Tumor mutational load is prognostic for progression to therapy among high-count monoclonal B-cell lymphocytosis.

ABSTRACT: High-count monoclonal B-cell lymphocytosis (HCMBL) is a precursor condition to chronic lymphocytic leukemia (CLL). We have shown that among individuals with HCMBL, the CLL-International Prognostic Index (CLL-IPI) is prognostic for time-to-first therapy (TTFT). Little is known about the prognostic impact of somatically mutated genes among individuals with HCMBL. We sequenced DNA from 371 individuals with HCMBL using a targeted sequencing panel of 59 recurrently mutated genes in CLL to identify high-impact mutations. We compared the sequencing results with that of our treatment-naïve CLL cohort (N = 855) and used Cox regression to estimate hazard ratios and 95% confidence intervals (CIs) for associations with TTFT. The frequencies of any mutated genes were lower in HCMBL (52%) than CLL (70%). At 10 years, 37% of individuals with HCMBL with any mutated gene had progressed requiring treatment compared with 10% among individuals with HCMBL with no mutations; this led to 5.4-fold shorter TTFT (95% CI, 2.6-11.0) among HCMBL with any mutated gene vs none, independent of CLL-IPI. When considering individuals with low risk of progression according to CLL-IPI, those with HCMBL with any mutations had 4.3-fold shorter TTFT (95% CI, 1.6-11.8) vs those with none. Finally, when considering both CLL-IPI and any mutated gene status, we observed individuals with HCMBL who were high risk for both prognostic factors had worse prognosis than patients with low-risk CLL (ie, 5-year progression rate of 32% vs 21%, respectively). Among HCMBL, the frequency of somatically mutated genes at diagnosis is lower than that of CLL. Accounting for both the number of mutated genes and CLL-IPI can identify individuals with HCMBL with more aggressive clinical course.

Prediction of outcomes for high-count monoclonal B lymphocytosis using an epigenetic and immunogenetic signature.

ABSTRACT: Monoclonal B-cell lymphocytosis (MBL) progresses to chronic lymphocytic leukemia (CLL) requiring therapy at 1% to 5% per year. Improved prediction of progression would greatly benefit individuals with MBL. Patients with CLL separate into 3 distinct epigenetic subtypes (epitypes) with high prognostic significance, and recently the intermediate epitype has been shown to be enriched for high-risk immunoglobulin lambda variable (IGLV) 3-21 rearrangements, impacting outcomes for these patients. Here, we employed this combined strategy to generate the epigenetic and light chain immunoglobulin (ELCLV3-21) signature to classify 219 individuals with MBL. The ELCLV3-21 high-risk signature distinguished MBL individuals with a high probability of progression (39.9% and 71.1% at 5 and 10 years, respectively). ELCLV3-21 improved the accuracy of predicting time to therapy for individuals with MBL compared with other established prognostic indicators, including the CLL international prognostic index (c-statistic, 0.767 vs 0.668, respectively). Comparing ELCLV3-21 risk groups in MBL vs a cohort of 226 patients with CLL revealed ELCLV3-21 high-risk individuals with MBL had significantly shorter time to therapy (P = .003) and reduced overall survival (P = .03) compared with ELCLV3-21 low-risk individuals with CLL. These results highlight the power of the ELCLV3-21 approach to identify individuals with a higher likelihood of adverse clinical outcome and may provide a more accurate approach to classify individuals with small B-cell clones.

Association of Medicaid expansion with 2-year survival and time to treatment initiation in gastrointestinal cancer patients: A National Cancer Database study.

