Need For Salvage Therapy Research Articles

Recent Trends and Effectiveness of Antiretroviral Regimens Among Men Who Have Sex With Men Living With HIV in the United States: The Multicenter AIDS Cohort Study (MACS) 2008-2017.

ObjectiveWe evaluated trends and population effectiveness (tolerability, HIV suppression) of current combination antiretroviral therapy (cART) regimens mindful of treatment guidelines.MethodTrend analyses included 18 017 person-visits (1457 men) on cART during 2008–2017 in the Multicenter AIDS Cohort Study. Effectiveness analyses of current regimens used 3598 person-visit–pairs (745 men) on cART in 2014–2017. Inverse-probability-of-treatment-and-censoring weighted Poisson regression with robust variances was used to evaluate the association between regimens and switching, adherence and HIV RNA <20 copies/mL.ResultsIntegrase strand transfer inhibitor (INSTI)-based regimen usage has increased since 2008. Almost 90% of cART initiators started with INSTI-cART in 2016–2017; cART adherence was stable around 90% and 83%–85% suppressed virus (<20 cp/mL). Commonly used regimens in 2014–2017 contained disoproxil fumarate/emtricitabine (TDF/FTC) backbone with efavirenz (EFV, n = 1161 person-visits), elvitegravir/cobicistat (EVG/c, n = 551), rilpivirine (RPV, n = 492), darunavir/ritonavir (DRV/r, n = 351), or atazanavir (ATV)/r (n = 333). Others were dolutegravir/abacavir/lamivudine (DTG/ABC/3TC, n = 401) and EVG/c/tenofovir alafenamide/FTC (EVG/c/TAF/FTC, n = 309). Compared to EFV/TDF/FTC users, ATV/r+TDF/FTC users switched more (rate ratio [RR] = 1.80, 95% confidence interval (CI), 1.17–2.76), while those on DTG/ABC/3TC (RR [95% CI] = 0.16 [0.08–0.31]) or EVG/c/TAF/FTC (RR [95% CI] = 0.12 [0.06–0.27]) switched less. The rate of suppressed HIV RNA was 15% (95% CI, 2%–26%) lower among younger EVG/c/TDF/FTC users and 18% (95% CI, 3%–34%) higher in older DRV/r+TDF/FTC users; adherence did not differ by regimen.ConclusionsConsistent with guidelines, recent cART initiators started with INSTI-cART, which was associated with less switching early after initiation. Factors beyond those studied here, such as need for salvage therapy, unique personal characteristics, drug interactions, and cost may influence treatment decisions.

Hodgkin’s Lymphoma: Analysis Results of Volgograd Regional Registry

Background. The present paper discusses feasibility of first-and second-line therapies as well as the significance of different risk factors in the population of all patients with newly diagnosed Hodgkin's lymphomas (HL) in a 14-year period based on the data of Volgograd regional registry. Materials &amp; Methods. During the period 2003 to 2017 the population registry of Department of Hematology of Volgograd Regional Clinical Oncology Dispensary included the data of all the patients with newly diagnosed HL (n = 622): 272 (44 %) men and 350 (56 %) women aged 18 to 84 years (mean age 38 years, median age 33 years). There were 97 (16 %) patients with early stages and without risk factors, 165 (27 %) patients with early stages and risk factors, 360 (59 %) patients with advanced stages, 308 (50 %) patients with toxic symptoms (stage B), and 179 (29 %) patients with bulky tumor lesions (&gt; 10 cm). ABVD treatment regimen was administered in 190 (30.5 %) patients, in-creased-dose BEACO(D)PP in 39 (6 %) patients, BEACO(D) PP-14 in 159 (26 %) patients, standard BEACO(D)PP in 200 (32 %) patients, IVDG in 25 (4 %) patients, and other regimens in 9 (1.5 %) patients. The second-line treatment was administered in 120 (19 %) out of 622 patients. By the end of August 2018, the number of followed-up patients was 514 (83 %), 108 (17 %) patients had died. The prognostic value of the International Prognostic Score (IPS), PET, and other factors was assessed by means of Cox's multivariate regression analysis. Pharmacoeconomic analysis of differences between options of first-line therapy was based on Markov model. Results. In the group of patients with advanced HL stages treated with escalated BEACO(D)PP (the increased-dose regimen and BEACO(D)PP-14) 5- and 10-year overall survival (OS) was 83 % and 74 %, respectively, OS median was not reached. On standard BEACO(D)PP patients with advanced HL stages had OS median of 139 months (11.6 years) and 5-and 10-year OS of 68 % and 54 %, respectively (p = 0,012). In the group of patients with early stages and poor prognosis treated with escalated regimens BEACO(D)PP 5- and 10-year OS was 100 % and 90 %, respectively, in the combined group treated with ABVD and standard BEACO(D)PP it was 83 % and 75 % (p = 0.035). Replacement of procarbazine with dacarbazine in the standard and increased-dose BEACOPP regimens did not affect treatment efficacy. Markov analysis demonstrated the advantages of the escalated regimens for treatment of early stages with poor prognosis and advanced stages in terms of life years gained. Out of 7 IPS factors male sex, age &gt; 45 years, hemoglobin &lt; 105 g/L, and albumin &lt; 40 mg/L significantly impacted OS. Based on these data an adjusted prognostic index was suggested. Conclusion. The advantage of the escalated strategy of first-line therapy in HL is reflected in survival parameters and is based on pharmacoeconomic evidence. The significance of some laboratory IPS risk factors can be reviewed; most obvious is increasing importance of PET for predicting the need for salvage therapy.

