Outcomes of carcinoma ex pleomorphic adenoma compared to de novo adenocarcinoma of major salivary glands.

BACKGROUND AND OBJECTIVES: Carcinoma ex pleomorphic adenoma (CXPA) is a rare disease of the major salivary glands that remains poorly characterized. Our objective was to compare the clinical outcomes of patients with CXPA of the major salivary glands to those with de novo adenocarcinomas. METHODS: Review of the NCDB between 2004 and 2016 to compare cases of CXPA and adenocarcinoma of major salivary glands. Demographics, clinical characteristics, and survival were analyzed. RESULTS: We identified 1181 patients with CXPA and 3326 patients with adenocarcinoma of major salivary glands. Adenocarcinomas presented with higher rates of nodal metastasis (54.7% vs. 30.4%, p < .001). Five-year survival of adenocarcinoma (55.8%) was worse than that of CXPA (68.5%, p < .001). When stratified by nodal status, there was no significant difference in 5-year survival between CXPA and adenocarcinoma node-negative (75.3% vs. 71.6%, respectively) and node-positive (40.4% vs. 36.1%, respectively) patients. CONCLUSIONS: CXPAs of the major salivary glands present at an earlier stage with lower rates of regional metastasis compared to adenocarcinomas. After controlling for lymph node metastases, the outcomes are quite similar.

Improved survival in women versus men with merkel cell carcinoma.

BACKGROUND: Studies have observed that women have better outcomes than men in melanoma, but less is known about the influence of sex differences on outcomes for other aggressive cutaneous malignancies. OBJECTIVE: To investigate whether women and men have disparate outcomes in Merkel cell carcinoma (MCC). METHODS: Patients with nonmetastatic MCC undergoing surgery and lymph node evaluation were identified from the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier analysis and Cox proportional hazards regression models were used for overall survival, and competing-risks analysis and Fine-Gray models were used for cause-specific and other-cause mortality. RESULTS: The NCDB cohort (n = 4178) included 1516 (36%) women. Women had a consistent survival advantage compared with men in propensity score-matched analysis (66.0% vs 56.8% at 5 years, P < .001) and multivariable Cox regression (hazard ratio, 0.68; 95% confidence interval, 0.61-0.75; P < .001). Similarly, women had a survival advantage in the SEER validation cohort (n = 1202) with 457 (38.0%) women, which was entirely due to differences in MCC-specific mortality (5-year cumulative incidence: 16.4% vs 26.7%, P = .002), with no difference in other-cause mortality (16.8% vs 17.8%, P = .43) observed in propensity score-matched patients. LIMITATIONS: Potential selection bias from a retrospective data set. CONCLUSION: In MCC, women have improved survival compared with men, driven by MCC-related mortality.

Human papillomavirus and survival of patients with sinonasal squamous cell carcinoma.

BACKGROUND: To the authors' knowledge, the question of whether human papillomavirus (HPV) infection is associated with outcomes in patients with sinonasal squamous cell carcinoma (SNSCC) is not well studied at this time. In the current study, the authors investigated patterns of HPV testing and its association with survival in patients with SNSCC using the National Cancer Data Base. METHODS: The authors selected all SNSCC cases diagnosed between 2010 and 2016. HPV testing practices, clinicodemographic factors, treatments, and survival were analyzed. Multivariable Cox regression and propensity score-matched survival analyses were performed. RESULTS: A total of 6458 SNSCC cases were identified. Of these, only 1523 cases (23.6%) were tested for HPV and included in the current study. The median patient age was 64 years and the majority had advanced stage tumors (overall AJCC stage III-IV, 721 patients; 62.1%). HPV-positive SNSCC comprised 31.5% (447 of 1418 cases) of the final study cohort. Among 15 hospitals that routinely tested nonoropharyngeal SCCs for HPV, the percentage of HPV-positive SNSCCs was smaller (24.6%; P = .04). Patients with HPV-positive SNSCC were younger (aged 60 years vs 65 years; P < .001), with tumors that were more likely to be high grade (55.3% vs 41.7%; P < .001), and attributed to the nasal cavity (62.2% vs 44.0%; P < .001). HPV-positive SNSCC was associated with significantly improved overall survival in multivariable regression analysis (hazard ratio, 0.45; 95% CI, 0.28-0.72 [P = .001]) and propensity score-matched (hazard ratio, 0.61; 95% CI, 0.38-0.96 [P = .03]) analyses controlling for clinicodemographic and treatment factors. CONCLUSIONS: Currently, only a minority of patients with SNSCC are tested for HPV. However, a sizable percentage of SNSCC cases may be HPV related; furthermore, HPV-positive SNSCC is associated with improved overall survival. Routine HPV testing may be warranted in patients with SNSCC.

