Reporting time toxicity in prospective cancer clinical trials: A scoping review.

PURPOSE: This review aimed to assess the measurement and reporting of time toxicity (i.e., time spent receiving care) within prospective oncologic studies. METHODS: On July 23, 2023, PubMed, Scopus, and Embase were queried for prospective or randomized controlled trials (RCT) from 1984 to 2023 that reported time toxicity as a primary or secondary outcome for oncologic treatments or interventions. Secondary analyses of RCTs were included if they reported time toxicity. The included studies were then evaluated for how they reported and defined time toxicity. RESULTS: The initial query identified 883 records, with 10 studies (3 RCTs, 2 prospective cohort studies, and 5 secondary analyses of RCTs) meeting the final inclusion criteria. Treatment interventions included surgery (n = 5), systemic therapies (n = 4), and specialized palliative care (n = 1). The metric "days alive and out of the hospital" was used by 80% (n = 4) of the surgical studies. Three of the surgical studies did not include time spent receiving ambulatory care within the calculation of time toxicity. "Time spent at home" was assessed by three studies (30%), each using different definitions. The five secondary analyses from RCTs used more comprehensive metrics that included time spent receiving both inpatient and ambulatory care. CONCLUSIONS: Time toxicity is infrequently reported within oncologic clinical trials, with no standardized definition, metric, or methodology. Further research is needed to identify best practices in the measurement and reporting of time toxicity to develop strategies that can be implemented to reduce its burden on patients seeking cancer care.

Management of Intrahepatic Cholangiocarcinoma: A Narrative Review.

The management of resectable intrahepatic cholangiocarcinoma remains a challenge due to the high risk of recurrence. Numerous clinical trials have identified effective systemic therapies for advanced biliary tract cancer; however, fewer trials have evaluated systemic therapies in the perioperative period. The objective of this review is to summarize the current recommendations regarding the diagnosis, surgical resection, and systemic therapy for anatomically resectable intrahepatic cholangiocarcinoma. Our review demonstrates that surgical resection with microscopic negative margins and lymphadenectomy remains the cornerstone of treatment. High-level evidence regarding specific systemic therapies for use in resectable intrahepatic cholangiocarcinoma remains sparse, as most of the evidence is extrapolated from trials involving heterogeneous tumor populations. Targeted therapies are an evolving practice for intrahepatic cholangiocarcinoma with most evidence coming from phase II trials. Future research is required to evaluate the use of neoadjuvant therapy for patients with resectable and borderline resectable disease.

Locally Advanced Gastric Cancer Management: A Cost-Effectiveness Analysis.

Across the nation, patients with locally advanced gastric cancer (LAGC) are managed with modalities including upfront surgery (US) and perioperative chemotherapy (PCT). Preoperative therapies have demonstrated survival benefits over US and thus long-term outcomes are expected to vary between the options. However, as these 2 modalities continue to be regularly employed, we sought to perform a decision analysis comparing the costs and quality-of-life associated with the treatment of patients with LAGC to identify the most cost-effective option. We designed a decision tree model to investigate the survival and costs associated with the most commonly utilized management modalities for LAGC in the United States: US and PCT. The tree described costs and treatment strategies over a 6-month time horizon. Costs were derived from 2022 Medicare reimbursement rates using the third-party payer perspective for physicians and hospitals. Effectiveness was represented using quality-adjusted life-years (QALYs). One-way, two-way, and probabilistic sensitivity analyses were utilized to test the robustness of our findings. PCT was the most cost-effective treatment modality for patients with LAGC over US with a cost of $40,792.16 yielding 3.11 QALYs. US has a cost of $55,575.57 while yielding 3.15 QALYs; the incremental cost-effectiveness ratio (ICER) was $369,585.25. One-way and two-way sensitivity analyses favored PCT in all variations of variables across their standard deviations. Across 100,000 Monte Carlo simulations, 100% of trials favored PCT. In our model simulating patients with LAGC, the most cost-effective treatment strategy was PCT. While US demonstrated improved QALYs over PCT, the associated cost was too great to justify its use.

