Hoag Memorial Hospital Presbyterian

RET fusions appear in 1%-2% of non-small cell lung cancers (NSCLCs). The results from the ARROW study (ClinicalTrials.gov identifier: NCT03037385) supported US Food and Drug Administration approval of pralsetinib, an oral selective RET inhibitor, for metastatic RET-altered NSCLC and RET fusion-positive thyroid cancers. ARROW was a phase I/II open-label study of pralsetinib 400 mg once daily in RET fusion-positive NSCLCs. Coprimary end points were overall response rate (ORR) and safety. Key secondary end points included duration of response, progression-free survival, and overall survival (OS). At data lock (May 20, 2024), 281 patients initiated pralsetinib (median treatment duration, 15.0 months). ORR (measurable disease patients; n = 259) was 78% (95% CI, 69 to 86) for treatment-naïve patients and 63% (95% CI, 54 to 71) for prior platinum-based chemotherapy patients. Median OS was 44.3 months (95% CI, 30.9 to 53.1), 50.1 months (95% CI, 28.3 to not reached) in treatment-naïve patients, and 39.7 months (95% CI, 27.8 to 53.2) in prior platinum patients. Common grade ≥3 treatment-related adverse events were anemia (21%), hypertension (15%), and decreased neutrophils (13%). Three treatment-related deaths occurred (pneumonia, n = 2; interstitial lung disease and rhabdomyolysis, n = 1 each). Safety was consistent with previous ARROW reports; no hypersensitivity was reported in patients receiving prior immunotherapies. Pralsetinib produced robust, durable responses with manageable safety in treatment-naïve and previously treated patients with RET fusion-positive NSCLCs, confirming previous findings with longer follow-up.

The use of prophylactic subgaleal vancomycin powder for preventing surgical site infections (SSI) has gained traction among cranial surgeons. However, its broad application remains controversial as the studies supporting its use are skewed toward high infection risk pathologies and have significant limitations. This study aimed to evaluate the efficacy of vancomycin powder in reducing SSIs in a cohort of patients with nonmalignant cranial pathologies. A retrospective chart review was conducted for 987 patients who underwent cranial surgeries for nonmalignant pathologies between July 2021 and June 2024 at a major academic center. Patients were divided into 2 groups: those who received prophylactic vancomycin powder (682 patients) and those who did not (305 patients). Data on demographics, comorbidities, procedure types, and SSI occurrences were collected. Established infection risk characteristics were nonsignificantly different between groups. There was no significant SSI difference when comparing patients not receiving vancomycin vs those who received the antibiotic (0.3% vs 0.7%, P = .578). There were 6 infections in total, 3/6 (50%) occurred with atypical meningiomas, 2/6 (33%) occurred with schwannomas, and 1/6 (17%) occurred with an amoebic abscess. Supratentorial craniotomies (odds ratio 0.95, P = .810) and posterior fossa craniotomies (odds ratio 1.18, 0.545) were the most common procedures and were nonsignificantly different between the cohorts. Meningiomas represented the largest portion of pathologies and were equally represented in both groups. This study suggests that the routine use of prophylactic vancomycin powder in nonmalignant cranial surgeries may be unnecessary, given an overall low incidence and lack of significant difference in SSIs between groups. These findings advocate for a more tailored approach to antibiotic prophylaxis, weighing the potential benefits against the known risks.

Retrospective cohort study using a multicenter, prospectively collected adult spinal deformity (ASD) database. To determine whether achieving the ideal L1 pelvic angle (L1PA) in minimally invasive surgery (MIS) for ASD correction is associated with reduced mechanical failure and improved clinical outcomes. Prior research has shown that achieving ideal L1PA-defined as (0.5×pelvic incidence)-21-is linked to lower reoperation risk in open ASD correction. Its relevance in MIS has not been well established. A total of 1104 ASD patients across 13 centers were included (criteria: scoliosis ≥20°, SVA ≥5cm, PT ≥25°, or TK ≥60°, with ≥2-year follow-up). Radiographic parameters and patient-reported outcomes (PROs) were collected preoperatively, at six weeks, and at final follow-up. Ideal L1PA was defined as within ±5° of the calculated target. MIS was defined as circumferential MIS (LLIF/ALIF with percutaneous posterior fixation). Associations between alignment and outcomes (reoperation, PROs) were analyzed using linear regression and t tests. Ideal L1PA was achieved in 63% of MIS cases and 61% of open cases ( P =0.342). Among MIS patients, ideal L1PA correlated with lower reoperation rates (15% vs. 33%, P <0.01) and greater improvement in SRS-22 total (Δ0.85 vs. Δ0.40, P <0.01) and SF-36 PCS scores (Δ9.1 vs. Δ4.6, P =0.04). In contrast, ideal L1PA was not associated with reduced reoperation in the open group. Across all patients, each 1° deviation from ideal L1PA increased reoperation risk by 1.8% ( P =0.04). Ideal L1PA is achievable in MIS at similar rates as open surgery. In MIS-treated ASD patients, achieving ideal alignment is associated with reduced reoperation and improved clinical outcomes, supporting its role as a key surgical target.

