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Background: In the phase 2 EMPOWER-CSCC-1 study (NCT02760498), cemiplimab demonstrated antitumor activity against metastatic (mCSCC) and locally advanced cutaneous squamous cell carcinoma (laCSCC)., Objectives: To report final analysis of weight-based cemiplimab in mCSCC and laCSCC (Groups 1 and 2), fixed-dose cemiplimab in mCSCC (Group 3), and primary analysis of fixed-dose cemiplimab in mCSCC/laCSCC (Group 6)., Methods: Patients received cemiplimab (3 mg/kg intravenously [IV] every 2 weeks [Groups 1 and 2]) or cemiplimab (350 mg IV [Groups 3 and 6]) every 3 weeks. The primary endpoint was objective response rate (ORR). Duration of response (DOR) and progression-free survival (PFS) are presented per protocol, according to post-hoc sensitivity analyses that only include the period of protocol-mandated imaging assessments., Results: At 42.5 months, ORR for Groups 1-3 (n=193) was 47.2%, estimated 12-month DOR was 88.3%, and median PFS was 26.0 months. At 8.7 months, ORR for Group 6 (n=165 patients) was 44.8%; median DOR and median PFS were not reached. Serious treatment-emergent adverse event rates (grade ≥3) were Groups 1-3: 31.1% and Group 6: 34.5%., Limitations: Non-randomized study, non-survival primary endpoint., Conclusion: EMPOWER-CSCC-1 provides the largest prospective data on long-term efficacy and safety for anti-programmed cell death-1 therapy in advanced CSCC., (Copyright © 2024. Published by Elsevier Inc.)

Basal cell carcinoma (BCC) is the most common type of cancer with an estimated 3.6 million cases diagnosed annually in the US alone. While most cases are treatable with low recurrence rates, 1-10% progress to an advanced stage which can behave aggressively, leading to local destruction and posing substantial challenges in management. The pathogenesis often involves dysregulation of the patched/hedgehog protein family, a pivotal pathway targeted by recently approved therapies. Furthermore, the role of immunotherapy is evolving in this type of tumor as we learn more about tumor microenvironment dynamics. In recent years, there have been advancements in the therapeutic landscape of advanced BCC, offering patients new hope and options for managing this complex and potentially life-threatening condition. In this review, we aim to provide a comprehensive overview of this disease, including the risk factors, underlying pathogenesis, current treatment options of advanced disease, and the ongoing exploration and development of novel therapies.

Objectives: Anaplastic thyroid cancer (ATC) is the most aggressive and fatal thyroid malignancy. Currently, there still exists a paucity of literature studying the relationship between available ATC-targeted therapy, immunotherapy, and survival. We aim to investigate how systemic therapies affect survival outcomes in ATC., Methods: A single-tertiary-institution chart review of patients diagnosed with advanced-stage ATC, and who underwent surgery as part of their treatment, was performed between 2000 and 2023, with 41 patients included. Demographics, clinical characteristics, and survival data were collected and analyzed via Kaplan-Meier and Cox proportional hazards analyses., Results: 54% of patients were female, and average age was 67.4 years old. The most common mutations identified were BRAF (15 patients), p53 (9 patients), and p63 (2 patients). A total of 18 patients utilized targeted or immunotherapy, with Trametinib and Dabrafenib (9 patients) as the most common agents used. Two-year overall survival was 24%, and 5-year overall survival was 23%, with median survival time of 7.6 months. Kaplan-Meier analysis demonstrated improved survival in patients who received chemotherapy (p = 0.048). Cox proportional hazards analysis demonstrated that patients treated with immunotherapy or targeted therapy had a statistically significant increase in survival compared with patients who did not receive these therapies (p = 0.016). Additionally, females and those with a p63 mutation demonstrated improved survival outcomes (p = 0.010, p = 0.001)., Conclusions: Targeted therapy and immunotherapy use should be strongly considered when treating patients with ATC. Further studies into novel drugs targeting immune checkpoints and combination therapy are needed to better optimize treatment of patients with ATC., Level of Evidence: 3 Laryngoscope, 2024., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: Crohn's disease can present with complex surgical pathologies, posing a significant risk of morbidity and mortality for patients. The implementation of a loop ileostomy for selected patients may help minimize associated risks., Methods: In this retrospective cohort study, we investigated the utilization of temporary fecal diversion through the creation of a loop ileostomy in Crohn's surgery. Closure of all ostomies involved a hand-sewn single-layer technique. We then conducted bivariate analysis on 30-day outcomes for closures, focusing on favorable recovery defined as the restoration of bowel continuity without the occurrence of two challenges in recovery: newly developed organ dysfunction or the necessity for reoperation., Results: In total, 168 patients were included. The median age of the patients was 38 years (IQR 27-51). The most common indication for a loop ostomy was peritonitis (49%). After ileostomy closure, 163 patients (97%) achieved favorable recovery, while five encountered challenges; four (2.4%) underwent abdominal surgery, and one (0.6%) developed acute renal failure requiring dialysis. Two patients (1.2%) had a re-creation of ileostomy. Patients encountering challenges were older (56 [IQR 41-61] vs. 37 [IQR 27-50]; p 0.039) and more often required secondary intention wound healing (40% vs. 6.7%; p 0.049) and postoperative parenteral nutrition following their index surgery (83% vs. 26%; p 0.006)., Conclusion: Selectively staging the Crohn's disease operations with a loop ileostomy is a reliable practice with low morbidity and high restoration rates of bowel continuity. Our hand-sewn single-layer technique proves effective in achieving successful surgical recovery., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Describe the safety, complications, and need for urgent surgery in patients requiring inpatient rescue infliximab for acute Crohn's disease (CD) flare., Background: Infliximab is increasingly used for patients hospitalized with acute severe ulcerative colitis as rescue therapy; however, optimal management for patients hospitalized for CD flares remains unclear., Methods: A single-institution retrospective study of patients aged 18+ admitted from 2008 to 2020 with acute Crohn's flare requiring induction of rescue infliximab therapy. Outcomes included postoperative and medication-related complications and need for urgent surgery., Results: 52 patients were included in analysis; 8% required surgery on index admission, and 19% required surgery within 90 days of infliximab. Postoperative complications included 1 anastomotic leak, 3 superficial wound infections, 3 prolonged ileus, and 1 urinary infection. There were no adverse reactions to infliximab infusion, and medical complication rates were low. Patients with penetrating disease were more likely to undergo surgery within 90 days of infliximab (43% vs 8%; P = .01). Mean LOS was longer for patients undergoing surgery within 90 days of therapy compared to those who did not (13.4 vs 8.3 days, P = .04)., Conclusion: Inpatient rescue infliximab is safe for treating acute Crohn's disease flare in addition to standard steroid therapy. The majority of patients hospitalized with Crohn's flare requiring rescue infliximab avoided surgery with low postoperative and medication-related complications. More research is needed to clarify the optimal rescue infliximab therapy dosage., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Using a comprehensive Australian cohort, we quantified the incidence and determined the independent predictors of intraoperative and postoperative complications associated with antireflux and hiatus hernia surgeries. In addition, we performed an in-depth analysis to understand the complication profiles associated with each independent risk factor., Background: Predicting perioperative risks for fundoplication and hiatus hernia repair will inform treatment decision-making, hospital resource allocation, and benchmarking. However, available risk calculators do not account for hernia anatomy or technical aspects of surgery in estimating perioperative risk., Methods: Retrospective analysis of all elective antireflux and hiatus hernia surgeries in 36 Australian hospitals over 10 years. Hierarchical multivariate logistic regression analyses were performed to determine the independent predictors of intraoperative and postoperative complications accounting for patient, surgical, anatomic, and perioperative factors., Results: A total of 4301 surgeries were analyzed. Of these, 1569 (36.5%) were large/giant hernias and 292 (6.8%) were revisional procedures. The incidence rates of intraoperative and postoperative complications were 12.6% and 13.3%, respectively. The Charlson Comorbidity Index, hernia size, revisional surgery, and baseline anticoagulant usage independently predicted both intraoperative and postoperative complications. These risk factors were associated with their own complication profiles. Finally, using risk matrices, we visualized the cumulative impact of these 4 risk factors on the development of intraoperative, overall postoperative, and major postoperative complications., Conclusions: This study has improved our understanding of perioperative morbidity associated with antireflux and hiatus hernia surgery. Our findings group patients along a spectrum of perioperative risks that inform care at an individual and institutional level., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Gastric cancers commonly spread to the peritoneum. Its presence significantly alters patient prognosis and treatment-intent; however, current methods of peritoneal staging are inaccurate. Peritoneal tumor DNA (ptDNA) is tumor-derived DNA detectable in peritoneal lavage fluid. ptDNA positivity may indicate peritoneal micrometastasis and may be more sensitive than cytology in staging the peritoneum. In this meta-analysis, we evaluated the prognostic potential of ptDNA in gastric cancer., Methods: PubMed, Embase, Scopus, and Web of Science databases were searched using PRISMA guidelines. Studies published between January 1, 1990, and April 30, 2023, containing quantitative data relating to ptDNA in gastric cancer were meta-analyzed., Results: Six studies were analyzed. Of the total 757 patients with gastric adenocarcinoma, 318 (42.0%) were stage I, 311 (41.0%) were stage II/III, 116 (15.3%) were stage IV, and 22 (2.9%) were undetermined. Overall, ptDNA detected cytology-positive cases with a sensitivity and specificity of 85.2% (95% CI, 66.5 to 100.0) and 91.5% (95% CI, 86.5 to 96.6), respectively. Additionally, ptDNA was detected in 54 (8.5%) of 634 cytology-negative patients. The presence of ptDNA negatively correlated with pathological stage I (relative risk [RR], 0.29 [95% CI, 0.13 to 0.66]) and positively correlated with pathological stage IV (RR, 8.61 [95% CI, 1.86 to 39.89]) disease. Importantly, ptDNA positivity predicted an increased risk of peritoneal-specific metastasis (RR, 13.81 [95% CI, 8.11 to 23.53]) and reduced 3-year progression-free (RR, 5.37 [95% CI, 1.39 to 20.74]) and overall (hazard ratio, 4.13 [95% CI, 1.51 to 11.32]) survival., Conclusion: ptDNA carries valuable prognostic information and can detect peritoneal micrometastases in patients with gastric cancer. Its clinical utility in peritoneal staging for gastric cancer deserves further investigation.

