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.

Dosimetric evaluation of 4 different treatment modalities for curative-intent stereotactic body radiation therapy for isolated thoracic spinal metastases.

To investigate the dosimetric characteristics of 4 SBRT-capable dose delivery systems, CyberKnife (CK), Helical TomoTherapy (HT), Volumetric Modulated Arc Therapy (VMAT) by Varian RapidArc (RA), and segmental step-and-shoot intensity-modulated radiation therapy (IMRT) by Elekta, on isolated thoracic spinal lesions. CK, HT, RA, and IMRT planning were performed simultaneously for 10 randomly selected patients with 6 body types and 6 body + pedicle types with isolated thoracic lesions. The prescription was set with curative intent and dose of either 33Gy in 3 fractions (3F) or 40Gy in 5F to cover at least 90% of the planning target volume (PTV), correspondingly. Different dosimetric indices, beam-on time, and monitor units (MUs) were evaluated to compare the advantages/disadvantages of each delivery modality. In ensuring the dose-volume constraints for cord and esophagus of the premise, CK, HT, and RA all achieved a sharp conformity index (CI) and a small penumbra volume compared to IMRT. RA achieved a CI comparable to those from CK, HT, and IMRT. CK had a heterogeneous dose distribution in the target as its radiosurgical nature with less dose uniformity inside the target. CK had the longest beam-on time and the largest MUs, followed by HT and RA. IMRT presented the shortest beam-on time and the least MUs delivery. For the body-type lesions, CK, HT, and RA satisfied the target coverage criterion in 6 cases, but the criterion was satisfied in only 3 (50%) cases with the IMRT technique. For the body + pedicle-type lesions, HT satisfied the criterion of the target coverage of ≥90% in 4 of the 6 cases, and reached a target coverage of 89.0% in another case. However, the criterion of the target coverage of ≥90% was reached in 2 cases by CK and RA, and only in 1 case by IMRT. For curative-intent SBRT of isolated thoracic spinal lesions, RA is the first choice for the body-type lesions owing to its delivery efficiency (time); the second choice is CK or HT; HT is the preferential choice for the body + pedicle-type lesions. This study suggests further clinical investigations with longer follow-up for these studied cases.

Dose Evaluation of Fractionated Schema and Distance From Tumor to Spinal Cord for Spinal SBRT with Simultaneous Integrated Boost: A Preliminary Study.

BACKGROUND This study investigated and quantified the dosimetric impact of the distance from the tumor to the spinal cord and fractionation schemes for patients who received stereotactic body radiation therapy (SBRT) and hypofractionated simultaneous integrated boost (HF-SIB). MATERIAL AND METHODS Six modified planning target volumes (PTVs) for 5 patients with spinal metastases were created by artificial uniform extension in the region of PTV adjacent spinal cord with a specified minimum tumor to cord distance (0-5 mm). The prescription dose (biologic equivalent dose, BED) was 70 Gy in different fractionation schemes (1, 3, 5, and 10 fractions). For PTV V100, Dmin, D98, D95, and D1, spinal cord dose, conformity index (CI), V30 were measured and compared. RESULTS PTV-to-cord distance influenced PTV V100, Dmin, D98, and D95, and fractionation schemes influenced Dmin and D98, with a significant difference. Distances of ≥2 mm, ≥1 mm, ≥1 mm, and ≥0 mm from PTV to spinal cord meet dose requirements in 1, 3, 5, and 10 fractionations, respectively. Spinal cord dose, CI, and V30 were not impacted by PTV-to-cord distance and fractionation schemes. CONCLUSIONS Target volume coverage, Dmin, D98, and D95 were directly correlated with distance from the spinal cord for spine SBRT and HF-SIB. Based on our study, ≥2 mm, ≥1 mm, ≥1 mm, and ≥0 mm distance from PTV to spinal cord meets dose requirements in 1, 3, 5 and 10 fractionations, respectively.

Long non-coding RNA MVIH is associated with poor prognosis and malignant biological behavior in breast cancer.

In recent years, with the development of transcriptomics, the effect of long non-coding RNAs (LncRNAs) on the regulation of biological processes is being elucidated. LncRNAs play an important role in tumor occurrence and development. LncRNA associated with microvascular invasion in hepatocellular carcinoma (LncRNA MVIH) was first identified in hepatocellular carcinoma and is associated with angiogenesis, tumor growth and metastasis upregulation, and poor recurrence-free survival. MVIH has an important role in non-small cell lung cancer, in which it promotes cell proliferation and metastasis, and high MVIH expression indicates poor overall survival. However, the involvement of MVIH in breast cancer is unclear. Our research revealed that the expression levels of MVIH in breast cancer tissues were higher than in adjacent noncancerous tissues, and high MVIH expression was correlated with Ki67 expression. Moreover, breast cancer patients with high MVIH expression levels showed poor overall survival and disease-free survival. Multivariate analysis results indicated that MVIH was an independent prognostic factor in breast cancer. In addition, upregulated MVIH expression levels promoted cell proliferation and cell cycle, and inhibited cell apoptosis, while reduced MVIH expression showed the converse. In summary, our findings suggest that MVIH may have an important role in breast cancer and may serve as a new biomarker and a potential therapeutic target.

