Fatores preditores associados a ocorrência de lesão por pressão em pacientes em cuidados paliativos oncológicos / Predictive factors associated with the occurrence of pressure injuries in patients undergoing cancer palliative care / Factores predictivos asociados con la aparición de lesiones por presión en pacientes sometidos a cuidados paliativos oncológicos

Objetivo: Avaliar os fatores preditores para ocorrência de lesão por pressão em pacientes oncológicos em cuidados paliativos. Métodos: Estudo epidemiológico observacional, analítico, com delineamento transversal e abordagem quantitativa. A coleta de dados foi realizada com 105 participantes, no período de maio a outubro de 2019, em uma Clínica de Cuidados Paliativos Oncológicos de um Centro de Alta Complexidade em Oncologia. Os foram inseridos no software Biostat 5.0, em que foi realizada primeiramente a análise de regressão logística univariada, e posteriormente foram selecionadas as variáveis para a regressão logística múltipla e assim definiram-se os fatores preditivos para lesão por pressão. Resultados: A prevalência identificada foi de 19,04% para lesão por pressão. A maioria da amostra eram mulheres (60%), com idade menor que 70 anos (70%). Dois terços apresentavam risco muito alto (15%), para lesão por pressão segundo a Escala de Braden, e possuíam como diagnóstico primário câncer de próstata (20%), seguido de colo uterino (15%). Conclusão: A presença de lesão medular e o uso de fralda descartável demonstrou forte correlação com o desenvolvimento de lesão por pressão, sendo estes os fatores preditivos identificados neste estudo. Conhecer o perfil desses pacientes auxilia na elaboração e sistematização das condutas de enfermagem, visando melhor qualidade e segurança no cuidado. (AU)

Objective: To evaluate the predictive factors for the occurrence of pressure injuries in cancer patients undergoing palliative care. Methods: Observational, analytical, cross-sectional epidemiological study with a quantitative approach. Data collection was carried out with 105 participants, from May to October 2019, in an Oncology Palliative Care Clinic of a High Complexity Oncology Center. The data were entered into the Biostat 5.0 software, in which the univariate logistic regression analysis was first performed, and then the variables for the multiple logistic regression were selected, thus defining the predictive factors for pressure injury. Results: The identified prevalence was 19.04% for pressure injuries. Most of the sample were women (60%), aged under 70 years (70%). Two-thirds were at very high risk (15%) for pressure injury according to the Braden Scale, and had prostate cancer as a primary diagnosis (20%), followed by cervix (15%). Conclusion: The presence of spinal cord injury and the use of a disposable diaper showed a strong correlation with the development of pressure injury, which are the predictive factors identified in this study. Knowing the profile of these patients helps in the elaboration and systematization of nursing procedures, aiming at better quality and safety in care. (AU)

Objetivo: Evaluar los factores predictivos de la ocurrencia de lesiones por presión en pacientes oncológicos sometidos a cuidados paliativos. Métodos: Estudio epidemiológico observacional, analítico, transversal con enfoque cuantitativo. La recolección de datos se realizó con 105 participantes, de mayo a octubre de 2019, en una Clínica de Cuidados Paliativos Oncológicos de un Centro Oncológico de Alta Complejidad. Los datos se ingresaron en el software Biostat 5.0, en el cual se realizó primero el análisis de regresión logística univariante, y luego se seleccionaron las variables para la regresión logística múltiple, definiendo así los factores predictivos de lesión por presión. Resultados: La prevalencia identificada fue del 19,04% para las lesiones por presión. La mayoría de la muestra fueron mujeres (60%), menores de 70 años (70%). Dos tercios tenían un riesgo muy alto (15%) de lesión por presión según la escala de Braden y tenían cáncer de próstata como diagnóstico primario (20%), seguido del cuello uterino (15%). Conclusión: La presencia de lesión medular y el uso de pañal desechable mostró una fuerte correlación con el desarrollo de lesión por presión, que son los factores predictivos identificados en este estudio. Conocer el perfil de estos pacientes ayuda en la elaboración y sistematización de los procedimientos de enfermería, buscando una mejor calidad y seguridad en la atención. (AU)

Metastatic Hepatoblastoma in Adolescence: A Clinical Case Report and Literature Review.

Hepatoblastoma is the most common hepatic neoplasm in children. However, its incidence is infrequent beyond age five. We present the case of a 15-year-old female diagnosed with metastatic hepatoblastoma during hospitalization for liver function deterioration. The patient presented with abdominal distension, jaundice, and other symptoms indicative of advanced disease. Imaging and biopsy confirmed stage IV epithelial hepatoblastoma with pulmonary metastases. This case underscores the importance of considering hepatoblastoma in older pediatric patients or young adults presenting with hepatic masses despite lacking traditional risk factors for liver malignancies.

