Cost-effectiveness analysis of pembrolizumab for treatment of US patients with persistent, recurrent, or metastatic cervical cancer.

OBJECTIVE: The effectiveness of pembrolizumab for persistent, recurrent, or metastatic cervical cancer has been demonstrated. We aimed to evaluate its cost-effectiveness from the United States (US) healthcare payers perspective. METHODS: A partitioned survival model over a 30-year lifetime horizon was developed to compare the cost and effectiveness of pembrolizumab versus placebo based on clinical data from the KEYNOTE-826 phase 3 randomized trial. Costs and health state utilities were obtained from literature and publicly available databases. The incremental cost-effectiveness ratio (ICER) was measured. One-way and probabilistic sensitivity analyses were conducted. RESULTS: For the Intention-to-Treat patients, pembrolizumab was associated with an additional 0.74 quality-adjusted life-year (QALY) at an additional cost of $182,271 when compared with placebo. The ICER was $247,663/QALY. For patients with a programmed death-ligand 1 combined positive score ≥ 1 and 10, the ICER was $253,322/QALY and $214,212/QALY, respectively. One-way sensitivity analyses showed that pembrolizumab had the greatest impact on the ICER. Probabilistic sensitivity analyses showed that the probability of pembrolizumab being cost-effective was zero at the current willingness-to-pay threshold of $150,000/QALY. The price of pembrolizumab had to reduce at least to $28.336 (55.8% of the current price) for it to be cost-effective in a 50% of chance. CONCLUSION: The addition of pembrolizumab to chemotherapy is costly and might not be cost-effective for persistent, recurrent, or metastatic cervical cancer at the current price in the US.

Association between definitive chemoradiotherapy wait-time and survival in locally-advanced cervical cancer: Implications during the coronavirus pandemic.

OBJECTIVE: The current coronavirus pandemic caused a significant decrease in cancer-related encounters resulting in a delay in treatment of cancer patients. The objective of this study was to examine the survival effect of delay in starting concurrent chemo-radiotherapy (CCRT) in women with locally-advanced cervical cancer. METHODS: This is a retrospective observational study querying the National Cancer Database from 2004 to 2016. Women with stage IB2-IVA squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix who received definitive CCRT with known wait-time for CCRT initiation after cancer diagnosis were eligible (N=13,617). Cox proportional hazard regression model with restricted cubic spline transformation was fitted to assess the association between CCRT wait-time and all-cause mortality in multivariable analysis. RESULTS: The median wait-time to start CCRT was 6 (IQR 4-8) weeks. In a multivariable analysis, older age, non-Hispanic black and Hispanic ethnicity, recent year of diagnosis, Medicaid and uninsured status, medical comorbidities, and absence of nodal metastasis were associated with longer CCRT wait-time (P<.05). Women with aggressive tumor factors (poorer differentiation, large tumor size, nodal metastasis, and higher cancer stage) were more likely to have a short CCRT wait-time (P<.05). After controlling for the measured covariates, CCRT wait-time of 6.1-9.8 weeks was not associated with increased risk of all-cause mortality compared to a wait-time of 6 weeks. Similar association was observed when the cohort was stratified by histology, cancer stage, tumor size, or brachytherapy use. CONCLUSION: An implication of this study for the current coronavirus pandemic is that in the absence of aggressive tumor factors, a short period of wait-time to start definitive CCRT may not be associated with increased risk of mortality in women with locally-advanced cervical cancer.

Large-Volume Hyperthermia for Safe and Cost-Effective Targeted Drug Delivery Using a Clinical Ultrasound-Guided Focused Ultrasound Device.

