Geographic and Demographic Disparities in Colorectal Cancer: A National Cancer Database Analysis.

BACKGROUND AND OBJECTIVES: Area of residence may adversely affect survival and outcomes in many cancers. The objective of this study was to evaluate the impact of geographical and demographic disparities on survival of patients with colorectal cancer. MATERIALS AND METHODS: Data were obtained from the National Cancer Database (NCDB) colon, rectosigmoid, and rectal datasets. Patients were categorized by area of residence, namely, metropolitan (MA), urban (UA), or rural (RA). Sociodemographic and tumor-related data were collected and analyzed to evaluate variables affecting overall survival (OS). RESULTS: In total, 973,139 patients between 2004 and 2013 were included in the study, of which 83%, 15%, and 2% were MA, UA, and RA residents, respectively. RA and UA patients were mostly white male with low income and no comorbidities. In univariate analysis, OS was worse for RA (hazard ratio [HR] 1.10) and UA (HR 1.06) colorectal cancer patients than that for MA colorectal cancer patients. In multivariate analysis revealed significant association between OS and geographic residence, with worse OS for RA (HR 1.02, p = 0.04) and UA (HR 1.01, p = 0.003) patients. Black (HR 1.14) and Native American (HR 1.17) patients had worse outcomes, while Asians (HR 0.8), women (HR 0.88), and patients with higher income had improved OS (HR 0.88). CONCLUSION: The differences in the OS for RA and UA patients with colorectal cancer were significantly driven by economic disparity. Area of residence represents an important factor independently limiting access to care, particularly in geographically isolated individuals.

Efficacy of Prophylactic High-Dose Gabapentin and Venlafaxine on Reducing Oral Mucositis Pain Among Patients Treated With Chemoradiation for Head and Neck Cancer: A Single-Institution, Phase 2, Randomized Clinical Trial.

PURPOSE: Given the paucity of level 1 evidence, the optimal regimen to control oral mucositis pain remains unclear. Although national guidelines allow consideration of prophylactic gabapentin, prior trials showed improved pain control with venlafaxine among patients with diabetic neuropathy. We sought to investigate the role of prophylactic high-dose gabapentin with venlafaxine to reduce oral mucositis pain among patients with head and neck cancer. METHODS AND MATERIALS: We performed a single-institution, phase 2 randomized trial on nonmetastatic squamous cell carcinoma of the head and neck treated with chemoradiation. Patients were randomized to either prophylactic gabapentin (3600 mg daily) with or without venlafaxine (150 mg daily). Primary endpoint was differences in pain levels at the end of chemoradiation. Secondary endpoint was toxicity profiles, quality of life changes, opioid use, and feeding tube placement. Differences between the 2 arms at multiple time points were evaluated using a generalized linear mixed regression model with Sidak correction. RESULTS: Between May 2018 and March 2021, a total of 62 patients were enrolled and evaluable for analysis (n = 32 for the gabapentin alone arm, n = 30 for the gabapentin + venlafaxine arm). Over 90% of patients tolerated gabapentin well. Head and neck pain level showed a mean value of 45 (standard deviation, 23) and 43 (standard deviation, 21) for the gabapentin alone and the gabapentin + venlafaxine arms, respectively (P = .65). No statistically significant differences were observed in adverse events, opioid use, feeding tube placement, or quality of life. CONCLUSIONS: The addition of venlafaxine to prophylactic gabapentin did not result in improvements in pain control and quality of life among patients with head and neck cancer.

Breast and Cervical Cancer Screening Disparities in Transgender People.