Hypofractionated Helical Tomotherapy for Older Aged Patients With Prostate Cancer: Preliminary Results of a Phase I-II Trial.

In our center, the feasibility and related acute toxicities of hypofractionated helical tomotherapy have been evaluated in older aged patients with prostate cancer . Between February 2009 and February 2014, 67 patients (older than 65 years) were enrolled in a prospective phase I-II study (registered number, ChiCTR-ONC-13004037). Patients in cohort 1 (n = 33) and cohort 2 (n = 34) received 76 Gy in 34 fractions (2.25 Gy/F) and 71.6 Gy in 28 fractions (2.65 Gy/F), respectively, to the prostate and seminal vesicles, while 25 patients in cohort 2 also received integrated elective lymph node irradiation (50.4 Gy). All patients were treated with helical tomotherapy, and daily image guidance was performed before each treatment. Acute toxicities were assessed with Radiation Therapy Oncology Group (RTOG)/European Organization for Research on Treatment of Cancer (EORTC) criteria. No significant difference was detected between the 2 cohorts in the incidence of acute toxicities. In cohort 1, the incidences of grade 1 and 2 genitourinary and gastrointestinal toxicities were 45.5% and 45.4%, respectively, and without grade 3 and 4 toxicities. In cohort 2, the incidences of acute grade 1 and 2 genitourinary and gastrointestinal toxicities were 47.1% and 55.9%, respectively, and grade 3 genitourinary toxicity (hematuria) was noted only in 1 patient. No significant difference was detected in the incidence of acute toxicities between the patients receiving integrated elective lymph node irradiation and those receiving irradiation to prostate and seminal vesicle in cohort 2. Univariate and multivariate analyses were performed with clinical parameters. Only the baseline weight was found negatively correlated with genitourinary toxicities at a weak level (relative risk = 0.946, 95% confidence interval 0.896-0.998], P = .043). This study shows that 2 hypofractionation regimens (76 Gy/34F and 71.6 Gy/28F) delivered with HT are well tolerated in older aged patients having prostate cancer without significant difference for acute toxicities between the 2 cohorts. Late toxicities and treatment outcomes for these patients are under investigation.

Downregulation of the long noncoding RNA EGOT correlates with malignant status and poor prognosis in breast cancer.

Eosinophil granule ontogeny transcript (EGOT) is a long noncoding RNA involved in the regulation of eosinophil granule protein transcript expression. However, little is known about the role of EGOT in malignant disease. This study aimed to assess the potential role of EGOT in the pathogenesis of breast cancer. Quantitative real-time polymerase chain reaction was performed to detect the expression levels of EGOT in 250 breast cancerous tissues and 50 adjacent noncancerous tissues. The correlation of EGOT expression with clinicopathological features and prognosis was also analyzed. EGOT expression was lower in breast cancer compared with the adjacent noncancerous tissues (P < 0.001), and low levels of EGOT expression were significantly correlated with larger tumor size (P = 0.022), more lymph node metastasis (P = 0.020), and higher Ki-67 expression (P = 0.017). Moreover, patients with low levels of EGOT expression showed significantly worse prognosis for overall survival (P = 0.040), and this result was further validated in a larger cohort from a public database. Multivariate analysis suggested that low levels of EGOT were a poor independent prognostic predictor for breast cancer patients (HR = 1.857, 95 % CI = 1.032-3.340, P = 0.039). In conclusion, EGOT may play an important role in breast cancer progression and prognosis and may serve as a new potential prognostic target in breast cancer 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.

Oligodendroglioma of the ciliary body: a unique case report and the review of literature.

BACKGROUND: To date, there is no report in the international literature of an oligodendroglioma of the ciliary body, nor is there an analysis of the possible origins of this lesion. CASE PRESENTATION: Here we report on a 52-year-old man admitted to our hospital with a ciliary body tumor revealed by clinical examination and ultrasound, computed tomography and magnetic resonance imaging studies. Following enucleation, pathological and immunohistochemical analyses were performed. Postoperative histopathological staining results included OLIGO-2(+) and GFAP(-), leading to a pathological diagnosis of oligodendroglioma of the ciliary body in the right eye (WHO grade II). CONCLUSIONS: Since malignant gliomas derive from transformed neural stem cells, the presence of oligodendroglioma in the ciliary body supports the hypothesis that gliomas can occur wherever neural stem cells exist. Tumors of the ciliary body derived from oligodendrocytes are difficult to diagnose; pathological analyses are essential.

Effects of radiation on the expression of nerve growth factor in rat submandibular gland.

