scholarly journals EPCT-18. A TWO-PART, PHASE 1 STUDY OF RHENIUM-186 NANOLIPOSOME (186RNL) DELIVERED BY CONVECTION ENHANCED DELIVERY FOR RECURRENT, REFRACTORY, OR PROGRESSIVE EPENDYMOMA AND HIGH-GRADE GLIOMA (HGG) AND NEWLY DIAGNOSED DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i50-i51
Author(s):  
Ashley Plant ◽  
Stewart Goldman ◽  
Sandi Lam ◽  
Michael DeCuypere ◽  
Gregory Stein ◽  
...  
Keyword(s):  
Specific Activity ◽  
Phase 1 ◽  
High Specific Activity ◽  
External Beam Radiation ◽  
Central Component ◽  
Normal Brain ◽  
Newly Diagnosed ◽  
Convection Enhanced Delivery ◽  
Beam Radiation ◽  
Dose Limiting Toxicity

Abstract Ependymoma, HGG, and DIPG are gliomas that are often difficult to treat, frequently aggressive, and often carry an extremely poor prognosis. While external beam radiation therapy (EBRT) remains a central component of the management of pediatric gliomas, it is limited by tolerance of the surrounding normal brain tissue. Rhenium-186 NanoLiposome (186RNL) permits the selective delivery of beta-emitting radiation of high specific activity with excellent retention in the tumor. In a Phase 1 trial in adults with recurrent glioblastoma (NCT01906385), the mean absorbed dose to the tumor when coverage was 75% or greater (n=10) was 392 Gy (CI 306 – 478). Thus far, the therapy has been well tolerated, no dose-limiting toxicity has been observed, and no treatment-related serious adverse events have occurred despite markedly higher absorbed doses than typically delivered by EBRT (n=18). Methods This is a two-part, Phase 1 dose-finding study followed by an expansion cohort to explore efficacy. Part 1 will enroll up to 18 subjects to determine the maximum feasible dose (MFD) of 186RNL administered by convection enhanced delivery (CED). Tumor size will be limited to a diameter of 4 cm in the longest axis and a volume of 34 mL. The dose limiting toxicity period (DLT) is 28 days post infusion. Part 2 will independently evaluate 186RNL in 3 different cohorts: Cohort A: up to 12 subjects with a diagnosis of recurrent, refractory, or progressive ependymoma; Cohort B: up to 12 subjects with a diagnosis of recurrent, refractory, or progressive HGG; Cohort C: up to 15 subjects with newly diagnosed DIPG. The primary endpoint is overall response rate (ORR) by Radiographic Assessment in Pediatric Neuro-Oncology (RAPNO) criteria. Secondary endpoints are PFS-24 and OS-24 in Cohort A and PFS-12 and OS-12 in Cohorts B and C. Planned enrollment will begin in H2 2021.

CONVECTION-ENHANCED DELIVERY OF CINTREDEKIN BESUDOTOX (INTERLEUKIN-13-PE38QQR) FOLLOWED BY RADIATION THERAPY WITH AND WITHOUT TEMOZOLOMIDE IN NEWLY DIAGNOSED MALIGNANT GLIOMAS

Neurosurgery ◽  
2007 ◽  
Vol 61 (5) ◽  
pp. 1031-1038 ◽  
Author(s):  
Michael A. Vogelbaum ◽  
John H. Sampson ◽  
Sandeep Kunwar ◽  
Susan M. Chang ◽  
Mark Shaffrey ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Malignant Gliomas ◽  
External Beam Radiation ◽  
Newly Diagnosed ◽  
Convection Enhanced Delivery ◽  
Beam Radiation ◽  
Interleukin 13 ◽  
Grade 3 ◽  
Dose Limiting Toxicity ◽  
Final Cohort

