External validation and diagnostic value of the Elderly Functional Index version 2.0 for assessing functional status and frailty in older Danish patients with gastrointestinal cancer receiving chemotherapy: A prospective, clinical study.

INTRODUCTION: Patient perspectives on functioning are often overlooked in oncology practice. This study externally validates the ELderly Functional Index (ELFI), a patient-reported measure for assessing multidimensional functioning, in older patients with gastrointestinal cancer receiving chemotherapy. The study compares ELFI scoring methods, evaluates its diagnostic value with geriatric oncology tools, and proposes a cut-off point for clinical use. MATERIALS AND METHODS: Danish patients aged ≥70 years with gastrointestinal cancer undergoing chemotherapy from a prospective, observational study were included. Two ELFI scoring methods, item-based and domain-based, were compared. Internal consistency reliability, validity, and correlations between ELFI, its component scales, and measures of functioning/frailty (including Eastern Cooperative Oncology Group Performance Status [ECOG-PS], Geriatric-8 [G8], Vulnerable Elders Survey-13 [VES-13], Timed-Up-and-Go [TUG], and 30-s chair stand test [30CST]) were investigated. Sensitivity and specificity analyses evaluated the ability of ELFI to predict frailty outcomes and identified frailty thresholds. Receiver operating characteristic analyses assessed the diagnostic ability of ELFI, alongside other measures, for oncological outcomes and frailty differentiation. Equipercentile equating methods enabled ECOG-PS, ELFI, and G8 mapping. RESULTS: One hundred fifty-four patients (median age 73.5 years, range 70-85) undergoing curative- or palliative-intent chemotherapy (49%) were included. ELFI demonstrated good internal consistency (Cronbach's alpha = 0.82) and acceptable convergent, structural, and discriminant validity. ELFI showed moderate to very strong correlations with its component scales (r = 0.40-0.93), and weaker correlations with frailty measures (r = 0.02-0.60). ELFI score < 80 indicated frailty risk, with almost fivefold risk of ECOG-PS 2 at follow-up (odds ratio[OR] = 4.8, 95% confidence interval [CI] 1.4-15.9), and predicted G8, VES-13, TUG, and 30CST frailty at follow-up, not completing planned chemotherapy (OR = 3.1; 95%CI 1.5-6.2), mono-therapy (OR = 3.5; 95%CI 1.5-8.1), initial dose reduction (OR = 4.9; 95%CI 2.0-12.1), and shorter overall survival (hazard ratio = 2.0, 95%CI 1.4-3.0). A preliminary crosswalk between ECOG-PS, ELFI, and G8 was established. DISCUSSION: ELFI was validated as a concise patient-reported measure of functional status in older patients with cancer and its relationship to frailty. ELFI demonstrated comparable predictive ability to other tools for oncological outcomes. Both scoring methods yielded similar results, with the domain-based method (ELFI v2.0) endorsed for consistency. ELFI v2.0 score of 80 was suggested as the frailty threshold in this population, supporting its clinical utility.

The effect of comprehensive geriatric assessment on care received, treatment completion, toxicity, cancer-related and geriatric assessment outcomes, and quality of life for older adults receiving systemic anti-cancer treatment: A systematic review.

INTRODUCTION: This systematic review aims to summarise the available literature on the effect of geriatric assessment (multidimensional health assessment across medical, social, and functional domains; "GA") or comprehensive geriatric assessment (geriatric assessment with intervention or management recommendations; "CGA") compared to usual care for older adults with cancer on care received, treatment completion, adverse treatment effects, survival and health-related quality of life. MATERIALS AND METHODS: A systematic search of MEDLINE, EMBASE, CINAHL, and PubMed was conducted to identify randomised controlled trials or prospective cohort comparison studies on the effect of GA/CGA on care received, treatment, and cancer outcomes for older adults with cancer. RESULTS: Ten studies were included: seven randomised controlled trials (RCTs), two phase II randomised pilot studies, and one prospective cohort comparison study. All studies included older adults receiving systemic therapy, mostly chemotherapy, for mixed cancer types (eight studies), colorectal cancer (one study), and non-small cell lung cancer (one study). Integrating GA/CGA into oncological care increased treatment completion (three of nine studies), reduced grade 3+ chemotherapy toxicity (two of five studies), and improved quality of life scores (four of five studies). No studies found significant differences in survival between GA/CGA and usual care. GA/CGA incorporated into care decisions prompted less intensive treatment and greater non-oncological interventions, including supportive care strategies. DISCUSSION: GA/CGA integrated into the care of an older adult with cancer has the potential to optimise care decisions, which may lead to reduced treatment toxicity, increased treatment completion, and improved health-related quality of life scores.

