Overall Survival and Cancer-Specific Mortality in Patients with Prostate Cancer Undergoing Definitive Therapies: A Narrative Review.

The overall survival (OS) of patients with prostate cancer (PCa) who receive locally definitive therapy is generally better than that of patients who do not receive definitive therapy. There is no difference in the incidence of local recurrence or distant metastasis between treatment modalities. Because the prognosis of PCa is relatively good, many studies have focused on quality of life after treatment as an endpoint. However, a limited number of patients develop biochemical recurrence after definitive treatment for PCa and subsequently develop distant metastasis or die from PCa. Therefore, we believe that preventing local recurrence and distant metastasis and prolonging the OS should be emphasized when selecting a treatment modality for PCa. In this review, the significance and usefulness of radical prostatectomy and radiation therapy as the main modalities of definitive therapies for local PCa and locally advanced PCa were evaluated, as well as the outcomes of OS and PCa-specific mortality and the treatment options after biochemical recurrence to improve the oncological outcomes.

Management considerations and treatment outcomes for newly diagnosed prostate cancer in advanced age patients (≥80 years): real-world data from a single urological center over a 10-year period.

Background: There is ongoing debate regarding prostate cancer (PCa) screening in advanced age males, leading to treatment decisions often based on tumor staging and life expectancy. A critical gap in clinical evidence and tailored guidelines for the advanced age with PCa persists. This study aims to compare survival outcomes of various treatment approaches in this demographic. Methods: We analyzed data from a large urological center for advanced age patients suspected of having PCa between 2012 and 2022. We collected clinical and pathological characteristics and evaluated treatment modalities, including palliative therapy and definitive therapy. Propensity score matching (PSM) analysis was implemented to reduce bias between treatment modalities. Kaplan-Meier and multivariate Cox proportional hazard regression analyses were conducted to evaluate progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Results: Out of 4,333 suspected patients, 376 individuals aged 80 years and older underwent prostate biopsy. The overall detection rate of PCa was 78.7%, with a high prevalence of high-grade tumors [International Society of Urological Pathology (ISUP) grade ≥2]. Most patients (86.5%) received palliative therapy, while 13.5% underwent definitive therapy. Patients in the definitive therapy group had lower prostate-specific antigen (PSA) values, lower tumor stage, and Charlson Comorbidity Index (CCI), longer life expectancy, and a higher Geriatric 8 (G8) score compared to the palliative therapy group. The median OS for the entire cohort was 72.0 months, with 70.0 months for palliative therapy and 96.0 months for definitive therapy. Multivariable analyses identified lymphatic and bone metastasis, as well as definitive therapy, as independent prognostic factors for PFS, CSS, and OS. Conclusions: Advanced age patients, although a small group, have distinct characteristics, including higher PSA levels, positive biopsy rates, and pathological grading and staging. In medically fit elderly patients, especially those with localized PCa and a life expectancy of ≥5 years, definitive therapy could improve survival outcomes.

Escalated-dose radiotherapy for unresected locally advanced pancreatic cancer: Patterns of care and survival in the United States.

INTRODUCTION: With locally advanced pancreatic cancer (LAPC), uncontrolled local tumor growth frequently leads to mortality. Advancements in radiotherapy (RT) techniques have enabled conformal delivery of escalated-dose RT (EDR), which may have potential local control and overall survival (OS) benefits based on retrospective and early prospective studies. With evidence for EDR emerging, we characterized the adoption of EDR across the United States and its associated outcomes. METHODS: We searched the National Cancer Database for nonsurgically managed LAPC patients diagnosed between 2004 and 2019. Pancreas-directed RT with biologically effective doses (BED10) ≥39 and ≤70 Gy was labeled conventional-dose RT (CDR), and BED10 >70 and ≤132 Gy was labeled EDR. We identified associations of EDR and OS using logistic and Cox regressions, respectively. RESULTS: Among the definitive therapy subset (n = 54,115) of the entire study cohort (n = 91,493), the most common treatments were chemotherapy alone (69%), chemotherapy and radiation (29%), and RT alone (2%). For the radiation therapy subset (n = 16,978), use of pancreas-directed RT remained between 13% and 17% over the study period (ptrend > 0.999). Using multivariable logistic regression, treatment at an academic/research facility (adjusted odds ratio [aOR] 1.46, p < 0.001) and treatment between 2016 and 2019 (aOR 2.54, p < 0.001) were associated with greater receipt of EDR, whereas use of chemotherapy (aOR 0.60, p < 0.001) was associated with less receipt. Median OS estimates for EDR and CDR were 14.5 months and 13.0 months (p < 0.0001), respectively. For radiation therapy subset patients with available survival data (n = 13,579), multivariable Cox regression correlated EDR (adjusted hazard ratio 0.85, 95% confidence interval 0.80-0.91; p < 0.001) with longer OS versus CDR. DISCUSSION AND CONCLUSIONS: Utilization of EDR has increased since 2016, but overall utilization of RT for LAPC has remained at less than one in five patients for almost two decades. These real-world results additionally provide an estimate of effect size of EDR for future prospective trials.