INTRODUCTION: We evaluated whether Medicaid expansion (ME) was associated with improved 2-year survival and time to treatment initiation (TTI) among patients with gastrointestinal (GI) cancer. METHODS: GI cancer patients diagnosed 40-64 years were queried from the National Cancer Database. Those diagnosed from 2010 to 2012 were considered pre-expansion; those diagnosed from 2014 to 2016 were considered post-expansion. Cox models estimated hazard ratios and 95% confidence intervals (CIs) for 2-year overall survival. Generalized estimating equations (GEE) estimated odds ratios (OR) and 95% CI of TTI within 30- and 90 days. Multivariable Difference-in-Difference models were used to compare expansion/nonexpansion cohorts pre-/post-expansion, adjusting for patient, clinical, and hospital factors. RESULTS: 377,063 patients were included. No significant difference in 2-year survival was demonstrated across ME and non-ME states overall or in site-based subgroup analysis. In stage-based subgroup analysis, 2-year survival significantly improved among stage II cancer, with an 8% decreased hazard of death at 2 years (0.92; 0.87-0.97). Those with stage IV had a 4% increased hazard of death at 2 years (1.04; 1.01-1.07). Multivariable GEE models showed increased TTI within 30 days (1.12; 1.09-1.16) and 90 days (1.22; 1.17-1.27). Site-based subgroup analyses indicated increased likelihood of TTI within 30 and 90 days among colon, liver, pancreas, rectum, and stomach cancers, by 30 days for small intestinal cancer, and by 90 days for esophageal cancer. In subgroup analyses, all stages experienced improved odds of TTI within 30 and 90 days. CONCLUSION: ME was not associated with significant improvement in 2-year survival for those with GI cancer. Although TTI increased after ME for both cohorts, the 30- and 90-day odds of TTI was higher for those from ME compared with non-ME states. Our findings add to growing evidence of associations with ME for those diagnosed with GI cancer.

Impact of Medicaid Expansion on Stage at Diagnosis for US Adults with Pancreatic Cancer: a Population-Based Study.

INTRODUCTION: We evaluated whether Medicaid expansion is associated with earlier stage at diagnosis for pancreatic cancer taking into account key demographic, clinical, and geographic factors. METHODS: We obtained Surveillance, Epidemiology, and End-Results (SEER-18) data on individuals diagnosed with pancreatic cancer from 2007 to 2016 (< 65 years of age). We defined non-metastatic as either local or regional disease (vs. metastatic disease). To estimate the association of Medicaid expansion with pancreatic cancer stage at diagnosis, we used a difference-in-differences model, at the individual level, comparing those from early-adopting states in 2014 to non-early-adopting states. We utilized cluster-robust standard errors and explored the role of demographic factors (race, sex, insurance at diagnosis), clinical indicator (disease in the head of the pancreas), and county characteristics (Urban Influence Code, Social Deprivation Index). RESULTS: In the univariable setting, the probability of non-metastatic disease at diagnosis increased by 3.9 percentage points (ppt) for those from Medicaid expansion states post-expansion (n = 36,609). After adjustment for covariates, the ppt was attenuated to 2.7. Of particular note, we observed evidence of interactions with sex and race. The beneficial effect was less pronounced for men (increase in the probability of non-metastatic stage at diagnosis by 2.1ppt) than women (3.6ppt) and non-existent for blacks (- 3.1ppt) compared to whites (4.9ppt) and other races (4.8ppt). CONCLUSION: Medicaid expansion is associated with increased probability of non-metastatic stage at diagnosis for pancreatic cancer; however, this beneficial effect is not uniform across sex and race. This underscores the need to investigate the impact of policy and implementation strategies on pancreatic cancer survival disparities.

Design and rationale of GUARDD-US: A pragmatic, randomized trial of genetic testing for APOL1 and pharmacogenomic predictors of antihypertensive efficacy in patients with hypertension.

