-
JAMA Otolaryngology-- Head & Neck... Nov 2023Due to lack of data from high-powered randomized clinical trials, the differences in functional and survival outcomes for patients with oropharyngeal squamous cell...
Differences in Functional and Survival Outcomes Between Patients Receiving Primary Surgery vs Chemoradiation Therapy for Treatment of T1-T2 Oropharyngeal Squamous Cell Carcinoma.
IMPORTANCE
Due to lack of data from high-powered randomized clinical trials, the differences in functional and survival outcomes for patients with oropharyngeal squamous cell carcinoma (OPSCC) undergoing primary transoral robotic surgery (TORS) vs primary radiation therapy and/or chemoradiation therapy (RT/CRT) are unclear.
OBJECTIVES
To compare 5-year functional (dysphagia, tracheostomy dependence, and gastrostomy tube dependence) and survivorship outcomes in patients with T1-T2 OPSCC receiving primary TORS vs RT/CRT.
DESIGN, SETTING, AND POPULATION
This national multicenter cohort study used data from a global health network (TriNetX) to identify differences in functional and survival outcomes among patients with OPSCC who underwent primary TORS or RT/CRT in 2002 to 2022. After propensity matching, 726 patients with OPSCC met inclusion criteria. In the TORS group, 363 (50%) patients had undergone primary surgery, and in the RT/CRT group, 363 (50%) patients had received primary RT/CRT. Data analyses were performed from December 2022 to January 2023 using the TriNetX platform.
EXPOSURE
Primary surgery with TORS or primary treatment with radiation therapy and/or chemoradiation therapy.
MAIN OUTCOMES AND MEASURES
Propensity score matching was used to balance the 2 groups. Functional outcomes were measured at 6 months, 1 year, 3 years, 5 years, and more than 5 years posttreatment and included dysphagia, gastrostomy tube dependence, and tracheostomy dependence according to standard medical codes. Five-year overall survivorship was compared between patients undergoing primary TORS vs RT/CRT.
RESULTS
Propensity score matching allowed a study sample with 2 cohorts comprising statistically similar parameters with 363 (50%) patients in each. Patients in the TORS cohort had a mean (SD) age of 68.5 (9.9) vs 68.8 (9.7) years in RT/CRT cohort; 86% and 88% were White individuals, respectively; 79% of patients were men in both cohorts. Primary TORS was associated with clinically meaningful increased risk of dysphagia at 6 months (OR, 1.37; 95% CI, 1.01-1.84) and 1 year posttreatment (OR, 1.71; 95% CI, 1.22-2.39) compared with primary RT/CRT. Patients receiving surgery were less likely to be gastrostomy tube dependent at 6 months (OR, 0.46; 95% CI, 0.21-1.00) and 5 years posttreatment (risk difference, -0.05; 95% CI, -0.07 to -0.02). Differences in overall rates of tracheostomy dependence (OR, 0.97; 95% CI, 0.51-1.82) between groups were not clinically meaningful. Patients with OPSCC, unmatched for cancer stage or human papillomavirus status, who received RT/CRT had worse 5-year overall survival than those who underwent primary surgery (70.2% vs 58.4%; hazard ratio, 0.56; 95% CI, 0.40-0.79).
CONCLUSIONS AND RELEVANCE
This national multicenter cohort study of patients undergoing primary TORS vs primary RT/CRT for T1-T2 OPSCC found that primary TORS was associated with a clinically meaningful increased risk of short-term dysphagia. Patients treated with primary RT/CRT had an increased risk of short- and long-term gastrostomy tube dependence and worse 5-year overall survival than those who underwent surgery.
Topics: Male; Humans; Aged; Female; Squamous Cell Carcinoma of Head and Neck; Oropharyngeal Neoplasms; Cohort Studies; Treatment Outcome; Deglutition Disorders; Robotic Surgical Procedures; Head and Neck Neoplasms
PubMed: 37422846
DOI: 10.1001/jamaoto.2023.1944 -
European Journal of Surgical Oncology :... Jul 2024Transoral Robotic Surgery (TORS) and radiotherapy are considered oncologically equivalent primary treatment options for early-stage HPV-positive oropharyngeal squamous... (Meta-Analysis)
Meta-Analysis Comparative Study
Quality of life outcomes comparing primary Transoral Robotic Surgery (TORS) with primary radiotherapy for early-stage oropharyngeal squamous cell carcinoma: A systematic review and meta-analysis.
