Correlation of the Ki67 Working Group prognostic risk categories with the Oncotype DX Recurrence Score in early breast cancer.

BACKGROUND: The relationship between Ki67 assessed by immunohistochemistry (IHC) and the Oncotype DX Recurrence Score (RS) is unclear. The objective of this study was to determine the correlation between the 21-gene RS and IHC-measured Ki67 with the prognostic classification groups recommended by the International Ki67 Working Group (IKWG). METHODS: The authors performed a retrospective chart review of women who had hormone receptor (HR)-positive, human epidermal growth factor receptor 2-negative early breast cancer with zero to three positive lymph nodes and both Ki67 and the 21-gene RS performed at their institution from 2013 to 2021. Patients were categorized into low (≤5%), intermediate (6%-29%), and high Ki67 groups (≥30%) according to IKWG recommendations. Overall agreement and risk-stratified agreement between Ki67 and RS were assessed with the proportion of agreement and the κ statistic. RESULTS: The study included 525 patients with HR-positive breast cancer. Among the 49% of patients with intermediate Ki67 values of 6%-29%, the distribution of low (0-10), intermediate (11-25), and high RS (26-100) was 19%, 66%, and 15%, respectively. There was slight agreement (κ = 0.01-0.20) between Ki67 and RS (κ = 0.027) in the overall population, although this was not significant (p = .1985). There was fair agreement (κ = 0.21-0.40) between high Ki67 and RS values (κ = 0.280; p < .0001). A higher progesterone receptor percentage was associated with lower RS values (p > .0001) but not lower Ki67 values. A positive nodal status and a larger tumor size were associated with higher Ki67 values (p = .0059 and p < .0001) but not with RS. CONCLUSIONS: In this group of patients selected to have a 21-gene RS, there was no significant correlation between Ki67 and RS in the overall population, and there was fair agreement between high Ki67 and high RS values. LAY SUMMARY: In patients with early-stage, hormone receptor-positive breast cancer, decisions on adjuvant chemotherapy are based on certain biological features of the cancer and genomic assays such as the Oncotype DX Recurrence Score (RS). The goal of this study was to determine the correlation between Ki67, a marker of proliferation, and the Oncotype DX RS, a 21-gene assay demonstrated to be predictive of an adjuvant chemotherapy benefit in patients with early-stage breast cancer. In 525 patients, the authors did not find a significant correlation between Ki67 and RS.

Filanesib plus bortezomib and dexamethasone in relapsed/refractory t(11;14) and 1q21 gain multiple myeloma.

Filanesib is a first-in-class kinesin spindle protein inhibitor which demonstrated safety and encouraging activity in combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma in a preliminary analysis of dose-escalation phase results. This multicenter study included first a dose-escalation phase to determine maximum tolerated dose of two schedules of filanesib, bortezomib, and dexamethasone and a subsequent dose-expansion phase using the maximum tolerated doses. In the dose-expansion phase, 28 patients were evaluable for safety and efficacy. The most common grade ≥3 adverse events were neutropenia (21%) and anemia (18%), which were noncumulative and reversible, and hypertension (18%). The overall response rate was 43% with median duration of response not yet reached (range, 2.8-23.7+ months) with median follow-up of 6.3 months. A post hoc analysis incorporated 29 dose-escalation phase patients who received therapeutic filanesib doses, with an overall response rate of 39% and median duration of response of 18.0 months among the 57 total patients with median progression-free survival of 8.5 months. Notably, the PFS of high risk patients was comparable at 8.5 months, driven by the patients with 1q21 gain, characterized by increased MCL-1 expression, with a PFS of 9.1 months versus 3.5 months for the remainder of high risk patients. Patients with t(11;14) also had an encouraging PFS of 15.0 months. The combination of filanesib, bortezomib, and dexamethasone continues to show safety and encouraging activity in relapsed/refractory multiple myeloma, particularly in those patients with 1q21 gain and t(11;14).

