Objective performance indicators during specific steps of robotic right colectomy can differentiate surgeon expertise.

BACKGROUND: Current surgical assessment tools are subjective and nonscalable. Objective performance indicators, calculated from robotic systems data, provide automated data regarding surgeon movements and robotic arm kinematics. We identified objective performance indicators that significantly differed among expert and trainee surgeons during specific steps of robotic right colectomy. METHODS: Endoscopic videos were annotated to delineate surgical steps during robotic right colectomies. Objective performance indicators were compared during mesenteric dissection, ascending colon mobilization, hepatic flexure mobilization, and bowel preparation for transection. RESULTS: Twenty-five robotic right colectomy procedures (461 total surgical steps) performed by 2 experts and 8 trainees were analyzed. Experts exhibited faster camera acceleration and jerk during all steps, as well as faster dominant and nondominant arm acceleration and dominant arm jerk during all steps except distal bowel preparation. During mesenteric dissection, experts used faster camera and dominant arm velocity. During medial-to-lateral ascending colon mobilization, experts used less-dominant wrist yaw and pitch, faster nondominant arm velocity, shorter dominant arm path length, and shorter moving times for camera, dominant arm, and nondominant arm. During lateral-to-medial ascending colon mobilization, experts had faster dominant and nondominant arm velocity and third-arm acceleration. During hepatic flexure mobilization, experts exhibited more camera movements, greater velocity for camera, dominant and nondominant arms, and faster third-arm acceleration. During distal bowel preparation, experts used greater dominant wrist articulation, faster camera velocity, and longer nondominant arm path length. During proximal bowel preparation, experts demonstrated faster nondominant arm velocity. CONCLUSION: Objective performance indicators can differentiate experts from trainees during distinct steps of robotic right colectomy. These automated, objective and scalable metrics can provide personalized feedback for trainees.

Patterns of Treatment Failure in Primary Central Nervous System Lymphoma.

OBJECTIVES: Progression of PCNSL remains a challenge with salvage therapies, including the risk of substantial morbidity and mortality. We report patterns of first tumor progression to inform opportunities for improvement. METHODS: This is an institutional retrospective review from 2002 to 2021 of 95 consecutive patients with pathologically confirmed PCNSL, of whom 29 experienced progressive disease. Kaplan-Meier method, log-rank test, and Cox proportional hazard models are used to characterize associations of patient, tumor, and treatment variables with LC, PFS, and patterns of first failure. RESULTS: Most patients were below 65 years old (62%) with KPS >70 (64%) and negative CSF cytology (70%). In 70 patients with MRIs, the median tumor volume was 12.6 mL (range: 0.5 to 67.8 mL). After a median follow-up of 11 months, 1-year PFS was 48% and 1-year LC was 80%. Of the 29 patients with progression, 24% were distant only, 17% were distant and local, and 59% were local only. On MVA, LC was associated with age (HR: 1.08/y, P =0.02), KPS (HR: 0.10, P =0.02), completion of >6 cycles of HD-MTX (HR: 0.10, P <0.01), and use of intrathecal chemotherapy (HR: 0.03, P <0.01). On UVA, local only first failure trended to be increased with >14 mL tumors (OR: 5.06, P =0.08) with 1-year LC 83% (<14 mL) versus 64% (>14mL). There were no significant associations with LC and WBRT ( P =0.37), Rituximab ( P =0.12), or attempted gross total resection ( P =0.72). CONCLUSIONS: Our findings reaffirm the importance of systemic and intrathecal therapies for local control in PCNSL. However, bulky tumors trend to fail locally, warranting further investigation about the role of local therapies or systemic therapy intensification.

Intensity-Modulated Reirradiation Therapy With Nivolumab in Recurrent or Second Primary Head and Neck Squamous Cell Carcinoma: A Nonrandomized Controlled Trial.

