SDF-1α predicts poor prognosis in patients with locally advanced esophageal squamous cell carcinoma receiving definitive concurrent chemoradiotherapy.

BACKGROUND: Stromal cell-derived factor-1α (SDF-1α) is a chemokine associated with tumor progression in various types of cancers. The current study aimed to evaluate whether pre-treatment or kinetics of SDF-1α can predict the prognosis in patients with esophageal squamous cell carcinoma (ESCC) receiving definitive concurrent chemoradiotherapy (CCRT). METHODS: A total of 97 patients with ESCC were identified at Kaohsiung Chang Gung Memorial Hospital between January 2010 and December 2015. Serum concentration of SDF-1α was measured at day 0 (pre-treatment) and chemotherapy day 28 to determine its kinetics and the cut-off level of pre-chemotherapy SDF-1α was 1.5 ng/mL. Two ESCC cell lines, TE1 and KYSE30, were selected to evaluate the function of SDF-1α. RESULTS: Univariate and multivariate analyses showed that pre-treatment SDF-1α ≥ 1.5 ng/mL and an increased SDF-1α level after treatment were significantly associated with worse progression-free survival (p = 0.021 and p = 0.008, respectively) and overall survival (p = 0.005 and p < 0.001, respectively). In addition, patients with pre-treatment SDF-1α ≥ 1.5 ng/mL and increased SDF-1α levels after treatment were found to have poor response to CCRT. Moreover, these cell lines were treated with chemotherapeutic agents (cisplatin or 5-FU) and SDF-1α, alone or in combination. Our in vitro study results showed SDF-1α promoted the proliferation of tumor cells and overcame the cytotoxic effect of chemotherapy (p < 0.001). CONCLUSION: Our study suggested that SDF-1α plays an important role in ESCC disease progression and that pre-treatment SDF-1α level and kinetics of SDF-1α are the independent prognostic factors for ESCC patients receiving definitive CCRT. Periodic determinations of serum SDF-1α level may be valuable to predict prognosis of ESCC in clinical practice.

The Radiation Dose to the Left Supraclavicular Fossa is Critical for Anastomotic Leak Following Esophagectomy - A Dosimetric Outcome Analysis.

Purpose: For locally advanced esophageal cancer, definitive concurrent chemoradiotherapy (CCRT) with a radiation dose of 50-50.4 Gy/25-28 Fx is prescribed, followed by adjuvant esophagectomy for better local control or salvage treatment if locoregional recurrence occurs. However, radiation injury before surgery may delay wound healing. We performed cervical anastomosis directly inside the left supraclavicular fossa (SCF), the irradiation target for esophageal cancer. The significance of radiation injury in patients with cervical anastomotic leak (AL) remains unclear. Thus, we assessed the influence of radiation on cervical AL in patients undergoing preoperative CCRT followed by esophagectomy. Patients and Methods: We defined the SYC zone, a portion of the region overlapping the left SCF. The radiation dose to the SYC zone was analyzed and correlated with AL in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who were administered preoperative CCRT (radiation dose with 50-50.4 Gy/25-28 Fx to the primary esophageal tumor) followed by esophagectomy between October 2009 and January 2018. Receiver operating characteristic curve analysis and logistic regression were used to identify the optimal radiation factor to predict AL and the cutoff value. Results: The optimal radiation factor to predict AL was the mean dose to the SYC zone (area under the curve (AUC)=0.642), and the cutoff point of the mean dose was 48.55 Gray (Gy). For a mean SYC zone dose ≥48.55 Gy, the AL risk was sevenfold greater than that for <48.55 Gy (OR = 7.805; 95% CI: 1.184 to 51.446; P value = 0.033). Conclusion: Recognizing the SYC zone as an organ at risk and performing radiation evaluation are meaningful. A reduced mean dose of the SYC zone below 48.55 Gy results in a lower cervical AL rate following esophagectomy.

The Impact of Weight Loss during Chemoradiotherapy for Unresectable Esophageal Cancer: Real-World Results.