Exploring the perspective of adolescent childhood cancer survivors on follow-up care and their concerns regarding the transition process-A qualitative content analysis.

PURPOSE: In Germany, children diagnosed with cancer survive their initial disease in more than 80%, and the majority will become long-term survivors. Around the age of 18, survivors are transferred to adult healthcare. The transition can be a critical period in the process of care at which many childhood cancer survivors discontinue to participate in regular follow-up care. Hence, the objective of the paper was to explore (a) survivors' attitudes towards pediatric follow-up care and (b) their concerns regarding the transition process to draw conclusions for optimizing pediatric care and transition processes. METHODS: We conducted semi-structured interviews with 21 adolescent childhood cancer survivors between the ages of 14 and 20. The survivors were recruited via a pediatric oncology department of a university hospital in Germany. Based on the principles of qualitative content analysis, a deductive-inductive method according to Kuckartz was applied. RESULTS: Based on the interview guide and derived from the exploratory research questions, two key categories were generated: (a) Survivors' attitudes towards pediatric follow-up care, which encompasses all formal and emotional aspects of survivors regarding follow-up care, and (b) their concerns regarding transition from pediatric to adult healthcare, where hindering and facilitating factors for a successful transition occur. Our results show high satisfaction among survivors with follow-up care. Nevertheless, they wish to be more integrated into processes and the organization of their follow-up care. Most adolescent survivors do not feel ready for transition. CONCLUSION: The integration of survivors into the organization processes and routines, and the promotion of emotional detachment from pediatric health care professionals (HCPs) are important to reduce concerns and uncertainties of adolescent survivors regarding the transition process and to promote subjective readiness for transition. To gain confidence in the adult healthcare, it is crucial to provide tailored education depending on individual requirements and needs and to build trusting relationships between survivors and adult HCPs.

Effect of a 3D-printed reconstruction automated matching system for selecting the size of a left double-lumen tube: a study protocol for a prospective randomised controlled trial.

INTRODUCTION: Lung isolation is primarily accomplished using a double-lumen tube (DLT) or bronchial blocker. A precise and accurate size of the DLT is a prerequisite for ensuring its accurate placement. Three-dimensional (3D) reconstruction technology can be used to accurately reproduce tracheobronchial structures to improve the accuracy of DLT size selection. Therefore, we have developed automatic comparison software for 3D reconstruction based on CT data (3DRACS). In this study, we aimed to evaluate the efficiency of using 3DRACS to select the DLT size for endobronchial intubation in comparison with using the 'blind' DLT intubation method to determine the DLT size, which is based on height and sex. METHODS AND ANALYSIS: This is a prospective, single-centre, double-blind randomised controlled trial. In total, 200 patients scheduled for lung resection using a left DLT will be randomly allocated to the 3D group or the control group at a 1:1 ratio. A 3DRACS will be used for the 3D group to determine the size of the DLT, while in the case of the control group, the size of the DLT will be determined according to patient height and sex. The primary outcome is the success rate of placement of the left DLT without fibreoptic bronchoscopy (FOB). The secondary outcomes include the following: successful intubation time, degree of pulmonary atrophy, grade of airway injury, oxygenation during one-lung ventilation, postoperative sore throat and hoarseness, and number of times FOB is used. ETHICS AND DISSEMINATION: Ethical approval has been obtained from our local ethics committee (approval number: SCCHEC-02-2022-155). Written informed consent will be obtained from all participants before randomisation, providing them with clear instructions about the purpose of the study. The results will be disseminated through peer-reviewed publications and conferences. TRIAL REGISTRATION NUMBER: NCT06258954.

Preoperative walking exercise to improve prognosis in patients with supratentorial brain tumours after craniotomy: protocol for a randomised controlled trial.

