Predictors Of Disease Control Research Articles

Direct antiviral drugs in the treatment of hepatitis C-infected rheumatoid arthritis Egyptian cohort: safety and clinical impact.

Data about the safety and efficacy of direct-acting antivirals (DAAs) in the treatment of hepatitis C virus (HCV) patients with concomitant rheumatoid arthritis (RA) are scarce. We assessed the impact and safety of DAAs treatment of hepatitis C on rheumatoid arthritis disease activity. Prospectively, we enrolled 65 patients with RA and HCV. A clinico-laboratory evaluation was done at baseline, including liver assessment and RA disease activity score-28 (DAS28). At 12 weeks of post-DAAs treatment, sustained virologic response (SVR12) and DAS28 were reevaluated. The SVR12 was achieved in 59 (90.8%) patients. RA control was achieved in 47 (79.9%) patients. The post SVR12 DAS28 score was significantly lower than the baseline (3.32 ± 0.93 vs. 4.37 ± 0.90; P < 0.001). There was a significant decline in the mean values of serum anticyclic citrullinated peptide, rheumatoid factor, erythrocyte sedimentation rate and C-reactive protein after achieving an SVR12 (30.47 ± 12.37 vs. 57.61 ± 15.91 U/ml; 29.78 ± 19.58 vs. 55.14 ± 16.89 IU/ml; 17.13 ± 10.84 vs. 29.68 ± 14.32 mm/h and 5.76 ± 1.57 vs. 11.44 ± 4.13 mg/l, respectively; P < 0.05). RA activity and antirheumatic drugs were stepped-down [12 (20.3%) and 35 (59.3%) patients showed good and moderate RA response, respectively]. The baseline viral load, absence of cirrhosis and SVR12 were the only predictors of disease control (P < 0.05). No drug-related adverse events or drug-related discontinuation. Unlike interferon, HCV elimination by DAAs significantly improves RA activity and treatment outcome with high safety and efficacy.

Predictors of Disease Control After Endoscopic Sinus Surgery Plus Long-Term Local Corticosteroids in CRSwNP.

in the era of new biological agents it is important to identify patients who may benefit from conventional therapies such as endoscopic sinus surgery (ESS) plus long-term local corticosteroids from those with patterns of inflammation that are more difficult to control post-operatively and who may benefit from other therapies. determine if preoperative assessment of type and grade of inflammation and clinical factors can predict disease control with ESS plus long-term local corticosteroids in chronic rhinosinusitis with nasal polyps (CRSwNP). Eighty patients treated with ESS plus mometasone-furoate 200 μg BID for CRSwNP and followed for at least 1 year were enrolled (November 2017-December 2018) in this prospective observational study. Type and grade of inflammation were evaluated preoperatively by nasal cytology. Based on cellular pattern, patients were grouped as neutrophilic (n = 20), eosinophilic (n = 38), or mixed eosinophil-neutrophilic (n = 22). SNOT-22 and Lund-Kennedy Endoscopic Score were evaluated at baseline and at 3, 6, 9, and 12 months after surgery and used to define disease control. The cumulative probability of remaining free of significant modification of endoscopic score (Lund-Kennedy Endoscopic Score >2) at 3, 6, 9, and 12 months was 0.84, 0.76, 0.71, and 0.68, respectively. At 12-month postoperative evaluation good disease control was observed in 54 of 80 patients (67.5%). Compared to those with good post-operative disease control, those with poor control had a significantly higher pre-operative mean count of eosinophils and neutrophils (p < 0.05). The preoperative inflammatory pattern was associated with relative risk of poor control: neutrophilia (RR: 3.10; CI:1.24-7.71), eosinophilia (RR:8.42; CI:2.72-15.12), and mixed eosinophilic and neutrophilic (RR:25.11; CI:19.41-30.01). We also confirmed that asthma, allergy, blood eosinophilia, and ASA triad could predict poor control. The type and load of inflammation evaluated preoperatively and selected clinical factors can predict poor control of CRSwNP treated with ESS and local corticosteroids.

Albumin-globulin ratio is a predictive biomarker of antitumor effect of anti-PD-1 antibody in patients with non-small cell lung cancer.