Abstract OBJECTIVE Cintredekin besudotox (CB), a recombinant cytotoxin consisting of interleukin-13 and truncated Pseudomonas exotoxin, binds selectively to interleukin-13Rα2 receptors overexpressed by malignant gliomas. This study assessed the safety of CB administered by convection-enhanced delivery followed by standard external beam radiation therapy (EBRT) with or without temozolomide (Temodar; Schering-Plough, Kenilworth, NJ) in patients with newly diagnosed malignant gliomas. METHODS After gross total resection of the tumor, two to four intraparenchymal catheters were stereotactically placed and CB (0.25 or 0.5 μg/mL) was infused for 96 hours. This was followed, 10 to 14 days later, by EBRT (5940–6100 cGy, 5 d/wk for 6–7 wk) with or without temozolomide (75 mg/m2/d, 7 d/wk during EBRT). Safety was assessed during an 11-week observation period after catheter placement RESULTS Twenty-two patients (12 men, 10 women; median age, 55 yr; 21 with glioblastoma multiforme and one with an anaplastic mixed oligoastrocytoma) were enrolled. None of the patients experienced dose-limiting toxicities in the first two cohorts (0.25 μg/mL CB + EBRT [n = 3] and 0.25 μg/mL CB + EBRT + temozolomide [n = 3]). One patient experienced a dose-limiting toxicity (Grade 4 seizure) in the third cohort (0.5 μg/mL CB + EBRT [n = 6]). Six patients in the final cohort (0.5 μg/mL CB + EBRT + temozolomide [n = 10]) completed treatment, and one patient experienced a dose-limiting toxicity (Grade 3 aphasia and confusion). Four patients were not considered evaluable for a dose decision and were replaced. CB related adverse events occurring in more than one patient were fatigue, gait disturbance, nystagmus, and confusion. No Grade 3 to 4 hematological toxicities were observed. CONCLUSION CB (0.5 μg/mL) administered via convection-enhanced delivery before standard radiochemotherapy seems to be well tolerated in adults with newly diagnosed malignant gliomas. Further clinical study assessment is warranted.

scholarly journals RADT-24. HIGH ABSORBED DOSES OF RHENIUM-186 NANOLIPOSOMES (RNL) IN RECURRENT GBM: A PHASE 1 STUDY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii186-ii186
Author(s):  
Andrew Brenner ◽  
John Floyd ◽  
Ande Bao ◽  
William Phillips ◽  
Vibhudutta Awasthi ◽  
...  
Keyword(s):  
Phase 1 ◽  
High Specific Activity ◽  
Absorbed Dose ◽  
External Beam Radiation ◽  
Whole Body ◽  
Recurrent Glioma ◽  
Normal Brain ◽  
Beam Radiation ◽  
Absorbed Doses ◽  
The Mean

Abstract INTRODUCTION While external beam radiation therapy (EBRT) remains a central component of the management of primary brain tumors, it is limited by tolerance of the surrounding normal brain tissue. Nanoliposomal BMEDA-chelated-186Rhenium (RNL™) permits the delivery of beta-emitting radiation of high specific activity with excellent retention in the tumor. We report on the phase 1 results in recurrent glioma. METHODS A phase 1 dose-escalation study of RNL in recurrent glioma utilizing a standard 3 + 3 design was undertaken to determine the maximum tolerated dose of RNL following stereotactic biopsy. RNL is administered with the BrainLab Flexible Catheter by convection enhanced delivery (CED) with placement guided using iPlan Flow and the Varioguide system. Infusion is followed under whole body planar imaging and SPECT/CT. Repeat SPECT/CT imaging is performed immediately following, and at 1, 3, 5, and 8 days after RNL infustion to obtain dosimetry and distribution. RESULTS Thirteen patients have been treated to-date, 12 were recurrent glioblastoma, and 54% failed treatment with bevacizumab. The infused dose was progressively increased from 1.0 mCi to 13.4 mCi and the volume of infusate from 1.0 mL to 5.28 mL using 1 – 2 CED catheters. The mean absorbed dose to the distribution volume was 175 Gy (CI 97 – 254). The maximum absorbed dose to the tumor volume was 593 Gy. The mean retention of the administered dose at 24 hours was 61.4% (CI 45.4 – 77.5). The therapy has been well tolerated and no dose-limiting toxicity has been observed with no treatment related adverse effects despite markedly higher absorbed doses than EBRT in patients with prior treatment. The plan is to increase the dose to 22.3 mCi and the infusate volume to 8.8 mL. CONCLUSION Intratumoral RNL can deliver up to twenty times the absorbed dose of radiation administered by EBRT without significant toxicity.

