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PubMed2004

Response prediction by FDG-PET after neoadjuvant radiochemotherapy and combined regional hyperthermia of rectal cancer: correlation with endorectal ultrasound and histopathology.

Accurate response assessment after neoadjuvant therapy is essential in patients with rectal cancer. The aim of this study was to assess the value of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting response of locally advanced rectal cancer to preoperative multimodal treatment. Twenty-two consecutive patients with locally advanced (uT3/4) primary rectal cancer were entered in this prospective pilot study. FDG-PET was performed before and after neoadjuvant radiochemotherapy (RCT) with combined regional hyperthermia (RHT). Treatment consisted of external-beam radiotherapy (45 Gy), chemotherapy (folinic acid and 5-fluorouracil) and regional pelvic hyperthermia followed by curative tumour resection 6-8 weeks later. Semi-quantitative measurements (SUV) of tumour FDG uptake were made before and 2-4 weeks after completion of neoadjuvant treatment. Two patients who did not receive post-therapeutic restaging by FDG-PET were excluded from the analysis. Results were correlated with findings on endorectal ultrasound (EUS, n=17 patients) and histopathology. Histopathological evaluation of the resected tumour revealed complete response in one patient, partial response in 12 and stable disease in seven. SUV reduction in tumours was significantly greater in responders than in non-responders [60% (+/-15%) vs 30% (+/-18%), P=0.003, CI=95%). Using a minimum post-therapeutic SUV reduction of 36% to define response, FDG-PET revealed a sensitivity of 100% (EUS: 33%) and a specificity of 86% (EUS: 80%) in response prediction; the corresponding positive and negative predictive values were 93% (EUS: 80%) and 100% (EUS: 33%), respectively. FDG-PET results were statistically significant (P<0.001, CI=95%). FDG-PET has great potential in the assessment of tumour response to neoadjuvant RCT in combination with RHT and is superior to EUS for this purpose.

Adolescent↗
PubMed2006

Extent of viability to predict response to cardiac resynchronization therapy in ischemic heart failure patients.

UNLABELLED: The response to cardiac resynchronization therapy (CRT) varies significantly among individuals. Preliminary data suggest that the presence of myocardial viability may be important for response to CRT. The aim of this study was to evaluate whether the extent of viability could predict response to CRT after 6 mo. METHODS: Sixty-one consecutive patients with advanced heart failure, left ventricular ejection fraction < 35%, QRS duration > 120 ms, and chronic coronary artery disease were included. To determine the extent of viability all patients underwent nuclear imaging with 18F-FDG SPECT before implantation. Clinical and echocardiographic parameters were assessed at baseline and after 6 mo of follow-up. RESULTS: The presence of myocardial viability was directly related to an increase in left ventricular ejection fraction after 6 mo of CRT. Furthermore, the extent of viability in responders (n = 38) was significantly larger compared with that of nonresponders (n = 23; 12 +/- 3 vs. 7 +/- 3 viable segments, P < 0.01). Moreover, the optimal cutoff value to predict clinical response to CRT was identified at an extent of 11 viable segments or more (in a 17-segment model), yielding a sensitivity of 74% and a specificity of 87%. CONCLUSION: The presence of myocardial viability is directly related to response to CRT in patients with ischemic heart failure. Interestingly, using a cutoff level of 11 viable segments or more, the extent of viability could be used to predict response. Therefore, evaluation for myocardial viability may be considered in the selection process for CRT.

Aged↗
PubMed1990

Does melancholia predict response in major depression?

We examined the value of the melancholic distinction for predicting response to 1 week of hospitalization without antidepressant drugs and to a 4-week fixed plasma level desipramine (DMI) trial in patients with unipolar non-psychotic major depression. Both DSM-III and III-R criteria were tested. Response to hospitalization (HDRS less than or equal to 12) was much less common in DSM-III melancholic than in non-melancholic patients (1 of 19 vs. 18 of 37, chi 2 = 8.69, df = 1, P less than 0.001) and severity did not account for this association. DSM-III-R melancholia criteria were also associated with poor hospital response but slightly less predictive. Melancholic patients, however, diagnosed with either set of criteria, were not more likely to respond to drug treatment on any of the measures examined.