BACKGROUND
Transoral Robotic Surgery (TORS) and radiotherapy are considered oncologically equivalent primary treatment options for early-stage HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). Quality of Life (QoL) and Patient Reported Outcome Measures (PROMs) are therefore imperative in supporting clinical decision-making and optimising patient-centred care. The aim of this article is to evaluate how these primary treatment modalities compare in terms of QoL.
MATERIALS AND METHODS
Systematic review and meta-analysis of studies comparing primary TORS and primary radiotherapy for OPSCC using validated QoL tools. Swallowing and global QoL were the primary endpoints with secondary endpoints including all other QoL domains. An inverse variance random-effects model was employed to calculate the weighted estimate of the treatment effects across trials.
RESULTS
A total of six studies collectively reporting on 555 patients were included (n = 236 TORS and n = 319 radiotherapy). Meta-analysis showed no significant difference for swallowing (mean difference = -0.24, p = 0.89) and global QoL (mean difference = 4.55, p = 0.14). For the remaining QoL domains (neck/shoulder impairment, neurotoxicity, voice, xerostomia, speech, and distress), the scarcity of data did not permit meta-analysis. However, the existing data showed no significant difference for any except for xerostomia where TORS appears favourable in the sole study reporting on this.
CONCLUSIONS
TORS and radiotherapy appear to be comparable primary treatment options for early stage OPSCC when it comes to QoL. However, a substantial proportion of patients in the TORS group received adjuvant (chemo)radiotherapy rendering it difficult to establish the 'true' QoL outcomes following surgery alone. There are also minimal studies reporting QoL outcomes beyond swallowing and global QoL. Further research is therefore needed, including more randomised trials adequately powered to detect differences in QoL outcomes.
Topics: Humans; Robotic Surgical Procedures; Quality of Life; Oropharyngeal Neoplasms; Patient Reported Outcome Measures; Neoplasm Staging; Carcinoma, Squamous Cell; Deglutition
PubMed: 38795678
DOI: 10.1016/j.ejso.2024.108434 -
JMIR Public Health and Surveillance Aug 2023The incidence of oropharyngeal squamous cell carcinomas (OPSCC) has increased in recent decades, and human papillomavirus (HPV) infection is the main cause of OPSCC. The...
BACKGROUND
The incidence of oropharyngeal squamous cell carcinomas (OPSCC) has increased in recent decades, and human papillomavirus (HPV) infection is the main cause of OPSCC. The data regarding causes of death (CODs) are vitally important in informing follow-up strategies and revising treatment strategies to deal with any possible preventable treatment-related COD. However, limited studies have assessed the competing COD by HPV status in patients with OPSCC.
OBJECTIVE
We aimed to analyze the distribution of the competing COD according to HPV status in OPSCC.
METHODS
We retrospectively included stage I-IVB patients with OPSCC from the Surveillance, Epidemiology, and End Results database between 2010 and 2015. The association between HPV status and head and neck cancer-specific mortality (HNCSM), second primary cancer mortality (SPCM), and noncancer-caused mortality (NCCM) were analyzed. The chi-square test, Kaplan-Meier analysis, and Fine and Gray model were used for statistical analysis.
RESULTS
We included 5852 patients in this study and 73.2% (n=4283) of them had HPV-related tumors. A total of 1537 (26.3%) patients died, including 789 (51.3%), 333 (21.7%), and 415 (27%) patients who died from head and neck cancer, second cancer, and noncancer causes, respectively. The 5-year HNCSM, SPCM, NCCM, and overall mortality were 14.7%, 6.5%, 7.7%, and 26.4%, respectively. Those with HPV-positive disease had a lower cumulative incidence of HNCSM (subdistribution hazard ratio [sHR] 0.362, 95% CI 0.315-0.417; P<.001), SPCM (sHR 0.400, 95% CI 0.321-0.496; P<.001), and NCCM (sHR 0.460, 95% CI 0.378-0.560; P<.001) than those with HPV-negative disease. The 5-year risk of HNCSM was 26.9% and 10.7% in those with HPV-negative and HPV-positive disease, respectively (P<.001). The 5-year risk of SPCM was 12.4% and 4.6% in those with HPV-negative and HPV-positive disease, respectively (P<.001). The 5-year risk of NCCM of death was 13.7% and 5.8% in those with HPV-negative and HPV-positive disease, respectively (P<.001). Using the Fine and Gray competing-risks model, our results show that those with HPV-negative tumors had a significantly higher risk of HNCSM (P<.001), SPCM (P<.001), and NCCM (P<.001) than those with HPV-negative tumors.