Safety and feasibility of rhenium-186 nanoliposome (186RNL) in recurrent glioma: The ReSPECT phase 1 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2061-2061
Author(s):  
Andrew J. Brenner ◽  
Ande Bao ◽  
William Phillips ◽  
Gregory Stein ◽  
Vibhudutta Awasthi ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Tumor Volume ◽  
Phase 1 ◽  
Absorbed Dose ◽  
External Beam Radiation ◽  
Whole Body ◽  
Recurrent Glioma ◽  
Normal Brain ◽  
Beam Radiation ◽  
The Mean

2061 Background: While external beam radiation therapy (EBRT) remains a central component of the management of primary brain tumors, it is limited by tolerance of the surrounding normal brain tissue. Rhenium-186 NanoLiposome (186RNL) permits the delivery of beta-emitting radiation of high specific activity with excellent retention in the tumor. We report the results of the phase 1 study in recurrent glioma. Methods: A Phase 1 dose-escalation study of 186RNL in recurrent glioma utilizing a standard 3+3 design was undertaken to determine the maximum tolerated dose of 186RNL. 186RNL is administered by convection enhanced delivery (CED). Infusion is followed under whole body planar imaging and SPECT/CT. Repeat SPECT/CT imaging is performed immediately following, and at 1, 3, 5, and 8 days after 186RNL infusion to obtain dosimetry and distribution. Subjects were followed until disease progression by RANO criteria. Results: Eighteen subjects were treated across 6 cohorts. The mean tumor volume was 9.4 mL (range 1.1 – 23.4). The infused dose ranged from 1.0 mCi to 22.3 mCi and the volume of infusate ranged from 0.66 mL to 8.80 mL. From 1 – 4 CED catheters were used. The maximum catheter flow rate was 15 µl/min. The mean absorbed dose to the tumor volume was 239 Gy (CI 141 – 337; range 9 - 593), to normal brain was 0.72 Gy (CI 0.34 – 1.09; range 0.005 – 2.73), and to total body was 0.07 Gy (CI 0.04 – 0.10; range 0.001 – 0.23). The mean absorbed dose to the tumor volume when the percent tumor volume in the treatment volume was 75% or greater (n = 10) was 392 Gy (CI 306 – 478; range 143 – 593). Scalp discomfort and tenderness related to the surgical procedure did occur in 3 subjects. The therapy has been well tolerated, no dose-limiting toxicity has been observed, and no treatment-related serious adverse events have occurred despite markedly higher absorbed doses typically delivered by EBRT in patients with prior treatment. Responses have been observed supporting the clinical activity. Final results from the dose escalation will be presented. Conclusions: 186RNL administered by CED to patients with recurrent glioma results in a much higher absorbed dose of radiation to the tumor compared to EBRT without significant toxicity. The recommended Phase 2 dose is 22.3 mCi in 8.8 mL of infusate. Clinical trial information: NCT01906385. [Table: see text]

The Clinical Value of Radioembolization in the Treatment of Inoperable Liver Cancer

2009 ◽  
Vol 05 (01) ◽  
pp. 65
Author(s):  
Laura E Moreno-Luna ◽  
James C Andrews ◽  
Lewis R Roberts ◽  
◽  
◽  
...  
Keyword(s):  
Specific Activity ◽  
High Specific Activity ◽  
Liver Parenchyma ◽  
External Beam Radiation ◽  
Clinical Value ◽  
Beam Radiation ◽  
Vein Thrombosis ◽  
Selective Targeting ◽  
Iodine 131 ◽  
Radioactive Iodine 131