Implementation of a referral pathway for cancer survivors to access allied health services in the community.

BACKGROUND: The growing demands for multidisciplinary cancer survivorship care require new approaches to address the needs of people living after a cancer diagnosis. Good Life-Cancer Survivorship is a self-management support survivorship program delivered by community allied health (AH) services for people diagnosed with cancer. A pilot study established the benefits of Good Life-Cancer Survivorship to help survivors manage their health and wellbeing in the community health setting. This study expanded the program to four community health services and evaluated the implementation outcomes of the referral pathway to the survivorship program. METHODS: Eligible cancer survivors attending hospital oncology services were referred to the survivorship program. Data was collected between 19/02/2021-22/02/2022 and included allied health service utilisation, consumer surveys, and interviews to understand consumer experience with the referral pathway. Interviews and focus groups with hospital and community health professionals explored factors influencing the referral uptake. Implementation outcomes included Adoption, Acceptability, Appropriateness, Feasibility, and Sustainability. RESULTS: Of 35 eligible survivors (mean age 65.5 years, SD = 11.0; 56% women), 31 (89%) accepted the referral. Most survivors had two (n = 14/31; 45%) or more (n = 11/31; 35%) allied health needs. Of 162 AH appointments (median appointment per survivor = 4; range = 1-15; IQR:5), 142/162 (88%) were scheduled within the study period and 126/142 (89%) were attended. Consumers' interviews (n = 5) discussed the referral pathway; continuation of survivorship care in community health settings; opportunities for improvement of the survivorship program. Interviews with community health professionals (n = 5) highlighted the impact of the survivorship program; cancer survivorship care in community health; sustainability of the survivorship program. Interviews (n = 3) and focus groups (n = 7) with hospital health professionals emphasised the importance of a trusted referral process; a holistic and complementary model of care; a person-driven process; the need for promoting the survivorship program. All evaluations favourably upheld the five implementation outcomes. CONCLUSIONS: The referral pathway provided access to a survivorship program that supported survivors in self-management strategies through tailored community allied health services. The referral pathway was well adopted and demonstrated acceptability, appropriateness, and feasibility. This innovative care model supports cancer survivorship care delivery in community health settings, with clinicians recommending sustaining the referral pathway.

Integrated Geriatric Assessment and Treatment Effectiveness (INTEGERATE) in older people with cancer starting systemic anticancer treatment in Australia: a multicentre, open-label, randomised controlled trial.

BACKGROUND: The effectiveness of comprehensive geriatric assessment (CGA) in improving health outcomes in cancer settings is unclear. We evaluated whether CGA can improve health-related quality of life (HRQOL) in older people with cancer who are starting systemic anticancer treatment. METHODS: INTEGERATE is a multicentre, open-label, pragmatic, parallel-group, randomised controlled trial that was done at three hospitals in Australia. Participants aged 70 years and older with solid cancer or diffuse large B-cell lymphoma planned for chemotherapy, targeted therapy, or immunotherapy, were randomly assigned (1:1; using a central computer-generated minimisation algorithm with a random element, balancing treatment intent, cancer type, age, sex, and performance status) to receive CGA integrated into oncology care (integrated oncogeriatric care) or usual care only. Group assignment was not concealed from the participants and clinicians. The primary outcome was HRQOL over 24 weeks, assessed at baseline, week 12, week 18, and week 24, using the Elderly Functional Index (ELFI; score range 0-100). Analyses were by intention to treat. The trial is registered with ANZCTR.org.au, ACTRN12614000399695, and is completed. FINDINGS: Between Aug 18, 2014, and Sept 5, 2018, 154 participants were randomly assigned to integrated oncogeriatric care (n=76) or usual care (n=78). 13 participants died by week 12 and 130 (92%) of the remaining 141 participants completed two or more ELFI assessments. Participants assigned to integrated oncogeriatric care reported better adjusted ELFI change scores over 24 weeks compared with those in the usual care group (overall main effect of group: t=2·1, df=213, p=0·039; effect size=0·38), with maximal between-group differences at week 18 (mean difference in change 9·8 [95% CI 2·4-17·2]; p=0·010, corrected p=0·030, effect size=0·48). The integrated oncogeriatric care group also had significantly fewer unplanned hospital admissions at 24 weeks (multivariable-adjusted incidence rate ratio 0·60 [95% CI 0·42-0·87]; p=0·0066). No statistically significant between-group difference was observed in overall survival. INTERPRETATION: CGA led to better quality of life and health-care delivery in older people receiving systemic anticancer treatment. Routine CGA-based interventions should be considered in at-risk older people starting systemic anticancer treatment. FUNDING: National Health and Medical Research Council (Australia), Monash University, and Eastern Health.

