Current patterns of care and outcomes for dermatofibrosarcoma protuberans: An international multi-institutional collaborative.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a cutaneous sarcoma with an infiltrative growth pattern that makes it challenging to clear margins. High quality data regarding DFSP natural history, management, and outcomes are limited. METHODS: Data were retrospectively collected for adult DFSP patients who underwent resection at 10 institutions in eight countries. Demographics, tumor characteristics, treatment strategies, and outcomes were analyzed. RESULTS: Analysis included 347 patients consisting of young (median, 42 years), White (76.2%), males (54.2%) with truncal lesions (57.3%). The majority (76.8%) were symptomatic at presentation. Preoperative imaging was used in 55.9% of cases. Diagnosis was established with excisional biopsy in 50.9% versus incisional biopsy in 25.0% of cases. Despite planned margins of >1.0 cm in 67.4% of cases, only 69.0% of patients achieved R0 resection. Twenty-two percent of patients underwent at least one re-excision. R0 resection was achieved at a second procedure in 80.2% and a third procedure in 86.2%. Ultimately, R0 resection was feasible in 89.5% of all patients. Fibrosarcomatous transformation (FST) was observed in 12.6%. In total, 6.6% (N = 23) recurred (17 local, six distant). Of the six distant recurrences, 50.0% had FST. With a median follow-up of 47.0 months, disease-specific survival rate was 98.8%. In multivariable analysis, R0 margins at index resection were associated with wider circumferential margins and non-FST histology. CONCLUSIONS: In this international, multicenter collaborative, DFSP practice patterns were heterogeneous but achieved favorable recurrence rates and survival. Multiple excisions to clear margins remain commonplace and can inform future efforts to optimize margin selection.

Factors associated with self-neglect from a salutogenic perspective among community-dwelling older adults: A cross-sectional correlational study.

OBJECTIVES: To identify the associated factors of self-neglect in older adults from a salutogenic perspective. METHODS: A cross-sectional correlational study was conducted in two communities in Beijing with 486 older adults recruited from April to December 2022. Data were collected by a set of questionnaires. RESULTS: Sense of coherence (ß=-0.138), socio-demographic generalized resistance resources (GRRs) (smoking: ß=0.156), social GRRs (living alone: ß=0.093), psychological GRRs (self-esteem: ß=-0.126), and motivational GRRs (powerful others locus of control: ß=-0.199, chance locus of control: ß=0.119) were all associated with self-neglect among older adults (p<0.05). CONCLUSIONS: Sense of coherence and GRRs are vital to improve self-neglect in older adults. It is suggested to increase the level of self-esteem and the tendency of the health locus of control to largely facilitate self-neglect management in older adults.

Factors Associated With Racial and Ethnic Disparities in Locally Advanced Rectal Cancer Outcomes.

Importance: Hispanic and non-Hispanic Black patients receiving neoadjuvant therapy and surgery for locally advanced rectal cancer (LARC) achieve less favorable clinical outcomes than non-Hispanic White patients, but the source of this disparity is incompletely understood. Objective: To assess whether racial and ethnic disparities in treatment outcomes among patients with LARC could be accounted for by social determinants of health and demographic, clinical, and pathologic factors known to be associated with treatment response. Design, Setting, and Participants: The National Cancer Database was interrogated to identify patients with T3 to T4 or N1 to N2 LARC treated with neoadjuvant therapy and surgery. Patients were diagnosed between January 1, 2004, and December 31, 2017. Data were culled from the National Cancer Database from July 1, 2022, through December 31, 2023. Exposure: Neoadjuvant therapy for rectal cancer followed by surgical resection. Main Outcomes and Measures: The primary outcome was the rate of pathologic complete response (pCR) following neoadjuvant therapy. Secondary outcomes were rate of tumor downstaging and achievement of pN0 status. Results: A total of 34 500 patient records were reviewed; 21 679 of the patients (62.8%) were men and 12 821 (37.2%) were women. The mean (SD) age at diagnosis was 59.7 (12.0) years. In terms of race and ethnicity, 2217 patients (6.4%) were Hispanic, 2843 (8.2%) were non-Hispanic Black, and 29 440 (85.3%) were non-Hispanic White. Hispanic patients achieved tumor downstaging (48.9% vs 51.8%; P = .01) and pN0 status (66.8% vs 68.8%; P = .02) less often than non-Hispanic White patients. Non-Hispanic Black race, but not Hispanic ethnicity, was associated with less tumor downstaging (odds ratio [OR], 0.86 [95% CI, 0.78-0.94]), less frequent pN0 status (OR, 0.91 [95% CI, 0.83-0.99]), and less frequent pCR (OR, 0.81 [95% CI, 0.72-0.92]). Other factors associated with reduced rate of pCR included rural location (OR, 0.80 [95% CI, 0.69-0.93]), lack of or inadequate insurance (OR for Medicaid, 0.86 [95% CI, 0.76-0.98]; OR for no insurance, 0.65 [95% CI, 0.54-0.78]), and treatment in a low-volume center (OR for first quartile, 0.73 [95% CI, 0.62-0.87]; OR for second quartile, 0.79 [95% CI, 0.70-0.90]; OR for third quartile, 0.86 [95% CI, 0.78-0.94]). Clinical and pathologic variables associated with a decreased pCR included higher tumor grade (OR, 0.58 [95% CI, 0.49-0.70]), advanced tumor stage (OR for T3, 0.56 [95% CI, 0.42-0.76]; OR for T4, 0.30 [95% CI, 0.22-0.42]), and lymph node-positive disease (OR for N1, 0.83 [95% CI, 0.77-0.89]; OR for N2, 0.73 [95% CI, 0.65-0.82]). Conclusions and Relevance: The findings of this cohort study suggest that disparate treatment outcomes for Hispanic and non-Hispanic Black patients are likely multifactorial in origin. Future investigation into additional social determinants of health and biological variables is warranted.

