Genetic architecture of disease resistance and tolerance in Douglas-fir trees.

Understanding the genetic basis of how plants defend against pathogens is important to monitor and maintain resilient tree populations. Swiss needle cast (SNC) and Rhabdocline needle cast (RNC) epidemics are responsible for major damage of forest ecosystems in North America. Here we investigate the genetic architecture of tolerance and resistance to needle cast diseases in Douglas-fir (Pseudotsuga menziesii) caused by two fungal pathogens: SNC caused by Nothophaeocryptopus gaeumannii, and RNC caused by Rhabdocline pseudotsugae. We performed case-control genome-wide association analyses and found disease resistance and tolerance in Douglas-fir to be polygenic and under strong selection. We show that stomatal regulation as well as ethylene and jasmonic acid pathways are important for resisting SNC infection, and secondary metabolite pathways play a role in tolerating SNC once the plant is infected. We identify a major transcriptional regulator of plant defense, ERF1, as the top candidate for RNC resistance. Our findings shed light on the highly polygenic architectures underlying fungal disease resistance and tolerance and have important implications for forestry and conservation as the climate changes.

Clinical Outcomes of De Novo Versus Relapsed Early Metastatic Testicular Seminoma Treated With Contemporary Radiation Therapy.

PURPOSE: Chemotherapy (CHT) or radiation therapy (RT) are first-line treatments for clinical stage II (CS-II) testicular seminoma. Historically, clinical stage I (CS-I) seminoma was also treated with CHT or RT, but in the past 2 decades practice has shifted toward active surveillance for CS-I with RT or CHT reserved for patients with progression to CS-II. Limited data exist on contemporary RT techniques and patient stratification (ie, de novo [CS-II at orchiectomy] vs relapsed [CS-II diagnosed during surveillance after orchiectomy for CS-I]). We investigated outcomes in CS-II patients treated with RT in the modern era across 2 institutions. METHODS AND MATERIALS: A retrospective review identified 73 patients treated with RT for CS-II A or B seminoma between 2001 and 2022. Recurrence-free survival (RFS) was calculated by the Kaplan-Meier method and univariate analyses were performed with log-rank or Cox proportional hazard regression. Recurrence was defined as biopsy-proven metastatic seminoma after RT completion. Second malignancies were defined as a biopsy-proven malignancy originating in the prior RT field. RESULTS: Thirty-eight (52%) patients presented with de novo CS-II and 35 (48%) patients had relapsed CS-II. Median follow-up was 4.8 years (IQR: 2.3-8.1). Five-year RFS was 82% overall (92% in relapsed patients and 73% in de novo patients). Relapsed CS-II disease had lower recurrence rates after RT compared with de novo CS-II disease. All recurrences occurred outside the prior RT field and were salvaged. Disease-specific survival was 100%. Two second malignancies occurred (prostate, colorectal cancer at 67 months and 119 months post-RT, respectively). CONCLUSIONS: In patients with CS-II seminoma treated with modern RT, there were no in-field recurrences. Presentation with de novo CS-II is associated with out-of-field recurrence. Subject to further larger-scale validation, our results suggest that compared with CS-II at time of relapse, de novo CS-II may portend more aggressive or micrometastatic disease beyond the retroperitoneum, raising the possibility of benefit from CHT after radiation.

Differences in branch hydraulic architecture related to the aridity of growing sites and seed sources of coastal Douglas-fir saplings.

