MD Anderson Cancer Center Experience Research Articles

High-Grade Pleomorphic Sarcomas Treated with Immune Checkpoint Blockade: The MD Anderson Cancer Center Experience.

Undifferentiated pleomorphic sarcomas (UPSs) are amongst the most common subtypes of soft-tissue sarcomas. Few real-world data on the use of immune checkpoint blockade (ICB) in UPS patients and other high-grade pleomorphic STS patients are available. The purpose of our study is to describe the efficacy and toxicity of ICB in patients with advanced UPSs and other high-grade pleomorphic sarcomas treated at our institution. This is a retrospective, observational study of all patients with metastatic high-grade pleomorphic sarcomas treated with FDA-approved ICB at MD Anderson Cancer Center between 1 January 2015 and 1 January 2023. Patients included in trials for which results are not yet published were excluded. Thirty-six patients with advanced/metastatic pleomorphic sarcomas were included. The median age was 52 years. A total of 26 patients (72%) had UPSs and 10 patients (28%) had other high-grade pleomorphic sarcomas. The median follow-up time was 8.8 months. The median PFS was 2.9 months. The 3-month PFS and 6-month PFS were 46% and 32%, respectively. The median OS was 12.9 months. The 12-month OS and 24-month OS were 53% and 29%, respectively. The best response, previous RT, and type of ICB treatment were significantly and independently associated with shorter PFS (p = 0.0012, p = 0.0019 and p = 0.036, respectively). No new safety signal was identified, and the toxicity was overall manageable with no toxic deaths and only four patients (11%) stopping treatment due to toxicity. Real-world retrospective data are consistent with the published literature, with a promising 6-month PFS of 32%. Partial or stable responders to ICB treatment have significantly improved PFS compared to progressors.

Proton Craniospinal Irradiation for Treatment of Leptomeningeal Metastasis in Patients with Solid Malignancy: The MD Anderson Cancer Center Experience (S27.006)

Proton Craniospinal Irradiation for Treatment of Leptomeningeal Metastasis in Patients with Solid Malignancy: The MD Anderson Cancer Center Experience (S27.006)

Clinical outcomes of frontline GemFLP in advanced urachal and non-urachal adenocarcinomas of the urinary tract: The MD Anderson Cancer Center (MDACC) experience.

Clinical outcomes of frontline GemFLP in advanced urachal and non-urachal adenocarcinomas of the urinary tract: The MD Anderson Cancer Center (MDACC) experience.

P641 Faecal calprotectin determines non-response to corticosteroids in patients with immune checkpoint inhibitor colitis

Abstract Background Immune checkpoint inhibitor (ICI) therapy has improved survival outcomes in patients with advanced malignancy. ICI colitis (ICI-C) is one of the most common adverse events which often leads to cessation of an otherwise effective therapy.1,2 Corticosteroid therapy remains first-line treatment in patients with ICI-C. The aim of this study was to assess predictors of non-response to corticosteroid therapy to help guide early escalation to biologic therapy. Methods Multicentre retrospective analysis of adults hospitalized with ICI-C between July 2018 to March 2023. ICI-C was defined by patients who had current or prior immunotherapy who presented with diarrhoea with negative infective faeces PCR testing and admission diagnosis of ICI-C by their treating Physician. Baseline demographic, clinical, biochemical, and endoscopic data were collected. Grading of clinical severity on presentation and response to immunosuppression was defined by CTCAE diarrhoea grading with response defined as improvement to grade 1 or less. Results 82 patients were analysed. 31 (38%) female, median age was 65.5 years (IQR 59-72)], 27 (33%) failed corticosteroid therapy and required biologic therapy. 34 (42%) had a faecal calprotectin on admission. On univariable analysis faecal calprotectin emerged as the sole predictor of corticosteroid non-response. ROC analysis identified an optimal faecal calprotectin cut-off of 620 mcg/g to identify corticosteroid non-responders [Sensitivity 75% (57.6-92.7), Specificity 77.8% (52.4-93.6), Accuracy 76.5%, PLR 3.37 (1.36-8.38), NLR 0.32 (0.13-0.78), AUROC 0.76 (0.616-0.911), OR 10.5 (2.24-49.3), PPV 75 (47.6-92.7), NPV 77.8 ( 52.4-93.6)].12/16 (75%) of patients with a faecal calprotectin ≥ 620 required biologic therapy. Conclusion Faecal calprotectin is a predictor of non-response to corticosteroid therapy in patients with immune checkpoint inhibitor colitis. This study identified a faecal calprotectin threshold of 620mcg/g as the optimal cut-off to identify corticosteroid non-response and need for second-line immunosuppression. These findings may help to reduce the need for endoscopic assessment and guide early escalation to biologic therapy. REFERENCES: 1. Fujii T, Colen RR, Bilen MA, et al. Incidence of immune-related adverse events and its association with treatment outcomes: The MD Anderson Cancer Center experience. Invest New Drugs. 2018;36(4):638-646. doi:10.1007/s10637-017-0534-0 2. Wang Y, Abu-Sbeih H, Mao E, et al. Endoscopic and Histologic Features of Immune Checkpoint Inhibitor-Related Colitis. Inflamm Bowel Dis. 2018;24(8):1695-1705. doi:10.1093/ibd/izy104.

