Propensity score matching analysis of a phase II study on simultaneous modulated accelerated radiation therapy using helical tomotherapy for nasopharyngeal carcinomas.

BACKGROUND: Using propensity score matching method (PSM) to evaluate the feasibility and clinical outcomes of simultaneous modulated accelerated radiation therapy (SMART) using helical tomotherapy (HT) in patients with nasopharyngeal carcinoma (NPC). METHODS: Between August 2007 and January 2016, 381 newly diagnosed NPC patients using HT were enrolled in pre-PSM cohort, including 161 cases in a prospective phase II study (P67.5 study, with a prescription dose of 67.5Gy in 30 fractions to the primary tumour and positive lymph nodes) and 220 cases in a retrospective study (P70 study, with a prescription dose of 70Gy in 33 fractions to the primary tumour and positive lymph nodes). Acute and late toxicities were assessed according to the established RTOG/EORTC criteria and Common Terminology Criteria for Adverse Events (CTCAE) V 3.0. Survival rate were assessed with Kaplan-Meier method, log-rank test and Cox regression. RESULTS: After matching, 148 sub-pairs of 296 patients were generated in post-PSM cohort. The incidence of grade 3-4 leukopenia, thrombocytopenia and anemia in the P67.5 group was significantly higher than in the P70 study, but no significant different was found in other acute toxicities or late toxicities between the two groups. The median follow-up was 33 months in the P67.5 and P70 group, ranging 12-54 months and 6-58 months, respectively. No significant differences in 3-year local-regional recurrence free survival (LRRFS), distant metastasis-free survival (DMFS), disease free survival (DFS) and overall survival (OS) were observed between the 2 groups. Univariate analysis showed that age, T stage, clinical stage were the main factors effecting survival. Cox proportional hazards model showed that 67.5Gy/30F pattern seemed superior in 3-year OS (HR = 0.476, 95% CI: 0.236-0.957). CONCLUSIONS: Through increasing fraction dose and shortening treatment time, the P67.5 study achieved excellent short-term outcomes and potential clinical benefits, with acceptable acute and late toxicities. TRIAL REGISTRATION: The trial was registered at Chinese Clinical Trial Registry on 5 July 2014 with a registration code of ChiCTRONC-14,004,895.

Treatment of nasopharyngeal carcinoma using simultaneous modulated accelerated radiation therapy via helical tomotherapy: a phase II study.

BACKGROUND: The aim of the study was to evaluate short-term safety and efficacy of simultaneous modulated accelerated radiation therapy (SMART) delivered via helical tomotherapy in patients with nasopharyngeal carcinoma (NPC). METHODS: Between August 2011 and September 2013, 132 newly diagnosed NPC patients were enrolled for a prospective phase II study. The prescription doses delivered to the gross tumor volume (pGTVnx) and positive lymph nodes (pGTVnd), the high risk planning target volume (PTV1), and the low risk planning target volume (PTV2), were 67.5 Gy (2.25 Gy/F), 60 Gy (2.0 Gy/F), and 54 Gy (1.8 Gy/F), in 30 fractions, respectively. Acute toxicities were evaluated according to the established RTOG/EORTC criteria. This group of patients was compared with the 190 patients in the retrospective P70 study, who were treated between September 2004 and August 2009 with helical tomotherapy, with a dose of 70-74 Gy/33F/6.5W delivered to pGTVnx and pGTVnd. RESULTS: The median follow-up was 23.7 (12-38) months. Acute radiation related side-effects were mainly problems graded as 1 or 2. Only a small number of patients suffered from grade 4 leucopenia (4.5%) or thrombocytopenia (2.3%). The local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), local-nodal relapse-free survival (LNRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 96.7%, 95.5%, 92.2%, 92.7% and 93.2%, at 2 years, respectively, with no significant difference compared with the P70 study. CONCLUSIONS: Smart delivered via the helical tomotherapy technique appears to be associated with an acceptable acute toxicity profile and favorable short-term outcomes for patients with NPC. Long-term toxicities and patient outcomes are under investigation.

