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1.
Oncologist ; 28(3): 268-275, 2023 03 17.
Article in English | MEDLINE | ID: mdl-36302223

ABSTRACT

BACKGROUND: Widespread implementation of immune checkpoint inhibitors (ICI) and targeted therapies for metastatic melanoma has led to a decline in melanoma-related mortality but increased healthcare costs. We aimed to determine how healthcare utilization varied by systemic, non-adjuvant melanoma treatment from 2016 to 2020. PATIENTS AND METHODS: Adults with presumed stage IV metastatic melanoma receiving systemic therapy from 2016 to 2020 were identified in Optum, a nationwide commercial claims database. Treatment groups were nivolumab, pembrolizumab, ipilimumab+nivolumab (combination-ICI), or BRAF+MEK inhibitor (BRAFi+MEKi) therapy. Outcomes included hospitalizations, days hospitalized, emergency room (ER) visits, outpatient visits, and healthcare costs per patient per month (pppm). Multivariable regression models were used to analyze whether cost and utilization outcomes varied by treatment group, with nivolumab as reference. RESULTS: Among 2018 adult patients with metastatic melanoma identified, mean (SD) age was 67 (15) years. From 2016 to 2020, nivolumab surpassed pembrolizumab as the most prescribed systemic melanoma therapy while combination-ICI and BRAFi+MEKi therapies remained stable. Relative to nivolumab, all other therapies were associated with increased total healthcare costs (combination-ICI: ß = $47 600 pppm, 95%CI $42 200-$53 100; BRAFi+MEKi: ß = $3810, 95%CI $365-$7260; pembrolizumab: ß = $6450, 95%CI $4420-$8480). Combination-ICI and BRAFi+MEKi therapies were associated with more inpatient hospital days. CONCLUSIONS: Amid the evolving landscape of systemic therapy for advanced melanoma, nivolumab monotherapy emerged as the most used and least costly systemic treatment from 2016 to 2020. Its sharp increase in use in 2018 and lower costs relative to pembrolizumab may in part be due to earlier adoption of less frequent dosing intervals.


Subject(s)
Melanoma , Nivolumab , Aged , Humans , Delivery of Health Care , Health Care Costs , Ipilimumab/therapeutic use , Melanoma/pathology , Nivolumab/therapeutic use , Patient Acceptance of Health Care , Middle Aged
2.
Pediatr Dermatol ; 40(5): 829-834, 2023.
Article in English | MEDLINE | ID: mdl-37439382

ABSTRACT

BACKGROUND: Dermatologists and other providers play essential roles in managing the dermatologic care of pediatric patients. This study aims to identify patterns and elucidate factors associated with receiving dermatologic care in the United States. METHODS: The National Ambulatory Medical Care Survey (NAMCS) was used to identify pediatric patients with dermatologic diagnoses from 2009 to 2015. Clinical and demographic information were evaluated, and visit diagnoses were stratified based on provider type (dermatologists vs. non-dermatologists). Multivariate logistic regression analysis was used to identify key predictors of outpatient dermatology care for pediatric patients. National estimates of diagnoses were procured using weights provided within the NAMCS database to project disease incidence. RESULTS: A total of 85,217,557 pediatric patients (survey-weighted) were observed during the study period. Of the sampled patients, 29.3% were evaluated by dermatologists, while 70.7% were seen by non-dermatology providers. Atopic dermatitis was the most common diagnosis encountered by dermatologists in ages 0-3 years, while unspecified contact dermatitis was the most common diagnosis reported by non-dermatologists in all age groups. On multivariable logistic regression, ≥1 year of age, Caucasian race, private insurance versus Medicaid, residence in a metropolitan area, referral from another provider, and longer appointment wait time were associated with an increased likelihood of being evaluated by a dermatologist compared to a non-dermatologist. CONCLUSIONS: Non-dermatologists are responsible for the majority of pediatric dermatologic care. For pediatric patients, health disparities by race, insurance status, and rurality present significant challenges to being evaluated by a dermatologist.


