Temecula Valley Unified School District

Over the last decade, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have steadily leaned towards granting regulatory approval based on earlier phase trials and surrogate endpoints. Despite obtaining regulatory approval, many countries hold additional standards to assess the value of a new drug approval. The ESMO-MCBS is a tool created to evaluate the values and reduce bias or hype of drug approvals using various metrics: efficacy, quality of life, and duration of response. In 2023, the ESMO-MCBS:H was created for hematological malignancies. We aimed to evaluate recent drug approvals using the new ESMO-MCBS:H criteria for hematologic malignancies. We included all drugs approved for a hematologic malignancy between 2019 and 2024. Drugs were assessed using ESMO-MCBS:H forms 2a, 2b, 2c, or 3 depending on the trial type and primary endpoints leading to drug approval. Approvals were independently scored by two reviewers with a third reviewer to adjudicate scoring differences. 66 drugs were approved by either FDA or EMA during this time. 88% (n=58) were approved by both EMA and FDA, 12% (n=8) by FDA alone. No drugs were approved by the EMA alone without preceding or subsequent FDA approval. 4 drug approvals were for pediatric indications. 36 approvals (n=35/66, 53 %) were based on early phase 1 and/or 2 trial data. Approvals were for leukemias (n=16; 24%), lymphomas (n=25, 38%), myeloma (n=18, 27%), or CLL/SLL (n=6; 9%). 13% of approvals (n=9/66) were for drugs with a biomarker matched indication. Substantial benefit criteria were met by 15 of 66 approvals (23%). Substantial benefit criteria were met by 0% (N=0/8) of drug indication by approved by FDA alone versus 26% of drugs approved by both the FDA and EMA (n=15/58).Approvals based on early phase (phase 1 and/or 2) trials met criteria in 17% (n=6/35) of trials and 29% of later phase (phase 3) trials met criteria (n=9/31) without statistical significance (p=0.25). No significant difference in approvals meeting substantial benefit were seen for biomarker matched therapies (33%; n=3/9) versus unmatched therapies (21%; n=12/57) (p=0.41). No therapies approved for a pediatric indication met criteria for substantial benefit (n=0/4). Few drugs approved by both agencies met the rigorous ESMO-MCBS:H criteria for substantial benefit. Recent approvals meeting substantial benefit criteria were not statistically correlated with approval agency, phase of trial utilized for approval, or biomarker selection of therapies. Drug approvals must balance proven benefit to access to innovative and new therapies. Ryan Hirsh, Justin Moyers, David Benjamin, Aysche Stern. Evaluating recent drug approvals for hematologic malignancies utilizing the New European Society of Medical Oncology Magnitude of Clinical Benefit Scale for Hematology (ESMO-MCBS:H) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3568.

9006 Background: The ASCO annual meeting is the world’s preeminent meeting of oncology professionals. Giving an oral presentation at the ASCO annual meeting is a landmark in a career. We examined the training and geographic diversity of presenters. Methods: We identified all oral abstract or moderator presentations from the ASCO Annual Meeting 2021-2024 using asco.org. Further information on each speaker was gathered from publicly available information through internet searches of institutional websites and professional social media. We queried degree, pronoun use, medical school, institutions of post-graduate training and years of graduation. Institutions were classified by geographic region (country, state, and U.S. Census Geographic Area), type (academic versus community) and NCI-designation. Presentations per population (PPP) of 10^6 persons were standardized by state and region level 2020 US Census data. Study was IRB exempt at investigators respective institutions. Results: Between 2021-2024, there were 1563 oral presentations in abstract sessions from 1310 speakers representing 491 institutions. 253 (19%) presented more than once (range: 1-5). 57% use the ‘he’ pronoun. Most presenters were from US institutes (66.7%; n=1043), 6.3% (n=99) from China, 4.0% (n=63) from France, and 3.2% (n=50) from the UK. 69.7% (n=1090) were from North America, 17.6% (n=275) from Europe/UK, 10.2% (n=16) from Asia, and 2% (n=31) from Australia. Few presentations were given by speakers from institutions in the Middle East (0.1%, n=2) or South America (all Brazil; 0.3%, n=4), and no presentations were given by speakers from African institutions. 22% (n=347) of presentations were from the top 5 presenting institutions, all of which were in the US and 3 of 5 on East coast. 87.1% (n=768) of presentations from US institutions were from NCI-designated centers. 21 of 33 (64%) US based plenary presenters were from New England or Mid Atlantic states, while 25% (n=11/44) were from non-US institutions. PPP were highest in northeast 6.0/10^6 compared to Midwest (2.9/10^6), South (2.6/10^6), and West (2.2/10^6). Highest PPP states were MA (15.5/10^6), DC (11.6/10^6), and CT (8.6/10^6) while 13 states had no presenters. Presenters were a median of 13.0 (SD: 9.2) years post training (YPT). By ASCO definitions, 6.8% (n=63) were students/trainees, 6.1% (n=57) were early career (<3 YPT), 53.8% (4-15 YPT) were mid-career, and 35.1% (n=326) were later career (>15 YPT). Trainee and early career speakers gave 0 plenary presentations, 9.6% (n=91) of oral abstract presentations, and 22.1% (n=40) of rapid oral abstracts (p=<0.001). Conclusions: Oral presenters were most frequently mid to late career, medical oncologists and from Northeastern, US, academic, NCI-designated centers while few speakers were from community sites or early career/trainees suggesting there is room for continued diversification to represent all oncologists and those they treat.

