Probability Of Disease Progression Research Articles

Progression prediction model for solid tumors with clinical and immunological parameters.

2539 Background: The immune system has well-known relation to tumor progression. Numerous immune-related parameters exist, but only a minor part could be used as biomarkers, especially dynamic ones. We trained a progression prediction model based on clinical features and peripheral immune system assessments. Methods: Patients with immunogenic (melanoma, 295, kidney cancer, 81), non-immunogenic (soft tissue sarcoma, 47, colorectal cancer, 26) and multiple primary tumors (29) with immunologic assessments before treatment (23.5%), on therapy (58.3), and in follow-up after the treatment (18.2%) were randomly divided in 7:3 ratio to the training and test groups. Counts of lymphocytes, T-, B, NK cells, cytotoxic lymphocytes, T-helpers were used as immunologic parameters. Age, sex, disease, stage, therapy, mutational status, last response on treatment, disease and therapy duration, previous treatments were used as clinical ones. The model was trained to predict disease progression in the next three months using “Catboost” gradient boosting. We used ROC AUC to test model performance and Yoden’s index for optimal cutoff calculation. We also studied the influence of model prediction on overall survival (OS) and time to progression (TTP) on the test dataset using the Kaplan-Meyer method and Cox regression. Results: We used 1682 assessments of immune parameters (immune status, IS) done in 354 patients (average 5 per patient) to train the model and 616 IS in 124 patients for validation. All IS of one patient were in the same group. The ROC AUC value of the model was 0.801. The model prediction of progression increased the probability of progressive disease from 37.5 to 62% and decreased the response rate from 37,5% to 8.4% (p = 0.016). The model prediction did not add information over known prognostic factors for OS in the multifactorial model but was an independent prognostic factor for TTP (HR 2.204, p = 0.011). False-positive results separate the group of patients with poor prognosis (OS 16 months, TTP 6 months) among patients with clinical benefit from patients with favorable prognosis (OS 61 months, TTP 18 months, p < 0.001), who had a truly negative model prediction. The possibility of prognosis improvement with therapy change was an essential factor for OS and TTP prediction (р < 0.001). The model was useful in predicting higher OS in patients with disease progression (p = 0.033) and shorter response duration in patients with clinical benefit (р = 0.03). Conclusions: Our progression prediction model provides clinically useful information and can be used for decision making in several clinical situations. Its utility should be tested in a prospective trial.

The paradoxical prognostic role of 1q21 Gain/Amplification in multiple myeloma: every coin has two sides

The prognostic value of 1q21 Gain/Amplification (1q21 Gain/Amp) in multiple myeloma (MM) has always been controversial. A total of 419 newly diagnosed MM patients were included in this retrospective study. The positive rate of 1q21 Gain/Amp was 48.6%. MM patients with 1q21 Gain/Amp were characterized as being in more advanced clinical stages and were more likely to be accompanied by del(13q14), t(4;14) or complex karyotypes (CKs) as well as with more severe anemia and worse renal function. In these patients, the percentage of complete remission (CR) or very good partial response (VGPR) was higher, however, in the early treatment period, the probability of progressive disease (PD) was also higher. No significant difference on progression free survival (PFS) and overall survival (OS) was showed between the group of 1q21Amp and 1q21Gain. The prognostic impact of 1q21 Gain/Amp on PFS of MM patients was heterogeneous and was in accordance with the accompanying parameters.

Detection and classification of systemic sclerosis-related interstitial lung disease: a review.

Systemic sclerosis (SSc) is a heterogeneous disease with a variable disease course. Interstitial lung disease (ILD) is one of the leading causes of morbidity and mortality in patients with SSc. The present review highlights recent advances in the classification, diagnosis, and early detection of SSc-associated ILD (SSc-ILD). Risk stratification through measurement of disease extent on high-resolution computed tomography (HRCT) of the chest, longitudinal declines in pulmonary function tests (PFTs), and mortality prediction models have formed the basis for classifying clinically significant ILD. HRCT may be preferred over PFTs for screening, as PFTs lack sensitivity and have a high false-negative rate. Novel imaging modalities and biomarkers hold promise as adjunct methods for assessing the presence and severity of SSc-ILD, and predicting risk for progressive disease. Further validation is required prior to their use in clinical settings. Classification of SSc-ILD has shifted to a personalized approach that considers an individual patient's probability of progressive disease through identification of risk factors, measurement of disease extent on HRCT, longitudinal declines in PFTs, and mortality prediction models. There remains an unmet need to develop screening guidelines for SSc-ILD.