Importance: Intensity-modulated radiation therapy (IMRT) reirradiation of nonmetastatic recurrent or second primary head and neck squamous cell carcinoma (HNSCC) results in poor progression-free survival (PFS) and overall survival (OS). Objective: To investigate the tolerability, PFS, OS, and patient-reported outcomes with nivolumab (approved standard of care for patients with HNSCC) during and after IMRT reirradiation. Design, Setting, and Participants: In this multicenter nonrandomized phase 2 single-arm trial, the treatment outcomes of patients with recurrent or second primary HNSCC who satisfied recursive partitioning analysis class 1 and 2 definitions were evaluated. Between July 11, 2018, and August 12, 2021, 62 patients were consented and screened. Data were evaluated between June and December 2023. Intervention: Sixty- to 66-Gy IMRT in 30 to 33 daily fractions over 6 to 6.5 weeks with nivolumab, 240 mg, intravenously 2 weeks prior and every 2 weeks for 5 cycles during IMRT, then nivolumab, 480 mg, intravenously every 4 weeks for a total nivolumab duration of 52 weeks. Main Outcomes and Measures: The primary end point was PFS. Secondary end points included OS, incidence, and types of toxic effects, including long-term treatment-related toxic effects, patient-reported outcomes, and correlatives of tissue and blood biomarkers. Results: A total of 62 patients were screened, and 51 were evaluable (median [range] age was 62 [56-67] years; 42 [82%] were male; 6 [12%] had p16+ disease; 38 [75%] had salvage surgery; and 36 [71%.] had neck dissection). With a median follow-up of 24.5 months (95% CI, 19.0-25.0), the estimated 1-year PFS was 61.7% (95% CI, 49.2%-77.4%), rejecting the null hypothesis of 1-year PFS rate of less than 43.8% with 1-arm log-rank test P = .002 within a 1-year timeframe. The most common treatment-related grade 3 or higher adverse event (6 [12%]) was lymphopenia with 2 patients (4%) and 1 patient each (2%) exhibiting colitis, diarrhea, myositis, nausea, mucositis, and myasthenia gravis. Functional Assessment of Cancer Therapy-General and Functional Assessment of Cancer Therapy-Head and Neck Questionnaire quality of life scores remained stable and consistent across all time points. A hypothesis-generating trend favoring worsening PFS and OS in patients with an increase in blood PD1+, KI67+, and CD4+ T cells was observed. Conclusions and Relevance: This multicenter nonrandomized phase 2 trial of IMRT reirradiation therapy and nivolumab suggested a promising improvement in PFS over historical controls. The treatment was well tolerated and deserves further evaluation. Trial Registration: ClinicalTrials.gov Identifier: NCT03521570.

Targeting TRIP13 in favorable histology Wilms tumor with nuclear export inhibitors synergizes with doxorubicin.

Wilms tumor (WT) is the most common renal malignancy of childhood. Despite improvements in the overall survival, relapse occurs in ~15% of patients with favorable histology WT (FHWT). Half of these patients will succumb to their disease. Identifying novel targeted therapies remains challenging in part due to the lack of faithful preclinical in vitro models. Here we establish twelve patient-derived WT cell lines and demonstrate that these models faithfully recapitulate WT biology using genomic and transcriptomic techniques. We then perform loss-of-function screens to identify the nuclear export gene, XPO1, as a vulnerability. We find that the FDA approved XPO1 inhibitor, KPT-330, suppresses TRIP13 expression, which is required for survival. We further identify synergy between KPT-330 and doxorubicin, a chemotherapy used in high-risk FHWT. Taken together, we identify XPO1 inhibition with KPT-330 as a potential therapeutic option to treat FHWTs and in combination with doxorubicin, leads to durable remissions in vivo.

Quantification of surgical workflow during robotic proctectomy.

