Proton therapy for the management of localized prostate cancer: Long-term clinical outcomes at a comprehensive cancer center.

BACKGROUND AND PURPOSE: Proton therapy (PT) has emerged as a standard-of-care treatment option for localized prostate cancer at our comprehensive cancer center. However, there are few large-scale analyses examining the long-term clinical outcomes. Therefore, this article aims to evaluate the long-term effectiveness and toxicity of PT in patients with localized prostate cancer. MATERIALS AND METHODS: Review of 2772 patients treated from May 2006 through January 2020. Disease risk was stratified according to National Comprehensive Cancer Network guidelines as low [LR, n = 640]; favorable-intermediate [F-IR, n = 850]; unfavorable-intermediate [U-IR, n = 851]; high [HR, n = 315]; or very high [VHR, n = 116]. Biochemical failure and toxicity were analyzed using Kaplan-Meier estimates and multivariate models. RESULTS: The median patient age was 66 years; the median follow-up time was 7.0 years. Pelvic lymph node irradiation was prescribed to 28 patients (1%) (2 [0.2%] U-IR, 11 [3.5%] HR, and 15 [12.9%] VHR). The median dose was 78 Gy in 1.8-2.0 Gy(RBE) fractions. Freedom from biochemical relapse (FFBR) rates at 5 years and 10 years were 98.2% and 96.8% for the LR group; 98.3% and 93.6%, F-IR; 94.2% and 90.2%, U-IR; 94.3% and 85.2%, HR; and 86.1% and 68.5%, VHR. Two patients died of prostate cancer. Overall rates of late grade ≥ 3 GU and GI toxicity were 0.87% and 1.01%. CONCLUSIONS: Proton therapy for localized prostate cancer demonstrated excellent clinical outcomes in this large cohort, even among higher-risk groups with historically poor outcomes despite aggressive therapy.

Long-term Outcomes of Bevacizumab and Chemoradiation for Locoregionally Advanced Nasopharyngeal Carcinoma: A Nonrandomized Controlled Trial.

Importance: The long-term outcomes associated with adding bevacizumab, a vascular endothelial growth factor inhibitor, to standard chemoradiation have continued to be favorable for a group of patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Objective: To assess long-term toxic effects and clinical outcomes associated with chemotherapy, radiation therapy (RT), and bevacizumab for NPC. Design, Setting, and Participants: This single-arm phase II nonrandomized controlled trial was conducted by the National Cancer Trials Network group and NRG Oncology (formerly Radiation Therapy Oncology Group), with accrual from December 13, 2006, to February 5, 2009, and data analysis from June 26 to July 1, 2019. The study was conducted at 19 cancer centers with a median (IQR) follow-up of 9.0 (7.7-9.3) years. Included patients were adults (aged ≥18 years) with NPC that was World Health Organization (WHO) histologic grade I to IIb or III, American Joint Committee on Cancer stage IIB or greater, and with or without lymph node involvement. Interventions: Patients received 3 cycles of bevacizumab (15 mg/kg) concurrently with standard cisplatin (100 mg/m2) and RT (69.96 Gy) followed by 3 cycles of adjuvant bevacizumab (15 mg/kg) given concurrently with cisplatin (80 mg/m2) and fluorouracil (1000 mg/m2/d). Main Outcomes and Measures: The primary end point was grade 4 hemorrhage or grade 5 adverse events in the first year. Secondary end points were locoregional progression-free (LRPF) interval, distant metastasis-free (DMF) interval, progression-free survival (PFS), overall survival (OS), and other adverse events. Long-term toxic effects and clinical outcomes were reported due to the limited follow-up in the initial report for this trial and the importance of long-term outcomes when combining bevacizumab with chemoradiation. Results: Among 46 patients with NPC who were enrolled, 44 patients were analyzed (29 males [65.9%]; 23 Asian [52.3%], 2 Black [4.5%], and 16 White [36.4%]; 38 not Hispanic [86.4%]; median [IQR] age, 48.5 [39.0-56.0] years). There were 33 patients with a Zubrod performance status of 0, indicating that they were fully functional and asymptomatic (75.0%); 32 patients with a WHO histologic grade of IIb or III (72.7%); and 39 patients with stage III or IVB disease (88.6%). Among analyzed patients, 42 individuals received radiation therapy of 69.96 Gy or greater (95.5%; dose range, 65.72-70.00 Gy); 30 patients received 3 cycles of cisplatin (68.2%) with RT, and 31 patients received 3 cycles of bevacizumab with RT (70.5%); this was followed by 3 cycles of adjuvant cisplatin in 21 patients (47.7%), fluorouracil in 24 patients (54.5%), and bevacizumab in 23 patients (52.3%). No grade 4 hemorrhage or grade 5 AEs were reported in the first year or thereafter. Late grade 3 AEs occurred in 16 patients (36.4%), including 7 patients with dysphagia (15.9%), 6 patients with hearing impairment (13.6%), and 2 patients with dry mouth (4.5%). The 1- and 5-year rates of feeding tube use were 5 of 41 patients (12.2%) and 0 of 27 patients, respectively. There were 19 patients (43.2%) who progressed or died without disease progression (6 patients with locoregional progression [13.6%], 8 patients with distant progression [18.2%], and 5 patients who died without progression [11.4%]). The 5- and 7-year rates were 79.5% (95% CI, 67.6%-91.5%) and 69.7% (95% CI, 55.9%-83.5%) for OS, 61.2% (95% CI, 46.8%-75.6%) and 56.3% (95% CI, 41.5%-71.1%) for PFS, 74.9% (95% CI, 61.4%-86.6%) and 72.3% (95% CI, 58.4%-84.7%) for LRPF interval, and 79.5% (95% CI,66.4%-90.0%) for both times for DMF interval. Among 13 patients who died, death was due to disease in 8 patients (61.5%). Conclusions and Relevance: In this nonrandomized controlled trial, no grade 4 hemorrhage or grade 5 AEs were reported in the first year or thereafter among patients with NPC receiving bevacizumab combined with chemoradiation. The rate of distant metastasis was low although 89% of patients had stage III to IVB disease, suggesting that further investigation may be warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT00408694.