Lyso-thermosensitive liposomes (LTSLs) are specifically designed to release chemotherapy agents under conditions of mild hyperthermia. Preclinical studies have indicated that magnetic resonance (MR)-guided focused ultrasound (FUS) systems can generate well-controlled volumetric hyperthermia using real-time thermometry. However, high-throughput clinical translation of these approaches for drug delivery is challenging, not least because of the significant cost overhead of MR guidance and the much larger volumes that need to be heated clinically. Using an ultrasound-guided extracorporeal clinical FUS device (Chongqing HAIFU, JC200) with thermistors in a non-perfused ex vivo bovine liver tissue model with ribs, we present an optimised strategy for rapidly inducing (5-15 min) and sustaining (>30 min) mild hyperthermia (ΔT <+4°C) in large tissue volumes (≤92 cm3). We describe successful clinical translation in a first-in-human clinical trial of targeted drug delivery of LTSLs (TARDOX: a phase I study to investigate drug release from thermosensitive liposomes in liver tumours), in which targeted tumour hyperthermia resulted in localised chemo-ablation. The heating strategy is potentially applicable to other indications and ultrasound-guided FUS devices.

Assessment of liver metastases radiomic feature reproducibility with deep-learning-based semi-automatic segmentation software.

BACKGROUND: Good feature reproducibility enhances model reliability. The manual segmentation of gastric cancer with liver metastasis (GCLM) can be time-consuming and unstable. PURPOSE: To assess the value of a semi-automatic segmentation tool in improving the reproducibility of the radiomic features of GCLM. MATERIAL AND METHODS: Patients who underwent dual-source computed tomography were retrospectively reviewed. As an intra-observer analysis, one radiologist segmented metastatic liver lesions manually and semi-automatically twice. Another radiologist re-segmented the lesions once as an inter-observer analysis. A total of 1691 features were extracted. Spearman rank correlation was used for feature reproducibility analysis. The times for manual and semi-automatic segmentation were recorded and analyzed. RESULTS: Seventy-two patients with 168 lesions were included. Most of the GCLM radiomic features became more reliable with the tool than the manual method. For the intra-observer feature reproducibility analysis of manual and semi-automatic segmentation, the rates of features with good reliability were 45.5% and 62.3% (P < 0.02), respectively; for the inter-observer analysis, the rates were 29.3% and 46.0% (P < 0.05), respectively. For feature types, the semi-automatic method increased reliability in 6/7 types in the intra-observer analysis and 5/7 types in the inter-observer analysis. For image types, the reliability of the square and exponential types was significantly increased. The mean time of semi-automatic segmentation was significantly shorter than that of the manual method (P < 0.05). CONCLUSION: The application of semi-automated software increased feature reliability in the intra- and inter-observer analyses. The semi-automatic process took less time than the manual process.

Assessment of the role of Ga-68 PSMA I&T PET/CT in response evaluation to docetaxel therapy in castration resistant prostate cancer patients. / Evaluación del papel de la PET/TC con [68Ga]Ga-PSMA I&T en la evaluación de la respuesta a la terapia con docetaxel en pacientes con cáncer de próstata resistente a la castración.

OBJECTIVE: There have been only few studies investigating the role of PSMA ligands in the therapy response assessment of metastasized castration resistant prostate cancer (mCRPC) cases. In this study we aimed at evaluating the capability of 68Ga- prostate-specific membrane antigen (PSMA) I&T positron emission tomography/computerized tomography (PET/CT) in the assessment of therapeutic response in patients under docetaxel therapy for prostate cancer (PCa). MATERIAL AND METHODS: The clinical records of all mCRPC patients treated with docetaxel and referred to our department for 68Ga-PSMA I&T PET/CT imaging were retrospectively analysed. Sixteen patients (mean age 69 years, range 52-82 years) with castration-resistant prostate cancer patients receiving palliative docetaxel therapy and had undergone 68Ga-PSMA I&T PET/CT scan were included in the study. 68Ga-PSMA I&T PET/CT imaging was done and prostate specific antigen (PSA) levels were measured at baseline before administration of docetaxel (PET1) and after at least 3 cycles (range 4-12) of chemotherapy (PET2). Patient-based as well as lesion-based comparison of PET2 findings with PET1 findings were done. RESULTS: The change (decrease) observed in lymph node and prostate gland/prostatic bed SUVmax values after treatment compared to pretreatment was found to be statistically significant (P=.033). 3/16 patients (19%) were classified as progressive disease (PD), 4/16 (25%) as stable disease (SD), 9/16 (56%) as partial remission (PR) radiologically. An increasing PSA trend (IT) was observed in 4 patients (25%) and a decreasing PSA trend (DT) in 3 patients (18%). Nine patients showed a PSA response of ≥ 50% (56%). Of the 4 patients showing SD, 3 had IT, 3 had BR. Of the 9 patients who showed PR on PET studies, 8 patients showed BR and 1 patient showed DT. CONCLUSION: Imaging with 68Ga-PSMA PET/CT showed great concordance with biochemical response evaluation in terms of PSA levels, especially in patients showing good response to therapy. 68Ga-PSMA PET/CT was also successful in identifying progressive disease in patients showing paradoxical decline in PSA levels.

