Treatment-related Side Effects Research Articles

Vestibular Neurostimulation for Parkinson’s Disease: A Novel Device-Aided Non-Invasive Therapeutic Option

Dopaminergic replacement therapy remains the mainstay of symptomatic treatment for Parkinson’s disease (PD), but many unmet needs and gaps remain. Device-based treatments or device-aided non-oral therapies are typically used in the advanced stages of PD, ranging from stereotactic deep brain stimulation to levodopa or apomorphine infusion therapies. But there are concerns associated with these late-stage therapies due to a number of procedural, hardware, or long-term treatment-related side effects of these treatments, and their limited nonmotor benefit in PD. Therefore, there is an urgent unmet need for low-risk adjuvants or standalone therapies which can address the range of burdensome motor and nonmotor symptoms that occur in PD. Recent studies suggest that non-invasive neurostimulation of the vestibular system may be able to address these gaps through the stimulation of the vestibular brainstem sensory network which extensively innervates brain regions, regulating both motor and a range of nonmotor functions. Therapeutic non-invasive vestibular stimulation is a relatively modern concept that may potentially improve a broad range of motor and nonmotor symptoms of PD, even at early stages of the disease. Here, we review previous studies supporting the therapeutic potential of vestibular stimulation for the treatment of PD and discuss ongoing clinical trials and potential areas for future investigations.

From Diagnosis to Recovery: The Life-Changing Benefits of Exercise for Cancer Patients

Physical activity has emerged as a crucial component in the comprehensive care of oncological patients, offering significant benefits across the cancer continuum—from prevention to treatment, recovery, and survivorship. This article provides an in-depth exploration of the role of exercise in cancer care, highlighting its potential to improve physical function, reduce treatment-related side effects, enhance mental well-being, and improve overall quality of life. Epidemiological evidence supports the protective effect of regular physical activity in reducing the risk of developing certain cancers, such as breast, colorectal, and endometrial cancer, through mechanisms like hormonal regulation, inflammation reduction, and immune function enhancement. During active cancer treatment, exercise helps combat common side effects such as fatigue, muscle wasting, and cardiovascular decline, while also offering psychological benefits like reduced anxiety and depression. Tailored exercise programs, developed in collaboration with healthcare professionals, are essential for addressing the unique needs of cancer patients, considering factors like cancer type, treatment stage, and comorbidities. Post-treatment, physical activity continues to play a vital role in rehabilitation, reducing the risk of recurrence, and supporting long-term survivorship. Despite the clear benefits, barriers such as physical limitations, psychological distress, and lack of access to resources can hinder patients' ability to engage in regular exercise. Addressing these challenges through personalized care plans, patient education, and supportive interventions is crucial. As research in exercise oncology advances, integrating physical activity into routine cancer care holds promise for improving outcomes and enhancing the overall well-being of cancer patients.

Low-magnitude high-frequency vibration reduces prostate cancer growth and extravasation in vitro

Prostate cancer (PCa) continues to rank among the most common malignancies in Europe and North America with significant mortality rates despite advancements in detection and treatment. Physical activity is often recommended to PCa patients due to its benefits in preventing disease recurrence and managing treatment-related side effects. However, physical activity may be challenging for elderly or bedridden patients. As such, vibration therapy has been proposed as a safe, effective, and easy to perform alternative treatment that may confer similar effects as physical exercise. Specifically, low-magnitude high frequency (LMHF) vibration has been shown to decrease breast cancer extravasation into the bone and reduce other types of cancer proliferation by impacting cell viability. Here, we investigated the effects of daily application of LMHF vibration (0.3 ​g, 60 ​Hz, 1 ​hour/day for 3 days) on prostate cancer growth and bone metastasis in vitro. Our findings suggest that LMHF vibration significantly reduces colony formation through a decrease in cell growth and proliferation. Moreover, using a 3D cell culture model, LMHF vibration significantly reduces PC3 spheroid size. Additionally, LMHF vibration reduces PCa cell extravasation into the bone microenvironment through the stimulation of osteocytes and subsequent osteocyte-endothelial cell cross talk. These findings highlight the potential of LMHF vibration for managing PCa growth and metastasis.

Validity of a single-item indicator of treatment side effect bother in patients with head and neck cancer.

