Prognostic Value Of Response Research Articles

A comparison of the prognostic performance of the Lugano 2014 and RECIL 2017 response criteria in patients with NHL from the phase III GOYA and GALLIUM trials.

The Lugano 2014 criteria are the standard for response assessment in lymphoma. We compared the prognostic performance of Lugano 2014 and the more recently developed response evaluation criteria in lymphoma (RECIL 2017), which relies primarily on computed tomography and uses unidimensional measurements, in patients with previously untreated diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) from the phase III GOYA and GALLIUM trials, respectively. Concordance between responses according to the Lugano 2014 and RECIL 2017 criteria was analyzed. Landmark analyses of progression-free survival (PFS) and overall survival (OS) by end of treatment (EOT) and end of induction (EOI) response status according to RECIL 2017 and Lugano 2014 criteria, and prognostic value of response at EOT/EOI were also compared. Overall, 1333 patients were included from GOYA and 502 from GALLIUM. Complete response (CR) status according to RECIL 2017 criteria showed high concordance with complete metabolic response (CMR) status by Lugano 2014 criteria in both GOYA (92.5%) and GALLIUM (92.4%). EOT and EOI CR/CMR status by both criteria was highly prognostic for PFS in GOYA (RECIL 2017 [CR]: hazard ratio [HR], 0.35 [95% confidence interval [CI] 0.26-0.46]; Lugano 2014 [CMR]: HR, 0.35 [95% CI 0.26-0.48]; both p<.0001) and GALLIUM (RECIL 2017 [CR]: HR, 0.35 [95% CI 0.23-0.53]; Lugano 2014 [CMR]: HR, 0.21 [95% CI 0.14-0.31]; both p<.0001). In conclusion, response categorization by RECIL 2017 is similar to that by Lugano 2014 criteria, with high concordance observed. Both were prognostic for PFS and OS.

Complete Response Status According to RECIL 2017 Criteria Shows High Concordance with Lugano 2014 Criteria and Is Highly Prognostic for Outcome in Previously Untreated Patients with CD20-Positive Diffuse Large B-Cell Lymphoma (DLBCL)

Complete Response Status According to RECIL 2017 Criteria Shows High Concordance with Lugano 2014 Criteria and Is Highly Prognostic for Outcome in Previously Untreated Patients with CD20-Positive Diffuse Large B-Cell Lymphoma (DLBCL)

1175P - Prognostic value of response according to tumour growth rate in a phase I trial on vaccine therapy

1175P - Prognostic value of response according to tumour growth rate in a phase I trial on vaccine therapy

Abstract P3-13-03: NEOS: A randomized, open label, phase 3 trial of adjuvant chemotherapy for postmenopausal breast cancer patients who responded to neoadjuvant letrozole: First report of long-term outcome and prognostic value of response to neoadjuvant endocrine therapy

