Abstract PO1-11-10: Use of a standardized tool for the evaluation and treatment of cancer related cognitive impairment (chemo-brain) among breast cancer patients

BackgroundInflammatory signaling is linked with cancer-related cognitive impairment (CRCI), potentially through modulation of brain-derived neurotrophic factor (BDNF) expression. Here, we evaluate associations between plasma cytokines and BDNF and their relationship with cognition in a longitudinal study of adolescent and young adult cancer patients (AYAC) receiving chemotherapy and non-cancer controls (NC) (Clinicaltrials.gov: NCT03476070).MethodsNewly diagnosed AYAC (15–39 years old) and age-matched NC completed the Functional Assessment of Cancer Therapy-Cognitive Function questionnaire (FACT‐Cog), the Cambridge Neuropsychological Test Automated Battery (CANTAB), and blood draws every 3–6 months up to 12 months (AYAC) or 6 months (NC) from baseline. Plasma levels of cytokines and BDNF were quantified using a multiplexed immunoassay and ELISA, respectively. Biomarker-cognition and cytokine-BDNF associations were analyzed using mixed-effects models with interactions for chemotherapy status for AYAC (during chemotherapy vs. > 30 days post-chemotherapy).ResultsOne-hundred and seventy-seven participants were included, with 66 AYAC and 111 NC. AYAC had a higher frequency of clinically significant cognitive impairment during and post-chemotherapy compared to NC. In trends unique to AYAC, higher IL-10 was associated with better self-perceived cognition, IL-8 with better multi-tasking, IL-6 with worse multi-tasking, response speed, and attention, and TNF-α with better memory (p < 0.05). Higher BDNF was associated with better memory and response speed (p < 0.05). IL-4, IL-10, TNF-α, and IFN-γ were associated with BDNF levels among AYAC and NC (p < 0.05).ConclusionsOur large, age-matched study implicates dysregulated cytokine signaling and altered BDNF expression in CRCI among AYAC during and post-chemotherapy. As precision medicine becomes integrated into AYA patient care, plasma BDNF and cytokines may serve as important predictors of CRCI onset.Trial registrationThe study was prospectively registered on ClinicalTrials.gov (NCT03476070) on March 3, 2018.

Background: Granulocyte Colony Stimulating Factors (GCSF) is high-cost agents commonly recommended for primary and secondary prophylaxis of chemotherapy-induced neutropenia and febrile neutropenia. GCSFs have been shown to be beneficial in some patient subgroups, although they are probably overused in clinical settings. The American Society of Clinical Oncology (ASCO) guidelines summarize current data on the appropriate use of CSFs. The aim of this study was to assess and audit the use of GCSF in a tertiary care center according to the recommendation of ASCO guideline.Subjects and Methods: A prospective observational study from November 2014 to June 2015 was performed on all patients prescribed with filgrastim in the large teaching hospital (Isfahan, Iran). Data was collected on demographics, indication, dosing regimen and duration of treatment, the Absolute Neutrophil Count (ANC) and patient outcome.Results: 91 patients were recorded over the period of the study. 63.7% of prescription complied with the ASCO guideline. Febrile neutropenia post chemotherapy/radiotherapy was the most common appropriate indication (29.3%) followed by primary prophylaxis (25.8%). Fourteen (32%) patients showed ANC recovery in 1-3 days and 16 (37%) within 4-7 days. Ten patients (23%) showed no recovery. The overall mortality was 8 (8.8%) patients.Conclusion: This study revealed that at least one-third of prescribed GCSF was not in accordance with ASCO guideline. Considering the high cost of GCSF in our country and limitation of our resources, we proposed cost-effectiveness studies on GCSF treatment and also the development of a national guideline for optimizing GCSF use.

