Treatment-related Outcomes Research Articles

Influence of religion and spirituality on head and neck cancer patients and their caregivers: a protocol for a scoping review

IntroductionHead and neck cancers (HNC) are devastating, thus imposing a negative impact on the appearance of an individual as well as vital activities such as eating, swallowing, speaking, and breathing. Therefore, HNC patients undergo distress, while their caregivers become overburdened. Religion and spirituality can be helpful for patients and their caregivers from diverse cultural backgrounds to cope with cancer. Though well established in palliative care, religion and spirituality are rarely incorporated into usual early oncological care. Despite the availability of heterogeneous literature examining the influence of religion and spirituality on cancer patients, there is notably limited research on this topic across the HNC trajectory. Therefore, this scoping review attempts to answer “What is the influence of religion or spirituality on HNC patients and their caregivers in different contexts?” and will map the evidence on the influence of religion and spirituality on HNC patients and their caregivers in different contexts including geographical areas, cultures, health care systems, and different study settings.MethodsThis scoping review was formulated using the guidelines of Joanna Briggs Institute (JBI) manual for evidence synthesis: scoping reviews and will be reported confirming to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR checklist). A comprehensive search strategy will include Embase, CINAHL, Scopus, and APA PsycINFO. The OPENGREU.EU and Google Scholar will be used as gray literature sources complimented by manual searches. Our eligibility criteria follow the population, concept, and context (PCC) framework. Patients aged ≥ 18 years diagnosed with HNC and their informal, nonpaid caregivers aged > 18 years will be included. The data will be extracted using piloted data extraction form on sociodemographic, disease-related, and treatment-related factors and outcomes, and the data will be analyzed through descriptive statistics and thematic analysis. The results will be narratively synthesized.Conclusions/discussionThis review will aim to explore existing literature and summarize the findings of studies that examine the influence of religion and spirituality among HNC patients and their caregivers and vice versa over a range of physical, psychological, and social outcomes including quality of life. We also aim to identify existing research gaps. The findings of this review would generate evidence to better inform health care providers in countries and cultures in the management of patients diagnosed with HNC in usual oncological care with due consideration to caregivers.

Exercise and Nutrition to Improve Cancer Treatment-Related Outcomes (ENICTO).

Chemotherapy treatment-related side effects are common and increase the risk of suboptimal outcomes. Exercise interventions during cancer treatment improve self-reported physical functioning, fatigue, anxiety, and depression, but it is unclear whether these interventions improve important clinical outcomes, such as chemotherapy relative dose intensity. The National Cancer Institute funded the Exercise and Nutrition to Improve Cancer Treatment-Related Outcomes (ENICTO) Consortium to address this knowledge gap. This article describes the mechanisms hypothesized to underpin intervention effects on clinically relevant treatment outcomes, briefly outlines each project's distinct research aims, summarizes the scope and organizational structure of ENICTO, and provides an overview of the integrated common data elements used to pursue research questions collectively. In addition, the article includes a description of consortium-wide activities and broader research community opportunities for collaborative research. Findings from the ENICTO Consortium have the potential to accelerate a paradigm shift in oncology care such that patients with cancer could receive exercise and nutrition programming as the standard of care in tandem with chemotherapy to improve relative dose intensity for a curative outcome.

Evaluating Treatment-Related Outcomes in the Era of Targeted Therapy for Rosai Dorman and Erdheim Chester Disease

Evaluating Treatment-Related Outcomes in the Era of Targeted Therapy for Rosai Dorman and Erdheim Chester Disease