Anti-programmed cell death receptor (PD)-1 antibody treatment results in better prognosis than standard chemotherapy in patients with non-small cell lung cancer (NSCLC), especially those with high PD-ligand 1 (PD-L1) expression. However, several studies have reported a lack of antitumor effect of PD-1 antibody, even in patients with high PD-L1 expression. Therefore, reliable predictors of treatment response are urgently needed. The albumin-globulin ratio (AGR) is associated with prognosis in several cancers. We aimed to determine whether AGR is a predictive biomarker of anti-PD-1 antibody response in patients with NSCLC. Seventy-four NSCLC patients treated with anti-PD-1 antibody were retrospectively enrolled. Patients with driver mutations were excluded. The mean AGR was significantly higher in the disease control (DC) group than in the progressive disease (PD) group (p < 0.001). Receiver operating characteristic curve analysis revealed an AGR cutoff value for dividing patients into the DC or PD groups of 1.17. Multivariate logistic regression analysis showed that a high AGR (≥1.17, cutoff value) was an independent predictor of DC (p = 0.001). Progression-free survival (PFS) and overall survival (OS) were significantly longer in the high-AGR group than in the low-AGR group (p = 0.008, p = 0.002, respectively). Multivariate Cox regression analysis of PFS and OS showed that high AGR was an independent prognostic factor (p = 0.020, p < 0.001, respectively). Pretreatment serum AGR may be a useful predictor for DC and prognostic factor of anti-PD-1 antibody in patients with NSCLC. The clinical utility of AGR still needs to be confirmed in a prospective analysis.

High Dose-Rate Tandem and Ovoid Brachytherapy in Cervical Cancer: Dosimetric Predictors of Disease Control and Toxicity

High Dose-Rate Tandem and Ovoid Brachytherapy in Cervical Cancer: Dosimetric Predictors of Disease Control and Toxicity

Margin to tumor thickness ratio – A predictor of local recurrence and survival in oral squamous cell carcinoma

To assess whether small oral squamous cell carcinomas (OSCC) require the same margin clearance as large tumors. We evaluated the association between the ratio of the closest margin to tumor size (MSR) and tumor thickness (MTR) with local control and survival. The clinicopathologic and follow up data were obtained for 501 OSCC patients who had surgical resection with curative intent at our institution. MTR and MSR were computed and their associations with local control and survival were assessed using multivariable Cox-regression model. Survival curves were generated using the Kaplan-Meier method. MTR was a better predictor of disease control than MSR. MTR was a predictor of local failure (p=0.033) and disease specific death (p=0.038) after adjusting for perineural invasion, lymphovascular involvement, nodal status, and radiotherapy. A threshold MTR value of 0.3 was identified, above which the risk of local recurrence was low. The ratio of margin to tumor thickness was an independent predictor for local recurrence and disease specific death in this cohort. A MTR>0.3 can serve as a useful tool for adjuvant therapy planning as it combines tumor thickness and margin clearance, two well established prognostic factors. The minimum safe margin can be calculated by multiplying the tumor thickness by 0.3. Further prospective studies in other institutions are warranted to confirm the prognostic utility of MTR and assess the generalizability of our threshold values.

Conocimientos de hipertensión en una población hipertensa colombiana

Background. Patients' knowledge of high blood pressure is a predictor of disease control. Knowledge about hypertension has barely been studied in the Colombian population suffering high blood pressure. Such knowledge must be assessed to facilitate educational intervention for improving hypertension control. Objective. Ascertaining knowledge about high blood pressure in a Colombian hypertensive population. Materials and methods. A questionnaire was developed and content validated by experts from the Universidad Nacional de Colombia and the Virrey Solis IPS's Research Committee. The questionnaire was used with 150 hypertensive patients in face-to-face interviews during their medical visits. Results. 70% of the surveyed population knew that hypertension is a preventable disease; however, barely 48% knew that it cannot be cured. Only 23% knew that, in most cases, high blood pressure does not cause headaches and 44% did not know that medication should never be suspended, even when there might be a lack of symptoms. Good knowledge was shown about lifestyle modifications and complications arising from high blood pressure whilst the risk of an ophthalmological complication was the least known. People having received less formal education and those having had a recent diagnosis had less knowledge. Conclusions. Severe deficiencies were revealed in the surveyed population regarding their knowledge about high blood pressure. Doctors and healthcare teams must play a more active role in patients' education to improve their knowledge concerning such serious disorder.

Predictors of disease control in patients treated with platinum-based chemotherapies for metastatic squamous-cell esophageal cancer: First results of the e-DIS trial.

