 2.39, p < 0.001) were associated with a worse OS, as confirmed by TSA. Nestin positivity was linked to a poor PFS (HR = 2.08, p < 0.001), but ALDH1 was not linked to DFS, RFS, MFS, or PFS, and TSA showed that more studies were needed. Subgroup analysis by tumor type indicated that ALDH1 positivity may be associated with shorter OS in breast, head and neck cancers, but there was no association with colorectal cancer. Subgroup analysis by study source showed that ALDH1 positivity was correlated with a worse OS for Japanese (HR = 1.94, p = 0.002) and European patients (HR = 4.15, p < 0.001), but there was no association for Chinese patients. Subgroup analysis by survival rate showed that ALDH1 positivity correlated with poor OS at ⩾ 5 years (HR = 2.33, p < 0.001) or 10 years (HR = 1.76, p = 0.038).Conclusions:ALDH1 may be more valuable as an effective therapeutic target than Nestin for improving the long-term survival rate of advanced cancer. Additional prospective clinical trials are needed across different cancer types.

Improving communication about prognosis on an academic inpatient solid tumor oncology consult service.

46 Background: As the number of patients living with cancer increases, a growing proportion of hospital inpatients will have an advanced cancer diagnosis. Data suggests that an unscheduled hospitalization for a patient with advanced cancer strongly predicts a median survival of less than 6 months. As hospitalists more frequently become the primary team taking care of admitted cancer patients, communication between a patient's oncologic care team and inpatient primary providers is crucial. We sought to implement and assess the impact of improved oncology consult documentation of patient prognosis on outcomes of advanced cancer patients admitted to our hospitalist medicine teaching services. Methods: We implemented an EMR-based oncology consult note template which required documentation of prognosis, potential future treatment options (if available), and advance care planning. We reviewed all patients with stage IV solid tumors admitted to the hospitalist teaching service for 8 weeks prior and 8 weeks post-template implementation for comparison. We utilized descriptive statistics and chi-squared testing as appropriate for analysis. Results: We evaluated 51 patients in the pre- and 36 patients in the post-intervention groups. Post-intervention, there was an improvement in documentation of prognosis (29.4% vs. 52.8%, p = 0.03), advanced care planning (37.2% vs. 83.3%, p &lt; 0.0001), and in number of palliative care consults (58.8% vs. 83.3%, p = 0.02). On average, goals of care conversations occurred 2 days earlier in the post-intervention group (11 vs 9 days). Similarly, there was a decrease in inpatient chemotherapy administration (3 cases vs. 0), unit codes (2 vs. 0) and in-hospital death (23.5% vs. 11.1%). Conclusions: Creation of an oncology consult note template which incorporates current oncologic prognostic information improved documentation of prognosis and advance care planning as well as outcomes for advanced solid tumor oncology patients and enhanced inter-service communication. Based on these results, continued and targeted interventions are planned to further improve interservice communication.

Standardizing documentation and improving communication on an academic inpatient solid tumor oncology consult service.

171 Background: As the number of patients living with cancer increases, a growing proportion of hospital inpatients will have an advanced cancer diagnosis. Data suggests that an unscheduled hospitalization for a patient with advanced cancer strongly predicts a median survival of less than 6 months. As hospitalists more frequently become the primary team taking care of admitted cancer patients, communication between a patient's oncologic care team and inpatient primary providers is crucial. We sought to implement and assess the impact of improved oncology consult documentation of patient prognosis on outcomes of advanced cancer patients admitted to our hospitalist medicine teaching services. Methods: We implemented an EMR-based oncology consult note template which required documentation of prognosis, potential future treatment options (if available), and advance care planning. We reviewed all patients with stage IV solid tumors admitted to the hospitalist teaching service for 8 weeks prior and 8 weeks post-template implementation for comparison. We utilized descriptive statistics and chi-squared testing as appropriate for analysis. Results: We evaluated 51 patients in the pre- and 36 patients in the post-intervention groups. Post-intervention, there was an improvement in documentation of prognosis (29.4% vs. 52.8%, p = 0.03), advanced care planning (37.2% vs. 83.3%, p &lt; 0.0001), and in number of palliative care consults (58.8% vs. 83.3%, p = 0.02). On average, goals of care conversations occurred 2 days earlier in the post-intervention group (11 vs 9 days). Similarly, there was a decrease in inpatient chemotherapy administration (3 cases vs. 0), unit codes (2 vs. 0) and in-hospital death (23.5% vs. 11.1%). Conclusions: Creation of an oncology consult note template which incorporates current oncologic prognostic information improved documentation of prognosis and advance care planning as well as outcomes for advanced solid tumor oncology patients and enhanced inter-service communication. Based on these results, continued and targeted interventions are planned to further improve inter-service communication.