Low dose rate brachytherapy for primary treatment of localized prostate cancer: A systemic review and executive summary of an evidence-based consensus statement.

PURPOSE: The purpose of this guideline is to present evidence-based consensus recommendations for low dose rate (LDR) permanent seed brachytherapy for the primary treatment of prostate cancer. METHODS AND MATERIALS: The American Brachytherapy Society convened a task force for addressing key questions concerning ultrasound-based LDR prostate brachytherapy for the primary treatment of prostate cancer. A comprehensive literature search was conducted to identify prospective and multi-institutional retrospective studies involving LDR brachytherapy as monotherapy or boost in combination with external beam radiation therapy with or without adjuvant androgen deprivation therapy. Outcomes included disease control, toxicity, and quality of life. RESULTS: LDR prostate brachytherapy monotherapy is an appropriate treatment option for low risk and favorable intermediate risk disease. LDR brachytherapy boost in combination with external beam radiation therapy is appropriate for unfavorable intermediate risk and high-risk disease. Androgen deprivation therapy is recommended in unfavorable intermediate risk and high-risk disease. Acceptable radionuclides for LDR brachytherapy include iodine-125, palladium-103, and cesium-131. Although brachytherapy monotherapy is associated with increased urinary obstructive and irritative symptoms that peak within the first 3 months after treatment, the median time toward symptom resolution is approximately 1 year for iodine-125 and 6 months for palladium-103. Such symptoms can be mitigated with short-term use of alpha blockers. Combination therapy is associated with worse urinary, bowel, and sexual symptoms than monotherapy. A prostate specific antigen <= 0.2 ng/mL at 4 years after LDR brachytherapy may be considered a biochemical definition of cure. CONCLUSIONS: LDR brachytherapy is a convenient, effective, and well-tolerated treatment for prostate cancer.

Balancing the Blood Component Transfusion Ratio for High- and Ultra High-Dose Cell Salvage Cases.