Adult↗
PubMed1995

Factors predicting response to chemotherapy and survival in patients with metastatic or recurrent squamous cell cervical carcinoma: a multivariate analysis.

Different regimens of chemotherapy have been proposed with contradictory results in patients with metastatic and recurrent cervical carcinoma: this seems mainly due to the lack of information about prognostic factors. This study was aimed at identifying significant factors predicting response to treatment and survival in 140 patients treated with chemotherapy for advanced, recurrent, or persistent squamous cell cervical carcinoma. Age, performance status, histologic type and grade, previous irradiation, interval from start of primary treatment and from irradiation, site of tumor, and therapeutic regimen were considered as possible predictors of response and survival in multivariate analysis. By multivariate analysis, only performance status and interval from irradiation (> 1 year) were significant in predicting response to treatment, whereas interval from first diagnosis, site of tumor, and response to treatment were significant in predicting survival. None of the polychemotherapy regimens significantly improved survival, despite a fourfold increase in the costs when compared to the least expensive monochemotherapy regimen. Ethical and economical concerns should be considered when proposing aggressive regimens to the patients. Factors such as site of tumor, performance status, and interval from first treatment should be considered as minimal requirements for correct evaluation of newly proposed regimens.

Adult↗
PubMed1993

High complete remission rate from 2-chloro-2'-deoxyadenosine in previously treated patients with B-cell chronic lymphocytic leukemia: response predicted by rapid decrease of blood lymphocyte count.

PURPOSE: This study attempted to characterize the response of previously treated patients with B-cell chronic lymphocytic leukemia (CLL) to the purine analog 2-chloro-2'-deoxyadenosine (CdA) and to assess factors that predict response. PATIENTS AND METHODS: We treated 18 CLL patients with about-monthly courses of five daily 2-hour intravenous infusions of 0.12 mg CdA/kg. RESULTS: Complete remissions (CRs) were achieved in seven patients (39%), with a total response rate of 67%. CR patients received a median of 4.5 courses. One patient with CR relapsed and died 14 months from start of CdA treatment, whereas the other six patients with CR remain in remission following a mean observation period of 14 months. The median duration of partial remissions (PRs) was 9 months, with a median treatment-free interval of 15 months. Thrombocytopenia was the most common dose-limiting toxicity. Non-responding patients had a median survival of 3.5 months, and systemic fungal infections were the most common cause of death. Immunoglobulin (Ig) levels improved significantly in hypogammaglobulinemic patients during CdA treatment. Responses were predicted by a rapid decrease of blood lymphocyte counts following the first treatment course. CONCLUSION: A high CR rate was achieved with limited toxicity. A treatment strategy to enable high-quality response and limitation of treatment-related toxicity is provided.

Adult↗
PubMed1991

Do blood pressure and age predict response to tacrine (THA) in Alzheimer's disease? A preliminary report.

Recent studies in major depression suggest that a pretreatment systolic orthostatic blood pressure (PSOP) fall of greater than or equal to 10 mm Hg in response to changing from a supine to a standing position may predict response to antidepressant treatment in older depressed patients. Because orthostatic blood pressure response is regulated, in part, by central cholinergic and noradrenergic systems, and both are implicated in Alzheimer's disease, PSOP was assessed as a predictor of initial response in Alzheimer's disease outpatients in a treatment protocol with tacrine, a cholinesterase inhibitor. We found that the magnitude of PSOP fall and increasing age each contributed to the prediction of response to tacrine. These results may suggest a relatively greater involvement of other neurotransmitter systems in younger, nonresponding Alzheimer's disease patients, and the results differ from those of a previous study.

Adult↗
PubMed2003

Atrophy of the substantia innominata on magnetic resonance imaging predicts response to donepezil treatment in Alzheimer's disease patients.

