Bladder Dose-Volume Parameters Are Associated with Urinary Incontinence After Post-operative Intensity-Modulated Radiation Therapy for Prostate Cancer

Publication date: Available online 19 December 2015
Source:Practical Radiation Oncology
Author(s): Christina H. Son, James Melotek, Chuanhong Liao, Greg Hubert, Charles A. Pelizzari, Scott E. Eggener, Stanley L. Liauw
PurposeUrinary incontinence is a potential side-effect of prostatectomy and intensity modulated radiation therapy (IMRT) for prostate cancer. There are limited data on dosimetric parameters that may predict for poor continence recovery in men who receive post-operative IMRT.Materials and MethodsEighty-seven men with non-metastatic prostate cancer who underwent prostatectomy followed by adjuvant (13%) or salvage (87%) IMRT were identified. The Expanded Prostate Cancer Index composite (EPIC) questionnaire was prospectively collected at baseline, 6 weeks, and 6, 12, 18, 24, 36, and 48 months post-IMRT. Relevant critical structures were contoured and dose-volume metrics collected. The primary endpoint was urinary continence global score. Longitudinal analysis using a generalized estimating equation model was performed.ResultsThere was no statistically significant change in EPIC urinary continence global scores over time as compared to baseline (all p>0.05). In univariate analysis, bladder V70Gy and penile bulb V70Gy were associated with urinary continence (OR 0.82, p<0.05). In a multivariable model that included body mass index, distance between vesicourethral junction and genitourinary diaphragm, time from surgery, use of anti-hypertensive medications, age, diabetes, and bladder V70Gy, only bladder V70Gy (OR 0.82, p=0.03) was associated with outcome. After 2 years, there was a significant difference in global score for those with V70Gy < 42.27 vs. ≥ 42.27 cc (all p<0.05 at 2 and 3 years post-IMRT).ConclusionThere was no significant change in patient-reported urinary continence scores after post-prostatectomy IMRT. Bladder V70Gy was independently associated with a decrease in urinary continence scores. Further evaluation is necessary to optimize quality of life in these men.



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Acute Gastrointestinal Toxicity and Bowel Bag Dose-Volume Parameters for Pre-Operative Radiotherapy for Retroperitoneal Sarcoma

Publication date: Available online 19 December 2015
Source:Practical Radiation Oncology
Author(s): Kimberley S. Mak, John G. Phillips, Constance M. Barysauskas, Leslie K. Lee, Edward G. Mannarino, Liam Van Benthuysen, Chandrajit P. Raut, John T. Mullen, Mark Fairweather, Thomas F. DeLaney, Elizabeth H. Baldini
PurposeAcute gastrointestinal (GI) toxicity has been studied in GI and gynecological (GYN) cancers, with V15<830 cc, V25<650 cc, and V45<195 cc identified as dose constraints for the peritoneal space [bowel bag (BB)]. There are no reported constraints derived from retroperitoneal sarcoma (RPS), and prospective trials for RPS have adopted some of the GI and GYN constraints. This study quantified GI toxicity during pre-operative RT for RPS, assessed toxicity using published constraints, and evaluated predictors for toxicity.Methods and MaterialsFrom 2003-2013, 56 patients with RPS underwent pre-operative RT at two institutions. Toxicity was scored using Radiation Therapy Oncology Group (RTOG) criteria for upper and lower acute GI toxicity. BB was contoured on planning CT scans per RTOG atlas guidelines with review by a radiologist. Relationships between toxicity, clinical factors and BB dose were analyzed.ResultsThree patients (5%) developed Grade ≥3 acute GI toxicity: two Grade 3 toxicities (anorexia and nausea) and one Grade 5 toxicity (tumor-bowel fistula). Thirty-six patients (64%) had Grade 2 toxicity (nausea, 55%; diarrhea, 23%; pain, 20%).Tumor size was the only significant clinical predictor of Grade ≥2 acute GI toxicity. Larger mean BB volumes predicted for Grade ≥2 toxicity (p=0.001). On ROC analysis, V30 was the best discriminator for toxicity (p=0.0001). Median BB V15 was 1,375 cc; 75% of patients had V15 ≥830 cc. Median V25 was 1,083 cc; 68% had V25 ≥650 cc. Median V45 was 575 cc; 82% had V45 ≥195 cc. V25 ≥650 cc was significantly associated with Grade ≥2 toxicity (p=0.01).ConclusionsAmong patients treated with pre-operative RT for RPS, significant acute GI toxicity was very low despite BB dose exceeding established constraints for most cases. Acceptable dose constraints for RPS may be higher than those for GI or GYN cancers. Further assessment of dose-volume constraints for RPS is needed.