Racial disparities in conditional survival of patients with bladder cancer: a population-based study.

BACKGROUND: Traditional estimates can only provide static predictions of cancer outcomes and cannot assess the evolving effect of race on patient survival. This study aims to reveal the dynamic survival of patients with bladder cancer and to explore the evolving effect of race on patient prognosis. METHODS: Using data from the Surveillance, Epidemiology, and End Results (SEER) registry, 99,590 white, 6,036 African American, and 4,685 Asian/Pacific Islander (API) patients with bladder cancer were identified. Conditional cancer-specific survival (CSS) rates, which could reflect the dynamic survival prediction of cancer patients, represented the primary outcomes, and were estimated by the Kaplan-Meier algorithm. The evolving effect of race on patient survival was evaluated by multivariable Cox regression in combination with conditional survival (CS) estimates. RESULTS: The 5-year CSS for African American patients who had survived 1, 2, 3, 4, or 5 years after definitive therapy improved from the baseline calculation by + 5.8 (84.4%), + 9.5 (87.4%), + 12.8 (90.0%), + 14.4 (91.3%), and + 14.7% (91.5%), respectively. The increasing trend also held for overall white and API patients, and for all patient subsets when CS was calculated according to different levels of sex, age, and disease stage. African Americans, despite having the worst survival at baseline, could have CSS comparable to their white and API counterparts after 4 years of survivorship. In addition, the risk of death for African Americans tended to decrease with increasing survival, and the risk was no longer significantly different from that of whites after 4 years of survival. CONCLUSIONS: While having the worst initial predicted outcomes, African Americans may eventually achieve comparable survival to white and API patients given several years of survivorship. As patient survival increases, African American race may lose its role as an indicator of poorer prognosis.

Comparative Effectiveness of Ampicillin/Sulbactam versus Cefazolin as Targeted Therapy for Bacteremia Caused by Beta-Lactamase-Producing Methicillin-Sensitive Staphylococcus aureus: A Single-Center Retrospective Study.

Cefazolin (CFZ) is the first-line treatment for beta-lactamase-producing methicillin-sensitive Staphylococcus aureus (BP-MSSA) infection. In 2019, Japan experienced a CFZ shortage because of foreign object inclusion in a batch. Ampicillin/sulbactam (SAM) was preferred in many cases as definitive therapy for the treatment of BP-MSSA bacteremia to preserve broad-spectrum antibiotic stock. However, there are no previous studies reporting the clinical efficacy of SAM for BP-MSSA bacteremia. We aimed to compare the clinical efficacy and adverse effects of SAM versus CFZ in patients with BP-MSSA bacteremia. In total, 41 and 30 patients treated with SAM and CFZ, respectively, were identified. The baseline characteristics were similar in both groups. No significant differences were observed in length of hospital stay and all 30-day mortality between the two groups (p = 0.270 and 0.643, respectively). Moreover, no intergroup difference in 90-day mortality was found (hazard ratio 1.02, 95% confidential interval 0.227-4.53). Adverse effects, such as liver dysfunction, were less in the CFZ group than in the SAM group (p = 0.030). Therefore, in cases of poor CFZ supply or in patients allergic to CFZ and penicillinase-stable penicillins, SAM can be an effective therapeutic option for bacteremia due to BP-MSSA with attention of adverse effects, such as liver dysfunction.

