TMEM60 Promotes the Proliferation and Migration and Inhibits the Apoptosis of Glioma through Modulating AKT Signaling.

Glioma is a highly fatal malignancy with aggressive proliferation, migration, and invasion metastasis due to aberrant genetic regulation. This work aimed to determine the function of transmembrane protein 60 (TMEM60) during glioma development. The level of TMEM60 in glioma tissues and normal tissues and its correlation with glioma prognosis were checked in The Cancer Genome Atlas (TCGA) database. The levels of TMEM60 in glioma cell lines and normal astrocytes were determined by quantitative real-time PCR and western blotting assay. TMEM60 knockdown and overexpression were conducted, followed by detection of cell viability, migration, invasion, and apoptosis. CCK-8 and colony formation assay were adopted to detect cell viability proliferation. Transwell assay was performed to measure cell migration and invasion. Cell apoptosis was evaluated by flow cytometry. The alternation of key proteins in the PI3K/Akt signaling pathway was measured by western blotting. TMEM60 expression was significantly higher in glioma tissues than that in the healthy control and was correlated with poor overall survival of patients. The protein and mRNA levels of TMEM60 were both elevated in glioma cell lines in comparison with the normal cell lines. Elevated level of TMEM60 led to enhanced proliferation, migration, and invasion and suppressed cell apoptosis. TMEM60 promoted the activation of PI3K/Akt signaling. Our data suggested that TMEM60 plays an oncogenic role in glioma progression via activating the PI3K/Akt signaling pathway.

C-C motif chemokine ligand 2/C-C receptor 2 is associated with glioma recurrence and poor survival.

Several studies have explored the mechanisms of C-C motif chemokine ligand (CCL)2/CC receptor (R)2 function in tumorigenesis and inflammation. However, little is known about the role of CCL2/CCR2 in tumor recurrence, especially after radiotherapy. The present study aimed to determine the association between CCL2/CCR2 and glioma relapse. Moreover, the difference in the expression of CCL2/CCR2 between post-radiation and non-radiation recurrent glioma tissues was compared. A retrospective analysis of 80 patients with glioma who underwent tumor resection twice was performed. Primary group refers to glioma patients who received glioma resection surgery for the first time. Recurrent group refers to glioma patients who received glioma resection surgery after first relapse. In total, 10 patients with brain trauma who underwent partial resection of the normal brain as decompression treatment were used as controls. Protein expression levels of CCL2 and CCR2 were evaluated using immunohistochemistry. Prognostic analyses of patient survival using Kaplan-Meier curves and Cox regression models were performed. The expression levels of CCL2 and CCR2 were higher in recurrent glioma compared with the primary group. There was a positive correlation between tumor grade and protein expression of CCL2/CCR2. Furthermore, irradiation had a significant effect on CCR2 protein expression (P=0.014), but not on CCL2 protein expression (P=0.626). However, the expression of CCL2 and CCR2 showed no significant difference between primary and secondary glioblastoma. After adjusting for sex, radiotherapy and location of tumors in these gliomas, CCL2 was a prognostic factor for disease-free and overall survival (OS) times, as well as age and tumor grade. In the multivariate Cox modeling for glioma, CCR2 was significantly associated with OS rather than DFI. The significant correlations between CCL2/CCR2 expression and glioma tumor grade suggested that CCL2/CCR2 has a role in glioma progression. Combined with previous in vitro experiments, it was proposed that irradiation (radiotherapy)-induced expression of CCL2 is transient, while irradiation-induced expression of CCR2 is lasting. Therefore, CCL2/CCR2 is a potential therapeutic target for patients with glioma.

Comprehensive analyses of PBRM1 in multiple cancer types and its association with clinical response to immunotherapy and immune infiltrates.