Cancer-related cognitive impairment (CRCI) is a mild but meaningful decline in cognitive function among cancer patients, affecting domains such as memory, attention, and executive functions. Emerging evidence suggests that physical exercise is a promising non-pharmacological strategy to mitigate these symptoms. Although several systematic reviews and meta-analyses have examined this topic, no umbrella review has yet synthesized the full body of evidence. This umbrella review aims to integrate findings on the effects of exercise on different cognitive domains in cancer populations, considering both self-reported and objective outcomes. The review will follow PRIOR guidelines and apply a PRISMA-based search strategy across four databases (MEDLINE/PubMed, Scopus, Web of Science, and SPORTDiscus). Eligibility criteria will follow the PICOS framework, including systematic reviews with or without meta-analyses evaluating exercise interventions and their impact on cognitive outcomes in individuals with cancer. Data on intervention characteristics, cognitive domains, and effect sizes will be extracted, and methodological quality will be assessed using GRADE and AMSTAR-2. This review will offer a comprehensive synthesis of current evidence on exercise and CRCI, helping identify the most responsive cognitive domains, effective exercise modalities, and key methodological gaps to inform future research and evidence-based recommendations for cancer survivors’ cognitive health.

Dissemination of use of the hematopoietic colony-stimulating factors (CSFs) is unprecedented in oncology, with almost all physicians having experience with granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) shortly after the drugs received Food and Drug Administration (FDA) approval in 1991. The American Society of Clinical Oncology (ASCO) Health Services Research Committee sought to assess patterns of use of CSFs before dissemination of its first-ever publication of ASCO guidelines. A questionnaire describing clinical scenarios was mailed to American oncologists and hematologists who practice medical oncology. In each scenario, the physician was asked whether he would prefer to use a CSF to prevent or treat neutropenia. The response rate to the mailed survey was 49% (N = 475). Most physicians preferred to use CSFs for secondary prophylaxis in patients receiving chemotherapy at rates of 44% to 85%, rather than reduce doses. Patterns of use did not differ for palliative, curative, or adjuvant chemotherapy. While the majority of CSF patterns of care were similar to those recommended in the ASCO guidelines, more than half of the physicians chose to use CSFs in the treatment of febrile neutropenia, an area not supported in the subsequent guidelines. In general, physicians at academic medical centers and in Health Maintenance Organization (HMO) practices were more likely to prefer dose-reduction strategies over addition of CSFs, while fee-for-service physicians preferred the opposite strategies. Variations in CSF preferences for use were related to differences in clinical characteristics (history of afebrile v febrile neutropenia), drug characteristics (G-CSF or GM-CSF), and physician practice characteristics (HMO or fee-for-service setting). However, before dissemination of the guidelines, the majority of American oncologists preferred strategies that were subsequently included in the ASCO CSF guidelines. CSF guidelines would be most likely to reduce CSF use for treatment of afebrile and uncomplicated febrile neutropenia.

To assess whether physicians comply with American Society of Clinical Oncology (ASCO) guidelines for the use of CSFs, a prospective survey was performed in 15 Paris university hospitals involved in cancer treatment in 1997. If 45% of the prescriptions complied with the guidelines, primary prophylactic administration, which represented 52% of cases, did not comply with ASCO guidelines. These results suggested that primary prophylactic administration was one major clinical situation in which physicians could benefit from guidance to use a CSFs and that criteria defined by ASCO to allow primary prophylactic administration were not applied in clinical practice.

