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PubMed2026

Patient-derived organoids predict responses to chemotherapy and PARP inhibitors in advanced ovarian cancer.

BACKGROUND: While tumor organoids hold promise for personalized medicine, clinical validation of epithelial ovarian cancer (EOC) organoids as predictors of therapeutic efficacy-particularly for PARP inhibitors (PARPi)-remains unestablished. METHODS: Patient-derived organoids (PDOs) were established from treatment-naive EOC specimens and characterized by H&E staining, immunohistochemistry, and whole-exome sequencing. Drug sensitivity testing (DST) was performed using carboplatin, paclitaxel, and PARPi (olaparib and niraparib). Clinical homologous recombination deficiency (HRD) status was assessed by tumor sequencing. Organoid responses were prospectively compared to patient outcomes after first-line chemotherapy (carboplatin/paclitaxel) and PARPi maintenance. RESULTS: PDOs were successfully established from 21 of 30 patients (70%) across multiple EOC subtypes and preserved the histopathological features and genomic landscapes of their corresponding primary tumors. Organoid-based DST accurately predicted responses to first-line carboplatin/paclitaxel, with a sensitivity of 100% (95% CI 62.88-100%), specificity of 66.67% (95% CI 12.53-98.23%), accuracy of 91.67% (95% CI 61.52-99.79%), AUC of 0.95 (95% CI 0.85-1.00), and Cohen's kappa of 0.75 (95% CI 0.30-1.00). In evaluating PARPi response, organoids revealed discrepancies between genomic HRD status and actual drug responses. One HRD-positive PDO was PARPi-resistant, consistent with patient non-response, while two HRR-proficient PDOs showed PARPi sensitivity and corresponding clinical benefit. CONCLUSIONS: EOC-derived PDOs provide a robust platform for predicting chemotherapy response and offer added value in assessing PARPi efficacy beyond genomic profiling. Combination of organoid-based testing with genomic analysis may improve precision treatment strategies in EOC.

Humans↗
PubMed2006

Predicting response to treatment in chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVE: To discover whether Inflammatory Neuropathy Cause and Treatment Group (INCAT) electrophysiological criteria for demyelinating neuropathy predict response to immunotherapy in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: This was a retrospective case note study of patients who had attended Guy's Hospital Peripheral Nerve Clinic between January 2001 and March 2004, been diagnosed as having CIDP, and given treatment with corticosteroids, intravenous immunoglobulin (IVIg), or plasma exchange (PE). Patients' nerve conduction studies (NCS) were reviewed for evidence of demyelination and whether the abnormalities fulfilled modified INCAT electrophysiological criteria. Patients whose NCS fulfilled the criteria were assigned to the neurophysiologically definite CIDP group, while those that did not were labelled as neurophysiologically probable CIDP. Responses to any of the three immunotherapy agents were compared between the two groups. RESULTS: Out of 50 patients, 27 (54%) were classified as neurophysiologically definite and 23 (46%) as neurophysiologically probable CIDP patients. Twenty (74%) neurophysiologically definite and 17 (73.9%) neurophysiologically probable CIDP patients responded to treatment. CONCLUSIONS: INCAT electrophysiological criteria did not predict a higher rate of response to immunotherapy. Neurophysiologically probable CIDP patients should be given a trial of immunotherapy.

Adolescent↗
PubMed2004

Predicting response to omalizumab, an anti-IgE antibody, in patients with allergic asthma.

