Predictors Of Disease Response Research Articles

High-intensity Focused Ultrasound (HIFU) as salvage therapy for radio-recurrent prostate cancer: predictors of disease response.

ABSTRACTBackgroundSome men with localized radio-recurrent prostate cancer may benefit from salvage high-intensity focused ultrasound (HIFU). Herein, we describe oncologic outcomes and predictors of disease response after salvage whole gland HIFU from our prospective cohort.Materials and MethodsPatients with localized radio-recurrent prostate cancer were prospectively enrolled from January 2005 to December 2014. Participants had to meet both biochemical and histological definitions of recurrence. Exclusion criteria included the receipt of prior salvage therapy, presence of metastatic disease, and administration of ADT in the 6-months prior to enrollment. Participants were treated with a single session of whole-gland HIFU ablation with the AblathermTM device (EDAP, France). The primary endpoint was recurrence-free survival (RFS), defined as a composite endpoint of PSA progression (Phoenix criteria), receipt of any further salvage therapy, receipt of ADT, clinical progression, or death. Kaplan-Meier survival analysis was used to determine the primary end-point and stratifications were used to determine the significance of 6 pre-specified predictors of improved RFS (TRUS biopsy grade, number of study entry TRUS biopsy cores positive, palpable disease at study enrollment, pre-HIFU PSA, an undetectable post-HIFU PSA nadir, and receipt of prior hormone therapy). Survival analysis was performed on participants with a minimum of 1-year follow-up.ResultsTwenty-four participants were eligible for study inclusion with a median follow-up of 31.0 months. Median PSA at study entry was 4.02ng/ml. Median time to PSA nadir was 3 months after treatment and median post-HIFU PSA nadir was 0.04ng/ml. Median 2-year and 5-year RFS was 66.3% and 51.6% respectively. Of our 6 prespecified predictors, an undetectable PSA nadir was the only significant predictor of improved RFS (HR 0.07, 95% CI 0.02-0.29, log-rank P<0.001). One participant underwent an intervention for a urethral stricture. No participants developed osteitis pubis or rectourethral fistulae.ConclusionsSalvage HIFU allows for disease control in selected patients with localized radio-recurrent prostate cancer. An undetectable PSA nadir serves as an early predictor of disease response.

The Clinical Value of FDG-PET/MRI in Treatment Planning and as a Predictor of Disease Response in High–Dose Rate Interstitial Brachytherapy for Locally Advanced Gynecologic Malignancies

The Clinical Value of FDG-PET/MRI in Treatment Planning and as a Predictor of Disease Response in High–Dose Rate Interstitial Brachytherapy for Locally Advanced Gynecologic Malignancies

High-intensity focused ultrasound (HIFU) as salvage therapy for radio-recurrent prostate cancer: Predictors of disease response.

135 Background: Some patients with localized radio-recurrent prostate cancer (PCa) may have long-term recurrence-free (RFS) survival with salvage high-intensity focused ultrasound (HIFU). In this study, we describe our previously unreported oncologic outcomes and predictors of disease response after salvage HIFU. Methods: Participants were prospectively enrolled in this study from January 2005 to December 2014 if they had localized radio-recurrent prostate cancer. Participants had to meet both biochemical (PSA nadir+ 2ng/ml) and histologic (positive biopsy) definitions of recurrence. Study exclusion criteria included the receipt of prior salvage therapy, presence of metastastatic disease, and receipt of ADT in the 6-months prior to enrollment. Participants were treated with a single session of whole-gland HIFU ablation with the Ablatherm device (EDAP, France). The primary endpoint of this study was RFS, defined as a composite endpoint of PSA progression (PSA nadir + 2 ng/ml), receipt of any further salvage therapy, receipt of ADT, clinical progression, or death. Kaplan-Meier survival analysis was used to determine the primary end-point and stratifications were used to determine the significance of 6 pre-specified predictors of improved RFS (undetectable PSA nadir, low TRUS biopsy grade, &gt;3 TRUS biopsy cores positive, pre-HIFU PSA&lt;4ng/ml, receipt of prior ADT and presence of pre-HIFU palpable disease). Survival analysis was performed on participants with a minimum of 1-year follow-up. Results: Twenty-four participants were eligible for study inclusion with a median follow-up of 31.0 months. Median PSA at study entry was 4.02 ng/ml. Median time to PSA nadir was 3 months after treatment and median post-HIFU PSA nadir was 0.04 ng/ml. 2-year and 5-year RFS were 66.3% and 51.6% respectively. An undetectable PSA nadir was the only significant predictor of improved RFS (HR 0.07, 95% CI 0.02-0.29, log-rank P&lt;0.001). No participants developed a rectourethral fistula. Conclusions: Salvage HIFU allows for disease control in select patients with localized radio-recurrent prostate cancer. An undetectable PSA nadir serves as an early predictor of disease response.

