Construction of refined staging classification systems integrating FIGO/T-categories and corpus uterine invasion for non-metastatic cervical cancer.

BACKGROUND: To investigate the prognostic value of corpus uterine invasion (CUI) in cervical cancer (CC), and determine the necessity to incorporate it for staging. METHODS: A total of 809 cases of biopsy-proven, non-metastatic CC were identified from an academic cancer center. Recursive partitioning analysis (RPA) method was used to develop the refined staging systems with respect to overall survival (OS). Internal validation was performed by using calibration curve with 1000 bootstrap resampling. Performances of the RPA-refined stages were compared against the conventional FIGO 2018 and 9th edition TNM-stage classifications by the receiver operating characteristic curve (ROC) and decision curve analysis (DCA). RESULTS: We identified that CUI was independently prognostic for death and relapse in our cohort. RPA modeling using a two-tiered stratification by CUI (positive and negative) and FIGO/T-categories divided CC into three risk groupings (FIGO I'-III'/T1'-3'), with 5-year OS of 90.8%, 82.1%, and 68.5% for proposed FIGO stage I'-III', respectively (p ≤ 0.003 for all pairwise comparisons), and 89.7%, 78.8%, and 68.0% for proposed T1'-3', respectively (p < 0.001 for all pairwise comparisons). The RPA-refined staging systems were well validated with RPA-predicted OS rates showed optimal agreement with actual observed survivals. Additionally, the RPA-refined stages outperformed the conventional FIGO/TNM-stage with significantly higher accuracy of survival prediction (AUC: RPA-FIGO vs. FIGO, 0.663 [95% CI 0.629-0.695] vs. 0.638 [0.604-0.671], p = 0.047; RPA-T vs. T, 0.661 [0.627-0.694] vs. 0.627 [0.592-0.660], p = 0.036). CONCLUSION: CUI affects the survival outcomes in patients with CC. Disease extended to corpus uterine should be classified as stage III/T3.

Clinical utility of pretreatment serum squamous cell carcinoma antigen for prognostication and decision-making in patients with early-stage cervical cancer.

Background: To investigate the prognostic role of pretreatment squamous cell carcinoma antigen (SCCA) in early-stage cervical cancer (CC). Methods: We enrolled 487 cases of pathology-proven early-stage [International Federation of Gynecology and Obstetrics (FIGO) I/II] squamous or adenosquamous CC that were treated from 2012 to 2015. Restricted cubic splines (RCS) with a full Cox regression model were used to evaluate the association between SCCA levels and survival outcomes. Recursive partitioning analysis (RPA) was used to construct a risk stratification model for overall survival (OS). The performance of the RPA-based model was assessed using a receiver operating characteristic (ROC) curve. Results: RCS analysis revealed an association between SCCA and OS and disease-free survival (DFS); SCCA ⩾2.5 ng/mL was robust for risk discrimination in our cohort. SCCA had an interaction effect with FIGO classification: Patients with FIGO I and SCCA ⩾2.5 ng/mL overlapped with those with FIGO II and SCCA < 2.5 ng/mL for OS [hazard ratio, 1.04 (95% confidence interval (CI): 0.49-2.24), p = 0.903] and DFS [1.05 (0.56-1.98), p = 0.876]. RPA modeling incorporating SCCA (<2.5 ng/mL and ⩾2.5 ng/mL) and FIGO classification divided CC into three prognostic groups: RPA I, FIGO stage I, and SCCA < 2.5 ng/mL; RPA II, FIGO stage I, and SCCA ⩾ 2.5 ng/mL, or FIGO stage II and SCCA < 2.5 ng/mL; and RPA III, FIGO stage II, and SCCA ⩾ 2.5 ng/mL; with 5-year OS of 94.0%, 85.1%, and 73.5%, respectively (p < 0.001). ROC analysis confirmed that the RPA model outperformed the FIGO 2018 stage with significantly improved accuracy for survival prediction [area under the curve: RPA versus FIGO, 0.663 (95% CI: 0.619-0.705] versus 0.621 (0.576-0.664), p = 0.045]. Importantly, the RPA groupings were associated with the efficacy of treatment regimens. Surgery followed by adjuvant treatment had a higher OS (p < 0.01) and DFS (p = 0.024) than other treatments for RPA III, whereas outcomes were comparable among treatment regimens for RPA I-II. Conclusion: Herein, the role of SCCA for prognostication was confirmed, and a robust clinicomolecular risk stratification system that outperforms conventional FIGO classification in early-stage squamous and adenosquamous CC was presented. The model correlated with the efficacy of different treatment regimes.

