Multi-institutional Experience Research Articles

Endoscopic Endonasal Approach for Residual and Recurrent Craniopharyngioma after Transcranial Approach: A Multi-institutional Experience

Abstract Objectives While the endoscopic endonasal approach (EEA) has become a well-established surgery for resection of craniopharyngiomas (CP), the utility of this procedure following subtotal resection from open transcranial approach (TCA) surgery has yet to be explored. Here we present a multi-institutional case series of patients who underwent EEA for treatment of recurrent CP originally treated by TCA, demonstrating the viability of this approach as salvage surgery. Design Retrospective cohort. Setting Loyola University Medical Center and University of Pittsburgh Medical Center. Participants Patients who underwent EEA for recurrent CP following an initial TCA between 2003 and 2018. Main Outcome Measures Gross total resection (GTR) rate, surgical complications, visual outcomes, and endocrine outcomes Results Patients who underwent EEA for recurrent CP following a prior TCA had a GTR rate of 77%. EEA reoperation was not associated with worsening of visual outcomes as compared with the primary TCA (0% visual worsening after EEA reoperation vs. 40% after primary TCA, p = 0.055). While primary TCA resulted in worsening endocrinopathies in 100% of patients (including seven patients with permanent diabetes insipidus), subsequent EEA for re-resection of CP resulted in stable (30.8%) or improved (69.2%) endocrine function in all patients (p < 0.001). Conclusions EEA achieves reasonable GTR rates and is an effective, safe surgical option for recurrent CP postinitial TCA. This approach demonstrated stable or improved visual and endocrinologic outcomes in all patients within our two-institution series. Thus, EEA should be considered as an efficacious form of retreatment in cases of progressive and recurrent CP.

Abstract PO4-12-06: Interstitial Lung Disease (ILD) in Sequential Antibody Drug Conjugate (ADC) use in patients with Metastatic Breast Cancer (MBC): A Multi-Institutional experience

Abstract Introduction: Interstitial Lung Disease (ILD) is a known adverse event associated with Antibody Drug Conjugates (ADCs), causing fibrosis of the lung. In the DESTINY-Breast 04, TROPICS-02, and ASCENT trials the rate of ILD/Pneumonitis was 12.1%, 0.4%, and 0% respectively. In these studies, the time to first cross-sectional imaging after initiation of ADC was 6 weeks. However, prior treatment with a topoisomerase-1 inhibitor ADC was not permitted in these studies, so the influence of sequential ADC treatments remains unknown. Here, we aimed to characterize the frequency and management of ILD in sequential use of ADCs in a multi-institution retrospective analysis. Methods: We identified patients (pts) with HR+/HER2-low and HR-/HER2-low MBC who had received both Trastuzumab-deruxtecan (T-DXd) and Sacituzumab govitecan (SG) monotherapy (in either order, with or without intervening therapies) who were treated at five academic centers between 2020-2023. Patients had received treatment with the ADC in either routine clinical treatment or as a prior participant on a clinical trial with ADC monotherapy. Information regarding ILD diagnosis, imaging, timing of onset, peak and resolution along with management information was collected and analyzed. Retrospective assessment of ILD toxicity was graded using CTCAE v5.0, based on available clinical and radiographic reports. Results: 10/60 pts who received ADC therapy in this multi-institutional cohort were diagnosed with ILD (all grades). No differences in age or BMI were observed in those who developed ILD versus those who did not, and 9/10 pts were White, 1 was Asian, with a median age of 59 years (47-79 years). Pertinent history in these pts included 3/10 had a prior smoking history, 8/10 had a prior cardiac or pulmonary comorbidity (including sleep apnea, lung cancer, hypertension, hyperlipidemia, thrombosis, or stroke). Prior to receiving their first ADC, 7/10 patients had metastatic disease to the lung. All 10 patients were diagnosed with ILD during treatment with T-DXd. 4 pts initially received T-DXd, then developed ILD and then upon recovery, subsequently received SG. The remaining 6 pts initially received SG (with no reports of ILD), and then received T-DXd and subsequently developed ILD. In the entire cohort, the median time from ADC initiation to first CT scan was 8 weeks (range 1-22 weeks). Within the cohort that developed ILD, the median time from initiation of T-DXd to first CT scan was also 8 weeks (range 6-13 weeks). The median time to diagnoses of ILD was 3 months after initiation of T-DXd (range 0.4-14.5 months). Dyspnea was the most common presenting symptom in 9/10 pts and at diagnosis of ILD, dyspnea was graded as III in 6/10 pts, II in 3/10 pts, and I in 1/10 pts. Diagnostic evaluation included CT chest (9/10), pulmonary consultation (8/10), pulmonary function testing (2/10), and bronchoscopy (1/10). 4/10 patients presented at their highest-grade toxicity at diagnosis. All patients stopped T-DXd treatment, 7 were hospitalized, 7 required supplemental oxygen, and 8 were prescribed steroids for treatment. Of those receiving steroids, the most common starting dose was prednisone 1 mg/kg and doses ranged from 0.5 mg/kg to 9mg/kg prednisone equivalents. No patient received a secondary immunosuppressive agent. The steroid treatment duration ranged from 1-4 months. None of the 10 pts underwent re-challenge with T-DXd and 3/10 developed grade V ILD (death). Conclusion: We observed a 16.6% incidence of all grade ILD (5% grade V ILD) with T-DXd and 0% with SG. In this small cohort study, we did not observe a clear increased risk for ILD with sequential treatment of ADCs. Practice patterns were consistent with recommended diagnostic evaluation and steroid management. Additional strategies are needed to characterize pts most at risk for developing ILD and to identify situations where re-challenge may be safe. Citation Format: Sarah Premji, Laura Huppert, Reshma Mahtani, Samantha Fisch, Naomi Dempsey, Angelina Raimonde-Taylor, Saya Jacob, Laura Quintal, Jo Chien, Michelle Melisko, Ana Sandoval-Leon, Lauren Carcas, Manmeet Ahluwalia, Natasha Harpalani, Jenna Hoppenworth, Dame Idossa, Ruta Rao, Hope Rugo, Karthik Giridhar. Interstitial Lung Disease (ILD) in Sequential Antibody Drug Conjugate (ADC) use in patients with Metastatic Breast Cancer (MBC): A Multi-Institutional experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-12-06.

