The individualized delineation of clinical target volume for primary nasopharyngeal carcinoma based on invasion risk of substructures: A prospective, real-world study with a large population.

BACKGROUND AND PURPOSE: The delineation of clinical target volume (CTV) for primary nasopharyngeal carcinoma (NPC) is currently controversial and the international guideline still recommend a uniform border for CTV regardless of the tumor extent. We conducted this prospective, real-world study to evaluate the clinical outcomes of our individualized CTV delineation method based on distance plus substructures. MATERIALS AND METHODS: We preliminarily investigated the local extension patterns of NPC on 354 newly diagnosed patients and defined the structures surrounding the nasopharynx as Level-1 to Level-4 substructures stratified by the risk of invasion. We then enrolled patients with newly diagnosed NPC without distant metastasis to investigate our individualized CTV delineation protocol. All patients received intensity modulated radiotherapy. CTV1 and CTV2 were prescribed doses of 60 Gy and 54 Gy in 30 âˆ¼ 33 fractions. The primary endpoint was local recurrence-free survival (LRFS); secondary endpoints included regional control and survival, estimated using the Kaplan-Meier method. The local failure patterns were also analyzed. RESULTS: From January 2008 to December 2012 and from January 2013 to September 2019, 356 and 648 patients were enrolled, named as training set and validation set, respectively. With a median follow-up of 104.6 (interquartile, 73.1-126.9) and 51.4 (39.5-78.5) months, 31 (8.7 %) and 38 (5.9 %) patients in training and validation sets experienced local recurrence, and the 5-year LRFS was 93.0 % and 93.2 %, respectively; 63 (17.7 %) and 39 (6 %) patients died in training and validation sets, and the 5-year overall survival (OS) was 88.5 % and 93.4 %, respectively. For the whole study cohort (N = 1004) with a median follow-up of 66.6 (41.5-98.0) months, the 5-year LRFS and OS was 93.2 % and 91.5 %. The grade 3 late toxicities included xerostomia, subcutaneous fibrosis, hearing impairment, trismus, visuality impairment and skin atrophy, with a total incidence of 1.5 %. Sixty-seven of 69 (97.1 %) local recurrence was in high-dose area. CONCLUSION: Our individualized CTV delineation method can achieve favorable local tumor control and long-term survival outcomes with acceptable late toxicities.

Low-Cost iPhone-Assisted Processing to Obtain Radiotherapy Bolus Using Optical Surface Reconstruction and 3D-Printing.

Patient specific boluses can increase the skin dose distribution better for treating tumors located just beneath the skin with high-energy radiation than a flat bolus. We introduce a low-cost, 3D-printed, patient-specific bolus made of commonly available materials and easily produced using the "structure from motion" and a simple desktop 3D printing technique. Nine pictures were acquired with an iPhone camera around a head phantom. The 3D surface of the phantom was generated using these pictures and the "structure from motion" algorithm, with a scale factor calculated by a sphere fitting algorithm. A bolus for the requested position and shape based on the above generated surface was 3D-printed using ABS material. Two intensity modulated radiation therapy plans were designed to simulate clinical treatment for a tumor located under the skin surface with a flat bolus and a printed bolus, respectively. The planned parameters of dose volume histogram, conformity index (CI) and homogeneity index (HI) were compared. The printed bolus plan gave a dose coverage to the tumor with a CI of 0.817 compared to the CI of 0.697 for the plan with flat bolus. The HIs of the plan with printed bolus and flat bolus were 0.910 and 0.887, respectively.

The bulk compressive creep and recovery behavior of human dentine and resin-based dental materials.