95 Background: There is little evidence that chemotherapy (CT) impacts on outcome of patients with MSEC. We designed an ongoing randomized phase 2 trial to detect a progression-free survival benefit of CT continuation over CT discontinuation in disease-controlled and ECOG≤2 patients at 6 weeks after an initial CT treatment. The aim of the present study was to identify predictors of disease control at 6 weeks (DC6wkx) in MSEC patients receiving platinum-based CTs as first-line treatment for metastatic disease. Methods: Among 68/70 evaluable patients included between 1/2011 and 7/2013 who received at least 1 CT cycle, 58 were evaluable for disease assessment at 6 weeks. Ten patients were not evaluable (early death: 4, patient’s decision: 2, concomitant disease 1, early progressive disease 1, other reasons: 2). Baseline demographic, clinical, biological, and tumor characteristics were tested for prediction of DC6wkx. Significant variables for DC6wkx were identified with the chi-squared test and logistic regression. Results: Baseline patients characteristics were as follows: median age: 61.5yo; male: 57/68; ECOG 0/1/2: 13/42/13; metachronous/synchronous MSEC: 38/30; number of metastatic sites 1/2/&gt;2: 35/20/13; metastatic location: lung 36, liver 23, bone 11, nodes 37, other 11; prior exposure to CT: 37/68; time from previous CT exposure: ≤ 6m 6/37, 6-12m 14/37, &gt; 12m 17/37; gr&gt;2 dysphagia (Atkinson) 19/67; BMI&lt;18.5kg/m²: 13/68. Current CTs were FU-CDDPq3w 2/68, LV5FU2-CDDPq2w 15/68, FOLFOX 51/68, and patients received the following number of cycles 1/2/&gt;2: 5/7/54. DC6wkx rate was 65.7%, with 16/68 PR (23.5%) and 28/68 SD (42.2%). Albumin (p&lt;0.01), BMI (p&lt;0.02), bone metastases (p&lt;0.005), gender (p&lt;0.047) and ECOG status (p&lt;0.05) were predictive of DC6wkx. Normal or overweight BMI, grade 0 albumin, and no bone metastases, were predictive of DC6wkx in multivariate analysis. Conclusions: DC at 6 wks was 65.7% in MSEC receiving platinum-based CTs as first line treatment for metastatic disease. Normal or overweight BMI, normal albumin, and the absence of bone metastasis were significant predictors of DC6wkx in this prospective phase 2 trial. Clinical trial information: NCT01248299.

Performance status is an important prognostic factor in second line treatment of pancreaticobiliary adenocarcinoma.

To define the factors related with disease control and survival in patients with pancreaticobiliary adenocarcinoma treated with second-line therapy. We retropectively reviewed the data of 39 pancreaticobiliary adenocarcinoma patients treated with second-line chemotherapy between 2000 and 2012. Age, gender, origin of tumor, location of tumor, stage at diagnosis, Eastern Cooperative Oncology Group (ECOG) performance status, progression site, progression free survival (PFS) for first-line therapy, disease control at first-line therapy and chemotherapy protocols are analyzed for disease control rate, PFS and overall survival (OS). Disease control was recorded in 21 (53.8%) patients (20 stable disease, 1 partial response). Disease control rate was higher in patients with good performance status (p=0.03). Disease control at first-line therapy was not a predictor of disease control at second-line (p=0.6). Response to first-line therapy and other prognostic factors was not related with disease control. Progression free survival and OS was significantly longer in patients with good ECOG performance status (0-1) (p=0.01, p=0.006). Choice of chemotherapy (single agent or combination) and other factors did not have any impact on PFS and OS. In multivariate analysis; disease control was independent prognostic factor for both PFS and OS (p<0.001), (p<0.001). Disease control and performance status are two important prognostic factors. Chemotherapy regimen has no impact on disease control and survival. Salvage chemotherapy can be considered for patients with good performance status whether they are resistant to first-line therapy or not.