Purpose Data from the Focal Lesion Ablative Microboost in Prostate Cancer (FLAME) trial suggests a dose response for achieving local control of the dominant intraprostatic lesion (DIL). They reported a dose of ≥ 85 Gy achieves a 7-year probability of local control of almost 100%. Investigations using brachytherapy to microboost the DIL have been ongoing for decades and deliver a much higher dose than 85 Gy. Considering this, the purpose of this study is to perform a systematic review on brachytherapy microboost of the DIL to evaluate clinical outcomes and toxicities with this treatment approach. Materials and Methods This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Databases including Pubmed, Embase, and Google Scholar were queried from 2001-2022 using search terms: “boost”, “prostate cancer”, “dominant intraprostatic lesion”, and “brachytherapy”. The results were reviewed by three authors (MK, AB, MK). From the initial 357 studies, 305 were excluded as they were irrelevant. 52 reports were sought for retrieval and were assessed for eligibility. 15 studies met our inclusion criteria which were that the study included clinical and toxicity outcomes. PSA failure was most commonly defined using the Phoenix criteria and toxicities were most commonly assessed either using CTCAE or RTOG/EORTC scales. Results There were 10 studies that used HDR for microboosting on a total of 496 patients. Most patients treated were either intermediate or high-risk. Mean pre-treatment PSA ranged from 5.4-25.6ng/mL. Androgen deprivation therapy (ADT) was used in 8/10 studies. HDR dose (EQD2 assuming alpha/beta of 1.5) to the DIL ranged from 90-180 Gy. Median follow-up ranged from 18-98 months. PSA control rates at 5-8 years ranged from 69-100%. Acute G3-4 GU events were seen in 2 studies and there were no G3-4 acute GI events. Late G3-4 GU events were seen in 1 study and GI in 2 studies. There were 5 studies that used LDR microboosting on a total of 756 patients. Most patients had intermediate or high-risk disease. Mean pre-treatment PSA ranged from 5-9ng/mL. ADT was used in 4/5 studies. Studies tried to microboost the DIL to 130-150% of the whole gland prescription. Median follow-up ranged from not reported to 86 months. PSA control rates at 5 years ranged from 84-98%. Acute G3-4 GU events were seen in 1 study and there were no G3-4 acute GI events. Late G3-4 GU events were seen in 1 study and GI in 1 study. Conclusions Over 1,000 patients have been treated with a brachytherapy microboost in the published literature. Severe toxicities acute/late appear limited. Efficacy relative to outcomes from the FLAME trial are difficult to evaluate given the wide range of risk groups treated and microboost doses utilized. Prospective studies with standardized DIL definitions and dosing are needed to better evaluate the potential merits of this treatment approach. Data from the Focal Lesion Ablative Microboost in Prostate Cancer (FLAME) trial suggests a dose response for achieving local control of the dominant intraprostatic lesion (DIL). They reported a dose of ≥ 85 Gy achieves a 7-year probability of local control of almost 100%. Investigations using brachytherapy to microboost the DIL have been ongoing for decades and deliver a much higher dose than 85 Gy. Considering this, the purpose of this study is to perform a systematic review on brachytherapy microboost of the DIL to evaluate clinical outcomes and toxicities with this treatment approach. This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Databases including Pubmed, Embase, and Google Scholar were queried from 2001-2022 using search terms: “boost”, “prostate cancer”, “dominant intraprostatic lesion”, and “brachytherapy”. The results were reviewed by three authors (MK, AB, MK). From the initial 357 studies, 305 were excluded as they were irrelevant. 52 reports were sought for retrieval and were assessed for eligibility. 15 studies met our inclusion criteria which were that the study included clinical and toxicity outcomes. PSA failure was most commonly defined using the Phoenix criteria and toxicities were most commonly assessed either using CTCAE or RTOG/EORTC scales. There were 10 studies that used HDR for microboosting on a total of 496 patients. Most patients treated were either intermediate or high-risk. Mean pre-treatment PSA ranged from 5.4-25.6ng/mL. Androgen deprivation therapy (ADT) was used in 8/10 studies. HDR dose (EQD2 assuming alpha/beta of 1.5) to the DIL ranged from 90-180 Gy. Median follow-up ranged from 18-98 months. PSA control rates at 5-8 years ranged from 69-100%. Acute G3-4 GU events were seen in 2 studies and there were no G3-4 acute GI events. Late G3-4 GU events were seen in 1 study and GI in 2 studies. There were 5 studies that used LDR microboosting on a total of 756 patients. Most patients had intermediate or high-risk disease. Mean pre-treatment PSA ranged from 5-9ng/mL. ADT was used in 4/5 studies. Studies tried to microboost the DIL to 130-150% of the whole gland prescription. Median follow-up ranged from not reported to 86 months. PSA control rates at 5 years ranged from 84-98%. Acute G3-4 GU events were seen in 1 study and there were no G3-4 acute GI events. Late G3-4 GU events were seen in 1 study and GI in 1 study. Over 1,000 patients have been treated with a brachytherapy microboost in the published literature. Severe toxicities acute/late appear limited. Efficacy relative to outcomes from the FLAME trial are difficult to evaluate given the wide range of risk groups treated and microboost doses utilized. Prospective studies with standardized DIL definitions and dosing are needed to better evaluate the potential merits of this treatment approach.