Weight loss is a common phenomenon presented in unresectable esophageal cancer (EC) patients during their definitive chemoradiotherapy (dCRT) treatment course. This study explored the prognostic value of weight changes during dCRT in unresectable EC patients. From 2009 to 2017, 69 cT4b thoracic EC patients undergoing complete curative dCRT without baseline malnutrition were included. Clinical factors were analyzed via the Cox proportional hazards model and survival was analyzed by the Kaplan−Meier method. During dCRT, the median weight loss percentage was 5.51% (IQR = 2.77−8.85%), and the lowest body weight was reached at 35 days (IQR = 23−43 days). Median OS of these patients was 13.5 months. Both univariate and multivariate analysis demonstrated that weight loss ≤ 4% during dCRT was significantly associated with superior OS with a hazard ratio of 2.61 (95% CI: 1.40−4.85, p = 0.002). The median OS for patients with weight loss ≤ 4% and >4% during dCRT was 59.6 months and 9.7 months, respectively (p = 0.001). Our study demonstrated that weight loss ≤ 4% during dCRT course is a favorable prognostic factor for cT4b EC patients. This index could serve as a nutrition support reference for unresectable EC patients receiving dCRT in the future.

Significant Reduction in Vertebral Artery Dose by Intensity Modulated Proton Therapy: A Pilot Study for Nasopharyngeal Carcinoma.

Intensity modulated proton therapy (IMPT) with the vertebral artery (VA)-sparing technique has been initially proposed in our institution. This pilot study was conducted to compare the dose to VAs between IMPT and volumetric-modulated arc therapy (VMAT) for patients with nasopharyngeal carcinoma (NPC). A total of six patients with NPC treated by IMPT were enrolled in the study. Target volumes and organs at risk (OARs) were delineated, including 12 samples of right and left VAs, respectively, for each patient. Treatment planning by IMPT and dual-arc VMAT was carried out for comparison. The IMPT plan significantly reduced VA mean dose, V10, V20, V30, V40, and V50, compared to the VMAT plan in all 12 samples (p < 0.001). The average mean dose to VAs for IMPT was 35.2% (23.4-46.9%), which was less compared to VMAT (p < 0.001). Adequate dose coverage was achieved with both IMPT and VMAT plans for three different dose levels of target volumes for all patients. IMPT significantly reduces VA dose while maintaining adequate dose coverage of all target volumes. For patients with head and neck cancer who seek to preserve their blood flow to the brain in order to decrease late vascular and neurologic sequelae, IMPT should be considered. A prospective study with longer follow-up is ongoing to confirm our preliminary results.

Definitive chemoradiotherapy for clinical T4b esophageal cancer - Treatment outcomes, failure patterns, and prognostic factors.

PURPOSE: The management of cT4b thoracic esophageal cancer (EC) is challenging. The optimal treatment remains unclear, and prospective or large-scale retrospective reports on treatment outcomes are lacking. The present study was conducted to investigate the treatment outcomes, failure patterns, treatment responses, and prognostic factors focusing on cT4b thoracic EC treated by definitive concurrent chemoradiotherapy (dCRT). METHODS: A retrospective review of cT4b thoracic EC patients treated with curative intent dCRT at our institution between 2009 and 2017 was conducted. Survival analysis was calculated using the Kaplan-Meier method, and prognostic factors were examined by the Cox proportional hazards model. RESULTS: A total of 95 cT4b EC patients were included, and the median survival was 11.4 months. The 1-year, 3-year, and 5-year survival rates were 49.4%, 22.2%, and 19.0%, respectively. Forty-six patients (48.4%) experienced locoregional failure, 3 patients (3.2%) developed distant metastasis, and 11 patients had synchronous locoregional and distant failure. The corresponding 1-year, 3-year, and 5-year locoregional failure rates were 62.6%, 74.5%, and 79.2%, respectively. The treatment response rate was 76.9%, and clinical complete response was achieved in 25.3% of patients. Multivariable analysis revealed that age ≤ 65 (p = 0.003), pre-dCRT body mass index (BMI) > 21 (p < 0.001), clinical N stage 0-1 (p = 0.014), and tumor length ≤ 6 cm (p = 0.026) were independent prognosticators for better survival. CONCLUSION: Our study revealed that long-term survival is achievable for cT4b EC patients treated by dCRT, with a 3-year survival rate of more than 20%. Locoregional recurrence was the most common failure pattern. Age, BMI, N stage, and tumor length were significant prognosticators for survival in this group of patients.

