Management Of Side Effects Research Articles

Psoriasis in the Era of Targeted Cancer Therapeutics: A Systematic Review on De Novo and Pre-existing Psoriasis in Oncologic Patients Treated with Emerging Anti-neoplastic Agents.

New advancements in medicine have paved the way for targeted therapies and immune checkpoint inhibitors (ICIs), which have become mainstays of cancer therapy. Targeted therapies work by pinpointing specific molecules in cancer pathways and inhibiting their function, while ICIs target irregularities in the immune system and DNA repair, participating in the induction of cell death. Although these agents have demonstrated great efficacy in treating a diverse set of cancers, they can frequently provoke serious dermatologic adverse effects. The side effects caused by an ICI are classified as immune-related adverse events since ICIs are immunomodulating, while the cutaneous side effects of targeted therapies are known as dermatologic adverse effects. Multiple studies have reported psoriasis and psoriasiform eruptions among the side effects observed in neoplastic patients receiving targeted therapies or ICIs. Psoriasis is an immune-mediated disease characterized by overactive T-cells and keratinocytes. To conduct this review, we retrieved 1363 studies from the PubMed database published between 2008 and 2023 using the terms "psoriasis" AND "cancer treatment." Many of these studies aimed to understand how patients with cancer receiving treatment may develop or even achieve psoriasis remission. Given that cancer and psoriasis involve a delicate balance between immune activation and suppression, ICIs and targeted therapies might produce varying effects. The aim of this review was to explore the relationship between psoriasis and cancer therapeutics while also highlighting the need to prioritize proper management of cutaneous side effects in neoplastic patients.

The Evolving Role of Chlorthalidone and Hydrochlorothiazide as First-Line Treatments for Hypertensive Patients.

Hypertension is attributable long-term to various negative health outcomes, including atherosclerotic cardiovascular disease and, more broadly, to cardiovascular events such as congestive heart disease, myocardial infarction, heart failure, and stroke. Effective hypertension treatment is essential to lower the risk of these outcomes. Treatment of hypertension includes both nonpharmacologic and, if necessary, pharmacologic interventions. The drug classes proven in trials to decrease the risk of cardiovascular disease events in cases with hypertension include angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, thiazide diuretics, and calcium channel blockers. When considering thiazide diuretics as a first-line treatment, chlorthalidone (CTD) is currently recommended by the American College of Cardiology over hydrochlorothiazide (HCTZ). Previous studies have demonstrated that CTD is superior to HCTZ in preventing cardiovascular disease events. However, more recent studies have revealed that there is no significant difference in the results of patients treated with HCTZ versus those treated with CTD. Additionally, studies have revealed CTD has worse outcomes regarding side effects when compared to HCTZ. In this regard, it is essential to carefully consider which medication will best improve the outcomes of patients with hypertension while also causing few or easily manageable side effects.

Application and Challenges of Antifungal Drugs in the Treatment of Fungal Sinusitis

This article discusses the application and challenges of antifungal drugs in the treatment of fungal sinusitis. The article first discusses the characteristics and pathological mechanisms of fungal sinusitis, and then analyzes in detail the mechanism of action and clinical application of antifungal drugs, including the main challenges they face, such as the development of drug resistance and the management of drug side effects. The paper also emphasizes the importance of personalized medicine and looks forward to future development trends, pointing out that future research will focus on developing new drugs, optimizing existing drug formulations, and advancing personalized medicine. The article concludes by emphasizing the importance of interdisciplinary collaboration in future research.

Failure of the PD-1 Blocking Agent Pembrolizumab to Benefit a Patient with Renal Squamous Cell Cancer.

Renal squamous cell carcinoma (SCC) is a neoplasm with an extremely rare occurrence compared to other renal malignancies. The classic presentation includes a palpable mass and flank pain; however, the presentation is seldom non-specific. Our study describes the significance of programmed death ligand-1 (PD-L1) expression in renal cancer and its association with clinical outcomes, alongside available treatment options. An 80-year-old female with a history of hypertension and cerebral aneurysm presented with right flank pain and blood in urine and was diagnosed with pyelonephritis and left renal mass/phlegmon. A biopsy revealed SCC of the kidney with metastasis to the lung and aortocaval lymph node. Positron emission tomography (PET) scan confirmed malignancy in the kidney and lung. Treatment with pemrolizumab and carboplatin plus paclitaxel was initiated but poorly tolerated as the haemoglobin dropped rapidly. SCC poses a diagnostic challenge due to its rarity and non-specific symptoms, often leading to advanced stage diagnosis. PD-L1 expression is pivotal in assessing tumour aggressiveness and prognosis. PD-L1 inhibitors offer promise, but their efficacy in renal SCC warrants further investigation. Radical nephrectomy and systemic chemotherapy show potential in advanced cases, necessitating vigilant management of treatment-related side effects. This case emphasises the need for ongoing research to refine therapeutic approaches and enhance outcomes in renal SCC patients. PD-L1 expression is pivotal in assessing tumour aggressiveness and prognosis of renal cell carcinoma.PD-L1 inhibitors hold promise as a therapeutic intervention in renal squamous cancer.Radical nephrectomy and systemic chemotherapy show potential in managing advanced renal cancer.

