B. Qu

Clinical observation of 73 nasopharyngeal carcinoma patients treated by helical tomotherapy: the China experience.

The preliminary short-term clinical outcome of 73 nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy at our cancer institute has been evaluated. Between September 2007 and September 2009, 73 newly diagnosed NPC patients were treated with helical tomotherapy. The distributions of clinical stages according to the UICC 2002 Staging System were: 6, 27, 24, and 16 for Stage I, IIa-b, III, and IVa-b, respectively. The prescription dose was 70–74 Gy/33F to planning gross tumor volume containing the primary tumor and positive lymph nodes, with 60–62.7 Gy/33F to high risk planning target volume, while delivering 52–56 Gy/33F to low risk planning target volume. Twenty-four patients were treated with radiation therapy as single modality, 25 with concurrent cisplatin-based chemotherapy with or without anti-EGFR monoclonal antibody therapy, and 24 with concurrent anti-EGFR monoclonal antibody therapy. Setup errors were analyzed. Side-effects were evaluated with the established RTOG/EORTC criteria. Average beam-on-time was 468.8 sec/F (396.7–696.1 sec). The setup errors in the lateral, longitudinal and vertical directions were 0.00 ± 1.79 mm, −0.55 ± 2.17 mm and 0.38 ± 1.43 mm, corresponding to 3.80 mm, 4.20 mm, and 2.46 mm as the CTV-PTV margin in these directions. The grade 0, 1, 2 and 3 acute skin toxicity was 2.7%, 76.7%, 13.8% and 6.8%; the grade 0, 1, 2 and 3 acute mucositis was 1.4%, 32.9%, 60.2% and 5.5%; and the grade 0, 1, 2 and 3 acute xerostomia was 4.0%, 45.3%, 50.7% and 0, respectively. Only 5 patients suffered from grade 3 or 4 leucopenia. Xerostomia resolved with passing of time and no grade 2 or more xerostomia was noted one year after radiation therapy. Concurrent chemotherapy significantly increased incidence of severe acute toxicities. One month after radiation therapy the remission rates of primary tumor and positive lymph nodes were 91.8% and 98.1%, respectively. The median follow-up was 14.8 months. The one-year relapse-free survival, distant metastasis-free survival and overall survival was 95.6%, 97.2% and 94.8%, respectively. In conclusion, the incidence of severe acute toxicities and late xerostomia was relatively infrequent for NPC patients treated with helical tomotherapy. The long-term clinical outcome for these patients is under investigation.

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.

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.

Association of DNA repair gene polymorphisms with the risk of radiation pneumonitis in lung cancer patients

A total of 149 lung cancer patients were recruited to receive intensity modulated radiation therapy (IMRT). The association of developing radiation pneumonitis (RP) with genetic polymorphism was evaluated. The risks of four polymorphic sites in three DNA repair related genes (ERCC1, rs116615:T354C and rs3212986:C1516A; ERCC2, rs13181:A2251C; XRCC1, rs25487:A1196G) for developing grade ≥ 2 RP were assessed respectively. It was observed that ERCC1 T354C SNP had a significant effect on the development of grade ≥ 2 RP (CT/TT vs. CC, adjusted HR = 0.517, 95% CI, 0.285–0.939; adjusted P = 0.030). It is the first time demonstrating that CT/TT genotype of ERCC1 354 was significantly associated with lower RP risk after radio therapy.

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 cm3 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.

GSTP1 Ile105Val polymorphism might be associated with the risk of radiation pneumonitis among lung cancer patients in Chinese population: A prospective study

Background: Growing data suggest that DNA damage repair and detoxification pathways play crucial roles in radiation-induced toxicities. To determine whether common functional single-nucleotide polymorphisms (SNPs) in candidate genes from these pathways can be used as predictors of radiation pneumonitis (RP), we conducted a prospective study to evaluate the associations between functional SNPs and risk of RP. Methods: We recruited a total of 149 lung cancer patients who had received intensity modulated radiation therapy (IMRT). GSTP1 and XRCC1 were genotyped using the SurPlexTM-xTAG method in all patients. RP events were prospectively scored using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Kaplan-Meier analysis was used to determine the cumulative probability of RP of grade ≥ 2. Cox proportional hazard regression was performed to identify clinical variables and SNPs associated with risk of RP grade ≥ 2, using univariate and multivariate analysis, respectively. Results: With a median follow-up of 9 months, the incidence of RP of grade ≥ 2 was 38.3%. A predicting role in RP was observed for the GSTP1 SNP (adjusted hazard ratio 3.543; 95% CI 1.770-7.092; adjusted P< 0.001 for the Ile/Val and Val/Val genotypes versus Ile/Ile genotype). Whereas, we found that patients with XRCC1 399Arg/Gln and Gln/Gln genotypes had a lower risk of RP compares with those carrying Arg/Arg genotype (adjusted HR 0.653; 95% CI 0.342-1.245), but with no statistical significance observed (adjusted P = 0.195). Conclusions: Our results suggested a novel association between GSTP1 SNP 105Ile/Val and risk of RP development, which suggests the potential use of this genetic polymorphism as a predictor of RP. In addition, genetic polymorphisms of XRCC1 399Arg/Gln may also be associated with RP.