Long-term outcomes of endovascular therapy for right subclavian artery occlusive lesions: A multi-center experience.

To review our multi-institutional experience with endovascular therapy for right subclavian artery occlusive disease and to evaluate the long-term outcomes. We retrospectively evaluated all patients with right subclavian artery stenosis and occlusive disease who underwent endovascular therapy between March 2014 and September 2022 at two institutions. Patient baseline demographics, lesion characteristics, treatment strategies, and in-hospital and follow-up outcomes were prospectively collected and retrospectively analyzed. Between March 2014 and September 2022, 73 patients underwent endovascular treatment at the two institutions. The dominant cause of lesions in this cohort was atherosclerosis. Three different types of lesions were summarized, and the corresponding endovascular strategies were performed. 66 patients (90.4%) underwent successful endovascular treatment, and 62 patients (84.9%) underwent balloon-expandable stent deployment. The mean perioperative in-hospital stay was 4.0days (range, 3-6days). Two patients died due to myocardial infarction, and one died of cerebral hemorrhage resulting from a traffic accident within 30days of the intervention. The median follow-up time was 31.6months (range, 12-96 months). No complications, including death, stroke, stent fractures, or migration, were noted in any patient during the follow-up period. The overall complication rate was 7/73 (9.6%), and 5/7 (6.9%) of the complications required reintervention. Endovascular treatment of right subclavian artery lesions is safe, effective, and technically achievable. The reasonable use of balloon-expandable stents can achieve satisfactory outcomes with accurate orientation and promising patency.

Association Between Time From Surgery to Radiation Therapy and Multimodality Treatment Outcomes in HPV+ Head and Neck Cancer: A Multi-Institutional Cohort Experience

Association Between Time From Surgery to Radiation Therapy and Multimodality Treatment Outcomes in HPV+ Head and Neck Cancer: A Multi-Institutional Cohort Experience

Robotic-Assisted Laparoscopic Pyeloplasty in Challenging Cases of Ureteropelvic Junction Obstruction in the Pediatric Population: A Multicenter Review.

Purpose: To report a multi-institutional international experience in performing robotic pyeloplasty for complicated cases of ureteropelvic junction obstruction (UPJO) in the pediatric population and assess feasibility and outcomes. Materials and Methods: Retrospective chart review of all pediatric patients who underwent robotic-assisted laparoscopic pyeloplasty (RALP) for UPJO in challenging cases between 2013 and 2021 was included. Demographics, perioperative surgical data, complications, and results are described. Challenging cases were defined as bilateral UPJO, failure of previous open pyeloplasty (thus re-do cases), correction of UPJO in kidneys with anatomical variations, huge hydronephrosis, and low-weight infants (<6 kg). Results: Over an 8-year period, 36 children (62% males and 38% females) met the inclusion criteria for our study. Fifteen patients underwent RALP for recurrent UPJO; among them, 2 children required simultaneous surgery for renal stones, 3 cases of lower pole UPJO in double collecting system, 3 cases of pelvic and horseshoe kidneys, 10 cases of infants weighing <6 kg, 3 cases of huge hydronephrosis, and 2 cases of bilateral UPJO. The median age and weight were 36 months (interquartile range [IQR] 14-84) and 12 kg (IQR 10-20.5), respectively. All robotic cases were completed successfully with no conversion to an open procedure. The median operative time was 120 minutes (IQR 90-135). The mean length of hospital stay was 2.6 days. Four patients (17%) had postoperative complications-1 ileus (Clavien-Dindo grade [CDG] I) and 3 urinary tract infections (CDG II). No CDG III or higher complication was encountered. At a median follow-up of 36 months, the success rate was 95% with 1 patient requiring another re-do procedure due to recurrent obstruction. Conclusions: Our data suggest that RALP is safe and effective even for challenging cases of UPJO in children.

Autologous stem cell boost improves persistent immune effector cell associated hematotoxicity following BCMA directed chimeric antigen receptor T (CAR T) cell therapy in multiple myeloma.