Real-time estimation of nephron activity with a linear measurement system (RENAL-MS) predicts postoperative estimated glomerular filtration rate.

OBJECTIVE: To determine whether a simple point-of-care measurement system estimating renal parenchymal volume using tools ubiquitously available could be used to replace nuclear medicine renal scintigraphy (NMRS) in current clinical practice to predict estimated glomerular filtration rate (eGFR) after nephrectomy by estimating preoperative split renal function. PATIENTS AND METHODS: We performed a retrospective review of patients who underwent abdominal cross-sectional imaging (computed tomography/magnetic resonance imaging) and mercaptoacetyltriglycine (MAG3) NMRS prior to total nephrectomy at a single institution. We developed the real-time estimation of nephron activity with a linear measurement system (RENAL-MS) method of estimating postoperative renal function via the following technique: renal parenchymal volume of the removed kidney relative to the remaining kidney was estimated as the product of renal length and the average of six renal parenchymal thickness measurements. The utility of this value was compared to the utility of the split renal function measured by MAG3 for prediction of eGFR and new onset Stage 3 chronic kidney disease (CKD) at ≥90 days after nephrectomy using uni- and multivariate linear and logistic regression. RESULTS: A total of 57 patients met the study criteria. The median (interquartile range [IQR]) age was 69 (61-80) years. The median (IQR) pre- and postoperative eGFR was 74 (IQR 58-90) and 46 (35-62) mL/min/1.73 m2 , respectively. [Correction added on 29 December 2023, after first online publication: The data numbers in the preceding sentence have been corrected.] Correlations between actual and predicted postoperative eGFR were similar whether the RENAL-MS or NMRS methods were used, with correlation using RENAL-MS being slightly numerically but not statistically superior (R = 0.82 and 0.76; P = 0.138). Receiver operating characteristic curve analysis using logistic regression estimates incorporating age, sex, and preoperative creatinine to predict postoperative Stage 3 CKD were similar between RENAL-MS and NMRS (area under the curve 0.93 vs. 0.97). [Correction added on 29 December 2023, after first online publication: The data numbers in the preceding sentence have been corrected.] CONCLUSION: A point-of-care tool to estimate renal parenchymal volume (RENAL-MS) performed equally as well as NMRS to predict postoperative eGFR and de novo Stage 3 CKD after nephrectomy in our population, suggesting NMRS may not be necessary in this setting.

Attitudes About the Human Papillomavirus Vaccine Among Patients With and Without Cervical Dysplasia.

OBJECTIVES: The aims of the study are to examine the perception of the human papillomavirus (HPV) vaccine among those with and without a history of cervical dysplasia and to examine perceptions of the vaccine for their children. MATERIALS AND METHODS: Patients were recruited to complete a survey about the HPV vaccine for both themselves and their children. Patients in a colposcopy clinic with a history of abnormal cervical cytology and patients in a benign gynecology clinic without a history of abnormal cervical cytology were recruited. Participants' medical records were reviewed. Demographics and survey answers were described, and Fisher exact test was used to compare the groups. RESULTS: One hundred eighty-three patients participated: 73 in colposcopy clinic and 110 in benign clinic. The majority self-identified as Black (74% colposcopy, 71% benign, p = .588) and reported an income less than $39,000 a year (77% colposcopy, 65% benign, p = .089). Fifty-six percent in benign clinic agreed the HPV vaccine is a good way to protect oneself from disease compared with 48% in colposcopy clinic ( p = .022). When examining results based on cytology, fewer patients in the highest-grade cytology group agreed the vaccine was effective (30% high-grade, 48% normal, 57% low-grade, p = .027) or a good way to protect themselves from disease (29% high-grade, 53% normal, 62% low-grade, p = .002). There was otherwise no statistically significant difference between the groups on questions regarding self or child vaccination. CONCLUSIONS: In a majority Black, low-income population, patients without a history of abnormal cervical cytology have more favorable perceptions of the HPV vaccine's effectiveness in preventing disease. Those with the highest-grade cytology had more negative perceptions of the vaccine's effectiveness and protectability.

