The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia.

Targeting critical epigenetic regulators reverses aberrant transcription in cancer, thereby restoring normal tissue function1-3. The interaction of menin with lysine methyltransferase 2A (KMT2A), an epigenetic regulator, is a dependence in acute leukaemia caused by either rearrangement of KMT2A or mutation of the nucleophosmin 1 gene (NPM1)4-6. KMT2A rearrangements occur in up to 10% of acute leukaemias and have an adverse prognosis, whereas NPM1 mutations occur in up to 30%, forming the most common genetic alteration in acute myeloid leukaemia7,8. Here, we describe the results of the first-in-human phase 1 clinical trial investigating revumenib (SNDX-5613), a potent and selective oral inhibitor of the menin-KMT2A interaction, in patients with relapsed or refractory acute leukaemia (ClinicalTrials.gov, NCT04065399). We show that therapy with revumenib was associated with a low frequency of grade 3 or higher treatment-related adverse events and a 30% rate of complete remission or complete remission with partial haematologic recovery (CR/CRh) in the efficacy analysis population. Asymptomatic prolongation of the QT interval on electrocardiography was identified as the only dose-limiting toxicity. Remissions occurred in leukaemias refractory to multiple previous lines of therapy. We demonstrate clearance of residual disease using sensitive clinical assays and identify hallmarks of differentiation into normal haematopoietic cells, including differentiation syndrome. These data establish menin inhibition as a therapeutic strategy for susceptible acute leukaemia subtypes.

Tumor-intrinsic and Cancer-associated Fibroblast Subtypes Independently Predict Outcomes in Pancreatic Cancer.

OBJECTIVE: To assess the utility of tumor-intrinsic and cancer-associated fibroblast (CAF) subtypes of pancreatic ductal adenocarcinoma (PDAC) in predicting response to neoadjuvant therapy (NAT) and overall survival. BACKGROUND: PDAC remains a deadly disease with limited treatment options, and both the tumor as well as the microenvironment play an important role in pathogenesis. Gene expression-based tumor-intrinsic subtypes (classical and basal-like) have been shown to predict outcomes, but tumor microenvironment subtypes are still evolving. METHODS: RNA-sequencing was performed on 114 deidentified resected PDAC tumors. Clinical data were collected by retrospective chart review. Single sample classifiers (SSCs) were used to determine classical and basal-like subtypes as well as tumor-permissive permCAF and tumor-restraining restCAF subtypes. Survival was analyzed using log-rank test. RESULTS: Patients who received NAT had an increase in overall survival (OS), with median survival of 27.9 months compared to 20.1 months for those who did not receive NAT, but the difference did not reach statistical significance (HR 0.64, P=0.076). Either tumor-intrinsic or CAF subtypes alone were associated with OS regardless of NAT or no NAT, and patients with classical or restCAF subtype had the best outcomes. When evaluated together, patients with classical-restCAF subtype had the best OS and basal-permCAF the worst OS (P<0.0001). NAT patients with classical-restCAF subtype demonstrated the longest OS compared to the other groups (P=0.00041). CONCLUSIONS: CAF subtypes have an additive effect over tumor-intrinsic subtypes in predicting survival with or without neoadjuvant FOLFIRINOX in PDAC. Molecular subtyping of both tumor and CAF compartments of PDAC may be important steps in selecting first-line systemic therapy.

Lymph node metastases in young patients with gastrointestinal stromal tumor: A nationwide analysis.

BACKGROUND: Children, adolescents, and young adults (CAYA) (age ≤39 years) with GIST have high rates of LNM, but their clinical relevance is undefined. This study analyzed the impact of LNM on overall survival (OS) for CAYA with GIST. METHODS: The National Cancer Database was queried for patients with resected GIST and pathologic nodal staging data from 2004-2019. Factors associated with LNM were identified. Survival was assessed stratified by presence of LNM. RESULTS: Of 4420 patients with GIST, 238 were CAYA (5.4%). When compared to older adults, CAYA more often had small intestine primaries (51.8% vs. 36.6%, p < 0.0001), T4 tumors (30.7% vs. 24.5%, p = 0.0275) and pN1 disease (11.3% vs. 4.7%, p < 0.0001). Within a multivariable Cox proportional hazards regression model adjusting for age, comorbid disease, mitotic rate, tumor size, and primary site, LNM were associated with increased hazard of death for older adults (hazard ratio [HR]: 1.83; confidence interval [CI]: 1.35-2.42; p < 0.0001), but not CAYA (HR: 3.38; CI: 0.50-14.08; p = 0.13). For CAYA, only high mitotic rate predicted mortality (HR: 4.68; CI: 1.41-18.37: p = 0.02). CONCLUSIONS: LNM are more commonly identified among CAYA with resected GIST who undergo lymph node evaluations, but do not appear to impact OS as observed in older adults. High mitotic rate remains a predictor of poor outcomes for CAYA with GIST.