Efficacy of Different Chemotherapy Regimens in Patients with Locally Advanced Synchronous Esophageal and Head/Neck Squamous Cell Carcinoma Receiving Curative Concurrent Chemoradiotherapy.

Esophageal squamous cell carcinoma (ESCC) and head/neck squamous cell carcinoma (HNSCC) are very common cancers worldwide, and there is higher incidence of synchronous ESCC/NSCC in Taiwan. The aim of the current study was to investigate the efficacy of different chemotherapy regimens in patients with locally advanced synchronous ESCC/HNSCC who received curative concurrent chemoradiotheapy (CCRT). A total of 75 patients were identified and assigned to one of two groups: 45 patients receiving cisplatin/5-fluorouracil (5-FU) regime in one group and 30 patients receiving a weekly cisplatin regime in the other. Overall survival (OS) was calculated from the date of diagnosis of the ESCC or HNSCC to the date of death from any cause or the most recent follow-up. Kaplan-Meier curves and log-rank tests were used to estimate OS and differences between the two groups, respectively. There was no significant difference in the analysis of OS between the cisplatin/5-FU and the weekly cisplatin groups. However, patients that interrupted their CCRT were found to have worse OS compared to those without interruptions (5.4 months versus 18.8 months, p = 0.002). In subgroup analysis, patients without interruptions of CCRT had a better OS than those with interruptions in the cisplatin/5-FU group (13.0 months versus 5.4 months, p = 0.041) as well as in the weekly cisplatin group (21.4 months versus 5.0 months, p = 0.017). Interruption of CCRT was the only independently poor prognostic factor of OS in the univariate and multivariate (hazard ratio 0.18, p < 0.001) analyses. Most interruption of CCRT resulted from adverse events (AEs) or serious AEs. Although there was no significant difference in the incidence of AEs between these two groups, lower incidence of adverse events was mentioned in the weekly cisplatin group. Our study suggests that interruption of CCRT is an independently poor prognostic factor of OS, and that completion of CCRT without interruption is more important than the choice of chemotherapeutic regimen for patients with synchronous ESCC/HNSCC.

The Clinical Outcomes of Locally Advanced Cervical Esophageal Squamous Cell Carcinoma Patients Receiving Curative Concurrent Chemoradiotherapy: A Population-Based Propensity Score-Matched Analysis.

This study investigated the clinical outcome of locally advanced cervical esophageal squamous cell carcinoma (ESCC) patients who received curative concurrent chemoradiotherapy (CCRT) and their differences from thoracic ESCC patients. Among 411 enrolled ESCC patients, including 63 with cervical and 348 with thoracic ESCC, 63 thoracic patients were propensity score-matched to the 63 cervical patients. For cervical ESCC, T4b and high tumor grade were independent prognostic factors of a worse overall survival (OS) in univariate and multivariate analyses. The response rates to curative CCRT between cervical and the matched thoracic ESCC groups were similar but cervical ESCC had a better OS than that of the matched thoracic group (21.4 versus 10.1 months, p = 0.012). Better OS was mentioned to be in the patients with complete response (CR), whether in the cervical or matched thoracic ESCC group. For patients without CR, patients who underwent esophagectomy had superior OS than those without operation in the matched thoracic ESCC group (11.6 versus 11.9 months, p = 0.73). Only three patients received operation in the cervical ESCC group, thus the survival difference was not significant. Curative CCRT may be a reasonable treatment for cervical ESCC in clinical practice, and the role of surgery should be considered as salvage therapy if residual disease is evident.

Analysis of prognostic factors and clinical outcomes in uterine cervical carcinoma with isolated para-aortic lymph node recurrence.