Phase I study of adjuvant immunotherapy with autologous tumor-infiltrating lymphocytes in locally advanced cervical cancer.

BACKGROUNDAdoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) has achieved remarkable clinical efficacy in metastatic cancers such as melanoma and cervical cancer (CC). Here, we explored the safety, feasibility, and preliminary tumor response and performed translational investigations of adjuvant immunotherapy using infusion of autogenous TILs (auto-TILs) following concurrent chemoradiotherapy (CCRT) in patients with CC who had locally advanced disease.METHODSTwenty-seven patients with CC with stage III-IV disease were recruited in this single-center, phase I study. TILs were isolated from lesions in the uterine cervix and generated under good manufacturing practice (GMP) conditions and then infused after CCRT plus i.m. IL-2 injections.RESULTSTILs from 20 of the 27 patients were successfully expanded, with a feasibility of 74.1%. Twelve patients received TILs following CCRT. Adverse events (AEs) were primarily attributable to CCRT. Only 1 (8.3%) patient experienced severe toxicity with a grade 3 hypersensitivity reaction after TIL infusion. No autoimmune AEs, such as pneumonitis, hepatitis, or myocarditis, occurred, and there were no treatment-related mortalities. Nine of 12 patients (75.0%) attained a complete response, with a disease control duration of 9-22 months. Translational investigation showed that the transcriptomic characteristics of the infused TIL products and some immune biomarkers in the tumor microenvironment and serum of patients with CC at baseline were correlated with the clinical response.CONCLUSIONTIL-based ACT following CCRT was safe in an academic center setting, with potentially effective responses in patients with locally advanced CC. "Hot" inflammatory immune environments were beneficial to the clinical efficacy of TIL-based ACT as adjuvant therapy.TRIAL REGISTRATIONClinicalTrials.gov NCT04443296.FUNDINGNational Key R&D Program; Sci-Tech Key Program of the Guangzhou City Science Foundation; the Guangdong Province Sci-Tech International Key Program; the National Natural Science Foundation of China.

Circulating Epstein-Barr virus DNA level post induction chemotherapy contributes to prognostication in advanced-stage nasopharyngeal carcinoma.

BACKGROUND: To investigate the value of post-induction chemotherapy (IC) cell-free Epstein-Barr virus DNA (cfEBV DNApostIC) for prognostication in locally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: A total of 910 histologically proven LA-NPC undergoing radical IC + concurrent chemo-radiotherapy (CCRT) or targeted radiotherapy (CTRT) or both (CTCRT) were involved. The concentration of cfEBV DNA was measured by quantitative polymerase chain reaction pre-IC (cfEBV DNApreIC) and at IC completion. CfEBV DNApostIC was classified as undetectable (0 copy/ml) and detectable (>0 copy/ml). Recursive partitioning analysis (RPA) with respect to the overall survival (OS) was applied to construct a risk stratification system incorporating cfEBV DNApostIC and critical risk factors. RESULTS: We observed that 660 (72.5%) and 250 (27.5%) patients had cfEBV DNApostIC undetectable and detectable respectively. CfEBV DNApostIC positive was associated with a significant inferior 5-year OS (76.2% versus 85.9%), metastasis-free survival (DMFS, 71.7% versus 86.4%) and disease-free survival (DFS, 57.7% versus 80.1%) than cfEBV DNApostIC negative (P < 0.001 for all). Additionally, cfEBV DNApostIC was independently significant for OS (hazard ratio [HR] 1.90, 95% CI 1.40-2.59), DMFS (1.99, 1.45-2.71) and DFS (2.38, 1.86-3.06) in multivariate analyses (P < 0.001 for all). RPA modelling yielded three distinct risk groups: low-risk (N0-1 and undetectable cfEBV DNApostIC or N2-3 and pre-treatment cfEBV DNA [cfEBV DNApreIC] <7000), median-risk (N0-1 and detectable cfEBV DNApostIC or N2-3 and cfEBV DNApreIC ≥7000 with undetectable cfEBV DNApostIC) and high-risk (N2-3 and cfEBV DNApreIC ≥7000 with detectable cfEBV DNApostIC), with 5-year OS of 88.1%, 79.2% and 66.9%, respectively. Our risk stratification outperformed TNM classification for predicting death (AUC, 0.631 versus 0.562; P = 0.012) and distant metastasis (0.659 versus 0.562; P = 0.004). CONCLUSIONS: CfEBV DNApostIC represents an effective indicator of prognostication in LA-NPC. We developed a risk classification system that provides improved OS prediction over the current staging system by combining cfEBV DNApostIC, cfEBV DNApreIC and N-stage classification in LA-NPC.

