The emerging predictive and prognostic role of HER2 in HER2-negative early breast cancer: a retrospective study.

PURPOSE: Many patients with early breast cancer (eBC) undergoing neoadjuvant chemotherapy do not achieve pathological complete response (pCR), which is a prognostic factor. We examined the role of HER2-low expression in predicting pCR and prognosis in HER2-negative eBC. METHODS: We evaluated patients with stage I-III HER2-negative BC, treated between 2013 and 2023 at The Royal Marsden NHS Foundation Trust, London. Tumors were classified based on estrogen receptor (ER) status and into HER2-low and HER2-zero subgroups. We analyzed pCR rates, relapse-free survival (RFS) and overall survival (OS). RESULTS: 754 patients were included in the analysis. pCR rate was 8.9% in the ER+ /HER2-low, 16.5% in the ER+ /HER2-zero, 38.9% in the ER- ER-/HER2-low and 35.9% in the ER-/HER2-zero eBC (p < 0.001). Multivariable analysis showed a significantly lower pCR rate in HER2-low compared to HER2-zero BC in the ER+ subgroup. At a median follow-up of 63.8 months (59.9-67.4), we observed longer OS in HER2-low compared to HER2-zero patients in the overall and in the ER+ population. There was no predictive or prognostic impact of HER2-low status in the ER- population. CONCLUSION: This study supports the interpretation of HER2 status as a possible prognostic and predictive biomarker for HER2-negative eBC, especially among patients with ER+ disease.

Implementation of a geriatric oncology service at the Royal Marsden Hospital.

INTRODUCTION: Despite significant evidence supporting the benefits of comprehensive oncogeriatric assessment in the management of older patients with cancer, the adoption of specialised geriatric oncology programs in the United Kingdom remains limited. Descriptions of clinic structure and models, patient demographics and baseline characteristics, resource utilisation, and predictors of resource utilisation are lacking in this population, which may complicate or impede the planning, resourcing, and development of further services in this subspecialty on a national and regional basis. MATERIALS AND METHODS: Between November 2021 and April 2023, 244 patients commencing systemic anticancer treatment at the Royal Marsden Hospital, London underwent geriatric screening using the Senior Adult Oncology Programme-3 (SAOP3) screening tool. Baseline clinical factors (sex, age, Charlson Comorbidity Index score, Cumulative Illness Rating Scale-Geriatric [CIRS-G] score, Katz Index score, Barthel Index score, treatment intent, and Eastern Cooperative Oncology Group Performance Status [ECOG-PS]) were assessed as predictors of geriatric impairments and need for multidisciplinary referral and intervention using a negative binomial regression analysis. Referral rates to multidisciplinary teams were assessed against ECOG-PS score using point-biserial correlation, as well as against a historical control using descriptive statistics. RESULTS: The median age of participants was 77; 75.8% were female. Breast cancer was the most prevalent diagnosis (61.9%). Most patients (67.6%) were undergoing treatment in the palliative setting. Two hundred eleven (86.5%) patients were identified as having at least one geriatric impairment. Six hundred forty-nine multidisciplinary referrals were made, of which 583 (86.7%) were accepted by the referred patient. Higher ECOG PS was positively associated with geriatric impairments in physiotherapy, occupational therapy, dietetics, pharmacy, and welfare rights domains, as well as with the overall number of geriatric impairments. DISCUSSION: The Royal Marsden Senior Adult Oncology Programme represents the first geriatric oncology service in a tertiary cancer centre in the United Kingdom. Following implementation of SAOP3 screening, we observed a substantial increase in referrals to all multidisciplinary teams, suggestive of previously underrecognized needs among this population. The need for multidisciplinary intervention was strongly correlated with baseline ECOG-PS score, but not with other measured clinical variables, including comorbidity or functional indices.

Geriatric Oncology as an Unmet Workforce Training Need in the United Kingdom-A Narrative Review by the British Oncology Network for Undergraduate Societies (BONUS) and the International Society of Geriatric Oncology (SIOG) UK Country Group.

Cancer is a disease associated with ageing. Managing cancer in older adults may prove challenging owing to pre-existing frailty, comorbidity, and wider holistic needs, as well as the unclear benefits and harms of standard treatment options. With the ongoing advances in oncology and the increasing complexity of treating older adults with cancer, the geriatric oncology field must be a priority for healthcare systems in education, research, and clinical practice. However, geriatric oncology is currently not formally taught in undergraduate education or postgraduate training programmes in the United Kingdom (UK). In this commentary, we outline the landscape of geriatric oncology undergraduate education and postgraduate training for UK doctors. We highlight current challenges and opportunities and provide practical recommendations for better preparing the medical workforce to meet the needs of the growing population of older adults with cancer. This includes key outcomes to be considered for inclusion within undergraduate and postgraduate curricula.