BACKGROUND: Surgical workflow assessments offer insight regarding procedure variability. We utilised an objective method to evaluate workflow during robotic proctectomy (RP). METHODS: We annotated 31 RPs and used Spearman's correlation to measure the correlation of step time and step visit frequency with console time (CT) and total operative time (TOT). RESULTS: Strong correlations were seen with CT and step times for inferior mesenteric vein dissection and ligation (ρ = 0.60, ρ = 0.60), lateral-to-medial splenic flexure mobilisation (SFM) (ρ = 0.63), left rectal dissection (ρ = 0.64) and mesorectal division (ρ = 0.71). CT correlated strongly with medial-to-lateral (ρ = 0.75) and supracolic SFM visit frequency (ρ = 0.65). TOT correlated strongly with initial exposure time (ρ = 0.60), and medial-to-lateral (ρ = 0.67) and supracolic SFM visit frequency (ρ = 0.65). CONCLUSION: This study correlates surgical steps with CT and TOT through standardised annotation, providing an objective approach to quantify workflow.

Phase II trial of nivolumab and metformin in patients with treatment-refractory microsatellite stable metastatic colorectal cancer.

BACKGROUND: Preclinical studies showed metformin reduces exhaustion of tumor-infiltrating lymphocytes and potentiates programmed cell death protein-1 (PD-1) blockade. We hypothesized that metformin with nivolumab would elicit potent antitumor and immune modulatory activity in metastatic microsatellite stable (MSS) colorectal cancer (CRC). We evaluated this hypothesis in a phase II study. METHODS: Nivolumab (480 mg) was administered intravenously every 4 weeks while metformin (1000 mg) was given orally, two times per day following a 14-day metformin only lead-in phase. Patients ≥18 years of age, with previously treated, stage IV MSS CRC, and Eastern Cooperative Oncology Group 0-1, having received no prior anti-PD-1 agent were eligible. The primary endpoint was overall response rate with secondary endpoints of overall survival (OS) and progression-free survival (PFS). Correlative studies using paired pretreatment/on-treatment biopsies and peripheral blood evaluated a series of immune biomarkers in the tumor microenvironment and systemic circulation using ChipCytometry and flow cytometry. RESULTS: A total of 24 patients were enrolled, 6 patients were replaced per protocol, 18 patients had evaluable disease. Of the 18 evaluable patients, 11/18 (61%) were women and the median age was 58 (IQR 50-67). Two patients had stable disease, but no patients had objective response, hence the study was stopped for futility. Median OS and PFS was 5.2 months (95% CI (3.2 to 11.7)) and 2.3 months (95% CI (1.7 to 2.3)). Most common grade 3/4 toxicities: Anemia (n=2), diarrhea (n=2), and fever (n=2). Metformin alone failed to increase the infiltration of T-cell subsets in the tumor, but combined metformin and nivolumab increased percentages of tumor-infiltrating leukocytes (p=0.031). Dual treatment also increased Tim3+ levels in patient tissues and decreased naïve CD8+T cells (p=0.0475). CONCLUSIONS: Nivolumab and metformin were well tolerated in patients with MSS CRC but had no evidence of efficacy. Correlative studies did not reveal an appreciable degree of immune modulation from metformin alone, but showed trends in tumorous T-cell infiltration as a result of dual metformin and PD-1 blockade despite progression in a majority of patients.

Quantification of Surgical Workflow during Robotic Proctectomy.

