Immune checkpoint inhibitors: immune-related adverse events, healthcare utilization, and costs among commercial and Medicare Advantage patients.

BACKGROUND: Immune checkpoint inhibitors (ICI) are increasingly used across multiple cancer types and stages and little is known about real-world outcomes. This study sought to determine healthcare utilization, costs, immune-related adverse events (irAEs), and all-cause mortality of single-agent versus combination ICI in the USA. MATERIALS AND METHODS: This is a retrospective study conducted with 2016-2018 data from the HealthCore Integrated Research Database, consisting of commercial and Medicare-insured adult patients with a cancer diagnosis using ICI in the USA. Outcomes were healthcare utilization, costs, and irAEs (FDA-recognized and others) up to 1-year post-index between patients using ICI monotherapy (mono, PD-1/PD-L1 inhibitor) and combination therapy (combo, PD-1/PD-L1 with CTLA-4 inhibitors). RESULTS: In total, 9084 patients received monotherapy and 904 patients received combo therapy. Mean age 65 years for mono and 58 years for combo. Overall, the combo arm had higher rates of FDA-recognized irAEs (67.4% vs. 45.9%), especially endocrinopathies (27.7% vs 14.7%) and dermatitis (25.9% vs. 12.4%). All-cause mortality over 1-year follow-up was similar, 30.7% in mono vs 30.8% in combo arms. The combo group had higher rates of all-cause inpatient hospitalizations (55.4% mono vs 65.6% combo) and emergency department (ED) visits (33.7% mono vs 41.4% combo). IrAE-related hospitalizations were higher in combo (55.2% vs 42.1%). IrAE-related ED visits were 15.7% mono vs 22.7% combo. This increased toxicity and health care utilization was reflected in significant differences in healthcare costs. Stark differences were seen in all-cause medical costs as well as costs related to inpatient and ED utilization and costs attributed to irAEs. CONCLUSIONS: Higher rates of irAEs, healthcare utilization, and costs occur with combination immunotherapy. As further indications are approved for combination ICI, our study highlights the real-world tradeoffs involved with combination therapy regarding burdens of toxicity and increased healthcare utilization.

Association between body mass index and response to duloxetine for aromatase inhibitor-associated musculoskeletal symptoms in SWOG S1202.

BACKGROUND: Aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS) negatively impact adherence to and persistence with therapy. In SWOG S1202, patients with AIMSS who were treated with duloxetine, a serotonin norepinephrine reuptake inhibitor, reported improvement in pain by 12 weeks compared with placebo. Based on the authors' prior observation that responses to pain interventions differ between obese and nonobese patients, the current study examined whether response to duloxetine therapy differed by obesity status. METHODS: In SWOG S1202, a total of 299 AI-treated postmenopausal women with stage I to III (AJCC 7th Edition) breast cancer who developed new or worsening average pain were enrolled, randomized to duloxetine or placebo, and treated for 12 weeks. Patient-reported outcomes were obtained at baseline and through 12 weeks. Patients were categorized into nonobese (body mass index [BMI] <30 kg/m2 ) or obese (BMI ≥30 kg/m2 ). The authors tested the interaction between intervention and obesity with respect to average pain at 12 weeks in the 289 eligible patients, using a P value of .05 to indicate statistical significance. RESULTS: In approximately 54% of evaluable patients with a BMI ≥30 kg/m2 , the reduction in the mean average pain score between baseline and 12 weeks was statistically significantly greater for patients treated with duloxetine compared with those receiving placebo (-2.73 vs -1.64 points; P = .003). Conversely, in the nonobese patients, the reduction in the mean average pain score was similar in the 2 cohorts (-2.46 vs -2.34 points; P = .75). The P value for interaction was .02, thereby meeting the threshold criteria of the current study. Similar findings were evident for other pain-related patient-reported outcomes. CONCLUSIONS: In this trial, obese patients with AIMSS obtained more analgesic benefit from duloxetine compared with nonobese patients. Additional studies are warranted to determine the biologic basis for these findings.

Omega-3 fatty acid use for obese breast cancer patients with aromatase inhibitor-related arthralgia (SWOG S0927).