This methodology paper highlights the surgical nuances of a rodent model of venous thrombosis, specifically in the context of cancer-associated thrombosis (CAT). Deep venous thrombosis is a common complication in cancer survivors and can be potentially fatal. The current murine venous thrombosis models typically involve a complete or partial mechanical occlusion of the inferior vena cava (IVC) using a suture. This procedure induces a total or partial stasis of blood and endothelial damage, triggering thrombogenesis. The current models have limitations such as higher variability in clot weights, significant mortality rate, and prolonged learning curve. This report introduces surgical refinements using vascular clips to address some of these limitations. Using a syngeneic colon cancer xenograft mouse model, we employed customized vascular clips to ligate the infrarenal vena cava. These clips allow residual lip space similar to a 5-0 polypropylene suture after IVC ligations. Mice with the suture method served as controls. The vascular clip method resulted in a consistent reproducible partial vascular occlusion and greater clot weights with less variability than the suture method. The larger clot weights, greater clot mass, and clot to the IVC luminal surface area were expected due to the higher pressure profile of the vascular clips compared to a 6-0 polypropylene suture. The approach was validated by gray scale ultrasonography, which revealed consistently greater clot mass in the infrarenal vena cava with vascular clips compared to the suture method. These observations were further substantiated with the immunofluorescence staining. This study offers an improved method to generate a venous thrombosis model in mice, which can be employed to deepen the mechanistic understanding of CAT and in translational research such as drug discovery.

Purpose: This open-label, single-arm, phase II study evaluated the vascular endothelial growth factor receptor 2 (VEGFR2) tyrosine kinase inhibitor (TKI) rivoceranib in patients with recurrent or metastatic (R/M) adenoid cystic carcinoma (ACC)., Patients and Methods: Eligible patients had confirmed disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) with ≥20% increase in radiologically or clinically measurable lesions or appearance of new lesions within the preceding 6 months. Patients received oral rivoceranib 700 mg once daily. Primary outcomes were objective response rate (ORR) by investigator review and by blinded independent review committee (BIRC)., Results: Eighty patients were enrolled and 72 were efficacy evaluable. Seventy-four patients had distant metastases and 49 received prior systemic treatment (14 received VEGFR TKIs). Per investigator and BIRC, respectively, ORR was 15.3% [95% confidence interval (95% CI), 7.9-25.7] and 9.7% (95% CI, 4.0-19.0); median duration of response was 14.9 months (95% CI, 4.9-17.3) and 7.2 months (95% CI, 3.5-8.4); and median progression-free survival was 9.0 months (95% CI, 7.3-11.5) and 9.0 months (95% CI, 7.7-11.5). Grade ≥3 treatment-related adverse events occurred in 56 patients (70.0%); the most common were hypertension (34, 42.5%) and stomatitis (6, 7.5%). Four grade 5 events occurred with one attributed to rivoceranib (epistaxis). Sixty-eight patients (85.0%) had ≥1 dose modifications and 16 patients (20.0%) discontinued rivoceranib for toxicity., Conclusions: In patients with progressing R/M ACC, rivoceranib demonstrated antitumor activity and a manageable safety profile consistent with other VEGFR TKIs., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: Revisional antireflux surgery, including hiatus hernia repair, is increasingly common. Mesh-augmented hiatal closure at the time of index operation is controversial but commonly performed. Although a meta-analysis of randomized data has demonstrated no additional benefit of routine mesh placement, it is unclear whether this practice results in harm, particularly at the time of revisional antireflux surgery. We determined whether pre-existing mesh at the hiatus increases morbidity during and after revisional antireflux surgery., Methods: Analysis of prospectively-maintained databases of all elective revisional antireflux surgery cases in 36 hospitals across Australia took place over 10 years. Intraoperative and postoperative outcomes of patients with and without prior hiatal mesh were compared. Propensity score-matched analysis was used to validate primary findings., Results: A total of 346 revisional cases (35 with pre-existing mesh) were analyzed. The 2 groups had comparable baseline characteristics. In total, 77 (22.2%) patients had 148 intraoperative adverse events. Pre-existing mesh was associated with a higher risk of intraoperative complications (48.6% vs 22.5%, odds ratio 3.25, 95% confidence interval 1.63-6.38, P = .002), secondary to bleeding, and lacerations to pleura, lung, and liver. Overall, 63 (18.2%) patients developed postoperative complications. Pre-existing mesh was associated with increased postoperative morbidity (37.1% vs 16.1%, odds ratio 3.09, 95% confidence interval 1.50-6.43, P = .005), particularly due to bleeding and respiratory complications. Importantly, pre-existing mesh independently predicted the occurrence of intraoperative and postoperative complications., Conclusion: Prior hiatal mesh significantly increases morbidity during and after revisional antireflux surgery. Given that revisional surgery is increasingly being performed, our findings discourage routine mesh use during primary antireflux surgery., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To investigate the effect of the timing of chemoprophylaxis on venous thromboembolisms (VTEs) and bleeding rates in patients undergoing major abdominal surgery., Background: Postoperative bleeding and VTE incur significant morbidity, mortality, and health care costs. Chemoprophylaxis is used routinely to prevent VTEs but increases bleeding risk. The perioperative timing of chemoprophylaxis initiation may influence both VTE and bleeding risks. The optimal window for commencing chemoprophylaxis in the perioperative period is unclear., Methods: MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were searched using PRISMA guidelines. Randomized trials and cohort studies published between January 1, 2000 to May 10, 2022, which reported on chemoprophylaxis timing as well as the incidence of VTE and bleeding after elective abdominal surgery were meta-analyzed., Results: From 6175 studies, 14 (24,922 patients) were meta-analyzed. Bariatric (4 studies), antireflux (1 study), hepato-pancreatic-biliary (5 studies), colorectal (1 study), ventral hernia (1 study), and major intra-abdominal surgeries (2 studies) were included. Chemoprophylaxis was initiated before skin closure in 10,403 patients, and postoperatively in 14,519 patients. Both symptomatic [risk ratios (RR), 0.81; 95% CI, 0.45-1.43; P =0.460] and overall (RR, 0.74; 95% CI, 0.45-1.24; P =0.250) VTE rates were comparable between study groups. Compared with postoperative chemoprophylaxis, early usage increased the risk of all bleeding (RR, 1.56; 95% CI, 1.13-2.15; P =0.007), major bleeding (RR, 1.63; 95% CI, 1.16-2.28; P =0.005), blood transfusion (RR, 1.48; 95% CI, 1.24-1.76; P <0.001), and reintervention (RR, 1.94; 95% CI, 1.19-3.18; P =0.008)., Conclusions: Our findings advocate for initiating chemoprophylaxis postoperatively in elective abdominal surgery to minimize bleeding risk without compromising VTE protection., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

To examine reader characteristics associated with diagnostic efficacy in the interpretation of screening mammograms. A systematic search of the literature was conducted using databases such as Cochrane, Scopus, Medline, Embase, Web of Science, and PubMed. Search terms were combined with "AND" or "OR" and included: "Radiologist's characteristics AND performance"; "radiologist experience AND screening mammography"; "annual volume read AND diagnostic efficacy"; "screening mammography performance OR diagnostic efficacy". Studies were included if they assessed reader performance in screening mammography interpretation, breast readers, used a reference standard to assess the performance, and were published in the English language. Twenty-eight studies were reviewed. Increasing reader's age was associated with lower false positive rates. No association was found between gender and performance. Half of the studies showed no association between years of reading mammograms and performance. Most studies showed that high reading volume was more likely to be associated with increased sensitivity, cancer detection rates (CDR), lower recall rate, and lower false positive rates. Inconsistent associations were found between fellowship training in breast imaging and reader performance. Specialization in breast imaging was associated with better CDR, sensitivity, and specificity. Limited studies were available to establish the association between performance and factors such as time spent in breast imaging (n = 2), screening focus (n = 1), formal rotation in mammography (n = 1), owner of practice (n = 1), and practice type (n = 1). No individual characteristics is associated with versatility in diagnostic efficacy, albeit reading volume and specialization in breast imaging appear to be associated with with increased sensitivity and CDR without significantly affecting other performance metrics., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: This phase 1 study (NCT03440437) evaluated the safety, tolerability, pharmacokinetics (PK), and activity of FS118, a bispecific antibody-targeting LAG-3 and PD-L1, in patients with advanced cancer resistant to anti-PD-(L)1 therapy., Patients and Methods: Patients with solid tumors, refractory to anti-PD-(L)1-based therapy, received intravenous FS118 weekly with an accelerated dose titration design (800 μg to 0.3 mg/kg) followed by 3+3 ascending dose expansion (1 to 20 mg/kg). Primary objectives were safety, tolerability, and PK. Additional endpoints included antitumor activity, immunogenicity, and pharmacodynamics., Results: Forty-three patients with a median of three prior regimens in the locally advanced/metastatic setting, including at least one anti-PD-(L)1 regimen, received FS118 monotherapy. FS118 was well tolerated, with no serious adverse events relating to FS118 reported. No dose-limiting toxicities (DLT) were observed, and an MTD was not reached. The recommended phase 2 dose of FS118 was established as 10 mg/kg weekly. The terminal half-life was 3.9 days. Immunogenicity was transient. Pharmacodynamic activity was prolonged throughout dosing as demonstrated by sustained elevation of soluble LAG-3 and increased peripheral effector cells. The overall disease control rate (DCR) was 46.5%; this disease control was observed as stable disease, except for one late partial response. Disease control of 54.8% was observed in patients receiving 1 mg/kg or greater who had acquired resistance to PD-(L)1-targeted therapy., Conclusions: FS118 was well tolerated with no DLTs observed up to and including 20 mg/kg QW. Further studies are warranted to determine clinical benefit in patients who have become refractory to anti-PD-(L)1 therapy. See related commentary by Karapetyan and Luke, p. 835., (©2022 American Association for Cancer Research.)

