Histology-specific clinical trial of lenvatinib and pembrolizumab in patients with sarcoma.

PURPOSE: Survival of patients with metastatic sarcoma remains poor, and there is pressing need for new therapies. Most sarcoma subtypes are not responsive to immune checkpoint inhibition alone. Lenvatinib, a multi-receptor tyrosine kinase inhibitor targeting tumor vasculature, has immunomodulatory activity that contributes to its antitumor effects. Therefore we hypothesized that combination of lenvatinib and pembrolizumab would lead to improved clinical outcomes in patients with sarcoma. METHODS: This was an open-label, single-arm study of lenvatinib and pembrolizumab in the following cohorts A: leiomyosarcoma, B: undifferentiated pleomorphic sarcoma (UPS), C: vascular sarcomas (angiosarcoma and epithelioid hemangioendothelioma), D: synovial sarcoma or malignant peripheral nerve sheath tumor (MPNST), and E: bone sarcomas (osteosarcoma and chondrosarcoma). The primary endpoint was best overall response (BOR) rate documented by RECIST v1.1 by 27 weeks in each cohort, with a threshold of ≥2 responses among 10 patients. Secondary endpoints included progression-free survival, overall survival, duration of response and safety. RESULTS: Forty-six patients were evaluable for the primary endpoint which was met in the UPS and MPNST/synovial cohorts (BOR rates by 27 weeks of 25% and 30%,respectively). There were 7 partial responses overall with additional responses noted in angiosarcoma and osteosarcoma. Treatment-related adverse events of any grade, and Grade 3 or higher, occurred in 50/51 (98%) and 29/51 (57%) of patients respectively. CONCLUSIONS: We observed durable responses in MPNST, synovial sarcoma and osteosarcoma. Patients with UPS and angiosarcoma also responded. Further exploration of this approach is warranted to confirm activity and determine optimal dosing schedules.

Growth Rate and Outcomes in Locally Recurrent Extremity and Truncal Soft Tissue Sarcoma.

Importance: Improved prognostic tools are needed for patients with locally recurrent extremity or truncal soft tissue sarcoma (STS). Objective: To examine the association between average local recurrence (LR) growth rate and outcomes following resection of locally recurrent extremity or truncal STS. Design, Setting, and Participants: This retrospective cohort study used a prospectively maintained database from a single high-volume tertiary sarcoma referral center in the US to identify patients 16 years of age or older who underwent repeat resection of a locally recurrent extremity or truncal STS between July 1, 1982, and December 31, 2021. Patients with atypical lipomatous tumors, desmoid tumors, dermatofibrosarcoma protuberans, angiosarcomas, and prior or synchronous distant recurrence were excluded. Data were analyzed from November 1, 2022, to June 17, 2024. Exposure: Average LR growth rate, defined as the sum of recurrent tumor maximal diameters divided by the disease-free interval after index operation. Main Outcomes and Measures: The primary outcomes were cumulative incidences of disease-specific death (DSD), with death from other causes as a competing risk, and second LR, with death from any cause as a competing risk. Results: The study cohort included 253 patients (median [IQR] age, 64 [51-73] years; 140 [55.3%] male). The 5-year cumulative incidence of DSD after repeat resection was 29%. Multivariable analysis indicated that LR growth rate (hazard ratio [HR], 1.12 [95% CI, 1.08-1.18]; P < .001), younger age (HR, 0.98 [95% CI, 0.97-0.99]; P = .002), R1 or R2 margins (HR, 1.71 [95% CI, 1.03-2.84]; P = .04), high LR grade (HR, 2.90 [95% CI, 1.17-7.20]; P = .02), and multifocality (HR, 2.92 [95% CI, 1.70-5.00]; P < .001) were independently associated with higher incidence of DSD. Using the minimum P value method, the optimal cutoff for growth rate was found to be 0.68 cm/mo. Patients with values above this cutoff had higher 5-year incidences of DSD following repeat resection (63% vs 19%; permutation test P < .001) and higher amputation rates (19% vs 7%; P = .008). Only R1 margins were independently associated with higher incidence of second LR (HR, 1.81 [95% CI, 1.19-2.78]; P = .006). Conclusions and Relevance: In this cohort study of patients undergoing resection of a locally recurrent extremity or truncal STS, LR growth rate was independently associated with DSD. These findings suggest that patients with growth rates higher than 0.68 cm/mo who undergo LR resection may have high disease-specific mortality and amputation rates and should be considered for perioperative systemic therapy.