PURPOSE: Although aromatase inhibitors (AIs) prolong survival in post-menopausal breast cancer (BC) patients, AI-associated arthralgia can lead to discontinuation. Obese patients have higher rates of AI arthralgia than non-obese patients, but treatment options are limited. Omega-3 fatty acid (O3-FA) treatment for AI arthralgia has produced mixed results. METHODS: We performed an exploratory analysis of SWOG S0927, a multicenter randomized placebo-controlled trial of O3-FA use for AI arthralgia. Post-menopausal women with stage I-III BC taking an AI were randomized to 24 weeks of O3-FAs or placebo. Brief Pain Inventory (BPI) questionnaires and fasting serum were collected at baseline, 12, and 24 weeks. The BPI assessment included worst pain, average pain, and pain interference scores (range 0-10). RESULTS: Among the 249 participants, 139 had BMI < 30 kg/m2 (56%) and 110 had BMI ≥ 30 kg/m2 (44%). Among obese patients, O3-FA use was associated with significantly lower BPI worst pain scores at 24 weeks compared with placebo (4.36 vs. 5.70, p = 0.02), whereas among non-obese patients, there was no significant difference in scores between treatment arms (5.27 vs. 4.58, p = 0.28; interaction p = 0.05). Similarly, O3-FA use was associated with lower BPI average pain and pain interference scores at 24 weeks compared with placebo among obese patients, but no significant difference between treatment arms in non-obese patients (interaction p = 0.005 and p = 0.01, respectively). CONCLUSIONS: In obese BC patients, O3-FA use was associated with significantly reduced AI arthralgia compared to placebo.

Real-World Impact of a Decision Support Tool on Colony-Stimulating Factor Use and Chemotherapy-Induced Febrile Neutropenia Among Patients With Breast Cancer.

Background: White blood cell colony-stimulating factors (CSFs) decrease the incidence of chemotherapy-induced febrile neutropenia (FN). Widespread use of CSFs that is not guideline-concordant has been reported. Among patients with breast cancer receiving chemotherapy, the ability of evidence-based decision support tools to promote risk-appropriate reductions in CSF use without increased incidence of FN has not been examined. Methods: A retrospective cohort design and US commercial claims data were used. The impact of CSF decision support was analyzed among women with breast cancer receiving first-cycle chemotherapy from April 1, 2013, to March 30, 2015. The tool was implemented as part of a prior authorization process in 9 states starting July 1, 2014. Patients were assigned to intervention (ie, states where the decision support tool had been implemented) or nonintervention states (ie, 39 states where the tool had not been implemented). CSF use and subsequent incidence of FN were compared using difference-in-difference (DID) regressions adjusting for baseline differences in FN risk factors such as comorbidities and various infections. Results: The study sample of 7,224 patients (intervention states: pre-implementation, 1,991 and post-implementation, 2,010; nonintervention states: pre-implementation, 1,569 and post-implementation, 1,654) showed no significant difference in risk factors. Before and after implementation, a significant decrease in the proportion of patients with CSF use was observed in the intervention states (75% to 69%) compared with no significant change in the nonintervention (72% to 71%) states (DID, -5.4%; 95% CI, -6.0% to -4.7%; P=.006). No significance increase in FN incidence occurred in intervention (5.0% to 5.5%) and nonintervention (5.4% to 4.8%) states (DID, 0.2%; 95% CI, -0.20 to 0.30; P=.78). Similar results were obtained in subgroups by comorbidities and in sensitivity analyses by claims-based FN definitions. Conclusions: CSF use decreased modestly after implementation of the decision support tool, with no observed changes in FN rates. Such tools can reduce practice variation to improve care standards.

Effect of Acupuncture vs Sham Acupuncture or Waitlist Control on Joint Pain Related to Aromatase Inhibitors Among Women With Early-Stage Breast Cancer: A Randomized Clinical Trial.

Importance: Musculoskeletal symptoms are the most common adverse effects of aromatase inhibitors and often result in therapy discontinuation. Small studies suggest that acupuncture may decrease aromatase inhibitor-related joint symptoms. Objective: To determine the effect of acupuncture in reducing aromatase inhibitor-related joint pain. Design, Setting, and Patients: Randomized clinical trial conducted at 11 academic centers and clinical sites in the United States from March 2012 to February 2017 (final date of follow-up, September 5, 2017). Eligible patients were postmenopausal women with early-stage breast cancer who were taking an aromatase inhibitor and scored at least 3 on the Brief Pain Inventory Worst Pain (BPI-WP) item (score range, 0-10; higher scores indicate greater pain). Interventions: Patients were randomized 2:1:1 to the true acupuncture (n = 110), sham acupuncture (n = 59), or waitlist control (n = 57) group. True acupuncture and sham acupuncture protocols consisted of 12 acupuncture sessions over 6 weeks (2 sessions per week), followed by 1 session per week for 6 weeks. The waitlist control group did not receive any intervention. All participants were offered 10 acupuncture sessions to be used between weeks 24 and 52. Main Outcomes and Measures: The primary end point was the 6-week BPI-WP score. Mean 6-week BPI-WP scores were compared by study group using linear regression, adjusted for baseline pain and stratification factors (clinically meaningful difference specified as 2 points). Results: Among 226 randomized patients (mean [SD] age, 60.7 [8.6] years; 88% white; mean [SD] baseline BPI-WP score, 6.6 [1.5]), 206 (91.1%) completed the trial. From baseline to 6 weeks, the mean observed BPI-WP score decreased by 2.05 points (reduced pain) in the true acupuncture group, by 1.07 points in the sham acupuncture group, and by 0.99 points in the waitlist control group. The adjusted difference for true acupuncture vs sham acupuncture was 0.92 points (95% CI, 0.20-1.65; P = .01) and for true acupuncture vs waitlist control was 0.96 points (95% CI, 0.24-1.67; P = .01). Patients in the true acupuncture group experienced more grade 1 bruising compared with patients in the sham acupuncture group (47% vs 25%; P = .01). Conclusions and Relevance: Among postmenopausal women with early-stage breast cancer and aromatase inhibitor-related arthralgias, true acupuncture compared with sham acupuncture or with waitlist control resulted in a statistically significant reduction in joint pain at 6 weeks, although the observed improvement was of uncertain clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT01535066.