Neoantigens are peptides derived from non-synonymous mutations presented by human leukocyte antigens (HLAs), which are recognized by antitumour T cells 1-14 . The large HLA allele diversity and limiting clinical samples have restricted the study of the landscape of neoantigen-targeted T cell responses in patients over their treatment course. Here we applied recently developed technologies 15-17 to capture neoantigen-specific T cells from blood and tumours from patients with metastatic melanoma with or without response to anti-programmed death receptor 1 (PD-1) immunotherapy. We generated personalized libraries of neoantigen-HLA capture reagents to single-cell isolate the T cells and clone their T cell receptors (neoTCRs). Multiple T cells with different neoTCR sequences (T cell clonotypes) recognized a limited number of mutations in samples from seven patients with long-lasting clinical responses. These neoTCR clonotypes were recurrently detected over time in the blood and tumour. Samples from four patients with no response to anti-PD-1 also demonstrated neoantigen-specific T cell responses in the blood and tumour to a restricted number of mutations with lower TCR polyclonality and were not recurrently detected in sequential samples. Reconstitution of the neoTCRs in donor T cells using non-viral CRISPR-Cas9 gene editing demonstrated specific recognition and cytotoxicity to patient-matched melanoma cell lines. Thus, effective anti-PD-1 immunotherapy is associated with the presence of polyclonal CD8 + T cells in the tumour and blood specific for a limited number of immunodominant mutations, which are recurrently recognized over time., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To determine whether early (before skin closure) versus postoperative chemoprophylaxis affects the incidence of venous thromboembolism (VTE) and bleeding following major abdominal surgery, in a high thromboembolic risk population., Background: Major abdominal surgery incurs both VTE and bleeding risks. Patients with high preoperative VTE risk derive the most benefit from chemoprophylaxis, but carry an increased risk of bleeding. The optimal window for chemoprophylaxis in the perioperative period, whereby both VTE and bleeding risks are minimized, is unknown., Methods: Analysis of pooled data from 5 multicenter studies including only high thromboembolic risk (Caprini score >4) patients. Clinical VTE was defined as radiographically proven symptomatic disease <30 days postsurgery. Major bleeding was defined as the need for blood transfusion, reintervention, or >20 g/L fall in hemoglobin., Results: From 5501 cases, chemoprophylaxis was initiated early in 1752 (31.8%) patients and postoperatively in 3749 (68.2%) patients. Baseline characteristics were similar between study groups. The incidence of clinical VTE was not associated with chemoprophylaxis timing [early 0.7% vs. postop 0.7%, odds ratio (OR): 1.11, 95% confidence interval (CI): 0.60-2.15, P =0.730]. Contrastingly, compared with postoperative chemoprophylaxis, early usage increased the risk of all bleeding (5.1% vs. 2.6%, OR: 2.04, 95% CI: 1.52-2.73, P <0.001) major bleeding (3.6% vs. 1.8%, OR: 1.99, 95% CI: 1.40-2.81, P <0.001), and reintervention (2.0% vs. 1.0%, OR: 2.10, 95% CI: 1.32-3.35, P =0.003). Early chemoprophylaxis independently predicted postoperative bleeding (OR: 1.71, 95% CI: 1.25-2.34, P <0.001), but not VTE., Conclusions: In high VTE risk patients undergoing major abdominal surgery, chemoprophylaxis commenced postoperatively reduces bleeding risk without affecting clinical VTE risk., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Expert consensus on the potential benefits of early cancer detection does not exist for most cancer types. We convened 10 practicing oncologists using a RAND/UCLA modified Delphi panel to evaluate which of 20 solid tumors, representing >40 American Joint Committee on Cancer (AJCC)-identified cancer types and 80% of total cancer incidence, would receive potential clinical benefits from early detection. Pre-meeting, experts estimated how long cancers take to progress and rated the current curability and benefit (improvement in curability) of an annual hypothetical multi-cancer screening blood test. Post-meeting, experts rerated all questions. Cancers had varying estimates of the potential benefit of early cancer detection depending on estimates of their curability and progression by stage. Cancers rated as progressing quickly and being curable in earlier stages (stomach, esophagus, lung, urothelial tract, melanoma, ovary, sarcoma, bladder, cervix, breast, colon/rectum, kidney, uterus, anus, head and neck) were estimated to be most likely to benefit from a hypothetical screening blood test. Cancer types rated as progressing quickly but having comparatively lower cure rates in earlier stages (liver/intrahepatic bile duct, gallbladder, pancreas) were estimated to have medium likelihood of benefit from a hypothetical screening blood test. Cancer types rated as progressing more slowly and having higher curability regardless of stage (prostate, thyroid) were estimated to have limited likelihood of benefit from a hypothetical screening blood test. The panel concluded most solid tumors have a likelihood of benefit from early detection. Even among difficult-to-treat cancers (e.g., pancreas, liver/intrahepatic bile duct, gallbladder), early-stage detection was believed to be beneficial. Based on the panel consensus, broad coverage of cancers by screening blood tests would deliver the greatest potential benefits to patients., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: LS, SA, HB, JB, GTB, LC, MC, PC, BJM, DJW reported consulting fees from Partnership for Health Analytic Research (PHAR), LLC and GRAIL, LLC, a subsidiary of Illumina, Inc., currently held separate from Illumina, Inc. under the terms of the Interim Measures Order of the European Commission dated 29 October 2021. ARK and AK are employees of GRAIL, LLC, a subsidiary of Illumina, Inc., currently held separate from Illumina, Inc. under the terms of the Interim Measures Order of the European Commission dated 29 October 2021, who supported this study, and reported stock or stock options in Illumina (parent company of GRAIL, LLC, a subsidiary of Illumina, Inc., currently held separate from Illumina, Inc. under the terms of the Interim Measures Order of the European Commission dated 29 October 2021). MSB, IY, and CC are employees of Partnership for Health Analytic Research (PHAR), LLC which was paid by the following to conduct research related to the work described in the manuscript: Abbvie, Amgen, AstraZeneca, Biomarin Pharmaceuticals, BMS, Celgene, Dompe, Eisai, Exact Sciences Corporation, Genentech, GRAIL, LLC, a subsidiary of Illumina, Inc., currently held separate from Illumina, Inc. under the terms of the Interim Measures Order of the European Commission dated 29 October 2021, Ionis, Jazz, Kite, Novartis, Otsuka, Recordati, Regeneron, Sanofi US Services, Takeda Pharmaceuticals USA. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2022 Schwartzberg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Head and neck squamous cell cancers (HNSCCs) represent a diverse group of tumors emerging within different mucosal surfaces of the oral cavity, nasopharynx, oropharynx, larynx, and hypopharynx. HNSCCs share common clinical risk factors and genomic features, including smoking, alcohol, age, male sex, aneuploidy, and TP53 mutations. Viral initiating and contributing events are increasingly recognized in HNSCCs. While both Epstein-Barr Virus (EBV) and human papilloma virus (HPV) are observed, EBV is more frequently associated with nasopharyngeal cancers whereas HPV is associated with oropharyngeal cancers. HNSCCs are associated with high tumor mutational burden and loss of tumor suppressor gene function, especially in TP53 and X-linked genes. Multiple lines of evidence suggest that HNSCCs are subject to immunologic surveillance and immune-induced evolutionary pressure that correlate with negative clinical outcomes. This review will discuss genomic mechanisms related to immune-mediated pressures and propose prognostic and therapeutic implications of detectable immune escape mechanisms that drive tumorigenesis and disease progression.

Anaplastic thyroid cancer represents a rare, highly aggressive form of thyroid cancer with a poor prognosis and an overall survival ranging from 5 to 12 months. Unfortunately, treatment options remain limited, even for patients with a targetable driver mutation. Here, we present a case of a patient with a BRAF V600E-mutated, PD-L1 positive (tumor proportion score of 95%) anaplastic thyroid cancer refractory to standard therapies, including debulking surgery, followed by chemoradiation, who had further progressed on PD-1 monotherapy, and was unable to tolerate BRAF/MEK inhibition. Ongoing treatment with FS118, a bispecific LAG-3/PD-L1 antagonist, has afforded 3 years of disease control, including a late confirmed partial response, with excellent tolerability. Given this response, further investigation is required to delineate the mechanism by which dual PD-L1/LAG-3 blockade by FS118 overcomes initial PD-1 pathway resistance, and therefore, identify which patients are most likely to benefit. Simultaneously, expanded use should be considered for those with refractory disease, especially if PD-L1 positive. Insights Dual PD-L1/LAG-3 blockade may be an effective treatment strategy for refractory metastatic tumors, including anaplastic thyroid cancer., Competing Interests: Competing interests: MJK, J-BH and OS have no relevant competing interests. LK, MM, and CJS are employees of F-star Therapeutics and hold stock options in F-STAR Therapeutics. DJW has received research funding paid directly to the institution from FSTAR Therapeutics., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Dose-intensified rescue therapy with infliximab for hospitalized patients with ulcerative colitis has become increasingly popular in recent years. However, there is ongoing debate about both the efficacy of these regimens to reduce the rate of colectomy and the associated risks of increased infliximab exposure., Objective: The purpose of this study was to compare the colectomy and postoperative complication rates in hospitalized patients with severe ulcerative colitis receiving standard infliximab induction therapy (3 doses of 5 mg/kg at weeks 0, 2, and 6) and dose-intensified regimens including a higher weight-based dosing or more rapid interval., Design: This was a retrospective cohort study., Settings: This study was conducted at an academic tertiary care hospital., Patients: A total of 145 adult patients received inpatient rescue infliximab therapy for the treatment of ulcerative colitis between 2008 and 2020., Main Outcome Measures: The primary outcome was colectomy rate within 3 months of rescue therapy. Secondary outcomes include mid-term colectomy rates, as well as perioperative complications in patients receiving colectomy within 3 months of rescue infliximab initiation., Results: The proportion of dose-intensified regimens increased over time. Unadjusted 3-month colectomy rates were 14% in patients who received standard rescue infliximab dosing, 16% in patients given a single dose-escalated dose, and 24% in patients given multiple inpatient dose-escalated doses. These rates were not statistically significantly different. Of the patients requiring colectomy within 3 months of infliximab rescue, those who received multiple inpatient doses of dose-escalated therapy had a higher percentage of colectomy during the initial hospitalization but a lower rate of perioperative complications., Limitations: This study was limited by the use of retrospective data and the limited power to account for the heterogeneity of disease., Conclusions: No significant difference was found in colectomy rates between patients receiving standard or dose-intensified regimens. However, dose-intensified regimens, including multiple inpatient doses given to patients with more severe disease, were not associated with a greater risk of perioperative complications. See Video Abstract at http://links.lww.com/DCR/B864 ., La Terapia De Rescate Con Dosis Intensificada De Infliximab En Colitis Ulcerosa Grave No Reduce Las Tasas De Colectoma a Corto Plazo Ni Aumenta Las Complicaciones Posoperatorias: ANTECEDENTES:La terapia de rescate de dosis intensificada con infliximab para pacientes hospitalizados con colitis ulcerosa se ha vuelto cada vez más popular en los últimos años. Sin embargo, existe un debate en curso sobre la eficacia de estos regímenes para reducir la tasa de colectomía y los riesgos asociados a una mayor exposición al infliximab.OBJETIVO:El propósito de este estudio fue comparar las tasas de colectomía y complicaciones posoperatorias en pacientes hospitalizados con colitis ulcerosa grave que recibieron terapia estándar de inducción de infliximab (3 dosis de 5 mg/kg en las semanas 0, 2, 6) y regímenes de dosis intensificada que incluyen una dosificación más alta basada en el peso o intervalo más rápido.DISEÑO:Fue un estudio de cohorte retrospectivo.ENTORNO CLÍNICO:Este estudio se realizó en un hospital académico de tercer nivel.PACIENTES:Un total de 145 pacientes adultos que recibieron terapia de rescate con infliximab para el tratamiento de la colitis ulcerosa entre 2008 y 2020.PRINCIPALES MEDIDAS DE VALORACIÓN:El resultado principal fue la tasa de colectomía dentro de los 3 meses posteriores a la terapia de rescate. Los resultados secundarios incluyen tasas de colectomía a mediano plazo, así como las complicaciones perioperatorias en pacientes que reciben colectomía dentro de los 3 meses posteriores al inicio de infliximab de rescate.RESULTADOS:La proporción de regímenes de dosis intensificada aumentó con el tiempo. Las tasas de colectomía de 3 meses no ajustadas fueron del 14% en los pacientes que recibieron dosis estándar de infliximab de rescate, del 16% en los pacientes que recibieron una dosis única escalonada y del 24% en los pacientes que recibieron múltiples dosis hospitalarias escalonadas. Estas tasas no fueron estadísticamente significativas. De los pacientes que requirieron colectomía dentro de los 3 meses posteriores al rescate de infliximab, aquellos que recibieron terapia de múltiples dosis hospitalarias escalonadas tuvieron un mayor porcentaje de colectomía durante la hospitalización inicial pero una menor tasa de complicaciones perioperatorias.LIMITACIONES:Datos retrospectivos y poder limitado para explicar la heterogeneidad de la enfermedad.CONCLUSIONES:No se encontraron diferencias significativas en las tasas de colectomía entre los pacientes que recibieron regímenes estándar o de dosis intensificada. Sin embargo, los regímenes de dosis intensificadas, incluidas múltiples dosis hospitalarias administradas a pacientes con enfermedad más grave, no se asociaron con un mayor riesgo de complicaciones perioperatorias. Consulte Video Resumen en http://links.lww.com/DCR/B864 . (Traducción-Dr. Ingrid Melo )., (Copyright © The ASCRS 2022.)