Cisplatin Versus Carboplatin and Paclitaxel in Radiochemotherapy for Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: The implementation of a platinum-containing regimen is recommended for definitive and adjuvant therapy of patients with locally advanced head and neck tumour. We compared the conditions for the use of cisplatin or carboplatin/paclitaxel or for changing between these two regimens on a clinic-specific basis. PATIENTS AND METHODS: We evaluated 150 patients with advanced head and neck squamous cell carcinoma who received simultaneous radiochemotherapy at our institution between 2012 and 2017. Chemotherapy with weekly doses of cisplatin (40 mg/m2, group 1) or, in cases of impaired renal and/or cardiac function, with weekly doses of carboplatin AUC2 and paclitaxel (45 mg/m2, group 2), was performed as a first-choice therapy. If toxicities occurred in group 1, treatment was switched to the carboplatin/paclitaxel regimen (group 3). Patient- and therapy-related parameters, toxicity and survival data were compared across groups. RESULTS: We examined 99, 30, and 21 patients in each group who received at least 1 course of chemotherapy. Group 3 patients switched from cisplatin to carboplatin/paclitaxel after a median of 3 courses due to nephrotoxicity (95.2%). The target of at least 5 chemotherapy courses was most frequently achieved by patients in group 1 (69.7%), followed by group 3 (61.9%) and then group 2 (40.0%). Multivariate analysis revealed that patients who switched groups were more likely to be over 60 years old (p=0.021), undergo definitive radiochemotherapy (p=0.049) and develop higher nephrotoxicity (p=0.036) than group 1 patients. Outcomes did not differ between groups. CONCLUSION: When cisplatin application is contraindicated due to renal- or cardiotoxicity, carboplatin/paclitaxel is an appropriate option.

The Effects of Statins on Prostate Cancer Patients Receiving Androgen Deprivation Therapy or Definitive Therapy: A Systematic Review and Meta-Analysis.

Mortality associated with statin use has been reported in prostate cancer (PCa) patients treated with androgen deprivation therapy (ADT) or definitive therapy in several observational studies, although the results have varied. This study aimed to analyze the association of statin use with all-cause mortality and cancer-specific mortality among PCa patients receiving ADT or definitive therapy as their primary treatment and to examine the effect of statin initiation (pre-ADT) timing on outcomes. A systematic literature search of PubMed, the Cochrane library, and Embase was conducted from database inception to 4 October 2021. In total, 12 eligible studies from 976 references were included in the final analysis. The results showed that statin use was associated with a significant reduction in the risks of all-cause mortality (hazard ratio (HR) = 0.73, 95% confidence interval (CI) = 0.64-0.84, p < 0.0001) and cancer-specific mortality (HR = 0.61, 95% CI = 0.49-0.77, p < 0.0001) in PCa patients receiving ADT. However, statin use before ADT initiation did not significantly lower the risk of all-cause mortality (HR = 0.87, 95% CI = 0.66-1.16, p = 0.35) or cancer-specific mortality (HR = 0.84, 95% CI = 0.62-1.13, p = 0.25) in advanced PCa patients receiving ADT. In contrast, statin use was not associated with a significantly reduced risk of all-cause mortality (HR = 0.69, 95% CI = 0.39-1.21, p = 0.20), but it was associated with a reduced risk of cancer-specific mortality (HR = 0.82, 95% CI = 0.68-0.98, p = 0.03) in PCa patients receiving definitive therapy. This review indicated that statin use in combination with ADT was correlated with better all-cause and cancer-specific mortality in PCa patients. However, the beneficial effect might not come from statin use before ADT initiation. In addition, statin use in combination with definitive therapy was correlated with a reduced risk of cancer-specific mortality in PCa patients. In the future, randomized controlled trials are needed to validate the efficacy of statin use in combination with primary treatment for PCa among PCa patients.

Evaluation of step-down oral antibiotic therapy for uncomplicated streptococcal bloodstream infections on clinical outcomes.

