Comprehensive pharmacological geriatric assessment compared to usual care in an older adult with cancer in the absence of polypharmacy.

INTRODUCTION: Medication reconciliation as part of a Comprehensive Geriatric Assessment by a specialist pharmacist is a process that has been shown to be beneficial in terms of medication adherence in patients taking oral anticancer medication and potentially cost-effective in cancer patients. Medication review guidelines in older adults with cancer suggest using polypharmacy (≥ 5 medications) as an indication for medication review in older adults with cancer. CASE REPORT: We present a case where a medication review as part of a Comprehensive Geriatric Assessment in the absence of polypharmacy resulted in two pharmacist interventions when standard care resulted in no intervention. A 71-year-old male prescribed capecitabine for rectal cancer had a medication reconciliation done as standard care before starting an oral anticancer medication. He then proceeded to get a medication review as part of a Comprehensive Geriatric Assessment and was deemed to have a potentially excessive anticholinergic burden and underprescribed gastro protection. This case is interesting as it occurred in a patient who would not have met the current inclusion criteria for a medication review as part of a Comprehensive Geriatric Assessment. MANAGEMENT AND OUTCOME: As a result of the Comprehensive Geriatric Assessment, a letter was written to the patient's general practitioner, recommending a change to anti-depressant therapy to optimise anticholinergic burden, as well as introducing a proton-pump inhibitor upon completion of the Capecitabine protocol concurrent with radiotherapy, to confer gastro-protection against the antidepressant medication, as per the START criteria. Upon discharge from medical oncology, neither of the changes had been adopted by the patient's general practitioner. This highlights one of the challenges facing clinical pharmacists in an outpatient setting, where evidence-based recommendations are not always implemented as care transitions from tertiary to primary care. CONCLUSION: Comprehensive Geriatric Assessment is a process that identifies potential issues in older adults with cancer that aren't identified with standard medication review. This is also evident for medication reviews as part of a Comprehensive Geriatric Assessment, and where resources allow, and recommendations are likely to be accepted, it should be offered to all older adults with cancer. Pharmacists are still faced with challenges in implementing recommendations from medication reviews, particularly in healthcare systems where pharmacist prescribing has yet to be introduced.

Metastatic gastroesophageal cancer in older patients - is this patient cohort represented in clinical trials?

BACKGROUND: Older patients are underrepresented in the clinical trials that determine the standards of care for oncological treatment. We conducted a review to identify whether there have been age-restrictive inclusion criteria in clinical trials over the last twenty five years, focusing on patients with metastatic gastroesophageal cancer. METHODS: A search strategy was developed encompassing Embase, PubMed and The Cochrane Library databases. Completed phase III randomised controlled trials evaluating systemic anti-cancer therapies in metastatic gastroesophageal malignancies from 1st January 1995 to 18th November 2020 were identified. These were screened for eligibility using reference management software (Covidence; Veritas Health Innovation Ltd). Data including age inclusion/exclusion criteria and median age of participants were recorded. The percentage of patients ≥ 65 enrolled was collected where available. The change over time in the proportion of studies using an upper age exclusion was estimated using a linear probability model. RESULTS: Three hundred sixty-three phase III studies were identified and screened, with 66 trials remaining for final analysis. The majority of trials were Asian (48%; n = 32) and predominantly evaluated gastric malignancies, (86%; n = 56). The median age of participants was 62 (range 18-94). Thirty-two percent (n = 21) of studies specified an upper age limit for inclusion and over half of these were Asian studies. The median age of exclusion was 75 (range 65-80). All studies prior to 2003 used an upper age exclusion (n = 12); whereas only 9 that started in 2003 or later did (17%). Among later studies, there was a very modest downward yearly-trend in the proportion of studies using an upper age exclusion (-0.02 per year; 95%CI -0.05 to 0.01; p = 0.31). Fifty-two percent (n = 34) of studies specified the proportion of their study population who were ≥ 65 years. Older patients represented only 36% of the trial populations in these studies (range 7-60%). CONCLUSIONS: Recent years have seen improvements in clinical trial protocols, with many no longer specifying restrictive age criteria. Reasons for poor representation of older patients are complex and ongoing efforts are needed to broaden eligibility criteria and prioritise the inclusion of older adults in clinical trials.

Pregnancy-associated breast cancer: evaluating maternal and foetal outcomes. A national study.