Objectives/hypothesis: Psychosocial distress is common among patients with head and neck cancer (HNC) and is associated with poorer quality of life and clinical outcomes. Despite these risks, distress screening is not widely implemented in HNC care. In this study, we investigated the prevalence of psychosocial distress and its related factors in routine care of patients with HNC., Methods: Data from medical records between September 2017 and March 2020 were analyzed. Psychosocial distress was measured by the National Comprehensive Cancer Network's Distress Thermometer (DT), and a modified HNC-specific problem list; depression and anxiety were assessed using the Patient Health Questionnaire-4. Descriptive statistics and logistic regression were conducted to report prevalence of distress, depression and anxiety, and factors associated with clinical distress. Implementation outcomes, including rates of referrals and follow-up for distressed patients, are also reported., Results: Two hundred and eighty seven HNC patients completed the questionnaire (age 64.3 ± 14.9 years), with a mean distress score of 4.51 ± 3.35. Of those, 57% (n = 163) reported clinical distress (DT ≥ 4). Pain (odds ratio [OR] = 3.31, 95% CI = 1.75-6.26), fatigue (OR = 2.43, 95% CI = 1.1.7-5.05), anxiety (OR = 1.63, 95% CI = 1.30-2.05), and depression (OR = 1.51, 95% CI = 1.04-2.18) were significantly associated with clinical distress (P < .05). Of patients identified as distressed, 79% received same-day psychosocial evaluation., Conclusions: Clinical distress was identified in 57% of patients who completed the questionnaire, suggesting that an ultra-brief psychosocial screening protocol can be implemented in routine ambulatory oncology care, and identifies patients whose distress might otherwise go unrecognized., Level of Evidence: 4 Laryngoscope, 132:1600-1608, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Abdominal visceral resections incur relatively higher rates of postoperative bleeding and venous thromboembolism (VTE). While guidelines recommend the use of perioperative chemical thromboprophylaxis, the most appropriate time for its initiation is unknown. Here, we investigated whether early (before skin closure) versus postoperative commencement of chemoprophylaxis affected VTE and bleeding rates following abdominal visceral resection., Methods: Retrospective review of all elective abdominal visceral resections undertaken between January 1, 2018, and June 30, 2019, across four tertiary-referral hospitals. Major bleeding was defined as the need for blood transfusion, reintervention, or > 20 g/L fall in hemoglobin from baseline. Clinical VTE was defined as imaging-proven symptomatic disease < 30 days post-surgery., Results: A total of 945 cases were analyzed. Chemoprophylaxis was given early in 265 (28.0%) patients and postoperatively in 680 (72.0%) patients. Mean chemoprophylaxis exposure doses were similar between the two groups. Clinical VTE developed in 14 (1.5%) patients and was unrelated to chemoprophylaxis timing. Postoperative bleeding occurred in 71 (7.5%) patients, with 57 (80.3%) major bleeds, requiring blood transfusion in 48 (67.6%) cases and reintervention in 31 (43.7%) cases. Bleeding extended length-of-stay (median (IQR), 12 (7-27) versus 7 (5-11) days, p < 0.001). Importantly, compared to postoperative chemoprophylaxis, early administration significantly increased the risk of bleeding (10.6% versus 6.3%, RR 1.45, 95% CI 1.05-1.93, p = 0.038) and independently predicted its occurrence., Conclusions: The risk of bleeding following elective abdominal visceral resections is substantial and is higher than the risk of clinical VTE. Compared with early chemoprophylaxis, postoperative initiation reduces bleeding risk without an increased risk of clinical VTE., (© 2022. The Author(s).)

Background: This phase 1b study investigated safety and activity of combined checkpoint inhibition (CPI) with programmed death-ligand 1 (PD-L1) antibody atezolizumab plus cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor ipilimumab in NSCLC., Patients and Methods: Eligible patients had previously treated locally advanced or metastatic non-small cell lung cancer (NSCLC) or melanoma. A standard 3+3 dose escalation investigated atezolizumab (600-1200 mg IV every 3 weeks) plus ipilimumab starting at 1 mg/kg, administered as a single dose or 4 doses, administered every 3 weeks. The expansion stage included a cohort previously treated with atezolizumab. Patients were monitored for safety and tolerability; response was evaluated every 6 weeks., Results: Twenty-seven patients were enrolled, 4 with melanoma and 23 with NSCLC; here, we focus on data for the NSCLC population. Three of 23 patients (13.0%) received prior CPI. No dose-limiting toxicities were reported during dose escalation; dose expansion occurred with atezolizumab 1200 mg plus 1 cycle of ipilimumab 1 mg/kg. Most common treatment-emergent adverse events were dyspnea (39%) and cough (35%); treatment-related Grade ≥3 adverse events occurred in 11 patients (48%), most frequently pneumonitis (17%) and amylase or lipase elevation (9% each). Six of 23 NSCLC patients (26%) achieved confirmed responses, 5 of whom (25%) were CPI naive. Median duration of response was 23.0 (95% CI, 3.2-36.9) months overall and 36.9 (95% CI, 2.9-36.9) months in CPI-naive patients., Conclusion: Preliminary efficacy of atezolizumab plus ipilimumab was observed in metastatic NSCLC. The combination had manageable toxicity, with a safety profile consistent with those of the individual agents., Competing Interests: Disclosure Dr. Wong reports grants from Genentech, Inc, during the conduct of the study; grants from Lilly, grants from Merck, Sharp & Dohme, grants from KURA Oncology, grants and personal fees from Bristol Myers Squibb, grants from Genentech, grants from AstraZeneca, grants from Astellas, grants and personal fees from Sanofi-Aventis, grants and personal fees from Regeneron, personal fees from Blueprint Medicine, grants from FSTAR, grants from Enzychem, grants from Elevar Therapeutics, outside the submitted work. Dr. Bauer reports grants from Genentech, Inc, during the conduct of the study; grants from Daiichi Sankyo, grants from Medpacto, grants from Incyte, grants from Mirati Therapeutics, grants from MedImmune, grants from Abbvie, grants and personal fees from AstraZeneca, grants from MabVax, grants from Stemline Therapeutics, grants from Merck, grants, personal fees and non-financial support from Lilly, grants from GlaxoSmithKline, grants from Novartis, grants from Genentech, grants from Deciphera, grants from Merrimack, grants from Immunogen, grants from Millennium, grants from Phosplatin Therapeutics, grants from Calithera Biosciences, grants from Kolltan Pharmaceuticals, grants from Principa Biopharma, grants from Peleton, grants from Immunocore, grants from Roche, grants from Aileron Therapeutics, grants, personal fees and non-financial support from Bristol Myers Squibb, grants from Amgen, grants from Onyx, grants from Sanofi, grants from Boehringer-Ingelheim, grants from Astellas Pharma, grants from Five Prime Therapeutics, grants from Jacobio, grants from Top Alliance BioScience, grants from Janssen, grants from Clovis Oncology, grants from Takeda, grants from Karyopharm Therapeutics, grants, personal fees and non-financial support from Foundation Medicine, grants from ARMO Biosciences, grants and other from Leap Therapeutics, grants, non-financial support and other from Ignyta, grants, non-financial support and other from Moderna Therapeutics, grants, personal fees and other from Pfizer, grants, personal fees and non-financial support from Loxo, grants, personal fees and non-financial support from Bayer, personal fees and non-financial support from Guardant Health, personal fees from Exelixis, personal fees from Blueprint Medicines, outside the submitted work. Dr. Gordon reports other from Medimmune, other from Merck, other from BMS, other from Amgen, other from Tesaro, other from Beigene, other from AbbVie, other from Aeglea, personal fees and other from Agenus, other from Arcus, other from Astex, other from BluePrint, other from Calithera, other from CellDex, other from Corcept, other from Clovis, other from Eli Lilly, other from Endocyte, other from RedHill Biopharma, other from Veru, other from Five Prime, other from Genocea, personal fees and other from ImaginAB, personal fees and other from Neon, other from Plexxicon, personal fees from Imaging Endpoints, other from Revolution Medicine, other from IgM Biosciences, other from Seattle Genetics, other from Serono, other from SynDevRx, other from Tolero, personal fees and other from Tracon, personal fees and other from Deciphera, personal fees and other from Salarius, personal fees and other from Daiichi, other from Syndax, other from Incyte, outside the submitted work. Dr. Bene Tchaleu reports employment from F. Hoffmann-La Roche, Ltd., and stock holding of Roche/Genentech, outside the submitted work. Dr. Zhu reports employment from Genentech, Inc., and stock holding of Roche/Genentech, outside the submitted work. Dr. Zhang reports employment from Genentech, Inc., and stock holding of Roche/Genentech, outside the submitted work. Dr. Cha reports employment from Genentech, Inc., and stock holding of Roche/Genentech, outside the submitted work., (Copyright © 2021. Published by Elsevier Inc.)