Persistent Immune Effector Cell Associated Hematotoxicity (ICAHT) is a significant side effect of BCMA CAR T-Cell therapy in patients with relapsed multiple myeloma (MM). The use of stem cell boosts in ICAHT has been described, however studies have been limited by small patient numbers and short follow up. Herein, we report on our multi-institutional experience of ICAHT, defined by an absolute neutrophil count (ANC) of ≤ 1000, thrombocytopenia with a platelet count ≤ 50,000 or/and anemia as hemoglobin (hgb) ≤9 g/dL, in patients who received BCMA CAR T therapy, and the effects of subsequent stem cell boost on hematopoietic reconstitution and clinical outcome. In this study, ICAHT was observed in 60% (n = 61/101) of patients at D + 21, and risk factors for its development included history of a prior ASCT, higher number of prior lines of therapy, a decreased platelet count prior to lymphodepletion and history of ICANS. 28% of patients with ICAHT received a stem cell boost at a median of 116 days due to profound and prolonged cytopenias often requiring ongoing transfusion support. Stem cell boost significantly improved cytopenias at 3 and 6 months follow up without any adverse effects on PFS and OS, underscoring the safety of this procedure.

(053) Penile Entrapment Due to Metal Constriction Rings: Removal, Recovery and Complications

Abstract Introduction Penile incarceration due to a metal constriction ring is a rare urologic emergency. Improper ring sizing, use of makeshift rings or prolonged length of use can cause penile/penoscrotal entrapment with resulting sequelae including genital ischemia, necrosis, and urinary retention. Metal rings are prone to this exigent situation, as they tend to be denser and thicker than typical constriction rings which presents a challenge for safe removal. Objective We aim to report a multi-institutional experience characterizing the presentation, removal methods, and outcomes after prolonged penile entrapment in patients with metal constriction rings. Methods We performed a retrospective chart review from 2000 to 2023 at participating institutions to identify men presenting with penile incarceration due to metal constriction ring use using the following ICD-10 codes: S30.842A, S30.843, W49.04XA, S31.24X, and T19.4. Operative/procedural tools and duration were recorded from the initial emergency room encounter and follow-up notes were reviewed for any subsequent complications. Results Twelve patients with median age 55 with interquartile range (IQR) of 26 were identified (Table 1). The metal rings varied in size, and most were composed of stainless steel. The length of time the constriction ring was in place before seeking medical attention ranged from 3 hours to 10 days with a median time of 42 hours, (IQR, 60). Removal instruments included a powered drill cutting tool, ring cutter, and bolt cutters. Median operative/procedural time was 90 minutes (IQR, 63). Cool irrigation was used in all cases where powered rotary cutting tool was used in combination with a mechanism to protect the underlying skin such as a metal retractor. Additionally, a barrier such as saline-soaked towels and/or lubricating jelly was used to protect the surrounding skin during operative intervention with a powered tool. Most patients reported full recovery despite prolonged entrapment; however, one patient developed a urethrocutaneous fistula and one patient reported diminished erectile function. Interestingly, one patient with concomitant substance abuse and vasoconstrictive agents use presented with penile skin necrosis requiring concurrent debridement which was further complicated by Fournier’s gangrene 1 month later in the setting of continued substance use and non-adherence to prescribed antibiotics. Conclusions Penile incarceration by metal constriction ring is a rare urologic emergency. This study represents the first multi-institutional and largest investigation evaluating the management of this condition. Manual and powered cutting tools are effective in removing metal constriction rings. If powered tools are employed, irrigation and retractors are necessary to prevent thermal injury. Despite most patients fully recovering after removal, significant complications have been observed. Therefore, prompt management and proper follow-up are recommended. Disclosure No.

Clinical efficacy of lurbinectedin in metastatic neuroendocrine carcinomas of the genitourinary tract: Multi-institutional real-world experience.

601 Background: Neuroendocrine carcinomas (NEC) of the genitourinary (GU) tract, including small cell (SC) NEC and large cell (LC) NEC, are rare aggressive malignancies. Although highly sensitive to cisplatin-based chemotherapy, GU metastatic NEC (mNEC) have limited data to support next therapies. Lurbinectedin, a marine-derived alkylating drug and a selective inhibitor of oncogenic transcription and DNA repair pathways, is FDA-approved for small cell lung cancer (SCLC) after progression on frontline platinum-based therapy, with a disease control rate (DCR) of 68.6%. It is unknown whether DCR is similar in SCLC and GU mNEC. Methods: We report the first multi-institutional series (n=14) of lurbinectedin in GU mNEC. Imaging-based best overall responses (BOR) were noted as complete (CR), partial (PR), stable (SD), progressive (PD) or non-evaluable (NE). DCR includes CR, PR, and SD. We use the Kaplan-Meier method for overall survival (OS) and progression-free survival (PFS) from lurbinectedin start date. We define duration of response (DoR) from response date to progression or last contact date for patients (pts) with CR or PR. Results: Most pts had a median age at metastasis of 70.5 years (ICR: 64-74.5) [Table]. Primary locations were bladder (7/14, 50%), prostate (5/14, 35.7%) and ureter (2/14, 12.3%). Histology at diagnosis mostly consisted of mixed or pure SCNEC, with one exception of LCNEC. Most pts had visceral disease, prior immunotherapy and at least 2 prior lines of therapy for mNEC before lurbinectedin (8/14, 57.1%). DCR was 6/14 (42.8%), including 5 bladder pts and 1 prostate pt. Among bladder pts, BOR included one CR (1/7, 14.3%) for the LCNEC case, 2 PR (2/7, 28.6%), 2 SD (2/7, 28.6%) and 2 PD (2/7, 28.6%). Most prostate and ureteral pts either progressed on lurbinectedin or were NE (Prostate: 1 PR, 2 PD, and 2 NE; Ureteral: 1 PD and 1 NE). For all 14 pts, median OS was 11.47 months (95% CI: 2.17-13.63) and median PFS was 2.8 mo (1.4-10.9). Median DoR was 7.38 mo (2.3-9.53) for 4 responding pts (CR or PR). Treatment was stopped due to progression (9/14, 64.3%), three adverse events [thrombocytopenia, electrolyte abnormalities, cerebrovascular accident] (3/14, 21.4%), and pt preference (1/14, 7.1%). Conclusions: Lurbinectedin offers encouraging responses (DCR: 5/7, 71.4%) close to those in SCLC, in previously treated bladder mNEC. One CR was noted for a bladder pt with LCNEC. Responses were less appreciated in prostate and ureteral mNEC due to NE responses and limited number. Larger cohorts are needed to confirm survival benefit and genetic analyses are warranted to identify characteristics of responders. [Table: see text]

