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Advances in Radiation Oncology Apr 2024For patients with head and neck squamous cell carcinoma (HNSCC), locoregional failure and second primary tumors are common indications for adjuvant reirradiation...
PURPOSE
For patients with head and neck squamous cell carcinoma (HNSCC), locoregional failure and second primary tumors are common indications for adjuvant reirradiation (re-RT). Given an absence of clear consensus on the role of adjuvant re-RT, we sought to assess histopathologic risk factors of patients with HNSCC and their resulting outcomes after adjuvant re-RT with proton therapy.
METHODS AND MATERIALS
We conducted a retrospective analysis of patients with HNSCC who underwent salvage surgery at our institution followed by adjuvant re-RT with proton therapy over 1.5 years. All included patients received prior radiation therapy. The Kaplan-Meier method was used to evaluate locoregional recurrence-free survival and overall survival.
RESULTS
The cohort included 22 patients, with disease subsites, including oropharynx, oral cavity, hypopharynx, larynx, and nasopharynx. Depending on adverse pathologic features, adjuvant re-RT to 66 Gy (32% of cohort) or 60 Gy (68%), with (59%) or without (41%) concurrent systemic therapy was administered. The majority (86%) completed re-RT with no reported treatment delay; 3 patients experienced grade ≥3 acute Common Terminology Criteria for Adverse Events toxicity and no patient required enteral feeding tube placement during re-RT. Median follow-up was 21.0 months (IQR, 11.7-25.2 months). Five patients had biopsy-proven disease recurrences a median of 5.9 months (IQR, 3.8-9.7 months) after re-RT. Locoregional recurrence-free survival was 95.2%, 70.2%, 64.8% at 6, 12, and 24 months, respectively. OS was 100%, 79.2%, and 79.2% at 6, 12, and 24 months, respectively. Four patients had osteoradionecrosis on imaging a median of 13.2 months (IQR, 8.7-17.4 months) after re-RT, with 2 requiring surgical intervention.
CONCLUSIONS
Adjuvant re-RT for patients with HNSCC was well-tolerated and offered reasonable local control in this high-risk cohort but appears to be associated with a risk of osteoradionecrosis. Additional study and longer follow-up could help define optimal patient management in this patient population.
PubMed: 38778826
DOI: 10.1016/j.adro.2023.101418 -
World Journal of Oncology Jun 2024This study assessed clinical outcomes of three-dimensional-printed template (3DPT)-guided radioactive seed brachytherapy (RSBT) via a submental approach for recurrent...
BACKGROUND
This study assessed clinical outcomes of three-dimensional-printed template (3DPT)-guided radioactive seed brachytherapy (RSBT) via a submental approach for recurrent base of tongue and floor of mouth cancer.
METHODS
Thirty-one patients with recurrent lingual and floor of mouth squamous cell carcinoma after surgery and radiotherapy were treated with 3DPT-guided RSBT from 2015 to 2022. Seeds were implanted through a submental approach guided by 3DPTs. Local control (LC), overall survival (OS), disease control (DC) and quality of life (QOL) were evaluated.
RESULTS
The median follow-up was 13.7 months. The 1-, 3- and 5-year LC rates were 66.1%, 66.1%, and 55.1% respectively. The 1-, 3- and 5-year OS rates were 63.4%, 33.4%, and 8.3%. The 1-, 3- and 5-year DC rates were 37.8%, 26.5%, and 21.2%. Univariate analysis showed tumor size significantly affected LC (P = 0.031). The presence of extraterritorial lesions affected DC and OS on multivariate analysis (P < 0.01). QOL improved significantly in domains of pain, swallowing, chewing, taste, and emotion after treatment compared to baseline. Four patients (13%) developed necrosis and osteoradionecrosis.
CONCLUSIONS
3DPT-guided submental RSBT provided favorable LC and QOL for recurrent tongue/floor of mouth cancer with minimal toxicity; moreover, severe toxicity should be noted.
PubMed: 38751702
DOI: 10.14740/wjon1775 -
Scientific Reports May 2024Our study aimed to estimate the prevalence of total free flap failure following free flap reconstruction for mandibular osteoradionecrosis (mORN) and assess the impact... (Meta-Analysis)
Meta-Analysis
Our study aimed to estimate the prevalence of total free flap failure following free flap reconstruction for mandibular osteoradionecrosis (mORN) and assess the impact of potential moderators on this outcome. A comprehensive systematic literature search was independently conducted by two reviewers using the Medline, Scopus, Web of Science and Cochrane Library databases. Quality assessment of the selected studies was performed, and prevalence estimates with 95% confidence intervals (CI) were calculated. Outlier and influential analyses were conducted, and meta-regression analyses was employed to investigate the effects of continuous variables on the estimated prevalence. Ultimately, forty-six eligible studies (involving 1292 participants and 1344 free flaps) were included in our meta-analysis. The findings of our study revealed a prevalence of 3.1% (95% CI 1.3-5.4%) for total free flap failure after reconstruction for mORN. No study was identified as critically influential, and meta-regression analysis did not pinpoint any potential sources of heterogeneity. These findings provide valuable insights for researchers and serve as a foundation for future investigations into the management of mandibular osteoradionecrosis and the prevention of free flap failure in this context.
