Sinae Kim

Reduction in Tumor Volume by Cone Beam Computed Tomography Predicts Overall Survival in Non-Small Cell Lung Cancer Treated With Chemoradiation Therapy

PURPOSE We sought to evaluate whether tumor response using cone beam computed tomography (CBCT) performed as part of the routine care during chemoradiation therapy (CRT) could forecast the outcome of unresectable, locally advanced, non-small cell lung cancer (NSCLC). METHODS AND MATERIALS We manually delineated primary tumor volumes (TV) of patients with NSCLC who were treated with radical CRT on days 1, 8, 15, 22, 29, 36, and 43 on CBCTs obtained as part of the standard radiation treatment course. Percentage reductions in TV were calculated and then correlated to survival and pattern of recurrence using Cox proportional hazard models. Clinical information including histologic subtype was also considered in the study of such associations. RESULTS We evaluated 38 patients with a median follow-up time of 23.4 months. The median TV reduction was 39.3% (range, 7.3%-69.3%) from day 1 (D1) to day 43 (D43) CBCTs. Overall survival was associated with TV reduction from D1 to D43 (hazard ratio [HR] 0.557, 95% CI 0.39-0.79, P=.0009). For every 10% decrease in TV from D1 to D43, the risk of death decreased by 44.3%. For patients whose TV decreased ≥39.3 or <39.3%, log-rank test demonstrated a separation in survival (P=.02), with median survivals of 31 months versus 10 months, respectively. Neither local recurrence (HR 0.791, 95% CI 0.51-1.23, P=.29), nor distant recurrence (HR 0.78, 95% CI 0.57-1.08, P=.137) correlated with TV decrease from D1 to D43. Histologic subtype showed no impact on our findings. CONCLUSIONS TV reduction as determined by CBCT during CRT as part of routine care predicts post-CRT survival. Such knowledge may justify intensification of RT or application of additional therapies. Assessment of genomic characteristics of these tumors may permit a better understanding of behavior or prediction of therapeutic outcomes.

Thoracic Vertebral Body Irradiation Contributes to Acute Hematologic Toxicity During Chemoradiation Therapy for Non-Small Cell Lung Cancer.

PURPOSE To determine the relationships between radiation doses to the thoracic bone marrow and declines in blood cell counts in non-small cell lung cancer (NSCLC) patients treated with chemoradiation therapy (CRT). METHODS AND MATERIALS We included 52 patients with NSCLC treated with definitive concurrent carboplatin-paclitaxel and RT. Dose-volume histogram (DVH) parameters for the thoracic vertebrae (TV), sternum, scapulae, clavicles, and ribs were assessed for associations with changes in blood counts during the course of CRT. Linear and logistic regression analyses were performed to identify associations between hematologic nadirs and DVH parameters. A DVH parameter of Vx was the percentage of the total organ volume exceeding x radiation dose. RESULTS Grade ≥ 3 hematologic toxicity including neutropenia developed in 21% (n=11), leukopenia in 42% (n=22), anemia in 6% (n=3), and throbocytopenia in 2% (n=1) of patients. Greater RT dose to the TV was associated with higher risk of grade ≥ 3 leukopenia across multiple DVH parameters, including TV V20 (TVV) (odds ratio [OR] 1.06; P=.025), TVV30 (OR 1.07; P=.013), and mean vertebral dose (MVD) (OR 1.13; P=.026). On multiple regression analysis, TVV30 (β = -0.004; P=.018) and TVV20 (β = -0.003; P=.048) were associated with white blood cell nadir. Additional bone marrow sites (scapulae, clavicles, and ribs) did not affect hematologic toxicity. A 20% chance of grade ≥ 3 leukopenia was associated with a MVD of 13.5 Gy and a TTV30 of 28%. Cutoff values to avoid grade ≥ 3 leukopenia were MVD ≤ 23.9 Gy, TVV20 ≤ 56.0%, and TVV30 ≤ 52.1%. CONCLUSIONS Hematologic toxicity is associated with greater RT doses to the TV during CRT for NSCLC. Sparing of the TV using advanced radiation techniques may improve tolerance of CRT and result in improved tolerance of concurrent chemotherapy.