Use of Paracervical Block Before Laparoscopic Supracervical Hysterectomy.

BACKGROUND AND OBJECTIVE: Some patients who undergo laparoscopic hysterectomy request overnight admission for pain management, thus increasing costs for a surgery that is safe for same-day discharge. We wanted to evaluate whether a paracervical block of bupivacaine with epinephrine before laparoscopic supracervical hysterectomy would decrease overnight admission rates, postoperative pain, and pain medication requirement. METHODS: This was a randomized, double-blind, placebo-controlled, parallel-group trial (Canadian Task Force classification I) at an academic medical center. Patients undergoing laparoscopic supracervical hysterectomy were randomized to a 20-mL paracervical injection of either 0.25% bupivacaine with epinephrine or 20 mL normal saline before skin incision. All providers, except the circulating nurse, were blinded. The primary outcome was overnight hospital admission rate. Secondary outcomes included postoperative pain medication use and pain scores. Analysis included t test, χ2, Wilcoxon, and ANOVA. RESULTS: One hundred thirty-two patients were enrolled-68 in the treatment group and 64 in the placebo group. Demographics were similar between groups. The unplanned overnight admission rate was 34% for the treatment group and 27% for the placebo group (P = .25). After discharge, the treatment group used on average 8.5 tablets of narcotics, whereas the placebo group used 11.7 tablets (P = .07). The treatment group took 13.1 tablets of nonnarcotic analgesics compared to 11.2 in the placebo group (P = .57). Both groups reported similar pain scores. CONCLUSION: Paracervical block with bupivacaine and epinephrine before laparoscopic supracervical hysterectomy did not decrease overnight admission rate or affect postoperative pain. Postoperative opiate use was minimally decreased.

The impact of radiation treatment planning technique on unplanned hospital admissions.

PURPOSE: Treatment burdens and toxicities related to palliative radiation therapy (RT) may lead to unplanned hospital admissions (UHAs). The likelihood for these toxicities may be related to treatment technique. We compared rates of UHA between patients receiving nonconformal (2-dimensional) and conformal (3-dimensional or higher) radiation treatments to bone metastases involving the vertebral column. METHODS AND MATERIALS: We retrospectively analyzed patients treated with RT for bone metastases at a single tertiary care center between 2010 and 2017. We compared rates of RT-related UHA within 90 days of receiving radiation using Cox competing risk regression models. RESULTS: We identified 326 patients with bone metastases involving the vertebral column, 139 of whom received radiation by nonconformal technique and 187 by conformal technique. On multivariable analysis, conformal techniques were associated with a reduced risk of 90-day UHA (hazard ratio [HR]: 0.35; 95% confidence interval [CI], 0.14-0.88). Other significant factors include hematologic cancer (HR: 0.17; 95% CI, 0.03-0.82) and baseline Eastern Cooperative Oncology Group score ≥2 (HR: 3.02; 95% CI, 1.05-8.69). CONCLUSIONS: The utilization of conformal (non-2-dimensional) radiation treatment plans may help reduce treatment-related toxicities and consequently UHAs after palliation of bone metastases.

Neurologic injury and patient displacement in gynecologic laparoscopic surgery using a beanbag and shoulder supports.

OBJECTIVE: To quantify the incidence of peripheral neuropathy in gynecologic laparoscopic surgery using a combination of beanbag, eggcrate foam, and shoulder supports; and to assess patient displacement during surgery in a steep Trendelenburg position and determine variables correlated with displacement. METHODS: A retrospective study included all gynecologic laparoscopic surgeries performed by one high-volume surgeon at a US center between September 15, 2007, and September 15, 2012. Data included neurologic deficits or extremity pain, any other complications, and-for the final study year-surgical time as well as patient and beanbag displacement. RESULTS: Among 967 patients, no long-term neuropathy was reported, 6 (0.6%) patients had transient shoulder pain beyond the first 24 hours (resolved by initial postoperative visit), and 7 (0.7%) were lost to follow-up. No neurologic complications were reported. Median beanbag and total patient displacement were 0 cm (interquartile range 0-0) and 0 cm (interquartile range 0-2), respectively. Patient displacement relative to the table was correlated with the total surgical time (P=0.025) and patient weight (P=0.023). The median displacement was greater in hysterectomy than non-hysterectomy procedures (P=0.003). CONCLUSION: Use of beanbags with shoulder supports and convoluted foam armboard pads was associated with minimal patient displacement and risk of arm and leg neurologic injury.