Socioeconomic determinants of the surgical treatment of colorectal liver metastases.

OBJECTIVE: We hypothesized that differences in resection rates of colorectal liver metastases exist based on socioeconomic status (SES) inequalities. METHODS: The NCDB was utilized to study patients of different median household income diagnosed with colon adenocarcinoma from 2010 to 2015. RESULTS: A total of 21,258 patients met inclusion criteria, of whom 3,587 (16.9%) underwent metastasectomy. Patients of the highest income quartile were more likely to undergo metastasectomy compared to the lowest quartile (OR 1.20, CI 1.07-1.37, p = 0.003). Overall, patients in the highest income quartile had a median OS of 17.1 months compared with 13.0 months for the lowest quartile (HR 0.85, CI 0.81-0.90, p < 0.001). While metastasectomy was associated with improved OS across all groups, the disparity by income quartile widened (29.2 vs. 22.0 months, respectively; HR 0.51, CI 0.49-0.54, p < 0.001). CONCLUSION: Higher income patients were more likely to undergo metastasectomy compared with lower income patients and were associated with longer OS.

Increased assessment of HER2 in metastatic gastroesophageal cancer patients: a nationwide population-based cohort study.

BACKGROUND: Addition of trastuzumab to first-line palliative chemotherapy in gastroesophageal cancer patients with HER2 overexpression has shown to improve survival. Real-world data on HER2 assessment and administration of trastuzumab are lacking. The aim of this study was to assess HER2 testing, trastuzumab administration, and overall survival (OS) in a nationwide cohort of metastatic gastroesophageal cancer patients. METHODS: Data of patients with synchronous metastatic gastroesophageal adenocarcinoma diagnosed in 2010-2016 that received palliative systemic treatment (n = 2846) were collected from the Netherlands Cancer Registry and Dutch Pathology Registry. The ToGA trial criteria were used to determine HER2 overexpression. Proportions of HER2 tested patients were analyzed between hospital volume categories using Chi-square tests, and over time using trend analysis. OS was tested using the Kaplan Meier method with log rank test. RESULTS: HER2 assessment increased annually, from 18% in 2010 to 88% in 2016 (P < 0.01). Median OS increased from 6.9 (2010-2013) to 7.9 months (2014-2016; P < 0.05). Between the hospitals, the proportion of tested patients varied between 29-100%, and was higher in high-volume hospitals (P < 0.01). Overall, 77% of the HER2 positive patients received trastuzumab. Median OS was higher in patients with positive (8.8 months) and negative (7.4 months) HER2 status, compared to non-tested patients (5.6 months; P < 0.05). CONCLUSION: Increased determination of HER2 and administration of trastuzumab have changed daily practice management of metastatic gastroesophageal cancer patients receiving palliative systemic therapy, and possibly contributed to their improved survival. Further increase in awareness of HER2 testing and trastuzumab administration may improve quality of care and patient outcomes.

Facilities that service economically advantaged neighborhoods perform surgical metastasectomy more often for patients with colorectal liver metastases.