Survey of Surgeon-reported Postoperative Protocols for Deep Inferior Epigastric Perforator Flap in Breast Reconstruction.

Background: The use of deep inferior epigastric perforator (DIEP) flaps is a well-established breast reconstruction technique. Methods: A 29-question survey was e-mailed to 3186 active American Society of Plastic Surgeons members, aiming to describe postoperative monitoring practice patterns among surgeons performing DIEP flaps. Results: From 255 responses (8%), 79% performing DIEP surgery were analyzed. Among them, 34.8% practiced for more than 20 years, 34.3% for 10-20 years, and 30.9% for less than 10 years. Initial 24-hour post-DIEP monitoring: intensive care unit (39%) and floor (36%). Flap monitoring: external Doppler (71%), tissue oximetry (41%), and implantable Doppler (32%). Postoperative analgesia: acetaminophen (74%), non-steroidal anti-inflammatory drugs (69%), neuromodulators (52%), and opioids (4.4%) were administered on a scheduled basis. On postoperative day 1, 61% halt intravenous fluids, 67% allow ambulation, 70% remove Foley catheter, and 71% start diet. Most surgeons discharged patients from the hospital on postoperative day 3+. Regardless of experience, patients were commonly discharged on day 3. Half of the surgeons are in academic/nonacademic settings and discharge on/after day 3. Conclusions: This study reveals significant heterogeneity among the practice patterns of DIEP surgeons. In light of these findings, it is recommended that a task force be convened to establish standardized monitoring protocols for DIEP flaps. Such protocols have the potential to reduce both the length of hospital stays and overall care costs all while ensuring optimal pain management and vigilant flap monitoring.

A dosimetric analysis of rectal hydrogel spacer use in patients with recurrent prostate cancer undergoing salvage high-dose-rate brachytherapy.

PURPOSE: We hypothesize rectal hydrogel spacer (RHS) improves rectal dosimetry in patients undergoing salvage high-dose-rate brachytherapy (HDR-BT) for intact, recurrent prostate cancer (PC). METHODS AND MATERIALS: A prospectively collected institutional database was queried for recurrent PC patients treated with salvage HDR-BT from September 2015 to November 2021. Patients were offered RHS beginning June 2019. Dosimetric variables were compared between RHS and no-RHS groups for the average of two fractions using Wilcoxon rank-sum tests. Primary outcomes were rectal volume receiving 75% of prescription dose (V75%) and prostate volume receiving 100% of prescription dose (V100%). Generalized estimating equation (GEE) model was used to evaluate the association between other planning variables and rectal V75%. RESULTS: Forty-one PC patients received salvage HDR-BT, of whom 20 had RHS. All patients received 2400cGy in 2 fractions. Median RHS volume was 6.2cm3 (Standard deviation [SD]: ± 3.5cm3). Median follow-up was 4 months and 17 months in the RHS and no-RHS groups, respectively. Median rectal V75% with and without RHS were 0.0cm3 (IQR: 0.0-0.0cm3) and 0.06cm3 (IQR: 0.0-0.14cm3), respectively (p<0.001). Median prostate V100% with and without RHS were 98.55% (IQR: 97.86-99.22%) and 97.78% (IQR: 97.50-98.18%), respectively (p = 0.007). RHS, rectum, and prostate volumes did not significantly affect rectal V75% per GEE modeling. There was 10% G1-2 and 5% G3 rectal toxicity in RHS group. There was 9.5% G1-2 and no G3+ rectal toxicities in the no-RHS group. CONCLUSIONS: Absolute improvement in rectal V75% and prostate V100% was significant with RHS in PC patients undergoing salvage HDR-BT, but clinical benefit is marginal.

Gender differences in cardiothoracic surgery letters of recommendation.