Patients with head/neck squamous cell carcinomas (HNSCC) experience significant tumor- and treatment-related side effects. No efficient summary measure capturing the totality of side effect burdencurrently exists. We examined associations between a single patient-reported outcome (PRO) item evaluating side effect bother (FACT GP5, "I am bothered by side effects of treatment") with overall side effects in HNSCC. We performed a retrospective secondary analysis of development of the Functional Assessment of Cancer Therapy (FACT) Head/Neck Symptom Index (FHNSI-10), which included completing FACT-HN (including Head/Neck Cancer Subscale (HNCS) and Trial Outcome Index (TOI)) and the pain intensity numeric rating scale (NRS). We calculated Spearman's correlations between GP5 and these measures of patient-reported global health, head/neck side effects, and pain intensity NRS. A correlation of > 0.4 was considered sufficient evidence of association. Ninety-seven patients completed baseline and 85 completed 3-month follow-up surveys. GP5 was highly correlated with FACT-HN total score (baseline r = 0.66, 3months r = 0.67) and FHNSI-10 (baseline r = 0.63, 3months r = 0.65). GP5 correlated with multiple FACT-HN subscales including FACT-G, physical well-being, functional well-being, HNCS, and TOI (range baseline r = 0.53-0.77, range 3months r = 0.49-0.77). Worsening GP5 score was associated with worsening overall HNCS (p = 0.002), worsening FHNSI-10 score (p < 0.001), and worsening mean pain intensity (p < 0.001). GP5 exhibited validity within HNSCC, exhibiting substantial correlations with a number of HNSCC-related PRO measures including FACT-HN and FHNSI-10. Worsening GP5 was associated with worsening HNCS, FHNSI summary score, and pain intensity. GP5 has promise as a summary indicator of symptom and side effect bother in HNSCC.

Long-term efficacy and safety of cannabidiol in patients with tuberous sclerosis complex: 3-year results from the cannabidiol expanded access program.

The cannabidiol (CBD) Expanded Access Program provided compassionate access to CBD for patients with treatment-resistant epilepsy, including tuberous sclerosis complex (TSC), at 35 US epilepsy centers. Here, we present the long-term efficacy and safety outcomes for add-on CBD treatment in patients with TSC. Patients received plant-derived, highly purified CBD (Epidiolex® 100 mg/mL, oral solution), increasing from 2 to 10 mg/kg/d to tolerance or maximum of 25-50 mg/kg/d. Efficacy endpoints were percentage change from baseline in median monthly convulsive, focal, and total seizure frequency and ≥ 50%, ≥75%, and 100% responder rates across 12-week visit windows through 144 weeks. Adverse events (AEs) are reported through 233 weeks. Thirty-four patients with confirmed TSC were included. Mean age was 12.4 years (range, 1.8-31.2), and patients were receiving a median of 3 (range, 1-7) antiseizure medications (ASMs) at baseline. Median CBD dose was 25-28 mg/kg/d for 36 weeks and then 20-50 mg/kg/d through 228 weeks. Dose reduction from baseline occurred for most ASMs, except topiramate. Median reduction in the frequency of convulsive, focal, and total seizures was 44%-81%, 51%-87%, and 44%-87%, respectively, through 144 weeks. Responder rates (≥50%, ≥75%, and 100% reduction) were 43%-71%, 14%-58%, and 0%-25% for convulsive seizures; 52%-75%, 35%-60%, and 7%-32% for focal seizures; and 46%-79%, 26%-65%, and 0%-13% for total seizures. A total of 94% of patients experienced ≥1 AE; 47% had serious AEs, considered treatment unrelated by the investigator. Treatment-related AEs (TRAEs) occurred in 71% of patients. The most frequently reported TRAEs were somnolence, diarrhea, and ataxia. Two patients experienced AEs leading to discontinuation. There were no deaths. Long-term add-on CBD use was associated with reduced seizure frequency through 144 weeks. The safety profile was consistent with previous reports. In this study, we evaluated efficacy and safety of cannabidiol (CBD) treatment in patients with tuberous sclerosis complex receiving CBD in addition to other antiseizure treatments in an Expanded Access Program. After starting CBD, 46%-79% of patients had at least 50% reduction and 26%-65% had at least 75% reduction in the number of seizures per month; up to 13% had no seizures through 144 weeks. Safety results were similar to prior studies; sleepiness and diarrhea were common treatment-related side effects. These results show that long-term CBD treatment was associated with fewer seizures and mild/moderate side effects.

Recent Advances in Immunotherapy and Targeted Therapy of Triple Negative Breast Cancer.