Left bundle branch area pacing too far away from the tricuspid annulus may cause pacing induced cardiomyopathy.

BACKGROUND: Physiologic pacing through left bundle branch area pacing (LBBAP) has recently been shown to be a very promising alternative for cardiac resynchronization therapy (CRT) and to avoid pacing induced cardiomyopathy. However, it is not clear whether the position of LABBP lead may affect the clinical outcomes. CASE REPORT: We here report a case of likely LBBAP induced worsening heart failure and cardiomyopathy reversed by re-positioning of the pacing lead towards a more annular position. A 70-year-old male with a previous history of non-ischemic dilated cardiomyopathy (ejection fraction 40%) who developed intermittent complete heart block and required permanent ventricular pacing. LBBAP was performed with the lead positioned to a position relatively far away from the tricuspid annulus (3.7 cm), due to difficulty in fixating the lead deep into the septum at a more annular position. One month post procedure, the patient's heart failure symptoms worsened, and his EF decreased to 31% despite good heart failure management. He underwent CRT upgrade with successful revision of the originally implanted LBBAP lead to a more annular position, using a deflectable delivery sheath. This resulted in further narrowing of the paced QRS duration from 135 to 106 ms. Two months post procedure, his heart failure symptoms improved by one functional class, and EF improved to 41% by echocardiogram. CONCLUSIONS: LBBAP may be harmful when the lead is placed too far away from the annulus and may cause paced induced cardiomyopathy.

Use and Costs of Sentinel Lymph Node Biopsy in Non-Ulcerated T1b Melanoma: Analysis of a Population-Based Registry.

BACKGROUND: The utility of sentinel lymph node biopsy (SLNB) for non-ulcerated T1b melanoma is debated and associated costs are poorly characterized. Prior work using institutional registries may overestimate the incidence of nodal positivity in this population. OBJECTIVE: The aim of this study was to estimate the use of SLNB, positivity prevalence, and procedural costs in patients with non-ulcerated T1b melanoma using a population-based registry. METHODS: We identified patients with clinically node-negative, non-ulcerated melanoma 0.8-1.0 mm thick (T1b according to the 8th edition standard of the American Joint Committee on Cancer) in the Surveillance, Epidemiology, and End Results database from 2010 to 2016. The prevalence of SLNB procedures and positive sentinel nodes were calculated. Factors associated with SLNB and sentinel node positivity were assessed using logistic regression. Medicare reimbursement costs and patient out-of-pocket expenses for SLNB and wide local excision (WLE) versus WLE alone were estimated. RESULTS: Among 7245 included patients, 3835(53%) underwent SLNB, 156 (4.1%, 95% confidence interval 3.5-4.7) of whom had a positive SLNB. Younger age, >1 mitosis per mm2, female sex, and truncal tumor location were associated with higher odds of positivity. The estimated SLNB cost to identify one patient with stage III disease was $71,700 (range $54,648-$83,172). Out-of-pocket expenses for a Medicare patient were estimated to be $652 for a WLE and SLNB and $79 for a WLE alone. CONCLUSIONS: In this population-based study, only 4% of selected non-ulcerated T1b patients had a positive SLNB, which is lower than prior reports. At the population level, SLNB is associated with high costs per prognostic information gained.

Direct Comparison of In-Person Versus Virtual Interviews for Complex General Surgical Oncology Fellowship in the COVID-19 Era.