OBJECTIVE: To investigate whether or not gender influences letters of recommendation for cardiothoracic surgery fellowship. METHODS: From applications to an Accreditation Council Graduate Medical Education cardiothoracic surgery fellowship program between 2016 and 2021, applicant and author characteristics were examined with descriptive statistics, analysis of variance, and Pearson χ2 tests. Linguistic software was used to assess communication differences in letters of recommendation, stratified by author and applicant gender. An additional higher-level analysis was then performed using a generalized estimating equations model to examine linguistic differences among author-applicant gender pairs. RESULTS: Seven hundred thirty-nine recommendation letters extracted from 196 individual applications were analyzed; 90% (n = 665) of authors were men and 55.8% (n = 412) of authors were cardiothoracic surgeons. Compared with women authors, authors who are men wrote more authentic (P = .01) and informal (P = .03) recommendation letters. When writing for women applicants, authors who are men were more likely to display their own leadership and status (P = .03) and discuss women applicants' social affiliations (P = .01), like occupation of applicant's father or husband. Women authors wrote longer letters (P = .03) and discussed applicants' work (P = .01) more often than authors who are men. They also mentioned leisure activities (P = .03) more often when writing for women applicants. CONCLUSIONS: Our work identifies gender-specific differences in letters of recommendation. Women applicants may be disadvantaged because their recommendation letters are significantly more likely to focus on their social ties, leisure activities, and the status of the letter writer. Author and reviewer awareness of gender-biased use of language will aid in improvements to the candidate selection process.

Timing of Unplanned Reoperation After Lower Extremity Free Flap Reconstruction: What Are the Roles of Procedure Indication and Defect Etiology?

BACKGROUND: Advancements in lower extremity (LE) microsurgery have allowed for the expansion of indications for LE reconstructions. This project aims to better understand the temporal pattern and risk factors associated with LE free flap failure based on the clinical indication. MATERIALS AND METHODS: We analyzed all patients undergoing LE free flap reconstruction from the American College of Surgeons National Surgical Quality Improvement Program 2012-2019 prospectively collected data to determine rates and timing of reoperation. Free flaps were stratified by indication, type, and timing of reoperation. Weibull survival models were used to compare rates of takebacks among time intervals. Multivariable logistic regression was used to identify independent predictors for unplanned reoperation. RESULTS: Four hundred seven of LE free flaps were analyzed. There was a 14.5% rate (59/407) of unplanned reoperation within the first 30 postoperative days (PODs) after surgery. When stratified by the indication necessitating reoperation, patients with an underlying vascular indication had the highest rate of reoperation (40.9%). The reoperation rates were significantly different between indications (P < 0.05) The mean daily proportion of patients experiencing reoperation was highest during POD 0 to 2 (1.47% reoperations per day), which dropped significantly during POD 3 to 10 (0.55% per day) and again during POD 11 to 30 (0.28% per day, P < 0.05). African American race as well as malignant, prosthetic/implant, and wound/infectious indications were significant independent predictors for unplanned reoperation. CONCLUSIONS: Lower extremity reconstruction is an important reconstructive option for the coverage of a myriad of defects. Understanding the differences between postoperative reoperation timelines among indication subtypes is important for updated flap monitoring protocols, optimizing ERAS pathways, and beginning dangle protocols.

Neoadjuvant Chemotherapy with Accelerated Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Patients with Muscle-invasive Bladder Cancer: A Retrospective Age-stratified Analysis on Safety and Efficacy.

BACKGROUND: The standard of care (SOC) for muscle-invasive bladder cancer (MIBC) includes cisplatin-based combination chemotherapy in the neoadjuvant setting followed by radical cystectomy. Older patients often do not receive SOC due to perceived toxicity concerns despite guideline-directed recommendations. OBJECTIVE: To characterize the safety and efficacy of neoadjuvant accelerated methotrexate, vinblastine, adriamycin, and cisplatin (aMVAC) in MIBC patients as a function of age. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis was conducted in 186 MIBC patients treated at Fox Chase Cancer Center between January 1, 2002 and December 31, 2018. Adults with histologically proven muscle-invasive urothelial cancer were eligible. The exclusion criteria included nonurothelial histology, lack of muscularis propria invasion, and primary upper tract or metastatic disease. INTERVENTION: Neoadjuvant chemotherapy with aMVAC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients were stratified by age (<65, 65-74, and >75 yr old). Renal function was assessed at baseline and at time points after treatment. Clinicopathologic variables were compared between age groups to determine efficacy. RESULTS AND LIMITATIONS: There were no statistically significant differences in dose reductions, treatment interruptions, time to surgery, or adverse events when patients were stratified by age in univariate and multivariate analyses. Full safety data were not available due to the retrospective nature of the study. Baseline renal function was significantly worse among older patients, and the percent decline in creatinine clearance was greater with older age. We found comparable efficacy of aMVAC regardless of age. CONCLUSIONS: Accelerated MVAC was safe and demonstrated efficacy in MIBC irrespective of age in this single-center, retrospective study. Careful selection based on clinical variables, and not age, should identify patients able to receive neoadjuvant chemotherapy. PATIENT SUMMARY: We examined the feasibility of the standard cisplatin-based chemotherapy regimen given prior to surgery in patients with muscle-invasive bladder cancer. Elderly patients experienced a greater decline in kidney function with treatment but not more complications than younger patients and tolerated therapy with minimal dose changes, resulting in benefit regardless of age.