Hepatocellular carcinoma (HCC) is a common malignancy worldwide. HCC-related mortality is high because most cases are diagnosed at an advanced stage. HCCs are relatively resistant to radiation and the liver is unable to tolerate the radiation doses required to achieve tumoricidal effects by standard external-beam radiation. Focal radiation techniques employing a 3D approach have been shown to safely permit higher levels of radiation to targeted regions within the liver. Delivery of therapy through hepatic artery branches preferentially affects HCC tumors and spares the surrounding liver parenchyma. Selective targeting of radionuclides to tumors has been shown to achieve high radiation dose ratios. Transarterial radionuclide therapies have been developed with the objective of achieving selective intra-arterial delivery of radiotherapy, including radioactive iodine-131 (131I), rhenium-188 (188Re), yttrium-90 (90Y) (resin or glass microspheres), and others. These treatments have been used to treat HCC via a selective transarterial approach as an alternative to TACE. Portal vein thrombosis (PVT) is a relative contraindication to transarterial chemoembolization (TACE); in contrast, high specific activity radiomicrospheres do not occlude a significant portion of the hepatic arterial vascular bed and can therefore be used in patients with PVT. The devices, toxicities, and results with use of the available radioembolic devices are reviewed in this article.

A phase II trial of radiation and cetuximab followed by irinotecan/cetuximab for children with newly diagnosed diffuse pontine tumors and high-grade astrocytomas.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 10030-10030 ◽  
Author(s):  
Margaret Macy ◽  
Mark W. Kieran ◽  
Susan N. Chi ◽  
Kenneth J. Cohen ◽  
Tobey MacDonald ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Phase 1 ◽  
Progression Free Survival ◽  
External Beam Radiation ◽  
High Grade ◽  
Newly Diagnosed ◽  
Beam Radiation ◽  
Phase 2 Trial ◽  
Correlative Studies ◽  
Grade 3

10030 Background: Diffuse intrinsic pontine gliomas (DIPG) and high-grade astrocytomas (HGA) have dismal prognoses. We previously demonstrated in a phase 1 study that cetuximab and irinotecan was a safe and tolerable regimen. Consequently, we initiated this 2-strata phase 2 trial to investigate the safety and efficacy of weekly cetuximab given with involved field external beam radiation therapy followed by 10 cycles of cetuximab and irinotecan for DIPG and HGA as determined by the 1-year progression-free survival. Methods: Eligible patients aged 3-21 years with newly diagnosed HGA or DIPG were enrolled to parallel strata. All patients received radiation therapy (5940 cGy) with concurrent cetuximab at 250mg/m2 IV weekly for 6 weeks. Following radiation, patients received cetuximab (250mg/m2 IV) weekly and irinotecan (16mg/m2/day IV) daily x 5 for two weeks every 21 days for 30 weeks. Tumor, serum, and CSF samples were collected for correlative studies. Sera collected at the onset of rash were analyzed for inflammatory and immune-related cytokines. Results: Forty-eight patients (27 DIPG, 21 HGA) were enrolled and 45 were treated (median age 8 years; range: 3–19). Toxicities were manageable; the most common adverse events were fatigue, gastrointestinal complaints, neutropenia, rash, headache, electrolyte abnormalities, elevated ALT/AST, and fever. Grade 3-4 events in ≥10% of patients were hypokalemia and lymphopenia. 4 patients experienced cetuximab-related hypersensitivity reactions (2 grade 3 reactions). The median PFS was 9.5 months (95% CI: 7.0-12.2) for HGA and 7.8 months (7.0-8.6) for DIPG with a 1-year PFS±SE of 24±10% and 25%±10% respectively. The median OS for HGA was 17.7 months (95% CI: 14.1-18.0) and 11.5 months (8.8-14.2) for DIPG. Biological correlative studies will be presented. Conclusions: Cetuximab and radiation therapy followed by cetuximab and irinotecan is well tolerated in children. Based on the 1-year PFS, this regimen may deserve further investigation in patients with DIPG. Biological correlative studies will delineate the mechanisms of the rash and possible implications for EGFR-targeted therapeutics in such patients. Clinical trial information: NCT01012609.