Association between patients' perception of the comorbidity burden and symptoms in outpatients with common solid tumors.

BACKGROUND: Cancer patients' symptom burden is commonly attributed to their cancer and treatment. Increasingly, cancer patients have many other chronic comorbid conditions. However, the degree to which these comorbid conditions may contribute to the patient-reported symptom burden is unclear. METHODS: This study explored the relations between the presence of comorbid conditions, the symptom experience and burden, and the perceived bother from cancer or comorbid conditions in 3106 cancer patients. The associations between the number of comorbidities (identified from current medications), the patient-reported symptom burden (the number of symptoms scored as ≥7 on the 13-item MD Anderson Symptom Inventory physical scale), the patient-reported bother from comorbid conditions and from cancer (from "not at all" to "extremely"), and the clinician-reported difficulty in caring for patients' symptoms were examined. RESULTS: According to medication lists, 19% of the patients had at least 5 of 12 comorbid conditions. Approximately 39% rated at least 1 symptom as ≥ 7, and this proportion increased with an increasing number of comorbid conditions (48% with ≥ 5 comorbid conditions vs 36% with 1 comorbid condition). One-third of the patients reported moderate or worse bother, and this was significantly associated with an increased number of comorbid conditions (odds ratio [OR], 2.4) and an increased symptom burden (OR, 1.22). Clinician ratings of difficulty in managing patients' symptoms were significantly associated with bother from cancer (OR, 2.0), comorbid conditions (OR, 1.6), and symptom burden (OR, 1.1). CONCLUSIONS: Comorbidity is common in cancer patients and is associated with a greater symptom burden and clinician reports of difficulty in managing patients' symptoms. Greater attention to comorbid conditions is needed to optimize the symptom management of cancer patients with multimorbidity. Cancer 2017;123:3835-3842. © 2017 American Cancer Society.

Impact of the timing of hepatitis B virus identification and anti-hepatitis B virus therapy initiation on the risk of adverse liver outcomes for patients receiving cancer therapy.

BACKGROUND: Data on the incidence of adverse liver outcomes are limited for cancer patients with chronic (hepatitis B surface antigen [HBsAg]-positive/hepatitis B core antibody [anti-HBc]-positive) or past (HBsAg-negative/anti-HBc-positive) hepatitis B virus (HBV) after chemotherapy. This study was aimed at determining the impact of test timing and anti-HBV therapy on adverse liver outcomes in these patients. METHODS: Patients with solid or hematologic malignancies who received chemotherapy between 2004 and 2011 were retrospectively studied. HBV testing and anti-HBV therapy were defined as early at the initiation of cancer therapy and as late after initiation. Outcomes included hepatitis flares, hepatic impairment, liver failure, and death. Time-to-event analysis was used to determine incidence, and multivariate hazard models were used to determine predictors of outcomes. RESULTS: There were 18,688 study patients (80.4% with solid tumors). The prevalence of chronic HBV was 1.1% (52 of 4905), and the prevalence of past HBV was 7.1% (350 of 4905). Among patients with solid tumors, late identification of chronic HBV was associated with a higher risk of hepatitis flare (hazard ratio [HR], 4.02; 95% confidence interval [CI], 1.26-12.86), hepatic impairment (HR, 8.48; 95% CI, 1.86-38.66), liver failure (HR, 9.38; 95% CI, 1.50-58.86), and death (HR, 3.90; 95% CI, 1.19-12.83) in comparison with early identification. Among patients with hematologic malignancies and chronic HBV, the risk of death was 7.8 (95% CI, 1.73-35.27) times higher for persons with late initiation of anti-HBV therapy versus early initiation. Patients with late identification of chronic HBV had late or no anti-HBV therapy. Chronic HBV predicted liver failure in patients with solid or hematologic malignancies, whereas male sex and late identification were predictors for patients with solid tumors. CONCLUSIONS: Early identification correlates with early anti-HBV therapy and reduces the risk of liver failure and death in chronic HBV patients receiving chemotherapy. Cancer 2017;123:3367-76. © 2017 American Cancer Society.