Exercise as a supportive care strategy in men with prostate cancer receiving androgen deprivation therapy at a regional cancer centre: a survey of patients and clinicians.

PURPOSE: To understand how frequently exercise is discussed and/or prescribed as a supportive care measure and the barriers and facilitators to exercise uptake for men with prostate cancer receiving androgen deprivation therapy (ADT) at a regional cancer centre. METHODS: An observational, cross-sectional study was conducted at a regional cancer centre in three stages: (1) Retrospective chart review of men with prostate cancer undergoing ADT to identify the frequency of discussion and/or prescription of supportive care measures; (2) prospective patient survey exploring barriers and facilitators to exercise; and (3) prospective clinician survey exploring barriers, facilitators and awareness of exercise guidelines in men with prostate cancer. RESULTS: Files of 100 men receiving ADT (mean age 73 years; mean ADT duration =12 months) in the medical oncology (n = 50) and radiation oncology (n = 50) clinics were reviewed. Exercise was discussed with 16% of patients and prescribed directly to 5%. Patient survey (n = 49). 44.2% of patients reported participating in exercise at a high level. Common barriers to exercise participation included fatigue (51.0%), cancer/treatment-related weakness (46.9%) and joint stiffness (44.9%). 36.7% of patients reported interest in a supervised exercise program. Clinician survey (n = 22). 36.4% identified one or more exercise guidelines, and 40.9% correctly identified national exercise guidelines. Clinicians reported low knowledge of referral pathways to a supervised exercise program (27.3%). Clinicians believe physiotherapists (95.5%) are most suited to exercise prescription and 72.7% stated that exercise counselling should be part of supportive care. Limited time (63.6%) and patient safety (59.1%) were the two most common barriers to discussing exercise with patients. Clinicians reported that only 21.9% of their patients asked about exercise. The most endorsed facilitators to increase exercise uptake were patient handouts (90.9%) and integration of exercise specialists into the clinical team (86.4%). CONCLUSION: Despite a third of patient respondents indicating an interest in a supervised exercise program, only 16% of patients with prostate cancer undergoing ADT at a regional cancer centre engaged in a discussion about exercise with their treating clinicians. Physical limitations and fatigue were the greatest barriers for patients. Clinicians indicated a need for more clinician education and better integration of exercise specialists into clinical care. A tailored, integrated approach is needed to improve the uptake of exercise in men with prostate cancer.

Cognitive Assessment Tools Recommended in Geriatric Oncology Guidelines: A Rapid Review.

Cognitive assessment is a cornerstone of geriatric care. Cognitive impairment has the potential to significantly impact multiple phases of a person's cancer care experience. Accurately identifying this vulnerability is a challenge for many cancer care clinicians, thus the use of validated cognitive assessment tools are recommended. As international cancer guidelines for older adults recommend Geriatric Assessment (GA) which includes an evaluation of cognition, clinicians need to be familiar with the overall interpretation of the commonly used cognitive assessment tools. This rapid review investigated the cognitive assessment tools that were most frequently recommended by Geriatric Oncology guidelines: Blessed Orientation-Memory-Concentration test (BOMC), Clock Drawing Test (CDT), Mini-Cog, Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Short Portable Mental Status Questionnaire (SPMSQ). A detailed appraisal of the strengths and limitations of each tool was conducted, with a focus on practical aspects of implementing cognitive assessment tools into real-world clinical settings. Finally, recommendations on choosing an assessment tool and the additional considerations beyond screening are discussed.