scholarly journals DDRE-21. PNOC015: PHASE 1 STUDY OF MTX110 DELIVERED BY CONVECTION ENHANCED DELIVERY (CED) IN CHILDREN WITH NEWLY DIAGNOSED DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) PREVIOUSLY TREATED WITH RADIATION THERAPY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii66-ii66
Author(s):  
Sabine Mueller ◽  
Cassie Kline ◽  
Javier Villanueva-Meyer ◽  
Carly Hoffman ◽  
Shannon Raber ◽  
...  
Keyword(s):  
Phase 1 ◽  
Volume Ratio ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Newly Diagnosed ◽  
Convection Enhanced Delivery ◽  
Catheter Position ◽  
Pharmacodynamic Effects ◽  
Distribution Volume Ratio ◽  
Previously Treated ◽  
Grade 3

Abstract OBJECTIVE To determine safety and distribution of MTX110 delivered by CED in newly diagnosed DIPG patients. METHODS DIPG patients (3–21 years) were enrolled after radiation. CED of MTX110 combined with gadoteridol was completed based on dose levels (DL) (30–90 µM with volumes ranging from 3 cc (single dose) to 2 consecutive doses of 6 cc; total number of DL=7). Catheter position was chosen to maximize tumor coverage. Distribution of infusate was monitored with real-time MR imaging. Repeat CED was performed every 4–8 weeks if tolerated. Quality of life (QOL) assessments using PedsQL Generic Core and Brain Tumor modules were obtained at baseline (n=5), 3-months (n=3), and end of therapy (n=2). Single-cell RNA sequencing and analysis of histone modifications was performed to assess pharmacodynamic effects on DIPG cells. RESULTS Between May 2018-Dec 2019, 6 patients were enrolled (median age 8 years, range 5–21). Dose limiting toxicities included: grade 3 gait disturbance (DL7; cycle 1); grade 3 muscle weakness/vagus nerve disorder (DL5; cycle 4) and grade 2 intolerable dysphagia (DL7; cycle 4). Twelve CED procedures were completed at DL7 and repeated cycles ranged from 2 to 7. Infusion to distribution volume ratio was approximately 1:3.5. There were no significant changes in self-reported QOL. Parent ratings of patients’ worry (p = 0.04) and overall QOL (p = 0.03) significantly decreased at 3-months. CONCLUSION Repeat CED of MTX110 at the highest dose is tolerable. Tissue concentrations are likely to be substantially higher compared to oral dosing. Pharmacodynamic effects will be presented.

A phase II study of chemoradiation followed by adjuvant temozolomide and poly-ICLC in patients with newly diagnosed glioblastoma: 12- and 18-month survival data (NABTT 0501)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2002-2002
Author(s):  
M. R. Rosenfeld ◽  
M. Chamberlain ◽  
S. A. Grossman ◽  
D. M. Peereboom ◽  
G. J. Lesser ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adjuvant Treatment ◽  
Survival Data ◽  
Cell Activation ◽  
Killer Cell ◽  
External Beam Radiation ◽  
Newly Diagnosed ◽  
Beam Radiation ◽  
Entire Cohort ◽  
Newly Diagnosed Glioblastoma