OBJECTIVE: To assess the ratio of non-red blood cell to red blood cell components required to avoid coagulopathy when transfusing large amounts of salvaged blood using laboratory test-guided therapy. DESIGN: Retrospective cohort study. SETTING: Single-center, academic hospital. PARTICIPANTS: Thoracoabdominal and abdominal open aortic surgery patients. MEASUREMENT AND MAIN RESULTS: Thirty-eight patients in whom at least 1,000 mL of salvaged red blood cells were transfused were identified and divided into the following 2 cohorts: 1,000-to-2,000 mL of salvaged red blood cells (high dose) (n = 20) and >2,000 mL of salvaged red blood cells (ultra-high dose) (n = 18). Compared with the high-dose cohort, the ultra high-dose cohort received ∼4 times more salvaged red blood cells (1,240 ± 279 mL v 5,550 ± 3,801 mL). With transfusion therapy guided by intraoperative coagulation tests and thromboelastography, the adjusted ratio of non-red blood cell to red blood cell components (plasma + platelets + cryoprecipitate:allogeneic + salvaged red blood cells) was 0.59 ± 0.66 in the high-dose and 0.93 ± 0.27 in the ultra high-dose cohorts. Multiple coagulation parameters were normal and similar between cohorts at the end of surgery, as determined by the mean, median, and 95% confidence intervals. CONCLUSIONS: When transfusing large volumes of salvaged blood, it is important to balance the ratio between non-red blood cell and red blood cell components. Through a laboratory test-guided approach, coagulopathy was not detected when transfusing blood in ratios of approximately 1:2 for patients receiving 1,000-to-2,000 mL of salvaged blood and 1:1 for patients receiving >2,000 mL of salvaged blood.

Comparative changes of pre-operative autologous transfusions and peri-operative cell salvage in the United States.

BACKGROUND: With improved safety of allogeneic blood supply, the use of preoperative autologous donations (PADs) and perioperative autologous cell salvage (PACS) has evolved. This study evaluated temporal trends in PAD and PACS use in the United States. METHODS: The National Inpatient Sample database, a stratified probability sample of 20% of hospitalizations in the United States, was used to compare temporal trends in hospitalizations reporting use of PADs and PACS from 1995 to 2015. Factors associated with their use were examined between 2012 and 2015 with use of multivariable Poisson regression. Sampling weights were applied to generate nationally representative estimates. RESULTS: There was a steady decrease in hospitalizations reporting PAD transfusions from 27.90 per 100 000 in 1995 to 1.48 per 100 000 hospitalizations in 2015 (P-trend <.001). In contrast, PACS increased from a rate of 1.16 per 100 000 in 1995 to peak of 20.51 per 100 000 hospitalizations in 2008 and then steadily declined (P-trend<.001). Higher odds of PACS and PADs were observed in older patients, elective procedures (vs urgent), and urban teaching/nonteaching hospitals (vs rural hospitals) (P < .001). PACS was more common in hospitalizations in patients with higher levels of severity of illness as compared to those with minor severity (adjusted prevalence ratio [adjPR], 2.39; 95% confidence interval [CI], 2.08-2.73; P<.001), while PADs were performed less often in patients with higher underlying severity of illness (All Patient Refined Diagnosis Related Groups, 4 vs 1, adjPR, 0.61; 95% CI, [0.39-0.95]; P = .028). CONCLUSIONS: There was a significant decrease in PAD red blood cell transfusions, while PACS has increased and subsequently decreased; PACS plays an important role in surgical blood conservation. The subsequent decline in PACS likely reflects further optimization of transfusion practice through patient blood management programs and improvement of surgical interventions.

The effects of zinc on radiation-induced dysgeusia: a systematic review and meta-analysis.

PURPOSE: Many head and neck cancer patients who receive radiation therapy experience radiation-induced dysgeusia (RID), which has no standard treatment. The only supplement controlled clinical trials have evaluated for the treatment of RID is zinc. However, the results of these and other studies investigating the use of zinc for RID have been inconsistent. To assess the validity of zinc as a treatment for RID, we conducted a systematic literature search and performed a meta-analysis to determine the extent to which zinc affects RID incidence and the degree to which ongoing RID responds to zinc. METHODS: We searched the Ovid MEDLINE, Ovid Embase, PubMed, and Cochrane Library databases to identify studies investigating the use of zinc-based therapy for RID in head and neck cancer patients treated with radiation that were published between January 1, 2003, and November 9, 2017. Using American Society of Clinical Oncology criteria, we selected studies with a high level of evidence for inclusion in the meta-analysis. RESULTS: Of the 32 full-text articles eligible for inclusion, three were included in the final review and meta-analysis. The meta-analysis showed that, compared with placebo, zinc reduces the incidence of RID (risk ratio, 0.72; 95% confidence interval, 0.67-0.92) but does not improve taste acuity more rapidly following radiation therapy (risk ratio, 2.58; 95% confidence interval, 0.97-6.88). CONCLUSION: Our findings indicate that zinc-based therapy reduces the incidence of RID but has a minimal effect on ongoing RID. Our findings also highlight the need for additional evidence-based research on this topic.