Genome-Derived Ampullary Adenocarcinoma Classifier and Postresection Prognostication.

Importance: Ampullary adenocarcinoma (AA) is characterized by clinical and genomic heterogeneity. A previously developed genomic classifier defined biologically distinct phenotypes with greater accuracy than standard histologic classification. External validation is needed before routine clinical use. Objective: To test external validity of the prognostic value of the hidden genome classifier of AA. Design, Setting, and Participants: This retrospective cohort study took place at 6 international academic institutions. Consecutive patients (n = 192) who underwent curative-intent resection of histologically confirmed AA were included. The data were analyzed from January 2005 through July 2020. Exposures: The multilevel meta-feature regression model previously trained on a prospectively sequenced cohort of 3411 patients (1001 pancreatic adenocarcinoma, 165 distal bile duct adenocarcinoma, and 2245 colorectal adenocarcinoma) was applied to AA sequencing data to quantify the relative proportions of parental cell of origin. Main Outcome and Measures: Genomic classification was correlated with immunohistologic subtype (intestinal [INT] or pancreatobiliary [PB]) and with overall survival (OS), using the log-rank test and Cox proportional hazard models. Results: Among 192 patients with AA (median age, 69.0 [IQR, 60.0-74.0] years and 134 were male [64%]), concordance between immunohistologic and genomic subtypes was 55%. Most INT subtype tumors were categorized into the colorectal genomic subtype (43 of 57 [72.9%]). Of the 114 PB subtype tumors, 29 had a pancreatic genomic profile (25.4%) and 24 had a distal bile duct genomic profile (21.1%). Whereas the standard immunohistologic subtypes were not associated with survival (log rank P = .26), predicted genomic probabilities were correlated with survival probability. Genomic scores with higher colorectal probability were associated with higher survival probability; higher pancreatic and distal bile duct probabilities were associated with lower survival probability. Conclusions and Relevance: The AA genomic classifier is reproducible with available molecular testing in a diverse international cohort of patients and improves stratification of the divergent clinical outcomes beyond standard immunohistologic classification. These data provide a molecular classification that may be incorporated into clinical trials for prospective validation.

Distinct clinical outcomes and biological features of specific KRAS mutants in human pancreatic cancer.

KRAS mutations in pancreatic ductal adenocarcinoma (PDAC) are suggested to vary in oncogenicity but the implications for human patients have not been explored in depth. We examined 1,360 consecutive PDAC patients undergoing surgical resection and find that KRASG12R mutations are enriched in early-stage (stage I) disease, owing not to smaller tumor size but increased node-negativity. KRASG12R tumors are associated with decreased distant recurrence and improved survival as compared to KRASG12D. To understand the biological underpinnings, we performed spatial profiling of 20 patients and bulk RNA-sequencing of 100 tumors, finding enhanced oncogenic signaling and epithelial-mesenchymal transition (EMT) in KRASG12D and increased nuclear factor κB (NF-κB) signaling in KRASG12R tumors. Orthogonal studies of mouse KrasG12R PDAC organoids show decreased migration and improved survival in orthotopic models. KRAS alterations in PDAC are thus associated with distinct presentation, clinical outcomes, and biological behavior, highlighting the prognostic value of mutational analysis and the importance of articulating mutation-specific PDAC biology.

Comparison of perioperative outcomes between colorectal operations performed on weekends vs those performed on weekdays.