Genome-wide association and pathway analysis of left ventricular function after anthracycline exposure in adults.

BACKGROUND: Anthracyclines are important chemotherapeutic agents, but their use is limited by cardiotoxicity. Candidate gene and genome-wide studies have identified putative risk loci for overt cardiotoxicity and heart failure, but there has been no comprehensive assessment of genomic variation influencing the intermediate phenotype of anthracycline-related changes in left ventricular (LV) function. The purpose of this study was to identify genetic factors influencing changes in LV function after anthracycline chemotherapy. METHODS: We conducted a genome-wide association study (GWAS) of change in LV function after anthracycline exposure in 385 patients identified from BioVU, a resource linking DNA samples to de-identified electronic medical record data. Variants with P values less than 1×10 were independently tested for replication in a cohort of 181 anthracycline-exposed patients from a prospective clinical trial. Pathway analysis was performed to assess combined effects of multiple genetic variants. RESULTS: Both cohorts were middle-aged adults of predominantly European descent. Among 11 candidate loci identified in discovery GWAS, one single nucleotide polymorphism near PR domain containing 2, with ZNF domain (PRDM2), rs7542939, had a combined P value of 6.5×10 in meta-analysis. Eighteen Kyoto Encyclopedia of Gene and Genomes pathways showed strong enrichment for variants associated with the primary outcome. Identified pathways related to DNA repair, cellular metabolism, and cardiac remodeling. CONCLUSION: Using genome-wide association we identified a novel candidate susceptibility locus near PRDM2. Variation in genes belonging to pathways related to DNA repair, metabolism, and cardiac remodeling may influence changes in LV function after anthracycline exposure.

Nurse and patient characteristics predict communication about complementary and alternative medicine.

BACKGROUND: The aim of this study was to identify nurse factors (eg, knowledge, practices, and clinical habits regarding complementary and alternative medicine [CAM] as well as demographic factors) and patient characteristics (eg, age, sex, and treatment status) associated with nurses' CAM inquiry and referral patterns. METHODS: Baseline data were collected with nurse/patient questionnaires about CAM use and knowledge as part of a multicenter CAM educational clinical trial. Frequencies and nested regression models were used to assess predictors of nurses' inquiries about and referral to CAM therapies. RESULTS: Six hundred ninety-nine patients participated in the study. For patients, female sex (odds ratio [OR], 1.50; P = .019) and cancer recurrence (OR, 1.45; P = .05) were predictive of nurses' inquiries about and referral to CAM therapies. A total of 175 nurses with a mean age of 45 years and a mean experience of 20 years participated; 79% were staff nurses, and 11% were nurse practitioners. Fifty-three percent asked at least 1 of their last 5 patients about CAM use; 42% referred patients to CAM therapy. Nurses who reported being "somewhat comfortable" (OR, 2.70; P = .0001) or "very comfortable" (OR, 3.88; P < .0001) about discussing CAM, self-reported use of massage (OR, 2.20; P < .0001), and had formal CAM education (OR, 4.14; P = .0001) were more likely to ask about CAM use. Nurses who reported being "somewhat comfortable" (OR, 2.54; 95% confidence interval, 1.47-4.41; P = .0008) or "very comfortable" (OR, 7.46; P < .00001) and had formal CAM education (OR, 2.96; P < .0001) were also more likely to refer patients to CAM therapies. CONCLUSIONS: Both patient and nurse characteristics were associated with discussions about CAM. Oncology institutions that prioritize evidence-based medicine should consider introducing CAM education to their nursing staff. Cancer 2016;122:1552-9. © 2016 American Cancer Society.

Working after a metastatic cancer diagnosis: Factors affecting employment in the metastatic setting from ECOG-ACRIN's Symptom Outcomes and Practice Patterns study.

