High Expression of Plasma Extracellular HSP90α is Associated With the Poor Efficacy of Chemotherapy and Prognosis in Small Cell Lung Cancer.

Purpose: eHSP90α is closely related to tumor progression and prognosis. This study aimed to investigate the significance of eHSP90α in the response evaluation and prediction of small cell lung cancer. Methods: We analyzed the relationship between eHSP90α expression and clinicopathological features in 105 patients with small cell lung cancer. Univariate and multivariate analyses were used to determine the association of parameters and ratios with response assessment, progression-free survival (PFS), and overall survival (OS). Results: In SCLC patients, eHSP90α and NSE were positively correlated. The cutoff values of eHSP90α in OS, PFS, and response evaluation were 61.2 ng/ml, 48.7 ng/ml, and 48.7 ng/ml, respectively. eHSP90α could better predict OS, PFS, and response evaluation (AUC OS 0.791, PFS 0.662, 0.685). Radiotherapy and eHSP90α were independent variables for effective chemotherapy through univariate and multivariate analysis. In contrast, radiotherapy, eHSP90α, NSE, and M stage were independent variables for OS. eHSP90α, and M stage were independent variables for PFS. Kaplan-Meier analysis showed that higher eHSP90α expression predicted poorer OS and earlier progression in patients. Conclusions: This study aims to provide new evidence for the efficacy response and prognostic assessment of SCLC. eHSP90α may be a better biomarker for SCLC.

Stereotactic Ablative Radiotherapy for oligo-progressive disease refractory to systemic therapy in Non-Small Cell Lung Cancer: A registry-based phase II randomized trial (SUPPRESS-NSCLC).

BACKGROUND: Management of Non-Small Cell Lung Cancer (NSCLC) patients with oligoprogression remains controversial. There is limited data to support the strategy of Stereotactic Ablative Radiotherapy (SABR) targeting the oligoprogressive disease in combination with ongoing systemic treatment. We aim to assess the benefit of this approach compared to standard of care in the treatment of oligoprogressive NSCLC. METHODS: This phase II study will enroll 68 patients with oligoprogressive NSCLC, defined as 1-5 progressive extracranial lesions ≤5 cm involving ≤3 organs. Patients on active systemic therapy (chemotherapy, immunotherapy, targeted therapy or a combination) will be randomized 1:1 to either continue their current systemic therapy in combination with SABR to all lesions or the standard of care (switch to the next line of treatment, continue same treatment or observation). The co-primary endpoints are progression-free survival (PFS) and overall survival (OS). Secondary endpoints include time to next systemic treatment, patient-reported quality of life, cost effectiveness as well as translational analysis to characterize both adaptive immunity and immunogenic cell death markers in the peripheral blood. DISCUSSION: There is an unmet need to carefully examine the efficacy, safety and quality of life impact of SABR in the context of oligoprogressive disease. The present study will provide higher level randomized evidence on the role of SABR in oligoprogressive NSCLC.

The role of volumetric method in the assessment of chemotherapy response and predicting survival in malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a pleural tumor with high mortality rate and short-term survival expectancy after diagnosis. Assessment of the response to chemotherapy, which is the first choice in treatment of MPM, is important for the transition to alternative chemotherapy protocols and immunotherapy. There is no clarity in the response to chemotherapy treatment. OBJECTIVE: Our study aims to compare the assessment of chemotherapy response using the Modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria and volumetric measurements and to correlate with median survival. MATERIALS AND METHODS: Thirty-two patients (16 females and 16 males) were included in the study, and their ages ranged from 28 to 78 years. Chemotherapy response was determined by both mRECIST and volumetric approach. Tumor volume was measured by linear interpolation and semi-automatic segmentation. Log-rank multiple cutoff analysis was used to determine appropriate cutoff values of volumetric response criteria. RESULTS: According to both mRECIST and volumetric approach, median survival times in partial response, stable disease, and progressive disease groups were 24, 15, and 9 months, respectively. The survival times of the three groups were different (logrank: 17.76; P < 0.001) by mRECIST. The survival of the progressive disease group was shorter than that of the other groups (logrank: 18.91; P < 0.001) by volumetric approach. CONCLUSIONS: In the assessment of chemotherapy response, even though classifications obtained according to the mRECIST criteria and volumetric measurements are statistically compatible, we think that the measurement of the volumetric values will increase the standardization. In our study, threshold values for volumetric measurements were determined; however, these values should be supported by large-scale multicenter studies.

