CCR6 Is a Predicting Biomarker of Radiosensitivity and Potential Target of Radiosensitization in Rectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study aimed to explore the functions and mechanisms of C-C motif chemokine receptor 6 (CCR6), a gene associated with progression and metastasis of colorectal cancer (CRC), in radiosensitivity of rectal cancer (RC). MATERIALS AND METHODS: RNA sequencing and immunohistochemical analysis on CCR6 expression were performed in pretreatment tissues of RC patients exhibiting different therapeutic effects of radiotherapy. Colonogenic survival assay was conducted in different CRC cell lines to assess their radiosensitivity. And the impact of CCR6 expression on radiosensitivity was validated through RNA interference. The DNA damage repair (DDR) abilities of cell lines with different CCR6 expression were evaluated through immunofluorescence-based γH2AX quantification. RESULTS: The CCR6 mRNA level was higher in patients without pathologic complete remission (pCR) than in those with pCR (fold changed, 2.11; p=0.004). High-level expression of CCR6 protein was more common in the bad responders than in the good responders (76.3% vs. 37.5%, p < 0.001). The CRC cell lines with higher CCR6 expression (LoVo and sw480) appeared to be more radioresistant, compared with the sw620 cell line which had lower CCR6 expression. CCR6 knockdown made the LoVo cells more sensitive to ionizing radiation (sensitization enhancement ratio, 1.738; p < 0.001), and decreased their DDR efficiency. CONCLUSION: CCR6 might affect the RC radiosensitivity through DDR process. These findings supported CCR6 as a predicting biomarker of radiosensitivity and a potential target of radiosensitization for RC patients.

Surgery with versus without preoperative concurrent chemoradiotherapy for mid/low rectal cancer: an interim analysis of a prospective, randomized trial / 癌症

<p><b>INTRODUCTION</b>Multimodality therapy, including preoperative chemoradiotherapy (CRT) and total mesorectal excision (TME), has effectively reduced local recurrence rates of rectal cancer over the past decade. However, the benefits and risks of the addition of neoadjuvant CRT to surgery need to be evaluated. This study was to compare the efficacy of TME with versus without preoperative concurrent chemoradiotherapy (CCRT) involving XELOX regimen (oxaliplatin plus capecitabine) in Chinese patients with stages II and III mid/low rectal adenocarcinoma.</p><p><b>METHODS</b>We randomly assigned patients to the TME group (TME without preoperative CCRT) or CCRT + TME group (TME with preoperative CCRT). The primary endpoint was disease-free survival (DFS); the secondary endpoints were overall survival (OS), local and distant recurrence, tumor response to CRT, toxicity, sphincter preservation, and surgical complications. An interim analysis of the potential inferiority of DFS in the CCRT + TME group was planned when the first 180 patients had been followed up for at least 6 months.</p><p><b>RESULTS</b>A total of 94 patients in the TME group and 90 patients in the CCRT + TME group were able to be evaluated. The 3-year DFS and OS rates were 86.3 % and 91.5 % in the whole cohort, respectively. The 3-year DFS rates of the TME and CCRT + TME groups were 85.7% and 87.9 % (P = 0.766), respectively, and the 3-year OS rates were 90.7 % and 92.3 % (P = 0.855), respectively. The functional sphincter preservation rates of the TME and CCRT + TME groups were 71.3 % and 70.0 % (P = 0.849), respectively. In the TME group, 16 (17.0 %) patients were proven to have pTNM stage I disease after surgery. In the CCRT + TME group, 32 (35.6 %) patients achieved a pathologic complete response (pCR).</p><p><b>CONCLUSIONS</b>Preliminary results indicated no significant differences in the DFS, OS, or functional sphincter preservation rates between the TME and CCRT + TME groups. However, preoperative CCRT with XELOX yielded a high pCR rate. Newer techniques are needed to improve the staging accuracy, and further investigation is warranted.</p><p><b>CLINICAL TRIAL REGISTRATION NUMBER</b>Chi CTR-TRC-08000122.</p>

Research progress on pathologic complete response after neoadjuvant chemoradiotherapy for locally advanced rectal cancer / 中华胃肠外科杂志

Neoadjuvant chemoradiotherapy followed by surgery is the standard treatment for patients with locally advanced rectal cancer. Controversy on whether patients should receive radical surgery after pathological complete response (pCR) after neoadjuvant chemoradiotherapy has remained since pCR patients have shown favorable long-term outcome. Progress in multidisciplinary modalities has been made, including MRI, PET/CT imaging studies, genetic expression profiling, etc. The methods of predicting pCR response are inspiring. In this article, we review the methods for prediction and prognostic effect of pCR response when patients with locally advanced rectal cancer are treated with neoadjuvant chemoradiotherapy.