BACKGROUND: Weekend surgical time is an underused asset. Concerns over a possible weekend effect (substandard care) may be a barrier. METHODS: This study examined whether a weekend effect applies to elective colorectal surgery via a single-center retrospective analysis comparing outcomes between patients who underwent elective colorectal surgery on a weekend vs a weekday. Demographics, length of stay (LOS), operative and anesthesia time, the rate of reoperation within 30 days, and the rate of major complications were compared between patient groups. RESULTS: Of the 2008 patients identified, 1721 (85.7%) underwent surgery on a weekday, and 287 (14.3%) underwent surgery on a weekend. The proportion of operations with an open approach was higher on weekends than weekdays (49.5% vs 41.8%, P = .017). Patients who underwent surgery on the weekend tended to have a shorter mean (SE) for LOS (4.2 [0.2] vs 6.1 [0.2], P < .001), anesthesia time (233.8 [6.5] vs 307.6 [3.3] minutes, P < .001), and operative time (225.4 [6.4] vs. 297.6 [3.3] minutes, P < .001). On multivariable analysis, patients who had an operation on a weekend had a 38% lower chance of having a prolonged LOS (>75th percentile of LOS) compared with those who had an operation on a weekday (adjusted odds ratio = 0.62; 95% CI 0.42-0.92). There were no differences in rates of complications or reoperation for patients undergoing surgery on a weekend compared with a weekday. CONCLUSION: At centers with experienced anesthesiologists, appropriately trained nursing staff, and expert surgeons, colorectal surgery performed on a weekend has similar safety outcomes as surgeries performed on a weekday.

Safety of Selective Operative Drainage After Pancreatic Resection: A Retrospective Analysis of 2,607 Patients.

OBJECTIVE: To assess whether selective omission of operative drains after pancreaticoduodenectomy (PD) and distal pancreatectomy (DP) is associated with adverse perioperative outcomes. BACKGROUND: The routine use of operative drains after pancreatectomy is widely practiced; however, prospective randomized clinical trials and retrospective analyses have shown mixed results. METHODS: Patients who underwent PD or DP between November 2009 and May 2021 were reviewed and stratified by operative drain placement. Patient demographics, morbidity, the need for additional procedures, and mortality were compared between patients who did or did not develop a clinically relevant post-operative pancreatic fistula (CR-POPF). RESULTS: In total, 1,855 PD and 752 DP cases were analyzed. Among PD patients with a CR-POPF (N=259, 14%), 160 (62%) had an operative drain placed, of whom 141 (88%) required at least 1 additional procedure. Within this subgroup, grade ≥ 4 complications (7.5% vs. 11.1%, P=0.37), 90-day mortality (3.8% vs. 6.1%, P=0.54), length of stay (LOS) (median 12 vs. 13 d, P=0.19) and readmission rates (63.1% vs. 54.6%, P=0.19) were similar between drained and non-drained patients. Of note, drained PD patients without a CR-POPF had a longer hospital stay (8 vs. 7 d, respectively, P=0.004) and more thromboembolic events (2.4% vs. 1.1%, respectively, P=0.04) Among DP patients with a CR-POPF (n=129), 44 had an operative drain, with 37 (84%) requiring an additional procedure. Within this subgroup, grade ≥ 4 complications (4.6% vs. 5.9%, P>0.95), 90-day mortality (0%), LOS (median 7 d for both, P=0.88) and readmission rates (72.7% vs. 80%, P=0.38) were similar in drained and non-drained patients. CONCLUSION: This study confirms that selective omission of operative drains does not compromise perioperative outcomes, as initially reported in our prospective randomized trial.

Impact of Delirium Onset and Duration on Mortality in Patients With Cancer Admitted to the ICU.