STUDY OBJECTIVE: To determine baseline characteristics predictive of response to omalizumab, an anti-IgE antibody, in patients with allergic asthma. DESIGN: Pooled analysis of two multicenter, double-blind, randomized, placebo-controlled phase III studies with omalizumab. PATIENTS: One thousand seventy allergic asthma patients symptomatic despite moderate-to-high doses (mean, 725 micro g/d) of inhaled beclomethasone dipropionate (BDP). INTERVENTIONS: Omalizumab (n = 542) or placebo (n = 528) were administered at a 4-weekly subcutaneous dose of at least 0.016 mg/kg/IgE (IU/mL) for 16 weeks in addition to stable BDP therapy. MEASUREMENTS AND RESULTS: Univariate logistic regression was performed to explore baseline variables predictive of best response. Various aspects of response (reduced symptom scores, reduced usage of rescue medication, improved lung function, improved quality of life [QoL]) were explored as well as a composite definition of response (response in at least one of these four aspects with no asthma exacerbation during 16 weeks of treatment). Time to onset of response as well as the ability to predict eventual response were also determined for the composite definition of response. A consistent pattern of predictive covariates was seen over all definitions of response (except for QoL). For the composite definition, a history of emergency asthma treatment in the past year was the factor most predictive (p = 0.015) of best response on active treatment (response rate for those with such history was 67% for omalizumab and 42% for placebo; for those without a history the response rates were 63% and 54%, respectively). Another factor predictive of best response on active treatment was high BDP dose (p = 0.037; response rate for those treated with >or= 800 micro g/d was 65% for omalizumab and 40% for placebo; for those treated with < 800 micro g/d, the response rates were 63% and 55%, respectively). A low FEV(1) was also predictive (p = 0.072; response rates for those with FEV(1) or= 65% predicted, the response rates were 67% and 53%, respectively). Seventy-six percent of patients had at least one of these factors. This subgroup showed odds of being a responder (composite definition) 2.25 times higher (95% confidence interval, 1.68 to 3.01) than placebo. Some 38% of patients treated with omalizumab showed a response (composite definition) at the first evaluation time point at 4 weeks, increasing to 64% at week 16 (vs 48% for placebo; p < 0.001). Among omalizumab responders at 16 weeks, only 61% had responded at 4 weeks whereas 87% had responded at 12 weeks. CONCLUSIONS: Patients who benefit most when omalizumab is administered as add-on therapy are those receiving high doses of BDP, those with a history of frequent emergency asthma treatment, and those with poor lung function. Patients should be treated with omalizumab for a minimum duration of 12 weeks.

Adolescent↗
PubMed1992

Predicting responses of nonlinear neurons in monkey striate cortex to complex patterns.

The overwhelming majority of neurons in primate visual cortex are nonlinear. For those cells, the techniques of linear system analysis, used with some success to model retinal ganglion cells and striate simple cells, are of limited applicability. As a start toward understanding the properties of nonlinear visual neurons, we have recorded responses of striate complex cells to hundreds of images, including both simple stimuli (bars and sinusoids) as well as complex stimuli (random textures and 3-D shaded surfaces). The latter set tended to give the strongest response. We created a neural network model for each neuron using an iterative optimization algorithm. The recorded responses to some stimulus patterns (the training set) were used to create the model, while responses to other patterns were reserved for testing the networks. The networks predicted recorded responses to training set patterns with a median correlation of 0.95. They were able to predict responses to test stimuli not in the training set with a correlation of 0.78 overall, and a correlation of 0.65 for complex stimuli considered alone. Thus, they were able to capture much of the input/output transfer function of the neurons, even for complex patterns. Examining connection strengths within each network, different parts of the network appeared to handle information at different spatial scales. To gain further insights, the network models were inverted to construct "optimal" stimuli for each cell, and their receptive fields were mapped with high-resolution spots. The receptive field properties of complex cells could not be reduced to any simpler mathematical formulation than the network models themselves.

Animals↗
PubMed1989

Reduced REM latency predicts response to tricyclic medication in depressed outpatients.

Forty-two outpatients with major depressive disorder entered a double-blind, randomized trial of either desipramine or amitriptyline for a minimum of 6 weeks. Pretreatment polysomnographic and clinical measures were used to predict response. Response was defined as a 17-item Hamilton Rating Scale for Depression score less than or equal to 9 at the end of treatment. There was a 61.1% response rate for patients treated with amitriptyline and a 66.7% response rate for patients treated with desipramine. Reduced REM latency (2-night mean less than or equal to 65.0 min) predicted a positive response to these tricyclic antidepressants. REM latency did not differentiate between desipramine or amitriptyline responders. More patients with reduced REM latency (80%) responded to treatment compared with patients with nonreduced REM latency (50%). The 80% response rate in reduced REM latency depressed patients confirms our previous findings in a mixed inpatient and outpatient sample. Contrary to our hypothesis, in this sample, endogenous depression was not associated with a good response to tricyclic medication.