Clinical Utility of Autologous Salvaged Blood: a Review.

INTRODUCTION: Autologous salvaged blood, commonly referred to as "cell saver" or "cell salvage" blood, is an important method of blood conservation. Understanding the mechanism of action and summarizing the existing evidence regarding the safety, efficiency, and the relative costs of cell salvage may help educate clinicians on how and when to best utilize autotransfusion. METHODS: This review focuses on issues concerning the quality of red blood cells (RBC), efficiency, and the cost effectiveness relative to autotransfusion. The key considerations of safe use and clinical applicability are described along with the challenges for wider dissemination. RESULTS: Cell salvage can reduce requirements for allogeneic transfusions, along with the associated risks and costs. Autologous salvaged RBCs provide high-quality transfusion, since the cells have not been subjected to the adverse effects of storage as occurs with banked blood. The risks for RBC alloimmunization and transfusion-related infectious diseases are also avoided. With a careful selection of cases, salvaged blood can be more cost effective than donor blood. Cell salvage may have a role in cardiac, major vascular, orthopedic, transplant, and trauma surgeries. However, there remain theoretical safety concerns in cases with bacterial contamination or in cancer surgery. CONCLUSION: In addition to other methods of blood conservation used in patient blood management programs, autologous salvaged blood adds value and is cost effective for appropriate surgical cases. Evidence suggests that autologous salvaged blood may be of higher quality and confer a cost reduction compared with the allogeneic banked blood, when used appropriately.

Predicting treatment Response based on Dual assessment of magnetic resonance Imaging kinetics and Circulating Tumor cells in patients with Head and Neck cancer (PREDICT-HN): matching 'liquid biopsy' and quantitative tumor modeling.

BACKGROUND: Magnetic resonance imaging (MRI) has improved capacity to visualize tumor and soft tissue involvement in head and neck cancers. Using advanced MRI, we can interrogate cell density using diffusion weighted imaging, a quantitative imaging that can be used during radiotherapy, when diffuse inflammatory reaction precludes PET imaging, and can assist with target delineation as well. Correlation of circulating tumor cells (CTCs) measurements with 3D quantitative tumor characterization could potentially allow selective, patient-specific response-adapted escalation or de-escalation of local therapy, and improve the therapeutic ratio, curing the greatest number of patients with the least toxicity. METHODS: The proposed study is designed as a prospective observational study and will collect pretreatment CT, MRI and PET/CT images, weekly serial MR imaging during RT and post treatment CT, MRI and PET/CT images. In addition, blood sample will be collected for biomarker analysis at those time intervals. CTC assessments will be performed on the CellSave tube using the FDA-approved CellSearch® Circulating Tumor Cell Kit (Janssen Diagnostics), and plasma from the EDTA blood samples will be collected, labeled with a de-identifying number, and stored at - 80 °C for future analyses. DISCUSSION: The primary objective of the study is to evaluate the prognostic value and correlation of weekly tumor response kinetics (gross tumor volume and MR signal changes) and circulating tumor cells of mucosal head and neck cancers during radiation therapy using MRI in predicting treatment response and clinical outcomes. This study will provide landmark information as to the utility of CTCs ('liquid biopsy) and tumor-specific functional quantitative imaging changes during treatment to guide personalization of treatment for future patients. Combining the biological information from CTCs and the structural information from MRI may provide more information than either modality alone. In addition, this study could potentially allow us to determine the optimal time to obtain MR imaging and/ or CTCs during radiotherapy to assess tumor response and provide guidance for patient selection and stratification for future dose escalation or de-escalation strategies. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT03491176 ). Date of registration: 9th April 2018. (retrospectively registered). Date of enrolment of the first participant: 30th May 2017.

Second salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer.