Value of postoperative adjuvant chemotherapy in locally advanced rectal cancer patients with ypT1-4N0 after neo-adjuvant chemoradiotherapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The purpose of this study was to investigate the value of postoperative chemotherapy for locally advanced rectal cancer patients who reached pathological ypT1-4N0 after neo-adjuvant chemoradiotherapy.</p><p><b>METHODS</b>We performed a retrospective study of 104 patients treated with preoperative chemoradiotherapy followed by radical resection, who achieved pathological ypT1-4N0, between Mar 2003 and Dec 2010. There were 73 patients who received postoperative adjuvant chemotherapy, and the other 31 patients did not. The distribution of final pathologic stages for these patients was ypT1-2N0 in 39 cases and ypT3-4N0 in 65 cases.</p><p><b>RESULTS</b>The median follow-up was 41 months. The 3-year overall survival rate (OS) and recurrence-free survival rate (RFS) for the whole group (ypT1-4N0) were 93.4% and 85.3%, respectively. The 3-year OS and RFS in the adjuvant chemotherapy group and non-adjuvant chemotherapy group were 95.5%, 88.6% and 88.6%, 77.2%, respectively. There were no significant differences in 3-year RFS (P = 0.108) and OS (P = 0.106) between the two groups. The 3-year local recurrence and distant metastasis rates in the adjuvant chemotherapy group were 4.1% (3/73) and 5.5% (4/73), while for the non-adjuvant chemotherapy group, the 3-year local recurrence rate and distant metastasis rate were 3.2% (1/31) and 16.1% (5/31), respectively. Significant difference was found in distant metastasis rates (P = 0.030) between the two groups, but not in local recurrence rates (P = 0.676).Further subgroup analysis indicated that for the ypT1-2N0 patients, there were no significant differences in 3-year OS (P = 0.296) and RFS (P = 0.939) between the adjuvant and non-adjuvant chemotherapy groups, while negative results displayed in 3-year local recurrence rates (P = 0.676) and distant metastasis rates (P = 0.414). However, for patients with ypT3-4N0, significant differences were showed in both the 3-year OS (P = 0.034) and RFS (P = 0.025), and further analysis revealed that the 3-year distant metastasis rate was significantly higher in the non-adjuvant chemotherapy group than in the adjuvant chemotherapy group (P = 0.010) , but with non-significant difference in the 3-year local recurrence (P = 0.548).</p><p><b>CONCLUSIONS</b>Adjuvant chemotherapy may not improve survival for ypT1-2N0 patients. However, it may be clinically meaningful for ypT3-4N0 patients by decreasing distant metastasis rate. Further randomized controlled clinical trials are needed to confirm our results.</p>

Clinical analysis of 6 cases of primary small cell carcinoma of the larynx / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To study the clinical characteristics, pathological features, diagnosis, therapy and prognosis of primary small cell carcinoma of the larynx (PSCCL).</p><p><b>METHODS</b>Six cases of PSCCL collected from 1990 to 2009 was retrospectively analyzed. The diagnosis was confirmed by pathological examination. Among six patients, one case belonged to stage III, and the others were in stage IVA. One case abandoned treatment; one case received chemotherapy; one case underwent supraglottic hemilaryngectomy and adjuvant chemoradiotherapy; one case underwent induction chemotherapy, radiotherapy and consolidation chemotherapy. Two cases received induction chemotherapy, concurrent chemoradiation and consolidation chemotherapy. The drug regimens included bleomycin, fluorouracil, cisplatin, etoposide and taxel for 3-6 cycles. The radiotherapy technique included conventional radiotherapy, CT-Sim and three dimensional conformal radiation therapy with (60)Co or 4 MV X-ray for 60 - 66 Gy during 6 - 7 weeks.</p><p><b>RESULTS</b>The time of follow-up was 3 - 24 months and the median was 13 months. Two patients applied with concurrent chemoradiation were alive without tumor. The patient abandoning therapy died of respiratory failure, and the others died of lung or liver metastasis after 8 - 12 months.</p><p><b>CONCLUSIONS</b>PSCCL is a disseminated disease, so the pretreatment evaluation is necessary. Concurrent chemoradiation is an ideal treatment model for this disease.</p>