Anti-C1q Antibody as a Predictor of Chronic HCV Genotype 4 Response to Treatment in Egyptian Children

Background: Hepatitis C virus (HCV) infection has been reported to be the most common blood born pathogen all over the world. The prevalence of HCV in children in developed countries ranges between 0.1 and 0.4 %, and is generally lower than in adults. Combinedpegylated interferon and ribavirin is still the only standard of care treatment in spite of its side effects, high costs and low sustained virological response (SVR) rates. Hence, this provides a compelling reason for the identification of biomarker predictors of disease response to treatment. Objective: To evaluate anti-C1q antibody as a predictor of chronic HCV response to treatment with combined pegylated interferon alpha-2b and ribavirin in Egyptian children. Methodology: This study was conducted on forty-four chronic HCV-infected children (Male/Female: 30/14; aged 12.02±3.1 years) from the outpatient clinic, Pediatric Hepatology Department, National Liver Institute, Menoufiya University. They were given combined pegylated interferon alpha-2b (Peg-IFN-α-2b) and ribavirin (RBV) for 48 weeks and a quantitative polymerase chain reaction (PCR) for hepatitis C virus Ribonucleic acid was performed at 12, 24, 48 weeks during treatment and after another 24 weeks post-treatment. Anti-HCV antibody and Real-time PCR for HCV-RNA was performed (the detection limit was 15 IU/mL). Anti-C1q antibodies were performed by enzyme-linked immunosorbent assay (ELISA). Results: Serum levels of Anti-C1q antibodies were significantly higher (P = 0.001) in the Non-responders group (mean = 14.61± 6.749ng/ml) compared to the SVR one (mean = 2.27 ± 3.77ng/ml). No statistically significant difference (P > 0.05) had been found between SVR and Non-responders regarding the age, ALT, viral load, or hepatic necroinflammatory activity and liver fibrosis. Anti-C1q at a cutoff value of9.05ng/ml, had sensitivity and specificity of 84.6% and 75% respectively and 92% positive predictive value. No significant correlation between the serum level of anti-C1q antibodies and the age, sex or HCV viral load, liver enzymes, and the degree of fibrosis and necroinflammatory activity was found (P> 0.05) for all parameters. Conclusion: Anti-C1q could be a good predictor for HCV treatment and should be included in pretreatment laboratory assessment for proper choice of chronic HCV children patients who will benefit from combination therapy.

Prospective evaluation of RRM1 as a predictor of response to gemcitabine/carboplatin (GC) in non-small cell lung cancer (NSCLC)

7054 Background: RRM1 is the regulatory subunit of ribonucleotide reductase. It is a molecular target of G. RRM1 increases upon continuous exposure of cell lines to G. Preliminary data suggest improved survival for patients with low as opposed to high tumoral expression of RRM1 when treated with G-based chemotherapy. Methods: We determined the efficacy of G and C as induction therapy in patients with locally advanced NSCLC. Trial eligibility included measurable disease, no prior chemotherapy or RT, PS 0–1, and no weight loss. Patients were staged with CT, PET, and brain MRI. GC consisted of two 28-day cycles of G, 1,000 mg/m2 d1&amp;8 and C, AUC 5 d 1. Unidimensional tumor measurements were obtained before and after GC. The study required tumor collection prior to therapy by core needle biopsy. Specimens were frozen in LN. Tumor cells were collected by LCM. Real-time quantitative RT-PCR gene analysis was performed in triplicate per sample for RRM1 and 18SrRNA. Results: Between 11/03 and 7/05, 30 eligible patients were enrolled, and the required tumor biopsies were obtained in all. In one patient, a pneumothorax developed that required chest tube placement. Disease response ranged from a 9% increase to a 100% decrease. 14/26 had SD, 11/26 PR, and 1/26 CR. The patients’ age was 47- 87 years; 12 were women; 13 had IIIA and 13 IIIB; 10 had sq, 7 ad, and 9 LC or NOS NSCLC. RRM1 expression ranged from 0.18 to 129.3. There was a significant (p = 0.014) inverse correlation (r = −0.474) between RRM1 expression and disease response. When grouping patients into those with response (CR/PR) and without response (SD), RRM1 expression was significantly (p = 0.027) associated with response. No significant association was found between RRM1 expression and other parameters. Conclusions: In a prospective clinical trial intratumoral RRM1 expression was significantly and inversely correlated with disease response to gemcitabine and carboplatin. These results strongly suggest that tumoral RRM1 expression is a major predictor of disease response to gemcitabine-based chemotherapy. No significant financial relationships to disclose.

