PET Imaging and Rate of Pathologic Complete Response in Esophageal Squamous Cell Carcinoma.

BACKGROUND: For locally advanced esophageal squamous cell carcinoma (ESCC), chemoradiation (ChemoRT) followed by surgery offers the best chance of cure, with a 35-50% pathologic complete response (pCR) rate. Given the morbidity of esophagectomy and the possibility of pCR with ChemoRT, a 'watch and wait' strategy has been proposed, particularly for squamous cell carcinoma. The ability to accurately predict which patients will have pCR from ChemoRT is critical in treatment decision making. This study assessed positron emission tomography (PET) in predicting pCR after neoadjuvant ChemoRT for ESCC. METHODS: ESCC patients treated with ChemoRT followed by surgery were identified. Maximum standard uptake value (SUV), metabolic tumor volume, total lesion glycolysis, and first-order textual features of standard deviation, kurtosis and skewness were measured from PET. Univariable and multivariable generalized linear method analyses were performed. A metabolic complete response (mCR) was defined as a post-therapy PET scan with maximum SUV < 4.0. RESULTS: Twenty-seven patients underwent ChemoRT followed by surgery, with overall pCR seen in 11 (41%) patients and radiographic mCR seen in 12 (44%) patients. Final pathology for these 12 patients revealed pCR (ypT0N0M0) in 5 (42%) patients and persistent disease in 7 (58%) patients. Univariate analysis did not reveal PET parameters predictive of pCR. CONCLUSION: Treatment of ESCC with ChemoRT often results in a robust clinical response. Among patients with an mCR after ChemoRT, disease persistence was found in 58%. The inability of PET to predict pCR is important in the context of a 'watch and wait' strategy for ESCC treated with ChemoRT.

Does Residual Cancer Burden Predict Local Recurrence After Neoadjuvant Chemotherapy?

BACKGROUND: The extent of residual disease after neoadjuvant chemotherapy (NAC) can be quantified by the Residual Cancer Burden (RCB), a prognostic tool used to estimate survival outcomes in breast cancer. This study investigated the association between RCB and locoregional recurrence (LRR). METHODS: The study reviewed 532 women with breast cancer who underwent NAC between 2010 and 2016. Relapse in the ipsilateral breast, skin/subcutis at the surgical site, chest wall, pectoralis, or regional lymph nodes defined an LRR. The LRR cumulative incidence (LRCI) was estimated using the Fine and Gray competing-risks model, with death and distant recurrence defined as competing events. The association of LRCI with prognostic variables was evaluated. RESULTS: Overall, 5.5% of the patients experienced an LRR after a median follow-up period of 65 months. The 5-year LRCI rates by RCB were as follows: RCB-0 (0.9%), RCB-1 (3.2%), RCB-2 (6.0%), and RCB-3 (12.9%). In the univariable analysis, LRCI varied significantly by RCB (p = 0.010). The multivariable analysis showed a significant association of LRCI with increasing RCB, and the patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) phenotype were at lower risk for LRR than those with HER2+ and triple-negative cancers (p < 0.032). The patients with RCB-3 were at a higher risk for local relapse than those with RCB-0 (hazard ratio, 13.78; confidence interval, 2.25-84.45; p = 0.04). Type of operation (p = 0.04) and use of adjuvant radiation (p = 0.046) were statistically significant in the multivariable model. CONCLUSIONS: The study results demonstrate a significant association between LRCI and increasing RCB, although distant recurrence is a substantial driver of disease outcomes. Future prospective studies should examine the role of RCB in clinical decisions regarding indications for adjuvant therapy.

Residual Cancer Burden Class Associated with Survival Outcomes in Women with Different Phenotypic Subtypes of Breast Cancer After Neoadjuvant Chemotherapy.