Outcomes of patients with multiple myeloma and 1q gain/amplification receiving autologous hematopoietic stem cell transplant: the MD Anderson cancer center experience

The prognostic impact of additional copies of chromosome 1q (1q + ) on outcomes of newly-diagnosed multiple myeloma (NDMM) patients undergoing autologous transplantation (autoSCT) is unclear. We conducted a retrospective single-center analysis of NDMM patients with 1q21 gain/amplification (3 or ≥4 copies of 1q, respectively) that received autoSCT between 2008–2018. 213 patients were included (79% 1q gain; 21% 1q amplification). The most commonly used induction regimen was bortezomib, lenalidomide, and dexamethasone (41%). At day100 post-autoSCT and at best post-transplant response, 78% and 87% of patients achieved ≥VGPR, and 38% and 50% achieved MRD-negative ≥VGPR, respectively. Median PFS and OS for the entire cohort were 35.5 months and 81.4 months, respectively. On multivariable assessment for PFS, MRD negative ≥VGPR before autoSCT (HR 0.52, p = 0.013) was associated with superior PFS, whereas 1q amplification was associated with inferior PFS (2.03, p = 0.003). On multivariate analysis for OS, achieving MRD negative ≥VGPR at best post-transplant response was associated with superior survival (0.29, p < 0.001), whereas R-ISS III and concomitant del17p or t(4:14) were associated with inferior survival (6.95, p = 0.030, 2.33, p = 0.023 and 3.00, p = 0.047, respectively). In conclusion, patients with 1q+ NDMM, especially 1q amplification, have inferior survival outcomes compared to standard-risk disease after upfront autoSCT, though outcomes are better than other high-risk cytogenetic abnormalities.

Incidence of Venous Thromboembolism in Pediatric Cancer Patients with COVID-19: MD Anderson Cancer Center Experience

Background: Patients with COVID-19 are at increased risk of venous thromboembolism (VTE) due to a hypercoagulable state. Multisystem inflammatory syndrome in children (MIS-C) is a unique entity in the pediatric population affected by COVID-19 which also increases the risk of VTE. This has been described in the literature and guidelines have been established across different institutions regarding anticoagulation prophylaxis. It is well known that cancer increases the risk of VTE greater than four-fold to that of the general population and, for patients receiving active chemotherapy, the risk is up to 6.5 times greater. Studies have shown that adults patients with active cancer and COVID-19 infection had increased risk of mortality due to VTE associated complications. Contrary to that, some reports have shown that incidence of VTE does not appear to be increased in adults with cancer compared to non-cancer patients. Hence, the data is yet scarce as well as conflictive. Anecdotally, we observed a decreased number of cases of VTE associated with COVID-19 infection in our pediatric cancer patients. There are limited studies that evaluate COVID-19 infection with VTE incidents and complications in this population. In this study, we report a retrospective analysis of pediatric cancer patients at our center during a span of three years to determine the incidence of COVID-19 infection with VTE and related complications. Objectives: Primary objective: Investigate the incidence of VTE in pediatric cancer patients with COVID-19 infection. Secondary objectives: Investigate COVID-19 associated complications, comorbidities in pediatric cancer patients. Methods: This is a single center retrospective cohort study. Data was extracted from COVID-19 database established at MD Anderson Cancer Center since the start of the pandemic. Patients 0 to 18 years of age affected by COVID-19 infection who were seen at MD Anderson Cancer Center from March 2020 to March 2023 were included. VTE inclusion criteria was development of thrombosis event from 14 days prior up to three months after COVID-19 infection. All cancer types were included. ICD 10 codes for diagnosis of COVID-19 infection and VTE were used to search for patients meeting the above criteria. Foundry database software was used to analyze the data and validation was done by the software checks by two independent reviewers and accordingly modified our search terms. Results: Three cohorts ( figure 1) were identified; patients with COVID-19 infection with or without VTE (Group 1), patients with VTE with or without COVID-19 infection (Group 2), and patients with both COVID-19 infection and VTE (Group 3). From group 1 (pediatric cancer with COVID infection with and without VTE), a total of 235 cancer patients ranging between 0 to 18 years of age were found affected by COVID-19 infection (Mean = 11.1 years, median = 12 years). The majority of patients were Caucasians (57.4%). Fifty percent of patients were male. From group 2 (pediatric cancer patients with VTE with or without COVID-19 infection), 272 patients were identified who had developed VTE of which 55.5% were males, and 54% were Caucasians with similar age distribution (mean = 13.1 years, median =15 years). In our study population, we identified three patients with VTE events who had COVID-19 infection (group 3, see table 1). Conclusion: The incidence of VTE in pediatric cancer patients affected by COVID-19 infection was lower compared to COVID-19 negative pediatric cancer patients. Our findings suggest that COVID-19 infection does not appear to be an additional risk factor for the development of VTE in pediatric cancer patients. Further studies are currently ongoing to investigate co-morbidities and COVID-associated complications other than VTE.