Effectiveness of Sequential Chemoradiation vs Concurrent Chemoradiation or Radiation Alone in Adjuvant Treatment After Hysterectomy for Cervical Cancer: The STARS Phase 3 Randomized Clinical Trial.

IMPORTANCE: There is no current consensus on the role of chemotherapy in addition to radiation for postoperative adjuvant treatment of patients with early-stage cervical cancer with adverse pathological factors. OBJECTIVE: To evaluate the clinical benefits of sequential chemoradiation (SCRT) and concurrent chemoradiation (CCRT) compared with radiation alone (RT) as a postoperative adjuvant treatment in early-stage cervical cancer. DESIGN, SETTING, AND PARTICIPANTS: After radical hysterectomy at 1 of 8 participating hospitals in China, patients with FIGO (International Federation of Gynecology and Obstetrics) stage IB to IIA cervical cancer with adverse pathological factors were randomized 1:1:1 to receive adjuvant RT, CCRT, or SCRT. Data were collected from February 2008 to December 2018. INTERVENTIONS: Patients received adjuvant RT (total dose, 45-50 Gy), CCRT (weekly cisplatin, 30-40 mg/m2), or SCRT (cisplatin, 60-75 mg/m2, plus paclitaxel, 135-175 mg/m2) in a 21-day cycle, given 2 cycles before and 2 cycles after radiotherapy, respectively. MAIN OUTCOMES AND MEASURES: The primary end point was the rate of disease-free survival (DFS) at 3 years. RESULTS: A total of 1048 women (median [range] age, 48 [23-65] years) were included in the analysis (350 in the RT group, 345 in the CCRT group, and 353 in the SCRT group). Baseline demographic and disease characteristics were balanced among the treatment groups except that the rate of lymph node involvement was lowest in the RT group (18.3%). In the intention-to-treat population, SCRT was associated with a higher rate of DFS than RT (3-year rate, 90.0% vs 82.0%; hazard ratio [HR], 0.52; 95% CI, 0.35-0.76) and CCRT (90.0% vs 85.0%; HR, 0.65; 95% CI, 0.44-0.96). Treatment with SCRT also decreased cancer death risk compared with RT (5-year rate, 92.0% vs 88.0%; HR, 0.58; 95% CI, 0.35-0.95) after adjustment for lymph node involvement. However, neither DFS nor cancer death risk was different among patients treated with CCRT or RT. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, conducted in a postoperative adjuvant treatment setting, SCRT, rather than CCRT, resulted in a higher DFS and lower risk of cancer death than RT among women with early-stage cervical cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00806117.

KPNA2 promotes migration and invasion in epithelial ovarian cancer cells by inducing epithelial-mesenchymal transition via Akt/GSK-3ß/Snail activation.