CONCLUSIONS
HPV-positive OPSCC has a lower NCSM, SPCM, and NCCM as compared to those with HPV-negative OPSCC. HPV positivity is a favorable prognostic factor in the context of overcoming cancer as well as in terms of reducing the risk of other CODs in OPSCC. Our finding supports the need to tailor patient follow-up based on the HPV status of patients with OPSCC.
Topics: Humans; Human Papillomavirus Viruses; Papillomavirus Infections; Cause of Death; Retrospective Studies; Data Analysis; Carcinoma
PubMed: 37642982
DOI: 10.2196/47579 -
Head and Neck Pathology Sep 2023Survival rates of head and neck squamous cell carcinoma (HNSCC) have only marginally improved in the last decades. Hence there is a need for predictive biomarkers for...
BACKGROUND
Survival rates of head and neck squamous cell carcinoma (HNSCC) have only marginally improved in the last decades. Hence there is a need for predictive biomarkers for long-time survival that can help to guide treatment decisions and might lead to the development of new therapies. The phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway is the most frequently altered pathway in HNSCC, genes are often mutated, amplificated and overexpressed causing aberrant signaling affecting cell growth and differentiation. Numerous genetic alterations of upstream and downstream factors have currently been clarified. However, their predictive value has yet to be established. Therefore we assess the predictive value of p-mTOR, p-ERK and PTEN expression.
METHODS
Tissue microarrays (TMA's) of HPV-negative patients with oropharyngeal (n = 48), hypopharyngeal (n = 16) or laryngeal (n = 13) SCC, treated with primary chemoradiation (cisplatin/carboplatin/cetuximab and radiotherapy), were histologically stained for p-mTOR, PTEN and p-ERK. Expression was correlated to overall survival (OS), disease free survival (DFS) and locoregional control (LRC). Also p-mTOR was histologically stained in a separate cohort of HNSCC organoids (n = 8) and correlated to mTOR-inhibitor everolimus response.
RESULTS
High p-mTOR expression correlated significantly with worse OS in multivariate analysis in the whole patient cohort [Hazar Ratio (HR) 1.06, 95%CI 1.01-1.11, p = 0.03] and in the cisplatin/carboplatin group with both worse OS (HR 1.09, 95%CI 1.02-1.16, p = 0.02) and DFS (HR 1.06, 95%CI 1.00-1.12, p = 0,04). p-ERK expression correlated significantly with DFS in univariate analysis in the whole patient cohort (HR 1.03, 95%CI 1.00-1.05, p = 0.04) and cisplatin/carboplatin group (HR 1.03, 95%CI 1.00-1.07, p = 0.04). PTEN-expression did not correlate with OS/DFS/LRC. Better organoid response to everolimus correlated significantly to higher p-mTOR expression (Rs = - 0.731, p = 0.04).
CONCLUSIONS
High p-mTOR expression predicts and high p-ERK expression tends to predict worse treatment outcome in HPV negative HNSCC patients treated with chemoradiation, providing additional evidence that these markers are candidate prognostic biomarkers for survival in this patient population. Also this study shows that the use of HNSCC organoids for biomarker research has potential. The role of PTEN expression as prognostic biomarker remains unclear, as consistent evidence on its prognostic and predictive value is lacking.
Topics: Humans; Biomarkers, Tumor; Biopsy; Carboplatin; Carcinoma, Squamous Cell; Cisplatin; Everolimus; Head and Neck Neoplasms; Papillomavirus Infections; Phosphatidylinositol 3-Kinases; Prognosis; PTEN Phosphohydrolase; Squamous Cell Carcinoma of Head and Neck; TOR Serine-Threonine Kinases; Extracellular Signal-Regulated MAP Kinases
PubMed: 37486536
DOI: 10.1007/s12105-023-01576-4 -
Anticancer Research Sep 2023Otorhinolaryngology tradition is that tonsillectomy (TE) is conducted among children and adolescents for obstructive sleep apnea secondary to adenotonsillar hypertrophy... (Meta-Analysis)
Meta-Analysis Review
Tonsillectomy as Prevention of Tonsil and Base of Tongue Cancer: Systematic Review and Meta-analysis on the Immuno-Oncological Effect of One Among the Most Common Surgeries in the World.