BACKGROUND: The residual cancer burden class informs survival outcomes after neoadjuvant chemotherapy. We evaluated the prognostic ability of the RCB for survival outcomes in women with different phenotypic subtypes of breast cancer treated with neoadjuvant chemotherapy. Additional variables were assessed for inclusion with the RCB to further improve the model's discriminative ability. PATIENTS AND METHODS: We conducted a retrospective review of patients completing at least 75% of the recommended cycles of neoadjuvant chemotherapy between 1 January 2010 and 31 December 2016. Phenotypic subtypes were defined by hormone receptor and human epidermal growth factor receptor 2 (HER2) status at diagnosis, classified as HR+/HER2-, HER2+, or triple-negative breast cancer (TNBC). The RCB class was calculated and survival endpoints of overall survival, recurrence-free survival, and distant recurrence-free survival were analyzed using Kaplan-Meier and Cox proportional hazards methods. The discriminative ability of the models was quantified by Harrell's C-index. RESULTS: Overall, 532 women met the inclusion criteria. Median follow-up was 65 months. In univariate models, RCB was significantly associated with OS, RFS, and DRFS. The RCB class had good discriminative ability for OS, RFS, and DRFS survival, with Harrell's C-indices of 0.68, 0.67, and 0.68, respectively. The RCB class discriminated well for each survival endpoint within HER2+ and TNBC, but did not discriminate well for HR+/HER2- (OS Harrell's C-indices of 0.77, 0.75, and 0.52, respectively). CONCLUSIONS: The RCB class was prognostic for OS, RFS, and DRFS after neoadjuvant chemotherapy, but prognostic discrimination between patients with subtype HR+/HER2- was not observed during the follow-up period for which the overall event rate was low.

Extremity Soft Tissue Sarcoma: A Multi-Institutional Validation of Prognostic Nomograms.

BACKGROUND: Prognostic nomograms for patients with resected extremity soft tissue sarcoma (STS) include the Sarculator and Memorial Sloan Kettering (MSKCC) nomograms. We sought to validate these two nomograms within a large, modern, multi-institutional cohort of resected primary extremity STS patients. METHODS: Resected primary extremity STS patients from 2000 to 2017 were identified across nine high-volume U.S. institutions. Predicted 5- and 10-year overall survival (OS) and distant metastases cumulative incidence (DMCI), and 4-, 8-, and 12-year disease-specific survival (DSS) were calculated with Sarculator and MSKCC nomograms, respectively. Predicted survival probabilities stratified in quintiles were compared in calibration plots to observed survival assessed by Kaplan-Meier estimates. Cumulative incidence was estimated for DMCI. Harrell's concordance index (C-index) assessed discriminative ability of nomograms. RESULTS: A total of 1326 patients underwent resection of primary extremity STS. Common histologies included: undifferentiated pleomorphic sarcoma (35%), fibrosarcoma (13%), and leiomyosarcoma (9%). Median tumor size was 8.0 cm (IQR 4.5-13.0). Tumor grade distribution was: Grade 1 (13%), Grade 2 (9%), Grade 3 (78%). Median OS was 172 months, with estimated 5- and 10-year OS of 70% and 58%. C-indices for 5- and 10-year OS (Sarculator) were 0.72 (95% CI 0.70-0.75) and 0.73 (95% CI 0.70-0.75), and 0.72 (95% CI 0.69-0.75) for 5- and 10-year DMCI. C-indices for 4-, 8-, and 12-year DSS (MSKCC) were 0.71 (95% CI 0.68-0.75). Calibration plots showed good prognostication across all outcomes. CONCLUSIONS: Sarculator and MSKCC nomograms demonstrated good prognostic ability for survival and recurrence outcomes in a modern, multi-institutional validation cohort of resected primary extremity STS patients. External validation of these nomograms supports their ongoing incorporation into clinical practice.

A multi-institutional validation study of prognostic nomograms for retroperitoneal sarcoma.