INTRODUCTION: Cardiopulmonary complications and cognitive impairment following craniotomy have a significantly impact on the general health of individuals with brain tumours. Observational research indicates that engaging in walking is linked to better prognosis in patient after surgery. This trial aims to explore whether walking exercise prior to craniotomy in brain tumour patients can reduce the incidence of cardiopulmonary complications and preserve patients' cognitive function. METHODS AND ANALYSIS: In this randomised controlled trial, 160 participants with supratentorial brain tumours aged 18-65 years, with a preoperative waiting time of more than 3-4 weeks and without conditions that would interfere with the trial such as cognitive impairment, will be randomly assigned in a ratio of 1:1 to either receive traditional treatment or additional combined with a period of 3-4 weeks of walking exercise of 10 000-15 000 steps per day. Wearable pedometer devices will be used to record step counts. The researchers will evaluate participants at enrolment, baseline, 14 days preoperatively, 3 days prior to surgery and 1 week after surgery or discharge (select which occurs first). The primary outcomes include the incidence of postoperative cardiopulmonary complications and changes in cognitive function (gauged by the Montreal Cognitive Assessment test). Secondary outcomes include the average length of hospital stay, postoperative pain, participant contentment, healthcare-associated costs and incidence of other postoperative surgery-related complications. We anticipate that short-term preoperative walking exercises will reduce the incidence of surgery-related complications in the short term after craniotomy, protect patients' cognitive function, aid patients' postoperative recovery and reduce the financial cost of treatment. ETHICS AND DISSEMINATION: The study protocol has been approved by Ethics Committee of Xiangya Hospital of Central South University (approval number: 202305117). The findings of the research will be shared via publications that have been reviewed by experts in the field and through presentations at conferences. TRIAL REGISTRATION NUMBER: NCT05930288.

Landscape of cancer clinical trials in India - a comprehensive analysis of the Clinical Trial Registry-India.

Background: Cancer is one of the leading causes of morbidity and mortality in India. Clinical trials are critical for driving innovation in cancer therapy, diagnosis, and prevention. This study aims to depict the evolving landscape of cancer clinical trials in India by analysing the clinical trials registered in Clinical Trial Registry-India (CTRI). Methods: We identified cancer trials registered in CTRI (between 2007 and 2021) using search terms adapted from the cancer types defined by the National Cancer Institute (USA). We then collated and analysed the publicly available information from CTRI (cancer subtypes, type of trial, treatment intent, type of intervention, sponsor type, recruitment countries) and used descriptive statistics to illustrate the overall as well as year-to-year trend. Findings: In total, we identified 1988 cancer trials, the majority of which focused on treating cancer (63%) and rest of the trials aimed at optimising the operational aspects of surgery (19%), mitigating treatment-related toxicity (10.6%), or treating cancer-related symptoms (7.8%). Focusing on trials with the intent of treating cancer, we found that most were investigating solid tumours as opposed to haematological malignancies with the most prominent cancer subtypes being breast cancer (17%), head and neck cancer (9.8%), lung cancer (9.6%), and cervical cancer (6.6%). The number of trials conducted in a given cancer subtype from our analysis overall correlated to the incidence, mortality, and 5-year prevalence of the respective cancer subtype in India; however, head and neck cancer and cervical cancer were underrepresented in trials as compared with the disease burden. The most common type of intervention was investigational drugs. The most common sponsor types were global pharmaceutical industry (26%) and research institution and hospital (26%). Despite a relatively high cancer burden, the availability of cancer trials in the Northeastern states of India was limited. Interpretation: There is a pressing need for clinical cancer research in India to be better aligned with the nation's healthcare needs and disease burden, focusing on prevalent and deadly cancers while ensuring the availability of clinical trials across geographic regions and underserved populations. Funding: Pi Health USA, a fully owned subsidiary of BeiGene Ltd.

AI-based pipeline for early screening of lung cancer: integrating radiology, clinical, and genomics data.

Background: The prognosis of lung carcinoma has changed since the discovery of molecular targets and their specific drugs. Somatic Epidermal Growth Factor Receptor (EGFR) mutations have been reported in lung carcinoma, and these mutant proteins act as substrates for targeted therapies. However, in a resource-constrained country like India, panel-based next-generation sequencing cannot be made available to the population at large. Additional challenges such as adequacy of tissue in case of lung core biopsies and locating suitable tumour tissues as a result of innate intratumoral heterogeneity indicate the necessity of an AI-based end-to-end pipeline capable of automatically detecting and learning more effective lung nodule features from CT images and predicting the probability of the EGFR-mutant. This will help the oncologists and patients in resource-limited settings to achieve near-optimal care and appropriate therapy. Methods: The EGFR gene sequencing and CT imaging data of 2277 patients with lung carcinoma were included from three cohorts in India and a White population cohort collected from TCIA. Another cohort LIDC-IDRI was used to train the AIPS-Nodule (AIPS-N) model for automatic detection and characterisation of lung nodules. We explored the value of combining the results of the AIPS-N with the clinical factors in the AIPS-Mutation (AIPS-M) model for predicting EGFR genotype, and it was evaluated by area under the curve (AUC). Findings: AIPS-N achieved an average AP50 of 70.19% in detecting the location of nodules within the lung region of interest during validation and predicted the score of five lung nodule properties. The AIPS-M machine learning (ML) and deep learning (DL) models achieved AUCs ranging from 0.587 to 0.910. Interpretation: The AIPS suggests that CT imaging combined with a fully automated lung-nodule analysis AI system can predict EGFR genotype and identify patients with an EGFR mutation in a cost-effective and non-invasive manner. Funding: This work was supported by a grant provided by Conquer Cancer Foundation of ASCO [2021IIG-5555960128] and Pfizer Products India Pvt. Ltd.