Multi-institutional experience of MR-guided stereotactic body radiation therapy for adrenal gland metastases

PurposeWhile dose escalation is associated with improved local control (LC) for adrenal gland metastases (AGMs), the proximity of gastrointestinal (GI) organs-at-risk (OARs) limits the dose that can be safely prescribed via CT-based stereotactic body radiation therapy (SBRT). The advantages of magnetic resonance-guided SBRT (MRgSBRT), including tumor tracking and online plan adaptation, facilitate safe dose escalation. MethodsThis is a multi-institutional review of 57 consecutive patients who received MRgSBRT on a 0.35-T MR linac to 61 AGMs from 2019 to 2021. The Kaplan-Meier method was used to estimate overall survival (OS), progression-free survival (PFS), and LC, and the Cox proportional hazards model was utilized for univariate analysis (UVA). ResultsMedian follow up from MRgSBRT was 16.4 months (range [R]: 1.1–39 months). Median age was 67 years (R: 28–84 years). Primary histologies included non-small cell lung cancer (N = 38), renal cell carcinoma (N = 6), and melanoma (N = 5), amongst others. The median maximum diameter was 2.7 cm (R: 0.6–7.6 cm), and most AGMs were left-sided (N = 32). The median dose was 50 Gy (R: 30–60 Gy) in 5–10 fractions with a median BED10 of 100 Gy (R: 48–132 Gy). 45 cases (74 %) required adaptation for at least 1 fraction (median: 4 fractions, R: 0–10). Left-sided AGMs required adaptation in at least 1 fraction more frequently than right-sided AGMs (88 % vs 59 %, p = 0.018). There were 3 cases of reirradiation, including 60 Gy in 10 fractions (N = 1) and 40 Gy in 5 fractions (N = 2). One-year LC, PFS, and OS were 92 %, 52 %, and 78 %, respectively. On UVA, melanoma histology predicted for inferior 1-year LC (80 % vs 93 %, p = 0.012). There were no instances of grade 3+ toxicity. ConclusionsWe demonstrate that MRgSBRT achieves favorable early LC and no grade 3 + toxicity despite prescribing a median BED10 of 100 Gy to targets near GI OARs.

Maxillary sinus and hard palate squamous cell carcinoma: Multi-institutional experience

Maxillary sinus and hard palate squamous cell carcinoma: Multi-institutional experience

The Effect of Stem Cell Infusion on Immune Effector Cell Associated Hematotoxicity with BCMA CAR T in Multiple Myeloma