Background: This study examined patients with advanced non-small-cell lung cancer who received long-term avelumab (anti-PD-L1) in a large phase Ib trial (JAVELIN Solid Tumor). Methods: Patients receiving >2 years of avelumab were reviewed and exploratory descriptive analyses were conducted. Results: Individuals with varying baseline characteristics who had received up to 6 years of avelumab were reviewed. Overall, 37/340 (10.9%) had received ≥2 years of treatment; in this subgroup, best response was complete response in 5.4%, partial response in 59.5% and stable disease in 29.7%; 51.4% had continued treatment beyond disease progression. Conclusions: In this study, 11% of patients with advanced non-small-cell lung cancer received ≥2 years of avelumab treatment and experienced prolonged response or continued clinical benefit. Clinical Trial Registration: NCT02395172 (ClinicalTrials.gov).

Purpose: To determine whether SD-101, a Toll-like receptor 9 agonist, potentiates the antitumor activity of anti-PD-1 antibodies in patients with anti-PD-1/PD-L1 naïve, recurrent/metastatic head and neck squamous cell carcinoma (HNSCC)., Patients and Methods: Patients with PD-1 Ab-naïve HNSCC received either 2 mg SD-101 injected in one to four lesions or 8 mg SD-101 injected into a single lesion weekly × 4 doses then every 3 weeks × 7 doses. Pembrolizumab was administered at 200 mg every 3 weeks., Results: A total of 28 patients received 2 mg and 23 received 8 mg per injection, respectively. A total of 76% of patients had received prior systemic therapy. Combined positive score was ≥1 to < 20 in 35 patients (70%) and ≥ 20 in 15 patients (30%) of 50 patients with available data. There were 12 patients with grade ≥3 treatment-related adverse events (24%), and no treatment-related deaths. The objective response rate was 24% including 2 complete and 10 partial responses. The median duration of response was 7.0 [95% confidence interval (CI): 2.1-11.1] months. The response rate was higher in human papillomavirus-positive (HPV+) patients (44%, N = 16). Responses were not associated with PD-L1 expression levels or IFNγ-related gene expression at baseline. Responses were observed both in injected (32%) and in noninjected lesions (29%). Progression-free and overall survival at 9 months were 19.0% (95% CI: 9.1-31.7) and 64.7% (95% CI: 45.3-78.7), respectively., Conclusions: SD-101 combined with pembrolizumab induced objective responses, especially in HPV+ tumors, which were frequently associated with increased intratumoral inflammation and effector immune cell activity., (©2021 The Authors; Published by the American Association for Cancer Research.)

This Phase Ib study combined programmed death-ligand 1 inhibitor, atezolizumab, with other immunomodulatory agents in locally advanced and metastatic solid tumors. Arms B-D evaluated atezolizumab plus interferon-α, with/without vascular endothelial growth factor inhibitor, bevacizumab, in renal cell carcinoma (RCC) and other solid tumors. Arm B predominantly recruited patients with previously treated RCC or melanoma to receive atezolizumab plus interferon α-2b. Arm C investigated atezolizumab plus polyethylene glycol (PEG)-interferon α-2a in previously treated RCC. Arm D evaluated atezolizumab plus PEG-interferon α-2a and bevacizumab. Primary objectives were safety and tolerability; secondary objectives included clinical activity. Combination therapy was well tolerated, with safety profiles consistent with known risks of individual agents. The most frequent treatment-related toxicities were fatigue, chills, and pyrexia. The objective response rate (ORR) in arm B was 20.0% overall and 17.8% in patients with previously treated checkpoint inhibitor-naive RCC ( n = 45). No responses were reported in arm C. The highest ORR in arm D was 46.7% in patients with treatment-naive RCC ( n = 15). Data showed preliminary clinical activity and acceptable tolerability of atezolizumab plus interferon α-2b in patients with previously treated checkpoint inhibitor-naive RCC and of atezolizumab plus PEG-interferon α-2a and bevacizumab in patients with treatment-naive RCC.

Background: The emergency department plays a common and critical role in the treatment of postoperative patients. However, many quality improvement databases fail to record these interactions. As such, our understanding of the prevalence and etiology of postoperative emergency department visits in contemporary colorectal surgery is limited. Visits with potentially preventable etiologies represent a significant target for quality improvement, particularly in the current era of rapidly evolving postoperative and ambulatory care patterns., Objective: We aimed to characterize postoperative emergency department visits and identify factors associated with these visits for potential intervention., Design: This was a retrospective cohort study., Settings: The study was conducted at an academic medical center., Patients: Consecutive patients undergoing colectomy or proctectomy within the division of colorectal surgery at an academic medical center between 2014 and 2018 were included., Main Outcome Measures: Frequency and indication for emergency department visits, as well as clinical and sociodemographic factors associated with emergency department visits in the postoperative period, were included measures., Results: From the 1763 individual operations, there were 207 emergency department visits from 199 patients (11%) within 30 days of discharge. Two thirds of emergency department visits led to readmission. Median (interquartile range) time to presentation was 8 days (4-16 d). Median time in the emergency department was 7.8 hours (6.0-10.1 h). One third of visits were identified as potentially preventable, most commonly for pain (17%) and stoma complications (excluding dehydration; 13%). A primary language other than English was associated with any postoperative emergency department visit risk ratio of 2.7 (95% CI, 1.3-5.3), as well as a preventable visit risk ratio of 3.6 (95% CI, 1.7-8.0)., Limitations: This was a single-center study and a retrospective review., Conclusions: One third of emergency department visits after colorectal surgery are potentially preventable. Special attention should be directed toward those patients who do not speak English as a primary language. See Video Abstract at http://links.lww.com/DCR/B648., Se Pueden Evitar Las Visitas Al Servicio De Urgencia Despus De Una Ciruga Colorectal: ANTECEDENTES:Las unidades de emergencia tienen un rol fundamental en el periodo posterior a una cirugía. Sin embargo muchos de los registros en las bases de datos de estas secciones no son de buena calidad. Por esto analizar la prevalencia y etiología de las visitas postoperatorias en cirugía colorectal resulta ser bastante limitada. Para lograr una mejoría en la calidad es fundamental analizar las causas potencialmente evitables, especialmente al considerer la rapida evolucion de los parametros de medición actuales.OBJETIVO:Nuestro objetivo es caracterizar las visitas postoperatorias al servicio de urgencias e identificar los factores asociados potencialmente evitables.DISEÑO:Estudio de cohorte retrospectivo.AJUSTE:Centro médico académico, 2014-2018.PACIENTES:Pacientes consecutivos sometidos a colectomía o proctectomía dentro de la división de cirugía colorrectal en un centro médico académico entre 2014 y 2018.PRINCIPALES MEDIDAS DE RESULTADO:Frecuencia e indicación de las visitas al servicio de urgencias en el period postoperatorio: factores clínicos y sociodemográficos.RESULTADOS:De 1763 operaciones individuales, hubo 207 visitas al departamento de emergencias de 199 pacientes (11%) en los 30 días posteriores al alta. Dos tercios de las visitas al servicio de urgencias dieron lugar a readmisiones. La mediana [rango intercuartílico] de tiempo hasta la presentación fue de 8 [4-16] días. La mediana de tiempo en el servicio de urgencias fue de 7,8 [6-10,1] horas. Un tercio de las visitas se identificaron como potencialmente evitables, más comúnmente dolor (17%) y complicaciones del estoma (excluida la deshidratación) (13%). En los pacientes con poco manejo del inglés se asoció con una mayor frecuencia razón de visitas al departamento de emergencias posoperatorias [IC del 95%] 2,7 [1,3-5,3], así como opetancialmente evitables con un RR de 3,6 [1,7-8,0].LIMITACIONES:Estudio de un solo centro y revisión retrospectiva.CONCLUSIÓN:Al menos un tercio de las visitas al servicio de urgencias después de una cirugía colorrectal son potencialmente evitables. Se debe prestar especial atención a los pacientes que no hablan inglés como idioma materno. Consulte Video Resumen en http://links.lww.com/DCR/B648., (Copyright © The ASCRS 2021.)

