Protective Effect of Pyxinol, One Active Ingredient of Lichenes on Cisplatin-Induced Nephrotoxicity via Ameliorating DNA Damage Response.

Background: Cisplatin is a valuable chemotherapeutic agent against malignant tumors. However, the clinical use of cisplatin is limited by its side effects such as renal injury. Pyxinol is an active constituent of Lichenes and its effects on cisplatin-induced nephrotoxicity is currently unknown. This study aims to examine the potential protective effects of pyxinol on cisplatin-induced renal injury and explore the underlying mechanisms. Methods: In vivo rat model of cisplatin-induced nephrotoxicity was induced by intraperitoneal (i.p) administration of cisplatin. The blood urea nitrogen and creatinine levels were measured and renal histological analysis was conducted to evaluate the renal function; The TUNEL staining, western blotting and real-time PCR assays were conducted to examine related molecular changes. Finally, the in vivo anti-tumor efficacy was examined in the xenograft tumor model using nude mice. Results: Pretreatment with pyxinol attenuated cisplatin-induced increase in blood urea nitrogen, creatinine and urinary protein excretion and the magnitude of injury in the renal tubules. Pyxinol ameliorated the activation of p53 via attenuating the DNA damage response, which then attenuated the tubular cell apoptosis. Finally, pyxinol could potentiate the in vivo anti-tumor efficacy of cisplatin against the xenograft tumor of cervical cancer cells in nude mice. Conclusions: Combining pyxinol with cisplatin could alleviate cisplatin-induced renal injury without decreasing its therapeutic efficacy, which might represent a beneficial adjunct therapy for cisplatin-based chemotherapeutic regimens in the clinic.

Tirbanibulin Attenuates Pulmonary Fibrosis by Modulating Src/STAT3 Signaling.

Tirbanibulin (KX-01) is the first clinical Src inhibitor of the novel peptidomimetic class that targets the peptide substrate site of Src providing more specificity toward the Src kinase. This study assessed the impact of KX-01 on cobalt chloride (CoCl2)-treated L929 cells and bleomycin (BLM)-induced pulmonary fibrosis in rats to evaluate the efficacy of this compound in vitro and in vivo, respectively. In CoCl2-treated L929 cells, KX-01 significantly reduced the expression of smooth muscle actin (α-SMA), collagen I, collagen III, hypoxia inducing factor (HIF-1α), signal transducers and transcriptional activators (p-STAT3), and p-Src. In BLM-induced pulmonary fibrosis rats, KX-01 reduced pathological scores, collagen deposition, α-SMA, collagen I, collagen III, p-Src, HIF-1α, and p-STAT3. Overall, these findings revealed that KX-01 can alleviate experimental pulmonary fibrosis via suppressing the p-SRC/p-STAT3 signaling pathways.

Association of High Expression of Mitochondrial Fission Regulator 2 with Poor Survival of Patients with Esophageal Squamous Cell Carcinoma.

Mitochondrial fission regulator 2 (MTFR2) is associated with mitochondrial fission, while few studies have assessed the associations between MTFR2 expression and clinical characteristics or prognosis of esophageal squamous cell carcinoma (ESCC). In this study, we compared the expression of MTFR2 in 6 ESCC tumors and relative normal tissues by immunohistochemistry (IHC). To assess the effect of MTFR2 expression on clinicopathologic characteristics and survival, 115 paraffin embedded ESCC tissue samples were assessed by IHC staining. Furthermore, the association between clinicopathological properties and MTFR2 expression in patients with ESCC was examined. The survival analysis was performed using the Cox regression models. We found that MTFR2 expression was significantly increased in ESCC tumors compared with normal esophageal epithelial cells. IHC analysis of 115 paraffin embedded ESCC tumor specimens of the patients showed that the expression of MTFR2 was significantly associated with clinical stage (P < 0.001), tumor classification (P < 0.001), histological grade (P < 0.001), and other clinicopathological characteristics. Both univariate and multivariate analyses showed that MTFR2 expression was inversely correlated with the survival of ESCC patients. In conclusion, the expression of MTFR2 is significantly associated with clinicopathologic characteristics and prognosis of ESCC. Thus, MTFR2 expression could serve as a potentially important prognostic biomarker and clinical target for patients with ESCC.