[miR-29b Reduces Cisplatin Resistance of Gastric Cancer Cell by Targeting PI3K/Akt Pathway].

OBJECTIVE: To investigate the regulatory effect of miR-29b on gastric cells' resistance to cisplatin. METHODS: The expression of miR-29b in gastric cancer cell line treated with cisplatin concentration gradient was detected using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blotting. CCK8 was used to measure the cell viability after cisplatin treatment in condition of miR-29b knock-down and overexpression. RESULTS: The expression of miR-29b was significantly upregualted by cisplatin treatment,while its target gene AKT2 was downregulated. The up-regulation of miR-29b enhanced the sensitivity of gastric cancer cells to cisplatin,while the knock-down of miR-29b enhanced the cisplatin resistance. Rescue experiments demonstrated that the miR-29b might regulate cisplatin resistance of gastric cancer cell by targeting PI3K/Akt pathway. The expressions of the other two members of miR-29 family, miR-29a/c, were promoted by cisplatin treatment,but they had no significant effect on gastric cancer cell's resistance to cisplatin. CONCLUSION: miR-29b can enhance the sensitivity of S gastric cancer cell by directly targeting PI3K/Akt pathway.

[Efficacy of Liangxue Jiedu Huoxue Decoction in prevention of radiation pneumonitis: a randomized controlled trial].

BACKGROUND: Radiation pneumonitis is one of the most common complications during radiotherapy of thoracic tumors. It impacts the quality of life of the patients and has life-threatening danger. However, there is a lack of drugs for prevention and treatment of this disease. OBJECTIVE: To evaluate the efficacy of Liangxue Jiedu Huoxue Decoction, a compound traditional Chinese herbal medicine, in prevention of radiation pneumonitis. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A prospective randomized clinical study was conducted. A total of 100 patients diagnosed with lung cancer from Department of Radiotherapy, Chinese PLA General Hospital, who were planning to receive radiotherapy, were randomly assigned into treatment group and control group, with 50 patients in each group. In the treatment group 3 cases were lost to follow-up and one case was excluded, while in the control group 6 cases were lost to follow-up and 2 cases were excluded. Patients in the treatment group were treated with Liangxue Jiedu Huoxue Decoction in addition to radiotherapy, while patients in the control group were treated with radiotherapy alone. MAIN OUTCOME MEASURES: The incidence rates of radiation pneumonitis in the two groups were calculated. Acute radiation injury scoring criteria by Radiation Therapy Oncology Group (RTOG), clinical-radiographic-physiologic (CRP) score system, and Karnofsky Performance Status Scale (KPS) were used to evaluate the status of the patients. RESULTS: The incidence rate of radiation pneumonitis was lower in the treatment group than in the control group (13.04% versus 33.33%, P<0.05). According to the RTOG scale, the extent of lung injury was improved in the treatment group as compared with that in the control group (P<0.05). The CRP score in the treatment group was significantly lower than that in the control group (P<0.05). The KPS score in the treatment group was significantly higher than that in the control group (P<0.05). CONCLUSION: Liangxue Jiedu Huoxue Decoction can decrease the incidence rate of radiation pneumonitis, reduce the extent of the lung injury, alleviate the symptoms of radiation pneumonitis, and improve life quality of the patients.

Actual anatomical and dosimetric changes of parotid glands in nasopharyngeal carcinoma patients during intensity modulated radiation therapy.

The goal of this study was to evaluate the actual anatomical and dosimetric changes of parotid glands in nasopharyngeal carcinoma patients during intensity modulated radiation therapy. With helical tomotherapy, its planning system, and adaptive software, weekly anatomical and dosimetric changes of parotid glands in 35 NPC patients were evaluated. Interweekly parotid volume varied significantly (P < 0.03). The rate of volume change reached the highest level at the 16th fraction. The average V 1 increased by 32.2 (left) and 28.6 (right), and the average D 50 increased by 33.9 (left) and 24.93 (right), respectively. Repeat data comparison indicated that the V 1 and D 50 varied significantly among different fractions (both with P = 0.000). The variation of parotid volume was inversely correlated with that of the V 1 and D 50 (both with P = 0.000). In conclusion, parotid volume and actual dose vary significantly in NPC patients during IMRT. Replanning at the end of the fourth week of IMRT may have clinical benefits.