Timing of palliative care access and outcomes of advanced cancer patients referred to an inpatient palliative care consultation team in Brazil.

Little is known about the outcomes of cancer patients referred to palliative care (PC) teams in developing countries. Our aim was to examine the timing of PC access and outcomes of patients with advanced cancer referred to an inpatient PC consultation team in Brazil. Retrospective study of consecutive patients with advanced cancer admitted to a tertiary care general hospital (April 2015-December 2016) and referred for the first time to an inpatient PC consultation team. Patients' demographics, clinical features, time from first consult to death or discharge, and outcomes on medication use, clinical interventions, and end-of-life preferences were retrieved. An analysis was performed before and after PC. One hundred eleven patients were included. Median age was 68; 72% had an Eastern Cooperative Oncology Group performance status ≥3. The median timing of PC access was 9 days (first interquartile = 3, third interquartile = 19). The use of analgesics (from 75% to 85%, p = 0.001) and opioids (from 50% to 73%, p < .001) increased. A lower proportion was receiving antibiotics (68% vs 48%, p < 0.001), thromboprophylaxis (44% vs 26%, p < 0.001), antihypertensives (28% vs 15%, p = 0.001), and antiemetic agents (64% vs 54%, p = 0.027). Chemotherapy use was lower (39-25%, p < 0.001). More patients had an end-of-life preference (39% to 25%, p < 0.001) and were not willing to receive intubation (32% vs 60%, p < 0.001), intensive care treatment (30% vs 55%, p < 0.001), cardiopulmonary resuscitation (35% vs 62%, p < 0.001), and artificial nutrition (22% vs 34%, p < 0.001). Although PC referrals occurred exceedingly late during the cancer disease trajectory, positive changes were observed in medication profiles, clinical interventions use, and end-of-life preferences of patients with advanced cancer referred to a specialized inpatient PC consultation team in Brazil. Further efforts are needed to improve early palliative cancer care in developing countries.

Nutrition support and clinical outcome in advanced cancer patients.

Newly diagnosed cancer patients are frequently found suffering from a metastatic disease, which poses additional challenges to the delivery of effective therapies. Chemotherapy and radiotherapy are associated with side effects which reduce tolerance to treatment and likelihood of tumour response. Identifying preventable factors of reduced response to therapy would translate into better care of cancer patients. Among other factors, malnutrition, as diagnosed by non-volitional weight loss, and cachexia, as revealed by sarcopenia, are universally recognised negative prognostic factors. Less certainty exists on the role of nutrition therapy in improving cancer patients' body composition and clinical outcome. The reasons for the lack of convincing evidence are manifold, mostly related to the poor design of nutritional trials. Metastatic cancer patients should receive a quantitatively and qualitatively adequate diet, and in case of reduced tolerance of food, artificial nutrition is indicated. Most importantly, nutritional care should target the underlying mechanisms of reduced food intake/impaired anabolic response, and aim at minimising the impact of catabolic crisis, to maximise the recovery phase. The combined and early use of supplemental energies and proteins, as well as modulators of inflammatory response has been shown to improve nutritional status and may also benefit clinical outcome. When part of early palliative care, nutrition therapy improves cancer patients' quality of life and may prolong survival at a fraction of the costs of developing new drugs.

Wearable activity monitors to assess performance status and predict clinical outcomes in advanced cancer patients

