Concurrent Chemoradiotherapy Response Research Articles

Efficacy of fluoro-2-deoxy-d-glucose positron emission tomography to evaluate responses to concurrent chemoradiotherapy for head and neck squamous cell carcinoma

This study evaluates the utility of fluorodeoxyglucose-positron emission tomography (FDG-PET) in patients with head and neck squamous cell carcinoma (HNSCC) who received concurrent chemoradiotherapy (CCRT). Sixty-five patients were recruited for this study between November 2002 and April 2007. The FDG-PET scan was performed before treatment and 4-6 weeks after treatment. The mean of maximum standardized uptake value (SUVmax) before treatment at the primary tumor site was 8.1 (range, 2-22). The sensitivity of FDG-PET for the diagnosis of primary tumor site was 98%. The mean of SUVmax after treatment was 2.6 (range, 2-5). The sensitivity, specificity, and accuracy of FDG-PET for the diagnosis of primary tumor site after treatment were 100%, 40%, and 46%, respectively. The mean of SUVmax before treatment at the nodal site was 4.7 (range, 2-16). The mean of SUVmax after treatment was 2.0 (range, 2-6.7). The pre-treatment SUVmax of T2, T3, and T4 stages were significantly higher than that of the T1 stage. The N stage had no correlation in terms of the pre-treatment nodal site SUVmax. Our results indicate that FDG-PET is a useful imaging method for evaluating the response of CCRT in patients with HNSCC. However, performing FDG-PET 4-6 weeks after treatment may be too early as it may give false-positive results due to fibrosis and scarring.

Use of Germline Polymorphisms in Predicting Concurrent Chemoradiotherapy Response in Esophageal Cancer

To identify germline polymorphisms to predict concurrent chemoradiation therapy (CCRT) response in esophageal cancer patients. A total of 139 esophageal cancer patients treated with CCRT (cisplatin-based chemotherapy combined with 40 Gy of irradiation) and subsequent esophagectomy were recruited at the National Taiwan University Hospital between 1997 and 2008. After excluding confounding factors (i.e., females and patients aged ≥70 years), 116 patients were enrolled to identify single nucleotide polymorphisms (SNPs) associated with specific CCRT responses. Genotyping arrays and mass spectrometry were used sequentially to determine germline polymorphisms from blood samples. These polymorphisms remain stable throughout disease progression, unlike somatic mutations from tumor tissues. Two-stage design and additive genetic models were adopted in this study. From the 26 SNPs identified in the first stage, 2 SNPs were found to be significantly associated with CCRT response in the second stage. Single nucleotide polymorphism rs16863886, located between SGPP2 and FARSB on chromosome 2q36.1, was significantly associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.62-10.30) under additive models. Single nucleotide polymorphism rs4954256, located in ZRANB3 on chromosome 2q21.3, was associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.57-10.87). The predictive accuracy for CCRT response was 71.59% with these two SNPs combined. This is the first study to identify germline polymorphisms with a high accuracy for predicting CCRT response in the treatment of esophageal cancer.

Toxicities and response of concurrent chemoradiotherapy for stage IIB-IIIB cervical cancer.

e15549 Background: Cervical cancer is the most common cancer in women in Vietnam. Concurrent chemoradiotherapy (CCRT) has been proved survival benefit and emerged as the standard treatment of locally advanced cervical cancer. However, it significantly increases early toxicities. This study evaluated the acute toxicities and responses of CCRT in treatment of stage IIB-IIIB cervical cancer in Vietnam. Methods: From November 2006 to December 2007, 60 patients with stage IIB-IIIB cervical cancer were treated by CCRT. EBRT consisted of 40 Gy/20 fractions, followed by 10 Gy boost to the parametrium and intracavitary HDR brachytherapy 7 Gy to point A/fraction/week in 3 fractions. Chemotherapy with cisplatin 40 mg/m2/weekly for 6 cycles started by the first day of EBRT. Results: All the patients completed treatment protocol. Grade 3-4 leukopenia, neutropenia, and thrombocytopenia were 40%, 33.3%, 8.3% respectively. 19 cases (31.7%) had renal toxicity (grade 1: 16 cases, grade 2: 2 cases, and grade 3: 1 case). Grade 3-4 toxicities increased sharply after the fourth cycle of chemotherapy. Mean overall treatment time is 72 days. 15 patients (25%) had to delay treatment mainly due to hematologic toxicity (10/15 cases). The overall response rate was 96.7% (complete response: 81.7%; partial response: 15%). Conclusions: CCRT is relatively high hematologic toxicities and high response rate. This study pointed out the relationship between the risk of toxicities and number of chemotherapy cycles. CCRT with 5 cycles of chemotherapy would decrease toxicities and overall treatment time. No significant financial relationships to disclose.