Adaptive radiotherapy based on statistical process control for oropharyngeal cancer.

PURPOSE: The purpose of this study is to quantify dosimetric changes throughout the delivery of oropharyngeal cancer treatment and to investigate the application of statistical process control (SPC) for the management of significant deviations during the course of radiotherapy. METHODS: Thirteen oropharyngeal cancer patients with daily cone beam computed tomography (CBCT) were retrospectively reviewed. Cone beam computed tomography images of every other fraction were imported to the Velocity software and registered to planning CT using the 6 DOF (degrees of freedom) couch shifts generated during patient setup. Using Velocity "Adaptive Monitoring" module, the setup-corrected CBCT was matched to planning CT using a deformable registration. Volumes and dose metrics at each fraction were calculated and rated with plan values to evaluate interfractional dosimetric variations using a SPC framework. T-tests between plan and fraction volumes were performed to find statistically insignificant fractions. Average upper and lower process capacity limits (UCL, LCL) of each dose metric were derived from these fractions using conventional SPC guidelines. RESULTS: Gross tumor volume (GTV) and organ at risk (OAR) volumes in the first 13 fractions had no significant changes from the pretreatment planning CT. The GTV and the parotid glands subsequently decreased by 10% at the completion of treatment. There were 3-4% increases in parotid mean doses, but no significant differences in dose metrics of GTV and other OARs. The changes were organ and patient dependent. Control charts for various dose metrics were generated to assess the metrics at each fraction for individual patient. CONCLUSIONS: Daily CBCT could be used to monitor dosimetric variations of targets and OARs resulting from volume changes and tissue deformation in oropharyngeal cancer radiotherapy. Treatment review with the guidance of a SPC tool allows for an objective and consistent clinical decision to apply adaptive radiotherapy.

Risk of radiation-associated intracranial malignancy after stereotactic radiosurgery: a retrospective, multicentre, cohort study.

BACKGROUND: A major concern of patients who have stereotactic radiosurgery is the long-term risk of having a secondary intracranial malignancy or, in the case of patients with benign tumours treated with the technique, the risk of malignant transformation. The incidence of stereotactic radiosurgery-associated intracranial malignancy remains unknown; therefore, our aim was to estimate it in a population-based study to assess the long-term safety of this technique. METHODS: We did a population-based, multicentre, cohort study at five international radiosurgery centres (Na Homolce Hospital, Prague, Czech Republic [n=2655 patients]; Ruber International Hospital, Madrid, Spain [n=1080], University of Pittsburgh Medical Center, Pittsburgh, PA, USA [n=1027]; University of Virginia, Charlottesville, VA, USA [n=80]; and NYU Langone Health System, New York, NY, USA [n=63]). Eligible patients were of any age, and had Gamma Knife radiosurgery for arteriovenous malformation, trigeminal neuralgia, or benign intracranial tumours, which included vestibular or other benign schwannomas, WHO grade 1 meningiomas, pituitary adenomas, and haemangioblastoma. Patients were excluded if they had previously had radiotherapy or did not have a minimum follow-up time of 5 years. The primary objective of the study was to estimate the incidence of stereotactic radiosurgery-associated intracranial malignancy, including malignant transformation of a benign lesion or development of radiation-associated secondary intracranial cancer, defined as within the 2 Gy isodose line. Estimates of age-adjusted incidence of primary CNS malignancies in the USA and European countries were retrieved from the Central Brain Tumor Registry of the United States (CBTRUS) and the International Agency for Research on Cancer (IARC) Global Cancer statistics. FINDINGS: Of 14 168 patients who had Gamma Knife stereotactic radiosurgery between Aug 14, 1987, and Dec 31, 2011, in the five contributing centres, 4905 patients were eligible for the analysis (had a minimum follow-up of 5 years and no history of previous radiation therapy). Diagnostic entities included vestibular schwannomas (1011 [20·6%] of 4905 patients), meningiomas (1490 [30·4%]), arteriovenous malformations (1089 [22·2%]), trigeminal neuralgia (565 [11·5%]), pituitary adenomas (641 [13·1%]), haemangioblastoma (29 [0·6%]), and other schwannomas (80 [1·6%]). With a median follow-up of 8·1 years (IQR 6·0-10·6), two (0·0006%) of 3251 patients with benign tumours were diagnosed with suspected malignant transformation and one (0·0002%) of 4905 patients was considered a case of radiosurgery-associated intracranial malignancy, resulting in an incidence of 6·87 per 100 000 patient-years (95% CI 1·15-22·71) for malignant transformation and 2·26 per 100 000 patient-years (0·11-11·17) for radiosurgery-associated intracranial malignancy. Two (0·0004%) of 4905 patients developed intracranial malignancies, which were judged unrelated to the radiation field. Overall incidence of radiosurgery-associated malignancy was 6·80 per 100 000 patients-years (95% CI 1·73-18·50), or a cumulative incidence of 0·00045% over 10 years (95% CI 0·00-0·0034). The overall incidence of 6·8 per 100 000, which includes institutions from Europe and the USA, after stereotactic radiosurgery was found to be similar to the risk of developing a malignant CNS tumour in the general population of the USA and some European countries as estimated by the CBTRUS and IARC data, respectively. INTERPRETATION: These data show that the estimated risk of an intracranial secondary malignancy or malignant transformation of a benign tumour in patients treated with stereotactic radiosurgery remains low at long-term follow-up, and is similar to the risk of the general population to have a primary CNS tumour. Although prospective cohort studies with longer follow-up are warranted to support the results of this study, the available evidence suggests the long-term safety of stereotactic radiosurgery and could support physicians counselling patients on Gamma Knife stereotactic radiosurgery. FUNDING: None.