Aim: Assessments of surgical workflow offer insight regarding procedure variability, case complexity and surgeon proficiency. We utilize an objective method to evaluate step-by-step workflow and step transitions during robotic proctectomy (RP). Methods: We annotated 31 RPs using a procedure-specific annotation card. Using Spearman's correlation, we measured strength of association of step time and step visit frequency with console time (CT) and total operative time (TOT). Results: Across 31 RPs, a mean (± standard deviation) of 49.0 (± 20.3) steps occurred per procedure. Mean CT and TOT were 213 (± 90) and 283 (± 108) minutes. Posterior mesorectal dissection required most visits (8.7 ± 5.0), while anastomosis required most time (18.0 [± 8.5] minutes). Inferior mesenteric vein (IMV) ligation required least visits (1.0 ± 0.0) and lowest duration (0.9 [± 0.5] minutes). Strong correlations were seen with CT and step times for IMV dissection and ligation (ρ = 0.60 for both), lateral-to-medial splenic flexure mobilization (SFM) (ρ = 0.63), left rectal dissection (ρ = 0.64) and mesorectal division (ρ = 0.71). CT correlated strongly with medial-to-lateral and supracolic SFM visit frequency (ρ = 0.75 and ρ = 0.65). There were strong correlations with TOT and initial exposure time (ρ = 0.60), as well as visit frequency for medial-to-lateral (ρ = 0.67) and supracolic SFM (ρ = 0.65). Descending colon mobilization was nodal, rectal mobilization convergent and rectal transection divergent. Conclusion: This study correlates individual surgical steps with CT and TOT through standardized annotation. It provides an objective approach to quantify workflow.

NEO-GAP: A Single-Arm, Phase II Feasibility Trial of Neoadjuvant Gemcitabine, Cisplatin, and Nab-Paclitaxel for Resectable, High-Risk Intrahepatic Cholangiocarcinoma.

PURPOSE: Most patients with intrahepatic cholangiocarcinoma (IHCC) develop recurrence after resection. Adjuvant capecitabine remains the standard of care for resected IHCC. A combination of gemcitabine, cisplatin, and nab-paclitaxel (GAP) was associated with a 45% response rate and 20% conversion rate among patients with unresectable biliary tract cancers. The aim of this study was to evaluate the feasibility of delivering GAP in the neoadjuvant setting for resectable, high-risk IHCC. METHODS: A multi-institutional, single-arm, phase II trial was conducted for patients with resectable, high-risk IHCC, defined as tumor size > 5 cm, multiple tumors, presence of radiographic major vascular invasion, or lymph node involvement. Patients received preoperative GAP (gemcitabine 800 mg/m2, cisplatin 25 mg/m2, and nab-paclitaxel 100 mg/m2 on days 1 and 8 of a 21-day cycle) for a total of 4 cycles prior to an attempt at curative-intent surgical resection. The primary endpoint was completion of both preoperative chemotherapy and surgical resection. Secondary endpoints were adverse events, radiologic response, recurrence-free survival (RFS), and overall survival (OS). RESULTS: Thirty evaluable patients were enrolled. Median age was 60.5 years. Median follow-up for all patients was 17 months. Ten patients (33%) experienced grade ≥ 3 treatment-related adverse events, the most common being neutropenia and diarrhea; 50% required ≥ 1 dose reduction. The disease control rate was 90% (progressive disease: 10%, partial response: 23%, stable disease: 67%). There was zero treatment-related mortality. Twenty-two patients (73%, 90% CI 57-86; p = 0.008) completed all chemotherapy and surgery. Two patients (9%) who successfully underwent resection had minor postoperative complications. Median length of hospital stay was 4 days. Median RFS was 7.1 months. Median OS for the entire cohort was 24 months and was not reached in patients who underwent surgical resection. CONCLUSION: Neoadjuvant treatment with gemcitabine, cisplatin, and nab-paclitaxel is feasible and safe prior to resection of intrahepatic cholangiocarcinoma and does not adversely impact perioperative outcomes.

Ratio of Economy of Motion: A New Objective Performance Indicator to Assign Consoles During Dual-Console Robotic Proctectomy.