To better understand hydraulic adaptations of coastal Douglas-fir (Pseudotsuga menziesii var. menziesii (Mirb.) Franco) to local climate, we examined genetic (G) and environmental (E) responses of branch hydraulic architecture of 7-year-old saplings from dry and wet climates of origin grown at a relatively dry and a relatively wet common garden site in western Oregon. We sampled 2 years of branch growth from three dry-source and three wet-source families grown at both sites (72 branches, total). Overall, only 4 of the 11 traits had significant genetic (G) effects, whereas 9 traits had significant environmental (E) effects (P < 0.05). Both dry and wet sources had higher leaf-specific conductance (kl) at the dry than the wet site, but the values were achieved by different mechanisms and driven by G × E effects for leaf area/sapwood area (Al/As), shoot length (L), specific conductivity (Ks) and leaf-specific conductivity (Kl). Dry sources achieved higher kl in the dry site through higher Kl (via a lower Al/As and no change in Ks) with no difference in L. Wet sources achieved higher kl at the dry site through no difference in Kl (via no effect on Al/As, despite decreases in Al and As, and lower Ks) with lower L. Vulnerability to embolism (measured as percentage loss of conductivity at 4 MPa) had no G effect but an E effect, with slightly lower values at the dry site. Specific leaf area had G and E effects, with lower values for the dry sources and site. There were no G or E effects on wood density. The different responses of dry and wet sources to site aridity suggest that populations are differentially adapted to the aridity of growing sites. Population variation in response to aridity should be considered when selecting seed sources for establishing forests for future climates.

Practice Patterns and Outcomes Among Patients With N0M0 Prostate Cancer and a Very High Prostate-Specific Antigen Level.

BACKGROUND: Management of patients with a very high prostate-specific antigen (PSA) level (≥98.0 ng/mL) but clinically localized (N0M0) prostate cancer is challenging. This study sought to determine practice patterns and outcomes among these patients. PATIENTS AND METHODS: A total of 748,825 patients with prostate cancer from 2004 through 2012 were identified using the National Cancer Database. These patients were subdivided by PSA level (0-9.9, 10.0-19.9, 20.0-39.9, 40.0-59.9, 60.0-79.9, 80.0-97.9, and ≥98.0 ng/mL), nodal status (N0 vs N1), and distant metastases (M0 vs M1). Rates of locoregional treatment and 5-year overall survival (OS) in each group were determined. Survival was compared using Cox regression after adjusting for multiple patient-specific factors. RESULTS: The rate of locoregional treatment for patients with N0M0 disease and PSA level ≥98.0 ng/mL was significantly lower than for those with N1M0 disease (52.6% vs 60.4%; P<.001) or N0M0 disease and PSA level <98.0 ng/mL (52.6% vs 86.6%; P<.001). The 5-year OS rate was similar for patients with N1M0 disease and those with N0M0 disease and a very high PSA level (63.2% vs 59.1%; adjusted hazard ratio [aHR], 0.91; P=.063). The survival benefit associated with locoregional treatment was higher among those with N0M0 disease and a very high PSA level than among those with N1M0 disease (aHR, 0.28 vs 0.44; P<.001). CONCLUSIONS: Patients with clinical N0M0 disease and a very high PSA level (≥98.0 ng/mL) have outcomes similar to those with N1 disease but receive locoregional treatment at a lower rate. Future work is needed to investigate the utility of locoregional treatment in this population.

Productivity and nutritive value of elephant grass pastures under organic and conventional production systems.

Elephant grass (EG) (Pennisetum purpureum Schum.) have great importance in tropical and subtropical climates, especially on dairy farms. Normally, EG is established alone under high fertilization levels. EG in organic production system can improve low production costs and environmental issues, are still little known. The aim of this research was to evaluate the performance of herbage yield, nutritive value, extraction/ export nutrient and forage yield and animal responses. Three production systems of EG were analyzed: (i) EG mixed spontaneous-growing species (SGE) in warm-season and ryegrass (R) in cool-season under organic production; (ii) EG mixed SGE + R under conventional system (positive control); and (iii) EG based under conventional production (control). Holstein cows were used in a rotational stocking. Forage samples were collected to evaluate the pasture and animal responses. Seven grazing cycles were performed during the experimental period (312 days). Herbage yield, forage intake, and stocking rate were 12548; 10270; 19168 kg ha-1 and 2.5; 2.6; 2.7% and 3.3; 2.1; 4.5 AU ha-1 day-1, respectively. Crude protein of EG was 17.9; 15.4; 16.4%, respectively. Mixed pastures, in conventional and organic production, had a better forage distribution throughout the seasons. Highest forage yield and extraction/ export nutrient was reported in pure EG within the conventional system.