To investigate whether atrophy of the substantia innominata as shown on magnetic resonance imaging (MRI), reflecting degeneration of cholinergic neurons in the nucleus basalis of Meynert, predicts response to donepezil treatment in patients with Alzheimer's disease (AD), we studied correlations between the thickness of the substantia innominata and clinical efficacy. Eighty-two patients were divided into responders, including transiently and continuously responding groups, and nonresponders, based on the changes in the Mini-Mental State Examination (MMSE) score from baseline at 3 months and at 12 months. Atrophy of the substantia innominata was more pronounced in transiently and continuously responding groups than nonresponders, but no significant change in the thickness between transiently and continuously responding groups was found. The MMSE score changes from baseline at 3 months and at 12 months significantly inversely correlated with the thickness of the substantia innominata. Logistic regression analysis revealed that the overall discrimination rate with the thickness of the substantia innominata was 70% between responders and nonresponders. We conclude that atrophy of the substantia innominata on MRI helps to predict response to donepezil treatment in patients with AD.

Aged↗
PubMed1991

Does learned resourcefulness predict response to cognitive therapy in depressed outpatients?

Thirty-seven unipolar, nonpsychotic, outpatients with major depression were treated with cognitive therapy in an ongoing study designed to identify which depressions respond to cognitive therapy. Pretreatment levels of learned resourcefulness, assessed by Rosenbaum's (1980) Self Control Schedule (SCS), were used to predict response to cognitive therapy (according to the 17-item Hamilton Rating Scale for Depression and the 21-item Beck Depression Inventory). Pretreatment SCS scores did not predict response to cognitive therapy according to either measure.

Adaptation, Psychological↗
PubMed2006

Velocity vector imaging to quantify ventricular dyssynchrony and predict response to cardiac resynchronization therapy.

Velocity vector imaging is a novel quantitative echocardiographic technique that was applied to routine grayscale echocardiographic images of 23 patients with heart failure who underwent cardiac resynchronization therapy. The hypothesis was tested that velocity vector imaging can quantify left ventricular mechanical dyssynchrony and predict response to resynchronization therapy. Tissue velocities were determined by the automated tracking of periodic B-mode image patterns on digital cine loops from standard apical 4-chamber, 2-chamber, and long-axis views, with the user tracing the mid left ventricular wall from a single frame. Dyssynchrony was determined as the greatest opposing wall peak longitudinal systolic velocity delay from the 3 views. Responders, defined as those with >or=15% increases in the ejection fraction, had greater baseline dyssynchrony than nonresponders (opposing wall velocity delays of 131 +/- 83 vs 52 +/- 60 ms, p <0.05), and >or=75 ms predicted response with 85% sensitivity and 80% specificity when followed 8 +/- 5 months after resynchronization therapy. Baseline electrocardiographic QRS duration was not predictive in the same patients. In conclusion, echocardiographic velocity vector imaging has potential for clinical utility.

Blood Flow Velocity↗
PubMed2004

Skin testing in predicting response to nasal provocation with alternaria.

OBJECTIVE: Examine the efficacy of epicutaneous and intradermal testing in predicting response to nasal provocation with Alternaria antigen. STUDY DESIGN AND SETTING: Prospective study. Subjects were tested with the Multi-Test II (MT) epicutaneous testing device. Subjects with negative wheals were then tested with a 1:500 weight:volume intradermal injection of Alternaria. They had baseline assessment of nasal cross-sectional area (CSA) using acoustic rhinometry and underwent nasal provocation with increasing Alternaria concentrations. CSA was assessed at each concentration. A nasal allergen provocation score (NAP) of nasal symptoms as well as a nasal visual analogue scale (VAS) were also completed with each concentration. RESULTS: Sensitivity and specificity of MT in predicting nasal response to Alternaria were poor at 42% and 44%, respectively. The addition of intradermal testing increased sensitivity only modestly to 58%. hierarchical linear modeling analysis demonstrated that subjects positive to Alternaria on skin testing did not show a significant reduction in nasal CSA on acoustic rhinometry or significant elevations in two nasal symptom scores with direct nasal provocation. CONCLUSION AND SIGNIFICANCE: Skin testing with either epicutaneous or intradermal testing may not be an accurate or sufficient technique in the assessment of Alternaria reactivity. These results suggest that mold allergies may involve more complex immune mechanisms than simply an immunoglobulin (Ig)E mediated type I immediate hypersensitivity response alone. An alternate model for mold sensitivity, as well as modifications in testing methods, may be required in the evaluation of mold allergy.