PURPOSE: Pregnancy-associated breast cancer (PABC) is defined as breast cancer diagnosed during the gestational period (gp-PABC) or in the first postpartum year (pp-PABC). Despite its infrequent occurrence, the incidence of PABC appears to be rising due to the increasing propensity for women to delay childbirth. We have established the first retrospective registry study of PABC in Ireland to examine specific clinicopathological characteristics, treatments, and maternal and foetal outcomes. METHODS: This was a national, multi-site, retrospective observational study, including PABC patients treated in 12 oncology institutions from August 2001 to January 2020. Data extracted included information on patient demographics, tumour biology, staging, treatments, and maternal/foetal outcomes. Survival data for an age-matched breast cancer population over a similar time period was obtained from the National Cancer Registry of Ireland (NCRI). Standard biostatistical methods were used for analyses. RESULTS: We identified 155 patients-71 (46%) were gp-PABC and 84 (54%) were pp-PABC. The median age was 36 years. Forty-four patients (28%) presented with Stage III disease and 25 (16%) had metastatic disease at diagnosis. High rates of triple-negative (25%) and HER2+ (30%) breast cancer were observed. We observed an inferior 5-year overall survival (OS) rate in our PABC cohort compared to an age-matched breast cancer population in both Stage I-III (77.6% vs 90.9%) and Stage IV disease (18% vs 38.3%). There was a low rate (3%) of foetal complications. CONCLUSION: PABC patients may have poorer survival outcomes. Further prospective data are needed to optimise management of these patients.

Happy Talk: A pilot effectiveness study of a targeted-selective speech-language and communication intervention for children from areas of social disadvantage.

BACKGROUND: Despite the public health implications of language difficulties associated with social disadvantage, there is a dearth of effectiveness studies investigating the effects of targeted speech and language programmes in this area. AIMS: To determine the effects of a targeted selective community-based child language intervention programme (Happy Talk), which simultaneously engaged with parents and early childhood educators, in the Republic of Ireland. METHODS & PROCEDURES: A mixed methods methodology was applied with quantitative outcome and qualitative process data collected. Effectiveness was examined using a quasi-experimental single blind study design comparing Happy Talk with 'usual care' across four preschools. Qualitative process data were also gathered to examine the acceptability and feasibility of the Happy Talk approach in practice, and to identify factors to improve the probability of successful wider implementation. Child language (PLS-5) and quality-of-life measures were administered pre- and immediately post- the 11-week intervention. Responsiveness was assessed as the parental outcome, and the oral language environment of preschools was measured using the Communication Supporting Classroom Observation Tool (CSCOT). Retrospective acceptability was analysed with reference to the theoretical framework of acceptability (v 2). OUTCOMES & RESULTS: Pre-/post-expressive and composite language scores were collected for 58 children, and receptive scores for 54 children. Multiple linear regression revealed significant intervention effects for comprehension and total language with large and moderate effect sizes, respectively (0.60 and 0.46 SD). No significant effect was shown for parental responsiveness. No effects were found for the preschool environment or children's quality of life. Preschool staff deemed the programme to be an acceptable method of enhancing children's speech and language skills and rated the intervention positively. CONCLUSIONS & IMPLICATIONS: The Happy Talk pilot effectiveness trial shows that comprehension can be improved (with a large effect) in preschool children from areas of social disadvantage, following an 11-week intervention, in which parents and preschool staff are simultaneously engaged. The ecological validity of the programme, as well as feasibility and acceptability to staff, make it a suitable programme to be delivered at scale. WHAT THIS PAPER ADDS: What is already known on the subject Up to 50% of children from socially disadvantaged areas enter preschool with speech and language difficulties. The majority of intervention studies are (1) researcher led; (2) efficacy trials carried out in ideal conditions; and (3) focus on working with parents or early childhood educators rather than engaging with both groups simultaneously. Many studies omit child language outcomes, and those that include them tend to show relatively modest effects for expressive language and negligible effects for receptive language. What this paper adds to existing knowledge This pilot study shows that the Happy Talk programme, which is embedded in the community and which simultaneously engages with parents and early childhood educators, is highly effective in improving children's receptive language skills. These findings are particularly important in the context of (1) the study taking place in real world conditions; and (2) the programme being designed and refined by speech and language therapy services, rather than one which is researcher led. What are the potential or actual clinical implications of this work? Implementing an 11-week targeted selective community-based language intervention can result in a large positive effect on receptive language for children from areas of social disadvantage. The study findings highlight the importance of embedding intervention programmes in the community and of simultaneously engaging with parents and preschool staff.