Nontuberculous Mycobacterial Musculoskeletal Infection Cases from a Tertiary Referral Center, Colorado, USA.

Nontuberculous mycobacteria represent an uncommon but important cause of infection of the musculoskeletal system. Such infections require aggressive medical and surgical treatment, and cases are often complicated by delayed diagnosis. We retrospectively reviewed all 14 nonspinal cases of nontuberculous mycobacterial musculoskeletal infections treated over 6 years by orthopedic surgeons at a university-affiliated tertiary referral center. All patients required multiple antimicrobial agents along with aggressive surgical treatment; 13 of 14 patients ultimately achieved cure. Four patients required amputation to control the infection. Half these patients were immunosuppressed by medications or other medical illness when they sought care at the referral center. Six cases involved joint prostheses; all ultimately required hardware removal and placement of an antimicrobial spacer for eradication of infection. Our findings highlight the importance of vigilance for nontuberculous mycobacterial musculoskeletal infection, particularly in patients who are immunosuppressed or have a history of musculoskeletal surgery.

Identifying anomalous nuclear radioactive sources using Poisson kriging and mobile sensor networks.

Nuclear security is a critical concept for public health, counter-terrorism efforts, and national security. Nuclear radioactive materials should be monitored and secured in near real-time to reduce potential danger of malicious usage. However, several challenges have arose to detect the anomalous radioactive source in a large geographical area. Radiation naturally occurs in the environment. Therefore, a non-zero level of radiation will always exist with or without an anomalous radioactive source present. Additionally, radiation data contain high levels of uncertainty, meaning that the measured radiation value is significantly affected by the velocity of the detector and background noise. In this article, we propose an innovative approach to detect anomalous radiation source using mobile sensor networks combined with a Poisson kriging technique. We validate our results using several experiments with simulated radioactive sources. As results, the accuracy of the model is extremely high when the source intensity is high or the anomalous source is close enough to the detector.

Adverse Health Outcomes in Relationship to Hypogonadism After Chemotherapy: A Multicenter Study of Testicular Cancer Survivors.

BACKGROUND: This study examined the prevalence of hypogonadism, its clinical and genetic risk factors, and its relationship to adverse health outcomes (AHOs) in North American testicular cancer survivors (TCS) after modern platinum-based chemotherapy. PATIENTS AND METHODS: Eligible TCS were <55 years of age at diagnosis and treated with first-line platinum-based chemotherapy. Participants underwent physical examinations and completed questionnaires regarding 15 AHOs and health behaviors. Hypogonadism was defined as serum testosterone levels ≤3.0 ng/mL or use of testosterone replacement therapy. We investigated the role of 2 single nucleotide polymorphisms (rs6258 and rs12150660) in the sex hormone-binding globulin (SHBG) locus implicated in increased hypogonadism risk in the general population. RESULTS: Of 491 TCS (median age at assessment, 38.2 years; range, 18.7-68.4 years), 38.5% had hypogonadism. Multivariable binary logistic regression analysis identified hypogonadism risk factors, including age at clinical evaluation (odds ratio [OR], 1.42 per 10-year increase; P= .006) and body mass index of 25 to <30 kg/m2 (OR, 2.08; P= .011) or ≥30 kg/m2 (OR, 2.36; P= .005) compared with <25 kg/m2. TCS with ≥2 risk alleles for the SHBG SNPs had a marginally significant increased hypogonadism risk (OR, 1.45; P= .09). Vigorous-intensity physical activity appeared protective (OR, 0.66; P= .07). Type of cisplatin-based chemotherapy regimen and socioeconomic factors did not correlate with hypogonadism. Compared with TCS without hypogonadism, those with hypogonadism were more likely to report ≥2 AHOs (65% vs 51%; P= .003), to take medications for hypercholesterolemia (20.1% vs 6.0%; P<.001) or hypertension (18.5% vs 10.6%; P= .013), and to report erectile dysfunction (19.6% vs 11.9%; P= .018) or peripheral neuropathy (30.7% vs 22.5%; P= .041). A marginally significant trend for increased use of prescription medications for either diabetes (5.8% vs 2.6%; P= .07) or anxiety/depression (14.8% vs 9.3%; P= .06) was observed. CONCLUSIONS: At a relatively young median age, more than one-third of TCS have hypogonadism, which is significantly associated with increased cardiovascular disease risk factors, and erectile dysfunction. Providers should screen TCS for hypogonadism and treat symptomatic patients.

