Abstract
Background and Purpose
Customized mouth-opening-tongue-depressing-stents (MOTDs) may reduce toxicity in patients with head and neck cancers (HNC) receiving radiotherapy (RT). However, making MOTDs requires substantial resources, which limits their utilization. Previously, we described a workflow for fabricating customized 3D-printed MOTDs. This study reports the results of a prospective trial testing the non-inferiority of 3D-printed to standard and commerciallyavailable (TruGuard) MOTDs as measured by patient reported outcomes (PROs).
Materials and Methods
PROs were collected at 3 time points: (t1) simulation, (t2) prior to RT, (t3) between fractions 15–25 of RT. Study participants received a 3D-printed MOTDs (t1, t2, t3), a waxpattern (t1), an acrylic-MOTDs (t2, t3) and an optional TruGuard (t1, t2, t3). Patients inserted the stents for 5–10 minutes and completed a PRO-questionnaire covering ease-of-insertion and removal, gagging, jaw-pain, roughness and stability. Inter-incisal opening and tongue-displacement were recorded. With 39 patients, we estimated 90% power to detect a non-inferiority margin of 2 at a significance level of 0.025. Matched pairs and t-test were used for statistics.
Results
41 patients were evaluable. The 3D-printed MOTDs achieved a significantly better overall PRO score compared to the wax-stent (p=0.0007) and standard-stent (p=0.0002), but was not significantly different from the TruGuard (p=0.41). There was no difference between 3D-printed and standard MOTDs in terms of inter-incisal opening (p=0.4) and position reproducibility (p=0.98). The average 3D-printed MOTDs turn-around time was 8 vs 48 hours for the standard-stent.
Conclusions
3D-printed stents demonstrated non-inferior PROs compared to TruGuard and standard-stents. Our 3D-printing process may expand utilization of MOTDs.
Keywords: 3D printing, Head and Neck Cancer, Oral Stent, Radiation Therapy
INTRODUCTION
Head and neck cancer (HNC) is the eighth most common cancer worldwide, with more than 830,000 new cases and 408,000 deaths projected annually [1]. Radiation therapy (RT) has become an essential component in the treatment regimen of these patients, regardless of the tumor stage [2]. RT provides a non-invasive alternative that can efficiently control the local disease and improve patients’ survival [2–4]. However, these benefits are challenged by radiation induced toxicities. While delivering high radiation doses to the tumor is necessary to improve the outcomes, the tolerance of the surrounding healthy tissue to radiation remains a major concern. Radiation-induced oral mucositis (RIOM), dysgeusia, and xerostomia are common side effects in patients with HNC [5–7]. These side effects detract from patients’ quality of life and may lead to unplanned treatment breaks [8, 9]. Improved radiation delivery methods and the utilization of toxicity sparing devices have lessened the side effects experienced by patients [10, 11]. One such toxicity sparing device is the oral radiation stent. Oral radiation stents have been utilized for decades in HNC patients undergoing RT, as they displace the healthy tissue and improve the therapeutic index of RT [12–17].
The hand crafted customized (standard of care) oral radiation stents are typically made by oralmaxillofacial specialists with oncology-specific training in collaboration with radiation oncologists. The fabrication of the stents typically requires three separate appointments. First, providers acquire the impression of patient’s teeth and associated tissues, and bite registration to create a stone model with the appropriate maxillo-mandibular relationship. These models are used to hand sculpt a wax pattern with the desired stent features. In the second appointment, the wax pattern is verified intraorally for positioning and fit. Then, the wax pattern is transformed to fabricate a definitive acrylic (standard) stent which will be delivered to the patient and verified in the third and final visit. Standard stents fabricated in this fashion provide reliable and reproducible jaw positioning during the course of RT. However, utilization of fully customized oral radiation stents outside large highvolume academic centers is likely low, owing to lack of availability of specialists who can make the devices.