BACKGROUND: Improved survival for individuals with metastatic cancer accentuates the importance of employment for cancer survivors. A better understanding of how metastatic cancer affects employment is a necessary step toward the development of tools for assisting survivors in this important realm. METHODS: The ECOG-ACRIN Symptom Outcomes and Practice Patterns study was analyzed to investigate what factors were associated with the employment of 680 metastatic cancer patients. Univariate and multivariate logistic regression analyses were conducted to compare patients stably working with patients no longer working. RESULTS: There were 668 metastatic working-age participants in the analysis: 236 (35%) worked full- or part-time, whereas 302 (45%) had stopped working because of illness. Overall, 58% reported some change in employment due to illness. A better performance status and non-Hispanic white ethnicity/race were significantly associated with continuing to work despite a metastatic cancer diagnosis in the multivariate analysis. The disease type, time since metastatic diagnosis, number of metastatic sites, location of metastatic disease, and treatment status had no significant impact. Among the potentially modifiable factors, receiving hormonal treatment (if a viable option) and decreasing symptom interference were associated with continuing to work. CONCLUSIONS: A significant percentage of the metastatic patients remained employed; increased symptom burden was associated with a change to no longer working. Modifiable factors resulting in work interference should be minimized so that patients with metastatic disease may continue working if this is desired. Improvements in symptom control and strategies developed to help address workplace difficulties have promise for improving this aspect of survivorship.

The Utility of Point-of-Care Biomarkers to Detect Cardiotoxicity During Anthracycline Chemotherapy: A Feasibility Study.

BACKGROUND: Anthracycline chemotherapy is associated with an increased risk of developing heart failure (HF). The current standard for detecting HF or cardiotoxicity during chemotherapy involves episodic cardiac imaging typically at prescribed intervals and there are limited studies examining techniques beyond measuring left ventricular (LV) function. This study explores whether cardiac biomarkers troponin I (TnI) and B-type natriuretic peptide (BNP) could be part of a screening strategy for early detection of the development of cardiotoxicity in patients undergoing anthracycline chemotherapy. METHODS AND RESULTS: Patients were enrolled from a single medical center. Cardiac biomarkers (TnI, BNP) were measured before and within 24 hours after completion of anthracycline administration for each cycle of therapy. Cardiac imaging was obtained at baseline and at completion of chemotherapy (commonly at 6 or 12 months) or based on clinical suspicion of a cardiac event. Of the enrolled 109 patients, 11 (10.1%) experienced cardiac events; all of these patients had at least 1 BNP value >100 pg/mL before the cardiac event. Significant reduction in LV ejection fraction as defined for cardiotoxicity occurred in only 3 of 10 patients (30%) with a cardiac event. CONCLUSIONS: The use of cardiac biomarkers, particularly BNP, may allow early detection of cardiotoxicity related to anthracycline chemotherapy.

Advanced cancer patients' reported wishes at the end of life: a randomized controlled trial.

CONTEXT: Conversations about end-of-life (EOL) wishes are challenging for many clinicians. The Go Wish card game (GWG) was developed to facilitate these conversations. Little is known about the type and consistency of EOL wishes using the GWG in advanced cancer patients. METHODS: We conducted a randomized controlled trial to assess the EOL wishes of 100 patients with advanced cancer treated at The University of Texas MD Anderson Cancer Center. The purpose of this study was to determine the EOL wishes of patients with advanced cancer and to compare patients' preference between the GWG and List of wishes/statements (LOS) containing the same number of items. Patients were randomized into four groups and completed either the GWG or a checklist of 35 LOS and one opened statement found on the GWG cards; patients were asked to categorize these wishes as very, somewhat, or not important. After 4-24 h, the patients were asked to complete the same or other test. Group A (n = 25) received LOS-LOS, group B (n = 25) received GWG-GWG, group C (n = 26) received GWG-LOS, and group D (n = 24) received LOS-GWG. All patients completed the State-Trait Anxiety Inventory (STAI) for adults before and after the first test. RESULTS: Median age (interquartile range = IQR): 56 (27-83) years. Age, sex, ethnicity, marital status, religion, education, and cancer diagnosis did not differ significantly among the four groups. All patients were able to complete the GWG and/or LOS. The ten most common wishes identified as very important by patients in the first and second test were to be at peace with God (74 vs. 71 %); to pray (62 vs. 61 %); and to have family present (57 vs. 61 %). to be free from pain (54 vs. 60 %); not being a burden to my family (48 vs. 49 %); to trust my doctor (44 vs. 45 %); to keep my sense of humor (41 vs. 45 %); to say goodbye to important people in my life (41 vs. 37 %); to have my family prepared for my death (40 vs. 49 %); and to be able to help others (36 vs. 31 %). There was significant association among the frequency of responses of the study groups. Of the 50 patients exposed to both tests, 43 (86 %) agreed that the GWG instructions were clear, 45 (90 %) agreed that the GWG was easy to understand, 31 (62 %) preferred the GWG, 39 (78 %) agreed that the GWG did not increase their anxiety and 31 (62 %) agreed that having conversations about EOL priorities was beneficial. The median STAI score after GWG was 48 (interquartile range, 39-59) vs. 47 (interquartile range, 27-63) after LOS (p = 0.2952). CONCLUSION: Patients with advanced cancer assigned high importance to spirituality and the presence/relationships of family, and these wishes were consistent over the two tests. The GWG did not worsen anxiety.