Risk stratifying in real life.

Risk stratifying in real life.

Stereotactic Radiosurgery in the Management of Limited (1-4) Brain Metasteses: Systematic Review and International Stereotactic Radiosurgery Society Practice Guideline.

Guidelines regarding stereotactic radiosurgery (SRS) for brain metastases are missing recently published evidence. To conduct a systematic review and provide an objective summary of publications regarding SRS in managing patients with 1 to 4 brain metastases. Using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was conducted using PubMed and Medline up to November 2016. A separate search was conducted for SRS for larger brain metastases. Twenty-seven prospective studies, critical reviews, meta-analyses, and published consensus guidelines were reviewed. Four key points came from these studies. First, there is no detriment to survival by withholding whole brain radiation (WBRT) in the upfront management of brain metastases with SRS. Second, while SRS on its own provides a high rate of local control (LC), WBRT may provide further increase in LC. Next, WBRT does provide distant brain control with less need for salvage therapy. Finally, the addition of WBRT does affect neurocognitive function and quality of life more than SRS alone. For larger brain metastases, surgical resection should be considered, especially when factoring lower LC with single-session radiosurgery. There is emerging data showing good LC and/or decreased toxicity with multisession radiosurgery. A number of well-conducted prospective and meta-analyses studies demonstrate good LC, without compromising survival, using SRS alone for patients with a limited number of brain metastases. Some also demonstrated less impact on neurocognitive function with SRS alone. Practice guidelines were developed using these data with International Stereotactic Radiosurgery Society consensus.

Hyaluronic acid formulation of near infrared fluorophores optimizes surgical imaging in a prostate tumor xenograft

The presence of positive surgical margins confers an increased risk of biochemical relapse and need for salvage therapy in men undergoing radical prostatectomy. Image-guided surgery using near-infrared (NIR) fluorescent contrast agents is a potential method to detect remaining cancerous tissue. The objective of this study was to evaluate three hyaluronic acid (HA) nanoparticle (NP) formulations loaded with NIR fluorophore for their ability to contrast-enhance prostate cancer. HA was modified by conjugation with the hydrophobic ligand, aminopropyl-1-pyrenebutanamide to drive nanoparticle self-assembly. Indocyanine green (ICG) was physicochemically entrapped in the HA-NP, termed NanoICG. Alternatively, Cy7.5 was directly conjugated to amphiphilic HA, termed NanoCy7.5. NanoCy7.5 was synthesized with two HA molecular weights to determine the HA size contribution to delivery to PC3 prostate tumor xenografts. Contrast-enhancement of the tumors and relative biodistribution were assessed by a series of fluorescence imaging, image-guided surgery with spectroscopy, and microscopic techniques. Intravenously administered NanoICG improved tumor signal-to-noise ratio (SNR) at 24 h over ICG by 2.9-fold. NanoCy7.5 with 10 kDa and 100 kDa HA improved tumor SNR by 6.6- and 3.1-fold over Cy7.5 alone, respectively. The PC3 xenograft was clearly identified with the image-guided system providing increased contrast enhancement compared to surrounding tissue for NanoICG and NanoCy7.5 with 10 kDa HA. NIR fluorescence microscopy showed that Cy7.5 in NPs with 10 kDa HA were distributed throughout the tumor, while NanoCy7.5 with 100 kDa HA or NanoICG delivered dye mainly to the edge of the tumor. CD31 staining suggested that PC3 tumors are poorly vascularized. These studies demonstrate the efficacy of a panel of HA-derived NPs in identifying prostate tumors in vivo, and suggest that by tuning the structural properties of these NPs, optimized delivery can be achieved to poorly vascularized tumors. Statement of SignificanceWe have demonstrated the potential of a panel of near-infrared fluorescent (NIRF) nanoparticles (NPs) for image-guided surgery in a prostate cancer xenograft model. Image-guided surgery and imaging of organs ex vivo showed greater tumor signal and contrast when mice were administered NIRF dyes that were covalently conjugated to (NanoCy7.510k-PBA) or physicochemically entrapped in (NanoICGPBA) hyaluronic acid (HA) NPs, compared to free dyes. These results show the potential to use these NPs as tools to detect the margins of tumors and to differentiate healthy and tumor tissue intraoperatively. Moreover, this project provides insight into selecting optimal formulation strategies for poorly vascularized tumors.