As a solution to the lack of availability of providers who make customized oral stents, we demonstrated the feasibility of fabricating customized mouth-opening tongue-depressing (MOTD) stents utilizing computer-aided design (CAD) and 3D printing technology [18]. Additionally, we demonstrated that 3D printed MOTD stents can achieve a high level of reproducibility and accuracy [19]. Here, we prospectively evaluated whether the customized 3D printed MOTD stent can achieve non-inferior levels of patient-reported outcomes (PROs) as compared to standard stents and a commercially available stent (TruGuard) in patients with HNC receiving RT. Additionally, we evaluated the position reproducibility of the 3D printed stent, and measured the cost and time required to manufacture an oral stent using 3D printing technology.
MATERIALS AND METHODS
Study enrollment criteria
This prospective clinical trial (2017–0269) was approved by the MD Anderson Cancer Center (MDACC) Institutional Review Board (IRB). All patients who enrolled received treatment for their HNC within the institution and signed informed consent. Criteria for study enrollment included: 1) Patient was dispositioned to receive definitive or adjuvant RT for treatment of a diagnosed HNC; 2) Treating radiation oncologist prescribed a MOTDs; 3) Age 18 or older; 4) Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0–2, 5) and agreed to participate for duration of study. Patients with the following criteria were excluded from the study: 1) Prior head and neck radiotherapy; 2) Severe trismus with an incisal opening of <10 mm; 3) Inability to comply with study procedures; 4) Patients who have received MOTDs fabricated outside of MDACC; and 5) Patients younger than 18 years.
Stent Design and Fabrication
Oral oncologists at MDACC customized the standard MOTD stents for each participant with the same technical standards as a team of researchers (MZ, NB, HB), who made the customized 3D printed MOTD stents using a workflow that was previously described.[19]
Evaluation of the stents
All patients in the study received a standard MOTD stent and a 3D printed MOTD stent. (Figure 1A, 1B and 1C) In addition, patients could receive an optional TruGuard, a semi-customized, commercially available stent (Figure 1D). Neither the 3D printed MOTD stent nor the TruGuard were used for patient radiation treatment. Patient reported outcomes (PROs) were recorded at three time points: 1) baseline (before simulation) to compare the wax pattern stent and the 3D printed MOTD stent; 2) time just prior to starting RT to compare the standard stent and the 3D printed MOTD stent; and 3) once the patient had completed 15–25 fractions of RT. When the patients agreed to participate, the optional TruGuard stent was also evaluated during these time points. At each time point, patients were asked to insert the stent in their mouth for 5–10 minutes in the supine position and then complete a PRO questionnaire, derived from a validated instrument for assessing outcomes during RT [20]. The PRO questionnaire for this study included a set of seven questions ranging in response from 0 (none at all) to 10 (as bad as you can imagine) that covered the design domains of MOTD stents, including ease of insertion and removal, gagging, jaw pain, roughness against tongue and stability in treatment position (Supplementary Figure 1). Other measurements such as inter-incisal mouth opening and tongue displacement while wearing the 3D printed stents and the standard one, were recorded at three time points. Patients were taken off study after completing the three time points (Figure 2).
Figure 1:
Radiation stents: (A) Wax-pattern of the stent (B) Standard (acrylic) stent (C) 3D-printed stent (D) TruGuard stent
Figure 2:
Study design
Statistical analysis and sample size justification
We anticipated that the differences between the 3D printed and standard stents to be clinically negligible. Given the high volume of head and neck cancer patients treated at MDACC, we proposed a sample size of 50 patients for this initial pilot study, of which 39 patients were expected to be evaluable. A sample size of 39 achieves 90% power to detect non-inferiority using one-sided t-test at a significance level of 0.025, when the margin of equivalence is 2 and the true difference between the comparison groups is 1.2, assuming a standard deviation of 1.5 for the difference [21].
To address our primary objective of demonstrating non-inferiority of the 3D printed stent compared to the standard stent, we used the PRO questionnaire data at the three time points. Afterwards we conducted a non-inferiority test for paired data with a non-inferiority margin of 2 between the following: 1) the 3D printed stent vs the wax pattern at the first time point; 2) the 3D printed stent vs the standard stent at the second and third time points combined; and 3) the 3D printed stent scoring in the second vs the third time point. In an exploratory exercise, we conducted the same test for the TruGuard scoring vs the 3D printed stent in the three time points for the eligible patients. A p-value of ≤ 0.025 was considered statistically significant.