RATIONALE AND OBJECTIVE: APOL1 risk alleles are associated with increased cardiovascular and chronic kidney disease (CKD) risk. It is unknown whether knowledge of APOL1 risk status motivates patients and providers to attain recommended blood pressure (BP) targets to reduce cardiovascular disease. STUDY DESIGN: Multicenter, pragmatic, randomized controlled clinical trial. SETTING AND PARTICIPANTS: 6650 individuals with African ancestry and hypertension from 13 health systems. INTERVENTION: APOL1 genotyping with clinical decision support (CDS) results are returned to participants and providers immediately (intervention) or at 6 months (control). A subset of participants are re-randomized to pharmacogenomic testing for relevant antihypertensive medications (pharmacogenomic sub-study). CDS alerts encourage appropriate CKD screening and antihypertensive agent use. OUTCOMES: Blood pressure and surveys are assessed at baseline, 3 and 6 months. The primary outcome is change in systolic BP from enrollment to 3 months in individuals with two APOL1 risk alleles. Secondary outcomes include new diagnoses of CKD, systolic blood pressure at 6 months, diastolic BP, and survey results. The pharmacogenomic sub-study will evaluate the relationship of pharmacogenomic genotype and change in systolic BP between baseline and 3 months. RESULTS: To date, the trial has enrolled 3423 participants. CONCLUSIONS: The effect of patient and provider knowledge of APOL1 genotype on systolic blood pressure has not been well-studied. GUARDD-US addresses whether blood pressure improves when patients and providers have this information. GUARDD-US provides a CDS framework for primary care and specialty clinics to incorporate APOL1 genetic risk and pharmacogenomic prescribing in the electronic health record. TRIAL REGISTRATION: ClinicalTrials.govNCT04191824.

Frailty and risk of mortality in older cancer survivors and adults without a cancer history: Evidence from the National Health and Nutrition Examination Survey, 1999-2014.

BACKGROUND: Epidemiologic evidence reporting the role of frailty in survival among older adults with a prior cancer diagnosis is limited. METHODS: A total of 2050 older adults (≥60 years old) surviving for at least 1 year after a cancer diagnosis and 9474 older adults without a cancer history from the National Health and Nutrition Examination Survey (1999-2014) were included for analysis. The exposure variable, a 45-item frailty index (FI), was categorized on the basis of validated cutoffs (FI ≤ 0.10 [fit], 0.10 < FI ≤ 0.21 [prefrail], and FI > 0.21 [frail]). All-cause mortality was ascertained via the National Death Index. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence interval (CIs) for the FI, and this was followed by restricted cubic splines depicting dose-response curves. RESULTS: For older cancer survivors, the mean age at the baseline was 72.6 years (SD, 7.1 years); 5.9% were fit, 38.2% were prefrail, and 55.9% were frail. Older adults without a cancer history were slightly younger (mean age, 70.0 years) and less frail (47.9% were frail). At each level of the FI, cancer survivors (1.9 per 100 person-years for FI ≤ 0.10, 3.4 per 100 person-years for 0.10 < FI ≤ 0.21, and 7.5 per 100 person-years for FI > 0.21) had higher mortality than their cancer-free counterparts (1.4 per 100 person-years for FI ≤ 0.10, 2.4 per 100 person-years for 0.10 < FI ≤ 0.21, and 5.4 per 100 person-years for FI > 0.21). The multivariable model suggested a positive association between the FI and all-cause mortality for survivors (aHR for FI > 0.21 vs FI ≤ 0.10, 2.80; 95% CI, 1.73-4.53) and participants without a cancer history (aHR for FI > 0.21 vs FI ≤ 0.10, 2.75; 95% CI, 2.29-3.32). Restricted cubic splines indicated that all-cause mortality risk increased with the FI in a monotonic pattern. CONCLUSIONS: Frailty is associated with a higher risk of death in older cancer survivors and the elderly without a cancer history.

Impact of Medicaid Expansion on Pancreatic Cancer: An Examination of Sociodemographic Disparity in 1-Year Survival.

