Reducing Target Volumes of Intensity Modulated Radiation Therapy After Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: Long-Term Results of a Prospective, Multicenter, Randomized Trial.

PURPOSE: The objective of this study was to estimate the long-term survival, late toxicity profile, and quality of life of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with combined induction chemotherapy (IC) and concurrent chemoradiotherapy from a clinical trial focused on reducing the target volume of intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS: This prospective, randomized clinical trial was conducted across 6 Chinese hospitals and included 212 patients with stage III-IVB NPC who were randomly allocated to a pre-IC or post-IC group. Eligible patients were treated with 2 cycles of IC + CCRT. All patients underwent radical IMRT. Gross tumor volumes of the nasopharynx were delineated according to pre-IC and post-IC tumor extent in the pre-IC and post-IC groups, respectively. RESULTS: After a median follow-up of 98.4 months, 32 of 97 (32.9%) and 33 of 115 (28.7%) patients experienced treatment failure or died in the pre-IC and post-IC groups, respectively. None of the patients developed grade 4 late toxicity. Late radiation-induced toxicity predominantly manifested as grade 1 to 2 subcutaneous fibrosis, hearing loss, tinnitus, and xerostomia, whereas grade 3 late toxicity included xerostomia and hearing loss. The 5-year estimated overall, progression-free, locoregional recurrence-free, and distant metastasis-free survival rates in the pre-IC and post-IC groups were 78.2% versus 83.3%, 72.0% versus 78.1%, 90.2% versus 93.5%, and 78.1% versus 82.1%, respectively. The pre-IC group had a significantly higher incidence of xerostomia and hearing damage than the post-IC group. In terms of quality of life, compared with the pre-IC group, the post-IC group showed significant improvement in cognitive function (P = .045) and symptoms including dry mouth (P = .004), sticky saliva (P = .047), and feeling ill (P = .041). CONCLUSIONS: After long-term follow-up, we confirmed that reducing the target volumes of IMRT after IC in locoregionally advanced NPC showed no inferiority in terms of the risk of locoregional relapse and potentially improved quality of life and alleviated late toxicity.

Investigation on the regulatory T cells signature and relevant Foxp3/STAT3 axis in esophageal cancer.

BACKGROUND: Regulatory T cells (Tregs) have an important role in accelerating the immunosuppression of tumor. Tregs regulation is a hopeful strategy to improve the dismal prognosis of Esophageal cancer (EC), while its mechanisms have not yet been fully clarified. METHODS: To characterize the role of Tregs in EC, we comprehensively explored its prognostic value, clinical pathology partnership, related biological functions and potential mechanisms at transcriptome level. Through the integrated analysis of GEO and TCGA datasets, we comprehensively evaluated the Tregs infiltration patterns in EC patients. The correlation between Tregs infiltration and genomic characteristics, as well as biological functions were analyzed by a variety of computational algorithms. RESULTS: We observed that Tregs were significantly upregulated in EC and involved in various immune processes. According to TCGA and GEO transcriptional classification schemes, Tregs specific genes were observed to be highly expressed in tumor samples, as well as were closely associated with poor prognosis and worse clinical outcomes. In addition, EC patients can be stratified into high-risk and low-risk immune subgroups according to Tregs/macrophages infiltration level, and the results showed significant differences in tumor development, biological processes and probe gene expression pattern. The multi-variate analysis revealed that the interaction between STAT3 and Foxp3 was a potential prognostic signature of Tregs in EC, especially the modulation effect of STAT3 on Foxp3 expression, which has not been well studied in EC. We also identified that STAT3 and Foxp3 expression presented a high accuracy in predicting Tregs infiltration level in EC patients (AUC: 0.817; 95% CI: 0.756-0.878). CONCLUSIONS: Our results revealed that Tregs have the potential to predict prognosis and tumor deterioration in EC patients. A comprehensive landscape of Tregs regulation mechanisms will help us interpret the immunosuppression of tumor microenvironment (TME) and novel strategies for EC immunotherapy.

Nutritional outcomes after radiotherapy target volume reduction for nasopharyngeal cancer: a Phase III trial.