OBJECTIVES: The population of individuals who identify as transgender (TG) is increasing in the United States, yet disparities in cancer screening services are widening. It is imperative that interpersonal and systemic barriers to cancer care are identified and removed for this vulnerable population. Our study sought to examine the difference in self-reported breast and cervical cancer screening rates between TG and cisgender (CG) people. MATERIALS AND METHODS: Cross-sectional data from the 2014 to 2016 and 2018 Behavioral Risk Factor Surveillance System (BRFSS) was obtained on individuals who identified as CG or TG (male-to-female [MTF] and female-to-male [FTM]), including their responses to questions regarding breast and cervical screening history and their primary care access and associated barriers. RESULTS: Compared with the CG population, TG participants were less likely to adhere to or have undergone breast (FTM: odds ratio [OR] 0.47 and 0.32; MTF: OR 0.04 and 0.02, respectively; all P<0.001) and cervical cancer (FTM: OR 0.42 and 0.26, respectively; all P<0.001) screening. They were also less likely to have a primary care physician (FTM: OR 0.79; MTF: OR 0.58; all P<0.001) and less likely to seek primary care within a year owing to medical costs (FTM: OR 1.44; MTF: OR 1.36; all P<0.001). CONCLUSIONS: Disparities exist in the uptake of routine cancer screening in the TG population despite their increased risk for breast and cervical cancer. Interventions are urgently needed to mitigate delays to cancer screening, close gaps in provider and patient knowledge about cancer screening, and improve health care experiences of gender minorities in the United States.

Restrictive Intraoperative Fluid Rate is Associated with Improved Outcomes in Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Management of patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CS/HIPEC) has historically favored liberal fluid administration owing to lengthy duration of surgery and hyperthermia. This practice has been challenged in recent years with studies demonstrating improved outcomes with restrictive fluid administration. METHODS: Patients who underwent CS/HIPEC between March 2010 and September 2018 were included for analysis. Patients who received an above-median fluid rate (high-IVF) versus below-median fluid rate (low-IVF) were compared, and multivariate analyses were performed for length of stay, 90-day unplanned readmissions, and major complications. RESULTS: The 167 patients had a mean age of 56.7 ± 11.4 years and body mass index of 29.5 ± 6.9 kg/m2. The median rate of total intraoperative crystalloid and colloid was 7.4 mL/kg/h. The low-IVF group had less blood loss (183 vs. 330 mL, p = 0.002), were less likely to need intraoperative vasopressor drip (2.4% vs. 11.9%, p = 0.018), and experienced fewer cardiac complications (2.4% vs. 10.7%, p = 0.031), pneumonias (0% vs. 6.0%, p = 0.024), and Clavien-Dindo grade 3-5 complications (14.5% vs. 33.3%, p = 0.004). Multivariate analyses identified bowel resection (HR 4.65, p = 0.0008) as a risk factor for 90-day unplanned readmission, while bowel resection, intraoperative fluid rate, and estimated blood loss were associated with increased length of stay. CONCLUSION: Higher intraoperative fluid intake was associated with multiple postoperative complications and increased length of stay, and represents a potentially avoidable risk factor for morbidity in CS/HIPEC.

Testicular, Spermatic Cord, and Scrotal Soft Tissue Sarcomas: Treatment Outcomes and Patterns of Failure.

INTRODUCTION: Paratesticular sarcomas are defined as tumors that arise within the scrotum and include the subsites of epididymis, spermatic cord, and tunica vaginalis and represent the most common type of GU sarcoma. The mainstay of treatment is often surgical resection, combined with histology specific chemotherapy and radiotherapy. Due to the rare nature of the disease, there are limited data to guide management. We present our single-institution retrospective experience regarding the management and treatment of paratesticular sarcomas. MATERIALS AND METHODS: We queried our oncology registry database for patients treated for testicular, spermatic cord, and scrotal soft tissue sarcomas between 1971 and 2017. Patients in this series had pathological confirmation of a sarcoma diagnosis by a sarcoma-specialized pathologist. Only patients with localized disease were included in this analysis with the exception of patients with a diagnosis of rhabdomyosarcoma where patients with both localized and metastatic disease were included on this study. RESULTS: A total of 34 patients were included in this retrospective analysis. The median was 24 (range, 5-78), and the median tumor size was 6.25 cm. Twenty-six patients had localized disease (76.6%) at the time of diagnosis. A predominance of patients had tumors involving the spermatic cord (45.5%), and the most common histology was rhabdomyosarcoma (35.3%), leiomyosarcoma (26.5%), and well-differentiated liposarcoma (23.5%). The median follow-up was 71.0 months (range, 2.5-534.4 months). A total of 7 patients experienced an isolated local failure (20.6%), four patients developed distant metastatic disease (11.8%), and one patient (2.9%) with synovial sarcoma of the spermatic cord experienced a regional recurrence. The median progression-free survival (PFS) was 99.6 months, 95% CI (45.8-534.3 months), with a three-year PFS rate of 71%, 95% CI (53%-83%), and a 5-year PFS rate of 64% (range, 46%-78%). We did not find any statistically significant associations based on surgery type (p=0.15), the use of chemotherapy, (p=0.36), or final margin status (p=0.21). Two patients who were treated with preoperative radiotherapy had significant wound healing complication with chronic sinus tracts, though these patients did not experience a local recurrence. CONCLUSIONS: We provide a characterization of the natural history and treatment patterns of paratesticular sarcomas. While effective at reducing a local recurrence, preoperative radiotherapy was associated with significant toxicity. As a result, we prefer the use of postoperative radiotherapy in patients as clinically indicated. We did not find any specific treatment patterns associated with an improvement in clinical outcomes.