Cost-effectiveness analysis of first-line treatments for early-stage, low-grade follicular lymphoma.

6619 Background: Low-grade follicular lymphoma (FL) can present as localized stage I to II disease in up to one-third of patients. Upfront involved-site radiation therapy (RT) to 24-30Gy is the preferred first-line management strategy for these patients. However, the National LymphoCare Study found that less than one quarter of patients with early-stage, low-grade FL received upfront RT, while more than half received either chemoimmunotherapy or observation. Methods: We performed a cost-effectiveness analysis using a Markov state-transition model to simulate the progression of early-stage, low-grade FL in a cohort of 60-year-old men. The following first-line treatments were compared: RT, observation, rituximab induction (RI), rituximab and bendamustine (BR), and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP). Patients who relapsed received second-line therapies that were dependent on their first-line treatment: RT for RI and observation, RCHOP for RT and BR, and BR for RCHOP. Disease-progression probabilities and other model inputs were from published trials. Results: First-line RT followed by RCHOP for relapses had a quality-adjusted life expectancy (QALE) of 11.4 years, superior to first-line observation, RI, BR, and RCHOP strategies. First-line RT strongly dominated observation, BR, and RCHOP. Compared with RI, first-line RT resulted in an incremental cost-effectiveness ratio of $2,740 per quality-adjusted life year. The probability of dying from other causes, the probability of a complete response to RT, and the probability of relapse had the greatest impact on both cost and effectiveness expected values. Conclusions: In contrast to current practice patterns, first-line RT is the most effective upfront treatment for patients with early-stage, low-grade FL. Further, first-line RT paired with RCHOP for relapses is a cost-effective treatment paradigm, relative to other strategies. [Table: see text]

Early Cerebral Blood Volume Changes Predict Progression After Convection-Enhanced Delivery of Topotecan for Recurrent Malignant Glioma

To assess whether early changes in enhancing tumor volume (eTV) and relative cerebral blood volume (rCBV) 1 month after convection-enhanced delivery of topotecan in patients with recurrent malignant glioma correlated with 6-month disease progression status. Sixteen patients were enrolled in a Phase Ib trial of convection-enhanced delivery of topotecan for recurrent malignant glioma. Each patient was evaluated with serial follow-up magnetic resonance imaging at baseline and at 4- to 8-week intervals. Changes at 1 month compared with baseline in eTV and rCBV were evaluated as potential predictors of 6-month progression status, classified as either progressive disease or nonprogressive disease. Relationships between percent changes in eTV and rCBV at 1 month with the probability of progressive disease at 6 months were estimated by the use of logistic regression analysis. Receiver operating characteristic curves for varying percent change thresholds in eTV and rCBV were evaluated by the use of 6-month progressive disease as the reference. There was a significant difference in the percent change in rCBV at 1 month in patients with progressive disease compared with those with nonprogressive disease at 6 months (+12% vs. -29%, P = 0.02). Logistic regression analysis demonstrated on average that a 10% increase in rCBV at 1 month after convection-enhanced delivery of topotecan was associated with 1.7 times the odds of developing progressive disease at 6 months (95% confidence interval [CI] 1.0-2.9 P = 0.05). Receiver operating characteristic analysis for determining progressive disease at 6 months showed a greater area under the curve with rCBV (0.867; 95% CI 0.66-1.00) than with change in enhancing tumor volume (0.767; 95% CI 0.51-1.00). In this selected population of patients with recurrent malignant glioma treated with convection-enhanced delivery of topotecan, early changes in rCBV at 4 weeks after therapy may help predict progression status at 6 months.

Cumulative doses of radioiodine in the treatment of differentiated thyroid carcinoma: knowing when to stop

Evaluate the efficacy of cumulative doses (CDs) of 131I-iodide therapy (RIT) in differentiated thyroid cancer (DTC). The probability of progressive disease according to CDs was evaluated in patients < 45 years old and > 45 years old and correlated to tumor-node-metastasis (TNM), thyroglobulin values, histological types and variants, age, and zduration of the disease. At the end of a follow-up period of 69 ± 56 months, 85 out of 150 DTC patients submitted to fixed doses RIT had no evidence of disease, 47 had stable disease and 18 had progressive disease. Higher CDs were used in the more aggressive variants (p < 0.0001), higher TNM stages (p < 0.0001), and follicular carcinomas (p = 0.0034). Probability of disease progression was higher with CDs > 600 mCi in patients > 45 years old and with CDs > 800 mCi in patients < 45 years. Although some patients may still respond to high CDs, the impact of further RIT should be carefully evaluated and other treatment strategies may be warranted.