Profiling Protein Markers Associated with the Sensitivity to Concurrent Chemoradiotherapy in Human Cervical Carcinoma

Concurrent chemoradiotherapy (CCRT) is recently recommended as the primary and standard treatment modality for cervical cancer. The aim of this study is to investigate the protein biomarkers associated with CCRT sensitivity, so as to better understand the mechanisms underlying CCRT resistance. Fresh tumor tissues from five cases for each group of CCRT-highly sensitive (CCRT-HS) and CCRT-lowly sensitive (CCRT-LS) were analyzed by 2-D electrophoresis coupled with MALDI-TOF-MS, followed by Western blot for four candidate proteins including S100A9, galectin-7, nuclear matrix protein-238 (NMP-238), and heat shock protein-70 (HSP-70). In randomly selected CCRT-HS (n = 60) and CCRT-LS (n = 35) cases, these four differentially expressed proteins were detected by tissue microarray with immunohistochemistry staining to explore the association between these interested proteins and CCRT sensitivity. Nineteen proteins differentially expressed more than four times between two groups were identified. An association was revealed between CCRT sensitivity and increased S100A9 and galectin-7, but decreased NMP-238 and HSP-70 expression (p < 0.001, respectively). Although none of these four protein markers could be used as an independent predictive factor, a recurrence prediction model was generated by combining S100A9, galectin-7, NMP-238, and HSP-70 as a full predictive factor. The proteomic analysis combined with tissue microarray provides us a dramatic tool in predicting CCRT response. The increased expression of S100A9 and galectin-7, but decreased expression of NMP-238 and HSP-70, suggests a significantly increased sensitivity to CCRT in cervical cancer.

A phase II study of weekly docetaxel/cisplatin and concurrent radiotherapy followed by surgery in patients with stage III non-small cell lung cancer (NSCLC)

7586 Background: Concurrent chemoradiotherapy (CRT) is standard of care in stage III NSCLC. Optimal chemotherapy has yet to be defined and the role of surgery is still unclear. This prospective study analyzed the feasibility and efficacy of weekly docetaxel/cisplatin (DC) and concurrent involved-field thoracic radiotherapy (CRT) followed by surgery in patients with stage IIIA/B NSCLC. Primary endpoint is radiologic response of DC and CRT. Secondary endpoints included toxicity, efficacy of surgery, postoperative morbidity and mortality, time to progression and overall survival. Methods: DC consisted of IV docetaxel 20 mg/m2 and cisplatin 20mg/m2 at days 1, 8, 15, 22, 29 and 36. CRT was given in once-daily fractions of 1.8 Gy, 5 fractions a week to a total dose of 45 Gy during days 8 to 36. (Non-)invasive investigations were performed after CRT in order to restage the mediastinum. When mediastinal downstaging was achieved, surgery was performed in order to achieve radical resection. Results: Between January 2005 until August 2006, 45 patients were included, of whom 42 patients were evaluable. The median follow-up time was 26.2 months (95 % CI: 24.6–27.7). Stage IIIB disease was present in 17 patients (cT4N2=10, cT4N0/N1=4 and cN3=3) and 25 had stage IIIA-N2 disease. A radiologic response was seen in 20 patients (48%) and eight (19%) showed progressive disease. Toxicity was mild. Twenty patients (48%) of the twenty-three operated patients underwent a radical resection without residual mediastinal malignant disease, ten pneumonectomies (8 left sided) were performed. The mean survival time for this group was 20.3 months (95% CI: 16.5–24.1) vs 16 months (95% CI: 10.4–21.7) for the patients without operation (p=0.068, median was not reached). The 30 days mortality was 4%. Twenty-one patients of 42 showed progression (50%), of which 16 patients developed distant metastasis (38%). Conclusions: Weekly DC and involved-field CRT is possible in stage III NSCLC, with limited toxicity. Radiologic response was seen in 20 patients (48%) and 14 patients showed stable disease. Nearly half of the treated patients (48%) could undergo a radical surgical resection (R0) with a mean survival benefit of 4.3 months. No significant financial relationships to disclose.