MP34-15 PROSTATE CANCER QUALITY OF CARE DISPARITIES AND THEIR IMPACT ON PATIENT OUTCOMES

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History II1 Apr 2018MP34-15 PROSTATE CANCER QUALITY OF CARE DISPARITIES AND THEIR IMPACT ON PATIENT OUTCOMES Keith Lawson, Katherine Daignault, Olli Saarela, Robert Abouassaly, and Antonio Finelli Keith LawsonKeith Lawson More articles by this author , Katherine DaignaultKatherine Daignault More articles by this author , Olli SaarelaOlli Saarela More articles by this author , Robert AbouassalyRobert Abouassaly More articles by this author , and Antonio FinelliAntonio Finelli More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1107AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The ability to rigorously measure disparities in care that drive poor patient outcomes is essential for developing effective strategies for quality improvement. As real-world case-mix adjusted quality variations have yet to be reported in prostate cancer, our objective was to apply a data-driven analytical framework to determine the validity of expert-defined quality indicators (QIs) in order to reveal true disparities in prostate cancer care and their impact on patient outcomes. METHODS Hospital-level quality of care was assessed according to 10 published, expert-defined QIs utilizing data derived from the United States National Cancer Database (NCDB). Case-mix adjusted hospital benchmarking was performed using indirect standardization methodology and multivariable regression models as previously described by our group [1]. In a training set of hospitals, a composite measure of hospital quality, the Prostate Cancer Quality Score (PC-QS), was derived from those individual QIs that discriminated hospital performance in a manner associated with poor patient outcomes; including the need for salvage therapy, initiation of androgen deprivation therapy, 30- and 90-day mortality, and overall mortality. Subsequently, associations between the PC-QS and hospital volume, academic affiliation, and patient outcomes (as above) were determined in a separate validation set of hospitals. RESULTS Collectively, data from over 1100 hospitals were analyzed, with widespread variation observed across all QIs. In the training set, between 3-36% of hospitals were identified as poor outliers compared to the national average level of care for a given QI. Based on associations between outlier status and the aforementioned patient outcomes, 5 individual QIs were incorporated into the PC-QS. In the validation set, lower PC-QS hospitals displayed smaller referral volumes and were less likely to be academic hospitals than those with higher PC-QS (p < 0.001). Higher PC-QS was associated with lower rates of salvage therapy, ADT initiation and 30-day mortality (adjusted hazard ratio [confidence interval]: 0.85 [0.79-0.91], 0.94 [0.91-0.98], adjusted odds ratio 0.92 [0.87-0.97] per PC-QS unit increase, respectively). CONCLUSIONS Data-driven benchmarking of hospital-level quality performance reveals the widespread disparities that exist in prostate cancer care. This data supports the use of our novel PC-QS composite metric as a benchmarking tool for quality improvement. 1. Lawson KA et. al. Eur Urol 2017; 72: 379-386. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e443 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Keith Lawson More articles by this author Katherine Daignault More articles by this author Olli Saarela More articles by this author Robert Abouassaly More articles by this author Antonio Finelli More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

A core outcome set for localised prostate cancer effectiveness trials.

To develop a core outcome set (COS) applicable for effectiveness trials of all interventions for localised prostate cancer. Many treatments exist for localised prostate cancer, although it is unclear which offers the optimal therapeutic ratio; which is confounded by inconsistencies in the selection, definition, measurement and reporting of outcomes in clinical trials. A list of 79 outcomes was derived from a systematic review of published localised prostate cancer effectiveness studies and semi-structured interviews with 15 patients with prostate cancer patients. A two-stage consensus process involving 118 patients and 56 international healthcare professionals (HCPs; cancer specialist nurses, urological surgeons and oncologists) was undertaken, consisting of a three-round Delphi survey followed by a face-to-face consensus panel meeting of 13 HCPs and eight patients. The final COS included 19 outcomes. In all, 12 apply to all interventions: death from prostate cancer, death from any cause, local disease recurrence, distant disease recurrence/metastases, disease progression, need for salvage therapy, overall quality of life, stress urinary incontinence, urinary function, bowel function, faecal incontinence, and sexual function. Seven were intervention-specific: perioperative deaths (surgery), positive surgical margin (surgery), thromboembolic disease (surgery), bothersome or symptomatic urethral or anastomotic stricture (surgery), need for curative treatment (active surveillance), treatment failure (ablative therapy), and side-effects of hormonal therapy (hormone therapy). The UK-centric participants may limit the generalisability to other countries, but trialists should reason why the COS would not be applicable. The default position should not be that a COS developed in one country will automatically not be applicable elsewhere. We have established a COS for trials of effectiveness in localised prostate cancer, applicable across all interventions that should be measured in all localised prostate cancer effectiveness trials.

Phase 2 Randomized Trial Comparing Standard RCHOP Versus Brcap (bortezomib, rituximab, cyclophosphamide, adriamycin and prednisone) As First Line Treatment in Young Patients with High-Risk Diffuse Large B-Cell Lymphoma (DLBCL). a Study from Spanish Group Geltamo

Phase 2 Randomized Trial Comparing Standard RCHOP Versus Brcap (bortezomib, rituximab, cyclophosphamide, adriamycin and prednisone) As First Line Treatment in Young Patients with High-Risk Diffuse Large B-Cell Lymphoma (DLBCL). a Study from Spanish Group Geltamo

Corticosteroid Dosing in Pediatric Acute Severe Ulcerative Colitis: A Propensity Score Analysis.

We aimed to explore the optimal dosing of intravenous-corticosteroids (IVCS) using a robust statistical method on the largest pediatric cohort of acute severe colitis to date. Two hundred eighty-three children treated with IVCS for ulcerative colitis were included and studied for 1 year (46% boys, age 12.1 ± 3.9 years, disease duration 2 (interquartile range [IQR] 0-14) months, baseline Pediatric Ulcerative Colitis Activity Index 69 ± 13 points). Confounding by indication was addressed by matching high- and low-IVCS dose patients according to the propensity score method, using 3 cutoffs (1 mg · kg · methylprednisolone to 40 mg · day, 1.25 mg · kg to 50 mg · day and 2 mg · kg to 80 mg · day). The median IVCS dose in the entire cohort was 1.0 mg · kg · day (IQR 0.8-1.4) and 44 mg · kg · day (32-60). Ninety-four of 283 children were matched in the low-dose cutoff (1 mg · kg · day), 218 of 283 were matched in the middle cutoff (1.25 mg · kg · day), and 86/283 in the high dose cutoff (2 mg · kg · day). No differences were found in 25 pretreatment baseline variables in the three cutoffs, implying successful matching. There were no statistical differences in the outcomes of the two lower cutoffs (including need for salvage therapy during admission and by 1 years, admission duration, and day-5 Pediatric Ulcerative Colitis Activity Index<35 points; all P > 0.05). In the high cutoff, the higher doses were somewhat better but this benefit reversed in a sensitivity analysis excluding one center. High doses were not associated with better outcome also in a propensity score-weighted regression model on the entire cohort. Our data support present guidelines that doses of IVCS >1 to 1.5 mg · kg · day (maximum 40-60 mg · kg · day) are not justified in acute severe colitis.