Comparison study of different indoleamine-2,3 dioxygenase inhibitors from the perspective of pharmacodynamic effects.

INTRODUCTION: Indoleamine 2,3-dioxygenase (IDO) was a potential tumor immunotherapy target. IDO inhibitors showed inconsistent results in clinical trials, but no preclinical comparative study was reported. The purpose of this study was to evaluate the differences of representative IDO inhibitors (PCC0208009, INCB024360, NLG919) from the pharmacological perspective. METHODS: In vitro experiments included: inhibition effects on IDO activity in cell and enzyme-based assay, effects on IDO expression in HeLa cells, and enhancement of proliferation and activation of peripheral blood mononuclear cell (PBMC). In vivo experiments included: pharmacokinetics and tumor distribution in CT26-bearing mice, effects on Kyn/Trp and anti-tumor effect and immunological mechanism in CT26 and B16F10 tumor-bearing mice. RESULTS: Compared with INCB024360 and NLG919, PCC0208009 effectively inhibited IDO activity at lower dose 2 nM and longer duration more than 72 h, had higher enhancements on PBMC proliferation and activation, and could inhibit the IDO expression in Hela cells. The pharmacokinetics characteristics of three IDO inhibitors were similar in CT26-bearing mice. In CT26 and B16F10 tumor-bearing mice, PCC0208009 and INCB024360 had similar effects in Kyn/Trp reduction, and more potent than NLG919; three IDO inhibitors had similar effects in tumor suppression, changes of the percentages of CD3+CD8+ and CD3+CD4+ T cells, and activation of tumor infiltrating lymphocytes, while PCC0208009 had a better tendency than INCB024360 and NLG919. CONCLUSION: PCC0208009, INCB024360, and NLG919 were all effective IDO inhibitors, but the comprehensive pharmacological activity of PCC0208009 was better than INCB024360 and NLG919, which was basically consistent with the results or progresses of clinical trials.

Highly expressed microRNA-124 inhibits migration and promotes apoptosis of esophageal cancer cells by degrading PDCD6.

PURPOSE: To investigate whether microRNA (miR)-124 could affect the proliferation, migration and apoptosis of esophageal cancer cells and participate in the occurrence of esophageal cancer through regulating PDCD6 expression. METHODS: The expression of miR-124 in cancer tissues and adjacent tissues of esophageal cancer patients were detected by quantitative real time-polymerase chain reaction (qRT-PCR). Esophageal cancer cells TE-1 and SKYE30 were cultured. The effects of miR-124 on tumor size and metastasis were analyzed. The functions of miR-124 in cell proliferation, migration and apoptosis were detected by cell counting kit-8 (CCK-8), transwell and flow cytometry, respectively. Rescue experiments were performed to assess whether miR-124 could regulate the proliferation, migration and apoptosis of esophageal cancer cells by inhibiting PDCD6 expression. RESULTS: The expression of miR-124 in cancer tissues of esophageal cancer patients were lower than that of the control group. In addition, its expression in patients with stage III-IV esophageal cancer was remarkably lower than that in patients with stage I-II. Based on the level of miR-124, we divided the patients into high and low expression group, and found significant differences in tumor size, tumor metastasis and lymph node metastasis between the two groups. Also, overexpression of miR-124 reduced the proliferation and migration of TE-1 and SKYSE30 cells and increased the apoptosis, and vice versa. Luciferase reporting assay results confirmed that PDCD6 was one of the target genes of miR-124. A further mechanism study demonstrated that overexpression of PDCD6 in TE-1 and SKYSE30 cells could partially reverse the effect of miR-124 on cell apoptosis. CONCLUSIONS: The low expression of miR-124 can promote the proliferation as well as migration of esophageal cancer cells and inhibit cell apoptosis. The mechanism may be that miR-124 can regulate the expression of PDCD6.

Involved-field irradiation for elderly bladder cancer patients.