Post-mastectomy Radiation Therapy in Breast Cancer Patients with Nodal Micrometastases.

BACKGROUND: Recent data support the use of post-mastectomy radiation therapy (PMRT) in women with one to three positive lymph nodes; however, the benefit of PMRT in patients with micrometastatic nodal disease (N1mi) is unknown. We evaluated the survival impact of PMRT in patients with N1mi within the National Cancer Database. METHODS: The pattern of care and survival benefit of PMRT was examined in women with pT1-2N1mi breast cancer who underwent mastectomy without neoadjuvant chemotherapy. Univariable and multivariable Cox proportional hazard models were employed for survival analysis, and subanalyses of high-risk patients and a propensity score-matched (PSM) cohort were completed. RESULTS: From 2004 to 2014, we identified 14,019 patients who fitted the study criteria. PMRT was delivered in 18.5% of patients and its use increased over the study period. Patients treated with PMRT were younger, had better performance status and larger primaries, were estrogen receptor (ER)-negative, had higher grade, lymphovascular invasion and positive surgical margins, and more often received systemic therapy. PMRT was significantly associated with overall survival (OS) in univariable analysis (hazard ratio [HR] 0.75 [0.64-0.89]), but was not significant in multivariable analysis (adjusted HR 1.01 [0.84-1.20]). There was no survival benefit to PMRT in ER-negative, high-grade, and/or young patients. There were 2 (0.9%) death events in the sentinel lymph node biopsy (SLNB) + PMRT group versus 21 (2.9%) in the SLNB-alone group (log-rank p = 0.053), and 8 (3.9%) death events in the axillary lymph node biopsy (ALNB) + PMRT group versus 27 (3.6%) in the axillary lymph node dissection-alone group (p = 0.82). There was no significant association between PMRT and OS within the PSM subgroup. CONCLUSION: In this largest reported retrospective study, no OS differences were associated with PMRT, which suggests that PMRT may not benefit every patient with microscopic nodal disease.

Dose-volume factors correlating with trismus following chemoradiation for head and neck cancer.