The use of a segmental endoscopic score may improve the prediction of clinical outcomes in acute severe ulcerative colitis.

Acute severe colitis (ASC) remains a challenging complication of ulcerative colitis. The early identification of patients who will not respond to optimal therapy is warranted. Increasing evidence suggests that endoscopy may play a role in predicting important outcomes in acute severe colitis. The endoscopic activity of consecutive patients with acute severe colitis was evaluated using the Mayo endoscopic sub-score (Mayo) and the ulcerative colitis endoscopic index of severity (UCEIS). Two segmental indexes were also produced by summing the scores of the rectum and sigmoid (seg-Mayo and seg-UCEIS, respectively). Endpoints included the need for salvage therapy with infliximab or cyclosporine, refractoriness to corticosteroids, and colectomy. Of one hundred and eight patients enrolled in the study, 60 (55.6%) were male; with a median age of 34.5 years (range 15-80). All patients received intravenous steroids. Fifty-nine patients (55.6%) showed an incomplete or absent response to steroids, 35 patients (34.3%) received salvage therapy with infliximab or cyclosporine and 38 patients (33.3%) were colectomized during the index hospitalization or within the first year of follow-up. All scores were able to predict the need for surgery, but only the seg-UCEIS significantly predicted refractoriness to steroids. There was a strong correlation between endoscopic severity and unfavorable outcomes. The UCEIS outperformed the Mayo endoscopic sub-score in all important outcomes. Segmental scoring further improved the performance of the UCEIS.

Efficacy and toxicity profile of pegylated liposomal doxorubicin in patients with advanced ovarian cancer.

The prognosis of patients with non-platinum-sensitive recurrent ovarian cancer is poor. There is a need for salvage therapies with anti-tumor activity and acceptable toxicity for maintaining quality of life. Pegylated liposomal doxorubicin (PLD, Caelyx(®)) is a promising drug fulfilling these demands. We present retrospective data of patients with advanced epithelial ovarian cancer (EOC) who were treated with pegylated liposomal doxorubicin at the University of Heidelberg between 2007 and 2009. Eligible patients for this retrospective study had advanced ovarian cancer and were treated in a palliative setting with PLD at the university hospital of Heidelberg, Germany. Primary objectives were toxicity and efficacy of PLD. 34 patients were included in this study between November 2007 and December 2009; one patient received PLD twice as palliative treatment. The median age of the 34 patients enrolled in this study was 59.9years (range 27-77years). The median weight of the patients was 69kg (range 47-109kg), the median height 164cm (range 140-176cm). Pegylated liposomal doxorubicin was administered every 4weeks with a dosage of 40mg/m(2) body surface. PLD was administered for three cycles in median (range 1-9 cycles). Dose reduction was necessary in only four patients. In our study time to progression and overall survival was 8.74 and 14.23months. In conclusion, this retrospective study showed the efficacy and low toxicity of pegylated liposomal doxorubicin in patients with advanced EOC. Further observations are needed to confirm these preliminary experiences on a larger number of patients.

Determining the Optimal Management of Patients With Limited-Brain Metastases: A Cost Analysis Approach

Multiple radiation therapy treatment options exist for patients with limited (1-3) brain metastases including stereotactic radiosurgery (SRS) with or without whole-brain radiation therapy (WBRT). The natural history, treatment patterns, and cancer-related costs for these patients were analyzed to determine the benefit, if any, of WBRT in the modern era. From 2011-2013, 144 patients were treated with primary SRS, and 22 patients were treated with SRS+WBRT for limited-brain metastasis, at the discretion of the treating physician. A retrospective review was performed of the patient records for determination of clinical outcomes and patterns of failure. Cost analyses were performed using detailed institutional cost data captured by the cancer institute during inpatient and outpatient hospital encounters, including direct and indirect diagnosis-related costs. Survival times were calculated using the Kaplan-Meier method from date of initial radiation procedure. The median age at brain metastasis diagnosis for all patients was 63.5 years, the median KPS was 80, and the median time from diagnosis of the patient's primary disease to brain metastasis was 6.1 months. The 1-year overall survival and distant brain recurrence-free survival were 46% and 50% for patients treated with primary SRS, and 26% and 70% for those treated with SRS+WBRT, respectively (P=.14 and .09). Of the patients treated with primary SRS, 35 (24%) underwent an additional SRS session, 10 (7%) underwent ≥ 2 SRS sessions, and 15 (10%) patients were treated with salvage WBRT at the time of each intracranial relapse. Eight patients (6%) treated with primary SRS and 3 patients (14%) treated with SRS+WBRT were diagnosed with radiation necrosis. Neurologic death occurred in 19 patients (13%) treated with SRS and 6 (27%) treated with SRS+WBRT. The median total cost of care for all patients was $81,142 (R: $8,649 - $429,912): $84,501 for those undergoing primary SRS over a median of 31 clinical encounters and $54,033 ($12,828 - $226,426) over a median of 20 clinical encounters for those undergoing SRS+WBRT (P=.16). The median total cost of care per month survival was similar between the two groups ($10,356 SRS vs $10,285 GKS+WBRT, P=.74). Although patients with limited-brain metastases are at increased risk for distant intracranial failure without upfront WBRT, primary SRS provides comparable local control, risk of neurologic death, and overall survival with a lower risk of treatment-related toxicity. Even when accounting for additional close monitoring, more frequent imaging, and need for salvage therapies for patients undergoing primary GKS, the cost of care per month and overall cost of care remain comparable between single modality and multi-modality radiation treatments.