BACKGROUND: This study examined the effect of Medicaid expansion on 1-year survival of pancreatic cancer for nonelderly adults. We further evaluated whether sociodemographic and county characteristics alter the association of Medicaid expansion and 1-year survival. STUDY DESIGN: We obtained data from the Surveillance Epidemiology and End-Results dataset on individuals diagnosed with pancreatic cancer from 2007 to 2015. A Difference-in-Differences model compared those from early-adopting states to non-early-adopting states, before and after adoption (2014), while taking into consideration sociodemographic and county characteristics to estimate the effect of Medicaid expansion on 1-year survival. RESULTS: In the univariable Difference-in-Differences model, the probability of 1-year survival for pancreatic cancer increased by 4.8 percentage points (ppt) for those from Medicaid expansion states postexpansion (n = 35,347). After adjustment for covariates, the probability of 1-year survival was reduced to 0.8 ppt. Interestingly, after multivariable adjustment the effect of living in an expansion state on 1-year survival was similar for men and women (0.6 ppt for men vs 1.2 ppt for women), was also similar for Whites (2.6 ppt), and was higher in those of other races (5.9 ppt) but decreased for Blacks (-2.0 ppt). Those who were insured (-0.1 ppt) or uninsured (-2.2 ppt) experienced a decrease in the probability of 1-year survival; however, those who were covered by Medicaid at diagnosis experienced an increase in the probability of 1-year survival (7.4 ppt). CONCLUSIONS: Medicaid expansion during or after 2014 is associated with an increase in the probability of 1-year survival for pancreatic cancer; however, this effect is attenuated after adjustment for sociodemographic characteristics. Of note, the positive association was more pronounced in certain categories of key covariates suggesting further inquiry focused on these subgroups.

Novel plasma glycoprotein biomarkers predict progression-free survival in surgically resected clear cell renal cell carcinoma.

INTRODUCTION: Limited data exists on utilization of protein post-translational modifications as biomarkers for clear cell renal cell carcinoma (ccRCC). We employed high-throughput glycoproteomics to evaluate differential expression of glycoprotein-isoforms as novel markers for ccRCC progression-free survival (PFS). METHODS: Plasma samples were obtained from 77 patients treated surgically for ccRCC. Glycoproteomic analyses were carried out after liquid chromatography tandem mass spectrometry. Age-adjusted Cox proportional hazard models were constructed to evaluate PFS. Optimized Harrell's C-index was employed to dichotomize the collective for the construction of Kaplan-Meier curves. RESULTS: The average length of follow-up was 3.4 (range: 0.04-9.83) years. Glycoproteomic analysis identified 39 glycopeptides and 14 non-glycosylated peptides that showed statistically significant (false discovery rate P ≤ 0.05) differential expression associated with PFS. Five of the glycosylated peptides conferred continuous hazard ratio (HR) of > 6 (range 6.3-11.6). These included prothrombin A2G2S glycan motif (HR = 6.47, P = 9.53E-05), immunoglobulin J chain FA2G2S2 motif (HR = 10.69, P = 0.001), clusterin A2G2 motif (HR = 7.38, P = 0.002), complement component C8A A2G2S2 motif (HR = 11.59, P = 0.002), and apolipoprotein M glycopeptide with non-fucosylated and non-sialylated hybrid-type glycan (HR = 6.30, P = 0.003). Kaplan-Meier curves based on dichotomous expression of these five glycopeptides resulted in hazard ratios of 3.9 to 10.7, all with P-value < 0.03. Kaplan-Meyer plot using the multivariable model comprising 3 of the markers yielded HR of 11.96 (P < 0.0001). CONCLUSION: Differential glyco-isoform abundance of plasma proteins may be a useful source of biomarkers for the clinical course and prognosis of ccRCC.

UGT1A1 Guided Cancer Therapy: Review of the Evidence and Considerations for Clinical Implementation.

