"You have to be sure that the patient has the full picture": Adaptation of the Best Case/Worst Case communication tool for geriatric oncology.

BACKGROUND: Shared decision making (SDM) is especially important for older adults with cancer given the risks of over- and undertreatment, uncertainty regarding benefits/harms worsened by research underrepresentation, and individual preferences. We aimed to adapt the Best Case/Worst Case (BC/WC) communication tool, which improves SDM in geriatric surgery, to geriatric oncology. METHODS: We conducted focus groups with 40 stakeholders (fourteen older adults with lung cancer, twelve caregivers, fourteen medical oncologists) to elicit perspectives on using the BC/WC tool for geriatric oncology and to identify components needing refinement. During each focus group, participants viewed a BC/WC demonstration video and answered questions modified from the Decision Aid Acceptability Scale. We analyzed transcripts using deductive and inductive thematic analyses. DISCUSSION: Participants believed that the BC/WC tool could help patients understand their cancer care choices, explore tradeoffs and picture potential outcomes, and deliberate about decisions based on their goals, preferences, and values. Oncologists also reported the tool could guide conversations to address points that may frequently be skipped (e.g., alternative options, treatment goals). Participant preferences varied widely regarding discussion of the worst-case scenario and desire for statistical information. CONCLUSION: The BC/WC tool is a promising strategy that may improve SDM in geriatric oncology and patient understanding of alternative options and treatment goals. Based on participant input, adaptations will include framing cancer care as a series of decisions, eliciting patient preferences and asking permission before offering the worst-case scenario, and selection of the two most relevant options to present if multiple exist.

Changes in older adults' life space during lung cancer treatment: A mixed methods cohort study.

BACKGROUND: Maintenance of function during cancer treatment is important to older adults. Characteristics associated with pretreatment life-space mobility and changes during non-small cell lung cancer (NSCLC) treatment remain unknown. METHODS: This mixed methods cohort study recruited adults age ≥65 with advanced NSCLC starting palliative chemotherapy, immunotherapy, and/or targeted therapy from a Comprehensive Cancer Center, Veterans Affairs, and safety-net clinic. Patients completed geriatric assessments including Life-Space Assessment (LSA) pretreatment and at 1, 2, 4, and 6 months after treatment initiation. LSA scores range from 0 to 120 (greater mobility); LSA <60 is considered restricted. We used mixed-effects models to examine pretreatment LSA, change from 0 to 1 month, and change from 1 to 6 months. A subgroup participated in semistructured interviews pretreatment and at 2 and 6 months to understand the patient experience of life-space change. For each interview participant, we created joint displays of longitudinal LSA scores juxtaposed with illustrative quotes. RESULTS: Among 93 patients, median age was 73 (range 65-94). Mean pretreatment LSA score was 67.1. On average, LSA declined 10.1 points from pretreatment to 1 month and remained stable at 6 months. Pretreatment LSA score was associated with several demographic, clinical, geriatric assessment, and symptom characteristics. LSA decline at 1 month was greater among patients with high anxiety (slope = -12.6 vs. -2.3, p = 0.048). Pretreatment body mass index <21 kg/m2 was associated with LSA improvement from 1 to 6 months (slope = 4.1 vs. -0.04, p = 0.003). Joint displays illustrated the impact of different life-space trajectories on patients' lives in their words. CONCLUSION: Older adults with NSCLC have low pretreatment life space with many developing restricted life space during treatment. Incorporating life-space assessments into clinical cancer care may help older adults concretely visualize how treatment might impact their daily function to allow for informed decision making and identify early changes in mobility to implement supportive interventions.

Changes in functional status associated with radiation for prostate cancer in older veterans.