Background: Increased karyopherin alpha 2 (KPNA2) expression has been demonstrated in epithelial ovarian carcinoma (EOC) tissue. However, its role in the disease is not clear. Here, we investigate the mechanism of involvement of KPNA2 in EOC. Methods: Stable cell lines expressing KPNA2, or KPNA2 shRNAs, were constructed. The effects of KPNA2 overexpression and knockdown on EOC cell migration, invasion, and epithelial-to-mesenchymal transition (EMT) were evaluated using relevant assays and western blot analysis. Key components of the Akt/GSK-3ß/Snail signaling pathway were detected using western blotting and immunofluorescence. Results: KPNA2 overexpression increased the migration and invasion of EOC cells (EFO-21 and SK-OV3); these cells also exhibited characteristics of EMT. Key proteins in the Akt/GSK-3ß/Snail signaling pathway were also upregulated in cells overexpressing KPNA2. In contrast, knockdown of KPNA2 effectively suppressed migration and invasion of these EOC cells. Conclusions: KPNA2 may reduce the migration and invasion of EOC by inhibiting the Akt/GSK-3ß/Snail signaling pathway and suppressing EMT.

KPNA2 is a potential diagnostic serum biomarker for epithelial ovarian cancer and correlates with poor prognosis.

This study aimed to determine whether serum karyopherin alpha 2 levels can be used as a diagnostic biomarker for epithelial ovarian carcinoma. Karyopherin alpha 2 protein was detected by enzyme-linked immunosorbent assay in serum samples from 162 epithelial ovarian carcinoma patients and 48 healthy controls. Serum karyopherin alpha 2 levels in epithelial ovarian carcinoma patients were significantly higher than in healthy controls ( p < 0.001). When a karyopherin alpha 2 serum level of 2.52 µg/mL was used as a cut-off, the sensitivity and specificity of the assay for diagnosing epithelial ovarian carcinoma were 71.4% and 81.2%, respectively. High serum karyopherin alpha 2 levels (>485 µg/mL) correlated with International Federation of Gynecology and Obstetrics stage ( p < 0.0001), lymphatic metastasis ( p = 0.045), overall survival ( p = 0.001), and disease-free progression ( p = 0.006). Serum karyopherin alpha 2 represents a potential diagnostic biomarker for epithelial ovarian carcinoma.

3D-image-guided high-dose-rate intracavitary brachytherapy for salvage treatment of locally persistent nasopharyngeal carcinoma.

BACKGROUND: To evaluate the therapeutic benefit of 3D-image-guided high-dose-rate intracavitary brachytherapy (3D-image-guided HDR-BT) used as a salvage treatment of intensity modulated radiation therapy (IMRT) in patients with locally persistent nasopharyngeal carcinoma (NPC). METHODS: Thirty-two patients with locally persistent NPC after full dose of IMRT were evaluated retrospectively. 3D-image-guided HDR-BT treatment plan was performed on a 3D treatment planning system (PLATO BPS 14.2). The median dose of 16 Gy was delivered to the 100% isodose line of the Gross Tumor Volume. RESULTS: The whole procedure was well tolerated under local anesthesia. The actuarial 5-y local control rate for 3D-image-guided HDR-BT was 93.8%, patients with early-T stage at initial diagnosis had 100% local control rate. The 5-y actuarial progression-free survival and distant metastasis-free survival rate were 78.1%, 87.5%. One patient developed and died of lung metastases. The 5-y actuarial overall survival rate was 96.9%. CONCLUSIONS: Our results showed that 3D-image-guided HDR-BT would provide excellent local control as a salvage therapeutic modality to IMRT for patients with locally persistent disease at initial diagnosis of early-T stage NPC.

A real-time in vivo dosimetric verification method for high-dose rate intracavitary brachytherapy of nasopharyngeal carcinoma.