The truancy of representation of the estrogen, progesterone, and human epidermal growth factor receptors occurs during TNBC. TNBC is recognized for the upper reappearance and has a poorer diagnosis compared with rest breast cancer (BC) types. Presently, as such, no targeted therapy is approved for TNBC and treatment options are subjected to chemotherapy and surgery, which have high mortality rates. Hence, the current article focuses on the scenario of TNBC vital pathways and discusses the latest advances in TNBC treatment, including immune checkpoint inhibitors (ICIs), PARP suppressors, and cancer vaccines. Immunotherapy and ICIs, like PD 1 and PD L1 suppressors, displayed potential in clinical trials (CTs). These suppressors obstruct the mechanisms which allow tumor cells to evade the system thereby boosting the body's defense against TNBC. Immunotherapy, either alone or combined with chemotherapy has demonstrated patient outcomes such as increased survival rates and reduced treatment-related side effects. Additionally, targeted therapy approaches include BRCA/2 mutation poly ribose polymerase inhibitors, Vascular Endothelial Growth Factor Receptor (VEGFR) inhibitors, Epidermal growth factor receptor inhibitors, Fibroblast growth factor inhibitors, Androgen Receptor inhibitors, PIK3/AKT/mTOR pathway inhibitors, Cyclin-dependent kinase (CDK) inhibitors, Notch signaling pathway inhibitors, Signal transducer and activator of transcription 3 (STAT3) signaling pathway inhibitors, Chimeric antigen receptor T (CAR-T) cell therapy, Transforming growth factor (TGF) -β inhibitors, Epigenetic modifications (EPM), Aurora Kinase inhibitors and antibody-drug conjugates. We also highlight ongoing clinical trials and potential future directions for TNBC therapy. Despite the challenges in treating TNBC, recent developments in understanding the molecular and immune characteristics of TNBC have opened up new opportunities for targeted therapies, which hold promise for improving outcomes in this aggressive disease.

The time course of health-related Quality of Life in rectal cancer patients undergoing combined modality treatment

Background and purposeThis exploratory prospective observational study investigated the changes in Health-related Quality of Life (HRQoL) in rectal cancer patients (RCPs), from diagnosis to one-year-post-surgery follow-up and explored the role of physical symptoms and psychological determinants on HRQoL at the different time points. Materials and methodsWe assessed HRQoL, psychological distress, coping, affectivity, alexithymia and social support in 43 RCPs treated with preoperative (chemo)radiation and surgery, at three different assessment time points: diagnosis (T0), one month after the end of preoperative treatment (T1), one month after resection surgery (T2), and at follow-up (T3). ResultsThe data showed that HRQoL decreased during active treatments, especially between T1 and T2 (p = 0.005), before increasing again at follow-up (p = 0.002).Baseline intestinal symptoms (p < 0.001) and negative affectivity trait (p = 0.03) significantly predicted HRQoL at T0. Baseline pain (p < 0.001), intestinal (p = 0.003) and urinary (p = 0.009) symptoms at T1 significantly predicted HRQoL at T1. A fatalistic coping style at T1 (p = 0.013), psychological distress (p = 0.003), mouth symptoms (p = 0.001) at T2 significantly predicted HRQoL at T2. Similarly, a fatalistic coping style at T1 (p = 0.006), psychological distress (p = 0.004), mouth (p = 0.002) and pain symptoms (p = 0.002) at T3 significantly predicted HRQoL at T3. ConclusionSeveral physical and psychological factors are involved in the changes occurring after diagnosis in RCPs’ HRQoL. While cancer-related symptoms and treatment-related physical side effects are the main predictors of HRQoL at diagnosis and during active treatments, early psychological reactions have a higher predictive weight in post-treatment HRQoL.These data emphasise the importance of active screening, early diagnosis, and preventive psychological interventions immediately after diagnosis to improve HRQoL and psychological health outcomes.

Radiation therapy and IRreversible electroporation for intermediate risk prostate cancer (RTIRE)

IntroductionRadiation Therapy and IRreversible Electroporation for Intermediate Risk Prostate Cancer (RTIRE) is a phase II clinical trial testing combination of radiation therapy and irreversible electroporation for intermediate risk prostate cancerBackgroundPCa is the most common non-cutaneous cancer in men and the second leading cause of cancer death in men. PCa treatment is associated with long term side effects including urinary, sexual, and bowel dysfunction. Management of PCa is based on risk stratification to prevent its overtreatment and associated treatment-related toxicity. There is increasing interest in novel treatment strategies, such as focal therapy, to minimize treatment associated morbidity. Focal therapy alone has yet to be included in mainstream guidelines, given ongoing concerns with potentially higher risk of recurrence. We hypothesize combining focal therapy with whole gland, reduced dose radiotherapy will provide acceptable oncologic efficacy with minimal treatment associated morbidity. RTIRE is a phase II single institution, investigator-initiated study combining a local ablative technique though local irreversible electroporation (IRE) with MR guided RT (MRgRT) to treat the entire prostate. The goal is to provide excellent oncologic outcomes and minimize treatment related side effects through leveraging benefits of locally ablative therapy with established radiation treatment techniques.MethodsA total of 42 men with intermediate risk PCa per NCCN guidelines and focal grade group (GG) 2 or 3, Gleason Score (GS) 3 + 4 or GS 4 + 3, cancer in an MRI target will be enrolled. Patients with MRI visible foci of GG2/GG3 will undergo focal therapy with IRE of this lesion. Following successful focal therapy, patients will then undergo a course of reduced dose, whole gland MRgRT with either 32.5 Gy in 5 Fractions or 22 Gy in 2 fractions. The primary objective of the study is to determine safety. Secondary outcomes include evaluation of oncologic efficacy (as measured by the proportion of patients free of clinically significant cancer as defined as > Grade Group 1 at 1-year follow-up biopsy), imaging characteristics of patients pre and post RTIRE, impact on quality of life (QoL), and PSA kinetics.DiscussionCombining IRE with a reduced dose radiotherapy may offer a new treatment paradigm for PCa by both reducing treatment effects of full dose radiotherapy and minimizing the risk of recurrence observed with focal therapy.Trial RegistrationClinicaltrials.gov identifier: NCT05345444. Date of registration: April 25, 2022. Protocol Version: 6.0, July 7, 2023.