Prostate Cancer Screening Patterns Among Sexual and Gender Minority Individuals.

One in six gay and bisexual men will be diagnosed with prostate cancer in their lifetime. Lesbian, gay, bisexual, and transgender (LGBT) populations are under-represented in cancer research, and guidelines on prostate-specific antigen (PSA) screening are limited. We performed a cross-sectional study to assess patterns of PSA screening and decision-making in this cohort. The Behavioral Risk Factor Surveillance System database was queried for LGBT adults for 2014-2016 and 2018, when PSA questions were asked in the annual survey. Multivariable logistic regression was performed to evaluate the association of LGBT status with PSA screening and informed and shared decision-making. A total of 164 370 participants were eligible for PSA screening, representing a weighted estimate of 1.2 million LGBT individuals. Compared to cisgender (CG) straight individuals, CG gay/bisexual cohorts were more likely to participate in PSA screening (CG gay: odds ratio [OR] 1.07; p < 0.001; CG bisexual: OR 1.06; p < 0.001). CG gay participants were more likely to make informed decisions (OR 1.10; p < 0.001) and engage in shared decision-making (OR 2.55; p < 0.001). Select gay populations were more likely to undergo PSA screening recommended by their clinicians and participate in informed and shared decision-making. PATIENT SUMMARY: This large study of sexual and gender minorities in the USA suggests that gay and bisexual individuals were more likely to undergo prostate cancer screening and that select gay individuals were more likely to make informed and shared decisions. However, transgender individuals were less likely to have prostate cancer screening and make informed decisions.

Tivozanib mediated inhibition of c-Kit/SCF signaling on Tregs and MDSCs and reversal of tumor induced immune suppression correlates with survival of HCC patients.

The immune modulatory effect of tivozanib, a tyrosine kinase inhibitor, and the underlying immune mechanisms impacting survival of HCC patients have not been investigated. Pre-clinical studies have shown that tivozanib reduces Tregs and MDSCs accumulation through inhibition of c-Kit/SCF axis. We rationalized that c-Kit/SCF axis antagonism by tivozanib may reverse tumor-induced immune suppression in HCC patients. The frequency of circulating Tregs, MDSCs, CTLA-4+Tregs, PD-1+T cells, c-Kit+pERK-2+Tregs, and c-Kit+pERK-2+MDSCs were quantified in HCC patients at baseline and two time points during tivozanib treatment. We report for the first time that reduction in Tregs after tivozanib treatment and increased levels of baseline CD4+PD-1+T cells correlated with significant improvement in overall survival (OS) of the patients and these signatures may be potential biomarkers of prognostic significance. This immune modulation resulted from tivozanib-mediated blockade of c-Kit/SCF signaling, impacting ERK2 phosphorylation on Tregs and MDSCs. Low pre-treatment CD4+T cells: Treg ratio and reduction in the frequencies of Foxp3+c-Kit+pERK+Tregs after tivozanib treatment correlated significantly with progression free survival. In a comparative analysis of tivozanib vs sorafenib treatment in HCC patients, we demonstrate that decrease in the baseline numbers or frequencies of Foxp3+Tregs, MDSCs and exhausted T cells was significantly greater following tivozanib treatment. Additionally, greater increase in CD4+T cell: Treg ratio after tivozanib treatment was associated with significant improvement in OS compared to sorafenib treatment, highlighting the greater efficacy of tivozanib. These insights may help identify patients who likely would benefit from c-Kit/SCF antagonism and inform efforts to improve the efficacy of tivozanib in combination with immunotherapy.