PURPOSE: Salvage treatments for localized radiorecurrent prostate cancer can be performed safely when a focal and image guided approach is used. Due to the low toxicity, the opportunity exists to investigate a second salvage treatment when a second locally recurrent prostate cancer occurs. Here, we describe a second salvage treatment procedure of 4 patients. MATERIAL AND METHODS: Four patients with a pathologically proven second local recurrence were treated in an outpatient magnetic resonance imaging (MRI)-guided setting with a single fraction of 19 Gy focal high-dose-rate brachytherapy (HDR-BT). Delineation was performed using choline-PET-CT or a 68Ga-PSMA PET in combination with multiparametric 3 Tesla MRI in all four patients. Toxicity was measured using common toxicity criteria for adverse events (CTCAE) version 4.0. RESULTS: With a median follow-up of 12 months (range, 6-15), there were 2 patients with biochemical recurrence as defined by the Phoenix-definition. There were no patients with grade 3 or more toxicity. In all second salvage HDR-BT treatments, the constraints for rectum, bladder, and urethra were met. Median treatment volume (GTV) was 4.8 cc (range, 1.9-6.6 cc). A median of 8 catheters (range, 6-9) were used, and the median dose to the treatment volume (GTV) was a D95: 19.3 Gy (SD 15.5-19.4 Gy). CONCLUSIONS: Second focal salvage MRI-guided HDR-BT for a select group of patients with a second locally recurrent prostate cancer is feasible. There was no grade 3 or more acute toxicity for these four patients.

Focal MRI-Guided Salvage High-Dose-Rate Brachytherapy in Patients With Radiorecurrent Prostate Cancer.

INTRODUCTION: Whole-gland salvage treatment of radiorecurrent prostate cancer has a high rate of severe toxicity. The standard of care in case of a biochemical recurrence is androgen deprivation treatment, which is associated with morbidity and negative effects on quality of life. A salvage treatment with acceptable toxicity might postpone the start of androgen deprivation treatment, might have a positive influence on the patients' quality of life, and might even be curative. Here, toxicity and biochemical outcome are described after magnetic resonance imaging-guided focal salvage high-dose-rate brachytherapy in patients with radiorecurrent prostate cancer. MATERIALS AND METHODS: Seventeen patients with pathologically proven locally recurrent prostate cancer were treated with focal high-dose-rate brachytherapy in a single 19-Gy fraction using magnetic resonance imaging for treatment guidance. Primary radiotherapy consisted of external beam radiotherapy or low-dose-rate brachytherapy. Tumors were delineated with Ga-68-prostate-specific membrane antigen or F18-choline positron emission tomography in combination with multiparametric magnetic resonance imaging. All patients had a prostate-specific antigen level of less than 10 ng/mL at the time of recurrence and a prostate-specific antigen doubling time of ≥12 months. Toxicity was measured by using the Common Terminology Criteria for Adverse Events version 4. RESULTS: Eight of 17 patients had follow-up interval of at least 1 year. At a median follow-up interval of 10 months (range 3-40 months), 1 patient experienced a biochemical recurrence according to the Phoenix criteria, and prostate-specific membrane antigen testing revealed that this was due to a distant nodal metastasis. One patient had a grade 3 urethral stricture at 2 years after treatment. CONCLUSION: Focal salvage high-dose-rate brachytherapy in patients with radiorecurrent prostate cancer showed grade 3 toxicity in 1 of 17 patients and a distant nodal metastasis in another patient. Whether this treatment option leads to cure in a subset of patients or whether it can successfully postpone androgen deprivation treatment needs further investigation.

Biological responses of human solid tumor cells to X-ray irradiation within a 1.5-Tesla magnetic field generated by a magnetic resonance imaging-linear accelerator.