Evaluation of spirometry as a parameter of response to chemotherapy in advanced lung cancer patients: A pilot study.

CONTEXT: Spirometry is an important tool to monitor treatment response in diseases such as chronic obstructive pulmonary disease and asthma. However, there is lack of evidence to support its application to evaluate response to chemotherapy in advanced lung cancer. It might be a useful adjunct to the imaging-based response evaluation which lacks functional assessment of lungs. AIMS: The study was conducted to evaluate the change in spirometry in lung cancer patients after chemotherapy and to find its correlation with change in physical tumor size. SUBJECTS AND METHODS: Sixty-two advanced lung cancer patients who were eligible for palliative chemotherapy were enrolled. Baseline tumor size evaluation using Response Evaluation Criteria in Solid Tumor (RECIST)-based scoring system, and spirometry was done. Four cycles of double agent (platinum doublets) chemotherapy were administered, after which treatment response was evaluated. Repeat spirometry was analyzed and correlated with changes in physical tumor size. RESULTS: Twenty-five patients showed a response (all partial response) to four cycles of chemotherapy. Small cell carcinoma showed a better response rate than non-small cell carcinoma (78% vs. 39%). There was statistically significant improvement in forced expiratory volume in 1 (FEV1) (P = 0.01) and forced vital capacity (P = 0.03) in responders as compared to nonresponders. Change in FEV1 showed a statistically significant correlation with the change in tumor size (RECIST score) (r = -0.34; P = 0.04). CONCLUSIONS: Improvement in spirometry correlates with the tumor response as judged using RECIST criteria after chemotherapy. Further studies with bigger sample size are required to consolidate the results.

[Exploration of the rational therapeutic regimen for advanced lung cancer patients with mild tumor enlargement].

Objective: To investigate the factors that impacts of therapeutic effect in advanced non-small cell lung cancer (NSCLC) patients with mild tumor enlargement and the rational therapeutic strategy for them. Methods: The clinicopathological features and prognostic data of advanced NSCLC patients whose sum of tumor longest diameters with 0 to 20% increase were retrospectively explored, and the Cox proportional hazards model was used to analyze the independent prognostic factors in patients. Results: The median progression-free survival (PFS) of 54 patients with the original regimen was 87 days, significantly less than 168 days of the median PFS of 49 patients with replacing regimen (P<0.001). The median PFS of other chemotherapeutic regiems (154 days) and the targeted therapy (287 days) were longer than the origional therapy (P<0.05 for all). The left 7 patients received radiotherapy. Receiver operating characteristic (ROC) curve indicated a significant difference in the PFS when the maximal cut-off value of tumor enlargement ratio was 7%. Univariate analysis of patients with targeted therapy after disease progression showed that gender, pathological type, clinical stage, lung metastasis and tumor enlargement ratio were the prognostic factors (all of P<0.05). Multivariate analysis showed that the tumor enlargement ratio was an independent prognostic factor (P=0.001). Single factor analysis showed that the chemotherapeutic regimens before and after disease progression were prognostic factors of patients received chemotherapy after disease progression (P<0.05). Cox multivariate analysis showed that the chemotherapeutic regimen after disease progression was an independent prognostic factor of patients (P=0.004). In the patients whose tumor enlargement ratio was 0 to 7%, Univariate analysis showed that chemotherapeutic regimen before tumor enlargement was a prognostic factor (P=0.030), while Cox multivariate analysis showed that it was not an independent prognostic factor (P=0.560). In the patients whose tumor enlargement ratio was 7.1% to 20%, single factor analysis showed that pathological type, bone metastasis and chemotherapeutic regimen after disease progression were prognostic factors (all of P<0.05), and Cox multivariate analysis showed that all of them were independent prognostic factors of these patients (all of P<0.05). Conclusions: To the advanced NSCLC patients whose tumor enlargement ratio is 0 to 20%, the PFS of patients receive replacing regimen is longer than that of patients receive original regimen. There is a significant difference in the PFS when the maximal cut-off value of tumor enlargement ratio is 7%. To patients undergo second-line chemotherapy before disease progression and the tumor enlargement ratio is 7.1% to 20%, the PFS of patients receive replacing regimen is significantly extended. Dual drug replacing regimen is especially benefit to the adenocarcinoma patients without bone metastasis.