To address our secondary objective of demonstrating mandibular and soft tissue displacement and position reproducibility, we similarly performed non-inferiority test for paired data with a non-inferiority margin of 2 between the following: 1) the Inter-incisal mouth opening between the 3D printed stent vs the wax pattern at the 1st time point 2) the inter-incisal mouth opening between the 3D printed stent and the standard stent at the 2nd time point 3) the change in the inter-incisal opening while using the 3D printed stent across the 3 time points. A p-value of ≤ 0.025 was considered statistically significant.
RESULTS
Patient population
Prospectively, we identified and consented 50 patients who were dispositioned to receive definitive RT for HNC malignancies, of which 41 were evaluable. All patients received standard MOTD stents (fabricated by oral oncologists) and 3D printed MOTD stents. 19 patients agreed to test the optional TruGuard. Nine patients were excluded from the study due to either receiving RT outside the institution main campus or declining to complete one or more of the three time points (Figure 3). The patient population consisted of 34 males and seven females, with median diagnosis age of 62 years. 39 patients had primary oropharyngeal cancer, while two patients had carcinoma of nasal cavity. The median fractional radiation dose delivered was 210 cGy to clinical tumor volume 1 (CTV1). Clinical and demographic characteristics of the patients are shown in table (1).
Figure 3:
Sample size and eligibility criteria. * Patient who completed the 3 time points and filled PROs for both 3D printed stent and standard stent
Table 1:
Patient demographics and clinical characteristics
| Characteristic | All patients (n = 41) |
|---|---|
| Age, median (min, max) | 62 (34, 75) |
| Gender, No. (%) | |
| Male | 34 (82.9) |
| Female | 7 (17.1) |
| Race, No. (%) | |
| White | 32 (78.1) |
| Hispanic/Latino | 5 (12.2) |
| Black | 3 (7.3) |
| American Indian/Alaska Native | 1 (2.4) |
| T-stage, No. (%) | |
| T0 | 1 (2.4) |
| T1 | 14 (34.1) |
| T2 | 13 (31.7) |
| T3 | 5 (12.2) |
| T4 | 8 (19.5) |
| N-stage, No. (%) | |
| N0 | 6 (14.6) |
| N1 | 21 (51.2) |
| N2 | 13 (31.7) |
| Nx | 1 (2.4) |
| M-stage, No. (%) | |
| M0 | 40 (97.6) |
| M1 | 1 (2.4) |
| Cancer type, no. (%) | |
| Squamous cell carcinoma | 37 (90.2) |
| Adenoid cystic carcinoma | 2 (5) |
| Undifferentiated carcinoma | 1 (2.4) |
| Unspecified | 1 (2.4) |
| Primary cancer site, No. (%) | |
| Oropharyngeal | |
| Base of tongue | 28 (68.3) |
| Tonsil | 9 (22) |
| Buccal sulcus | 1 (2.4) |
| Floor of mouth | 1 (2.4) |
| Nasal cavity | 2 (4.9) |
| RT Dose/Fraction, median (min, max), Gy | 210 (197, 212) |
| No. of RT Fractions, median (min, max) | 33 (30, 35) |
| Concurrent chemotherapy, No. (%) | |
| Yes | 27 (65.9) |
| No | 14 (34.1) |
| Degree of mucositis, No. (%) | |
| None | 1 (2.4) |
| Mild | 16 (39) |
| Moderate | 20 (48.8) |
| Severe | 4 (9.8) |
Patients reported outcomes (PROs)
1. The 3D printed stents vs the wax pattern
At the first time point, the 3D printed stent achieved a significantly better (lower) PRO score (mean difference=−3.6, 95%CI [−5.6, −1.6], p=0.0007) with an average score of 3.7, compared to 7.3 for the wax pattern (Figure 4A).
Figure 4:
Comparison of PRO scoring between the three stents at the first time point (A); and the second and third time points combined (B) and separately (C=second & D=third).