To evaluate clinical outcomes and to identify prognostic factors in isolated para-aortic lymph node (PALN) recurrence, we retrospectively reviewed 65 patients who developed PALN recurrence as the first site of tumor progression from a total of 1521 patients who were treated with curative pelvic radiation therapy (RT) for uterine cervical carcinoma between May 1993 and January 2017. Forty-five of the 65 patients received salvage therapy. The median salvage PALN radiation dose was 54 Gy (range: 18 to 62 Gy). Prognostic factors for overall survival (OS) and distant metastases (DMs) were analyzed with univariate and multivariate Cox regression. The median follow-up period for surviving patients was 61 months (4-202 months). The median OS was 27.7 months (0.3-202 months). The highest level of PALN metastases at or above the L1 spinal level (hazard ratio [HR] 9.88, 95% confidence interval [CI] 3.44-28.38, P<0.001) and the presence of leg edema and/or back pain at recurrence (HR 3.25, 95% CI 1.57-6.75, P=0.002) were significantly associated with worse OS. A significantly higher incidence of DMs (HR 5.97, 95% CI 2.05-17.35, P=0.001) was found in the patients with a high level (≥L1) of PALN metastases. Salvage RT (HR 0.35, 95% CI 0.17-0.71, P=0.004) and restaging with positron emission tomography/computed tomography (PET/CT) (HR 0.2, 95% CI 0.04-0.93, P=0.039) were independent predictors of a better OS. In conclusion, a high level (≥L1) of PALN metastases predicts poor survival and a high rate of DMs. Periodic surveillance for early detection and restaging by PET/CT imaging to identify the optimal treatment at recurrence is recommended.

Platelet-to-lymphocyte ratio is an independent prognosticator in patients with esophageal squamous cell carcinoma receiving esophagectomy.

BACKGROUND: Systemic inflammation response is a crucial prognostic factor for various cancers. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are two inflammation-based prognostic scores. The significance of preoperative NLR and PLR in patients with esophageal squamous cell carcinoma (ESCC) receiving curative esophagectomy remains largely undefined. Hence, this study aimed to evaluate the significance of preoperative NLR and PLR in patients with ESCC receiving curative esophagectomy in southern Taiwan. METHODS: A consecutive group of 107 patients with ESCC undergoing esophagectomy between January 2001 and December 2012 were retrospectively reviewed. The NLR and PLR of these 107 patients were calculated and correlated with clinicopathological parameters, overall survival (OS), and disease-free survival (DFS). RESULTS: NLR ≥2.5 was significantly correlated with higher T classification (P=0.006) and advanced clinical AJCC 7th stage (P=0.047). PLR ≥150 was significantly associated with higher T classification (P=0.009). Univariate survival analysis showed that NLR ≥2.5 and PLR ≥150 were associated with poor OS (P=0.009 and P=0.007, respectively) and poor DFS (P=0.006 and P=0.005, respectively). On multivariate comparison, PLR ≥150 was independently associated with poor OS [P=0.001, hazard ratio (HR): 2.475] and poor DFS (P<0.001, HR: 2.509). The 5-year overall and DFS rates were, respectively, 33.3% and 25.0% in patients with PLR ≥150, and 54% and 46% in patients with PLR <150. CONCLUSIONS: The PLR is an independent prognosticator for patients with ESCC undergoing esophagectomy in southern Taiwan.

Neck Lymph Node Metastasis as A Poor Prognostic Factor in Thoracic Esophageal Squamous Cell Carcinoma Patients Receiving Concurrent Chemoradiotherapy: A Propensity Score-Matched Analysis.