OBJECTIVE: To evaluate and compare the viscoelastic properties of dentine and resin-based dental materials by bulk compressive test and the Burgers model. MATERIALS AND METHODS: Sound dentine, three resin composites as well as a resin-based cement were prepared into cylindrical specimens (n = 8). A bulk compressive creep test was applied with a constant load of 300 N (23.9 MPa) for 2 h, followed by another 2 h recovery. The maximum strain, creep stain, percentage of recovery and permanent set was measured using a linear variable displacement transducer. The viscoelastic properties were characterized via the Burgers model, and the instantaneous elastic, viscous as well as elastic delayed deformation were separated from the total strain. Data were analysed via ANOVA (or Welch's Test) and Tukey (or Games-Howell Test) with a significance level of 0.05. RESULTS: Sound dentine presented the lowest maximum strain, creep strain, permanent set and the highest percentage of recovery, followed by 3 resin composites with comparable parameters, while the cement showed a significantly higher maximum strain, permanent set and lower percentage of recovery (p < 0.001). The Burgers model presented acceptable fits for characterization viscoelastic processes of both dentine and resin-based dental materials. Viscous and elastic delayed strain of dentine was significantly lower than those for tested materials (p < 0.001) with the highest instantaneous elastic strain percentage. Similar viscous and delayed strain was found among the 4 resin-based materials (p > 0.05). SIGNIFICANCE: Sound dentine exhibited superior creep stability compared to resin-based dental materials. The viscous deformation in sound dentine could be ignored when loading parallel to dentine tubules.

Correction to: Retrospective dosimetry study of intensity-modulated radiation therapy for nasopharyngeal carcinoma: measurement-guided dose reconstruction and analysis.

The original version of this article [1] unfortunately contained a mistake.

Retrospective dosimetry study of intensity-modulated radiation therapy for nasopharyngeal carcinoma: measurement-guided dose reconstruction and analysis.

BACKGROUND: Conventional phantom-based planar dosimetry (2D-PBD) quality assurance (QA) using gamma pass rate (GP (%)) is inadequate to reflect clinically relevant dose error in intensity-modulated radiation therapy (IMRT), owing to a lack of information regarding patient anatomy and volumetric dose distribution. This study aimed to evaluate the dose distribution accuracy of IMRT delivery for nasopharyngeal carcinoma (NPC), which passed the 2D-PBD verification, using a measurement-guided 3D dose reconstruction (3D-MGR) method. METHODS: Radiation treatment plans of 30 NPC cases and their pre-treatment 2D-PBD data were analyzed. 3D dose distribution was reconstructed on patient computed tomography (CT) images using the 3DVH software and compared to the treatment plans. Global and organ-specific dose GP (%), and dose-volume histogram (DVH) deviation of each structure was evaluated. Interdependency between GP (%) and the deviation of the volumetric dose was studied through correlation analysis. RESULTS: The 3D-MGR achieved global GP (%) similar to conventional 2D-PBD in the same criteria. However, structure-specific GP (%) significantly decreased under stricter criteria, including the planning target volume (PTV). The average deviation of all inspected dose volumes (DV) and volumetric dose (VD) parameters ranged from - 2.93% to 1.17%, with the largest negative deviation in V100% of the PTVnx of - 15.66% and positive deviation in D1cc of the spinal cord of 6.66%. There was no significant correlation between global GP (%) of 2D-PBD or 3D-MGR and the deviation of the most volumetric dosimetry parameters (DV or VD), when the Pearson's coefficient value of 0.8 was used for correlation evaluation. CONCLUSION: Even upon passing the pre-treatment phantom based dosimetric QA, there could still be risk of dose error like under-dose in PTVnx and overdose in critical structures. Measurement-guided 3D volumetric dosimetry QA is recommended as the more clinically efficient verification for the complicated NPC IMRT.

Incidence and dosimetric parameters for brainstem necrosis following intensity modulated radiation therapy in nasopharyngeal carcinoma.

OBJECTIVES: To clarify the incidence of brainstem toxicity and perform a dose-volume analysis for the brainstem after long-term follow-up of a large cohort of nasopharyngeal carcinoma (NPC) patients who underwent intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS: All patients with NPC treated with IMRT at Sun Yat-sen University Cancer Center between April 2009 and March 2012 were retrospectively reviewed. A total of 1544 patients with follow-up >12months and detailed treatment plan data were included. Radiotherapy was administered using the simultaneous integrated boost technique in 2.0-2.48Gy per fractions/28-33 fractions. Brainstem necrosis was defined as lesions with high signal intensity on T2-weighted images and low signal intensity on T1-weighted images, with or without enhancement after administration of contrast in follow-up MRI. RESULTS: After median follow-up of 79.7months (range, 12.2-85.6months), 2/1544 (0.13%) patients developed brainstem necrosis after intervals of 12.3 and 18.5months. Actuarial incidence of brainstem necrosis was 0.07%, 0.13%, 0.13% and 0.13% after 1, 2, 3 and 5years, respectively. Overall, 384 (24.9%), 153 (9.9%), 67 (4.3%), 39 (2.5%), 78 (5.1%), and 114 (7.4%) patients had excessive doses of Dmax≥64Gy, D1cc>59Gy, D2cc>59Gy, aV50>5.9cc, aV55>2.7cc and aV60>0.9cc respectively, of whom only two developed brainstem necrosis. CONCLUSIONS: Brainstem necrosis is rare in NPC. The definitive criteria based on conventional radiotherapy cannot accurately predict the occurrence of brainstem necrosis after IMRT, thus more flexible definitive criteria with strict restrictions need to be defined.