2002 Background: Polyinosinic-polycytidylic (poly-ICLC), is a double-stranded RNA that stimulates a variety of host defense mechanisms including T-cell and natural killer cell activation, cytokine release and specific anti-proliferative and anti-viral effects. The objective of this study was to determine the safety and efficacy of poly-ICLC when added to adjuvant treatment for newly diagnosed glioblastoma. Methods: Newly diagnosed patients > 18 years with histologically proven glioblastoma received standard external beam radiation with concurrent low-dose temozolomide (TMZ) (75 mg/m2) followed by adjuvant cycles of TMZ for 5 days (150–200 mg/m2) (week 1) then intramuscular injections of poly-ICLC (20 mcg/kg) 3 times a week (weeks 2–8; total 21 injections) with week 9 off and no limit to the number of adjuvant cycles (TMZ + poly-ICLC). Imaging evaluations were performed before every cycle. Results: There were 97 patients enrolled (60 men); median age 56 yrs (range 21–85); median KPS 90 (range 60–100). Fourteen patients did not start adjuvant treatment (5 patient request and 4 investigator withdrawal; 2 progressive disease; 1 death; 1 toxicity; 1 other). The most frequent CTC grade 3–4 toxicities occurring in > 5% of subjects at least possibly related to poly-ICLC were leukopenia (20%), thrombocytopenia (14%), anemia (13%), neutropenia (10%), and SGPT (9%) or alkaline phosphatase (7%) elevation. Two deaths during adjuvant treatment were considered unlikely related to poly-ICLC. To date 71 of 97 patients have survived at least 12 months from diagnosis. The estimated median survival for the entire cohort was 17.2 months (95% CI: 15.5–19.3 months). Overall survival for the cohort at 12 months was 73.2% (95% CI: 63%-82%) and at 18 months 47.4% (95% CI: 37–58%). For only those subjects 18–70 years, overall survival at 18 months was 51.8% (95% CI: 41–63%). This is contrasted with EORTC 26981/22981 that reported an 18 month overall survival of 39.4% (95% CI: 33.8–45.1). Conclusions: The addition of poly-ICLC to a modified adjuvant treatment regimen for newly diagnosed GB is well-tolerated. Survival data at 12 and 18 months suggest increased efficacy compared to chemoradiation with adjuvant TMZ only. [Table: see text]

Disease-specific survival outcomes in lymph node–positive patients with prostate cancer treated with radiotherapy.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 182-182 ◽  
Author(s):  
G. Crehange ◽  
V. K. Weinberg ◽  
A. Izaguirre ◽  
C. C. Hsu ◽  
I. J. Hsu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Disease Free Survival ◽  
External Beam Radiation ◽  
Survival Outcomes ◽  
Primary Therapy ◽  
Newly Diagnosed ◽  
Beam Radiation ◽  
Androgen Ablation ◽  
Disease Free

182 Background: Involvement of regional lymph nodes (LN+) at the time of prostate cancer (PCa) diagnosis is widely regarded as an adverse prognostic factor associated with poor outcome. No commonly utilized treatment, composed of any combination of androgen ablation, surgery and radiation, has proven to be superior for survival. This study will evaluate the clinical survival outcomes of patients (pts) with newly diagnosed LN+ PCa at the University of California San Francisco (UCSF). Methods: All newly diagnosed LN+ PCa pts treated with External Beam Radiation Therapy (EBRT) as primary therapy or after surgery, each with and without androgen ablation between 1987 and 2009 were included. All pts had confirmed pathologic or radiologic LN+ whereas none had evidence of metastases on the work up. Cause Specific Survival (CSS), Disease Free survival (DFS) and biochemical control were measured from the start of treatment. PSA failure was determined by the Phoenix definition after EBRT and by a confirmed PSA >1 ng/mL following RP+EBRT. Results: A retrospective analysis identified 91 pts with LN+ at the time of diagnosis (75.8% high risk pts) with disease follow-up. Thirty-four (37%) were managed with exclusive EBRT alone (eRT), 18 pts (20%) with a combination of radical prostatectomy (RP) and adjuvant EBRT (RP+aRT) and 39 pts (43%) were treated with a combination of RP + salvage RT (RP+sRT). Overall 78% of patients also received hormone therapy (HT): 74.0% with eRT, 89% with RP+aRT and 79% with RP+sRT. The 10 years CSS estimates was 89% for eRT, 0% after RP+aRT and 88% after RP+sRT. The 10 years DFS estimates was 33% for eRT, 0% after RP+aRT and 75% after RP+sRT. Among pts remaining disease free the median follow-up is 38 mos for eRT, 26 mos for RP+aRT and 64 mos for RP+sRT. The last PSA for these patients was <0.1 for 85% of all patients which included 47% following eRT, 100% after RP+aRT and 97% after RP+sRT. There were 7 deaths due to PCa occurring between 5 and 73 mos from the start of EBRT. Conclusions: The results of the current analysis indicate that some pts with LN+ from PCa have prolonged disease free outcomes; and for these men, aggressive treatment may be appropriate. No significant financial relationships to disclose.