BACKGROUND: In the era of coronavirus disease 2019 (COVID-19), many Complex General Surgical Oncology (CGSO) fellowship programs implemented virtual interviews (VI) during the 2020 interview season. At our institution, we had the unique opportunity to conduct an in-person interview (IPI) prior to the pandemic-related travel restrictions, and a VI after the restrictions were in place. OBJECTIVE: The goal of this study was to understand how the VI model compares with the traditional IPI approach. METHODS: Online surveys were distributed to both groups, collecting feedback on their interview experience. Responses were evaluated using a two-sample t test assuming equal variances. RESULTS: Twenty-three of 26 (88%) applicants completed the survey. Most applicants reported that the interview gave them a satisfactory understanding of the CGSO fellowship (100% IPI, 92% VI) and the majority in both groups felt that the interview experience allowed them to accurately represent themselves (92% and 82%, respectively). All participants in the IPI group felt they were able to get an adequate understanding of the culture of the program, while only 64% in the VI group agreed with that statement (p = 0.02). IPI applicants were more likely to agree that the interview experience was sufficient to allow them to make a ranking decision (92% vs. 54%; p = 0.04). CONCLUSIONS: While the VI modality offers several advantages over the IPI, it still falls short in conveying some of the more subjective aspects of the programs, including program culture. Strategies to provide applicants with better insight into these areas during the VI will be important moving forward.

Allyship in Surgical Residents: Evidence for LGBTQ Competency Training in Surgical Education.

BACKGROUND: Studies have shown poorer health outcomes for people who identify as sexual and/or gender minority (LGBTQ+) compared to heterosexual peers. Our goal was to establish baseline levels of LGBTQ Ally Identity Measure (AIM) scores: (1) Knowledge and Skills, (2) Openness and Support, and (3) Awareness of Oppression of the LGBTQ+ in surgical trainees, and implement a pilot training in LGBTQ + cultural competency. MATERIALS AND METHODS: General surgery residents from a single academic medical center participated in a 2-h educational training developed from the existing Health Care Safe Zone training at our institution. Utilizing the previously validated LGBTQ Ally Identity Measure (AIM), residents responded to 19 items on Likert-type scales from 1 to 5 pretraining and 6 wk posttraining. The residents' perceptions of the utility of the training were also assessed. Data were analyzed by MANOVA, repeated measures MANOVA, and subsequent univariate analysis. RESULTS: 27 residents responded to the pretraining survey (52%), 22 residents participated in the training, and 10 responded at 6 wk posttraining (19%). The average baseline scores were Knowledge and Skills 19.38 ± 4.64, Openness and Support 25.96 ± 4.31, and Awareness of Oppression 17.15 ± 2.20. Participants who identified as women scored 4.46 (95% CI 0.77-8.15) points higher in Openness and Support compared to males. Of those respondents who completed pretraining and posttraining surveys (n = 10), training had a significant effect on AIM scores with an improvement in Knowledge and Skills (P = 0.024) and Openness and Support (P = 0.042). Residents found the training relevant to surgery patient care (71%), increased their competency in LGBTQ + patient care (86%), and all participants indicated they were better LGBTQ allies following the training. CONCLUSIONS: Assessing LGBTQ + allyship in surgical residents, we found that training improved AIM scores over time with significant improvement in the Knowledge and Skills, and Openness and Support scales, suggesting a viable and valuable curriculum focused on sexual and gender identity-related competencies within the graduate medical education for surgical trainees.

Socioeconomic factors in timing of esophagectomy and association with outcomes.

BACKGROUND AND OBJECTIVES: Disparities in esophageal cancer are well-established. The standard treatment for locally advanced esophageal cancer is chemoradiation followed by surgery. We sought to evaluate the association between socioeconomic factors, time to surgery, and patient outcomes. METHODS: All patients ≥18 years old diagnosed with T2/3/4 or node-positive esophageal cancer between 2004 and 2016 and who underwent chemoradiation and esophagectomy in the National Cancer Database were included. Multivariable regression was used to assess the association between socioeconomic variables and time to surgery (grouped into <56, 56-84, and 85-112 days). RESULTS: A total of 12 157 patients were included. Five-year overall survival was 39%, 35%, and 35% for the three groups examined. Postoperative 30- and 90-day mortality was increased in both the 56-84 days to surgery group (odds ratio [OR]: 1.30 and 1.20, respectively) and the 85-112 days group (OR: 1.37 and 1.56, respectively) when compared to <56 days. Patients of a minority race, public insurance, or lower income were more likely to have a longer time to surgery. CONCLUSION: Longer time to surgery is associated with increased postoperative mortality and is more common in patients with lower socioeconomic status. Further research exploring reasons for delays to esophagectomy among disadvantaged patients could help target interventions to reduce disparities.