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Angiotensin system inhibitors and survival in patients with metastatic renal cell carcinoma treated with VEGF targeted therapy: A pooled secondary analysis of clinical trials

Abstract

Use of angiotensin system inhibitors (ASIs; angiotensin receptor blockers or angiotensin converting enzyme inhibitors) have been reported to be associated with improved survival in metastatic renal cell carcinoma (mRCC), particularly when used with vascular endothelial growth factor targeted therapies. This study was a secondary pooled analysis of two Phase-III randomized controlled trials (RCTs) of patients with mRCC: NCT00334282 comparing pazopanib to placebo, and NCT00720941 comparing pazopanib to sunitinib. ASI users were defined as patients using an ASI at baseline. Association with overall survival (OS; primary outcome) and progression-free survival (PFS) was evaluated using Cox proportional hazards regression. The association was adjusted in multivariable analysis for baseline systolic blood pressure (SBP), use of other antihypertensive drugs, and prognostic factors comprising the Heng risk criteria for mRCC. Of 1,545 patients pooled from the two RCTs, 649 (42%) were using one or more antihypertensive drugs at baseline, 385 (59%) of which were using an ASI. In the multivariable analysis of patients using pazopanib or sunitinib, no significant association was observed between baseline ASI use and OS (hazard ratio [HR] 0.97 [95% confidence interval (CI); 0.80 – 1.18], P=0.80), or PFS (HR 0.88 [95% CI 0.73 – 1.06], P=0.17). Exploratory subgroup analysis of NCT00720941 highlighted that the effect of baseline ASI use on OS may differ between patients treated with sunitinib and pazopanib. In conclusion, use of ASIs at baseline was not a significant independent prognostic factor for improved survival in a pooled analysis of mRCC patients treated with pazopanib or sunitinib. This article is protected by copyright. All rights reserved.

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Vandetanib as a potential new treatment for estrogen receptor-negative breast cancers

Abstract

The receptor tyrosine kinase RET is implicated in the progression of luminal breast cancers (BC) but its role in estrogen receptor (ER) negative tumors is unknown. Here we investigated the expression of RET in breast cancer patients tumors and patient-derived xenografts (PDX) and evaluated the therapeutic potential of Vandetanib, a tyrosin kinase inhibitor with strong activity against RET, EGFR and VEGFR2, in ER negative breast cancer PDX.

The RT-PCR analysis of RET expression in breast tumors of 446 patients and 57 PDX, showed elevated levels of RET in ER+ and HER2+ subtypes and in a small subgroup of triple-negative breast cancers (TNBC). The activity of Vandetanib was tested in vivo in three PDX models of TNBC and one model of HER2+ BC with different expression levels of RET and EGFR. Vandetanib induced tumor regression in PDX models with high expression of RET or EGFR. The effect was associated with inhibition of RET/EGFR phosphorylation and MAP kinase pathway and increased necrosis. In a PDX model with no expression of RET nor EGFR, Vandetanib slowed tumor growth without inducing tumor regression. In addition, treatment by Vandetanib decreased expression of murine Vegf receptors and the endothelial marker Cd31 in the four PDX models tested, suggesting inhibition of tumor vascularisation.

In summary, these preclinical results suggest that Vandetanib treatment could be useful for patients with ER negative breast cancers overexpressing Vandetanib's main targets. This article is protected by copyright. All rights reserved. © 2014 Wiley Periodicals, Inc.