Out-of-pocket payment and financial risk protection for breast cancer treatment: a prospective study from India.

Background: Available data on cost of cancer treatment, out-of-pocket payment and reimbursement are limited in India. We estimated the treatment costs, out-of-pocket payment, and reimbursement in a cohort of breast cancer patients who sought treatment at a publicly funded tertiary cancer care hospital in India. Methods: A prospective longitudinal study was conducted from June 2019 to March 2022 at Tata Memorial Centre (TMC), Mumbai. Data on expenditure during each visit of treatment was collected by a team of trained medical social workers. The primary outcome variables were total cost (TC) of treatment, out-of-pocket payment (OOP), and reimbursement. TC included cost incurred by breast cancer patients during treatment at TMC. OOP was defined as the total cost incurred at TMC less of reimbursement. Reimbursement was any form of financial assistance (cashless or repayment), including social health insurance, private health insurance, employee health schemes, and assistance from charitable trusts, received by the patients for breast cancer treatment. Findings: Of the 500 patients included in the study, 45 discontinued treatment (due to financial or other reasons) and 26 died during treatment. The mean TC of breast cancer treatment was ₹258,095/US$3531 (95% CI: 238,225, 277,934). Direct medical cost (MC) accounted for 56.3% of the TC. Systemic therapy costs (₹50,869/US$696) were higher than radiotherapy (₹33,483/US$458) and surgery costs (₹25,075/US$343). About 74.4% patients availed some form of financial assistance at TMC; 8% patients received full reimbursement. The mean OOP for breast cancer treatment was ₹186,461/US$2551 (95% CI: 167,666, 205,257), accounting for 72.2% of the TC. Social health insurance (SHI) had a reasonable coverage (33.1%), followed by charitable trusts (29.6%), employee health insurance (5.1%), private health insurance (4.4%) and 25.6% had no reimbursement. But SHI covered only 40.1% of the TC of treatment compared to private health insurance that covered as much as 57.1% of it. Both TC and OOP were higher for patients who were younger, belonged to rural areas, had a comorbidity, were diagnosed at an advanced stage, and were from outside Maharashtra. Interpretation: In India, the cost and OOP for breast cancer treatment are high and reimbursement for the treatment flows from multiple sources. Though many of the patients receive some form of reimbursement, it is insufficient to prevent high OOP. Hence both wider insurance coverage as well as higher cap of the insurance packages in the health insurance schemes is suggested. Allowing for the automatic inclusion of cancer treatment in SHI can mitigate the financial burden of cancer patients in India. Funding: This work was funded by an extramural grant from the Women's Cancer Initiative and the Nag Foundation and an intramural grant from the International Institute of Population Sciences, Mumbai.

Role of a mental health physician in the management of oncology patients: a case vignette and the need for collaboration.

There is an interplay between oncology and mental health, resulting in a high prevalence of mental disorders among cancer patients. Out of the several interventions developed to target cancer specifics, collaborative care is indicated due to its efficacy. The perspective delves into the efficacy of collaborative care models, spotlighting a culturally informed strategy designed to harmonize mental and physical health interventions to bolster the overall wellbeing and resilience of individuals battling cancer. Central to our discussion is a compelling case vignette of Raliat, a patient diagnosed with ovarian cancer whose narrative exemplifies the multifaceted challenges cancer patients face, including stigma, psychological distress, and social isolation. Raliat's story illuminates the profound impact of cultural beliefs on patient experiences and the critical importance of a sensitive, holistic approach to care that respects cultural contexts. Through this lens, our analysis reveals that addressing emotional and situational stressors through collaborative care can significantly reduce oxidative stress, potentially decelerating the progression of both cancer and accompanying mental health disorders. We advocate for integrating mental health services into oncological care, drawing on the case vignette to argue for policies that facilitate such merger by employing validated collaborative care models. We conclude with a call for public education to diminish cancer stigma and improve social outcomes, emphasizing the use of a culture-informed PACER (physical, affective, cognitive, environmental, and relationship) strategy in providing comprehensive care for cancer patients and their families.

Gastric cancer actionable genomic alterations across diverse populations worldwide and pharmacogenomics strategies based on precision oncology.