Optimising hypoxia PET imaging and its applications in guiding targeted radiation therapy for non-small cell lung cancer: a scoping review.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death. Definitive treatment includes chemotherapy and radiation therapy. Tumour hypoxia impacts the efficacy of these treatment modalities. Novel positron-emission tomography (PET) imaging has been developed to non-invasively quantify hypoxic tumour subregions, and to guide personalised treatment strategies. This review evaluates the reliability of hypoxia imaging in NSCLC in relation to various tracers, its correlations to treatment-related outcomes, and to assess if this imaging modality can be meaningfully applied into radiation therapy workflows. A literature search was conducted on the Medline (Ovid) and Embase databases. Searches included terms related to 'hypoxia', 'positron-emission tomography', 'magnetic resonance imaging' and 'lung cancer'. Results were filtered to exclude studies prior to 2011, and animal studies were excluded. Only studies referring to a confirmed pathology of NSCLC were included, while disease staging was not a limiting factor. Full-text English language and translated literature examined included clinical trials, clinical cohort studies and feasibility studies. Quantification of hypoxic volumes in a pre-treatment setting is of prognostic value, and indicative of treatment response. Dosimetric comparisons have highlighted potential to significantly dose escalate to hypoxic volumes without risk of additional toxicity. However, clinical data to support these strategies are lacking. Heterogenous study design and non-standardised imaging parameters have led to a lack of clarity regarding the application of hypoxia PET imaging in NSCLC. PET imaging using nitroimidazole tracers is the most investigated method of non-invasively measuring tumour hypoxia and has potential to guide hypoxia-targeted radiation therapy. Further clinical research is required to elucidate the benefits versus risks of dose-escalation strategies.

Repeated intravesical injections of platelet-rich plasma are safe and effective in the treatment of interstitial cystitis/bladder pain syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a challenging chronic inflammatory condition affecting the urinary bladder, with limited treatment options. This study aims to assess the clinical efficacy of repeated intravesical platelet-rich plasma (PRP) injections for promoting urothelial regeneration and reducing inflammation in patients with IC/BPS and investigate its correlation with subjective and objective treatment-related outcomes. Four monthly intravesical PRP injections were given to 98 patients with non-Hunner-type IC/BPS. Treatment outcomes were assessed using a global response assessment (GRA) score 3 months posttreatment. In addition, clinical symptom scores, pain severity, voiding diary data, uroflowmetry parameters, and GRA scores were compared before and after treatment and between different treatment outcome groups (satisfactory: GRA≥2 unsatisfactory: GRA<2). Baseline urine biomarkers were analyzed to identify potential treatment outcome predictors. After four PRP injections, 54 (55.1%) patients reported satisfactory outcomes. Lower urinary tract symptoms, bladder pain, urinary frequency, anxiety, and flow rate significantly improved from baseline (P < 0.05) in all patients, regardless of the treatment outcome. All patients experienced improved treatment outcomes and increased maximum bladder capacity with successive PRP treatments, and no major complications were reported. Urine biomarkers indicated elevated inflammation and oxidative stress biomarkers in patients with IC/BPS compared to controls. Repeated PRP injections are safe and effective for reducing symptoms and bladder pain and improving bladder capacity in a majority of IC/BPS patients, with better outcomes observed in patients with a mild form of bladder inflammation. These results support PRP as a promising novel bladder therapy for IC/BPS.

The Pharmacogenomics Global Research Network Implementation Working Group: global collaboration to advance pharmacogenetic implementation.

Pharmacogenetics promises to optimize treatment-related outcomes by informing optimal drug selection and dosing based on an individual's genotype in conjunction with other important clinical factors. Despite significant evidence of genetic associations with drug response, pharmacogenetic testing has not been widely implemented into clinical practice. Among the barriers to broad implementation are limited guidance for how to successfully integrate testing into clinical workflows and limited data on outcomes with pharmacogenetic implementation in clinical practice. The Pharmacogenomics Global Research Network Implementation Working Group seeks to engage institutions globally that have implemented pharmacogenetic testing into clinical practice or are in the process or planning stages of implementing testing to collectively disseminate data on implementation strategies, metrics, and health-related outcomes with the use of genotype-guided drug therapy to ultimately help advance pharmacogenetic implementation. This paper describes the goals, structure, and initial projects of the group in addition to implementation priorities across sites and future collaborative opportunities.