Devices that combine magnetic resonance imaging with linear accelerators (MRL) represent a novel tool for MR-guided radiotherapy. However, whether magnetic fields (MFs) generated by these devices affect the radiosensitivity of tumors is unknown. We investigated the influence of a 1.5-T MF on cell viability and radioresponse of human solid tumors. Human head/neck cancer and lung cancer cells were exposed to single or fractionated 6-MV X-ray radiation; effects of the MF on cell viability were determined by cell plating efficiency and on radioresponsiveness by clonogenic cell survival. Doses needed to reduce the fraction of surviving cells to 37% of the initial value (D0s) were calculated for multiple exposures to MF and radiation. Results were analyzed using Student's t-tests. Cell viability was no different after single or multiple exposures to MRL than after exposure to a conventional linear accelerator (Linac, without MR-generated MF) in 12 of 15 experiments (all P > 0.05). Single or multiple exposures to MF had no influence on cell radioresponse (all P > 0.05). Cells treated up to four times with an MRL or a Linac further showed no changes in D0s with MF versus without MF (all P > 0.05). In conclusion, MF within the MRL does not seem to affect in vitro tumor radioresponsiveness as compared with a conventional Linac. Bioelectromagnetics. 37:471-480, 2016. © 2016 Wiley Periodicals, Inc.

2,3-Diphosphoglycerate Concentrations in Autologous Salvaged Versus Stored Red Blood Cells and in Surgical Patients After Transfusion.

BACKGROUND: Stored red blood cells (RBCs) are deficient in 2,3-diphosphoglycerate (2,3-DPG), but it is unclear how autologous salvaged blood (ASB) compares with stored blood and how rapidly 2,3-DPG levels return to normal after transfusion. Therefore, we compared levels of 2,3-DPG in stored versus ASB RBCs and in patients' blood after transfusion. METHODS: Twenty-four patients undergoing multilevel spine fusion surgery were enrolled. We measured 2,3-DPG and the oxyhemoglobin dissociation curve (P50) in samples taken from the ASB and stored blood bags before transfusion and in blood samples drawn from patients before and after transfusion. RESULTS: The mean storage duration for stored RBCs was 24 ± 8 days. Compared with fresh RBCs, stored RBCs had decreased 2,3-DPG levels (by approximately 90%; P < 0.0001) and a decreased P50 (by approximately 30%; P < 0.0001). However, ASB RBCs did not exhibit these changes. The mean 2,3-DPG concentration decreased by approximately 20% (P < 0.05) in postoperative blood sampled from patients who received 1 to 3 stored RBC units and by approximately 30% (P < 0.01) in those who received ≥4 stored RBC units. 2,3-DPG was unchanged in patients who received no stored blood or ASB alone. After surgery, 2,3-DPG levels recovered gradually over 3 postoperative days in patients who received stored RBCs. CONCLUSIONS: Stored RBCs, but not ASB RBCs, have decreased levels of 2,3-DPG and a left-shift in the oxyhemoglobin dissociation curve. Postoperatively, 2,3-DPG levels remain below preoperative baseline levels for up to 3 postoperative days in patients who receive stored RBCs but are unchanged in those who receive only ASB RBCs.

Proton Beam Therapy for Localized Prostate Cancer: Results from a Prospective Quality-of-Life Trial.

PURPOSE: To report prostate cancer outcomes, toxicity, and quality of life (QOL) in men treated with proton beam therapy (PBT). PATIENTS AND METHODS: Patients were enrolled in a prospective trial. All participants received 75.6 to 78 Gy (RBE). Up to 6 months of luteinizing hormone-releasing hormone agonist therapy was allowed. The Phoenix definition defined biochemical failure. Modified Radiation Therapy Oncology Group criteria defined toxicity. Expanded Prostate Cancer Index Composite questionnaires objectified QOL. Clinically significant QOL decrement was defined as ≥0.5 × baseline standard deviation. RESULTS: In total, 423 men were analyzed. The National Comprehensive Cancer Network risk classification was used (low 43%; intermediate 56%; high 1%). At the 5.2-year median follow-up, overall and disease-specific survival rates were 99.8% and 100%, respectively. Cumulative biochemical failure rate was 5.2% (95% confidence interval [CI] = 3.0%-8.3%); acute grade 2 genitourinary (GU) toxicity was 46.3%; acute grade 2 gastrointestinal (GI) toxicity was 5.0% (95% CI = 3.1%-7.3%). There was no acute grade ≥3 GI or GU toxicity. Cumulative late grade 2 GU and GI toxicity was 15.9% (95% CI = 13%-20%) and 9.7% (95% CI = 6.5%-12%), respectively. There were 2 grade 3 late GI toxicities (rectal bleeding) and no late grade ≥3 GU toxicity. The 4-year mean Expanded Prostate Cancer Index Composite urinary, bowel, sexual, and hormonal summary scores (range; standard deviation) were 89.7 (43.8-100; 11), 91.3 (41.1-94.6; 10), 57.8 (0.0-96.2; 27.1), and 92.2 (25-95.5; 10.5), respectively. Compared with baseline, there was no clinically significant decrement in urinary, sexual, or hormonal QOL after treatment completion. A modest (<10 points), yet clinically significant, decrement in bowel QOL was appreciated throughout follow-up. CONCLUSION: Contemporary PBT resulted in excellent biochemical control, minimal risk of higher-grade toxicity, and modest QOL decrement. Further investigation comparing PBT with alternative prostate cancer treatment strategies are warranted.