Introduction: In recent pivotal clinical trials and real-world studies of patients undergoing BCMA CAR-therapy for multiple myeloma (MM), a significant percentage have exhibited persistent Immune Effector Cell Associated Hematotoxicity (ICAHT). The resulting, sometimes profound and long lasting cytopenias, are associated with increased morbidity, such as high rates of infections and bleeding and complicate further anti-MM therapy once the patient relapses post CAR-T cell therapy. While growth factor support is widely applied in patients with ICAHT, the effects are usually short lived. Consequently, the use of CD34 selected stem cell boost in ICAHT as a more permanent solution has been described, however studies have been limited by small patient numbers and short follow up. Herein, we report on our multi-institutional experience at ICAHT in patients who received autologous BCMA CAR T therapy both in commercial and clinical trial settings. Methods: We included recipients of autologous BCMA CAR T therapy at 2 large academic centers between 2020 and 2023. For this study, neutropenia was defined as an absolute neutrophil count (ANC) of ≤ 1000, thrombocytopenia as platelet counts ≤ 70,000 and anemia as hemoglobin ≤9 g/dL. ICAHT was characterized by the presence of any of these hematological abnormalities. The variables were assessed at 21 days, 3 months, and 6 months post CAR-T infusion. Median follow up time was 23 months. Results : A total of 108 patients received BCMA CAR T therapy, 42 (39%) were treated on a clinical trial, 52 (48%) received commercial Idecabtagene vicleucel and 14/108 (13%) commercial Ciltacabtagene autoleucel. Baseline characteristics of the whole patient cohort are shown in table 1. The median age was 68 (range 57-69) years, with 63/107 (60%) being male. About 11% (n=12) patients were Black. 97/108 (90%) received at least one prior ASCT and the median prior lines of therapy was 5 (range 4-6). At D+21, ICAHT was observed in 68% (n=69/102) of patients, which reduced to 35% (n=30/86) and 27% (n=21/78) at the 3-month and 6-month assessments, respectively. Risk factors for ICAHT were the following: history of a prior ASCT, higher number of prior lines of therapy, a decreased platelet count prior to lymphodepletion and history of ICANS, which interestingly occurred in 11/69 (16%) patients who developed ICAHT but was not seen in those without ICAHT. About 97%(n=67/69) of patients with ICAHT had stem cells in storage and 26% (n=17/69) received a stem cell boost. The median time to stem cell boost following CAR T infusion was 116 (range 49-166) days. The median dose of stem cell infused was 3.91 (range 2.11-5.12) x10 6 CD34/kg cells. Unsurprisingly, patients with ICAHT who received a stem cell boost had significantly worse cytopenias prior to stem cell boost compared to those ICAHT patients without stem cell infusions at 120 days. Hgb was 8.4g/dL vs 10.2g/dL, p=0.02, and mean platelet levels were 30x10 9/L vs 54x10 9/L, p=0.01, compared to ICAHT patients without stem cell support. ANC levels were not significantly different between those two ICAHT groups (1700/mL vs 1500/mL), likely due to a higher use G-CSF support in ICAHT patients who received stem cell support (75% vs 55%, NS). Stem cell infusion significantly improved Hgb levels at 3 and 6 months follow up with an increase to 10.6g/dL, p=0.002, and 10.5g/dl, p=0.02, respectively. Similarly, platelet counts at 3- and 6-months post stem cell boost improved significantly to 131x10 9/L, p=&amp;lt;0.001, and 150x10 9/L, p=&amp;lt;0.001, respectively. ANC levels showed a nonsignificant increase to 2.8/mL and 3.9/mL at 3 and 6 months, yet, G-CSF support was no longer required. We further investigated whether the occurrence of secondary AML/MDS was associated with ICAHT, however these events were rare and developed in only 2 patients, one who had no ICAHT and the other one who had ICAHT without stem cell boost. Conclusion: Nearly one-third of the patients who underwent BCMA CAR T therapy continued to experience ICAHT even at the 6-month post-infusion period. The utilization of a stem cell boost for managing ICAHT lead to significantly improved Hgb and platelet counts at 3 and 6 months follow up with also substantial improvement in ANC without further G-CSF requirements. These results suggest that the use of stem cell infusions in CAR-T cell induced ICAHT can improve cytopenia associated morbidities and facilitate further anti MM therapy post CAR-T relapse.

Use of Eltrombopag for Post-CAR T Cytopenias: A Multi-Institutional Experience

Background: Cytopenias following chimeric antigen receptor T (CAR T) cell therapy are common and can be profound and/or prolonged, leading to increased morbidity and mortality. Supportive care is the mainstay of management but strategies to reduce the duration and severity of cytopenias have yet to be optimized. One such strategy extrapolated from experience in aplastic anemia is the use of thrombopoietin (TPO) receptor agonists, like eltrombopag. Eltrombopag has been used off-label for several years for this indication, however, limited data exists regarding the safety and efficacy of its use after CAR T-cell therapy. Methods: Patients ≥ 18 years of age treated with CAR T-cell therapy for either lymphoma or myeloma at two academic medical centers between January 2018 and January 2023 were included in a retrospective analysis. Use of eltrombopag was initiated at the KUMC for patients who had received CAR T and subsequently had persistent cytopenias at day +30 as evidenced by at least one of four criteria: grade 3 or 4 leukopenia, grade 4 thrombocytopenia, growth factor dependency, or platelet transfusion dependency. Use of eltrombopag was initiated at the MUSC for patients who had received CAR T and had grade 4 thrombocytopenia at day +21 and beyond post-CAR T infusion. Baseline patient and disease characteristics as well as variables describing safety and efficacy of eltrombopag for the treatment of persistent high-grade leukopenia and/or thrombocytopenia beyond day +21 post CAR T infusion were collected and summarized using descriptive statistics. Results: A total of 185 patients were included in this analysis. Of these, 163 (88%) experienced thrombocytopenia or leukopenia at day +30 post-CAR T infusion. A total of 42 patients met institutional criteria for eltrombopag treatment and initiated therapy. Median time to initiation of eltrombopag was 33 days (range 28-50) from infusion, with no significant differences between the two institutions (30 days at KUMC vs 36 days at MUSC, p=0.19). Median duration for the use of eltrombopag was 63 days (range 32-172) and KUMC used eltrombopag for a longer duration than MUSC (108 days vs 32 days, p=0.03). There were no statistically significant differences in bleeding events in the eltrombopag vs non-eltrombopag groups, p=0.053, and no reported cases of deep vein thrombosis or pulmonary embolism (DVT/PE) after initiating eltrombopag. Patients on eltrombopag were more likely to have infections (24 (57%) vs 42 (35%), p&amp;lt;0.01) and admission to intensive care unit (16 (38%) vs 20 (17%), p&amp;lt;0.01) when compared to the non-eltrombopag group. At day +30, 74 (45%) patients in the entire study population had grade 3 or higher leukopenia or thrombocytopenia, with 39 (93%) and 25 (29%) patients in the eltrombopag and non-eltrombopag groups with grade 3 or higher cytopenias, respectively ( p&amp;lt;0.001). By day +90, only 18 (35%) patients in the evaluable population had grade 3 or higher leukopenia or thrombocytopenia, with 12 (50%) and 6 (22%) patients in the eltrombopag and non-eltrombopag groups with grade 3 or higher cytopenias, respectively ( p=0.046). By day +180, all but ten patients in the evaluable population had not recovered to less than a grade 3 cytopenia with no significant difference in cytopenias between the two groups. With a median follow up of 12 months (range 1-34) for the entire patient population, median PFS was lower for the eltrombopag group (13 months) compared to the non-eltrombopag group (16 months, p=0.02). When stratified by disease, this association was observed only for the lymphoma patients, with a median PFS of 8.5 months in the eltrombopag group compared to a median PFS of 17 months in the non-eltrombopag group, p=0.01 (Table 1). Similarly, for the entire patient population, median OS was lower for the eltrombopag group (14 months) compared to the non-eltrombopag group (18 months, p=0.01). When stratified by disease, this association was observed only for the lymphoma patients, with a median OS of 14 months in the eltrombopag group compared to 18 months in the non-eltrombopag group ( p&amp;lt;0.01). Conclusions: In this first of its kind real-world experience, use of eltrombopag for post-CAR T leukopenia and thrombocytopenia was considered effective in recovery of counts and prevention of bleeding in a high-risk patient population. The use of eltrombopag for post-CAR T cytopenias was considered safe without any significant toxicities of thrombosis or myelodysplasia.