BACKGROUND AND OBJECTIVES: Prognostic nomograms for patients undergoing resection of retroperitoneal sarcoma (RPS) include the Sarculator and Memorial Sloan Kettering (MSK) sarcoma nomograms. We sought to validate the Sarculator and MSK nomograms within a large, modern multi-institutional cohort of patients with primary RPS undergoing resection. METHODS: Patients who underwent resection of primary RPS between 2000 and 2017 across nine high-volume US institutions were identified. Predicted 7-year disease-free (DFS) and overall survival (OS) and 4-, 8-, and 12-year disease-specific survival (DSS) were calculated from the Sarculator and MSK nomograms, respectively. Nomogram-predicted survival probabilities were stratified in quintiles and compared in calibration plots to observed survival outcomes assessed by Kaplan-Meier estimates. Discriminative ability of nomograms was quantified by Harrell's concordance index (C-index). RESULTS: Five hundred and two patients underwent resection of primary RPS. Histologies included leiomyosarcoma (30%), dedifferentiated liposarcoma (23%), and well-differentiated liposarcoma (15%). Median tumor size was 14.0 cm (interquartile range [IQR], 8.5-21.0 cm). Tumor grade distribution was: Grade 1 (27%), Grade 2 (17%), and Grade 3 (56%). Median DFS was 31.5 months; 7-year DFS was 29%. Median OS was 93.8 months; 7-year OS was 51%. C-indices for 7-year DFS, and OS by the Sarculator nomogram were 0.65 (95% confidence interval [CI]: 0.62-0.69) and 0.69 (95%CI: 0.65-0.73); plots demonstrated good calibration for predicting 7-year outcomes. The C-index for 4-, 8-, and 12-year DSS by the MSK nomogram was 0.71 (95%CI: 0.67-0.75); plots demonstrated similarly good calibration ability. CONCLUSIONS: In a diverse, modern validation cohort of patients with resected primary RPS, both Sarculator and MSK nomograms demonstrated good prognostic ability, supporting their ongoing adoption into clinical practice.

Enhanced Recovery After Surgery and Perioperative Laryngectomy Outcomes.

OBJECTIVE: Patients undergoing laryngectomy are particularly vulnerable to postoperative complications secondary to social and nutritional barriers, substance abuse, and prior cancer treatment. Enhanced Recovery After Surgery (ERAS) programs may mitigate this vulnerability and improve postoperative complications and oncologic outcomes. The objective of this study is to evaluate the postoperative complication rate and oncologic outcomes of patients undergoing laryngectomy before and after ERAS program implementation. METHODS: A historic cohort of 50 patients who underwent laryngectomy at the Levine Cancer Institute, Charlotte, North Carolina from 2014 to 2019 (pre-ERAS) was compared to 33 patients who underwent laryngectomy after ERAS implementation from 2019 to 2020. The primary outcomes included length of stay (LOS), Clavien-Dindo postoperative complications through 30 days following discharge, overall survival (OS), and recurrence-free survival between pre-ERAS and ERAS groups. RESULTS: Demographic characteristics between the two groups were similar. ERAS pathway implementation led to core care element consistency and improvement in the clinical perioperative course, including preoperative nutritional intervention (p = 0.009), postoperative ventilator independence (p = 0.0004), and refractory nausea/emesis (p = 0.18). Severe (≥ grade 3) complications (p = 0.49) and LOS (p = 0.68) were similar between groups. No significant difference in Cox proportional modeling of OS (p = 0.60) or recurrence-free survival (p = 0.17) was noted. CONCLUSIONS: ERAS did not improve LOS, major postoperative complications, or oncologic outcomes in this cohort of patients who underwent laryngectomy. However, ERAS positively influenced secondary endpoints within the laryngectomy perioperative course, conferring qualitative health care benefits. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2262-2268, 2024.

Factors Associated with Early Discharge after Non-Emergent Right Colectomy for Colon Cancer: A NSQIP Analysis.

The National Surgical Quality Improvement Project (NSQIP) dataset was used to identify perioperative variables associated with the length of stay (LOS) and early discharge among cancer patients undergoing colectomy. Patients who underwent non-emergent right colectomy for colon cancer from 2012 to 2019 were identified from the NSQIP and colectomy-targeted databases. Postoperative LOS was analyzed based on postoperative day (POD) of discharge, with patients grouped into Early Discharge (POD 0-2), Standard Discharge (POD 3-5), or Late Discharge (POD ≥ 6) cohorts. Multivariable ordinal logistic regression was performed to identify risk factors associated with early discharge. The NSQIP query yielded 26,072 patients: 3684 (14%) in the Early Discharge, 13,414 (52%) in the Standard Discharge, and 8974 (34%) in the Late Discharge cohorts. The median LOS was 4.0 days (IQR: 3.0-7.0). Thirty-day readmission rates were 7% for Early Discharge, 8% for Standard Discharge, and 12% for Late Discharge. On multivariable regression analysis, risk factors significantly associated with a shorter LOS included independent functional status, minimally invasive approach, and absence of ostomy or additional bowel resection (all p < 0.001). Perioperative variables can be used to develop a model to identify patients eligible for early discharge after right colectomy for colon cancer. Efforts to decrease the overall median length of stay should focus on optimization of modifiable risk factors.