Addition of bevacizumab to compensate for the negative influence of attenuated relative dose intensity of cytotoxic agents on the outcome in patients with metastatic colorectal cancer.

e14614 Background: We reported that relative dose intensity (RDI) of key cytotoxic agents, irinotecan (IRI) and oxaliplatin (OX), is a significant predictor of disease control in patients with metastatic colorectal cancer (mCRC). However, in concomitant therapy with bevacizumab (BEV), the influence of adding BEV on the relation between RDI of cytotoxic agents and outcomes are unclear. In this study, we evaluate the impact of BEV on RDI of IRI and OX-based chemotherapy on the outcome of mCRC. Methods: A retrospective analysis of mCRC patients entered into three prospective clinical trials, testing FOLFIRI (CCOG-0502), mFOLFOX6 (CCOG-0704), FOLFIRI plus BEV and mFOLFOX6 plus BEV (CCOG-0801), was performed. RDI was calculated as the delivered dose intensity divided by standard dose intensity calculated for each regimen and compared to response rate (RR), disease control rate (DCR) and progression-free survival (PFS). Results: In FOLFIRI therapy, higher RDI (IRI, &gt;median: 80%) group achieved significant better RR, DCR and PFS than lower RDI (&lt;median) group (RR: 65 vs. 6% [p=0.001], DCR: 100 vs. 41% [p=0.003] and PFS: 9.9 vs. 5.6 months [p=0.002]). The other hand, in FOLFIRI plus BEV therapy, there were no difference between higher and lower RDI (IRI, median: 76%) group in ORR, DCR and PFS (RR: 31 vs. 27% [p=0.779], DCR: 75 vs. 53% [p=0.208] and PFS: 6.2 vs. 7.3 months [p=0.903]). In mFOLFOX6 therapy, higher RDI (OX, &gt;median: 79%) group achieved better disease control than lower RDI group (RR: 47 vs. 33% [p=0.456], DCR: 100 vs. 73% [p=0.032] and PFS: 8.5 vs. 6.2 months [p=0.064]). In addition of BEV, there were no difference between higher and lower RDI (OX, median: 76%) group in any outcomes (RR: 54 vs. 74% [p=0.159], DCR: 88 vs. 91% [p=0.672] and PFS: 11.6 vs. 11.7 months [p=0.797]). Conclusions: RDI of key cytotoxic agents is a significant predictor of disease control, especially in IRI-based regimen. Nevertheless, in concomitant therapy with BEV, there were no relations between RDI of cytotoxic agents and outcomes. These results suggest that BEV could have ‘covering effect’ to reduce the influence of dose modification of cytotoxic agents in mCRC patients.

Adrenal inclusion in testicular: about six cases

The adrenal enzyme deficiency leads pseudopuberty in later diagnosis or in the absence of treatment. The existence of testicular enlargement in boys can be related to adrenal inclusion. We report two observations about this pathology: A boy of 10 years old with 11β hydroxylase and another patients of 6 years old with 21 hydroxylase deficiency. The reason of consultation was the development of the penis and pubic hair with a testicular enlargement. Hormonal balance was in favor of early pseudo puberty. Testicular ultrasonography objectified increased volume and testicular hypoechoic nodules. Tumor markers (βHCG, ACE) were negative. Replacement and suppressive therapy by glucocorticoids is undertaken. The evolution was marked by regression of secondary sexual characteristics, reduced testicular size, increased its echogenecity and loss of nodules. During a reevaluation ten years later, a large heterogeneous testicular nodule is found in one patient. Tumor markers were elevated. Orchidopexy is decided. Histological study was in favor of bilateral Leydig tumor. The intratesticular adrenal inclusion is rare. It is the result of a cortical defect with a delay in diagnosis. Reduction of testicular volume after glucocorticoid therapy is a good predictor of disease control. However, a long term of follow up is necessary because a possibility of tumor degeneration. Keywords Congenital adrenal hyperplasia, Adrenal inclusion Intratesticular, Ultrasound, Tumor leydig, Glucocorticoids

Impact of relative dose intensity on the outcome of metastatic colorectal cancer.

508 Background: Relative dose intensity (RDI) is the ratio of delivered dose intensity of chemotherapy to standard dose intensity. There is established evidence supporting the significance of RDI in patients with various cancer, however data in patients with metastatic colorectal cancer (mCRC) are limited. In this study, we evaluate the significance of RDI of irinotecan and oxaliplatin-based chemotherapy on the outcome of mCRC. Methods: A retrospective analysis of mCRC patients entered into two prospective clinical trials, testing FOLFIRI (CCOG-0502) and mFOLFOX6 (CCOG-0704), was performed. RDI was calculated as the delivered dose intensity divided by standard dose intensity calculated for each regimen and compared to objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS). Results: The median RDI of irinotecan in FOLFIRI and oxaliplatin in mFOLFOX6 were 80% and 79%. ORRs In higher RDI (&gt;median) group and lower RDI (&lt;median) group were 64.7% and 5.9% of irinotecan (p=0.001), and 46.7% and 33.3% of oxaliplatin (p=0.456). DCRs in higher and lower group were 100% and 41.2% in FOLFIRI (p=0.003), and 100 and 73.3% in mFOLFOX6 (p=0.032). PFS in higher and lower group were 9.9 and 5.6 months in FOLFIRI (p=0.002), and 8.5 and 6.2 months in mFOLFOX6 (p=0.064). Conclusions: RDI of key cytotoxic agents is a significant predictor of disease control in patients with mCRC, especially in irinotecan-based regimen. Dose reductions and treatment delays could be minimized to achieve an RDI of at least 80%.