Risk of Upgrading and Upstaging Among 10 000 Patients with Gleason 3+4 Favorable Intermediate-risk Prostate Cancer.

BACKGROUND: It is unknown whether active surveillance can be safely offered to patients with Gleason 3+4 favorable intermediate-risk (FIR) prostate cancer. OBJECTIVE: To examine the incidence and predictors of upgrading and upstaging among patients with Gleason 3+4 FIR disease. DESIGN, SETTING, AND PARTICIPANTS: The study involved 10 089 patients in the National Cancer Database diagnosed from 2010 to 2012 with Gleason 3+4 disease, prostate-specific antigen (PSA) <10ng/ml, and cT1c-2a prostate cancer with <50% positive biopsy cores (PBCs) who underwent radical prostatectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic regression was used to examine predictors of upgrading (pathologic Gleason ≥4+3 or tertiary Gleason 5 in a Gleason 7 tumor) or upstaging (pT3-4/N1). RESULTS AND LIMITATIONS: Some 30.3% of Gleason 3+4 FIR patients were upgraded or upstaged. On multivariable analysis, predictors included higher PSA, percentage PBC, age, and cT2a versus cT1c (all p<0.001), but not black race (p=0.895). When stratified into ordinal variables, PSA 8.1-9.9 versus ≤4.0ng/ml (adjusted odds ratio [AOR] 1.93, 38.3% vs 24.4%), PBC 37.5-49.9% versus <12.5% (AOR 1.79, 37.8% vs 25.1%); highest age quartile (≥67 yr) versus lowest (≤55 yr; AOR 1.46, 35.7% vs 24.7%); and cT2a versus cT1c (AOR 1.33, 34.3% vs 29.8%) were associated with a higher risk of upgrading or upstaging (all p<0.001). Men with PBC <12.5% and PSA ≤4.0ng/ml had a 21.7% risk of more advanced disease. This increased to 44.3% for PBC 37.5-49.9% and PSA 8.1-9.9ng/ml. A limitation of the study is its retrospective nature. CONCLUSIONS: Approximately one in three patients with Gleason 3+4 FIR harbored disease of higher grade or stage. Younger patients with low percentage PBC and PSA and cT1c disease have a lower risk and may be candidates for active surveillance. However, widely available clinical information is insufficient for predicting the risk of more advanced disease, and the development and incorporation of additional tools, including magnetic resonance imaging and genomic tests, are necessary. PATIENT SUMMARY: Nearly one-third of patients with Gleason 3+4 favorable intermediate-risk prostate cancer harbor disease of higher grade or higher stage than their biopsy and clinical examination suggest. These patients would therefore be poor candidates for active surveillance.

Quantitative lymph node burden as a 'very-high-risk' factor identifying head and neck cancer patients benefiting from postoperative chemoradiation.