RE: Exercise and Nutrition to Improve Cancer Treatment-Related Outcomes (ENICTO).

RE: Exercise and Nutrition to Improve Cancer Treatment-Related Outcomes (ENICTO).

Effect of stroke etiology on treatment-related outcomes in young adults with large vessel occlusion: Results from a retrospective cohort study

Large vessel occlusion-acute ischemic stroke (LVO-AIS) is infrequent in young adults and exhibits distinct stroke mechanisms compared to older adults. This study sought to evaluate the impact of varying stroke etiologies on treatment-related outcomes in young adults with LVO-AIS, an aspect that remains unclear. This retrospective cohort study included patients aged 18-50 presenting with AIS from January 2017 to December 2021 within our multi-center stroke network. Patients with LVO on CTA/MRA at presentation were included. We assessed demographics, stroke etiology (TOAST classification), and treatment-related outcomes. Based on intervention received, patients were divided into 5 groups [IV-thrombolysis (IVT) only, Mechanical Thrombectomy (MT) only, IVT+MT, no treatment, unsuccessful MT]. Among 1210 AIS patients, 220 with LVO were included. The median age was 42 (36, 46). 75 (34.1 %) patients underwent successful MT (46.7 % received IVT+MT). 26 (11.8 %) received IVT only, 110 (50 %) received neither intervention, and 9 (4.1 %) underwent unsuccessful MT. Per TOAST, 17.4 % had large artery atherosclerosis (LAA), 19.2 % cardio-embolism, 28.6 % stroke of other etiology, and 34.7 % had undetermined etiology. Favorable thrombectomy outcomes (TICI 2b/2c/3) were observed in 87.2 %. Discharge NIH Stroke Scale (NIHSS) scores improved for patients with IVT+MT in all TOAST categories except LAA. Young adults with LVO-AIS had good outcomes irrespective of stroke etiology, except LAA, which was associated with a higher discharge NIHSS. Moreover, 50 % of young adults in our study received no intervention, a quarter of those owing to delayed presentation. Further studies are needed to identify barriers in seeking acute treatment in young adults with LVO-AIS.

A systematic review of health-related quality of life outcomes in patients with advanced breast cancer treated with palbociclib.

Aim: To evaluate the impact of palbociclib treatment on health-related quality of life (HRQoL) in patients with hormone receptor-positive, human epidermal growth factor 2-negative advanced breast cancer (HR+/HER2- aBC) or metastatic breast cancer (mBC) in both the clinical and real-world setting. Materials & methods: A systematic literature review was conducted to identify clinical trials and real-world evidence studies up to June 2023 that reported HRQoL outcomes in patients with HR+/HER2- aBC or mBC treated with Palbociclib. Results: 15 unique studies reported across 35 records were identified. Of these, seven were randomized controlled trials (RCTs), three were single-arm clinical trials and five were real-world evidence (RWE) studies. HRQoL was generally found to be maintained in patients with HR+/HER2- aBC or mBC across RCTs, single-arm clinical trials and RWE studies. HRQoL measures across instruments, study types and line of therapy, were largely reported to be at least maintained if not improved from baseline among patients treated with palbociclib and were observed to be comparable or better in the palbociclib group versus monotherapy control arm in RCTs. Similar results were seen for treatment-related outcomes (e.g., sexual functioning, upset by hair loss, systemic therapy side effects etc.), and important individual patient outcomes, including pain, fatigue and physical functioning. Findings were also consistent across key clinical characteristics (visceral metastases, neutropenia), as well as patient populations often underrepresented in clinical trials (Asian patients, older adults). Conclusion: Overall, current evidence suggests that HRQoL is largely preserved with the addition of palbociclib to endocrine therapy in patients with HR+/HER2- aBC or mBC across study types and populations.