BACKGROUND: Little is known on the effects of delirium onset and duration on outcome in critically ill patients with cancer. OBJECTIVES: To determine the impact of delirium onset and duration on intensive care unit (ICU) and hospital mortality and length of stay (LOS) in patients with cancer. METHODS: Of the 915 ICU patients admitted in 2018, 371 were included for analysis after excluding for terminal disease, <24-h ICU stay, lack of active cancer and delirium. Delirium was defined as early if onset was within 2 days of ICU admission, late if onset was on day 3 or later, short if duration was 2 days or less, and long if duration was 3 days or longer. Patients were placed into 4 combination groups: early-short, early-long, late-short, and late-long delirium. Multivariate analysis controlling for sex, age, metastatic disease, and predelirium hospital LOS was performed to determine ICU and hospital mortality and LOS. Exploratory analysis of long-term survival was also performed. Restricted cubic splines were performed to confirm the use of 2 days to distinguish between early versus late onset and short versus long duration. RESULTS: A total of 32.9% (n = 122) patients had early-short, 39.1% (n = 145) early-long, 16.2% (n = 60) late-short, and 11.9% (n = 44) late-long delirium. Late-long delirium was independently associated with increased ICU (OR 4.45, CI 1.92-10.30; P < .001) and hospital (OR 2.91, CI 1.37-6.19; P = .005) mortality and longer ICU (OR 1.97, CI 1.58-2.47; P < .001) LOS compared to early-short delirium. Early delirium had better overall survival at 18 months than late delirium. Long-term survival further improved when delirium duration was 2 days or less. Prediction heatmaps confirm the use of a 2-day cutoff. CONCLUSION: Late delirium, especially with long duration, significantly worsens outcome in ICU patients with cancer and should be considered a harbinger of poor overall condition.

Immune reconstitution, vaccine responses, and rituximab use after ex-vivo CD34-selected myeloablative allogenic hematopoietic cell transplantation.

Myeloablative T cell depleted (CD34-selected) hematopoietic cell transplantation (HCT) is associated with less acute and chronic graft versus host disease (GVHD). We aimed to examine vaccine responses in relation to immune reconstitution and post HCT rituximab administration in this population. This single center retrospective study included 251 patients with hematological malignancies who received a first CD34-selected HCT between 2012 and 2015. Of 251 patients, 190 were alive 1 year after HCT. Among the entire population, 77 (30.7%) patients were vaccinated. After vaccine administration, 35/44 (80%), 30/75 (40%), 27/36 (75%), 33/65 (51%), 34/51 (51%), 22/28 (79%) and 20/34 (59%) of evaluable patients had protective antibody titers for haemophilus influenzae type B (Hib), Pneumococcus, Tetanus, Diphtheria, Pertussis, hepatitis A (HAV), and hepatitis B (HBV) respectively. Responders to the pneumococcal vaccine had a higher CD45RA T cell count than non responders, with 12/18 patients (66.7%) vs 11/32 (34.4%) p = 0.04. For pneumococcal vaccine, there was also a trend to higher total lymphocyte B cell count in responders vs non responders p = 0.06. Rituximab post HCT was given to 59/251 (23.5%) patients. No difference was found in immune reconstitution patterns for rituximab use between vaccine responders and not. Recipients of CD34-selected HCT may respond to vaccination, and T and B cell subsets could be useful to predict vaccine response.

Randomized Prospective Trial of Epidural Analgesia after Open Hepatectomy.

OBJECTIVE: To evaluate whether patient-controlled epidural analgesia (PCEA) improves postoperative pain during ambulation following elective open hepatectomy. BACKGROUND: Strategies to alleviate postoperative pain are a critical element of recovery after surgery. However, the optimal postoperative pain management strategy following open hepatectomy remains unclear. METHODS: We conducted a prospective, nonblinded, randomized comparison of PCEA (intervention) versus intravenous patient-controlled analgesia (IV PCA; control) for postoperative pain following elective open hepatectomy. The primary end point was pain during ambulation on postoperative day (POD) 2. The study was powered to detect a clinically significant 2-point difference on the pain numeric rating scale (NRS). Secondary end points included pain at rest, morbidity, time to return of bowel function, and length of stay. RESULTS: From 2015 to 2020, 231 patients were randomized (116 patients in the PCEA arm and 115 in the IV PCA arm). The incidence of epidural failure was 3% (n=4/116), with no epidural-related complications. Patients in the PCEA arm had a <2-point difference in NRS pain scores during ambulation on POD 2 vs. IV PCA (median 4.0 vs. 5.0, P <0.001). There was no difference in overall complications between the PCEA and IV PCA arms (33% vs. 40%, P =0.276). Secondary outcomes, including pain scores at rest, were similar between the study arms. CONCLUSIONS: PCEA was safe following open hepatectomy and was associated with a small difference in pain with activity on POD 2 that did not reach our pre-specified definition of clinical significance.