Photothermal Temperature-Modulated Cancer Metastasis Harnessed Using Proteinase-Triggered Assembly of Near-Infrared II Photoacoustic/Photothermal Nanotheranostics.

Here we demonstrate that cancer metastasis could be modulated by the judicious tuning of physical parameters such as photothermal temperature in nanoparticle-mediated photothermal therapy (PTT). This is supported by theranostic nanosystem design and characterization, in vitro and in vivo analyses, and transcriptome-based gene profiling. In this work, the highly efficient near-infrared II (NIR-II) photoacoustic image (PA)-guided PTT are selectively activated using our developed matrix metalloproteinase (MMP)-triggered in situ assembly of gold nanodandelions (GNDs@gelatin). Unlike other "always-on" NIR PTT agents lacking specific bioactivation and suffering from the intrinsic nonspecific pseudosignals and treatment-related side effects such as metastasis, our GNDs@gelatin possesses important advantages while deployed in cancer PTT that include the following: (1) The theranostic effects could be "turned on" only after specific MMP-2/-9 activity and with acidity in the tumor microenvironment. (2) The quantitative PA diagnosis allows for precise PTT planning for better cancer treatment. (3) GNDs@gelatin could noninvasively quantify MMP activity and efficiently harness NIR-I (808 nm) and NIR-II (1064 nm) energies for tumor ablation. (4) The multibranched nanostructures reabsorb scattered laser photons, thus enhancing the surface plasmons for the pronounced photothermal conversion of aggregated GNDs@gelatin in situ. (5) It is noteworthy that in situ tumor eradication at higher PTT temperature (>55 °C) mediated by GNDs@gelatin could induce subsequent metastasis, which could be otherwise abolished at lower PTT temperatures (50 °C > T > 43 °C). (6) Furthermore, the gene profiling using transcriptome-based microarray including GO and KEGG analyses revealed that 315 differentially expressed genes were identified in higher PTT temperature treated tumors compared with lower PTT temperature ones. These were enriched into some well-known cancer-related pathways, such as cell migration pathway, signal transductions, cell proliferation, wound healing, PPAR signaling, and metabolic pathways. These observations suggest a new perspective of "moderate-is-better" in nanoparticle-mediated PTT for maximizing its therapeutic/prognosis benefits and translational potential with metastasis inhibition.

Adverse Events with Hypoglossal Nerve Stimulation in the Treatment of Obstructive Sleep Apnea-A Systematic Review of Clinical Trials and Real-World Data.