Impact of Diet Modifications on Body Weight, Body Composition, Treatment Outcomes, and Quality of Life During Primary Treatment for Breast Cancer: A Systematic Review.

Breast cancer is a significant public health challenge, with 290 000 new cases annually and significant healthcare costs. Treatment advancements have led to improvements in survival, but common adverse effects include weight gain, fatigue, nausea, and taste changes, decreasing quality of life. This review aims to assess the impact of diet and lifestyle interventions during primary treatment for breast cancer and their effects on body weight, body composition, treatment-related adverse outcomes, and patient-reported quality of life. A search of PubMed, CINAHL, and EMBASE conducted through May 10, 2023, identified 31 publications describing 27 interventions including diet or diet plus exercise. The Cochrane Risk of Bias tool assessed the quality of publications. The findings suggest that whole foods, aerobic and strength-training exercises, and intermittent fasting during treatment may improve body weight and composition, treatment-related outcomes, and quality of life. Limitations include variation in study duration, small sample sizes, and limited sociodemographic data. Improvements seen with increased diet quality and reduced caloric intake, with or without exercise, challenge current standard-of-care recommendations during treatment for breast cancer. While there is a need for additional research, healthcare teams can confidently promote healthy diets and exercise during primary treatment for breast cancer to manage weight and improve treatment-related side effects and quality of life. PROSPERO registration no. 42023425613.

Brain Stem Glioma Recurrence: Exploring the Therapeutic Frontiers.

Gliomas of the brainstem represent a small percentage of central nervous system gliomas in adults. Due to the proximity of the tumor to critical structures, radical surgery is highly challenging and limited to selected cases. In addition, postoperative treatments, which become exclusive to non-operable patients, do not guarantee satisfactory disease control, making the progression of the disease inevitable. Currently, there is a lack of therapeutic options to control tumor growth after the diagnosis of recurrence. The rarity of these tumors, their distinct behavioral characteristics, and the limited availability of tumor tissue necessary for the development of prognostic and predictive biomarkers contribute to the absence of a standardized approach for treating recurrent brainstem gliomas. A salvage radiotherapy (RT) retreatment could represent a promising approach for recurrent brainstem gliomas. However, to date, it has been mainly evaluated in pediatric cases, with few experiences available to assess the most appropriate RT dose, safety, and clinical responses in adult patients. This comprehensive review aims to identify instances of adult patients with recurrent brainstem gliomas subjected to a secondary course of RT, with a specific focus on the analysis of treatment-related toxicity and outcomes. Through this investigation, we endeavor to contribute valuable insights into the viability and efficacy of salvage RT retreatment in managing recurrent brainstem gliomas in the adult population.

Moderately hypofractionated prostate-only versus whole-pelvis radiotherapy for high-risk prostate cancer: A retrospective real-world single-center cohort study

The benefit of prophylactic whole pelvis radiation therapy (WPRT) in prostate cancer has been debated for decades, with evidence based mainly on conventional fractionation targeting pelvic nodes. This retrospective cohort study aimed to explore the impact of adding moderately hypofractionated pelvic radiotherapy to prostate-only irradiation (PORT) on prognosis, toxicity, and quality of life in real-world settings. Patients with high-risk and conventionally staged prostate cancer (cT1-3N0M0) treated with moderately hypofractionated WPRT or PORT, using external beam radiotherapy alone or combined with high-dose-rate brachytherapy, at Örebro University Hospital between 2008 and 2021 were identified. Biochemical failure-free survival (BFFS), metastasis-free survival (MFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were compared using Kaplan-Meier method and Cox proportional hazards. Toxicity and quality of life measures were also analysed. Among 516 patients (227 PORT, 289 WPRT), 5-year BFFS rates were 77% (PORT) and 74% (WPRT), adjusted HR=1.50 (95% CI=0.88-2.55). No significant differences were found in MFS, PCSS, or OS in main analyses. WPRT was associated with a higher risk of acute grade≥2 and 3 genitourinary toxicities whereas no differences in late toxicities or quality of life between PORT and WPRT were observed. We found no significant differences in oncological outcomes or quality of life when comparing moderately hypofractionated PORT to WPRT. Some differences in toxicity patterns were observed. Despite caveats related to study design, our findings support the need for further research on WPRT's impact on treatment-related and patient-reported outcomes.