Economic evaluation of robotic and laparoscopic paraesophageal hernia repair.

BACKGROUND: Robotic approach in paraesophageal hernia (PEH) repair may improve outcomes over laparoscopic approach, though at additional cost. This study aimed to compare cost-effectiveness of robotic and laparoscopic PEH repair. METHODS: A decision tree was created analyzing cost-effectiveness of robotic and laparoscopic PEH repair. Costs were obtained from 2021 Medicare data and were accumulated within 60 months after surgery. Effectiveness was measured in quality-adjusted life-years (QALYs). Branch-point probabilities and costs of robotic surgery consumables were obtained from published literature. The primary outcome of interest was incremental cost-effectiveness ratio (ICER). One-way, two-way, and probabilistic sensitivity analyses were performed. A secondary analysis including attributable capital and maintenance costs of robotic surgery was conducted as well. RESULTS: Laparoscopic repair yielded 3.660 QALYs at $35,843.82. Robotic repair yielded 3.661 QALYs at $36,342.57, with an ICER of $779,488.62/QALY. Robotic repair was favored when rates of open conversion and symptom recurrence were low, or with reduced cost of robotic instruments. A probabilistic sensitivity analysis favored laparoscopic repair in 100% of simulations. When accounting for costs of robotic technology, robotic approach was preferred only in unrealistic clinical scenarios. CONCLUSIONS: Laparoscopic repair is likely more cost-effective for most institutions, though results were relatively similar. With experienced surgeons who surpass the initial learning curve, robotic surgery may improve outcomes enough to be cost-effective, but only when excluding capital and maintenance fees.

Sentinel lymph node biopsy for head and neck cutaneous squamous cell carcinoma using the Brigham and Women's staging system: a cost analysis.

The objective is to determine the cost-effectiveness of sentinel lymph node biopsy (SLNB) for cutaneous squamous cell carcinoma (CSCC) according to the Brigham and Women's Hospital (BWH) Tumor Staging system. A decision analysis was utilized to examine costs and outcomes associated with the use of SLNB in patients with high-risk head and neck CSCC. Decision tree outcome probabilities were obtained from published literature. Costs were derived from Medicare reimbursement rates (US$) and effectiveness was represented by quality-adjusted life-years (QALYs). The primary outcome was the incremental cost-effectiveness ratio (ICER), with a willingness-to-pay set at $100,000 per QALY gained. SLNB was found to be a cost-effective tool for patients with T3 tumors, with an ICER of $18,110.57. Withholding SLNB was the dominant strategy for both T2a and T2b lesions, with ICERs of - $2468.99 and - $16,694.00, respectively. Withholding SLNB remained the dominant strategy when examining immunosuppressed patients with T2a or T2b lesions. In patients with head and neck CSCC, those with T3 or T2b lesions with additional risk factors not accounted for in the staging system alone, may be considered for SLNB, while in other tumor stages it may be impractical. SLNB should only be offered on an individual patient basis.

Perineal reconstruction after radical pelvic surgery: A cost-effectiveness analysis.

BACKGROUND: Radical resection of pelvic and low rectal malignancies leads to complex reconstructive challenges. Many pelvic reconstruction options have been described including primary closure, omental flaps, and various fasciocutaneous and myocutaneous flaps. Little consensus exists in the literature on which of the various options in the reconstructive armamentarium provides a superior outcome. The authors of this study set out to determine the costs and quality-of-life outcomes of primary closure, vertical rectus abdominus muscle flap, gluteal thigh flap, and gracilis flap to aid surgeons in identifying an optimal reconstructive algorithm. METHODS: A decision tree analysis was performed to analyze the cost, complications, and quality-of-life associated with reconstruction by primary closure, gluteal thigh flap, vertical rectus abdominus muscle flap, and gracilis flap. Costs were derived from Medicare reimbursement rates (FY2021), while quality-adjusted life-years were obtained from the literature. RESULTS: Gluteal thigh flap was the most cost-effective treatment strategy with an overall cost of $62,078.28 with 6.54 quality-adjusted life-years and an incremental cost-effectiveness ratio of $5,649.43. Gluteal thigh flap was always favored as the most cost-effective treatment strategy in our 1-way sensitivity analysis. Gracilis flap became more cost-effective than gluteal thigh flap, in the scenario where gluteal thigh flap complication rates increased by roughly 4% higher than gracilis flap complication rates. CONCLUSION: Our data suggest that, when available, gluteal thigh flap be the first-line option for reconstruction of pelvic defects as it provides the best quality-of-life at the most cost-effective price point. However, future studies directly comparing outcomes of gluteal thigh flap to vertical rectus abdominus muscle and gracilis flap are needed to further delineate superiority.