BACKGROUND: Despite the severity and frequency of streptococcal bloodstream infections (BSIs), the effectiveness of oral definitive therapy remains unknown. The objective of this study was to evaluate the clinical outcomes of step-down oral antibiotics for the treatment of uncomplicated streptococcal BSIs. METHODS: In this retrospective cohort study, adult patients admitted with uncomplicated streptococcal BSI between June 2015 and June 2017 were included. Patients were excluded if they received <48 h of antibiotic therapy; therapy was started >48 h after first positive culture; had complicated infections of endocarditis, bone and joint infections, or central nervous system infections; Pitt bacteremia score (PBS) ⩾ 4; or failed to respond to effective therapy necessitating continued intravenous (IV) therapy. Patients were grouped by receipt of step-down oral antibiotic therapy (PO group) versus continued IV therapy (IV group). Outcomes included hospital length of stay (LOS), 30-day recurrence of BSI, 30-day readmission, 30-day all-cause mortality, and catheter-related or drug-related adverse events (AEs). RESULTS: Of 244 patients included, 40% received step-down oral therapy (n = 98). Overall, the most common source of BSI was pneumonia (22%), followed by skin and soft tissue infections (SSTI) (18%). Severity of illness measured by intensive care unit (ICU) admission and PBS was similar. The IV group had significantly longer LOS [median 10 (interquartile range [IQR] = 5-21) versus 5 (4-6) days, p < 0.01] compared with the PO group. BSI recurrence, readmission, all-cause mortality within 30 days, and AEs were similar between the groups (p = ns). CONCLUSION: In uncomplicated streptococcal BSI, patients treated with step-down oral antibiotic therapy had significantly shorter LOS compared with continued IV therapy without compromise of clinical outcomes.

The Potential for Overtreatment With Total Neoadjuvant Therapy (TNT): Consider One Local Therapy Instead.

With increased therapeutic options in rectal cancer, a central question has become how to tailor therapy to patient preferences to avoid both over and under treatment. Total Neoadjuvant Therapy (TNT), defined as delivering all planned chemotherapy and radiation therapy (RT) before surgery, was developed with the primary goal of improving overall survival through early elimination of micrometastatic disease. In this narrative review assessing patients with operable adenocarcinoma of the rectum, we sought to evaluate TNT versus alternative options with regard to both quality of life (QoL) and oncologic outcomes. Survey data of patient preferences reveal that an increased focus on QoL when discussing options is essential. While evidence favors TNT improving distant metastases-free survival, this has not yet translated to a clear OS benefit. The improved pathologic complete response rate with TNT compared to short course RT or chemoradiation alone suggests proceeding to surgery might result in overtreatment, lending support to a watch-and-wait option for patients with a goal for nonoperative management if a clinical complete response is achieved. Similarly, for select low-risk patients, surgery may be the only local therapy required allowing for safe omission of RT. In the treatment of rectal cancer, the future appears to be moving toward one local therapy. As an alternative to TNT, there is growing support for the concept we define herein as total definitive therapy instead: chemoradiation followed by consolidation chemotherapy, saving surgery only for incomplete responders rather than as part of the initial treatment plan. Also, selective use of RT should be considered for low-risk patients. By thoroughly assessing how these treatment de-escalation options compare to more traditional treatment algorithms, this narrative review provides guidance on how to honor patient preferences for QoL by avoiding treatments that might offer negligible benefits in oncologic outcomes.

Clinical analysis of 117 cases with synchronous multiple primary esophageal squamous cell carcinomas.

BACKGROUND/AIMS: We aimed to study the clinical characteristics, treatment modality, and the prognosis of synchronous multiple primary esophageal squamous cell carcinomas (SMPESCC). METHODS: A total of 117 SMPESCC cases were evaluated retrospectively from 2010 to 2015. RESULTS: The most common locations of SMPESCC were mid- and lower thoracic segments (n = 208, 84.9%). The 1-, 2-, and 3-year overall survival rates were 53.8%, 30.8%, and 15.4%, respectively; the median survival time (MST) was 12.5 months. With definitive radiotherapy and surgery, respectively, the MST of stage I/II patients were 34.2 and 26.7 months, of stage III patients were 8.3 and 13.2 months (p = 0.163), and of stage IV patients were and 8 and 12.6 months (p = 0.379). Clinical stage, family history of cancer, and Karnofsky performance status were independent prognostic factors for the whole cohort by Cox multivariate regression analysis (hazard ratio [HR] = 0.859, p < 0.001; HR = 0.579, p = 0.032; and HR = 0.586, p = 0.013). CONCLUSION: Although the prognosis of SMPESCC is poor, stage I/II patients can achieve long-term survival with aggressive treatment, especially those with a Karnofsky performance score 90 or higher and who have no family history of cancer. Definitive radiotherapy could achieve a similar survival rate to definitive surgery at different clinical stages.

