Tolerability Of Treatment Research Articles

DEX Immunotherapy Pharmaco-Biotechnological Advances in Multimodal Therapy for Cancer

This article reviews the synergy between pulsed dendritic cell exosome (DEX) immunotherapy and chemotherapy in cancer treatment. DEX exosomes, which act as immune system modulators, enhance chemotherapy efficacy by modifying the tumor microenvironment and activating an immune response targeted against tumor cells. This combination not only amplifies cancer cell destruction but also protects healthy cells, thus reducing systemic adverse effects of chemotherapy. The article highlights preclinical and clinical advances demonstrating the effectiveness of this combined strategy, showing promising results in tumors resistant to conventional treatments. Despite the benefits, challenges such as the high production cost of exosomes and the need to optimize treatment protocols for different cancer types are identified. Additionally, future research directions are presented, focusing on improving personalized treatments through genetically modified exosomes. In conclusion, the combination of DEX and chemotherapy has the potential to revolutionize cancer treatment, enhancing both treatment tolerance and clinical efficacy.

Long-term safety and efficacy of antibody ALXN2220 for depletion of cardiac amyloid transthyretin: results of treatment beyond 12 months in the open-label extension of study NI006-101

Abstract Introduction ALXN2220 (formerly NI006) is an investigational human monoclonal antibody in development for the treatment of transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). ALXN2220 is designed to deplete cardiac amyloid transthyretin (ATTR) deposits in patients with ATTR-CM on top of standard of care. Data from the first-in-human, ascending dose study NI006-101 show that ALXN2220 is safe and well tolerated. A reduction of surrogate markers of cardiac amyloid load and cardiac biomarkers was observed in participants receiving doses of ≥ 10mg/kg of ALXN2220 over a period of 12 months of treatment. Purpose Long-term safety, tolerability and efficacy of ALXN2220 treatment beyond 12 months was studied in a prolonged Open-Label Extension (OLE) of the NI006-101 study. Methods Participants completing 12 months in dose cohorts ≤ 30 mg/kg were allowed to receive additional 6 to 12 monthly open-label ALXN2220 infusions with up-titration of all participants to 30 mg/kg. Cardiac biomarkers were measured centrally, and serial cardiac imaging was performed with echocardiography and cardiac MRI or scintigraphy. Results Out of 27 participants completing 12 months, 23 (18 ATTRwt, all male, median age 70 years at screening (range 28-83)) continued treatment in the prolonged OLE. Median number of infusions of ALXN2220 received and median time followed across the full study were 20 infusions (range 11-24) and 125 weeks (range 83-153). Overall adherence to treatment was high in the prolonged OLE, 97% of planned infusions administered, 87% of participants received all planned doses. No severe or serious adverse events were considered related to ALXN2220 or resulted in the discontinuation during OLE, and no events of cytokine release syndrome or thrombocytopenia were observed. None of the participants had anti-drug antibodies throughout the trial. Cardiac biomarkers (NT-proBNP, troponin) and cardiac imaging indicated continued treatment effects beyond 12 months and supported the up-titration of participants who previously received lower doses of ALXN2220. Conclusions Up-titration and long-term treatment at a dose level of 30 mg/kg in the OLE was safe and well tolerated, with overall good adherence to treatment. Cardiac imaging and cardiac biomarker data indicated continued treatment effects beyond 12 months and supported the up-titration of patients to 30 mg/kg.

Body mass index and clinical outcomes in patients with diabetes and stable coronary artery disease in THEMIS