Efficacy of X-ray stereotactic radiotherapy on brain metastases and prognostic analysis / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>X-ray stereotactic radiotherapy (SRT) is one of the effective treatments for brain metastases (BM). This study was to evaluate the efficacy of SRT on BM, and investigate prognostic factors.</p><p><b>METHODS</b>Between July 1999 and December 2004, a total of 122 intracranial lesions in 78 patients with BM were treated using SRT in our Center. Forty-nine patients had a solitary lesion and 29 had multiple (2-6) lesions. The median SRT dose was 15 Gy (11-24 Gy) in single fraction for 38 lesions, and 24 Gy (11-40 Gy) in 2-6 fractions for 84 lesions. SRT was combined with whole brain radiotherapy (WBRT) of 30-40 Gy for 39 patients. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method. Univariate and multivariate analyses were performed by the log-rank test and Cox model, respectively.</p><p><b>RESULTS</b>The median survival time was 12.9 months (1.7-77.4 months). The 1-year intracranial PFS rate was 87.4%. The 1-and 2-year OS rates were 53.9% and 25.8%, respectively. Univariate analysis showed that the 1-year OS rates were higher in the patients with pretreatment KPS of >/= 70, extracranial lesions controlled, or SRT combined with WBRT than in those with KPS of < 70 (60.7% vs. 29.4%, P = 0.002), extracranial lesions uncontrolled (69% vs. 44.9%, P = 0.005), or SRT alone (64.1% vs. 43.4%, P = 0.03). The benefit of treating with WBRT in combination was mainly achieved in the patients with extracranial lesions controlled or with more than one intracranial lesion. Multivariate analysis showed that KPS score and status of extracranial lesions were independent prognostic factors for OS.</p><p><b>CONCLUSIONS</b>SRT is an effective and safe modality for BM. SRT combined with WBRT may prolong the survival time of the patients with extracranial lesions controlled or multiple intracranial lesions. Independent prognostic factors for OS are KPS score and status of extracranial lesions.</p>

Multi-center phase II clinical trial of humanized anti-epidermal factor receptor monoclonal antibody h-R3 combined with radiotherapy for locoregionally advanced nasopharyngeal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safty of the humanized anti-epidermal factor receptor monoclonal antibody h-R3 in combination with radiotherapy for locoregionally advanced nasopharyngeal carcinoma.</p><p><b>METHODS</b>Totally, 137 patients from 7 medical center around China were randomly divided into combined therapy group or control group. There was no difference in Karnofsky performance score between two groups. All patients in both groups received radical conventionally fractionated radiotherapy to the total dose of D(T) 70-76 Gy. For the combined therapy group, h-R3 was added at a dose of 100 mg i.v. weekly for 8 weeks started at the beginning of radiotherapy.</p><p><b>RESULTS</b>Of the 137 eligilbe patients, 70 were in the combined therapy group treated by h-R3 plus radiotherapy and 67 in the control group by radiotherapy alone. The intent-to-treat (ITT) population consisted of 130 patients, while the per-protocol (PP) population was composed of 126 patients. The efficacy was assessed respectively at three point of time: the end of treatment, the 5th- and 17th-week after treatment. The complete response (CR) of the combined therapy group was significantly higher than that of the control group in both ITT and PP (ITT: 65.63%, 87.50%, 90.63% versus 27.27%, 42.42%, 51.52%; PP: 67.21%, 90.16%, 93.44% versus 27.69%, 43.08%, 52.31%; P < 0.05, respectively). The most common h-R3-related adverse reactions were fever (4.3%), hypotension (2.9%), nausea (1.4%), dizziness (2.9%) and rash (1.4%), which could be reversible if treated properly. Radiotherapy combined with 100 mg h-R3 i. v. weekly was tolerable and did not aggravate the side effects of radiation. The quality of life in the combined therapy group was comparable to that in the control group.</p><p><b>CONCLUSION</b>This phase 1 multicenter clinical trial shows that h-R3 in combination with radiotherapy is effective and well-tolerated for the treatment of locoregionally advanced nasopharyngeal carcinoma.</p>

