Rapid Selection of Patients Suitable for Deep Inspiration Breath-Hold Using an Automatic Delineating System and RapidPlan Model in Left Breast Cancer Patients undergoing Adjuvant Radiotherapy with IMRT.

PURPOSE: This study aimed to determine whether radiotherapy plans created using an automatic delineating system and a RapidPlan (RP) module could rapidly and accurately predict heart doses and benefit from deep inspiratory breath-hold (DIBH)in left breast cancer patients. METHODS AND MATERIALS: One hundred thirty-six clinically approved free breathing (FB) plans for patients with left breast cancer were included, defined as manual delineation-manual plan (MD-MP). A total of 104/136 plans were selected for RP model training. A total of 32/136 patients were automatically delineated by software, after which the RP generated plans, defined as automatic delineation-RapidPlan (AD-RP). In addition, 40 patients who used DIBH were included to analyze differences in heart benefits from DIBH. RESULTS: Two RP models were established for post breast-conserving surgery (BCS) and post modified radical mastectomy (MRM). There were no significant differences in most of the dosimetric parameters between the MD-MP and AD-RP. The heart doses of the two plans were strongly correlated in patients after BCS (0.80 ≤ r ≤ 0.88, P < 0.05) and moderately correlated in patients after MRM (0.46 ≤ r ≤ 0.58, P < 0.05). The RP model predicted the mean heart dose (MHD) within ± 59.67 cGy and ± 63.32 cGy for patients who underwent the two surgeries described above. The heart benefits from DIBH were significantly greater in patients with FB-MHD ≥ 4 Gy than in those with FB-MHD < 4 Gy. CONCLUSIONS: The combined automatic delineation RP model allows for the rapid and accurate prediction of heart dose under FB in patients with left breast cancer. FB-MHD ≥ 4 Gy can be used as a dose threshold to select patients suitable for DIBH.

Prognostic impact of pretherapeutic gamma-glutamyltransferase on patients with nasopharyngeal carcinoma.

BACKGROUND: Gamma-glutamyltransferase (GGT) is a membrane-bound enzyme involved in the metabolism of glutathione. Studies suggested that GGT played an important role in the tumor development, progression, invasion and drug resistance and prognosis. The association between GGT and prognosis of patients with nasopharyngeal carcinoma (NPC) was unknown. This study was conducted to investigate the association of pretherapeutic serum level of GGT with clinical-pathological parameters and survival in patients with NPC. METHODS: Two hundred and twenty-two patients with NPC were recruited in this study and were stratified into two GGT risk groups (≤ 34.5 U/L, > 34.5 U/L). The association of pretherapeutic serum GGT levels with clinical-pathological parameters was examined. Univariate and multivariate survival analyses were performed. FINDINGS: The pretherapeutic serum level of GGT was not associated with gender, age, pathology, T stage, N stage, TNM stage, chemotherapy or radiotherapy in patients with NPC. Patients in the high-risk GGT group had a poorer survival than the low-risk GGT group (3-year overall survival, 74.2% vs. 50.2%, P = 0.001; 3-year progression-free survival, 76.4% vs. 47.1%, P < 0.001; 3-year loco-regional relapse-free survival, 76.4% vs. 51.3%, P < 0.001; 3-year distant metastasis-free survival, 89.5% vs. 66.4%, P < 0.001). Multivariate analysis suggested that patients in the high-risk GGT group had 2.117 (95% confidence interval [CI], 1.225 ∼ 3.659, P = 0.007) times the risk of death, 2.836 (95% CI, 1.765 ∼ 4.557, P < 0.001) times the risk of progression, 2.551 (95% CI, 1.573 ∼ 4.138, P < 0.001) times the risk of relapse, and 3.331 (95% CI, 1.676 ∼ 6.622, P < 0.001) times the risk of metastasis compared with those in the low-risk GGT group. CONCLUSION: The pretherapeutic serum level of GGT might serve as a novel independent prognostic factor for overall-survival, progression-free survival, loco-regional relapse-free survival and distant metastasis-free survival in patients with NPC.

The important role of the receptor for activated C kinase 1 (RACK1) in nasopharyngeal carcinoma progression.

BACKGROUND: The receptor for activated C kinase 1 (RACK1) is involved in various cancers, but its roles in nasopharyngeal carcinoma (NPC) have not yet been fully elucidated. METHODS: Initially, RACK1 expression was analyzed by immunohistochemistry in NPC and normal nasopharyngeal (NP) tissues. It was also detected by qPCR and Western blot in NPC cells. Confocal microscope and immunofluorescence were performed to detect the subcellular compartmentalization of RACK1. Subsequently, after up- or down-regulating RACK1 in NPC cells, cell proliferation and migration/invasion were tested using in vitro assays including MTT, EdU, colony formation, Transwell and Boyden assays. Furthermore, several key molecules were detected by Western blot to explore underlying mechanism. Finally, clinical samples were analyzed to confirm the relationship between RACK1 expression and clinical features. RESULTS: Receptor for activated C kinase 1 expression was much higher in NPC than NP tissues. And RACK1 was mainly located in the cytoplasm. Overexpression of RACK1 promoted NPC cell proliferation and metastasis/invasion, whereas depletion of this protein suppressed NPC cell proliferation and metastasis/invasion. Mechanistically, RACK1 deprivation obviously suppressed the activation of Akt and FAK, suggesting the PI3K/Akt/FAK pathway as one of functional mechanisms of RACK1 in NPC. Furthermore, clinical sample analysis indicated a positive correlation between in vivo expression of RACK1 with lymph node invasion and clinical stage of NPC. CONCLUSION: Our results demonstrate that RACK1 protein plays an important role in NPC development and progression. The upregulation of RACK1 can promote the proliferation and invasion of NPC by regulating the PI3K/Akt/FAK signal pathway. Thus, this study contributes to the discovery of a potential therapeutic target for NPC.

High expression of nuclear Snail, but not cytoplasmic staining, predicts poor survival in nasopharyngeal carcinoma.

BACKGROUND: Transcription factor Snail has been shown to promote tumor progression and metastasis in various cancers. However, its clinical significance in nasopharyngeal carcinoma (NPC) is still scanty. We have explored the clinical significance of Snail expression and its association with patient outcome in NPC. METHODS: Immunohistochemistry was used to examine the expression levels of Snail in 122 patients with NPC. RESULTS: Cytoplasmic Snail was detected in 37.7 %, and nuclear staining was detected in 49.2 % of primary tumors, respectively. No significant associations were found between cytoplasmic Snail and the clinicopathologic variables except lymph node metastasis (P = 0.042). However, nuclear Snail was significantly associated with tumor stage (P = 0.003), T classification (P = 0.045), lymph node metastasis (P = 0.019), distant metastasis (P = 0.003), and reduced E-cadherin expression (P = 0.021). Patients with high nuclear Snail expression, but not cytoplasmic staining, had significantly shorter survival than those with low expression (P < 0.001). Significantly, nuclear Snail was an independent prognostic predictor for NPC (P < 0.001). Furthermore, the prognostic impact was largely limited to stage III-IV patients. CONCLUSIONS: We demonstrated first that nuclear Snail, but not cytoplasmic staining, predicts worse outcome. In addition, the prognostic value in stage III-IV suggests that nuclear Snail could be a potential therapeutic target for late stage of NPC patients.