The present study investigated the clinical impact of neck lymph node (LN) metastasis in locally advanced inoperable thoracic esophageal squamous cell carcinoma (ESCC) patients who underwent concurrent chemoradiotherapy (CCRT) with a curative intent. There were 404 ESCC patients enrolled, including 35 patients with neck LN metastasis and 369 patients without such metastasis. Through the propensity score matching method, 35 patients of the 369 patients without neck LN metastasis were matched to the 35 patients with neck LN metastasis. Progression-free survival (PFS) and overall survival (OS) were found to be significantly worse in the neck LN metastasis group compared to the full non-neck LN metastasis group (9.8 months versus 5.9 months, P < 0.001, and 18.2 months versus 9.7 months, P = 0.001) and the matched non-neck LN metastasis group (9.9 months versus 5.9 months, P = 0.006, and 19.4 months versus 9.7 months, P = 0.007). In order to determine the difference between neck LN and supraclavicular LN metastasis, seventy patients with supraclavicular LN metastasis were also selected from the 369 patients without neck LN metastasis for comparison. Subsequently, when compared to the ESCC patients with supraclavicular LN metastasis, significantly worse PFS (8.5 months versus 5.9 months, P = 0.026) and OS (17.2 months versus 9.7 months, P = 0.047) were still found in the ESCC patients with neck LN metastasis. Our study indicates that neck LN metastasis is an independent poor prognostic factor for locally advanced inoperable thoracic ESCC patients who have undergone CCRT.

Inflammation-based prognostic scores predict the prognosis of locally advanced cervical esophageal squamous cell carcinoma patients receiving curative concurrent chemoradiotherapy: a propensity score-matched analysis.

INTRODUCTION: The present study investigated the crucial role of inflammation-based prognostic scores in locally advanced cervical esophageal squamous cell carcinoma (ESCC) patients who underwent curative concurrent chemoradiotherapy (CCRT). METHODS: There were 411 ESCC patients enrolled, including 63 cervical ESCC patients. Using the propensity score matching method, 63 thoracic ESCC patients were matched to the 63 cervical ESCC patients. The inflammation-based prognostic scores included the neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), albumin level, c-reactive protein (CRP) level, modified Glasgow prognostic score (mGPS), and CRP/albumin ratio. The chi-square test and Kaplan-Meier method were used for categorical variable data and overall survival, respectively. A Cox regression model was performed for univariate and multivariable analyses. RESULTS: With respect to cervical ESCC, NLR ≥ 2.5 (P = 0.019), PLR ≥ 103 (P = 0.013), CRP value >10 mg/l (P = 0.040), mGPS ≥ 1 (P = 0.040), and CRP/albumin ratio ≥ 9.5 (P = 0.033) were significant predictors of worse overall survival (OS) in the univariate analysis. In a multivariable analysis, PLR ≥ 103 (P = 0.010, HR: 2.66, 95% CI [1.27-5.58]) and mGPS ≥ 1 (P = 0.030, HR: 2.03, 95% CI [1.07-3.86]) were the independent prognostic parameters of worse OS. The prognostic value of these biomarkers in the matched thoracic ESCC patients was similar and compatible with the results in the cervical ESCC group in the univariate and multivariable analyses. CONCLUSIONS: Our study suggests that these inflammation-based prognostic scores are helpful in clinical practice, and PLR and mGPS may predict the prognosis for locally advanced cervical ESCC patients who receive curative CCRT.

The crucial role of blood VEGF kinetics in patients with locally advanced esophageal squamous cell carcinoma receiving curative concurrent chemoradiotherapy.

BACKGROUND: To evaluate the role of blood vascular endothelial growth factor (VEGF) kinetics in patients with locally advanced esophageal squamous cell carcinoma (ESCC) receiving curative concurrent chemoradiotherapy (CCRT). METHODS: A total of 97 locally advanced ESCC patients were enrolled. All the patients had their blood drawn at three time points to determine their levels of VEGF, including pre-chemotherapy (day 0), post-chemotherapy (day 5), and pre-cycle 2 chemotherapy (day 28). The VEGF levels were evaluated according to the day 0 value, day 5 value, day 28 value, day 5/day 0 ratio, day 28/day 0 ratio, and day 28/day 5 ratio. A VEGF cut-off level of 80 pg/mL was applied. RESULTS: In the analysis of progression-free survival (PFS), the patients less than 60 years old had significantly superior PFS compared to those more than 60 years old. Patients who had VEGF < 80 pg/mL at day 28 and a day 28/day 5 ratio < 1 had better PFS than those with VEGF > 80 pg/mL and a day 28/day 5 ratio > 1, respectively. In the analysis of overall survival (OS), patients with N0-1 status had significantly superior OS compared to those with N2-3 status. Furthermore, patients who had VEGF < 80 pg/mL at day 28, a day 5/day 0 ratio < 1, and a day 28/day 5 ratio < 1 had superior OS compared to those patients with VEGF > 80 pg/mL, a day 5/day 0 ratio > 1, and a day 28/day 5 ratio > 1, respectively. In the multivariate analysis, only VEGF < 80 pg/mL at day 28 and a day 28/day 5 ratio < 1 represented independent prognostic factors of superior PFS and OS. CONCLUSIONS: Our study suggests that VEGF kinetics is a prognostic factor for locally advanced ESCC patients receiving curative CCRT. For these patients, lower post-treatment VEGF levels and decreasing levels of VEGF during CCRT are significantly associated with better clinical outcomes.