Impaired red blood cell deformability after transfusion of stored allogeneic blood but not autologous salvaged blood in cardiac surgery patients.

BACKGROUND: Both cardiopulmonary bypass (CPB) and red blood cell (RBC) storage are associated with detrimental changes in RBC structure and function that may adversely affect tissue oxygen delivery. We tested the hypothesis that in cardiac surgery patients, RBC deformability and aggregation are minimally affected by CPB with autologous salvaged blood alone but are negatively affected by the addition of stored allogeneic blood. METHODS: In this prospective cohort study, 32 patients undergoing cardiac surgery with CPB were divided into 3 groups by transfusion status: autologous salvaged RBCs alone (Auto; n = 12), autologous salvaged RBCs + minimal (<5 units) stored allogeneic RBCs (Auto+Allo min; n = 10), and autologous salvaged RBCs + moderate (≥5 units) stored allogeneic RBCs (Auto+Allo mod; n = 10). Ektacytometry was used to measure RBC elongation index (deformability) and critical shear stress (aggregation) before, during, and for 3 days after surgery. RESULTS: In the Auto group, RBC elongation index did not change significantly from the preoperative baseline. In the Auto+Allo min group, mean elongation index decreased from 32.31 ± 0.02 (baseline) to 30.47 ± 0.02 (nadir on postoperative day 1) (P = 0.003, representing a 6% change). In the Auto+Allo mod group, mean elongation index decreased from 32.7 ± 0.02 (baseline) to 28.14 ± 0.01 (nadir on postoperative day 1) (P = 0.0001, representing a 14% change). Deformability then dose-dependently recovered toward baseline over the first 3 postoperative days. Changes in aggregation were unrelated to transfusion (no difference among groups). For the 3 groups combined, mean critical shear stress decreased from 359 ± 174 mPa to 170 ± 141 mPa (P = 0.01, representing a 54% change), with the nadir at the end of surgery and returned to baseline by postoperative day 1. CONCLUSIONS: In cardiac surgery patients, transfusion with stored allogeneic RBCs, but not autologous salvaged RBCs, is associated with a decrease in RBC cell membrane deformability that is dose-dependent and may persist beyond 3 postoperative days. These findings suggest that autologous salvaged RBCs may be of higher quality than stored RBCs, since the latter are subject to the so-called storage lesions.

Allogeneic versus autologous blood transfusion and survival after radical prostatectomy.

BACKGROUND: Potential adverse effects of blood transfusion (BT) remain controversial, especially for clinical outcomes after curative cancer surgery. Some postulate that immune modulation after allogeneic BT predisposes to recurrence and death, but autologous superiority is not established. This study assessed whether BT is associated with long-term prostate cancer recurrence and survival with a large single-institutional radical prostatectomy (RP) database. STUDY DESIGN AND METHODS: Between 1994 and 2012, a total of 11,680 patients had RP with available outcome and transfusion data. A total of 7443 (64%) had complete covariate data. Clinical variables associated with biochemical recurrence-free survival (BRFS), cancer-specific survival (CSS), and overall survival (OS) were identified with Cox proportional hazards models for three groups: no BT (reference, 27.7%, n = 2061), autologous BT only (68.8%, n = 5124), and any allogeneic BT (with or without autologous, 3.5%, n = 258). RESULTS: Median (range) follow-up was 6 (1-18) years. Kaplan-Meier analysis showed significantly decreased OS (but not BRFS or PCSS) in the allogeneic group versus autologous and no BT groups (p = 0.006). With univariate analysis, any allogeneic BT had a hazard ratio (HR) of 2.29 (range, 1.52-3.46; p < 0.0001) for OS, whereas autologous BT was not significant (HR, 1.04 [range, 0.82-1.32], p = 0.752). In multivariable models, neither autologous nor allogeneic BT was independently associated with BRFS, CSS, or OS, and a dose response was not observed for allogeneic units and BRFS. CONCLUSION: Although allogeneic but not autologous BT was associated with decreased long-term OS, after adjustment for confounding clinical variables, BT was not independently associated with OS, BRFS, or CSS regardless of transfusion type. Notably, no association was observed between allogeneic BT and cancer recurrence. Observed differences in OS may reflect confounding.