Adolescent↗
PubMed1997

Linear and nonlinear spectral integration in type IV neurons of the dorsal cochlear nucleus. II. Predicting responses with the use of nonlinear models.

Two nonlinear modeling methods were used to characterize the input/output relationships of type IV units, which are one principal cell type in the dorsal cochlear nucleus (DCN). In both cases, the goal was to derive predictive models, i.e., models that could predict the responses to other stimuli. In one method, frequency integration was estimated from response maps derived from single tones and simultaneous pairs of tones presented over a range of frequencies. This model combined linear integration of energy across frequency and nonlinear interactions of energy at different frequencies. The model was used to predict responses to noisebands with varying width and center frequency. In almost all cases, predictions using two-tone interactions were better than linear predictions based on single-tone responses only. In about half the cases, reasonable quantitative fits were achieved. The fits were best for noisebands with narrow bandwidth and low sound levels. In the second nonlinear method, the spectrotemporal receptive field (STRF) was derived from responses to broadband stimuli. The STRF could account for some qualitative features of the responses to broad noisebands and spectral notches embedded in broad noisebands. Quantitatively, however, the STRFs failed to predict the responses of type IV units even to simple broadband noise stimuli. For narrowband stimuli, the STRF failed to predict even qualitative features (such as excitatory and inhibitory frequency bands). The responses of DCN type IV units presumably result from interactions of two inhibitory sources, a strong one that is preferentially activated by narrowband stimuli and a weaker one that is preferentially activated by broadband stimuli. The results presented here suggest that the STRF measures effects related to the broadband inhibition, whereas two-tone interactions measure mostly effects related to narrowband inhibition. This explains why models based on two-tone interactions predict the responses to narrow noisebands much better then models based on STRFs. It is concluded that a minimal stimulus set for characterizing type IV units must contain both broadband and narrowband stimuli, because each stimulus class by itself activates only partially the integration mechanisms that shape the responses of type IV units. Similar conclusions are expected to hold in other parts of the auditory system: when characterizing a complex auditory unit, it is necessary to use a range of stimuli to ensure that all integration mechanisms are activated.

Acoustic Stimulation↗
PubMed1990

Deoxyribonucleic acid flow cytometry in predicting response to radical radiotherapy of bladder cancer.

Using flow cytometry tumors can be classified according to their deoxyribonucleic acid content as diploid or aneuploid with 1 or several cell lines and to the ploidy level of the aneuploid cell lines, as well as to the proportion of proliferating cells. We used this technique in 73 patients with invasive transitional cell carcinoma of the bladder who received radical radiation therapy with followup of surviving patients for at least 5 years. The effects of therapy were related to the deoxyribonucleic acid patterns before irradiation. All diploid tumors disappeared, while aneuploid tumors with 1 cell line disappeared in 55% and those with several cell lines in 30% of the patients. Aneuploid tumors with cell lines exceeding 4c appeared to be more radiosensitive than those in the triploid region. Thus, tumors unresponsive to therapy as well as those that recurred after irradiation were mostly triploid. Since most of the tumors had high proliferation rates the proportion of S-phase cells was of only limited value for further classification of the various tumors. In the choice between radical radiotherapy, in which bladder function is maintained, and cystectomy an analysis of tumor ploidy provides at least some basis on which radiation response can be predicted. In the choice of therapy we must also consider the fact that almost 20% of the patients who failed to respond to therapy revealed aneuploidy only in bladder washings after irradiation, indicating existence of concomitant carcinoma in situ.

Aged↗
PubMed2005

Mesenteric pulsatility index analysis predicts response to azathioprine in patients with Crohn's disease.