Speckled lentiginous nevus (SLN), also referred to as nevus spilus, is a common benign melanocytic neoplasm typically occurring as a small, café-au-lait-colored “speckled” patch studded with numerous darkly pigmented macules or papules. Herein, we present a unique case of SLN arising on the sole of the right foot in a young woman, which was reported to be gradually enlarging since a pregnancy two years prior. The lesion was removed by shave biopsy, and histopathology confirmed the diagnosis and ruled out atypical features. While SLN is quite common, the occurrence on acral skin is extremely rare. SLN is considered a mosaic RASopathy due to its embryological development through a postzygotic activating HRAS genetic variant. Although small lesions usually remain isolated, underlying SLN syndrome should be considered in extensive cases with associated neurologic or musculoskeletal abnormalities. Secondary melanocytic neoplasms commonly arise within SLN, but overall, small lesions carry a low risk of malignant transformation, and prophylactic surgical treatment is not necessary. We briefly discuss SLN occurring in special sites and report this novel case with a review of the literature on SLN.

Background/Objectives: Dendritic cell vaccines are a promising cancer immunotherapy. AV-OVA-1 is a patient-specific vaccine consisting of autologous dendritic cells (DCs) loaded with autologous tumor antigens (ATA) from a lysate of irradiated self-renewing cells enriched for tumor-initiating cells (TICs). A multicenter, double-blind, randomized phase 2 trial was designed to determine manufacturing feasibility, safety, and efficacy. Methods: Patients had newly diagnosed stage 3 or 4 ovarian cancer. Short-term cell cultures were established from freshly resected tumor specimens. Patients were screened for randomization seven months after initial diagnosis, after completing neoadjuvant and/or adjuvant chemotherapy and surgery. Eligibility included a successful cell culture, cryopreservation of sufficient monocyte numbers for differentiation into DCs, and good performance status. Patients were stratified by whether they had persistent disease; then, they were randomized 2:1 to AV-OVA-1 or autologous monocytes (MC). Cryopreserved doses of AV-OVA-1 and MC were thawed and admixed with granulocyte–macrophage colony-stimulating factor just before subcutaneous injections at weeks 1, 2, 3, 8, 12, 16, 20, and 24. Results: Study accrual was terminated early during the SARS-CoV-2 pandemic. Manufacturing success rates for TICs, monocyte intermediate products, and AV-OVA-1 were 70/72 (97.2%) and 47/50 (94.0%), and 29/30 (96.7%), respectively. A total of 29 participants were treated with AV-OVA-1 and 15 with MC. Patients received an average of 7.4 injections. Adverse-event frequencies were similar in both arms, mild to moderate in severity, and self-limited. T-cell immune responses increased only after AV-OVA-1. There were no survival differences in this underpowered study. Conclusions: AV-OVA-1 was manufactured reliably and injections were well tolerated.

While vaginal estrogen (VE) is a common treatment option for women with genitourinary syndrome of menopause, VE can be cost-prohibitive, causing medication nonadherence. The objective of this study was to compare trends in VE pricing through retail pharmacies, Medicare Part D, the Mark Cuban Cost Plus Drug Company (CPD), and with the application of GoodRx coupons. For this economic study, data from CPD and GoodRx were reviewed to obtain listed prices for various VE types and formulations, including conjugated estrogen cream (Premarin), estradiol 0.01% cream (Estrace), and estradiol 10mcg tablets (Vagifem). GoodRx prices were obtained from 4 retail pharmacies within the most populous zip code from each U.S. state. Prices were adjusted to account for dosage and prescribed quantity to estimate an average cost per dosage unit ($/adu). Within zip codes, the mean $/adu of Premarin, Estrace, and Vagifem were $9.03, $3.45, and $9.86, with a standard deviation of 0.45 $/adu, 0.48 $/adu, and 0.56 $/adu. Comparing GoodRx to retail pricing, cost reductions were seen for all 3 medications, with an average saving of $7.45, $1.34, and $6.00 per dosing unit. Reduced prices for all medications were available through CPD versus GoodRx, with cost reduction of $0.35, $0.89, and $2.31 for each unit of Premarin, Estrace, and Vagifem. While significant price variations for prescriptions were seen on a regional level within zip codes and between pharmacies, notable price savings were consistently seen with CPD and GoodRx, offering a solution to the financial strain that these prescriptions may impose.

ABSTRACT Survival of glioblastoma (GBM) patients is unsatisfactory. Adding patient-specific vaccines to standard therapy may improve outcomes. Autologous dendritic cells (DC) loaded with autologous tumor antigens (ATA) from short-term cell lines established from autologous tumor are a promising therapeutic vaccine strategy. DC-ATA vaccines were tested in a single-arm phase 2 trial in newly diagnosed GBM patients. Tumor tissue was collected during surgical resection. DC were differentiated from peripheral blood monocytes. Intent-to-treat enrollment took place before standard concurrent radiation therapy and temozolomide (RT/TMZ). DC-ATA was manufactured during RT/TMZ, then injected subcutaneously over 6 months concurrently with adjuvant TMZ. DC-ATA was reliably manufactured; treatment was well tolerated. Fifty-seven patients started vaccine therapy; 69% received all eight vaccine doses. The 10.7-month median progression-free survival (PFS) is 57% greater than the average of medians from standard treatment arms in six randomized trials that also enrolled patients before RT/TMZ. Disease control and overall survival (OS) dropped precipitously once DC-ATA was completed. Survival curves stratified by prognostic variables did not separate until after DC-ATA was discontinued. Multivariate analysis identified receipt of all eight planned vaccine injections, MGMT promoter methylation, concurrent dexamethasone dose ≤2 mg, and receipt of six or more TMZ cycles as independent variables. Common features among the seven patients who were progression-free after 3 years were eight vaccine injections, ≤2 mg dexamethasone, age <60 years, and adjuvant TMZ given without concurrent bevacizumab. PFS was encouraging, and the data suggest that OS may be increased by extending vaccine treatment.