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Plasma Hyaluronic Acid level as a Prognostic and Monitoring Marker of Metastatic Breast Cancer

Abstract

Conventional tumor markers have limited value for prognostication and treatment monitoring in metastatic breast cancer (MBC) patients and novel circulating tumor markers therefore need to be explored. Hyaluronic acid (HA) is a major macropolysaccharide in the extracellular matrix and is reported to be associated with tumor progression. In our study, we investigated plasma HA level with respect to progression free survival (PFS) and overall survival (OS), as well as the treatment monitoring value in MBC patients. The prognostic value of plasma HA level was investigated in a discovery cohort of 212 MBC patients with 2.5-year follow-up and validated in an independent validation cohort of 334 patients with 5-year follow-up. The treatment monitoring value of plasma HA level was investigated in 61 MBC patients from discovery cohort who had been radiographically examined after 1^st complete cycle of chemo therapy. We found a robust association between high plasma HA level and poor prognosis of MBC patients in both discovery (p_PFS = 7.92 × 10⁻⁶ and p_OS = 5.27 × 10⁻⁵) and validation studies (p_PFS = 3.66 × 10⁻⁴ andp_OS = 1.43 × 10⁻⁴). In the discovery cohort, the plasma HA level displayed independent prognostic value after adjusted for age and clinicopathological factors, with respect to PFS and OS. Further, the decrease of plasma HA level displayed good concordance with treatment response evaluated by radiographic examination (AUC=0.79). Plasma HA level displays prognostic value, as well as treatment monitoring value for MBC patients. This article is protected by copyright. All rights reserved.

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Progression of HPV infection to detectable cervical lesions or clearance in adult women: Analysis of the control arm of the VIVIANE study

Abstract

The control arm of the phase III VIVIANE (Human PapillomaVIrus: Vaccine Immunogenicity ANd Efficacy; NCT00294047) study in women >25 years was studied to assess risk of progression from cervical HPV infection to detectable cervical intraepithelial neoplasia (CIN) . The risk of detecting CIN associated with the same HPV type as the reference infection was analysed using Kaplan-Meier and multivariable Cox models. Infections were categorised depending upon persistence as 6-month persistent infection (6MPI) or infection of any duration. The 4-year interim analysis included 2838 women, of whom 1073 (37.8%) experienced 2615 infections of any duration and 708 (24.9%) experienced 1130 6MPIs. Infection with oncogenic HPV types significantly increased the risk of detecting CIN grade 2 or greater (CIN2+) versus non-oncogenic types. For 6MPI, the highest risk was associated with HPV-33 (hazard ratio [HR]: 31.9 [8.3-122.2, p<0.0001]). The next highest risk was with HPV-16 (21.1 [6.3-70.0], p<0.0001). Similar findings were seen for infections of any duration. Significant risk was also observed for HPV-18, HPV-31 and HPV-45. Concomitant HPV infection or CIN grade 1 or greater associated with a different oncogenic HPV type increased risk. Most women (79.3%) with an HPV infection at baseline cleared detectable infections of any duration, and 69.9% cleared a 6MPI. The risk of progression of HPV infection to CIN2+ in women >25 years in this study was similar to that in women 15-25 years in PATRICIA. This article is protected by copyright. All rights reserved.

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Associations between unprocessed red and processed meat, poultry, seafood and egg intake and the risk of prostate cancer: A pooled analysis of 15 prospective cohort studies

Abstract

Reports relating meat intake to prostate cancer risk are inconsistent. Associations between these dietary factors and prostate cancer were examined in a consortium of 15 cohort studies. During follow-up, 52,683 incident prostate cancer cases, including 4,924 advanced cases, were identified among 842, 149 men. Cox proportional hazard models were used to calculate study-specific relative risks (RR) and then pooled using random effects models. Results do not support a substantial effect of total red, unprocessed red and processed meat for all prostate cancer outcomes, except for a modest positive association for tumors identified as advanced stage at diagnosis (advanced(r)). For seafood, no substantial effect was observed for prostate cancer regardless of stage or grade. Poultry intake was inversely associated with risk of advanced and fatal cancers (pooled multivariable RR [MVRR], 95% confidence interval, comparing ≥45 vs. <5 g/d: advanced 0.83, 0.70-0.99; trend test p-value 0.29), fatal, 0.69, 0.59-0.82, trend test p-value 0.16). Participants who ate ≥25 vs <5 g/d of eggs (1 egg ∼ 50 g) had a significant 14% increased risk of advanced and fatal cancers (MVRR: advanced 1.14, 1.01-1.28, trend test p-value 0.01; fatal 1.14, 1.00-1.30, trend test p-value 0.01). When associations were analyzed separately by geographical region (North America vs. other continents), positive associations between unprocessed red meat and egg intake, and inverse associations between poultry intake and advanced, advanced(r) and fatal cancers were limited to North American studies. However, differences were only statistically significant for eggs. Observed differences in associations by geographical region warrant further investigation. This article is protected by copyright. All rights reserved.

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