Comparative Outcomes of Second-line Topoisomerase-I Inhibitor Therapies on Neuroendocrine Carcinoma.

INTRODUCTION: This investigation aims to assess the outcomes for second-line therapies to treat extrapulmonary neuroendocrine carcinoma (EP-NEC) after first-line platinum-based chemotherapy. METHODS: With IRB approval, we conducted a retrospective study of EP-NEC patients that progressed on first-line platinum chemotherapy from 2008 to 2018. Demographic data and treatment-related characteristics were collected and represented as descriptive statistics. The primary endpoints include overall survival (OS) and progression-free survival (PFS). OS and PFS were estimated and stratified by site of primary (gastroenteropancreatic [GEP] versus non-GEP) and type of second-line therapy (irino/topotecan versus others). Log-rank test and Kaplan-Meier curves were used to compare survival distributions between groups. RESULTS: Forty-seven patients met eligibility, with median age 65 (range 31-82), 62% male, and 83% White; 22 were GEP and 25 were non-GEP primary. Thirty patients (63.8%) received second-line therapy where 11 received irinotecan/topotecan (ir/to), while 19 received other agents (temozolomide, other platinum agents, gemcitabine, paclitaxel, pembrolizumab, and sunitinib). The median OS was 10.3 months in the ir/to group versus 13.4 months for other therapies, p = 0.10. The median PFS for ir/to therapy compared to other therapies was 2.0 months versus 1.8 months, respectively, p = 0.72. The OS and PFS with and without ir/to were not significantly different by the primary site (p = 0.61 and p = 0.21). DISCUSSION/CONCLUSION: Many EP-NEC patients undergo second-line therapies. Interestingly, outcomes for ir/to-containing second-line therapies were not statistically different from other agents, regardless of the site of primary. With approval of new second-line therapies for small cell lung cancer, further research in therapeutic options is needed for this aggressive disease.

Assessing Oncologists' Adoption of Biomarker Testing in Metastatic Colorectal Cancer Using Real-World Data.

BACKGROUND: Despite national guideline recommendations for universal biomarker testing (KRAS, NRAS, BRAF, and mismatch repair and microsatellite instability [MMR/MSI]) in all patients with metastatic colorectal cancer (mCRC), little is known regarding adherence to these recommendations in routine practice. METHODS: We retrospectively reviewed patients with mCRC diagnosed between January 1, 2013, and December 27, 2018, from a de-identified electronic health record-derived database. We analyzed disparities in KRAS, NRAS, BRAF, and MMR/MSI testing by race, age, sex, and insurance status using χ2 tests and t tests. We evaluated changes in biomarker testing over time with attention to changes around dates of landmark publications and guideline updates using χ2 tests and Cochran-Armitage tests. RESULTS: A total of 20 333 patients were identified of which 66.6% had test results for any biomarker. Rates of test results for all 4 biomarkers statistically significantly increased over time (P < .001). However, as of June 30, 2018, the rate of test results was only 46% for NRAS, 56% for KRAS, and 46% for BRAF. As of December 31, 2017, the rate of MMR/MSI testing was 59%. Higher documented testing rates were associated with younger age, lower Eastern Cooperative Oncology Group performance status, and commercial insurance. There were no clinically meaningful and/or statistically significant differences in documented testing rates by tumor sidedness, race, sex, or initial stage. CONCLUSIONS: Increased rates of documented testing for NRAS, BRAF, and MMR/MSI in mCRC was seen between 2013 and 2018 reflecting adoption of guideline recommendations. However, the rate of documented testing remains lower than expected and warrants additional research to understand the extent to which this may represent a clinical practice quality concern.

Critical Importance of the First Postoperative Days After Head and Neck Free Flap Reconstruction: An Analysis of Timing of Reoperation Using the National Surgical Quality Improvement Program Database.