Outcomes of Patients with Multiple Myeloma and 1q Gain/Amplification Receiving Autologous Hematopoietic Stem Cell Transplant: The MD Anderson Cancer Center Experience

Background: There is contradictory data regarding the prognostic impact of additional copy numbers of chromosome 1q (1q+) on the outcomes of newly diagnosed multiple myeloma (NDMM) patients, and there is scarce data in the context of autologous stem cell transplantation (autoSCT). In this report, we studied outcomes of NDMM patients with 1q+ who received induction with contemporary anti-myeloma agents, followed by autoSCT and post-transplant maintenance therapy. Methods: We conducted a retrospective single-center chart review analysis of adult NDMM patients with 1q21 gain or amplification (3 or ≥4 copies of 1q, respectively; 1q+) detected by fluorescence in situ hybridization (FISH) that received autoSCT between 2008-2018. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints. Results: 213 NDMM patients with 1q+ were included in the analysis, with a median age of 62.5 years and 53% were male. Overall, 169 (79%) patients had 1q gain, while 44 (21%) patients had 1q amplification. The most commonly used induction and conditioning regimens were bortezomib, lenalidomide, and dexamethasone (VRD) (41%) and melphalan (77%), respectively (Table 1). At day 100 after autoSCT and at best post-transplant response, 78% and 87% of patients achieved ≥VGPR, 34% and 56% achieved CR, 38% and 50% achieved MRD negative ≥VGPR, respectively. The median PFS and OS for the entire cohort were 35.5 months and 81.4 months, respectively. 1q amplification was associated with inferior PFS compared to 1q gain (HR=2.03, 95% CI 1.36-3.03, p&amp;lt;0.001; Figure 1). On multivariable assessment (MVA) for PFS, MRD negative &amp;gt;VGPR before autoSCT and at day 100 post-transplant [(HR=0.56, 95% CI 0.36-0.86, p=0.009) and (HR=0.64, 95% CI 0.44-0.94, p=0.022), respectively] were associated with better PFS, whereas 1q amplification was associated with inferior PFS (HR=1.94, 95% CI 1.29-2.92, p=0.001). On MVA for OS, R-ISS stage III (HR=4.08, 95% CI 1.07-15.50, p=0.039) was associated with inferior OS, whereas achieving MRD negative &amp;gt;VGPR at best post-transplant response was associated with superior OS (HR=0.45, 95% CI 0.24-0.85, p=0.014). Notably, the percentage of cells with 1q+ was not associated with PFS nor with OS, both when evaluated as a continuous variable and when evaluated as a categorical variable using thresholds of either 30% or 50%. The presence of additional high-risk cytogenetic abnormalities did not adversely affect survival outcomes. Conclusions: Patients with NDMM and 1q+, especially 1q amplification, have poor survival outcomes, despite the use of contemporary induction regimens, upfront autoSCT and post-transplant maintenance. These patients may benefit from novel treatment modalities, such as CAR-T and bispecific antibodies, earlier in their disease course.

Long-Term Oncological Outcomes in Patients Diagnosed With Nonmetastatic Plasmacytoid Variant of Bladder Cancer: A 20-Year University of Texas MD Anderson Cancer Center Experience.