Methods for frailty screening and geriatric assessment in older adults with cancer.

PURPOSE OF REVIEW: This review highlights the latest development in the use of geriatric assessment(GA) and frailty assessment for older adults with cancer. RECENT FINDINGS: From 2019, there were six large randomized controlled trials (RCTs) completed of GA for older adults with cancer, as well as several studies of frailty screening tools. SUMMARY: The findings in this review highlight the benefits of implementing GA, followed by interventions to address the identified issues (GA -guided interventions). Four of six RCTs that implemented GA for older adults with cancer showed positive impact on various outcomes, including treatment toxicity and quality of life. GA implementation varied significantly between studies, from oncologist acting on GA summary, geriatrician comanagement, to full GA by a multidisciplinary team. However, there were several barriers reported to implementing GA for all older adults with cancer, such as access to geriatrics and resource issues. Future research needs to elucidate how to best operationalize GA in various cancer settings. The authors also reviewed frailty screening tools and latest evidence on their use and impact.

Screening Tools for Identifying Older Adults With Cancer Who May Benefit From a Geriatric Assessment: A Systematic Review.

IMPORTANCE: Older adults with cancer are at risk of overtreatment or undertreatment when decision-making is based solely on chronological age. Although a geriatric assessment is recommended to inform care, the time and expertise required limit its feasibility for all patients. Screening tools offer the potential to identify those who will benefit most from a geriatric assessment. Consensus about the optimal tool to use is lacking. OBJECTIVE: To appraise the evidence on screening tools used for older adults with cancer and identify an optimal screening tool for older adults with cancer who may benefit from geriatric assessment. EVIDENCE REVIEW: Systematic review of 4 databases (MEDLINE, Embase, CINAHL [Cumulative Index to Nursing and Allied Health Literature], and PubMed) with narrative synthesis from January 1, 2000, to March 14, 2019. Studies reporting on the diagnostic accuracy and use of validated screening tools to identify older adults with cancer who need a geriatric assessment were eligible for inclusion. Data were analyzed from March 14, 2019, to March 23, 2020. FINDINGS: Seventeen unique studies were included, reporting on the use of 12 screening tools. Most studies were prospective cohort studies (n = 11) with only 1 randomized clinical trial. Not all studies reported time taken to administer the screening tools. The Geriatric-8 (G8) (n = 12) and the Vulnerable Elders Survey-13 (VES-13) (n = 9) were the most frequently evaluated screening tools. The G8 scored better in sensitivity and the VES-13 in specificity. Other screening tools evaluated include the Groningen Frailty Index, abbreviated comprehensive geriatric assessment, and Physical Performance Test in 2 studies each. All other screening tools were evaluated in 1 study each. CONCLUSIONS AND RELEVANCE: To date, the G8 and VES-13 have the most evidence to recommend their use to inform the need for geriatric assessment. When choosing a screening tool, clinicians will need to weigh the tradeoffs between sensitivity and specificity. Future research needs to further validate or improve current screening tools and explore other factors that can influence their use, such as ease of use and resourcing.

The Elderly Functional Index (ELFI), a patient-reported outcome measure of functional status in patients with cancer: a multicentre, prospective validation study.