Background/Objectives: Hypoglossal nerve stimulation (HNS) emerged as an alternative treatment for patients with obstructive sleep apnea (OSA) a decade ago. Long-term clinical trials and real-world data show that HNS treatment provides significant and sustained improvements in both OSA disease control and quality-of-life measures over time. Given the nature of HNS treatment, with the requirement of using an implantable neurostimulation system, patient safety is a critical domain in the assessment of this technology. The objective of this review was to evaluate adverse events (AEs) and complications with HNS therapy in a systematic review of published evidence. Methods: Medline, Cochrane, and Web of Science were systematically searched to identify randomized controlled and real-world observational studies reporting relevant outcomes with HNS therapy for treatment of OSA that included procedure-, device-, and treatment-related AEs. Results: Out of 418 articles screened, 27 were reviewed for eligibility, and 17 studies, the majority found to have low-to-moderate risk of bias, with data on 1962 patients were included for further analysis. Across included studies, reporting of AEs was heterogeneous with regard to the classifications used and the extent of reporting. Over an average follow-up duration of 17.5 ± 16.9 months, the pooled mortality rate was 0.01% (95% CI = 0.0 to 0.2%), with all reported deaths being unrelated to HNS treatment. The HNS system survival probability over the follow-up time of 60 months was 0.9834 (95% CI = 0.9768 to 0.9882), with infections and request for removal by patients being the most common indications. The pooled surgical revision rate was 0.08% (95% CI 0.0 to 0.2%). Most reported treatment-related side effects were transient stimulation-related discomfort (0.08%, 95% CI = 0.0 to 0.2%) and tongue abrasions (0.07%, 95% CI = 0.0 to 0.2%). Based on the systematic review, a standardized set of endpoints was defined, aiming to harmonize safety data relevant to HNS therapy. Conclusions: In this systematic review, HNS therapy for treatment of OSA is associated with a positive patient safety profile. AEs occur mainly at device implantation and during the treatment acclimatization period. Due to a lack of available evidence, partially implantable HNS systems are underrepresented in this review, which limits the generalizability of the results. Significant heterogeneity was found for adverse event reporting. A framework for reporting HNS outcomes that includes AEs and side effects is proposed to facilitate comparability of the reported data.

Psychometric properties of patient-reported outcomes Common Terminology Criteria for adverse events (PRO-CTCAE®) in breast cancer patients: The prospective observational multicenter VIP study

Patients’ self-reporting is increasingly considered essential to measure quality-of-life and treatment-related side-effects. However, if multiple patient-reported instruments are used, redundancy may represent an overload for patients.Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) are a tool allowing direct patients’ reporting of side-effects.We tested psychometric properties of a selected list of PRO-CTCAE items, in a cohort of 303 breast cancer patients, using validated instruments for quality of life assessment as anchors.The analysis of convergent validity with HADS (Hospital Anxiety and Depression Scale) and EORTC BR-23 sub-scales, and the analysis of responsiveness with the PGIC (Patients Global Impression of Change) score supported that a selected list of PRO-CTCAE symptoms might represent a standardized, agile tool for both research and practice settings to reduce patient burden without missing relevant information on patient perceptions.Among patients using digital devices, those with a higher education levels required shorter time to fulfil questionnaires.In conclusion, a selected list of PRO-CTCAE items can be considered as a standardized, agile tool for capturing crucial domains of side-effects and quality of life in patients with breast cancer.The study is registered on clinicaltrials.gov (NCT04416672).

Heart failure in patients with congenital heart disease after a cancer diagnosis.

Individuals with congenital heart disease (CHD) are at an increased risk for cancer. As cancer survival rates improve, the prevalence of late side effects, such as heart failure (HF), is becoming more evident. This study aims to evaluate the risk of developing HF following a cancer diagnosis in patients with CHD, compared with those without CHD and with CHD patients who do not have cancer. CHD patients (n=69799) and randomly selected non-CHD controls (n=650406), born in Sweden between 1952 and 2017, were identified from the Swedish National Health Registers and Total Population Register (excluding those with syndromes and transplant recipients). CHD patients who developed cancer (n=1309) were propensity score-matched with non-CHD patients who developed cancer (n=9425), resulting in a cohort of 1232 CHD patients with cancer and 2602 non-CHD controls with cancer (after exclusion of individuals with HF prior to cancer diagnosis). In a separate analysis, CHD patients with cancer were propensity score-matched with CHD patients without cancer (n=68490). A total of 1233 CHD patients with cancer and 2257 CHD patients without cancer were included in the study. Among CHD patients with cancer, 73 (5.9%) developed HF during a mean follow-up time of 8.5±8.7. Comparatively, in the propensity-matched control population, 29 (1.1%) non-CHD cancer patients (mean follow-up time of 7.3±7.5) and 101 (4.5%) CHD patients without cancer (mean follow-up time of 9.9±9.2) developed HF. CHD patients exhibited a significantly higher risk of HF post-cancer diagnosis compared with the non-CHD control group [hazard ratio (HR) 4.39, 95% confidence interval (CI) 2.83-6.81], after adjusting for age at cancer diagnosis and comorbidities. In the analysis between CHD patients with cancer and those without cancer, the results indicated a significantly higher risk of developing HF in CHD patients with cancer (HR 1.53, 95% CI 1.13-2.07). CHD patients face a more than four-fold increased risk of developing HF after a cancer diagnosis compared with cancer patients without CHD. Among CHD patients, the risk of HF is only modestly higher for those with cancer than for those without cancer. This suggests that the increased HF risk in CHD patients with cancer, relative to non-CHD cancer patients, may be more attributable to CHD itself than to cancer treatment-related side effects.