The treated natural history of nonmetastatic plasmacytoid variant of bladder cancer (PV-BCa) is poorly understood owing to its rarity. We sought to examine the disease recurrence and metastasis patterns in this select group of patients in order to identify opportunities for intervention. We conducted a natural language processing algorithm-augmented retrospective chart review of 56 consecutive patients who were treated with curative intent for nonmetastatic PV-BCa at our institution between 1998 and 2018. Kaplan-Meier and multivariable Cox regression methods were used for survival analyses. The stage at presentation was: ≤ cT2N0 in 22 (39.3%), cT3N0 in 15 (26.8%), cT4N0 in 13 (23.2%), and ≥ cN1 in 6 patients (10.7%). Forty-nine patients (87.5%) received chemotherapy, and 42 (75%) were able to undergo the planned surgery. Notably, only 4 patients (7.2%) had pT0 stage, while 22 (52.4%) had pN+ disease at the time of surgery. At 36-month follow-up, 28.4% of patients (95% CI: 22.1%-34.5%) were alive and 22.2% (95% CI: 16.1%-28.5%) were free of metastatic disease. The benefit of surgical extirpation was stage specific: successful completion of surgery was associated with improved metastasis-free survival (at 36 months 32.4% vs 0%, log-rank P < .001) in patients with localized or locally advanced disease (≤cT2N0/cT3N0); however, in patients with regionally advanced disease (cT4N0/≥cN1), consolidative surgery following chemotherapy was not associated with improved metastasis-free survival (12.5% vs 10% at 36 months, log-rank P = .49). The median time to metastasis from primary treatment end was 6.5 months (IQR: 2.9-14.7). The predominant site of recurrence/metastasis was the peritoneum (76.1%), either in isolation or along with extraperitoneal lesions. Salvage immunotherapy in these patients significantly reduced the risk of death (HR = 0.11, P = .001). PV-BCa is a disease with high lethality. Despite multimodal treatment, a vast majority of patients develop atypical intraperitoneal metastasis soon after therapy and rapidly succumb to it. Clinical trials evaluating utility of hyperthermic intraperitoneal chemotherapy and/or immunotherapy may be warranted in this high-risk population.

How to Build a Successful Phase I Clinical Trials Unit: Lessons Based on the MD Anderson Cancer Center Experience

How to Build a Successful Phase I Clinical Trials Unit: Lessons Based on the MD Anderson Cancer Center Experience

Cardiometabolic healthcare for men with prostate cancer: an MD Anderson Cancer Center experience

BackgroundMen diagnosed with prostate cancer are at risk for competing morbidity and mortality due to cardiometabolic disease given their advanced age at diagnosis, high prevalence of pre-existing risk factors, and receipt of systemic therapy that targets the androgen receptor (AR). Expert panels have stressed the importance of cardiometabolic risk assessment in the clinic and proposed evaluating key risks using consensus paradigms. Yet, there is a gap in real-world evidence for implementation of comprehensive cardiometabolic care for men with prostate cancer.MethodsThis is a retrospective, descriptive study of patients with prostate cancer who were referred and evaluated in the Healthy Heart Program at MD Anderson Cancer Center, which was established to mitigate cardiometabolic risks in men with prostate cancer. Patients were seen by a cardiologist and exercise physiologist to evaluate and manage cardiometabolic risk factors, including blood pressure, cholesterol, blood glucose, tobacco use, and coronary artery disease, concurrent with management of their cancer by a medical oncologist.ResultsFrom December 2018 through October 2021, the Healthy Heart Program enrolled 55 men with prostate cancer, out of which 35 had biochemical, locoregional recurrence or distant metastases, while all received at least a single dose of a luteinizing hormone-releasing hormone (LHRH) analog. Ninety-three percent of men were overweight or obese, and 51% had an intermediate or high risk of atherosclerotic cardiovascular disease at 10 years based on the pooled cohort equation. Most men had an overlap of two or more cardiometabolic diseases (84%), and 25% had an overlap of at least 4 cardiometabolic diseases. Although uncontrolled hypertension and hyperlipidemia were common among the cohort (45% and 26%, respectively), only 29% of men followed up with the clinic.ConclusionsMen with prostate cancer have a high burden of concurrent cardiometabolic risk factors. At a tertiary cancer center, the Healthy Heart Program was implemented to address this need, yet the utility of the program was limited by poor follow-up possibly due to outside cardiometabolic care and inconvenient appointment logistics, a lack of cardiometabolic labs at the time of visits, and telemedicine visits.