BACKGROUND: Our group investigates objective performance indicators (OPIs) to analyze robotic colorectal surgery. Analyses of OPI data are difficult in dual-console procedures (DCPs) as there is currently no reliable, efficient, or scalable technique to assign console-specific OPIs during a DCP. We developed and validated a novel metric to assign tasks to appropriate surgeons during DCPs. METHODS: A colorectal surgeon and fellow reviewed 21 unedited, dual-console proctectomy videos with no information to identify the operating surgeons. The reviewers watched a small number of random tasks and assigned "attending" or "trainee" to each task. Based on this sampling, the remainder of task assignments for each procedure was extrapolated. In parallel, we applied our newly developed OPI, ratio of economy of motion (rEOM), to assign consoles. Results from the 2 methods were compared. RESULTS: A total of 1811 individual surgical tasks were recorded during 21 proctectomy videos. A median of 6.5 random tasks (137 total) were reviewed during each video, and the remainder of task assignments were extrapolated based on the 7.6% of tasks audited. The task assignment agreement was 91.2% for video review vs rEOM, with rEOM providing ground truth. It took 2.5 hours to manually review video and assign tasks. Ratio of economy of motion task assignment was immediately available based on OPI recordings and automated calculation. DISCUSSION: We developed and validated rEOM as an accurate, efficient, and scalable OPI to assign individual surgical tasks to appropriate surgeons during DCPs. This new resource will be useful to everyone involved in OPI research across all surgical specialties.

Loss of the endocytic tumor suppressor HD-PTP phenocopies LKB1 and promotes RAS-driven oncogenesis.

Oncogenic RAS mutations drive aggressive cancers that are difficult to treat in the clinic, and while direct inhibition of the most common KRAS variant in lung adenocarcinoma (G12C) is undergoing clinical evaluation, a wide spectrum of oncogenic RAS variants together make up a large percentage of untargetable lung and GI cancers. Here we report that loss-of-function alterations (mutations and deep deletions) in the gene that encodes HD-PTP (PTPN23) occur in up to 14% of lung cancers in the ORIEN Avatar lung cancer cohort, associate with adenosquamous histology, and occur alongside an altered spectrum of KRAS alleles. Furthermore, we show that in publicly available early-stage NSCLC studies loss of HD-PTP is mutually exclusive with loss of LKB1, which suggests they restrict a common oncogenic pathway in early lung tumorigenesis. In support of this, knockdown of HD-PTP in RAS-transformed lung cancer cells is sufficient to promote FAK-dependent invasion. Lastly, knockdown of the Drosophila homolog of HD-PTP (dHD-PTP/Myopic) synergizes to promote RAS-dependent neoplastic progression. Our findings highlight a novel tumor suppressor that can restrict RAS-driven lung cancer oncogenesis and identify a targetable pathway for personalized therapeutic approaches for adenosquamous lung cancer.

PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection.

BACKGROUND: The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response. OBJECTIVES: The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19. METHODS: In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline. RESULTS: Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: -30%; 95% CI: -53.40% to -6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: -56% vs -21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: -37.50%; 95% CI: -68.20% to -6.70%). CONCLUSIONS: PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105).

Engagement and outcomes of cancer patients referred to a tobacco cessation program at a National Cancer Institute-designated cancer center.

INTRODUCTION: Tobacco cessation is a critical but challenging intervention for cancer patients. Our National Cancer Institute-designated Comprehensive Cancer Center instituted a tobacco cessation program in 2019. This manuscript reports on the first 2 years of our experience. METHODS: Patients were referred to the program by their care team, and a certified tobacco treatment specialist contacted patients remotely and provided behavioral therapy and coordinated pharmacotherapy. We retrospectively captured data from patients with a cancer diagnosis referred to the tobacco cessation program. Univariate and multivariable logistic regression analyses with the backward elimination approach were performed to determine factors associated with patient acceptance of referral to the tobacco cessation program. Tobacco cessation rates after referral to the program were also captured. RESULTS: Between July 2019 and August 2021, 194 patients were referred to the tobacco cessation program. Of the 194 patients referred, 93 agreed to enroll in the tobacco cessation program (47.9%), of which 84 requested pharmacotherapy (90.3%). Twenty-four were able to cease tobacco use (25.8%). Only 7 patients out of the 101 patients (6.9%) who declined cessation services were successful (p < 0.001). On univariate logistic regression, race (p = 0.027) and marital status (p = 0.020) were associated with referral acceptance. On multivariable analysis, single patients (odds ratio [OR] = 0.33) and Caucasian patients (OR = 0.43) were less likely to accept a referral. CONCLUSIONS: Access to tobacco cessation services is a critical component of comprehensive cancer care. Our experience highlights the need to understand patient-specific factors associated with engagement with a tobacco cessation program during cancer treatment. The use of pharmacotherapy is also a critical component of successful tobacco cessation.

