Citations

Extremely severe nausea was experienced by four subjects positioned prone on a 7T scanner table with their arm extended overhead for a wrist examination and their head positioned approximately 10–20 cm above the magnet's central axis. Movement through the large static and spatial field gradients of current 7T MRI scanner magnets typically causes mild vestibular activation which is well tolerated by most individuals. However, when positioned off‐axis, the head moves through regions of even larger and more rapidly changing magnetic fields which in the current study were sufficient to induce the extremely severe nausea. Ensuring the head remains on‐axis mitigates this effect.

Abstract Purpose: DICER1-related tumor predisposition increases risk for a spectrum of benign and malignant tumors. In 2018, the International Pleuropulmonary Blastoma (PPB)/DICER1 Registry published guidelines for testing- and imaging-based surveillance of individuals with a known or suspected germline DICER1 pathogenic or likely pathogenic (P/LP) variant. One of the goals of the Registry is to continue to refine these guidelines as additional data become available. Experimental Design: Individuals were enrolled in the International PPB/DICER1 Registry, the International Ovarian and Testicular Stromal Tumor Registry, and/or the NCI Natural History of DICER1 Syndrome study. Results: Review of participant records identified 713 participants with a germline DICER1 P/LP variant from 38 countries. To date, 5 cases of type I and 29 cases of type Ir PPB have been diagnosed by surveillance in enrolled individuals. One hundred and three individuals with a germline P/LP variant developed a primary ovarian Sertoli–Leydig cell tumor at a median age of 14 years (range: 11 months–66 years); 13% were diagnosed before 8 years of age, the current age of onset of pelvic surveillance. Additionally, 4% of Sertoli–Leydig cell tumors were diagnosed before 4 years of age. Conclusions: Ongoing data collection highlights the role of lung surveillance in the early detection of PPB and suggests that imaging-based detection and early resection may decrease the risk of advanced PPB. DICER1-related ovarian tumors were detected before 8 years of age, prompting the Registry to recommend earlier initiation of ovarian surveillance with pelvic ultrasound beginning at the time of detection of a germline DICER1 P/LP variant.

Erythromelalgia is a rare disorder characterized by episodic burning pain with redness and warmth of the extremities. Topical and systemic medications are the mainstay of management. We reviewed the published evidence for using procedural interventions to manage erythromelalgia, including their proposed mechanism of action and possible adverse effects, and included information in this review on epidural infusion, sympathetic ganglion block, sympathectomy, pulsed radiofrequency, spinal cord stimulation, dorsal root ganglion stimulation, brain stimulation, transcranial magnetic stimulation, and botulinum toxin injections. Both successful and unsuccessful outcomes have been reported. Although these procedural interventions extend the therapeutic options for erythromelalgia, the evidence for their use is limited. Case reports and small case series comprise most of the evidence. Based on our review, a multidisciplinary approach to management may be needed for patients with erythromelalgia.

Purpose To evaluate the effectiveness of microfragmented adipose tissue (MFAT) for pain relief and improved joint functionality in osteoarthritis (OA) of the knee in a randomized controlled clinical trial with 1‐year follow‐up. Methods Seventy‐five patients were stratified by baseline pain level and randomized to 1 of 3 treatment groups: MFAT, corticosteroid (CS), or saline control (C) injection. Patients 18 years of age or older, diagnosed with symptomatic OA of the knee, with radiographic evidence of OA of the knee and a visual analog pain scale score of 3 of 10 or greater were included. Patients were excluded if they had any previous intra‐articular knee injection, current knee ligamentous instability, or an allergy to lidocaine/corticosteroid. The visual analog pain scale, Western Ontario and McMaster Universities Osteoarthritis Index, and the Knee Injury and Osteoarthritis Outcome score (KOOS) were recorded preprocedure and at 2 weeks, 6 weeks, 3 and 6 months, and 1‐year follow‐up. Results MFAT demonstrated consistent and statistically significant improvements across all primary outcome measures for joint pain and functionality compared with C. For MFAT, there was a significant improvement over baseline at each follow‐up, with median (95% confidence interval) KOOS Pain score changes of 18.1 (11.1‐26.4) at week 2 to 27.8 (19.4‐37.5) at 1 year. For CS, the median KOOS pain score reached a maximum of 22.2 (15.3‐30.6) at week 2, only to level off to 13.9 (–2.8 to 29.2), a level not statistically different from baseline, at 1 year. The median changes for C hovered around 6 to 11 points, with statistically significant improvements over baseline indicating a placebo effect. Similar trends were seen for the Western Ontario and McMaster Universities Osteoarthritis Index Pain score and VAS Pain score. Conclusions In this study, MFAT demonstrated a clinically significant improvement in primary outcome scores compared with the C group, whereas the CS group only showed statistically significant improvement compared with the C group at 2 and 6 weeks. This finding indicates that MFAT may be a viable alternative treatment for patients with OA of the knee who fall into the orthopaedic treatment gap. Level of Evidence Level II, partially blinded, randomized controlled clinical trial.