Racial disparities in local therapy for early stage non-small-cell lung cancer.

OBJECTIVES: This study investigated disparities in the delivery of definitive therapy for early stage non-small-cell lung cancer (ESNSCLC) between Caucasian (CS) and African American (AA) populations. METHODS: The National Cancer Data Base was queried for AA and CS patients, diagnosed with c stage I Non small cell lung cancer between 2004 and 2015. Trends in surgery, stereotactic ablative radiotherapy (SABR), or external beam radiation therapy (EBRT) were compared. Kaplan-Meier and Cox hazards models were used to compare 5-year overall survival (5YOS). RESULTS: A total of 174,338 (90.6%) patients were CS and 18,077 (9.4%) patients were AA. AA patients were less likely to receive surgery (60.3% vs. 66.9%; p < .001) and more likely to receive EBRT (12.4% vs. 10.6%; p < .001); however, there was no significant difference in rates of SABR (8.8% vs. 9.2%; p = .066). From 2004 to 2015, the surgery rates increased for AA patients from 44.4% to 61.8% and for CS patients from 57.6% to 65.6%. AA patients had worse 5YOS on an unadjusted analysis (46.7% vs. 47.9%; p = .009). When adjusted for definitive treatment, AA patients had improved survival (hazard ratio = 0.97, 95% confidence interval = 0.94-0.99). CONCLUSION: Improvements in the delivery of surgery and equal utilization of definitive radiation therapy are at least partially responsible for closing the survival gap between AA and CS patients with ESNSCLC.

Definitive Cefazolin Therapy for Stabilized Adults with Community-Onset Escherichia coli, Klebsiella Species, and Proteus mirabilis Bacteremia: MIC Matters.

BACKGROUND: Cefazolin is in vitro active against wild isolates of Escherichia coli, Klebsiella species, and Proteus mirabilis (EKP), but clinical evidence supporting the contemporary susceptibility breakpoint issued by the Clinical and Laboratory Standards Institute (CLSI) are limited. METHODS: Between 2010 and 2015, adults with monomicrobial community-onset EKP bacteremia with definitive cefazolin treatment (DCT) at two hospitals were analyzed. Cefazolin minimum inhibitory concentrations (MICs) were correlated with clinical outcomes, including primary (treatment failure of DCT) and secondary (30-day mortality after bacteremia onset, recurrent bacteremia, and mortality within 90 days after the end of DCT) outcomes. RESULTS: Overall, 466 bacteremic episodes, including 340 (76.2%) episodes due to E. coli, 90 (20.2%) Klebsiella species, and 16 (3.6%) P. mirabilis isolates, were analyzed. The mean age of these patients was 67.8 years and female-predominated (68.4%). A crude 15- and 30-day mortality rate was 0.7% and 2.2%, respectively, and 11.2% experienced treatment failure of DCT. A significant linear-by-linear association of cefazolin MICs, with the rate of treatment failure, 30-day crude mortality, recurrent bacteremia or 90-day mortality after the DCT was present (all γ = 1.00, p = 0.01). After adjustment, the significant impact of cefazolin MIC breakpoint on treatment failure and 30-day crude mortality was most evident in 2 mg/L (>2 mg/L vs. ≤2 mg/L; adjusted hazard ratio, 3.69 and 4.79; p < 0.001 and 0.02, respectively). CONCLUSION: For stabilized patients with community-onset EKP bacteremia after appropriate empirical antimicrobial therapy, cefazolin might be recommended as a definitive therapy for cefazolin-susceptible EKP bacteremia, based on the contemporary CLSI breakpoint.

Definitive Cefazolin Treatment for Community-Onset Enterobacteriaceae Bacteremia Based on the Contemporary CLSI Breakpoint: Clinical Experience of a Medical Center in Southern Taiwan.