Subject(s)
Dermatitis, Atopic , Dermatitis, Contact , Dermatology , Skin Diseases , Humans , Child , United States/epidemiology , Ambulatory Care , Health Care Surveys , Skin Diseases/diagnosis , Skin Diseases/epidemiology , Skin Diseases/therapy , White
3.
World J Urol ; 39(8): 2995-3003, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33471163

ABSTRACT

PURPOSE: To assess the incidence, risk factors, and clinical outcomes associated with (Clostridioides difficile infection) CDI following urological surgery, which is the leading cause of nosocomial diarrhea and a growing public health burden. METHODS: We queried the National Surgical Quality Improvement Program (NSQIP) to identify patients undergoing urological surgery in 2015-2016. We evaluated the 30-day incidence and factors associated with postoperative CDI and 30-day hospital readmission and length of stay as secondary outcomes. Among the subset of patients undergoing radical cystectomy with urinary diversion (surgery with highest CDI incidence) we used multivariable logistic regression analysis to evaluate independent clinical and demographic factors associated with postoperative CDI. RESULTS: We identified 98,463 patients during the study period. The overall 30-day incidence of CDI was 0.31%, but varied considerably across surgery type. The risk of CDI was greatest following radical cystectomy with urinary diversion (2.72%) compared to all other urologic procedures (0.19%) and was associated with increased risk of hospital readmission (p < 0.0001), re-operation (p < 0.0001), and longer mean length of stay (p < 0.0001) in this cohort. Among patients undergoing radical cystectomy with urinary diversion, multivariable logistic regression revealed that preoperative renal failure (OR: 5.30, 95% CI 1.13-24.9, p = 0.035) and blood loss requiring transfusion (OR: 1.67, 95% CI 1.15-2.44, p = 0.0075) were independently associated with CDI. CONCLUSIONS: In a nationally representative cohort, the incidence of CDI was low but varied substantially across surgery types. CDI was most common following radical cystectomy and associated with potentially modifiable factors such as blood transfusion and significantly longer length of stay.


Subject(s)
Clostridium Infections , Cross Infection , Cystectomy , Postoperative Complications , Urinary Diversion , Urologic Surgical Procedures , Clostridium Infections/diagnosis , Clostridium Infections/drug therapy , Clostridium Infections/epidemiology , Clostridium Infections/etiology , Cross Infection/diagnosis , Cross Infection/drug therapy , Cross Infection/epidemiology , Cross Infection/etiology , Cystectomy/adverse effects , Cystectomy/methods , Female , Humans , Incidence , Male , Middle Aged , Postoperative Complications/drug therapy , Postoperative Complications/epidemiology , Postoperative Complications/microbiology , Reoperation/statistics & numerical data , Risk Assessment/statistics & numerical data , Risk Factors , United States/epidemiology , Urinary Diversion/adverse effects , Urinary Diversion/methods , Urologic Surgical Procedures/adverse effects , Urologic Surgical Procedures/classification , Urologic Surgical Procedures/methods
4.
World J Urol ; 39(4): 1141-1151, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32562045

ABSTRACT

PURPOSE: To evaluate practice patterns of planned post-operative radiation therapy (RT) among men with positive surgical margins (PSM) at radical prostatectomy. METHODS: We identified 43,806 men within the National Cancer Database with pathologic node-negative prostate cancer diagnosed in 2010 through 2014 with PSM. The primary endpoint was receipt of planned (RT) within a patient's initial course of treatment. We examined post-RP androgen deprivation therapy (ADT) with RT as a secondary endpoint. We evaluated patterns of post-operative management and characteristics associated with planned post-prostatectomy RT. RESULTS: Within 12 months of RP, 87.0% received no planned RT, 8.5% RT alone, 1.3% ADT alone, and 3.1% RT with ADT. In a multivariable logistic regression model, planned RT use was associated with clinical and pathologic characteristics as estimated by surgical Cancer of the Prostate Risk Assessment (CAPRA-S) category (intermediate versus low, OR = 2.87, 95% CI 2.19-3.75, P < 0.001; high versus low, OR = 10.23, 95% CI 7.79-13.43, P < 0.001), treatment at community versus academic centers (OR = 1.24, 95% CI 1.15-1.34, P < 0.001), shorter distance to a treatment facility (OR = 0.97 for each 10-mile, 95% CI 0.96-0.98, P < 0.001), and uninsured status (OR = 1.39, 95% CI 1.10-1.77, P = 0.005). The odds of receiving planned RT were lower in 2014 versus 2010 (OR = 0.76, 95% CI 0.68-0.85, P < 0.001). There was no significant change in the use of ADT with RT. High versus low CAPRA-S category was associated with the use of ADT in addition to RT (OR = 5.13, 95% CI 1.57-16.80, P = 0.007). CONCLUSION: The use of planned post-prostatectomy RT remained stable among patients with PSM and appears driven primarily by the presence of other adverse pathologic features.