Background: Adjuvant chemoradiation (CRT) is standard for head and neck squamous cell carcinoma (HNSCC) patients with positive margins or extranodal extension (ENE) following surgery. However, emerging evidence suggests the number of positive lymph nodes (LNs) is the dominant determinant of survival in non-oropharyngeal HNSCC and thus may better identify those benefiting from treatment intensification. Patients and methods: Patients from the National Cancer Database diagnosed with non-oropharyngeal HNSCC (oral cavity, larynx, hypopharynx) between 2004 and 2014 and undergoing surgical resection, neck dissection, and postoperative radiotherapy (RT) were included. Multivariable regression with first-order interaction terms was used to model the interaction between postoperative CRT and continuous number of positive LNs with respect to overall survival. Results: In total, 7144 patients met inclusion criteria. In multivariable analysis, increasing number of positive LNs was associated with both increasing mortality (P < 0.001) and increasing benefit from postoperative CRT versus RT alone (interaction P < 0.001). While there was no benefit from postoperative CRT in patients with 0-2 LN+ [hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.86-1.07, P = 0.47], increased benefit was seen in those with 3-5 LN+ (HR 0.84, 95% CI 0.70-1.00, P = 0.05) and those with ≥6 LN+ (HR 0.65, 95% CI 0.51-0.82, P < 0.001) in multivariable models. By contrast, margin status and ENE did not reliably identify patients benefitting from postoperative CRT based on statistical tests of interaction. Even in patients with ENE, positive margins, or both, only those with ≥6 LN+ had improved survival with postoperative CRT. Conclusion: Increasing metastatic nodal burden was associated with increased benefit from CRT compared with RT alone, surpassing conventional high-risk factors in identifying patients benefiting from CRT. Stratification by metastatic LN number may characterize a very-high-risk patient cohort best suited for treatment intensification.

Long-term outcomes of partial prostate treatment with magnetic resonance imaging-guided brachytherapy for patients with favorable-risk prostate cancer.

BACKGROUND: Partial prostate treatment has emerged as a potential method for treating patients with favorable-risk prostate cancer while minimizing toxicity. The authors previously demonstrated poor rates of biochemical disease control for patients with National Comprehensive Cancer Network (NCCN) intermediate-risk disease using partial gland treatment with brachytherapy. The objective of the current study was to estimate the rates of distant metastasis and prostate cancer-specific mortality (PCSM) for this cohort. METHODS: Between 1997 and 2007, a total of 354 men with clinical T1c disease, a prostate-specific antigen (PSA) level < 15 ng/mL, and Gleason grade ≤3 + 4 prostate cancer underwent partial prostate treatment with brachytherapy to the peripheral zone under 0.5-Tesla magnetic resonance guidance. The cumulative incidences of metastasis and PCSM for the NCCN very low-risk, low-risk, and intermediate-risk groups were estimated. Fine and Gray competing risk regression was used to evaluate clinical factors associated with time to metastasis. RESULTS: A total of 22 patients developed metastases at a median of 11.0 years (interquartile range, 6.9-13.9 years). The 12-year metastasis rates for patients with very low-risk, low-risk, and intermediate-risk disease were 0.8% (95% confidence interval [95% CI], 0.1%-4.4%), 8.7% (95% CI, 3.4%-17.2%), and 15.7% (95% CI, 5.7%-30.2%), respectively, and the 12-year PCSM estimates were 1.6% (95% CI, 0.1%-7.6%), 1.4% (95% CI, 0.1%-6.8%), and 8.2% (95% CI, 1.9%-20.7%), respectively. On multivariate analysis, NCCN risk category (low risk: hazard ratio, 6.34 [95% CI, 1.18-34.06; P = .03] and intermediate risk: hazard ratio, 6.98 [95% CI, 1.23-39.73; P = .03]) was found to be significantly associated with the time to metastasis. CONCLUSIONS: Partial prostate treatment with brachytherapy may be associated with higher rates of distant metastasis and PCSM for patients with intermediate-risk disease after long-term follow-up. Treatment of less than the full gland may not be appropriate for this cohort.

Increased Vulnerability to Poorer Cancer-Specific Outcomes Following Recent Divorce.