An objective evaluation of patient performance status (PS) is difficult because patients spend the majority of their time outside of the clinic, self-report to providers, and undergo dynamic changes throughout their treatment experience. Real-time, objective activity data may allow for a more accurate assessment of PS and physical function, while reducing the subjectivity and bias associated with current assessments. Consenting patients with advanced cancer wore a wearble activity monitor for three consecutive visits in a prospective, single-cohort clinical trial. Provider-assessed PS (ECOG/Karnofsky) and NIH PROMIS® patient-reported outcomes (PROs) were assessed at each visit. Associations between wearable activity monitor metrics (steps, distance, stairs) and PS, clinical outcomes (adverse events, hospitalizations, survival), and PROs were assessed using correlation statistics and in multivariable logistic regression models. Thirty-seven patients were evaluated (54% male, median 62 years). Patients averaged 3700 steps, 1.7 miles, and 3 flights of stairs per day. Highest correlations were observed between average daily steps and ECOG-PS and KPS (r = 0.63 and r = 0.69, respectively p < 0.01). Each 1000 steps/day increase was associated with reduced odds for adverse events (OR: 0.34, 95% CI 0.13, 0.94), hospitalizations (OR: 0.21 95% CI 0.56, 0.79), and hazard for death (HR: 0.48 95% CI 0.28–0.83). Significant correlations were also observed between activity metrics and PROs. Our trial demonstrates the feasibility of using wearable activity monitors to assess PS in advanced cancer patients and suggests their potential use to predict clinical and patient-reported outcomes. These findings should be validated in larger, randomized trials.

Incidence of hypophosphatemia in advanced cancer patients: a recent report from a single institution

Recent approval of molecular-targeted agents has contributed to improving the therapeutic outcomes of advanced cancer patients. However, they result in unusual adverse events that rarely occur with cytotoxic agents, such as hypertension, hypomagnesemia, and an acne-like rash. Although hypophosphatemia can be induced by various agents, some kinds of molecular-targeted agents are known to induce it. In addition, cancer survivors may be at a risk of hypophosphatemia. One hundred and seventy patients, who visited the Department of Clinical Oncology at Akita University from 1 April 2014 to 31 August 2016 were enrolled in this study after providing informed consent. Serum inorganic phosphorus levels were examined along with other routine clinical examinations. Correlation between the serum inorganic phosphorus level and other clinical data were also analyzed. Grade ≥2 severe hypophosphatemia (<2.5mg/dL of phosphorus) was detected in 49.4% of patients, and grade ≥3 (<2.0mg/dL of phosphorus) was observed in 22.9% patients. These results indicated that the presence of bone metastasis (p<0.001), history of bone-modifying agents (p<0.001) and molecular-targeted drugs (p=0.001), and time from the date of the first visit to the date of minimum serum phosphorus level (p<0.001) might correlate with hypophosphatemia. Multivariate logistic regression analysis showed that disease duration might be a risk factor (p=0.0466). As hypophosphatemia can be induced by various factors in advanced cancer patients, the serum phosphorus level of cancer patients at risk should be cautiously examined.

A preliminary randomised controlled study of short-term Antrodia cinnamomea treatment combined with chemotherapy for patients with advanced cancer

BackgroundAntrodia cinnamomea (AC) is a popular medicinal mushroom in Taiwan that has been widely used for treatment of various cancers. Few clinical studies have reported its application and efficiency in therapeutic chemotherapy strategies. We performed a double-blind, randomized clinical study to investigate whether AC given for 30 days had acceptable safety and efficacy in advanced cancer patients receiving chemotherapy.MethodsPatients with advanced and/or metastatic adenocarcinoma, performance status (PS) 0–2, and adequate organ function who had previously been treated with standard chemotherapy were randomly assigned to receive routine chemotherapy regimens with AC (20 ml twice daily) orally for 30 days or placebo. The primary endpoint was 6-month overall survival (OS); the secondary endpoints were disease control rate (DCR), quality of life (QoL), adverse event (AE), and biochemical features within 30 days of treatment.ResultsFrom August 2010 to July 2012, 37 subjects with gastric, lung, liver, breast, and colorectal cancer (17 in the AC group, 20 in the placebo group) were enrolled in the study. Disease progression was the primary cause of death in 4 (33.3 %) AC and 8 (66.7 %) placebo recipients. Mean OSs were 5.4 months for the AC group and 5.0 months for the placebo group (p = 0.340), and the DCRs were 41.2 and 55 %, respectively (p = 0.33). Most hematologic, liver, or kidney functions did not differ significantly between the two groups, but platelet counts were lower in the AC group than in the placebo group (p = 0.02). QoL assessments were similar in the two groups, except that the AC group showed significant improvements in quality of sleep (p = 0.04).ConclusionsAlthough we found a lower mortality rate and longer mean OS in the AC group than in the control group, A. cinnamomea combined with chemotherapy was not shown to improve the outcome of advanced cancer patients, possibly due to the small sample size. In fact, the combination may present a potential risk of lowered platelet counts. Adequately powered clinical trials will be necessary to address this question.Trial registrationClinicalTrials.gov NCT01287286.