Otorhinolaryngology tradition is that tonsillectomy (TE) is conducted among children and adolescents for obstructive sleep apnea secondary to adenotonsillar hypertrophy and in adults for chronic disease of the tonsils and adenoids (recurrent tonsillitis). Nevertheless, over the last 50 years, we have observed a decline in TE worldwide. As a result, there is an emerging concern of a correlated possible increased risk of tonsil cancer (TC) and other subtypes of oropharyngeal squamous cell carcinoma. Since the available data on such topics are limited and controversial, our aim was to elucidate the impact of TE on the incidence mainly of TC through a systematic review of the literature and a meta-analysis of the studies. After a thorough search, 7 retrospective studies were considered eligible for review and meta-analysis (MA). At MA, patients with a history of TE seem to show a reduced risk of TC but a higher predisposition for base of tongue (BOT) cancer (p<0.001): however, the elevated heterogeneity of the studies hampers drawing firm and convincing conclusions (statistical inconsistency >95%). In future, randomized control trials will be welcome to elucidate the prophylactic role of TE against TC and its real impact on BOT cancer.
Topics: Adolescent; Adult; Child; Humans; Palatine Tonsil; Tonsillectomy; Tongue Neoplasms; Retrospective Studies; Oropharyngeal Neoplasms; Tonsillar Neoplasms; Laryngeal Neoplasms; Head and Neck Neoplasms
PubMed: 37648322
DOI: 10.21873/anticanres.16575 -
JAMA Otolaryngology-- Head & Neck... Nov 2023There is growing interest in the use of circulating plasma tumor human papillomavirus (HPV) DNA for diagnosis and surveillance of patients with HPV-associated...
IMPORTANCE
There is growing interest in the use of circulating plasma tumor human papillomavirus (HPV) DNA for diagnosis and surveillance of patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Recent advances in the assays, combining the identification of circulating HPV tumor DNA and tumor DNA fragment analysis (tumor tissue-modified viral [TTMV]-HPV DNA), have been shown to be highly accurate. However, use of these newer techniques has been limited to small cohort studies and clinical trials.
OBJECTIVE
To establish the clinical efficacy of plasma TTMV-HPV DNA testing in the diagnosis and surveillance of HPV-associated OPSCC in a contemporary clinical setting.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective observational cohort study included patients with OPSCC who underwent TTMV-HPV DNA testing between April 2020 and September 2022 during the course of routine clinical care. For the diagnosis cohort, patients with at least 1 TTMV-HPV DNA measurement prior to initiation of primary therapy were included. Patients were included in the surveillance cohort if they had at least 1 TTMV-HPV DNA test performed after completion of definitive or salvage therapy.
MAIN OUTCOMES AND MEASURES
Per-test performance metrics, including sensitivity, specificity, positive predictive value, and negative predictive value, for TTMV-HPV DNA testing.
RESULTS
Of 399 patients included in the analysis, 163 were in the diagnostic cohort (median [IQR] age, 63 [56-68.5] years; 142 [87.1%] male), and 290 were in the surveillance cohort (median [IQR] age, 63 [57-70] years; 237 [81.7%] male). Of the 163 patients in the diagnostic cohort, 152 (93.3%) had HPV-associated OPSCC while 11 (6.7%) had HPV-negative OPSCC. The TTMV-HPV DNA sensitivity in pretreatment diagnosis was 91.5% (95% CI, 85.8%-95.4% [139 of 152 tests]), and the specificity was 100% (95% CI, 71.5%-100% [11 of 11 tests]). In the surveillance cohort, 591 tests conducted in 290 patients were evaluated. A total of 23 patients had molecularly confirmed pathologic recurrences. The TTMV-HPV DNA test demonstrated sensitivity of 88.4% (95% CI, 74.9%-96.1% [38 of 43 tests]) and specificity of 100% (95% CI, 99.3%-100% [548 of 548 tests]) in detecting the recurrences. Positive predictive value was 100% (95% CI, 90.7%-100% [38 of 38 tests]), and negative predictive value was 99.1% (95% CI, 97.9%-99.7% [548 of 553 tests]). The median (range) lead time from positive TTMV-HPV DNA test to pathologic confirmation was 47 (0-507) days.
