Primary Tumor Response Rate Research Articles

Epidermal growth factor receptor tyrosine kinase inhibitors combined with thoracic radiotherapy or chemoradiotherapy for advanced or metastatic non-small cell lung cancer: A systematic review and meta-analysis of single-arm trials.

Background:Preclinical in vitro experiments demonstrated that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) might have synergistic effect in combination with radiotherapy on Non-small cell lung cancer (NSCLC), but the clinical trials showed inconsistence results in NSCLC patients with EGFR status unknow or mutations. This study aimed to determine if added TKIs to Thoracic radiotherapy (TRT) improve primary disease response rate (RR) and survival outcomes in advanced or metastatic NSCLC.Methods:We searched MEDLINE, EMBASE, and Cochrane Library from January 2000 to December 2017 for eligible studies where patients received concurrent EGFR TKIs and TRT or CRT. Concerned outcomes were primary tumor RR, overall survival (OS), and adverse events (AEs). The meta-analysis was performed using Stata software (version 12.0). Random effects models were used to pool outcomes across studies. Sensitivity analysis was performed to determine if the results would be different.Results:We found 16 prospective clinical trials with mature results for meta-analyses. Twelve studies including 446 patients reported the RR and survival outcomes of TRT combined TKIs. The CR, PR, SD, and PD, respectively, were 0.06 (95% CI 0.03–0.09, I2 = 0%), 0.44 (95% CI 0.38–0.49, I2 = 64.9%), 0.29 (95% CI 0.24–0.34, I2 = 78.4%), and 0.15 (95% CI 0.11–0.19, I2 = 84.2%). One- and 2-year OS, respectively, were 0.52 (95% CI 0.44–0.60, I2 = 38.8%) and 0.26 (95% CI 0.18–0.33, I2 = 0%). Four studies including 182 patients reported the RR and survival outcomes of CRT combined TKIs. The pooled CR, PR, SD, and PD, respectively, were 0.12 (95% CI 0.02–0.22, I2 = 69.1%), 0.41 (95% CI 0.27–0.55, I2 = 71.6%), 0.31 (95% CI 0.16–0.46, I2 = 79%), and 0.14 (95% CI −0.01–0.30, I2 = 87.8%). Only 1 study reported the survival event rate, 1- and 2-year OS, respectively, were 0.83 (95% CI 0.71–0.94) and 0.67 (95% CI 0.54–0.81). There were not severe adverse events (SAEs) reported either TRT combined TKIs or CRT combined TKIs.Conclusion:There is evidence, albeit of low quality, that added the TKIs to TRT or CRT may improve RR and survival outcomes in patients with EGFR mutant status unknown advanced or metastatic NSCLC relative to other studies of TKIs alone, TRT alone or CRT.

Results of neoadjuvant chemoradiotherapy with docetaxel, cisplatin, and 5-fuluorouracil for advanced esophageal cancer.

171 Background: We previously reported a phase I study of neoadjuvant chemoradiotherapy (CRT ) with docetaxel, cisplatin, and 5-fuluorouracil (DCF) for advanced esophageal cancer. After that, we continued to conduct neoadjuvant CRT with DCF as phase II study and here, we report the results of this study including phase I. Methods: We performed neoadjuvant CRT with DCF chemotherapy and concurrent radiation therapy (40Gy including irradiation field) in patients with advanced esophageal squamous cell carcinoma. Dose of chemotherapy were as follows: docetaxel 25mg/m2 (level 1 n=17), or 30mg/m2 (level 2 n=4) on day 1,15,29 and 43 and cisplatin 70mg/m2 on day 1,29 and 5-fuluorouracil on day 1-4 and 29-32. The tumors were resected during weeks 10-13. Results: From Dec 2009 to Aug 2012, 21patients were enrolled and 19 patients underwent thoracic surgery. There were 17 male and four female subjects of ages ranging from 38 to 72 years (median, 61 years). Of these, 6 patients had stage IIIA esophageal cancer and two had stage IIIB esophageal cancer. All the patients had squamous cell carcinoma. Pathological complete response of primary tumor was achieved in 12 patients (63%) and complete pathological response of both primary tumor and lymph node was seen in eight patients (42%). During CRT, the most common grade 3/4 non-hematological toxicity were anorexia (29%) and esophagitis (29%). During CRT, septic shock caused by infection via catheter was observed and re-operation was performed in one patient with reconstructed gastric tube necrosis.One patient developed recurrent gastric tube ulcer in the anastomotic part 4years after esophagectomy. 10 patients are alive more than 5 years and 5-year overall survival is 47.6% and three of them were level II cases. Conclusions: This preoperative CRT regimen using triplets result in favorite prognosis, but treatment plan should be reconsidered because of relative high toxicity. Because high complete response rate of primary tumor were observed and long-term survival has been obtained at a high rate in the case of level II, we planned new phase I/II study of CRT with DCF without preventive irradiation field. Clinical trial information: R000002555.