Chemoselection As a Strategy for Organ Preservation in Advanced Oropharynx Cancer: Response and Survival Positively Associated With HPV16 Copy Number

To test induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CRT) or surgery/radiotherapy (RT) for advanced oropharyngeal cancer and to assess the effect of human papilloma virus (HPV) on response and outcome. Sixty-six patients (51 male; 15 female) with stage III to IV squamous cell carcinoma of the oropharynx (SCCOP) were treated with one cycle of cisplatin (100 mg/m(2)) or carboplatin (AUC 6) and with fluorouracil (1,000 mg/m(2)/d for 5 days) to select candidates for CRT. Those achieving a greater than 50% response at the primary tumor received CRT (70 Gy; 35 fractions with concurrent cisplatin 100 mg/m(2) or carboplatin (AUC 6) every 21 days for three cycles). Adjuvant paclitaxel was given to patients who were complete histologic responders. Patients with a response of 50% or less underwent definitive surgery and postoperative radiation. Pretreatment biopsies from 42 patients were tested for high-risk HPV. Fifty-four of 66 patients (81%) had a greater than 50% response after IC. Of these, 53 (98%) received CRT, and 49 (92%) obtained complete histologic response with a 73.4% (47 of 64) rate of organ preservation. The 4-year overall survival (OS) was 70.4%, and the disease-specific survival (DSS) was 75.8% (median follow-up, 64.1 months). HPV16, found in 27 of 42 (64.3%) biopsies, was associated with younger age (median, 55 v 63 years; P = .016), sex (22 of 30 males [73.3%] and five of 12 females [41.7%]; P = .08), and nonsmoking status (P = .037). HPV titer was significantly associated with IC response (P = .001), CRT response (P = .005), OS (P = .007), and DSS (P = .008). Although the numbers in this study are small, IC followed by CRT is an effective treatment for SCCOP, especially in patients with HPV-positive tumors; however, for patients who do not respond to treatment, alternative treatments must be developed.

Clinical benefit response of concurrent chemoradiotherapy with protracted 5-fluorouracil infusion in patients with locally advanced pancreatic cancer

Background Pancreatic cancer is a highly virulent disease with a poor prognosis. Although objective tumor response to chemotherapy and/or radiotherapy is low, some patients show an improvement in their symptoms after treatments, without obvious tumor regression.

Concurrent chemoradiotherapy followed by surgery for advanced stage III non-small cell lung cancer (NSCLC): Katakami N. Matsumoto H. Tomioka H. Okazaki M. Hasegawa T. Sakamoto H. Pulmonary Unit, Kobe City General Hospital, Kobe. Jpn J Cancer Chemother 1995;22:531–537

Forty-two patients with stage IIIA (bronchoscopically T3 and/or bulky N2) and stage IIIB NSCLC were treated with concurrent chemoradiotherapy (CRT). Treatment consisted of CDDP, 20 mg/m2 and etoposide, 40 mg/m2 by continuous infusion (day 1-5) of weeks 1 and 5 simultaneously with chest radiotherapy (RT), 50 Gy, 2 Gy/Fx, 5 Fx/week. Surgery was attempted 3-5 weeks after RT in pts clinically downstaged. Between 10/90 and 12/92, 43 previously untreated pts were enrolled and 42 were eligible. Pts characteristics were: male/female = 37/5; mean age, 61 yrs (range, 31-74 yrs); stage IIIA/IIIB = 10/32; 15 adenocarcinoma, 24 squamous cell, 2 large cell, 1 unclassified; PS 0/1/2 = 11/24/7. Excluding 1 ineligible pts, 42 pts were evaluated for CRT response. The response rate was 81% (1 CR, 33 PR, 5 NC, 1 PD, 2 NE). Clinical downstaging was achieved in 20 pts (48%). Twenty-one pts (50%) received surgery and 19 of them were completely resected. In 7 resection specimens, no tumor was observed. Toxicity of CRT was well tolerable (Grade 4 leukopenia, 15%; Grade 2-3 esophagitis, 15%). We conclude that this intensive combined modality therapy is acceptable and appears to increase the response rate as well as resectability. Prospective randomized studies should be conducted for further evaluation of this treatment modality.