Replanning Criteria and Timing Definition for Parotid Protection-Based Adaptive Radiation Therapy in Nasopharyngeal Carcinoma.

The goal of this study was to evaluate real-time volumetric and dosimetric changes of the parotid gland so as to determine replanning criteria and timing for parotid protection-based adaptive radiation therapy in nasopharyngeal carcinoma. Fifty NPC patients were treated with helical tomotherapy; volumetric and dosimetric (D mean, V 1, and D 50) changes of the parotid gland at the 1st, 6th, 11th, 16th, 21st, 26th, 31st, and 33rd fractions were evaluated. The clinical parameters affecting these changes were studied by analyses of variance methods for repeated measures. Factors influencing the actual parotid dose were analyzed by a multivariate logistic regression model. The cut-off values predicting parotid overdose were developed from receiver operating characteristic curves and judged by combining them with a diagnostic test consistency check. The median absolute value and percentage of parotid volume reduction were 19.51 cm(3) and 35%, respectively. The interweekly parotid volume varied significantly (p < 0.05). The parotid D mean, V 1, and D 50 increased by 22.13%, 39.42%, and 48.45%, respectively. The actual parotid dose increased by an average of 11.38% at the end of radiation therapy. Initial parotid volume, initial parotid D mean, and weight loss rate are valuable indicators for parotid protection-based replanning.

Clinical study of nasopharyngeal carcinoma treated by helical tomotherapy in China: 5-year outcomes.

BACKGROUND: To evaluate the outcomes of nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy (HT). METHODS: Between September 2007 and August 2012, 190 newly diagnosed NPC patients were treated with HT. Thirty-one patients were treated with radiation therapy as single modality, 129 with additional cisplatin-based chemotherapy with or without anti-EGFR monoclonal antibody therapy, and 30 with concurrent anti-EGFR monoclonal antibody therapy. RESULTS: Acute radiation related side effects were mainly grade 1 or 2. Grade 3 and greater toxicities were rarely noted. The median followup was 32 (3-38) months. The local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were 96.1%, 98.2%, 92.0%, and 86.3%, respectively, at 3 years. Cox multivariate regression analysis showed that age and T stage were independent predictors for 3-year OS. CONCLUSIONS: Helical tomotherapy for NPC patients achieved excellent 3-year locoregional control, distant metastasis-free survival, and overall survival, with relatively minor acute and late toxicities. Age and T stage were the main prognosis factors.

Clinical study on the changes of the tumor target volume and organs at risk in helical tomotherapy for nasopharyngeal carcinoma.

BACKGROUND: Helical tomotherapy (HT) is a new image-guided intensity-modulated radiation therapy (IMRT). The aim of this study was to evaluate the changes in the target volume and organs at risk (OARs) of patients with nasopharyngeal carcinoma (NPC) during helical tomotherapy. METHODS: Forty-three patients with NPC and treated via HT from March 2008 to January 2010 were reviewed retrospectively. Repeated CT scanning and plan adaptation were conducted at the 20th fraction during radiotherapy. The volumetric differences between the two scans were evaluated for nasopharyngeal tumor and retro-pharyngeal lymph nodes (GTVnx), neck lymph nodes (GTVnd), and parotid glands, as well as the axial diameter of the head. RESULTS: The median interval between the two scans was 25 days (23 - 28 days). The volumetric decrease in GTVnx was 30.1% (median, 29.8%) and in GTVnd 41.6% (median, 45.9%). The variation in the GTVnd volume was correlated with the weight loss of the patient. The volume of the left parotid gland decreased by 35.5% (median, 33.4%) and of the right parotid glands decreased by 36.8% (median, 33.5%). The axial diameter of the head decreased by 9.39% (median, 9.1%). CONCLUSIONS: The target volume and OARs of patients with NPC varied considerably during HT. These changes may have potential dosimetric effects on the target volume and/or OARs and influence the clinical outcome. Repeated CT scanning and replanning during the HT for NPC patients with a large target volume or an obvious weight loss are recommended.