Multi-gene assays often include UGT1A1 and, in certain instances, may report associated toxicity risks for irinotecan, belinostat, pazopanib, and nilotinib. However, guidance for incorporating UGT1A1 results into therapeutic decision-making is mostly lacking for these anticancer drugs. We summarized meta-analyses, genome-wide association studies, clinical trials, drug labels, and guidelines relating to the impact of UGT1A1 polymorphisms on irinotecan, belinostat, pazopanib, or nilotinib toxicities. For irinotecan, UGT1A1*28 was significantly associated with neutropenia and diarrhea, particularly with doses ≥ 180 mg/m2, supporting the use of UGT1A1 to guide irinotecan prescribing. The drug label for belinostat recommends a reduced starting dose of 750 mg/m2 for UGT1A1*28 homozygotes, though published studies supporting this recommendation are sparse. There was a correlation between UGT1A1 polymorphisms and pazopanib-induced hepatotoxicity, though further studies are needed to elucidate the role of UGT1A1-guided pazopanib dose adjustments. Limited studies have investigated the association between UGT1A1 polymorphisms and nilotinib-induced hepatotoxicity, with data currently insufficient for UGT1A1-guided nilotinib dose adjustments.

Identification of DNA methylation signatures associated with poor outcome in lower-risk Stage, Size, Grade and Necrosis (SSIGN) score clear cell renal cell cancer.

BACKGROUND: Despite using prognostic algorithms and standard surveillance guidelines, 17% of patients initially diagnosed with low risk clear cell renal cell carcinoma (ccRCC) ultimately relapse and die of recurrent disease, indicating additional molecular parameters are needed for improved prognosis. RESULTS: To address the gap in ccRCC prognostication in the lower risk population, we performed a genome-wide analysis for methylation signatures capable of distinguishing recurrent and non-recurrent ccRCCs within the subgroup classified as 'low risk' by the Mayo Clinic Stage, Size, Grade, and Necrosis score (SSIGN 0-3). This approach revealed that recurrent patients have globally hypermethylated tumors and differ in methylation significantly at 5929 CpGs. Differentially methylated CpGs (DMCpGs) were enriched in regulatory regions and genes modulating cell growth and invasion. A subset of DMCpGs stratified low SSIGN groups into high and low risk of recurrence in independent data sets, indicating that DNA methylation enhances the prognostic power of the SSIGN score. CONCLUSIONS: This study reports a global DNA hypermethylation in tumors of recurrent ccRCC patients. Furthermore, DMCpGs were capable of discriminating between aggressive and less aggressive tumors, in addition to SSIGN score. Therefore, DNA methylation presents itself as a potentially strong biomarker to further improve prognostic power in patients with low risk SSIGN score (0-3).

Creation of a primary tumor tissue expression biomarker-augmented prognostic model for patients with metastatic renal cell carcinoma.

BACKGROUND: Clinical and pathological factors alone have limited prognostic ability in patients with metastatic clear cell renal cell carcinoma (ccRCC). Bim, a downstream pro-apoptotic molecule in the PD-1 signaling pathway, has recently been associated with survival in other malignancies. We sought to determine if tissue biomarkers including Bim, added to a previously reported clinical metastases score, improved prediction of cancer-specific survival (CSS) for patients with metastatic ccRCC. METHODS: Patients with metastatic ccRCC who underwent nephrectomy between 1990 and 2004 were identified using our institutional registry. Sections from paraffin-embedded primary tumor tissue blocks were used for immunohistochemistry staining for Bim, PD-1, B7-H1 (PD-L1), B7-H3, CA-IX, IMP3, Ki67, and survivin. Biomarkers that were significantly associated with CSS after adjusting for the metastases score were used to develop a biomarker-specific multivariable model using a bootstrap resampling approach and forward selection. Predictive ability was summarized using a bootstrap-corrected c-index. RESULTS: The cohort included 602 patients: 192 (32%) with metastases at diagnosis and 410 (68%) who developed metastases after nephrectomy. Median follow-up was 9.6 years (IQR 4.2-12.8), during which 504 patients died of RCC. Bim, IMP3, Ki67, and survivin expression were significantly associated with CSS after adjusting for the metastases score, and were eligible for biomarker-specific model inclusion. After variable selection, high Bim (hazard ratio [HR] = 1.44; 95% confidence interval [CI] 1.16-1.78; P <0.001), high survivin (HR = 1.35; 95% CI 1.08-1.68; P = 0.008), and the metastases score (HR = 1.13 per 1 point; 95% CI 1.10-1.16; P <0.001) were retained in the final multivariable model (c-index = 0.69). CONCLUSION: We created a prognostic model combining the clinical metastases score and 2 primary tumor tissue expression biomarkers, Bim and survivin, for patients with metastatic renal cell carcinoma who underwent nephrectomy.