Subject(s)
Margins of Excision , Practice Patterns, Physicians' , Prostatectomy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/radiotherapy , Aged , Humans , Male , Middle Aged , Postoperative Period , Prostatectomy/methods , Prostatic Neoplasms/surgery , Retrospective Studies , United States
5.
Dermatol Ther ; 34(1): e14461, 2021 01.
Article in English | MEDLINE | ID: mdl-33112465

ABSTRACT

Tyrosine kinase inhibitors are a class of targeted anticancer drugs that inhibit cancer cell proliferation by inactivating proteins involved in signal transduction cascades. Various cutaneous adverse events have been observed after tyrosine kinase inhibitor administration, including Sweet syndrome. We queried the PubMed database to identify 14 cases of Sweet syndrome thought to be secondary to tyrosine kinase inhibitors. Tyrosine kinase inhibitor-induced Sweet syndrome had a median of 2 months latency following drug administration. All cases but one had morphologic features classic for Sweet syndrome (erythematous and tender papules, plaques, or nodules). All cases also had classic histopathologic findings (dermal neutrophilic infiltrate without vasculitis or necrosis). Using diagnostic criteria for drug-induced Sweet syndrome and the Naranjo Drug Reaction Probability Scale for a drug-induced cutaneous eruption, we found that six cases favored a drug-induced etiology over malignancy, two cases favored a malignancy-associated Sweet syndrome, and the remaining eight met drug-induced Sweet syndrome criteria but had low Naranjo scores. Nine cases resulted in medication discontinuation, while five cases continued anticancer therapy and were treated only with corticosteroids with quick resolution of skin lesions. Dermatologists should be aware of this adverse cutaneous reaction to tyrosine kinase inhibitors and should treat on a case-by-case basis, though limited evidence in this review suggests that oncologic therapy may safely be continued with prompt corticosteroid treatment.


Subject(s)
Drug Eruptions , Neoplasms , Sweet Syndrome , Drug Eruptions/diagnosis , Drug Eruptions/etiology , Humans , Neoplasms/drug therapy , Protein Kinase Inhibitors/adverse effects , Skin , Sweet Syndrome/chemically induced , Sweet Syndrome/diagnosis
6.
Dermatol Online J ; 27(8)2021 Aug 15.
Article in English | MEDLINE | ID: mdl-34755954

ABSTRACT

BACKGROUND: Although hematogenous malignancy is a risk factor for poorer prognosis in Merkel cell carcinoma (MCC), current guidelines make no specific recommendations for surveillance. OBJECTIVE: We aim to characterize MCC-specific mortality compared to other causes of death for patients with hematologic malignancy in MCC, which will guide workup and surveillance strategies. METHODS: The Surveillance, Epidemiology, and End Results-18 registry was queried for MCC patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin lymphoma (NHL). RESULTS: Of 8519 patients with MCC, 146 (1.7%) had CLL and 234 (2.8%) had NHL. Chronic lymphocytic leukemia patients had 5-year cumulative incidence of MCC-specific mortality of 38.4% versus 28.4% in patients without CLL/NHL. For both cohorts, oncologic risk was highest within the first three years of diagnosis with competing risks favored thereafter. On competing risk regression, a history of CLL trended toward statistical significance with poorer MCC-specific mortality (subdistribution hazard ratio: 1.33, 95% CI: 0.963-1.834, P=0.084), while NHL was not prognostic. CONCLUSIONS: Merkel cell carcinoma patients with CLL may benefit from more aggressive initial management. Surveillance for similar length in CLL patients with MCC may be appropriate; this co-morbidity did not affect the timeframe by which the risk of competing causes of death exceeded oncologic risks.


Subject(s)
Carcinoma, Merkel Cell/complications , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Lymphoma, Non-Hodgkin/complications , Aged , Aged, 80 and over , Analysis of Variance , Carcinoma, Merkel Cell/therapy , Female , Humans , Male , Regression Analysis , Risk Assessment , SEER Program , Survival Analysis
7.
Plant Dis ; 104(12): 3159-3165, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33079630