Considerations for Evaluating Older Adults with Cancer for Depression: A Qualitative Survey of Experts

ABSTRACT Objectives The objective of this study was to engage national experts in geriatric psychiatry and oncology in qualitative interviews to develop consensus regarding how older adult cancer survivors (OACS) experience depressive symptoms, and how best to assess OACs for depression. Methods Expert clinicians in geriatric oncology disciplines were interviewed about approaches to assessing depression in OACs. Interviews were audio-recorded and transcribed, and conducted until thematic saturation was achieved. Thematic Content Analysis was utilized to identify key themes. Results Experts (N = 8) were board certified geriatric psychiatrists and oncologists with specialization in geriatric medicine. Two conceptual domains were identified: Key indicators of depression in OACs (e.g. anhedonia; loss of meaning and purpose; loneliness and social withdrawal) and unique considerations for depression assessment in OACs (e.g. alternative phrasing to “depression,” disentangling mood and cancer or treatment-related side effects). Conclusions The approaches identified tended to depart from traditional diagnostic criteria for depression. Clinical implications Results provide additional insight into the limitations of existing depression measures for OACs. The themes and practices identified in the present study suggest that a revised measure of depression for OACs may be useful. Future research will continue to shed light on best practices for depression assessment in OACs.

Assessing the longevity of attribute framing in attenuating the nocebo effect to brand and generic medication.

The perception of taking a generic, relative to brand, medication has been demonstrated to exacerbate the nocebo effect. Conversely, positive attribute framing has been shown to attenuate the nocebo effect. However, little is known about the longevity of positive attribute framing nor how it interacts with generic versus brand treatment cues. Healthy participants (N = 205) were randomised to receive either sham-modafinil capsules with a brand or generic appearance, in conjunction with standard negative side effect framing (brand-negative: N = 42; generic-negative: N = 41) or positive side effect framing (brand-positive: N = 40; generic-positive: N = 40). The remainder were randomised to a no-treatment control (N = 42). Participants were informed that modafinil could enhance alertness and cognitive performance and reduce fatigue. Critically, modafinil was described as having several potential side effects. Treatment-related side effects, alertness, fatigue and cognitive performance were measured at baseline, 30-min post-treatment and 24 h later. Nocebo and placebo effects were observed across modafinil-treated participants relative to control. Positive framing significantly reduced warned side effects for 24 h. Perceived side effect likelihood, severity, and worry mediated the nocebo, but not framing, effect. Results have important implications for the presentation of side effect information, providing a potential route to reduce unwanted negative effects of generic medication.

Role of MRI in Assessment of Central Nervous System Lesions and Post Treatment Complications in Pediatric Patents with Leukemia

Abstract Background In terms of pediatric oncology, leukemia is one of the most frequent deadly illnesses. Early CNS problem identification and appropriate therapy were enhanced by MRI. Aim Describe the MRI results brought on by leukemia's involvement in CNS structures and treatment-related CNS side effects, and evaluate their efficacy for early therapy and preventing long-term adverse effects. Patients and Methods A prospective observational study included 52 children with leukemia. All patients undergone MR examination including conventional MRI, MR diffusion imaging and MR venography (MRV). Results Regarding MRI finding of CNS, leukemic infiltration was found in 57.7%, sub volimic changes in mild manner in 50% and about 26% in a moderate manner while absent in 23.1%, PRES was present in 19.2%, venous thrombosis present in 30.8% and post treatment complications were found in 7.7%. Conclusion Diffusion-weighted MRI proved very helpful in the early diagnosis and distinction of various CNS lesions seen in young patients with leukemia and post-treatment CNS sequelae. These techniques included conventional, post- contrast, MR venography, and diffusion-weighted MRI.

P-336 Efficacy of Gonadotrophin (GnRH) antagonists for endometriosis-associated pelvic pain - A systematic review and meta-analysis