OBJECTIVES: Considering that adjuvant radiation therapy is one of the most common treatment methods and the influence of the clinical target volume to treatment-related toxicity, this study aimed to observe the differences in treatment failures about involved-field irradiation (IFI) without lymph node areas versus elective nodal irradiation (ENI) with lymph node areas in elderly patients with bladder cancer. MATERIAL AND METHODS: Ninety-two elderly bladder cancer patients were analyzed from January 2010 to December 2014 in one institution. The primary inclusion criteria were previous after transurethral resection of bladder tumor or partial cystectomy with adjuvant radiotherapy, and the radiation techniques included IFI or ENI. The study required that elderly patients did not received radiotherapy before treatment. We observed treatment-related toxicity and tumor failures, evaluated local progression-free survival, estimated the 3-year overall survival, and analyzed prognostic factors, after IFI and ENI in elderly bladder cancer patients. The outcomes were determined by chi square tests, Kaplan-Meier method and Cox multiple factors analysis. RESULTS: In the experimental group, 42 patients (45.65%) received IFI, and a matched group of 50 patients (54.35%) received ENI. With a median follow-up of 31.47 months (range 4.00-86.00 months), the Kaplan-Meier analysis with a log-rank test demonstrated a statistical difference between the IFI group and the ENI group in acute toxicity (45.23% vs 72.00%, P = 0.008). However, there were no statistical differences in the 3-year overall survival rate (45.20% vs 48.00%, P = 0.860) or the duration of local progression-free survival (24.98 vs 34.30, P =0.729). CONCLUSIONS: IFI is feasible in elderly bladder cancer patients, as shown by a decrease in acute toxicity and no increase in local failure. We need a large number of clinical trials and data to further confirm these results.

PCC0208009 enhances the anti-tumor effects of temozolomide through direct inhibition and transcriptional regulation of indoleamine 2,3-dioxygenase in glioma models.

Indoleamine 2,3-dioxygenase (IDO), which is highly expressed in human glioblastoma and involved in tumor immune escape and resistance to chemotherapy, is clinically correlated with tumor progression and poor clinical outcomes, and is a promising therapeutic target for glioblastoma. IDO inhibitors are marginally efficacious as single-agents; therefore, combination with other therapies holds promise for cancer therapy. The aim of this study was to investigate the anti-tumor effects and mechanisms of the IDO inhibitor PCC0208009 in combination with temozolomide. The effects of PCC0208009 on IDO activity inhibition, and mRNA and protein expression in HeLa cells were observed. In the mouse glioma GL261 heterotopic model, the effects of PCC0208009 on l-kynurenine/tryptophan (Kyn/Trp), tumor growth, flow cytometry for T cells within tumors, and immunohistochemistry for IDO and Ki67 were examined. In the rat glioma C6 orthotopic model, animal survival, flow cytometry for T cells within tumors, and immunohistochemistry for proliferating cell nuclear antigen (PCNA) and IDO were examined. The results show that PCC0208009 is a highly effective IDO inhibitor, not only directly inhibiting IDO activity but also participating in the gene regulation of IDO expression at the transcription and translation levels. PCC0208009 significantly enhanced the anti-tumor effects of temozolomide in GL261 and C6 models, by increasing the percentages of CD3+, CD4+, and CD8+ T cells within tumors and suppressing tumor proliferation. These findings indicate that PCC0208009 can potentiate the anti-tumor efficacy of temozolomide and suggest that combination of IDO inhibitor-based immunotherapy with chemotherapy is a potential strategy for brain tumor treatment.

Efficacy and safety of late-course hypofractionated radiation therapy for muscle-invasive bladder carcinoma after bladder-conserving surgery.

AIM: To evaluate the efficacy and safety of late-course hypofractionated radiation treatment of muscle-invasive bladder carcinoma after bladder-conserving surgery. METHODS: Seventy-six patients with transitional cell bladder carcinoma, stage II (T2-4N0M0), after transurethral resection, were enrolled. Pirarubicin was given at 30 mg/m2 and 100 mL physiological saline once weekly (QW) for 12 weeks through and after intravesical instillation postoperatively. Radiation schedule delivered 46 Gy in 20 fractions for planning target volume, with an additional 20 Gy in five fractions for gross tumor volume as late-course radiation. Chemotherapy was stopped if Radiation Therapy Oncology Group grade 3 or higher bladder or bowel toxicity occurred. The primary end points were acute toxicity, local control and patients' survival. RESULTS: One-, three- and five-year overall survival rates were 98, 78 and 69.5%, respectively. Mean survival time was 58.4 months (95% CI: 52.6, 64.2). In addition, 1-, 3- and 5-year local control rates were 100, 80.5 and 76.1%, respectively. Mean local control time was 60.7 months (95% CI: 55.1, 66.3). The cumulative incidence of local/regional failure and distant failure was 28.9%. The rate of single local/regional failure was 13.2%, but distant failure rate was 21.1%. CONCLUSIONS: Concurrent pirarubicin-based late-course hypofractionated radiation therapy showed desirable local control rate and acceptable toxicity. It could be used after bladder-conserving surgery to allow patients to preserve their bladder.