Adolescent↗
PubMed2002

Predicted responses for a particulate detection system in a continuous stack monitor.

Predicted counting rate responses were developed for a particulate detection system that is used for continuous monitoring for the presence of radioactive particulates in the effluent air from a research reactor. The particulate detection system consists of a moving filter paper assembly, a plastic scintillation detector, and a rate meter output, and is part of a comprehensive stack monitoring system. A predicted response was derived for the case of a steady-state activity distribution across the surface of the moving filter paper that is in proximity to the detector and was determined to be 1.59 x 10(7) cpm per unit airborne concentration of 138Cs (expressed in units of Bq cm(-3)), where 138Cs was used as an indicator for a hypothetical fission product release. The corresponding response model provided by the manufacturer was found to underestimate airborne activity concentrations by about an order of magnitude. A predicted response also was derived for the case of a rapid change in airborne activity concentration, which was formulated based on the kinetics of the rate meter circuit and was used to establish alarm settings and detection limits for the particulate detection system.

Air Pollutants, Radioactive↗
PubMed1998

A multivariate analysis of tumour biological factors predicting response to cytotoxic treatment in advanced breast cancer.

The study was designed to identify factors that could predict response to chemotherapy in breast cancer. A total of 173 patients with measurable or evaluable metastatic breast cancer were enrolled in a randomized trial between November 1987 and January 1991 to receive a monthly dose of 5-fluorouracil (500 mg m(-2)), epirubicin (60 mg m(-2)) and cyclophosphamide (500 mg m(-2)) either administered in four weekly doses or in an every-4-week dose as first-line cytotoxic treatment. In 103 evaluable patients we performed a multivariate analysis of the tumour biological factors, i.e. histological grade, oestrogen receptor (ER), progesterone receptor (PR), S-phase fraction (SPF), ploidy, p53, c-erbB-2, Bcl-2 and Bax expression, which showed significance in the univariate analysis according to treatment response, time to progression (TTP) or overall survival (OS). In the univariate analysis only SPF, grade and the proapoptotic protein Bax correlated with the response to cytotoxic treatment. In the multivariate analysis SPF had the strongest correlation, followed by grade and Bax. In the univariate analysis grade, PR, Bax and Bcl-2 correlated significantly with TTP, whereas in the multivariate analysis only PR showed a statistically significant correlation. In the univariate analysis PR and Bax correlated with OS and both retained its significance in the multivariate analysis. The factors that correlated significantly with the response to cytotoxic treatment in the univariate analysis, i.e. grade, SPF and Bax, seemed to predict independently the response to treatment in the multivariate analysis also. TTP and OS could be predicted partly by the same factors, although the association was quite weak. More studies and new tumour biological factors are needed to identify the group of breast cancer patients who get the most benefit from chemotherapy.

Analysis of Variance↗
PubMed1983

Chronic low back pain: predicting response to nonsurgical treatment.

The effectiveness of several measures in predicting response to conservative treatment for chronic low back pain was studied. The measures included pretreatment demographic variables, the Minnesota Multiphasic Personality Inventory (MMPI), patient ratings of pain caused by daily activities as measured by the Activities Discomfort Scale (ADS), and physician ratings. The subjects consisted of 135 patients treated at a university hospital back clinic who completed questionnaires six months or more after the initiation of treatment. The only significant predictor of how successful treatment had been in relieving pain was the MMPI hypochondriasis scale. The best predictor of patient-rated average pain intensity at follow-up was the ADS. Physicians' predictions of pain relief and return to normal activities, the ADS and the hypochondriasis scale each was associated significantly with patient ratings of return to normal activities after treatment, and to about the same extent. In general, statistical combinations of pretreatment variables did not increase the power of prediction. The ADS appears to be a promising predictor of patient-rated pain intensity after treatment, and may be useful in identifying poor risk patients.