BACKGROUND: The prognostic value of polybromo 1 (PBRM1) gene mutations in clear cell renal carcinoma (CCRCC) with anti-programmed death-ligand 1 (PD-L1) therapy remains controversial, and few studies have reported the impact of PBRM1 mutations in other cancer types. METHODS: The patient information was obtained from cBioPortal and the Tumor Immune Estimation Resource (TIMER) databases. Mann-Whitney U test were used for correlation analysis. For survival analyses, Kaplan-Meier survival curves were used and compared using the log-rank test. Cox's regression model was used to perform univariable and multivariable analyses. RESULTS: Our study, for the first time, performed comprehensive analyses of PBRM1 mutation frequency, PBRM1 expression, relationship of PBRM1 mutations with clinical benefit from immunotherapy, and PBRM1 expression with immune infiltrates in diverse cancer types. The results showed that the expression of PBRM1 was significantly lower in diverse cancer types compared with normal tissues. Based on multivariable analysis, PBRM1 mutations trended towards worse clinical outcomes from anti-PD-L1 in CCRCC, lung adenocarcinoma (LUAD), bladder urothelial carcinoma (BLCA), and skin cutaneous melanoma (SKCM), and a significant association was observed in LUAD and BLCA. PBRM1 mutations were associated with higher TMB in diverse cancer types and significant associations were observed in LUAD and BLCA. The expression of PBRM1 was found to positively correlate with immune infiltrates in diverse cancer types. CONCLUSIONS: Our findings suggested caution in starting immunotherapy alone in PBRM1 mutant patients. Further studies are needed to improve treatment for PBRM1 mutant patients.

G protein gamma 7 suppresses progression of lung adenocarcinoma by inhibiting E2F transcription factor 1.

G protein gamma 7 (GNG7) has been found to be aberrantly expressed in some kinds of malignant tumors. In this study, we mainly discuss the antitumor role of it in lung adenocarcinoma (LUAD) cells. Protein levels of GNG7 in LUAD tissues were measured by western blot and immunohistochemical analysis. Cell proliferation, invasion and migration were detected by CCK-8 assay, 5-ethynyl-2'-deoxyuridine (EdU), and Transwell assay. In our study, GNG7 was down-regulated in LUAD, which significantly correlated with survival of LUAD patients. Functional experiments revealed that GNG7 significantly inhibited LUAD cell proliferation, migration, and invasion in vitro and E2F1 overexpression reversed these properties. GNG7 suppressed xenograft tumorigenesis in nude mice models in vivo. In conclusion, GNG7 functions as a tumor suppressor in LUAD cells through inhibiting E2F1.

Programmed cell death-ligand 1 expression in hepatocellular carcinoma and its correlation with clinicopathological characteristics.

BACKGROUND AND AIM: Programmed cell death-ligand 1 (PD-L1) immunohistochemistry score has been approved as the predictive biomarker for anti-PD1/PD-L1 therapy in several advanced malignancies. Although its predictive role remained inconclusive in hepatocellular carcinoma, ongoing study of anti-PD1/PD-L1 therapy showed promising results. However, less is known about the PD-L1 immunohistochemistry score and factors correlated with it in hepatocellular carcinoma. We investigated PD-L1 immunohistochemistry scores in a large cohort of hepatocellular carcinoma, as well as its correlation with various clinical and genomic factors. METHODS: Immunohistochemistry was performed to detect the expression of PD-L1 protein in 315 hepatocellular carcinoma tissues. All slides were independently reviewed by three senior pathologists. Next-generation YS panel (450 genes) sequencing was performed on 309 patients. RESULTS: Higher PD-L1 expression as measured by combined positive score (CPS) was associated with increased Edmondson-Steiner grade (grade III vs II, P = 0.041) and TP53 mutations (P = 0.021). PD-L1 CPS had no correlation with tumor mutational burden (Spearman's correlation coefficient 0.067). PD-L1 CPS was not significantly associated with hepatitis B virus infection. CONCLUSIONS: Our data indicated that patients with higher Edmondson-Steiner grade (grade III) had significantly higher PD-L1 CPS than patients with lower Edmondson-Steiner grade (grade II). Patients with TP53 mutations had significantly higher PD-L1 expression.

The role of tolvaptan in managing hyponatremia in small cell lung cancer patients with SIADH: a retrospective study of 23 cases.