45. Outcomes of Targeted Muscle Reinnervation and Regenerative Peripheral Nerve Interface in Oncologic Amputees: The MD Anderson Cancer Center Experience

PURPOSE: The outcomes of targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) in oncologic amputees have been limited to small series. Herein, we report the MD Anderson experience with the surgical and postamputation outcomes of TMR and RPNI in the oncologic population. METHODS: We conducted a retrospective cohort study of consecutive patients who underwent oncologic amputation followed by TMR or RPNI from November 2018 to May 2022. Patient-reported Outcomes Measurement System (PROMIS) and Numerical Rating Scales for residual limb pain (RLP) and phantom limb pain (PLP) were obtained and compared with published benchmarked outcomes. RESULTS: We compared 68 patients with oncologic amputation at our institution with 727 patients with benchedmarked outcomes. Patients had mean follow-up period of 10.9±8.7 months. Oncologic amputees experienced significant reductions in pain intensity (-5.39; 95%CI,-4.28, -6.50; p<0.001), interference (-11.98; 95%CI, -8.19, -15.8; p<0.001), behavior (-32.95; 95%CI, -25.5,-40.4; p<0.001) and global health (-26.25; 95%CI, -22.09, -30.42; p<0.001) following TMR or RPNI from baseline to final follow-up. Delayed wound healing was the most common complication (14.7%) and tumor recurrence occurred in 36.8% of patients. Compared with benchedmarked outcomes, oncologic amputees who underwent TMR or RPNI demonstrated significantly lower median PLP (0.0 vs. 4.0, p<0.001), RLP (1.0 vs. 4, p<0.001), pain intensity (6.0 vs. 46.6, p<0.001), pain interference (9.5 vs. 55.9, p<0.001), and pain behavior (36.0 vs. 56.7, p<0.001) scores. CONCLUSION: Oncologic amputees who underwent TMR and RPNI demonstrated significant reductions in postamputation pain compared with their baseline and benchedmarked outcomes with relatively low postoperative complications rate.

Safety and Efficacy of Immune Checkpoint Inhibitors in Patients with Cancer and Viral Hepatitis: The MD Anderson Cancer Center Experience.

Despite the clinical benefit of immune checkpoint inhibitors (ICIs), patients with a viral hepatitis have been excluded from clinical trials because of safety concerns. The purpose of this study was to determine the incidence rate of adverse events (AEs) in patients with viral hepatitis who received ICIs for cancer treatment. We conducted a retrospective study in patients with cancer and concurrent hepatitis B or C, who had undergone treatment with ICI at MD Anderson Cancer Center from January 1, 2010 to December 31, 2019. Of the 1076 patients screened, we identified 33 with concurrent hepatitis. All 10 patients with HBV underwent concomitant antiviral therapy during ICI treatment. Sixteen of the 23 patients with HCV received it before the initiation of ICI. The median follow-up time was 33 months (95% CI, 23-45) and the median duration of ICI therapy was 3 months (IQR, 1.9-6.6). Of the 33 patients, 12 (39%) experienced irAEs (immune-related adverse events) of any grade, with 2 (6%) having grade 3 or higher. None of the patients developed hepatitis toxicities. ICIs may be a therapeutic option with an acceptable safety profile in patients with cancer and advanced liver disease.

532 - Single-Agent Lenalidomide Maintenance after Upfront Autologous Stem Cell Transplant for Newly Diagnosed Multiple Myeloma: The MD Anderson Cancer Center Experience

532 - Single-Agent Lenalidomide Maintenance after Upfront Autologous Stem Cell Transplant for Newly Diagnosed Multiple Myeloma: The MD Anderson Cancer Center Experience

Autologous Stem Cell Transplantation for Patients with Multiple Myeloma with Translocation (4;14): The MD Anderson Cancer Center Experience