BACKGROUND: Prior studies have only considered the association between static marital status and cancer-specific outcomes. We aim to measure the effect of recent divorce on cancer-specific outcomes. METHODS: There were 83,804 patients with 2 malignancies, diagnosed 12 to 60 months apart, from 1973-2006 from the Surveillance, Epidemiology, and End Results database. Patients were identified as newly divorced if married at their first diagnosis and single/divorced at their second. Multivariable logistic regression and competing-risks regression were used to analyze the association of becoming newly divorced or newly married with cancer-specific outcomes from the second malignancy, including advanced diagnosis (T4 or N1 or M1), receipt of treatment, and cancer-specific survival. RESULTS: Four percent became newly divorced and 3.4% became newly married. Compared with long-term married, newly divorced patients were most likely to be diagnosed with advanced disease (adjusted odds ratio [AOR] 1.31; 95% confidence interval [CI], 1.19-1.43), followed by long-term divorced (AOR 1.18; 95% CI, 1.11-1.25), and were least likely to receive curative treatment (AOR 0.74; 95% CI, 0.67-0.81). Newly divorced patients had the worst cancer-specific survival (adjusted hazard ratio [AHR] 1.17; 95% CI, 1.05-1.30, P = .005), followed by long-term divorced (AHR 1.08; 95% CI, 1.01-1.16, P = .032), while newly married patients had similar cancer-specific survival to long-term married (AHR 0.96; 95% CI, 0.85-1.08, P = .46). CONCLUSION: Recent divorce, which represents an acute disruption of a patient's social support network, was associated with the worst cancer outcomes, followed by long-term divorce. Clinicians should consider recent divorce as a risk factor for worse cancer outcomes, and encourage appropriate screening, treatment, and access to social and financial supports for recently divorced patients.

Predicting Cardiovascular Disease Among Testicular Cancer Survivors After Modern Cisplatin-based Chemotherapy: Application of the Framingham Risk Score.

BACKGROUND: Testicular cancer survivors (TCSs) are at increased risk of cardiovascular disease (CVD) after cisplatin-based chemotherapy (CBCT). Identifying at-risk survivors would allow early intervention, but risk prediction tools such as the Framingham Risk Score (FRS) have not been applied to TCSs given modern chemotherapy. METHODS: TCSs > 1 year post-CBCT were evaluated. Associations between FRS and clinical, socioeconomic, and lifestyle measures and treatment regimen (4 cycles, etoposide and cisplatin [EP × 4]); 3 or 4 cycles, bleomycin plus EP (BEP × 3, BEP × 4) were analyzed with general linear multivariable models. Controls from the National Health and Nutrition Examination Survey were matched 1:1 to TCSs by age, race, and education with differences in mean FRS evaluated with 2-sided t tests. RESULTS: Of 787 TCSs (median age, 37.3 years; median follow-up, 4.2 years), 284, 342, and 161 received EP × 4, BEP × 3, or BEP × 4, respectively. TCSs had higher median systolic blood pressure (126 vs. 119 mm Hg; P < .001), but fewer were smokers (8.4% vs. 28.2%; P < .001) than controls. In multivariable analysis, no significant differences in FRS between EP × 4, BEP × 3, and BEP × 4 were observed, but less than college education (P < .001) and lack of vigorous exercise (P = .006) were associated with higher FRS. Mean FRS did not differ between TCSs and controls (6.8% vs. 7.3%; P = .67). CONCLUSION: This is the first study to apply the office-based FRS to TCSs. Chemotherapy regimen (BEP × 3 vs. EP × 4) was not associated with FRS, but less educated and less vigorously active patients had higher FRS, and present a high-risk subgroup for intense follow-up and counseling.

Clinical and Genetic Risk Factors for Adverse Metabolic Outcomes in North American Testicular Cancer Survivors.