Impressive response to Pralseltinib in KIAA1468 RET-fusion anaplastic thyroid cancer: a case report and literature review

Anaplastic thyroid carcinoma (ATC) is a severe, aggressive form of cancer with low survival rates. Multimodal therapies are currently employed with limited success and targeting molecular subgroups of ATC, such as those with RET translocation, is an active area of research. In this case report, we present a patient with metastatic ATC harboring a RET translocation, treated with two RET-specific tyrosine kinase inhibitors (TKIs), Pralsetinib and Selpercatinib. Pralsetinib resulted in a significant and rapid reduction in lung metastasis complicated by a pneumothorax effects. The initial efficacy of Pralsetinib in our patient underscores the potential of RET-specific TKIs in the management of RET-altered ATC and highlights the risk of adverse events associated with tumor response in high tumor burden diseases. Meticulous management of side effects remains essential to improve patient outcomes.

Improving the nutritional care of oncology patients - Validation of a multidisciplinary protocol in the Spanish clinical setting

malnutrition is a very frequent problem in oncology patients and can have serious repercussions. Adequate nutritional management is cost-effective in terms of health and survival in this population, but it requires multidisciplinary coordination, specific training, and continuous follow-up. to validate the applicability and efficacy of a multidisciplinary nutritional support protocol in oncology patients. a multidisciplinary nutritional protocol was developed for oncology patients, with guidelines for screening and assessment of malnutrition, treatment, re-evaluation, and management of side effects, as well as guidance on supplementation and eating patterns. The protocol would be implemented in various clinical centers, collecting data through a structured questionnaire, registering variables before and after implementation. the protocol and its impact were implemented and evaluated in 39 centers. An improvement in nutritional care was observed, evidenced by an earlier initiation of nutritional assessment and an increase in the number of patients receiving adequate care following the protocol implementation. Problems related to inadequate malnutrition coding in the centers, limited resources, and the need for greater interdepartmental collaboration were identified. the conduct of this study provides insights into how the implementation of a multidisciplinary nutritional support protocol can improve the nutritional care received by patients and informs about the main obstacles to adequate implementation.

Tumor Board Practice and Current Approach of Oncologists in Türkiye

Objective: Interdisciplinary cooperation is essential in treating and following up cancer disease. The primary objective of multidisciplinary tumor councils (MDTCs) is to identify the most suitable and effective treatment strategies for cancer patients through the collective decision-making of experts in oncology. MDTC plays a key role in breaking traditional taboos, providing the most up-to-date approach to the patient, sharing responsibility and accountability, and encouraging interdisciplinary communication and collaboration. Material and Methods: In this study, the perspectives, expectations, and experiences of medical oncologists regarding tumor boards were evaluated. The survey consisted of 10 questions and was conducted as an online survey at the '7th National Immunotherapy and Oncology Congress'. This study was cross-sectional and online. While those who were actively working as medical oncologists and those who wanted to voluntarily participate in the survey were included in the study, those who were not medical oncologists, those who were not actively working, and those who worked in private clinics were not included in the study. Participants were asked various questions about multidisciplinary tumor boards. They were asked about the specialties they most needed on the boards, the other clinics participating in the boards, and the clinics they felt were essential. The necessity of genetic clinics and molecular boards in shaping the future of oncology through molecular assessments was also assessed. The impact of board decisions on patient treatment and management was investigated. Results: A total of 624 oncologists participated in the survey. The majority of the participants were young oncologists. Most participants worked in tertiary healthcare units, including university hospitals and training and research hospitals. Almost all of the participants stated that they did MDTC. The most frequent and regular councils are; thoracic cancers and gastrointestinal cancers. The most needed and hard to reach branch was the medical genetics department. Conclusion: Cancer treatment is a complex process that cannot be confined to a single expertise. Multidisciplinary tumor boards (MDTB) are one of the cornerstones of a comprehensive approach to cancer treatment. In multidisciplinary tumor boards, various topics such as medical treatment planning for patients, diagnosis, surgical and radiotherapy planning, side effect management, and palliative care can be examined. MDTB not only provides effective treatment for cancer patients from a broad perspective but also ensures rapid and comprehensive solutions in case of potential complications.