Abstract Background Physiologic changes due to extremes of body weight may affect the efficacy and tolerability of antiplatelet treatment. However, it remains unclear whether the risks and benefits of intensified antiplatelet therapy among patients with diabetes and stable coronary artery disease (CAD) are affected by body mass index (BMI). Purpose To assess the relationship between baseline BMI and major adverse cardiovascular (CV) events, and to determine if the effects of ticagrelor vs. placebo varied across the BMI spectrum, in patients with diabetes and stable CAD. Methods THEMIS was a randomized, controlled trial of 19,220 individuals aged ≥50 years with type 2 diabetes and stable CAD, randomly allocated to ticagrelor or placebo on top of aspirin. Patients with a prior myocardial infarction (MI) or stroke, or already on dual antiplatelet therapy, were excluded. The primary efficacy outcome was a composite of CV death, MI, or stroke. The primary safety outcome was TIMI major bleeding. We examined prognostic implications of BMI using 1) restricted cubic splines for the overall trends with outcomes; 2) Cox regression models with predefined BMI intervals (<25 kg/m2, 25-29.9 kg/m2, and ≥30 kg/m2) adjusted for demographic, clinical, and laboratory variables; and 3) Cox regression models for the effects of ticagrelor vs. placebo on outcomes across the spectrum of BMI values (test for interaction). A two-sided P-value <0.01 was considered statistically significant to control the overall chance of type I errors. Results BMI was available in 19,202 (99.9%) participants, with a median of 29 kg/m2 (interquartile range: 26-33). A total of 3352 (17.5%) individuals had a BMI <25 kg/m2, 7644 (39.8%) had a BMI 25-29.9 kg/m2, and 8206 (42.7%) had a BMI ≥30 kg/m2. Median follow-up was 39.9 months (range 0-57), with 1554 primary efficacy events and 306 primary safety events occurring over the course of the study. BMI was not associated with the primary efficacy or safety outcome, or with their individual components. However, BMI was significantly associated with hospitalization for heart failure (HHF) (BMI <25 kg/m2: reference; hazard ratio [HR] for BMI 25-29.9 kg/m2: 1.07, 95% confidence interval [CI], 0.82 to 1.40; HR for BMI ≥30 kg/m2: 1.41, 95% CI, 1.07 to 1.84) and with the composite of HHF or CV death (comparable estimates) after multivariable adjustment (Figure). BMI was also significantly, positively associated with serious adverse events (BMI <25 kg/m2: reference; HR for BMI 25-29.9 kg/m2: 0.99, 95% CI, 0.93 to 1.06; HR for BMI ≥30 kg/m2: 1.20, 95% CI, 1.12 to 1.29). BMI did not modify the risks and benefits of ticagrelor vs. placebo. Conclusions BMI was independently associated with the risk of HHF and the composite of HHF or CV death, but not with other efficacy or safety outcomes, in patients with stable CAD and type 2 diabetes. Ticagrelor was of similar benefit on the primary efficacy outcome vs. placebo across the full range of BMI.

Role of Autologous Micrografting Technology through Rigenera® System in the Treatment of Androgenetic Alopecia

Introduction: Androgenetic alopecia (AGA) is a common form of baldness, affecting 60–70% of the adult population worldwide, and may have a negative effect on quality life. AGA leads to a progressive thinning of scalp hair and is characterized by a progressive miniaturization of the hair follicle with a specific pattern distribution. Although AGA is a very frequent condition, compelling therapeutic options are still limited. Methods: Herein, we present the protocol of autologous micrografting technology through Rigenera® system allowing to obtain a suspension of autologous micrografts ready to be injected on scalp. This paper combines the results of two studies that evaluated the effects of micrografts in patients with AGA. The first study involved 17 patients who received one micrografts session with a 6-month follow-up. The second study 13 patients who received two micrografts sessions 6 months apart with a follow-up of 6 months after the second session. Clinical assessment involved global photography evaluation and patient’s satisfaction before and after the treatment. Hair measures using TrichoLab were also performed. Results: Most of the patients had a moderate improvement after investigator’s assessment in terms of hair loss reduction and hair density improvement. The assessment of patients was satisfactory in terms of hair improvement and treatment tolerability. Conclusion: In summary, we conclude that this new regenerative approach can be a promising tool for clinicians to obtain a viable, sterile and ready to use micrografts that can be immediately injected into the scalp to improve AGA condition.

Chasing sleep physicians: ChatGPT-4o on the interpretation of polysomnographic results.

From a healthcare professional's perspective, the use of ChatGPT (Open AI), a large language model (LLM), offers huge potential as a practical and economic digital assistant. However, ChatGPT has not yet been evaluated for the interpretation of polysomnographic results in patients with suspected obstructive sleep apnea (OSA). To evaluate the agreement of polysomnographic result interpretation between ChatGPT-4o and a board-certified sleep physician and to shed light into the role of ChatGPT-4o in the field of medical decision-making in sleep medicine. For this proof-of-concept study, 40 comprehensive patient profiles were designed, which represent a broad and typical spectrum of cases, ensuring a balanced distribution of demographics and clinical characteristics. After various prompts were tested, one prompt was used for initial diagnosis of OSA anda further for patients with positive airway pressure (PAP) therapy intolerance. Each polysomnographic result was independently evaluated by ChatGPT-4o and a board-certified sleep physician. Diagnosis and therapy suggestions were analyzed for agreement. ChatGPT-4o and the sleep physician showed 97% (29/30) concordance in the diagnosis of the simple cases. For the same cases the two assessment instances unveiled 100% (30/30) concordance regarding therapy suggestions. For cases with intolerance of treatment with positive airway pressure (PAP) ChatGPT-4o and the sleep physician revealed 70% (7/10) concordance in the diagnosis and 44% (22/50) concordance for therapy suggestions. Precise prompting improves the output of ChatGPT-4o and provides sleep physician-like polysomnographic result interpretation. Although ChatGPT shows some shortcomings in offering treatment advice, our results provide evidence for AI assisted automation and economization of polysomnographic interpretation by LLMs. Further research should explore data protection issues and demonstrate reproducibility with real patient data on a larger scale.