Ten Essential Practices for Developing or Reforming a Biostatistics Core for a NCI Designated Cancer Center.

There are 69 National Cancer Institute (NCI) designated Cancer Centers (CCs) in the United States. Biostatistical collaboration is pivotal in cancer research, and support for a cancer biostatistics shared resource facility (C-BSRF) is included in the award. Although the services and staff needed in a C-BSRF have been outlined in general terms and best practices for biostatistical consultations and collaboration in an academic health center have been agreed upon, implementing these practices in the demanding setting of cancer centers interested in pursuing or maintaining NCI designation remains challenging. We surveyed all C-BSRF websites to assess their organizational charts, governance, size, services provided, and financial models and have identified 10 essential practices for the development of a successful C-BSRF. Here, we share our success with, and barriers to, implementation of these practices. Showcasing development plans for these essential practices resulted in an NCI score of "Excellent to Outstanding" for our C-BSRF in 2015, and performance metrics in 2016-2017 demonstrated notable improvement since our original Cancer Center Support Grant (CCSG) application in 2014. We believe that the essential practices described here can be adapted and adjusted, as needed, for CCs of various sizes and with different types of cancer research programs.

Safety, feasibility and learning curve of robotic single-site surgery in gynecology.

BACKGROUND: Robotic single-site (RSS) surgery has emerged as a novel minimally invasive approach in gynecology. METHODS: Retrospective cohort study of consecutive RSS gynecologic procedures undertaken between October 2013 and March 2014. RESULTS: The 25 RSS completed cases consisted of 11 adnexal and 14 hysterectomy cases of which three included pelvic lymphadenectomies. Mean age, body mass index and estimated blood loss were 51 years, 25 kg/m(2) , 30 mL in the adnexal group, respectively, and 58 years, 27 kg/m(2) , 96 mL in the hysterectomy group, respectively. Mean console time was 20 and 45 min and mean total operative time was 56 and 93 min in adnexal and hysterectomy cases, respectively. The CUSUM method identified two learning phases with significant reduction in console time after the 7th adnexal case and the 5th hysterectomy. CONCLUSION: When performed by advanced minimally invasive surgeons and in appropriately selected patients, RSS surgery is feasible and safe. Copyright © 2015 John Wiley & Sons, Ltd.

Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle-invasive bladder cancer.

BACKGROUND: Gemcitabine plus cisplatin (GC) has been adopted as a neoadjuvant regimen for muscle-invasive bladder cancer despite the lack of Level I evidence in this setting. METHODS: Data were collected using an electronic data-capture platform from 28 international centers. Eligible patients had clinical T-classification 2 (cT2) through cT4aN0M0 urothelial cancer of the bladder and received neoadjuvant GC or methotrexate, vinblastine, doxorubicin, plus cisplatin (MVAC) before undergoing cystectomy. Logistic regression was used to compute propensity scores as the predicted probabilities of patients being assigned to MVAC versus GC given their baseline characteristics. These propensity scores were then included in a new logistic regression model to estimate an adjusted odds ratio comparing the odds of attaining a pathologic complete response (pCR) between patients who received MVAC and those who received GC. RESULTS: In total, 212 patients (146 patients in the GC cohort and 66 patients in the MVAC cohort) met criteria for inclusion in the analysis. The majority of patients in the MVAC cohort (77%) received dose-dense MVAC. The median age of patients was 63 years, they were predominantly men (74%), and they received a median of 3 cycles of neoadjuvant chemotherapy. The pCR rate was 29% in the MVAC cohort and 31% in the GC cohort. There was no significant difference in the pCR rate when adjusted for propensity scores between the 2 regimens (odds ratio, 0.91; 95% confidence interval, 0.48-1.72; P = .77). In an exploratory analysis evaluating survival, the hazard ratio comparing hazard rates for MVAC versus GC adjusted for propensity scores was not statistically significant (hazard ratio, 0.78; 95% confidence interval, 0.40-1.54; P = .48). CONCLUSIONS: Patients who received neoadjuvant GC and MVAC achieved comparable pCR rates in the current analysis, providing evidence to support what has become routine practice.