PURPOSE: A real-time in vivo dosimetric verification method using metal-oxide-semiconductor field effect transistor (MOSFET) dosimeters has been developed for patient dosimetry in high-dose rate (HDR) intracavitary brachytherapy of nasopharyngeal carcinoma (NPC). METHODS: The necessary calibration and correction factors for MOSFET measurements in (192)Iridium source were determined in a water phantom. With the detector placed inside a custom-made nasopharyngeal applicator, the actual dose delivered to the tumor was measured in vivo and compared to the calculated values using a commercial brachytherapy planning system. RESULTS: Five MOSFETs were independently calibrated with the HDR source, yielding calibration factors of 0.48 ± 0.007 cGy∕mV. The maximum sensitivity variation was no more than 7% in the clinically relevant distance range of 1-5 cm from the source. A total of 70 in vivo measurements in 11 NPC patients demonstrated good agreement with the treatment planning. The mean differences between the planned and the actually delivered dose within a single treatment fraction were -0.1% ± 3.8% and -0.1% ± 3.7%, respectively, for right and left side assessments. The maximum dose deviation was less than 8.5%. CONCLUSIONS: In vivo measurement using the real-time MOSFET dosimetry system is possible to evaluate the actual dose to the tumor received by the patient during a treatment fraction and thus can offer another line of security to detect and prevent large errors.

Dose-volume parameters and clinical outcome of CT-guided free-hand high-dose-rate interstitial brachytherapy for cervical cancer.

Currently, image-based 3-dimentional (3D) planning brachytherapy allows for a better assessment of gross tumor volume (GTV) and the definition and delineation of target volume in cervix cancer. In this study, we investigated the feasibility of our novel computed tomography (CT)-guided free-hand high-dose-rate interstitial brachytherapy (HDRISBT) technique for cervical cancer by evaluating the dosimetry and preliminary clinical outcome of this approach. Dose-volume histogram (DVH) parameters were analyzed according to the Gynecological GEC-ESTRO Working Group recommendations for image-based 3D treatment in cervical cancer. Twenty cervical cancer patients who underwent CT-guided free-hand HDRISBT between March 2009 and June 2010 were studied. With a median of 5 (range, 4-7) implanted needles for each patient, the median dose of brachytherapy alone delivered to 90% of the target volume (D90) was 45 (range, 33-54) Gyα/ß10 for high-risk clinical target volume (HR-CTV) and 30 (range, 20-36) Gyα/ß10 for intermediate-risk clinical target volume (IR-CTV). The percentage of the CTV covered by the prescribed dose (V100) of HR-CTV with brachytherapy alone was 81.9%-99.2% (median, 96.7%). With an additional dose of external beam radiotherapy (EBRT), the median D90 was 94 (range, 83-104) Gyα/ß10 for HR-CTV and 77 (range, 70-87) Gyα/ß10 for IR-CTV; the median dose delivered to 100% of the target volume (D100) was 75 (range, 66-84) Gyα/ß10 for HR-CTV and 65 (range, 57-73) Gyα/ß10 for IR-CTV. The minimum dose to the most irradiated 2 cc volume (D2cc) was 73-96 (median, 83) Gyα/ß3 for the bladder, 64-98 (median, 73) Gyα/ß3 for the rectum, and 52-69 (median, 61) Gyα/ß3 for the sigmoid colon. After a median follow-up of 15 months (range, 3-24 months), two patients experienced local failure, and 1 showed internal iliac nodal metastasis. Despite the relatively small number of needles used, CT-guided HDRISBT for cervical cancer showed favorable DVH parameters and clinical outcome.

[Risk factors associated with prognosis in patients with radiation proctitis].

OBJECTIVE: To investigate risk factors associated with prognosis in patients with radiation proctitis (RP). METHODS: Between August 2007 and February 2010, 33 patients diagnosed with radiation proctitis were identified. Data pertaining to treatments and quality of life(QOL) were analyzed retrospectively. RESULTS: Indication for radiation included cervical cancer(n=22), prostate cancer (n=3), ovary cancer (n=2), rectal cancer (n=2), endometrial cancer(n=2), cervical cancer (n=1), and vaginal cancer(n =1). Data regarding radiation were available in 18 patients, and the mean dose was (61.3±12.9) Gy with a median dose of 61 Gy. Eleven were treated with enema therapy, 9 formalin dab, 12 surgical operations. Clinical improvement was noticed in 75% of the patients with a mean QOL score of 63.79±20.92. Prognosis was favorable in 75% of the patients. Surgical treatment was effective in 91.7% of the patients with severe complications. Univariate analysis showed that gender was associated with the prognosis of RP, while the severity of RP and treatment method were not predictive for RP prognosis. CONCLUSIONS: Gender but not disease severity is associated with the prognosis of radiation proctitis. Surgery may be beneficial to RP patients with severe complications.