Tailored Treatment Strategies in First Line Therapy for Ovarian Cancer Patients: A Critical Review of the Literature.

Ovarian cancer (OC) is a significant cause of cancer-related mortality in women globally, with a five-year survival rate of approximately 49%. Standard therapy involves cytoreductive surgery followed by chemotherapy. Its poor prognosis has driven interest in alternative therapies such as targeted molecular agents like bevacizumab and poly (ADP-ribose) polymerase inhibitors (PARPi). This review systematically searched PubMed from January 2018 to December 2023 for studies on PARPi in OC. Emphasis was on identifying relevant Phase III trials, extracting data on study design, patient demographics, and outcomes. Special focus was on assessing PARPi efficacy, safety, impact on quality of life, and ongoing trials, including those on Clinicaltrials.gov. The efficacy of PARPi in first-line therapy for OC has been extensively studied. Trials like SOLO-1, PRIMA, and ATHENA-MONO have demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS), particularly in patients with BRCA mutations. Additionally, the combination of PARPi with other agents like bevacizumab has shown promising results in extending PFS. However, PARPi treatment is associated with various adverse effects, including hematologic toxicities like anemia, thrombocytopenia, and neutropenia. While most adverse events are manageable, some patients may require dose adjustments or discontinuation of treatment. Importantly, PARPi maintenance therapy has not adversely affected health-related quality of life (HRQoL), with studies reporting similar HRQoL scores between PARPi-treated and placebo-treated patients. PARPi offer effective treatment with manageable side effects, suitable even for medically fragile patients. Individualized dosing can optimize benefits while minimizing adverse events. Exploring diverse treatment approaches, particularly in patients with limited life expectancy or high disease burden, could improve outcomes. Ongoing research is investigating alternative therapies and combinations to broaden treatment options. Combining bevacizumab with PARPi may be justified for first-line and recurrent maintenance therapy. Regardless of mutational status, PARPi should be considered for maintenance therapy in newly diagnosed advanced OC. Platinum sensitivity remains crucial for treatment decisions and predicting survival outcomes.

Volumizing Threads (Jamber) in the Midface and Managing Side Effects: Clinical Cases.

The clinical application of polydioxanone (PDO) threads, traditionally utilized for tissue lifting, is now being explored for its volumizing effects in midface rejuvenation. The novel approach involves employing PDO volumizing threads to achieve physical augmentation akin to a "solid filler." The study introduces a more convenient insertion method for these threads, prioritizing ease and efficacy. Clinical cases demonstrate the efficacy of volumizing threads in addressing midface concerns, such as nasolabial folds and midcheek grooves. Additionally, the integration of volumizing threads to provide support in sagging areas is examined for achieving natural-looking enhancements. While highlighting positive outcomes, potential side effects like thread protrusion are addressed, along with strategies for their mitigation. Volumizing threads are presented as a suitable procedure for patients wary of traditional fillers or seeking subtle enhancements, with the recommendation of combining them with cog threads for those desiring more pronounced changes in facial contour. In summary, volumizing thread offers a minimally invasive alternative with fewer side effects for midface rejuvenation.

Patient perceptions of advanced practice radiation therapists prescribing medication in radiation therapy

IntroductionThe purpose of this study was to determine patient perceptions of an advanced practice radiation therapist (APRT) prescribing medication for radiation therapy treatment-related side effects. By comprehending patient perceptions, it is important to implement change in order to improve patients’ quality of life. MethodsA literature review was conducted on advanced practice (AP) roles in Canada and world-wide; the roles searched were: APRT, nurse practitioner and pharmacist. The search focused on evidence demonstrating improvements made to patient care due to the implementation of these roles. Based on this review and input from a team of experts a qualitative semi-structured interview survey was designed, and pilot tested. The survey consisted of five open-ended questions, which were designed to determine patient satisfaction of an APRT prescribing medication over the course of their radiation therapy treatments. Patients undergoing head and neck radiation therapy treatments at a large, academic cancer centre were invited to participate. Six patients who had a head and neck APRT involved in their treatment were interviewed. A comprehensive thematic analysis was then conducted using the transcripts created from these interviews, which was followed by two independent blinded analyses to ensure validity of the results. DiscussionThe thematic analysis produced four salient themes which were: side effect management, care provided by the APRT in comparison to other healthcare workers, patients’ access to care, and overall patient satisfaction. Common medications for head and neck radiation therapy treatment related side effects were discussed and these were: Magic Mouthwash, Xylocaine, Nystatin, Benadryl, Advil, Tylenol, Dexamethasone, Tantum, Biotene, Mucaine, Flamazine, Hydrocortisone, Ondansetron, Senokot, and narcotics. ConclusionThis study was valuable to understand patient experiences and provide evidence to change processes in order to improve quality of patient centered care. The study revealed that although patients were happy with the process of prescribing medication, they all agreed that having an advanced practice radiation therapist prescribe would improve care. Patient responses further demonstrated the need for future research in regards to side effect management as a whole by APRTs as well as how role clarification can impact patient perceptions of APRTs.