Abstract Background: Whether adjuvant chemotherapy is required for patients (pts) with intermediate-risk endocrine-responsive postmenopausal breast cancer (BC) remains unknown. Sufficient data have not been available about the long-term prognosis of patients with neoadjuvant endocrine therapy (ET). NEOS is a randomized phase III study that assessed the long-term prognosis of estrogen receptor positive (ER+) primary breast cancer (PBC) pts who received neoadjuvant ET with/without adjuvant chemotherapy. Methods: Postmenopausal BC pts with ER +/HER2 negative, T1c-2, clinically node negative, under 76 years old were enrolled at primary registration. Pts were treated by leterozole (LET) in weeks 24-28 after primary enrollment. Pts experienced progression (PD) during neoadjuvant phase were excluded at randomization and received any systemic therapy driven by investigators before or after surgery. The long-term prognosis was followed in all registered pts including PD pts. Response to neoadjuvant ET was evaluated as complete response (CR), partial response (PR) or stable disease (SD) using calipers, ultrasound and MRI (or CT) at the baseline and end of treatment before surgery. Pts who met eligibility criteria were randomized 1:1 to LET for 4.5-5 years after chemotherapy or LET alone for 4.5-5 years without chemotherapy after surgery. Pts excluded at second registration were treated any systemic therapies driven by investigators. The primary endpoint was disease-free survival (DFS) and secondary endpoints included overall survival (OS), clinical response rate in neoadjuvant phase, pathological response, and breast-conserving surgery rate. The randomization code have been blinded to the investigators. Results: Between May 2008 and June 2013, 904 patients were enrolled at primary registration from 100 institutions in Japan (median follow-up: 4.0 years) and 24 pts were withdrawn during neoadjuvant phase. The median age was 63 years, T1c:37%, T2:63%, and PgR+:78%. Clinical response rates (CR, PR, SD and PD) were2% (16pts), 48% (421pts), 45% (400pts) and 5% (43pts), respectively and, in each response category, 0% (0/16), 5.5% (23/421), 7.8% (31/400), and 20.9% (9/43) experienced DFS events. DFS in PD pts to neoadjuvant ET were statistically significantly worse than CR, PR, SD pts (p&amp;lt;0.0001, hazard ratio 4.7 (95% CI:2.3-9.5). The prognosis after surgery in 669 randomized pts was good regardless with/without chemotherapy, forty four pts (6.6%) experienced DFS events after surgery. The predictive markers of PD for neoadjuvant ET were yet unclear among evaluated clinical factors. Conclusion: This is the first report of DFS in the largest neoadjuvant ET trial (NEOS). The DFS of postmenopausal, ER+/HER2-, PBC pts excluding PD pts to neoadjuvant ET is highly good regardless with/without chemotherapy. Neoadjuvant ET with utilization of PD response as a prognostic marker can be considered as a standard treatment option for these patients. Clinical trial information: UMIN000001090. Citation Format: Iwata H, Masuda N, Fujisawa T, Toyama T, Ohtani S, Yamamoto Y, Kashiwaba M, Taira N, Sakai T, Hasegawa Y, Nakamura R, Akabane H, Shibahara Y, Sasano H, Yamaguchi T, Ohashi Y. NEOS: A randomized, open label, phase 3 trial of adjuvant chemotherapy for postmenopausal breast cancer patients who responded to neoadjuvant letrozole: First report of long-term outcome and prognostic value of response to neoadjuvant endocrine therapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-13-03.

Overexpression of CREPT confers colorectal cancer sensitivity to fluorouracil.

AIMTo investigate expression of cell cycle-related and expression-elevated protein in tumor (CREPT) in colorectal cancer (CRC) and determine its prognostic value in response to 5-fluorouracil (5-FU).METHODSThe relative expression of CREPT in CRC tumor samples was determined using immunohistochemistry. The protein content in cell lines was analyzed by immunoblotting. Cell viability was measured with the CCK-8 assay. Cell cycle and apoptosis analyses were performed with flow cytometry.RESULTSCREPT was overexpressed in CRC tissues and correlated with histological grade. Clinicopathological analysis indicated that CREPT was positively related to tumor progression. Exogenous expression of CREPT stimulated cell proliferation and accelerated the cell cycle. More importantly, high expression of CREPT sensitized CRC cells to 5-FU treatment. Furthermore, we demonstrated that 5-FU elicited significant apoptosis in CREPT-positive cells.CONCLUSIONAberrant overexpression of CREPT contributes to tumorigenesis of CRC by promoting cell proliferation and accelerating the cell cycle, and confers sensitivity to 5-FU. CREPT is a potential prognostic biomarker for 5-FU in CRC.

Copeptin, resistant hypertension and renal sympathetic denervation

Background: Renal denervation is used as a treatment option for patients with resistant hypertension. But only a subgroup of patients benefits from renal sympathetic denervation (RDN). Biomarkers might be helpful to identify patients who respond to RDN. Copeptin as a surrogate for vasopressin levels is increased in hypertension and other cardiovascular diseases. This study aims to evaluate the effect of RDN on Copeptin and its prognostic value for response to RDN.Method and results: A total of 40 patients have been included in the study. The responder rate was 47.5% on 24 h ambulatory blood pressure measurements. The mean systolic 24 h blood pressure dropped from 152 ± 10 mmHg to 147 ± 17 mmHg (p = .044) in the six month follow up. The mean baseline level of Copeptin was 7.4 pmol/l (interquartile range 3.7–11.6) for responders and 8.4 pmol/l (interquartile range 5.7–11–8) for non-responders (p = .53). The Copeptin levels did not change over time after renal denervation.Conclusion: Baseline measurements of Copeptin in patients undergoing RDN for resistant hypertension have no predictive value for response to RDN. Despite lowering the blood pressure RDN has no influence on Copeptin levels in this short time follow up period.