Integrating lifestyle medicine into cancer care: A new paradigm.

179 Background: Amid rising global cancer rates and obesity-related cancer risks, oncology must blend traditional cancer treatments with evidence-based lifestyle medicine (LM) to enhance patient outcomes. LM—evidence-based interventions in nutrition, exercise, sleep, avoiding substances, and social connection —emerges as a critical tool in the care spectrum. ASCO and ACS guidelines incorporating lifestyle interventions are limited, and existing ones have notable implementation gaps. This study advocates for integration of LM into cancer care. Such interventions, supported by growing research, offer significant promise in reducing cancer treatment side effects and improving outcomes, highlighting an urgent need for their incorporation into oncological protocols. Methods: The Department of Preventive Medicine at Cleveland Clinic Abu Dhabi (CCAD) launched an LM program at the Oncology Institute. Oncologists refer to LM physicians who assess patients using an LM-validated questionnaire. Cardiometabolic risk factors: body composition, waist circumference, lipid profile, hemoglobin A1c, high-sensitivity CRP, liver function, and liver elastography are tested at baseline and 3 months. Patients receive personalized LM treatment by certified physicians, dieticians, physiatrists, and psychologists, aimed at reducing treatment side effects and enhancing cancer outcomes while improving cardiometabolic health. Follow-ups at 6 weeks and 3 months post-intervention ensure progress tracking and reassessment. Results: Initiated in January 2021, it began as a pilot program for breast cancer patients and has since expanded to all cancer patients. To date, it enrolled 425 patients, evidencing sustainability and acceptance within the patient community. Referral rates from oncologists have shown a steady increase, reflecting the program's growing credibility and utility. Patient satisfaction levels are reported to be high. Preliminary outcomes indicate improvements in both physical and psychological health metrics, suggestive of the program's comprehensive impact. Conclusions: The pioneering oncology LM program at CCAD established a transformative model that seamlessly integrates LM into traditional oncology care and acts as a bridge to survivorship. By ensuring sustained access to lifestyle interventions from the point of diagnosis through post-treatment, the program aligns with the latest research and ASCO/ACS guidelines, pioneering a new standard in cancer treatment. It can effectively address cardiometabolic risks, including obesity, and reduce treatment-related adverse outcomes. This program demonstrates the feasibility and a replicable global model, one that merges evidence-based lifestyle practices with standard oncological care to create a unified approach that could be adopted by healthcare systems worldwide, marking a significant step in the evolution of patient-centered cancer care.

A Modified Floxuridine Reduced-Dose Protocol for Patients with Unresectable Colorectal Liver Metastases Treated with Hepatic Arterial Infusion.

Most patients treated with the standard dosing protocol (SDP) of hepatic arterial infusion (HAI) floxuridine require dose holds and reductions, thereby limiting their HAI therapy. We hypothesized that a modified dosing protocol (MDP) with a reduced floxuridine starting dose would decrease dose holds, dose reductions, and have similar potential to convert patients with unresectable colorectal liver metastases (uCRLM) to resection. We reviewed our institutional database of patients with uCRLM treated with HAI between 2016 and 2022. In 2019, we modified the floxuridine starting dose to 50% (0.06 mg/kg) of the SDP (0.12 mg/kg). We compared treatment related outcomes between the SDP and MDP cohorts. Of n = 33 patients, 15 (45%) were treated on the SDP and 18 (55%) with our new institutional MDP. The MDP cohort completed more cycles before a dose reduction (mean 4.2 vs. 2), received more overall cycles (median 7.5 vs. 5), and averaged 39 more days of treatment (all P < 0.05). The SDP experienced more dose reductions (1.4 vs. 0.61) and dose holds (1.2 vs. 0.2; both P < 0.01). Of the patients in each group potentially convertible to hepatic resection, three patients (23%) in the SDP and six patients (35%) in the MDP group converted to resection (P = 0.691). Overall, four patients (27%) in the SDP developed treatment ending biliary toxicity compared with one patient (6%) in the MDP. A 50% starting dose of HAI floxuridine provides fewer treatment disruptions, more consecutive floxuridine cycles, and a similar potential to convert patients with initially uCRLM for disease clearance.