Comparison between PET/CT and MRI in diagnosing lymph node metastasis and N staging of nasopharyngeal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To compare the clinical significance of PET/CT and MRI in diagnosing lymph node metastasis and N staging of nasopharyngeal carcinoma (NPC).</p><p><b>METHODS</b>116 NPC patients had undergone PET/CT and MRI before therapy. The findings of PET/CT and MRI in diagnosing lymph node metastasis and N staging were compared according to the results of follow-up.</p><p><b>RESULTS</b>A total of 614 lymph nodes in 116 patients were analyzed. 340 positive nodes and 274 negative nodes interpreted by image findings were verified during follow-up. The sensitivity, specificity and accuracy of PET/CT in diagnosing node metastasis was 93.2%, 98.2% and 95.4%, while that of MRI was 88.8%, 91.2% and 89.9%, respectively, with statistically significant difference in each between PET/CT and MRI (P < 0.05). Based on Fuzhou Staging System, 109 patients (94.0%) were correctly staged by PET/CT, and 103 patients (88.8%) by MRI, while according to UICC Staging System, 108 patients (93.1%) were correctly staged by PET/CT, and 100 patients (86.2%) by MRI.</p><p><b>CONCLUSION</b>PET/CT is superior to MRI in diagnosing lymph node metastasis and N staging of nasopharyngeal carcinoma. The false-positive and false-negative assessment based on PET-CT scan findings may be caused by: (1) inflammatory hyperplastic node; (2) node with large areas of necrosis; (3) node in diameter less than spatial resolution limitation of PET.</p>

Chemotherapy and radiotherapy for non-Hodgkin's lymphomas of the nasal cavity / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effects of different treatments on the prognosis of patients with non-Hodgkin's lymphomas of the nasal cavity.</p><p><b>METHODS</b>A retrospective study of 59 patients who suffered from stage I(E) primary non-Hodgkin's lymphomas of the nasal cavity was presented. They were treated by radiotherapy and chemotherapy of CHOP regimen, in which 33 patients received chemotherapy plus radiotherapy, 8 patients received radiotherapy plus chemotherapy, 10 patients received chemotherapy alone, and 8 patients received radiotherapy alone. Survival analysis was performed by Kaplan-Meier method, the difference between groups was evaluated by log-rank test, and the comparison of rates was carried out by chi(2) test.</p><p><b>RESULTS</b>The overall 1-, 3- and 5-year survival rates were 71.2%, 42.0% and 38.5%, respectively. There was no significant difference among the patients received different treatments (chi(2) = 2.98, P = 0.3943), but the patients received radiotherapy plus chemotherapy seemed to have a better survival curve than other patients. The 1-, 3- and 5-year survival rates were 84.2%, 67.7% and 62.0% for lesion limited in nasal cavity but 50.0%, 14.3% and 14.3% for lesion extended and involved the adjacent structures (chi(2) = 10.46, P = 0.0012). As the initial therapy, 24 patients who received chemotherapy of more than 3 cycles, and 16 patients who received radiotherapy of more than 40 Gy, and the complete response (CR) rates were 25.0% and 75.0% (chi(2) = 9.697, P = 0.002). Among 43 patients received chemotherapy, the CR rates for those who received 2, 3 - 4 and 5 - 6 cycles were 10.5%, 25.0% and 25.0%, respectively (chi(2) = 1.467, P = 0.48). Patients who received chemotherapy plus radiotherapy have higher rates of both complication and treatment-related mortality, but the difference was not statistically significant (P = 0.202 and 0.693).</p><p><b>CONCLUSION</b>For stage I non-Hodgkin's lymphomas of the nasal cavity, radiotherapy should be the first treatment to get early local control. Chemotherapy may be followed at the discretion of the pathological grade and clinical staging, or IPI.</p>

Radiosensitivity detected by "comet" assay in two human tumor cell lines / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the value of the "comet" assay in detecting the radiosensitivity in human tumor cell lines.</p><p><b>METHODS</b>The radiation-induced primary DNA damage and repair were detected by the comet assay in CNE-1 and 973 cell lines. The tail moment was used as the end point, to quantitate the primary DNA damage and subsequent repair ability. The cell-survival curve was plotted by the classical colony assay, to detect the D(0) value and Dq value. The results from the above two assays were compared.</p><p><b>RESULTS</b>1. With the increment of irradiation doses, under the same experimental condition, the radiation-induced primary DNA damage was more severe in CNE-1 cells than in 973 cells (P < 0.01). From the cell-survival curves, the D(0) value was 1.631 and 1.822 in CNE-1 and CNE-1 973 cells respectively, indicating that CNE-1 cells were more sensitive to irradiation than 973 cells. The radiosensitivity detected by comet assay and by colony assay in the two cell lines tended to be consistent. 2. The half-repair time of 973 and CNE-1 cell line was 33 min and 41 min detected by comet assay, which indicats that the ability of DNA damage and repair in CNE-1 cells was weaker than in 973 cells. The Dq value of the cell survival curve was 2.152 for 973 and 0.626 for CNE-1 cell line detected by the colony assay, which indicates that the sublethal damage repair in 973 cells being much faster than in CNE-1 cells. The repair ability reflected by the results in the two cell lines was consistent.</p><p><b>CONCLUSION</b>The radiosensitivities reflected by the results of the primary DNA damage and repair detected by both comet assay and colony assay in CNE-1 and 973 cells are consistent. It suggests that comet assay is a good method for detecting the radiosensitivity of tumor cells.</p>