Designing for impact: identifying stakeholder-driven interventions to support recovery after major cancer surgery.

PURPOSE: Complex bladder and colorectal cancer surgeries are associated with significant patient morbidity, yet few resources exist to prepare patients for the high levels of distress and complications they may experience. After ethnographic research to identify design challenges, we held a user-centered design (UCD) workshop to begin to develop patient- and caregiver-centered interventions to support preparation for and recovery after complex cancer surgery. METHODS: Concepts that emerged from brainstorming sessions were visually represented on storyboards and rated. Highly scored concepts were further developed in break-out prototyping sessions and then presented to the entire group for review in person and during subsequent webinars. We collected workshop products (worksheets, prototypes, and recordings) for analysis to identify opportunities for intervention. The workshop, held in late 2014, was attended by three colorectal/oncologic surgeons, three urologic surgeons, five ostomy nurses, one quality improvement leader, three patients, one caregiver, and three experienced UCD facilitators. RESULTS: Three opportunity areas were identified: (1) enhanced patient education including tele-health and multi-media tools (available at hospitals/clinics or online in any setting), (2) personalized discharge assessment and care planning, and (3) integrated symptom monitoring and educational interventions. Stakeholders reached consensus that enhanced patient education was the most important direction for subsequent intervention development. CONCLUSIONS: We engaged diverse stakeholders in a participatory, UCD process and concluded that research and practice improvement should prioritize the development of educational interventions in the pre-operative period to set the groundwork for improving appropriate self-care during recovery from major colorectal and bladder cancer surgeries.

Impact of Location of Readmission on Outcomes After Major Cancer Surgery.

BACKGROUND: The burden of readmissions after major cancer surgery is high. Prior work suggests that one-third of readmitted patients are readmitted to a different hospital than where the surgery was performed. The impact of this location of readmission needs to be more thoroughly understood. METHODS: This retrospective cohort study was performed on Surveillance, Epidemiology, and End Results (SEER)-Medicare patients with bladder, esophagus, lung, or pancreas cancer diagnosed from 2001 to 2007 who underwent extirpative surgery and were readmitted within 90 days. Readmission location was classified as 'index' if readmission was at the hospital where surgery was performed, or 'different' if readmission was elsewhere. Outcomes including complications, reoperations, in-hospital mortality, 90-day mortality, and 90-day total costs were compared based on the location of readmission using a propensity score inverse probability treatment weight analysis. RESULTS: Overall, 7903 (28 %) patients were readmitted within 90 days of index hospitalization. Thirty-three percent were readmitted to a different hospital (bladder 30 %, esophagus 34 %, lung 34 %, pancreas 34 %). Ninety-day mortality and total costs of care were not significantly different between the readmission location groups (all p > 0.05); however, substantial differences in the types of patients, and timing of and reasons for readmission were observed between the two groups. CONCLUSIONS: Patients readmitted to different hospitals after major cancer surgery are a different group of patients than those readmitted to the index hospital. Accounting for this, we did not find significant differences in short-term clinical outcomes or costs of care based on readmission location; however, differences in long-term outcomes were observed that should be further explored in future studies.

Multidisciplinary Approach to the Management of Esophageal Malignancies.

INTRODUCTION: A multidisciplinary approach in the management of complex malignancies is becoming more common, and likewise, adopting such an approach to the care of patients with locally advanced esophageal is recommended in order to optimize clinical outcomes. METHODS: In this review, we discuss both the surgical and medical oncology perspectives in the management of patients with locally advanced esophageal cancer. We review the data supporting the current standard-of-care approach, namely trimodality therapy with neoadjuvant chemo-radiotherapy followed by surgery. Other aspects of managing these patients including the control of dysphagia and pain as well as nutritional support are discussed. Finally, we review data that support the importance of incorporating a multidisciplinary streamlined approach in the management of these patients. RESULTS: Rather than having patients see each provider separately, a multidisciplinary approach to esophageal cancer allows for the seamless flow of communication and proactive management of the patient's symptoms. These benefits include increasing the likelihood of evidence-based decision making, shorter time to treatment, and increased patient quality of life, all of which can result in improved patient outcomes. CONCLUSION: The use of a multidisciplinary team can lead to a more accurate staging paradigm and thereby, better management decisions that translate to improved clinical outcomes. Therefore, optimizing the multidisciplinary approach for the care of patients with locally advanced esophageal cancer is essential for successful and individualized patient care.