Randomized controlled double-blind trial of transversus abdominis plane block versus trocar site infiltration in gynecologic laparoscopy.

OBJECTIVE: The objective of the study was to determine whether transversus abdominis plane (TAP) block reduces postoperative pain when compared with trocar site infiltration of bupivacaine in gynecological laparoscopy. STUDY DESIGN: This was a prospective, randomized, double-blinded clinical trial using patients as their own controls. Women undergoing gynecologic laparoscopy using a 4-port symmetrical technique were randomly assigned to right- or left-sided TAP block using 30 mL of 0.25% bupivacaine with epinephrine. Two cohorts of patients were studied. Cohort 1 consisted of anesthesiologist-administered ultrasound-guided TAP block. Cohort 2 consisted of surgeon-administered laparoscopic-guided TAP block. In both cohorts, contralateral port sites were infiltrated with an equal amount of bupivacaine in divided doses. All patients received intraoperative acetaminophen and ketorolac. Postoperative abdominal pain was assessed at 1, 2, 4, 6, 8, 12, 18, 24, and 48 hours on the block and contralateral sides, before and after palpation, using the 10 point visual analog scale. A 2 point difference in the reported pain scores was considered clinically meaningful. RESULTS: Eighty-eight patients were eligible for statistical analysis: 45 and 43 patients in cohorts 1 and 2, respectively. In both cohorts, most patients reported equal pain on the block side and local side. In cohort 1, there was a statistically significant difference in mean reported pain scores at 2 hours and across time favoring the ultrasound-guided block; however, this did not reach clinical significance. There was no statistically significant difference found at all other time points or when pain scores were objectively assessed after palpation of the incisions. When comparing laparoscopic-guided block with local infiltration, there was no statistically significant difference in reported mean pain scores at all time points or after palpation. CONCLUSION: As part of this multimodal analgesic regimen, neither block method provided a significant clinical benefit compared with trocar site bupivacaine infiltration.

Predictive value of combined serum biomarkers for adverse pregnancy outcomes.

OBJECTIVE: To determine if a combination of first and second trimester serum biomarkers (pregnancy-associated plasma protein A (PAPP-A), free ßhCG, and maternal serum alpha-fetoprotein (msAFP)) may be utilized to develop a predictive model for adverse pregnancy outcomes. STUDY DESIGN: We conducted a retrospective analysis including all women who delivered at our institution between 2007 and 2010. We estimated the area under the ROC curve (AUC) to compare predictive abilities of PAPP-A, free ßhCG, and msAFP singularly, and in combination for adverse pregnancy outcomes. We sought to predict the risks of preeclampsia, preterm delivery (PTD, <37 weeks gestational age) and low birth weight (LBW, <2500g). Using logistic regression analysis, we created models that controlled for maternal age, race, parity, body mass index, and histories of chronic hypertension and tobacco use. RESULTS: The final sample included 2199 women. Determining the AUC and optimal cutoff probability values for each of the biomarkers, we found that for PTD and LBW, the combination of all three biomarkers was most predictive, while for preeclampsia the combination of msAFP and PAPP-A was most predictive. The AUC of the three biomarker combination to detect adverse pregnancy outcomes are as follows: LBW 67%, PTD 72%, and preeclampsia 77%. We created race-specific logistic regression models to predict the risk probabilities. To illustrate, the predictive probability for a 33-year-old African American, nullipara with a BMI of 50, chronic hypertension, tobacco use, PAPP-A 0.3, msAFP 2.0 and free ßhCG 0.98 MOMs are: PTD 59%, LBW 61% and Preeclampsia 91%. CONCLUSION: The combination of biomarkers currently utilized in Down syndrome screening may also be used to predict additional adverse pregnancy outcomes. Further studies are needed to determine optimal maternal and fetal surveillance, if and when increased risks are identified.