Introduction: Gastric cancer is one of the most prevalent types of cancer worldwide. The World Health Organization (WHO), the International Agency for Research on Cancer (IARC), and the Global Cancer Statistics (GLOBOCAN) reported an age standardized global incidence rate of 9.2 per 100,000 individuals for gastric cancer in 2022, with a mortality rate of 6.1. Despite considerable progress in precision oncology through the efforts of international consortia, understanding the genomic features and their influence on the effectiveness of anti-cancer treatments across diverse ethnic groups remains essential. Methods: Our study aimed to address this need by conducting integrated in silico analyses to identify actionable genomic alterations in gastric cancer driver genes, assess their impact using deleteriousness scores, and determine allele frequencies across nine global populations: European Finnish, European non-Finnish, Latino, East Asian, South Asian, African, Middle Eastern, Ashkenazi Jewish, and Amish. Furthermore, our goal was to prioritize targeted therapeutic strategies based on pharmacogenomics clinical guidelines, in silico drug prescriptions, and clinical trial data. Results: Our comprehensive analysis examined 275,634 variants within 60 gastric cancer driver genes from 730,947 exome sequences and 76,215 whole-genome sequences from unrelated individuals, identifying 13,542 annotated and predicted oncogenic variants. We prioritized the most prevalent and deleterious oncogenic variants for subsequent pharmacogenomics testing. Additionally, we discovered actionable genomic alterations in the ARID1A, ATM, BCOR, ERBB2, ERBB3, CDKN2A, KIT, PIK3CA, PTEN, NTRK3, TP53, and CDKN2A genes that could enhance the efficacy of anti-cancer therapies, as suggested by in silico drug prescription analyses, reviews of current pharmacogenomics clinical guidelines, and evaluations of phase III and IV clinical trials targeting gastric cancer driver proteins. Discussion: These findings underline the urgency of consolidating efforts to devise effective prevention measures, invest in genomic profiling for underrepresented populations, and ensure the inclusion of ethnic minorities in future clinical trials and cancer research in developed countries.

The inclusion of the gender perspective in oncology research with Spanish participation.

The gender perspective is important for a better diagnosis and treatment of diseases, especially in the field of oncology. This study aimed to analyse the gender approach in scientific articles in the field of oncology by studying the gender composition of the authorship of papers and the gender inclusion in the research carried out. A bibliographic search of articles and reviews signed by at least one Spanish institution published between 2010 and 2019 was carried out using the Science Citation Index Expanded database in the Oncology category. A total of 7523 studies were classified according to the gender composition determined by the author's name and a randomised sample was used to evaluate the inclusion of gender perspectives using a checklist. This study revealed a lack of gender parity in the authorship of oncology publications involving Spanish participation. Papers without author gender parity were eight times higher than papers with parity and showed a greater presence of male than female authorship (58 % versus 31 %). Regarding the introduction of the gender perspective, a negative response of 68 % referring to compliance with the entire checklist was obtained, and only a fifth of the articles presented gender balance in the study sample. Moreover, there is a positive correlation between gender parity in authorship and gender perspective integration in published research. In conclusion, there is a great need to advance the inclusion of gender perspectives in cancer research to overcome gender bias and promote better prevention, detection, and intervention for cancer.

Case study with dosimetric analysis: Total body irradiation to a patient with a left ventricular assist device.

Key Clinical Message: A patient presented with cardiogenic shock, requiring the implantation of a left ventricular assist device (LVAD), and acute myeloblastic leukemia. This necessitated total body irradiation (TBI) while balancing dose reduction to the LVAD components to avoid potential radiation damage. Here we outline our treatment approach and dose estimates to the LVAD. Abstract: This case report discusses the delivery of TBI to a patient with an LVAD. This treatment required radiation-dose determinations and consequential reductions for the heart, LVAD, and an external controller connected to the LVAD. The patient was treated using a traditional 16MV anterior posterior (AP)/posterior anterior (PA) technique at a source-to-surface-distance of 515 cm for 400 cGy in two fractions. A 3 cm thick Cerrobend block was placed on the beam spoiler to reduce dose to the heart and LVAD to 150 cGy. The external controller was placed in a 1 cm thick acrylic box to reduce neutron dose and positioned as far from the treatment fields as achievable. In vivo measurements were made using optically stimulated luminescence dosimeters (OSLDs) placed inside the box at distances of 2 cm, 8.5 cm, and 14 cm from the field edge, and on the patient along the central axis and centered behind the LVAD block. Further ion chamber measurements were made using a solid water phantom to more accurately estimate the dose delivered to the LVAD. Neutron dose measurements were also conducted. The total estimated dose to the controller ranged from 135.3 cGy to 91.5 cGy. The LVAD block reduced the surface dose to the patient to 271.6 cGy (68.1%). The block transmission factors of the 3 cm Cerrobend block measured in the phantom were 45% at 1 cm depth and decreased asymptotically to around 30% at 3 cm depth. Applying these transmission factors to the in vivo measurements yielded a dose of 120 cGy to the implanted device. The neutron dose the LVAD region is estimated around 0.46 cGy. Physical limitations of the controller made it impossible to completely avoid dose. Shielding is recommended. The block had limited dose reduction to the surface, due to secondary particles, but appropriately reduced the dose at 3 cm and beyond. More research on LVADs dose limits would be beneficial.