BACKGROUND: Existing studies have shed light on the treatment of small cell lung cancer (SCLC), but data on tolvaptan for the treatment of hyponatremia in SCLC patients remain scarce. Furthermore, the most appropriate initial dose has not been identified. This study aimed to assess the effectiveness, safety, and survival rate associated with tolvaptan in regard to controlling hyponatremia in SCLC patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and to explore the appropriate initial dose. METHODS: A total of 23 SCLC patients with SIADH treated with tolvaptan were retrospectively reviewed between 2011 and 2019, and the efficacy and safety of tolvaptan were evaluated and compared between a 3.75 mg dose and doses higher than 3.75 mg. Then, the Kaplan-Meier method was used to calculate overall survival (OS) and draw survival curves. RESULTS: In our center, patients had a mean age of 61.7±8.2 years. The mean plasma sodium level after hypertonic saline treatment was (120.7±7.5) mmol/L. The doses of tolvaptan were distributed as follows: 3.75 mg (10 patients), 5 mg (5 patients), 7.5 mg (4 patients), and 15 mg (4 patients). After 3 days of tolvaptan treatment, the mean plasma sodium level was (136.0±4.1) mmol/L, which was significantly higher than the plasma sodium level on admission and before tolvaptan treatment (P<0.05). The mean time for tolvaptan to correct the plasma sodium level was (3.7±5.8) days, and no significant difference was found between the 3.75 mg group and the above 3.75 mg group (P>0.05). Adverse events were observed in 1 patient who presented with severe lethargy and confusion. The median OS was 14.1 months. CONCLUSIONS: In summary, no significant difference was found between the 3.75 mg group and the above 3.75 mg group. Less than 15 mg of tolvaptan is enough to stabilize sodium levels for most patients. There is a risk of overcorrection of plasma sodium when using 15 mg of tolvaptan. Tolvaptan can quickly improve performance status and may bring survival benefits to patients. The effect of tolvaptan in patients with SCLC and SIADH should be confirmed.

Risk-Adapted Postmastectomy Radiotherapy Decision Based on Prognostic Nomogram for pT1-2N1M0 Breast Cancer: A Multicenter Study.

PURPOSE: The aim of this study was to develop a widely accepted prognostic nomogram and establish a risk-adapted PMRT strategy based on locoregional recurrence for pT1-2N1M0 breast cancer. METHODS AND MATERIALS: A total of 3,033 patients with pT1-2N1M0 breast cancer treated at 6 participating institutions between 2000 and 2016 were retrospectively reviewed. A nomogram was developed to predicted locoregional recurrence-free survival (LRFS). A propensity score-matched (PSM) analyses was performed in risk-adapted model. RESULTS: With the median follow-up of 65.0 months, the 5-year overall survival (OS), disease free survival (DFS) and LRFS were 93.0, 84.8, and 93.6%, respectively. There was no significant difference between patients who received PMRT or not for the entire group. A nomogram was developed and validated to estimate the probability of 5-year LRFS based on five independent factors including age, primary tumor site, positive lymph nodes number, pathological T stage, and molecular subtype that were selected by a multivariate analysis of patients who did not receive PMRT in the primary cohort. According to the total nomogram risk scores, the entire patients were classified into low- (40.0%), moderate- (42.4%), and high-risk group (17.6%). The 5-year outcomes were significantly different among these three groups (P<0.001). In low-risk group, patients who received PMRT or not both achieved a favorable OS, DFS, and LRFS. In moderate-risk group, no differences in OS, DFS, and LRFS were observed between PMRT and no PMRT patients. In high-risk group, compared with no PMRT, PMRT resulted in significantly different OS (86.8 vs 83.9%, P = 0.050), DFS (77.2 vs 70.9%, P = 0.049), and LRFS (90.8 vs. 81.6%, P = 0.003). After PSM adjustment, there were no significant differences in OS, DFS, and LRFS in low-risk and moderate-risk groups. However, in the high-risk group, PMRT still resulted in significantly better OS, DFS and improved LRFS. CONCLUSIONS: The proposed nomogram provides an individualized risk estimate of LRFS in patients with pT1-2N1M0 breast cancer. Risk-adapted PMRT for high-risk patients is a viable effective strategy.

[Effect of Nutrition Intervention on Skeletal Muscle during Concurrent Chemoradiotherapy for Esophageal Cancer].