Abstract Study question Are Gonadotropin-releasing hormone (GnRH) antagonists effective and safe in managing pain associated with endometriosis? Summary answer GnRH antagonists seem effective and safe in managing endometriosis-associated pain for at least 12 weeks of use. There is uncertainty with the evidence. What is known already GnRH agonists are commonly used as effective second-line treatment for endometriosis-associated pain. However, these agonists have drawbacks and are not well-tolerated by many women. GnRH antagonists, offer potential advantages over the agonists while providing similar efficacy. They lack the initial stimulatory effects thereby avoiding the initial flare-up of symptoms, which is common with agonists. Furthermore, unlike agonists, which are mainly available as injections, the antagonist are also available as oral preparations, which allow titration of doses. In-vitro and animal studies have shown antagonists to induce regression of endometriotic lesions by apoptosis. However, their efficacy in relieving endometriosis-related pains remains uncertain. Study design, size, duration Extensive electronic search was conducted by the Cochrane Gynaecology and Fertility group, up to October 2023 to identify randomised controlled trials (RCTs) evaluating efficacy of GnRH antagonists in managing endometriosis-related pains compared with placebo and/or GnRH agonists. The main searched databases included CENTRAL, MEDLINE and EMBASE. Screening and selection of suitable studies were undertaken. Study eligibility criteria included treatment for ≥12 weeks, laparoscopically confirmed endometriosis and assessment of pelvic pain scores as the primary endpoint. Participants/materials, setting, methods Primary end-point was a change in endometriosis-related pain score after 12-week treatment with GnRH antagonists compared with placebo and/or GnRH agonists. Changes in pain and quality of life (QoL) scores and adverse-events of GnRH-antagonists were compared between the antagonist versus the agonist/placebo groups. Data were analysed using RevMan software (V5.4) to calculate the standard mean difference (SMD) for continuous data, and the risk ratios (RRs) with 95% confident intervals (95% CI) for categorical data. Main results and the role of chance Seven eligible RCTs (n = 3043) were included, all of which compared GnRH-antagonist versus placebo, and only three also compared versus GnRH-agonist (leuprorelin). The GnRH-antagonists included ASP1707, Elagolix, Linzagolix and Relugolix. Meta-analysis of overall pelvic pain data from seven RCTs (n = 1684) showed significantly greater reduction in pain scores after 12 weeks of GnRH-antagonist versus placebo at low (SMD -0.29 95%CI -0.39 to -0.19; I2=0) and high doses (SMD-0.53 95%CI -0.63 to -0.43, I2=38%). Similarly, meta-analysis of other pains (dysmenorrhoea, non-menstrual pain, and dyspareunia) showed significantly greater pain score reduction with GnRH-antagonists versus placebo. Meta-analysis of overall pelvic pain from two RCTs (n = 263) comparing GnRH-antagonist versus leuprorelin showed comparable reduction in pain scores after 12 weeks at low (SMD 0.33 95%CI 0.09 to 0.58, I2=44%) and high doses (SMD 0.06 95%CI -0.19 to 0.30, I2=0%). Similarly, meta-analysis of other forms of pain revealed comparable reductions of pain scores between both drugs. Meta-analysis of QoL data (2RCTs, n = 259) revealed significantly greater improvements in scores with leuprorelin versus antagonists at low (SMD 0.74 95% CI 0.46 to 1.01; I2=98%) and high doses (SMD 0.35, 95%CI, 0.09 to 0.60, I2=97%). The most frequently reported treatment-related side-effects were hot-flushes, headaches and nasopharyngitis. No life-threatening side-effects were reported. Limitations, reasons for caution There was high heterogeneity between studies (e.g. differences in antagonists and pain scoring systems). No information was provided on prior endometriosis surgery, which is a confounding factor. Additionally, declared COI by authors of all trials could introduce high risk of bias. Evidence certainty was therefore deemed low to very low. Wider implications of the findings GnRH-antagonists seem to offer a promising treatment for endometriosis-related pain, with comparable efficacy to the agonists, but with several potential advantages. However, given the low quality and uncertainty of the evidence in this meta-analysis, high quality RCTs with robust designs are needed before making any firm recommendations for clinical practice. Trial registration number not applicable

The neurocognitive and neuropsychiatric manifestations of Susac syndrome: a brief review of the literature and future directions.

Encephalopathy is part of the clinical triad of Susac syndrome, but a detailed understanding of the neurocognitive and neuropsychiatric profile of this condition is lacking. Existing literature indicates that cognitive deficits range in severity from subtle to profound. Executive function and short-term recall are affected frequently. Psychiatric manifestations may be absent or may include anxiety, mood disorders or psychosis. If psychiatric phenomena develop during the disease course, it can be hard to disentangle whether symptoms directly relate to the pathology of Susac syndrome or are secondary to treatment-related side effects. In this article, we review what is known about the cognitive and psychiatric morbidity of Susac syndrome and identify areas where knowledge is deficient. Importantly, we also provide a framework for future research, arguing that better phenotyping, understanding of pathophysiology, evaluation of treatments on cognitive and psychiatric outcomes, and longitudinal data capture are vital to improving patient outcomes.

Exploring the interagency collaboration between a pediatric oncology health care setting and community schools.