Declining use of brachytherapy for the treatment of prostate cancer.

PURPOSE: To analyze the recent trends in the utilization of external beam radiation therapy (EBRT) and brachytherapy (BT) for the treatment of prostate cancer. METHODS AND MATERIALS: Using the Surveillance, Epidemiology, and End Results (SEER) database, information was obtained for all patients diagnosed with localized prostate adenocarcinoma between 2004 and 2009 who were treated with radiation as local therapy. We evaluated the utilization of BT, EBRT, and combination BT+EBRT by the year of diagnosis and performed a multivariable analysis to determine the predictors of BT as treatment choice. RESULTS: Between 2004 and 2009, EBRT monotherapy use increased from 55.8% to 62.0%, whereas all BT use correspondingly decreased from 44.2% to 38.0% (BT-only use decreased from 30.4% to 25.6%, whereas BT+EBRT use decreased from 13.8% to 12.3%). The decline of BT utilization differed by patient race, SEER registry, median county income, and National Comprehensive Cancer Network risk categorization (all p<0.001), but not by patient age (p=0.763) or marital status (p=0.193). Multivariable analysis found that age, race, marital status, SEER registry, median county income, and National Comprehensive Cancer Network risk category were independent predictors of BT as treatment choice (all p<0.001). Moreover, after controlling for all available patient and tumor characteristics, there was decreasing utilization of BT with increasing year of diagnosis (odds ratio for BT=0.920, 95% confidence interval: 0.911-0.929, p<0.001). CONCLUSIONS: Our analysis reveals decreasing utilization of BT for prostate cancer. This finding has significant implications in terms of national health care expenditure.

Improvement in prostate cancer survival over time: a 20-year analysis.

PURPOSE: This study aimed to evaluate the changes in outcome for men with localized prostate cancer treated with definitive external beam radiation therapy during a 20-year period at a comprehensive cancer center. METHODS: We categorized 2675 men with prostate cancer treated at MD Anderson Cancer Center with definitive external beam radiation therapy with or without androgen deprivation therapy into 3 treatment eras: 1987 to 1993 (n = 722), 1994 to 1999 (n = 828), and 2000 to 2007 (n = 1125). To help adjust for stage migration, patients were stratified according to risk group as defined by the National Comprehensive Cancer Network. Biochemical (Phoenix definition), local, distant, and any clinical failure, prostate-cancer specific survival, and overall survival were analyzed according to the Kaplan-Meier method. RESULTS: Median age was 68.5 years and median follow-up was 6.4 years. Fewer men in the most recent era had high-risk disease, and a higher proportion received 72 Gy or higher (99% vs 4%) and androgen deprivation therapy (60% vs 6%) than the earliest era. All risk groups treated in the modern era experienced improved rates of biochemical, local, and distant failure. In high-risk patients, decreased rates of distant failure and clinical failure led to improved prostate cancer-specific survival and overall survival. Local control was improved for intermediate- and high-risk patients, with a trend toward improvement in low-risk patients. On multivariate analysis, recent treatment era was closely correlated with a dose of 72 Gy or higher and treatment with androgen deprivation therapy and predicted for lower rates of biochemical, local, and distant failure. Androgen deprivation therapy, higher dose, and more recent treatment era predicted for improved prostate cancer-specific survival. DISCUSSION: During the last 20 years of prostate cancer irradiation, disease control outcomes have improved in all patients, leading to improved prostate cancer-specific survival and overall survival for men with high-risk disease. This may reflect advances in workup, staging accuracy, and prostate cancer treatment in the modern era.