BACKGROUND: Head and neck free flaps remain associated with considerable rates of take-back and prolonged hospital length of stay. However, there have been no studies on a national level benchmarking the timeline and predictors of head and neck free flap take-back. METHODS: Patients undergoing head and neck free flap reconstruction from the American College of Surgeons National Surgical Quality Improvement Program 2012-2019 database were analyzed to determine the rates of take-back. Timing and rates of unplanned head and neck free flap take-backs were stratified by tissue type and postoperative day (POD) over the first month. Weibull survival models were used to compare rates of take-backs among time intervals. Multivariable logistic regression was used to identify the independent predictors of take-back. RESULTS: Three thousand nine hundred six head and neck free flaps were analyzed. The mean daily proportion of patients experiencing take-back during PODs 0 to 1 was 0.95%; this dropped significantly to a mean daily proportion of 0.54% during POD 2 (P < 0.01). In addition, there were significant drops in take-back when comparing POD 2 (0.54%) to POD 3 (0.26%) and also when comparing POD 4 (0.20%) with PODs 5 to 30 (0.032% per day) (P < 0.05). The soft tissue and osseous flap populations demonstrated a similar trend in unplanned take-back. CONCLUSION: This is the first national study to specifically analyze the timing of take-back in the head and neck reconstruction population. These data highlight the importance of flap monitoring during the first 5 PODs, with ERAS pathway optimization aiming for discharge by the end of the first postoperative week.

Real-world frequency of BRAF testing and utilization of therapies in patients with advanced melanoma.

Both BRAF/MEK targeted agents and immunotherapy are approved for the treatment of advanced melanoma. BRAF testing is recommended at the time of advanced melanoma diagnosis. In addition, little is known regarding the treatment trends for patients with BRAF mutated tumors. This investigation aims to assess the real-world prevalence of molecular testing and treatment trends for patients with BRAF mutated tumors. Using a de-identified database, patients of age ≥18 years with advanced melanoma from 2013 to 2018 were examined. Molecular testing performed within 3 months of advanced diagnosis was considered to have the test performed at the time of diagnosis. Test prevalence was calculated and compared in groups stratified by the patient, tumor and treatment factors. In total 4459 patients were included; 1936 (43.4%) stage III, 1191 (26.7%) stage IV and 1332 (29.9%) recurrent. Totally 50.4% of patients received systemic treatment; 76.4% stage IV, 71% recurrent patients and 26.7% stage III patients. However, 73.5% received first-line immunotherapy. In total 73.8% of patients had molecular testing, and 50.5% had tested at the time of advanced diagnosis. Of those tested 42% had a BRAF mutated tumor. In total 48% of these patients received first-line immunotherapy whereas 43% received a BRAF inhibitor, with increasing immunotherapy use seen over time. The majority of patients with advanced melanoma undergo molecular testing at the time of advanced diagnosis. Immunotherapy is the most commonly prescribed treatment regardless of BRAF mutational status. These results provide real-world data on the frequency of molecular testing and treatment trends for patients with advanced melanoma.

The Role of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma: A Real-World Multi-Institutional Analysis.

PURPOSE: The role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) was challenged by the results of the CARMENA trial. Here we evaluate the role of CN in mRCC patients, including those receiving modern therapies. MATERIALS AND METHODS: We included patients with synchronous mRCC between 2011-2020 from the de-identified nationwide Flatiron Health database. We evaluated 3 groups: systemic therapy alone, CN followed by systemic therapy (up-front CN [uCN]) and systemic therapy followed by CN (deferred CN [dCN]). The primary outcome was median overall survival (mOS) in patients receiving systemic therapy alone vs uCN. Secondary outcome was overall survival in patients receiving uCN vs dCN. First-treatment, landmark and time-varying covariate analyses were conducted to overcome immortal time bias. Weighted Kaplan-Meier curves, log-rank tests and Cox proportional hazards regressions were used to assess the effect of therapy on survival. RESULTS: Of 1,910 patients with mRCC, 972 (57%) received systemic therapy, 605 (32%) received uCN, 142 (8%) dCN and 191 (10%) CN alone; 433 (23%) patients received immunotherapy-based therapy. The adjusted mOS was significantly improved in first-treatment, landmark and time-varying covariate analysis (mOS 26.6 vs 14.6 months, 36.3 vs 21.1 months and 26.1 vs 12.2 months, respectively) in patients undergoing CN. Among patients receiving CN and systemic therapy, the timing of systemic therapy relative to CN was not significantly related to overall survival (HR=1.0, 95% CI 0.76-1.32, p=0.99). CONCLUSIONS: Our findings support an oncologic role for CN in select mRCC patients. In patients receiving both CN and systemic therapy, the survival benefit compared to systemic alone was similar for up-front and deferred CN.

Tumor mutational burden and somatic mutation status to predict disease recurrence in advanced melanoma.