3D-CT implanted interstitial brachytherapy for T2b nasopharyngeal carcinoma.

BACKGROUND: To compare the results of external beam radiotherapy in combination with 3D- computed tomography (CT)-implanted interstitial high dose rate brachytherapy (ERT/3D-HDR-BT) versus conventional external beam radiotherapy (ERT) for the treatment of stage T2b nasopharyngeal carcinoma (NPC). METHODS: Forty NPC patients diagnosed with stage T2b NPC were treated with ERT/3D-HDR-BT under local anesthesia. These patients received a mean dose of 60 Gy, followed by 12-20 Gy administered by 3D-HDR-BT. Another 101 patients diagnosed with non-metastatic T2b NPC received a mean dose of 68 Gy by ERT alone during the same period. RESULTS: Patients treated with ERT/3D-HDR-BT versus ERT alone exhibited an improvement in their 5-y local failure-free survival rate (97.5% vs. 80.2%, P = 0.012) and disease-free survival rate (92.5% vs. 73.3%, P = 0.014). Using multivariate analysis, administration of 3D-HDR-BT was found to be favorable for local control (P = 0.046) and was statistically significant for disease-free survival (P = 0.021). The incidence rate of acute and chronic complications between the two groups was also compared. CONCLUSIONS: It is possible that the treatment modality enhances local control due to improved conformal dose distributions and the escalated radiation dose applied.

[Application of interstitial brachytherapy via parapharynx involvement transnasal approach to enhance dose in radiotherapy for nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Although intracavitary irradiation (ICI) is usually applied to enhance dose in radiotherapy for early stage nasopharyngeal carcinoma (NPC), its use in parapharyngeal enhancing dose is limited because of dislocation and poor repetition of conventional catheterization. This study was to evaluate the application of a new technique, interstitial brachytherapy via parapharynx involvement transnasal approach, to enhance dose in radiotherapy for NPC. METHODS: Twenty-three naive and recurrent NPC patients with tumor residue of more than 1 cm under nasopharyngeal mucosa or restricted tumor residue in the parapharyngeal space received interstitial brachytherapy between Sep. 2005 and Aug. 2006 via parapharynx involvement transnasal approach under the guidance of sinus endoscopy. The 3-dimensional (3D) planning system was used to delineate target volume, optimize dose distribution, and perform interstitial brachytherapy after CT scan. The depths of catheters under mucosa on the moment of inserting and pulling out were measured. The efficacy and complications were assessed. RESULTS: All catheters were intubated into tumors successfully; the veracity of catheter location was 100%. The submucosa depths of catheters were (9.59+/-2.72) mm when inserted and (9.43+/-2.30) mm when pulled out, without significant difference (t = 0.23,P > 0.05); the shift length was (0.75+/-0.75) mm. The patients were followed up from 3 to 15 months (median, 6 months), and no one dropt out. Three cases of irradiation-associated turbinate adhesion occurred and were cured after lysis; no infection, serious bleeding, palatal perforation, nasopharyngeal necrosis, and other serious complications occurred. All tumors disappeared in 3 months after treatment. No local recurrence and distant metastasis occurred. CONCLUSIONS: The nasopharyngeal and parapharyngeal catheterization with sinus endoscopy guidance is accurate, steady, safe, and feasible. Interstitial brachytherapy is effective for tumor residue in the nasopharynx or parapharyngeal space of NPC patients after radiotherapy without serious complications.