BACKGROUND: Functional assessment of patients with cancer can be challenging and is often undertaken by the clinician with minimal direct input from the patient. We developed and aimed to validate the Elderly Functional Index (ELFI), a composite measure of self-reported functioning in older patients with cancer. METHODS: In this multicentre, prospective validation study, we validated ELFI in adult patients attending five oncology practices in Australia. ELFI is a 12-item composite measure of self-reported functioning derived from functional scales of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ): physical, role, and social functioning, and mobility. For evaluation of validity and internal consistency, participants self-completed ELFI, cognitive functioning and emotional functioning scales of the EORTC QLQ Core-30, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), instrumental activities of daily living (IADL), and Clinical Frailty Scale (CFS) at baseline. For evaluation of test-retest reliability, participants opted in to repeat ELFI, cognitive functioning scale, emotional functioning scale, and ECOG-PS 1 week later, as well as completing the Global Rating of Change. Internal consistency reliability was assessed using Cronbach's α and test-retest reliability was assessed using intraclass correlation (ICC). We assessed ELFI for convergent and discriminant validity (Spearman's r), known-groups validity (ANOVA), and structural validity (exploratory factor analysis). FINDINGS: Between May 6 and Dec 15, 2017, 877 participants with cancer returned a total of 869 baseline questionnaires and 482 retest questionnaires. 621 (71%) participants (192 [31%] aged ≥70 years) were included in evaluations of validity and internal consistency and 278 (32%) participants (106 [38%] aged ≥70 years) in evaluations of test-retest reliability. ELFI demonstrated excellent internal consistency reliability (Cronbach's α=0·93 for all participants; p<0·0001) and test-retest reliability (overall ICC 0·90, 95% CI 0·87-0·92; p<0·0001). Hypotheses regarding convergent and discriminant validity were confirmed, with all item-scale correlations exceeding 0·40 except for one on the physical functioning scale. ELFI was better than its component scales and other function measures at differentiating between groups with different function and frailty scores (known-groups validity). Exploratory factor analysis provided empirical support to the structural validity of ELFI. Strong correlation was observed between ELFI and its component scales (r ranging from 0·67 to 0·79), ECOG-PS (-0·79), IADL (0·69), and CFS (-0·73). INTERPRETATION: ELFI is a validated and simple person-reported multidimensional measure of functional status, which captures broad dimensions of functioning. ELFI has enhanced statistical efficiency relative to its components, reducing the sample size required to detect a given effect. ELFI could be used as a clinical trial endpoint to assess functional domains of health-related quality of life. FUNDING: National Health and Medical Research Council, Monash University, Eastern Health.

Anthracycline-related cardiotoxicity in older patients with acute myeloid leukemia: a Young SIOG review paper.

The incidence of acute myeloid leukemia (AML) increases with age. Intensive induction chemotherapy containing cytarabine and an anthracycline has been part of the upfront and salvage treatment of AML for decades. Anthracyclines are associated with a significant risk of cardiotoxicity (especially anthracycline-related left ventricular dysfunction [ARLVD]). In the older adult population, the higher prevalence of cardiac comorbidities and risk factors may further increase the risk of ARLVD. In this article of the Young International Society of Geriatric Oncology group, we review the prevalence of ARLVD in patients with AML and factors predisposing to ARLVD, focusing on older adults when possible. In addition, we review the assessment of cardiac function and management of ARLVD during and after treatment. It is worth noting that only a minority of clinical trials focus on alternative treatment strategies in patients with mildly declined left ventricular ejection fraction or at a high risk for ARLVD. The limited evidence for preventive strategies to ameliorate ARLVD and alternative strategies to anthracycline use in the setting of cardiac comorbidities are discussed. Based on extrapolation of findings from younger adults and nonrandomized trials, we recommend a comprehensive baseline evaluation of cardiac function by imaging, cardiac risk factors, and symptoms to risk stratify for ARLVD. Anthracyclines remain an appropriate choice for induction although careful risk-stratification based on cardiac disease, risk factors, and predicted chemotherapy-response are warranted. In case of declined left ventricular ejection fraction, alternative strategies should be considered.

Arti Hurria and the progress in integrating the geriatric assessment into oncology: Young International Society of Geriatric Oncology review paper.

Until recently, the progress in the diagnosis and management of cancer has not been matched by similar progress in the assessment of the increasing numbers of older and more complex patients with cancer. Dr. Arti Hurria identified this gap at the outset of her career, which she dedicated toward studying the geriatric assessment (GA) as an improvement over traditional methods used in oncology to assess vulnerability in older patients with cancer. This review documents the progress of the GA and its integration into oncology. First, we detail the GA's origins in the field of geriatrics. Next, we chronicle the early rise of geriatric oncology, highlighting the calls of early thought-leaders to meet the demands of the rapidly aging cancer population. We describe Dr. Hurria's early efforts toward meeting these calls though the implementation of the GA in oncology research. We then summarize some of the seminal studies constituting the evidence base supporting GA's implementation. Finally, we lay out the evolution of cancer-focused guidelines recommending the GA, concluding with future needs to advance the next steps toward more widespread implementation in routine cancer care. Throughout, we describe Dr. Hurria's vision and its execution in driving progress of the GA in oncology, from her fellowship training to her co-authored guidelines recommending GA for all older adults with cancer-published in the year of her untimely death.