Cefazolin is traditionally active against Escherichia coli, Klebsiella species, and Proteus mirabilis (EKP) isolates. The Clinical and Laboratory Standards Institute (CLSI) has twice updated cefazolin susceptibility breakpoints for EKP since 2010, but its role in the definitive treatment of cefazolin-susceptible EKP bacteremia remains debated. To assess its efficacy as a definitive agent, the 8-year cohort study consisted of 941 adults with monomicrobial cefazolin-susceptible EKP bacteremia, based on the CLSI criteria issued in 2019, was retrospectively established in a medical center. Based on the definitive antimicrobial prescription, eligible patients were categorized into the cefazolin (399 patients, 42.4%) and broader-spectrum antibiotic (BSA) (542, 57.6%) groups. Initially, fewer proportions of patients with fatal comorbidities (the McCabe classification) and the critical illness (a Pitt bacteremia score ≥4) at the onset and day 3 of the bacteremia episode were found in the cefazolin group, compared to the BSA group. After propensity-score matching, no significant difference of patient proportions between the cefazolin (345 patients) and BSA (345) groups was observed, in terms of the elderly, types and severity of comorbidities, bacteremia severity at the onset and day 3, major bacteremia sources, and the 15-day and 30-day crude mortality. In early outcomes, lengths of time to defervescence, intravenous (IV) antimicrobial administration, and hospitalization were similar in the two matched groups; lower costs of IV antimicrobial administration were observed in the cefazolin group. Notably, for late outcomes, lower proportions of post-treatment infections caused by antimicrobial-resistant pathogens (ARPs) and post-treatment mortality rates were evidenced in the cefazolin group. Conclusively, cefazolin is definitively efficacious and cost-effective for adults with community-onset cefazolin-susceptible EKP bacteremia in this one-center study, compared to BSAs. However, a prospective multicenter study should be conducted for external validation with other communities.

Time from definitive therapy to onset of metastatic disease predicts outcomes in men with metastatic hormone sensitive prostate cancer.

PURPOSE: Contemporary treatment for metastatic hormone sensitive prostate cancer (mHSPC) includes androgen deprivation therapy (ADT) plus abiraterone or docetaxel. While these intensified regimens have improved efficacy, they are also associated with increased cost and toxicities. Not all men with mHSPC may be candidates for these intensified regimens, yet there are no clinical models or biomarkers used to optimize treatment selection. Herein, we hypothesized that longer time from prior definitive therapy (DT), either radical prostatectomy, definitive radiotherapy, or both, to onset of metastatic disease is associated with improved survival outcomes in men with newly diagnosed mHSPC. METHODS: This multicenter retrospective study included men initiating systemic therapy with ADT for new mHSPC. Kaplan-Meier and COX proportional hazard models assessed time to metastatic castration-resistant prostate cancer (mCRPC) and overall survival (OS) by receipt of prior DT. RESULTS: Of the 253 men with new mHSPC, 115 (45%) had received prior DT. In a multivariate analysis, increasing years from DT to the start of ADT was an independent predictor of time to mCRPC (per year: hazard ratio 0.91 95% confidence interval 0.84-0.99, P = 0.020) and improved OS (per year: hazard ratio 0.87, 95% confidence interval 0.74-0.99, P = 0.0025) in patients with new mHSPC, and may assist with risk stratification in these patients at time of mHSPC. CONCLUSION: Time from DT to start of ADT is an independent predictor of time to mCRPC and OS in men with new mHSPC, and may assist with risk stratification of these patients for systemic therapy selection.

Localized prostate cancer with pelvic arteriovenous malformation treated with low-dose-rate brachytherapy after transcatheter embolization: Two case reports.