Abstract PR07: Precision genomic medicine improves clinical outcomes in advanced cancer patients

Abstract Background: The advent of Next-Generation Sequencing (NGS), and other diagnostic technologies, has enabled the use of genomic information to guide targeted treatment in cancer patients. Utilizing these technologies, we established a precision medicine program within a large, integrated healthcare delivery system. We then monitored the outcomes, including progression free survival and treatment delivery costs, associated with the delivery of precision medicine for patients with advanced cancer. We report the structure of our program and an analysis of the clinical outcomes associated with precision cancer medicine. Methods: We conducted a matched cohort study of 72 patients from July 01, 2013 to December 31, 2014, with metastatic cancer of diverse subtypes. The outcomes of 36 patients treated with precision cancer medicine were compared to 36 historical control patients who received standard chemotherapy. Study and control patients were matched according to age, gender, histological diagnosis, and number of previous treatment lines. Progression free survival was compared between the two groups using a Cox Proportional Hazard model for survival and accounting for potential confounders. Costs included subsequent ED visits, hospitalizations, NGS costs, and costs for targeted treatment or standard therapy. Results: Establishing a precision cancer medicine program for advanced cancer patients was feasible and scalable. Evaluation of the outcomes revealed that progression free survival was 22.9 weeks for the treatment group and 12.0 weeks for the historical control group (p = 0.002). Patients receiving precision cancer medicine compared to conventional treatment patients had a hazard ratio of 0.47 (95% confidence interval of 0.29-0.75) when adjusting for age, gender, histological diagnosis and previous treatment lines. Cost per week was $3,204 in the treatment group and $3501 in the historical control group, p = 0.22 Conclusions: Precision cancer medicine appears to significantly improve survival for patients with advanced cancer when compared to control patients who received conventional chemotherapy. The additional survival is not associated with increased health care costs. While the results of this study warrant further investigation, this genomics-based approach appears to be a viable, and perhaps superior, option for patients with advanced or metastatic cancer. This abstract is also presented as Poster 16. Citation Format: Lincoln D. Nadauld, Burke Van Norman, Gail Fulde, David newman, Allison Butler, Brian Tudor, Heather Gilbert, Karen Lin, Gary Stone, Anish Konde, Iva Petrovchich, James M. Ford, Derrick Haslem. Precision genomic medicine improves clinical outcomes in advanced cancer patients. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr PR07.

Characteristics and outcomes of advanced cancer patients admitted to an acute palliative care unit (PCU) with severe dyspnea receiving high flow oxygen (HFO).