Background: Testicular cancer survivors (TCS) are at significantly increased risk for cardiovascular disease (CVD), with metabolic syndrome (MetS) an established risk factor. No study has addressed clinical and genetic MetS risk factors in North American TCS. Patients and Methods: TCS were aged <55 years at diagnosis and received first-line chemotherapy. Patients underwent physical examination, and had lipid panels, testosterone, and soluble cell adhesion molecule-1 (sICAM-1) evaluated. A single nucleotide polymorphism in rs523349 (5-α-reductase gene, SRD5A2), recently implicated in MetS risk, was genotyped. Using standard criteria, MetS was defined as ≥3 of the following: hypertension, abdominal obesity, hypertriglyceridemia, decreased high-density lipoprotein (HDL) cholesterol level, and diabetes. Matched controls were derived from the National Health and Nutrition Examination Survey. Results: We evaluated 486 TCS (median age, 38.1 years). TCS had a higher prevalence of hypertension versus controls (43.2% vs 30.7%; P<.001) but were less likely to have decreased HDL levels (23.7% vs 34.8%; P<.001) or abdominal obesity (28.2% vs 40.1%; P<.001). Overall MetS frequency was similar in TCS and controls (21.0% vs 22.4%; P=.59), did not differ by treatment (P=.20), and was not related to rs523349 (P=.61). For other CVD risk factors, TCS were significantly more likely to have elevated low-density lipoprotein (LDL) cholesterol levels (17.7% vs 9.3%; P<.001), total cholesterol levels (26.3% vs 11.1%; P<.001), and body mass index ≥25 kg/m2 (75.1% vs 69.1%; P=.04). On multivariate analysis, age at evaluation (P<.001), testosterone level ≤3.0 ng/mL (odds ratio [OR], 2.06; P=.005), and elevated sICAM-1 level (ORhighest vs lowest quartile, 3.58; P=.001) were significantly associated with MetS. Conclusions and Recommendations: Metabolic abnormalities in TCS are characterized by hypertension and increased LDL and total cholesterol levels but lower rates of decreased HDL levels and abdominal obesity, signifying possible shifts in fat distribution and fat metabolism. These changes are accompanied by hypogonadism and inflammation. TCS have a high prevalence of CVD risk factors that may not be entirely captured by standard MetS criteria. Cancer treatment-associated MetS requires further characterization.

Contemporary Treatment Patterns and Outcomes for Clinical Stage IS Testicular Cancer.

BACKGROUND: Controversy exists regarding the optimal management strategy for clinical stage IS seminomatous (SGCT) and nonseminomatous germ cell tumors (NSGCT) of the testis. OBJECTIVE: To assess contemporary treatment patterns and outcomes for clinical stage IS testicular cancer. DESIGN, SETTING, AND PARTICIPANTS: Using the National Cancer Data Base (2004-2012), we identified 1362 patients with clinical stage IS SGCT and NSGCT of the testis, treated with either adjuvant treatment (AT) or observation. OUTCOME MEASURES AND STATISTICAL ANALYSIS: We calculated the annual percent change (APC) to assess treatment trends. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and Cox regression analyses were used to compare overall survival (OS) between AT and observation groups. Analyses were stratified by histologic type. RESULTS AND LIMITATIONS: Overall, there were 581 (43%) and 781 (57%) men with SGCT and NSGCT, respectively. Among men with SGCT, the use of AT decreased over the study period (APC=-2.7, 95% confidence interval [CI]: -4.4, -1.1, p=0.001). The 5-yr IPTW-adjusted rates of OS were 99% and 97% in the AT and observation groups, respectively (hazard ratio = 0.36, 95% CI: 0.12, 1.14, p=0.08). Among men with NSGCT, the use of AT remained stable over the study period (APC = +0.8, 95% CI: -0.7, +2.2, p=0.29). The 5-yr IPTW-adjusted rates of OS were 97% and 95% in the AT and observation groups, respectively (HR=0.66, 95% CI: 0.27, 1.61, p=0.36). Limitations include the lack of full treatment details and cancer-specific survival information. CONCLUSIONS: Trends in the use of AT significantly decreased over time for SGCT, while it remained stable for NSGCT. Nonetheless, we report 5-yr OS rates of ≥95% for both histologies without any significant benefit with the use of AT. Further studies are warranted to confirm these findings. PATIENT SUMMARY: We evaluated treatment trends and outcomes for stage IS testicular cancer. We found that treatment changed over time for seminoma and remained stable for nonseminoma; there was no significant survival benefit in the use of adjuvant treatment versus observation for both seminomatous and nonseminomatous germ cell tumors.