Individualized Radiation Dose Escalation Based on the Decrease in Tumor FDG Uptake and Normal Tissue Constraints Improve Survival in Patients With Esophageal Carcinoma.

BACKGROUND: To determine whether individualized radiation dose escalation after planned chemoradiation based on the decrease in tumor and normal tissue constraints can improve survival in patients with esophageal carcinoma. METHODS: From August 2005 to December 2010, 112 patients with squamous esophageal carcinoma were treated with radical concurrent chemoradiation. Patients received positron emission tomography-computer tomography scan twice, before radiation and after radiation dose of 50.4 Gy. All patients were noncomplete metabolic response groups according to the Response Evaluation Criteria in solid tumors. Only 52 patients with noncomplete metabolic response received individualized dose escalation based on tumor and normal tissue constraints. Survival and treatment failure were observed and analyzed using SPSS (13.0). RESULTS: The rate of complete metabolic response for patients with noncomplete metabolic response after dose escalation reached 17.3% (9 of 52). The 2-year overall survival rates for patients with noncomplete metabolic response in the conventional and dose-escalation groups were 20.5% and 42.8%, respectively( P = .001). The 2-year local control rates for patients were 35.7% and 76.2%, respectively ( P = .002). When patients were classified into partial metabolic response and no metabolic response, 2-year overall survival rates for patients with partial metabolic response were significantly different in conventional and dose-escalation groups (33.8% vs 78.4%; P = .000). The 2-year overall survival rates for patients with no metabolic response in two groups (8.6% vs 15.1%) did not significantly differ ( P = .917). CONCLUSION: Individualized radiation dose escalation has the potential to improve survival in patients with esophageal carcinoma according to increased rate of complete metabolic response. However, further trials are needed to confirm this and to identify patients who may benefit from dose escalation.

A genetic variant in CHRNB3-CHRNA6 increases risk of esophageal squamous cell carcinoma in Chinese populations.

Nicotinic acetylcholine receptors are important regulators of smoking behavior and tobacco carcinogenesis. We studied the association of the CHRNB3-A6 variant rs13280604 in relation to esophageal squamous cell carcinoma (ESCC) in Chinese populations. Two independent case-control studies were conducted. The first case-control study, consisted of 866 ESCC patients and 1621 healthy controls from Northern China, and the second case-control study consisted of 853 ESCC patients and 860 unrelated controls from Southern China. A logistic regression model was used to evaluate the associations of rs13280604 with cancer risk. We found that Rs13280604 GG/AG genotypes were significantly associated with increased risk for ESCC in both case-control studies from Northern [odds ratio (OR), 1.42, 95% confidence interval (CI), 1.19-1.70, P = 1.1×10(-4)], Southern China (OR, 1.56, 95% CI, 1.26-1.93, P = 5.2×10(-5)), and the combined population of both studies (OR, 1.44, 95% CI, 1.26-1.65, P = 8.7×10(-8)), respectively. Our results suggest that this CHRNB3-A6 variant confers susceptibility to ESCC risk. However, future larger studies are needed to validate our finding.

Preparation, pharmacokinetics, biodistribution, antitumor efficacy and safety of Lx2-32c-containing liposome.