Objective To evaluate the role of nutritional intervention during concurrent chemoradiotherapy (CCRT) for esophageal cancer and investigate the incidence and risk factors of skeletal muscle loss after CCRT.Methods The clinical data of patients with esophageal cancer who underwent CCRT in our center from April 2017 to November 2019 were retrospectively collected.The CT images before and after CCRT were analyzed.The incidence of skeletal muscle loss,changes in nutritional indicators,and chemoradiotherapy delay were recorded,and the risk factors associated with declined skeletal muscle index (SMI) were analyzed.Results In the nutritional intervention group,the average daily energy intake per person in the oral nutritional supplement (ONS) subgroup,parenteral nutrition (PN) subgroup,and ONS+PN subgroup were (273.5±252.8), (310.6±311.2),and (745.3±637.8) kcal (1 kcal=4.1868 kJ),respectively,and the difference was statistically significant (F=5.870,P=0.005).After CCRT,the incidence of sarcopenia was 40.3% (n=40) in the nutrition intervention group,which was significantly lower than that (45.2%,n=42) in the control group (χ2=4.247,P=0.038);the decline of SMI in the nutrition intervention group was (1.4±8.3) cm2/m2,which was significantly lower than that in the control group [ (5.4±9.1) cm2/m2] (t=2.187,P=0.031).In the nutrition intervention group,the radiotherapy delay and chemotherapy delay occurred in 18 patients and 10 patients,which were significantly lower than those in the control group [25 patients (χ2=4.501,P=0.039) and 19 patients (χ2=8.929,P=0.005) ].The duration of radiotherapy delay and chemotherapy delay in the nutrition intervention group was (2.3±4.4) and (0.9±1.3) days,which were significantly shorter than those in the control group [ (4.2±5.3) (t=0.691,P=0.047) and (2.2±3.2) days (t=0.847,P=0.041) ].The incidence of sarcopenia was 75.2% before CCRT,which was significantly lower than that (88.2%) after CCRT (χ2=5.183,P=0.023).Multivariate linear regression analysis showed that T stage (P=0.007),N stage (P<0.001),and nutritional intervention (P=0.014) at baseline had significant effects on the decrease of SMI in patients with esophageal cancer after radiotherapy and chemotherapy.Conclusions Nutrition intervention can reduce the incidence of delayed chemoradiotherapy during esophageal cancer CCRT and reduce skeletal muscle loss.The decline of SMI is mainly related to the T stage,N stage,and nutrition intervention at baseline.

The role of metabolic tumor volume (MTV) measured by [18F] FDG PET/CT in predicting EGFR gene mutation status in non-small cell lung cancer.

Many noninvasive methods have been explored to determine the mutation status of the epidermal growth factor receptor (EGFR) gene, which is important for individualized treatment of non-small cell lung cancer (NSCLC). We evaluated whether metabolic tumor volume (MTV), a parameter measured by [18F] fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) might help predict EGFR mutation status in NSCLC. Overall, 87 patients who underwent EGFR genotyping and pretreatment PET/CT between January 2013 and September 2016 were reviewed. Clinicopathologic characteristics and metabolic parameters including MTV were evaluated. Univariate and multivariate analyses were used to assess the independent variables that predict mutation status to create prediction models. Forty-one patients (41/87) were identified as having EGFR mutations. The multivariate analysis showed that patients with lower MTV (MTV≤11.0 cm3, p=0.001) who were non-smokers (p=0.037) and had a peripheral tumor location (p=0.033) were more likely to have EGFR mutations. Prediction models using these criteria for EGFR mutation yielded a high AUC (0.805, 95% CI 0.712-0.899), which suggests that the analysis had good discrimination. In conclusion, NSCLC patients with EGFR mutations showed significantly lower MTV than patients with wild-type EGFR. Prediction models based on MTV and clinicopathologic characteristics could provide more information for the identification of EGFR mutations.

Preservation of laryngeal function improves outcomes of patients with hypopharyngeal carcinoma.

This study compares clinical characteristics and survival between patients with and without laryngeal function (LF) preservation during surgical treatment for hypopharyngeal carcinoma. We retrospectively reviewed 485 cases of hypopharyngeal carcinoma treated at a single institution for analysis. There were 337 cases with and 148 cases without LF preservation after surgery. Preservation of LF was complete in 237 patients and partial in 100 patients. There were significant statistical differences between the preservation group and the group without preservation in T-stage (P < 0.001), overall staging (P < 0.001), and tumor sites (P < 0.001) except the N-stage (P = 0.240). The patients with LF preservation had significantly better overall survival (log-rank, P = 0.005) and a lower risk of death than those without LF preservation (HR 0.62, 95% CI 0.43-0.97), after multivariable adjustment. Treatment with surgery in combination with radiotherapy is still the favorable choice for patients with hypopharyngeal carcinoma. The maximal restoration of pharyngoesophageal continuity and function improves survival for patients whose tumors are excised completely for the preservation of LF and laryngeal and pharyngeal reconstruction.