Breast cancer in women: a descriptive analysis of the national cancer database.

BACKGROUND AND AIM OF THE WORK: Breast cancer is the most common cancer in women in the United States. National Cancer Database (NCDB) is one of the largest tumor databases of the United States. This study aimed to evaluate the features of breast cancer in women from a large updated database. METHODS: We describe and analyze the frequencies and percentages of the clinical and pathological features of women diagnosed with breast cancer registered in NCDB, in a period from 2004 to 2015. RESULTS: A total of 2,423,875 women were diagnosed with breast cancer between 2004 and 2015. The nationally representative analysis demonstrated that the incidence of breast cancer among women increased over the years. Upper-outer quadrant was the most frequent primary tumor site, and the intraductal carcinoma was the most frequent histology. The prevalence of breast cancer increased with age. The most frequent grade at diagnosis was grade II. Broadly, invasive characteristics were noted more frequently in younger patients. Left and right breast were affected with almost the same frequency, with a slight predominance of the left breast. The most frequent surgical treatment was a partial mastectomy. Reconstruction with implant was the most frequent choice. Post-mastectomy radiation therapy was administered in the majority of patients. CONCLUSIONS: To the authors' knowledge, the current study is the largest descriptive analysis to date on the clinical and pathological features of breast cancer in a population-based database. The increase in incidence over the years indicates an important need for etiologic research and innovative approaches to improve breast cancer prevention.

Chronic Tenosynovitis of the Upper Extremities Caused by Mycobacterium kansasii : A Clinical Case and Systematic Review of Literature.

Background Chronic tenosynovitis of the upper extremities caused by Mycobacterium kansasii ( M. kansasii ) is uncommon, but symptoms may overlap with other more common diseases. Late diagnosis and treatment can lead to disfiguration of structures and rupture of tendons, resulting in worse cosmetic outcomes after reconstruction. Methods We present a clinical case and literature review of M. kansasii in patients with chronic tenosynovitis of upper extremities. PubMed was queried for cases of upper extremities tenosynovitis caused by M. kansasii . The keywords " M. kansasii ," "tenosynovitis" and synonyms were used for search in different combinations. Manuscripts, with no specific data or another condition, where the infection was not located in the upper extremities, were reviews, or not in English, were excluded from the study. Results We described 23 reported cases of tenosynovitis of the upper extremity caused by M. kansasii . An immunosuppressed state was present in eight (34.8%) cases, and 12 (52.2%) patients received immunosuppressive treatment. A long-time period between the first appearance of symptoms and the definitive diagnosis was identified (median: 7 months, interquartile range: 9). The most frequent symptoms were local swelling (65.2%), pain (56.5%), mass effect (26%), and stiffness (13%). Tendon rupture was found in three (13%) patients as a complication of the disease. Moreover, seven (30.4%) patients underwent previous surgeries to try to relieve the symptoms before definitive diagnosis was achieved. Conclusion M. kansasii is an important differential causal pathogen for tenosynovitis of the upper extremities. Although rare, raising awareness about this infectious disease is imperative to avoid inadequate management and hazardous aesthetic sequelae.

Bioimpedance Spectroscopy for Assessment of Breast Cancer-Related Lymphedema: A Systematic Review.