Multicenter, randomized, double-blind phase 2 trial of FOLFIRI with regorafenib or placebo as second-line therapy for metastatic colorectal cancer.

BACKGROUND: Regorafenib, a multikinase inhibitor that inhibits angiogenesis, growth, and proliferation, prolongs survival as monotherapy in patients with refractory colorectal cancer. This international, double-blind, placebo-controlled, multicenter trial assessed the efficacy of regorafenib with folinic acid, fluorouracil, and irinotecan (FOLFIRI) as a second-line treatment for metastatic colorectal cancer. METHODS: Patients with metastatic colorectal cancer who progressed on first-line oxaliplatin and fluoropyrimidine enrolled at 45 sites in the United States and Ireland. Patients, stratified by prior bevacizumab use, were randomized 2:1 to regorafenib or placebo. The treatment consisted of FOLFIRI on days 1 and 2 and days 15 and 16 with 160 mg of regorafenib or placebo on days 4 to 10 and days 18 to 24 of every 28-day cycle. Crossover was not allowed. The primary endpoint was progression-free survival (PFS). Under the assumption of a 75% event rate, 180 patients were required for 135 events to achieve 90% power to detect a hazard ratio (HR) of 0.65 with a 1-sided α value of .1. RESULTS: One hundred eighty-one patients were randomized (120 to regorafenib-FOLFIRI and 61 to placebo-FOLFIRI) with a median age of 62 years. Among these, 117 (65%) received prior bevacizumab or aflibercept. PFS was longer with regorafenib-FOLFIRI than placebo-FOLFIRI (median, 6.1 vs 5.3 months; HR, 0.73; 95% confidence interval [CI], 0.53-1.01; log-rank P = .056). The median overall survival was not longer (HR, 1.01; 95% CI, 0.71-1.44). The response rate was higher with regorafenib-FOLFIRI (34%; 95% CI, 25%-44%) than placebo-FOLFIRI (21%; 95% CI, 11%-33%; P = .07). Grade 3/4 adverse events with a >5% absolute increase from regorafenib included diarrhea, neutropenia, febrile neutropenia, hypophosphatemia, and hypertension. CONCLUSIONS: The addition of regorafenib to FOLFIRI as second-line therapy for metastatic colorectal cancer only modestly prolonged PFS over FOLFIRI alone. Cancer 2018. © 2018 American Cancer Society.

Neoadjuvant hyperfractionated chemoradiation and liver transplantation for unresectable perihilar cholangiocarcinoma in Canada.

BACKGROUND AND OBJECTIVES: Neoadjuvant chemoradiation and liver transplantation may be offered for unresectable perihilar cholangiocarcinoma (pCCA). This study aimed to determine the dropout rate and survival of patients who entered a national tri-modality protocol. METHOD: Patients enrolled Jan 2009-Aug 2015 were included. Enrolment criteria: ≤65 years, brush biopsy-proven unresectable pCCA <3.5 cm diameter. Conformal radiotherapy was given concurrently with Capecitabine. Following surgical staging, patients received maintenance Cisplatin and Gemcitabine until transplant or progression. Time to event analyses were performed from start of neoadjuvant therapy. RESULTS: Of 43 patients screened, 18 started treatment; median age 53.9 (26.7-62.8) years, tumour diameter 2.7 (2.0-3.4) cm. 11/18 dropped out due to metastatic disease identified during chemoradiation (n = 2), surgical staging (n = 6), or maintenance chemotherapy (n = 3). Six patients underwent transplantation. Median follow up was 17.6 (4.9-57.7) months and overall survival 16.4 months. One and two year survival was 70.6% and 35.3%, respectively. One and 2 year post transplant survival was 83.3% and 55.6%. Median progression free survival was 11.5 months. CONCLUSION: Neoadjuvant chemoradiation and liver transplantation for unresectable early stage pCCA is feasible, although with high rates of dropout and disease progression. Further research is required to determine factors to help select patients for treatment.

Management of Locally Advanced and Metastatic Esophageal Cancer in the Older Population.

PURPOSE OF REVIEW: This review aims to synthesise the current literature on the management of early-stage and metastatic esophageal cancers, focusing on the older population. In particular, we aim to dissect out the elderly-specific data from the relevant trials and to discuss the issues unique to this population. RECENT FINDINGS: While surgery is the curative modality in esophageal malignancies, the CROSS, MAGIC and FLOT trials demonstrate a clear advantage to neoadjuvant therapy (chemotherapy and chemoradiotherapy). These trials, however, included few elderly patients. There is a similar lack of elderly-specific data in the metastatic setting. Esophageal malignancies remain highly lethal with increasing incidence with age. Despite the relative lack of elderly-specific data, the fit older population appear to similarly benefit from multimodal therapy in early-stage and palliative therapy in metastatic disease.