Lx2-32c is a novel taxane that has been demonstrated to have robust antitumor activity against different types of tumors including several paclitaxel-resistant neoplasms. Since the delivery vehicles for taxane, which include cremophor EL, are all associated with severe toxic effects, liposome-based Lx2-32c has been developed. In the present study, the pharmacokinetics, biodistribution, antitumor efficacy and safety characteristics of liposome-based Lx2-32c were explored and compared with those of cremophor-based Lx2-32c. The results showed that liposome-based Lx2-32c displayed similar antitumor effects to cremophor-based Lx2-32c, but with significantly lower bone marrow toxicity and cardiotoxicity, especially with regard to the low ratio of hypersensitivity reaction. In comparing these two delivery modalities, targeting was superior using the Lx2-32c liposome formulation; it achieved significantly higher uptake in tumor than in bone marrow and heart. Our data thus suggested that the Lx2-32c liposome was a novel alternative formulation with comparable antitumor efficacy and a superior safety profiles to cremophor-based Lx2-32c, which might be related to the improved pharmacokinetic and biodistribution characteristics. In conclusion, the Lx2-32c liposome could be a promising alternative formulation for further development.

Association of GSTP1 Ile105Val polymorphism with risk of esophageal cancer: a meta-analysis of 21 case-control studies.

BACKGROUND: The association of glutathione s-transferase P1 (GSTP1) Ile105Val polymorphism with risk of esophageal cancer (EC) has been evaluated in many studies; however, the results from these studies are controversial. Thus, further analysis on association between GSTP1 Ile105Val polymorphism and risk of EC is needed among a larger study population. METHOD: We searched the relevant electronic databases and performed a meta-analysis based on 21 published case-control studies. The Chi-square based I(2)-statistic test was performed to evaluate possible heterogeneity across the studies. Additionally, random-effects models were used to calculate crude pooled odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Overall, this meta-analysis did support a significant association between GSTP1 Ile105Val polymorphism and risk of EC (pooled OR 1.25, 95% CI, 1.05-1.49). Furthermore, the stratified analysis showed that, in comparison to GSTP1 Ile105Val Ile/Ile genotype, the Val/Val genotype was significantly associated with risk of esophageal squamous cell carcinoma (ESCC) (pooled OR 1.45, 95% CI, 1.07-1.96), particularly in the Caucasian population (pooled OR 1.41, 95% CI, 1.01-1.95). Such a significant association was not observed for esophageal adenocarcinoma (EAC) patients or subjects of an Asian ethnicity. Moreover, substantial evidence of heterogeneity among the studies was not observed. CONCLUSION: The results from this meta-analysis support a significant association between the GSTP1 Ile105Val polymorphism and risk of EC, particularly in a subgroup with ESCC and in the Caucasian population. Further studies with larger sample sizes are needed to validate our findings.

Prognostic significance of 18F-fluorodeoxyglucose positron emission tomography (PET)-based parameters in neoadjuvant chemoradiation treatment of esophageal carcinoma.

AIMS AND BACKGROUND: The purpose of the research was to study the prognostic value of tumor 18F-FDG PET-based parameters in neoadjuvant chemoradiation for patients with squamous esophageal carcinoma. METHODS: Sixty patients received chemoradiation therapy followed by esophagectomy and two 18FDG-PET examinations at pre- and post-radiation therapy. PET-based metabolic-response parameters were calculated based on histopathologic response. Linear regression correlation and Cox proportional hazards models were used to determine prognostic value of all PET-based parameters with reference to overall survival. RESULTS: Sensitivity (88.2%) and specificity (86.5%) of a percentage decrease of SUVmax were better than other PET- based parameters for prediction of histopathologic response. Only percentage decrease of SUVmax and tumor length correlated with overall survival time (linear regression coefficient ß: 0.704 and 0.684, P<0.05). The Cox proportional hazards model indicated higher hazard ratio (HR=0.897, P=0.002) with decrease of SUVmax compared with decrease of tumor size (HR=0.813, P=0.009). CONCLUSION: Decrease of SUVmax and tumor size are significant prognostic factors in chemoradiation of esophageal carcinoma.

Moderately hypofractionated conformal radiation treatment of thoracic esophageal carcinoma.

