Treatment and prognosis analysis of perineural invasion on sinonasal adenoid cystic carcinoma / 中华肿瘤杂志

Objective: To analyze the efficacy of sinonasal adenoid cystic carcinoma (ACC) with perineural invasion (PNI), and explore the prognostic value of PNI on sinonasal adenoid cystic carcinoma. Methods: The clinical data of 105 patients with sinonasal ACC admitted to Cancer Hospital, Chinese Academy of Medical Sciences from January 2000 to December 2016 were retrospectively reviewed. All patients were restaged according to American Joint Committee on Cancer 8th edition. Follow-up visits were conducted to obtain information of treatment failure and survival outcome. The Log rank test was used for univariate analysis of prognostic factors, and Cox regression model was used for multivariate prognostic analysis. Results: The maxillary sinus (n=59) was the most common primary site, followed by the nasal cavity (n=38). There were 93 patients with stage Ⅲ-Ⅳ. The treatment modalities included surgery alone (n=14), radiotherapy alone (n=13), preoperative radiotherapy plus surgery (n=10), and surgery plus postoperative radiotherapy (n=68). The median follow-up time was 91.8 months, the 5-year local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 72.6%, 73.0%, 52.9% and 78.0%, respectively. There were 33 patients (31.4%) with PNI-positive. The 5-year DMFS, PFS, and OS rates of PNI-positive group were 53.7%, 29.4% and 56.5%, respectively, which were significantly inferior to those of PNI-negative group (80.8%, 63.0% and 86.8%, respectively, P<0.05), while there was no significant difference in the 5-year LC rate between both groups (64.5% vs 76.5%, P=0.273). The multivariate Cox regression analysis showed PNI was one of the poor prognostic factors of DMFS (HR=3.514, 95%CI: 1.557-7.932), PFS (HR=2.562, 95%CI: 1.349-4.866) and OS (HR=2.605, 95%CI: 1.169-5.806). Among patients with PNI-positive, the 5-year LC, PFS and OS rates of patients received surgery combined with radiotherapy were 84.9%, 41.3% and 72.7%, respectively, which were significantly higher than 23.3%, 10.0% and 26.7% of patients receiving surgery or radiotherapy alone (P<0.05). Conclusion: The presence of PNI increases the risk of distant metastasis in patients with sinonasal ACC. Compared with patients with PNI-negative, the prognosis of patients with PNI-positive is relatively poor, and surgery combined with radiotherapy for PNI-positive sinonasal ACC results in good clinical outcomes.

Fractionated stereotactic radiotherapy with vagina carotica protection technique for local residual nasopharyngeal carcinoma after primary radiotherapy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Local failure of nasopharyngeal carcinoma (NPC) after radiotherapy (RT) remains one of the major treatment failures. This study aimed to evaluate the clinical efficacy and complications of fractionated stereotactic radiotherapy (FSRT) with vagina carotica protection technique for local residual of NPC patients after the primary RT.</p><p><b>METHODS</b>From August 2006 to August 2010, FSRT with vagina carotica protection technique was applied to 36 patients in our department, the patients aged between 13 and 76 years with a median of 41.3 years, 25 of them were male and 11 were female. According to 2002 Union for International Cancer Control (UICC) Staging System, the stages before primary radiotherapy were: IIa 2, IIb 5, III 18, IVa 7, IVb 4. In the first course of radiotherapy, 9 patients received conventional RT, 27 patients received intensity modulated radiotherapy (IMRT) and 20 out of the 36 patients received concurrent chemoradiotherapy. The total dose in the first course of RT was 69.96 - 76.90 Gy (median, 72.58 Gy). The intervals between the primary RT and FSRT ranged from 12 to 147 days (median, 39.8 days). Target volumes ranged from 1.46 to 32.98 cm(3) (median, 14.94 cm(3)). The total FSRT doses were 10.0 - 24.0 Gy (median, 16.5 Gy) with 2.0 - 5.0 Gy per fraction. The most common regimen was 15 Gy in 5 fractions of 3 Gy, the irradiation dose to vagina carotica was less than 2 Gy per fraction.</p><p><b>RESULTS</b>The median follow-up time was 34 months (range, 12 - 59 months). The 3-year local control rate was 100%; the 3-year overall survival rate was 94.4%; the 3-year disease-free survival rate was 77.8%. In this study, we had one case of cranial nerve injury, two cases of temporal lobe necrosis, and no nasopharyngeal massive hemorrhage was observed.</p><p><b>CONCLUSION</b>FSRT with vagina carotica protection technique is an effective and safe RT regimen for local residual of NPC with reduction of radiation-related neurovascular lesions.</p>