Adrenal Inclusion in Testicular about Two Cases

The adrenal enzyme deficiency leads pseudopuberty in later diagnosis or in the absence of treatment. The existence of testicular enlargement in boys can be related to adrenal inclusion. We report two observations about this pathology: A boy of 10 years old with 11β hydroxylase and another patients of 6 years old with 21 hydroxylase deficiency. The reason of consultation was the development of the penis and pubic hair with a testicular enlargement. Hormonal balance was in favor of early pseudo puberty. Testicular ultrasonography objectified increased volume and testicular hypoechoic nodules. Tumor markers (βHCG, ACE) were negative. Replacement and suppressive therapy by glucocorticoids is undertaken. The evolution was marked by regression of secondary sexual characteristics, reduced testicular size, increased its echogenecity and loss of nodules. During a reevaluation ten years later, a large heterogeneous testicular nodule is found in one patient. Tumor markers were elevated. Orchidopexy is decided. Histological study was in favor of bilateral Leydig tumor. The intratesticular adrenal inclusion is rare. It is the result of a cortical defect with a delay in diagnosis. Reduction of testicular volume after glucocorticoid therapy is a good predictor of disease control. However, a long term of follow up is necessary because a possibility of tumor degeneration.

Molecular predictors of response to tyrosine kinase inhibitors in patients with Non-Small-Cell Lung Cancer

IntroductionEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have become a treatment option in non-small-cell lung cancer (NSCLC) patients. However, despite their use in this disease, a significant number of patients will eventually develop resistance and relapse. In this study, we aimed to characterize several molecular events involved in potential resistance mechanisms to anti-EGFR treatment and correlate our findings with clinical outcome.Material and methodsThe medical records of patients with NSCLC who received anti-EGFR TKIs in any line within the participating centers were reviewed and available paraffin embedded tissue was retrieved. Mutational analysis for EGFR, KRAS, BRAF and intron-exon 14 deletions of MET; FISH analysis for chromosomal gain or amplification for EGFR, MET and the deletion marker D7S486 were performed. Furthermore, the expression of EGFR and MET were analysed by immunohistochemistry. All results were correlated with treatment outcomes.ResultsBetween 10/2001 and 12/2009 from an initial cohort of 72 treated patients, 59 cases (28 gefitinib/ 31 erlotinib) were included in the analysis. The majority had adenocarcinoma histology (68%), and received treatment in the second line setting (56%). Disease control rate (DCR) was 25.4% for all patients. EGFR and RAS mutational rates were 33% and 10% respectively, no other mutations were identified. High EGFR expressing tumors were found in 7 of 45 cases and pEGFR positivity (IHC) was found in 56% of the cases; MET expression was found in 48% of tumors. EGFR gene amplification was found in 4 cases, two cases showed high polysomy; overall, 13% cases were FISH positive for EGFR. High polysomy of MET gene was detected in 1/43 cases tested. D7S486 locus deletion was detected in 15/37 (40%) of cases. EGFR mutational status and gene gain were both associated with more favorable DCR. No other associations between examined biomarkers and DCR or survival were noted.ConclusionsEGFR mutational status is a predictor for disease control in patients with NSCLC treated with anti-EGFR TKIs. The predictive role of several other molecules involved in potential resistance to anti-EGFR TKIs is worthy of additional investigation.