PD47-11 PREDICTORS OF QUALITY OF LIFE IN MEN WITH LOCALIZED PROSTATE CANCER: THE ROLE OF TREATMENT DECISION MAKING SATISFACTION, NEUROTICISM, AND SEXUAL FUNCTIONING

pathology. In the present study, our objective was to determine if MetS is associated with adverse final pathology and risk of treatment failure in men undergoing radical prostatectomy (RP). METHODS: Patients undergoing RP (2004-2013) were identified using our prospectively maintained institutional database. Salvage RPs and men who received neoadjuvant therapies were excluded. MetS required any 3 of 5 components (obesity, diabetes or impaired fasting glucose, hypertension, low HDL-cholesterol, and high triglycerides). The outcomes were PC grade and stage on final RP pathology, and RP treatment failure, defined by a post-RP serum PSA 0.2, or use of salvage therapies such as radiation or androgen deprivation therapy (patients were censored if adjuvant radiation was given). Multivariable logistic regression, Kaplan-Meier analyses, and Cox-proportional Hazards models were used. RESULTS: Of final cohort of 1939 men, 439 (22.6%) had MetS. Median follow up was 36 months. On RP pathology, there were 1321 (68.1%) with Gleason 7 disease, 113 (5.8%) with Gleason 8-10 disease, and 663 (34.2%) men with extraprostatic disease ( pT3). Increasing number of MetS components was associated with a progressively increasing probability of higher grade (p-trend1⁄40.002) and higher stage (p-trend1⁄40.02) disease. In multivariable logistic regression analyses, MetS was associated with an increased risk of Gleason 8-10 disease ( 3 vs. 0 components: OR1⁄42.51, 95%CI1⁄41.33-4.71, p1⁄40.004) and extraprostatic disease ( 3 vs. 0 components: OR1⁄41.36, 95%CI1⁄41.02-1.81, p1⁄40.04). Decreased use of nerve-sparing in men with MetS was noted, suggestingmoreaggressive resection. Inunadjustedanalyses,MetSwas associated with an increased risk of need for salvage therapy (HR1⁄41.38, 95%CI1⁄41.04-1.83, p1⁄40.03). These associations were attenuated upon adjusting for stage and grade, suggesting these parameters are driving the associations. Overall probability of RP failure was similar between men with and without MetS (5-yr failure-free survival: 71.4% vs. 75.5%). CONCLUSIONS: MetS is associated with an increased risk of harbouring extraprostatic and high-grade disease on final RP pathology (with a biological gradient present), which appears to drive an increased risk of needing salvage therapy after RP. However, with more aggressive resection, similar failure-free outcomes can be achieved in wellselected patients.

Seven Year Followup for Bystander Vaccine Therapy in Mantle Cell Lymphoma (MCL)

Background:A Phase I study revealed that vaccination of cancer patients with irradiated autologous tumor cells and GM.CD40L bystander cells (engineered to secrete GM-CSF and express CD40L) is safe, recruits/activates dendritic cells, and elicits tumor-specific T cell responses. We report final results using this vaccine strategy in patients with MCL, an aggressive and incurable B-cell malignancy.Methods:After lymph node resection for autologous tumor harvest, 4-6 cycles of chemotherapy, and restaging (CT, endoscopy, bone marrow biopsy), patients with usable vaccine who achieved a PR or CR lasting 1 month were vaccinated x4 at 28-day intervals with IL-2 (0.5 x 106 U SC BID x 14 d/cycle). Patients were monitored for toxicity, tumor response, tumor-specific immune responses, and median EFS/OS.Results:43 were enrolled, including 21 with relapsed MCL, 20 with int/high MIPI, and 6 with blastoid MCL. Twenty never received vaccine: 2 withdrew, 1 progressed prior to nodal harvest, 7 had insufficient or contaminated specimens, and 10 progressed/died during chemotherapy. The unvaccinated were older (68.4y vs 62.8y; p=.026) but otherwise did not differ significantly by stage, LDH, MIPI, de novo status, or number of prior treatments.Among 23 treated, 10 had relapsed disease (median of 3 prior therapies), 10 had an int/high MIPI, and 2 had blastoid MCL. Pre-vaccination response following chemotherapy included 7 CR, 15 PR, and 1 SD. At 6 months after vaccination, 2 pts in PR had resolution of MRD within the bone marrow, 10 progressed (including 3 who progressed after 1-2 vaccines), and 11 had no change. Grade 3 toxicities were observed in three patients, and consisted of leukocytosis, neutropenia, and cough, none of which were attributed to vaccination. One patient remains in CR at 84 mo. A second who relapsed at 64mo remains without need for salvage therapy at 82 mo, suggestive of more indolent relapse post vaccination. Median EFS and OS are calculated from receipt of first vaccine. Median EFS is 9 mo, and median OS is 101 mo (median follow-up 81 mo).DTH was not observed. Biopsy of vaccine sites revealed lymphocytic response in 62%, however, this was not correlated with EFS or OS. Increased IFN gamma post vaccination was observed in 76%, and accompanied by an increase in EFS (p=.06). Increased GMCSF post vaccination was observed in 89%, with a trend for improved survival among those with higher peak levels.Conclusions:Extended follow up continues to show a sustained benefit in regards to overall survival for patients with de novo (85% alive at 81 months) and relapsed MCL (median OS 25 months), and support therefore the need for further studies of vaccination strategies in the context of new immunotherapeutic agents that are improving the outcomes of MCL patients. [Display omitted] DisclosuresShah:Seattle Genetics, Inc.: Research Funding; NCCN: Consultancy; Celgene: Consultancy, Speakers Bureau; SWOG: Consultancy; Pharmacyclics: Consultancy; Janssen: Consultancy. Off Label Use: SGN-CD19A is an investigational agent being studied in patients with B-cell malignancies. SGN-CD19A is not approved for use. .