BACKGROUND: Although older men value maintaining independence and avoiding functional decline, little is known about their functional trajectories with receipt of prostate radiation. METHODS: We performed a retrospective cohort study including veterans age 65+ with localized prostate cancer who resided in a VA nursing facility while receiving prostate radiation from 2005 to 2015. We evaluated the change in Minimum Data Set (MDS) activities of daily living (ADL) score during 6 months from the start of treatment. Because prior studies have shown Charlson Comorbidity Index (CCI) to be a strong predictor of treatment-related toxicity, analysis included interaction with CCI. RESULTS: We identified 487 patients with median age 73 (range 65-94). For the average patient in our cohort, the predicted MDS-ADL score worsened from 2.9 (95% CI 2.4-3.6) at the start of radiation to 3.8 (95% CI 3.1-4.8) at 3 months and then 4.5 (95% CI 3.5-5.7) at month 6. Patients with greater comorbidity (CCI ≥ 4) had worse functional outcomes in months 0-3 compared to patients with less comorbidity (CCI 0-3). MDS-ADL score worsened by 1.9 in the CCI ≥4 patients compared to 0.3 in the CCI 0-3 group During months 3-6, patients in both Charlson groups experienced similar worsening of MDS-ADL score. CONCLUSIONS: In a vulnerable population of older patients with localized prostate cancer, radiation was associated with a decline in functional independence. Patients with higher comorbidity experienced more severe functional decline within the first 3 months of radiation therapy. In all comorbidity levels, functional status had not returned to baseline by 6 months.

Embedded palliative care for patients with metastatic colorectal cancer: a mixed-methods pilot study.

PURPOSE: Palliative care is recommended for patients with metastatic cancer, but there has been limited research about embedded palliative care for specific patient populations. We describe the impact of a pilot program that provided routine, early, integrated palliative care to patients with metastatic colorectal cancer. METHODS: Mixed methods pre-post intervention cohort study at an academic cancer center. Thirty control then 30 intervention patients with metastatic colorectal cancer were surveyed at baseline and 1, 3, 6, 9, and 12 months thereafter about symptoms, quality-of-life, and likelihood of cure. We compared survey responses, trends over time, rates of advance care planning, and healthcare utilization between groups. Patients, family caregivers, and clinicians were interviewed. RESULTS: Patients in the intervention group were followed for an average of 6.5 months and had an average of 3.5 palliative care visits. At baseline, symptoms were mild (average 1.85/10) and 78.2% of patients reported good/excellent quality-of-life. Half (50.9%) believed they were likely to be cured of cancer. Over time, symptoms and quality-of-life metrics remained similar between groups, however intervention patients were more realistic about their likelihood of cure (p = 0.008). Intervention patients were more likely to have a surrogate documented (83.3% vs. 26.7%, p < 0.0001), an advance directive completed (63.3% vs. 13.3%, p < 0.0001), and non-full code status (43.3% vs. 16.7%, p < 0.03). All patients and family caregivers would recommend the program to others with cancer. CONCLUSIONS: We describe the impact of an embedded palliative care program for patients with metastatic colorectal cancer, which improved prognostic awareness and rates of advance care planning.

Clinicopathologic Characteristics and Impact of Oophorectomy for Ovarian Metastases from Colorectal Cancer.

BACKGROUND: As survival with metastatic colorectal cancer (CRC) and imaging modalities improve, detection of ovarian metastases may be increasing. The ovary may serve as a sanctuary site for malignant cells; however, there is a paucity of data regarding the role for oophorectomy. METHODS: This is a single-institution retrospective study of patients with CRC with ovarian metastases from 2009 to 2017. We evaluated patient, disease, and treatment related factors associated with overall survival (OS) from initial diagnosis of metastatic CRC. RESULTS: Of 108 patients assessed, the median age was 50, 19% had localized disease at initial presentation, 64% had ovarian metastases at initial CRC diagnosis, and 77% underwent oophorectomy. Median OS was 29.6 months across all patients, and it was 36.7 months in patients who underwent oophorectomy versus 25.0 months in patients who did not (hazard ratio [HR] 0.54). In multivariate analysis, the effect of oophorectomy on OS suggested protection but was not statistically significant (HR 0.57). Resection of primary tumor was performed in 71% of patients, which was independently associated with improved OS (HR 0.21). Twelve patients (11%) remained alive at 5 years after diagnosis of metastatic disease. CONCLUSION: Although it has been previously reported that patients with CRC with ovarian metastases have poor prognosis, the median OS for this cohort was comparable to existing OS data for patients with metastatic CRC. In patients treated with chemotherapy, we did not find the ovarian metastasis to frequently serve as a sanctuary site of disease. However, we found that in carefully selected patients, oophorectomy may confer a survival benefit. IMPLICATIONS FOR PRACTICE: In colorectal cancer (CRC) ovarian metastasis is not necessarily associated with worse prognosis than metastasis to other sites. In carefully selected patients with ovarian metastases from CRC, oophorectomy may confer a survival benefit. Specifically, development of ovarian metastasis early in the disease course, resection of the primary tumor, and limited extraovarian metastatic disease are clinical features that are potentially associated with benefit from oophorectomy. A subset of patients with ovarian metastasis from CRC have potential to become long-term survivors (>5 years).