Blastulation rates decline in a linear fashion from euploid to aneuploid embryos with single versus multiple chromosomal errors.

OBJECTIVE: To test the hypothesis that the blastulation rate is higher in euploid embryos than in aneuploid embryos as assessed by cleavage-stage biopsy with array-comprehensive genomic hybridization (aCGH). DESIGN: Retrospective cohort study. SETTING: University-affiliated institution. PATIENT(S): Forty-one patients with 48 in vitro fertilization (IVF) cycles and 385 embryos that underwent cleavage-stage preimplantation genetic screening (PGS) with aCGH at the Continuum Reproductive Center between January 2010 and September 2013. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Probability of blastocyst and/or fully expanded or hatching blastocyst (FEHB) progression depending on number of chromosomal abnormalities. RESULT(S): Euploid embryos are twice as likely to progress to blastocyst and three times as likely to progress to FEHB than aneuploid embryos: 76% versus 37% and 56% versus 18%, respectively. For every additional chromosomal abnormality, the likelihood of progressing to the blastocyst stage decreases by 22% and the likelihood of progressing to FEHB decreases by 33%. CONCLUSION(S): Euploid embryos are far more likely than aneuploid embryos to progress to the blastocyst and FEHB stages. There is a linear decrease in probability of blastulation with the increasing number of chromosomal abnormalities.

Long-term outcome of ablation of anal high-grade squamous intraepithelial lesions: recurrence and incidence of cancer.

BACKGROUND: High-grade dysplasia is the anal carcinoma precursor. Clinicians ablate high-grade dysplasia with laser, electrocautery, and infrared coagulation to prevent cancer. OBJECTIVE: The aim of this study was to determine the long-term effectiveness of high-grade dysplasia ablation and the incidence of cancer. DESIGN: This study is a retrospective chart review of patients who were treated for high-grade dysplasia from February 1998 until May 2012. SETTING: This study was conducted in a surgical practice screening patients for anal cancer and high-grade dysplasia. PATIENTS: The patients identified were HIV-positive and -negative men who have sex with men. INTERVENTION: The ablation of high-grade dysplasia was performed. MAIN OUTCOME MEASURES: The primary outcomes measured were the probability of high-grade dysplasia recurrence postablation and the incidence of cancer. RESULTS: Four hundred fifty-six HIV-positive men who have sex with men (mean age, 45 ± 9 years) and 271 HIV-negative men who have sex with men (mean age, 41 ± 11 years) followed for a median of 2.2 (range, 0.2-13) years underwent high-grade dysplasia ablation by laser, infrared coagulation, and/or electrocautery. Median time to recurrence was 6.8 and 6.9 months for HIV-positive and -negative patients. Kaplan-Meier curves predict a rate of recurrence 1 year after the first ablation for HIV-positive and -negative patients of 53% (95% CI, 49%-58%) and 49% (95% CI, 43%-55%). At 2 and 3 years, the rate of recurrence was 68% (95% CI, 63%-73%) and 77% (95% CI, 7%2-82%) for HIV-positive patients and 57% (95% CI, 51%-64%) and 66% (95% CI, 59%-73%) for HIV-negative patients. The median number of recurrent lesions was ≤2 for HIV-positive patients and ≤1 for HIV-negative patients. Recurrence increased with HIV infection (HR, 1.3; 95% CI, 1.1-1.6) and each additional lesion treated (HR 1.6, 95% CI, 1.1-1.2). Five HIV-positive men who have sex with men developed cancer. The Kaplan-Meier probability of cancer 3 years postablation was 1.97% (95% CI, 0.73%-5.2%). LIMITATIONS: This is a retrospective study by 1 surgeon who has extensive experience treating anal dysplasia. There was no pathology review, and the type of recurrence cannot be definitively determined because the location could be inaccurate. CONCLUSIONS: Patients undergoing ablation of intra-anal high-grade dysplasia have high recurrence, but the probability of developing anal cancer is low. HIV infection and increased number of high-grade dysplasias increases the risk of recurrence.