Adherence to Hidradenitis Suppurativa Treatment.

Hidradenitis suppurativa (HS) is a chronic, debilitating skin condition that requires multimodal treatment. Adherence remains a significant challenge for many patients due to complex nature of treatment, thus presenting a barrier to management success. This review summarizes the current literature on the factors associated with adherence to medications, and lifestyle behaviors in patients with HS and proposes strategies to improve adherence. In February 2023, a systematic literature search was conducted by two independent authors on PubMed and EMBASE for articles from 2000 to 2023 on hidradenitis suppurativa adherence. A total of 21 articles met inclusion/exclusion criteria for this review. Of the studies, 11 addressed systemic medication adherence, 3 addressed topical medication adherence, 2 addressed both systemic and topical medication adherence, and 5 addressed lifestyle/behavioral modification adherence. The generalizability of results was limited by differences in study design, outcome measures, and sample size. English-only articles with full texts were used. The most reported reasons for non-adherence included presence of side effects, cost of medications, low efficacy, and unclear instructions. Proposed strategies to improve adherence in HS patients include management of side effects, use of reminder systems, improved patient education, patient support groups, aid of family and caregivers, personalization of the medication regimen, and regular follow-ups with patients. PROSPERO Registration Number: CRD42023488549.

Navigating cancer care through digital dialogue: Analyzing key phrases shared by patients in real-time exchange messages using an electronic patient-reported outcome measure (ePROM).

e13661 Background: Cancer is a complex ailment, giving rise to a myriad of symptoms, side effects, and questions that may arise unexpectedly. There is a growing interest in adopting more efficient approaches for the continuous monitoring of patients, particularly through virtual platforms. This study focuses on analyzing the word frequency in the context of cancer assistance using an ePROM. Methods: We conducted an analysis of an ePROM embedded in a mobile app designed for monitoring patients undergoing cancer treatment. Developed collaboratively by medical oncologists and software engineers, this app empowers patients to document their symptoms, quality of life, emotions, emergency room visits, and hospitalizations. Upon app registration, patients willingly share their data with their medical team, along with essential demographic information. A standout feature is the online chat facilitating real-time communication with the medical team, consolidating all information securely in one place. This patient-centric app is provided free of charge. Our study involved a retrospective and descriptive analysis focusing solely on data related to exchanged messages in the online chat between cancer patients and the medical team. These conversations spanned from February 2022 to January 2024 and included patients referred by physicians recommending our platform. The analysis centered on the frequency of non-technical words used in real-time conversations, clustered into semantic groups. Results: Our findings revealed a total exchange of 470,597 words across 684 conversations over a two-year period. In the healthcare context, the most frequent words were categorized as follows: 1) Seeking in-person assistance (568; 0.12%): hospital (424 mentions), emergency (82), urgent/urgency (51), and primary care (UBS, Portuguese acronym) (11); 2) Doubts regarding anything (979; 0.20%): doubt (694 mentions) and question (285); 3) Non-technical one-word symptoms (5213; 1.10%): pain (1821 mentions), nausea (961), tiredness (514), diarrhea (428), vomit (364), fever (304), cough (221), numbness (197), dizziness (162), insomnia (130), constipation (101), and wheezing (10). Conclusions: Our analysis showed two key insights: first, doubts persist throughout treatment, intertwined with the management of side effects; and second, the burden on patients is substantial, whether stemming from uncertainty about the next steps or the necessity for in-person assistance. Cancer's mental and physical toll underscores the importance of having a readily available team to provide guidance, even on simple instructions. In this light, virtual platforms may represent the future of care delivery. Continuous patient monitoring emerges as pivotal for enhancing healthcare assistance, treatment, and outcomes across various cancer types.