MicroRNA-218 is a prognostic indicator in colorectal cancer and enhances 5-fluorouracil-induced apoptosis by targeting BIRC5.

One major reason for the failure of advanced colorectal cancer (CRC) treatment is the occurrence of chemoresistance to fluoropyrimidine (FU)-based chemotherapy. Various reports showed that ectopic expression and function of microRNAs (miRNAs) played key roles to mediate apoptosis at the post-transcriptional level. To further explore the possible mechanisms, we evaluated the prognostic effect of miR-218 in patients with CRC receiving 5-FU-based treatment and investigated the proapoptotic role of miR-218 in vitro. Primary tumour specimens and adjacent non-tumour sites were used to determine miR-218 expression distribution and explore its potential prognostic value in response to 5-FU-based treatment in patients with CRC. HCT116 and HT29 cells were transfected with precursor miR-218 or negative control, followed by assays to investigate its influence on apoptosis, cell proliferation and pathways involved in molecular mechanisms of chemoresistance to 5-FU. Results showed that high miR-218 expression was associated with positive response to firstline 5-FU treatment in CRC patients. MiR-218 promoted apoptosis, inhibited cell proliferation and caused cell cycle arrest in CRC cells by suppressing BIRC5 expression. Furthermore, miR-218 enhanced 5-FU cytotoxicity in CRC cells by suppressing the 5-FU targeted enzyme, thymidylate synthase (TS). In conclusion, we demonstrated that high miR-218 expression had a positive prognostic value in 5-FU-based treatments for CRC patients and discovered a novel mechanism mediated by miR-218 to promote apoptosis and to function synergistically with 5-FU to promote chemosensitivity by suppressing BIRC5 and TS in CRC. These suggest the unique potential of miR-218 as a novel candidate for developing miR-218-based therapeutic strategies in CRC.

Prognostic significance of radiologic and histologic response to neoadjuvant chemotherapy in localized synovial sarcoma.

10578 Background: The role of neoadjuvant and adjuvant chemotherapy in localized synovial sarcoma (SS) is still controversial. Histologic response to neoadjuvant chemotherapy is an independent prognostic variable in bone sarcomas. Data regarding the prognostic value of response to noeadjuvant chemotherapy in STS are limited. Methods: 68 patients with localized STS, treated with neoadjuvant anthracycline/ifosfamide-based chemotherapy and assessable for response to chemotherapy were included prospectively in the French Sarcoma Group (GSF) database from 1985 to 2011. All the cases were reviewed by the pathology subcommittee of the GSF. Radiological response to chemotherapy was assessed according to RECIST criteria. Good response was defined as partial response or stable disease according to RECIST and ≤10% recognizable tumor cells in the surgical specimen. Poor response was defined as stable or progressive disease according to RECIST and ≥ 50% recognizable tumors cells in the surgical specimen. All the other cases were defined as intermediate response. Results: Median age was 38 years. Median tumor size was 8 cm (range 2-20). 56% of tumors were located in the limbs and 52% were grade 3. Response to chemotherapy was considered as good in 9 cases (13%), intermediate in 20 cases (29.5%) and poor in 39 cases (57.5%). Median metastasis-free (MFS) and overall (OS) survivals were 45 (95% CI 11-79) and 84 months (95%CI 88-120), respectively. On univariate analysis, grade, tumor size and response to chemotherapy were significantly associated with metastasis-free survival (MFS). Radiological response according to RECIST has no prognostic value. On multivariate analysis, grade was the sole variable independently associated with MFS (HR=3.4, 95% CI 1.5-7.5, p=0.003). On univariate analysis, grade, and response to chemotherapy were significantly associated with overall survival (OS). On multivariate analysis, grade was the sole factor independently associated with OS (HR=2.5, 95% CI 1.2-5.7, p=0.03). Conclusions: Response to neoadjuvant chemotherapy may not have prognostic value in patients with SS. Grade represents the most significant predictive factor of outcome in this setting.