Reporting of older subgroups in registration breast cancer trials 2012-2021.

INTRODUCTION: Adequate reporting of data specific to older populations enrolled to breast cancer trials is critical, given the high incidence of the disease among this demographic. This study aimed to examine the completeness of reporting of older subgroups among patients recruited to registration clinical trials investigating systemic treatments for breast cancer. METHODS: Clinical trials leading to a US food and drug administration (FDA) approval in breast cancer between 2012 and 2021 were included. Primary study reports and and all available secondary publications were systematically and objectively assessed with regard to the availability of data regarding efficacy, baseline characteristics, safety, and health-related quality of life (HRQOL) outcomes among older subgroups. RESULTS: 27 trials and 216 publications were assessed. 20.3% of patients were aged ≥65. 70.0% of patients had an eastern cooperative oncology group (ECOG) performance status of 0. Although complete reporting of primary endpoints was adequate (72.7%), most protocol-defined primary endpoints were surrogate endpoints (84.8%). Overall survival data among older populations was unavailable in 50.0% of studies. Reporting was poor for secondary efficacy endpoints (81.8% unreported), baseline characteristics (70.4% unreported), toxicity (55.6% unreported), and health-related quality of life outcomes (87.5% unreported). CONCLUSION: The findings underline significant deficits in the reporting of age-specific data in breast cancer registration trials. The underreporting of key efficacy, safety, and HRQOL outcomes highlights the need for mandatory reporting standards and a dedicated emphasis on older populations' priorities and needs in the reporting of registration clinical trials.

Geriatric assessment for older people with cancer: policy recommendations.

Most cancers occur in older people and the burden in this age group is increasing. Over the past two decades the evidence on how best to treat this population has increased rapidly. However, implementation of new best practices has been slow and needs involvement of policymakers. This perspective paper explains why older people with cancer have different needs than the wider population. An overview is given of the recommended approach for older people with cancer and its benefits on clinical outcomes and cost-effectiveness. In older patients, the geriatric assessment (GA) is the gold standard to measure level of fitness and to determine treatment tolerability. The GA, with multiple domains of physical health, functional status, psychological health and socio-environmental factors, prevents initiation of inappropriate oncologic treatment and recommends geriatric interventions to optimize the patient's general health and thus resilience for receiving treatments. Multiple studies have proven its benefits such as reduced toxicity, better quality of life, better patient-centred communication and lower healthcare use. Although GA might require investment of time and resources, this is relatively small compared to the improved outcomes, possible cost-savings and compared to the large cost of oncologic treatments as a whole.

Healthcare providers' experiences of continuing care for older adults with cancer during the COVID-19 pandemic.

PURPOSE: The COVID-19 pandemic has caused great strain on older adults with cancer and their healthcare providers. This study explored healthcare providers' reported changes in cancer care, clinical barriers to care, patient questions, and the overall experiences of caring for older adults with cancer during the COVID-19 crisis. METHODS: The Advocacy Committee of the Cancer and Aging Research Group and the Association of Community Cancer Centers developed a survey for healthcare providers of adults with cancer, inquiring about their experiences during the pandemic. Responses from the survey's four open-ended items were analyzed by four independent coders for identification of common themes using deductive and inductive methods. RESULTS: Participants (n = 137) represented a variety of demographic and clinical experiences. Six overall themes emerged, including (1) telehealth use, (2) concerns for patient mental health, (3) patient physical and social isolation, (4) patient fear of contracting COVID-19, (5) continued disruptions to cancer care, and (6) patients seeking guidance, particularly regarding COVID-19 vaccination. Questions fielded by providers focused on the COVID-19 vaccination's safety and efficacy during older adults' cancer treatment. CONCLUSIONS: Additional resources (e.g., technology support, established care guidelines, and sufficient staffing) are needed to support older adults with cancer and healthcare providers during the pandemic. Future research should explore universally effective in-person and virtual treatment strategies for older adults with cancer. IMPLICATIONS FOR CANCER SURVIVORS: Persistence of telehealth barriers, particularly a lack of infrastructure to support telehealth visits, social isolation, and restrictive visitor policies as a result of COVID-19, negatively impacted the mental health of older adults with cancer.