Improved local control following dose-escalated stereotactic ablative radiation therapy (SABR) for metastatic sarcomas: An international multi-institutional experience

BackgroundWe aimed to characterize local control (LC) and overall survival (OS) following stereotactic ablative radiation therapy (SABR) for extracranial sarcoma metastases. MethodsA prospectively-maintained institutional registry was queried for patients with metastases from sarcoma primaries managed with SABR. Kaplan-Meier analysis was utilized for univariate analyses to assess potential prognostic factors regarding LC and OS. A Cox proportional hazards multivariate (MVA) model was employed to further assess initially identified independent variables. ResultsA total of 94 patients with 118 lesions with LC information were identified. Common metastatic sites treated were lung (77), non-spinal bone (15), and spine (10). The median biologically effective dose (BED4) was 175 Gy4 (range56.3 Gy4–360 Gy4) with a median dose/fractionation schedule of 50 Gy/5 fractions. One- and 2-year OS rates were 81.3 % (95 % CI: 71.2–88.1 %6) and 50.5 % (95 % CI: 38.6–61.3 %, respectively. On Cox MVA, advanced age and non-lung metastases were associated with inferior OS (p < 0.03) with patients with 0–2 of these risk factors having estimated 2-year OS of 65.1 %, 38.9 %, and N/A, respectively. One- and 2-year LC rates were 85.3 % (95 % CI: 77.7–90.9 %) and 78.2 % (95 % CI: 67.9–85.6 %), respectively. On MVA, only BED4 < 175 Gy was associated with inferior LC (hazard ratio (HR) = 3.33; p = 0.01). Ten of 118 treated lesions had treatment-related toxicities (all Grade 1–2). ConclusionAge and lung vs. non-lung metastases were prognostic of OS and should be considered in patient selection for SABR. Dose escalation when feasible with BED4 ≥ 175 Gy is recommended given durable LC achieved without a subsequent increase in toxicity.

Laparoscopic versus robotic TAPP/TEP inguinal hernia repair: a multicenter, propensity score weighted study.

The objective of this retrospective study was to assess safety and comparative clinical effectiveness of laparoscopic inguinal hernia repair (LIHR) and robot-assisted inguinal hernia repair (RIHR) from multi-institutional experience in Taiwan. Medical records from a total of eight hospitals were retrospectively collected and analyzed. Patients primarily diagnosed of inguinal hernia, recurrent inguinal hernia or incarceration groin hernia patients who either underwent laparoscopic or robot-assisted inguinal hernia repair between January 2018 and December 2022 were included in the study. Baseline characteristics, intra-operative and post-operative results were analyzed. To compare two cohorts, overlap weighting was employed to balance the significant inter-group differences. We also conducted subgroup analyses by state of a hernia (primary or recurrent/incarceration) and laterality (unilateral or bilateral) that indicated complexity of surgery. A total of 1,080 patients who underwent minimally invasive inguinal hernia repair from 8 hospitals across Taiwan were collected. Following the application of inclusion criteria, there were 279 patients received RIHR and 763 patients received LIHR. In the baseline analysis, RIHR was more often performed in recurrent/incarceration (RIHR 18.6% vs LIHR 10.3%, p = 0.001) and bilateral cases (RIHR 81.4 vs LIHR 58.3, p < 0.001). Suturing was dominant mesh fixation method in RIHR (RIHR 81% vs LIHR 35.8%, p < 0.001). More overweight patients were treated with RIHR (RIHR 58.8% vs LIHR 48.9%, p = 0.006). After overlap weighting, there were no significant difference in intraoperative and post-operative complications between RIHR and LIHR. Reoperation and prescription rates of pain medication (opioid) were significantly lower in RIHR than LIHR in overall group comparison (reoperation: RIHR 0% vs. LIHR 2.9%, p = 0.016) (Opioid prescription: RIHR 3.34mg vs LIHR 10.82mg, p = 0.001) while operation time was significantly longer in RIHR (OR time: RIHR 155.27min vs LIHR 95.30min, p < 0.001). This real-world experience suggested that RIHR is a safe, and feasible option with comparable intra-operative and post-operative outcomes to LHIR. In our study, RIHR showed technical advantages in more complicated hernia cases with yielding to lower reoperation rates, and less opioid use.