Background: Recurrent and/or metastatic (R/M) disease develops in approximately 65% of patients with squamous cell carcinoma of the head and neck (SCCHN) and is associated with a poor prognosis. Immune checkpoint inhibitors have proven effective in multiple tumor types, including R/M SCCHN. We report the efficacy and safety of avelumab (antiprogrammed death ligand 1 antibody) in an expansion cohort of patients with platinum-refractory/ineligible R/M SCCHN enrolled in the phase I JAVELIN Solid Tumor trial (NCT01772004)., Methods: Eligible patients with R/M SCCHN were aged ≥18 years and had received ≥1 line of platinum-based chemotherapy with disease progression or recurrence within 6 months of the last dose or were ineligible for platinum-based chemotherapy. All patients received avelumab 10 mg/kg every 2 weeks. Tumor assessments were carried out by a blinded independent review committee (IRC) and investigators according to Response Evaluation Criteria in Solid Tumors V.1.1 (RECIST 1.1). Key endpoints included best overall response, duration of response (DOR) and progression-free survival (PFS) assessed by IRC and investigator per RECIST 1.1, overall survival (OS), and safety., Results: Between April 24, 2015, and November 13, 2015, 153 patients were enrolled. Patients had a median of two prior lines of therapy for metastatic or locally advanced disease (range 0-6); 12 patients (7.8%) were not eligible for platinum-based chemotherapy. At data cut-off (December 31, 2017), the confirmed objective response rate was 9.2% (95% CI 5.1% to 14.9%) assessed by IRC and 13.1% (95% CI 8.2% to 19.5%) assessed by investigator. Median DOR was not reached (95% CI 4.2 to not estimable) based on IRC assessment. Median PFS was 1.4 months (95% CI 1.4 to 2.6) assessed by IRC and 1.8 months (95% CI 1.4 to 2.7) assessed by investigator; median OS was 8.0 months (95% CI 6.5 to 10.2). Any-grade treatment-related adverse events (TRAEs) occurred in 83 patients (54.2%) and were grade ≥3 in 10 patients (6.5%). The most common TRAEs were fatigue (n=19, 12.4%), fever (n=14, 9.2%), pruritus (n=12, 7.8%), and chills (n=11, 7.2%), and there were no treatment-related deaths., Conclusion: Avelumab showed clinical activity and was associated with a low rate of grade ≥3 TRAEs in heavily pretreated patients with platinum-refractory/ineligible R/M SCCHN., Competing Interests: Competing interests: JG reports providing a consulting or advisory role for AstraZeneca, Bristol Myers Squibb, Merck, MSD, Nanobiotix, and Innate Pharma; and has received research funding from Bristol Myers Squibb, Chugai Pharmaceutical Co., Merck and GlaxoSmithKline. K-WL reports providing a consulting or advisory role for Bayer and ISU ABXIS; has received honoraria from Bristol Myers Squibb, Eli Lilly, and Genexine; and received research funding from ABL Bio, ALX Oncology, AstraZeneca/MedImmune, BeiGene, Daiichi Sankyo, Five Prime Therapeutics, GC Pharma, Genexine, LSK BioPharma, MacroGenics, MSD, Merck, Oncologie, Ono Pharmaceutical, Pfizer, Pharmacyclics, Taiho Pharmaceutical, Y-BIOLOGICS, and Zymeworks (to his institution for conducting clinical trials). MRP has received honoraria from AbbVie, Bayer, Genentech, Janssen Pharmaceutical, Pharmacyclics, and Pfizer; provided speakers services for Celgene, Merck, and Exelixis; and research funding from Acerta Pharma, ADC Therapeutics, Agenus, Aileron Therapeutics, AstraZeneca, Bicycle Therapeutics, BioNTech, Boehringer Ingelheim, Calithera Biosciences, Celgene, Checkpoint Therapeutics, Ciclomed, Covis Pharma, Curis, Cyteir Therapeutics, Daiichi Sankyo, eFFECTOR Therapeutics, Eli Lilly, Merck, Evelo Biosciences, Forma Therapeutics, Genentech/Roche, Gilead, GlaxoSmithKline, H3 Biomedicine, Hengrui Therapeutics, Hutchinson MediPharma, Ignyta, Incyte, Jacobio Pharmaceuticals, Janssen Pharmaceutical, Jounce Therapeutics, KLUS Pharma, Kymab, Loxo Oncology, LSK Biopartners, Lycera, MacroGenics, Merck, Millennium Pharmaceuticals, Mirati Therapeutics, Moderna, Pfizer, Phoenix Molecular Designs, Placon Therapeutics, Portola Pharmaceuticals, Prelude Therapeutics, Qilu Puget Sound Biotherapeutics, Revolution Medicines, Ribon Therapeutics, Seven and Eight Biopharmaceuticals, Stemline Therapeutics, Syndax, Synthorx, Taiho Pharmaceutical, Takeda, Tesaro, TopAlliance, Vedanta Biosciences, Verastem Oncology, Vigeo Therapeutics, and Xencor. AD reports providing a consulting or advisory role for and receiving reimbursement for travel and accommodation expenses from Bristol Myers Squibb and Merck. DW reports providing a consulting or advisory role for Bristol Myers Squibb and Sanofi-Aventis, and has received research funding from Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Enzychem Lifesciences, F-star, Genentech, Iovance Biotherapeutics, Kura Oncology, MSD, Merck, Pfizer, Regeneron, and Sanofi. MSG reports providing a consulting or advisory role for Deciphera Pharmaceuticals, ImaginAb, Redhill Biopharma, and TRACON Pharmaceuticals; and owns stock in Caremission and Medilus. MG reports providing a consulting or advisory role for Guardant360; speakers services for Merck; has received research funding from Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Care Progress, Celgene, Compass Therapeutics, Constellation Pharmaceuticals, CytRx, Eisai, Esanex, Genentech, Incyte, Infinity Pharmaceuticals, Janssen, Karyopharm Therapeutics, MedImmune, Merck, Mirati Therapeutics, Moderna, Pfizer, Regeneron, Sanofi, Seattle Genetics, Tesaro, and Vendata Biosciences; owns stock in Cota Healthcare; and is an employee of Reginal Cancer Care Associates. AB reports providing speakers services for AstraZeneca, Bristol Myers Squibb, Eli Lilly, Genentech, and Merck; and has received research funding from Arcus Biosciences, Bristol Myers Squibb, Genentech, GlaxoSmithKline, MedImmune, and Merck. CLT has received honoraria from Amgen, AstraZeneca, Bristol Myers Squibb, Merck, GlaxoSmithKline, MSD, Nanobiotix, Rakuten, Roche, and Seattle Genetics; provided a consulting or advisory role for Idem Healthcare; and reimbursement for travel and accommodation expenses from AstraZeneca, Bristol Myers Squibb, Merck, and MSD. DV reports providing a consulting or advisory role for Nestlé and Nutricia. PS has received honoraria from Blueprint Medicines, Boehringer Ingelheim, and Deciphera Pharmaceuticals; provided a consulting or advisory role for Adaptimmune, Advanced Medical, Blueprint Medicines, Boehringer Ingelheim, Deciphera, Ellipses Pharma, Exelixis, Guided Clarity, Intellisphere, Medscape, and Transgene; research funding from CoBioRes, Eisai, G1 Therapeutics, Novartis, and PharmaMar; and reimbursement for travel and accommodation expenses from Boehringer Ingelheim, Ipsen, and MSD. HJG is an employee of Merck Healthcare KGaA, Darmstadt, Germany. DZ is an employee of Merck Serono (Beijing) Pharmaceutical R&D Co., Ltd. Beijing, China, an affiliate of Merck KGaA. MB is an employee of Merck Healthcare KGaA, Darmstadt, Germany. All other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Events mediated by the P-selectin/PSGL-1 pathway play a critical role in the initiation and propagation of venous thrombosis by facilitating the accumulation of leukocytes and platelets within the growing thrombus. Activated platelets and endothelium express P-selectin, which binds P-selectin glycoprotein ligand-1 (PSGL-1) that is expressed on the surface of all leukocytes. We developed a pegylated glycomimetic of the N terminus of PSGL-1, PEG40-GSnP-6 (P-G6), which proved to be a highly potent P-selectin inhibitor with a favorable pharmacokinetic profile for clinical translation. P-G6 inhibits human and mouse platelet-monocyte and platelet-neutrophil aggregation in vitro and blocks microcirculatory platelet-leukocyte interactions in vivo. Administration of P-G6 reduces thrombus formation in a nonocclusive model of deep vein thrombosis with a commensurate reduction in leukocyte accumulation, but without disruption of hemostasis. P-G6 potently inhibits the P-selectin/PSGL-1 pathway and represents a promising drug candidate for the prevention of venous thrombosis without increased bleeding risk., (© 2021 by The American Society of Hematology.)

Enhanced Recovery after Surgery (ERAS) pathways in colorectal surgery improve outcomes and reduce disparities, but pathway adherence rates are variable. Sustainability of adherence following initial implementation, particularly in academic settings with trainee involvement, is underexplored. This study measures and describes ERAS adherence for 163 consecutive patients undergoing elective colorectal resection in an academic colorectal surgery department with a well-established ERAS pathway. Providers, including residents and nursing staff, were surveyed regarding pathway knowledge and obstacles to adherence. Adherence was higher preoperatively (80%) and intraoperatively (93%) than postoperatively (61%). Opioid-sparing analgesia and bowel motility agents were underdosed on up to 63% of hospital days, without clinical rationale in ≥50% of cases. Providers cited peer teaching (71%) as the primary source of pathway knowledge and identified individual surgeon preferences as an obstacle to adherence. Formalized ERAS pathway education, communication, and coordination among attending physicians are needed to reduce provider-driven deviation in an academic setting., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Problem: Health professions education does not routinely incorporate training in innovation or creative problem solving. Although some models of innovation education within graduate medical education exist, they often require participants' full-time commitment and removal from clinical training or rely upon participants' existing expertise. There is a need for curricula that teach innovation skills that will enable trainees to identify and solve unmet clinical challenges in everyday practice. To address this gap in surgical graduate education, the authors developed the Surgical Program in Innovation (SPIN)., Approach: SPIN, a 6-month workshop-based curriculum, was established in 2016 in the Beth Israel Deaconess Medical Center Department of Surgery to teach surgical trainees the basics of the innovation process, focusing on surgeon-driven problem identification, product design, prototype fabrication, and initial steps in the commercialization process. Participating surgical residents and graduate students attend monthly workshops taught by medical, engineering, and medical technology (MedTech) industry faculty. Participants collaborate in teams to develop a novel device, fabricate a protype, and pitch their product to a panel of judges., Outcomes: From academic years 2015-2016 to 2017-2018, 49 trainees, including 41 surgical residents, participated in SPIN. Across this period, 13 teams identified an unmet need, ideated a solution, and designed and pitched a novel device. Ten teams fabricated prototypes. The 22 SPIN participants who responded to both pre- and postcourse surveys reported significant increases in confidence in generating problem statements, computer-aided design, fabrication of a prototype, and initial commercialization steps (product pitching and business planning)., Next Steps: Incorporating innovation education and design thinking into clinical training will prove essential in preparing future physicians to be lifelong problem finders and solvers. The authors plan to expand SPIN to additional clinical specialties, as well as to assess its impact in fostering future innovation and collaboration among program participants., (Copyright © 2021 by the Association of American Medical Colleges.)

Interleukin (IL)-10 has anti-inflammatory and CD8+ T-cell-stimulating properties. Pegilodecakin (pegylated recombinant human IL-10) induces intratumoral antigen-specific CD8 + T-cells and upregulates IFNγ and major histocompatibility complexes (MHC) I and II. Pegilodecakin has single-agent activity with manageable toxicity in advanced renal cell carcinama (aRCC) (data cutoff 24 March 2016). Pegilodecakin with pembrolizumab or nivolumab revealed clinical activity in aRCC (data cutoff 1 July 2018). Here, we report for the first time the results of pegilodecakin+ pazopanib, and final results for monotherapy and long-term follow-up with pegilodecakin + anti-programmed cell death 1 (anti-PD-1) inhibitors (data cutoff 19 February 2019). Phase 1/1b multi-cohort dose escalation IVY study enrolled 353 patients. Sixty-six patients with aRCC were treated with pegilodecakin alone or with pazopanib or anti-PD-1 inhibitor in cohorts A, G, H and I (data cutoff 19 February 2019). Primary endpoints included safety and tolerability. Secondary endpoint was tumor response by immune-related response criteria (irRC). Pegilodecakin plus nivolumab or pembrolizumab yielded median progression-free survival (mPFS) of 13.9 months and 6-month PFS probability of 60%, 76% 1-year overall survival (OS) probability and 61% 2-year OS probability. Pegilodecakin monotherapy produced mPFS of 1.8 months, 6-month PFS probability 25%, 1-year OS 50%, and 2-year OS 17%. Median OS was not reached in both combinations. Objective response rates (ORRs) were 33% with pazopanib and 43% with anti-PD-1. Most common Grade 3/4 treatment-related adverse events included anemia, thrombocytopenia and hypertriglyceridemia. In these heavily pretreated renal cell carcinama cohorts of IVY, pegilodecakin+anti-PD-1 inhibitor showed promising clinical activity. Safety profile of pegilodecakin alone and with anti-PD-1 inhibitors was consistent as previously reported., (© 2021 Eli Lilly and Company. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.)