Topics: Humans; Osteoradionecrosis; Free Tissue Flaps; Prevalence; Plastic Surgery Procedures; Mandibular Diseases; Mandibular Reconstruction; Mandible
PubMed: 38750124
DOI: 10.1038/s41598-024-61862-1 -
Clinical and Translational Radiation... Jul 2024Current segmentation approaches for radiation treatment planning in head and neck cancer patients (HNCP) typically consider the entire mandible as an organ at risk,...
BACKGROUND
Current segmentation approaches for radiation treatment planning in head and neck cancer patients (HNCP) typically consider the entire mandible as an organ at risk, whereas segmentation of the maxilla remains uncommon. Accurate risk assessment for osteoradionecrosis (ORN) or implant-based dental rehabilitation after radiation therapy may require a nuanced analysis of dose distribution in specific mandibular and maxillary segments. Manual segmentation is time-consuming and inconsistent, and there is no definition of jaw subsections.
MATERIALS AND METHODS
The mandible and maxilla were divided into 12 substructures. The model was developed from 82 computed tomography (CT) scans of HNCP and adopts an encoder-decoder three-dimensional (3D) U-Net structure. The efficiency and accuracy of the automated method were compared against manual segmentation on an additional set of 20 independent CT scans. The evaluation metrics used were the Dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), and surface DSC (sDSC).
RESULTS
Automated segmentations were performed in a median of 86 s, compared to manual segmentations, which took a median of 53.5 min. The median DSC per substructure ranged from 0.81 to 0.91, and the median HD95 ranged from 1.61 to 4.22. The number of artifacts did not affect these scores. The maxillary substructures showed lower metrics than the mandibular substructures.
CONCLUSIONS
The jaw substructure segmentation demonstrated high accuracy, time efficiency, and promising results in CT scans with and without metal artifacts. This novel model could provide further investigation into dose relationships with ORN or dental implant failure in normal tissue complication prediction models.
PubMed: 38712013
DOI: 10.1016/j.ctro.2024.100780 -
Acta Oncologica (Stockholm, Sweden) May 2024
Topics: Humans; Osteoradionecrosis; Head and Neck Neoplasms; Risk Factors; Male; Middle Aged; Female; Radiotherapy Dosage; Aged; Mandibular Diseases; Adult
PubMed: 38711314
DOI: 10.2340/1651-226X.2024.35222 -
International Journal of Radiation... Apr 2024Osteoradionecrosis (ORN) of the mandible remains a significant complication in the intensity modulated radiation therapy (IMRT) era. Dental dose cannot be predicted from...
PURPOSE
Osteoradionecrosis (ORN) of the mandible remains a significant complication in the intensity modulated radiation therapy (IMRT) era. Dental dose cannot be predicted from heterogeneous IMRT dose distributions; mandibular dose metrics cannot guide dentist avulsion decisions in high-risk ORN situations. Using a mapping tool to report dental root dose, avulsions, and ORN sites, we re-examined ORN risk factors in a case-control study.
METHODS AND MATERIALS
From 2008 to 2019, 897 consecutive patients with oral cavity/oropharynx or unknown primary cancer undergoing IMRT were analyzed to identify ORN cases. These were matched (1 ORN/2 controls) retrospectively for tumor location, surgery, and tobacco consumption in a monocentric case-control study. Univariate and multivariate analyses integrated ORN factors and accurate dental dose data (grouped into 4 mandibular sectors). Generalizability was investigated in a simulated population database.
RESULTS
A total of 171 patients were included. The median follow-up was 5.2 and 4.5 years in the ORN and control groups, respectively. The median time to ORN was 12 months. In univariate analysis, post-IMRT avulsions at the ORN site (hazard ratio [HR] = 3.6; 95% confidence interval [CI] = 1.5-8.9; P = .005), tumor laterality (HR, 4.4; 95% CI, = 1.4-14, P = .01), mean mandibular dose (HR, 1.1; 95% CI, = 1.01-1.1; P = .018) and mean dose to the ORN site (HR, 1.1; 95% CI, = 1.1-1.2; P < .001) correlated with higher ORN risk. In multivariate analysis, mean dose to the ORN site (HR, 1.1; 95% CI, = 1.1-1.2; P < .001) and post-IMRT avulsions at the ORN site (HR, 4.6; 95% CI, = 1.5-14.7; P = .009) were associated with ORN. For each increase in gray in dental dose, the ORN risk increased by 12%. Simulations confirmed study observations.