Effect of self-efficacy among persons who inject drugs treated with direct-acting antivirals on Hepatitis C treatment initiation, duration, completion, adherence, and cure

Self-efficacy, a patient-level factor, has been shown to facilitate patient engagement in treatment and optimize treatment-related outcomes in various health contexts. Research on interventions supporting hepatitis C virus (HCV) direct-acting antiviral (DAA) treatment uptake and adherence among persons who inject drugs (PWID) is needed, but whether self-efficacy factors influence DAA treatment cascade outcomes in this population has been less studied. Using the HERO study data, we analyzed a subset of participants with any general health self-efficacy data (n=708) measured at baseline and end-of-treatment time points using a 5-items instrument (facets: 'goal setting', 'goal attainment', 'having a positive effect', 'being in control', and 'working to improve'). The cascade outcomes included DAA treatment initiation, duration, adherence, completion, and sustained virologic response (SVR). The effect of baseline and change (Δ) scores for composite and item-level self-efficacy on the cascade outcomes was assessed using logistic regression and generalized linear models. Higher baseline composite self-efficacy [adjusted odds ratio (95 % confidence interval) =1.57 (1.07, 2.29)], 'goal attainment' [1.31 (1.03, 1.67)] and 'having a positive effect' [1.33 (1.03, 1.74)] were associated with greater likelihood of treatment initiation. 'Δ Goal attainment' was significantly associated with SVR [1.63 (1.04, 2.53)]. 'Δ Being in control' and 'Δ working to improve' were associated with treatment adherence and duration, respectively. General health self-efficacy positively influences DAA treatment initiation among PWID. 'Goal attainment' facilitates the achievement of DAA treatment-related outcomes. Further studies should assess the effect of self-efficacy related to performing healthcare tasks specific to DAAs on the treatment-related outcomes.

One-stage prosthodontically driven jaw reconstruction in patients with benign and malignant pathologies: A 7- to 11-year cohort study.

One stage functional jaw reconstructionis defined as the resection and reconstruction of segmental defects in conjunction with the placement of dental implants in an ideal prosthetic position and loaded with a provisional restoration, during one surgical procedure. The aim of the study is to describe clinical outcomes of patients who underwent one stage functional jaw reconstruction. Patients who underwent one-stage functional jaw reconstruction, from January 2013 to March 2016 were recalled in 2022 and 2023. Planning and execution for the reconstruction utilized either analogue or digital techniques. Outcome parameters recorded were treatment-related outcomes at patient level, implant-related outcomes and patient-reported outcome measures. Eighteen patients underwent one-stage jaw reconstruction with a total of 57 implants. Four patients had maxillary and 14 had mandibular reconstructions. Ten patients underwent postoperative radiotherapy. Ten patients were planned using analogue and eight by digital planning. Three patients had partial flap necrosis, three patients had plate fractures, implant loss was seen in one patient and four patients died during the period. A functional prosthesis was provided in 16 out of the 18 patients. One-stage functional jaw reconstruction is a predictable method for providing rehabilitation with successful outcomes at 7-11 years. However, caution should be exercised when the treatment modality is carried out in patients with malignant pathologies who have undergone radiotherapy.

Pharmacokinetics and Safety of Remdesivir in Pregnant and Nonpregnant Women With COVID-19: Results From IMPAACT 2032.