Therapy-Induced Senescence Contributes to the Efficacy of Abemaciclib in Patients with Dedifferentiated Liposarcoma.

PURPOSE: We conducted research on CDK4/6 inhibitors (CDK4/6i) simultaneously in the preclinical and clinical spaces to gain a deeper understanding of how senescence influences tumor growth in humans. PATIENTS AND METHODS: We coordinated a first-in-kind phase II clinical trial of the CDK4/6i abemaciclib for patients with progressive dedifferentiated liposarcoma (DDLS) with cellular studies interrogating the molecular basis of geroconversion. RESULTS: Thirty patients with progressing DDLS enrolled and were treated with 200 mg of abemaciclib twice daily. The median progression-free survival was 33 weeks at the time of the data lock, with 23 of 30 progression-free at 12 weeks (76.7%, two-sided 95% CI, 57.7%-90.1%). No new safety signals were identified. Concurrent preclinical work in liposarcoma cell lines identified ANGPTL4 as a necessary late regulator of geroconversion, the pathway from reversible cell-cycle exit to a stably arrested inflammation-provoking senescent cell. Using this insight, we were able to identify patients in which abemaciclib induced tumor cell senescence. Senescence correlated with increased leukocyte infiltration, primarily CD4-positive cells, within a month of therapy. However, those individuals with both senescence and increased TILs were also more likely to acquire resistance later in therapy. These suggest that combining senolytics with abemaciclib in a subset of patients may improve the duration of response. CONCLUSIONS: Abemaciclib was well tolerated and showed promising activity in DDLS. The discovery of ANGPTL4 as a late regulator of geroconversion helped to define how CDK4/6i-induced cellular senescence modulates the immune tumor microenvironment and contributes to both positive and negative clinical outcomes. See related commentary by Weiss et al., p. 649.

Rehabilitation of pediatric retinoblastoma patients with ocular prostheses and their subsequent modifications: A 15-year retrospective study.

PURPOSE: Enucleation is a common treatment modality performed for pediatric retinoblastoma patients, and the resultant defects are reconstructed using an ocular prosthesis. The prostheses are modified or replaced periodically, as the child develops due to orbital growth and patient-error. The purpose of this report is to evaluate the replacement frequency of prostheses in the pediatric oncologic population. METHODS: A retrospective review was completed by the two senior research investigators, of patients that had ocular prostheses fabricated following enucleation of their retinoblastoma from 2005 to 2019 (n = 90). Data collected from the medical records of the patient included the pathology, date of surgery, date of prosthesis delivery, and the replacement schedule of the ocular prosthesis. RESULTS: During the 15-year study period, 78 enucleated observations (ocular prosthesis fabricated) were included for analysis. The median age of the patients at the time of delivery of their first ocular prosthesis was calculated to be 2.6 years (range 0.3-18 years). The median time to the first modification of the prosthesis was calculated to be 6 months. The time to modification of the ocular prosthesis was further stratified by age. CONCLUSION: Pediatric patients require modification of their ocular prostheses throughout their growth and development period. Ocular prostheses are reliable prostheses with predictable outcomes. This data is helpful to set an expectation among the patient, parent, and provider.

Immune-related Adverse Events after Immune Checkpoint Blockade-based Therapy Are Associated with Improved Survival in Advanced Sarcomas.