Staging CT and Diagnostic Laparoscopy With Cytology Prior to the Treatment of Pancreatic Adenocarcinoma: A Case Series.

INTRODUCTION: Initial staging of pancreatic ductal adenocarcinoma (PDAC) is performed with computed tomography (CT). Laparoscopy with peritoneal cytology at staging can uncover occult disease undetected by CT. This case series assessed clinical course following staging laparoscopy with cytology in patients with PDAC. METHODS: This single-center study examined patients with non-metastatic PDAC diagnosed from 2017 to 2020. Patients underwent CT and subsequent laparoscopy with cytology prior to treatment. Demographics, clinicopathologic status, treatment course, and survival were compared. RESULTS: Eight patients were identified. All had negative laparoscopies. Five cytologies were negative, two were atypical, and one was positive. Two patients with negative cytology received neoadjuvant chemotherapy and underwent resection, with an average follow-up time of 32.9 months since diagnosis. Of the three remaining patients with negative cytology, none underwent resection. One received delayed chemotherapy, while the others could not due to medical contraindications. The average survival was 3.5 months (n=2). Of two patients with atypical cytology, neither underwent resection. One could not receive chemotherapy due to medical contraindication, while the other was lost to follow-up shortly after diagnosis. The average survival was 1.3 months (n=1). The patient with positive cytology received definitive chemotherapy without resection and survived for 21.6 months. CONCLUSIONS: The patient with positive cytology may have been spared non-therapeutic surgery. Remaining unresected patients showed poor survival, though the lack of immediate chemotherapy may contribute to this finding. Further research is needed to determine optimal candidates for invasive staging and implications of atypical cytology.

Endoscopic Versus Laparoscopic Drainage of Pancreatic Pseudocysts: a Cost-effectiveness Analysis.

BACKGROUND: Both endoscopic and laparoscopic interventions have a high therapeutic success rate in the management of symptomatic pancreatic pseudocysts; however, neither has been established as the gold standard. METHODS: A decision tree analysis was performed to examine the costs and outcomes of intervening on pancreatic pseudocysts endoscopically versus laparoscopically. Within the model, a theoretical patient cohort was separated into two treatment arms: endoscopic drainage and laparoscopic drainage. Variables within the model were selected from the published literature. Medicare reimbursements rates (US$) were used to represent costs accumulated during a 3-month perioperative period. Effectiveness was characterized by quality-adjusted life-years (QALYs). A willingness-to-pay of $100,000 per 1 year of perfect health (1 QALY) gained was used as the cost-effectiveness threshold. The model was validated using one-way, two-way, and probabilistic sensitivity analysis. RESULTS: Endoscopic management of symptomatic pancreatic pseudocysts was the dominant strategy, producing 0.22 QALYs more while saving $23,976.37 in comparison to laparoscopic management. This result was further validated by one-way, two-way, and probabilistic sensitivity analysis. CONCLUSIONS: For patients presenting with symptomatic pancreatic pseudocysts amenable to either endoscopic or laparoscopic management, endoscopic drainage should be considered first-line therapy.

Racial disparities in minimally invasive esophagectomy and gastrectomy for upper GI malignancies.