Principal factor analysis of predictive markers of response and resistance to primary chemo-endocrine treatment in elderly breast cancer (BC) patients

618 Background: This study was undertaken to identify protein expression patterns able to predict response and resistance to chemo-endocrine therapy in elderly BC patients enrolled in a randomised phase II study. Methods: 114 women with T2–4 N0–1, estrogen receptor positive BC were randomly assigned to 6 months of primary Letrozole (L) (2,5 mg/daily) or L plus oral “metronomic” cyclophosphamide (50 mg/daily) (LC). Expression of 24 markers was assessed before treatment on TMAs. Markers were involved in signalling and angiogenic/hypoxia pathways as follow; erbB2, T regulatory cells, caspase3, BNIP3, phosphorylated ERaplha, CCDN1, mTor, Hif-1α, phd1, phd2, phd3, CA9, COX2, p38, p44, EGFr, PI3k, pAkt, CD31, VEGF, Ki67, p53, bcl2, herb2. Principal factor (PF) analysis attempts to identify underlying factors that explain the correlation patterns within a set of observed variables; here, PF analysis was used to reduce the marker expression data by identifying a small number of PFs that explained most of the variance observed. These PFs were introduced in a multivariate logistic regression (MLR) to study basal protein expression profiles with response to chemo-endocrine treatment. Clinical variables such as treatment, age, tumor size, nodal status, grading and histotype were also included in MLR. Results: 91 out of 113 evaluable patients (80.5%) attained a disease response, 48 patients a complete response (CR) (42.5%) whereas 22 did not respond (19.5%). The first 12 extracted PFs from PF analysis explained 80% of the expression data variance; these were considered in a MLR together with clinical variables. The 4th PF, mainly representing Hif-1α and p44 expression, and at lower degree EGFr expression, was the only independent predictor of disease response (OD=0.22, p=0.003). The 6th PF, mainly representing phosphorylated ERalpha expression, was the only independent factor associated with CR (OD=2.036, p=0.023). There was no interaction between these PFs and treatment randomisation. Conclusion: The activated form of ERalpha is with complete response, whereas Hif-1α and p44 were able to discriminate patients resistant to chemo-endocrine treatment. In this latter cohort, specific target therapies can be recommended. No significant financial relationships to disclose.

Clinicopathologic significance of transitional cell carcinoma pattern in nonlocalized ovarian epithelial tumors (stages 2-4).

The transitional cell carcinoma (TCC) pattern has been associated with favorable outcome in patients with late-stage ovarian epithelial tumors who receive chemotherapy. We examined the clinicopathologic significance of TCC and explored other histopathologic prognostic indicators for patients with ovarian epithelial tumor. The surgical records of patients at the University of California at Davis Medical Center who underwent treatment for stages 2 to 4 ovarian epithelial tumor were studied retrospectively; the histopathologic features were correlated with outcome. The TCC pattern was identified in 32 of 136 ovarian epithelial tumors (23.5%): 18 (13.2%) as a predominant (> 50%) and 14 (10.3%) as a focal (< or = 50% but > 25%) histologic pattern. The other predominant histopathologic types were serous (65.4%), mucinous (11.7%), endometrioid (3.6%), clear cell (3.6%), and small cell (1.5%) carcinoma. Architectural grade was as follows: low malignant potential, 13 cases; grade I, 34 cases; grade II, 63 cases; grade III, 26 cases. Nuclear grade was as follows: low grade, 27 cases; high grade, 109 cases. One hundred seven patients had dominant ovarian tumors, and 29 had diffuse primary peritoneal epithelial tumor. One hundred twenty-three cases (90%) of peritoneal disease were invasive; 11 (10%) were noninvasive. Peritoneal disease histopathologic density was 50% or less cross-sectional involvement in 68 patients (50%) and greater than 50% in 68 (50%). Follow-up data were available for 118 patients: 46 patients had persistent disease that was unresponsive to chemotherapy; 36 of these patients died of disease at 0 to 41 months (mean, 15.6 months; median, 23.5 months). Ten patients were alive at 16 to 40 months (mean, 24.5 months; median, 20.5 months). Thirty-six patients had recurrent disease after 6 to 66 months (mean, 23.5 months; median, 18.5 months); 20 of these patients died of disease after 10 to 69 months (mean, 33.7 months; median, 30 months), and 16 were alive after 12 to 159 months (mean, 33.7 months; median, 30 months). Thirty-six patients had no evidence of disease at 12 to 159 months of follow-up (mean, 49.5 months; median, 31 months). The TCC pattern, either predominant or focal, was not associated with disease status or survival time (P > .05). Predictors of recurrent or persistent disease and survival, respectively, were invasive peritoneal disease (P < .05, P < .0001) and greater than 50% cross-sectional area histologic density of peritoneal disease (P < .01, P < .01). Grade, histologic type, and diffuse primary peritoneal vs ovarian location were not predictors of outcome. The TCC pattern was present in at least a focal (> 25%) component in 23% of epithelial tumors; however, this finding did not reach significance as a predictor of outcome in this study. The histologic pattern of the peritoneal disease (invasiveness and density) was a much stronger predictor of disease response and survival.