Tumor mutational burden (TMB) has recently been identified as a biomarker of response to immune checkpoint inhibitors in many cancers, including melanoma. Co-assessment of TMB with inflammatory markers and genetic mutations may better predict disease outcomes. The goal of this study was to evaluate the potential for TMB and somatic mutations in combination to predict the recurrence of disease in advanced melanoma. A retrospective review of 85 patients with stage III or IV melanoma whose tumors were analyzed by next-generation sequencing was conducted. Fisher's exact test was used to assess differences in TMB category by somatic mutation status as well as recurrence locations. Kaplan-Meier estimates and Cox-proportional regression model were used for survival analyses. The most frequently detected mutations were TERT (32.9%), CDKN2A (28.2%), KMT2 (25.9%), BRAF V600E (24.7%), and NRAS (24.7%). Patients with TMB-L + BRAFWT status were more likely to have a recurrence [hazard ratio (HR), 3.43; confidence interval (CI), 1.29-9.15; P = 0.01] compared to TMB-H + BRAF WT. Patients with TMB-L + NRASmut were more likely to have a recurrence (HR, 5.29; 95% CI, 1.44-19.45; P = 0.01) compared to TMB-H + NRAS WT. TMB-L tumors were associated with local (P = 0.029) and in-transit (P = 0.004) recurrences. Analysis of TMB alone may be insufficient in understanding the relationship between melanoma's molecular profile and the body's immune system. Classification into BRAFmut, NRASmut, and tumor mutational load groups may aid in identifying patients who are more likely to have disease recurrence in advanced melanoma.

Total neoadjuvant therapy for pancreatic adenocarcinoma increases probability for a complete pathologic response.

BACKGROUND: Multiple neoadjuvant therapy protocols have been proposed in the treatment of pancreatic adenocarcinoma, including chemotherapy (CT), chemoradiation (CRT), and total neoadjuvant therapy (TNT), defined as a CT plus CRT. A pathologic complete response (pCR) can be achieved in a minority of cases. We hypothesize that TNT is more likely to confer pCR than other neoadjuvant therapies, which may improve overall survival (OS). METHODS: A retrospective review of the National Cancer Database (NCDB) from 2006 to 2016 was performed, identifying patients who underwent any neoadjuvant therapy followed by definitive pancreatic resection for locally advanced or borderline resectable pancreatic adenocarcinoma. A pathologic complete response was defined as down-staging from any clinical stage to pathologic stage 0. RESULTS: A total of 5402 patients who received neoadjuvant therapy followed by resection were identified. 177 patients (3.3%) achieved a pCR. Of the patients who achieved a pCR, 57 received CT, 41 CRT and 79 received TNT. On multivariate analysis, TNT was more likely to confer a pCR than CRT (OR 1.67, CI 1.13-2.46, p = 0.0103) or CT (OR 2.61, CI 1.83-3.71, p < 0.0001). Patients who achieved pCR had a significantly higher OS, with median survival of 64.9 months, compared to 21.6 months in patients who did not achieve pCR (p < 0.0001). CONCLUSION: TNT may be more likely to achieve a pCR than CT or CRT. Patients who achieve a pCR have a significant OS benefit as compared to those who have residual disease. TNT should be considered for patients requiring neoadjuvant therapy, as it may increase the likelihood of achieving a pCR, thus potentially improving OS.

Safety of neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer and malignant ureteric obstruction.

OBJECTIVES: To determine whether patients with carcinoma invading bladder muscle (MIBC) and ureteric obstruction can safely receive cisplatin-based neoadjuvant chemotherapy (C-NAC), and to determine whether such patients require relief of obstruction with a ureteric stent or percutaneous nephrostomy prior to beginning C-NAC. PATIENTS AND METHODS: We performed a single-institution retrospective analysis of MIBC patients receiving C-NAC and falling into three groups: no ureteric obstruction (NO); relieved ureteric obstruction (RO); and unrelieved ureteric obstruction (URO). To address whether patients with obstruction can safely receive C-NAC, we compared patients with NO to those with RO, with the primary outcome of premature chemotherapy discontinuation. To investigate whether patients with obstruction should have the obstruction relieved prior to NAC, we compared RO to URO patients using a primary composite outcome of grade ≥ 3 adverse events, premature chemotherapy discontinuation, dose reduction, or dose interruption. The primary outcomes were compared using multivariable logistic regression. Sensitivity analyses were performed for the RO vs URO comparison, in which patients with only mild degrees of obstruction were excluded from the URO group. RESULTS: A total of 193 patients with NO, 49 with RO, and 35 with URO were analysed. There were no statistically significant differences between those with NO and those with RO in chemotherapy discontinuation (15% vs 22%; P = 0.3) or any secondary outcome. There was no statistically significant difference between those with RO and URO in the primary composite outcome (51% vs 53%; P = 1) or any secondary outcome. CONCLUSION: Patients with ureteric obstruction can safely receive C-NAC. Relief of obstruction was not associated with increased safety of C-NAC delivery.