The association between immune-related AEs (irAE) and outcome in patients with sarcoma is not known. We retrospectively reviewed a cohort of patients with advanced sarcoma treated with immune checkpoint blockade (ICB)-based therapy. Association of irAEs with survival was assessed using a Cox regression model that incorporated irAE occurrence as a time-dependent covariate. Tumor samples with available RNA sequencing data were stratified by presence of an irAE to identify patterns of differential gene expression. A total of 131 patients were included. Forty-two (32%) had at least one irAE of any grade and 16 (12%) had at least one grade ≥ 3 irAE. The most common irAEs were hypothyroidism (8.3%), arthralgias (5.3%), pneumonitis (4.6%), allergic reaction (3.8%), and elevated transaminases (3.8%). Median progression-free survival (PFS) and overall survival (OS) from the time of study entry were 11.4 [95% confidence interval (CI), 10.7-15.0) and 74.6 weeks (CI, 44.9-89.7), respectively. On Cox analysis adjusting for clinical covariates that were significant in the univariate setting, the HR for an irAE (HR, 0.662; CI, 0.421-1.041) approached, but did not reach statistical significance for PFS (P = 0.074). Patients had a significantly lower HR for OS (HR, 0.443; CI, 0.246-0.798; P = 0.007) compared with those without or before an irAE. Gene expression profiling on baseline tumor samples found that patients who had an irAE had higher numbers of tumor-infiltrating dendritic cells, CD8+ T cells, and regulatory T cells as well as upregulation of immune and inflammatory pathways. SIGNIFICANCE: irAE after ICB therapy was associated with an improved OS; it also approached statistical significance for improved PFS. Patients who had an irAE were more likely to have an inflamed tumor microenvironment at baseline.

Persistence of Telemedicine Usage for Breast and Prostate Cancer after the Peak of the COVID-19 Pandemic.

While COVID-19 catalyzed a shift to telemedicine, little is known about the persistence of remote cancer care in non-emergent times. We assessed telemedicine use at a high-volume academic cancer center in New York City and analyzed breast and prostate cancer visits pre-COVID-19, peak COVID-19, and post-peak. Descriptive statistics assessed visit mode (in person, telemedicine) and type (new, follow-up, other) by department/specialty, with Fisher's exact tests comparing peak/post-peak differences. The study included 602,233 visits, with telemedicine comprising 2% of visits pre-COVID-19, 50% peak COVID-19, and 30% post-peak. Notable variations emerged by department/specialty and visit type. Post-peak, most departments/specialties continued using telemedicine near or above peak levels, except medicine, neurology, and survivorship, where remote care fell. In psychiatry, social work, and nutrition, nearly all visits were conducted remotely during and after peak COVID-19, while surgery and nursing maintained low telemedicine usage. Post-peak, anesthesiology and neurology used telemedicine seldom for new visits but often for follow-ups, while nursing showed the opposite pattern. These trends suggest department- and visit-specific contexts where providers and patients choose telemedicine in non-emergent conditions. More research is needed to explore these findings and evaluate telemedicine's appropriateness and impact across the care continuum.

Hepatic disease control in patients with intrahepatic cholangiocarcinoma correlates with overall survival.

PURPOSE: The role of locoregional therapy compared to systemic chemotherapy (SYS) for unresectable intrahepatic cholangiocarcinoma (IHC) remains controversial. The importance of hepatic disease control, either as initial or salvage therapy, is also unclear. We compared overall survival (OS) in patients treated with resection, hepatic arterial infusion pump (HAIP) chemotherapy, or SYS as it relates to hepatic recurrence or progression. We also evaluated recurrence after resection to determine the efficacy of locoregional salvage therapy. PATIENTS AND METHODS: In this single-institution retrospective analysis, patients with biopsy-proven IHC treated with either curative-intent resection, HAIP (with or without SYS), or SYS alone were analyzed. Propensity score matching (PSM) was used to compare patients with liver-limited, advanced disease treated with HAIP versus SYS. The impact of locoregional salvage therapies in patients with liver-limited recurrence was analyzed in the resection cohort. RESULTS: From 2000 to 2017, 714 patients with IHC were treated, 219 (30.7%) with resectable disease, 316 (44.3%) with locally advanced disease, and 179 (25.1%) with metastatic disease. Resected patients were less likely to recur or progress in the liver (hazard ratio [HR] 0.41, 95% CI 0.34-0.45) versus those that received HAIP or SYS (HR 0.58, 95% CI 0.50-0.65 vs. HR 0.63, 95% CI 0.57-0.69, respectively). In resected patients, 161 (64.4%) recurred, with 65 liver-only recurrences. Thirty of these patients received subsequent locoregional therapy. On multivariable analysis, locoregional therapy was associated with improved OS after isolated liver recurrence (HR 0.46, 95% CI 0.29-0.75; p = 0.002). In patients with locally advanced unresectable or multifocal liver disease (with or without distant organ metastases), PSM demonstrated improved hepatic progression-free survival in patients treated with HAIP versus SYS (HR 0.65; 95% CI 0.46-0.91; p = 0.01), which correlated with improved OS (HR 0.59, 95% CI 0.43-0.80; p < 0.001). CONCLUSION: In patients with liver-limited IHC, hepatic disease control is associated with improved OS, emphasizing the potential importance of liver-directed therapy.