Adenoid cystic carcinoma of maxillary sinus: diagnosis, treatment and prognostic factors / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To study the clinical characters, the outcomes of treatments and the factors affecting long-term treatment results of adenoid cystic carcinoma (ACC) of the maxillary sinus.</p><p><b>METHODS</b>The clinical data of 80 patients with ACC of the maxillary sinus treated initially were analyzed retrospectively. Survival rate, local recurrence and distant metastasis were analyzed using Kaplan-Meier method. Prognosis factors were analyzed by Log-rank test and Cox regression.</p><p><b>RESULTS</b>The 5-, 10- and 15-year cumulative overall survival rates were 65.2%, 37.1%, 26.3% respectively and 5-, 10-, and 15-year disease-free survival rates 50.7%, 30.7% and 24.5% respectively. The 5-, 10- and 15-year cumulative local control rates were 68.5%, 47.3% and 47.3% respectively and the cumulative distant metastasis rate were 32.8%, 48.8% and 48.8% respectively. Prognostic factors affecting survival included T stage, pathologic grade and the modes of treatment (P < 0.05). Patients with combined therapy composed of surgery and radiation had a better local control, compared with surgery or radiation alone (χ(2) = 18.33, P < 0.01), and surgery combined with postoperative radiation was prior to preoperative radiation combined with surgery (χ(2) = 6.64, P < 0.05). Patients treated with surgery combined with preoperative radiation, either with doses of ≥ 60 Gy or with negative margins, had a better local control, compared with doses < 60 Gy and with positive margins (χ(2) = 5.06, P < 0.05). The most of patients (62.8%) died of local recurrence.</p><p><b>CONCLUSIONS</b>The most of failure was due to recurrence. Combined therapy composed of surgery and radiation improves the local control and survival in patients with ACC of the maxillary sinus, compared with surgery or radiation alone. Surgery combined with postoperative radiation provides the best overall survival and local control and should be the first choice of treatments.</p>

Stereotactic radiotherapy--an approach to improve local control of nasopharyngeal carcinoma / 癌症

Radiotherapy is the primary curative treatment of nasopharyngeal carcinoma (NPC) with the dose-response relationship. Local recurrence is one of the major treatment failure patterns. With high accuracy, high tumor dose, high therapeutic enhancement ratio and low normal tissue dose, stereotactic radiotherapy (SRT) is used as boost irradiation for residual lesions and is able to improve the local control rate. Residual lesions involving the carotid artery or cavernous sinus, or with tumor necrosis are treatment contraindications to SRT boost irradiation; while the old patients, patients with hypertension, diabetes mellitus, and severe nasopharyngeal infection are relative treatment contraindications to SRT boost irradiation. Fractionated SRT can spare vessels and nerves better than stereotactic radiosurgery (SRS). SRT can definitely improve the outcome for the boost of NPC residual lesions. Proper patient selection, individualized fractionated regimen, and balance of the benefit of tumor control and the risk of normal tissue damage are of paramount importance to ensure the satisfactory clinical outcome and quality of life.

Postoperative radiotherapy for primary intraosseous carcinoma of the jaws / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the indication, location and dose of postoperative radiotherapy for primary intraosseous carcinoma (PIOC) of the jaws.</p><p><b>METHODS</b>From October 1969 to November 2005, 13 patients with PIOC were treated at the Cancer Hospital of Chinese Academy of Medical Sciences. Forty six cases with complete clinical data were collected from 27 published reports. Twenty-seven of the 59 patients were treated with surgery plus postoperative radiotherapy, and 22 with surgery alone.</p><p><b>RESULTS</b>All of the 13 cases in our series had advanced disease, and overall 1-, 2- and 3-year survival rats were 59.2%, 33.8% and 12.7% , respectively. For the reported 59 cases in literature, the overall 1-, 2- and 3-year survival rats were 78.4%, 53.9% and 34.0%, respectively. They were 84.3%, 57.2% and 43.6% for the patients treated by surgery plus postoperative radiotherapy, whereas they were 81.8%, 71.2% and 35.1% for the patients by surgery alone (P = 0.908). It seemed that surgery plus postoperative radiotherapy could not improve the survival of PIOC patients with involvement of adjacent soft-tissues or positive neck nodes or partial excision of primary tumor when compared with surgery alone, if the bias of selection in the patients for postoperative radiotherapy was neglected.</p><p><b>CONCLUSION</b>Postopreative radiotherapy may improve the survival for the patient with primary intraosseous carcinoma of the jaws. Our suggestion is that postoperative radiotherapy should be applied to the patient with any of the following items: positive operative margin; tumor involvement of adjacent soft-tissues; positive neck nodes; partial excision of primary tumor. However, the location and dose of postoperative radiotherapy may be varying at different situation.</p>