Neutrophil and Lymphocyte Counts as Clinical Markers for Stratifying Low-Risk Prostate Cancer

UNLABELLED Appropriate patient selection for active surveillance is challenging.Our study of 217 patients demonstrated that the preoperative absolute neutrophil and lymphocyte counts were better predictors of aggressive oncologic features than were the neutrophil-to-lymphocyte ratio in the assessment of low-risk prostate cancer patients. Our findings suggest that routine hematologic workup could be used to further stratify low-risk prostate cancer patients. INTRODUCTION The neutrophil-to-lymphocyte ratio (NLR) has emerged as a ubiquitous prognostic biomarker in cancer-related inflammation, specifically in patients with metastatic castration-resistant prostate cancer (PCa). We evaluated the clinical utility of the preoperative NLR, absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) as a risk stratification tool for patients with low-risk PCa. MATERIALS AND METHODS We identified 217 low-risk PCa patients with preoperative hematologic data who had met the criteria for active surveillance but had undergone robot-assisted radical prostatectomy at our institution from 2006 to 2015. Logistic regression models were constructed to determine whether the baseline NLR, ANC, and ALC were associated with upstaging, upgrading, and biochemical recurrence (BCR). Survival analyses were performed using the Kaplan-Meier method. RESULTS On multivariate analysis, a higher prostate-specific antigen level (odds ratio [OR], 1.554; 95% confidence interval [CI], 1.148-2.104), a greater number of positive cores (OR, 2.098; 95% CI, 1.043-2.104), and a higher ALC (OR, 4.311; 95% CI, 1.258-14.770) were associated with upstaging. More importantly, the 5-year biochemical recurrence-free survival was significantly lower in the high ANC group (ANC > 4.0 × 10(9)/L) compared with that of the low ANC group (P = .011). The NLR was not associated with upstaging, upgrading, or BCR in our study cohort (P = .368, P = .573, and P = .504, respectively). The only significant association with upgrading was patient age (OR, 1.106; 95% CI, 1.043-1.173). CONCLUSION NLR was not useful in predicting adverse pathologic outcomes in our patients with low-risk PCa. However, relative neutrophilia and lymphocytosis might indicate an early manifestation of harboring a more aggressive PCa.

Evaluation of Diabetic Patients with Breast Cancer Treated with Metformin during Adjuvant Radiotherapy

Purpose. The purpose of this study was to evaluate acute locoregional toxicity in patients with breast cancer receiving concurrent metformin plus radiation therapy. Methods and Materials. Diabetic breast cancer patients receiving concurrent metformin and radiation therapy were matched with nondiabetic patients and diabetic patients using an alternative diabetes medication. Primary endpoints included the presence of a treatment break and development of dry or moist desquamation. Results. There was a statistically significant increase in treatment breaks for diabetic patients receiving concurrent metformin when compared to the nondiabetic patients (P value = 0.02) and a trend toward significance when compared to diabetic patients receiving an alternate diabetes medication (P value = 0.08). Multiple logistic regression analysis demonstrated concurrent metformin use as being associated with a trend toward the predictive value of determining the incidence of developing desquamation in diabetic patients receiving radiation therapy compared to diabetic patients receiving an alternate diabetes medication (P value = 0.06). Conclusions. Diabetic patients treated with concurrent metformin and radiation therapy developed increased acute locoregional toxicity in comparison with diabetic patients receiving an alternate diabetes medication and nondiabetic patients. Further clinical investigation should be conducted to determine the therapeutic ratio of metformin in combination with radiation therapy.

Oncoplastic breast surgery in the setting of breast-conserving therapy: A systematic review

Breast-conserving therapy (BCT), or breast-conserving surgery with adjuvant radiation therapy, has become a standard treatment alternative to mastectomy for women with early-stage breast cancer after many long-term studies have reported comparable rates of overall survival and local control. Oncoplastic breast surgery in the setting of BCT consists of various techniques that allow for an excision with a wider margin and a simultaneous enhancement of cosmetic sequelae, making it an ideal breast cancer surgery. Because of the parenchymal rearrangement that is routinely involved in oncoplastic techniques, however, the targeted tissue can be relocated, thus posing a challenge to localize the tumor bed for radiation planning. The goals of this systematic review are to address the challenges, outcomes, and cosmesis of oncoplastic breast surgery in the setting of BCT.