Gastric adenocarcinoma microRNA profiles in fixed tissue and in plasma reveal cancer-associated and Epstein-Barr virus-related expression patterns.

MicroRNA expression in formalin-fixed paraffin-embedded tissue (FFPE) or plasma may add value for cancer management. The GastroGenus miR Panel was developed to measure 55 cancer-specific human microRNAs, Epstein-Barr virus (EBV)-encoded microRNAs, and controls. This Q-rtPCR panel was applied to 100 FFPEs enriched for adenocarcinoma or adjacent non-malignant mucosa, and to plasma of 31 patients. In FFPE, microRNAs upregulated in malignant versus adjacent benign gastric mucosa were hsa-miR-21, -155, -196a, -196b, -185, and -let-7i. Hsa-miR-18a, 34a, 187, -200a, -423-3p, -484, and -744 were downregulated. Plasma of cancer versus non-cancer controls had upregulated hsa-miR-23a, -103, and -221 and downregulated hsa-miR-378, -346, -486-5p, -200b, -196a, -141, and -484. EBV-infected versus uninfected cancers expressed multiple EBV-encoded microRNAs, and concomitant dysregulation of four human microRNAs suggests that viral infection may alter cellular biochemical pathways. Human microRNAs were dysregulated between malignant and benign gastric mucosa and between plasma of cancer patients and non-cancer controls. Strong association of EBV microRNA expression with known EBV status underscores the ability of microRNA technology to reflect disease biology. Expression of viral microRNAs in concert with unique human microRNAs provides novel insights into viral oncogenesis and reinforces the potential for microRNA profiles to aid in classifying gastric cancer subtypes. Pilot studies of plasma suggest the potential for a noninvasive addition to cancer diagnostics.

Application of heterocyclic aldehydes as components in Ugi-Smiles couplings.

Efficient one-pot Ugi-Smiles couplings are reported for the use of furyl-substituted aldehyde components. In the presence of these heterocyclic aldehydes, reactions tolerated variations in amine components and led to either isolated N-arylamide Ugi-Smiles adducts or N-arylepoxyisoindolines, products of tandem Ugi-Smiles Diels-Alder cyclizations, in moderate yields. A thienyl-substituted aldehyde was also a competent component for Ugi-Smiles adduct formation.

Prognostic significance of tumor mitotic rate in T2 melanoma staged with sentinel lymphadenectomy.

BACKGROUND AND OBJECTIVES: Tumor mitotic rate (TMR) is an important prognostic variable for patients with thin melanoma. However it remains unclear what the significance of TMR is for more deeply invasive melanoma pathologically staged with a sentinel lymph node biopsy. We sought to determine the prognostic value of TMR in clinically node-negative T2 melanoma patients staged with sentinel lymphadenectomy. METHODS: A prospective IRB-approved database of cutaneous melanoma patients treated from 09/01/1997-03/01/2011 was used to identify patients with T2 melanoma staged with a SLN. Associations were evaluated using Fisher's Exact test, and Kaplan-Meier analysis. RESULTS: Three hundred thirteen T2 patients were included. 19% had ulceration, 11% a positive sentinel node (SLN), and 10% recurred. 44% of patients had TMR ≥ 1/mm(2). TMR ≥ 1/mm(2) did not predict SLN status. TMR ≥ 1/mm(2) was significantly associated with recurrence in SLN negative patients; only 3% of those with TMR < 1/mm(2) developed a recurrence compared to 16% of those with TMR ≥ 1/mm(2) (P < 0.0001). CONCLUSIONS: Although TMR ≥ 1/mm(2) is not associated with risk of SLN involvement in T2 melanoma, it is a significant risk factor for recurrence when SLN negative. As such, TMR could be used to stratify follow-up regimens in SLN negative T2 patients.

Abiraterone acetate plus prednisone versus prednisone alone in chemotherapy-naive men with metastatic castration-resistant prostate cancer: patient-reported outcome results of a randomised phase 3 trial.