247 Background: Dyspnea is very complex and distressing symptom in patients with advanced cancer. The therapeutic goal of its symptomatic management is to relieve the patient’s breathlessness sensation. Limited literature has addressed the characteristics and clinical outcomes of advanced cancer patients with severe dyspnea receiving HFO admitted to PCU. Methods: We reviewed the records of 101 advanced cancer patients with dyspnea receiving HFO and 110 matched PCU inpatients with dyspnea receiving regular O2 flow (NoHFO) between January 1 to December 31, 2012. Demographics, frequency and intensity of symptoms at PCU admission and follow-up, and outcomes were recorded. Results: Median age: 60 years, range (51, 69). 56% were Male. White(71%), Hispanic(13%), African American(10%), Asian (4%). Primary cancer: Lung (27%), Gastrointestinal (19%), Hematological (18%), Breast (13%), Gynecological (6%). Dyspnea was present in all cases and it was related mainly to: lung involvement by cancer (53%), pneumonia (40%), Congestive Heart Failure (6%), COPD (8%). ECOG: 4. No significant difference in age, ethnicity and type of cancer, ECOG, and possible cause of dyspnea among both groups. HFO and NoHFO were started the same day of admission. Median ESAS symptoms (Interquartile range: IQR) for HFO was Pain 4.5 (2, 7) vs. 5 (3, 7) for NoHFO, p = 0.1423; fatigue [7(5, 8) vs. 7 (5, 8), p = 0.450]; depression [3 (1, 5) vs. 3.5 (2, 5), p = 0.81]; anxiety 7 (4, 9) vs. 6 (3, 8), p = 0.01; dyspnea [7.5( 6, 9) vs. 5 (3, 8), p &lt; 0.0001]. Memorial Delirium Scale 5 (2, 15) vs. 7(2, 15), p = 0.77). Morphine Equivalent Daily Dose: 48 (36, 120) vs. 55 (30, 120), p = 0.72. The median difference among first and follow up ESAS was Pain 0 (-3, 1) vs. -1(-2, 1), p = 0.62; fatigue[(-2, 1) vs. 0 (-2, 0), p = 0.63]; depression [0 (-1, 1) vs. 0 (-1, 2), p = 0.93]; anxiety [0 (-2, 2) vs. 0 (-2, 2), p = 0.94; dyspnea [0( -1, 1) vs. -1 (-2, 1), p = 0.18]. Memorial Delirium Scale 0 (-1.5, 5.5) vs. 0 (-2, 3), p = 0.21).The median time (IQR) from HFO started to discharge was 10 days (6, 15) vs. 8.5 (5, 14) days for NoHFO, p = 0.07). The median time(IQR) from HFO started to Death was 10.5 (7, 19) vs. 13.5 (7, 26) days for NoHFO, p = 0.18. 77/101(76%) HFO patients vs. 56/110 (51%) NoHFO died at the hospital, p = 0.002. 24/101(23%) HFO patients were discharged alive weaned off HFO. The Odd ratio for hospital death in patients with HFO vs. NoHFO was 4.83 (95% CI: 1.72 – 13.59), p = 0.003. Conclusions: Severe dyspnea is significant at the end of life of advanced cancer patients. Patients with HFO require similar MEDD than NoHFO patients. Inpatient mortality is higher in patients with HFO. More research is needed.

Bone turnover marker (BTM) levels and clinical outcomes in advanced cancer patients (pts) treated with antiresorptive bone therapies.

e22236 Background: Advanced cancer pts with metastatic bone disease typically have elevated BTM levels. Antiresorptive agents such as denosumab (DMAB) and zoledronic acid (ZA) can significantly red...

Cardiovascular toxicity of multi-tyrosine kinase inhibitors in advanced solid tumors: a population-based observational study.

BackgroundTreatment with small molecule tyrosine kinase inhibitors (TKIs) has improved survival in many cancers, yet has been associated with an increased risk of adverse events. Warnings of cardiovascular events are common in drug labels of many TKIs. Despite these warnings, cardiovascular toxicity of patients treated with TKIs remains unclear. Here, we evaluate the cardiovascular outcomes of advanced cancer patients treated with small molecule tyrosine kinase inhibitors.MethodsA population based cohort study was undertaken involving adults aged >18 years in Ontario, Canada, diagnosed with any advanced malignancy between 2006 and 2012. Data were extracted from linked administrative governmental databases. Adults with advanced cancer receiving TKIs were identified and followed throughout the time period. The main outcomes of interest were rates of hospitalization for ischemic heart disease (acute myocardial infarction and angina) or cerebrovascular accidents and death.Results1642 patients with a mean age of 62.5 years were studied; 1046 were treated with erlotinib, 166 with sorafenib and 430 with sunitinib. Over the 380 day median follow-up period (range 6-1970 days), 1.1% of all patients had ischemic heart events, 0.7% had cerebrovascular accidents and 72.1% died. Rates of cardiovascular events were similar to age and gender-matched individuals without cancer. In a subgroup analysis of treatment patients with a prior history of ischemic heart disease, 3.3% had ischemic heart events while 1.2% had cerebrovascular accidents.ConclusionsTKIs do not appear to increase the cause-specific hazard of ischemic heart disease and cerebrovascular accidents compared to age and gender-matched individuals without advanced cancer.

A longitudinal study investigating quality of life and nutritional outcomes in advanced cancer patients receiving home parenteral nutrition.