CONCLUSIONS
Dental dose and avulsions are associated with ORN, with a 12% increase in risk with each additional gray. Accurate dose information can help dentists in their decisions after IMRT.
PubMed: 38685504
DOI: 10.1016/j.ijrobp.2024.04.019 -
Dentistry Journal Mar 2024Osteoradionecrosis of the jaw is a morbid complication of radiotherapy in patients with oral and oropharyngeal cancers that may be precipitated by dental extractions....
Prophylactic Use of Pentoxifylline and Tocopherol for Prevention of Osteoradionecrosis of the Jaw after Dental Extraction in Post-Radiated Oral and Oropharyngeal Cancer Patients: An Initial Case Series.
Osteoradionecrosis of the jaw is a morbid complication of radiotherapy in patients with oral and oropharyngeal cancers that may be precipitated by dental extractions. Pentoxifylline and tocopherol (PENTO) has been utilized in the management of osteoradionecrosis and as prophylaxis for post-radiated head and neck oncology patients requiring an invasive dental procedure. This observational study aims to report the outcome of the prophylactic use of PENTO in the prevention of osteoradionecrosis of the jaw after dental extractions in post-radiated oral and oropharyngeal cancer patients and to review the current literature on this topic. Four post-radiated oral and oropharyngeal oncology patients were referred to the dental oncology clinic of the University Dental Practice, University of Tennessee Health Sciences Center for dental extractions. All four patients were prescribed pentoxifylline 400 mg BID (twice a day) and tocopherol 400 IU BID (oral tablets) for 2 weeks before extraction(s) and for 6 weeks after extraction(s). All patients were followed up every week after the second week post-extraction if feasible until the extraction site(s) healed (covered by mucosa). The assessment endpoint was defined as 6 weeks post-extraction with the outcomes assessed as using four categories determined by the area of exposed bone: complete healing (complete mucosal coverage of extraction site); partial healing (reduction in size of extraction site); no change; and progression (increase in size of the extraction site). At the assessment endpoint, all patients had complete healing of all extraction sites. The ORN rate at the patient level (0/4) and individual tooth level (0/8) was 0%. All patients tolerated the PENTO medications and no adverse effects from the use of these medications were reported. This limited study in addition to the other reviewed studies estimates the rate of ORN at the patient level as 3.2% (14/436) for post-radiated head and neck oncology patients after dental extractions/invasive oral procedures. In conclusion, this PENTO regimen can reduce/prevent the incidence of ORN in post-radiated head and neck oncology patients. This safe and cost-effective protocol (PENTO regimen) should be further evaluated as prophylaxis for post-radiated head and neck oncology patients requiring an invasive dental procedure. We recommend large prospective studies to be carried out to further validate these findings.
PubMed: 38667995
DOI: 10.3390/dj12040083 -
Frontiers in Oncology 2024Major advances have been made in reconstructive surgery in the last decades to reduce morbidity in head and neck cancer. Flaps are now present in 80% of patients with... (Review)
Review
Reconstructive flap surgery in head and neck cancer patients: an interdisciplinary view of the challenges encountered by radiation oncologists in postoperative radiotherapy.
BACKGROUND
Major advances have been made in reconstructive surgery in the last decades to reduce morbidity in head and neck cancer. Flaps are now present in 80% of patients with oral cavity cancer to cover anatomic, functional, and cosmetic needs. However, gaps in interdisciplinary innovation transfer from surgery to postoperative radiotherapy (poRT) remain challenging. We aimed to provide an interdisciplinary view of the challenges encountered by radiation oncologists in planning head and neck postoperative radiotherapy.
METHODS
A systematic and critical review was conducted to address areas of optimization in surgery and radiology that may be relevant to poRT.
RESULTS
Despite extensive surgical literature on flap techniques and salvage surgery, 13 retrospective series were identified, where flap outcomes were indirectly compared between surgery alone or poRT. These low-evidence studies suggest that radiotherapy accelerates flap atrophy, fibrosis, and osteoradionecrosis and deteriorates functional outcomes. Preliminary evidence suggests that tumor spread occurs at the flap-tissue junction rather than in the flaps. One prospective 15-patient study showed 31.3% vs. 39.2% flap volume reduction without or with poRT. In an international consensus, experts recognized the needs for optimized flap-sparing poRT against flap-related functional deterioration and bone damage. CT, MRI, and PET-CT modalities show potential for the delineation of the junction area between native tissues and flap for flap segmentation and to characterize flap-specific changes quantitatively and correlate them with patterns of relapse or complications.