Target splitting non-coplanar RapidArc radiation therapy for a diffuse sebaceous carcinoma of the scalp: a novel delivery technique.

BACKGROUND AND PURPOSE: To compare conventional lateral photon-electron, fixed-beam intensity modulated radiation therapy (IMRT), coplanar and non-coplanar RapidArc for the treatment of a diffuse sebaceous gland carcinoma of the scalp. METHODS: Comprehensive dosimetry comparisons were performed among 3D-CRT, IMRT and various RapidArc plans. Target coverage, conformity index (CI), homogeneity index (HI) and doses to organs at risk (OAR) were calculated. Monitor unites (MUs) and delivery time of each treatment were also recorded to evaluate the execution efficiency. The influence of target splitting technique and non-coplanar planning on plan quality was discussed. RESULTS: IMRT was superior to 3D-CRT concerning targets' coverage at the sacrifice of larger irradiated brain volumes to low doses. CIs and HIs were better in coplanar RapidArc and non-coplanar RapidArc plans than 3D-CRT and IMRT. Best dose coverage and sparing of OARs were achieved in non-coplanar plans using target splitting technique. Treatment delivery time was longest in the IMRT plan and shortest in the coplanar RapidArc plan without target splitting. The 3%/3 mm gamma test pass rates were above 95% for all the plans. CONCLUSIONS: Target splitting technique and non-coplanar arcs are recommended for total scalp irradiation.

Water-filled balloon in the postoperative resection cavity improves dose distribution to target volumes in radiotherapy of maxillary sinus carcinoma.

Postoperative radiotherapy is a major treatment for patients with maxillary sinus carcinoma. However, the irregular resection cavity poses a technical difficulty for this treatment, causing uneven dose distribution to target volumes. In this study, we evaluated the dose distribution to target volumes and normal tissues in postoperative intensity-modulated radiotherapy (IMRT) after placing a water-filled balloon into the resection cavity. Three postoperative patients with advanced maxillary sinus carcinoma were selected in this trial. Water-filled balloons and supporting dental stents were fabricated according to the size of the maxillary resection cavity. Simulation CT scans were performed with or without water-filled balloons, IMRT treatment plans were established, and dose distribution to target volumes and organs at risk were evaluated. Compared to those in the treatment plan without balloons, the dose (D98) delivered to 98% of the gross tumor volume (GTV) increased by 2.1 Gy (P = 0.009), homogeneity index (HI) improved by 2.3% (P = 0.001), and target volume conformity index (TCI) of 68 Gy increased by 18.5% (P = 0.011) in the plan with balloons. Dosimetry endpoints of normal tissues around target regions in both plans were not significantly different (P > 0.05) except for the optic chiasm. In the plan without balloons, 68 Gy high-dose regions did not entirely cover target volumes in the ethmoid sinus, posteromedial wall of the maxillary sinus, or surgical margin of the hard palate. In contrast, 68 Gy high-dose regions entirely covered the GTV in the plan with balloons. These results suggest that placing a water-filled balloon in the resection cavity for postoperative IMRT of maxillary sinus carcinoma can reduce low-dose regions and markedly and simultaneously increase dose homogeneity and conformity of target volumes.

[Impact of changing gross tumor volume delineation of intensity-modulated radiotherapy on the dose distribution and clinical treatment outcome after induction chemotherapy for the primary locoregionally advanced nasopharyngeal carcinoma].