Inference-Based Cognitive Behavioral Therapy versus Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder: A Multisite Randomized Controlled Non-Inferiority Trial

Introduction: Although cognitive behavioral therapy (CBT) effectively treats obsessive-compulsive disorder (OCD), many patients refuse CBT or drop out prematurely, partly because of anxiety regarding exposure and response prevention (ERP) exercises. Inference-based cognitive behavioral therapy (I-CBT) focuses on correcting distorted inferential thinking patterns, enhancing reality-based reasoning, and addressing obsessional doubt by targeting underlying dysfunctional reasoning, without incorporating an ERP component. We hypothesized that I-CBT would be non-inferior to CBT. Additionally, we hypothesized that I-CBT would be more tolerable than CBT. Methods: 197 participants were randomly assigned to 20 sessions CBT or I-CBT and assessed at baseline, posttreatment, and 6 and 12 months’ follow-up. The primary outcome was OCD symptom severity measured using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS; non-inferiority margin: 2 points). The secondary outcome, treatment tolerability, was assessed using the Treatment Acceptability/Adherence Scale (TAAS). A linear mixed-effects model was used to assess the non-inferiority of the primary outcome and superiority of secondary outcomes. Results: Statistically significant within-group improvements in the primary and secondary outcomes were observed in both treatments. No statistically significant between-group differences in Y-BOCS were found at any assessment point, but the confidence intervals exceeded the non-inferiority threshold, making the results inconclusive. The estimated mean posttreatment TAAS score was significantly higher in the I-CBT group than in the CBT group. Conclusion: While both CBT and I-CBT are effective for OCD, whether I-CBT is non-inferior to CBT in terms of OCD symptom severity remains inconclusive. Nevertheless, I-CBT offers better tolerability and warrants consideration as an alternative treatment for OCD.

The Role of Parenteral Nutrition in Cancer in Indian Settings

Background: Almost 50% of patients with cancer suffer from malnutrition during their first hospital visit. However, it is often overlooked and undiagnosed and is associated with morbidity, mortality, poor tolerance to treatment, and treatment outcomes. Guidelines recommend supportive nutrition from the early stages of cancer treatment. However, in clinical practice, nutritional support is often prescribed only as an end-of-life intervention or is not prescribed at all; moreover, the use of parenteral nutrition (PN) is not well-defined. There are limited practical guidelines on the use of PN in patients with cancer. Methods: A multidisciplinary group of specialists in India formulated this consensus to guide oncologists on the judicious use of PN in Indian settings. It includes general and cancer-specific recommendations on the use of PN, supplemental PN (SPN), composition of PN, and monitoring patients to prevent adverse events associated with PN. Recommendations: The risk of malnutrition should be assessed at the very first presentation of a patient with cancer. These patients’ nutritional requirements are largely like those of the healthy population. Nutritional assessment of all cancer patients should begin at diagnosis and repeated regularly to initiate and monitor early nutritional intervention, before the general status is severely compromised. Oncologists and nutritionists need to be educated about using the appropriate nutrition support options according to the guidelines. While EN should be the preferred form of nutritional support, in specific circumstances PN might be a better option. Early PN in specific settings provides additional benefits, and is particularly important in some types of cancers. SPN as an additional nutritional support to EN can improve treatment tolerability and quality-of-life of patients with cancer. Education is also necessary for awareness about preventing and managing adverse effects of PN, which is the major reason for poor adoption of PN.

Drug Survival of Dupilumab, Methotrexate, and Cyclosporine A in Children With Atopic Dermatitis

Dupilumab, methotrexate (MTX), and cyclosporine A (CsA) are valuable treatment options for pediatric patients with refractory moderate to severe atopic dermatitis (AD). Yet, comparative data on these treatments in pediatric patients are scarce. To evaluate drug survival of dupilumab, MTX, and CsA, and identify associated predictors in a multicenter daily practice cohort study of pediatric patients with AD. This multicenter daily practice cohort study included patients with AD aged 2 to 17 years treated with dupilumab, MTX, and/or CsA in 5 tertiary centers in the Netherlands between 2013 and 2023. Data were extracted from the prospective BioDay and TREAT Netherlands registries and electronic medical records. Dupilumab, MTX, CsA. Drug survival was analyzed using Cox proportional hazard regression models. Univariable and multivariable Cox regression analyses were conducted to identify variables associated with drug discontinuation. A total of 502 treatment episodes in 362 unique patients were included, comprising 192 dupilumab episodes, 94 MTX episodes, and 216 CsA episodes. Overall, the mean (SD) age at treatment initiation was 12.9 (3.8) years, and 272 treatment episodes (54.2%) in female patients. The 1-year, 2-year, and 3-year overall drug survival rates, respectively, were 84.1%, 72.3%, and 62.0% for dupilumab; 60.7%, 39.3%, and 25.3% for MTX; and 43.9%, 21.5%, and 10.4% for CsA. Ineffectiveness was the most frequent reason for drug discontinuation, accounting for 178 episodes (35.5%), mostly in patients treated with CsA, followed by adverse effects in 94 patients (18.7%). Treatment with MTX and treatment with CsA were independently associated with a higher risk for drug discontinuation due to ineffectiveness (hazard ratio [HR], 4.45 [95% CI, 2.38-8.34] and HR, 10.88 [95% CI, 6.23-19.02], respectively) and adverse effects (HR, 4.39 [95% CI, 2.05-9.39] and HR, 3.83 [95% CI, 1.85-7.92], respectively) compared to treatment with dupilumab. Patients aged 12 to 17 years starting systemic treatment were independently associated with a higher risk for drug discontinuation due to ineffectiveness (HR, 1.55 [95% CI, 1.10-2.20]) and adverse effects (HR, 2.39 [95% CI, 1.33-4.30]). This multicenter daily practice cohort study demonstrated a superior 1-year, 2-year, and 3-year overall drug survival for dupilumab, followed by MTX, with the lowest rates observed for CsA in pediatric patients with AD. This study also identified characteristics associated with discontinuation. These results provide insight into drug survival resulting from the effectiveness, safety, and tolerability of these systemic treatments in pediatric patients with AD and contribute to the optimization of patient outcomes.