BACKGROUND: To investigate the dose-volume factors in mastication muscles that are implicated as possible causes of trismus in patients following treatment with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy for head and neck cancers. MATERIAL AND METHODS: All evaluable patients treated at our institution between January 2004 and April 2009 with chemotherapy and IMRT for squamous cell cancers of the oropharynx, nasopharynx, hypopharynx or larynx were included in this analysis (N = 421). Trismus was assessed using CTCAE 4.0. Bi-lateral masseter, temporalis, lateral pterygoid and medial pterygoid muscles were delineated on axial computed tomography (CT) treatment planning images, and dose-volume parameters were extracted to investigate univariate and multimetric correlations. RESULTS: Forty-six patients (10.9%) were observed to have chronic trismus of grade 1 or greater. From analysis of baseline patient characteristics, toxicity correlated with primary site and patient age. From dose-volume analysis, the steepest dose thresholds and highest correlations were seen for mean dose to ipsilateral masseter (Spearman's rank correlation coefficient Rs = 0.25) and medial pterygoid (Rs = 0.23) muscles. Lyman-Kutcher-Burman modeling showed highest correlations for the same muscles. The best correlation for multimetric logistic regression modeling was with V68Gy to the ipsilateral medial pterygoid (Rs = 0.29). CONCLUSION: Chemoradiation-induced trismus remains a problem particularly for patients with oropharyngeal carcinoma. Strong dose-volume correlations support the hypothesis that limiting dose to the ipsilateral masseter muscle and, in particular, the medial pterygoid muscle may reduce the likelihood of trismus.

Results of photon radiotherapy for unresectable salivary gland tumors: is neutron radiotherapy's local control superior?

BACKGROUND: The results of RTOG-MRC randomized trial of photon (n=15) versus neutron (n=17) therapy in the 1980's reported an improved local control (LC) with neutron radiotherapy for unresectable salivary gland tumors. Due to increased severe toxicity with neutron radiotherapy and the paucity of neutron-therapy centers, we analyzed our institution's results of photon radiotherapy for unresectable salivary gland tumors. PATIENTS AND METHODS: From 1990 to 2009, 27 patients with unresectable salivary gland cancer underwent definitive photon radiotherapy at our institution. Nodal involvement on presentation was found in 9 patients. Median dose of radiotherapy was 70 Gy. Chemotherapy was given to 18 patients, most being platinum-based regimens. Local control (LC), locoregional control (LRC), distant metastasis-free survival (DMFS), overall survival (OS), and toxicity outcomes were assessed. RESULTS: With a median follow-up of 52.4 months, the 2/5-year actuarial LC was 69% (95%CI ± 21.0%)/55% (± 24.2%), LRC was 65% (± 21.4%)/47% (± 21.6%), and DMFS was 71% (± 21.8%)/51% (± 22.8%), respectively using competing risk analysis. The median OS was 25.7 months, and the 2/5-year OS rates were 50% (± 19.0%)/29% (± 16.6%), respectively. Higher histologic grade was significant for an increased rate of DM (intermediate grade vs. low grade, p=0.04, HR 7.93; high grade vs. low grade, p=0.01, HR 13.50). Thirteen (48%) patient's experienced acute grade 3 toxicity. Late grade 3 toxicity occurred in three (11%) patients. CONCLUSIONS: Our data compares favorably to neutron radiotherapy with fewer late complications. Photon radiotherapy is an acceptable alternative to neutron radiotherapy in patients who present with unresectable salivary gland tumors.

Adjuvant Radiotherapy in Moderately Advanced (T3) Oral Cavity Cancers.

OBJECTIVE: To investigate the impact of adjuvant radiotherapy in isolated locally advanced oral cavity cancers (pT3N0M0) without adverse features. METHODS: We selected all patients from the National Cancer Database (2004-2019) who underwent surgical treatment where the final pathology was T3N0M0 with negative margins. Demographics, details of treatment, and outcomes were abstracted. The impact of radiotherapy on survival was assessed with univariable, multivariable, and propensity score-matched analyses. RESULTS: We identified 571 patients in our survival cohort. Most were male (348, 60.9%), and median age was 65. Less than one-third (176, 30.8%) received adjuvant radiotherapy. The median length of follow-up was 29 months. Overall, adjuvant radiotherapy was associated with improved survival (87.2% vs. 77.7%, at 2 years, p < 0.01). On multivariable analysis controlling for age and comorbidities, this survival difference persisted (HR: 0.62, 95% CI: 0.43-0.90, p = 0.01). In a propensity score-matched population of 278 patients matched on age and comorbidities, adjuvant radiotherapy was still associated with longer survival (87.4% vs. 78.5%, p = 0.014). CONCLUSION: In our study, adjuvant radiotherapy was associated with improved survival in completely excised locally advanced oral cavity tumors (T3N0M0). However, a significant proportion of patients do not receive adjuvant radiotherapy. These findings highlight the need for continued efforts to promote guideline-recommended care. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2236-2242, 2024.

A Radiation Therapy Contouring Atlas for Delineation of the Level I and II Axillae in the Prone Position: A Single-Institution Experience.