AIMS: To prospectively assess the efficacy and safety of moderately hypofractionated conformal radiotherapy in patients with thoracic esophageal cancer. METHODS AND MATERIALS: From Sept. 2002 to Oct. 2005, 150 eligible patients with T2-4N0-1M0 stage thoracic esophageal squamous cell cancers were enrolled to receive either conventional fractionated radiation (CFR) or moderately hypofractionated radiation (MHR) with a three- dimensional conformal radiation technique. Of the total, 74 received moderately hypofractionated radiation with total dose of 54-60 Gy/18-20 fractions for 3.5-4 weeks in the MHR arm, and 76 received conventional radiation with total dose of 60 Gy/30 fractions for 6 weeks in the CFR arm. Concurrent chemotherapy comprised of paclitaxel and cisplatin. Safety was evaluated, and local control and overall survival rates were calculated. RESULTS: Statistically significant differences between the CFR versus MHR arms were observed in local/regional failure rate (47.3% v 27.0%, P=0.034) and the percentage of patients with persistent local disease (26.3% v 10.8%, P=0.012). But 3 and 5-year overall survival rates (43.2%, 38.8% v 38.2%, 28.0%, respectively) were not different between the two arms (P=0.268). There were no significant differences in the incidences of grade 3 or higher acute toxicities (66.3% v 50.0%) and late complications rates (27.0% v 22.4%) between the MHR and CFR arms. CONCLUSIONS: Moderately hypofractionated, three-dimensional radiation treatment could improve the local control rate of esophageal cancer and potentially increase patient survival.

Clinicopathologic characteristics and prognostic factors in patients with operable HER-2 overexpressing breast cancer.

OBJECTIVE: To study the relationship between clinical pathologic characteristics, treatment modalities and prognostic factors in HER-2 (Human Epidermal growth factor Receptor-2) overexpressed breast carcinoma. MATERIALS AND METHODS: Major clinico-pathological factors including therapeutic modalities and survival status of 371 breast cancer patients with HER2 over-expression, teated at Yantai Yuhuangding Hospital from March of 2002 to December of 2010 were retrospectively studied, with special attention focused on survival-related factors. RESULTS: The median age of the total 371 patients in this study was 48 years at time of diagnosis, among which, the leading pathological type was infiltrating ductal carcinoma (92.5%); 62.8% presented with a primary tomor larger than 2 cm in diameter at diagnosis, 51.0% had axillary lymph node (ALN) metastases; ER (Estrogen receptor) /PR (Progesterone receptor) double negative occured in 52.8% of cases, and PCNA (proliferation cell nuclear antigen) (+ + +) was found in 55.1%. HER-2 overexpressed patients were usually in advanced stage when the diagnosis was made (72.8% at stages IIA~IIIC). The prognosis and survival were assessed in 259 patients with complete follow-up data. 5-year DFS (disease-free survival) and OS (overall survival) rate was 68.0% and 78.0% respectively. Univariate analysis revealed that age, tumor size, ALN metastases, LVSI (lymph-vascular space involvement), PCNA status, hormonal therapy, chemotherapy cycles, and HER-2 overexpression, correlated closely with the prognosis. ALN metastases, LVSI, PCNA status and chemotherapy cycles were independent predictors of survival. CONCLUSIONS: HER-2 overexpressed breast cancer has special clinical and pathological characteristics, with advanced clinical stages and high rate of ER/PR double negative. Lymph node metastases, LVSI, PCNA and chemotherapy cycles are independent predictors of prognosis.

Linear correlation between patient survival and decreased percentage of tumor [(18)F]fluorodeoxyglucose uptake for late-course accelerated hyperfractionated radiotherapy for esophageal cancer.