Aim: This study aimed to assess the nutritional status of patients with locoregionally advanced nasopharyngeal cancer, for whom intensity-modulated radiotherapy (IMRT) was planned using their pre- or post-induction chemotherapy (IC) nasopharyngeal gross tumor volume. Materials & methods: 212 cases of stage III-IVb nasopharyngeal cancer were randomized into groups A (n = 97) and B (n = 115). IMRT was planned for groups A and B using pre-IC and post-IC images, respectively. Results: There was a significant decrease in the nutritional parameters of group B compared with those of group A during radiotherapy. Multivariate analysis indicated that the T stage and nasopharyngeal gross tumor volume IMRT-planning protocol were prognostic factors of poor nutritional status. Conclusion: Decreasing the IMRT target volume through IC can improve nutritional status.

The volume of 99m Tc sulfur colloid SPET-defined active bone marrow can predict grade 3 or higher acute hematologic toxicity in locally advanced cervical cancer patients who receive chemoradiotherapy.

BACKGROUND: The purpose of the current study was to evaluate whether radiation dose-volume metrics to technetium-99m (99m Tc) sulfur colloid single-photon emission tomography (SPET)-defined active bone marrow (ABM) subregions can more accurately predict acute hematologic toxicity in locally advanced cervical cancer patients who receive chemoradiotherapy than conventional dosimetric parameters. METHODS AND MATERIALS: Thirty-nine patients with stage IB2-III cervical cancer who underwent 99m Tc sulfur colloid SPET imaging before treatment with cisplatin-based chemoradiation between January 2017 and March 2018 were analyzed. The total bone marrow (TBM) volume was defined as the external contours of all bones within the vertebral bodies from L4 to the coccyx, the pelvic bones, and the proximal femoral heads. The ABM volume was defined by SPET as the subregion of TBM with a nuclide uptake value greater than or equal to the mean total body nuclide uptake value. Student's t test was used to test for statistical significance between TBM and ABM dose-volume metrics. Receiver operating characteristic (ROC) curves were generated to compare the predictors of grade 3 or higher (grade 3+) hematologic toxicity. RESULTS: The mean ABM-V40 (23.22% ± 7.65%) and ABM-V30 (45.28% ± 9.20%) were significantly lower than the mean TBM-V40 (33.06% ± 6.72%) and TBM-V30 (53.08% ± 7.77%), respectively (t = 5.78, P = .001) (t = 4.13, P = .001). The ABM volume (<387.5 cm3 , AUC = 0.928, P = .001), ABM-V30 (>46.5%, AUC = 0.875, P = .001), and ABM-V40 (>23.5%, AUC = 0.858, P = .001) can predict the occurrence of grade 3+ hematologic toxicity. Among patients with an ABM volume < 387.5 cm3 , 16/19 (84.2%) had grade 3+ hematologic toxicity compared to 3/20 (15%) with an ABM volume > 387.5 cm3 . CONCLUSIONS: The ABM volume (<387.5 cm3 ) may be a better predictor of hematologic toxicity than conventional dose-volume metrics, but this finding needs to be further evaluated.

Treatment outcomes after reduction of the target volume of intensity-modulated radiotherapy following induction chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: A prospective, multi-center, randomized clinical trial.

PURPOSE: To investigate whether reducing the target volume of intensity-modulated radiotherapy (IMRT) after induction chemotherapy (IC) improves the quality of life (QOL) in locoregionally advanced nasopharyngeal carcinoma (NPC) without decreasing the local control and survival rate. PATIENTS AND METHODS: A total number of 212 NPC patients staged as III-IVb were randomly assigned to group A (n=97) or group B (n=115) in this prospective clinical trial. All patients received IC followed by cisplatin concurrent with IMRT. IMRT was planned using the images of pre-IC in group A and post-IC in group B. RESULTS: The dose received by normal tissues in group B was lower than that of group A (P<0.05). The recovery of the dry mouth symptoms in group B was significantly improved than group B. The quality of life (QOL) scores in group B were higher than group A. With a median follow-up of 35months, the 1-year estimated overall survival (OS), progression-free survival (PFS), locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS) in group A versus group B were 97.9% vs 97.3%, 90.7% vs 92,2%, 99.0% vs 98.2%, 91.8% vs 94.8%. The 2-year OS, PFS, LRFFS, DMFS in group A versus group B were 93.7% vs 92.9%, 83.4% vs 84.3%, 96.8% vs 95.5%, 86.5% vs 89.5%. The 3-year OS, PFS, LRFFS, DMFS in group A versus group B were 82.3% vs 87%, 74.7% vs 83.4%, 91.8 vs 93.9%, 81.3% vs 88.6%, respectively. CONCLUSION: Reducing the IMRT target volume after IC did not reduce the local control and survival rate in locoregionally advanced NPC but the doses received by normal tissues were decreased, and the QOL scores were improved.