BACKGROUND: Metastasectomy of isolated colorectal liver metastases (CRLM) requires significant clinical expertise and may not be readily available or offered. The authors hypothesized that hospitals that treat a greater percentage of patients from higher income catchment areas are more likely to perform metastasectomies regardless of patient or tumor characteristics. METHODS: Using the National Cancer Data Base, the authors classified facilities into facility income quartiles (FIQs) based on the percentage of patients from the wealthiest neighborhoods (by zip code). Quartile 1 included facilities with <2.1% of the patients residing within the highest income zip codes, quartile 2 included facilities with 2.2% to 15.6% of patients residing within the highest income zip codes, quartile 3 included facilities with 15.7% to 40.2% of patients residing within the highest income zip codes, and quartile 4 included facilities with 40.3% to 90.5% of patients residing within the highest income ZIP codes. Patient, tumor, and facility characteristics were analyzed using a multivariate logistic regression to identify associations between metastasectomy and FIQ. RESULTS: Patients with CRLM were more likely to undergo metastasectomy at facilities in the highest FIQ compared with the lowest FIQ (18% vs 11% in FIQ4; P = .001). This trend was not observed in the resection of primary tumors for nonmetastatic CRLM (rates of 95% vs 93%; P = .94). After adjusting for individual insurance status, distance traveled, zip code-level individual income, tumor, and host, patients who were treated at the highest FIQ facilities were found to be more likely to undergo metastasectomy (odds ratio, 1.29; 95% CI, 1.02-1.72 [P = .03]). CONCLUSIONS: Metastasectomy for CRLM is more likely to occur at facilities that serve a greater percentage of patients from high-income catchment areas, regardless of individual patient characteristics. This disparity uniquely affects those patients with advanced cancers for which specialized expertise for therapy is necessary.

Staging Laparoscopy is Underutilized in the Management of Gastric Adenocarcinoma.

BACKGROUND: Staging laparoscopy (SL) with peritoneal lavage is usually performed on a separate day from the planned resection and is recommended in patients with gastric adenocarcinoma as it can identify radiographically occult metastases and malignant cytology, thus altering prognosis and treatment. SL can be done on the same day as planned resection (SLSR) or with delayed resection (SLDR). The purpose of this study was to determine utilization of SL and factors associated with SLSR and SLDR, among patients diagnosed with gastric adenocarcinoma. METHODS: SEER-Medicare linked data were used to identify patients diagnosed with gastric adenocarcinoma from 2004 through 2013. SL were defined as a laparoscopy that occurred up to 3 months postdiagnosis. Multivariate logistic regression was used to identify factors associated with the utilization of SLSR and SLDR. RESULTS: Of the 5610 patients with gastric adenocarcinoma who underwent a surgical procedure, 733 (13%) had a SL. Utilization of SL increased annually from 6.4% to 22.2% (p < 0.01). Receipt of SL was associated with patient demographics, tumor location, and treatment at a National Cancer Institute (NCI) Designated Cancer Center (CC). Of the 733 patients who underwent SL, 475 (65%) received further surgical procedures; 367 (77%) underwent SLSR, while 108 patients (23%) underwent SLDR. Compared with SLSR, SLDR was more common among patients who were younger, treated at an NCI-Designated CC and had proximal tumors. CONCLUSIONS: SL for optimal preoperative staging remains underutilized in the management of gastric adenocarcinoma. Expanded use of laparoscopy as a distinct procedure could minimize unnecessary interventions.

Retooling a Blood-Based Biomarker: Phase I Assessment of the High-Affinity CA19-9 Antibody HuMab-5B1 for Immuno-PET Imaging of Pancreatic Cancer.