Ninety-day mortality following transoral robotic surgery or radiation at Commission on Cancer-accredited facilities.

BACKGROUND: Postoperative mortality for oropharynx squamous cell carcinoma (OPSCC) with transoral robotic surgery (TORS) varies from 0.2% to 6.5% on trials; the real-world rate is unknown. METHODS: NCDB study from 2010 to 2017 for patients with cT1-2N0-2M0 OPSCC with Charleson-Deyo score 0-1. Ninety-day mortality assessed from start and end of treatment at Commission on Cancer-accredited facilities. RESULTS: 3639 patients were treated with TORS and 1937 with radiotherapy. TORS cohort had more women and higher income, was younger, more often treated at academic centers, and more likely to have private insurance (all p < 0.05). Ninety-day mortality was 1.3% with TORS and 0.7% or 1.4% from start or end of radiotherapy, respectively. From end of therapy, there was no significant difference on MVA between treatment modality. CONCLUSIONS: There is minimal difference between 90-day mortality in patients treated with TORS or radiotherapy for early-stage OPSCC. While overall rates are low, for patients with expectation of cure, work is needed to identify optimal treatment.

Racial Disparities in Clinical Outcomes on Investigator-Initiated Breast Cancer Clinical Trials at an Urban Medical Center.

BACKGROUND: Black women are 40% more likely to die of breast cancer compared to White women. Inadequate representation of Black patients in clinical trials may contribute to health care inequity. We aimed to assess breast cancer clinical outcomes in Non-Hispanic Black (Black) versus Non-Hispanic White (White) women with metastatic breast cancer (MBC) enrolled on investigator-initiated clinical trials at Winship Cancer Institute at Emory University, given the significant number of patients from underrepresented minority groups seen at Winship. MATERIALS AND METHODS: Black and White women with MBC on investigator-initiated trials at Emory between 2009 and 2019 were retrospectively evaluated. Univariate analyses and multiple logistic regression models were used to assess clinical response and treatment toxicities. Differences in overall survival between groups was assessed using quantile analysis. RESULTS: Sixty-two women with MBC were included (66% White vs. 34% Black). Black patients had less clinical benefit from the trial therapy as only 57% had partial response or stable disease as best response compared to 78% of White women (P = .09). Quantile analysis showed significant difference in mean survival between Whites and Blacks by the end of follow up (64 vs. 38 months). There were no significant differences in toxicities between groups. CONCLUSION: Participation rates of Black women with MBC on investigator-initiated clinical trials at an urban cancer center were higher compared to key national trials. Black women had worse treatment response and survival. These results reinforce the need for assessment of tumor differences by ancestry and continued improvement in minority representation on clinical trials.

Post-transplant lymphoproliferative disorder risk and outcomes in renal transplant patients treated with belatacept immunosuppression.