ABSTRACT

Oxathiapiprolin is highly effective in the management of Phytophthora root rot of citrus; however, its uptake into plants after soil application is not known. This was investigated and compared with mefenoxam using potted citrus seedlings sampled 7, 10, 13, and 16 days after soil treatments. Bioassays and high-performance liquid chromatography tandem mass spectroscopy (HPLC-MS/MS) were used to quantify fungicide amounts in plant extracts. Distinct inhibition zones of mycelial growth of Phytophthora citrophthora were observed in bioassays when root, stem, or leaf extracts were added to filter paper disks on agar plates. Based on the two quantification methods, concentrations of both fungicides in the three tissue types and at all sampling times were above the mean effective concentration that provides 50% growth reduction values of the baseline sensitivities. Relative concentrations at the four sampling times sometimes varied between the two methods but, for both methods, concentrations of oxathiapiprolin were significantly higher in roots and leaves as compared with stems 10 days after treatment and statistically similar in the three tissues after 7 days. For mefenoxam, concentrations significantly increased in roots between 7 and 16 days after treatment and were significantly the highest in roots as compared with stems or leaves 16 days after treatment. Regressions of oxathiapiprolin and mefenoxam concentrations using HPLC-MS/MS on those calculated from bioassay standard curves indicated that the bioassays overestimated fungicide amounts in the extracts. The bioassay, however, can be considered an alternative option comparable with costly residue analyses in fungicide mobility studies in plants. Uptake of oxathiapiprolin at sufficient but low concentrations into plant roots provides an explanation for its long-lasting high activity in the management of Phytophthora root rot.


Subject(s)
Citrus , Phytophthora , Alanine/analogs & derivatives , Hydrocarbons, Fluorinated , Pyrazoles , Seedlings , Tandem Mass Spectrometry
8.
J Biol Chem ; 293(44): 17061-17069, 2018 11 02.
Article in English | MEDLINE | ID: mdl-30224356

ABSTRACT

The repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) is initiated by nucleolytic resection of the DNA break ends. The current model, being based primarily on genetic analyses in Saccharomyces cerevisiae and companion biochemical reconstitution studies, posits that end resection proceeds in two distinct stages. Specifically, the initiation of resection is mediated by the nuclease activity of the Mre11-Rad50-Xrs2 (MRX) complex in conjunction with its cofactor Sae2, and long-range resection is carried out by exonuclease 1 (Exo1) or the Sgs1-Top3-Rmi1-Dna2 ensemble. Using fully reconstituted systems, we show here that DNA with ends occluded by the DNA end-joining factor Ku70-Ku80 becomes a suitable substrate for long-range 5'-3' resection when a nick is introduced at a locale proximal to one of the Ku-bound DNA ends. We also show that Sgs1 can unwind duplex DNA harboring a nick, in a manner dependent on a species-specific interaction with the ssDNA-binding factor replication protein A (RPA). These biochemical systems and results will be valuable for guiding future endeavors directed at delineating the mechanistic intricacy of DNA end resection in eukaryotes.


Subject(s)
DNA Breaks, Double-Stranded , DNA Helicases/metabolism , DNA-Binding Proteins/metabolism , Exodeoxyribonucleases/metabolism , RecQ Helicases/metabolism , Replication Protein A/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/genetics , DNA Helicases/genetics , DNA Repair , DNA-Binding Proteins/genetics , Exodeoxyribonucleases/genetics , Homologous Recombination , RecQ Helicases/genetics , Replication Protein A/genetics , Saccharomyces cerevisiae/enzymology , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/genetics
9.
Cancer ; 125(2): 232-238, 2019 01 15.
Article in English | MEDLINE | ID: mdl-30561791

ABSTRACT

BACKGROUND: Patients treated for renal cell carcinoma (RCC) may be diagnosed with a metachronous, contralateral tumor. We evaluated the risks of contralateral tumor development using the Surveillance, Epidemiology, and End Results database. METHODS: Among RCC patients, we identified those with a metachronous, contralateral RCC diagnosed ≥1 year after primary diagnosis. We performed a competing risks analysis to evaluate associations between clinicopathologic factors and metachronous, bilateral RCC. Cumulative incidence and standardized incidence ratios (SIRs) were calculated. RESULTS: There were 80,403 cases of RCC identified, with a median follow-up of 8.3 years; of these, 1063 (1.3%) developed metachronous, contralateral RCC (median of 6 years after diagnosis). The cumulative incidence at 10, 20, and 30 years of follow-up was 1.5%, 3.1%, and 4.7%, respectively. An increased risk was observed among men (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.20-1.55), blacks (HR, 2.00; 95% CI, 1.71-2.33), and those with papillary histology (HR, 1.72; 95% CI, 1.41-2.10). Risk of metachronous disease decreased with increasing age at primary diagnosis (HR per 1-year increase, 0.97; 95% CI, 0.96-0.97). The SIRs were highest among those diagnosed at a younger age and remained elevated even after extended follow-up (>10 years). CONCLUSIONS: Our findings suggest that the cumulative incidence of metachronous, contralateral RCC may be higher than previously reported. Younger age, black race, papillary histology, and male sex increase the risk of metachronous, contralateral RCC development. The high SIRs seen in all demographic groups may support a rationale for lifelong surveillance, especially in high-risk subgroups with early disease onset.