The clinical impact of supraclavicular lymph node metastasis in patients with locally advanced esophageal squamous cell carcinoma receiving curative concurrent chemoradiotherapy.

BACKGROUND: To evaluate the clinical significance of supraclavicular lymph node (SCLN) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) receiving curative concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: We retrospectively analyzed all 369 locally advanced ESCC patients treated with CCRT between 2000 and 2015, including 70 patients with SCLN metastasis and 299 patients without SCLN metastasis. RESULTS: For these locally advanced ESCC patients treated with curative CCRT, N0-2 were significantly associated with superior progression-free survival (PFS) and overall survival (OS) in univariate and multivariable analyses. However, there were no significant differences in PFS and OS between the SCLN metastasis and non-SCLN metastasis groups; a subgroup analysis also revealed there was no significant differences in PFS and OS between patients with and without SCLN metastasis either in the N0-2 or in the N3 subgroup analysis. CONCLUSIONS: Our study suggests that SCLN metastasis is not a prognostic factor in locally advanced ESCC patients receiving curative CCRT, and that SCLNs should be considered to be regional LNs and treated with curative intent.

Pretreatment prognostic factors of survival and late toxicities for patients with nasopharyngeal carcinoma treated by simultaneous integrated boost intensity-modulated radiotherapy.

BACKGROUND: To scrutinize the pretreatment prognosticators on survival and late toxicities in a homogenous cohort of nasopharyngeal carcinoma (NPC) patients treated by simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT). METHODS: A total of 219 non-distant metastatic NPC patients consecutively treated by SIB-IMRT at a single institute were collected. The pretreatment factors including the socio-demographic variables, TNM stages, gross tumor volume (GTV), Epstein-Barr virus (EBV)-DNA, and hematologic inflammatory markers were analyzed. Cox model was used to screen the prognostic factors of late toxicities and four survival outcomes including locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), failure-free survival (FFS), and overall survival (OS). RESULTS: Statistically significant inter-correlations were observed between the values of EBV-DNA, some hematologic inflammatory markers, GTV, and N classification. The 5-year LRRFS, DMFS, FFS, and OS rates were 87.9%, 89.4%, 79.4%, and 81.3%, respectively. Multivariate analysis revealed that advanced N classification (N2-3 vs. N0-1) remained the only significant negative prognosticator for all the four survival outcomes. An increased monocyte percentage and a decreased lymphocyte-to-monocyte ratio were significantly associated with poorer FFS and OS, respectively. Larger GTV was observed to be predictive of poorer LRRFS. Patients with T3-4 (HR: 3.5, 95% CI: 1.0-12.1, p = 0.048) or higher GTV (HR: 1.006, 95% CI: 1.001-1.011, p = 0.027) were associated with higher incidence of radiation neuropathy. CONCLUSION: N classification remains the most significant survival predictor for NPC patients treated by SIB-IMRT after adjusting these biomarkers. GTV impacts not only on locoregional control but also radiation neuropathy.

Galectin-1 is a poor prognostic factor in patients with glioblastoma multiforme after radiotherapy.