Translocation between chromosomes 4 and 14, t(4;14), has been reported in 15% of patients with multiple myeloma (MM) and is considered a high-risk cytogenetic abnormality associated with inferior outcomes. Autologous hematopoietic stem cell transplantation (auto-HCT) is standard of care for patients with high-risk MM, yet there are scarce data on post-transplantation outcomes of patients with t(4;14) MM. The aim of the present study was to evaluate outcomes of MM patients with t(4;14) who underwent auto-HCT and received contemporary anti-myeloma agents for induction and post-transplantation maintenance. We conducted a retrospective analysis of MM patients with t(4;14), detected by fluorescence in situ hybridization (FISH), who underwent auto-HCT between 2008 and 2018 at MD Anderson Cancer Center. Primary endpoints were progression-free survival (PFS) and overall survival (OS), and secondary endpoints were hematologic response and minimal residual disease (MRD) status after auto-HCT. MRD status in the bone marrow biopsy was evaluated using 8-color next-generation flow cytometry with a sensitivity of 1/10-5 cells. Seventy-nine patients were included (52% male), with a median age of 60 years (range, 32 to 78 years). Forty-four patients (56%) had an additional high-risk cytogenetic abnormality. Fifty patients (63%) achieved at least a very good partial response (≥VGPR) prior to auto-HCT and 20 (25%) had MRD-negative ≥VGPR. At the best post-transplantation evaluation, 90% had ≥VGPR and 63% had MRD-negative ≥VGPR. The median follow-up for survivors was 35.7 months (range, 7.7 to 111.6 months). For the entire cohort, median PFS and OS were 22.9 months and 60.4 months, respectively. Patients with MRD-negative ≥VGPR prior to transplantation had improved PFS and OS on both univariate analysis (UVA) and multivariate analysis (MVA) (hazard ratio [HR], .35 [95% confidence interval (CI), .16 to .76; P=.008] and .12 [95% CI, .03 to .44; P=.002], respectively). The presence of additional high-risk cytogenetic abnormalities was not associated with inferior PFS (P=.57) or OS (P=.70). Post-transplantation lenalidomide-based combinations were associated with improved OS in both UVA and MVA (HR, .14; 95% CI, .04 to .45; P=.001), while their impact on PFS was not statistically significant (P=.37). Our results consolidate t(4;14) as a high-risk abnormality associated with poor outcomes despite novel agent induction, auto-HCT, and post-transplantation maintenance. Despite some inherent study design limitations, including a relatively small cohort and heterogeneity in treatment, we observed that deeper pretransplantation response and post-transplantation maintenance with lenalidomide-based combination were associated with improved outcomes. Novel immune and cellular therapies are needed to improve the outcomes in patients with t(4;14).

Characterization of recurrence patterns and outcomes of medulloblastoma in adults: The University of Texas MD Anderson Cancer Center experience.

Medulloblastoma in adults is rare and treatment decisions are largely driven from pediatric literature. We sought to characterize recurrent medulloblastoma in adults. From a single-institution dataset of 200 adult patients diagnosed with medulloblastoma during 1978-2017, those with recurrence were analyzed for clinical features, treatment, and outcome. Of the 200 patients, 82 (41%) with median age of 29 years (18-59) had recurrence after a median follow-up time of 8.4 years (95% CI = 7.1, 10.3). Of these, 30 (37%) were standard-risk, 31 (38%) were high-risk, and 21 (26%) had unknown-risk diseases at the time of initial diagnosis. Forty-eight (58%) presented with recurrence outside the posterior fossa, of whom 35 (43%) had distant recurrence only. Median Progression-free survival (PFS) and OS from initial surgery were 33.5 and 62.4 months, respectively. Neither PFS nor OS from initial diagnosis differed between the standard-risk and high-risk groups in those who experience recurrence (P = .505 and .463, respectively). Median OS from first recurrence was 20.3 months, also with no difference between the standard-risk and high-risk groups (P = .518). Recurrences were treated with combinations of re-resection (20 patients; 25%), systemic chemotherapy (61 patients; 76%), radiation (29 patients; 36%), stem cell transplant (6 patients; 8%), and intrathecal chemotherapy (4 patients; 5%). Patients who received radiation at recurrence had better OS (32.9 months) than those who did not (19.2 months) (P = .034). Recurrent medulloblastoma in adults has a poor prognosis irrespective of initial risk stratification. Recurrence commonly arises outside the posterior fossa years after initial diagnosis.

Autologous Stem Cell Transplantation for Patients with Multiple Myeloma with Translocation (4:14): The MD Anderson Cancer Center Experience

Autologous Stem Cell Transplantation for Patients with Multiple Myeloma with Translocation (4:14): The MD Anderson Cancer Center Experience

Management of Adverse Events in Early Clinical Trials by Advanced Practice Providers in the Outpatient Setting: The University of Texas MD Anderson Cancer Center Experience.

Background:Advanced practice providers (APPs) play important roles in enrolling, educating, and caring for patients in clinical trials. However, much remains unknown about the role of APPs in managing adverse events (AEs) in early (phase I to II) clinical trials. In this study, we assessed the outpatient management of grade 3 to 4 AEs by APPs in early trials and characterized the workflow of our APP Phase I to II Fast Track (FT) Clinic.Patients and Methods:We retrospectively reviewed records of patients with advanced or metastatic solid tumors enrolled in phase I to II clinical trials who were seen by APPs from September 2017 to August 2018 in the APP phase I to II FT clinic in the Department of Investigational Cancer Therapeutics.Results:A total of 808 patients enrolled in 159 clinical trials were seen in 2,697 visits (median 3 visits per patient; range 1–28) by 10 APPs. Treatment was interrupted in 6.9% of visits, and grade 3 to 4 AEs were seen in 5.4% of visits; however, patients from 1.4% of visits were sent to the emergency center (EC) and/or admitted. Patients referred to the EC and/or admitted were more likely to have baseline hypoalbuminemia, high lactate dehydrogenase, and poor Eastern Cooperative Oncology Group performance status (i.e., ECOG > 1; p < .001). There were no associations between EC referral and gender, APP years of experience, or type of treatment.Conclusions:The APP Phase I to II FT Clinic has an important role in the management of AEs by APPs in early clinical trials in the outpatient setting, potentially avoiding EC visits and admissions.