A phase II trial of second-line axitinib following prior antiangiogenic therapy in advanced hepatocellular carcinoma.

BACKGROUND: Second-line treatment options in advanced hepatocellular carcinoma (HCC) are limited. Axitinib, a selective potent tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor VEGF) receptors 1, 2, and 3, merits exploration in HCC. METHODS: This was a single-arm phase II trial of axitinib in advanced HCC. Eligible patients were Child-Pugh A/B7, with measurable progressive disease after TKIs/antiangiogenic drugs. Axitinib was started at 5 mg twice daily orally, titrated from 2 to 10 mg twice daily as tolerated. The primary end point was tumor control at 16 weeks by RECIST1.1; secondary end points were response rate, comparing response by RECIST1.1 to Choi and modified RECIST, exploring dynamic contrast-enhanced imaging models, safety, progression-free (PFS), and overall survival (OS). RESULTS: Thirty patients were treated. Of 26 patients evaluable for response, there were 3 partial responses (PR) per RECIST1.1; 13 PR by Choi, 6 PR and 1 complete response by modified RECIST. Tumor control rate at 16 weeks was 42.3%. Two-week perfusion changes were noted on functional imaging. Of 21 patients with evaluable α-fetoprotein response, 43% had >50% decrease from baseline. Most common axitinib-related grade 3/4 adverse events (AEs) were hypertension, thrombocytopenia and diarrhea. Of 11 patients with any grade hypertension, 7 had disease control >36 wks. Four patients discontinued treatment due to AEs. Median PFS was 3.6 months. Median OS was 7.1 months. CONCLUSIONS: With 42.3% tumor control at 16 weeks, primary endpoint was met. Axitinib has shown encouraging tolerable clinical activity in VEGF-pretreated HCC patients but further study should be in a selected population incorporating potential biomarkers of response.

Effects of Statin, Aspirin or Metformin Use on Recurrence-Free and Overall Survival in Patients with Biliary Tract Cancer.

BACKGROUND/AIMS: The impact of statins, aspirin and metformin use on recurrence-free (RFS) and overall survival (OS) of patients with biliary tract cancer (BTC) has not been evaluated. METHODOLOGY: Baseline demographics/comorbidity and use of statins, aspirin or metformin at diagnosis were evaluated in patients with BTC from January/1987-July/2013. RESULTS: Median age at diagnosis; 65.7 years, performance status < 2; 795 patients, male; 461 (50.5%). Among 913 patients; 151 (16.5%) reported statin use at diagnosis, 146 (16%) aspirin use, and 81 (9%) metformin use. Charlson Comorbidity index score was not significantly associated with RFS or OS. Stage was prognostic on multivariable analysis for RFS and OS (both P ≤ 0.001) and age, performance status ≥ 2 and site were also prognostic for OS (P < 0.05, P < 0.001, and P < 0.05 respectively). Recurrence-free and OS among statin-users and nonusers was similar (RFS Hazard Ratio [HR]1.11, 95% confidence interval [CI] 0.78 - 1.58, P = 0.57), (OS HR0.98, 95% CI 0.77-1.24, P = 0.86), and among aspirin-users and nonusers (RFS HR0.83, 95% CI 0.57-1.23, P = 0.35), (OS HR1.07, 95% CI 0.85 - 1.34, P = 0.58), and among metformin-users and non-users (RFS HR0.75, 95% CI 0.43-1.30, P = 0.30), (OS HR0.96, 95% CI 0.69-1.33, P = 0.79). CONCLUSION: In this large retrospective cohort of BTC patients, comorbidity, statin, aspirin or metformin use did not have significant effects on RFS or OS.

Statin use in older adults with cancer - Experience from a dedicated geriatric oncology service.