BACKGROUND: Galectin-1, a radioresistance marker, was found in our previous study to be a prognostic factor for cervical cancer. The aim of current study is to determine the prognostic significance of the galectin-1 expression level in patients with glioblastoma multiforme (GBM) undergoing adjuvant radiotherapy (RT). METHODS: We included 45 patients with GBM who were treated with maximal safe surgical resection or biopsy alone followed by adjuvant RT of EQD2 (equivalent dose in 2-Gy fractions) > or = 60 Gy for homogeneous treatment. Paraffin-embedded tissues acquired from the Department of Pathology were analyzed using immunohistochemical staining for galectin-1 expression. The primary endpoint was overall survival (OS). RESULTS: Patients with weak expression had a better median survival (27.9 months) than did those with strong expression (10.7 months; p = 0.009). We compared characteristics between weak and strong galectin-1 expression, and only the expression level of galectin-3 showed a correlation. The group with weak galectin-1 expression displayed a 3-year OS of 27.3% and a 3-year cancer-specific survival (CSS) of 27.3%; these values were only 5.9% and 7.6%, respectively, in the group with strong galectin-1 expression (p = 0.009 and 0.020, respectively). Cox regression was used to confirm that the expression level of galectin-1 (weak vs. strong) is a significant factor of OS (p = 0.020) and CSS (p = 0.022). Other parameters, such as the expression level of galectin-3, Eastern Cooperative Oncology Group (ECOG) performance, gender, surgical method, age ≥ 50 years, tumor size, or radiation field were not significant factors. CONCLUSION: The expression level of galectin-1 affects survival in patients with GBM treated with adjuvant RT. Future studies are required to analyze the effect of other factors, such as O(6)-methylguanine-DNA methyltransferase (MGMT)-promoter methylation status, in patients with weak and strong galectin-1 expression.

The prognostic significance of celiac lymph node metastasis in patients with locally advanced esophageal squamous cell carcinoma receiving curative concurrent chemoradiotherapy.

BACKGROUND: To evaluate the clinical outcomes of celiac lymph node (LN) metastasis in patients with locally advanced esophageal squamous cell carcinoma (ESCC) receiving curative concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: A total of 375 stage III ESCC patients were identified, including 51 patients with celiac LN metastasis and 324 patients without celiac LN metastasis. Among these 324 patients without celiac LN metastasis, 51 were matched with the 51 patients with celiac LN metastasis using the propensity score matching method. RESULTS: Overall, the celiac LN metastasis group had worse progression-free survival (PFS) and overall survival (OS) than the non-celiac LN metastasis group and the matched non-celiac LN metastasis group. For the ESCC patients with celiac LN metastasis, lower third ESCC was significantly associated with superior PFS and OS. For patients with upper/middle third ESCC, the celiac LN metastasis group had worse PFS and OS than the non-celiac LN metastasis group and the matched non-celiac LN metastasis group. For patients with lower third ESCC, there were no significant differences in PFS and OS between these groups. CONCLUSIONS: Our study suggests celiac LN metastasis is a poor prognostic factor for locally advanced ESCC patients receiving curative CCRT. Among these ESCC patients with celiac LN metastasis, tumor location is a strongly prognostic factor, indicating patients with lower third ESCC have better PFS and OS than those with upper/middle third ESCC. The 6th American Joint Committee on Cancer staging system seems more favorable than 7th edition in the definition of celiac LNs for those patients.

Treatment Outcomes of Patients with Locally Advanced Synchronous Esophageal and Head/Neck Squamous Cell Carcinoma Receiving Curative Concurrent Chemoradiotherapy.