Introduction: Post-transplant lymphoproliferative disorder (PTLD) is a rare but life-threatening malignancy that arises in the setting of immunosuppression (IS) after solid organ transplant. IS regimens containing belatacept have been associated with an increased risk of PTLD in Epstein-Barr virus (EBV)-seronegative renal transplant recipients, and the use of belatacept is contraindicated in this population. However, the impact of belatacept-based regimens on PTLD risk and outcomes in EBV-seropositive renal transplant recipients is less well characterized. Methods: A case-control study was conducted to investigate how combinatorial IS regimens impact the risk of PTLD and survival outcomes in renal transplant recipients at a large transplant center between 2010 and 2019. In total, 17 cases of PTLD were identified and matched 1:2 to controls without PTLD by age, sex, and transplanted organ(s). We compared baseline clinical characteristics, examined changes in IS regimen, viral loads, and renal function over time, and evaluated time-to-event analyses, including graft rejection and survival. Results: Cases of PTLD largely resembled matched controls in terms of baseline characteristics, although expected differences in EBV serostatus trended toward significance (42.9% of PTLD cases were donor-positive/recipient-negative vs. 8.3% controls, p = 0.063). PTLD cases were not more likely to have received belatacept than controls. Belatacept was not associated with graft rejection or failure, re-transplant, hospitalization, or decreased survival. Conclusions: Belatacept was not associated with an increased risk of PTLD, and was not associated with decreased survival in either PTLD cases or in the entire cohort. Our case-control study supports the concept that belatacept remains a safe and effective option for IS in EBV-seropositive renal transplant patients.

Robotic Proctectomy: Beyond the Initial Learning Curve.

BACKGROUND: Multiple authors have described an initial learning curve (LC) for robotic proctectomy (RP), but there is scant literature regarding continued technical progression beyond this stage. Total operating time is the most commonly used metric to measure proficiency. Our goal was to examine RP experience after the initial LC looking for evidence of further technical progression. METHODS: We reviewed our robotic surgery database for a single surgeon during operations 100 through 550 to identify 83 RPs for tumor. These were divided into quartiles by series order, indicating surgeon experience level over time. Demographics and outcomes were compared among the groups. We defined percent console time (PCT) as a new metric. PCT was defined as console time divided by total operative time (TOT). RESULTS: From March 2014 through March 2019, 450 robotic colorectal operations were performed, including 83 RPs for polyp or cancer. No significant differences were found among the quartiles in regard to demographics, tumor features, hospital stay, conversions, or readmissions. As experience was gained, there were significant increases in intracorporeal anastomosis (ICA), TOT, and PCT. Complications decreased with experience. Number of lymph nodes in the specimen increased. On multivariate analysis, later experience group, body mass index ≥30, and ICA were associated with increased PCT. DISCUSSION: ICA became a routine part of RP after the initial LC, with increases in TOT and PCT. Number of lymph nodes increased and number and severity of complications decreased with experience. Increased PCT may indicate increased expertise during RP.

Obesity-induced galectin-9 is a therapeutic target in B-cell acute lymphoblastic leukemia.

The incidence of obesity is rising with greater than 40% of the world's population expected to be overweight or suffering from obesity by 2030. This is alarming because obesity increases mortality rates in patients with various cancer subtypes including leukemia. The survival differences between lean patients and patients with obesity are largely attributed to altered drug pharmacokinetics in patients receiving chemotherapy; whereas, the direct impact of an adipocyte-enriched microenvironment on cancer cells is rarely considered. Here we show that the adipocyte secretome upregulates the surface expression of Galectin-9 (GAL-9) on human B-acute lymphoblastic leukemia cells (B-ALL) which promotes chemoresistance. Antibody-mediated targeting of GAL-9 on B-ALL cells induces DNA damage, alters cell cycle progression, and promotes apoptosis in vitro and significantly extends the survival of obese but not lean mice with aggressive B-ALL. Our studies reveal that adipocyte-mediated upregulation of GAL-9 on B-ALL cells can be targeted with antibody-based therapies to overcome obesity-induced chemoresistance.

Comparison of the Seventh and Eighth Edition of American Joint Committee on Cancer (AJCC) Staging for Selected and Nonselected Oropharyngeal Squamous Cell Carcinomas.