Dosimetric comparison between helical tomotherapy and intensity-modulated radiation therapy plans for non-small cell lung cancer.

BACKGROUND: Helical tomotherapy (HT) is a new image-guided intensity-modulated radiation therapy (IMRT) technique. It is reported that HT plan for non-small-cell lung cancer (NSCLC) can give better dose uniformity, dose gradients, and protection for the lung than IMRT plan. We compared the dosimetric characteristics of HT for NSCLC with those of conventional IMRT to observe the superiority of HT. METHODS: There was a comparative case series comprising 10 patients with NSCLC. Computed tomographic (CT) images of delineated targets were transferred to the PrecisePlan planning system (IMRT) and Tomo planning system (HT). The prescription doses were 70 Gy/33F for the gross tumor volume (GTV) and the visible lymph nodes (GTVnd), and 60 Gy/33F for the clinical target volume (CTV) and the clinical target volume of the visible lymph nodes (CTVnd). The dose restrictions for organs at risk were as follows: the maximum dose to spinal cord ≤ 45 Gy, V20 to the total lungs < 30%, V50 to the heart < 50%, and V55 to the esophagus < 50%. Both plans were evaluated by means of the dose coverage of the targets, dose-volume histograms (DVHs), and other dosimetric indices. RESULTS: The dose coverage, conformity, and homogeneity of the targets' volumes were found to be satisfactory in both plans, but the homogeneity of the HT plan was better than that of IMRT. The high-dose radiation volume (V20-V30) to the lung and the mean lung dose (MLD) decreased (P < 0.05), but the low-dose radiation volume (V5-V10) increased slightly in the HT plan (P > 0.05). The maximum doses to the spinal cord, heart, esophagus and trachea in the HT plan were lower than those in the IMRT plan, but the differences were not statistically significant. CONCLUSIONS: The HT plan provids better dose uniformity, dose gradients, and protection for the organs at risk. It can reduce the high-dose radiation volume for lung and the MLD, but may deliver a larger lung volume of low-dose radiation.

[Management of oral mucositis in patients with head and neck cancer receiving chemoradiotherapy and/or molecular targeted therapy].

OBJECTIVE: To investigate the prevalence and treatment of oral mucositis caused by concurrent chemoradiotherapy and/or molecular targeted therapy in the patients with advanced squamous cell carcinoma of the head and neck. METHODS: A retrospective study of the incidence and treatment of oral mucositis was performed in 179 patients (155 male and 24 female;124 patients at stage III and 55 patients at stage IV) receiving concurrent chemotherapy and (or) molecular targeted therapy between November 2007 and November 2010. Grade I, II, III and IV oral mucositis occurred respectively in 49, 50, 67 and 13 patients. All the patients received oral mucositis prophylaxis. After the occurrence of oral mucositis, conventional treatment of mucositis combined with quinolone antibiotics were applied. RESULTS: Of the patients, 99 patients with grade I or II and 4 patients with grade III oral mucositis were effectively managed by conventional treatment; 76 patients with grade III or IV oral mucositis were also significantly controled by conventional treatment plus antibiotics. After the treatments, all patients with oral mucositis were under control, with the decrease in the grade of oral mucositis, the reduction of oral pain and the improvement in ability to eat. None of them had radiation treatment breaks. CONCLUSIONS: Combined modality therapy can effectively control chemoradiation-induced oral mucositis in patients with head and neck squamous cell carcinoma, grade I and II oral mucositis were cured by conventional treatment and quinolone antibiotics play a key role in the treatments for grade III and IV oral mucositis.