Neoadjuvant pyrotinib and inetetamab in combination with chemotherapy for locally advanced HER2-positive breast cancer (NeoPICD study): A prospective, multicenter, open-label, single-arm study.

e12627 Background: Inetetamab, a novel monoclonal antibody targeting HER2, alters the Fc region amino acids, which induces ADCC stronger than trastuzumab. Pyrotinib is a small chemical inhibitor of pan-HER receptor tyrosine kinase. The globally recommended first-line neoadjuvant treatment for HER2-positive breast cancer is chemotherapy and two large-molecule monoclonal antibodies, which have unsatisfactory benefits for 50% of patients. This study aims to investigate the effectiveness and safety of targeted medicines, specifically inetetamab and pyrotinib, in conjunction with chemotherapy for patients diagnosed with locally advanced HER2-positive breast cancer. Methods: The trial was structured as a multicenter, open-label, single-arm, prospective study. 143 treatment-naive HER2-positive locally advanced breast cancer patients were planned for the trial. Eligible patients will be administered six cycles of neoadjuvant treatment, including carboplatin (AUC=6mg/mL×min, ivgtt), doxorubicin (75mg/m2, ivgtt), inetetamab (initial loading dosage of 8mg/kg, maintenance dose of 6mg/kg), and pyrotinib (400mg/day, po). The surgery was conducted after the neoadjuvant phase, subsequent to a one-year course of targeted therapy with inetetamab and pyrotinib. The primary endpoint of the study is the total pathologic complete response (tpCR). The secondary endpoints include event-free survival (EFS), disease-free survival (DFS), distant metastasis-free survival (DMFS), neurologic disease-free survival (NDFS), overall survival (OS), and safety. Results: A cohort of 70 patients was enrolled between Nov. 27, 2021 and Feb. 1, 2024. Most patients completed the six-cycle neoadjuvant therapy with inetetamab, pyrotinib, and chemotherapy. The pathological findings of 49 patients who had radical surgery revealed that 65.3% (32/49, 95% CI, 0.515-0.791) of them achieved tpCR (ypT0/Tis ypN0). The initial subgroup analysis revealed that among patients with negative hormone receptors, the rate of tpCR was 80.0% (24/30, 95% CI, 64.8-95.2). Moreover, hormone receptor was statistically determined to be an independent factor influencing the effectiveness of the new treatment regimen ( p=0.032). The prevailing grade 3 or more severe adverse events included anemia (12.8%), diarrhea (10.0%), leukopenia (4.2%), liver dysfunction (4.2%) and renal dysfunction (4.2%). As of now, no treatment-related deaths have been documented. Conclusions: The ongoing study is actively enrolling participants. Preliminary findings from the study indicate that the combination of neoadjuvant inetetamab and pyrotinib with chemotherapy has demonstrated satisfactory effectiveness and manageable side effects. This offers a promising alternative for patients with locally advanced breast cancer that is HER2-positive. Clinical trial information: NCT06234137 .

A phase IV study of ApricityCARE program for cancer adverse events rapid evaluation to improve treatment outcomes of ethnic/racial minority patients with non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICI).

TPS1642 Background: ICI have changed the treatment landscape of NSCLC, with many now FDA approved in not just advanced, but even early-stage disease. With the increase in ICI use, the incidence of immune-related adverse effects (irAEs) has also risen, occurring in up to 16% of ICI-treated patients. Prompt recognition and timely management are necessary to avert potential poor outcomes from direct toxicity and/or early treatment discontinuation. However, existing barriers to access care that disproportionately impact racial and ethnic minority patients may amplify challenges in early, effective management of irAEs. Using technology-enabled health interventions in a culturally competent manner can improve access to health care resources and reduce health disparities. These platforms need to be optimized at the technology and health literacy level of underserved minority communities and adapted to meet the community's needs. Methods: We have designed a multi-center phase IV clinical trial to 1) assess factors related to suboptimal and optimal use of the ApricityCARE, a virtual first-response clinical support (or coverage) to provide 24/7 symptom monitoring and side effect management and 2) determine the impact of the program on ICI toxicity management for NSCLC patients receiving ICIs in a highly diverse community. Eligible patients are those with a confirmed diagnosis of NSCLC who self-identify as a member of an ethnic minority or underserved population, prescribed for any treatment regimen that includes an ICI. The study entails a 50-patient run-in phase with two focus group discussions, stratified on a Likert-type scale based on the frequency of utilization, to determine factors impacting usability of the ApricityCare program. This data will inform optimal implementation of ApricityCare for the randomized phase of the study, where 230 patients will be assigned 1:1 to use of ApricityCare versus standard of care. The run-in phase of the study is currently accruing at Columbia University, and is planned to open at NYU, Mount Sinai, and Montefiore (NCT05812274). Clinical trial information: NCT05812274 .