BACKGROUND: Abiraterone acetate plus prednisone significantly improves radiographic progression-free survival in asymptomatic or mildly symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer compared with prednisone alone. We describe analyses of data for patient-reported pain and functional status in a preplanned interim analysis of a phase 3 trial. METHODS: Between April 28, 2009, and June 23, 2010, patients with progressive, metastatic castration-resistant prostate cancer were enrolled into a multinational, double-blind, placebo-controlled trial. Patients were eligible if they were asymptomatic (score of 0 or 1 on item three of the Brief Pain Inventory Short Form [BPI-SF] questionnaire) or mildly symptomatic (score of 2 or 3) and had not previously received chemotherapy. Patients were randomly assigned (1:1) to receive oral abiraterone (1 g daily) plus prednisone (5 mg twice daily) or placebo plus prednisone in continuous 4-week cycles. Pain was assessed with the BPI-SF questionnaire, and health-related quality of life (HRQoL) with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. We analysed data with prespecified criteria for clinically meaningful pain progression and deterioration in HRQoL. All patients who underwent randomisation were included in analyses. FINDINGS: 1088 patients underwent randomisation: 546 were assigned to abiraterone plus prednisone and 542 to placebo plus prednisone. At the time of the second prespecified interim analysis, median follow-up was 22·2 months (IQR 20·2-24·8). Median time to progression of mean pain intensity was longer in patients assigned to abiraterone plus prednisone (26·7 months [95% CI 19·3-not estimable]) than in those assigned to placebo plus prednisone (18·4 months [14·9-not estimable]; hazard ratio [HR] 0·82, 95% CI 0·67-1·00; p=0·0490), as was median time to progression of pain interference with daily activities (10·3 months [95% CI 9·3-13·0] vs 7·4 months [6·4-8·6]; HR 0·79, 95% CI 0·67-0·93; p=0·005). Median time to progression of worst pain was also longer with abiraterone plus prednisone (26·7 months [95% CI 19·4-not estimable]) than with placebo plus prednisone (19·4 months [16·6-not estimable]), but the difference was not significant (HR 0·85, 95% CI 0·69-1·04; p=0·109). Median time to HRQoL deterioration was longer in patients assigned to abiraterone plus prednisone than in those assigned to placebo plus prednisone as assessed by the FACT-P total score (12·7 months [95% CI 11·1-14·0] vs 8·3 months [7·4-10·6]; HR 0·78, 95% CI 0·66-0·92; p=0·003) and by the score on its prostate-cancer-specific subscale (11·1 months [8·6-13·8] vs 5·8 months [5·5-8·3]; HR 0·70, 95% CI 0·60-0·83; p<0·0001). INTERPRETATION: Abiraterone plus prednisone delays patient-reported pain progression and HRQoL deterioration in chemotherapy-naive patients with metastatic castration-resistant prostate cancer. These results provide further support for the efficacy of abiraterone in this population.

Clinical and Histological Response to Talimogene Laherparepvec Therapy in Advanced Melanoma: Impact on Overall Survival.

BACKGROUND: Talimogene laherparepvec (T-VEC) is an FDA-approved oncolytic herpesvirus therapy used for unresectable stage IIIB through IV metastatic melanoma. However, the correlation between clinical complete response (cCR) and pathologic complete response (pCR) in patients treated with T-VEC is understudied. STUDY DESIGN: We conducted a retrospective study from a prospectively maintained IRB-approved melanoma single-center database in patients treated with T-VEC from October 2015 to April 2022. Patients were categorized into 3 groups: cCR with pCR, cCR without pCR, and less than cCR. The primary endpoint was overall survival. We used descriptive statistics, chi-square tests, and Wilcoxon rank-sum tests to compare key covariates among exposure groups. We used survival analysis to compare survival curves and reported hazard ratio of death (95% CI) across exposure groups. RESULTS: We included 116 patients with a median overall survival (interquartile range) of 22.7 (14.8-39.3) months. The majority were men (69%) and White (97.4%), with a median age of 74.5 years. More than half of patients (n = 60, 51.6%) achieved cCR. Distribution among the groups was as follows: cCR with pCR (35.3%), cCR without pCR (16.3%), and less than cCR (48.4%). Median overall survival time (interquartile range) was 26.5 (18.6-36.0) months for cCR with pCR, 22.7 (14.4-35.5) months for cCR without pCR, and 17.8 (9.2-47.0) months for less than cCR (log-rank p value = 0.0033). CONCLUSIONS: Patients achieving cCR with pCR after T-VEC therapy have the most favorable overall survival outcomes, whereas those achieving cCR without pCR have inferior survival and those achieving less than cCR have the poorest overall survival outcomes. These findings emphasize the importance of histological confirmation and provide insights for optimizing T-VEC therapy in patients with advanced melanoma.