Emerging treatment options for BRAF-mutant colorectal cancer.

The personalization of cancer care is rooted in the premise that there are subsets of patients with tumors harboring clinically relevant targets for patient-specific treatments. Colorectal cancer (CRC) is a disease that has historically been notable for its dearth of biomarkers that are predictive of response to targeted therapies. In recent years, BRAFV600E-mutated CRC has emerged as a distinct biologic entity, typically refractory to standard chemotherapy regimens approved for the treatment of metastatic CRC and associated with a dismal prognosis. Multiple clinical trials sought to replicate the successes of targeted therapies seen in BRAFV600E-mutated melanoma without success; metastatic BRAFV600E-mutated CRC is clearly a distinct biologic entity. We review a number of recent studies demonstrating the evidence of modest responses to combinations of BRAF, EGFR, and/or MEK inhibition in patients with metastatic BRAFV600E-mutated CRC; however, despite advances, overall survival remains far inferior for these patients compared to their BRAF-wild-type counterparts. Development of combination therapies to impede signaling through the MAPK pathway through alternate targets remains an area of active investigation. Reflecting the rapid evolution of efforts for this small subset of CRC patients, the first-ever Phase III study is now underway evaluating the combination of BRAF, EGFR, and MEK inhibition. Immunotherapies are also an area of active research, particularly for the subset of patients with tumors that are also microsatellite instability (MSI) high. Here, we summarize the current landscape and emerging data on the molecular, clinical, and therapeutic aspects of BRAF-mutant CRC.

The Developing Role of Anti-Epidermal Growth Factor Receptor Agents in the Treatment of Advanced or Metastatic Colorectal Cancer.

The first studies of epidermal growth factor receptor (EGFR) inhibitors in metastatic colorectal cancer were begun before the predictive role of RAS mutations had been elucidated. Secondary analyses of many large randomized trials have shown that mutations in exons 2-4 of KRAS and NRAS, BRAF V600E mutation, and right-sided primary tumor all predict lack of response to EGFR inhibition in the first-line setting. However, even in patient populations defined by a lack of these negative predictors, there is still not uniform response to anti-EGFR therapy. Additionally, although older adults have been shown to have the potential to both tolerate and respond to anti-EGFR therapy, the criteria for selecting the most appropriate older patients for treatment remain unclear.

Adjuvant Therapy Trials.

In 2015, ramucirumab and TAS-102 became the 10th and 11th drugs approved by the Food and Drug administration for the treatment of patients with colorectal cancer, not counting leucovorin, and yet only 3 agents, 5-fluorouracil, capecitabine, and oxaliplatin, have proven benefit in adjuvant treatment. In fact, there have been no additions (and 1 subtraction levamisole) to our arsenal of therapies for patients with stages II and III colon cancer for more than a decade. How did we get here? Are we stuck? And how do we move forward?

Adherence to adjuvant endocrine therapy for breast cancer: importance in women with low income.

There are wide disparities in breast cancer-specific survival by patient sociodemographic characteristics. Women of lower income, for instance, have higher relapse and death rates from breast cancer. One possible contributing factor for this disparity is low use of adjuvant endocrine therapy-an extremely efficacious therapy in women with early stage, hormone receptor positive breast cancer, the most common subtype of breast cancer. Alone, adjuvant endocrine therapy decreases breast cancer recurrence by 50% and death by 30%. Data suggest that low use of adjuvant endocrine therapy is a potentially important and modifiable risk factor for poor outcome in low-income breast cancer patients.