Bioimpedance spectroscopy is currently used to evaluate patients with breast cancer-related lymphedema (BCRL). We aimed to describe published studies on the use of bioimpedance spectroscopy for assessment for BCRL. We queried the PubMed, Ovid Medline, and Embase databases to identify studies that evaluated the use of bioimpedance spectroscopy as an assessment tool. We searched for the keywords "bioimpedance" AND ("lymphedema" OR "lymphoedema"). We included English-language studies that reported the use of bioimpedance spectroscopy for assessment of BCRL. Out of 152, 116, and 235 articles identified in each database, respectively, only a total of 11 articles were included. Bioimpedance spectroscopy was studied as a method to assess and predict response to BCRL treatment, assess volume changes, and calibrate L-Dex scores for conversion to units of volume. All studies reported that bioimpedance spectroscopy is a promising tool for predicting response to BCRL treatment and measuring volume changes. Bioimpedance spectroscopy can be used for assessment of BCRL. However, the accuracy of bioimpedance spectroscopy for BCRL assessment has not been determined, and consequently further studies are needed.

National Analysis of Patients With Ulcerated Melanoma in the United States.

BACKGROUND/AIM: Ulceration is associated with unfavorable prognosis in patients with melanoma. The present study aimed to analyze the characteristics associated with ulcerated melanoma in the United States. It was hypothesized that patient disparities associated with increased odds of ulceration exist. PATIENTS AND METHODS: We searched the National Cancer Database for melanoma patients from 2004 to 2015. Data regarding patient demographics, facility characteristics, and tumor characteristics were analyzed. RESULTS: There were higher odds of ulceration in non-white patients, 50 years of age or older, and melanoma on the trunk and extremities. Lower odds were found in women, zip codes with higher income and education levels, and Metro or Urban counties. CONCLUSION: Age above 49 years, male sex, non-white race, living in rural areas, and living in zip codes with low income and low education were independently associated with ulcerated melanoma.

Concordance of PD-1 and PD-L1 (B7-H1) in paired primary and metastatic clear cell renal cell carcinoma.

OBJECTIVES: Previous studies noted discordance of programmed death-1 (PD-1) and one of its ligands (PD-L1) across patient-matched primary and metastatic clear cell renal cell carcinoma (ccRCC). There are inconsistencies if the primary or metastatic tumor has higher expression, and whether metastatic tumor expression is associated with patient outcome. Thus, we examined PD-1 and PD-L1 in patient-matched tumors using a large number of ccRCC patients with long follow-up. MATERIALS AND METHODS: We analyzed PD-1 and PD-L1 using immunohistochemistry in patient-matched primary and metastatic tumors from 110 ccRCC patients. Concordance was assessed among longitudinal metastatic tumors, as well as across patient-matched primary and metastatic tumors. Cox proportional hazards regression was used to evaluate the associations of metastatic tumor expression with cancer-specific survival. RESULTS: We observed inter-metastatic tumor heterogeneity of PD-1 in 25 (69%) of the 36 patients and of PD-L1 in seven (19%) patients. Concordance between patient-matched primary and metastatic tumors was 73% (Kappa = 0.16, 95% CI: -0.003-0.32). Similarly, concordance of PD-L1 between metastatic and patient-matched primary tumors was 78% (Kappa = 0.27, 95% CI: 0.09-0.46). Both markers demonstrated higher expression in primary vs metastatic tumors. Metastatic tumor expression of PD-1 was significantly associated with metastatic location (P < .0001) and ccRCC-specific survival (HR = 2.15, 95% CI: 1.06-4.36, P = .035). CONCLUSIONS: The expression of PD-1 and PD-L1 is discordant across patient-matched ccRCC tumors, with higher expression in primary tumors. Higher PD-1 expression was associated with metastatic location and lower cancer-specific survival. If validated, these results highlight the importance of evaluating these biomarkers in metastatic tissue specifically.