Automated pain intervention for underserved minority women with breast cancer.

BACKGROUND: Minority patients with breast cancer are at risk for undertreatment of cancer-related pain. The authors evaluated the feasibility and efficacy of an automated pain intervention for improving pain and symptom management of underserved African American and Latina women with breast cancer. METHODS: Sixty low-income African American and Latina women with breast cancer and cancer-related pain were enrolled in a pilot study of an automated, telephone-based, interactive voice response (IVR) intervention. Women in the intervention group were called twice weekly by the IVR system and asked to rate the intensity of their pain and other symptoms. The patients' oncologists received e-mail alerts if the reported symptoms were moderate to severe. The patients also reported barriers to pain management and received education regarding any reported obstacles. RESULTS: The proportion of women in both groups reporting moderate to severe pain decreased during the study, but the decrease was significantly greater for the intervention group. The IVR intervention also was associated with improvements in other cancer-related symptoms, including sleep disturbance and drowsiness. Although patient adherence to the IVR call schedule was good, the oncologists who were treating the patients rated the intervention as only somewhat useful for improving symptom management. CONCLUSIONS: The IVR intervention reduced pain and symptom severity for underserved minority women with breast cancer. Additional research on technological approaches to symptom management is needed.

Randomized phase 2 study of bone-targeted therapy containing strontium-89 in advanced castrate-sensitive prostate cancer.

BACKGROUND: Radiopharmaceutical use may improve the survival time of patients with castrate-resistant prostate cancer and bone metastases. Whether androgen-deprivation therapy (ADT) combined with bone-targeted therapy provides a clinical benefit to patients with advanced castrate-sensitive prostate cancer has not been investigated. METHODS: Eighty male patients were enrolled, and 79 were randomized: 40 to the control arm and 39 to the strontium-89 (Sr-89) arm. After randomization, patients in both study arms received ADT, doxorubicin, and zoledronic acid. Kaplan-Meier methodology was used to evaluate the progression-free survival (PFS) time. Multivariate Cox proportional hazards regression was used to evaluate the effects of Sr-89 after controlling for the number of bone metastases. RESULTS: The median follow-up time for the 29 patients alive at the last follow-up was 76.9 months (range, 0.07-103.4 months). The median PFS time was 18.5 months (95% confidence interval, 9.7-49.4 months) for the control arm and 12.9 months (95% confidence interval, 8.9-72.5 months) for the Sr-89 arm (P = .86). No patient developed myelodysplastic syndrome or a hematologic malignancy. An unplanned subgroup analysis suggested increased efficacy of bone-targeted therapy with a greater extent of bone involvement (ie, >6 bone metastases vs ≤6 bone metastases on the bone scan). CONCLUSIONS: The data showed that bone-targeted therapy using 1 dose of Sr-89 combined with chemohormonal ablation therapy did not favorably affect the PFS of patients with castrate-sensitive prostate cancer. The combined therapy was feasible and safe. Whether such bone-targeted therapy provides a favorable outcome for those patients with a greater tumor burden in the bone warrants further investigation.

Patterns and predictors of antidepressant use in ambulatory cancer patients with common solid tumors.

PURPOSE: Depressive symptoms and antidepressant use are prevalent among cancer patients. We sought to identify determinants of prescribing commonly used antidepressants. PATIENTS AND METHODS: This multi-institutional study enrolled 3106 ambulatory patients with cancer of the breast, prostate, colon/rectum, or lung. Five case-finding methods were used to identify patients with depressive symptoms. Logistic models were used to examine factors that impact antidepressant use. RESULTS: Approximately, 47% of patients were defined as having depressive symptoms. Clinicians rated being sad/depressed as one of the top three priority problems for 10.5% of patients. Antidepressants were prescribed in 19% of all patients, 25% with depressive symptoms and 14% nondepressed patients. After adjusting for other covariates, these variable categories were significantly associated with greater use of antidepressants: depressive symptoms, family history of depression, concurrent medication use, cancer treatment status, and certain other clinical and demographic variables. The strongest individual predictors were concurrent use of more than 10 medications (odds ratio [OR] = 3.3), a family history of depression (OR = 2.2), sedative use (OR = 2.1), non-Hispanic white race (OR = 2.0), and anxiolytics use (OR = 2.0). CONCLUSIONS: Depressive symptoms are found in nearly half of outpatients with cancer, and one-fourth of patients with depressive symptoms are taking an antidepressant. Patients receiving antidepressants are more often those taking multiple medications, those with a depression diathesis, and those with more extensive cancer treatment. Patients who were younger, white, and female were also more likely to be taking antidepressants.