PURPOSE: In patients with cancer who have an abnormal biomarker finding, the source of the biomarker in the bloodstream must be located for confirmation of diagnosis, staging, and therapy planning. We evaluated if immuno-PET with the radiolabeled high-affinity antibody HuMab-5B1 (MVT-2163), binding to the cancer antigen CA19-9, can identify the source of elevated biomarkers in patients with pancreatic cancer. PATIENTS AND METHODS: In this phase I dose-escalating study, 12 patients with CA19-9-positive metastatic malignancies were injected with MVT-2163. Within 7 days, all patients underwent a total of four whole-body PET/CT scans. A diagnostic CT scan was performed prior to injection of MVT-2163 to correlate findings on MVT-2163 PET/CT. RESULTS: Immuno-PET with MVT-2163 was safe and visualized known primary tumors and metastases with high contrast. In addition, radiotracer uptake was not only observed in metastases known from conventional CT, but also seen in subcentimeter lymph nodes located in typical metastatic sites of pancreatic cancer, which were not abnormal on routine clinical imaging studies. A significant fraction of the patients demonstrated very high and, over time, increased uptake of MVT-2163 in tumor tissue, suggesting that HuMab-5B1 labeled with beta-emitting radioisotopes may have the potential to deliver therapeutic doses of radiation to cancer cells. CONCLUSIONS: Our study shows that the tumor antigen CA19-9 secreted to the circulation can be used for sensitive detection of primary tumors and metastatic disease by immuno-PET. This significantly broadens the number of molecular targets that can be used for PET imaging and offers new opportunities for noninvasive characterization of tumors in patients.

Assessment of Circulating miRNA-17 and miRNA-222 Expression Profiles as Non-Invasive Biomarkers in Egyptian Patients with Non-Small-Cell Lung Cancer.

Background: Lung cancer is one of the main human health threats. Survival of lung cancer patients depends on the timely detection and diagnosis. Among the genetic irregularities that control cancer development and progression, there are microRNAs (miRNAs). This study aimed to assess the plasma level of circulating miRNA-17 and miRNA-222 as non-invasive markers in non-small-cell lung cancer (NSCLC) patients. Patients and methods: A total of 40 patients with NSCLC and 20 healthy controls who were matched in terms of age and sex with the patient group were included in this case-control study.. Estimation of miRNA-17 and miRNA-222 expression profiles in the plasma was done using quantitative real-time PCR (qRT-PCR). The relationship between both markers and their clinicopathological features were also determined. Receiver operating characteristic (ROC) curve analysis was done to evaluate the role of these microRNAs in NSCLC diagnosis and follow-up. Results: MiRNA-17 and miRNA-222 levels were significantly upregulated in NSCLC patients compared with controls (48.32±12.35 vs 1.16±0.19 and 34.53±3.1 vs 1.22±0.14) (P=0.000). Plasma miRNA-17 level was increased, and the miRNA-222 level was decreased across different stages of the disease; however, these differences d were not statistically significant (P=0.4, P=0.5, respectively). The miRNA-17 levels were higher in the lung cancer patients with metastasis , but miRNA-222 levels were lower patients without metastasis. We found no statistically significant difference in this regard(P=0.4 vs P=0.3, respectively). ROC curve analysis showed that the sensi¬tivity and specificity of miRNA-17 were 77.78% and 87.50% , and of miRNA-222 were 50% and 88.89%. Conclusion: MiRNA-17 and miRNA-222 can be considered as non-invasive biomarkers for detection of early lung carcinogenesis and metastasis in patients with NSCLC, hence providing a basis for the development of novel therapeutic approaches.

Prospective clinical trial of robotic sentinel lymph node assessment with isosulfane blue (ISB) and indocyanine green (ICG) in endometrial cancer and the impact of ultrastaging (NCT01818739).