Background: Large biobanks that link biological specimens with specimen donors’ health histories are a critical tool for precision medicine, and many health care institutions have invested significant resources in setting up and building up large collections for this purpose. As biobanks require consented participation from thousands of individual donors, much research has focused on the values and preferences of new and prospective donors who are actively contemplating an invitation to participate in the collection. Few studies, however, have focused on participants’ opinions about their biobank participation in the months and years following enrollment. Methods: We conducted a survey in a large, established biobank and evaluated participants’ levels of decisional regret regarding their decision to enroll in the biobank. Results: We found very low levels of decisional regret among established biobank participants. Multivariable regression analysis found that age, length of time in the biobank, lower educational attainment, inadequate health literacy, and previous invitations to research participation were all significant predictors of elevated regret. Discussion: Among those with elevated regret, several demographic factors may point to elevated likelihood of decisional regret. More research is needed to identify factors associated with long-term satisfaction with biobank participation and with elevated risk of regret and/or withdrawal from the collection.

8106 Background: Due to lack of prospective data, the optimal first line treatment approach for patients (pts) with pure LCNEC histology remains uncertain. Methods: Across 17 centers, we conducted a retrospective analysis of metastatic pure LCNEC (diagnosed at local institutions) who received 1st-line systemic therapy between 2015-2023. Pts were either treated with chemotherapy (chemo), immunotherapy (IO), or a combination (chemoIO). Clinical outcomes were progression-free survival (PFS), overall survival (OS), objective response rates (ORR), and treatment-related adverse events (trAE) as defined using CTCAE 5.0. Survival analysis by genomic alteration status ( TP53, RB1, STK11, KEAP1, KRAS) and PD-L1 status were performed. Results: We identified 161 pts with median age of 67 years (IQR: 58-83) at 1st line systemic therapy; 54% (n = 87) were males. Median follow-up was 55 months (mo), 62 mo, and 29 mo for the chemo, IO, and chemoIO groups, respectively. 79% (n = 127) were former or current smokers. 1st-line treatments were chemo (n = 94), IO (n = 11), or chemoIO (n = 56). Of 85 pts with PD-L1 status, 58 (68%) were 0% and 27 (32%) were ≥1%. The most common chemo regimen was platinum-etoposide (n = 72, 78%). ChemoIO regimens included carboplatin/etoposide/atezolizumab (n = 23, 43%) and carboplatin/pemetrexed/pembrolizumab (n = 17, 31%). In the IO group, 1 patient received dual IO. Lung (n = 74, 46%) and liver (n = 71, 41%) were the most common sites of metastasisThere was no significant difference in PFS across the groups (median PFS [mPFS] chemoIO: 5.7 mo, 95% CI: 5.0-6.3, chemo: 5.1 mo, 95% CI: 3.1-5.9; IO: 3.6 mo, 95% CI: 1.7-6.5) on multivariable analysis adjusting for ECOG and “M” stage (p = 0.2 and 0.24 for chemoIO-chemo and chemoIO-IO comparisons, respectively). There was no difference in OS (mOS chemo: 11 mo, 95% CI: 7.6-17.4; IO: 13.6 mo, 95% CI: 5.9-not reached; chemoIO: 12.2 mo, 95% CI: 7.4-20.6, p = 0.5 and 0.8 for chemoIO-chemo and chemoIO-IO comparisons, respectively). ORR was 35.2% (31/88) in chemo, 25% (2/8) in IO, and 35.7% (20/56) in chemoIO ( p= 0.46). There were no significant differences in PFS and OS outcomes by treatment group when divided by genetic profile (n = 79, methods), or by PD-L1 status (0% vs ≥1%). Any grade trAE occurred in 48 (51%), 5 (45%), and 28 (50%) pts treated with chemo, IO, and chemoIO, respectively. Grade ≥3 toxicity profiles are shown (table). Conclusions: For 1st-line treatment of LCNEC, similar PFS, OS, and ORR were seen for chemo, IO, and chemoIO. This questions the added benefit of chemoIO compared to chemo alone, and warrants future clinical trials to discern the optimal 1st line treatment. [Table: see text]