MO51-2 Impact of COVID-19 on cancer care in India: A multi-institutional experience

MO51-2 Impact of COVID-19 on cancer care in India: A multi-institutional experience

Multi-Institutional Experience of Proton Therapy for Osteosarcoma in the Proton Collaborative Group (PCG) Prospective Registry

To report on the utilization of dose-escalated radiotherapy, acute toxicities, and survival following definitive proton therapy (PT) for osteosarcoma patients in a prospective multi-institutional study. Data on patients with osteosarcoma treated with definitive intent PT were queried from the Proton Collaborative Group (PCG) prospective registry. A similar query was performed on an institutional database with IRB approval. Overall survival rates were calculated by Kaplan-Meier. Toxicities were scored using CTCAE v4.0. Forty osteosarcoma patients across 9 institutions received definitive intent PT between 2011-2021 and met the eligibility criteria. Median age was 32 years (Range: 6-86 years). Median PT dose was 66.6 GyRBE (Range: 50.4-80.0 GyRBE); 38 patients received proton therapy alone, whereas 2 received combined proton/photon therapy. Seventeen (42.5%) patients received doses ≥70 GyRBE. Median follow-up was 3.1 years (Range: 0.9-10.5 years). One-year and three-year overall survival rates were 83.5% and 59.1%, respectively, with 14 deaths due to disease. Excluding skin desquamation and alopecia, 22 patients (55.0%) developed any acute grade 2+ toxicity, and 5 patients (12.5%) developed any grade 3 toxicities. No acute grade 4-5 toxicities were reported. The most frequent grade 2+ non-skin toxicities were fatigue (37.5%), anorexia/weight loss (17.5%), mucositis/esophagitis (22.5%), pain (20.0%), and nausea/vomiting (10.0%). The most frequent grade 3 toxicities were anorexia/weight loss (5.0%), mucositis/esophagitis (5.0%), and neurologic symptoms (5.0%). In this multi-institutional study, 42.5% of osteosarcoma patients treated with PT received doses between 70-80 Gy, with 12.5% experiencing any grade 3 toxicity. Long-term outcomes for disease control, late toxicity, and quality-of-life are needed to more fully assess the benefits and risks of dose-escalated radiotherapy in this radioresistant tumor. The authors plan to assess the outcomes of osteosarcoma patients treated with dose-escalated radiotherapy for unresectable or gross residual disease in future studies.

Multi-Institutional Experience of Proton Therapy for Rhabdomyosarcoma and Ewing Sarcoma in the Proton Collaborative Group (PCG) Prospective Registry

To report on outcomes, acute toxicities, and the use of dose-escalation with proton therapy (PT) in patients with rhabdomyosarcoma and Ewing sarcoma in a prospective multi-institutional registry (PCG). Data on patients with primary rhabdomyosarcoma and Ewing sarcoma treated with definitive PT (defined as ≥45 Gy) were queried from the PCG registry. A similar query was performed of our institutional database with IRB approval. Overall survival rates were calculated by Kaplan-Meier. Toxicities were scored using CTCAE v4.0. A total of 354 patients across 10 institutions (203 rhabdomyosarcoma, 151 Ewing sarcoma) met the eligibility criteria. Median age was 9 years (Interquartile Range: 5-15). Median dose was 50.4 GyRBE for rhabdomyosarcoma patients (Range: 45-66 GyRBE) and 55.8 GyRBE for Ewing sarcoma patients (Range: 45-66 GyRBE). Median follow-up was 2.4 years (Range 0.3-12.3 years). Two-year overall survival rates were 81.1% (95% CI: 73.7%-88.5%) for rhabdomyosarcoma and 79.1% (95% CI: 71.7%-86.2%) for Ewing sarcoma. The Table lists the prescription doses delivered by tumor histology; 28.1% of rhabdomyosarcoma and 21.9% of Ewing sarcoma patients, respectively, received dose-escalated radiotherapy (defined as >50.4 Gy for rhabdomyosarcoma and >55.8 Gy for Ewing sarcoma). Excluding alopecia and skin desquamation, 153 patients (43.2%) developed any acute grade 2+ non-hematologic toxicity, while 49 patients (13.8%) developed one or more grade 3 toxicities. The most common grade 3 toxicities were anorexia/weight loss (7.3%), pain (7.3%) mucositis/esophagitis (4.8%), and nausea/vomiting (3.1%). One grade 4 toxicity (esophagitis) and no deaths were reported during treatment. In this multi-institutional prospective registry, 28.1% of rhabdomyosarcoma and 21.9% of Ewing sarcoma patients received dose-escalated PT, with 13.8% of patients developing grade 3 toxicities. Long-term outcomes for disease control and late toxicity and anticipated cooperative group trial results are needed to fully assess the benefits and risks of dose-escalated radiotherapy for these tumors.