Evaluating the Impact of Age and G8 Assessment on Definitive Treatment Strategies in Elderly Patients with Local Advanced Esophageal Carcinoma.

While chemoradiotherapy (CRT) is commonly employed as a curative approach for esophageal cancer, administering standard CRT to elderly patients often presents challenges in practical settings. The objective of this study was to compare treatment tolerance and survival outcomes between younger and elderly patients (aged ≥65 years) diagnosed with locally advanced esophageal cancer receiving curative-intent treatment. Additionally, it aims to assess the impact of the Geriatric 8 Health Status Screening Tool (G8 score) on treatment decisions in elderly patients. Ninety-seven patients treated with neoadjuvant or definitive CRT for locally advanced esophageal cancer were retrospectively evaluated at two centers from 2013 to 2023. We divided the patients by age (<65 and ≥65 years) and assessed their demographic, clinical, and treatment data, including pre- and post-treatment G8 scores. Radiotherapy (RT) was administered at a median dose of 50.4 Gy (45-66 Gy). Planned concurrent chemotherapy was completed in 73 (75.3%) of the patients. In the comparative study of 97 esophageal cancer patients, 48 geriatric (aged ≥65 years) and 49 younger individuals were followed up for a median of 20 and 21 months respectively. No significant statistical differences were noted between the groups concerning baseline and treatment characteristics. Surgical intervention rates were comparable, with 22.9% of geriatric and 36.7% of young patients undergoing surgery (p=0.184). There were no significant differences in pathological complete response, local recurrence, distant metastasis, progression, or death rates. The median progression-free survival (PFS) for geriatric and younger patients was 31 months (95% CI, 13.6-48.4) and 19 months (95% CI, 0-39.4), respectively (p=0.832). The median overall survival (OS) was 38 months (95% CI, 23.8-52.2) in geriatric patients, while it was not reached in younger patients (p=0.745). There was no significant difference between the two groups. The pretreatment and posttreatment G8 values of the geriatric patients were 9.25 (6-13.5) and 9.5 (6-14), respectively. Patients with increased G8 scores were found to have significantly higher PFS (median 85 mo vs. 11 mo, p=0.001) and OS (median 85 mo vs. 14 mo, p=0.001) compared to those with unchanged or decreased G8 scores. Age alone should not be the determining factor in the treatment decision of elderly patients diagnosed with locally advanced esophageal cancer. Moreover, CRT could be safely performed even in patients with low G8 scores, and although the G8 score may not directly influence treatment decision, its enhancement during the treatment process holds significant prognostic value.

INTEGRATING ALLIED HEALTH PROFESSIONALS DURING THE ONCOLOGICAL TREATMENT PHASE FOR GLIOBLASTOMA PATIENTS: A CASE STUDY AT A UK CANCER CENTRE