OBJECTIVES: To assess the performance sentinel lymph node (SLN) biopsy and effect of ultrastaging in clinically early stage endometrial cancer. METHODS: Patients with endometrial cancer prospectively enrolled after informed consent was obtained. The cervix was injected superficially with 1 mL of ISB and 1 mL of ICG (diluted 1:25) at 3 and 9 o'clock each. SLN biopsy was followed by complete pelvic lymphadenectomy (aortic lymphadenectomy at the discretion of the surgeon). Lymph nodes (LNs) were analyzed by standard sectioning with H&E; ultrastaging of SLN was done retrospectively and blinded to treating physicians. RESULTS: 204 patients received dye injections. In 184 (90.2%) patients at least one SLN was identified. Of all patients, 138 (68%) had bilateral mapping. In the patients with successful mapping of a hemipelvis, ICG detected SLNs in 83% and ISB in 64% of cases (p < 0.0001). Median BMI (kg/m2) for patients with successful mapping was 35.7 compared to 40.1 for those who did not map (p = 0.01). Twenty-three (11.3%) patients had positive LNs. Applying the SLN algorithm, positive nodes were detected in 21/23 (91.3%). The negative predictive value (NPV) was 98.9% (95% CI: 96.01% to 99.71%). Eleven patients had positive SLN with isolated tumor cells (ITCs) or micrometastases detected on ultrastaging. Including these patients, 34 (17%) had positive LNs, increasing the NPV to 99% and sensitivity to 94%. There were no recurrences in patients with ITCs only. CONCLUSIONS: SLN assessment in endometrial cancer is feasible and safe with high NPV (99%). ICG was more effective in detecting SLN compared to ISB. Although ultrastaging detected additional positive LNs, treatment based on standard sectioning appears reasonable but further research is needed.

Abbreviated MRI Protocols for the Abdomen.

Technical advances in MRI have improved image quality and have led to expanding clinical indications for its use. However, long examination and interpretation times, as well as higher costs, still represent barriers to use of MRI. Abbreviated MRI protocols have emerged as an alternative to standard MRI protocols. These abbreviated MRI protocols seek to reduce longer MRI protocols by eliminating unnecessary or redundant sequences that negatively affect cost, MRI table time, patient comfort, image quality, and image interpretation time. However, the diagnostic information is generally not compromised. Abbreviated MRI protocols have already been used successfully for hepatocellular carcinoma screening, for prostate cancer detection, and for screening for nonalcoholic fatty liver disease as well as monitoring patients with this disease. It has been reported that image acquisition time and costs can be considerably reduced with abbreviated MRI protocols, compared with standard MRI protocols, while maintaining a similar sensitivity and accuracy. Nevertheless, multiple applications still need to be explored in the abdomen and pelvis (eg, surveillance of metastases to the liver; follow-up of cystic pancreatic lesions, adrenal incidentalomas, and small renal masses; evaluation of ovarian cysts in postmenopausal women; staging of cervical and uterine corpus neoplasms; evaluation of müllerian duct anomalies). This article describes some successful applications of abbreviated MRI protocols, demonstrates how they can help in improving the MRI workflow, and explores potential future directions. ©RSNA, 2019.

Reproducibility of the peritoneal regression grading score for assessment of response to therapy in peritoneal metastasis.

AIMS: The four-tiered peritoneal regression grading score (PRGS) assesses the response to chemotherapy in peritoneal metastasis (PM). The PRGS is used, for example, to assess the response to pressurised intraperitoneal aerosol chemotherapy (PIPAC). However, the reproducibility of the PRGS is currently unknown. We aimed to evaluate the inter- and intraobserver variability of the PRGS. METHODS AND RESULTS: Thirty-three patients who underwent at least three PIPAC treatments as part of the PIPAC-OPC1 or PIPAC-OPC2 clinical trials at Odense University Hospital, Denmark, were included. Prior to each therapy cycle, peritoneal quadrant biopsies were obtained and three haematoxylin and eosin (H&E)-stained step sections were scanned and uploaded to a pseudonymised web library. For determining interobserver variability, eight pathologists assessed the PRGS for each quadrant biopsy, and Krippendorff's alpha and intraclass correlation coefficients (ICCs) were calculated. For determining intraobserver variability, three pathologists repeated their own assessments and Cohen's kappa and ICCs were calculated. A total of 331 peritoneal biopsies were analysed. Interobserver variability for PRGS of each biopsy and for the mean and maximum PRGS per biopsy set was moderate to good/substantial. The intraobserver variability for PRGS of each biopsy and for the mean and maximum PRGS per biopsy set was good to excellent/almost perfect. CONCLUSIONS: Our data support the PRGS as a reproducible and useful tool to assess response to intraperitoneal chemotherapy in PM. Future studies should evaluate the prognostic and predictive role of the PRGS.