Surface water quality along the Central John Muir Trail in the Sierra Nevada Mountains: coliforms and algae.

The John Muir Trail (JMT) in the Sierra Nevada Mountains of California is one of the most popular alpine wilderness trails in the United States, where backpackers depend on trailside water sources for more than 335 km (208 miles). This study addressed the risk of acquiring waterborne disease by analyzing prevalence and changes in coliform bacteria and Escherichia coli (E. coli) in lakes and streams adjacent to the central JMT. Chlorophyll-a levels were also measured as an indicator of high elevation eutrophication. Categories of environmental land use which might affect water quality were defined as: Pristine areas rarely traversed by humans; Backpack off-trail areas not traversed by pack or stock animals; and Multiuse areas with backpacker and animal use. We analyzed surface water at 36 different sites three separate times over an eight week period in the summer of 2008. Chlorophyll-a concentration increased significantly in Backpack and Multiuse sites over the summer months, but not in Pristine sites. Similar results were obtained for coliforms, with prevalence also increasing significantly over the summer months in Backpack and Multiuse sites. There was a much higher prevalence of E. coli in Multiuse sites compared to Pristine and Backpack sites. Our study provides evidence pack and stock animals serve as a source of microbial contamination of water along this section of trail.

Identification of structure-activity relationships for adverse effects of pharmaceuticals in humans. Part A: use of FDA post-market reports to create a database of hepatobiliary and urinary tract toxicities.

The Informatics and Computational Safety Analysis Staff at the US FDA's Center for Drug Evaluation and Research has created a database of pharmaceutical adverse effects (AEs) linked to pharmaceutical chemical structures and estimated population exposures. The database is being used to develop quantitative structure-activity relationship (QSAR) models for the prediction of drug-induced liver and renal injury, as well as to identify relationships among AEs. The post-market observations contained in the database were obtained from FDA's Spontaneous Reporting System (SRS) and the Adverse Event Reporting System (AERS) accessed through Elsevier PharmaPendium software. The database contains approximately 3100 unique pharmaceutical compounds and 9685 AE endpoints. To account for variations in AE reports due to different patient populations and exposures for each drug, a proportional reporting ratio (PRR) was used. The PRR was applied to all AEs to identify chemicals that could be scored as positive in the training datasets of QSAR models. Additionally, toxicologically similar AEs were grouped into clusters based upon both biological effects and statistical correlation. This clustering created a weight of evidence paradigm for the identification of compounds most likely to cause human harm based upon findings in multiple related AE endpoints.

Identification of structure-activity relationships for adverse effects of pharmaceuticals in humans: Part B. Use of (Q)SAR systems for early detection of drug-induced hepatobiliary and urinary tract toxicities.

This report describes the development of quantitative structure-activity relationship (QSAR) models for predicting rare drug-induced liver and urinary tract injury in humans based upon a database of post-marketing adverse effects (AEs) linked to approximately 1600 chemical structures. The models are based upon estimated population exposure using AE proportional reporting ratios. Models were constructed for 5 types of liver injury (liver enzyme disorders, cytotoxic injury, cholestasis and jaundice, bile duct disorders, gall bladder disorders) and 6 types of urinary tract injury (acute renal disorders, nephropathies, bladder disorders, kidney function tests, blood in urine, urolithiases). Identical training data sets were configured for 4 QSAR programs (MC4PC, MDL-QSAR, BioEpisteme, and Predictive Data Miner). Model performance was optimized and was shown to be affected by the AE scoring method and the ratio of the number of active to inactive drugs. The best QSAR models exhibited an overall average 92.4% coverage, 86.5% specificity and 39.3% sensitivity. The 4 QSAR programs were demonstrated to be complementary and enhanced performance was obtained by combining predictions from 2 programs (average 78.4% specificity, 56.2% sensitivity). Consensus predictions resulted in better performance as judged by both internal and external validation experiments.