Association of Remote Patient-Reported Outcomes and Step Counts With Hospitalization or Death Among Patients With Advanced Cancer Undergoing Chemotherapy: Secondary Analysis of the PROStep Randomized Trial.

BACKGROUND: Patients with advanced cancer undergoing chemotherapy experience significant symptoms and declines in functional status, which are associated with poor outcomes. Remote monitoring of patient-reported outcomes (PROs; symptoms) and step counts (functional status) may proactively identify patients at risk of hospitalization or death. OBJECTIVE: The aim of this study is to evaluate the association of (1) longitudinal PROs with step counts and (2) PROs and step counts with hospitalization or death. METHODS: The PROStep randomized trial enrolled 108 patients with advanced gastrointestinal or lung cancers undergoing cytotoxic chemotherapy at a large academic cancer center. Patients were randomized to weekly text-based monitoring of 8 PROs plus continuous step count monitoring via Fitbit (Google) versus usual care. This preplanned secondary analysis included 57 of 75 patients randomized to the intervention who had PRO and step count data. We analyzed the associations between PROs and mean daily step counts and the associations of PROs and step counts with the composite outcome of hospitalization or death using bootstrapped generalized linear models to account for longitudinal data. RESULTS: Among 57 patients, the mean age was 57 (SD 10.9) years, 24 (42%) were female, 43 (75%) had advanced gastrointestinal cancer, 14 (25%) had advanced lung cancer, and 25 (44%) were hospitalized or died during follow-up. A 1-point weekly increase (on a 32-point scale) in aggregate PRO score was associated with 247 fewer mean daily steps (95% CI -277 to -213; P<.001). PROs most strongly associated with step count decline were patient-reported activity (daily step change -892), nausea score (-677), and constipation score (524). A 1-point weekly increase in aggregate PRO score was associated with 20% greater odds of hospitalization or death (adjusted odds ratio [aOR] 1.2, 95% CI 1.1-1.4; P=.01). PROs most strongly associated with hospitalization or death were pain (aOR 3.2, 95% CI 1.6-6.5; P<.001), decreased activity (aOR 3.2, 95% CI 1.4-7.1; P=.01), dyspnea (aOR 2.6, 95% CI 1.2-5.5; P=.02), and sadness (aOR 2.1, 95% CI 1.1-4.3; P=.03). A decrease in 1000 steps was associated with 16% greater odds of hospitalization or death (aOR 1.2, 95% CI 1.0-1.3; P=.03). Compared with baseline, mean daily step count decreased 7% (n=274 steps), 9% (n=351 steps), and 16% (n=667 steps) in the 3, 2, and 1 weeks before hospitalization or death, respectively. CONCLUSIONS: In this secondary analysis of a randomized trial among patients with advanced cancer, higher symptom burden and decreased step count were independently associated with and predictably worsened close to hospitalization or death. Future interventions should leverage longitudinal PRO and step count data to target interventions toward patients at risk for poor outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04616768; https://clinicaltrials.gov/study/NCT04616768. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2021-054675.

Somatic structural variants drive distinct modes of oncogenesis in melanoma.

The diversity of structural variants (SVs) in melanoma and how they impact oncogenesis are incompletely known. We performed harmonized analysis of SVs across melanoma histological and genomic subtypes, and we identified distinct global properties between subtypes. These included the frequency and size of SVs and SV classes, their relation to chromothripsis events, and the role of topologically associated domain (TAD) boundary altering SVs on cancer-related genes. Following our prior identification of double-stranded break repair deficiency in a subset of triple wild-type cutaneous melanoma, we identified MRE11 and NBN loss-of-function SVs in melanomas with this mutational signature. Experimental knockouts of MRE11 and NBN, followed by olaparib cell viability assays in melanoma cells, indicated that dysregulation of each of these genes may cause sensitivity to PARPi in cutaneous melanomas. Broadly, harmonized analysis of melanoma SVs revealed distinct global genomic properties and molecular drivers, which may have biological and therapeutic impact.