INTRODUCTION: The increase in statin use, since their introduction, has been rapid and the broadening of indications has occurred seemingly without restriction. Once established on statin therapy, there is sparse research on discontinuation. Trials do not often address benefit in later life, or the impact of a life-limiting diagnosis. Data on primary prevention suggest that 100 patients need treatment for 2.5 years to prevent one major adverse cardiovascular event. Acknowledging this, we sought to determine the use of statins in a cohort of older adults with cancer, to highlight prevalence, and suggest a role for deprescribing. MATERIALS AND METHODS: Data were retrospectively collected from a prospectively maintained database of patients attending a single centre Geriatric Oncology clinic. Data collected included sex, age, cancer type and stage, systemic anti-cancer therapy (SACT) recommendation, comorbidities, non-SACT medications, and overall survival. For those receiving statin therapy, data were separated into primary prevention and stage IV cancer. RESULTS: In the group studied (n = 230), 135 (59%) were prescribed a statin, with 79 (58%) for primary prevention. Ninety-three (40%) had stage IV cancer. Of the 230 patients, 134 (58%) were recommended SACT. Within the primary prevention group, the median age was 79 years. Twenty-seven patients (34%) had stage III disease, while 36 (46%) had stage IV disease. Thirteen (16%) had diabetes mellitus. The median number of medications was seven (Interquartile range 5). Fifty patients (63%) were recommended SACT. In terms of survival, 31 (50%) were alive at one year, 18 (29%) alive at two years, and 14 (23%) alive beyond two and a half years. Within the stage IV disease group, 59 out of 93 (63%) were receiving statin therapy; 35 (59%) for primary prevention and seven (8%) for diabetes mellitus. Fifty-eight (63%) were recommended SACT. Twenty-four (29%) were alive at one year, 17 (21%) alive at two years, and 13 (16%) alive beyond two and a half years. DISCUSSION: Statin therapy is prevalent and continues into older age. Available data regarding statin therapy in older adults and survival seen in this study support deprescribing in primary prevention and life-limiting illness, such as stage IV cancer.

Hospitalisation and adverse drug events in a geriatric oncology setting: A systematic review of the literature.

BACKGROUND: Geriatric Oncology is a specialty where a multidisciplinary approach can address the unmet needs of older adults with cancer. Older adults are at increased risk of adverse drug events (ADE) due to age-related changes in pharmacokinetics and pharmacodynamics, increasing treatment complexity, and medication burden. OBJECTIVES: To review the literature to determine the incidence of unplanned hospitalisation due to ADE for all medications, both systemic anticancer therapy (SACT) and non-SACT medications. METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The search included the following databases: PubMed, CINAHL, and Embase. A manual search of Scopus was then performed. Study quality was assessed using the Cochrane Handbook for Systematic Reviews of Interventions, Mixed Methods Appraisal Tool (MMAT) and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. RESULTS: Overall, three studies were included. One observational study reported 19 % of unplanned hospital admissions due to ADE in patients aged ≥70 years with cancer. The first retrospective study reported 24 % of unplanned hospital admissions are due to ADE in patients aged ≥70 years with cancer, and the second retrospective study reported 26 % of patients with metastatic melanoma treated with immune checkpoint inhibitors had an unplanned hospital admission due to an ADE. CONCLUSION: There is a paucity of studies assessing unplanned hospitalisation due to ADE in older adults with cancer. Future studies are needed and should account for the reporting of potential ADE relative to supportive care, ancillary medications, and indeed chronic medications used to treat long-standing comorbidities.

Ageing-related considerations for medication used in supportive care in cancer.

Both randomized controlled trials (RCTs) and retrospective studies have shown that a comprehensive geriatric assessment (CGA) prior to a patient commencing systemic anti-cancer therapy (SACT) results in improved quality of life outcomes and is associated with a decreased risk of grade 3-5 toxicity; however, data are lacking in relation to adverse drug events (ADE) associated with supportive care medications. Supportive care medications are prescribed as prophylactic agents in a SACT regimen, for management of treatment related toxicity and for symptoms caused by the disease itself. While necessary, the commencement of SACT and supportive medications may cause, or exacerbate, a significant drug burden in older patients, some of whom may have existing comorbidities. For many medications, older adults are underrepresented in pharmacokinetic and pharmacodynamic modelling studies. In this article we will review ageing-related changes in pharmacokinetics and pharmacodynamics, as well as how these changes may impact supportive care medications. Additional considerations for prescribing these medications in older adults with cancer, such as polypharmacy, potentially inappropriate medications, drug-drug interactions, and anticholinergic burden, as well as ageing-related considerations and recommendations for supportive care medications commonly used in older adults with cancer are also reviewed.

Analysis of cell free DNA to predict outcome to bevacizumab therapy in colorectal cancer patients.