CONCLUSIONS AND RELEVANCE
This cohort study demonstrated that when evaluated in a clinical setting, the TTMV-HPV DNA assay demonstrated 100% specificity in both diagnosis and surveillance. However, the sensitivity was 91.5% for the diagnosis cohort and 88.4% for the surveillance cohort, signifying that nearly 1 in 10 negative tests among patients with HPV-associated OPSCC was a false negative. Additional research is required to validate the assay's performance and, if validated, then further research into the implementation of this assay into standard clinical practice guidelines will be required.
Topics: Humans; Male; Middle Aged; Female; Human Papillomavirus Viruses; Cohort Studies; Retrospective Studies; Papillomavirus Infections; Carcinoma, Squamous Cell; Oropharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Liquid Biopsy
PubMed: 37422913
DOI: 10.1001/jamaoto.2023.1937 -
JAMA Oncology Dec 2023Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma has an overall favorable prognosis, yet a subset of patients will experience devastating... (Review)
Review
IMPORTANCE
Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma has an overall favorable prognosis, yet a subset of patients will experience devastating disease recurrence. Current surveillance standards for detection of recurrent disease are imperfect. There is growing interest in improving detection of recurrent disease through the use of plasma-based assays able to detect circulating tumor HPV DNA.
OBSERVATIONS
Although most circulating tumor HPV DNA assays remain in the research domain, the circulating tumor tissue-modified viral HPV DNA assay became commercially available in the United States in early 2020 and has been increasingly used in the clinical setting. With the rapidly increasing incidence of HPV-positive oropharyngeal squamous cell carcinoma and concomitant expansion of biomarker capabilities for this disease, it is critical to reexamine current posttreatment surveillance practices and to determine whether emerging technologies may be used to improve outcomes for a growing survivor population. However, caution is advised; it is not yet known whether biomarker-based surveillance is truly beneficial, and as is true with any intervention, it has the capacity to cause harm.
CONCLUSIONS AND RELEVANCE
Using Margaret Pepe's classic 5 phases of biomarker development for early detection of cancer as a framework, this article reviews the current state of knowledge, highlights existing knowledge gaps, and suggests research that should be prioritized to understand the association between biomarker-based surveillance and patient outcomes. Specific attention is paid to the commercially available tumor tissue-modified viral HPV DNA assay, given its increasing clinical use. This review may serve as a road map for future research and a guide for clinicians considering its adoption in practice. Enrollment of patients into clinical trials incorporating biomarker-based surveillance should be prioritized.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Oropharyngeal Neoplasms; Papillomavirus Infections; Neoplasm Recurrence, Local; Head and Neck Neoplasms; Biomarkers; DNA, Viral; Papillomaviridae
PubMed: 37824111
DOI: 10.1001/jamaoncol.2023.4042 -
Head & Neck Sep 2023Treatment of patients with newly diagnosed HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) with neoadjuvant chemotherapy (NAC) results in a high rate of...
BACKGROUND
Treatment of patients with newly diagnosed HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) with neoadjuvant chemotherapy (NAC) results in a high rate of 5-year recurrence free survival with few patients requiring adjuvant treatment. We hypothesized that NAC enhances primary tumor HPV-specific T cell responses.
METHODS
HPV-specific responses in tumor infiltrating lymphocytes (TILs) before and after NAC were determined using autologous co-culture assays.
RESULTS
Greater HPV16-specific TIL responses, sometimes polyclonal, were observed after NAC compared to before in 8 of 10 patients (80%) with PCR-verified HPV16-positive tumors. A significant association was observed between net-negative change in HPV-specific TIL response and disease relapse (p = 0.04, Mann-Whitney test), whereas pathologic complete response at time of surgery did not correlate with recurrence.
CONCLUSIONS
NAC induces HPV-specific tumor T cell responses in patients with newly diagnosed HPV-associated OPSCC; whereas lack of an increase following NAC may associate with risk of relapse.
Topics: Humans; T-Lymphocytes; Prognosis; Neoadjuvant Therapy; Papillomavirus Infections; Neoplasm Recurrence, Local; Oropharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms
PubMed: 37480219
DOI: 10.1002/hed.27463 -
Journal of Oral Pathology & Medicine :... Nov 2023We aimed to establish image recognition and survival prediction models using a novel scoring system of cyclin D1 expression pattern in patients with human...