OBJECTIVE: to investigate the correlation between the expression of nerve growth factor (NGF) and tissue injury in irradiated rat submandibular gland. METHODS: the salivary gland regions of the rats were irradiated with a single dose of 15 Gy X-ray. The histopathological changes in the submandibular gland were observed, while the expression of NGF was determined by immunohistochemistry and real-time PCR. RESULTS: the weight of the body and submandibular gland decreased in the irradiated rats 30 days after irradiation, compared with the control group. There were also significant histopathological changes in the submandibular gland of the irradiated rats compared with the non-irradiated rats. The acinar cells and ducts were degenerated obviously. Fibrosis appeared around the ducts. The mRNA and protein expression of NGF in the submandibular gland decreased in the irradiated rats compared with the control group. Protein expression of NGF was even observed in the striated duct in the irradiated rats. conclusion: NGF may play an important role in protection of the submandibular glands of rats from radiation.

[Effect of radiation on the activity and expression of Ca(2+)-Mg(2+)-ATPase in rat masseter muscle].

OBJECTIVE: To investigate the activity and expression of Ca(2+)-Mg(2+)-ATPase in irradiated rat masseter muscle. METHODS: The rats were irradiated locally with a single dose of 20 Gy X-ray. The activities of Ca(2+)-Mg(2+)-ATPase were measured with colorimetric method. The protein expression of Ca(2+)-Mg(2+)-ATPase was determined by Western blotting and immunohistochemistry. RESULTS: The activities of Ca(2+)-Mg(2+)-ATPase in masseter muscle decreased by approximately 20% and 40% in irradiated rats on days 3 and 30 postirradiation. There was significant difference in the expression of Ca(2+)-Mg(2+)-ATPase protein between irradiated and nonirradiated rats on day 30 postirradiation. Ca(2+)-Mg(2+)-ATPase protein was found in the cytoplasm of masseter muscle. CONCLUSIONS: The decrease of ATPase activity played an important role in the cause of radiation-induced skeletal muscle injury, while there was no significant reduction in the expression of Ca(2+)-Mg(2+)-ATPase protein in irradiated rat masseter muscle.

[Dosimetric comparison between helical tomotherapy and step-and-shoot intensity modulated radiation therapy for endometrial carcinoma].

BACKGROUND AND OBJECTIVE: Helical tomotherapy (HT) has shown its dosimetric advantages in the radiotherapy for many cancers. To date, no published studies have performed a dosimetric evaluation of whole pelvic radiotherapy (WPRT) using HT for postoperative endometrial cancer. This study was to compare the dosimetric characteristics of HT and step-and-shoot intensity modulated radiation therapy (SaS-IMRT) for endometrial cancer patients undergoing postoperative WPRT, and to explore whether whole pelvic HT for postoperative endometrial cancer has the advantage of dosimetry. METHODS: Ten patients with endometrial cancer undergoing postoperative WPRT were enrolled in this study. SaS-IMRT and HT Plans were developed for each patient. The dose distributions of the targets, organs at risk and normal tissue were analyzed and compared. RESULTS: The mean PTV100 were 95.6% and 95.8% (P=0.72) for the SaS-IMRT and HT plans, respectively. The mean homogeneity indexes were 1.10 and 1. 07 (P=0.00). The mean conformity indexes were both 0.87. The mean doses to rectum and bladder for HT were decreased by 1.3 Gy and 3.0 Gy compared with SaS-IMRT, respectively, while the mean dose to pelvic bones was increased by 1.1 Gy. The volumes of small intestine and colon, pelvic bones receiving moderate and low dose also increased. The V5, V10 and V20 of normal tissue were increased by 13.0%, 18.0%, and 5.0% (P=0.00). The mean dose to normal tissue was increased by 2.5 Gy (P=0.00). CONCLUSIONS: Compared with SaS-IMRT, HT resulted in more homogeneous PTV dose distribution, better sparing of rectum and bladder. The volumes of small intestine and colon, pelvic bones and normal tissue receiving moderate and low dose for HT increased. The clinical significance of the dosimetric differences needs further investigations.

[Measurement and analysis of the imaging dose with megavoltage computed tomography for helical tomotherapy].

BACKGROUND & OBJECTIVE: During the helical tomotherapy process, megavoltage computed tomography (MVCT) images are usually used for guiding the precise setup of patients before/after treatment delivery, which would certainly increase the total dose for patients. This study was to investigate the imaging dose of MVCT using the body and head phantom on a tomotherapy machine. METHODS: A set of cylindrical body and head phantoms was adopted for scanning with different pitch values (1.0/2.0/3.0), lengths (4.8/7.2/9.6/12/14.4 cm) and patient setups on the couch of tomotherapy system. The average MVCT imaging doses were measured using A1SL chambers inserted in the phantoms with preset geometry. The dose uniformity was qualitatively analyzed. RESULTS: The MVCT scanning dose for the body phantom was between 0.599 and 2.876 cGy during each treatment delivery, while the dose for the head phantom was between 0.913 and 3.231 cGy. Two major parameters, the assigned pitch numbers and scanning lengths, were the most important impacts to the dose variation. The MVCT dose was inversely proportional to the CT pitch value. With respect to the scanning length, the doses responded differently along the radial direction of the phantoms with different setup criteria. CONCLUSION: The results may provide a reliable guidance for proper planning design of the scanning region, which is valuable to help minimize the extra doses to patient.