Postoperative Complications Associated with the Choice of Reconstruction in Head and Neck Cancer: An Outcome Analysis of 4,712 Patients from the ACS-NSQIP Database.

BACKGROUND: Microsurgical free flaps have largely supplanted pedicled flaps as the gold standard for head and neck cancer reconstruction. However, incidence of postoperative complications after accounting for patient comorbidities based on choice of reconstruction has not been well-defined in the literature in recent years. METHODS: Patients undergoing head and neck reconstruction were identified in the 2011-2016 ACS-NSQIP (American College of Surgeons National Surgical Quality Improvement Program) database and stratified into groups by free flap, myocutaneous pedicled flap, and other reconstruction. Demographics were analyzed and covariates balanced using overlap propensity score-based weighting. Logistic regression was used for binary outcomes and Gamma generalized linear model was used for length of stay. RESULTS: A total of 4,712 patients met inclusion criteria out of which 1,297 patients (28%) underwent free flap, 208 patients (4%) pedicled flap, and 3,207 patients (68%) had other, or no reconstruction performed. After adjusting for patient and disease-specific factors, pedicled flap reconstruction was associated with a higher risk of deep vein thrombosis (odds ratio [OR] = 2.64, confidence interval [CI] 1.02-6.85, p = 0.045), sepsis (OR = 2.95, CI 1.52-5.71, p = 0.001), and infection (OR = 2.03, CI 1.39-2.96, p <0.001) compared with free flap reconstruction. Free flaps had the longest mean operative time compared with the other two groups (unadjusted 578 vs. 440 vs. 326, p <0.001). Pedicled flaps had a lower incidence of bleeding requiring transfusion (adjusted OR = 0.65, CI 0.50-0.85, p = 0.002), and lower incidence of prolonged mechanical ventilation (adjusted OR = 0.33, CI 0.12-0.92, p = 0.034) compared with free flaps. There was no difference in rates of reoperation, hospital readmission, or hospital length-of-stay between pedicled and free flaps. CONCLUSION: Myocutaneous pedicled flaps are associated with higher overall short-term postoperative complications compared with free flaps in head and neck reconstruction, which demonstrate a more favorable morbidity profile without significantly impacting hospital readmission, reoperation, or length-of-stay.

Early Prostate-Specific Antigen Kinetics for Low- and Intermediate-Risk Prostate Cancer Treated With Definitive Radiation Therapy.

PURPOSE: This study used a patient-specific model to characterize and compare ideal prostate-specific antigen (PSA) kinetics for low- and intermediate-risk prostate cancer after definitive radiation treatment with conventionally fractionated, hypofractionated, stereotactic body radiation therapy, or brachytherapy, both high-dose and low-dose rate. METHODS AND MATERIALS: This retrospective analysis includes low- and intermediate-risk patients with prostate cancer treated between 1998 and 2018 at an National Cancer Institute-designated comprehensive cancer center. Demographics and treatment characteristics were prospectively collected. Patients had at least 2 PSA measurements within 24 months of treatment and were free from biochemical recurrence. The incidence of, time to, and risk factors for PSA nadir (nPSA) and bounce (bPSA) were analyzed at 24 months after radiation therapy. Ideal PSA kinetics were characterized for each modality and compared. RESULTS: Of 1042 patients, 45% had low-risk cancer, 37% favorable intermediate risk, and 19% unfavorable intermediate risk. nPSAs were higher for ablative modalities, both as absolute nPSA and relative to initial PSA. Median time to nPSA ranged from 14.8 to 17.1 months. Over 50% treated with nonablative therapy (conventionally fractionated, hypofractionated, and low-dose rate) reached an nPSA threshold of ≤0.5 ng/mL compared with 23% of stereotactic body radiation therapy and 33% of high-dose rate cohorts. The incidence of bPSA was 13.3% and not affected by treatment modality, Gleason score, or prostate volume. PSA decay rate was faster for ablative therapies in the 6- to 24-month period. CONCLUSIONS: Analysis of PSA within 24 months after radiation therapy revealed ablative therapies are associated with a latent PSA response and higher nPSA. Multivariable logistics modeling revealed younger age, initial PSA above the median, presence of bPSA, and ablative therapy as predictors for not achieving nPSA ≤0.5 ng/mL. PSA decay rate appears to be faster in ablative therapies after a latent period. Understanding the different PSA kinetic profiles is necessary to assess treatment response and survey for disease recurrence.