A multicentre phase 1b/2 study of tivozanib in patients with advanced inoperable hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of cancer-related death. It is a highly vascular tumour with multiple angiogenic factors, most importantly vascular endothelial growth factor (VEGF), involved in HCC progression. Tivozanib is an oral inhibitor of VEGFR-1/2/3 with promising activity against HCC in vivo. METHODS: We conducted a phase 1b/2 study of tivozanib in patients with advanced HCC. The safety, dosing, pharmacokinetics, pharmacodynamics, and preliminary antineoplastic efficacy of tivozanib were evaluated. RESULTS: Twenty-seven patients received at least one dose of tivozanib. Using a 3+3 design, the recommended phase 2 dose (RP2D) of tivozanib was determined to be 1 mg per os once daily, 21 days on-7 days off. The median progression-free and overall survival were 24 weeks and 9 months, respectively, for patients treated at RP2D. The overall response rate was 21%. Treatment was well tolerated. A significant decrease in soluble plasma VEGFR-2 was noted, assuring adequate target engagement. CONCLUSIONS: Although this study did not proceed to stage 2, there was an early efficacy signal with a very favourable toxicity profile. A phase 1/2 trial of tivozanib in combination with durvalumab is currently underway. TRIAL REGISTRATION: ClinicalTrials.gov NCT01835223, registered on 15 April 2013.

Impact of Firearm Availability and Gun Regulation on State Suicide Rates.

Past studies on suicide have investigated the association of firearm ownership and suicide risk in the United States. The aim of the present study was to build on previous work by examining the impact of firearm storage practices and the strictness of firearm regulation on suicide rates at the state level. Data were compiled from primarily three sources. Suicide and firearm ownership information was obtained from the Centers for Disease Control and Prevention. Strictness of handgun regulation was derived from figures available at the Law Center to Prevent Violence, and controls were taken from the US Bureau of the Census. Mixed models were fitted to the data. Household firearm ownership was strongly associated with both suicide by all mechanisms, and firearm suicide. Storage practices had especially elevated consequences on suicide rates. Percent with loaded guns and gun readiness increased suicide rates, and strictness of gun regulation reduced suicide rates. Ready access to firearms can make a difference between life and death. Loaded and unlocked firearms within reach become risk factors for fatal outcomes from suicidal behavior. Future research might want to examine ways of obtaining more recent data on individual firearm ownership. This study proposes several policy recommendations for suicide prevention.

Cognitive skills assessment during robot-assisted surgery: separating the wheat from the chaff.

OBJECTIVE: To investigate the utility of cognitive assessment during robot-assisted surgery (RAS) to define skills in terms of cognitive engagement, mental workload, and mental state; while objectively differentiating between novice and expert surgeons. SUBJECTS AND METHODS: In all, 10 surgeons with varying operative experience were assigned to beginner (BG), combined competent and proficient (CPG), and expert (EG) groups based on the Dreyfus model. The participants performed tasks for basic, intermediate and advanced skills on the da Vinci Surgical System. Participant performance was assessed using both tool-based and cognitive metrics. RESULTS: Tool-based metrics showed significant differences between the BG vs CPG and the BG vs EG, in basic skills. While performing intermediate skills, there were significant differences only on the instrument-to-instrument collisions between the BG vs CPG (2.0 vs 0.2, P = 0.028), and the BG vs EG (2.0 vs 0.1, P = 0.018). There were no significant differences between the CPG and EG for both basic and intermediate skills. However, using cognitive metrics, there were significant differences between all groups for the basic and intermediate skills. In advanced skills, there were no significant differences between the CPG and the EG except time (1116 vs 599.6 s), using tool-based metrics. However, cognitive metrics revealed significant differences between both groups. CONCLUSION: Cognitive assessment of surgeons may aid in defining levels of expertise performing complex surgical tasks once competence is achieved. Cognitive assessment may be used as an adjunct to the traditional methods for skill assessment during RAS.