Comparison of Urinary Tract Infection Rates Associated with Transurethral Catheterization, Suprapubic Tube and Clean Intermittent Catheterization in the Postoperative Setting: A Network Meta-Analysis

Purpose: We performed a network meta‐analysis of available randomized, controlled trials to elucidate the risks of urinary tract infection associated with transurethral catheterization, suprapubic tubes and intermittent catheterization in the postoperative setting. Materials and Methods: PubMed®, EMBASE® and Google Scholar™ searches were performed for eligible randomized, controlled trials from January 1980 to July 2015 that included patients who underwent transurethral catheterization, suprapubic tube placement or intermittent catheterization at the time of surgery and catheterization lasting up to postoperative day 30. The primary outcome of comparison was the urinary tract infection rate via a network meta‐analysis with random effects model using the netmeta package in R 3.2 (www.r‐project.org/). Results: Included in analysis were 14 randomized, controlled trials in a total of 1,391 patients. Intermittent catheterization and suprapubic tubes showed no evidence of decreased urinary tract infection rates compared to transurethral catheterization. Suprapubic tubes and intermittent catheterization had comparable urinary tract infection rates (OR 0.903, 95% CI 0.479–2.555). On subgroup analysis of 10 randomized, controlled trials with available mean catheterization duration data in a total of 928 patients intermittent catheterization and suprapubic tube were associated with significantly decreased risk of urinary tract infection compared to transurethral catheterization when catheterization duration was greater than 5 days (OR 0.173, 95% CI 0.073–0.412 and OR 0.142, 95% CI 0.073–0.276, respectively). Conclusions: Transurethral catheterization is not associated with an increased urinary tract infection risk compared to suprapubic tubes and intermittent catheterization if catheterization duration is 5 days or less. However, a suprapubic tube or intermittent catheterization is associated with a lower rate of urinary tract infection if longer term catheterization is expected in the postoperative period.

Risk of complications and urinary incontinence following cytoreductive prostatectomy: A multi-institutional study

Emerging evidence has suggested that cytoreductive prostatectomy (CRP) allows superior oncologic control when compared to current standard of care androgen deprivation therapy alone. However, the safety and benefit of cytoreduction in metastatic prostate cancer (mPCa) has not been proven. Therefore, we evaluated the incidence of complications following CRP in men newly diagnosed with mPCa. A total of 68 patients who underwent CRP from 2006 to 2014 at four tertiary surgical centers were compared to 598 men who underwent radical prostatectomy for clinically localized prostate cancer (PCa). Urinary incontinence was defined as the use of any pad. CRP had longer operative times (200 min vs 140 min, P < 0.0001) and higher estimated blood loss (250 ml vs 125 ml, P < 0.0001) compared to the control group. However, both overall (8.82% vs 5.85%) and major complication rates (4.41% vs 2.17%) were comparable between the two groups. Importantly, urinary incontinence rate at 1-year after surgery was significantly higher in the CRP group (57.4% vs 90.8%, P < 0.0001). Univariate logistic analysis showed that the estimated blood loss was the only independent predictor of perioperative complications both in the unadjusted model (OR: 1.18; 95% CI: 1.02-1.37; P = 0.025) and surgery type-adjusted model (OR: 1.17; 95% CI: 1.01-1.36; P = 0.034). In conclusion, CRP is more challenging than radical prostatectomy and associated with a notably higher incidence of urinary incontinence. Nevertheless, CRP is a technically feasible and safe surgery for selecting PCa patients who present with node-positive or bony metastasis when performed by experienced surgeons. A prospective, multi-institutional clinical trial is currently underway to verify this concept.

Trends in active surveillance for very low‐risk prostate cancer: do guidelines influence modern practice?