In 2012, guidelines from the American Society of Clinical Oncology (ASCO) summarized the literature on chemotherapy dosing based upon actual body weight versus ideal or adjusted body weight (Griggs et al, 2012). The conclusion, largely drawn from studies of solid tumor patients, was that chemotherapy administration based upon actual body weight did not increase short-term toxicities. This resulted in the recommendation against the use of empiric dose-reduction solely due to obesity status (Griggs et al, 2012). To better understand if this recommendation could be applied to patients with diffuse large B-cell lymphoma (DLBCL), we examined the associations between body mass index (BMI) and relative dose-intensity with the outcomes of febrile neutropenia and treatment-related mortality in a large cohort of DLBCL patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). We identified a retrospective cohort of patients with DLBCL within the United States Veterans Health Administration (VHA) using previously published methods and inclusion and exclusion criteria (Carson et al, 2012). Details of chemotherapy, radiotherapy, supportive care medications and hospitalizations were determined through chart abstraction. Weight and height measurements within 1 month of treatment initiation were used to calculate BMI and body surface area (BSA). Patients were categorized as underweight, normal-weight, overweight or obese in accordance with the World Health Organization (WHO) classification (WHO Expert Committee, 1995). The Romano comorbidity index was calculated using International Classification of Disease (ICD)-9 codes (Romano et al, 1993). Average relative dose-intensity was calculated utilizing methods previously published (Lyman et al, 2004). The expected number of chemotherapy cycles was 3 in stage I/II patients receiving radiotherapy and 6 in all other patients. Chemotherapy doses <85% of expected in the first cycle were considered ‘dose-reduced’. Febrile neutropenia was determined by chart abstraction, and was considered present based upon review of electronic medical records. Treatment-related mortality was defined as death within 30 d of last chemotherapy administration. Logistic regression evaluated variables associated with treatment-related mortality in the overall cohort and then among those without first cycle dose-reductions. Missing data on lactate dehydrogenase (LDH) level, stage, and B-symptoms were handled through use of multiple imputation (Sterne et al, 2009). All statistical analyses were performed using sas version 9.2 (SAS Institute, Cary, NC, USA). All P-values reported are 2-tailed and P-values <0·05 were considered significant. We identified a total cohort of 1241 DLBCL patients who received R-CHOP within the VHA system. Univariate comparisons stratified by BMI are presented in Table 1. There were no significant differences in the average relative dose-intensities or levels of granulocyte colony-stimulating factor (G-CSF) support among the BMI groups. Obese patients were not significantly more likely to undergo first cycle dose-reduction. The incidence of febrile neutropenia and treatment-related mortality among the three groups differed significantly, with obese patients experiencing less of both. Across all treatment cycles, obese patients were significantly less likely to experience febrile neutropenia (obese: 17·8%, overweight: 23·0%, normal-weight: 28·9%, age-adjusted P < 0·001). Obese patients were also significantly less likely to experience treatment-related mortality (obese: 5·5%, overweight: 8·1%, normal-weight: 11·3%, age-adjusted P = 0·017). In multivariate logistic regression controlling for age, stage, LDH level at diagnosis, B-symptoms, comorbidity score and G-CSF use, obesity was associated with decreased treatment-related mortality compared to normal-weight patients [Odds ratio (OR) 0·50; 95% confidence interval (CI) 0·28–0·90]. Overweight patients demonstrated a non-significant trend towards reduced treatment-related mortality (OR 0·73; 95% CI 0·46–1·14). Among patients without first cycle dose-reductions, obesity was still associated with decreased treatment-related mortality (OR 0·46; 95% CI 0·24–0·90), and overweight patients demonstrated a non-significant trend towards reduced treatment-related mortality (OR 0·69; 95% CI 0·42–1·14; Table 2). Consistent with the ASCO guidelines (Griggs et al, 2012), we found no evidence that treatment of overweight and obese DLBCL patients with actual body weight chemotherapy doses increased the incidence of febrile neutropenia or treatment-related mortality. In fact, we observed a significantly decreased incidence of febrile neutropenia among obese patients despite similar average relative dose-intensities and G-CSF support. Furthermore, obesity was associated with decreased treatment-related mortality after controlling for age, G-CSF use and other prognostic factors. This relationship held among patients who received >85% of expected doses in the first treatment cycle, suggesting that fears of excess febrile neutropenia and treatment-related mortality among obese patients are unfounded in this population. This is of particular importance in DLBCL as studies have suggested that achieving average relative dose-intensity >90% is associated with improved long-term outcomes (Bosly et al, 2008). The ASCO guidelines also raised the question of whether dose-reductions might compromise efficacy in obese patients (Griggs et al, 2012). Evidence suggests improved overall survival among patients experiencing neutropenia or leucopenia during chemotherapy (Shitara et al, 2011). Due to the confounding by indication that is inherent in observational studies, we were unable to fully answer this question (Jepsen et al, 2004). While a trial randomizing obese patients to R-CHOP doses based upon actual versus ideal body weight would provide a clear answer, it is unlikely that such a study will ever be performed. The strengths and limitations of this study should be highlighted. As the VHA is the largest integrated health system in the United States, we were able to assemble a large patient cohort with detailed patient information. However, consistent with the historic military demographics, this cohort was almost entirely men, which may limit the applicability of our findings. An additional limitation of our study is that we could not quantify differences in long-term toxicities among BMI groups. Doxorubicin is known to cause a significant, dose-dependent incidence of heart failure (Gharib & Burnett, 2002). The effect of doxorubicin dosing, based upon actual body weight, on the incidence of doxorubicin-induced cardiomyopathy remains unknown. Overall, this study supports the application of the ASCO obesity guidelines in overweight and obese DLBCL patients (Griggs et al, 2012). Specifically, we found no evidence that treatment with full weight-based therapy in overweight or obese patients increases the risk of febrile neutropenia or treatment-related mortality. Until data emerges suggesting otherwise, in the absence of other contraindications, oncologists treating overweight and obese DLBCL patients with R-CHOP should use actual body weight in dosing calculations. Conception and design: Arun Ganti, Graham A. Colditz, Kenneth R. Carson. Financial support: Arun Ganti, Graham A. Colditz, Kenneth R. Carson. Administrative support: Katiuscia O'Brian. Collection and assembly of data: Arun Ganti, Weijian Liu, Suhong Luo, Kristen M. Sanfilippo, Ryan Roop, Ryan Lynch, Peter Riedell, Katiuscia O'Brian. Data analysis and interpretation: Arun Ganti, Weijian Liu, Suhong Luo, Kristen M. Sanfilippo, Ryan Roop, Ryan Lynch, Peter Riedell, Graham A. Coldtiz, Kenneth R. Carson. Manuscript writing: Arun Ganti, Kristen M. Sanfilippo, Graham A. Coldtiz, Kenneth R. Carson. Final approval of manuscript: All authors. The authors have no competing interests to disclose. This study was funded in part by: The Barnes-Jewish Hospital Foundation, The American Cancer Society grant IRG 58-010-52, the American Society of Hematology Trainee Research Award, and the National Cancer Institute at the National Institutes of Health grants U54CA155496 and KM1CA15608. The content is solely the responsibility of the authors and does not necessarily represent the official views of: The United States Department of Veterans Affairs, Washington University, Saint Louis University, Barnes-Jewish Hospital, the American Cancer Society, the National Cancer Institute or the National Institutes of Health, or the American Society of Hematology.