Prognostic value of response assessed by RECIST and WHO criteria to neoadjuvant chemotherapy in locally advanced gastric cancer patients

e15647 Background: In metastatic gastric cancer, the response to chemotherapy is assessed by RECIST or WHO criteria according to the change of tumor size. There are no data, however, on the usefulness of those criteria in evaluating tumor response in the setting of neoadjuvant chemotherapy. The aim of this study was to evaluate the relationship between tumor response to neoadjuvant chemotherapy-as assessed by RECIST and WHO criteria-and clinical outcome in locally advanced gastric cancer (LAGC) patients. Methods: This study recruited LAGC patients who, from January 2003 through November 2005, entered the neoadjuvant arm of prospective randomized phase II trials comparing neoadjuvant chemotherapy to adjuvant chemotherapy. LAGC was defined as stage III or IV (M0) disease based on computed tomography (CT) according to the Japanese Classification of Gastric Carcinoma. Patients with measurable lesions received 3 cycles of neoadjuvant chemotherapy consisting of docetaxel (36 mg/m2) and cisplatin (40 mg/m2) on days 1 and 8 every 3 weeks, followed by surgery. Results: After chemotherapy, 40 (95%) patients underwent surgery and the remaining 2 patients showed new distant metastasis on CT scan. Thirty-five (83%) patients had curative R0 resection. Twenty-eight (67%) patients had a clinical response to neoadjuvant chemotherapy according to RECIST/WHO criteria. Although R0 resection rate (93% vs 64%, P = 0.03), median relapse-free survival (RFS) (43.2 vs 7.5 months, P = 0.14), and overall survival (OS) (not reached vs 27.0 months, P = 0.10) were better in responders than non-responders, they did not differ significantly in the subgroup that subsequently underwent surgery. When we redefined the decrease in tumor size judged as a response by RECIST (≥60% rather than ≥30%) and WHO (≥75% rather than ≥50%) criteria, response correlated significantly with both RFS (P = 0.03) and OS (P = 0.02). Conclusions: In the neoadjuvant setting, which frequently involves smaller measurable lesions than the metastatic setting, larger changes in tumor size than those specified by RECIST and WHO criteria are needed to predict postoperative outcome. No significant financial relationships to disclose.

Response to Nitroglycerin Does Not Predict an Ischemic Cause for Chest Pain

It is common wisdom that chest pain that improves with nitroglycerin is probably ischemic in origin. However, the diagnostic and prognostic value of response to nitroglycerin in patients with chest pain has not been properly assessed. In a prospective study of 459 patients presenting to an emergency department with chest pain, researchers assessed whether a decrease in pain after the administration of a single nitroglycerin dose indicates an ischemic cause of the pain. The cause of chest pain was considered ischemic if the patient had active coronary artery disease (CAD), as defined by the presence of appropriate symptoms and any one of …

Proliferation patterns in acute myeloid leukemia: leukemic clonogenic growth and in vivo cell cycle kinetics.

In a prospective study of 33 newly diagnosed patients with acute myeloid leukemia (AML), we analyzed the relationship of proliferation parameters with clinical parameters, response to induction therapy, and survival. The median follow-up was 26 months. The proliferative capacity of the leukemic progenitor cells was studied using colony-forming assays (number of colony-forming units, growth pattern, and spontaneous clonogenic growth capacity). The cell kinetic parameters of the bone marrow blasts were determined by in vivo labeling with iododeoxyuridine and subsequent flow cytometry: labeling index (LI), DNA synthesis time (Ts), potential doubling time. No or only weak relationships were observed between the experimental and clinical parameters such as age, sex, % blasts, white blood cell count, FAB subtype, cytogenetics, and % CD 34+ cells. This suggests that clonogenic growth and cell cycle kinetics of bone marrow blasts are independent cell biologic properties of AML. No association between the proliferation parameters and induction response rate was noticed. Analysis of the overall survival and event-free survival revealed trends to longer survival rates in patients with a below-median LI (< or = 7.6%) and below-median Ts value (< or = 14.3 h). These trends were more pronounced in the group of de novo AML (n = 23), where the prolonged event-free survival in patients with below-median Ts reached statistical significance (p = 0.02). None of the other parameters appeared significantly correlated with survival, although there was a trend to longer survival rates in patients who had no spontaneous clonogenic growth capacity (p = 0.13). In conclusion, proliferation parameters in leukemic cells provide additional information on the cell biologic characteristics of AML, and these parameters may have prognostic value for response and duration of survival in AML.