Abstract B78: Final results of a prospective observational study comparing African American and Caucasian patients receiving second-line treatment with pemetrexed for advanced non-small cell lung cancer (NSCLC)

Abstract Background: Few prospective studies have evaluated the impact of race and ethnicity on clinical outcomes, during lung cancer treatment. This prospective observational study evaluated the impact of ethnicity on disease control rate (DCR) in patients with NSCLC treated with second-line pemetrexed (P). Methods: Eligibility criteria included stage IIIB or IV NSCLC pts receiving single-agent P for second-line therapy in routine clinical practice. Sites were selected to ensure high minority representation. Due to persistent challenges in achieving desired enrollment of minority, the focus of the study was narrowed to a comparison of patients self-reporting as either Caucasian (C) or African American (AA). This report describes findings regarding the primary endpoint of the study, DCR. Non-inferiority was evaluated using logistic regression analysis for DCR controlling for predefined covariates: age, gender, income, marital status, insurance type, smoking status, ECOG performance score, disease stage, histology, comorbidities, time from end of first-line to initiation with P, prior exposure to first-line platinum, exposure to first-line paclitaxel, and number of first-line cycles. The DCR of AAs was considered non-inferior to Cs if the upper 95% confidence bound on the adjusted odds ratio (OR) for Cs vs AAs was less than 1.78, corresponding to a difference in proportion of 14% assuming Cs to have a DCR of approximately 50%. The pre-specified bound was chosen to be one-half of the anticipated difference between treatment and no second-line treatment. Secondary endpoints reported here include progression-free survival (PFS) and overall survival (OS). Results: The unadjusted DCR was 43.4% (116/267) for C and 45.8% (27/59) for AA (unadjusted OR=0.91). The adjusted OR for the comparison of C to AA in the final logistic regression model was 0.79 (95% CI, 0.41, 1.51). This upper 95% confidence bound was within the pre-specified acceptable bound of 1.78. Median PFS times were 2.7 months (95% CI: 2.4, 3.4) for Cs and 3.0 months (95% CI: 2.3, 4.7) for AAs (P=0.91). Median OS times were 6.7 months (95% CI, 5.7, 7.9) for Caucasians and 6.9 months (95% CI: 4.5, 8.9) for AAs (P=0.92). Conclusions: Based on pre-specified analyses, DCR of AAs was non-inferior to Cs. The adjusted and unadjusted OR (0.79 and 0.91) were in favor of AA. Hence, ethnicity is not considered a significant predictor of disease control following second-line treatment with P. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B78.

Abstract 3744: Acetylated tubulin (AT) levels predicts response to TPF chemotherapy in locally advanced head and neck squamous cell carcinoma (HNSCC)

Abstract Docetaxel acts by binding to β-tubulin, stabilizing microtubules, and causing cell cycle arrest in the G2/M phase of mitosis. Previous reports by our group suggest the absence of acetylated tubulin in tumor samples is a predictor for disease control in patients treated on a phase I trial with Docetaxel and Lonafarnib[1]. In this study, we hypothesize that patients with HNSCC with low levels of microtubule acetylation (i.e. highly dynamic microtubules) as measured by immunohistochemistry (IHC) would respond better to induction therapy with TPF (Docetaxel, Cisplatin and 5FU), and hence the level of acetylated tubulin (AT) would be a predictor of response to TPF. Method: Between July 5th 2006 and September 29th2009, 14 patients with HNSCC were enrolled in a Phase II clinical trial of induction chemotherapy with 3 cycles of TPF followed by local therapy. Patients underwent a biopsy of their primary tumor site prior to initiation of induction TPF. The IHC staining for AT expression was performed on formalin fixed paraffin embedded tissue. The scoring was based on intensity only since tumor cells displayed a homogeneous staining pattern. An AT score of 4 was considered to be high, whereas a stain of 0, 1, 2 or 3 was considered low. Primary tumor sites included oral cavity (OC; n=6), oropharynx (OP; n=5), larynx (L; n=1), sinus (S; n=1), and unknown primary (UP; n=1). All patients had stage IVa or IVb at presentation and had a performance status of 0-2 (Eastern Cooperative Oncology Group ECOG scale). All had at least one uni- or bi-dimensional measurable lesion on imaging. The study closed prematurely due to slow accrual and increased observed complications. A total of 9 patients were evaluated: OC/4, OP/5. Results: After 3 cycles of TPF induction chemotherapy, complete remission (CR) was achieved in 4/9(44.5%), partial remission (PR) in 4/9(44.5%), and progressive disease (PD) in 1/9(11%) of patients. There was a significant correlation between AT staining intensity and response to TPF (p=0.0476). Patients with complete response (CR) or good partial response (GPR) (&amp;gt;60% reduction in tumor measurement) had a significantly lower staining intensity. No correlation was observed between staining intensity and progression free survival (PFS) or overall survival (OS) perhaps due to the small sample size. Conclusion: AT expression seems to correlate with response to TPF chemotherapy in HNSCC. Predicting response to TPF may prove to be useful in customizing care for patients with HNSCC. We are planning a larger scale retrospective analysis of the value of AT expression in predicting outcome for patients with HNSCC. 1. Kauh J, et al., Defining the Interaction of Docetaxel and Lonafarnib in Patients with Advanced Malignancies. AACR meeting, 2008, LB-67, 2008. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3744.