Multi-institutional validation survey on Belong.life's conversational artificial intelligence (AI) oncology mentor, "Dave.

e13596 Background: Belong.life, a global oncology social network for patients and caregivers, recently launched “Dave” the first conversational AI oncology mentor and companion. “Dave’s” objectives are to provide uninterrupted support, clarify relevant clinical issues and guide patients and caregivers with relevant and empathetic information and education in all aspects of cancer, from diagnosis to treatment protocols and side effects management. “Dave” underwent training on Belong’s unique and large datasets of patients to physicians, and patients to patients’ interactions, as well as incorporating high quality information from the latest international cancer guidelines, providing it with a robust up-to-date supportive data and a wide understanding of the patients’ cancer journey. Methods: “Dave’s” responses to inquiries from Belong members were subjected to a validation survey conducted by eight oncologists, each specializing in various solid and haematological cancers and affiliated with several medical institutions. From the social network datasets, 471 questions from patients and caregivers were randomly selected and categorized into groups, including Breast, Gastrointestinal and Pancreatic, Genito-urinary, Bone, Haematological cancers, and Radiation therapy. The oncologists assessed the AI mentor's replies for their relevance and helpfulness, aligning them with evidence-based medicine, current recommendations, and guidelines. Results: Results were categorized into positive or negative assessments. Impressively, 432 out of 471 “Dave’s” responses (91.8%) received positive validation for providing suitable and relevant recommendations. Conversely, 39/471 responses (8.2%) received a negative validation, of which only 5/471 (1%) were graded as not at all helpful or relevant. Minor variations were observed within diagnostic groups, with positive validation rates as follows: Genito-urinary 100%, Breast 98.4%, Musculoskeletal 97%, Radiation therapy 88%, Gastrointestinal and Pancreatic 86%, and Haematological cancers 84%. Conclusions: The documented results on 471 patients’ posts are very promising, indicating that “Dave” provides valuable and reliable recommendations, achieving a positive validation rate of nearly 92%, with only 1% graded as not at all helpful or relevant. The findings also offer insights into the AI mentor's performance across distinct medical domains. This validation study provides a solid foundation and adds confirmation that the addition of an AI oncology mentor and companion, like “Dave”, improves patients’ knowledge and coping mechanisms and provides helpful and relevant guidance during their cancer journey, while supporting physicians in the daily management of their cancer patients.

Quantification of treatment-related time toxicity in patients with advanced stage cancer.

12137 Background: Treatment-related Time Toxicity (TrTT) in cancer patients is a recently proposed metric to describe the burden of time spent in pursuing medical care, including office/hospital visits, side effect management, lab tests, imaging scans, and travel time. Time toxicity is a valuable concept in patient-centered shared-decision making, especially in the palliative management of end-stage cancer patients with limited life expectancy. Despite tremendous progress in cancer treatment, most of the guideline-recommended treatment options convey short survival benefits of around 3-6 months when compared to supportive care. While medication toxicities are meticulously reviewed with patients, the cumulative burden and impact of time are rarely included in the discussion, partly due to the lack of standardized measurement of TrTT, and the absence of data from clinical trials. Thus, there is a compelling need for the quantification of time toxicity to guide clinical practice and patient preference. Methods: This was an observational analysis of the time toxicity from palliative treatment for patients with incurable solid tumors at a regional safety-net oncology office that focuses on underserved communities. Time toxicity is calculated as the number of days a patient spent with any healthcare-related encounters during a 3-month period from our medical record system. Results: The median age of the total 94 included patients was 57. 54% of the population were Hispanic. The ratios for mild, moderate, and severe time toxicity were 38%, 44%, and 18%, respectively. Immunotherapy was associated with significantly less time toxicity (TrTT = 8.5 days, 95% CI = 6.3-9.7) compared to chemotherapy (26.3 days, 95% CI = 18.3-34.4, P < 0.001), while targeted therapy (13.4, 95% CI = 7.0-19.8, P = 0.01) and hormone therapy (11.9, 95% CI = 4.1-19.7, P < 0.01) also has lower TrTT than chemotherapy. Patients with a worse performance status (ECOG PS 3-4, 30.1 days, 95% CI = 18.3-41.9) experienced higher time toxicity than fitter patients (PS 0-2, 16.7 days, 95% CI = 13.2-20.2, P < 0.05). Among different cancer types, gastrointestinal malignancies were associated with the highest time toxicity with average TrTT of 30.2 days/3 months (95% CI =22.5-37.2). Conclusions: This is the first comprehensive study to quantify real-world Treatment-Related Time Toxicity across multiple cancer and therapy types in an underserved population. We found 18% of patients with incurable solid malignancies experienced severe time toxicity (> 1 in 3 days). Higher TrTT was associated with cytotoxic chemotherapies, GI malignancies, and poor performance status. Time toxicity should be taken into account with other quality-of-life outcomes in treatment pathways and patient-centered oncology care.