Surgeon Assessment of Gastric Cancer Lymph Node Specimens with a Video of Technique.

INTRODUCTION: In the majority of US institutions, gastrectomy specimens are sent for pathologic examination without surgeon assessment or standardized technique of lymph node (LN) assessment for gastric cancer. We conducted a quality improvement project at a US cancer center utilizing surgeon assessment of gastric LNs, and created a video to illustrate a technique of standardized lymph node assessment. METHODS: Convenience sampling was employed among patients with gastric adenocarcinomas who underwent curative-intent D2 gastrectomy between July 2016 and June 2017. For each patient, a surgeon assessed gastric LNs by harvesting individual LNs, followed by conventional evaluation by a pathologist. RESULTS: We enrolled 17 patients for this quality improvement project. Eight patients underwent total gastrectomy, and nine patients underwent subtotal gastrectomy. Twelve patients underwent preoperative chemoradiation therapy, three underwent preoperative chemotherapy alone, and two underwent upfront surgery. The median number of examined LNs was 43. All patients had ≥ 16 LNs examined, and 88% of patients had ≥ 30 LNs examined. CONCLUSION: Surgeon assessment of gastric LN specimens was feasible and effective to provide high-quality pathologic LN assessment after gastrectomy in gastric adenocarcinoma patients. Standardization of the technical methods for gastric LN evaluation is needed to improve the accuracy and quality of gastric cancer staging in the US. The provided video can help inform standardization of gastric LN assessment.

Risk assessment of lymph node metastases in early gastric adenocarcinoma fulfilling expanded endoscopic resection criteria.

BACKGROUND AND AIMS: Early gastric cancer (EGC) is known to present a low rate of lymph node metastases (LNMs). Gastrectomy with D2 lymphadenectomy is usually curative for EGC. Endoscopic submucosal dissection (ESD) is a well-accepted treatment modality for lesions that meet the classic criteria: those mucosal differentiated adenocarcinoma measuring 20 mm or less, without ulceration. Expanded criteria for ESD have been proposed based on a null LNM rate from large gastrectomy series from Japan. Patients with LNM have been reported in Western centers, heightening the need for validation of expanded criteria. Our aim was to assess the risk of LNM in gastrectomy specimens of patients with EGC who met the expanded criteria for ESD. METHODS: We conducted an evaluation of gastrectomy specimens including LNM staging of patients submitted to gastrectomy for EGC in a 39-year retrospective cohort. RESULTS: A total of 389 surgical specimens were included. From them, 135 fulfilled criteria for endoscopic resection. None of the 31 patients with classic criteria had LNM. From the 104 patients with expanded criteria, 3 had LNM (n = 104 [2.9%], 95% confidence interval, .7%-8.6%), all of them with undifferentiated tumors without ulceration, measuring less than 20 mm. CONCLUSIONS: There is a small risk of LNM in EGC when expanded criteria for ESD are met. Refinement of the expanded criteria for the risk of LNM may be desirable in a Brazilian cohort. Meanwhile, the decision to complement the endoscopic treatment with gastrectomy will have to take into consideration the individual risk of perioperative morbidity and mortality.

A statistical tool for risk assessment as a function of the number of lymph nodes retrieved from rectal cancer patients.