Radiosensitization of paclitaxel combined with radiation on nasopharygneal carcinoma cells (CNE-I) in vitro / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the radiosensitization of paclitaxel combined with radiation on nasopharygneal carcinoma cells( CNE-I) in vitro.</p><p><b>METHODS</b>Human CNE-I cells were used for this study. Clonogenic assay was used to determine the drug dose of IC10, IC50 and IC90 for CNE-I Cells. The cells treated with different concentration of paclitaxel for 24 hours before or after radiation (dose ranged from 0 - 10 Gy ) were used to evaluate the radiosensitizing effect of paclitaxel combined with radiation. DNA flow cytometry was performed to define the cell cycle characteristics of cell populations treated for 0, 2, 6, 12, 18, 24 h with 0.1 nmol/L, 0.5 nmol/L, 1.0 nmol/L, 2.5 nmol/L paclitaxel, respectively.</p><p><b>RESULTS</b>The dose of IC10, IC50 and IC90 for paclitaxel in CNE-I cells was 0.05 nmol/L, 1.0 nmol/L and 2.5 nmol/L, respectively. Paclitaxel treatment at concentration of 0.05 nmol/L and 1.0 nmol/L for 24 hours combined with X-ray irradiation before or after radiation showed radiosensitivity-enhansing effects in CNE-I cells. G2/M block was present when the drug concentrations were 2.5 nmol/L and 10.0 nmol/L, and it peaked at 18 hours.</p><p><b>CONCLUSION</b>With an optimal paclitaxel/radiation combination, paclitaxel may exert a radiosensitizing effect on CNE-I cells. The effect might be related to the G2/M block caused by paclitaxel.</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>

Symptoms and prognosis of nasopharyngeal carcinoma / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the relationship between the symptoms and prognosis of nasopharyngeal carcinoma (NPC).</p><p><b>METHODS</b>The clinical data of 905 M0 NPC patients who received radical radiotherapy from January 1990 to May 1999 were retrospectively studied. Nodal distribution, cranial nerve paralysis, as well as the relationship between symptom duration and prognosis were analyzed.</p><p><b>RESULTS</b>The most common symptom in patients with NPC is neck node metastasis, with an incidence of 40.0% at the time of diagnosis, followed by blood-staining sputum (18.7%) and aural symptoms (17.0%). Node metastasis in the lower neck and supraclavicular region alone was seen in 10 patients (1.1%). Cranial nerve paralysis was found in 179 patients (19.8%). The 5-year overall survival and disease-free survival were significant lower in symptom duration more than 6 months group than in less than 6 months group (71.2% vs 79.8%, P = 0.008 and 51.9% vs 63.6%, P = 0.0008); however, the local control rate between these two group was not significantly different (79.4% vs 83.5%, P = 0.138).</p><p><b>CONCLUSION</b>The symptom duration is associated with the prognosis of NPC. Early diagnosis and treatment are the most important factors in improving the prognosis of NPC.</p>

Long-term results of different treatment modalities in 464 hypopharyngeal squamous-cell carcinoma patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To present the treatment results and to identify the most effective therapeutic plan of different therapeutic modalities in patients with squamous-cell carcinoma of hypopharynnx.</p><p><b>METHODS</b>A retrospective review of 464 patients with squamous-cell carcinoma of the hypopharynx treated between 1958 and 1998 was accomplished. The clinical characteristics, results of different treatments were analyzed by SPSS 10.0 statistic software.</p><p><b>RESULTS</b>Of 464 patients, the age ranged from 20 to 88 years (mean 56.3 years) and the male to female ratio was 5.5:1. The primary lesion of 383 were originated from the pyriform sinus, 40 from posterior pharyngeal wall and 41 from the postcricoid area. According to the UICC 1997 TNM staging system, 75% had T3 or T4 lesion or 92.2% stage III or IV on presentation. 65% had neck metastases. 202 patients were treated with preoperative radiation plus surgery (R + S), 22 with surgery plus postoperative radiation (S + R), 26 surgery alone (S), 40 patients with salvage surgery after radiotherapy failure (RF) and 174 patients with radiotherapy alone. The overall 5-year survival rate was 34.2%. The overall 5-year survival rate of R + S group was 46.3%, S + R group was 49.2%, S alone group 22.8%, RF group was 40.8%, radiotherapy alone group 18.0% (P < 0.01). The overall 5-year survival rate of R + S group was higher than that of S alone group (P = 0.046). The rate of larynx preservation in R + S group was 39.6% in contrast to that of S + R and S alone group of 16.7% (P = 0.003).</p><p><b>CONCLUSION</b>The survival rate of patients with squamous-cell carcinoma of the hypopharynx treated with combined therapy (R + S or S + R) is better than the other therapeutic modalities. R + S combined is able to offer an obviously higher rate of larynx preservation (39.6% vs 16.7%).</p>