Subject(s)
Carcinoma, Renal Cell/epidemiology , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/epidemiology , Kidney Neoplasms/pathology , Aged , Carcinoma, Renal Cell/surgery , Female , Humans , Incidence , Kidney Neoplasms/surgery , Male , Middle Aged , Neoplasm Recurrence, Local , Neoplasms, Second Primary/epidemiology , Risk Factors , SEER Program
10.
Dermatol Surg ; 45(9): 1125-1135, 2019 09.
Article in English | MEDLINE | ID: mdl-30829780

ABSTRACT

BACKGROUND: It remains controversial if Mohs surgery is superior to surgical excision in treating localized sebaceous carcinoma. OBJECTIVE: To compare Mohs surgery and surgical excision for treating patients with localized sebaceous carcinoma. MATERIALS AND METHODS: The US National Cancer Database was used to identify patients with histologically confirmed Stage 0 to 2 sebaceous carcinoma from 2004 to 2014. Clinicopathologic and socioeconomic factors were compared between treatment groups using the chi-square test. Overall survival (OS) was evaluated by log-rank test, multivariable Cox proportional hazard regression, and propensity score-matched analysis. Relative survival analyses compared with age- and sex-matched US population were performed. RESULTS: Of 1,265 patients, 234 received Mohs surgery and 1,031 received surgical excision. Mohs surgery had a higher rate of negative margin (p = .004). On multivariate Cox regression analysis, Mohs surgery was associated with longer OS than surgical excision (HR: 0.703, 95% CI: 0.496-0.995, p = .047). The survival benefit of Mohs surgery persisted on relative survival analysis and propensity score-matched analysis (p = .0385), after matching the 2 groups on patient and disease characteristics. CONCLUSION: Patients who received Mohs surgery had significantly longer OS when compared with those who received surgical excision. Prospective clinical trials comparing these treatment paradigms are warranted.


Subject(s)
Adenocarcinoma, Sebaceous/surgery , Dermatologic Surgical Procedures , Mohs Surgery , Sebaceous Gland Neoplasms/surgery , Adenocarcinoma, Sebaceous/pathology , Age of Onset , Aged , Aged, 80 and over , Female , Humans , Male , Margins of Excision , Middle Aged , Neoplasm Staging , Propensity Score , Proportional Hazards Models , Sebaceous Gland Neoplasms/pathology , Socioeconomic Factors
11.
Can J Urol ; 26(2): 9699-9707, 2019 04.
Article in English | MEDLINE | ID: mdl-31012833

ABSTRACT

INTRODUCTION: Approximately 7% of patients with localized upper tract urothelial cancer (UTUC) are treated without definitive therapy. Understanding outcomes and alternative therapy would aid in counseling older patients with comorbidities. MATERIALS AND METHODS: We utilized the National Cancer Database to identify patients with localized UTUC managed non-surgically between 2004 and 2013. Patient demographics, comorbidity, tumor grade, and chemotherapy and radiation utilization were recorded. Survival analyses were performed with the Kaplan-Meier method and a cox proportional hazard regression model. RESULTS: We identified 3157 (10.9%) patients with localized UTUC who did not receive definitive surgery. Median age was 79 years, 55% were males, 79% had government health insurance, and 68% had a Charlson-Deyo Score (CDS) of 0. Tumor grade was low (grade 1 or 2) in 632 (36.4%) and high (grade 3 or 4) in 1104 (63.6%). Median overall survival (OS) for the cohort was 2.2 years, significantly shorter for patients with greater comorbidities. Chemotherapy or radiation was performed in 294 (9.3%) and 197 (6.3%) patients respectively. There were no OS differences for individuals receiving chemotherapy. Of patients who received radiation therapy, the median OS was 1.4 versus 2.0 years, (p < 0.001) favoring no radiation. Those with high grade tumors had worse survival (1.9 versus 3.8 years (p < 0.001). Significant predictors of shorter OS included older age, male gender, higher CDS, and government insurance. CONCLUSIONS: In this population-based cohort, 10.9% of patients with localized UTUC were managed non-surgically. There was no OS advantage noted in cohorts receiving chemotherapy and radiation therapy. Median OS was significantly shorter for those with higher grade disease, increasing comorbidity profile, male gender, and those with government insurance status.