BACKGROUND: Esophageal cancer and gastric cancer are two important causes of upper GI malignancies. Literature has shown that minimally invasive esophagectomies (MIE) and gastrectomies (MIG), have shorter length of stay and fewer complications. However, limited literature exists about the association between race and access to MIE and MIG. This study aims to identify the racial disparities in the different approaches to esophagectomy and gastrectomy. We further evaluate the relationship between the race and postoperative complications. METHODS: This IRB-approved retrospective study utilized data from the American College of Surgeons National Quality Improvement Program. All recorded cases of MIE, MIG, open gastrectomy, and esophagectomy between 2012 and 2019 were isolated. Propensity score matching and univariate analysis was performed to assess the independent effect of black self-identified race on access and outcomes. p < 0.05 was required to achieve statistical significance. RESULTS: 7891 cases of esophagectomy and 5,132 cases of gastrectomy cases were identified. Using Propensity and logistic regression, we identified that black self-reported race is an independent predictor of open approach to gastrectomy (OR 1.6871943, 95% CI 1.431464-1.989829, p < 0.001). Black self-reported race was not predictive of operative approach among esophagectomy patients (OR 0.7942576, 95% CI 0.5698645-1.124228, p = 0.183). In contrast, black self-reported is an independent predictor of postoperative complications among esophagectomy patients only. Esophagectomy patients of black self-reported race were more likely to experience any complication (OR 1.4373437, 95% CI 1.1129239-1.8557096, p = 0.00537), severe complications (OR 1.3818966, 95% CI 1.0653087-1.7888454, p = 0.0144), and death (OR 2.00779762, 95% CI 1.08034921-3.56117535, p = 0.0211) within 30 days of their surgeries. CONCLUSION: Our analysis revealed a significant racial disparity in access to MIG and a higher incidence of post-operative complications amongst esophagectomy patients. Minimally invasive techniques are underutilized in racial minorities. The findings herein warrant further investigation to eliminate barriers and disparities.

Cost-effectiveness analysis of infected necrotizing pancreatitis management in an academic setting.

BACKGROUND AND AIMS: Traditional management for infected necrotizing pancreatitis (INP) often utilizes open necrosectomy, which carries high morbidity and complication rates. Thus, minimally invasive strategies have gained favor, specifically step-up approaches utilizing endoscopic or minimally-invasive surgery (MIS); however, the ideal management modality for INP has not been identified. METHODS: A decision tree model was designed to analyze costs and survival associated with open necrosectomy, endoscopic step-up, and MIS step-up protocols for management of INP after 4 weeks of necrosis development with adequate retroperitoneal access. Costs were based on a third-party payer perspective using Medicare reimbursement rates. The model's effectiveness was represented by quality-adjusted life-years (QALYs). Sensitivity analyses were performed to validate results. RESULTS: Endoscopic step-up was the dominant economic strategy with 7.92 QALYs for $90,864.09. Surgical step-up resulted in a decrease of 0.09 QALYs and a cost increase of $10,067.89 while open necrosectomy resulted in a decrease of 0.4 QALYs and an increased cost of $18,407.52 over endoscopic step-up. In 100,000 random-sampling simulations, 65.5% of simulations favored endoscopic step-up. MIS step-up was favored when MIS acute mortality rates fell and when MIS drainage success rates rose. CONCLUSIONS: In our simulated patients with INP, the most cost-effective management strategy is endoscopic step-up. Cost-effectiveness varies with changes in acute mortality and drainage success, which will depend on local expertise.

Preablation Diagnostic Whole-Body Scan vs Empiric Radioactive Iodine Ablation in Differentiated Thyroid Cancer: Cost-effectiveness Analysis.

OBJECTIVE: To perform a comparative analysis of postthyroidectomy radioactive iodine ablation dosing with or without the implementation of a diagnostic whole-body scan in patients with well-differentiated thyroid cancer. STUDY DESIGN: Decision analysis model. SETTING: Hospital or ambulatory center. METHODS: A decision tree model was created to determine the cost-effectiveness of radioactive iodine ablation dosed with diagnostic whole-body scans versus empiric radioactive iodine ablation in patients with differentiated thyroid cancer undergoing postthyroidectomy ablation. The decision tree was populated with values from the published literature. Costs were represented by 2020 Medicare reimbursement rates (US dollars), and morbidity and survival data were used to calculate quality-adjusted life-years. The incremental cost-effectiveness ratio was the primary outcome. RESULTS: Empiric radioactive iodine dosing was the dominant economic strategy, producing 0.94 more quality-adjusted life-years while costing $1250.07 less than management with a diagnostic whole-body scan. Sensitivity analyses upheld these results except in cases involving a large discrepancy in successful ablation rates between the diagnostic and empiric treatment arms. CONCLUSION: For patients with differentiated thyroid cancer requiring postthyroidectomy ablation, it is more cost-effective to administer radioactive iodine empirically.