The role of reoperation in pediatric cerebellar pilocytic astrocytoma.

OBJECTIVE: Cerebellar pilocytic astrocytomas (cPAs) in childhood have long been recognized to have a good prognosis after total resection, but the outcome after incomplete resective surgery remains largely unpredictable, with the incidence of radiological progressive disease ranging from 18% to 100%. It has been traditionally thought that gross-total resection was required for long-term survival, and small residuals were classically resected in a subsequent operation. METHODS: The authors analyzed their pediatric low-grade glioma (PLGG) database for cases treated between 1985 and 2020 and filtered for intracranial PAs, to determine what clinical or radiological factors precipitated revisional resective surgery in their single quaternary care center cohort. RESULTS: Using the pediatric low-grade glioma database, 283 patients were identified to have a histopathological diagnosis of intracranial PA between 1985 and 2020, of which 200 lesions were within the cerebellum (70.7%). The majority of patients with cPA were between 1 and 10 years of age (n = 145, 72.5%) without gender predominance (M/F = 99:101), usually presenting with 1 lesion (n = 197, 98.5%). Gross-total resection was achieved in 74.5% (n = 149) of initial surgeries for cPA. In patients with subtotal resection, the mean largest diameter of the postoperative residual tumor was 1.06 cm (range 0-2.95 cm). Seven patients with subtotal resection did not require a second resective intervention. In 31 patients the neuro-oncology multidisciplinary team recommended a second resection at a mean time interval of 22.9 months (range 0.13-81.6 months) from the initial surgery. Proportionally, the children who underwent multiple resections were also more likely to receive adjuvant chemo/radiotherapy. Functionally, the children in the multiple operation cohort experienced more complications of therapy including ongoing endocrinopathy, treatment-associated hearing deficit, and neurocognitive deficits. CONCLUSIONS: Residual disease in cPA should be maintained under clinicocoradiological surveillance postoperatively with adoption of a more conservative approach when residual disease is not significantly changing over time.

Physician-level variation in axillary surgery in older adults with T1N0 hormone receptor-positive breast cancer: A retrospective population-based cohort study.

INTRODUCTION: We sought to determine how considerations specific to older adults impact between- and within-surgeon variation in axillary surgery use in women ≥70 years with T1N0 HR+ breast cancer. MATERIALS AND METHODS: Females ≥70 years with T1N0 HR+/HER2-negative breast cancer diagnosed from 2013 to 2015 in SEER-Medicare were identified and linked to the American Medical Association Masterfile. The outcome of interest was axillary surgery. Key patient-level variables included the Charlson Comorbidity Index (CCI) score, frailty (based on a claims-based frailty index score), and age (≥75 vs <75). Multilevel mixed models with surgeon clusters were used to estimate the intracluster correlation coefficient (ICC) (between-surgeon variance), with 1-ICC representing within-surgeon variance. RESULTS: Of the 4410 participants included, 6.1% had a CCI score of ≥3, 20.7% were frail, and 58.3% were ≥ 75 years; 86.1% underwent axillary surgery. No surgeon omitted axillary surgery in all patients, but 42.3% of surgeons performed axillary surgery in all patients. In the null model, 10.5% of the variance in the axillary evaluation was attributable to between-surgeon differences. After adjusting for CCI score, frailty, and age in mixed models, between-surgeon variance increased to 13.0%. DISCUSSION: In this population, axillary surgery varies more within surgeons than between surgeons, suggesting that surgeons are not taking an "all-or-nothing" approach. Comorbidities, frailty, and age accounted for a small proportion of the variation, suggesting nuanced decision-making may include additional, unmeasured factors such as differences in surgeon-patient communication.

Anamnestic radiological metastases outcome surgical score (ARMO-S). A purpose of a predictive surgical scoring system for brain metastases.

BACKGROUND: Several risk stratification scores have been suggested to aid prognostication and guide treatment strategies for brain metastases (BMs). However, the current scores do not focus on the specific neurosurgical population, therefore not predicting short-term mortality and postoperative performance status. METHODS: This retrospective observational study of 362 consecutive patients treated with surgery for BMs aims to identify the factors associated with post-surgical outcomes and propose a surgery-specific prognostic score for patients with BMs candidate for open surgery. RESULTS: Factors significantly associated with OS and performance status in multivariate analysis were age, KPS, surgical site, synchronous debut of BM, number, tumor volume, seizure, extra-cranial metastases, and deep-seated location. The variables were incorporated into the Anamnestic Radiological Metastases Outcome Surgical score (ARMO-S). The values range between 0 and 10. Patients were divided into two groups (low-risk and high-risk) based on each significant subgroup's median survival and performance status with an optimal cutoff value determined as 4. The two groups have significant differences in OS (9.6 versus 14 months, p = 0.0048) postoperative KPS (90 versus 70, p = 0.012) and KPS at last follow-up evaluation (75 versus 30, p < 0.001) CONCLUSION: ARMO-S is a simple and comprehensive score for BM patients selected for neurosurgery, as it incorporates the main factors of the most important prognostic scores, implementing them with more surgery-specific predictive elements such as tumor location and volume, presence of seizures at onset, and involvement of eloquent brain areas.