Clinical efficacy and safety of mTOR inhibitor in patients with advanced unresectable epithelioid hemangioendothelioma (EHE).

e23540 Background: Epithelioidhemangioendothelioma is a rare vascular soft tissue sarcoma, 90% of which contains WWTR1-CAMTA1 fusion gene. Studies have shown that mTOR inhibitors may have a certain effect on EHE patients. Methods: A retrospective analysis of the efficacy and safety of mTOR inhibitor everolimus in the treatment of advanced unresectable epithelioidhemangioendothelioma in our hospital in the past one year. Patients with advanced epithelioidhemangioendothelioma (EHE) confirmed by consultation in the pathological center received this regimen, everolimus 10mg, once a day orally for 28 days, every 4 weeks as a treatment cycle until the disease progressed or showed intolerable toxicity. Results: There were 3 females and 5 males, and their average age was 41.8 years old. All of them were unresectable with liver, lung, and shoulder primary lesions, and lungs, liver, pleura and bone metastasis. Ki67 is from 2% to 10%. 3 patients who received molecular pathological examination were all identified the WWTR1-CAMTA1 fusion gene, and one of them also had EWSR1 chromosome translocation. Previous antineoplastic treatments included gemcitabine, cisplatin, albumin paclitaxel, epirubicin, dacarbazine chemotherapy, anlotinib targeting, and toripalimab immune therapy. 5 patients were treated with first-line drugs, 2 cases with second-line and 1 case with third-line. In terms of overall efficacy, 1 case was not evaluated, 2 cases lost follow-up due to poor tolerance and economic factors, 2 cases were included in the clinical trails after reaching tumor control for 3 months, and the other 3 cases achieved tumor remission with a median PFS of 11.0 months, and the best curative effect was SDa. Severe oral mucositis can greatly affect the medication experience of patients, which can be relieved after symptomatic medication, or when interstitial pneumonia and hemogram decrease significantly, we can consider the oral administration of everolimus 5mg. Conclusions: At present, there is no standard treatment for EHE, we can roughly see the efficacy of mTOR inhibitor everolimus in some EHE patients, mainly disease stability. Emphasis on side effect management, improve tolerance, and systematic treatment of EHE needs to be further explored.

Improving Quality and Cost of the Oncology Advanced Practice Provider Chemotherapy Privileging Process.

Managing antineoplastic orders, side effects, and symptoms is a primary role of oncology advanced practice providers (APPs). Antineoplastic management (ANM) is complex because of risk of medication errors, narrow therapeutic range of agents, frequent dose adjustments, and multiple drug regimens. This article describes an academic institution's review of current practice for ANM privileging and employing Plan-Do-Study-Act (PDSA) cycles to develop a revised process relevant to APP practice, addressing efficiency, accessibility, and cost-effectiveness. Using consecutive PDSA cycles, the team revised the didactic portion of the ANM privileging process and collaborated with nurses, pharmacists, and physicians for mentoring expertise. The revised process resulted in increased relevance of ANM didactic content while requiring 75% less time to complete. To date, all ANM-privileged APPs at the institution (N = 49) have completed the revised ANM privileging process, with a 100% pass rate on the competency assessment.

Real world experience of bispecific fusion protein in patients with metastatic uveal melanoma: Can we deliver?