Purpose: Mutations in the HRAS (m HRAS ) proto-oncogene occur in 4%-8% of patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Tipifarnib is a farnesyltransferase inhibitor that disrupts HRAS function. We evaluated the efficacy of tipifarnib in patients with R/M m HRAS HNSCC., Methods: We enrolled 30 patients with R/M HNSCC in a single-arm, open-label phase II trial of tipifarnib for m HRAS malignancies; one additional patient was treated on an expanded access program. After an ad hoc analysis of the first 16 patients with HNSCC with m HRAS variant allele frequency (VAF) data, enrollment was limited to those with a m HRAS VAF of ≥ 20% (high VAF). The primary end point was objective response rate. Secondary end points included assessing safety and tolerability. Patients received tipifarnib 600 or 900 mg orally twice daily on days 1-7 and 15-21 of 28-day cycles., Results: Of the 22 patients with HNSCC with high VAF, 20 were evaluable for response at the time of data cutoff. Objective response rate for evaluable patients with high-VAF HNSCC was 55% (95% CI, 31.5 to 76.9). Median progression-free survival on tipifarnib was 5.6 months (95% CI, 3.6 to 16.4) versus 3.6 months (95% CI, 1.3 to 5.2) on last prior therapy. Median overall survival was 15.4 months (95% CI, 7.0 to 29.7). The most frequent treatment-emergent adverse events among the 30 patients with HNSCC were anemia (37%) and lymphopenia (13%)., Conclusion: Tipifarnib demonstrated encouraging efficacy in patients with R/M HNSCC with HRAS mutations for whom limited therapeutic options exist (NCT02383927)., Competing Interests: Alan L. HoConsulting or Advisory Role: Bristol-Myers Squibb, Eisai, Genzyme, Merck, Novartis, Sun Pharma, Regeneron, TRM Oncology, Ayala Pharmaceuticals, AstraZeneca, Sanofi, CureVac, Prelude Therapeutics, Kura Oncology, McGivney Global Advisors, Rgenta, Exelixis, Genentech/Roche, AffyimmuneSpeakers' Bureau: Medscape, Omniprex America, NovartisResearch Funding: Lilly, Genentech/Roche, AstraZeneca, Bayer, Kura Oncology, Kolltan Pharmaceuticals, Eisai, Bristol-Myers Squibb, Astellas Pharma, Novartis, Merck, Pfizer, Ayala Pharmaceuticals, Allos Therapeutics, Daiichi Sankyo, Elevar TherapeuticsTravel, Accommodations, Expenses: Janssen Oncology, Merck, Kura Oncology, Ignyta, Ayala Pharmaceuticals, Klus Pharma Irene BranaConsulting or Advisory Role: Merck Sharp and Dohme, Rakuten Medical, Sanofi, Achilles Therapeutics, eTheRNA Immunotherapies, Cancer Expert NowSpeakers' Bureau: Bristol-Myers Squibb, Merck Serono, RocheResearch Funding: AstraZeneca, Bristol-Myers Squibb, Celgene, Gliknik, GlaxoSmithKline, Janssen Oncology, Kura Oncology, Merck Sharp and Dohme, Novartis, Orion Pharma GmbH, Pfizer, Roche, Shattuck Labs, Nanobiotix, Seattle GeneticsTravel, Accommodations, Expenses: AstraZeneca Spain, Merck Serono Robert HaddadEmployment: Dana-Farber Cancer InstituteLeadership: NCCNConsulting or Advisory Role: Celgene, Merck, Eisai, Bristol-Myers Squibb, AstraZeneca, Pfizer, Loxo, Genentech, Immunomic Therapeutics, GlaxoSmithKline, Gilead Sciences, Vaccinex, EMD Serono, BioNTech AG, Achilles TherapeuticsResearch Funding: Boehringer Ingelheim, Merck, Bristol-Myers Squibb, Celgene, AstraZeneca, VentiRx, Genentech, Pfizer, Kura OncologyPatents, Royalties, Other Intellectual Property: UpToDateOther Relationship: Nanobiotix, ISA Pharmaceuticals Jessica BaumanConsulting or Advisory Role: Pfizer, Bayer, AstraZeneca, Kura OncologyResearch Funding: Bristol-Myers SquibbTravel, Accommodations, Expenses: Trident Pharmaceuticals Sjoukje OostingResearch Funding: Celldex Deborah J. WongConsulting or Advisory Role: Bristol-Myers Squibb, Genentech/Roche, Sanofi/Aventis, Blueprint MedicinesResearch Funding: BioMed Valley Discoveries, Merck Serono, Merck Sharp and Dohme, ARMO BioSciences, AstraZeneca/MedImmune, Kura Oncology, Regeneron, Genentech/Roche, Bristol-Myers Squibb, FSTAR, Pfizer, Astellas Pharma, Enzychem Lifesciences, Lilly, Elevar Therapeutics Myung-Ju AhnHonoraria: AstraZeneca, Lilly, MSD, TAKEDAConsulting or Advisory Role: AstraZeneca, Boehringer Ingelheim, Lilly, MSD, TAKEDA, Alpha pharmaceutical Caroline EvenConsulting or Advisory Role: Innate Pharma, Bristol-Myers Squibb, MSD Oncology, Merck Serono Jerome FayetteHonoraria: AstraZeneca, Bristol-Myers Squibb, Merck Sharp and Dohme, Merck Serono, Innate Pharma, RocheConsulting or Advisory Role: AstraZeneca, Bristol-Myers Squibb, Merck Sharp and Dohme, Merck Serono, Innate Pharma, RocheResearch Funding: Bristol-Myers SquibbTravel, Accommodations, Expenses: Bristol-Myers Squibb, AstraZeneca, Merck Sharp and Dohme Kevin HarringtonHonoraria: Merck Sharp and Dohme, Amgen, Merck Serono, AstraZeneca/MedImmune, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Replimune, Oncolys BioPharma, MersanaConsulting or Advisory Role: Merck Sharp and Dohme, Merck Serono, AstraZeneca/MedImmune, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, ReplimuneSpeakers' Bureau: Merck Sharp and Dohme, Merck Serono, Bristol-Myers SquibbResearch Funding: AstraZeneca, Merck Sharp and Dohme, Boehringer Ingelheim, Replimune Sung-Bae KimHonoraria: DAEHWA Pharmaceutical, ISU ABXISConsulting or Advisory Role: Lilly, AstraZeneca, DAEHWA Pharmaceutical, ISU AbxisResearch Funding: Novartis, Dongkook Pharma, Genzyme Lisa LicitraConsulting or Advisory Role: Eisai, Boehringer Ingelheim, AstraZeneca, SOBI, Novartis, Bayer, MSD, Merck Serono, Roche, Bristol-Myers Squibb, Incyte, Doxapharma, GlaxoSmithKline, Nanobiotix, Debiopharm Group, Amgen, IpsenResearch Funding: AstraZeneca, Novartis, Roche, MSD, Eisai, Merck Serono, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Exelixis, IRX Therapeutics, Medpace, Pfizer, Debiopharm Group, RocheTravel, Accommodations, Expenses: Merck Serono, Bayer, Bristol-Myers Squibb, MSD, Eisai, AstraZeneca Nabil F. SabaHonoraria: Merck, Lilly, Pfizer, Bristol-Myers Squibb, CUE Biopharma, GlaxoSmithKline, Aduro Biotech, Kura Oncology, Genentech/RocheConsulting or Advisory Role: Pfizer, Bristol-Myers Squibb, Merck, Lilly, Bluprint, BiontechResearch Funding: Bristol-Myers Squibb, ExelixisTravel, Accommodations, Expenses: Bristol-Myers Squibb, Merck, Pfizer, Lilly, GlaxoSmithKline, Genentech/Roche, Bluprint Francis WordenHonoraria: Merck Sharp & Dohme, Eisai, Bristol-Myers Squibb, Bayer, RegeneronConsulting or Advisory Role: Merck, Loxo, Bristol-Myers Squibb, Eisai, Bayer, CUE Biopharma, Rakuten Medical, RegeneronResearch Funding: Pfizer, Merck, Eisai, Bristol-Myers Squibb, Loxo, Oragenics, LillyTravel, Accommodations, Expenses: Merck Sharp & Dohme, Bayer Binaifer BalsaraEmployment: Kura OncologyStock and Other Ownership Interests: Kura Oncology Mollie LeoniEmployment: Kura Oncology, Kyowa Kirin InternationalStock and Other Ownership Interests: Kura OncologyTravel, Accommodations, Expenses: Kura Oncology, Kyowa Kirin International Catherine ScholzEmployment: Kura Oncology, H3 BiomedicineStock and Other Ownership Interests: Kura OncologyPatents, Royalties, Other Intellectual Property: Methods of Treating Cancer Patients With Farnesyltransferase Inhibitors (FTI treatment of H-Ras mutant cancers), co-Inventor (014168-0011-999), Methods of Treating Cancer With Farnesyltransferase Inhibitors (FTI treatment of a CXCL12-expressing cancer), co-Inventor (014168-0021-999), Methods of Treating Cancer Patients With Farnesyltransferase Inhibitors (FTI treatment of Casitas B cell lymphoma [CBL] mutant cancers), co-Inventor (014168-0024-228), Therapies For Squamous Cell Carcinomas (FTI treatment of SCC with high frequencies of H-Ras mutant allele frequency), co-Inventor (014168-0051-888)Travel, Accommodations, Expenses: Kura OncologyNo other potential conflicts of interest were reported.