To predict outcome to combination bevacizumab (BVZ) therapy, we employed cell-free DNA (cfDNA) to determine chromosomal instability (CIN), nucleosome footprints (NF) and methylation profiles in metastatic colorectal cancer (mCRC) patients. Low-coverage whole-genome sequencing (LC-WGS) was performed on matched tumor and plasma samples, collected from 74 mCRC patients from the AC-ANGIOPREDICT Phase II trial (NCT01822444), and analysed for CIN and NFs. A validation cohort of plasma samples from the University Medical Center Mannheim (UMM) was similarly profiled. 61 AC-ANGIOPREDICT plasma samples collected before and following BVZ treatment were selected for targeted methylation sequencing. Using cfDNA CIN profiles, AC-ANGIOPREDICT samples were subtyped with 92.3% accuracy into low and high CIN clusters, with good concordance observed between matched plasma and tumor. Improved survival was observed in CIN-high patients. Plasma-based CIN clustering was validated in the UMM cohort. Methylation profiling identified differences in CIN-low vs. CIN high (AUC = 0.87). Moreover, significant methylation score decreases following BVZ was associated with improved outcome (p = 0.013). Analysis of CIN, NFs and methylation profiles from cfDNA in plasma samples facilitates stratification into CIN clusters which inform patient response to treatment.

Endoscopic or percutaneous biliary drainage for Klatskin tumors?

PURPOSE: Controversy exists regarding the preferred biliary drainage technique in patients with Klatskin tumors because few comparative studies exist. This study compared outcomes of endoscopic biliary drainage (EBD) and percutaneous transhepatic biliary drainage (PTBD). MATERIALS AND METHODS: Consecutive patients (N = 129) with Klatskin tumors treated with initial EBD or PTBD were identified, and their clinical histories were retrospectively reviewed. The primary endpoint was the time to therapeutic success (TTS), defined as the time between the first drainage and a total bilirubin measurement of 40 µmol/L or lower. RESULTS: EBD was the first biliary decompression procedure performed in 87 patients; PTBD was performed first in 42. Technical success rates (78% with EBD vs 98% with PTBD; P = .004) and therapeutic success rates (49% vs 79%, respectively; P = .002) were significantly lower in the EBD group than in the PTBD group. Forty-four patients in the EBD group (51%) subsequently underwent PTBD before therapeutic success was achieved or antitumoral treatment was started. Median TTSs were 61 days in the EBD group and 44 days in the PTBD group, and multivariate analysis showed a hazard ratio of 0.63 (95% confidence interval, 0.41-0.99; P = .045). In patients treated with surgery or chemotherapy with or without radiation therapy, median times to treatment were 76 and 68 days in the EBD and PTBD groups, respectively (P = .76). Cholangitis occurred in 25% and 21% of patients in the EBD and PTBD groups, respectively (P = .34). CONCLUSIONS: PTBD should be seriously considered for biliary decompression when treating patients with Klatskin tumor.

The prognostic value of the derived neutrophil-to-lymphocyte ratio (dNLR) in patients treated with immune checkpoint inhibitors.

BACKGROUND: The (derived) neutrophil-to-lymphocyte ratio (dNLR) is a potential predictive biomarker in the era of checkpoint inhibitors (CPI). An elevated dNLR is associated with worse outcomes across several malignancies. However, there is no clearly defined cut-off in the clinical setting. AIM: To compare outcomes in patients prescribed CPI with a baseline dNLR0 > 3 and dNLR0 ≤ 3. The dNLR6 was measured 6 weeks later to determine its impact on patient overall survival (OS). METHODS: Prospectively maintained pharmacy databases in a regional cancer centre were interrogated for patients who were prescribed CPI in the advanced setting between January 2017 and May 2020. RESULTS: There were 121 patients with advanced cancer and a median age of 68 (range 30 to 88) years. Forty-four percent (n = 53) received prior systemic therapy. Patients with an initial dNLR0 > 3 when compared with a dNLR0 ≤ 3 had significantly shorter median progression-free survival (PFS), 3 vs. 14 months (p = 0.001) and median OS, 6.4 vs. 30.2 months (p = 0.001). Patients with an initial dNLR0 > 3 and increased dNLR at 6 weeks (dNLR6) had significantly reduced median PFS (3.5 vs. 14.7 months, p = 0.03) and OS (5.7 vs. 16.3, p = 0.03) when compared with those whose dNLR decreased. In the dNLR0 ≤ 3 cohort, any increased dNLR when compared with decreased dNLR after 6 weeks of CPI had significantly reduced PFS (8.4 months vs. NR, p = 0.01) and OS (24.2 months vs. NR, p = 0.02). CONCLUSIONS: Lower pre-CPI treatment dNLR is associated with improved OS. A decrease in dNLR during treatment confers improved OS.