Globally, approximately 400,000 youth are diagnosed with pediatric cancer each year. Treatment-related side effects, psychosocial challenges, and frequent school absences may adversely impact learning and the education experience among these youth. Efforts to enhance interagency collaboration between health care settings and community schools are imperative to facilitate school reintegration. The Standards for the Psychosocial Care of Children with Cancer and Their Families outline specific guidelines related to the continuity of education for students impacted by pediatric cancer. In particular, the Academic Continuity and School Reentry Support and Monitoring and Assessment of Neuropsychological Outcomes standards of care highlighted within this article align with extant programmatic efforts for transitioning hospitalized school-aged children back into community schools. This article aims to describe systematic programmatic efforts within hospital-based psychosocial programs that are consistent with the Standards for the Psychosocial Care of Children with Cancer and Their Families, as well as interagency collaboration with community schools to support student-centered education for youth impacted by pediatric cancer. Resources for school psychologists, teachers, hospital-based programs, and others involved in student-centered education for pediatric cancer patients and survivors are presented. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Parents' perception of treatment-related toxicity in children treated according to the NOPHO ALL2008 protocol for acute lymphoblastic leukemia.

This study aimed to assess how parents perceived treatment-related side effects during acute lymphoblastic leukemia (ALL) treatment. Parents of children 1-17.9 years at diagnosis in Sweden, Finland, and Denmark who were alive and in first remission ≥6 months after end of ALL treatment were asked to respond on specific items regarding how their child was affected by side effects related to vincristine (VCR), corticosteroids, peg-asparaginase (ASP), and maintenance therapy, as well as overall impact of these treatments, complications in general, and their perception of impact on their child in comparison with other children with ALL. Parents of 307 children responded. More than a third reported that their child had been affected to a high extent by VCR (39.7%) and corticosteroids (35.8%), with walking difficulties, muscular weakness, pain, changes in appetite, and mood swings as the most common and severe symptoms. Reporting of these toxicities was lacking from the NOPHO ALL2008 database, except for peripheral paralysis (12.1%). For distinct toxicities reported in the NOPHO ALL2008 database, for example, thrombosis and pancreatitis, parent reports were similar to the database. Although a high overall negative impact during treatment was reported, parents generally rated the impact on their child as less, or similar, to other children with ALL. Parents perceived VCR and corticosteroid therapy, in particular, to have a negative impact on their child during ALL treatment, which was not captured in the NOPHO ALL2008 toxicity reporting. Our results highlight the importance of including patient/parent-reported outcomes in toxicity reporting.

Enhancing Diagnosis and Prognosis by Assessing the Clinical, Morphological, and Behavior Aspects in Soft Tissue Sarcomas.

Soft-tissue sarcomas (STSs) are an uncommon and diverse group of cancers, consisting of more than 80 different kinds, each showing unique mesenchymal differentiation as described by the World Health Organization (WHO). The prognostic factors at the time of diagnosis mostly depend on the size, depth, and histological grade of the lymphatic involvement. Improved prognostic indicators are necessary to identify patients at high risk who may derive advantages from adjuvant therapy and those at low risk who might avoid treatment-related side effects. Over a period of five years, a considerable number of patients experience the recurrence of the tumor in the same area or the metastasis of the disease to other parts of the body, even after the complete removal of the localized tumor through surgery. To further personalize and focus medicines, it is critical to enhance prediction accuracy and uncover new therapy targets. This is particularly important considering the high mortality and morbidity rate associated with metastatic STS. The significant diversity of STS poses difficulty in comprehending its pathobiology and in converting biological progress into therapeutic application. This prospective cohort study was carried out at a major university hospital to ascertain adult patients who were diagnosed with STS of the extremities between the period from 2018 to 2023. The inclusion criteria were individuals who were 18 years of age or older with a histological diagnosis of STS. The exclusion criteria encompassed individuals with malignancies other than STS and those with inadequate data on essential factors. Thorough assessments were conducted to analyze patient demographics, tumor features (including site, size, depth, neurovascular or bone invasion), and histologic type and grade (according to the French Federation of Cancer Centers (FNCLCC) grading system). The purpose was to find predictive markers and evaluate results. The results are consistent with previous research and enhance our current knowledge of STS prognosis. Key prognostic markers for metastasis and mortality risk include tumor size larger than 5 cm, histologic grade, and sarcoma subtype. Radical surgical procedures, such as amputation or disarticulation, did not show any survival advantage, probably because they were used in situations where the disease had already progressed locally and had significant involvement in the blood vessels. Histologic grading has been identified as the most important factor in predicting the likelihood of metastasis in adult STSs. The study found that most tumors were of high grade, and there was a statistically significant association between tumor grade, Ki67 levels, and overall survival. A small proportion of patients experienced prolonged longevity beyond five years, emphasizing the connection between early detection, tumors of lesser severity, and enhanced results. These observations emphasize the significance of accurate prognostic assessments and customized therapeutic approaches in the treatment of STS.