The quest to define optimal endocrine therapy for premenopausal women with early-stage breast cancer began more than 50 years ago but is still unfulfilled. Multiple strategies have emerged, including tamoxifen, ovarian function suppression (OFS) by surgery, luteinizing hormone–releasing hormone agonist or radiation, and combination strategies such as tamoxifen plus OFS or aromatase inhibitor plus OFS. An added confounder is that these strategies have frequently been assessed in the context of adjuvant chemotherapy, which is commonly used in premenopausal women and may have indirect endocrine effects because of chemotherapy-induced menopause. This complex landscape was reviewed in a 2011 American Society of Clinical Oncology (ASCO) endorsement of the 2010 Cancer Care Ontario guideline recommending against the routine use of OFS in addition to tamoxifen or chemotherapy and a 2014 ASCO guideline endorsing consideration of 10 years of tamoxifen for these young women with hormone-responsive disease. Against this backdrop, in the article that accompanies this editorial, Tevaarwerk et al report the final results of a phase III Eastern Cooperative Oncology Group trial (E-3193, INT-0142) in which 345 premenopausal women with lymph node–negative, hormone receptor–positive breast cancer measuring 3 cm were randomly assigned from 1994-1997 to receive 5 years of tamoxifen alone or 5 years of tamoxifen plus OFS; no chemotherapy was permitted. With a median follow-up of almost 10 years, there were no significant differences in the primary end points of disease-free survival (DFS; 87.9% v 89.7% P .62) or overall survival (95.2% v 97.6%; P .67). Secondary end points included toxicity and several patient-reported outcomes (PROs) including menopausal symptoms, sexual function, and health-related quality of life. These results suggest that tamoxifen plus OFS leads to increased toxicity, more menopausal symptoms, and reduced sexual function, peaking around year 3 and then diminishing over time. The strengths of this study include the importance of the question, the clean design that enabled the testing of hormone therapies in the absence of chemotherapy, the focus on hormone-responsive tumors, the balance between the arms, the long follow-up, and the assessment of PROs. The major limitation is, of course, that the study’s early closure as a result of poor accrual left it vastly underpowered for its primary end points; this trial fell victim to the 1997 report of National Surgical Adjuvant Breast and Bowel Project (NSABP) B20, which recommended the use of chemotherapy in addition to tamoxifen for women with axillary lymph node–negative, hormoneresponsive breast cancer, especially women younger than 50 years of age. However, E-3193 was a success in its collection of detailed PROs, and it is noteworthy that it met the prespecified target accrual for these secondary end points. Given the exceptional outcomes for patients enrolled onto this trial, which had greater than 95% overall survival in the absence of chemotherapy, such patient-reported data are valuable contributions to the discussion between physicians and patients about the risks and benefits of individual therapies. Several crucial questions remain. Given the statistical limitations of this trial, might the combination of OFS plus tamoxifen actually be better than tamoxifen? What about the combination of OFS plus an aromatase inhibitor, given the efficacy of aromatase inhibitors in postmenopausal hormone receptor–positive breast cancer? Three large trials are helping to address these two questions: ABCSG-12 (Austrian Breast and Colorectal Cancer Study Group trial 12), SOFT (Suppression of Ovarian Function Trial), and TEXT (Tamoxifen and Exemestane Trial). A lingering concern is how we can integrate the results of all of these trials that use 3 to 5 years of adjuvant endocrine therapy with the findings of the ATLAS (Adjuvant Tamoxifen: Longer Against Shorter) and aTTom (Adjuvant Tamoxifen—To Offer More?) trials, which support the use of 10 years of tamoxifen. In the SOFT trial, 3,066 premenopausal women with hormoneresponsive breast cancer were randomly assigned to 5 years of tamoxifen, tamoxifen plus OFS, or exemestane plus OFS; (neo)adjuvant chemotherapy was permitted as long as patients remained premenopausal at its completion. In the TEXT trial, 2,672 premenopausal patients with hormone-responsive breast cancer were randomly assigned to receive 5 years of tamoxifen plus OFS or exemestane plus OFS; endocrine therapy was started concurrently with chemotherapy if chemotherapy was planned. Because of lower than expected event rates, the statistical plans for these two trials were revised some years ago to enable a joint analysis of 4,690 women receiving tamoxifen plus OFS versus exemestane plus OFS. In contrast to E-3193, 42% of these women were lymph node positive, and 57% received some type of chemotherapy. At a median follow-up of 68 months, a significantly improved DFS was seen with exemestane plus OFS (91.1% v 87.3%; HR, 0.72; 95% CI, JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 32 NUMBER 35 DECEMBER 1