Treatment outcomes in patients (pts) with metastatic renal cell carcinoma (mRCC) with sarcomatoid and/or rhabdoid (S/R) features after progressive disease (PD) on immune checkpoint therapy (ICT): The MD Anderson Cancer Center experience.

351 Background: S/R mRCC is an aggressive disease that is associated with improved response to ICT. Studies performed prior to the approval of ICT demonstrated poor outcomes of S/R RCC with VEGF targeted therapies (TT). Here, we report outcomes of pts with S/R mRCC treated with VEGF TT after PD on ICT. Methods: We retrospectively reviewed the records of pts with mRCC with sarcomatoid (S), rhabdoid (R), or sarcomatoid plus rhabdoid (S+R) features who received VEGF TT after PD on ICT. Clinical endpoints of interest were time on VEGF TT and OS from treatment initiation. Directed acyclic graphs were used to identify confounders for adjustment in regression models. Hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated using multivariable Cox regression. Multivariable models adjusted for epithelial histology, IMDC risk, prior VEGF TT, and inclusion of cabozantinib in the post-ICT VEGF TT regimen. Results: 57 pts with metastatic S/R RCC (52 with clear cell and 5 with non-clear cell histology) received a VEGF TT after PD on ICT. 46% of pts received a VEGF TT prior to ICT. After PD on ICT, 67% of pts had IMDC intermediate-risk disease; the most commonly used VEGF TT were cabozantinib (44%), either sunitinib, pazopanib, or axitinib (24%), and a VEGF TT in combination with an ICT (21%). Pts with R RCC had significantly longer time on VEGF TT compared with S RCC (adjusted HR = 0.45, 95% CI 0.21-0.94, p = 0.034), whereas the OS comparison was inconclusive (adjusted HR = 0.77, 95% CI 0.36-1.62, p = 0.486). IMDC risk classification following ICT progression was predictive of OS (adjusted HR = 2.22, 95% CI 1.07-4.61, p = 0.032), whereas, its association with time on VEGF TT was less conclusive (adjusted HR = 1.78, 95% CI 0.88-3.60, p = 0.107). Conclusions: Patients with S/R mRCC derive clinical benefit from VEGF TT after progression on ICT, and it is similar to the benefit previously described for patients without S/R features. Our findings suggest that the type of S/R features present and IMDC risk score inform the clinical benefit that VEGF TT will produce in this setting.[Table: see text]

Long-Term Outcomes of Olfactory Neuroblastoma: MD Anderson Cancer Center Experience and Review of the Literature.

Olfactory neuroblastoma (ONB) is a rare sinonasal malignant neoplasm that is known to develop late recurrence. The aim of this study is to evaluate the long-term outcomes of patients with ONB and to determine the factors associated with prognosis. Retrospective study. A retrospective review of the medical records of 139 patients diagnosed with ONB at MD Anderson Cancer Center was performed between 1991 and 2016. Descriptive statistics were calculated, and Kaplan-Meier curves were utilized to assess survival. Median follow-up time was 75 months. Overall, 129 patients (92.8%) had surgery as part of their treatment and 82 (58.9%) patients received postoperative radiation therapy (PORT) or concurrent chemoradiotherapy. Endoscopic approaches were utilized for 72 patients, 69.4% of whom had pure endoscopic endonasal approaches. Five-year overall survival and disease-specific survival were 85.6% and 93.4%, respectively. Recurrence rate was 39.6% with a median time to recurrence of 42 months. Among the 31 patients who received elective nodal irradiation (ENI), two patients developed neck recurrence (6.4%) compared with 20 who developed neck recurrence when ENI was omitted (34.4%) (P=.003). Advanced Kadish stage, orbital invasion, intracranial invasion, and presence of cervical lymphadenopathy at the time of presentation were significantly associated with poor survival. ONB has an excellent survival. Surgical resection with PORT when indicated is the mainstay of treatment. Endoscopic approaches can be used as a good tool. Elective neck irradiation reduces the risk of nodal recurrence among patients with clinically N0 neck. Despite the excellent survival, recurrence rate remains high and delayed, highlighting the need for long-term surveillance. Level 4 Laryngoscope, 132:290-297, 2022.