BACKGROUND AND OBJECTIVE: The gross tumor volume (GTV) obviously reduces after induction chemotherapy (IC) for primary locoregionally advanced nasopharyngeal carcinoma (NPC). This study was to investigate the impact of changing gross tumor volume delineation on the dose distribution and clinical treatment outcome after IC. METHODS: From January 2008 to April 2009, 24 patients with Stage III-IVb primary locoregionally advanced NPC were treated with TPF regimen IC followed by intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy . The primary GTVs were delineated into two parts: the post-IC primary GTV (GTVpost-IC-NP), and the region of pre-IC primary GTV minus GTVpost-IC-NP (GTVpre-post-IC-NP). The dose distributions of two plans with GTVpost-IC-NP or pre-IC primary GTV were assessed by analyzing ten cases. The clinical treatment outcome and toxicity of all patients were observed. RESULTS: The post-IC GTV was significantly smaller than the pre-IC GTV (primary GTV 25.5 cm3 vs. 51.1 cm(3),P=0.001; lymph nodes GTV 9.1 cm(3) vs. 31.4 cm(3), P=0.035; primary + lymph nodes GTV 33.2 cm(3) vs. 82.6 cm(3),P=0.004), the overall GTV with an average shrinkage of 61%. The high dose region was also smaller after IC (volumes covered by 64.4 Gy were 422.9 cm3 vs. 457.9 cm3, P=0.003; 274.2 cm(3) vs.334.5 cm(3) by 68 Gy, P=0.041). The complete response rate was 38% after IC, and 100% three month after radiotherapy. The toxicity of following IMRT with concurrent chemotherapy was similar to that of IMRT with concurrent chemotherapy alone. With median follow-up of 9 months, the locoregionally control rate was 100% and only one patient presented metastasis 15 months after treatment. CONCLUSIONS: TPF regimen IC could significantly reduce tumor volume. The following IMRT with GTVpost-IC-NP plan reduced the high dose region, which didn't add toxicity while had excellent short-term treatment outcome.

[Quality control for multileaf collimator leaf position accuracy using amorphous silicon electronic portal imaging devices].

BACKGROUND AND OBJECTIVE: The multi-leaf collimator (MLC) leaf position deviation of the linear accelerator (LINAC) can result in dose distribution errors during intensity modulated radiotherapy (IMRT), which would cause treatment failure and serious injury to the patients. This study was to develop a simple method to control the MLC leaf position accuracy. METHODS: Elekta LINAC, Elekta iView aSi electronic portal imaging devices (EPIDs) and an 8MV photon beam were used. A digital image designed by a treatment planning system (TPS) was acquired using the EPIDs and was analyzed to compute the MLC leaf position coordinates. The position error was thus obtained by comparing the coordinates in the image with those in the TPS DicomRT file, which was used to quickly adjust the MLC leaf position. RESULT: The leaf deviation of leaf position accuracy was kept less than 1 mm. CONCLUSION: Quality control for MLC leaf position accuracy using EPIDs is simple and adequate.

[Application of amorphous silicon electronic portal imaging device (a-Si EPID) to dosimetry quality assurance of radiation therapy].

BACKGROUND & OBJECTIVE: Due to its good dosimetric properties, amorphous silicon electronic portal imaging device (a-Si EPID), as a rapid two-dimensional dosimetric measurement device, presents an attractive prospect in routine quality assurance (QA) test, dosimetric verification of intensity-modulated radiotherapy treatment (IMRT) and in vivo dose monitoring. This study was to explore the application of a-Si EPID as a detector for dosimetric QA of linear accelerator radiotherapy, and setup the calibration module. METHODS: The imaging calibration procedure of conventional a-Si EPID was modified for dosimetric measurement by acquiring the traditional "flush field" from integrated subfields to correct the dosimetric responding difference in pixel sensitivity. The energy dependence of the a-Si EPID detectors was analyzed through off-axis dose response curves. Calibrated dose profile obtained with a-Si EPID was compared with the measuring results of ion chamber in a 3-D water phantom. RESULTS: The calibrated dose profiles measured with a-Si EPID showed a deviation within 2% in high dose regions, but dropped much steeply in the penumbra region, as compared with that scanned using ion chamber in water. CONCLUSION: With the modeling management set up in this research, a-Si EPID can be applied for dosimetric QA of linear accelerator in radiotherapy.