Pregnant people with coronavirus disease 2019 (COVID-19) experience higher risk for severe disease and adverse pregnancy outcomes, but no pharmacokinetic (PK) data exist to support dosing of COVID-19 therapeutics during pregnancy. We report PK and safety data for intravenous remdesivir in pregnancy. IMPAACT 2032 was a phase 4 prospective, open-label, nonrandomized opportunistic study of hospitalized pregnant and nonpregnant women receiving intravenous remdesivir as part of clinical care. Intensive PK sampling was performed on infusion days 3, 4, or 5 with collection of plasma and peripheral blood mononuclear cells (PBMCs). Safety data were recorded from first infusion through 4 weeks after last infusion and at delivery. Geometric mean ratios (GMR) (90% confidence intervals [CI]) of PK parameters between pregnant and nonpregnant women were calculated. Fifty-three participants initiated remdesivir (25 pregnant; median gestational age, 27.6 weeks; interquartile range, 24.9-31.0 weeks). Plasma exposures of remdesivir, its 2 major metabolites (GS-704277 and GS-441524), and the free remdesivir fraction were similar between pregnant and nonpregnant participants. Concentrations of the active triphosphate (GS-443902) in PBMCs increased 2.04-fold (90% CI, 1.35-3.03) with each additional infusion in nonpregnant versus pregnant participants. Three adverse events in nonpregnant participants were related to treatment (1 grade 3; 2 grade 2 resulting in treatment discontinuation). There were no treatment-related adverse pregnancy outcomes or congenital anomalies detected. Plasma remdesivir PK parameters were comparable between pregnant and nonpregnant women, and no safety concerns were identified based on our limited data. These findings suggest no dose adjustments are indicated for intravenous remdesivir during pregnancy. NCT04582266.

Survival impact of KRAS mutation in metastatic colorectal cancer (mCCR) under first-line treatment.

3547 Background: Activating mutations in the MAPK pathway are predictive biomarkers in mCCR and 50% of patients (pts) present KRAS mutations. There is a large spectrum of molecular aberrations with a lack of data regarding tumor side correlations and their impact on treatment response and overall survival. Methods: Retrospective cohort of mCRC pts and KRAS activating mutations treated between 2019-2022 in a tertiary cancer center in Brazil. KRAS gene was analyzed by next-generation sequencing in tumor tissue samples. Electronic medical records were reviewed with case report forms registered in RedCap software. The primary endpoint was Overall survival (OS), estimated using Kaplan-Meir and compared with the log-rank test. Cox proportional models were applied to estimate hazard ratios (HR). Results: We included 490 patients with a mean age of 59 years (y), mostly male, 51.4%. Primary left-side location was present in 65.5% and liver metastasis in 66.7%. The spectrum of KRAS mutations found were G12D (31.2%), G12V (20.2%), G13D (15.1%), G12C (9.4%), G12A (4.9%), G12S (3.5%), and G12R (2%). First line regimen was 5-FU and Oxaliplatin (mFLOX) in 84.9% (n=388), with a median PFS of 9.2 months (95%CI 7.8 - 11.6) and OS of 21 months (95%CI;19-23) in this group. Treatment related outcomes in first-line therapy at first evaluation were 40% partial response, 20.4% stable disease, 30,9% disease progression and 1.3% complete response. G12S mutation was associated with better PFS 18.62 vs. 8.75m compared with other codon mutations (HR:0.52;95%CI 0.28-0.98) and OS NR vs. 21.58m HR (HR:0.48;95%CI;0.24-0.97). G12R was associated with worse PFS 5.31 vs. 9.90 m (HR:2.2;95%CI;1.09-4.47) and OS 17.89 vs. 21.88m (HR:1.61;0.79-3.24). Sideness was not associated with prolonged response or overall survival right-sided tumors 20.72 vs. vs. left-sided tumors 22.14m (HR:1.04;95%CI;0.82-1.31). Conclusions: Specific mutated codons in the KRAS gene impact PFS and OS independently of primary tumor sidedness. G12S mutation demonstrated an improved OS and PFS. [Table: see text]