Fly-CURE, a multi-institutional CURE using Drosophila, increases students' confidence, sense of belonging, and persistence in research.

The Fly-CURE is a genetics-focused multi-institutional Course-Based Undergraduate Research Experience (CURE) that provides undergraduate students with hands-on research experiences within a course. Through the Fly-CURE, undergraduate students at diverse types of higher education institutions across the United States map and characterize novel mutants isolated from a genetic screen in Drosophila melanogaster. To date, more than 20 mutants have been studied across 20 institutions, and our scientific data have led to eleven publications with more than 500 students as authors. To evaluate the impact of the Fly-CURE experience on students, we developed and validated assessment tools to identify students' perceived research self-efficacy, sense of belonging in science, and intent to pursue additional research opportunities. Our data, collected over three academic years and involving 14 institutions and 480 students, show gains in these metrics after completion of the Fly-CURE across all student subgroups analyzed, including comparisons of gender, academic status, racial and ethnic groups, and parents' educational background. Importantly, our data also show differential gains in the areas of self-efficacy and interest in seeking additional research opportunities between Fly-CURE students with and without prior research experience, illustrating the positive impact of research exposure (dosage) on student outcomes. Altogether, our data indicate that the Fly-CURE experience has a significant impact on students' efficacy with research methods, sense of belonging to the scientific research community, and interest in pursuing additional research experiences.

Primary Bladder Sarcoma: A multi-institutional experience from the Rare Cancer Network.

Primary sarcoma of the urinary bladder (SUB) is a rare but aggressive form of bladder cancer (BCa). Available evidence on SUB is limited to case reports and small series. The aim of the present multi-institutional study was to assess the clinical features, treatments, and outcomes of patients with SUB. Using a standardized database, 7 institutions retrospectively collected the demographics, risk factors, clinical presentation, treatment modalities and follow-up data on patients with SUB between January 1994 and September 2021. The main inclusion criteria included BCa with soft tissue tumor histology and sarcomatoid differentiation. Fifty-three patients (38 men and 15 women) were identified. Median follow-up was 18 months (range 1-263 months). Median age at presentation was 69 years (range 16-89 years). Twenty-six percent of patients had a prior history of pelvic radiotherapy (RT), and 37% were previous smokers. The main presenting symptoms at diagnosis were hematuria (52%), pelvic pain (27%), and both hematuria and pelvic pain (10%). American Joint Committee on Cancer (AJCC) 8 th edition stage II, III and IV at diagnosis were 21%, 63% and 16%, respectively. Treatment modalities included surgery alone (45%), surgery plus neo- or adjuvant-chemotherapy (17%), surgery plus neo- or adjuvant-RT (11%), RT with concurrent chemotherapy (4%), neo-adjuvant chemotherapy plus surgery plus adjuvant RT (2%) and palliative treatment (21%). Rates of local and distant recurrences were 49% and 37%, respectively. Five-year overall survival and progression-free survival (PFS) were 66.5% and 37.6%, respectively. No statistically significant differences in PFS between the treatment modalities were observed. Primary SUB is a heterogeneous disease group, commonly presenting at advanced stages and exhibiting aggressive disease evolution. In contrast to urothelial carcinoma, the primary pattern of recurrence of SUB is local, suggesting the need for multimodal approaches. Continuous international collaborative efforts seem warranted to provide guidance on how to best tailor treatments based on SUB-specific indices.

Trans oral robotic surgery for oropharyngeal cancer: A multi institutional experience

ObjectivesTrans Oral Robotic Surgery (TORS) has proved to be a safe and feasible treatment for oropharyngeal squamous cell carcinoma (OPSCC). The aim of this study is to analyse oncological outcomes of OPSCC patients treated with TORS. Materials and methodsThis study involved 139 patients with OPSCC, treated with TORS between 2008 and 2020. Clinicopathological characteristics, treatment details and oncological outcomes were evaluated retrospectively. ResultsThe management strategies included TORS alone in 42.5%, TORS-RT in 25.2% and TORS-CRT in 30.9%. The ENE was noted in 28.8% of neck dissections. In 19 patients clinically classified as unknown primaries, the primary was found in 73.7%. Rates of local, regional relapses and distant metastasis were 8.6%, 7.2%, and 6.5%, respectively. The 5 year- Overall Survival and Disease Free Survival were 69.6% and 71.3%, respectively. ConclusionTORS fits well in the modern management of OPSCC. Although definitive CRT remains a milestone, TORS is proving to be a valid and safe treatment option. The choice of the therapeutic strategy requires evaluation by a multidisciplinary team.