Characteristics, Treatments, and Outcomes of Patients with Lymphomatoid Granulomatosis—MD Anderson Cancer Center Experience

Introduction: Lymphomatoid granulomatosis (LyG) is a rare EBV associated B cell lymphoproliferative disorder with unique histopathologic features (angiocentric and angiodestructive lesions), heterogeneous disease course and variable response to different therapies. Few reports have ever been published, and many patients have a poor prognosis. In this study, we present the largest single center experience on the characteristics, management and the outcomes in patients (pts) with LyG according to current WHO classification system.Methods: This is an analysis of 19 pts with confirmed diagnosis of LyG evaluated at MDACC between 1994 and 2014. Following IRB approval, pts were identified from the institutional database and data was collected on the clinico-pathological features, treatments and clinical outcomes following therapy. Histopathological and immunohistochemistry data was collected on available cases. Progression free (PFS) and overall survival (OS) was defined from the time of initial diagnosis to treatment failure or death.Results: Median age was 56 years (range, 19 to 90) and 53% were males. Among the pts with available data, performance status was ≥1 in 12/14 (85%) pts, B symptoms were observed in 6/14 (43%) pts, and 100% pts had stage 4 disease, including nodal involvement 2/19 pts (10%). Extranodal involvement (with/without concordant involvement of other sites) was observed in all pts. The lung was the most common site of involvement (78%), followed by central nervous system (28%), skin (22%) and liver (17%). Mediastinal, adrenal, renal, breast and abdomino-pelvic involvement was rare. Two pts had marrow involvement at initial presentation. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) was noted in one patient 2 years prior to the diagnosis. Seven pts had a pre-existing cancer or a medical condition associated with immunosuppression (one patient with chronic myeloid leukemia, one chronic lymphocytic leukemia, one myelodysplastic syndrome, one with hypereosinophillic syndrome, one prostate cancer and 2 pts were on immunosuppressive therapy). One pt developed Hodgkin's lymphoma after the diagnosis. At baseline; anemia (Hb <11 g/dL) was seen in 46%, thrombocytopenia (platelet count <100 K/μL) and leucocytopenia (WBC <3 K/μL) was seen in 15% each. LDH > upper limit of normal was observed in 33% pts. PET-CT scan was performed in 7 pts, and was positive in 100%. Histopathologic studies showed that LyG grading was available in 10 pts of which 3 (30%) were grade 2 and 7 (70%) were grade 3. Immunohistochemically, CD20 was positive in 100%, CD30 in 100%, the median Ki-67% was 55% (range 20-70), and EBV-positive cells were noted by in situ hybridization in in 89% pts. In the 11 pts with treatment information, 4 received R-CHOP, 2 received R-EPOCH, 2 received rituximab alone, and 1 each received methotrexate and CHOP. Overall response to treatment was 55%, including complete remission in 36%. (3/4 pts achieved CR following R-CHOP). With a median follow up of 60 months, median progression free survival (after initial therapy) was 8.5 months. Median overall survival was 22 months (Figure-1 (A-B). Four patients died due to disease progression, 3 from unknown causes and 2 due to sepsis and pneumonia respectively.Conclusions: LyG remains a diagnostic and a therapeutic challenge to hematopathologists and clinicians. Although responses have been observed following rituximab containing combination therapy, most patients relapse and the optimal treatment strategy remains unknown. The rarity of the disease and lack of molecular data in LyG are major limiting factors to developing targeted approaches, and further studies interrogating the genomic landscape in LyG are ongoing at our institution. The high rates of CD20 and CD30 expression suggest targeted therapy may be of benefit, but require prospective study. Multicenter collaboration is needed to further develop successful approaches to study and treat this rare disease. [Display omitted] DisclosuresNastoupil:Janssen: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Genentech: Honoraria, Research Funding; TG Therapeutics: Honoraria, Research Funding; Gilead: Honoraria; Karus Therapeutics: Research Funding. Neelapu:Bristol-Myers Squibb: Research Funding; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karus: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectis Inc.: Research Funding; Poseida Therapeutics, Inc: Research Funding. Westin:Celgene: Membership on an entity's Board of Directors or advisory committees; Apotex: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees. Wang:Acerta Pharma: Consultancy, Research Funding; BeiGene: Research Funding; Celgene: Honoraria, Research Funding; Dava Oncology: Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; June Therapeutics: Research Funding; Kite Pharma: Research Funding; Onyx: Research Funding; Pharmacyclics: Research Funding; Proteolix: Honoraria, Research Funding; Asana Biosciences: Research Funding.