Abstract AIMS Primary brain tumour patients should be offered neurological rehabilitation assessment at diagnosis and every stage of follow With only 5% of glioblastoma patients surviving more than 5 years, specialist management that spans across all phases of the Dietz rehabilitation model is required to optimise function, treatment tolerance and Quality-of-life. At Guy’s cancer centre an Allied health multi-disciplinary team (Physiotherapy, Occupational therapy and Speech and language therapy) work alongside the oncologist-led clinic to support this patient group. METHOD Case history A 54-year-old, male, was diagnosed with right parietal Glioblastoma, WHO grade 4, IDH wildtype, MGMT 5.47% methylated (August 2023) on biopsy only. He underwent chemo/radiotherapy - 60gy/90 fractions with Temozolmide (TMZ) on 3/11/2023 Currently C4 of adjuvant TMZ. Dexamethazone 2mg was discontinued on 29/11/2023, he continues with Keppra 500mg twice daily. RESULTS Dietz Intervention approach in phases: PREVENTATIVE Fatigue management was introduced prior to radiotherapy including a physical activity review, advice on pacing, sleep hygiene and relaxation techniques. Given the patient’s history of shift work and altered sleep patterns, managing risks of treatment-related fatigue was of particular importance. Restorative & Supportive: A targeted and periodised exercise programme was initiated, comprising 1:1 gym based physiotherapy sessions. The aims included enhancing exercise confidence, improve balance, endurance, maintain strength, pain management and weight maintenance during chemo/radiotherapy and adjuvant TMZ. Education was deployed on adjusting activity levels based on chemotherapy cycle and day to day side effects, alongside ongoing fatigue management advice around pacing and sleep hygiene. CONCLUSION Learning and Recommendations Implementing tailored rehabilitation interventions early in the patient’s treatment pathway, enables proactive management to mitigate the impact of treatment-related side effects on their QOL. Based on our experience, early engagement with a dedicated therapy team is recommended to foster strong rapport with both the patient and their caregivers. This facilitates timely rehabilitation planning for optimal outcomes.

INVESTIGATING CUDC-101 EFFECT AND MECHANISM OF ACTION AGAINST GLIOBLASTOMA IN VITRO

Abstract AIMS Glioblastoma (GB) has complex pathophysiology, difficult treatment and resultant poor prognosis. Its median survival rate is approximately 15 months. The aggressive nature of GB results in rapid disease progression in 60-70% patients often within 12 weeks. Limited treatment options include maximal safe surgical resection, followed by radiotherapy and temozolomide (TMZ). The blood brain barrier restricts chemotherapeutic entry and increases dosage leading to increased side effects and decreased treatment tolerance. Furthermore, significant disease heterogeneity means reoccurrence is expected in most cases, for which there are no standard treatment routes. This coupled with inefficient treatment with temozolomide (TMZ) due to the blood brain barrier, highlights the requirement for novel treatments. METHOD Histone deacetylases (HDAC) and endothelial growth factor receptor (EGFR) are mutated and upregulated in GB allowing tumour infiltration and proliferation. CUDC-101 is known to target both HDAC and EGFR in other cancers making it a promising therapeutic to trial in GB. Cell viability of U251, T98G and U87MG human cells was measured post-CUDC-101 administration at 24, 48 and 72hrs. SVGp19 embryonic non-cancerous human glial cells were used as a control to establish CUDC-101 preliminary specificity. Targeting another major hallmark of GB, wound healing assays were performed to assess CUDC-101 capacity to inhibit migration. In addition to this, long-term cellular resistance was investigated through clonogenic assays. Western blotting was then used to identify non-/treated expression levels of activated EGFR and acetylated histone H3. Expression levels in non/-treated cells were then visualised with fluorescent microscopy. In addition, flow cytometry was utilised to observe cell cycle changes. RESULTS Overall, results indicate CUDC-101 has a dose-dependent effect on cell viability (long-term and short-term) and migration. Additionally, fluorescent images show treatment does increase histone acetylation and decrease total EGFR. CONCLUSION Future work will solidify these datasets and show changes in activated EGFR and acetylated histone H3 using western blotting.

Granulocyte colony-stimulating factor for stem cell mobilisation in acute myocardial infarction: a randomised controlled trial

BackgroundTo determine whether granulocyte colony-stimulating factor (G-CSF) improves clinical outcomes after large ST-elevation myocardial infarction (STEMI) when administered early in patients with left ventricular (LV) dysfunction after successful percutaneous coronary...

Efficacy of pharmacological interventions for ADHD: protocol for an updated systematic review and dose–response network meta-analysis

BackgroundAttention-deficit/hyperactivity disorder (ADHD) affects approximately 5% of children globally, with symptoms often persisting into adulthood. While pharmacological interventions are commonly employed for management, understanding the optimal dosing for efficacy and tolerability remains crucial. This study aims to conduct a dose–response network meta-analysis to estimate the efficacy of pharmacological treatments across different doses, aiming to inform clinical decision-making and improve treatment outcomes.MethodsThis updated systematic review will include randomized controlled trials evaluating ADHD medication efficacy in children, adolescents, and adults. An updated search from a 2018 NMA will be conducted across multiple electronic databases with no language restrictions, using specific eligibility criteria focused on randomized controlled trials. The primary outcome will assess the severity of ADHD core symptoms, while secondary outcomes will consider treatment tolerability. A dose–response Bayesian hierarchical model will be used to estimate dose–response curves for each medication, identifying optimal dosing strategies.DiscussionWith this dose–response network meta-analysis, we aim to better understand the dose–response relationship of pharmacological treatment in ADHD, which could help clinician to the identification of optimal doses.Systematic review registrationOSF https://doi.org/10.17605/OSF.IO/3MY4A.