Surgical management of cervical esophageal carcinoma with larynx preservation and reconstruction.

OBJECTIVES: There is no generally accepted treatment strategy for cervical esophageal carcinoma. The purpose of this study was to evaluate the operative outcomes of reconstruction after resection of cervical esophageal and hypopharynx-esophagus junction carcinoma with larynx preservation. METHODS: We retrospectively reviewed the data of 79 patients with carcinoma of the hypopharynx-esophagus junction and cervical esophagus. Transhiatal total esophagectomy without thoracotomy was carried out in 67 patients who underwent gastric pull-up (GP) or colon interposition (CI) techniques. Transcervical limited pharyngo-cervical esophagectomy was performed in the patients with the pectoralis major flap alone or combined with the split graft (PMF/CWSG) for reconstruction. Seventy-two patients received postoperative adjuvant therapy. RESULTS: The 3-year and 5-year overall survival rates were 66.4% and 45.5%, respectively. The average time to resumption of oral feeding was 25.2 days. All patients had preserved laryngeal function. The overall incidence of complications was 29.1% (23/79), which included cervical fistula, abdominal wound dehiscence, liquefaction necrosis of abdominal fat, and pleural effusion. CONCLUSIONS: Surgical resection of cervical esophageal carcinoma and laryngeal preservation is possible. Complete esophagectomy should be performed when the resection extends below the thoracic inlet. The reconstruction methods we performed were safe and effective for the immediate restoration of alimentary continuity after resection of cervical esophageal and pharyngo-cervical esophageal carcinoma; and the patients with PMF/CWSG reconstruction had a better survival than those with GP or CI reconstruction. Combined with radiotherapy, the resectability rate and survival rate of cervical esophageal carcinoma can be improved.

Definitive extended field intensity-modulated radiotherapy and concurrent cisplatin chemosensitization in the treatment of IB2-IIIB cervical cancer.

OBJECTIVE: To assess the toxicity of delivering extended field intensity-modulated radiotherapy (EF-IMRT) and concurrent cisplatin chemotherapy for locally advanced cervical carcinoma. METHODS: Forty-five patients who underwent EF-IMRT and concurrent cisplatin chemotherapy for the treatment of stage IB2 to IIIB cervical cancer were retrospectively reviewed. The clinical target volume included all areas of gross and potentially microscopic disease and regional lymph node regions. All patients underwent high-dose-rate brachytherapy. The acute and late toxicity were scored using the Common Terminology Criteria for Adverse Events and the Radiation Therapy Oncology Group late radiation morbidity scoring criteria, respectively. RESULTS: The median follow-up was 28 months (range, 5 to 62 months). Forty-two patients had a complete response, and three had a persistent disease. Of those 42 patients, 15 patients (35.7%) had recurrence. The regions of recurrence were in-field in 2 patients and out-field in 13 patients. Acute grade ≥3 gastrointestinal, genitourinary and hematologic toxicity occurred in 3, 1, and 9 patients, respectively. Three patients (6.7%) suffered from late grade 3 toxicities. Seven patients experienced ovarian transposition, 5 of those patients (71%) maintained ovarian function. Thirty-eight patients (84.4%) were alive at the last follow-up. CONCLUSION: Concurrent cisplatin chemotherapy with EF-IMRT was safe. The acute and late toxicities are acceptable. EF-IMRT provides an opportunity to preserve endocrine function for patients with ovarian transposition.

Extended-field intensity-modulated radiotherapy and concurrent cisplatin-based chemotherapy for postoperative cervical cancer with common iliac or para-aortic lymph node metastases: a retrospective review in a single institution.