Preimplantation genetic screening (PGS) with Comparative genomic hybridization (CGH) following day 3 single cell blastomere biopsy markedly improves IVF outcomes while lowering multiple pregnancies and miscarriages.

PURPOSE: To determine benefits of cleavage-stage preimplantation genetic screening (PGS) by array comparative genomic hybridization (CGH). METHODS: A retrospective case-control study was performed at a tertiary care university-affiliated medical center. Implantation rate was looked at as a primary outcome. Secondary outcomes included clinical and ongoing pregnancy rates, as well as multiple pregnancy and miscarriage rates. Thirty five patients underwent 39 fresh cycles with PGS by aCGH and 311 similar patients underwent 394 invitro fertilization cycles. RESULT(S): The implantation rate in the CGH group doubled when compared to the control group (52.63 % vs. 19.15 %, p = < 0.001), clinical pregnancy rate was higher (69.23 % vs. 43.91 %, p = 0.0002), ongoing pregnancy rate almost doubled (61.54 % vs. 32.49 %, p = < 0.0001), multiple pregnancy rate decreased (8.33 % vs. 34.38 %, p = 0.0082) and miscarriage rate trended lower (11.11 % vs. 26.01 %, p = 0.13). CONCLUSION: Cleavage stage PGS with CGH is a feasible and safe option for aneuploidy screening that shows excellent outcomes when used in fresh cycles. This is the first report of cleavage stage PGS by CGH showing improved ongoing pregnancy rates.

Prospective cohort study of the circadian rhythm pattern in allogeneic sibling donors undergoing standard granulocyte colony-stimulating factor mobilization.

INTRODUCTION: Prior in vivo murine studies suggest circadian oscillations for hematopoietic stem cell release, which are maintained following administration of granulocyte colony-stimulating factor (G-CSF) or plerixafor. Furthermore, retrospective data analysis of healthy donors who underwent G-CSF-induced mobilization demonstrated significantly increased CD34(+) cell yields when collected in the afternoon compared with the morning. METHODS: A prospective study was conducted to directly examine the number of peripheral blood CD34(+) and CD34(+)CD38- progenitor/stem cells at baseline and then every 6 hours for 24 hours on days 4 to 5 of G-CSF (10 µg/kg/day in the morning) mobilization in 11 allogeneic donors. Data were analyzed using mixed-model analysis of repeated measures. RESULTS: Whereas we observed a significant increase in CD34(+) cell counts toward the evening, counts were then sustained on the morning of day 5. The correlation between CD34(+)CD38- cell counts and the less defined CD34(+) populations was weak. CONCLUSIONS: Our results suggest that the pharmacodynamic activity and timing of G-CSF may alter endogenous progenitor rhythms. Donor age, medical history, and medications may also impact circadian rhythm. Further studies should examine the circadian rhythm at the peak of G-CSF mobilization and should consider potential confounders such as the time of G-CSF administration and the age of the subjects.

Trends and variations in utilization of nephron-sparing procedures for stage I kidney cancer in the United States.