Hospitalization due to adverse drug events in older adults with cancer: A retrospective analysis.

INTRODUCTION: Geriatric oncology is a rapidly evolving field of practice, where comprehensive geriatric assessments (CGA) and multidisciplinary team (MDT) input have the potential to improve patient outcomes. Polypharmacy and potential drug interactions (PDI) have been associated with an increased risk of adverse outcomes in older adults with cancer, receiving systemic anti-cancer therapy (SACT). Our aim was to assess the incidence of unplanned hospitalization in older adults with cancer attending medical oncology outpatient clinics and to determine whether an unplanned hospitalization was potentially due to an adverse drug event (ADE). MATERIALS AND METHODS: We identified patients who attended a medical oncology outpatient appointment from January 1 to March 31, 2018. Medical records were examined to identify any unplanned hospital admissions between the clinic visit date and three and six months after initial clinic visit. Incidences of unplanned hospitalization were assessed to determine if an ADE potentially occurred. RESULTS: Data collected from 174 patients were analyzed. Over half (57%) were female, median age was 75 years and 53% had a favorable performance status. The most common malignancies were gastrointestinal (GI) at 31% (n = 54), breast 29% (n = 51), and genitourinary 22% (n = 37). Seventy-two percent had advanced disease (stage III/IV) and 61% had systemic therapy (SACT and hormonal therapy). Polypharmacy (≥5 medications) was observed in 77% of patients. The total number of admissions at six months was 99, with 55% of these potentially due to an ADE. On multivariate analysis breast cancer (p ≤0.001), lung cancer (p = 0.034), performance status (p ≤0.001), monochemotherapy (p = 0.012), polychemotherapy (p ≤0.001), and radiotherapy (p = 0.048) were independent predictors of unplanned hospitalization. Breast cancer (p = 0.008), GI cancer (p = 0.019), monochemotherapy (p = 0.039), and polychemotherapy (p ≤0.001) were independent predictors of unplanned hospitalization due to ADE on multivariate analysis. DISCUSSION: We observed that older adults with cancer have a high risk of unplanned hospitalization due to ADE. Medication review as part of a CGA in newly diagnosed older adults with cancer by a clinical pharmacist is recommended. This may identify opportunities to avoid medications that could potentially lead to unplanned hospitalization.

Consensus statement on the surveillance of patients with gastrointestinal malignancies.

BACKGROUND: Improvements in early detection, screening and treatment of cancer have resulted in a significant improvement in cancer mortality and an increase in the number of cancer survivors globally. Accordingly, a significant rise in the number of cancer survivors in Ireland has been observed. The surveillance of survivors of gastrointestinal malignancies in Ireland is heterogeneous and represents an unmet need for standardisation. AIMS: There are currently no national guidelines in Ireland to guide follow-up practices for these patients. The aim of this study was to establish homogeneity nationally with respect to follow-up of these patients by medical oncologists. METHODS/RESULTS: A consensus group consisting of Irish oncologists with an interest in gastrointestinal malignancies was created to address this issue, and determined that it would be reasonable to adopt the NCCN guidelines for this purpose, but that this recommendation would not be prescriptive, and should be individualised to each patient. CONCLUSION: We hope that this initiative may help to homogenise survivorship practices in this cohort of Irish patients, and may support the implementation of survivorship initiatives by the National Cancer Control Programme (NCCP).

Economic evaluation of the Happy Talk pilot effectiveness trial: A targeted selective speech, language and communication intervention for children from areas of social disadvantage.

Purpose: This study presents a cost-effectiveness analysis of a targeted selective pre-school intervention programme, "Happy Talk", which focuses on language development, by simultaneously enhancing parental interaction and the pre-school environment.Method: Happy Talk (delivered to 77 children) is an add on intervention, and is compared to usual care, adopting a healthcare perspective. Cost-effectiveness analyses were carried out using the Pre-school Language Scale 5- Total (PLS-5) for baseline analysis and the Child Health Utility Instrument (CHU9D) in a secondary analysis.Result: Baseline cost-effectiveness analysis showed Happy Talk was more effective (6.3 point change in total PLS-5 standard score - effect size 0.463SD and more expensive (€82.06) than usual care (cost-effectiveness ratio is €13.02 per unit change). Employing a proxy to estimate monetary net benefit, the benefits outweigh the costs, showing that it is cost-effective. However, results do not persist when health-related quality of life outcome measures are considered.Conclusion: Findings suggest a targeted selective public health approach, could be considered value for money to reduce the societal burden of children with low levels of speech, language and communication. However, measurement of longer term outcomes and a larger trial are required, to definitively inform policy changes.