Healthcare providers' attitudes towards delay in cancer treatment during COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic has created unprecedented obstacles leading to delays in treatment for older adults with cancer. Due to limited resources at the height of the pandemic, healthcare providers were constantly faced with ethical dilemmas regarding postponing or rescheduling care for their patients. MATERIALS AND METHODS: Two survey-based studies were conducted at different time-points during the pandemic looking at factors affecting oncology care providers' attitudes towards delay in treatment for older adults with cancer. Eligible participants were recruited by email sent through professional organizations' listservs, email blasts, and social media. Change in provider attitude over time was analyzed by comparing responses from the 2020 and 2021 surveys. Data analysis included descriptive statistics and chi-squares. RESULTS: In 2020, 17.5% of respondents were strongly considering/considering postponing cancer treatment for younger patients (age 30 and below), while 46.2% were considering delaying treatment for patients aged >85. These responses were in stark contrast to the results of the 2021 survey, where only 1.4% of respondents strongly considered postponing treatment for younger patients, and 13.5% for patients aged >85. DISCUSSION: All recommendations to postpone treatment for older adults with cancer must be made after mutual discussion with the patient. Throughout the COVID-19 pandemic, oncology care providers had to consider multiple factors while treating patients, frequently making most decisions without appropriate institutional support.

Oncology-Led Early Identification of Nutritional Risk: A Pragmatic, Evidence-Based Protocol (PRONTO).

Nutritional issues, including malnutrition, low muscle mass, sarcopenia (i.e., low muscle mass and strength), and cachexia (i.e., weight loss characterized by a continuous decline in skeletal muscle mass, with or without fat loss), are commonly experienced by patients with cancer at all stages of disease. Cancer cachexia may be associated with poor nutritional status and can compromise a patient's ability to tolerate antineoplastic therapy, increase the likelihood of post-surgical complications, and impact long-term outcomes including survival, quality of life, and function. One of the primary nutritional problems these patients experience is malnutrition, of which muscle depletion represents a clinically relevant feature. There have been recent calls for nutritional screening, assessment, treatment, and monitoring as a consistent component of care for all patients diagnosed with cancer. To achieve this, there is a need for a standardized approach to enable oncologists to identify patients commencing and undergoing antineoplastic therapy who are or who may be at risk of malnutrition and/or muscle depletion. This approach should not replace existing tools used in the dietitian's role, but rather give the oncologist a simple nutritional protocol for optimization of the patient care pathway where this is needed. Given the considerable time constraints in day-to-day oncology practice, any such approach must be simple and quick to implement so that oncologists can flag individual patients for further evaluation and follow-up with appropriate members of the multidisciplinary care team. To enable the rapid and routine identification of patients with or at risk of malnutrition and/or muscle depletion, an expert panel of nutrition specialists and practicing oncologists developed the PROtocol for NuTritional risk in Oncology (PRONTO). The protocol enables the rapid identification of patients with or at risk of malnutrition and/or muscle depletion and provides guidance on next steps. The protocol is adaptable to multiple settings and countries, which makes implementation feasible by oncologists and may optimize patient outcomes. We advise the use of this protocol in countries/clinical scenarios where a specialized approach to nutrition assessment and care is not available.

Cancer literacy - Informing patients and implementing shared decision making.

In order to tailor treatment to their needs, cancer patients are encouraged to be more active and engaged in their care decisions and to be autonomous yet collaborative with their healthcare professionals when it comes to aspects of their treatment in order to get better results. However, this can only happen after providing them with accurate information about cancer and the different treatment alternatives and their potential side effects. However, sharing robust data-based information is often hindered by exposure to misleading information through different media and online platform, where patients might come across unscientifically founded health practices. Increasing health literacy and cancer-specific literacy is essential to fight this negative trend. The idea is that more knowledgeable patients will be able to debunk more easily misinformation they encounter. This is also related to inequalities among cancer patients. Not only levels of cancer literacy within Europe are uneven across and within countries, but there are social groups that, due to specific social determinants, are systematically less informed and skilled regarding cancer care. In this paper an overview of gaps in addressing literacy issues, and the importance of health literacy to empower patients in their journey through treatment is delineated, concluding with some recommendations to improve cancer literacy in Europe.

Translational enhancement by base editing of the Kozak sequence rescues haploinsufficiency.

A variety of single-gene human diseases are caused by haploinsufficiency, a genetic condition by which mutational inactivation of one allele leads to reduced protein levels and functional impairment. Translational enhancement of the spare allele could exert a therapeutic effect. Here we developed BOOST, a novel gene-editing approach to rescue haploinsufficiency loci by the change of specific single nucleotides in the Kozak sequence, which controls translation by regulating start codon recognition. We evaluated for translational strength 230 Kozak sequences of annotated human haploinsufficient genes and 4621 derived variants, which can be installed by base editing, by a high-throughput reporter assay. Of these variants, 149 increased the translation of 47 Kozak sequences, demonstrating that a substantial proportion of haploinsufficient genes are controlled by suboptimal Kozak sequences. Validation of 18 variants for 8 genes produced an average enhancement in an expression window compatible with the rescue of the genetic imbalance. Base editing of the NCF1 gene, whose monoallelic loss causes chronic granulomatous disease, resulted in the desired increase of NCF1 (p47phox) protein levels in a relevant cell model. We propose BOOST as a fine-tuned approach to modulate translation, applicable to the correction of dozens of haploinsufficient monogenic disorders independently of the causing mutation.