Cost-effectiveness of stereotactic radiosurgery with and without whole-brain radiotherapy for the treatment of newly diagnosed brain metastases.

Stereotactic radiosurgery (SRS) alone is increasingly used in patients with newly diagnosed brain metastases. Stereotactic radiosurgery used together with whole-brain radiotherapy (WBRT) reduces intracranial failure rates, but this combination also causes greater neurocognitive toxicity and does not improve survival. Critics of SRS alone contend that deferring WBRT results in an increased need for salvage therapy and in higher costs. The authors compared the cost-effectiveness of treatment with SRS alone, SRS and WBRT (SRS+WBRT), and surgery followed by SRS (S+SRS) at the authors' institution. The authors retrospectively reviewed the medical records of 289 patients in whom brain metastases were newly diagnosed and who were treated between May 2001 and December 2007. Overall survival curves were plotted using the Kaplan-Meier method. Multivariate proportional hazards analysis (MVA) was used to identify factors associated with overall survival. Survival data were complete for 96.2% of patients, and comprehensive data on the resource use for imaging, hospitalizations, and salvage therapies were available from the medical records. Treatment costs included the cost of initial and all salvage therapies for brain metastases, hospitalizations, management of complications, and imaging. They were computed on the basis of the 2007 Medicare fee schedule from a payer perspective. Average treatment cost and average cost per month of median survival were compared. Sensitivity analysis was performed to examine the impact of variations in key cost variables. No significant differences in overall survival were observed among patients treated with SRS alone, SRS+WBRT, or S+SRS with respective median survival of 9.8, 7.4, and 10.6 months. The MVA detected a significant association of overall survival with female sex, Karnofsky Performance Scale (KPS) score, primary tumor control, absence of extracranial metastases, and number of brain metastases. Salvage therapy was required in 43% of SRS-alone and 26% of SRS+WBRT patients (p < 0.009). Despite an increased need for salvage therapy, the average cost per month of median survival was $2412 per month for SRS alone, $3220 per month for SRS+WBRT, and $4360 per month for S+SRS (p < 0.03). Compared with SRS+WBRT, SRS alone had an average incremental cost savings of $110 per patient. Sensitivity analysis confirmed that the average treatment cost of SRS alone remained less than or was comparable to SRS+WBRT over a wide range of costs and treatment efficacies. Despite an increased need for salvage therapy, patients with newly diagnosed brain metastases treated with SRS alone have similar overall survival and receive more cost-effective care than those treated with SRS+WBRT. Compared with SRS+WBRT, initial management with SRS alone does not result in a higher average cost.

Adjuvant radiation therapy, local recurrence, and the need for salvage therapy in atypical meningioma.

The impact of adjuvant radiation in patients with atypical meningioma remains poorly defined. We sought to determine the impact of adjuvant radiation therapy in this population. We identified 91 patients with World Health Organization grade II (atypical) meningioma managed at Dana-Farber/Brigham and Women's Cancer Center between 1997 and 2011. A propensity score model incorporating age at diagnosis, gender, Karnofsky performance status, tumor location, tumor size, reason for diagnosis, and era of treatment was constructed using logistic regression for the outcome of receipt versus nonreceipt of radiation therapy. Propensity scores were then used as continuous covariates in a Cox proportional hazards model to determine the adjusted impact of adjuvant radiation therapy on both local recurrence and the combined endpoint of use of salvage therapy and death due to progressive meningioma. The median follow-up in patients without recurrent disease was 4.9 years. After adjustment for pertinent confounding variables, radiation therapy was associated with decreased local recurrence in those undergoing gross total resection (hazard ratio, 0.25; 95% CI, 0.07-0.96; P = .04). No differences in overall survival were seen in patients who did and did not receive radiation therapy. Patients who have had a gross total resection of an atypical meningioma should be considered for adjuvant radiation therapy given the improvement in local control. Multicenter, prospective trials are required to definitively evaluate the potential impact of radiation therapy on survival in patients with atypical meningioma.