Prognostic value of galectin-1 and galectin-3 expression in localized urothelial bladder cancer.

Background: Galectin-1 (Gal-1) and Galectin-3 (Gal-3) are carbohydrate binding proteins with a wide range of biological activity, including regulation of cellular adhesion, proliferation, and apoptosis in solid tumors. Prior small studies have reported that Gal-3 expression is associated with progression of disease in urothelial carcinoma (UC), from non-muscle invasive UC progression to muscle invasive UC. We assessed Gal-1 and Gal-3 protein expression H-score utilizing a tissue microarray (TMA) created from 301 cystectomy specimens. Methods: Immunohistochemistry for Gal-1 and Gal-3 was performed on TMA generated from tumor blocks from chemotherapy naïve cystectomy specimens. The variable of interest, H-score, was defined as the product of the percentage of cells staining positive (0-100) and intensity score (0-3) scored by a single pathologist. Survival end points were analyzed using Kaplan-Meier and Cox Proportional Hazards methods. Clinical data including Charlson Comorbidity Index (CCI), pathologic tumor (T) stage, tumor size, node stage, and surgical margins, were included in multivariable analysis. Results: We found that Gal-1 and Gal-3 expression correlated with intratumoral T stage (median Gal-1 H-score was 0 across non-invasive tissue types and 200 in invasive, P<0.01 and median Gal-3 score was 270 across non-invasive tissue types and 70 in invasive, P<0.01). However, the highest intratumoral H-score per cystectomy core did not independently predict for recurrence-free survival (RFS) (Gal-1: HR =1.02, P=0.44, Gal-3: HR =1.01, P=0.65) or OS (Gal-1: HR =1.02, P=0.44, Gal-3: HR =1.01, P=0.72) in this cohort. Significant intratumoral heterogeneity was present for both Gal-1 and Gal-3, with an average difference between the highest and lowest H score was 95 for Gal-1 and 109 for Gal-3 for cystectomy specimens with more than one biopsy. Conclusions: Gal-1 and Gal-3 H-score per bladder did not independently predict for RFS or OS. Intra-tumoral Gal-1/Gal-3 heterogeneity complicates the use of Gal-1 and Gal-3 expression as a prognostic biomarker. Future studies should consider the evaluation of serum and urinary galectins as an approach to mitigate tumor heterogeneity.

COVID-19 vaccine uptake trends in SARS-CoV-2 previously infected cancer patients.

Purpose: Cancer patients are at high risk of developing severe illness from SARS-CoV-2 infection, but risk is lowered with receipt of COVID-19 vaccine. COVID-19 vaccination uptake among previously infected cancer patients may be influenced by an assumption of natural immunity, predicted weak immune response, or concerns about vaccine safety. The objective of this study was to evaluate COVID-19 vaccine uptake trends in cancer patients previously infected with SARS-CoV-2. Materials and Methods: Medical records of 579 sequential cancer patients undergoing active treatment at Levine Cancer Institute who tested positive for COVID-19 between January 2020 and January 2021 were evaluated. Patients who died prior to vaccine eligibility were excluded from the analysis. Demographic, clinical, and COVID-19 related characteristics were analyzed to identify prognostic factors for COVID-19 vaccine uptake as this information could be important for health policy design for future pandemics. Results: Eighty-one patients died prior to the availability of COVID-19 vaccines. The acceptance rate of COVID-19 vaccination among 498 previously infected cancer patients was 54.6%. Of the patients with known vaccination dates, 76.8% received their first vaccine by April 17th, 2021. As of November 30, 2021, 23.7.% of eligible patients were boosted. In univariate models, older age, female sex, higher income, solid tumor cancer type, and hormone therapy were significantly associated with higher vaccine uptake, while Hispanic/Latino ethnicity was significantly associated with lower vaccine uptake. In a multivariable model, age (OR 1.18, 95% CI 1.10-1.28; p < 0.001), female sex (OR 1.80, 95% CI 1.22-2.66; p = 0.003), and higher income (OR 1.11, 95% CI 1.01-1.22; p = 0.032), were predictive of COVID-19 vaccine uptake. Conclusions: Overall, vaccine uptake was low among our cohort of previously infected cancer patients. Older age, female sex, and higher income were the only variables associated with COVID-19 vaccine uptake within this vulnerable patient population.