[Prospective study on long-term efficacy of external plus intracavitary radiotherapy on stage I-II nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: The dose distribution of brachytherapy is different from that of external radiotherapy. Combining these 2 modalities can enhance the conform degree of dose distribution. This study was to evaluate long-term efficacy of external plus intracavitary irradiation on stage I-II nasopharyngeal carcinoma (NPC). METHODS: A total of 321 patients were randomized into 2 groups: 223 in simplex group were given conventional irradiation in total doses of 66-74 Gy with lead block fitful fields; 98 in combination group were given the same external irradiation in total doses of 58-62 Gy and 15-20 Gy intracavitary irradiation. RESULTS: Within 5-year follow-up, in simplex group, 16 patients had tumor relapsed at the nasopharynx and 35 died, with 5-year overall survival rates of 90.63% for stage I patients and 80.82% for stage II patients (P=0.018)û in combination group, 1 patient had tumor relapsed at the nasopharynx and 6 died, with 5-year overall survival rates of 95.24% for stage I patients and 93.36% for stage II patients (P=0.025). There were fewer adverse events in combination group. CONCLUSION: The long-term efficacy of external plus intracavitary radiotherapy on stage I-II NPC is better than that of conventional external radiotherapy alone with fewer adverse events.

[Correlations of biomolecular markers, such as P53 protein and vascular endothelial growth factor, to radiosensitivity of nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: About 20%-40% nasopharyngeal carcinoma (NPC) patients, who are in the same staging group, receiving the same treatment modality and radiotherapy dose, relapse in the irradiated fields within 5 years. This is mainly due to the differences in internal radiosensitivity. This study was to analyze the proliferation, apoptosis, angiogenesis, and lymphogenesis of tumor cells, and to explore the correlation of these factors to radiosensitivity. METHODS: P53 protein, vascular endothelial growth factor (VEGF) protein, survivin protein, VEGF-C protein, Ki67 protein, and microvascular density (MVD) of 60 biopsy samples from radiosensitive group and 60 from radio-resistant group were detected by immunohistochemistry, respectively. Their correlations to clinical characteristics were analyzed. RESULTS: The positive rates of P53, VEGF, survivin, VEGF-C, Ki67 were 65.0%, 57.5%, 60.8%, 42.5%, 57.5%, respectively. The positive rates of P53 and VEGF, and MVD in the radio-sensitive group and in the radio-resistant group were (25.97+/-21.26)%, (18.50+/-19.86)%, 32.65+/-19.61 and (37.85+/-28.67)%, (30.83+/-23.94)%, 41.95+/-16.97, respectively (P<0.05). The positive rates of Survivin, VEGF-C, and Ki67 between the two groups had no statistic difference (P>0.05). The correlations between P53, VEGF, and MVD were obvious. CONCLUSION: P53 protein, VEGF protein and MVD might be biomolecular markers for evaluating the internal radiosensitivity of NPC patients.

[Retrospective analysis of 934 nasopharyngeal carcinoma patients treated with conventional external beam radiotherapy alone].

OBJECTIVE: To analyze the clinical outcome of 934 primary nasopharyngeal carcinoma treated with conventional external beam radiotherapy alone. METHODS: 34 patients were treated from Jan. 1, 1999 to Dec. 31, 1999. The radiation fields were delineated according to the CT/MRI imaging findings on disease extent. Two lateral opposing isocentric portals with customized blockings were used for the nasopharynx and upper neck. The dose delivered to tumor in the nasopharynx was 68-70 Gy/2 Gy fraction/7 weeks. The doses delivered to the neck was 60-70 Gy/6-7 weeks for patients with positive lymph nodes and 50 Gy/5 weeks for the patients with negative lymph node. RESULTS: The 1-, 2-, 3- and 4-year overall survival rate (OS) was 89.5%, 81.9%, 78.1% and 75.7%, and metastasis-free survival rate (MFS) was 84.0%, 77.2%, 74.4% and 72.0%, respectively. The 1-, 2-, 3- and 4-year disease-free survival rate (DFS) was 80.8%, 73.1%, 68.5% and 65.1%, and the relapse-free survival rate (RFS) was 95.5%, 92.7%, 90.3% and 87.3%, respectively. The overall failure rate was 30.9% (289/934). At the end of the radiotherapeutic course, the percentage of residual disease was 14.6%. The 4-year loco-regional recurrence and distant metastasis rates after radiotherapy were 7.2% and 9.2% with a median time of 19.3 months and 12.8 months. CONCLUSION: It may be helpful to improve radiotherapy curative effect when the target is individually designed through improving irradiation technique according to CT/MRI findings and by shortening the overall course time, enhancing irradiation dose and strictly implementing QA/QC measures.