Sometimes you can't make it on your own: the impact of a professionalism curriculum on the attitudes, knowledge, and behaviors of an academic plastic surgery practice.

INTRODUCTION: Professionalism is now recognized as a core competency for graduate medical education and maintenance of certification. However, few models exist in plastic surgery that define, teach, and assess professionalism as a competency. The purpose of this project was to evaluate the effectiveness of a professionalism curriculum in an academic plastic surgery practice. METHODS: We created and conducted a 6-wk, 12-h course for health care professionals in plastic surgery (faculty, residents, nurses, medical students). Teaching methods included didactic lectures, journal club, small group discussions, and book review. Topics included: (1) Professionalism in Our Culture, (2) Leadership Styles, (3) Modeling Professional Behavior, (4) Leading Your Team, (5) Managing Oneself, and (6) Leading While You Work. Using Kirkpatrick methodology to assess perception of the course (level 1 data), learning of the material (level 2 data), effect on behavior (level 3 data), and impact on the organization (level 4 data), we compiled participant questionnaires, scores from pre- and post-tests, and such metrics as incidence of sentinel events (defined as infractions requiring involvement by senior administrators), number of patient complaints reported to Patient Relations, and patient satisfaction (Press Ganey surveys), for the 6 mo before and after the course. RESULTS: Thirty health care professionals participated in a 6-wk course, designed to improve professionalism in plastic surgery. Level 1 data: Although only 56.5% of respondents felt that the course was a "good use of my time," 73.9% agreed that the course "will help me become a better professional" and 82.6% "would recommend the course to others." Level 2 data: Post-test scores increased from 48% to 70% (P < 0.05), and the ability to recall all six competencies increased from 22% to 73% (P < 0.01). Level 3 data: The number of sentinel events in our division decreased from 13 to three. After the course, one resident was placed on probation and resigned, and two other employees left the division after being counseled on issues of professionalism. Interestingly, these participants did very well on the post-test but were not considered to be "team players." Level 4 data: Patient complaints decreased from 14 to eight, and patient satisfaction increased from 85.5% to 90.5%. CONCLUSIONS: A focused curriculum in professionalism may improve the knowledge of participants and overall behavior of the group, but may not affect individual attitudes. Nevertheless, efforts toward assessing, teaching, and influencing professionalism in plastic surgery are very valuable and should be pursued by educators to help satisfy Graduate Medical Education/Maintenance of Certification requirements and to improve the performance of the organization.

Intraoperative electron radiation therapy as an important treatment modality in retroperitoneal sarcoma.

BACKGROUND: Local recurrence (LR) rates in patients with retroperitoneal sarcoma (RPS) are high, ranging from 40% to 80%, with no definitive studies describing the best way to administer radiation. Intraoperative electron beam radiation therapy (IOERT) provides a theoretical advantage for access to the tumor bed with reduced toxicity to surrounding structures. The goal of this study was to evaluate the role of IOERT in high-risk patients. METHODS: An institutional review board approved, single institution sarcoma database was queried to identify patients who received IOERT for treatment of RPS from 2/2001 to 1/2009. Data were analyzed using the Kaplan-Meier method, Cox regression, and Fisher Exact tests. RESULTS: Eighteen patients (median age 51 y, 25-76 y) underwent tumor resection with IOERT (median dose 1250 cGy) for primary (n = 13) and recurrent (n = 5) RPS. Seventeen patients received neoadjuvant radiotherapy. Eight high-grade and 10 low-grade tumors were identified. Median tumor size was 15 cm. Four patients died and two in the perioperative period. Median follow-up of survivors was 3.6 y. Five patients (31%) developed an LR in the irradiated field. Three patients with primary disease (25%) and two (50%) with recurrent disease developed an LR (P = 0.5). Four patients with high-grade tumors (57%) and one with a low-grade tumor (11%) developed an LR (P = 0.1). The 2- and 5-y OS rates were 100% and 72%. Two- and 5-y LR rates were 13% and 36%. CONCLUSIONS: Using a multidisciplinary approach, we have achieved low LR rates in our high-risk patient population indicating that IOERT may play an important role in managing these patients.