BackgroundIn cancer patients where gastrointestinal function is marginal and malnutrition significant enough to result in the requirement for intensive nutrition support, parenteral nutrition (PN) is indicated. This longitudinal study examined the quality of life (QoL) and nutritional outcomes in advanced cancer patients receiving home PN (HPN).MethodsFifty-two adult cancer patients (21 males, 31 females, average age 53 years) treated at a specialized cancer facility between April 2009 and November 2011 met criteria. QoL and nutritional status were measured at baseline and every month while on HPN using EORTC-QLQ-C30, Karnofsky Performance Status (KPS), and Subjective Global Assessment (SGA). Repeated measures ANOVA and Generalized Estimating Equations (GEE) were used to evaluate longitudinal changes in QoL and SGA.ResultsCancer diagnoses included pancreatic (n = 14), colorectal (n = 11), ovarian (n = 6), appendix (n = 5), stomach (n = 4) and others (n = 12). Average weight loss 6-months prior to HPN was 13.2 kg (16.9%). Average weight at initiation of HPN was 62.2 kg. In patients with available follow-up data after 1 month (n = 39), there was a significant improvement in SGA, weight (61.5 to 63.1 kg; p = 0.03) and KPS (61.6 to 67.3; p = 0.01) from baseline. Similarly, after 2 months (n = 22), there was an improvement in global QoL (37.1 to 49.2; p = 0.02), SGA, weight (57.6 to 60 kg; p = 0.04) and KPS (63.2 to 73.2; p = 0.01) from baseline. Finally, after 3 months (n = 15), there was an improvement in global QoL (30.6 to 54.4; p = 0.02), SGA, weight (61.1 to 65.9 kg; p = 0.04) and KPS (64.0 to 78.7; p = 0.002) from baseline. Upon GEE analysis, every 1 month of HPN was associated with an increase of 6.3 points in global QoL (p<0.001), 1.3 kg in weight (p = 0.009) and 5.8 points in KPS (p<0.001).ConclusionsHPN is associated with an improvement in QoL, KPS and nutritional status in advanced cancer patients, irrespective of their tumor type, who have compromised enteral intake and malnutrition. The greatest benefit was seen in patients with 3 months of HPN, although patients receiving HPN for 1 or 2 months also demonstrated significant improvements.

Erratum to: Characteristics and outcomes of advanced cancer patients who miss outpatient supportive care consult appointments

Erratum to: Characteristics and outcomes of advanced cancer patients who miss outpatient supportive care consult appointments

A longitudinal study investigating quality of life and nutritional outcomes in advanced cancer patients receiving home parenteral nutrition.

e17591 Background: In cancer patients where gastrointestinal function is marginal and malnutrition significant enough to result in the requirement for intensive nutrition support, parenteral nutrition (PN) is indicated. This longitudinal study examined the quality of life (QoL) and nutritional outcomes in advanced cancer patients with a life expectancy >90 days receiving home PN (HPN). Methods: Fifty-two adult cancer patients (21 males, 31 females, average age 53 years) treated at a specialized cancer facility between April 2009 and November 2011 met criteria. QoL and nutritional status were measured at baseline and every month while on HPN using EORTC-QLQ-C30, Karnofsky Performance Status (KPS), and Subjective Global Assessment (SGA). Repeated measures ANOVA and Generalized Estimating Equations (GEE) were used to evaluate longitudinal changes in QoL and SGA. Results: Cancer diagnoses included pancreatic (n=14), colorectal (n=11), ovarian (n=6), appendix (n=5), stomach (n=4) and others (n=12). Average weight loss 6-months prior to HPN was 13.2 kg (16.9%). Average weight at initiation of HPN was 62.2 kg. In patients with available follow-up data after 1 month (n=39), there was a significant improvement in SGA (10 to 7.9), weight (61.5 to 63.1 kg) and KPS (61.6 to 67.3) from baseline. Similarly, after 2 months (n=22), there was an improvement in global QoL (37.1 to 49.2), SGA (10 to 6.5), weight (57.6 to 60) and KPS (63.2 to 73.2) from baseline. Finally, after 3 months (n=15), there was an improvement in global QoL (30.6 to 54.4), SGA (10.1 to 5.5), weight (61.1 to 65.9) and KPS (64.0 to 78.7) from baseline. Upon GEE analysis, every 1 month of HPN was associated with an increase of 6.3 points in global QoL (p<0.001), 1.3 kg in weight (p=0.009), 5.8 points in KPS (p<0.001) and a decrease of 1.5 points in SGA (p<0.001). Conclusions: HPN is associated with an improvement in QoL, KPS and nutritional status in advanced cancer patients, irrespective of their tumor type, who have compromised enteral intake and malnutrition. The greatest benefit was seen in patients with 3 months of HPN, although patients receiving HPN for 1 or 2 months also demonstrated significant improvements.