2. The 3D printed stents vs the standard acrylic stent
At the second (just before RT) and third (between fractions 15–25) time points the 3D printed stent achieved a significantly better (lower) PRO score (mean difference= −2.7, 95%CI [−4.06, −1.3], p=0.0002) with an average combined score of 3.4, compared to the average combined score of 6.1 for the standard stent. There was no significant change (mean difference=0.1, 95%CI [−0.9, 1.3], p=0.76) between the patient scoring for the 3D printed stent at the second and third time points (Figure 4B); however there was a significant difference between the patient scoring for the standard stent at the second (average=4.9) and third (average=7.1) time points (mean difference = 2.1, 95%CI [5.5, 3.8], p=0.009). Separate analyses of the second and the third time points are shown in Figure 4C and D.
3. The 3D printed stents v. the TruGuard
At the first time point, there was no significant difference (mean difference= −0.3, 95%CI [−4.1, 4.7], p=0.88) between the 3D printed stent scoring compared to the TruGuard. Similarly, at the second and third time points combined, there was no significant difference (mean-difference=−0.82, 95%CI [−1.1, 2.8], p=0.41) between the 3D printed stent scoring and the TruGuard (Figure 4 A and B). Separate analyses of the second and the third time points are shown in Figure 4C and D.
Stent Positioning and Reproducibility
There was no significant difference between the inter-incisal opening obtained with the 3D printed stent and wax pattern at the first time point (mean difference= 1.8, 95% CI [−2.6, 6.2], mm p=0.4) and the standard stent at the second (mean difference=−0.29, 95%CI [−1, 0.4], mm, P=0.4) and third time points (mean difference =−0.29, 95%CI [−1, 0.4]) mm, P=0.4). The recorded inter-incisal mouth opening for the 3D printed stent did not show any significant change across the 3 time points (mean-difference=0.08 mm, 95%CI [−1.3, 2.9] p=0.98). When compared to the wax pattern and the standard stent, the visual assessment showed that the 3D printed stent similarly displaced the tongue as desired below the level of the dentition.
Time and Cost Involved
The average time consumed for the 3D printed stent was 8 hours/stent (SD±0.9), which is substantially less than standard of care production.
DISCUSSION
In this study, we investigated whether the fully customized 3D printed MOTD stents can achieve non-inferior levels of PROs as the customized standard MOTD stents and the commercially available semi-customized stents (TruGuard) in HNC patients receiving RT. Our results demonstrated that the 3D printed MOTD stents can achieve similar or better PROs compared to the other stents. Additionally, we showed how the 3D printed MOTD stents can obtain reproducible positioning and similar displacement of the soft tissue (principally the oral tongue) compared to the standard stents.
Importantly, the 3D printed MOTD stent may have a significant impact on the resources required for its fabrication which would help broaden their availability (table 2). Radiation stents have been developed and utilized over decades as they repeatedly position the oral cavity and its anatomic structures in a consistent position during each fraction of RT, which may help in minimizing the adverse effect of RT as well as maximizing local control of tumor [13–15]. Variable designs and degrees of customization exist, but the optimal radiation stent should exhibit a specific set of features that optimizes the therapeutic index. Kaanders et al [17] described the workflow for manual fabrication of radiation stents for HNC RT purposes. They set criteria for stent quality that included: 1) adequacy and reproducibility of the stent with regard to tissue positioning; 2) ease of insertion and removal; 3) patient tolerance and stability in the treatment position; 4) simplicity of design; and 5) safety (especially with reference to aspiration). In a similar fashion, we designed, fabricated, and evaluated our 3D printed MOTD stents with these criteria in mind. The symptom inventory questionnaire used to evaluate the PROs were derived from the criteria set by Kaanders et al for oral radiation stents. Consequently, the 3D printed MOTD stent achieved similar positioning and non-inferior PRO compared to the standard one, at all three time points of consideration.