International Survey on Frailty Assessment in Patients with Cancer.

BACKGROUND: Frailty negatively affects the outcomes of patients with cancer, and its assessment might vary widely in the real world. The objective of this study was to explore awareness and use of frailty screening tools among the ONCOassist healthcare professionals (HCPs) users. MATERIALS AND METHODS: We sent 2 emails with a cross-sectional 15-item survey in a 3-week interval between April and May 2021. Differences in the awareness and use of tools according to respondents' continents, country income, and job types were investigated. RESULTS: Seven hundred thirty-seven HCPs from 91 countries (81% physicians, 13% nurses, and 5% other HCPs) completed the survey. Three hundred and eighty-five (52%) reported assessing all or the majority of their patients; 518 (70%) at baseline and before starting a new treatment. Three hundred and four (43%) HCPs were aware of performance status (PS) scores only, 309 (42%) age/frailty/comorbidity (AFC) screening, and 102 (14%) chemotoxicity predictive tools. Five hundred and thirty-seven (73%) reported using tools; 423 (57%) just PS, 237 (32%) AFC, and 60 (8%) chemotoxicity ones. Reasons for tools non-use (485 responders) were awareness (70%), time constraints (28%), and uselessness (2%). There were significant differences in awareness and use of screening tools among different continents, country income, job types, and medical specialties (P < .001 for all comparisons). CONCLUSION: Among selected oncology HCPs, there is still a worldwide lack of knowledge and usage of frailty screening tools, which may differ according to their geography, country income, and education. Targeted initiatives to raise awareness and education are needed to implement frailty assessment in managing patients with cancer.

Chemotherapy and gene expression profiling in older early luminal breast cancer patients: An International Society of Geriatric Oncology systematic review.

BACKGROUND: The benefit of chemotherapy for older patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (EBC) is a key area of debate. Gene expression profiling (GEP) may identify patients deriving benefit, but their predictive role has not been established for older adults. We summarise evidence on efficacy, safety, and quality-of-life impacts of chemotherapy and on GEP use and impact in older HR-positive, HER2-negative EBC patients. METHODS: We conducted a literature search of PubMed and Embase on publications describing prospective studies evaluating chemotherapy in older adults with HR-positive, HER2-negative EBC and on publications describing retrospective and prospective studies evaluating GEP in older adults. RESULTS: Eight publications on chemotherapy use, including 2,035 older patients with EBC were selected. Only one trial evaluated chemotherapy survival benefits in older adults, showing no benefit. Of four studies comparing different regimens, only one showed the superiority of taxanes versus anthracyclines alone. Those investigating alternative regimens did not show improvements over standard regimens despite significant limitations. Five publications on GEP, including 445,323 older patients, were included and investigated Oncotype DX. Limited evidence shows that GEP aids treatment decisions in this population. GEP was offered less frequently to older versus younger patients. Higher Recurrence Score was prognostic for distant recurrence, but chemotherapy did not improve prognosis. CONCLUSIONS: In older patients with HR-positive, HER2-negative, chemotherapy survival benefits EBC are unclear and GEP is less used. Although its prognostic role is well established, its predictive role remains unknown.

Prevalence of Cardiovascular Disease in Patients With Potentially Curable Malignancies: A National Registry Dataset Analysis.

Background: Although a common challenge for patients and clinicians, there is little population-level evidence on the prevalence of cardiovascular disease (CVD) in individuals diagnosed with potentially curable cancer. Objectives: We investigated CVD rates in patients with common potentially curable malignancies and evaluated the associations between patient and disease characteristics and CVD prevalence. Methods: The study included cancer registry patients diagnosed in England with stage I to III breast cancer, stage I to III colon or rectal cancer, stage I to III prostate cancer, stage I to IIIA non-small-cell lung cancer, stage I to IV diffuse large B-cell lymphoma, and stage I to IV Hodgkin lymphoma from 2013 to 2018. Linked hospital records and national CVD databases were used to identify CVD. The rates of CVD were investigated according to tumor type, and associations between patient and disease characteristics and CVD prevalence were determined. Results: Among the 634,240 patients included, 102,834 (16.2%) had prior CVD. Men, older patients, and those living in deprived areas had higher CVD rates. Prevalence was highest for non-small-cell lung cancer (36.1%) and lowest for breast cancer (7.7%). After adjustment for age, sex, the income domain of the Index of Multiple Deprivation, and Charlson comorbidity index, CVD remained higher in other tumor types compared to breast cancer patients. Conclusions: There is a significant overlap between cancer and CVD burden. It is essential to consider CVD when evaluating national and international treatment patterns and cancer outcomes.