OBJECTIVE: Mesenteric blood flow measurement has been found to predict relapse after steroid-induced remission in patients with Crohn's disease (CD) and ulcerative colitis (UC). Therefore, we assessed prospectively the possible relationship between changes in mesenteric blood flow and prognosis in chronically active patients with need of immunosuppressive therapy with azathioprine (AZA) or 6-mercaptopurine (6-MP). METHODS: Doppler ultrasound (DUS) measurements of the pulsatility index (PI) of the superior mesenteric artery (SMA) and inferior mesenteric artery (IMA) were performed in 52 patients with chronically active inflammatory bowel disease (CD 31 patients; UC 21 patients) before beginning therapy with AZA/6-MP (US1) and during clinical remission (CD activity index <150, Truelove index score I) (US2). Patients were weaned from concomitant therapy with corticosteroids as soon as possible and were followed up for 12 months. RESULTS: After 1 year, 16 patients with CD (51.6%) and 13 patients with UC (61.9%) were in remission, whereas 23 patients had recurrent disease or had undergone surgery. A decreased SMA PI at US2 predicted clinical relapse in all patients with CD [100%; P < 0.001; mean (+/-SD) 77 +/- 67 d after US1], but only 4 of 8 patients (50%; difference not significant; mean 84 +/- 75 d after US1) with UC. Conversely, an increase of SMA PI was associated with sustained remission in the majority of CD patients (12/16 patients; 75%; P < 0.002), but in only 7 of 13 patients (54%) with UC. Flow measurements in the IMA and postprandial values for both arteries were less reliable. CONCLUSION: Repeated DUS measurements of the SMA PI predict response to AZA/6-MP in patients with chronic active CD.

Adult↗
PubMed2003

[Characteristics of MRI features in Alzheimer's disease patients predicting response to donepezil treatment].

We attempted to investigate whether morphological features as shown on magnetic resonance imaging (MRI) predict response to donepezil treatment in patients with Alzheimer's disease (AD). Sixty-three patients with AD were divided into responders (n = 16) and non-responders (n = 47) based on the changes in the MMSE score between baseline and endpoint. Atrophy of the substantia innominata was more pronounced in responders than non-responders. Although no significant difference in the medial temporal lobe atrophy between responders and non-responders was found, magnetization transfer ratios (MTRs) of the hippocampus and parahippocampus, indicators of structural damage, in the non-responder group were significantly reduced compared to those in the responder group. There were no significant differences in the severity of white matter lesions between the two groups. Logistic regression analysis revealed that the overall discrimination rate was 81%, with 85% of non-responders and 69% of responders, through measurement of the thickness of the substantia innominata and MTR of the hippocampus and parahippocampus. These results suggest that AD patients who show more severe cholinergic dysfunction and less severe structural damage of the hippocampus and parahippocampus as shown on MRI are likely to respond to donepezil treatment.

Aged↗
PubMedDate not supplied

Changes in water mobility measured by diffusion MRI predict response of metastatic breast cancer to chemotherapy.

The goal of oncology is the individualization of patient care to optimize therapeutic responses and minimize toxicities. Achieving this will require noninvasive, quantifiable, and early markers of tumor response. Preclinical data from xenografted tumors using a variety of antitumor therapies have shown that magnetic resonance imaging (MRI)-measured mobility of tissue water (apparent diffusion coefficient of water, or ADCw) is a biomarker presaging cell death in the tumor. This communication tests the hypothesis that changes in water mobility will quantitatively presage tumor responses in patients with metastatic liver lesions from breast cancer. A total of 13 patients with metastatic breast cancer and 60 measurable liver lesions were monitored by diffusion MRI after initiation of new courses of chemotherapy. MR images were obtained prior to, and at 4, 11, and 39 days following the initiation of therapy for determination of volumes and ADCw values. The data indicate that diffusion MRI can predict response by 4 or 11 days after commencement of therapy, depending on the analytic method. The highest concordance was observed in tumor lesions that were less than 8 cm3 in volume at presentation. These results suggest that diffusion MRI can be useful to predict the response of liver metastases to effective chemotherapy.

Adult↗
PubMed1972

Value of surface counting in predicting response to splenectomy in haemolytic anaemia.