8602 Background: LCNECs are a rare subtype of lung cancer, with limited clinical trial data and an unclear consensus on first-line treatment. Even less is known about the optimal treatment approach for pts with mixed LCNECs, a pathologic subtype where tumors contain both LCNEC histology as well as features of adenocarcinoma, squamous cell, or small cell lung cancer. Methods: We conducted an international multi-institutional retrospective analysis (n=13 institutions) of pts with advanced or metastatic mixed LCNECs who received 1st-line systemic therapy with either chemotherapy alone (chemo) or chemo-immunotherapy (chemoIO) between 2010-2023. Clinical outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and treatment-related adverse events (trAEs). Survival comparisons were made via the log-rank test. Results: Seventy-three pts with mixed LCNECs received either chemo (n=42, 57.5%) or chemoIO (n=31, 42.5%). The most common chemo regimens were carboplatin/etoposide (n=27) and cisplatin/etoposide (n=8), while the most common chemoIO was carboplatin/etoposide/atezolizumab (n=19). Median age at 1st-line therapy initiation was 65 (IQR: 60-72). 64% of pts were male (n=47). The majority were former smokers (n=41, 56.2%), with 22 current smokers (30.1%), and 10 non-smokers (13.7%). Mixed histologies included LCNEC/NSCLC (n=45, 56.2%), LCNEC/SCLC (n=17), LCNEC/carcinoid (n=1), and unspecified mixed LCNEC (n=10). Median PFS for chemo was 5 months (95% CI 2.7-9.2) vs. 6 months (95% CI 4.4-8.3) for chemoIO ( p=0.86). Median OS for chemo was 14.2 months (95% CI 10.4-22.5) vs. 17.2 months (95% CI 9.4-27.2) for chemoIO ( p=0.66). The ORR did not differ between chemo (n=18, 45%) and chemoIO (n=15, 48.4%) ( p=0.81). In the chemo group, 60% (n=25) experienced trAEs of any grade, with 23.8% (n=10) experiencing grade 3+ events and four requiring hospitalizations. For chemoIO pts, 61% (n=19) experienced trAEs, with 25.8% (n=8) experiencing grade 3+ events and six requiring hospitalizations. Neutropenia was the most common grade 3+ trAE for both chemo (n=5) and chemoIO (n=4). Overall, there were no significant differences between chemo or chemoIO groups for ORR ( p=0.81), all-grade trAEs ( p=0.88), grade 3+ trAEs ( p=0.84), PFS ( p=0.86), or median OS ( p=0.66). There were no significant differences in median PFS ( p=0.46) or OS ( p=0.99) for pts with mixed LCNEC/NSCLC vs. LCNEC/SCLC. Conclusions: For mixed LCNECs, there was no significant difference in PFS or OS between first-line treatment with chemo vs. chemoIO, suggesting limited benefit from immunotherapy for these pts. Additionally, survival outcomes did not differ between mixed LCNEC/NSCLC and LCNEC/SCLC, suggesting a biology primarily driven by their neuroendocrine component.

3053 Background: Recently, early studies have identified circulating stromal cells (CStCs), i.e. Cancer Associated Macrophage-Like cells (CAMLs), in patients (pts) with newly diagnosed invasive cancers, which are phagocytic myeloid immune cells emanating from primary tumors. However, no study has evaluated CAMLs as a pan solid tumor screening tool nor their clinical impact on pt outcomes. We analyzed the blood of untreated newly diagnosed cancer pts (n=441), or in non-malignant conditions (i.e. pancreatic cysts, n=77), or healthy controls (n=100). We found that CAMLs are prevalent (82%) in cancer pt blood, absent in healthy controls (0%) and less common in non-malignant conditions (36%), with correlations to worse clinical outcomes. Methods: Anonymized peripheral blood was taken from n=441 pts before or after confirmation of invasive malignancy [stage I (n=105), stage II (n=125), stage III (n=114), stage IV (n=97) with pathologically confirmed lung (n=84), pancreas (n=61), breast (n=73), prostate (n=65), esophageal (n=34), Renal Cell (n=29), Sarcoma (n=27), or Other (n=68). In addition, anonymized blood was taken from pts with untreated non-malignant conditions including benign breast masses (n=19), Lupus (n=11), liver Cirrhosis (n=6), rising PSA (n=24), or other benign mass (n=17); and from healthy control volunteers (n=100). CAMLs were isolated by CellSieve microfiltration, defined as enlarged polyploid cells with cytokeratin+ and/or CD45/CD14+. Pts were monitored for 0-8 years (median=2.6) for progression free survival (PFS) and overall survival (OS). Results: CAMLs were found in 82% of all cancer pts averaging 5.4 CAMLs, specifically, in 66% of Stage I, 85% Stage II, 84% Stage III, and 92% Stage IV. No CAMLs were found in any healthy controls, but were in 36% of non-malignant pts. CAML sensitivity in cancer vs healthy was 82% (CI95% 78-85%), specificity=100% (CI95% 96-100%), PPV=100% (CI95% 99-100%), NPV=55% (CI95% 50-60%). CAML sensitivity in cancer vs benign was 82% (CI95% 78-85%), specificity=64% (CI95% 32-44%), PPV=93% (CI95% 90-95%), NPV=38% (CI95% 32-44%). CAML presence was significantly associated with worse PFS (HR=2.0, 95%CI 1.4-2.9, p<0.0001) & OS (HR=2.2, 95%CI 1.4-3.3, p=0.0004), with engorged phagocytic CAMLs (>50um), highly significant for worse PFS (HR=3.3, 95%CI 2.5-4.5, p<0.0001) & OS (HR=3.0, 95%CI 2.1-4.3, p<0.0001). Further, in benign pts positive for CAMLs, 2 pts were in situ, 16 had histologies with increased cancer risk (i.e. IPMN, atypical hyperplasia), and 5 pts died within 3 years. Conclusions: CAMLs appear to be a highly sensitive blood based biomarker that can identify invasive carcinoma in all stages of cancer regardless of subtype, but are not found in healthy controls & rare in non-malignant conditions. Further, enlarged phagocytic CAMLs appeared to correlate with shorter PFS and OS prior to treatment induction.