A phase II, randomized, double blind trial of calcium aluminosilicate clay versus placebo for the prevention of diarrhea in patients with metastatic colorectal cancer treated with irinotecan.

PURPOSE: Calcium aluminosilicate clay (CASAD) is a naturally occurring clay that serves as a cation exchange absorbent. We hypothesized that oral administration of CASAD would reduce the rate of grade 3/4 diarrhea associated with irinotecan use for metastatic colorectal cancer (CRC) by adsorbing the SN-38 metabolite. METHODS: Patients receiving irinotecan-based chemotherapy were randomized equally between CASAD and placebo arms in this multicenter trial in order to assess differences in the proportions of patients with grade 3/4 diarrhea within 6 weeks. Additionally, we compared symptom severity between the two arms using the M.D. Anderson Symptom Inventory. RESULTS: Between May 2009 and May 2012, 100 patients were enrolled. In evaluable patients, 7 of 43 (16 %) on the CASAD arm compared to 3 of 32 (9 %) on the placebo arm experienced grade 3/4 diarrhea (P = 0.70). The rate of any diarrhea among all patients was similar (CASAD arm, 64 % vs. placebo arm, 70 %). The rate of study dropout was 14 % in the CASAD arm and 38 % in the placebo arm (P = 0.01). No differences were found in symptom severity, individual symptom items, and in serious adverse events between the two arms. CONCLUSION: Compared to placebo, CASAD use was safe but ineffective in preventing diarrhea in metastatic CRC patients treated with irinotecan-containing chemotherapy regimens. There were no distinct signals in terms of patient symptoms between arms, but there was significantly more patient dropout in the placebo arm. Future CASAD trials will focus on the active treatment of diarrhea.

Predictors of significant worsening of patient-reported fatigue over a 1-month timeframe in ambulatory patients with common solid tumors.

BACKGROUND: Understanding the determinants of fatigue worsening may help distinguish between different fatigue phenotypes and inform clinical trial designs. METHODS: Patients with invasive cancer of the breast, prostate, colon/rectum, or lung were enrolled from multiple sites. At enrollment during an outpatient visit and 4 or 5 weeks later, patients rated their symptoms on a numerical rating scale from zero to 10. A 2-point change on that scale was considered clinically significant for a change in fatigue. Effects of demographic and clinical factors on patient-reported fatigue were examined using logistic regression models. RESULTS: In total, 3123 patients were enrolled at baseline, and 3032 patients could be analyzed for fatigue change. At baseline, 23% of patients had no fatigue, 35% had mild fatigue, 25% had moderate fatigue, and 17% had severe fatigue. Key parameters in a model of fatigue worsening included fatigue at baseline (odds ratio [OR], 0.75), disease status (OR, 1.99), performance status (OR, 1.38), history of depression (OR, 1.28), patient perception of bother because of comorbidity (OR, 1.26), and treatment exposures, including recent cancer treatment (OR, 1.77) and receipt of corticosteroids (OR, 1.37). The impact of sex was examined only in patients with colorectal and lung cancer, and it was a significant factor, with men most likely to experience worsening of fatigue (OR, 1.46). CONCLUSIONS: Predictors of fatigue worsening included multiple factors that were difficult to modify, including the baseline fatigue level, sex, disease status, performance status, recent cancer treatment, bother because of comorbidity, and history of depression. Future fatigue prevention and treatment trial designs should account for key predictors of worsening fatigue.

Symptom burden among young adults with breast or colorectal cancer.