Small molecule anticancer drugs approved during 2021-2022: Synthesis and clinical applications.

Drugs have structural homology across similar biological targets. Small molecule drugs have the efficacy to target specific molecular targets within the cancer cells with enhanced cell membrane permeability, oral administration, selectivity, and specific affinity. The objective of this review is to highlight the clinical importance and synthetic routes of new small molecule oncology drugs approved by the FDA during the period 2021-2022. These marketed drugs are listed based on the month and year of approval in chronological order. We believed that an in-depth insight into the synthetic approaches for the construction of these chemical entities would enhance the ability to develop new drugs more efficiently.

Clinical trial design and treatment effects: a meta-analysis of randomised controlled and single-arm trials supporting 437 FDA approvals of cancer drugs and indications.

OBJECTIVES: This study aims to analyse the association between clinical trial design and treatment effects for cancer drugs with US Food and Drug Administration (FDA) approval. DESIGN: Cross-sectional study and meta-analysis. SETTING: Data from Drugs@FDA, FDA labels, ClincialTrials.gov and the Global Burden of Disease study. PARTICIPANTS: Pivotal trials for 170 drugs with FDA approval across 437 cancer indications between 2000 and 2022. MAIN OUTCOME MEASURES: Treatment effects were measured in HRs for overall survival (OS) and progression-free survival (PFS), and in relative risk for tumour response. Random-effects meta-analyses and meta-regressions explored the association between treatment effect estimates and clinical trial design for randomised controlled trials (RCTs) and single-arm trials. RESULTS: Across RCTs, greater effect estimates were observed in smaller trials for OS (ß=0.06, p<0.001), PFS (ß=0.15, p<0.001) and tumour response (ß=-3.61, p<0.001). Effect estimates were larger in shorter trials for OS (ß=0.08, p<0.001) and PFS (ß=0.09, p=0.002). OS (ß=0.04, p=0.006), PFS (ß=0.10, p<0.001) and tumour response (ß=-2.91, p=0.004) outcomes were greater in trials with fewer centres. HRs for PFS (0.54 vs 0.62, p=0.011) were lower in trials testing the new drug to an inactive (placebo/no treatment) rather than an active comparator. The analysed efficacy population (intention-to-treat, per-protocol, or as-treated) was not consistently associated with treatment effects. Results were consistent for single-arm trials and in multivariable analyses. CONCLUSIONS: Pivotal trial design is significantly associated with measured treatment effects. Particularly small, short, single-centre trials testing a new drug compared with an inactive rather than an active comparator could overstate treatment outcomes. Future studies should verify results in unsuccessful trials, adjust for further confounders and examine other therapeutic areas. The FDA, manufacturers and trialists must strive to conduct robust clinical trials with a low risk of bias.

Diagnostic staging and stratification in psychiatry and oncology: clarifying their conceptual, epistemological and ethical implications.

Staging and stratification are two diagnostic approaches that have introduced a more dynamic outlook on the development of diseases, thus participating in blurring the line between the normal and the pathological. First, diagnostic staging, aiming to capture how diseases evolve in time and/or space through identifiable and gradually more severe stages, may be said to lean on an underlying assumption of "temporal determinism". Stratification, on the other hand, allows for the identification of various prognostic or predictive subgroups based on specific markers, relying on a more "mechanistic" or "statistical" form of determinism. There are two medical fields in which these developments have played a significant role and have given rise to sometimes profound nosological transformations: oncology and psychiatry. Drawing on examples from these two fields, this paper aims to provide much needed conceptual clarifications on both staging and stratification in order to outline how several epistemological and ethical issues may, in turn, arise. We argue that diagnostic staging ought to be detached from the assumption of temporal determinism, though it should still play an essential role in adapting interventions to stage. In doing so, it would help counterbalance stratification's own epistemological and ethical shortcomings. In this sense, the reflections and propositions developed in psychiatry can offer invaluable insights regarding how adopting a more transdiagnostic and cross-cutting perspective on temporality and disease dynamics may help combine both staging and stratification in clinical practice.