e21504 Background: Effective treatments for patients with metastatic uveal melanoma has remained a longstanding unmet need. Poor response rates to checkpoint inhibitors has increased the need for patients to access new ways of targeting this disease. Tebentafusp is a first in class T Cell receptor bispecific fusion protein that has demonstrated an overall survival benefit. However although licensed it has yet to be approved in the UK for wider use. Methods: Prospective data collection on five patients receiving tebentafusp through the Managed Access Programme at a cancer centre that had not taken part in any trials of this therapy before. Patients were permitted with metastatic uveal melanoma; ECOG performance status 0-1 and were HLA-A*02:01 positive. Protocols were disseminated across the wider cancer teams for the management of side effects including cytokine release syndrome. Patients received extended monitoring for at least 16 hours, and vital signs (blood pressure, heart rate, temperature and pulse oximetry) taken every 2-4 hours. Drop in systolic BP < 20mmHg treated with IV fluids. Results: Five patients with advanced uveal melanoma participated in the Access Programme at one cancer site to assess efficacy, tolerability and workforce upskilling and capability with a first in class bispecific fusion protein therapy. All patients were HLA-A*02:01 positive. The patients commenced therapy between November 2021 and July 2023. All were male; median age 66. Four patients developed cytokine release syndrome commencing at cycle one. These patients required intravenous fluids for CRS grade 2, no patients required vasopressors. One patient required IV hydrocortisone. Four patients developed skin toxicity. These were managed with antihistamines and steroids. Three patients stopped due to confirmed disease progression, receiving 2-7 cycles; one made an informed decision to stop due to grade 3 skin toxicity. One patient continues on tebentafusp and has received 32 cycles to date. They recently had treatment paused for ablation and resection of oligometastatic disease that found residual uveal melanoma and have restarted. Conclusions: Real-world data suggests that using a gp100-targeting TCR/anti-CD3 bispecific fusion protein is tolerated and deliverable in new settings. Tebentafusp was delivered without any medical emergencies and CRS was successfully managed with proactive fluid management and steroids. The rate and grading of side effects reflects that described in the large randomised controlled trial. Patients with uveal melanoma can derive ongoing clinical benefit - including one patient who has received 32 cycles and proceeded to surgical resection of oligometastatic disease. Through workplace education and upskilling, the proactive management of the side effects including cytokine release syndrome can be managed in the oncology inpatients and seamlessly moved to outpatient settings.

Phase 1 clinical trial of AMG 340, a prostate-specific membrane antigen (PSMA)-targeted T-cell engager with a novel low-affinity CD3 binding domain designed to mitigate toxicity for the treatment of metastatic castration-resistant prostate cancer (mCRPC).

e14587 Background: PSMA, a transmembrane protein highly expressed on the surface of prostate cancer cells, is a validated target in prostate cancer; however, achieving a favorable therapeutic index has been challenging for PSMA-directed T-cell engagers (TCE’s). AMG 340, a PSMA-targeted TCE with a novel low-affinity CD3 binding domain specifically engineered to mitigate cytokine release syndrome (CRS) toxicity and maintain efficacy was investigated in a phase 1, open-label, dose-escalation study (NCT04740034). Methods: Patients (pts) with mCRPC who had received ≥2 prior lines of therapy were treated with AMG 340 monotherapy (1.5–800 mg intravenously every 3 weeks [Q3W]) during dose escalation. The primary outcome measures were dose-limiting toxicities, treatment-emergent adverse events (TEAEs), and pharmacokinetic profile. Secondary outcomes included prostate antigen specific (PSA) response and objective response per response evaluation criteria in solid tumors (RECIST). Results: As of September 6, 2023, a total of 42 pts (mean ± SD age, 68.5±7.8 years) received AMG 340 step up dosing across 11 cohorts. At doses up to 800 mg Q3W, AMG 340 had a manageable side effect profile. Any grade TEAEs reported in ≥30% of pts included CRS (52%), nausea (52%), vomiting (52%), fatigue (48%), diarrhea (38%), increased aspartate aminotransferase (36%), increased alanine aminotransferase (33%), and hypocalcemia (31%). Treatment-related toxicities included CRS (52%; Grade 1, 26%; Grade 2, 24%; Grade ≥3, 2%) and thrombocytopenia (24%; Grade 2, 10%; Grade ≥3, 14%). Step dosing was implemented at doses >40 mg and successfully mitigated CRS incidence and severity after the first dose. The maximal tolerated dose was not reached, as increasing the dose beyond 800 mg was predicted to minimally increase the potential AMG 340 activity. Exposure increased in an approximately dose-proportional manner with no evidence of clinically significant anti-drug antibodies. AMG 340 demonstrated evidence for pharmacodynamic engagement as shown by cytokine induction. Of the 41 PSA evaluable pts, PSA responses were seen across dose levels (PSA50, n=4), but were not dose dependent. Eight of 42 pts remained on treatment after 6 months. Among 27 RECIST evaluable pts, no RECIST responses were observed (n=14 stable disease, n=0 partial or complete response). Conclusions: Despite reaching high doses, no dose response was observed, and AMG 340 did not generate sufficient clinical activity to warrant further exploration. However, AMG 340 demonstrated manageable CRS toxicity showing that decreased CD3-binding strength mitigates CRS, the main toxicity of TCEs. Clinical studies are ongoing evaluating the PSMA protein as a molecular target for prostate cancer. Clinical trial information: NCT04740034 .