BACKGROUND: We describe two patients who underwent low-dose-rate prostate brachytherapy after embolization for pelvic arteriovenous malformation. CASE PRESENTATION: Case 1: A 76-year-old man was referred for definitive treatment of intermediate-risk prostate cancer (prostate-specific antigen 8.667 ng/mL, cT2aN0M0, Gleason score 3 + 4 = 7). We planned low-dose-rate brachytherapy. However, magnetic resonance imaging and computed tomography demonstrated a large pelvic arteriovenous malformation. We performed embolization of the arteriovenous malformation before initiating treatment to lower the risk of rupture of the arteriovenous malformation during low-dose-rate brachytherapy. Case 2: A 69-year-old man was referred for the definitive treatment of high-risk prostate cancer (prostate-specific antigen 5.81 ng/mL, cT2aN0M0, Gleason score 4 + 4 = 8) with a pelvic arteriovenous malformation. Similar to Case 1, we performed embolization of the arteriovenous malformation before initiating treatment. In both cases, low-dose-rate brachytherapy could be performed without complications. CONCLUSIONS: Low-dose-rate brachytherapy after transcatheter embolization of pelvic arteriovenous malformations can safely and effectively treat localized prostate cancer with pelvic arteriovenous malformations.

The Hypothetical Impact of Accelerate Pheno on Time to Effective Therapy and Time to Definitive Therapy for Bloodstream Infections Due to Drug-Resistant Gram-Negative Bacilli.

Strategies are needed to improve time to optimal therapy in patients with bloodstream infections (BSI) due to resistant Gram-negative (GN) pathogens. Accelerate Pheno (ACC) can provide antimicrobial susceptibility results within 7 h of a positive culture and may more rapidly optimize therapy. The primary objective of this study was to evaluate the hypothetical impact of ACC on time to effective therapy (TTET) and time to definitive therapy (TTDT) among patients with BSI due to resistant GN pathogens. ACC was performed on resistant GN BSI isolates, and results were not available to clinicians in real time. A potential benefit of having ACC on TTET or TTDT was determined if modifications to antimicrobial regimens could have been made sooner with ACC. Comparisons on the impact of ACC in the presence or absence of testing by the Verigene Gram-negative blood culture test (Verigene GN-BC) were performed. Sixty-one patients with resistant GN BSI were evaluated. The median actual TTET and TTDT in the cohort were 25.9 h (interquartile range [IQR], 18.5, 42.1) and 47.6 h (IQR, 24.9, 79.6), respectively. Almost half of the patients had potential improvement in TTET and/or TTDT with ACC. In patients who would have had a benefit the median potential decreases in TTET and TTDT were 16.6 h (IQR, 5.5 to 30.6) and 29.8 h (IQR, 13.6 to 43), respectively. The largest potential improvements were seen in patients for whom Verigene results were not available. In conclusion, among patients with resistant GN BSI in a setting where other rapid diagnostic technologies are utilized, ACC results could have further improved TTET and TTDT.

2016 guidelines for the use of antifungal agents in patients with invasive fungal diseases in Taiwan.

The Infectious Diseases Society of Taiwan, Medical Foundation in Memory of Dr. Deh-Lin Cheng, Foundation of Professor Wei-Chuan Hsieh for Infectious Diseases Research and Education, and CY Lee's Research Foundation for Pediatric Infectious Diseases and Vaccines have updated the guidelines for the use of antifungal agents in adult patients with invasive fungal diseases in Taiwan. This guideline replaces the 2009 version. Recommendations are provided for Candida, Cryptococcus, Aspergillus and Mucormycetes. The focus is based on up-to-date evidence on indications for treatment or prophylaxis of the most common clinical problems. To support the recommendations in this guideline, the committee considered the rationale, purpose, local epidemiology, and key clinical features of invasive fungal diseases to select the primary and alternative antifungal agents. This is the first guideline that explicitly describes the quality and strength of the evidence to support these recommendations. The strengths of the recommendations are the quality of the evidence, the balance between benefits and harms, resource and cost. The guidelines are not intended nor recommended as a substitute for bedside judgment in the management of individual patients, the advice of qualified health care professionals, and more recent evidence concerning therapeutic efficacy and emergence of resistance. Practical considerations for individualized selection of antifungal agents include patient factors, pathogen, site of infection and drug-related factors, such as drug-drug interaction, drug-food intervention, cost and convenience. The guidelines are published in the Journal of Microbiology, Immunology and Infection and are also available on the Society website.

2016 guideline strategies for the use of antifungal agents in patients with hematological malignancies or hematopoietic stem cell transplantation recipients in Taiwan.