Subject(s)
Antineoplastic Agents/therapeutic use , Chronic Disease/epidemiology , Conservative Treatment , Kidney Neoplasms , Radiotherapy , Ureteral Neoplasms , Aged , Cohort Studies , Comorbidity , Conservative Treatment/methods , Conservative Treatment/statistics & numerical data , Female , Humans , Kaplan-Meier Estimate , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Kidney Neoplasms/therapy , Male , Neoplasm Grading , Neoplasm Staging , Radiotherapy/methods , Radiotherapy/statistics & numerical data , Risk Factors , Ureteral Neoplasms/mortality , Ureteral Neoplasms/pathology , Ureteral Neoplasms/therapy
12.
Br J Haematol ; 181(2): 196-204, 2018 04.
Article in English | MEDLINE | ID: mdl-29602182

ABSTRACT

Systemic anaplastic lymphoma kinase positive (ALK+) anaplastic large cell lymphoma with extranodal involvement (ALCL-E) is a rare form of non-Hodgkin lymphoma. No large study in the literature has compared the survival outcomes among different primary extranodal sites of involvement in ALK+ ALCL-E. We identified 1306 patients with ALK+ ALCL-E diagnosed between 2004 and 2014 in the US National Cancer Database, among whom 387 had primary extranodal site in the chest/abdomen/pelvis, 103 in the bone, 62 in the central nervous system, 134 in the head and neck and 620 in the cutaneous/soft tissue. Younger age, lower Charlson-Deyo score, lower clinical stage, receipt of chemotherapy and receipt of radiotherapy were predictors of longer overall survival. Patients with extranodal involvement of central nervous system and chest/abdomen/pelvis had shorter overall survival than those with involvement of head and neck, bone, and cutaneous/subcutaneous tissue after adjusting for confounding variables. We recommend treating these patients upfront with more aggressive therapy.


Subject(s)
Anaplastic Lymphoma Kinase , Databases, Factual , Adult , Age Factors , Aged , Disease-Free Survival , Female , Humans , Lymphoma, Large-Cell, Anaplastic/enzymology , Lymphoma, Large-Cell, Anaplastic/mortality , Lymphoma, Large-Cell, Anaplastic/pathology , Lymphoma, Large-Cell, Anaplastic/therapy , Male , Middle Aged , Organ Specificity , Survival Rate , United States/epidemiology
13.
Br J Haematol ; 181(6): 752-759, 2018 06.
Article in English | MEDLINE | ID: mdl-29676444

ABSTRACT

Primary cutaneous CD30+ T cell lymphoproliferative disorders (PCLPD), the second most common type of primary cutaneous T cell lymphomas, accounts for approximately 25-30% of cutaneous T-cell lymphoma cases. However, only small retrospective studies have been reported. We aimed to identify prognostic factors and evaluate the overall survival (OS) of patients with PCLPD stratified by ethnicity. We identified 1496 patients diagnosed with PCLPD between 2004 and 2014 in the US National Cancer Database. Chi-square test and anova were used to evaluate differences in demographic and disease characteristics, socioeconomic factors and treatments received. OS was evaluated with the log-rank test, Cox proportional hazard regression analysis, and propensity score matching. The study included 1267 Caucasians, 153 African Americans (AA), 43 Asians, and 33 of other/unknown ethnicity. Older age, higher Charlson-Deyo score, higher clinical stage and receipt of chemotherapy were predictors of shorter OS. Primary disease site on a lower extremity was associated with shorter OS, while a head and neck location was associated with longer OS. AA patients had shorter OS when compared to Caucasian patients on multivariate analysis. This ethnic disparity persisted on propensity-score matched analysis and after matching Caucasian and AA patients on demographic and disease characteristics, socioeconomic factors and treatments received, and age and gender-matched relative survival analyses.


Subject(s)
Databases, Factual , Head and Neck Neoplasms , Lymphoproliferative Disorders , Skin Neoplasms , Adult , Age Factors , Aged , Disease-Free Survival , Female , Follow-Up Studies , Head and Neck Neoplasms/ethnology , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/therapy , Humans , Ki-1 Antigen , Lymphoproliferative Disorders/ethnology , Lymphoproliferative Disorders/mortality , Lymphoproliferative Disorders/therapy , Male , Middle Aged , Neoplasm Proteins , Retrospective Studies , Sex Factors , Skin Neoplasms/ethnology , Skin Neoplasms/mortality , Skin Neoplasms/therapy , Socioeconomic Factors , Survival Rate , T-Lymphocytes , United States/epidemiology , United States/ethnology
14.
BJU Int ; 121(1): 124-129, 2018 01.
Article in English | MEDLINE | ID: mdl-28972702