938 POST-CHEMOTHERAPY RESPONSE ASSESSED WITH COMPUTED TOMOGRAPHIC VOLUMETRIC ANALYSIS OF LYMPH-NODE METASTASIS IN NON-SEMINOMATOUS GERM CELL TUMORS

You have accessJournal of UrologyPenis/Testis/Urethra: Benign & Malignant Disease (III)1 Apr 2013938 POST-CHEMOTHERAPY RESPONSE ASSESSED WITH COMPUTED TOMOGRAPHIC VOLUMETRIC ANALYSIS OF LYMPH-NODE METASTASIS IN NON-SEMINOMATOUS GERM CELL TUMORS Carlos Basilio-de Leo, Carolina Culebro-García, Christian Villeda-Sandoval, Francisco Rodríguez-Covarrubias, Mariano Sotomayor-de Zavaleta, Guillermo Feria-Bernal, and Ricardo Castillejos-Molina Carlos Basilio-de LeoCarlos Basilio-de Leo México, D.F, Mexico More articles by this author , Carolina Culebro-GarcíaCarolina Culebro-García México, D.F, Mexico More articles by this author , Christian Villeda-SandovalChristian Villeda-Sandoval México, D.F, Mexico More articles by this author , Francisco Rodríguez-CovarrubiasFrancisco Rodríguez-Covarrubias México, D.F, Mexico More articles by this author , Mariano Sotomayor-de ZavaletaMariano Sotomayor-de Zavaleta México, D.F, Mexico More articles by this author , Guillermo Feria-BernalGuillermo Feria-Bernal México, D.F, Mexico More articles by this author , and Ricardo Castillejos-MolinaRicardo Castillejos-Molina México, D.F, Mexico More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.517AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Computed Tomography (CT) scan is the standard method for evaluation of retroperitoneal lymph node invasion for non-seminomatous germ cell tumors (NSGCT). RECIST criteria and volumetric analysis are used for some solid tumors, but never been evaluated for testicular tumor and lymph node metastasis. The purpose of this study is to evaluate volumetric assessment and RECIST criteria as new methodologies for follow-up in patients treated with chemotherapy for NSGCTs metastatic to retroperitoneal lymph nodes. METHODS Retrospective single center analysis of a testicular tumor database. Patients with the diagnosis of NSGCTs and retroperitoneal lymph node metastases were selected. We included patients who received chemotherapy (BEP) and had serial CT scans before and after treatment. Lymph nodes detected were measured in a venous contrast-phase. Volumetric analysis and RECIST criteria were used to calculate response rates, we proposed and used new cut-off values classification and also those proposed by RECIST. A correlation between volumetric and RECIST criteria with histological and clinical variables was calculated. RESULTS Seventeen patients met the inclusion criteria. The histologic distribution of primary tumor components was: 70% embryonic carcinoma, 47% teratoma and 47% seminoma. The mean baseline volume of retroperitoneal metastases was 439cc (range 5.3-5965 cc), and the mean volume post-chemotherapy was 30cc (range 0-193 cc). The response rate for all retroperitoneal metastases was 68% (range −57.3% to 100%). According to RECIST criteria the mean baseline diameter was 4.83cc (range 1.5-18.5 cc), and the mean diameter post-chemotherapy was 2.6cc (range 0-6.01 cc). The response rate by RECIST for all retroperitoneal metastasis was 43.02% (range −20% to 100%). Post-chemotherapy residual mass correlated in both classifications with teratoma (volumetric p=0.019, RECIST p=0.006); the response rate was associated with the need of a second treatment (lymphadenectomy [p= 0.027]). We propose a volumetric classification for chemotherapy response: this classification correlates with the need of further treatment (p=0.049), RECIST criteria did not have such correlation. CONCLUSIONS There are no previous studies evaluating and classifying the response rate of lymph node metastases after chemotherapy in NSGCT. RECIST criteria and volumetric analysis are adequate methods for assessing response. Our classification showed a correlation with the need of salvage therapy after failure to chemotherapy. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e386 Peer Review Report Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Carlos Basilio-de Leo México, D.F, Mexico More articles by this author Carolina Culebro-García México, D.F, Mexico More articles by this author Christian Villeda-Sandoval México, D.F, Mexico More articles by this author Francisco Rodríguez-Covarrubias México, D.F, Mexico More articles by this author Mariano Sotomayor-de Zavaleta México, D.F, Mexico More articles by this author Guillermo Feria-Bernal México, D.F, Mexico More articles by this author Ricardo Castillejos-Molina México, D.F, Mexico More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Single application of high‐intensity focused ultrasound as a first‐line therapy for clinically localized prostate cancer: 5‐year outcomes

Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? High-intensity focused ultrasound (HIFU) therapy has been proposed for the treatment of localized prostate cancer (PCa) for all risk levels of tumour recurrence. The study adds data on the efficacy of a single HIFU application in the treatment of PCa with different risks of recurrence. Durable cancer control was achieved in 81.7% of patients with low-risk disease, with rates of efficacy declining in intermediate- and high-risk tumours. The data suggest that the principal domain for minimal invasive HIFU should be low-risk disease. • To report cancer control results after a single application of high-intensity focused ultrasonography (HIFU) in patients with localized prostate cancer (PCa), stratified by tumour recurrence risk according to D'Amico risk classification. • In a retrospective single-centre study, we analysed the outcomes of patients with localized PCa who were treated with curative intent between December 2002 and October 2006 using an Ablatherm HIFU device (EDAP-TMS, France). • Transurethral resection of the prostate or adenomectomy were performed before HIFU to downsize large prostate glands. • Oncological failure was determined by the occurrence of biochemical relapse, positive biopsy and/or metastasis. Biochemical relapse was defined as a PSA nadir +1.2 ng/mL (Stuttgart definition), or as a rise in PSA level to ≥ 0.5 ng/mL if PSA doubling time was ≤ 6 months. Kaplan-Meier analysis was performed for survival estimates. • A total of 191 consecutive patients were included in the study. The median (range) patient age was 69.7 (51-82) years, and 38, 34 and 28% of these patients were in the low-, intermediate- and high-risk groups, respectively. • The median (range) follow-up was 52.8 (0.2-79.8) months. • At 5 years, overall and cancer-specific survival rates were 86.3% and 98.4%, respectively. • Stratified by risk group, negative biopsy rates were 84.2%, 63.6%, and 67.5% (P = 0.032), 5-year biochemical-free survival rates were 84.8%, 64.9% and 54.9% (P< 0.01), and 5-year disease-free survival rates were 81.7%, 53.2% and 51.2% (P < 0.01), respectively. • Single-session HIFU is recommended as a curative approach in elderly patients with low-risk PCa. Patients at higher risk of tumour progression should be counselled regarding the likely need for salvage therapy, including repeat HIFU.

Differentiation of lethal and non lethal prostate cancer: PSA and PSA isoforms and kinetics

Prostate-specific antigen (PSA) testing for the early diagnosis of prostate cancer has led to a decrease in cancer mortality. However, the high prevalence of low-grade prostate cancer and its long natural history, competing causes of death in older men and treatment patterns of prostate cancer, have led to dramatic overtreatment of the disease. Improved markers of prostate cancer lethality are needed to reduce the overtreatment of prostate cancer that leads to a reduced quality of life without extending life for a high proportion of men. The PSA level prior to treatment is routinely used in multivariable models to predict prostate cancer aggressiveness. PSA isoforms and PSA kinetics have been associated with more aggressive phenotypes, but are not routinely employed as part of prediction tools prior to treatment. PSA kinetics is a valuable marker of lethality post treatment and routinely used in determining the need for salvage therapy.

Reply to M.C. Chamberlain

regard to the safety of HA-WBRT, previous work by Gondi et al 4 evaluating 1,133 metastases in 371 patients revealed perihippocampal lesions in 8.6% of patients. Moreover, only 4.5% of patients who developed intracranial progression in Radiation Therapy Oncology Group trial RTOG 0933 progressed in the hippocampal-avoidance area. 2 Therefore, for the vast majority of patients undergoing WBRT, HA would be associated with a low risk of compromising intracranial disease control. Next, patients with a good performance status (Karnofsky performance status 70) and favorable long-term prognosis would likely benefit most from this technique and were specifically enrolled onto this trial. As a result of advancements in imaging techniques, better availability of and access to health care resources, and improvement in systemic therapies, we suspect that the proportions of these patients with favorable risk will continue to increase. Another concern raised addresses the role of HA-WBRT in the current era of stereotactic radiosurgery (SRS) given that focal therapies are quickly becoming the primary and adjuvant treatment of choice for patients with brain metastases. The updated National Cancer Center Network 2015 guidelines recommend either WBRT or SRS alone as primary treatment options for patients with multiple lesions ( 3 lesions). Despite the increasing adoption of primary SRS, randomized phase III trials have clearly demonstrated that the addition of WBRT improves local control and distant brain failure, minimizes the need for salvage therapies, and most importantly, decreases neurologic death. 5 Therefore, HA-WBRT may offer an attractive alternative treatment, especially in patients with a high probability of distant intracranial failure, with a reduced risk for neurocognitive deterioration. Over time, cooperative group trials in patients with brain metastases have transitioned from evaluating survival as the primary end point to focus on neurocognitive metrics. This was clearly fueled by additional analyses of the trials by Chang et al 6 and Kocher et al, 7 which demonstrated a decline in the Hopkin’s Verbal Learning TestRevised results and cognitive functioning, respectively, in patients who underwent WBRT. To compare their work with the previous research in this domain, Gondi et al 2 specifically evaluated a change in results measured by the Hopkin’s Verbal Learning Test-Revised as the primary end point for RTOG 0933. This decision was also supported by previous research by Li et al 8 who determined that memory function, unlike other neurocognitive domains, continued to decline after WBRT despite tumor shrinkage. Although a more complete battery of tests would be interesting to analyze, choosing the specific test that has been uniquely linked to neurocognitive deterioration after WBRT and used in previous studies has the advantage of being feasible and practical for study. Ultimately, the discovery of a reliable biomarker that correlates with neurocognitive functioning would allow survival to also be a recognized end point in future trials. In the current era of value-based care, cost-effectiveness studies are clearly needed when multiple treatment options exist. 9 In one of the few studies on this topic, Lal et al 10 used the economic data from the trial by Chang et al 6 to demonstrate the cost effectiveness and cost utility of primary SRS with observation when compared with SRS with WBRT. Although SRS with observation was associated with a higher cost, it was also associated with a higher effectiveness and cost effectiveness, even when considering additional salvage therapies, with a gain of cost per life-year well within the standards for other medical therapies. As more experience and economic data are generated in association with HA-WBRT, similar types of analyses will generate useful comparative data. In all, given the scrutiny on costs, future trials