It has been shown that there are differences in diagnostic accuracy of cancer detection on mammograms, from below 50% in developing countries to over 80% in developed world. One previous study reported that radiologists from a population in Asia displayed a low mammographic cancer detection of 48% compared with over 80% in developed countries, and more importantly, that most lesions missed by these radiologists were spiculated masses or stellate lesions. The aim of this study was to explore the performance of radiologists after undertaking a training test set which had been designed to improve the capability in detecting a specific type of cancers on mammograms. Twenty-five radiologists read two sets of 60 mammograms in a standardized mammogram reading room. The first test set focused on stellate or spiculated masses. When radiologists completed the first set, the system displayed immediate feedback to the readers comparing their performances in each case with the truth of cancer cases and cancer types so that the readers could identify individual-based errors. Later radiologists were asked to read the second set of mammograms which contained different types of cancers including stellate/spiculated masses, asymmetric density, calcification, discrete mass and architectural distortion. Case sensitivity, lesion sensitivity, specificity, receiver operating characteristics (ROC) and Jackknife alternative free-response receiver operating characteristics (JAFROC) were calculated for each participant and their diagnostic accuracy was compared between two sessions. Results showed significant improvement among radiologists in case sensitivity (+ 11.4%; P < 0.05), lesion sensitivity (+ 18.7%; P < 0.01) and JAFROC (+ 11%; P < 0.01) in the second set compared with the first set. The increase in diagnostic accuracy was also recorded in the detection of stellate/spiculated mass (+ 20.6%; P < 0.05). This indicated that the performance of radiologists in detecting malignant lesions on mammograms can be improved if an appropriate training intervention is applied after the readers' weakness and strength are identified.

Purpose: Regional anesthesia techniques may improve patient recovery beyond treating postoperative pain alone and may facilitate patients in their return to functional, psychological as well as emotional baselines. We hypothesized that the quality of recovery (QoR) experienced by patients following breast surgery was associated with the type of anesthesia received as well as the use of a regional anesthesia technique during surgery., Methods: We performed a single-center prospective, observational cohort study of patients undergoing elective breast procedures (both cancer and non-cancer surgery)., Results:  One hundred patients completed baseline QoR-15 questionnaires prior to surgery, of which 96 also completed QoR-15 questionnaires on postoperative day 1. The median (IQR) QoR-15 score at baseline was 133 (124-141), decreasing to 121 (106.75-136.25) on postoperative day 1. In multivariable linear regression analysis, paravertebral blocks (PVB) were associated with a 16.7 point higher overall QoR-15 score on postoperative day 1 compared to no block (95% Confidence Interval [CI]: 7.7-25.8, p<0.001); while the use of combination blocks was associated with a 21.8 point higher postoperative QoR-15 score compared to no block (95% CI: 12.8-30.8, p<0.001). PVB and combination blocks were further associated with better postoperative pain, physical comfort, physical independence and emotional state scores, compared with no block. The use of total intravenous anesthetic was not associated with differences in postoperative QoR-15 score versus volatile anesthetic, after covariate adjustment., Conclusion: Breast surgery patients receiving PVB or a combination of regional blocks during surgery have higher postoperative QoR-15 scores, after adjustment for other factors., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2021, Nair et al.)

Background Treatment options for pancreatic ductal adenocarcinoma (PDAC) are limited and checkpoint blockade inhibitors have been disappointing in this disease. Pegilodecakin has demonstrated single agent anti-tumor activity in immune-sensitive tumors. Phase 1 and preclinical data indicate synergy of pegilodecakin with 5-FU and platins. We assessed the safety and activity of pegilodecakin+FOLFOX in patients with PDAC. Methods IVY (NCT02009449) was an open-label phase 1b trial in the United States. Here we report on all enrolled patients from cohort C. Heavily pretreated patients were treated with pegilodecakin (self-administered subcutaneously daily at 2.5, 5, or 10 μg/kg) + 5-flurouracil/leucovorin/oxaliplatin (FOLFOX), dosed per manufacturers prescribing information, until tumor progression. Eligible patients had measurable disease per immune-related response criteria (irRC), were ≥ 18 years of age, and had ECOG performance status of 0 or 1. Patients were evaluated for primary(safety) and secondary (tumor response per irRC) endpoints. Results From 5 August 2014-12 July 2016, 39 patients enrolled in cohort C. All patients were evaluable for safety. In this advanced population, regimen had manageable toxicities with no immune-related adverse events (irAEs) greater than grade 1. The most common grade 3/4/5 TEAEs were thrombocytopenia (21[53.8%] of 39) and anemia (17[43.6%] of 39). In evaluable PDAC patients, the best overall response of pegilodecakin+FOLFOX was 3(14%) with CRs in 2(9%) patients. Conclusions Pegilodecakin+FOLFOX had an acceptable tolerability profile in PDAC, with no substantial irAEs seen, and promising efficacy with the combination yielding a 2-year OS of 24% (95% CI 10-42). These data led to the phase 3 study with pegilodecakin+FOLFOX as second-line therapy of PDAC (SEQUOIA).

For differentiated thyroid cancer (DTC), systemic therapy with radioactive iodine (RAI) is utilized for radiosensitive disease, while for radioiodine refractory (RAIR) disease, current standard of care is treatment with multikinase tyrosine kinase inhibitors (TKI). For BRAF-mutant DTC or anaplastic thyroid cancer (ATC), treatment with inhibitors targeting BRAF and MEK are important advances. RET-inhibitors for RET-mutated medullary thyroid cancer (MTC) recently have been FDA-approved for metastatic disease. Nevertheless, treatment of thyroid cancer resistant to current systemic therapies remains an important area of need. Resistance mechanisms are being elucidated, and novel therapies including combinations of BRAF and MEK inhibitors with RAI or other targeted therapies or TKIs combined with checkpoint inhibition are current areas of exploration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Porter and Wong.)

Background: To the authors' knowledge, there are no approved therapies for recurrent, metastatic (R/M) salivary gland carcinoma (SGC), but molecularly targeted therapies warrant ongoing investigation. In the current study, the authors have reported on the efficacy of tipifarnib in patients with aggressive HRAS-mutant, R/M SGC., Methods: The current prospective, nonrandomized, multicenter, international cohort study involved 8 centers and was conducted from May 2015 to June 2019. The median follow-up was 22 months (range, 6-55 months). Subjects with HRAS-mutant R/M SGC (any histology) and disease progression within the last 6 months were enrolled. Tipifarnib was dosed orally twice daily. The authors determined the objective response rate using Response Evaluation Criteria in Solid Tumors (version 1.1), duration of response, and molecular predictors of response., Results: A total of 13 patients with R/M SGC were enrolled; all had received prior systemic therapy (1-3 regimens). One objective response was observed; an additional 7 of 12 evaluable patients (58%) had stable disease as their best response with a median duration of 9 months (range, 3-14 months). Five of 7 patients had >10% tumor regression and 6 of 7 had stable disease lasting >6 months. Q61R was the most frequent activating HRAS mutation noted (7 of 13 patients; 54%), but gene variant and allele frequency did not correlate with outcomes. The median progression-free survival was 7 months (95% confidence interval, 5.9-10.1 months), and the median overall survival was 18 months (95% confidence interval, 9.6-22.4 months) with approximately 58.6% of patients alive at 1 year. Survival was similar regardless of HRAS mutant variant or co-occurring PIK3CA alterations. No participant discontinued treatment because of toxicity., Conclusions: Tipifarnib resulted in modest clinical activity with a promising disease control rate among patients with HRAS-mutant, R/M SGC who developed disease progression within the last 6 months., (© 2020 American Cancer Society.)

Background: The transversus abdominis plane (TAP) block is an important non-narcotic adjunct for post-operative pain control in abdominal surgery. Surgeons can use laparoscopic guidance for TAP block placement (LTAP), however, direct comparisons to conventional ultrasound-guided TAP (UTAPs) have been lacking. The aim of this study is to determine if surgeon placed LTAPs were non-inferior to anesthesia placed UTAPs for post-operative pain control in laparoscopic colorectal surgery., Methods: This was a prospective, randomized, patient and observer blinded parallel-arm non-inferiority trial conducted at a single tertiary academic center between 2016 and 2018 on adult patients undergoing laparoscopic colorectal surgery. Narcotic consumption and pain scores were compared for LTAP vs. UTAP for 48 h post-operatively., Results: 60 patients completed the trial (31 UTAP, 29 LTAP) of which 25 patients were female (15 UTAP, 10 LTAP) and the mean ages (SD) were 60.0 (13.6) and 61.5 (14.3) in the UTAP and LTAP groups, respectively. There was no significant difference in post-operative narcotic consumption between UTAP and LTAP at the time of PACU discharge (median [IQR] milligrams of morphine, 1.8 [0-4.5] UTAP vs. 0 [0-8.7] LTAP P = .32), 6 h post-operatively (5.4 [1.8-17.1] UTAP vs. 3.6 [0-12.6] LTAP P = .28), at 12 h post-operatively (9.0 [3.6-29.4] UTAP vs. 7.2 [0.9-22.5] LTAP P = .51), at 24 h post-operatively (9.0 [3.6-29.4] UTAP vs. 7.2 [0.9-22.5] LTAP P = .63), and 48 h post-operatively (39.9 [7.5-70.2] UTAP vs. 22.2 [7.5-63.8] LTAP P = .41). Patient-reported pain scores as well as pre-, intra-, and post-operative course were similar between groups. Non-inferiority criteria were met at all post-op time points up to and including 24 h but not at 48 h., Conclusions: Surgeon-delivered LTAPs are safe, effective, and non-inferior to anesthesia-administered UTAPs in the immediate post-operative period., Trial Registry: The trial was registered at clinicaltrials.gov Identifier NCT03577912.

Studies have shown that the use of artificial intelligence can reduce errors in medical image assessment. The diagnosis of breast cancer is an essential task; however, diagnosis can include 'detection' and 'interpretation' errors. Studies to reduce these errors have shown the feasibility of using convolution neural networks (CNNs). This narrative review presents recent studies in diagnosing mammographic malignancy investigating the accuracy and reliability of these CNNs. Databases including ScienceDirect, PubMed, MEDLINE, British Medical Journal and Medscape were searched using the terms 'convolutional neural network or artificial intelligence', 'breast neoplasms [MeSH] or breast cancer or breast carcinoma' and 'mammography [MeSH Terms]'. Articles collected were screened under the inclusion and exclusion criteria, accounting for the publication date and exclusive use of mammography images, and included only literature in English. After extracting data, results were compared and discussed. This review included 33 studies and identified four recurring categories of studies: the differentiation of benign and malignant masses, the localisation of masses, cancer-containing and cancer-free breast tissue differentiation and breast classification based on breast density. CNN's application in detecting malignancy in mammography appears promising but requires further standardised investigations before potentially becoming an integral part of the diagnostic routine in mammography., (© 2020 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.)