Delirium as a Risk Factor for Mortality in Critically Ill Patients With Cancer.

PURPOSE: Although delirium is known to negatively affect critically ill patients, little data exist on delirium in critically ill patients with cancer. METHODS: We analyzed 915 critically ill patients with cancer between January and December 2018. Delirium screening was performed using the Confusion Assessment Method for the intensive care unit (ICU), performed twice daily. Confusion Assessment Method-ICU incorporates four features of delirium: acute fluctuations in mental status, inattention, disorganized thinking, and altered levels of consciousness. Multivariable analysis controlling for admitting service, pre-ICU hospital length of stay (LOS), metastatic disease, CNS involvement, Mortality Probability Model II score on ICU admission, mechanical ventilation, and others was performed to determine precipitating factors for delirium, ICU, and hospital mortality and LOS. RESULTS: Delirium occurred in 40.5% (n = 317) of patients; 43.8% (n = 401) were female; the median age was 64.9 (interquartile range, 54.6-73.2) years; 70.8% (n = 647) were White, 9.3% (n = 85) were Black, and 8.9% (n = 81) were Asian. The most common cancer types were hematologic (25.7%, n = 244) and gastrointestinal (20.9%, n = 191). Delirium was independently associated with age (OR, 1.01; 95% CI, 1.00 to 1.02; P = .038), longer pre-ICU hospital LOS (OR, 1.04; 95% CI, 1.02 to 1.06; P < .001), not resuscitating on admission (OR, 2.18; 95% CI, 1.07 to 4.44; P = .032), CNS involvement (OR, 2.25; 95% CI, 1.20 to 4.20; P = .011), higher Mortality Probability Model II score (OR, 1.02; 95% CI, 1.01 to 1.02; P < .001), mechanical ventilation (OR, 2.67; 95% CI, 1.84 to 3.87; P < .001), and sepsis diagnosis (OR, 0.65; 95% CI, 0.43 to 0.99; P = .046). Delirium was also independently associated with higher ICU mortality (OR, 10.75; 95% CI, 5.91 to 19.55; P < .001), hospital mortality (OR, 5.84; 95% CI, 4.03 to 8.46; P < .001), and ICU LOS (estimate, 1.67; 95% CI, 1.54 to 1.81; P < .001). CONCLUSION: Delirium significantly worsens outcome in critically ill patients with cancer. Delirium screening and management should be integrated into the care of this patient subgroup.

Indicators of Clinical Trajectory in Patients With Cancer Who Receive Cardiopulmonary Resuscitation.

BACKGROUND: Patients with cancer who require cardiopulmonary resuscitation (CPR) historically have had low survival to hospital discharge; however, overall CPR outcomes and cancer survival have improved. Identifying patients with cancer who are unlikely to survive CPR could guide and improve end-of-life discussions prior to cardiac arrest. METHODS: Demographics, clinical variables, and outcomes including immediate and hospital survival for patients with cancer aged ≥18 years who required in-hospital CPR from 2012 to 2015 were collected. Indicators capturing the overall declining clinical and oncologic trajectory (ie, no further therapeutic options for cancer, recommendation for hospice, or recommendation for do not resuscitate) prior to CPR were determined a priori and manually identified. RESULTS: Of 854 patients with cancer who underwent CPR, the median age was 63 years and 43.6% were female; solid cancers accounted for 60.6% of diagnoses. A recursive partitioning model selected having any indicator of declining trajectory as the most predictive factor in hospital outcome. Of our study group, 249 (29%) patients were found to have at least one indicator identified prior to CPR and only 5 survived to discharge. Patients with an indicator were more likely to die in the hospital and none were alive at 6 months after discharge. These patients were younger (median age, 59 vs 64 years; P≤.001), had a higher incidence of metastatic disease (83.0% vs 62.9%; P<.001), and were more likely to undergo CPR in the ICU (55.8% vs 36.5%; P<.001) compared with those without an indicator. Of patients without an indicator, 145 (25%) were discharged alive and half received some form of cancer intervention after CPR. CONCLUSIONS: Providers can use easily identifiable indicators to ascertain which patients with cancer are at risk for death despite CPR and are unlikely to survive to discharge. These findings can guide discussions regarding utility of resuscitation and the lack of further cancer interventions even if CPR is successful.