Preliminary results of radiosurgery for uveal melanoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the clinical value of stereotactic radiosurgery (SRS) for uveal melanoma.</p><p><b>METHODS</b>From Jan, 1996 to March, 2004, 16 patients with uveal melanoma were treated with SRS, two by one session (35 Gy, 25 Gy) and fourteen by fractionated SRS (30-55 Gy/2-4F/4-16D). The follow-up period ranged from 3 to 100 months (median: 66 months).</p><p><b>RESULTS</b>All 16 patients were still alive though all were blind in the diseased eye during recent follow-up. Local control rate was 93.4%, 5-year survival rate of 13 patients who have been followed for more than 5 years, was 100% (13/13). However, 7 patients received eyeball enucleation due to corneal ulcer (n = 2), suspicion for uncontrolled tumor (n = 2) and secondary glaucoma (n = 3). One patient developed distant metastasis, though still alive.</p><p><b>CONCLUSION</b>Fractionated radiosurgery is safe and effective for uveal melanoma. It is indicated for lesions of limited size (longest diameter < 20 mm, depth < 15 mm) located in the posterior pole or behind the equator at the back of the eyeball.</p>

Prognostic factors and outcome of esthesioneuroblastoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the clinical feature, prognostic factors and the appropriate treatment modality of esthesioneuroblastoma (ENB).</p><p><b>METHODS</b>The data of 49 patients with ENB treated from Dec. 1978 to Dec. 2001 were retrospectively reviewed and analyzed. In this series, 3 patients had modified Kadish stage A disease, 15 stage B, 22 stage C, and 9 stage D lesion. The treatment modalities included surgery alone in 4 patients, and radiotherapy alone in 11, surgery plus radiotherapy in 19, radiotherapy plus chemotherapy in 8, surgery plus radiotherapy plus chemotherapy in 7. Statistic analysis was performed using software SPSS 10.0. Overall survival (OS) and disease free survival (DFS) were calculated using Kaplan-Meier method. Differences between survival curves were tested by Log rank method.</p><p><b>RESULTS</b>The 5-year OS and DFS of the whole group was 60.5% and 41.9%, respectively. The 5-year OS of patients with modified Kadish stage A or B disease and those with stage C or D was 78.4% and 49.7% (chi(2) = 2.10, P = 0.15), and the 5-year DFS was 47.1% and 38.4% (chi(2) = 0.08, P = 0.78), respectively. The 5-year OS of patients with or without neck lymph nodal metastasis was 17.8% and 70.8% (chi(2) = 2.32, P = 0.13), and the 5-year DFS was 0 and 53.4% (chi(2) = 11.67, P < 0.01), respectively. For patients with kfs > or = 80 and those with kfs < 80, the 5-year OS was 69.0% and 30.1% (chi(2) = 7.01, P < 0.01), and 5-year DFS was 46.7% and 24.9% (chi(2) = 6.37, P = 0.01), respectively. As regard to the treatment modality, The 5-year OS was 69.7% for the patients treated with combined modalities and 46.3% for those with surgery alone or radiotherapy alone (chi(2) = 3.49, P = 0.06), and the 5-year DFS were 52.2% and 21.8% (chi(2) = 7.03, P < 0.01), respectively. The 5-year OS was 71.1% for patients who received surgical treatment and 44.6% for those without it (chi(2) = 7.99, P < 0.01), and 5-year DFS was 54.0% and 24.1% (chi(2) = 6.41, P = 0.01), respectively. The 5-year OS and DFS of 11 patients who received radiotherapy alone were 47.7% and 30.7%, respectively. For 19 patients treated by radiotherapy with radical purpose (including patients who received combined modality with radiotherapy plus chemotherapy), the 5-year OS were 33.9% for < 70 Gy patients and 48.0% for > or = 70 Gy (chi(2) = 0.89, P = 0.35), and the 5-year DFS was 13.3% and 33.3% (chi (2) = 4.48, P = 0.03), respectively. For those who received chemotherapy or not, the 5-year OS was 50.0% and 64.9% (chi(2) = 0.91, P = 0.34), and the 5-year DFS was 38.9% and 43.1% (chi(2) = 0.01, P = 0.91), respectively.</p><p><b>CONCLUSION</b>Esthesioneuroblastoma is more prevalent in the young male adults than female, usually with locally advanced stage lesion when first diagnosed. Performance status and neck lymph node metastasis are significantly correlated with the prognosis. Combined treatment modality consisting of surgery may help to gain more favorable result. Radiotherapy plays an important role in the management of the disease.</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>