Quantitative analysis of somatostatin receptor subtypes (1–5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR

To determine whether the somatostatin receptor subtype (SSTR) expression profile correlates with hormonal and tumor volume responses to postsurgical octreotide long acting repeatable (OCT LAR) treatment. Quantitative real-time RT-PCR was used to evaluate the absolute mRNA copy numbers for all five SSTR subtypes in 22 somatotropinomas. Response to OCT LAR was studied by hormone levels (GH and IGF-I) and tumor volume (sella turcica magnetic resonance imaging). SSTR5 was present at the highest level followed by SSTR2, SSTR3, SSTR1, and SSTR4 (2327 (1046-5555), 2098 (194-23 954), 97 (0-460), 14 (0-29 480), and 0 (0-652) copies respectively). Positive correlations were found between SSTR2 levels and the percentage decrease of GH and IGF-I after 3 (r=0.49, P<0.027 and r=0.49, P<0.029 respectively) and 6 (r=0.59, P<0.006 and r=0.58, P<0.008 respectively) months of OCT LAR. A negative correlation was found between SSTR5 mRNA levels and the percentage decrease of GH after 3 months of OCT LAR (r=-0.52, P=0.016, n=21). A higher SSTR2/SSTR5 ratio was observed among patients who obtained hormonal control with OCT LAR, when compared with those uncontrolled (2.4 (0.7-10) vs 0.3 (0.1-7.7), P=0.001). A ROC curve analysis showed a SSTR2/SSTR5 ratio of 1.3 as the best predictor of disease control, with a sensitivity of 88% and a specificity of 92% - area under curve, 0.9. A positive correlation was also found between SSTR2 mRNA levels and the percentage decrease in tumor volume after 6 months of OCT LAR (r=0.79, P=0.002, n=12). Somatostatin receptor subtype 2 mRNA expression levels in somatotropinomas correlate positively with in vivo hormonal and tumor volume responses to OCT LAR.

Blood Concentrations of Tumor Necrosis Factor-Alpha in Malignant Lymphomas and Their Decrease as a Predictor of Disease Control in Response to Low-Dose Subcutaneous Immunotherapy with Interleukin-2

Tumor necrosis factor-alpha (TNF-alpha), a cytokine provided by both immunomodulating and inflammatory activities, has been described to be abnormally increased in the blood of patients affected by malignant lymphomas, particularly NHL. However, the biological and clinical significance of TNF-alpha secretion in malignant lymphomas is still controversial. The present study was carried out to further define TNF-alpha secretion in untreated malignant lymphomas and during low-dose IL-2 immunotherapy. The study included 80 malignant lymphoma patients, 54 of whom were affected by HD and the other 26 by NHL. The mean TNF-alpha serum concentrations observed in untreated lymphoma patients were significantly higher than those seen in the healthy controls, without significant differences between HD and NHL. Moreover, both HD and NHL lymphoma patients at clinical stage III-IV showed significantly higher mean TNF-alpha levels than those at clinical stage I-II. Finally, patients with systemic symptoms had higher mean TNF-alpha concentrations than those without any systemic symptoms, even though statistical significance was observed only for NHL patients. In a second study we have evaluated changes in TNF-alpha levels in seven evaluable lymphoma patients (NHL: 6; HD: 1)--who did not respond to conventional therapies--during subcutaneous low-dose IL-2 (3 MIU/day, 6 days/week for 4 weeks). Long-term stable disease was achieved in four patients with NHL, whereas the other three progressed. In patients with stable disease the mean TNF-alpha concentrations significantly decreased during treatment, whereas they increased in progressing patients. This study, by showing an abnormally enhanced TNF-alpha secretion in both NHL and HD patients with advanced disease and systemic symptoms and a decrease in its levels in patients who achieved disease control on IL-2 immunotherapy, appears to confirm the unfavorable prognostic significance of enhanced TNF-alpha levels in malignant lymphomas.