CONCLUSION
Flap management in poRT is insufficiently documented, but poRT seems to damage flaps. Current gaps in knowledge underscore the need for prospective flap assessment and interdisciplinary trials investigating flap morbidity minimization by flap-sparing poRT planning.
PubMed: 38665951
DOI: 10.3389/fonc.2024.1379861 -
MedRxiv : the Preprint Server For... Apr 2024Osteoradionecrosis of the jaw (ORNJ) is a severe iatrogenic disease characterized by bone death after radiation therapy (RT) to the head and neck. With over 9 published...
International Expert-Based Consensus Definition, Staging Criteria, and Minimum Data Elements for Osteoradionecrosis of the Jaw: An Inter-Disciplinary Modified Delphi Study.
PURPOSE
Osteoradionecrosis of the jaw (ORNJ) is a severe iatrogenic disease characterized by bone death after radiation therapy (RT) to the head and neck. With over 9 published definitions and at least 16 diagnostic/staging systems, the true incidence and severity of ORNJ are obscured by lack of a standard for disease definition and severity assessment, leading to inaccurate estimation of incidence, reporting ambiguity, and likely under-diagnosis worldwide. This study aimed to achieve consensus on an explicit definition and phenotype of ORNJ and related precursor states through data standardization to facilitate effective diagnosis, monitoring, and multidisciplinary management of ORNJ.
METHODS
The ORAL Consortium comprised 69 international experts, including representatives from medical, surgical, radiation oncology, and oral/dental disciplines. Using a web-based modified Delphi technique, panelists classified descriptive cases using existing staging systems, reviewed systems for feature extraction and specification, and iteratively classified cases based on clinical/imaging feature combinations.
RESULTS
The Consortium ORNJ definition was developed in alignment with SNOMED-CT terminology and recent ISOO-MASCC-ASCO guideline recommendations. Case review using existing ORNJ staging systems showed high rates of inability to classify (up to 76%). Ten consensus statements and nine minimum data elements (MDEs) were outlined for prospective collection and classification of precursor/ORNJ stages.
CONCLUSION
This study provides an international, consensus-based definition and MDE foundation for standardized ORNJ reporting in cancer survivors treated with RT. Head and neck surgeons, radiation, surgical, medical oncologists, and dental specialists should adopt MDEs to enable scalable health information exchange and analytics. Work is underway to develop both a human- and machine-readable knowledge representation for ORNJ (i.e., ontology) and multidisciplinary resources for dissemination to improve ORNJ reporting in academic and community practice settings.
PubMed: 38645105
DOI: 10.1101/2024.04.07.24305400 -
Radiotherapy and Oncology : Journal of... Apr 2024To assess osteoradionecrosis (ORN) incidence in a population of Irish Head and Neck cancer (HNC) patients, and assess precipitating factors that may contribute to ORN...
BACKGROUND AND PURPOSES
To assess osteoradionecrosis (ORN) incidence in a population of Irish Head and Neck cancer (HNC) patients, and assess precipitating factors that may contribute to ORN development to aid prevention.
MATERIALS AND METHODS
Review of 1050 HNC patients attending the Dental Oncology Clinic, CUDSH between 2010 and 2021 identified 47 cases of ORN. Medical, dental and radiotherapy records of these forty-seven patients were retrospectively reviewed. Patient-, tumour-, and treatment-related variables were investigated in association with osteoradionecrosis development. Analysis conducted using SPSS, Pearson's Chi-square test (p < 0.05), and ordinal regression model.
RESULTS
ORN incidence was 4.4 %. Median time from radiotherapy (RT) to ORN development was 9.5 months (range 1-98.5 months). ORN development within the mandibular surgical site was significant (p <.001), presenting at a higher Notani grade (p =.002), in mid-mandibular body region (p =.028), at radiation doses ≥ 60 Gy (p =.035), due to induced causes (p =.029), and without resolution (p =.019).
CONCLUSION
This is the first retrospective study of ORN in HNC patients in Ireland over 10-year period. ORN incidence was extremely low (4.4%). As patients reported high smoking/alcohol use and poor dental attendance pre-diagnosis, this suggests intensive dental intervention pre/post-diagnosis contributed to low ORN rates. Mandibular surgery pre-RT increased risk of developing ORN at the surgical site. Therefore, we recommend future treatment planning should contour the surgical site, designating it an organ at risk (OAR), assigning a dose constraint, where oncologically possible, with emphasis on reducing the hot-spot to this region; findings reinforce importance of life-long expert dental care to reduce ORN incidence.
PubMed: 38641259
DOI: 10.1016/j.radonc.2024.110286