PURPOSE: With transition from supine to prone position, tenting of the pectoralis major occurs, displacing the muscle from the chest wall and shifting the level I and II axillary spaces. For patients for whom we aim to treat the level I and II axillae using the prone technique, accurate delineation of these nodal regions is necessary. Although different consensus guidelines exist for delineation of nodal anatomy in supine position, to our knowledge, there are no contouring guidelines in the prone position that account for this change in nodal anatomy. METHODS AND MATERIALS: The level I and II nodal contours from the Radiation Therapy Oncology Group (RTOG) breast cancer supine atlas were adapted for prone position by 2 radiation oncologists and a breast radiologist based on anatomic changes observed from supine to prone positioning on preoperative diagnostic imaging. Forty-three patients from a single institution treated with prone high tangents from 2012 to 2018 were identified as representative cases to delineate the revised level I and II axillae on noncontrast computed tomography (CT) scans obtained during radiation simulation. The revised nodal contours were reviewed by an expanded expert multidisciplinary panel including breast radiologists, radiation oncologists, and surgical oncologists for consistency and reproducibility. RESULTS: Consensus was achieved among the panel in order to create modifications from the RTOG breast atlas for CT-based contouring of the level I and II axillae in prone position using bone, muscle, and skin as landmarks. This atlas provides representative examples and accompanying descriptions for the changes described to the caudal and anterior borders of level II and the anterior, posterior, medial, and lateral borders of level I. A step-by-step guide is provided for properly identifying the revised anterior border of the level I axilla. CONCLUSIONS: The adaptations to the RTOG breast cancer atlas for prone positioning will enable radiation oncologists to more accurately target the level I and II axillae when the axillae are targets in addition to the breast.

High-volume prostate biopsy core involvement is not associated with an increased risk of cancer recurrence following 5-fraction stereotactic body radiation therapy monotherapy.

PURPOSE: Percentage of positive cores involved on a systemic prostate biopsy has been established as a risk factor for adverse oncologic outcomes and is a National Comprehensive Cancer Network (NCCN) independent parameter for unfavorable intermediate-risk disease. Most data from a radiation standpoint was published in an era of conventional fractionation. We explore whether the higher biological dose delivered with SBRT can mitigate this risk factor. METHODS: A large single institutional database was interrogated to identify all patients diagnosed with localized prostate cancer (PCa) treated with 5-fraction SBRT without ADT. Pathology results were reviewed to determine detailed core involvement as well as Gleason score (GS). High-volume biopsy core involvement was defined as ≥ 50%. Weighted Gleason core involvement was reviewed, giving higher weight to higher-grade cancer. The PSA kinetics and oncologic outcomes were analyzed for association with core involvement. RESULTS: From 2009 to 2018, 1590 patients were identified who underwent SBRT for localized PCa. High-volume core involvement was a relatively rare event observed in 19% of our cohort, which was observed more in patients with small prostates (p < 0.0001) and/or intermediate-risk disease (p = 0.005). Higher PSA nadir was observed in those patients with low-volume core involvement within the intermediate-risk cohort (p = 0.004), which was confirmed when core involvement was analyzed as a continuous variable weighted by Gleason score (p = 0.049). High-volume core involvement was not associated with biochemical progression (p = 0.234). CONCLUSIONS: With a median follow-up of over 4 years, biochemical progression was not associated with pretreatment high-volume core involvement for patients treated with 5-fraction SBRT alone. In the era of prostate SBRT and MRI-directed prostate biopsies, the use of high-volume core involvement as an independent predictor of unfavorable intermediate risk disease should be revisited.

Vemurafenib and radiation therapy in melanoma brain metastases.

Brain metastases in malignant melanoma carries a poor prognosis with minimal response to any therapy. The purpose of this pilot analysis was to find the effectiveness of vemurafenib, an oral BRAF inhibitor, and radiation therapy in V600 mutated melanoma with brain metastases. BRAF mutation status of the melanoma patients was determined by real-time PCR assay. Retrospective analysis was performed on twelve patients who had the mutation and were treated with either stereotactic radiosurgery or whole brain radiation therapy prior to or along with vemurafenib at a dose of 960 mg orally twice a day. Clinical and radiological responses, development of new brain metastases, overall survival and toxicity were assessed. Improvement in neurological symptoms was seen in 7/11 (64 %) following therapy. Radiographic responses were noted in 36/48 (75 %) of index lesions with 23 (48 %) complete responses and 13 (27 %) partial responses. Six month local control, freedom from new brain metastases and overall survival were 75, 57 and 92 %. Four patients had intra-tumoral bleed prior to therapy and two patients developed steroid dependence. One patient experienced radiation necrosis. This retrospective study suggests that melanoma patients with brain metastases harboring BRAF mutation appear to be a distinct sub-group with a favorable response to vemurafenib and radiation therapy and acceptable morbidity.