OBJECTIVE: Retrospectively, to assess the toxicity of delivering postoperative extended-field intensity-modulated radiotherapy (EF-IMRT) and concurrent cisplatin chemotherapy for patients with cervical cancer with a pathologically confirmed positive common iliac node and/or a para-aortic node. METHODS: Each patient received postoperative EF-IMRT and concurrent cisplatin chemotherapy. The clinical target volume included regional lymph node regions (obturator; common, internal, and external iliac nodal regions; presacral region; and para-aortic regions) and the upper 2.0 cm of the vagina and paravaginal soft tissue lateral to the vagina. The acute and late toxicity were scored using the Common Terminology Criteria for Adverse Events (CTCAE) and the Radiation Therapy Oncology Group late radiation morbidity scoring criteria, respectively. RESULTS: Fifty-eight patients were treated with postoperative EF-IMRT and concurrent cisplatin chemotherapy. The median follow-up was 34 months. Eighteen patients (31%) had recurrence. The region of recurrence was in-field in 2 patients (3.4%) and out-field in 16 patients (27.6%). Acute grade 3 or higher gastrointestinal, genitourinary, and hematologic toxicity occurred in 2, 1, and 11 patients, respectively. Three patients (5.1%) had late grade 3 toxicities. Thirteen patients experienced ovarian transposition; of these, 10 patients (77%) maintained ovarian function. Forty-one patients (71%) were alive at the last follow-up. CONCLUSIONS: Concurrent cisplatin chemotherapy with postoperative EF-IMRT was safe and well tolerated. The acute and late toxicities are acceptable. The locoregional control rates are hopeful, although distant metastases continue to be the primary mode of failure. Postoperative EF-IMRT provides an opportunity to preserve endocrine function for patients with ovarian transposition.

Combination of anti-IGF-1R antibody A12 and ionizing radiation in upper respiratory tract cancers.

PURPOSE: The IGF1/IGF-1R signaling pathway has emerged as a potential determinant of radiation resistance in human cancer cell lines. Therefore we investigated the potency of monoclonal anti-IGF-1R antibody, A12, to enhance radiation response in upper respiratory tract cancers. METHODS AND MATERIALS: Cell lines were assessed for IGF-1R expression and IGF1-dependent response to A12 or radiation using viability and clonogenic cancer cell survival assays. In vivo response of tumor xenografts to 10 or 20 Gy and A12 (0.25-2 mg × 3) was assessed using growth delay assays. Combined treatment effects were also analyzed by immunohistochemical assays for tumor cell proliferation, apoptosis, necrosis, and vascular endothelial growth factor expression at Days 1 and 6 after start of treatment. RESULTS: A12 enhanced the radiosensitivity of HN5 and FaDu head-and-neck carcinomas in vitro (p < 0.05) and amplified the radioresponse of FaDu xenografts in a dose-dependent manner, with enhancement factors ranging from 1.2 to 1.8 (p < 0.01). Immunohistochemical analysis of FaDu xenografts demonstrated that A12 inhibited tumor cell proliferation (p < 0.05) and vascular endothelial growth factor expression. When A12 was combined with radiation, this resulted in apoptosis induction that persisted until 6 days from the start of treatment and in increased necrosis at Day 1 (p < 0.01, respectively). Combined treatment with A12 and radiation resulted in additive or subadditive growth delay in H460 or A549 xenografts, respectively. CONCLUSIONS: The results of this study strengthen the evidence for investigating how anti-IGF-1R strategies can be integrated into radiation and radiation-cetuximab regimen in the treatment of cancer of the upper aerodigestive tract cancers.

Enhanced response to C225 of A431 tumor xenografts growing in irradiated tumor bed.

BACKGROUND AND PURPOSE: We recently demonstrated that C225 maintenance therapy after completion of radiotherapy further increased tumor radiocurability. The present study assessed mechanisms underlying the observed improvement in C225 efficacy in pre-irradiated tissue (tumor bed). MATERIALS AND METHODS: A431 xenografts growing in pre-irradiated and non-irradiated tissue were treated with C225. Tumors were assessed for growth delay, cell proliferation, hypoxia, EGFR and VEGF expressions. In vitro clonogenic survival of cells derived from these tumors was also assayed. RESULTS: Pre-irradiation of tumor bed induced growth retardation, reduction in Ki-67 labeling, and overexpression of HIF-1alpha, CA IX, EGFR and VEGF biomarkers. C225 treatment dramatically inhibited tumor growth in the irradiated tumor bed (P<0.0001), which was associated with further reduction in Ki-67 labeling, and reduced expression of HIF-1alpha, CA IX, EGFR and VEGF. Cells derived from tumors in the pre-irradiated bed showed increased sensitivity to C225. C225 was more cytotoxic against hypoxic than well-oxygenated A431 cells grown in vitro. CONCLUSION: A431 xenografts growing in pre-irradiated tumor bed exhibit enhanced sensitivity to C225. Pre-irradiated tissue microenvironment seems to render tumor cells more susceptible to C225 cytostatic and cytotoxic actions. If confirmed in other tumor models these findings support the use of C225 maintenance therapy after completion of radiotherapy.