A model of cancer survivorship care within a community health setting: the Good Life Cancer Survivorship program.

PURPOSE: This study aimed to establish and evaluate the referral pathway from a hospital-based oncology service to a multidisciplinary community-based health service supporting survivors to engage in self-management. METHOD: The evaluation involved understanding patterns of health service utilisation and health professionals' perspectives on the implementation of the community-based model of survivorship care, the Good Life Cancer Survivorship (GLCS) program. Survivors referred to GLCS were undergoing or had completed cancer treatment and unable to participate in intensive ambulatory oncology rehabilitation. Health service utilisation was tracked over 5 months, and the perspectives of health professionals referring to and involved in the GLCS program were recorded using semi-structured interviews. RESULTS: The oncology service made 25 referrals. The most accessed services at Carrington Health were physiotherapy with 18 appointments, followed by psychology (12) and dietitian services (11). Four themes emerged from the interviews: (1) Allied health services are relevant to people with cancer; (2) Education and information needs; (3) Communication gaps; (4) A one-stop multidisciplinary and holistic care model. CONCLUSION: This project demonstrated that community health may be a valid setting to support cancer survivors in managing their health. Supporting ongoing awareness, education and understanding of services across both community and acute care settings will foster care coordination and strengthen referral pathways. IMPLICATIONS FOR CANCER SURVIVORS: Accessing appropriate community-based allied health services can support cancer survivors in developing self-management skills to manage their own health and improve their health outcomes and wellbeing in the survivorship phase.

Utilisation of geriatric assessment in oncology - a survey of Australian medical oncologists.

INTRODUCTION: Geriatric assessment (GA) is a multidimensional health assessment of the older person to evaluate their physical and cognitive function, comorbidities, nutrition, medications, psychological state, and social supports. GA may help oncologists optimise care for older patients with cancer. The aim of this study was to explore the views of Australian medical oncologists regarding the incorporation of geriatric screening tools, GA and collaboration with geriatricians into routine clinical practice. METHODS: Members of the Medical Oncology Group of Australia were invited to complete an online survey that evaluated respondent demographics, practice characteristics, treatment decision-making factors, use of GA, and access to geriatricians. RESULTS: Sixty-nine respondents identified comorbidities, polypharmacy, and poor functional status as the most frequent challenges in caring for older patients with cancer. Physical function, social supports and nutrition were the most frequent factors influencing treatment decision-making. The majority of respondents perceived value in GA and geriatrician review, although access was a barrier for referral. Such services would need to be responsive, providing reports within two weeks for the majority of respondents. CONCLUSION: Despite an emerging evidence base for the potential benefits of GA and collaboration with geriatricians, medical oncologists reported a lack of access but a desire to engage with these services.

Dementia with Lewy bodies presenting as probable epileptic seizure.

We discuss the case of an 83-year-old man admitted to the hospital after losing control of his vehicle due to an unexplained episode of altered consciousness. This occurred on a background of multiple similar episodes associated with acute confusion, superimposed on a gradual cognitive decline spanning 6 years. Organic aetiologies for delirium were excluded and CT and MRI of the brain were negative for cerebrovascular accidents or other epileptogenic foci. Electroencephalogram (EEG) was negative for epileptiform activity. A diagnosis of seizure in the setting of dementia with Lewy bodies (DLB) was deemed probable. Subsequent brain single-photon emission computed tomography (SPECT) and flurodeoxy glucose-positron emission tomography (FDG-PET) studies supported the underlying diagnosis of DLB. Acute changes in consciousness or cognition are often related to strokes or seizures in the older person. As illustrated in this case, however, it is important to consider alternative comorbidities that may coexist.

Multidisciplinary Prognostication Using the Palliative Prognostic Score in an Australian Cancer Center.