BackgroundCancer-related fatigue (CRF) is a debilitating condition which commonly affects cancer survivors. The management of CRF remains a challenge due to the lack of effective pharmacological interventions. Traditional Chinese medicine (TCM) could be a potential therapeutic option for CRF. The modified Xiang Bei Yang Rong Tang (XBYRT) is a TCM herbal decoction, formulated to improve fatigue symptoms in cancer survivors. This clinical trial aims to evaluate the efficacy and safety of XBYRT in improving CRF and quality of life (QOL) of cancer survivors.MethodsThis is a single centre, randomized, double-blind, placebo-controlled, parallel trial. Eighty cancer survivors will be recruited and randomized to receive the XBYRT or placebo decoction, in a ratio of 1:1. Participants will consume the XBYRT/placebo decoction daily for 8 weeks and undergo assessments at baseline and 4, 8 and 10 weeks after baseline. The participants will be assessed for patient-reported outcomes (PRO), blood biomarkers and adverse events at each time point. The primary outcome is the overall health and QOL status, at 8 weeks follow-up. The secondary outcomes are the effects of XBYRT on fatigue levels, cancer-related cognitive impairment and QOL, as assessed by PRO. The incidence of adverse events and the effects of the XBYRT decoction on blood biomarkers associated with CRF will also be evaluated.DiscussionEfficacy and safety outcomes from this trial will provide important clinical data to guide future large-scale randomized controlled trials, and the evaluation of the objective blood biomarkers can help to delineate the biological mechanisms of CRF.Trial registration numberClinicalTrials.govNCT04104113. Registered on 26 September 2019