scholarly journals The relationship between overactive bladder and prostate cancer: A scoping review

2021 ◽  
Vol 15 (9) ◽  
Author(s):  
Asher Khan ◽  
R. Trafford Crump ◽  
Kevin V. Carlson ◽  
Richard J. Baverstock
Keyword(s):  
Prostate Cancer ◽  
General Population ◽  
Overactive Bladder ◽  
External Beam Radiation ◽  
Treatment Modalities ◽  
Inverse Association ◽  
Newly Diagnosed ◽  
Beam Radiation ◽  
Pre Treatment ◽  
The Relationship

Introduction: The relationship between prostate cancer (PCa) and overactive bladder (OAB) is poorly understood. PCa and OAB are frequently diagnosed in elderly populations, so it could be expected that both conditions would be observed in older patients. Whether PCa and OAB occur independently with age, or the presence of PCa leads to the onset of OAB/lower urinary tract symptoms (LUTS) has not been explored. This review aimed to investigate whether men newly diagnosed with prostate cancer (PCa) are more likely to have overactive bladder (OAB) compared to the general population, and if the various treatment modalities for PCa are likely to impact the incidence or exacerbation of OAB. Methods: The University of Calgary’s databases for Medline and PubMed were searched for relevant publications. No restrictions were placed on the study design reported. Any publications reporting OAB and a PCa diagnosis and/or observation relating to PCa diagnosis and rates of OAB/LUTS in an adult population were included for full review. Results: Of the studies examining the relationship between PCa and LUTS, results varied, but frequently indicated an inverse association between PCa and LUTS in which patients newly diagnosed with prostate cancer were more unlikely to have LUTS compared to the general population. Following treatment, brachytherapy resulted in a higher prevalence of OAB symptoms compared to surgical treatment and external beam radiation therapy. Conclusions: Diverse evidence was found regarding the relationship between the prevalence of pre-treatment OAB and PCa diagnosis. However, limited evidence, as well as uncertainty regarding pre-treatment symptoms and their impact on post-treatment outcomes, restricts potential conclusions.

Establishing the Standard of Care for Patients with Newly Diagnosed and Recurrent Glioblastoma

2012 ◽  
pp. 112-117
Author(s):  
Mark R. Gilbert
Keyword(s):  
Signal Transduction ◽  
Tumor Resection ◽  
Standard Of Care ◽  
Recurrent Glioblastoma ◽  
External Beam Radiation ◽  
Standards Of Care ◽  
Successful Implementation ◽  
Newly Diagnosed ◽  
Current Standard ◽  
Beam Radiation

Overview: The current standard of care for patients with newly diagnosed glioblastoma includes maximal safe tumor resection followed by concurrent external-beam radiation with daily low-dose temozolomide followed by 6 to 12 months of adjuvant temozolomide, typically by using a cycle of 5 consecutive days out of 28. Efforts to improve on these results from the European Organisation for Research and Treatment of Cancer (EORTC)/National Cancer Institute of Canada (NCIC) trial using either dose-dense chemotherapy strategies or combinations with signal transduction modulators have, to date, been unsuccessful. Two large international randomized trials examining the efficacy of adding bevacizumab, an antiangiogenic agent, to the standard treatment have been completed, with expectations of results within in the next 2 years. For recurrent glioblastoma, there are no firmly established standards of care. Although intracavitary insertion of carmustine-impregnated polymers has been approved by the U.S. Food and Drug Administration (FDA), this strategy is not widely used. Bevacizumab has been FDA approved for recurrent glioblastoma, but no randomized trial has clearly demonstrated a survival benefit. Alternative dosing schedules of temozolomide (i.e., metronomic) has modest activity even in patients with prior temozolomide exposure. Clinical trials testing small-molecule signal transduction modulators have been disappointing, although most report a small response rate, suggesting that molecularly definable tumor subpopulations may help guide treatment decisions. Successful implementation of marker-based treatment would lead to personalized care and the creation of individualized standards of care.

Sign in / Sign up

Export Citation Format

Share Document