Hypofractionated versus standard fractionation radiotherapy for merkel cell carcinoma

Purpose/Objective(s)Merkel cell carcinoma (MCC) radiation treatment has historically consisted of standard 1.8–2 Gy fractions treated daily over 4–6 weeks. Hypofractionated treatment regimens have demonstrated tumor control and toxicity equivalence to standard fractionation regimens for common cutaneous malignancies such as basal cell and squamous cell carcinomas. Herein we report the outcomes of hypofractionated versus standard fractionation radiotherapy for MCC at our institution.Materials/MethodsThe study involved a retrospective review of MCC patients treated with radiotherapy. Treatment characteristics and patient outcomes, including acute toxicities, disease recurrence and survival data were collected. The cumulative incidence of local and distant failures was estimated, with death as a competing risk.ResultsA total of 29 treatment courses for 24 patients were included, of which 13 involved standard fractionation with curative intent, 10 involved hypofractionated radiotherapy with curative intent, and 6 involved single fraction (8 Gy) palliative radiation. Half the patients were treated to a head/neck site. A subset of patients treated adjuvantly with curative intent included 8 standard fractionation and 8 hypofractionated radiotherapy patients. No statistically significant differences in local and/or distant failure or overall survival was observed between the patient groups.ConclusionHypofractionated radiotherapy for MCC was associated with similar treatment outcomes relative to standard fractionation. In our limited patient sample, hypofractionated radiation treatment achieved similar results with similar toxicity and fewer treatments. Further analysis of a larger patient population with longer follow up is needed to confirm treatment tolerability and efficacy.

8604 Ectopic Cushing’s Syndrome Associated with a Metastatic Pancreatic Mixed Neuroendocrine Non-neuroendocrine Neoplasm (MiNEN) with Amphicrine Features

Abstract Disclosure: A. DeMarsilis: None. C. Jiang: None. O. Lavrynenko: None. D. Motavalli: None. C. Musurakis: None. Z.H. Taxin: None. E.D. Rosen: Advisory Board Member; Self; Source Bio, Inc.. Consulting Fee; Self; Novartis Pharmaceuticals, Gensaic. M.S. Irwig: None. Background: Ectopic Cushing’s Syndrome (CS) makes up 9-18% of ACTH-dependent CS cases, of which fewer than 15% are attributed to pancreatic neuroendocrine tumors (1). Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are rare, aggressive carcinomas, often driven by high-grade neuroendocrine components, with a poor prognosis (2). Amphicrine neoplasms contain neuroendocrine and exocrine components in the same cell. Clinical Case: A 34 year-old woman with asthma, hypertension, and depression presented with new onset lower extremity edema, facial hirsutism, mood changes, polyuria and polydipsia. She had an elevated morning serum cortisol of 52 ug/dL (normal < 20) with plasma ACTH 42 pg/mL (normal < 50), 24-hour urine free cortisol of 1003 mcg (normal < 50), K+ of 2.6 mEq/L, and fasting glucose 164 mg/dL. CT showed multiple hepatic lesions, pulmonary nodules, a pancreatic tail lesion, and lymphadenopathy concerning for metastatic disease. Her adrenal glands were thickened bilaterally without nodules. A pituitary MRI was normal. These findings were concerning for ectopic CS. She was admitted due to rapidly developing symptoms. Potassium, insulin, sitagliptin, and prophylactic anticoagulation were started. Spironolactone and ketoconazole were initiated while awaiting biopsy results of liver and pancreas lesions. Osilodrostat was not available and a trial of metyrapone was poorly tolerated. The liver and pancreatic tail lesion biopsy revealed metastatic MiNEN with amphicrine features, of pancreatic origin, with Ki67 proliferation index of 70%. Section staining of pancreas and liver biopsies were negative for ACTH. A Ga-68 Dotatate scan showed minimal uptake, so octreotide was not prescribed. Palliative chemotherapy was planned. Although ketoconazole was titrated to 1600 mg/day, urine free cortisol levels and serum free cortisol levels did not reach target. Cushing disease was considered but not suspected, as ACTH levels remained modest despite a relative decrease in cortisol level. Given significant morbidity from uncontrolled hypercortisolism, and plans for urgent initiation of systemic chemotherapy, after multidisciplinary discussion the patient was treated with a surgical bilateral adrenalectomy. Post-operative morning serum cortisol measured 8.3 ug/dL. After one week, palliative chemotherapy with FOLFIRINOX (oxaliplatin, leucovorin, fluorouracil, and irinotecan) was initiated. She was discharged home on stress dose steroids with plan for taper. Conclusion: Ectopic ACTH secretion is a rare phenomenon, particularly when presenting with a rare case of metastatic pancreatic MiNEN with amphicrine features, associated with significant morbidity. To improve tolerance and survival of further treatment, early surgical bilateral adrenalectomy should be considered.

Effectiveness and Safety of a Dermocosmetic Cream as an Adjunct to Adapalene for Mild and Moderate Acne in Indonesia: Results of a Multicenter Randomized Controlled Study.