e20570 Background: In 2008, 450,000 US cancer survivors were of reproductive age (18-45 years). Currently, oncologists receive little training about fertility preservation and counseling for patients. In 2006, the American Society of Clinical Oncology (ASCO) recommended oncologists “discuss the possibility of infertility during their reproductive years prior to chemotherapy.” This study aimed to evaluate adherence to these guidelines and determine if a chemotherapy consent form increased compliance. Methods: At a tertiary care center in New York on April 23, 2012, a specialized chemotherapy consent form, including a fertility risk statement and checkbox, was implemented. A retrospective chart review was conducted 250 days before April 23, 2012 (pre group) and 250 days after April 23, 2012 (post group). This study included patients 18-45 years old with a new malignant diagnosis who received fertility altering therapy. Patients with a prognosis less than 12 months were excludedfrom the study. Data collected included demographics, documentation of fertility discussions, presence of a signed chemotherapy consent form and the use of a fertility risk checkbox prior to initiation of treatment. Results: Of 645 new patient visits, 80 in the pre-group and 53 in the post-group met the inclusion criteria. The mean age (SD) for the pre and post groups was 35.6 (±6.7) and 36.8 (±6.7) respectively. Thirty-five (43.8%) patients had documented fertility counseling in the pre group compared to 16 (30.1%) in the post group. A Cochran–Mantel–Haenszel test determined that these 2 groups were not statistically different (p = 0.250). In the post group, 5 (12.8%) patients had both documented fertility counseling and a consent form; and only 3 (7.6%) patients had evidence of documented counseling, a consent form and the fertility risk box checked. Conclusions: Fertility counseling was documented in less than half of cancer patients for whom this procedure is recommended. The introduction of a specialized chemotherapy consent form did not improve the rates of documented fertility counseling. Further exploration is needed to identify the barriers to fertility counseling and identify the best resources and tools for providers to ensure compliance with ASCO guidelines.

Introduction:Chemotherapy-induced nausea and vomiting (CINV) is one of the scariest chemotherapy-induced adverse effects. We evaluated the adherence to the 2017 American Society of Clinical Oncology (ASCO), the latest guideline recommendations, for the management of acute CINV at our institute. Methods:During a 6-months cross-sectional study on outpatient’s cancer patients, we collected data from the prescription documents during temporary hospitalization and compared the results with ASCO guideline recommendations. Results:The most prescribed prophylactic regimens for the management of CINV were combination of aprepitant, granisetron, and dexamethasone and metoclopramide (51.8%). Regarding prescription compatibility in our center with ASCO guideline recommnedations, selection of different regimens for prophylaxis of acute CINV in our institute was compliant in 0 %, 22%, 4%, and 40% of high, moderate, low, and minimal emetogenic potential of chemotherapy regimen groupss, respectively. Conclusion:Although our hospital is a referral and university-affiliated center, adherence to the ASCO guideline recommendations for prophylaxis of CINV was poor.

e24079 Background: One of the most common concerns of cancer survivors is cancer-related cognitive impairment (CRCI), which affects an individual’s ability to return to work, school, or other life activities. The etiology of CRCI is poorly understood. Numerous studies have demonstrated a relationship between emotional distress and cognitive dysfunction, though the core psychological construct underlying this relationship has been elusive. Resilience, defined as the ability to function well despite adversity, reflects individual capacity to manage stress and reduce allostatic load. We hypothesized that low resilience contributes to stress-related cognitive symptoms in cancer survivors, and that improvement in resilience through the Relaxation Response Resiliency Program (3RP), a psychotherapy group that reduces emotional distress, would reduce cognitive symptoms in cancer survivors. Methods: Consistent with prior protocols, adult cancer survivors participated in the 3RP program, a 9-week resiliency mind-body group treatment led by psychologists and/or psychiatrists. Survivors completed measures of cognitive symptoms (Patient Reported Outcome Measure Information System – Cognitive function; PROMIS-Cog) and resilience (Current Experiences Scale; CES) before and after treatment. Pearson correlations evaluated relationships between resilience and cognition. Results: 46 cancer survivors (mean age = 57, 85% female, 94% White, 4% Asian, 2% Black) completed \ CES and PROMIS-Cog at therapy intake, with 41% of subjects reporting significant cognitive impairment at baseline (defined as scores of &lt; 1.0 SD on PROMIS-Cog). There was a significant correlation between these two scales prior to treatment (r = 0.33; p = 0.025), indicating that subjects with lower resilience reported poorer cognition. Thus far, 13 survivors have completed the 8-week therapy program, with 46% of these patients reporting significant cognitive difficulties. The post-treatment correlation between resilience and cognition was nonsignificant (r = 0.19;p = ns). Treatment effects were operationalized by change scores (follow up – baseline) for CES and PROMIS-Cog. The relationship between CES and PROMIS-Cog change scores was positive but not significant with the small sample size (r = 0.35; p = 0.028). Conclusions: This preliminary study suggests that there is a relationship between resilience and cognition in cancer survivors. Improvements in resilience through the 3RP treatment may reduce cognitive symptoms, though further work is needed to determine the significance of this effect.