The present study investigated clinical outcomes and prognostic factors of patients with locally advanced synchronous esophageal squamous cell carcinoma (ESCC) and head/neck squamous cell carcinoma (HNSCC) receiving curative concurrent chemoradiotherapy (CCRT), and determined whether synchronous ESCC/HNSCC patients had worse prognosis compared to isolated ESCC patients. Using propensity score matching method, we compared 60 locally advanced synchronous ESCC/HNSCC patients with 60 matched isolated ESCC patients. Compared to 60 matched isolated ESCC patients, synchronous ESCC/HNSCC patients had significantly worse prognosis (13.5 months versus 17.2 months, P = 0.01), more grade 3-4 CCRT toxicity, and higher percentage of CCRT interruption. For synchronous ESCC/HNSCC group, the 1-year and 2-year survival rates were 52% and 13%, respectively. Univariate analysis showed that early ESCC stage, non-T4b disease, and salvage operations were significantly associated with superior survival. In multivariate analysis, ESCC stage represented an independent prognosticator. For chemotherapy regimen during CCRT, cisplatin/5-fluorouracil had significantly more grade 3-4 mucositis/esophagitis and neutropenia than weekly cisplatin. In conclusion, synchronous ESCC/HNSCC patients receiving curative CCRT have worse prognosis and poorer compliance of CCRT compared to isolated ESCC patients. For these patients, ESCC stage and T4b disease were significantly associated with clinical outcomes, and salvage operation may improve overall survival.

The Therapeutic Benefit of Radical Resection for T4b Oral Cavity Squamous Cell Carcinoma with Partial or Complete Response After Radical Chemo-Intensity-Modulated Radiotherapy (IMRT).

BACKGROUND: This study investigated the therapeutic benefit of radical resection (SRR) for clinical T4b oral cavity squamous cell carcinoma (OSCC) with partial or complete response after radical chemoradiotherapy (CRT). METHODS: At the authors' institution, 79 patients with newly diagnosed non-metastatic T4b OSCC were treated with CRT from January 2009 to December 2014. All of them were irradiated using intensity-modulated radiotherapy (IMRT), with a radical dose (median 70 Gy; range 66-76 Gy) in the gross tumor area. Of the 65 cases achieving partial or complete response after CRT, 33 were treated further with SRR and 32 with adjuvant chemotherapy or observation. The locoregional control (LRC), overall survival (OS), and cancer-free survival (CFS) rates were compared between the two groups. RESULTS: The 3-year LRC, OS, and CFS rates were respectively 72.3, 75.1, and 72.6 % in the SRR group compared with 32.8, 47.7, and 44.3 % in the non-SRR group (p < 0.05). Multivariate analysis showed that SRR was the only statistically significant prognostic factor related to LRC, OS, and CFS. For those with SRR, pathologic downstaging was observed in 27 cases (81.8 %). Perioperative flap failure was observed in three cases (9.2 %) and neck wound necrosis in four cases (12.1 %). CONCLUSIONS: For T4b OSCC, incorporating SRR in the therapy is technically safe and has survival benefit, with a significant response after CRT applied by IMRT, with a radical dose in the gross tumor area.

Long-term late toxicities and quality of life for survivors of nasopharyngeal carcinoma treated with intensity-modulated radiotherapy versus non-intensity-modulated radiotherapy.

BACKGROUND: The purpose of this study was to investigate late toxicities and quality of life (QOL) of patients with nasopharyngeal carcinoma (NPC) with long-term survival after treatment by intensity-modulated radiotherapy (IMRT) versus non-IMRT. METHODS: An observational, cross-sectional study of QOL and late toxicities was conducted in 242 patients with NPC with survival of >5 years after treatment with IMRT (n = 100) or non-IMRT (n = 142) by using physician-assessed toxicities (Common Terminology Criteria for Adverse Events [CTCAE] version 4) and the patient-reported European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30-questions (EORTC QLQ-C30) and the Head and Neck 35-questions (EORTC QLQ-C30-H&N35) module. RESULTS: The IMRT group had both statistically (p < .05) and clinically (difference of predicted mean scores ≥10 points) better outcome in global QOL, cognitive functioning, social functioning, fatigue, and 11 scales of the head and neck module. Late toxicities, including neuropathy, hearing loss, dysphagia, xerostomia, and neck fibrosis were significantly less severe in the IMRT group. Multivariate analysis revealed that the radiotherapy (RT) technique was statistically significantly associated with late toxicities and QOL outcome after adjusting for other clinical and demographic variables. CONCLUSION: The use of the IMRT technique was associated with the improvement of physician-assessed late toxicities and patient-reported QOL in NPC survivors. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1026-E1032, 2016.