PURPOSE: The incidental detection of early-stage kidney tumors is increasing in the United States. Nephron-sparing approaches (NS) to managing these tumors are equivalent to radical nephrectomy (RN) in oncologic outcomes and have a decreased impact on renal function. Our objective was to evaluate trends in the use of NS over the past decade and the socioeconomic factors associated with its use. METHODS: The National Cancer Database was queried to identify patients with stage I kidney cancer between 2000 and 2008. Patients were classified by the type of surgery as NS (local destruction and local excision) or RN. Patients were further categorized by age, race, insurance status, and income. Log-binomial regression was used to estimate prevalence ratios (PR) for the proportion of NS to RN according to demographic and socioeconomic characteristics. RESULTS: From 2000 to 2008, there were 142,194 cases of kidney cancer reported to the NCDB. In these cases, 43,034 (30.3 %) patients had NS, and 86,431 (60.78 %) patients had RN. The prevalence of NS increased 10 % per year (PR = 1.10, p < 0.0001)-from 20.0 % in 2000 to 45.1 % in 2008. Older age, lower income, Black race, Hispanic ethnicity, and lack of health insurance were associated with a decreased prevalence of NS. CONCLUSIONS: NS as a treatment for stage I kidney cancer has increased steadily since 2000. Age, racial, and socioeconomic differences may exist in the utilization of NS. Additional analyses, with patient level data, are required to address the independent significance of these variables in an effort to develop strategies to mitigate these potential disparities.

Cytoreductive nephrectomy for metastatic renal cell carcinoma in the era of targeted therapy in the United States: a SEER analysis.

PURPOSE: Two randomized trials published in 2001 provided level 1 evidence for the use of cytoreductive nephrectomy (CyNx) for the treatment of metastatic renal cell carcinoma (mRCC). However, the regulatory approval of vascular endothelial growth factor tyrosine kinase inhibitors (VEGFR-TKI) in 2005 has left an "evidence void" regarding the use of CyNx. We evaluated the patterns in the use of CyNx in the cytokine and VEGFR-TKI eras, and the patient characteristics associated with the use of CyNx. METHODS: The Surveillance, Epidemiology, and End Results registry was used to identify patients with histologically or cytologically confirmed stage IV RCC between 2001 and 2008. Patients were classified as treated during the cytokine (2001-2005) or VEGFR-TKI (2006-2008) eras. A multivariate logistic regression analysis was performed to calculate the odds of undergoing CyNx according to treatment era and socioeconomic characteristics. RESULTS: Overall, 1,112 of 2,448 patients (45%) underwent CyNx. CyNx use remained stable between 2001 and 2005 (50%), but decreased to 38% in 2008. Logistic regression analysis revealed that older age (OR 0.82, 95% CI: 0.68, 0.99), black race (OR 0.64, 95% CI: 0.46, 0.91), Hispanic ethnicity (OR 0.71, 95% CI: 0.54, 0.93), and treatment in the VEGFR-TKI era (OR 0.82, 95% CI: 0.68, 0.99) were independently associated with decreased use of CyNx. CONCLUSIONS: Use of CyNx in the United States has declined in the VEGFR-TKI era. Older patients and minorities are less likely to receive CyNx. Results of ongoing phase III trials are needed to refine the role of this treatment modality.

Prevalence and characteristics of patients with metastatic cancer who receive no anticancer therapy.

BACKGROUND: A subset of patients who present with metastatic solid tumors never receive anticancer therapy. Reasons may include poor functional status, comorbidities, and patient preference. To the authors' knowledge, the prevalence and characteristics of this population have not previously been described. METHODS: The National Cancer Data Base was queried for patients diagnosed with metastatic (stage IV according to the American Joint Committee on Cancer) solid tumors (including those of the breast, cervix, colon, and kidney; small cell and nonsmall cell lung cancer [NSCLC]; and tumors of the prostate, rectum, and uterus) who received neither radiotherapy nor systemic therapy. Log-binomial regression analysis was used to estimate prevalence ratios (PRs) for the percentage of untreated to treated patients with stage IV cancer. RESULTS: Between 2000 and 2008, 773,233 patients with stage IV cancer were identified, 159,284 of whom (20.6%; 95% confidence interval, 20.5%-20.7%) received no anticancer therapy. Patients with NSCLC accounted for 55% of the untreated population. Patients with cancers of the kidney and lung had the highest rates of no treatment at 25.5% and 24.0%, respectively, whereas patients with prostate cancer had the lowest rate of no treatment at 11.1%. Across all cancer types, older age (PR range, 1.37-1.49; all P < .001), black race (PR range, 1.05-1.32; all P < .001), lack of medical insurance (PR range, 1.47-2.46; all P < .001), and lower income (except for cancer of the uterus; PR range, 0.91-0.98 for every $10,000-increase in income [all P < .001]) were associated with a lack of treatment. CONCLUSIONS: Approximately 20% of patients who present with stage IV solid tumors do not receive anticancer therapy. Although there are likely multiple reasons for this lack of treatment, including appropriate indications, these findings have potential implications with regard to health care policy and access to care.