Expression of BRCA1 and ERCC1 as predictive clinical outcome after radiochemotherapy in patients with locoregionally moderate-advanced nasopharyngeal carcinoma.

In this study, we examined ERCC1 and BRCA1 expression and clinical outcome of 201 phase-III-IV nasopharyngeal carcinoma patients who were treated with cisplatin-based induced chemotherapy and concurrent radiochemotherapy. The chemotherapy response rate of BRCA1- and BRCA1+ patients was 73.6% and 55.8%, respectively. In addition, the chemotherapy response rate of ERCC1- and ERCC1+ patients was 76.9% and 56.6%, respectively. In patients' tissues, ERCC1 expression associated with BRCA1 expression. The chemotherapy response rate of BRCA1- and ERCC1- patients was (82.1%) and higher than that of other groups (range 52.4-73.1%). The radiochemotherapy response rate of BRCA1- and ERCC1- patients was higher than that BRCA1+ and ERCC1+ patients. BRCA1- and ERCC1- patients showed higher 3-year overall survival, failure-free survival, locoregional failure-free survival and distant failure-free survival compared to BRCA1+ or ERCC1+ patients. Moreover, the 3-year overall survival, failure-free survival and distant failure-free survival of the BRCA1- and ERCC1- group were higher than that of other groups. TNM stage, ERCC1 expression and the correlation between BRCA1 and ERCC1 expression seemed significant overall survival factors. In conclusion, in nasopharyngeal carcinoma patients, ERCC1 and BRCA1 may be a predictor of response to platinum-based chemotherapy and concurrent radiochemotherapy.

Nasopharyngeal carcinoma with headaches as the main symptom: A potential diagnostic pitfall.

BACKGROUND: The aim of this study was to investigate medical-related reasons for misdiagnosis of nasopharyngeal carcinoma. (NPC) patients presenting with headaches alone or accompanied by other symptoms. PATIENTS AND METHODS: Two-hundred and nineteen NPC cases describing headaches as one of the initial symptoms during primary treatment were selected for this prospective study. Medical records were carefully collected and all data were summarized for final analyses. RESULT: Distributions of NPC stage in the patients were: Stage II, 1.4%; stage III, 46.6%; stage IVA, 36.1%; stage IVB, 7.7%; and stage IVC, 8.2%. The ratio of men to women was 2.42:1 (155/64 cases). The total misdiagnosis rate was 43.4%. Patients that only complained of headaches had the highest misdiagnosis rate of 86.4% (19/22 cases). The lowest misdiagnosis rate of 10.9% (5/46 cases) was observed in patients with both headaches and epistaxis. The misdiagnosis rate in rural hospitals was more than two times that in provincial hospitals. Neurosurgery departments had a 100% misdiagnosis rate. CONCLUSION: Frequently, headaches are the only prominent symptom of NPC. Due to the various clinical manifestations, NPC patients encounter a high misdiagnosis rate, which leads to unsatisfactory treatment outcomes. Improved awareness of the various nonspecific symptoms of NPC by nonspecialist physicians will be a pivotal step in decreasing the misdiagnosis rate. Mini Abstract: The misdiagnosis rate of nasopharyngeal carcinoma (NPC) patients with headaches was 43.4%. Improved awareness of the various nonspecific symptoms of NPC is a pivotal step in decreasing the misdiagnosis rate.