Background: Transthoracic echocardiographic (TTE) surveillance for left ventricular dysfunction following cardiotoxic chemotherapy, particularly anthracyclines, is a key component of cardio-oncology care. The 2017 American Society of Clinical Oncology (ASCO) guidelines recommend routine TTE screening in older adults after anthracycline-based chemotherapy, but it remains uncertain if these guidelines had an effect on physician TTE ordering frequency. Methods: The Surveillance, Epidemiology, and End Results (SEER) Medicare dataset was used to identify older adults (&gt;65 years) with HER2-negative breast cancer, lymphoma, or soft tissue sarcoma who received anthracyclines for a first cancer diagnosis from 2010-2020. Monthly TTE surveillance rates (TTEs per eligible patient-month) in the first year following chemotherapy initiation were compared before and after the ASCO guideline release in January 2017 using an interrupted time series approach. Results: Of 15,045 individuals included (mean age 74.1 ± 5.9 years, 64.9% female, 84.9% White), 9,611 (63.9%) had lymphoma, 5,106 (33.9%) breast cancer, and 328 (2.2%) sarcoma. An average of 43.6% ± 1.3% of individuals received a surveillance TTE during the first year after chemotherapy (mean 7.2 ± 0.9% per month). The monthly TTE surveillance frequency remained constant prior to 2017 (-0.003%/month, 95% CI -0.01% to +0.007%, p = 0.58) and after 2017 (+0.18%/month, 95% CI -0.57% to +0.92%, p = 0.65), with no significant change following the ASCO guideline release (+0.03%/month, 95% CI -0.005% to +0.06, p = 0.11) ( Figure ). Conclusion: TTE surveillance rates did not significantly change following the release of the 2017 ASCO guidelines among older Medicare beneficiaries receiving anthracycline chemotherapy for non-HER2+ malignancies. More than half of older anthracycline treated patients did not receive a post-anthracycline TTE in the year after their cancer treatment.

Clinical practice guidelines include recommendations intended to optimize patient care. In the last years, the introduction of immune checkpoint inhibitors is rapidly changing lung cancer management and therefore guidelines are essential to assist clinicians in such an evolving field. We reviewed the recommendations about the use of these immune checkpoint inhibitors in clinical practice guidelines issued by three scientific societies [European Society of Medical Oncology (ESMO); American Society of Clinical Oncology (ASCO); Italian Association of Medical Oncology (AIOM)] and one not-for-profit U.S. alliance [National Comprehensive Cancer Network (NCCN)] in order to underline their strengths and limitations. All the examined guidelines include some recommendations about use of immune checkpoint inhibitors in lung cancer patients. ASCO guidelines have a good methodologic background while their major limitation is their slow updating. NCCN guidelines, by contrast, are continuously updated but suffer from weak methodology and poor comparative tools. ESMO guidelines introduce a tool to assess the magnitude of clinical benefit for each recommended intervention that, although with some limitations, may improve clinical decision making. AIOM guidelines apply a robust methodology, but contain recommendations only on drugs reimbursed in Italy, thus limiting their applicability in different contexts. Clinical practice guidelines are useful tools that assist clinicians treating lung cancer patients with immune checkpoint inhibitors. Their use would improve homogeneity and appropriateness, even in this rapidly evolving field.