Exploration of the rational therapeutic regimen for advanced lung cancer patients with mild tumor enlargement / 中华肿瘤杂志

Objective@#To investigate the factors that impacts of therapeutic effect in advanced non-small cell lung cancer (NSCLC) patients with mild tumor enlargement and the rational therapeutic strategy for them.@*Methods@#The clinicopathological features and prognostic data of advanced NSCLC patients whose sum of tumor longest diameters with 0 to 20% increase were retrospectively explored, and the Cox proportional hazards model was used to analyze the independent prognostic factors in patients.@*Results@#The median progression-free survival (PFS) of 54 patients with the original regimen was 87 days, significantly less than 168 days of the median PFS of 49 patients with replacing regimen (P<0.001). The median PFS of other chemotherapeutic regiems (154 days) and the targeted therapy (287 days) were longer than the origional therapy (P<0.05 for all). The left 7 patients received radiotherapy. Receiver operating characteristic (ROC) curve indicated a significant difference in the PFS when the maximal cut-off value of tumor enlargement ratio was 7%. Univariate analysis of patients with targeted therapy after disease progression showed that gender, pathological type, clinical stage, lung metastasis and tumor enlargement ratio were the prognostic factors (all of P<0.05). Multivariate analysis showed that the tumor enlargement ratio was an independent prognostic factor (P=0.001). Single factor analysis showed that the chemotherapeutic regimens before and after disease progression were prognostic factors of patients received chemotherapy after disease progression (P<0.05). Cox multivariate analysis showed that the chemotherapeutic regimen after disease progression was an independent prognostic factor of patients (P=0.004). In the patients whose tumor enlargement ratio was 0 to 7%, Univariate analysis showed that chemotherapeutic regimen before tumor enlargement was a prognostic factor (P=0.030), while Cox multivariate analysis showed that it was not an independent prognostic factor (P=0.560). In the patients whose tumor enlargement ratio was 7.1% to 20%, single factor analysis showed that pathological type, bone metastasis and chemotherapeutic regimen after disease progression were prognostic factors (all of P<0.05), and Cox multivariate analysis showed that all of them were independent prognostic factors of these patients (all of P<0.05).@*Conclusions@#To the advanced NSCLC patients whose tumor enlargement ratio is 0 to 20%, the PFS of patients receive replacing regimen is longer than that of patients receive original regimen. There is a significant difference in the PFS when the maximal cut-off value of tumor enlargement ratio is 7%. To patients undergo second-line chemotherapy before disease progression and the tumor enlargement ratio is 7.1% to 20%, the PFS of patients receive replacing regimen is significantly extended. Dual drug replacing regimen is especially benefit to the adenocarcinoma patients without bone metastasis.

Comparison of the diagnostic performance of response evaluation criteria in solid tumor 1.0 with response evaluation criteria in solid tumor 1.1 on MRI in advanced breast cancer response evaluation to neoadjuvant chemotherapy.

OBJECTIVE: To compare the diagnostic performance in evaluating the response of neoadjuvant chemotherapy (NAC), between the response evaluation criteria in solid tumor (RECIST) 1.0 and RECIST 1.1, on magnetic resonance imaging (MRI) for advance breast cancer patients. MATERIALS AND METHODS: Breast cancer patients, who underwent NAC between 2005 and 2010, were included. Both prechemotherapy and post-chemotherapy MRIs were performed within 1-4 weeks before and after NAC. Only the patients with subsequent surgery were included. The response to NAC was assessed by using RECIST 1.0 and RECIST 1.1. Patients with a complete or partial response on MRI were considered as responders, and those with stable or progressive disease were considered as non-responders. Tumor necrosis > 50% on pathology was defined as responders and necrosis < 50% was defined as non-responders. The diagnostic accuracy of both RECIST 1.0 and RECIST 1.1 was analyzed and compared by receiver operating characteristic curve analysis. RESULTS: Seventy-nine females (mean age 51.0 ± 9.3 years) were included. Pathology showed 45 responders and 34 non-responders. There were 49 responders and 30 non-responders on RECIST 1.0, and in 55 patients, RECIST 1.0 results agreed with pathologic results (69.6%). RECIST 1.1 showed 52 responders and 27 non-responders. In 60 patients, RECIST 1.1 results were in accordance with pathology results (75.9%). The area under the ROC curve was 0.809 for RECIST 1.0 and 0.853 for RECIST 1.1. CONCLUSION: RECIST 1.1 showed better diagnostic performance than RECIST 1.0, although there was no statistically significant difference between the two.