The Infectious Diseases Society of Taiwan (IDST), the Hematology Society of Taiwan, the Taiwan Society of Blood and Marrow Transplantation, Medical Foundation in Memory of Dr. Deh-Lin Cheng, Foundation of Professor Wei-Chuan Hsieh for Infectious Diseases Research and Education, and CY Lee's Research Foundation for Pediatric Infectious Diseases and Vaccines cooperatively published this guideline for the use of antifungal agents in hematological patients with invasive fungal diseases (IFDs) in Taiwan. The guideline is the first one endorsed by IDST focusing on selection of antifungal strategies, including prophylaxis, empirical (or symptom-driven) and pre-emptive (or diagnostic-driven) strategy. We suggest a risk-adapted dynamic strategy and provide an algorithm to facilitate decision making in population level as well as for individual patient. Risk assessment and management accordingly is explicitly emphasized. In addition, we highlight the importance of diagnosis in each antifungal strategy among five elements of the antimicrobial stewardship (diagnosis, drug, dose, de-escalation and duration). The rationale, purpose, and key recommendations for the choice of antifungal strategy are summarized, with concise review of international guidelines or recommendation, key original articles and local epidemiology reports. We point out the interaction and influence between elements of recommendations and limitation of and gap between evidences and daily practice. The guideline balances the quality of evidence and feasibility of recommendation in clinical practice. Finally, this version introduces the concept of health economics and provides data translated from local disease burdens. All these contents hopefully facilitate transparency and accountability in medical decision-making, improvements in clinical care and health outcomes, and appropriateness of medical resource allocation.

Is salvage surgery for recurrent non-small-cell lung cancer after definitive non-operative therapy associated with reasonable survival?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether salvage pulmonary resection is possible and worthwhile for patients with recurrence of non-small-cell lung cancer (NSCLC) after prior definitive non-operative therapy. A total of nine reports were identified using the reported search, of which four represented the best available evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. All studies were retrospective. In total, 48 pulmonary salvage resections were performed in 47 patients after prior definitive radiation, chemoradiation or stereotactic body radiation therapy, of which 28 were lobectomies (including 1 sleeve lobectomy), 12 pneumonectomies, 4 bilobectomies and 4 sublobar resections (2 segmentectomies and 2 wedge resections). Postoperative complications ranged from 0 to 58% (mean from four studies 42.5%). Only one study reported any mortality (4%), the other three had zero mortality. Median postoperative survival was reported in two studies and ranged from 9 to 30 months. Experience with salvage lung resection for locally recurrent NSCLC, after prior definitive non-surgical treatment, remains limited. Therefore, this analysis was based on only 48 resections in 47 patients from four retrospective studies. Nevertheless, the published data suggest that salvage lung surgery for recurrent, previously non-operatively managed non-small-cell lung cancer is a worthwhile treatment option with good survival, acceptable morbidity and low mortality.

Prognostic impact of definitive local therapy of the primary tumor in men with metastatic prostate cancer at diagnosis: A population-based, propensity score analysis.

BACKGROUND: This study investigated whether definitive local therapy [radical prostatectomy (RP) or brachytherapy (BT)] of the primary tumor improves survival in men with metastatic prostate cancer (PrCA) at diagnosis. METHODS: Data on newly diagnosed metastatic PrCA cases (stage IV, N=7858) were obtained from the Surveillance Epidemiology and End Results (SEER) program. Conventional multivariable survival analysis and propensity score analysis were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (95% CI) comparing men who underwent definitive local therapy of the primary tumor to those who did not. RESULTS: After adjusting for sociodemographic and tumor attributes, having RP after diagnosis with metastatic PrCA was associated with 73% (HR=0.27, 95% CI: 0.20-0.38) lower risk of all-cause mortality and 72% (HR=0.28, 95% CI: 0.20-0.39) reduced risk of death from PrCA. Having BT also was associated with 57% (HR=0.43, 95% CI: 0.31-0.59) and 54% (HR=0.46, 95% CI: 0.33-0.64) lower risk of all-cause and PrCA-specific mortality. Similar results were observed in propensity score-adjusted analysis as well as when stratified by age and extent of tumor metastasis. CONCLUSIONS: These findings suggest that definitive local therapy improves survival in men with metastatic PrCA at diagnosis. Future work should consider comorbidities, diet, physical activity and smoking status.