The value of surface counting with (51)Cr-labelled red cells in predicting response to splenectomy in haemolytic anaemia has been analysed in 18 cases. The cases included six patients with congenital haemolytic anaemias, four with primary autoimmune haemolytic anaemias, and eight patients with secondary haemolytic anaemias (four with a positive antiglobulin test). All patients showed evidence of splenic accumulation of labelled cells and in 16 of the cases this was confined to the spleen. Improvement followed splenectomy in 17 of the cases although there was no close correlation between the magnitude of accumulation of radioactivity as measured by excess counts and the degree of response. The reasons for these discrepancies are discussed, The only patient who completely failed to respond to splenectomy had a sideroblastic element to the anaemia. It has been concluded that surface counting is of value in selecting patients for splenectomy but should not be depended upon without reference to other clinical and haematological factors, which are likely to influence the prognosis.

Adolescent↗
PubMed2000

Radiolabeled estradiol derivatives to predict response to hormonal treatment in breast cancer: a review.

Several radiolabeled steroidal and nonsteroidal estradiol derivatives of which the tumoral uptake is believed to relate quantitatively to the content and binding characteristics of the alpha-estrogen receptor (alphaER) receptor in the target tissue have been synthesized and their imaging potential and clinical usefulness evaluated in vivo in humans. Due to the use of different methodologies and cut-off values for the measurement of alphaER positivity, the use of both quantitative positron emission tomography and semiquantitative single-photon emission tomography, and the difference in patient populations studied, direct comparison of these data is not possible. Individual data, however, fail to substantiate a direct relationship between these radiolabeled estradiol derivatives and alphaER status, in keeping with recent pathophysiological findings demonstrating (1) estradiol sequestration and retention through other than alphaER-mediated, either membrane- or non-membrane-related, mechanisms and (2) an inverse relationship between estradiol uptake and local biosynthesis through aromatization and interconversion in alphaER-positive tumors. Additionally, given the discovery of very high affinity alphaER-like binding sites (Kd, dissociation constant, <0.1 nM), and the potential for underestimation of aER Kd when using ligand binding assays, at least part of the radiolabeled estradiol derivative uptake reflects tumoral perfusion rather than the ligand-receptor binding process. However, the reduction in cellular uptake, membrane sequestration and local biosynthesis of estradiol following tamoxifen treatment in alphaER-responsive tumors should allow early prediction of response to therapy through rapid sequential radiolabeled estradiol scintigraphy with higher accuracy than conventional alphaER estimations, as supported by recent data.

Binding Sites↗
PubMed2005

Role of p-glycoprotein expression in predicting response to neoadjuvant chemotherapy in breast cancer--a prospective clinical study.

BACKGROUND: Neoadjuvant chemotherapy (NACT) is an integral part of multi-modality approach in the management of locally advanced breast cancer. It is vital to predict response to chemotherapy in order to tailor the regime for a particular patient. The prediction would help in avoiding the toxicity induced by an ineffective chemotherapeutic regime in a non-responder and would also help in the planning of an alternate regime. Development of resistance to chemotherapeutic agents is a major problem and one of the mechanisms considered responsible is the expression of 170-k Da membrane glycoprotein (usually referred to as p-170 or p-glycoprotein), which is encoded by multidrug resistance (MDR1) gene. This glycoprotein acts as an energy dependent pump, which actively extrudes certain families of chemotherapeutic agents from the cells. The expression of p-glycoprotein at initial presentation has been found to be associated with refractoriness to chemotherapy and a poor outcome. Against this background a prospective study was conducted using C219 mouse monoclonal antibody specific for p-glycoprotein to ascertain whether pretreatment detection of p-glycoprotein expression could be utilized as a reliable predictor of response to neoadjuvant chemotherapy in patients with breast cancer. PATIENTS AND METHODS: Fifty cases of locally advanced breast cancer were subjected to trucut biopsy and the tissue samples were evaluated immunohistochemically for p-glycoprotein expression and ER, PR status. The response to neoadjuvant chemotherapy was assessed clinically and by using ultrasound after three cycles of FAC regime (cyclophosphamide 600 mg/m2, Adriamycin 50 mg/m2, 5-fluorourail 600 mg/m2 at an interval of three weeks). The clinical response was correlated with both the pre and post chemotherapy p-glycoprotein expression. Descriptive studies were performed with SPSS version 10. The significance of correlation between tumor response and p-glycoprotein expression was determined with chi square test. RESULTS: A significant relationship was found between the pretreatment p-glycoprotein expression and clinical response. The positive p-glycoprotein expression was associated with poor clinical response rates. When the clinical response was correlated with p-glycoprotein expression, a statistically significant negative correlation was observed between the clinical response and p-glycoprotein expression (p < 0.05). There was another significant observation in terms of development of post NACT p-glycoprotein positivity. Before initiation of NACT, 26 patients (52%) were p-glycoprotein positive and after three cycles of NACT, the positivity increased to 73.5% patients. CONCLUSION: The study concluded that pretreatment p-glycoprotein expression predicts and indicates a poor clinical response to NACT. Patients with positive p-glycoprotein expression before initiation of NACT were found to be poor responders. Thus pretreatment detection of p-glycoprotein expression may be utilized, as a reliable predictor of response to NACT in patients with breast cancer The chemotherapy induced p-glycoprotein positivity observed in the study could possibly explain the phenomenon of acquired chemoresistance and may also serve as an intermediate end point in evaluating drug response particularly if the adjuvant therapy is planned with the same regime.