Acne is a chronic inflammatory skin condition affecting mainly teenagers and adults as well. Guidelines recommend retinoids as a first-line treatment for mild-to-moderate acne. However, dermocosmetics in adjunct could potentially improve efficacy and tolerability. This study was conducted to determine the effectiveness and safety of a dermocosmetic cream containing salicylic acid, lipohydroxy acid, niacinamide, Aqua posae filiformis, procerad and zinc salt in the treatment of mild-to-moderate acne vulgaris in adjunct to different regimens of adapalene compared to adapalene only. This randomized, controlled, parallel-group, evaluator-blind study was conducted over 8weeks on male and female acne subjects at five teaching hospitals in Indonesia. A total of 291 participants were enrolled and divided into three treatment groups: Group A adapalene 0.1% cream nightly - Group B dermocosmetic cream daily + adapalene 0.1% cream every two nights - Group C dermocosmetic cream daily + adapalene 0.1% cream nightly. Clinical evaluations of treatment included scoring on Global Evaluation of Acne (GEA) scale, lesion count (Indonesian Acne Expert Meeting scale), treatment tolerability and treatment satisfaction. Evaluations were performed on Day28 and Day56 of treatment. After 28 and 56days of treatment, all groups exhibited improvements across the various measures. Data analysis, utilizing Anova for repeated measurements, revealed a statistically significant difference between GroupsC and A for reduction of GEA scores (p = 0.038) in favor of GroupC. On Day56, percentages of subjects with GEA Scale improvements of at least 1grade in comparison with baseline were in GroupC (61.7%) followed by GroupA (47.9%) and GroupB (45.3%). Better treatment tolerance and satisfaction scores were noted in GroupsB and C. Combination of the dermocosmetic cream with adapalene showed higher efficacy, tolerability and satisfaction in comparison to adapalene alone.

Barriers to serious illness conversations in patients with advanced cancer: A mixed methods study.

228 Background: Serious illness conversations (SICs) are discussions between oncology clinicians and patients with cancer about illness understanding and care preferences. SICs are associated with less intensive and more goal-concordant care near the end of life, but many patients die without an SIC. Methods: PATH-SIC is an ongoing, single-center randomized trial (NCT05629065) that enrolls adults without a documented SIC starting a treatment for breast, gastrointestinal, genitourinary, gynecologic, or lung cancers with an expected prognosis of less than one year. The trial examines the effects of clinician- and patient-nudges on SIC documentation within 60 days of patient’s randomization to one of four arms (no nudge, clinician nudge, patient nudge, or both). This embedded mixed methods study recruited patients who still did not have an SIC 60 days from randomization, their caregivers (if present at time of consent) and oncologists. Interviews explored patients’ and caregivers’ 1) experiences with SICs, 2) perceptions about why SICs may not occur, and 3) suggestions to empower others to initiate SICs. Participating oncologists were surveyed by email. We used qualitative content analysis and descriptive statistics to identify themes. Results: The study included 44 participants: 19 patients, 10 caregivers and 15 oncologists. Patients had a median age of 63 years, were 63% female and 58% White and 68% had gastrointestinal cancers. Though no patient had a documented SIC, patients and their oncologists often disagreed about whether an undocumented SIC had occurred previously (Table). Patients’ and caregivers’ reported barriers to SICs included patient factors (lack of readiness, desire to maintain hope, focus on the present), clinician factors (perceived discomfort with prognostic disclosure and SICs), and prognostic uncertainty (current disease control, unpredictable prognosis). Patients’ and caregivers’ reported facilitators to SICs included patient- (self-advocacy, SIC readiness), clinician- (comfortable rapport), disease- (progression, worsening symptoms), and family-related facilitators (advocates for the patient to engage in SICs). To increase SICs, patients and caregivers reported greater acceptance of interventions involving a personal touch (e.g. phone call) over automated processes. Oncologist survey responses were brief. They reported SICs were most frequently triggered by disease progression or treatment intolerance, and recommended longer appointment times and written materials to facilitate SIC. Conclusions: Patient, caregiver and oncologist feedback on barriers and facilitators to SICs provided useful insights to improve interventions to encourage SICs. Patient/oncologist dyad (n=16) concordance of prior SICs. # of dyads Agreed SIC occurred 7 Agreed SIC did not occur 2 Only oncologist reported SIC 6 Only patient reported SIC 1 Total patient/oncologist dyads 16

[Artículo traducido] Un nuevo paradigma en el tratamiento del prurito del cuero cabelludo: Hallazgos del estudio SCALP-PR