OBJECTIVES: The eighth edition American Joint Committee on Cancer (AJCC) Staging incorporates significant changes to the seventh edition in the staging of oropharyngeal squamous cell carcinomas (OPSCC). An important change was the inclusion of OPSCC associated with the human papilloma virus (HPV). Our goal is to compare the performance of both staging systems for patients with HPV-selected and unselected clinical characteristics for OPSCC. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, 2004-2016, we identified patients with likely HPV-associated OPSCC based on surrogate markers (white males aged <65 years old with squamous cell carcinomas of the tonsil and base of tongue), excluding those who underwent surgery. We re-classified these patients using seventh and eighth edition staging for HPV-selected OPSCC and compared the prediction performance of both staging editions for overall survival (OS) and disease-specific survival (DSS). We performed the same analysis for clinically unselected patients with OPSCC. RESULTS: Our analysis included 9554 patients with a median follow-up of 67 months. Comparing the eighth versus seventh edition for our HPV-selected cohort, clinical staging changed for 92.3% of patients and 10-year OS was 62.2%, 61.2%, 35.3%, and 15.5% for Stage I, II, III, and IV, versus 52.9%, 59.2%, 61.6%, 55.1%, 38.3%, and 15.5% for stage I, II, III, IVA, IVB, and IVC, respectively. A similar pattern was observed for 10-year DSS. The concordance statistics for our HPV-selected cohort were improved for both AJCC 7 (0.6260) and AJCC 8 (0.6846) compared with the unselected cohort, 0.5860 and 0.6457 for AJCC 7 and 8, respectively. CONCLUSION: The overall performance of discrimination improved from AJCC 7 to AJCC 8 for both clinically selected and unselected patients, but more notably for our HPV-selected cohort. Despite the lack of statistically significant differentiation between Stages I and II in AJCC 8 in either groups, markedly improved discrimination was observed between Stages I/II, III, and IV in the HPV-selected cohort.

Modern Linear Accelerator-Based Radiotherapy Is Safe and Effective in the Treatment of Secretory and Nonsecretory Pituitary Adenomas.

BACKGROUND: Adjuvant radiotherapy (RT) can help achieve local control (LC) and reduce hormonal overexpression for pituitary adenomas (PAs). Prior reports involved Gamma Knife or older linear accelerator (LINAC) techniques. The aim of this study was to report long-term outcomes for modern LINAC RT. METHODS: Institutional retrospective review of LINAC RT for PAs with minimum 3 years of magnetic resonance imaging follow-up was performed. Hormonal control was defined as biochemical remission in absence of medications targeting hormone excess. LC defined using Response Evaluation Criteria in Solid Tumors on surveillance magnetic resonance imaging. Progression-free survival defined as time alive with LC without return of or worsening hormonal excess from secretory PA. Kaplan-Meier and Cox proportional hazard models used. RESULTS: From 2003 to 2017, 140 patients with PAs (94 nonsecretory, 46 secretory) were treated with LINAC RT (105 fractionated RT, 35 radiosurgery) with median follow-up of 5.35 years. Techniques included fixed gantry intensity-modulated radiotherapy (51.4%), dynamic conformal arcs (9.3%), and volumetric modulated arc therapy (39.3%). Progression-free survival at 5 years was 95.3% for secretory tumors and 94.8% for nonsecretory tumors. Worse progression-free survival was associated with larger planning target volume on multivariable analysis (hazard ratio 2.87, 95% confidence interval 1.01-8.21, P = 0.049). Hormonal control at 5 years was 50.0% and associated with higher dose to tumor (hazard ratio 1.05, 95% confidence interval 1.02-1.09, P = 0.005) and number of surgeries (hazard ratio 1.74, 95% confidence interval 1.05-2.89, P = 0.032). Patients requiring any pituitary hormone replacement increased from 57.9% to 70.0% after RT. CONCLUSIONS: Modern LINAC RT for patients with PAs was safe and effective for hormonal control and LC. No difference in LC was noted for functional versus nonfunctional tumors, possibly owing to higher total dose and daily image guidance.