Chemotherapy Toxicity in Older Adults Optimized by Geriatric Assessment and Intervention: A Non-Comparative Analysis.

The Comprehensive Geriatric Assessment (CGA) is recommended to guide treatment choices in older patients with cancer. Patients ≥ 70 years referred to our oncology service with a new cancer diagnosis are screened using the G-8. Patients with a score of ≤14 are eligible to attend the Geriatric Oncology and Liaison (GOAL) Clinic in our institution, with referral based on physician discretion. Referred patients undergo multidimensional assessments at baseline. CGA domains assessed include mobility, nutritional, cognitive, and psychological status. Chemotherapy toxicity risk is estimated using the Cancer Aging and Research Group (CARG) calculator. We undertook a retrospective analysis of patients attending the GOAL clinic over a 30-month period to April 2021. The objective was to determine rates of treatment dose modifications, delays, discontinuation, and unscheduled hospitalizations as surrogates for cytotoxic therapy toxicity in these patients. These data were collected retrospectively. Ninety-four patients received chemotherapy; the median age was 76 (70-87) and 45 were female (48%). Seventy-five (80%) had an ECOG PS of 0-1. Seventy-two (77%) had gastrointestinal cancer, and most had stage III (47%) or IV (40%) disease. Chemotherapy with curative intent was received by 51% (n = 48) and 51% received monotherapy. From the CGA, the median Timed Up and Go was 11 s (7.79-31.6), and 90% reported no falls in the prior 6 months. The median BMI was 26.93 (15.43-39.25), with 70% at risk or frankly malnourished by the Mini Nutritional Assessment. Twenty-seven (29%) patients had impaired cognitive function. Forty-three (46%) had a high risk of toxicity based on the baseline CARG toxicity calculator. Twenty-six (28%) required dose reduction, 55% (n = 52) required a dose delay, and 36% (n = 34) had a hospitalization due to toxicity. Thirty-nine patients (42%) discontinued treatment due to toxicity. Despite intensive assessment, clinical optimization and personalized treatment decisions, older adults with cancer remain at high risk of chemotherapy toxicity.

The Uptake and Efficacy of Neoadjuvant Therapy in Older Adults with Locally Advanced Esophogastric Cancer.

BACKGROUND: Data on Neo+/- adjuvant treatment in older patients with cancer is sparse. The management of locally advanced esophagogastric cancer (LAEC) in older patients was evaluated to determine treatment modalities and identify factors associated with survival. METHODS: Patients diagnosed with LAEC (stage II or III) over 5 years were identified from the National Cancer Registry of Ireland. Treatment was classified as "best supportive care (BSC)," "surgery only," "neo/adjuvant treatment," and "chemo/radiation alone."Survival was assessed. Univariate and multivariate analysis (MVA) of clinicopathological factors and treatment was conducted. RESULTS: Forty-six percent (n = 580) of the 1251 patients were ≥ 70 years, 11% (n = 134) received BSC, 23% (n = 288) surgery only, 31% (n = 390) had chemo/radiation alone, and 35% (n = 439) had neo/adjuvant treatment. Forty-six percent, 10%, and 0% of patients < 75, ≥ 75, and ≥ 80 years of age, respectively, received neoadjuvant treatment. Age was associated with treatment received (p < 0.001). Older patients were less likely to receive neo/adjuvant treatment, surgery, and any treatment. Median survival (OS) decreased with age (< 70 years: 23 months; 70-74: 19 months; 75-79: 13 months; ≥ 80 years: 10 months). In MVA, older age, smoking, later stage, and higher grade were significantly associated with a higher risk of death. Patients receiving neo/adjuvant treatment had lower risk of death than any other treatment group regardless of age. CONCLUSION: Older patients were less likely to receive treatment for LAEC than younger patients. Patients aged ≥ 70 years benefit from neo/adjuvant treatment. Prospective clinical trials focusing on older patients and incorporating life expectancy, comorbidities, and geriatric assessment are needed to guide treatment.