BACKGROUND: Cancer incidence has increased among young adults (YAs) and survival rates have not improved compared with other age groups. Patient-reported outcomes may enhance our understanding of this vulnerable population. METHODS: In a multisite prospective study, patients completed a cancer symptom inventory at the time of enrollment (T1) and 4 weeks to 5 weeks later (T2). YAs (those aged ≤ 39 years) with breast or colorectal cancer were compared with older adults (those aged ≥ 40 years) with breast or colorectal cancer with regard to symptom severity, symptom interference, changes over time, and medical care. RESULTS: Participants included 1544 patients with breast cancer (96 of whom were YAs) and 718 patients with colorectal cancer (37 of whom were YAs). Compared with older adults, YAs with breast cancer were more likely to report moderate/severe drowsiness, hair loss, and symptom interference with relationships at T1. YAs with colorectal cancer were more likely to report moderate/severe pain, fatigue, nausea, distress, drowsiness, shortness of breath, and rash plus interference in general activity, mood, work, relationships, and life enjoyment compared with older adults. Compared with older adults, shortness of breath, appetite, and sore mouth were more likely to improve in YAs with breast cancer; vomiting was less likely to improve in YAs with colorectal cancer. Referrals for supportive care were few, especially among patients with colorectal cancer. YAs with breast cancer were somewhat more likely to be referred to nutrition and psychiatry services than older patients. CONCLUSIONS: YAs reported symptom severity, symptom interference, and variations over time that were distinct from older patients. Distinctions were found to differ by diagnostic group. These findings enhance the understanding of symptom burden in YAs and inform the development of targeted interventions and future research.

Prevalence and characteristics of moderate to severe fatigue: a multicenter study in cancer patients and survivors.

BACKGROUND: The effective management of fatigue in patients with cancer requires a clear delineation of what constitutes nontrivial fatigue. The authors defined numeric cutpoints for fatigue severity based on functional interference and described the prevalence and characteristics of fatigue in patients with cancer and survivors. METHODS: In a multicenter study, outpatients with breast, prostate, colorectal, or lung cancer rated their fatigue severity and symptom interference with functioning on the M. D. Anderson Symptom Inventory numeric scale of 0 to 10. Ratings of symptom interference guided the selection of numeric rating cutpoints between mild, moderate, and severe fatigue levels. Regression analysis identified significant factors related to reporting moderate=severe fatigue . RESULTS: The statistically optimal cutpoints were 4 for moderate fatigue and 7 for severe fatigue. Moderate=severe fatigue was reported by 983 of 2177 patients (45%) undergoing active treatment and was more likely to occur in patients receiving treatment with strong opioids (odds ratio [OR], 3.00), those with a poor Eastern Cooperative Oncology Group performance status (OR, 2.00), those who had >5% weight loss within 6 months (OR, 1.60), those who were receiving >10 medications (OR, 1.58), those with lung cancer (OR, 1.55), and those with a history of depression (OR, 1.42). Among survivors (patients with complete remission or no evidence of disease, and not currently receiving cancer treatment), 29% of patients (150 of 515 patients) had moderate=severe fatigue that was associated with poor performance status (OR, 3.48) and a history of depression (OR, 2.21). CONCLUSIONS: The current study statistically defined fatigue severity categories related to significantly increased symptom interference. The high prevalence of moderate=severe fatigue in both actively treated patients with cancer and survivors warrants the promoting of the routine assessment and management of patient-reported fatigue.

Patient-oncologist alliance as protection against suicidal ideation in young adults with advanced cancer.

BACKGROUND: Young adults with cancer are at an increased risk of suicidal ideation. To the authors' knowledge, the impact of the patient-oncologist alliance on suicidal ideation has not been examined to date. The current study examined the relationship between the patient-oncologist therapeutic alliance and suicidal ideation in young adults with advanced cancer. METHODS: A total of 93 young adult patients (aged 20 years-40 years) with incurable, recurrent, or metastatic cancer were evaluated by trained interviewers. Suicidal ideation was assessed with the Yale Evaluation of Suicidality scale, dichotomized into a positive and negative score. Predictors included diagnoses of major depressive disorder and posttraumatic stress disorder, physical quality of life, social support, and use of mental health and supportive care services. The Human Connection Scale, dichotomized into a strong (upper third) and weak (lower two-thirds) therapeutic alliance, assessed the strength of the patients' perceived oncologist alliance. RESULTS: Approximately 22.6% of patients screened positive for suicidal ideation. Patients with a strong therapeutic alliance were found to be at reduced risk of suicidal ideation after controlling for confounding influences of cancer diagnosis, Karnofsky performance status, number of physical symptoms, physical quality of life, major depressive disorder, posttraumatic stress disorder, and social support. A strong therapeutic alliance was also associated with a reduced risk of suicidal ideation after controlling for mental health discussions with health care providers and use of mental health interventions. CONCLUSIONS: The patient-oncologist alliance was found to be a robust predictor of suicidal ideation and provided better protection against suicidal ideation than mental health interventions, including psychotropic medications. Oncologists may significantly influence patients' mental health and may benefit from training and guidance in building strong alliances with their young adult patients.