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 / 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.

Phase 1 dose escalation study of rigosertib by 2-, 4-, or 8-hour infusion twice-weekly in patients with advanced cancer.

CONTEXT: Rigosertib, a potent, multi-kinase inhibitor that selectively induces mitotic arrest and apoptosis in cancer cells and is non-toxic to normal cells, is being developed for the treatment of solid tumors and hematological malignancies. AIMS: To determine the safety, doselimiting toxicities, and clinical activity of rigosertib administered by 2-, 4-, or 8-hour continuous IV infusion twice-a-week for 3 weeks out of a 4-week cycle in patients with advanced solid tumor or hematological malignancies; and to confirm the safety and tolerability of the recommended phase 2 dose (RPTD). SETTINGS AND DESIGN: Phase 1, open-label, dose-escalation study in men and women ≥18 years of age. MATERIALS AND METHODS: An escalation phase optimized the duration of infusion (2, 4, or 8 hours) of 3200 mg rigosertib twice-a-week for 3 weeks of a 4-week cycle; an expansion phase confirmed the maximum tolerated dose (MTD). STATISTICAL ANALYSIS USED: All data summaries were descriptive. PK parameters were estimated using compartmental analysis. RESULTS: 25 patients (16 male, 9 female, 26- 66 years, all Asian) were treated with rigosertib, 16 in the escalation phase; 9 in the expansion phase. MTD was determined to be 3200 mg as a 4-hour infusion and 2400 mg over 4 hours was declared to be the RPTD. Best response was stable disease in 5 of 14 evaluable patients, with a mean (range) of 90 (43-108) days. CONCLUSIONS: 2400 mg rigosertib as a 4-hour infusion was identified as the RPTD. Five patients achieved stable disease lasting 6-16 weeks.

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).