Activities of Daily Living↗
PubMed2003

Hepatic expression of type I interferon receptor for predicting response to interferon therapy in chronic hepatitis C patients: a comparison of immunohistochemical method vs. competitive polymerase chain reaction assay.

The focus of this study is to determine both mRNA and protein expression levels of the type I interferon (IFN) receptor subunits, IFNalpha receptor (IFNAR1) and IFNalpha/beta receptor (IFNAR2), in the liver, and to assess which quantification method is most useful in predicting response to IFN in chronic hepatitis C patients. Liver biopsy specimens from 41 chronic hepatitis C patients subsequently treated with IFN were immunostained with IFNAR1 and IFNAR2 antibodies, and also analyzed for both receptor subunit mRNA levels, using competitive polymerase chain reaction. Immunostaining of IFNAR1 and IFNAR2 was observed in the cell membrane and cytoplasm of hepatocytes in all liver specimens. Hepatic expression of IFNAR1 (r=0.45, P=0.012) or IFNAR2 mRNA (r=0.46, P=0.009) was weakly correlated with their protein expression in hepatocytes. The labeling indexes of IFNAR1 (136.7+/-94.1 vs. 77.4+/-76.8, P=0.032) and IFNAR2 (153.1+/-80.2 vs. 87.2+/-75.5, P=0.011) in liver specimens were significantly higher in sustained virologic responders (n=17) than in non-sustained virologic responders (n=24), while mRNA levels of either receptor subunit did not differ between response groups. These results suggest that protein expression of the type I IFN receptor in liver is a more useful measure than its mRNA expression in predicting response to IFN in chronic hepatitis C patients.

Journal Article↗
PubMed2003

O6-methyl-guanine-DNA methyltransferase methylation in serum and tumor DNA predicts response to 1,3-bis(2-chloroethyl)-1-nitrosourea but not to temozolamide plus cisplatin in glioblastoma multiforme.

PURPOSE: In glioblastoma multiforme (GBM), the cytotoxic effect of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and temozolamide is dependent on O(6) alkylation, which correlates inversely with expression of the DNA repair enzyme O(6)-methyl-guanine-DNA methyltransferase (MGMT). Thus, MGMT assessment can be useful in predicting response in GBM, but the scarcity of neoplastic cells limits the practicality of MGMT assessment in these tumors. Although GBM grows within the skull, we investigated the concordance of methylation in glioma tissue, and paired serum DNA and the potential correlation with response and time to progression. EXPERIMENTAL DESIGN: Using MSP assay, we assessed the methylation of MGMT, p16, DAPK, and RASSF1A in tumor and serum DNA from 28 GBM patients treated with BCNU or with temozolamide plus cisplatin. RESULTS: The concordance between methylation in tumor and serum was highly significant. Overall, response plus stable disease was noted in 10 of 11 (90.9%) patients with MGMT methylation and in 5 of 14 (35.7%) patients without (P = 0.01). In the 16 patients treated with temozolamide plus cisplatin, no significant correlation between MGMT methylation status and response was observed, whereas in BCNU-treated patients, a significant difference was observed in favor of those with methylated MGMT. Time to progression was 29.9 weeks in 12 patients with MGMT methylation and 15.7 weeks in 10 patients without (P = 0.006). No correlation was observed between response or time to progression and p16, DAPK, or RASSF1A methylation. CONCLUSIONS: Methylated MGMT, p16, DAPK, and RASSF1A were found in serum DNA of GBM patients, with a good correlation between serum and primary tumor tissue. Serum MGMT methylation predicted response and time to progression in BCNU-treated GBM patients. The methylation-specific PCR assay in serum DNA could be a good predictive tool for selecting GBM patients to be treated with BCNU or alternatively with the combination of temozolamide plus cisplatin.