ABSTRACT

OBJECTIVE: To investigate the outcomes of patients with upper tract urothelial carcinoma (UTUC) with non-definitive therapy, which currently remains unknown. PATIENTS AND METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify individuals with a localised, histologically confirmed kidney/renal pelvis and ureteric UC. Survival analysis using the Kaplan-Meier method was performed. A competing risk model evaluated the cumulative incidence and predictors of cancer-specific mortality (CSM). RESULTS: We identified 633 (7.6%) individuals who did not receive surgery. These individuals were significantly older (median age 81 vs 71 years, P < 0.001) than surgically managed patients. The median overall survival (OS) was significantly shorter compared to the surgical cohort (1.9 vs 7.8 years, P < 0.001). The 3-year disease-specific survival (DSS) for patients without surgery was significantly lower compared to those with surgery, at 73.7% vs 92.4%, respectively (P < 0.001). The 3-year DSS for patients with high-grade tumours was worse when compared to patients with low-grade tumours, at 65.1% vs 82.9%, respectively (P < 0.001). The 3-year cumulative CSM was 26.3%. On multivariable analysis, older age (hazard ratio [HR] 1.05, P < 0.001) and high tumour grade (HR 1.88, P < 0.001) were predictors of worse outcomes. CONCLUSIONS: In this population-based cohort, 7.6% of patients with UTUC were managed with a non-definitive approach. The median OS for the untreated cohort was significantly shorter compared to the surgical cohort (1.9 vs 7.8 years, respectively). These data may be helpful in counselling patients who are poor surgical candidates, as non-definitive therapy may provide reasonable oncological outcomes.


Subject(s)
Carcinoma, Transitional Cell/pathology , Carcinoma, Transitional Cell/therapy , Conservative Treatment/methods , Kidney Neoplasms/therapy , Ureteral Neoplasms/therapy , Age Factors , Aged , Aged, 80 and over , Carcinoma, Transitional Cell/mortality , Cohort Studies , Disease-Free Survival , Female , Geriatric Assessment/methods , Humans , Kaplan-Meier Estimate , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Male , Neoplasm Invasiveness/pathology , Neoplasm Staging , Patient Selection , Prognosis , Proportional Hazards Models , Risk Assessment , SEER Program , Survival Analysis , Treatment Outcome , United States , Ureteral Neoplasms/mortality , Ureteral Neoplasms/pathology
16.
Cancer ; 123(22): 4363-4371, 2017 Nov 15.
Article in English | MEDLINE | ID: mdl-28787086

ABSTRACT

BACKGROUND: Panel testing has been recently introduced to evaluate hereditary cancer; however, limited information is available regarding its use in kidney cancer. METHODS: The authors retrospectively reviewed test results and clinical data from patients who underwent targeted multigene panel testing of up to 19 genes associated with hereditary kidney cancer from 2013 to 2016. The frequency of positive (mutation/variant likely pathogenic), inconclusive (variant of unknown significance), and negative results was evaluated. A logistic regression analysis evaluated predictive factors for a positive test. RESULTS: Patients (n = 1235) had a median age at diagnosis of 46 years, which was significantly younger than the US population of individuals with kidney cancer (P < .0001). Overall, 6.1%, 75.5%, and 18.4% of individuals had positive, negative, and inconclusive results, respectively. The most commonly altered genes included folliculin (FLCN) and fumarate hydratase (FH), which were altered in 1.8% and 1.3% of patients, respectively. Tuberous Sclerosis Complex 2 (TSC2), mesenchymal epithelial transition factor proto-oncogene (MET), and PMS1 homolog 2 (PMS2) had the highest rates of variants of unknown significance, which were identified in 2.7%, 2.2%, and 1.7% of patients, respectively. Early age of onset was the only factor that was identified as predictive of a positive test on multivariate analysis (odds ratio, 0.975; P = .0052) and may be the only identifying characteristic of low-penetrant syndromes, such as those associated with MITF (melanogenesis-associated transcription factor) mutations, which do not have singular histology or a family history of kidney cancer. CONCLUSIONS: Panel tests may be particularly useful for patients who lack distinguishing clinical characteristics of known hereditary kidney cancer syndromes. The current results support the use of early age of onset for genetic counseling and/or testing. Cancer 2017;123:4363-71. © 2017 American Cancer Society.