Cost-effectiveness of palliative emergent surgery versus endoscopic stenting for acute malignant colonic obstruction.

BACKGROUND: Endoscopic stenting has demonstrated value over emergent surgery as a palliative intervention for patients with acute large bowel obstruction due to advanced colorectal cancer. However, concerns regarding high reintervention rates and the risk of perforation have brought into question its cost-effectiveness. METHODS: A decision tree analysis was performed to analyze costs and survival in patients with unresectable or metastatic colorectal cancer who present with acute large bowel obstruction. The model was designed with two treatment arms: self-expanding metallic stent (SEMS) placement and emergent surgery. Costs were derived from medicare reimbursement rates (US$), while effectiveness was represented by quality-adjusted life years (QALYs). The primary outcome measure was the incremental cost-effectiveness ratio (ICER). The model was tested for validation using one-way, two-way, and probabilistic sensitivity analyses. RESULTS: Endoscopic stenting resulted in an average cost of $43,798.06 and 0.68 QALYs. Emergent surgery cost $5865.30 more, while only yielding 0.58 QALYs. This resulted in an ICER of - $58,653.00, indicating that SEMS placement is the dominant strategy. One-way and two-way sensitivity analyses demonstrated that emergent surgery would require an improved survival rate in comparison to endoscopic stenting to become the favored treatment modality. In 100,000 probabilistic simulations, endoscopic stenting was favored 96.3% of the time. CONCLUSIONS: In patients with acute colonic obstruction in the presence of unresectable or metastatic disease, endoscopic stenting is a more cost-effective palliative intervention than emergent surgery. This recommendation would favor surgery over SEMS placement with improved surgical survival, or if the majority of patients undergoing stenting required reintervention.

Pancreatic Carcinosarcoma Clinical Outcome Analysis of the National Cancer Institute Database.

BACKGROUND: Pancreatic carcinosarcomas (PCS) are rare aggressive biphasic malignancies with a poor prognosis. We aimed to improve the understanding of PCS by analyzing variables that influence the mortality of PCS patients. METHODS: The Surveillance, Epidemiology, and End Results database was queried for cases of PCS from 1973 to 2016. Cases were analyzed for patient demographics, tumor characteristics, and surgical intervention. Kaplan-Meier and Cox regression analyses were applied to investigate the overall survival (OS) and prognostic factors. RESULTS: Thirty-nine cases of PCS were identified along with the disease demographics and characteristics. The majority of patients had a regionally invasive or metastatic disease. There was a significant decrease in OS with the increase of the tumor extension. Conversely, surgery showed to improve OS in the crude analysis, including patients that underwent lymphadenectomy. In addition, the unadjusted Cox regression results showed decreased hazard ratios with a local disease versus distant metastasis and with cancer-directed surgery versus no surgery. Nevertheless, the adjusted Cox regression results revealed that metastatic disease was the only significant predictor of survival. CONCLUSIONS: This population-based study provides some insight to a very rare disease by analyzing 39 cases of PCS. Our finding suggests considering PCS as a nonsurgical disease and reserving surgery solely for patients with a localized disease in combination or after neoadjuvant therapy. Consequently, there is a need to further investigate novel therapies for this aggressive malignancy.

Correction to: Treatment of Rare and Aggressive Pancreatic Carcinosarcoma.

[This corrects the article on p. e00379 in vol. 7, PMID: 32607379.].

Treatment of Rare and Aggressive Pancreatic Carcinosarcoma.