Comparison of the Diagnostic Performance of Response Evaluation Criteria in Solid Tumor 1.0 with Response Evaluation Criteria in Solid Tumor 1.1 on MRI in Advanced Breast Cancer Response Evaluation to Neoadjuvant Chemotherapy

OBJECTIVE: To compare the diagnostic performance in evaluating the response of neoadjuvant chemotherapy (NAC), between the response evaluation criteria in solid tumor (RECIST) 1.0 and RECIST 1.1, on magnetic resonance imaging (MRI) for advance breast cancer patients. MATERIALS AND METHODS: Breast cancer patients, who underwent NAC between 2005 and 2010, were included. Both prechemotherapy and post-chemotherapy MRIs were performed within 1-4 weeks before and after NAC. Only the patients with subsequent surgery were included. The response to NAC was assessed by using RECIST 1.0 and RECIST 1.1. Patients with a complete or partial response on MRI were considered as responders, and those with stable or progressive disease were considered as non-responders. Tumor necrosis > 50% on pathology was defined as responders and necrosis < 50% was defined as non-responders. The diagnostic accuracy of both RECIST 1.0 and RECIST 1.1 was analyzed and compared by receiver operating characteristic curve analysis. RESULTS: Seventy-nine females (mean age 51.0 +/- 9.3 years) were included. Pathology showed 45 responders and 34 non-responders. There were 49 responders and 30 non-responders on RECIST 1.0, and in 55 patients, RECIST 1.0 results agreed with pathologic results (69.6%). RECIST 1.1 showed 52 responders and 27 non-responders. In 60 patients, RECIST 1.1 results were in accordance with pathology results (75.9%). The area under the ROC curve was 0.809 for RECIST 1.0 and 0.853 for RECIST 1.1. CONCLUSION: RECIST 1.1 showed better diagnostic performance than RECIST 1.0, although there was no statistically significant difference between the two.

Imaging-based tumor treatment response evaluation: review of conventional, new, and emerging concepts.

Tumor response may be assessed readily by the use of Response Evaluation Criteria in Solid Tumor version 1.1. However, the criteria mainly depend on tumor size changes. These criteria do not reflect other morphologic (tumor necrosis, hemorrhage, and cavitation), functional, or metabolic changes that may occur with targeted chemotherapy or even with conventional chemotherapy. The state-of-the-art multidetector CT is still playing an important role, by showing high-quality, high-resolution images that are appropriate enough to measure tumor size and its changes. Additional imaging biomarker devices such as dual energy CT, positron emission tomography, MRI including diffusion-weighted MRI shall be more frequently used for tumor response evaluation, because they provide detailed anatomic, and functional or metabolic change information during tumor treatment, particularly during targeted chemotherapy. This review elucidates morphologic and functional or metabolic approaches, and new concepts in the evaluation of tumor response in the era of personalized medicine (targeted chemotherapy).

Imaging-Based Tumor Treatment Response Evaluation: Review of Conventional, New, and Emerging Concepts

Tumor response may be assessed readily by the use of Response Evaluation Criteria in Solid Tumor version 1.1. However, the criteria mainly depend on tumor size changes. These criteria do not reflect other morphologic (tumor necrosis, hemorrhage, and cavitation), functional, or metabolic changes that may occur with targeted chemotherapy or even with conventional chemotherapy. The state-of-the-art multidetector CT is still playing an important role, by showing high-quality, high-resolution images that are appropriate enough to measure tumor size and its changes. Additional imaging biomarker devices such as dual energy CT, positron emission tomography, MRI including diffusion-weighted MRI shall be more frequently used for tumor response evaluation, because they provide detailed anatomic, and functional or metabolic change information during tumor treatment, particularly during targeted chemotherapy. This review elucidates morphologic and functional or metabolic approaches, and new concepts in the evaluation of tumor response in the era of personalized medicine (targeted chemotherapy).