Pharmacogenomic diversity of clinically significant cancer treatment biomarkers in ancestrally diverse US population.

e15099 Background: Cancer Health Disparities (CHD), in the US is well documented. The is significant evidence of CHD treatment related outcomes along ancestry lines. Africans and Hispanics generally have higher rates of adverse drug reactions (ADR), and poorer survival and response rates when compared to Europeans and Asians. The causes of CHD treatment related outcomes are poorly understood but it is plausible to believe that CHD has a genetic basis, given that human genomic variations underlie both disease susceptibility and treatment outcomes. Our goal is to determine the genetic basis of CHD treatment related outcome, with a particular focus on under-represented and underserved populations. Methods: We will deploy pharmacogenomic (PGx) differentiation analyses using a comprehensive patient database and correlative banked tissue (~ 2,000 patients) from MCW, together with 3 international cohorts as comparators (Africans = 372, Asians = 1,250 and Europeans = 958) to: Interrogate clinically significant cancer treatment PGx biomarkers and characterize the variation across different populations. Assess the implications of genetic admixture on CHD treatment related outcomes. Evaluate the intersection of genetic diversity with pharmacogenomic diversity. Explore the distribution of age, gender, diagnosis, treatments, response, ADRs, survival, comorbidities, and concomitant medication. Results: Our initial results point to a significant genetic contribution to CHD treatment related outcomes. The enrichment of genetic risk factors for therapeutic failure, ADRs or poorer survival in patients of African vs European descent, explains the increased sensitivity to ADRs, poorer response rates, and decreased survival in patients of African vs European descent. We will extend this analysis to a multi-ethnic US cohort including Africans, Hispanics, Europeans, Asians, and First Nations. Conclusions: There is extensive PGx diversity within the US population, hence, coupling preemptive PGx testing with genetic testing is imperative for a truly equitable delivery of healthcare. There is a need for diversified representation of all population in cancer research to level the gaps in CHD. The identification of the genetic basis of CHD treatment related outcomes is imperative for predicting outcomes, and the implementation of preemptive PGx and precision medicine. [Table: see text]

Clinical implications of synovial tissue phenotypes in rheumatoid arthritis.

Autoimmune forms of inflammatory arthritis, such as Rheumatoid Arthritis (RA), are clinically heterogeneous in presentation and disease course. Treatment-related outcomes vary despite patient exposure to similar treatment strategies. It is likely that variation seen in synovial pathogenesis influences outcomes and is heterogeneous outcomes influenced by patient factors, including environmental exposures, microbiota, behaviors, timely access to therapy, and synovial cell variation. Patients' unique complex factors manifest as specific synovial phenotypes characterized by clusters of synovial cell types and states. Precision medicine aims to use such clinical and biological data to identify the right treatment for the right patient at the right time, enabling patients to achieve sustained remission. Identifying synovial targets susceptible to a given treatment, enabling the choice of effective therapy for a given patient, will realize the goals of precision medicine. Over the last 7 years, improved acquisition and processing of synovial tissue obtained by ultra-sound guided biopsy has enabled researchers to define synovial pathotypes using histologic features and predominant cell types associated with clinical manifestations. Technical advances have enabled single-cell simultaneous sequencing of proteins and gene expression that, through increasingly sophisticated bioinformatics methods, have taken transcriptional and proteomic data to identify diverse and novel cell types and states that cluster in the RA synovium to further define patient subgroups. Synovial pathotypes and endotypes are now integrated into clinical studies and trials to explain clinical heterogeneity in disease course and treatment response. Rapidly evolving clinical-translational research has linked an expanded understanding of RA synovial pathogenesis with clinically meaningful subgroups and treatment outcomes and the clinical heterogeneity in RA.