Reducing excess radiation from portal imaging of pediatric brain tumors.

Previously we have shown that our routine portal imaging (PI) of the craniofacial region in pediatric brain tumor patients contributed an additional 2%-3% of the prescribed dose and up to 200 cGy to the planning target volume (PTV) and nearby organs at risk (OARs). The purpose of this study is to quantify the reduction in dose to PTV and OARs from portal imaging (PI) of the craniofacial region of pediatric patients treated after the implementation of changes in our portal imaging practices. Twenty consecutive pediatric patients were retrospectively studied since the implementation of changes to our portal imaging procedure. Each received portal imaging of treatment fields and orthogonal setup fields to the craniofacial region. PI modifications included a reduction in the field size of setup orthogonal fields without loss of radiographic information needed for treatment verification. In addition, treatment fields were imaged using a single exposure, rather than double exposure. Dose-volume histograms were generated to quantify the dose to the target and critical structures through PI acquisition. These results were compared with our previous cohort of 20 patients who were treated using the former portal imaging practices. The mean additional target dose from portal imaging following the new guidelines was 1.5% of the prescribed dose compared to 2.5% prior to the new portal image practices (p < 0.001). With the new portal imaging practices, the percentage decrease in portal imaging dose to the brainstem, optic structures, cochlea, hypothalamus, temporal lobes, thyroid, and eyes were 25%, 35%, 35%, 51%, 45%, 80%, and 55%, respectively. Reductions in portal imaging doses were significant in all OARs with exception of the brainstem, which showed a trend towards significance. Changes to portal imaging practices can reduce the radiation dose contribution from portal imaging to surrounding OARs by up to 80%. This may have implications on both late toxicity and second cancer development in pediatric brain tumors.

Stereotactic Body Radiation Therapy versus Surgical Resection for Stage I/II Hepatocellular Carcinoma.

SBRT is an emerging locoregional treatment modality for hepatocellular carcinoma (HCC). Although local tumor control rates seem encouraging, large-scale survival data comparing SBRT to surgical resection are lacking. We identified patients with stage I/II HCC from the National Cancer Database amenable for potential surgical resection. Patients undergoing hepatectomy were matched by propensity score (1:2) with patients who underwent SBRT as primary treatment. A total of 3787 (91%) and 366 (9%) patients underwent surgical resection or SBRT between 2004 and 2015, respectively. After propensity matching, the 5-year overall survival was 24% (95% CI 19-30%) in the SBRT group versus 48% (95% CI 43-53%) in the surgery group (p < 0.001). The association of surgery with overall survival was consistent in all subgroups. In patients treated with SBRT, a biologic effective dose (BED) of ≥100 Gy (31%, 95% CI 22%-40%) compared with BED < 100 Gy (13%, 95% CI 8-22%) was associated with a higher 5-year overall survival rate (hazard ratio of mortality of 0.58, 95% CI 0.43-0.77; p < 0.001). Surgical resection may be associated with prolonged overall survival compared with SBRT in patients with stage I/II HCC.

Surgical Treatment in Very Advanced (T4b) Adenoid Cystic Carcinoma of the Head and Neck.

OBJECTIVE: To compare treatment outcomes for T4b head and neck adenoid cystic carcinoma (ACC). STUDY DESIGN: Historical cohort study. SETTING: National Cancer Database (NCDB). METHODS: Identified all T4b ACC of head and neck origin diagnosed 2004 to 2019 in the NCDB. Demographics, clinical characteristics, treatment details, and survival were analyzed. Treatment outcomes were analyzed using univariable and multivariable Cox regression. RESULTS: We identified 606 cases of T4b ACC. Less than half (284, 47.0%) underwent curative-intent treatment. Among these, most were treated with primary surgery: surgery + radiotherapy (RT) (122, 43.0%) or surgery + chemoradiotherapy (CRT) (42, 14.8%). The positive margin rate was 78.7%, and 90-day postoperative mortality was zero. Nonsurgical patients were treated with definitive RT (60, 21.1%) or definitive CRT (60, 21.1%). The median follow-up was 51.5 months. Overall survival was 77.8% at 3 years. Three-year survival was higher for patients treated with surgery compared to those treated nonsurgically (84% vs 70%; p = .005). Surgical treatment remained associated with higher survival on multivariable analysis (hazard ratio [HR]: 0.47, p = .005). This effect was most pronounced for oral cavity tumors (HR: 0.17, p = .01). Among matched cohorts of surgically treated patients, there was no difference in 3-year survival between clinical T4a and T4b tumors (83.3% vs 83.0%, p = .99). CONCLUSION: Long-term survival for T4b ACC of the head and neck could be expected. Primary surgical treatments can be performed safely and are associated with longer survival. A carefully selected subset of patients with very advanced ACC might benefit from the consideration of surgical treatments.