Table 2:
Production cost for the 3D printed stent, standard stent and TruGuard
| Capital Expenditures | Cost (USD) | Recurring Expenditures | Cost (USD) | Material Cost of 1 Stent (USD)* | |
|---|---|---|---|---|---|
| 3D Printed Stent | Einscan scanner | 1,399.00 | Resin tank LT | 99.00 | 12.00 |
| Form 2 printer | 3,350.00 | Dental SG resin – 1 Liter | 299.00 | ||
| Form wash | 499.00 | Isopropyl Alcohol | 26.00/gallon | ||
| Form cure | 699.00 | ||||
| Standard Stent | Curing Unit | 2,000.00 | Wax 5lb box | 65.00 | 35.00 |
| Acrylic clear | 475.00 | ||||
| Acrylic liquid – 5 Liter | 140.00 | ||||
| Proton bite block | 15.00/each | ||||
| TruGuard | N/A | N/A | 79.80* | ||
Personnel cost is reflected in the TruGuard price. Considering the time it takes to design and fabricate 3D printed stent versus the standard of care stent, 3D printed stent typically costs less than the standard one.
In addition to a comparison to the standard MOTDs, we included the commercially available TruGuard as an optional part of our study. TruGuard is a semi-customized stent made from thermoplastic material, which can be assembled and prepared in few minutes. It represents an economical and practical option for patients receiving RT when a fully customized stent is not available. However, it objectively lacks some of the key features essential for optimal positioning, such as lack of size customization, limited ventral tongue displacement, and inability to accommodate patients who have dental malocclusions, intraoral tumors or who are edentulous. Only 19/41 (46%) patients agreed to the optional TruGuard stent. This could be explained by the extra chair-side time (10–15 minutes) it warrants. The idea of putting a stent after being taken out of a hot water bath may also have been intimidating for the patients, and a reason for their declining the procedure. Despite the number of evaluated subjects that did not reach the predefined statistical power threshold (n=39), our evaluation showed that the TruGuard stent did not have any significant advantage over the 3D printed stent regarding PROs.
Evaluating the MOTD stents at three distinct time points added more value to this study. Comparing the 3D printed stent to the wax pattern, which is usually bulkier and less comfortable than the definitive one, helped to confirm that the questionnaire used in that study provides a quantitative readout that can differentiate what has been qualitatively observed. Also, comparing the 3D printed stent to the standard stent before and during the middle of the patients’ RT course provided an insight about the level of PRO after developing some adverse effects from RT. Finally, recording fit, inter-incisal opening, and dorsal tongue displacement at different time points allowed us to objectively assess positioning reproducibility achieved by 3D printed stents.
The turn-around time for the fabrication of 3D printed MOTD stent is significantly less (~8 hours) compared to the standard manually fabricated stent (~ 48 hours). It also proved to be affordable in terms of equipment, labor and expertise, with easier and faster re-fabrication in case of loss or damage, albeit digital equipment are needed (table 2). The workflow also showed high flexibility and efficiency in cases with anatomical and pathological variations such as malocclusions (Angle’s Class II and III malocclusions), mandibular reconstruction, and edentulism.
This study showed a few limitations. First, we relied on the stone models to acquire dental anatomy, which dictates an extra visit to the oral oncologist surgeon. Currently, we are investigating the utilization of an intraoral scanner (IOS) to acquire the oral anatomy in a second cohort of HNC patients. IOS has increasingly demonstrated superiority over stone models in terms of accuracy, dimensional change, retrieval, storage, and safety in patients with aspiration risks or respiratory distress [22–24]. Second, we used manual measurement and visual assessments to determine the positioning and the reproducibility. Currently, we are conducting an imaging study and radiation dosimetry analysis to comprehensively address the limitations with the qualitative methods we used here. Another limitation is the potential bias in the patients’ response to the PRO questionnaire. The perceived ‘novelty’ of the 3D printed stent and willingness to contribute to this digital workflow may have been a source of bias in their responses. However, utmost care was taken by the study personnel to be completely objective and impartial in their carrying out of the study activities. Finally, lack of complete automation may lead to design variability and delay. Future studies will investigate automated workflow and personalized design algorithms, and apply these principles to tongue deviating and lip protruding stents. Additionally, we are also conducting studies to compare the 3D printed resin with the standard polymethyl methacrylate (PMMA) resin, in terms of mechanical, surface microscopic properties and radiation sensitivity. Finally, a prospective study with 3D printed stents to measure the short and long-term benefits of the stents with regards to RT induced toxicities, stent stability (longitudinally), and downstream economic impact on management and delivery are planned.