PurposeThe “Impact of scalp pruritus in dermatological consultations in Spain: The SCALP-PR trial” was initiated to address the common yet often insufficiently examined issue of scalp pruritus in dermatology. This condition leads to an uncontrollable urge to scratch, affecting the patients’ quality of life and potentially causing scalp damage. This study aimed to explore the prevalence, patient profile, underlying conditions, and therapeutic approaches for scalp pruritus in Spain, and to assess the safety and efficacy profile, as well as the tolerability of a non-pharmacologic treatment. MethodsFrom 2021 through 2022, 75 dermatologists enrolled a total of 359 patients in a study on scalp pruritus, approved by the Bellvitge University Hospital Research Ethics Committee, Barcelona, Spain. This evidence-based research combined a meta-analysis with observational study techniques focused on real-world evidence to examine the therapeutic impact on quality of life (QoL). Utilizing the Dermatology Life Quality Index (DLQI) for QoL assessments, the study evaluated the effectiveness of the topical product over 15 days. Data collection was conducted via an eCRF and analyzed with statistical methods to provide reliable insights into the management of scalp pruritus. ResultsThe prevalence of scalp pruritus in Spain was found to be 6.9%, predominantly among women with a mean age of 52.5 years. The leading causes identified were seborrheic dermatitis and pruritus of undetermined etiology or sensitive scalp. Stress was noted as a key factor, with corticosteroids and hygienic measures being common therapies. The topical product demonstrated significant reductions in pruritus and scratching in more than 90% of patients after 15 days. Improvements were also seen in dermatological quality of life, with 87.1% of patients showing enhancements in DLQI scores. The product was well-received thanks to its cosmetic properties, with high ratings in texture, ease of application, and fragrance. ConclusionThe topical product studied is a safe, effective, and cosmetically appealing treatment, improving scalp pruritus in various etiologies for most patients. The results highlight the need for patient-center treatments in dermatology, providing important insights for clinical practice and future research.

Weekly carboplatin plus paclitaxel chemotherapy in advanced melanoma patients resistant to anti-PD-1 inhibitors: a retrospective, monocentric experience

Immunotherapy with anti-PD-1 antibodies significantly improved the prognosis in advanced melanoma patients, but most of them develop primary or secondary resistance to the treatment. In this study, we evaluated efficacy and safety of a chemotherapy regimen with weekly carboplatin plus paclitaxel (wCP) in patients previously treated with anti-PD-1 antibodies. We retrospectively identified 30 patients with advanced melanoma treated at our Institute over the last eight years with wCP. The co-primary endpoints of the study were overall survival (OS) and progression-free survival (PFS). In addition, we evaluated treatment tolerability. For this patient cohort, median PFS and OS were 3.25 and 7.69 months, respectively. All included patients had previously received anti-PD-1 immunotherapy, most of them had ECOG PS 0–1, and only 5 patients had a BRAF V600 mutation. In univariable analysis, we observed shorter OS in patients with > 2 involved metastatic sites, superficial spreading histology, and serum lactate dehydrogenase (LDH) values above the median. Liver metastases were associated with worse outcomes, while radiotherapy treatment of brain metastases was associated with improved OS. However, in a multivariable Cox regression model, only LDH above the median, superficial spreading histology, and female sex were significantly associated with worse OS. We reported grade 3 and 4 treatment-related toxicities in 4 and 0 patients, respectively. In conclusion, chemotherapy with wCP is a valid palliative treatment in advanced melanoma who progressed with anti-PD-1 antibodies.

Most Common Symptomatic Adverse Reactions of Cancer Treatments From US Drug Labels (2015-2021) to Inform Selection of Patient-Reported Outcomes

ObjectivesIncorporating patient-reported outcomes (PROs) to assess symptomatic adverse events (AEs) in cancer clinical trials (CTs) is important to characterize treatment tolerability. Cancer therapies approved over the past decade have expanded the types of expected toxicities. To inform future symptomatic AE PRO item selection, we identified the most common symptomatic adverse reactions from recently approved products. MethodsWe reviewed approvals from 2015 to 2021 for lung, breast, and hematologic cancer indications. Using United States Prescribing Information safety data, we recorded symptomatic adverse reactions reported in ≥20% of patients in the experimental arm of CTs supporting approvals. We calculated the proportion of arms reporting each symptomatic adverse reaction. ResultsIn total, 130 experimental arms were included (lung = 30, breast = 10, hematologic = 90). For all cancer types, fatigue and diarrhea were reported in >50% of the arms. Nausea was reported in ≥50% of the arms for all except lung. Vomiting, decreased appetite, and alopecia, were reported in ≥50% of breast cancer arms. Rash, musculoskeletal pain, and cough were reported in >50% of leukemia/lymphoma arms. Cough was common (50%) in multiple myeloma arms. ConclusionsHeterogeneity in symptomatic adverse reactions across CTs supports the use of item libraries when building a PRO strategy to assess tolerability. Fatigue, diarrhea, and nausea were the most frequent symptomatic adverse reactions reported in contemporary cancer CTs and could provide a starting point when selecting PRO symptomatic AE items. Additional symptomatic AE PRO items should be selected based on the mechanism of action, early clinical data, published literature, and patient and clinician input.