PURPOSE: The aims of this trial were to study whether a decreased percentage of tumor fluorodeoxyglucose (FDG) uptake (%DeltaSUVmax) correlated with overall survival and local control times for patients with esophageal cancer and which patients would benefit from a late-course accelerated hyperfractionated (LCHF) radiation scheme. METHODS AND MATERIALS: A total of 50 eligible patients with squamous esophageal cancer received positron-emission tomography examinations three times and were treated with the LCHF radiation scheme, with a dose of 68.4 Gy/41 fractions in 6.5 weeks. A %DeltaSUVmax value was calculated, and patients were stratified as highly radiosensitive (HR), moderately radiosensitive (MR), and low radiosensitivity (LR) according to %DeltaSUVmax values in the conventional fraction (CF) scheme. Then, a linear correlation was calculated between patients' survival time and %DeltaSUVmax. Local control and overall survival rates were compared after stratification. RESULTS: In the MR subgroup, there was no linear correlation between %DeltaSUVmax and the CF and LCHF schemes (correlation coefficient, R < 0.4; p > 0.05). In the other subgroups (HR and LR), %DeltaSUVmax values between the CF and LCHF schemes were correlated. Also, in the HR and LR subgroups, %DeltaSUVmax after radiation correlated with overall survival or local control rates (correlation coefficient, R ＞0.5, and p < 0.05). Three-year local control rates in the HR, MR, and LR subgroups were 100%, 81.5%, and 0%, respectively (p < 0.001). Also, 3-year overall survival rates were 92.4%, 58.8%, and 0% for HR, MR, and LR subgroups, respectively (p < 0.001). CONCLUSIONS: Postradiation %DeltaSUVmax was positively correlated with survival time for patients' with esophageal cancer. Patients who benefited from LCHF schedules were those with a decrease of 30% to 60% in tumor FDG uptake after the completion of CF radiation.

Feasibility of involved-field conformal radiotherapy for cervical and upper-thoracic esophageal cancer.

BACKGROUND: The aim of this study was to investigate the feasibility of involved-field irradiation (IFI) for the treatment of cervical and upper-thoracic esophageal cancer with concurrent chemoradiation. PATIENTS AND METHODS: 102 eligible patients with cervical or upper-thoracic esophageal cancer were treated with concurrent chemoradiation and randomized to either an IFI or elective nodal irradiation (ENI) group. RESULTS: Adverse events included infection (27.4 vs. 64.7%) and nausea (25.4 vs. 54.9%), with a statistically significant difference between the IFI and the ENI group (p = 0.008 and 0.028, respectively). No difference was seen for late radiation reaction. The cumulative incidence of local/regional failure (13.7 vs. 17.6%) and regional lymph failure (7.8 vs. 9.8%) showed no statistically significant difference between the IFI versus the ENI group (p = 0.837 and 0.837, respectively). A nodal out-field relapse rate of only 2% was seen in the IFI group. 3-year survival rates for the ENI and IFI group were 41.3 and 32.0%, respectively (p = 0.58), and 3-year local control rates were 85.7 and 80.1%, respectively (p = 0.34). CONCLUSION: IFI was acceptable for cervical and upper-thoracic esophageal cancer with a decrease in acute toxicities and no increase in lymph node failure.

Three-dimensional conformal radiation therapy for esophageal squamous cell carcinoma: is elective nodal irradiation necessary?

PURPOSE: To evaluate the local control, survival, and toxicity associated with three-dimensional conformal radiotherapy (3D-CRT) for squamous cell carcinoma (SCC) of the esophagus, to determine the appropriate target volumes, and to determine whether elective nodal irradiation is necessary in these patients. METHODS AND MATERIALS: A prospective study of 3D-CRT was undertaken in patients with esophageal SCC without distant metastases. Patients received 68.4 Gy in 41 fractions over 44 days using late-course accelerated hyperfractionated 3D-CRT. Only the primary tumor and positive lymph nodes were irradiated. Isolated out-of-field regional nodal recurrence was defined as a recurrence in an initially uninvolved regional lymph node. RESULTS: All 53 patients who made up the study population tolerated the irradiation well. No acute or late Grade 4 or 5 toxicity was observed. The median survival time was 30 months (95% confidence interval, 17.7-41.8). The overall survival rate at 1, 2, and 3 years was 77%, 56%, and 41%, respectively. The local control rate at 1, 2, and 3 years was 83%, 74%, and 62%, respectively. Thirty-nine of the 53 patients (74%) showed treatment failure. Seventeen of the 39 (44%) developed an in-field recurrence, 18 (46%) distant metastasis with or without regional failure, and 3 (8%) an isolated out-of-field nodal recurrence only. One patient died of disease in an unknown location. CONCLUSIONS: In patients treated with 3D-CRT for esophageal SCC, the omission of elective nodal irradiation was not associated with a significant amount of failure in lymph node regions not included in the planning target volume. Local failure and distant metastases remained the predominant problems.