CONCLUSIONS
A fully customized 3D printed MOTD stent can achieve non-inferior levels of patient reported outcomes in comparison to the traditional manually fabricated standard of care stents and the commercially available semi-customized stents (TruGuard). The 3D printed stents can achieve similar and reproducible intraoral positioning as the standard stent. Given the low cost, reduced fabrication time, and short digital learning curve the 3D printed stent dictates, it can be widely utilized in any radiation oncology practice. Future studies evaluating the clinical benefit(s) of customized 3D printed stents are warranted.
Supplementary Material
Highlights.
Prospectively evaluated customized 3D printed stents compared to standard stents
3D printed stents demonstrated non-inferior patient reported outcomes
3D printed stents achieved similar and reproducible intraoral positioning
3D printed stents have low production cost, and short fabrication time
3D printed stents can be widely utilized in any radiation oncology practice
Acknowledgement
We gratefully acknowledge partial support from the Andrew Sabin Family Fellowship, the Sheikh Ahmed Center for Pancreatic Cancer Research, institutional funds from The University of Texas MD Anderson Cancer Center, equipment support by GE Healthcare and the Center of Advanced Biomedical Imaging, Project Purple, and Cancer Center Support (Core) Grant CA016672 from the National Cancer Institute to MD Anderson. Dr. Eugene Koay was also supported by NIH (U54CA210181-01, U54CA143837 and U01CA196403).
Dr. Fuller is supported by Sabin Family Foundation, NIH (1R01DE025248-01/R56DE025248-01, 1R01CA214825-01, 1R01CA218148-01, P30CA016672, P50 CA097007-10) and National Science Foundation (NSF) (NSF 1557679). Dr. Fuller has received direct industry grant support and travel funding from Elekta AB.
Footnotes
Conflict of interest statement
Drs. Chung, Wilke, Fuller, Zaid, and Koay have a pending patent for the 3D printing process. We otherwise have no conflicts of interest to disclose.
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REFERENCES
- 1.Bray F, Ferlay J, Soerjomataram I, et al. , Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018. 68(6): p. 394–424. [DOI] [PubMed] [Google Scholar]
- 2.Bourhis J, Overgaard J, Audry H, et al. , Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis. The Lancet, 2006. 368(9538): p. 843–854. [DOI] [PubMed] [Google Scholar]
- 3.Bourhis J, Overgaard J, Audry H, et al. , Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis. Lancet, 2006. 368(9538): p. 843–54. [DOI] [PubMed] [Google Scholar]
- 4.Horiot JC, Bontemps P, van den Bogaert W, et al. , Accelerated fractionation (AF) compared to conventional fractionation (CF) improves loco-regional control in the radiotherapy of advanced head and neck cancers: results of the EORTC 22851 randomized trial. Radiother Oncol, 1997. 44(2): p. 111–21. [DOI] [PubMed] [Google Scholar]
- 5.Maria OM, Eliopoulos N, and Muanza T, Radiation-Induced Oral Mucositis. Frontiers in oncology, 2017. 7: p. 89–89. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Elting LS, Cooksley CD, Chambers MS, et al. , Risk, Outcomes, and Costs of Radiation-Induced Oral Mucositis Among Patients With Head-and-Neck Malignancies. Int J Radiat Oncol Biol Phys, 2007. 68(4): p. 1110–1120. [DOI] [PubMed] [Google Scholar]
- 7.Trotti A, Bellm LA, Epstein JB, et al. , Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review. Radiotherapy and Oncology, 2003. 66(3): p. 253–262. [DOI] [PubMed] [Google Scholar]
- 8.Sonis ST, Mucositis: The impact, biology and therapeutic opportunities of oral mucositis. Oral Oncology, 2009. 45(12): p. 1015–1020. [DOI] [PubMed] [Google Scholar]