A prospective study of p53 expression and its correlation with clinical response of radiotherapy in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a common malignant neoplasm of the head and neck that occurs in people in the southeastern Asian area, including Taiwan. The significant association of p53 expression in NPC suggested that p53 overexpression seemed to occur at an early stage in the development of NPC. Alterations of p53 status were probably the most commonly encountered in head and neck carcinomas, and there was extensive evidence that p53 status might determine tumor response to therapy. Ionizing radiation was studied extensively for the relationship between its damaging effect and p53 status in human cancer cells. This study was carried out to investigate whether there was any correlation between overexpression of p53 protein and locoregional tumor response in patients with NPC treated with 7000 cGy of radiotherapy. Sixty-eight patients (50 males, 18 females) with NPC who were diagnosed and treated with radiotherapy were studied prospectively. Before they had received a radiation dose of 7000 cGy in 35 fractions, five fractions a week, p53 status from a nasopharyngeal biopsy was studied using immunohistochemical staining (IHC). The locoregional response rate of primary tumor was analyzed statistically. Forty-seven patients (69.1%) showed positive p53 staining in their tumors. There were 5 positive stains in 6 squamous cell carcinomas (SCC; 83.3%), 34 positive in 53 non-keratinizing carcinomas (NKC; 64.2%), and 8 positive in 9 undifferentiated carcinomas (UC; 88.9%). The mean ages for patients with three different histopathologies were 48.5, 46.1, and 61.1 years. There were 8 patients (7 positive stains, 1 negative stain) with residual tumor after radiotherapy and all were NKC (6 males, 2 females). Therefore, the clinical response rate of primary tumor was 85.1% in positive p53 immunostaining (40 of 47 cases), 95.2% in those with no immunostaining (20 of 21 cases); the former was poorer in locoregional tumor response than the latter, but there was no significant difference (P > .05, chi2 test). We conclude that there is no statistically significant correlation in locoregional response of primary tumor between p53 overexpression and radiotherapy in patients with NPC (P > .05, Fisher exact test).

Final report of Intergroup Trial 0122 (ECOG PE-289, RTOG 90-12): Phase II trial of neoadjuvant chemotherapy plus concurrent chemotherapy and high-dose radiation for squamous cell carcinoma of the esophagus

Purpose: To determine the outcome of neoadjuvant chemotherapy followed by concurrent chemotherapy plus high-dose radiation therapy in patients with local/regional squamous cell carcinoma of the esophagus. Methods and Materials: Forty-five patients with clinical Stage T1-4N0-1M0 squamous cell carcinoma were entered on a prospective single-arm study, of which 38 were eligible. Patients received 3 monthly cycles of 5-FU (1000 mg/m 2/24 h × 5 days) and cisplatin (100 mg/m 2 day 1; neoadjuvant segment) followed by 2 additional monthly cycles of 5-FU (1000 mg/m 2/24 h × 5 days) and cisplatin (75 mg/m 2 day 1) plus concurrent 6480 cGy (combined modality segment). The median follow-up in surviving patients was 59 months. Results: For the 38 eligible patients, the primary tumor response rate was 47% complete, 8% partial, and 3% stable disease. The first site of clinical failure was 39% local/regional and 24% distant. For the total patient group, there were 6 deaths during treatment, of which 9% (4/45) were treatment related. The median survival was 20 months. Actuarial survival at 3 years was 30%, and at 5 years, 20%. Conclusion: This intensive neoadjuvant approach does not appear to offer a benefit compared with conventional doses and techniques of combined modality therapy. However, high dose radiation (6480 cGy) appears to be tolerable, and is being tested further in Intergroup Trial INT 0123.

Immunologic determinants of head and neck cancer response to induction chemotherapy.

Various measures of immune response were assessed prior to induction chemotherapy (intravenous [IV] cisplatin, fluorouracil [5-FU], and bleomycin) in 43 previously untreated head and neck cancer patients to derive a clinical response prediction model. These were parameters of functional cellular immunity (natural killer [NK] cell activity, lymphocyte blastogenesis response to mitogens), total lymphocyte and lymphocyte subset numbers and percentages, and circulating humoral immunity (total immunoglobulin, immunoglobulin classes, and C1q binding activity [C1q BA]). The C1q BA may reflect levels of circulating immune complexes within peripheral blood. The objective primary tumor response rate was 65% (16 complete responses and 12 partial responses). Univariate logistic regression analysis showed that failure to respond to therapy was significantly related to higher value (vis-à-vis response) of humoral immune parameters total immunoglobulin (Ig), P less than .01; IgG, P less than .01; and C1q BA, P less than .001. No association between cellular immune response measurements and response to chemotherapy was identified. By multivariate logistic regression analysis, only C1q BA levels were predictive of drug therapy responsiveness (P less than .001). Results extend our previous investigations regarding C1q BA measurement in head and neck cancer patients, and show that C1q BA levels add accuracy of prediction of subsequent chemotherapy response to that based solely on standard staging criteria and other parameters of immune status.