Stereotactic body radiation therapy in centrally and superiorly located stage I or isolated recurrent non-small-cell lung cancer.

PURPOSE: To evaluate the efficacy and adverse effects of image-guided stereotactic body radiation therapy (SBRT) in centrally/superiorly located non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: We delivered SBRT to 27 patients, 13 with Stage I and 14 with isolated recurrent NSCLC. A central/superior location was defined as being within 2 cm of the bronchial tree, major vessels, esophagus, heart, trachea, pericardium, brachial plexus, or vertebral body, but 1 cm away from the spinal canal. All patients underwent four-dimensional computed tomography-based planning, and daily computed tomography-on-rail guided SBRT. The prescribed dose of 40 Gy (n = 7) to the planning target volume was escalated to 50 Gy (n = 20) in 4 consecutive days. RESULTS: With a median follow-up of 17 months (range, 6-40 months), the crude local control at the treated site was 100% using 50 Gy. However, 3 of 7 patients had local recurrences when treated using 40 Gy. Of the patients with Stage I disease, 1 (7.7%) and 2 (15.4%) developed mediastinal lymph node metastasis and distant metastases, respectively. Of the patients with recurrent disease, 3 (21.4%) and 5 (35.7%) developed mediastinal lymph node metastasis and distant metastasis, respectively. Four patients (28.6%) with recurrent disease but none with Stage I disease developed Grade 2 pneumonitis. Three patients (11.1%) developed Grade 2-3 dermatitis and chest wall pain. One patient developed brachial plexus neuropathy. No esophagitis was noted in any patient. CONCLUSIONS: Image-guided SBRT using 50 Gy delivered in four fractions is feasible and resulted in excellent local control.

[Surgical treatment of tonsillar cancer].

OBJECTIVE: To study the surgical treatment of tonsillar cancer. METHODS: Twenty-four patients with tonsillar cancer were treated with surgery and postoperative radiotherapy. The choice of surgical procedure was decided on the condition of the lesion. The tumor was resected through the transoral approach, mandibular swing approach, mandibular resection approach or hyoid approach. Surgical defect was repaired by pectoralis major myocutaneous flap, sternohyoid myofascial flap, tongue flap or soft palate flap. RESULTS: The 3- and 5-year survival rates were 76.0% and 60.8%. Function of chewing, deglutition, respiration and speech was restored well. CONCLUSION: Method of total resection of the tonsillar carcinoma through the optimum approach is best chosen according to the condition of the lesion, while preserving the oropharyngeal function. When combined with postoperative radiotherapy, the survival rate and quality of life of patients can be improved.

[Preservation of laryngeal function in surgery for medial wall pyriform sinus cancer].

OBJECTIVE: To study the feasibility, surgical technique and results of laryngeal function preservation in surgical treatment for medial wall pyriform sinus cancer. METHODS: From 1992 to 1999, 31 patients with medial wall pyriform sinus cancer including stage I 1, II 4, III 14 and IV 12 lesions were treated. Partial resection of pyriform sinus and partial laryngectomy were performed, then, the remains of epiglottis and uni-pedicled sternohyoid myofascial flap were used to restore the defects of larynx. At last, the remaining hypopharyngeal mucosa was sutured to cover the wound of hypopharynx and for artificial rebuild-up. All patients received postoperative radiotherapy. RESULTS: The 3- and 5-year survival rates were 62.1% and 43.6% respectively, with 77.4% patients having laryngeal functions (voice, respiration and deglutition) completely restored and 32.6% partially restored (voice and deglutition). CONCLUSION: Conservative surgery so introduced is feasible for selected medial wall pyriform sinus cancer patients with the lesion completely resected.