BACKGROUND
We aimed to establish image recognition and survival prediction models using a novel scoring system of cyclin D1 expression pattern in patients with human papillomavirus-negative oral or oropharyngeal squamous cell carcinoma.
METHODS
The clinicopathological data of 610 patients with human papillomavirus-negative oral/oropharyngeal squamous cell carcinoma were analyzed retrospectively. Cox univariate and multivariate risk regression analyses were performed to compare cyclin D1 expression pattern scoring with the traditional scoring method-cyclin D1 expression level scoring-in relation to patients' overall and progression-free survival. An image recognition model employing the cyclin D1 expression pattern scoring system was established by YOLOv5 algorithms. From this model, two independent survival prediction models were established using the DeepHit and DeepSurv algorithms.
RESULTS
Cyclin D1 had three expression patterns in oral and oropharyngeal squamous cell carcinoma cancer nests. Superior to cyclin D1 expression level scoring, cyclin D1 expression pattern scoring was significantly correlated with the prognosis of patients with oral squamous cell carcinoma (p < 0.0001) and oropharyngeal squamous cell carcinoma (p < 0.05). Moreover, it was an independent prognostic risk factor in both oral squamous cell carcinoma (p < 0.0001) and oropharyngeal squamous cell carcinoma (p < 0.05). The cyclin D1 expression pattern-derived image recognition model showed an average test set accuracy of 78.48% ± 4.31%. In the overall survival prediction models, the average concordance indices of the test sets established by DeepSurv and DeepHit were 0.71 ± 0.02 and 0.70 ± 0.01, respectively.
CONCLUSION
Combined with the image recognition model of the cyclin D1 expression pattern, the survival prediction model had a relatively good prediction effect on the overall survival prognosis of patients with human papillomavirus-negative oral or oropharyngeal squamous cell carcinoma.
Topics: Humans; Carcinoma, Squamous Cell; Cyclin D1; Deep Learning; Head and Neck Neoplasms; Mouth Neoplasms; Oropharyngeal Neoplasms; Papillomavirus Infections; Prognosis; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck
PubMed: 37701976
DOI: 10.1111/jop.13482 -
Radiotherapy and Oncology : Journal of... Nov 2023Osteoradionecrosis (ORN) of the mandible is a severe complication following radiotherapy (RT). With a renewed interest in hypofractionation for head and neck...
BACKGROUND AND PURPOSE
Osteoradionecrosis (ORN) of the mandible is a severe complication following radiotherapy (RT). With a renewed interest in hypofractionation for head and neck radiotherapy, more information concerning ORN development after high fraction doses is important. The aim of this explorative study was to develop a model for ORN risk prediction applicable across different fractionation schemes using Equivalent Uniform Doses (EUD).
MATERIAL AND METHODS
We performed a retrospective cohort study in 334 oropharyngeal squamous cell carcinoma (OPSCC) patients treated with either a hypofractionated Stereotactic Body Radiation Therapy (HF-SBRT) boost or conventional Intensity Modulated Radiation Therapy (IMRT). ORN was scored with the CTCAE v5.0. HF-SBRT and IMRT dose distributions were converted into equivalent dose in 2 Gy fractions (α/β = 0.85 Gy) and analyzed using EUD. The parameter a that led to an EUD that best discriminated patients with and without grade ≥ 2 ORN was selected. Patient and treatment-related risk factors of ORN were analyzed with uni- and multivariable regression analysis.
RESULTS
A total of 32 patients (9.6%) developed ORN grade ≥ 2. An EUD(a = 8) best discriminated between ORN and non-ORN (AUC = 0.71). In multivariable regression, pre-RT extractions (SHR = 2.34; p = 0.012), mandibular volume (SHR = 1.04; p = 0.003), and the EUD(a = 8) (SHR = 1.14; p < 0.001) were significantly associated with ORN.
CONCLUSION
Risk models for ORN based on conventional DVH parameters cannot be directly applied to HF-SBRT fractionation schemes and dose distributions. However, after correcting for fractionation and non-uniform dose distributions using EUD, a single model can distinguish between ORN and non-ORN after conventionally fractionated radiotherapy and hypofractionated boost treatments.
PubMed: 37659662
DOI: 10.1016/j.radonc.2023.109889