A 42-year-old African American woman presented with 4 days of worsening midepigastric pain that radiated to her back. Computed tomography confirmed a diagnosis of acute pancreatitis and revealed a mass within the distal body and tail of the pancreas. After an endoscopic ultrasound with fine-needle aspiration yielding atypical cells suspicious for adenocarcinoma, the patient underwent an en bloc resection of the intra-abdominal mass with subtotal pancreatectomy, splenectomy, left colectomy, and left partial adrenalectomy. Histopathologic examination findings, in addition to immunohistochemical staining, revealed a diagnosis of pancreatic carcinosarcoma. Postoperatively, the patient has undergone 20 cycles of chemotherapy and has been transitioned to comfort measures at 16 months postoperatively because of progressive disease.

Malignant Granular Cell Tumor of the Bile Duct.

A 56-year-old man presented to the emergency department with painless jaundice and weight loss. Abdominal ultrasound detected dilation of the common bile duct and the intrahepatic bile ducts. Follow-up with endoscopic retrograde cholangiography exposed a stricture of the common hepatic duct, with cholangioscopy identifying an infiltrating tumor. Biopsy revealed a granular cell tumor, which was confirmed by positive S-100 immunohistochemical staining. Surgical excision confirmed granular cell tumor of the bile duct with morphological features suggestive of malignancy.

Design of an immunohistochemistry biomarker panel for diagnosis of pancreatic adenocarcinoma.

BACKGROUND: Challenges still exist in differentiating pancreatic adenocarcinoma from benign disease. The use of adjuvant testing of tissue biopsies has demonstrated potential diagnostic value. We designed a proof of concept study to first validate four individual immunohistochemistry biomarkers and then combine them into a panel to boost overall diagnostic sensitivity. METHODS: Malignant and benign pancreas from 27 pancreaticoduodenectomy specimens underwent immunohistochemistry staining with VHL, IMP3, S100A4, S100P. Using ROC curve analysis, threshold criteria for number of cells staining were chosen for each biomarker. Biomarkers were then evaluated as a panel for their ability to discriminate malignant from benign specimens. RESULTS: Diagnostic sensitivity of VHL, IMP3, S100A4, and S100P were 75.0%, 79.2%, 45.8%, and 0%. When VHL, IMP3, and S100A4 were grouped into a panel, they were able to distinguish cancer from normal tissue with a sensitivity of 100% and a specificity of 96%. CONCLUSIONS: The high diagnostic value of an IHC panel consisting of VHL, IMP3, and S100A4 on surgical specimens suggests the need for future prospective studies of these biomarkers on biopsy specimens.

Cost-Effectiveness of Sentinel Lymph Node Biopsy for Head and Neck Cutaneous Squamous Cell Carcinoma.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has shown promise in identifying subclinical nodal metastasis in patients with high-risk cutaneous squamous cell carcinoma. However, low metastasis rates may indicate that performing such a procedure in all patients may be unnecessary and costly. MATERIALS AND METHODS: A decision model was developed to analyze costs and survival in patients with head and neck cutaneous squamous cell carcinoma based on their tumor and nodal metastasis staging and whether or not they received an SLNB. Incremental cost-effectiveness ratios were calculated based on the change in quality-adjusted life years (QALYs) and costs (US$) between the different options, with a threshold of $100,000 to determine the most cost-effective strategy. One-way, two-way, and probabilistic sensitivity analyses were performed to validate the results. RESULTS: Not performing an SLNB results in 12.26 QALYs and a cost of $3712.98. Performing an SLNB resulted in a 0.59 decrease in QALYs and an increase in cost of $1379.58 for an incremental cost-effectiveness ratio of -2338.27. This trend remained the same across all tumor stages and remained consistent within most sensitivity analyses. CONCLUSIONS: In patients with head and neck cutaneous squamous cell carcinoma, the most cost-effective strategy is to not perform SLNBs, regardless of the patient's stage. Low rates of nodal metastasis in addition to low disease-specific death rates were the significant factors in this outcome. Increasing the sensitivity of SLNB would not impact this recommendation unless the rate of nodal metastasis was significantly higher.