Trends in the use of cytoreductive nephrectomy in the United States.

BACKGROUND: Two randomized trials published in 2001 established CyNx for patients with metastatic renal carcinoma (mRCC) as a treatment standard in the cytokine era. However, first-line systemic therapy for mRCC changed in 2005 with FDA approval of VEGFR TKIs. We evaluated the patterns of use of CyNx from 2000 to 2008. MATERIALS AND METHODS: The National Cancer Database was queried for patients diagnosed with mRCC. Patients who underwent CyNx were identified and were further categorized by pre-VEGFR versus VEGFR TKI era, race, insurance status, and hospital. For these subcategories, prevalence ratios (PRs) were generated using the proportion of patients with mRCC undergoing CyNx versus those not undergoing CyNx. RESULTS: Of the 47,417 patients (pts) identified with mRCC, the prevalence of cytoreductive nephrectomy increased 3% each year from 2000 to 2005 (P < .0001), then decreased 3% each year from 2005 to 2008 (P = .0048), with a significant difference between the eras (0.97 vs. 1.025; P < .0001). Black and Hispanic pts were less likely than Caucasian pts to undergo CyNx. Pts with Medicaid, Medicare, and no insurance were less likely than pts with private insurance to undergo CyNx. Pts diagnosed at community hospitals were significantly less likely than pts at teaching hospitals to undergo CyNx. CONCLUSION: The use of CyNx has declined in the VEGFR-TKI era. In addition, racial and socioeconomic disparities exist in the use of CyNx. The results of pending randomized trials evaluating the role of CyNx in the VEGFR-TKI era are awaited to optimize use of this modality and address potential disparities.

Morbidity and mortality in common variable immune deficiency over 4 decades.

The demographics, immunologic parameters, medical complications, and mortality statistics from 473 subjects with common variable immune deficiency followed over 4 decades in New York were analyzed. Median immunoglobulin levels were IgG, 246 mg/dL; IgA, 8 mg/dL; and IgM, 21 mg/dL; 22.6% had an IgG less than 100 mg/dL. Males were diagnosed earlier (median age, 30 years) than females (median age, 33.5 years; P = .004). Ninety-four percent of patients had a history of infections; 68% also had noninfectious complications: hematologic or organ-specific autoimmunity, 28.6%; chronic lung disease, 28.5%; bronchiectasis, 11.2%; gastrointestinal inflammatory disease, 15.4%; malabsorption, 5.9%; granulomatous disease, 9.7%; liver diseases and hepatitis, 9.1%; lymphoma, 8.2%; or other cancers, 7.0%. Females had higher baseline serum IgM (P = .009) and were more likely to develop lymphoma (P = .04); 19.6% of patients died, a significantly shorter survival than age- and sex-matched population controls (P < .0001). Reduced survival was associated with age at diagnosis, lower baseline IgG, higher IgM, and fewer peripheral B cells. The risk of death was 11 times higher for patients with noninfectious complications (hazard ratio = 10.95; P < .0001). Mortality was associated with lymphoma, any form of hepatitis, functional or structural lung impairment, and gastrointestinal disease with or without malabsorption, but not with bronchiectasis, autoimmunity, other cancers, granulomatous disease, or previous splenectomy.