Identifying Nonpatient Authors of Patient Portal Secure Messages in Oncology: A Proof-of-Concept Demonstration of Natural Language Processing Methods.

PURPOSE: Patient portal secure messages are not always authored by the patient account holder. Understanding who authored the message is particularly important in an oncology setting where symptom reporting is crucial to patient treatment. Natural language processing has the potential to detect messages not authored by the patient automatically. METHODS: Patient portal secure messages from the Memorial Sloan Kettering Cancer Center were retrieved and manually annotated as a predicted unregistered proxy (ie, not written by the patient) or a presumed patient. After randomly splitting the annotated messages into training and test sets in a 70:30 ratio, a bag-of-words approach was used to extract features and then a Least Absolute Shrinkage and Selection Operator (LASSO) model was trained and used for classification. RESULTS: Portal secure messages (n = 2,000) were randomly selected from unique patient accounts and manually annotated. We excluded 335 messages from the data set as the annotators could not determine if they were written by a patient or proxy. Using the remaining 1,665 messages, a LASSO model was developed that achieved an area under the curve of 0.932 and an area under the precision recall curve of 0.748. The sensitivity and specificity related to classifying true-positive cases (predicted unregistered proxy-authored messages) and true negatives (presumed patient-authored messages) were 0.681 and 0.960, respectively. CONCLUSION: Our work demonstrates the feasibility of using unstructured, heterogenous patient portal secure messages to determine portal secure message authorship. Identifying patient authorship in real time can improve patient portal account security and can be used to improve the quality of the information extracted from the patient portal, such as patient-reported outcomes.

Histology-Specific Prognostication for Radiation-Associated Soft Tissue Sarcoma.

PURPOSE: Radiation-associated sarcomas (RAS) are rare but aggressive malignancies. We sought to characterize the histology-specific presentation and behavior of soft tissue RAS to improve individualized prognostication. METHODS: A single-institutional prospectively maintained database was queried for all patients with primary, nonmetastatic RAS treated with surgical resection from 1982 to 2019. Patients presenting with the five most common RAS histologies were propensity-matched to those with sporadic tumors of the same histology. Incidence of disease-specific death (DSD) was modeled using cumulative incidence analyses. RESULTS: Among 259 patients with RAS, the five most common histologies were malignant peripheral nerve sheath tumor (MPNST; n = 19), myxofibrosarcoma (n = 20), leiomyosarcoma (n = 24), undifferentiated pleomorphic sarcoma (UPS; n = 55), and angiosarcoma (AS; n = 62). DSD varied significantly by histology (P = .002), with RAS MPNST and UPS having the highest DSD. In unadjusted analysis, RAS MPNST was associated with increased DSD compared with sporadic MPNST (75% v 38% 5-year DSD, P = .002), as was RAS UPS compared with sporadic UPS (49% v 28% 5-year DSD, P = .004). Unadjusted DSD was similar among patients with RAS AS, leiomyosarcoma, or myxofibrosarcoma and sporadic sarcoma of the same histology. After matching RAS to sporadic patients within each histology, DSD only differed between RAS and sporadic MPNST (83% v 46% 5-year DSD, P = .013). Patients with RAS AS presented in such a distinct manner to those with sporadic AS that a successful match was not possible. CONCLUSION: The aggressive presentation of RAS is histology-specific, and DSD is driven by RAS MPNST and UPS histologies. Despite the aggressive presentation, standard prognostic factors can be used to estimate risk of DSD among most RAS. In MPNST, radiation association should be considered to independently associate with markedly higher risk of DSD.