AIM: Although a minimum of 12 lymph nodes (LNs) has been recommended for examination in colorectal cancer patients there remains considerable debate with regard to rectal cancer. Inadequacy of examined LNs could lead to understaging and inappropriate treatment as a consequence. We describe a statistical tool that allows an estimate of the probability of false-negative nodes. METHOD: A total of 26 778 patients diagnosed between 2004 and 2013 with rectal adenocarcinoma [tumour stage (T stage) 1-3] who did not receive neoadjuvant therapies and had at least one histologically assessed LN were extracted from the Surveillance, Epidemiology and End Results (SEER) database. A statistical tool using beta-binomial distribution was developed to estimate the probability of missing a positive node as a function of the total number of LNs examined and T stage. RESULTS: The probability of falsely identifying a patient as node-negative decreased with increasing number of nodes examined for each stage. It was estimated to be 72%, 66% and 52% for T1, T2 and T3 patients, respectively, with a single node examined. To confirm an occult nodal disease with 90% confidence, 5, 9 and 29 nodes need to be examined for patients from stages T1, T2 and T3, respectively. CONCLUSION: The false-negative rate of the examined LNs in rectal cancer was verified to be dependent preoperatively on the clinical T stage. A more accurate nodal staging score was developed to recommend a threshold for the minimum number of examined nodes with regard to the favoured level of confidence.

The Impact of the Choosing Wisely Campaign in Urology.

OBJECTIVE: To determine if 3 of the Canadian Urological Association's Choosing Wisely recommendations (released in 2013-2014) related to urologic care altered physician and patient behavior. METHODS: Administrative data from Ontario, Canada between 2008 and 2017 was used. We identified 3 cohorts: First, we determined how many men >66 years of age had a serum testosterone level before starting testosterone therapy. Second, we determined how many boys undergoing an orchiopexy underwent abdominal imaging before their surgery. Third, we determined how many men with low risk prostate cancer underwent a Bone Scan after diagnosis. Piece-wise linear regression was used to evaluate for a significant change after Choosing Wisely. RESULTS: We identified 13,113 men who had their initial prescription for testosterone filled. Serum testosterone measurement increased over time, from approximately 43% to 68%. There were 9319 boys who underwent an orchiopexy. The use of pre-orchiopexy ultrasound was generally stable (approximately 55%). We identified 27,174 men with low risk prostate cancer. The use of bone scans after diagnosis decreased over time from approximately 24% to 20%. In all 3 of these groups, there was no significant change after Choosing Wisely (P = .74, P = .70, P = .72 respectively). CONCLUSION: In Ontario, there was no evidence of a significant change in 3 practice patterns that were featured in Choosing Wisely Urology recommendations. Further thought may be needed on how to translate these and future recommendations into behavior change.

External beam radiotherapy with or without androgen deprivation therapy in elderly patients with high metastatic risk prostate cancer.

OBJECTIVE: Several randomized controlled trials have documented significant overall survival benefit in high metastatic risk prostate cancer (PCa) patients treated with combination of androgen deprivation therapy (ADT) at radiotherapy (RT) relative to RT alone. Unfortunately, elderly patients are either not included or are underrepresented in these trials. In consequence, the survival benefit of combination of ADT at RT in the elderly warrants detailed reassessment, including its cost. METHODS: Between 1991 and 2009 within the Surveillance Epidemiology and End Results (SEER)-Medicare-linked database, we identified 3,692 patients aged 80 years or more with clinical T1-T2 PCa and WHO histological grade 3, or clinical T3-T4 PCa and any histological grade, treated with or without combination of ADT at RT. Competing risks analyses focused on cancer-specific mortality (CSM) and other-cause mortality, after accounting for confounders. All analyses were repeated in patients with no comorbidity and in most contemporary patients, treated between 2001 and 2009. Finally, we assessed median annual cost according to use of combination of ADT at RT, after adjusting for patient and tumor characteristics. RESULTS: In competing-risks multivariable analyses, no statistically significant difference was observed in CSM and other-cause mortality between patients treated with or without combination of ADT at RT. Same results were recorded in subgroup analyses of patients with no comorbidity and in most contemporary patients. The median annual costs of $36,140 and of $47,510 were recorded, respectively in patients treated without and with ADT at RT. CONCLUSION: Our findings failed to confirm that combination of ADT at RT reduces CSM rates in high metastatic risk PCa patients aged 80 years or more. Moreover, combination of ADT at RT resulted in a significant cost increase, relative to RT alone.