Oncologic outcomes following robot-assisted radical cystectomy with minimum 5-year follow-up: the Roswell Park cancer institute experience.

BACKGROUND: Long-term oncologic outcomes following robot-assisted radical cystectomy (RARC) remain scarce. OBJECTIVE: To report long-term oncologic outcomes following RARC at a single institution. DESIGN, SETTINGS, AND PARTICIPANTS: Retrospective review of 99 patients who underwent RARC for urothelial carcinoma of bladder between 2005 and 2009. INTERVENTION: RARC was performed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcomes included recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS), measured by the Kaplan-Meier method. The association between primary outcomes and perioperative and pathologic factors was assessed using a multivariable Cox proportional hazards model. RESULTS AND LIMITATIONS: Fifty-one (52%) patients had stage pT3 or higher disease. Eight (8%) patients had positive margins and 30 (30%) had positive lymph nodes (LNs), with a median of 21 LNs removed. Median follow-up for patients alive was 74 mo. The 5-yr RFS, CSS, and OS rates were 52.5%, 67.8%, and 42.4%, respectively. Tumor stage, LN stage, and margin status were each significantly associated with RFS, CSS, and OS. On multivariable analysis, tumor and LN stage were independent predictors of RFS, CSS, and OS, while positive margin status and Charlson comorbidity index predicted worse OS and CSS. Adjuvant chemotherapy predicted RFS only. Retrospective design and lack of open comparison are main limitations of this study. CONCLUSIONS: Long-term oncologic outcomes following RARC demonstrate RFS and CSS estimates similar to those reported in literature for open radical cystectomy. Randomized controlled trials can better define outcomes of any alternative technique. PATIENT SUMMARY: Survival data 5 yr after RARC for bladder cancer demonstrate that survival outcomes are dependent on the same oncologic parameters as previously reported for open surgery.

Health-related quality of life outcomes after robot-assisted and open radical cystectomy using a validated bladder-specific instrument: a multi-institutional study.

OBJECTIVE: To evaluate health-related quality of life (HRQL) using validated bladder-specific Bladder Cancer Index (BCI) and European Organization for Research and Treatment of Cancer Body Image scale (BIS) between open radical cystectomy (ORC) and robot-assisted radical cystectomy (RARC). METHODS: This was a retrospective case series of all patients who underwent radical cystectomy. Patients were grouped based on surgical approach (open vs robot assisted) and diversion technique (extracorporeal vs intracorporeal). Patients completed BCI and BIS preoperatively and at standardized postoperative intervals (at least 2). The primary exposure variable was surgical approach. The primary outcome measure was difference in interval and baseline BCI and BIS scores in each group. The Fisher exact, Wilcoxon rank-sum, and Kruskal-Wallis tests were used for comparisons. RESULTS: Eighty-two and 100 patients underwent RARC and ORC, respectively. Compared with RARC, more patients undergoing ORC had an American Society of Anesthesiology score≥3 (66% vs 45.1% RARC; P=.007) and shorter median operative time (350 vs 380 minutes; P=.009). Baseline urinary, bowel, sexual function, and body image were not different between both the groups (P=1.0). Longitudinal postoperative analysis revealed better sexual function in ORC group (P=.047), with no significant differences between both the groups in the other 3 domains (P=.11, .58, and .93). Comparisons regarding diversion techniques showed similar findings in baseline and postoperative HRQL data, with no significant differences in the HRQL and body image domains. CONCLUSION: RARC has comparable HRQL outcomes to ORC using validated BCI and BIS. The diversion technique used does not seem to affect patients' quality of life.