- 9.Elting LS, Cooksley CD, Chambers MS, et al. , Risk, outcomes, and costs of radiation-induced oral mucositis among patients with head-and-neck malignancies. Int J Radiat Oncol Biol Phys, 2007. 68(4): p. 1110–20. [DOI] [PubMed] [Google Scholar]
- 10.McDonald MW, Liu Y, Moore MG, et al. , Acute toxicity in comprehensive head and neck radiation for nasopharynx and paranasal sinus cancers: cohort comparison of 3D conformal proton therapy and intensity modulated radiation therapy. Radiation oncology (London, England), 2016. 11: p. 32–32. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Doi H, Tanooka M, Ishida T, et al. , Utility of intraoral stents in external beam radiotherapy for head and neck cancer. Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology, 2017. 22(4): p. 310–318. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Nayar S, Brett R, Clayton N, et al. , The Effect of a Radiation Positioning Stent (RPS) in the Reduction of Radiation Dosage to the Opposing Jaw and Maintenance of Mouth opening after Radiation Therapy. Eur J Prosthodont Restor Dent, 2016. 24(2): p. 71–7. [PubMed] [Google Scholar]
- 13.Allan E, Lu L, Hooman H, et al. , Dosimetric Verification of Dental Stent Efficacy in Head and Neck Radiation Therapy Using Modern Radiation Therapy Techniques: Quality of Life (QOL) and Treatment Compliance Implications. Int J Radiat Oncol Biol Phys, 2016. 94(4): p. 875–876. [Google Scholar]
- 14.Aggarwal H and Kumar P, Radiation stents: Minimizing radiation-induced complications. South Asian journal of cancer, 2014. 3(3): p. 185–185. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Verrone JR, Alves Fde A, Prado JD, et al. , Impact of intraoral stent on the side effects of radiotherapy for oral cancer. Head Neck, 2013. 35(7): p. E213–7. [DOI] [PubMed] [Google Scholar]
- 16.Johnson B, Sales L, Winston A, et al. , Fabrication of customized tongue-displacing stents: Considerations for use in patients receiving head and neck radiotherapy. The Journal of the American Dental Association, 2013. 144(6): p. 594–600. [DOI] [PubMed] [Google Scholar]
- 17.Kaanders JHAM, Fleming TJ, Ang KK, et al. , Devices valuable in head and neck radiotherapy. Int J Radiat Oncol Biol Phys, 1992. 23(3): p. 639–645. [DOI] [PubMed] [Google Scholar]
- 18.Wilke CT, Zaid M, Chung C, et al. , Design and fabrication of a 3D–printed oral stent for head and neck radiotherapy from routine diagnostic imaging. 3D Printing in Medicine, 2017. 3(1): p. 12. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Zaid M, Bajaj N, Burrows H, et al. , Creating customized oral stents for head and neck radiotherapy using 3D scanning and printing. Radiation Oncology, 2019. 14(1): p. 148. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Rosenthal DI, Mendoza TR, Chambers MS, et al. , Measuring head and neck cancer symptom burden: the development and validation of the M. D. Anderson symptom inventory, head and neck module. Head Neck, 2007. 29(10): p. 923–31. [DOI] [PubMed] [Google Scholar]
- 21.Walker E and Nowacki AS, Understanding equivalence and noninferiority testing. Journal of general internal medicine, 2011. 26(2): p. 192–196. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Patzelt SB, Emmanouilidi A, Stampf S, et al. , Accuracy of full-arch scans using intraoral scanners. Clin Oral Investig, 2014. 18(6): p. 1687–94. [DOI] [PubMed] [Google Scholar]
- 23.Naidu D and Freer TJ, Validity, reliability, and reproducibility of the iOC intraoral scanner: A comparison of tooth widths and Bolton ratios. American Journal of Orthodontics and Dentofacial Orthopedics, 2013. 144(2): p. 304–310. [DOI] [PubMed] [Google Scholar]
- 24.Cuperus AM, Harms MC, Rangel FA, et al. , Dental models made with an intraoral scanner: a validation study. Am J Orthod Dentofacial Orthop, 2012. 142(3): p. 308–13. [DOI] [PubMed] [Google Scholar]
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