What Factors Define Limb Salvage or Amputation Surgery in Osteosarcoma of the Upper Extremities?

BACKGROUND/AIM: Controversy exists between performing limb salvage or amputation to treat osteosarcoma of the upper extremities. Our aim was to review the characteristics associated with limb amputation due to osteosarcoma of the upper extremities. PATIENTS AND METHODS: A descriptive study was performed by querying the National Cancer Database from January 1, 2004 to December 31, 2015. Statistical analysis was performed using chi-squared test and a multivariate logistic regression model. RESULTS: A total of 777 patients diagnosed with osteosarcoma of the upper extremities who underwent surgery met the inclusion criteria. Patients between 61 and 80 years were less likely to undergo limb amputation. Moreover, facilities located in the South Atlantic region, and stage IV of the disease were factors independently positively associated with amputation. CONCLUSION: Patients in facilities located in the South Atlantic region and those with stage IV disease were more likely to undergo amputation.

Disparity on Unplanned Readmission in Melanoma Patients: A National Cancer Database Analysis.

BACKGROUND/AIM: This study aimed to analyze associated factors of 30-day hospital readmission after surgery for melanoma. PATIENTS AND METHODS: We conducted a retrospective analysis of postoperative 30-day unplanned readmission in patients with melanoma in the National Cancer Database (NCDB). RESULTS: Higher odds of unplanned readmission were found in non-white patients compared to white, uninsured patients compared to those with private insurance, tumors with invasive behavior compared to in situ, presence of ulceration, American Joint Committee on Cancer stages greater than II, and location in the extremities. Lower odds of unplanned readmission were found in women living in areas where the percentage of adults who did not graduate from high school was below 13.0% with an annual income of $38,000 or more, who were treated in Academic/Research Programs or Integrated Network Cancer Programs. CONCLUSION: Non-white patients and low-income zip-codes were associated with unplanned readmission.

Influence of Facility Characteristics on Access to Breast Reconstruction: A 12-Year National Cancer Database Analysis.

BACKGROUND/AIM: This study aimed to analyze facility characteristics contributing to disparities in breast reconstruction access in the United States. PATIENTS AND METHODS: Data from January 1, 2004, to December 31, 2015 were extracted from the National Cancer Database on patient, facility and treatment, and tumor characteristics. A total of 858,594 patients met the inclusion criteria of the study, including 553,517 (64.5%) patients who underwent mastectomy only (without breast reconstruction) and 305,077 (35.5%) patients who received breast reconstruction (implants or autologous tissue). RESULTS: Multivariate analysis showed that the odds of reconstruction were higher in Integrated Network Cancer Programs and Academic/Research Programs compared to Community Cancer Programs. Patients treated in the South, Midwest, and West regions had lower odds of reconstruction. Interestingly, patients treated in more than one Commission on Cancer facility had a higher likelihood of reconstruction. CONCLUSION: Facility characteristics and location impact on access to breast reconstruction.

Osteosarcoma of the Upper Extremities: A National Analysis of the US Population.

BACKGROUND/AIM: Osteosarcoma of the upper extremities is rare, and characteristics in this location have not been described before. We aimed to analyze the characteristics and survival rate of osteosarcoma of the upper extremities. MATERIALS AND METHODS: A retrospective cohort study was performed by querying the National Cancer Database. Statistical analysis was performed using a multivariate logistic regression model and Kaplan-Meier log-rank tests for survival. RESULTS: A total of 991 patients were diagnosed with osteosarcoma of the upper extremities. Most tumors were osteogenic and osteoblastic (66.8%), larger than 8 cm (47.9%), high grade (64.3%), lymph node-negative (7.9%), and without metastasis to lungs (39.0%). Osteosarcomas of the hand and wrist were less likely to be high-grade when compared to osteosarcomas of the forearm, arm, and shoulder. CONCLUSION: The results of this study help us to approach patients promptly and avoid total amputation, increasing functionality and prognosis of the disease.