Subject(s)
Early Detection of Cancer/methods , Early Detection of Cancer/trends , Genetic Testing/trends , Kidney Neoplasms/diagnosis , Neoplastic Syndromes, Hereditary/diagnosis , Transcriptome , Adult , DNA Mutational Analysis/methods , Female , Genetic Predisposition to Disease , Humans , Kidney Neoplasms/genetics , Male , Middle Aged , Neoplastic Syndromes, Hereditary/genetics , Proto-Oncogene Mas , Proto-Oncogene Proteins/genetics , Retrospective Studies , Tumor Suppressor Proteins/genetics
17.
Nephrol Dial Transplant ; 32(10): 1767-1773, 2017 Oct 01.
Article in English | MEDLINE | ID: mdl-28967967

ABSTRACT

BACKGROUND: For potential transplant recipients with a prior history of renal malignancy, no evidence-based recommendations currently exist with regard to waiting duration on dialysis. We aim to improve decision making by evaluating the impact of waiting duration on the outcomes of kidney cancer patients awaiting renal transplantation. METHODS: The United States Renal Data System was used to identify patients with a known cause of end-stage renal disease (ESRD) from 1983 to 2007. Evaluation of overall survival (OS) was performed with Kaplan-Meier estimates and Cox proportional hazards models. Fine-Gray competing risk models were used to assess cancer-specific mortality (CSM) and non-cancer-specific mortality (NCSM). RESULTS: Of 1 374 175 patients with ESRD, 228 984 (16.7%) received transplantation. Transplant recipients with renal malignancy-associated ESRD (RM-ESRD) had longer waiting durations than those with other known causes of ESRD (2.4 versus 1.3 years; P < 0.0001). RM-ESRD patients who had shorter waiting durations (0-2 years) had better OS than those who waited longer (2+ years) (10-year OS 69.0 versus 46.7%, respectively; P < 0.0001), with similar CSM (10-year CSM 10.3 versus 10.2%, respectively; P = 0.883), whereas NCSM was worse for those with longer waiting durations (10-year NCSM 20.7 versus 44.3%, respectively; P < 0.0001). On Cox modeling, the status of RM-ESRD was not a significant predictor (P = 0.07), while longer waiting duration remained significant (P < 0.0001). CONCLUSION: We found that CSM was not affected by waiting duration, while NCSM significantly improved with shorter wait times. These findings suggest that the OS of potential transplant recipients with RM-ESRD may be improved by reducing waiting duration.


Subject(s)
Kidney Neoplasms/mortality , Kidney Transplantation , Renal Dialysis/mortality , Waiting Lists/mortality , Adult , Aged , Female , Humans , Kidney Neoplasms/physiopathology , Male , Middle Aged , Survival Rate , Time Factors , Time-to-Treatment , Transplant Recipients , United States
18.
Pediatr Blood Cancer ; 64(5)2017 05.
Article in English | MEDLINE | ID: mdl-27805307

ABSTRACT

PURPOSE: Renal cell carcinoma (RCC) represents a small proportion of renal malignancies early in life. Distinguishing RCC from other malignancies is important as treatment strategies may differ. We analyze the Surveillance Epidemiology, and End Results (SEER) database to identify predictive factors of RCC in the pediatric population with renal tumors. METHODS: We queried SEER to identify patients from ages 0 to 19 diagnosed with a renal malignancy between 1973 and 2013. Cases were sorted using histology and site codes. Age-adjusted standardized incidence rates (SIR) were calculated. We compared differences in characteristics between cancer types. A logistic regression model and a nomogram were created to identify predictors of RCC. RESULTS: A total of 3,670 patients were identified, of which 281 (7.7%) were diagnosed with RCC. The SIR of RCC increased with age. After age 12, RCC was found in >50% of all newly diagnosed cases. On multivariate analysis, RCC was associated with smaller tumor size (P < 0.001), increasing age (P < 0.001), black race (P < 0.001), and localized stage (P < 0.001). The nomogram predicted RCC pathology with a concordance index of 0.965. CONCLUSIONS: RCC in childhood and adolescence is relatively uncommon; however, it accounts for >50% of renal malignancies after age 12. For every year of increasing age, the odds of having an RCC diagnosis are increased by 50%. The odds of a renal tumor being RCC are increased in black children, those with localized disease, and those with smaller tumors. In these specific populations, RCC should be favored in the differential diagnosis of the renal mass.


Subject(s)
Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/therapy , Kidney Neoplasms/diagnosis , Kidney Neoplasms/therapy , Organ Sparing Treatments/methods , Adolescent , Adult , Carcinoma, Renal Cell/pathology , Child , Child, Preschool , Female , Humans , Incidence , Infant , Kidney Neoplasms/pathology , Male , Multivariate Analysis , SEER Program/statistics & numerical data , Young Adult
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