Prognostic value of response to chemotherapy using ultrasound in lung cancer with metastatic liver involvement

Prognostic value of response to chemotherapy using ultrasound in lung cancer with metastatic liver involvement

The prognostic value of response to the first cycle of chemotherapy in small cell lung cancer. Results of a multicenter German trial

The prognostic significance of evaluation of response according to chest X-ray after only one cycle of treatment was investigated in patients with small cell lung cancer (SCLC). Three hundred and six patients entered a multicenter randomized German trial testing alternating vs. sequential chemotherapy. Decrease of tumor size after the first cycle was seen to be 78% in the alternating group and 70% in the sequential group. Stable disease occurred in 25% of the sequentially treated and 19% of the alternatingly treated patients. No substantial differences in pretreatment characteristics were noticed between patients with stable disease in sequential and alternating treatment. In sequential therapy, median survival was 323 days for patients with decrease of tumor size after the first cycle and 219 days for patients with no change. Only five out of 21 patients with no change after one cycle responded to continuous administration of this regimen including one complete remission. In alternating therapy, median survival was 347 days for patients with decrease in tumor size after the first cycle and 378 days for patients with no change indicating no difference in prognosis. Twelve out of 18 patients with no change responded to continuous administration of alternating treatment including six complete remissions. We concluded that response to the first cycle according to chest X-ray is a reliable and prognostically valid response criterion if sequential therapy is used. In this treatment modality no change in tumor size after the first cycle indicates poor prognosis, and improvement of the patients' outcome may be achieved by a switch to a second non-cross resistant drug combination.

Prognostic value of response after three MOPP cycles in hodgkin's disease ? stage III and IV

Sixty-eight patients with Hodgkin's disease stage III and IV were evaluated after three out of six MOPP cycles. At that time, 46 (68%) were classified as early responders and 22 as slow responders. The criteria of response were: disappearance of B symptoms, decrease in the size of the largest lymph nodes (by more than 50%) and significant reduction (more than 20%) of mediastinal enlargement. Out of 43 early responders, 38 were in complete remission after six MOPP cycles and only five out of 22 slow responders. Such an early response is only related to the absence of B symptoms at the time of diagnosis (p less than 0.05). The survival curves of early responders and slow responders were significantly different (p less than 0.02). A rapid erythrocyte sedimentation rate (ESR) (greater than 50 mm) was the most frequently abnormal sign found in the group not responding after three MOPP cycles (p less than 0.0001). Such a significant prognostic value of early response is observed for stage III but not for stage IV patients. We conclude that early clinical response after three MOPP cycles is a good prognostic factor which must be kept in mind in the formulation of the therapeutic regimen for Hodgkin's disease stage III and IV.

Relation of tumor content of estrogen and progesterone receptors with response of patient to endocrine therapy.

The levels of estrogen (E2R) and progesterone (PgR) receptors in 165 breast tumor biopsies have been determined. Seventy-seven percent of the specimens contained significant levels of E2R; 38.2% were positive for both receptors. Only four tumors displayed the unusual E2R=/PgR+ pattern. Tumors from pre- and postmenopausal patients had similar receptor characteristics. Two-thirds of the six patients with E2R+PgR+ tumors responded to hormonal therapy, whereas only 28.7% of the E2R+/PgR- tumors regressed after similar treatment. These data from a limited number of patients indicate that the presence of E2R and PgR in breast tumor biopsies is of higher prognostic value for response of the patient than in the presence of E2R alone.

Chemotherapy of Lymphoma With Mechlorethamine and Vinblastine

To determine the relative efficacy of mechlorethamine hydrochloride and vinblastine sulfate, 172 patients with Hodgkin's disease, lymphosarcoma, and reticulum cell sarcoma were randomly assigned to receive one or the other of these agents. If treatment with the first compound failed, each patient was to be treated with the second. No significant differences were found between the therapeutic results obtained with these two drugs in any of these illnesses. The Rye classification for Hodgkin's disease was not found to be of prognostic value for response to these agents. The patients with nodular, poorly differentiated lymphocytic lymphoma according to the Gall-Rappaport classification for non-Hodgkin's lymphoma, responded significantly better to mechlorethamine than to vinblastine, and their response rate with the alkylating agent was significantly higher than that of the other persons with non-Hodgkin's lymphoma.