As recommended by current NCCN guidelines, patients with very low‐risk prostate cancer may be treated with active surveillance (AS), but this may be underutilized. Using the National Cancer Database (NCDB), we identified men (2010–2013) with biopsy‐proven, very low‐risk prostate cancer that met AS criteria as suggested by Epstein (stage ≤ T1c; Gleason score (GS) ≤ 6; PSA < 10; and ≤2 [or <33%] positive biopsy cores) and aged ≤76, and low comorbidity index (Charlson‐Deyo score = 0). For those patients meeting this criteria, we performed generalized estimation equation (GEE) method with incorporation of correlation in patients clustered within facility to determine the likelihood of undergoing AS. Among the 448 773 patients in the NCDB with low‐risk prostate cancer, 40 839 patients met the inclusion criteria. AS was utilized in 5798 patients (14.2%), while within the very low‐risk patients receiving treatment, up to 52.2% received radical prostatectomy. In univariate analyses, AS utilization was associated with older age, uninsured status (compared to private insurance), farther distance from facility, academic/research institutions and particularly in the New England region (all P < 0.01). After adjustments of other predictors in multivariate analysis, patients preferentially received AS if they were older (all ORs > 1 compared to younger groups), uninsured (vs. any insurance type, ORs > 1); or treated at academic/research center (OR > 1). The overall use of AS increased from 11.6% (2010) to 27.3% (2013). We found a low, but rising rate of AS in a nationally representative group of very low‐risk prostate cancer patients. Disparities in the use of AS may be targeted to improve adherence to national guidelines.

Predicting clinically significant prostate cancer based on pre-operative patient profile and serum biomarkers

Previous studies have reported association of multiple preoperative factors predicting clinically significant prostate cancer with varying results. We assessed the predictive model using a combination of hormone profile, serum biomarkers, and patient characteristics in order to improve the accuracy of risk stratification of patients with prostate cancer. Data on 224 patients from our prostatectomy database were queried. Demographic characteristics, including age, body mass index (BMI), clinical stage, clinical Gleason score (GS) as well as serum biomarkers, such as prostate-specific antigen (PSA), parathyroid hormone (PTH), calcium (Ca), prostate acid phosphatase (PAP), testosterone, and chromogranin A (CgA), were used to build a predictive model of clinically significant prostate cancer using logistic regression methods. We assessed the utility and validity of prediction models using multiple 10-fold cross-validation. Bias-corrected area under the receiver operating characteristics (ROC) curve (bAUC) over 200 runs was reported as the predictive performance of the models. On univariate analyses, covariates most predictive of clinically significant prostate cancer were clinical GS (OR 5.8, 95% CI 3.1–10.8; P < 0.0001; bAUC = 0.635), total PSA (OR 1.1, 95% CI 1.06–1.2; P = 0.0003; bAUC = 0.656), PAP (OR 1.5, 95% CI 1.1–2.1; P = 0.016; bAUC = 0.583), and BMI (OR 1.064, 95% C.I. 0.998, 1.134; P < 0.056; bAUC = 0.575). On multivariate analyses, the most predictive model included the combination of preoperative PSA, prostate weight, clinical GS, BMI and PAP with bAUC 0.771 ([2.5, 97.5] percentiles = [0.76, 0.78]). Our model using preoperative PSA, clinical GS, BMI, PAP, and prostate weight may be a tool to identify individuals with adverse oncologic characteristics and classify patients according to their risk profiles.

Prognostic Impact of Missed Chemotherapy Doses During Chemoradiation Therapy for Non-Small Cell Lung Cancer.

Objective: The aim of this study is to investigate the impact of missed chemotherapy administrations (MCA) on the prognosis of non–small cell lung cancer (NSCLC) patients treated with definitive chemoradiation therapy (CRT). Materials and Methods: In total, 97 patients with NSCLC treated with definitive CRT were assessed for MCA due to toxicities. Logistic regression was used to determine factors associated with MCA. Kaplan-Meier curves, log-rank tests, and Cox Proportional Hazards models were conducted. Results: MCA occurred in 39% (n=38) of the patients. Median overall survival was 9.6 months for patients with MCA compared with 24.3 months for those receiving all doses (P=0.004). MCA due to decline in performance status was associated with the worst survival (4.6 mo) followed by allergic reaction (10.0 mo), hematologic toxicity (11 mo), and esophagitis (17.2 mo, P=0.027). In multivariate models, MCA was associated with higher mortality (hazard ratio, 1.97; P=0.01) and worse progression-free survival (hazard ratio, 1.96; P=0. 009). Conclusions: MCA correlated with worse prognosis and increased mortality. Methods to reduce toxicity may improve administration of all chemotherapy doses and increase overall survival in NSCLC treated with CRT.