CONTEXT: Accurate prognostication is important in oncology and palliative care. A multidisciplinary approach to prognostication provides a novel approach, but its accuracy and application is poorly researched. In this study, we describe and analyze our experience of multidisciplinary prognostication in palliative care patients with cancer. OBJECTIVES: To assess our accuracy of prognostication using multidisciplinary team prediction of survival (MTPS) alone and within the Palliative Prognostic (PaP) Score. METHODS: This retrospective study included all new patients referred to a palliative care consultation service in a tertiary cancer center between January 2010 and December 2011. Initial assessment data for 421 inpatients and 223 outpatients were analyzed according to inpatient and outpatient groups to evaluate the accuracy of prognostication using MTPS alone and within the PaP score (MTPS-PaP) and their correlation with overall survival. RESULTS: Inpatients with MTPS-PaP group A, B, and C had a median survival of 10.9, 3.4, and 0.7 weeks, respectively, and a 30-day survival probability of 81%, 40%, and 10%, respectively. Outpatients with MTPS-PaP group A and B had a median survival of 17.3 and 5.1 weeks, respectively, and a 30-day survival probability of 94% and 50%, respectively. MTPS overestimated survival by a factor of 1.5 for inpatients and 1.2 for outpatients. The MTPS-PaP score correlated better than MTPS alone with overall survival. CONCLUSION: This study suggests that a multidisciplinary team approach to prognostication within routine clinical practice is possible and may substitute for single clinician prediction of survival within the PaP score without detracting from its accuracy. Multidisciplinary team prognostication can assist treating teams to recognize and articulate prognosis, facilitate treatment decisions, and plan end-of-life care appropriately. PaP was less useful in the outpatient setting, given the longer survival interval of the outpatient palliative care patient group.

Candidate tumor-suppressor genes on chromosome arm 8p in early-onset and high-grade breast cancers.

Loss of genetic material from chromosome arm 8p occurs commonly in breast carcinomas, suggesting that this region is the site of one or more tumor-suppressor genes (TSGs). Comparative genomic hybridization analysis showed that 8p loss is more common in breast cancers from pre-menopausal compared with post-menopausal patients, as well as in high-grade breast cancers, regardless of the menopausal status. Subsequent high-resolution gene expression profiling of genes mapped to chromosome arm 8p, on an extended cohort of clinical tumor samples, indicated a similar dichotomy of breast cancer clinicopathologic types. Some of these genes showed differential downregulation in early-onset and later-onset, high-grade cancers compared with lower-grade, later-onset cancers. Three such genes were analysed further by in situ technologies, performed on tissue microarrays representing breast tumor and normal tissue samples. PCM1, which encodes a centrosomal protein, and DUSP4/MKP-2, which encodes a MAP kinase phosphatase, both showed frequent gene and protein loss in carcinomas. In contrast, there was an excess of cases showing loss of expression in the absence of reduced gene copy number of SFRP1, which encodes a dominant-negative receptor for Wnt-family ligands. These candidate TSGs may constitute some of the molecular drivers of chromosome arm 8p loss in breast carcinogenesis.

Detailed gene copy number and RNA expression analysis of the 17q12-23 region in primary breast cancers.

Chromosome region 17q12-23 commonly shows an increase in DNA copy number in breast cancers, suggesting that several oncogenes are located at this site. We performed a high-resolution expression array and comparative genomic hybridization analysis of genes mapped to the entire 17q12-23 region, to identify novel candidate oncogenes. We identified 24 genes that showed significant overexpression in breast cancers with gain of 17q12-23, compared to cancers without gain. These genes included previously identified oncogenes, together with several novel candidate oncogenes. FISH analysis using specific gene probes hybridized to tissue arrays confirmed the underlying amplification of overexpressed genes. This high-resolution analysis of the 17q12-23 region indicates that several established and novel candidate oncogenes, including a Wnt-signaling pathway member, are amplified and overexpressed within individual primary breast cancer samples. We were also able to confirm the presence of two apparently separate and reciprocally amplified groups of genes within this region. Investigation of these genes and their functional interactions will facilitate our understanding of breast oncogenesis and optimal management of this disease.