Pathologic Features, Treatment, and Clinical Outcomes of Lacrimal Gland Cancer.

OBJECTIVES: Lacrimal gland cancer is a rare malignancy with little data known about its pathologic characteristics or optimal management. We performed a large database analysis using the National Cancer Database (NCDB) to elucidate this unusual condition. METHODS: Patients with lacrimal gland cancer diagnosed between 2004 and 2018 were included in the analysis. Using available clinical data, we excluded all patients with histologies likely reflective of lacrimal sac or duct cancer, which are coded similarly to lacrimal gland cancer in the NCDB. Kaplan-Meier analysis was used to estimate overall survival (OS), and Cox proportional hazards models were used to indicate covariates associated with survival. RESULTS: A total of 440 cases of lacrimal gland cancer were included in the analysis, with a median follow-up of 52.9 months. The five-year OS for the entire cohort was 65.0%. Adenoid cystic carcinoma was the predominant histology (47.3%). Cox models showed that improved OS was associated with surgical resection (UVA: p < 0.001; MVA: p = 0.035). A detriment in OS was associated with increasing age, Charlson-Deyo score of 1, T4 stage, and positive margins and on UVA for adenocarcinoma and malignant mixed tumor histology. CONCLUSION: Adenoid cystic carcinoma comprises the plurality of lacrimal gland cancers. About half of patients with lacrimal gland carcinoma will live beyond 10 years, underscoring the importance of reduced morbidity of treatment. Surgical management is associated with improved prognosis. Further study will elucidate the role of surgical excision and radiotherapy in lacrimal gland cancer.

Adoption of adjuvant chemotherapy in high-risk salivary gland malignancies.

BACKGROUND: The present study characterizes national trends in the utilization of adjuvant chemotherapy to treat salivary gland malignancies. METHODS: The National Cancer Database was queried for salivary gland malignancies treated by surgery with radiation in 2004-2019. Proportions of patients receiving adjuvant chemotherapy over the study period were analyzed by linear regression. The impact of chemotherapy on overall survival was assessed using Kaplan-Meier and Cox proportional hazards analyses. RESULTS: Among 15 965 patients meeting inclusion criteria, 2355 (14.8%) received adjuvant chemotherapy. Chemotherapy utilization significantly increased from 4.9% to 16.5% over the study period (p < 0.001). No survival benefit was observed with adjuvant chemotherapy on propensity score-matched Kaplan-Meier analysis (HR: 0.98; 95% CI: 0.86-1.11; p = 0.72) or multivariable Cox regression (HR: 0.92; 95% CI: 0.78-1.09; p = 0.34). CONCLUSIONS: Adjuvant chemotherapy has been increasingly utilized to treat salivary gland malignancies in recent years. Our findings highlight the importance of obtaining high-quality prospective data regarding the benefit of chemotherapy.

Patterns of Care and Outcomes of Carcinosarcoma of the Major Salivary Glands.