Journal Article↗
PubMed1994

Expression of epidermal growth factor receptor and proliferating cell nuclear antigen predicts response of esophageal squamous cell carcinoma to chemoradiotherapy.

BACKGROUND: Multimodality therapy with chemotherapy and radiotherapy followed by surgery may improve survival in patients with esophageal squamous cell carcinoma compared with each of the individual treatment options. Histologic assessment of resected tumors after chemoradiotherapy shows that some patients have a complete response with no residual tumor, whereas other patients derive no benefit. The ability to predict response to chemoradiotherapy would allow treatment to be planned accordingly. METHODS: Expression of the tumor growth and proliferation proteins epidermal growth factor receptor (EGFR) and proliferating cell nuclear antigen (PCNA) was determined using immunohistochemical staining of pretreatment endoscopic biopsies from patients with esophageal squamous cell carcinoma who were randomized to chemoradiotherapy before surgery. Response to chemoradiotherapy was assessed by histologic examination of the resected specimens. Response to chemoradiotherapy and survival were correlated with EGFR and PCNA expression individually and with both markers combined as EGFR/PCNA: RESULTS: Of 14 patients available for study, 6 had a complete histologic response (CR) to chemoradiotherapy with no residual tumor in the resected specimen, 3 had a partial response (PR) to chemoradiotherapy, and the remaining 5 had minimal response (MR). Of the nine patients with a CR or PR, tumors of eight patients were negative for one or both markers. Of the five patients with an MR, four tumors were positive for both EGFR and PCNA (P < 0.05, Fisher's exact test). Comparison of survival from the date of randomization shows that patients with tumors negative for one or both markers had a significant survival advantage (P = 0.0003, log-rank test). CONCLUSIONS: Evaluation of PCNA and EGFR status of pretreatment biopsies may identify a group of patients likely to derive the greatest benefit from chemoradiotherapy before surgery in terms of histologic response and long term survival.

Adult↗
PubMed2002

Response predicting factors to recombinant human erythropoietin in cancer patients undergoing platinum-based chemotherapy.

BACKGROUND: The response to epoetin-alpha treatment is hard to predict in cancer patients receiving chemotherapy. METHODS: One hundred and seventeen patients were enrolled in this observational study. They had a hemoglobin (Hb) level less than or equal to 10.5 g/dL, were receiving platinum chemotherapy with three cycles pending, and they did not have an iron deficiency or hemolysis. Epoetin-alpha was administered subcutaneously three times a week at a dose of 150 IU/kg. Ninety patients were examined. RESULTS: Response was defined as an increase in Hb of at least 2 g/dL during the treatment period. The response rate was 63.3%. The following data were compared between responders and nonresponders at the onset of treatment and after 2 and 4 weeks of epoetin therapy: Hb, reticulocytes, serum iron, ferritin, transferrin, transferrin saturation index, and endogenous erythropoietin levels. At baseline, these variables were similar for responders and nonresponders; after 2 weeks, responders showed higher Hb (P = 0.001) and transferrin levels (P = 0.042) and reticulocyte counts (P = 0.003); after 4 weeks, only the Hb level showed a significant difference (P < 0.0005). Changes from baseline in Hb level after 2 and 4 weeks correlated significantly (P < 0.01) with response. The change in Hb level at Week 4 was the best predictor. A change in Hb level of less than 0.5 g/dL was associated with a lack of response (predictive power, 71%); a change in Hb greater than or equal to 0.5 g/dL was associated with response (predictive power, 89%). CONCLUSIONS: Response to epoetin-alpha treatment in cancer patients receiving platinum chemotherapy can be predicted from changes in Hb level after 4 weeks of therapy.