Understanding the Value of the Wellness Visit: A Descriptive Study.

INTRODUCTION: Clinical preventive services can reduce mortality and morbidity, but Americans receive only half of the recommended care. Although wellness visits protect time for clinicians to review needs and discuss care with patients, studies have not shown that having a wellness visit improves health outcomes. This study seeks to understand the types of discussions and volume of care delivered during wellness visits. METHODS: Using a sample of 1,008 patients scheduled for a wellness visit from 22 primary care clinicians across 3 states from 2018 to 2019, electronic health records were reviewed, and a subset of visits was audio recorded. The discussion and delivery of clinical preventive services, as recommended by the U.S. Preventive Services Task Force, were measured, and new diagnoses were identified from the clinical preventive services. Analyses were completed in 2020. RESULTS: Even though patients were up to date with 80% of the recommended clinical preventive services 3 months after the visit, only 0.5% of patients were up to date with all the recommended clinical preventive services. On average, 6.9 clinical preventive service discussions occurred during each wellness visit on the basis of electronic health records review, and 7.7 clinical preventive services discussions occurred on the basis of audio recordings. An average of 0.4 new diagnoses was identified, including cancer diagnoses, cardiovascular risks, and infections. CONCLUSIONS: Wellness visits are an important time for patients and clinicians to discuss prevention strategies and to deliver recommended clinical preventive services, leading to the identification of previously unrecognized diagnoses. This will improve patients' health. Policies and incentives that promote wellness visits are important, and efforts are needed to deliver them to those most in need.

Dexamethasone and postoperative hyperglycemia in diabetics undergoing elective hip or knee arthroplasty: a case control study in 238 patients.

BACKGROUND: Dexamethasone has been routinely used in the pre-operative setting to enhance analgesia and decrease the incidence of nausea and vomiting in patients undergoing primary arthroplasty. However, dexamethasone has the potential to increase blood glucose levels postoperatively, which is a known risk factor for complications after total joint arthroplasty. The aim of this study was to analyze the effect of dexamethasone administration on post-operative blood glucose levels in diabetic patients after primary hip and knee arthroplasty. METHODS: This study was a retrospective review of 238 diabetic patients who underwent primary hip and knee arthroplasty between May 1, 2014 and September 30, 2016 at a single urban academic medical center. A total of 77 patients (32.4%) received dexamethasone and 161 (67.7%) did not. Oral hyperglycemic agents were held during the inpatient stay and blood glucose was controlled either with sliding scale insulin or home insulin regimens were continued. All analyses were adjusted for age, BMI, gender, type of diabetes, pre-operative diabetic medication, type of surgical procedure, and pre-operative HgbA1c level. The primary outcome was post-operative hyperglycemia within 72 h of surgery defined as any blood glucose level greater than or equal to 200 mg/dL. RESULTS: Post-operative hyperglycemia was observed in 17.1 and 20.6% of the measurements during the first 24 and 72 h respectively. After controlling for confounding variables, patients who received dexamethasone had 4.07 (95% CI: 2.46, 6.72) and 3.08 (95% CI: 2.34, 4.04) higher odds of post-operative hyperglycemia in the first 24 and 72 h respectively. CONCLUSIONS: Dexamethasone administration in diabetic patients undergoing primary arthroplasty increases post-operative hyperglycemia during the first 24 and 72 h. While our data did not investigate causation, dexamethasone use in this patient population should be thoughtfully considered, as post-operative hyperglycemia is a known risk factor for complications.