Travel Distance as a Barrier to Receipt of Adjuvant Radiation Therapy After Radical Prostatectomy.

OBJECTIVES: Following radical prostatectomy (RP), adjuvant radiation therapy (RT) decreases biochemical recurrence and potentially improves metastasis-free and overall survival for patients with high-risk pathologic features. Since adjuvant RT typically occurs daily over several weeks, the logistical challenges of extensive traveling may be a significant barrier to its use. We examined the association between distance to treatment facility and use of adjuvant RT. MATERIALS AND METHODS: We identified 97,568 patients in the National Cancer Database diagnosed from 2004 through 2011 with cT1-4N0-xM0-x prostate cancer and found to have high-risk pathologic features (pT3-4 stage and/or positive surgical margins) at RP. Multivariable logistic regression adjusting for sociodemographic and clinicopathologic factors was used to examine the association between travel distance and receipt of adjuvant RT, defined as radiotherapy initiated within 12 months after RP. RESULTS: Overall, 10.6% (10,346) of the study cohort received adjuvant RT. On multivariable analysis, increasing travel distance was significantly associated with decreased use of adjuvant RT, with adjusted odds ratios of 1.0 (reference), 0.67, 0.46, 0.39, and 0.32 (all P<0.001) and prevalence of use at 12.6%, 8.8%, 6.3%, 4.9%, and 3.7% for patients living ≤25.0, 25.1 to 50.0, 50.1 to 75.0, 75.1 to 100.0, and >100.0 miles away, respectively. CONCLUSIONS: Increasing travel distance was strongly associated with decreased use of adjuvant RT in this national cohort of postprostatectomy patients with high-risk pathologic features. These results strongly suggest that the logistical challenges of extensive travel are a significant barrier to the use of adjuvant RT. Efforts aimed at improving access to radiotherapy and reducing treatment time are urgently needed.

Quantifying Decreased Radiation Exposure From Modern CT Scan Technology and Surveillance Programs of Germ Cell Tumors.

INTRODUCTION: Upgrading computerized tomography (CT) scanners to iterative reconstruction techniques (IRT) decreases radiation dose. This reduction, combined with changes in surveillance protocols in clinical stage I testicular cancer (CS1TC) measurably decrease the lifetime attributable risk (LAR) of dying of radiation-associated cancer. MATERIALS AND METHODS: This IRB-approved study enrolled 24 CS1TC patients who had CT scans on the same Toshiba Aquilion 64 CT before and after IRT software installation. Dose-length product and CT dose index volume were recorded. A physicist calculated effective doses. Radiation doses were compared using the Wilcoxon signed rank test. Median effective dose per scan was multiplied by scan number based on 16 versus 7 scans in 5-year AS protocols to calculate estimated cumulative dose (ECD). LAR of dying of radiation-associated solid tumor was estimated using ECD for a single exposure at age 35 with the excess absolute risk transport model from the BEIR VII analysis of long-term atomic bomb survivors. RESULTS: Median preupgrade and postupgrade effective doses were 12.5 and 7.7 mSv, respectively (P<0.0001). A linear regression model with a constrained zero intercept fit to the data found that IRT dose was estimated as 61% of filtered back projection dose (95% confidence interval, 0.56-0.66). The IRT upgrade reduced the LAR of the 16-scan protocol 35%. Combination of IRT upgrade and 7-scan protocol reduced surveillance LAR 72%. CONCLUSIONS: Modern CT technology combined with reduced scanning strategies can markedly decrease lifetime radiation exposure, further lowering the already small potential mortality of imaging-associated cancers.