Adult↗
PubMed1976

A rapid in vitro labeling index method for predicting response of human solid tumors to chemotherapy.

A rapid autoradiographic technique for measuring the [3H]thymidine-labeling index of human solid tumors has been adapted to assess the effect of anticancer drugs in vitro. The drugs tested were present unchanged or as metabolites in serum obtained from patients immediately post-treatment. In 15 patients, the drugs tested in vitro were also given in vivo. Tumor-labeling index fell significantly in 5 of 6 patients who were later found to have objective clinical response. Tumor-labeling index did not change significantly in 8 patients and rose significantly in 1 of 9 patients who lacked clinical response. If confirmed, this in vitro test may prove to be a useful method of predicting responsiveness of human solid cancers to chemotherapeutic agents.

Antineoplastic Agents↗
PubMed1990

Upper airway measurements predict response to uvulopalatopharyngoplasty in obstructive sleep apnea.

Although uvulopalatopharyngoplasty relieves obstructive sleep apnea in the majority of patients, the factors that determine a successful response are not well defined. To determine whether preoperative awake upper airway measurements predict the response to uvulopalatopharyngoplasty, presurgical lateral cephalometric radiographs were evaluated on 60 consecutive patients with symptomatic obstructive sleep apnea. Patients underwent overnight polysomnograms before uvulopalatopharyngoplasty and 3 months afterwards. Forty-eight (80%) patients had a good response as defined by a postoperative apnea index of less than or equal to 4 apneas/hour or a reduction in apnea index of greater than or equal to 60%. Responders had a significantly narrower inferior airway space (P less than .0005) and a smaller ratio of inferior airway space to tongue length (P less than .001). Improvement in apnea severity following uvulopalatopharyngoplasty was related to the degree of airway narrowing (r = 0.36; P less than .01). This study shows that upper airway measurements help predict response to uvulopalatopharyngoplasty in patients with obstructive sleep apnea. Patients with a narrow airway, particularly relative to tongue size, have good responses to uvulopalatopharyngoplasty.

Adolescent↗
PubMed1998

Early HCV RNA values after interferon predict response.

The aim of this study is to determine in patients infected with hepatitis C virus (HCV) whether early HCV RNA measurements at 48 hr following standard doses of interferon-alpha (IFN-alpha) (3 million IU) would predict response during six months of therapy. Twenty-three patients with HCV were treated with IFN-alpha 3 million IU three times a week and HCV RNA levels were quantified by branched-chain (b-)DNA analysis at baseline and 24 and 48 hr following IFN-alpha and at one, three, and six months. Mean baseline HCV RNA levels significantly declined from 6.0 +/- 1.6 Meq/ml at baseline to 2.4 +/- 0.7 Meq/ml 24 hr after IFN-alpha. However, HCV RNA values increased to 4.3 +/- 1.1 Meq/ml by 48 hr. Mean HCV RNA values at one and six months were not significantly lower than 48-hr values. In six patients in whom HCV RNA was negative by bDNA at 48 hr, three were negative by polymerase chain reaction at six months. Of the 17 patients who were positive by bDNA at 48 hr, all were positive at one and three months; and in the nine of nine who continued therapy for six months, there was no further decrease in HCV RNA levels. In patients receiving standard doses of IFN-alpha (3 million IU), serum RNA values 48 hr after the first injection predict long-term response.

Female↗