Adult↗
PubMed2005

Detection of response-predicting mutations in the kinase domain of the epidermal growth factor receptor gene in cholangiocarcinomas.

PURPOSE: Epidermal growth factor receptor (EGFR) signalings have recently been implicated in the genesis and progression of cholangiocarcinomas. Thus, the EGFR kinase inhibitor appears to be promising in the treatment of this cancer. The response-predicting mutations in the tyrosine kinase domain of EGFR gene have recently been detected in non-small cell lung cancers. This study was, therefore, to investigate if these mutations are also found in cholangiocarcinomas. METHODS: Twenty-two consecutive cholangiocarcinoma patients who underwent surgical resection were enrolled. Their resected paraffin-embedded cholangiocarcinoma specimens were used for mutation analysis, which was performed by DNA sequencing of exons 18, 19 and 21 in the EGFR gene. Clinical characteristics were compared between each group according to the presence or absence of mutations. RESULTS: Three patients (13.6%) harbored EGFR mutations. All the mutations found were deletions in exon 19. Mutations were more common in intra-hepatic or poorly differentiated tumors. Differences in age, sex, stage at diagnosis and survival were not observed between mutation-positive and -negative patients. CONCLUSIONS: This study, for the first time, demonstrates that a subset of cholangiocarcinoma patients has response-predicting EGFR mutations. Therefore, a highly selected application of the EGFR kinase inhibitor would be therapeutically effective in these patients.

Aged↗
PubMed2004

Sensitivity and specificity of prick and intradermal testing in predicting response to nasal provocation with timothy grass antigen.

OBJECTIVE: Examine the efficacy of epicutaneous and intradermal testing in predicting response to nasal provocation with timothy antigen. STUDY DESIGN AND SETTING: Prospective study. Subjects were tested with Multi-Test II (MT). Subjects with negative wheals were tested with a 1:500 intradermal injection of timothy. They had baseline assessment of nasal cross-sectional area (CSA) using acoustic rhinometry and underwent nasal provocation with increasing timothy concentrations. CSA was assessed and nasal visual analog scale (VAS) completed with each concentration. RESULTS: Sensitivity and specificity of MT in predicting nasal response to provocation were 87% and 86%. Intradermal testing increased sensitivity to 93%. Hierarchical linear modeling (HLM) demonstrated that subjects positive to skin testing had significant reductions in CSA and worsening VAS scores with increasing concentrations of nasally delivered antigen. CONCLUSION AND SIGNIFICANCE: Epicutaneous testing with the Multi-Test II offers 87% sensitivity and 86% specificity in assessing timothy grass reactivity.

Adult↗
PubMed2000

Predicting response to neoadjuvant chemotherapy in patients with cervical carcinoma: can we do without any longer?

The aim of the study was to identify variables that may predict the response to neoadjuvant chemotherapy (NACT) in patients with cervical cancer as maturing data from the literature indicate that this therapeutic strategy might be beneficial to some but harmful to others. Clinico-pathologic variables including age, histology, tumor differentiation, as well as immunohistochemical overexpression of p53, mdm2, c-erbB-2, and cathepsin D in 37 of these patients were evaluated as possible predictors of response to the NACT. Fifty-five patients with stage IIB cervical cancer submitted to two courses of cisplatin/ifosfamide/mesna prior to definitive treatment with radical surgery or radiation therapy were the subjects of this study. The clinical response rate was 80% but none of the variables was able to predict response to NACT. Unless methods are found enabling us to predict response and therefore to identify those patients that could benefit from including NACT in the treatment of locally advanced cervical cancer, only women with primarily resectable tumors should be selected for this multimodality approach as a result of the possibility of cross-resistance with radiation therapy in nonresponders.

Journal Article↗