Clinical features, treatment and prognosis of 136 patients with primary non-Hodgkin's lymphoma of the nasopharynx / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics, international prognostic index and treatment of primary non-Hodgkin's lymphoma (NHL) of the nasopharynx.</p><p><b>METHODS</b>From January 1983 to December 1997, 136 patients with previously untreated NHL of the nasopharynx were retrospectively reviewed. All patients were confirmed pathologically and classified by Working Formulation system. There were 18 patients with high-grade, 77 intermediate, 2 low-grade and 39 unclassifiable lymphoma. According to Ann Arbor classification, 25 patients had stage I, 91 stage II, 12 stage III and 8 stage IV lesions. Primary therapy was radiotherapy alone in 13 patients and radiotherapy combined with chemotherapy in 12 patients with stage I disease. In 88 patients with stage II, radiotherapy alone was given to 31 patients, and a combination of radiotherapy and chemotherapy to 57 patients. Chemotherapy was primary treatment for advanced stage III/IV diseases.</p><p><b>RESULTS</b>The overall survival rate (OS), cancer specific survival rate (CSS) and disease-free survival rate (DFS) at 5 and 10 years for all patients were 56.2%, 61.2%, 51.1% and 48.3%, 58.0%, 46.5%, respectively. As for international prognostic index (IPI), the 5-year CSS was 70.9% for 0 risk factor, 44.9% for 1 risk factor, 30.0% for 2 or 3 risk factors, respectively (P = 0.004). For stage I patients, the 5-year CSS was 83.1% for RT alone and 82.2% for combined modality therapy, respectively (P = 0.779). For patients with stage II, the 5-year CSS was 46.0% for radiotherapy alone and 70.9% for combined modality therapy. There was significant difference between them (P = 0.04). Multivariate analysis by Cox regression showed that Ann Arbor stage, B symptom and IPI were independent prognostic factors.</p><p><b>CONCLUSION</b>International prognostic index is an important prognostic factor for Non-Hodgkin's lymphoma of the nasopharynx and the combined modality therapy may be optimal for the stage II patients.</p>

Treatment of early stage primary tonsil non-Hodgkin's lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the treatment for patients with early stage primary tonsil non-Hodgkin's lymphoma (NHL).</p><p><b>METHODS</b>Two hundred and thirteen patients with previously untreated early stage primary tonsil NHL were reviewed. All patients were pathologically confirmed. According to Ann Arbor classification, 35 patients were stage I, 178 stage II. The primary treatment for stage I was radiotherapy alone in 12 and combined modality therapy (CMT) in 23 patients. The primary treatment for stage II was radiotherapy alone in 57,chemotherapy alone in 2, and CMT in 119 patients.</p><p><b>RESULTS</b>The 5-year overall survival, cancer specific survival (CSS) AND disease-free survival (DFS) for the early stage primary tonsil non-Hodgkin's lymphoma were 65%, 70% and 61%, respectively. The 5-year CSS was 63% for the radiotherapy alone group and 72% for the CMT group (p = 0.064), and the 5-year DFS were 56% for the radiotherapy alone group and 62% for the CMT group. For patients with stage I disease, The 5-year CSS were 100% in both radiotherapy alone and CMT groups, and the 5-year DFS were 100% and 80% in these two groups (p = 0.148), respectively. There was no significant difference of efficacy between the two treatment s for the patients with stage I disease. For the patients with stage II disease, the 5-year CSS was 58% in radiotherapy alone group and 66% in CMT group (p = 0.051). However, CMT significantly improved DFS in stage II disease, with a 5-year DFS of 46% for radiotherapy alone and 60% for CMT (P = 0.046).</p><p><b>CONCLUSION</b>Patients with stage I tonsil non-Hodgkin's lymphoma treated with radiotherapy alone or CMT can achieve an excellent outcome. CMT significantly improve the DFS in stage II patients. There was a trend that CMT improved the survival rates in the patient with early stage disease. It was suggested that CMT should be used for the patients with early stage primary tonsil non-Hodgkin's lymphoma.</p>