Introduction: Facial Onset Sensory and Motor Neuronopathy (FOSMN) typically presents with paresthesias in the trigeminal nerve distribution and weakness that progresses rostro-caudally. Objective: To present two new cases of FOSMN, summarize the current literature, and address areas for future study. Methods: Observational data was collected from two patients with FOSMN from our institution. A literature review of FOSMN was completed using PubMed. Results: We identified 100 cases of FOSMN, including our two new cases. 93% presented with facial paresthesias. 97% had bulbar symptoms. Five had family history of ALS. Abnormal Blink reflex was most common on EMG/NCS. CSF was typically normal, but a rare severe case showed elevated protein. Mutations included: TARDBP, OPMD, D90A-SOD1, CHCHD10, VCP, and SQSTM1. Neuropathological studies showed neurodegenerative changes without inflammation. Some cases have reported transient stabilization or improvement to immunomodulatory therapy. Case Reports: A 72-year-old man presented with right-sided trigeminal paresthesias that progressed in a rostro-caudal fashion, dysphagia, and hand weakness. He died 4-5 years after symptom onset. A 69-year-old man presented with left-sided jaw paresthesias, dysphagia and dysarthria. He was trialed on IVIG for 1.5 years without improvement and died 2.6 years after symptom onset. Conclusion: FOSMN is a rare disorder with a unique clinical and electrophysiological phenotype. The pathophysiology has been associated with neurodegeneration and multiple gene mutations have correlated to FOSMN. Some reports suggest transient response to immunomodulatory therapy, though prospective studies are lacking. CSF protein elevation may be seen in severe disease. Future studies will help further elucidate the approach to diagnosis, treatment, and prognostic counseling (biomarkers).

The diagnosis and treatment of the behaviors associated with attention-deficit/hyperactivity disorder (ADHD) predominantly involves pharmacological interventions. Many children experience significant negative side effects (e.g., appetite suppression, insomnia, headaches, stomachaches, irritability, and impaired height) from the initial and continued use of stimulant medication. Consequently, many parents are motivated to consider alternative treatments for ADHD such as neurofeedback. This paper presents an archival review of the improvements in auditory and visual attention and response control after 40 sessions of artifact-corrected neurofeedback for 51 children ages 6 to 17 with ADHD. Initially, the majority of these clients were identified as having severe to extreme auditory and visual attention impairments. The IVA-2 CPT was administered prior to treatment and after 20 and 40 treatment sessions were completed. After 20 sessions of neurofeedback significant improvements of both auditory and visual attention and response control were found with small to large size effects. The clients continued to improve after an additional 20 sessions, with medium to large size effects after 40 sessions. At completion of treatment the mean of eight of the nine attention and response control scores fell within the “normal” range.