Background: The global influence and demand for clinical oncology guidelines is increasing. National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), European Society of Medical Oncology (ESMO), and various other organizations develop clinical oncology guidelines, which are used across regions to provide evidence-based recommendations for the management of cancer.1 Aim: To identify and analyze utilization trends of clinical oncology guidelines outside the US. Methods: In 2017, NCCN distributed an electronic survey to 212,423 registered users of the NCCN Web site outside the US through a third party software. Participants were prompted to respond to the following statement “I consult the following guidelines regularly: (Select all that apply).” Options included several clinical oncology guidelines, as well as the option “I do not regularly consult clinical oncology guidelines.” The survey also included the following query: “In my opinion, the NCCN Guidelines are: (select one per row).” The survey then listed several descriptors and the respondents were asked to select strongly agree, agree, no opinion, disagree, or strongly disagree for each one. Results: NCCN received 1698 responses to the survey from oncology professionals outside of the US. Of this pool, 82% of respondents identified as physicians and 18% were other oncology professionals. Of respondents to the first query (n=1190), 89% selected the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), 55% ESMO Clinical Practice Guidelines, 50% ASCO Guidelines, 20% National Institute for Health and Care Excellence (NICE) guidelines, 15% local, national, or other oncology guidelines, 11% Sociedad Española de Oncología Médica (SEOM), 8% Cancer Care Ontario Guidelines, 7% Multinational Association of Supportive Care in Cancer (MASCC), 6% Japanese Society of Medical Oncology Clinical Guidelines, and 6% do not regularly consult clinical oncology guidelines. In response to the second query (n=1392), more than 90% of respondents outside of the US “strongly agree” or “agree” that the NCCN Guidelines are useful in patient care decision-making, a reliable reference, up-to-date, objective and balanced, evidence-based, and helpful in clinical teaching. Conclusion: Based on data presented, NCCN Guidelines are consulted more frequently than any other clinical oncology guideline outside the US. Previous research indicates similar utilization trends. We believe, in part, healthcare professionals outside the US consult the NCCN Guidelines frequently due to the descriptors listed in the survey results. Additional research is needed to identify the synergies between the relevance of international clinical oncology guidelines and local utilization trends to better serve the needs of patients globally.

Metastatic renal cell carcinoma (mRCC) is a fast-moving therapeutic field with multiple targeted agents approved and many more in development. In our expert agreement article [1], we evaluated available data together with our clinical experience to consider how we might optimize using targeted therapies in sequence, emphasizing the need continually to address the question, ‘‘what comes next?’’ Crucially, new phase III data presented at the American Society of Clinical Oncology (ASCO) 2011 annual meeting provide level 1 evidence that patients can receive continued clinical benefit when VEGF-targeted tyrosine kinase inhibitors (TKIs) are used sequentially [2, 3]. The randomized, open-label, phase III AXIS study compared second-line axitinib 5 mg bid (titrated to 7, then 10 mg bid, if tolerated) with sorafenib 400 mg bid in 723 patients with mRCC, more than half of whom had previously received the TKI sunitinib (n = 389) [2]. The study met the primary endpoint of superiority for axitinib, with median PFS 6.7 months, compared with 4.7 months for sorafenib (P \ 0.0001). Median PFS was lower in post-sunitinib than in the total patient population for both axitinib (4.8 months) and sorafenib (3.4 months; P \ 0.05 versus axitinib). Notably, and as discussed in our expert agreement article, this phenomenon was also seen in the phase III RECORD-1 study of everolimus in patients previously treated with sorafenib and/or sunitinib—prior sunitinib was prognostic of lower PFS and overall survival in a multivariate analysis [1]. The AXIS and RECORD-1 data, therefore, suggest that pre-treatment with effective VEGF-TKI therapy, such as sunitinib, has a detrimental effect on subsequent outcome with both VEGF-TKI therapy and mTOR inhibition. Therefore, cross-resistance between these two classes may be apparent. A further noteworthy publication at ASCO 2011, from Dr. Mhd Al-Marrawi on behalf of the International mRCC Database Consortium, showed that response to initial TKI therapy did not predict response to further TKI therapy [4]. This study did not report whether the sequence of TKIs received was important, but this question could be addressed in part by performing a similar analysis using the AXIS data—i.e., were ORR/stable disease/PFS with axitinib or sorafenib related to ORR/stable disease/PFS with sunitinib and were there differences between axitinib and sorafenib in this regard? Overall, the findings from AXIS, RECORD-1, and the International mRCC Database Consortium do not support the hypothesis that switching mode of action from VEGF inhibition to mTOR is the logical first step in the face of VEGF resistance. Re-challenging with VEGF-TKI therapy appears to be more attractive as the first treatment manipulation at present. Switching to mTOR as 3rd line or later, which is supported by randomized phase III data, gives us multiple lines of therapy with proven efficacy. On a further note, though it may be tempting to compare the efficacy data from AXIS with those for RECORD-1, there are a number of key differences between the studies, including patient population and study design, and so such comparisons are fundamentally flawed. Patient-reported outcomes from AXIS were also presented at ASCO [3]. Dr. David Cella showed that C. Porta (&) I.R.C.C.S. San Matteo University Hospital Foundation, Pavia, Italy e-mail: c.porta@smatteo.pv.it