OBJECTIVE: Carcinosarcoma of the salivary gland is a rare malignant biphasic tumor. The present study investigates the epidemiology and clinical behavior of carcinosarcoma of the major salivary glands using the National Cancer Database (NCDB). STUDY DESIGN: Historical cohort study. SETTING: NCDB. METHODS: All tumors were selected between 2004 and 2018. Patient demographics, tumor characteristics, treatments, and survival were analyzed. Cox regression analysis was performed in surgically treated patients. RESULTS: We identified 154 patients in the NCDB with carcinosarcoma of the salivary gland. Median age at diagnosis was 66 years (interquartile range, 55-76). Most patients were male (n = 92, 60%). The majority of tumors were in the parotid (n = 122, 79%), followed by submandibular gland (n = 21, 14%). The majority were high grade (n = 93, 95%), and a significant portion had locally advanced disease (pT3-4; n = 65, 62%). Nodal disease was present in more than one-third (n = 35, 36%). The most common treatment was surgery with adjuvant radiotherapy (n = 75, 49%). With a median follow-up of 36 months, the 3-year overall survival was 57.6% (95% CI, 48.7%-68.0%). In univariable analysis, advanced pT stage, pN+ disease, and positive margins were associated with worse survival. In multivariable analysis, age (hazard ratio, 1.02; 95% CI, 1.01-1.04; P = .03) and pT stage (hazard ratio, 2.51; 95% CI, 1.27-4.95; P = .008) remained significant. CONCLUSION: Carcinosarcoma is a rare salivary gland tumor that frequently presents at a locally advanced stage. Despite multimodality treatments, the outcomes are poor. In the absence of clinical trial data, these data from the NCDB could guide clinicians in the management of this rare disease.

Repeat re-irradiation with interstitial HDR-brachytherapy for an in-field isolated nodal recurrence in a patient with HPV-positive squamous cell carcinoma of the head and neck.

PURPOSE: Locoregionally recurrent head and neck cancer is a complex clinical scenario that often requires multimodality treatment. These patients have often previously received definitive treatment with a combination of surgery, radiation therapy, and systemic therapy, which can make further management difficult. A second isolated locoregional failure is rare and clinicians are faced with a challenge to optimize disease control while minimizing treatment-related toxicity. METHODS AND MATERIALS: In this report, we present the diagnosis, management, and outcomes of a patient with an isolated locoregional recurrence who was previously treated with two courses of radiation. The patient was treated with a second course of reirradiation using interstitial brachytherapy as well as a discussion regarding patient selection and optimal management for recurrent head and neck cancer. RESULTS: Repeat reirradiation using interstitial HDR-brachytherapy with the use of an alloderm spacer was successfully delivered to the patient for an in-field right neck nodal recurrence. He received a total EQD2/BED dose of 127.70/153.24 Gy. At 1-year followup, the patient was without evidence of recurrent disease or new significant side effects. CONCLUSION: Recurrent head and neck cancer should be managed with a multidisciplinary approach given the complex clinical scenario. Reirradiation is a commonly used salvage measure for recurrent head and neck cancer that requires careful planning and patient selection due to prior treatment-related effects and dose constraints. We reported a case of a second course of reirradiation using interstitial HDR-brachytherapy for locoregionally recurrent head and neck cancer and showed no recurrence of disease or worsening long term side effects at 1 year.

Stereotactic Body Radiation Therapy for the Curative Treatment of Prostate Cancer in Ultralarge (≥100 cc) Glands.

PURPOSE: Historically, toxicity concerns have existed in patients with large prostate glands treated with radiation therapy, particularly brachytherapy. There are questions whether this risk extends to stereotactic body radiation therapy (SBRT). In this retrospective review, we examine clinical outcomes of patients with prostate glands ≥100 cc treated curatively with SBRT. METHODS AND MATERIALS: We retrospectively analyzed a large institutional database to identify patients with histologically confirmed localized prostate cancer in glands ≥100 cc, who were treated with definitive-robotic SBRT. Prostate volume (PV) was determined by treatment planning magnetic resonance imaging. Toxicity was measured using Common Terminology Criteria for Adverse Events, version 5.0. Many patients received the Expanded Prostate Cancer Index Composite Quality of Life questionnaires. Minimum follow-up (FU) was 2 years. RESULTS: Seventy-one patients were identified with PV ≥100 cc. Most had grade group (GG) 1 or 2 (41% and 37%, respectively) disease. All patients received a total dose of 3500 to 3625 cGy in 5 fractions. A minority (27%) received androgen deprivation therapy (ADT), which was used for gland size downsizing in only 10% of cases. Nearly half (45%) were taking GU medications for urinary dysfunction before RT. Median toxicity FU was 4.0 years. Two-year rates of grade 1+ genitourinary (GU), grade 1+ gastrointestinal (GI), and grade 2+ GU toxicity were 43.5%, 15.9%, and 30.4%, respectively. Total grade 3 GU toxicities were very limited (2.8%). There were no grade 3 GI toxicities. On logistic regression analysis, pretreatment use of GU medications was significantly associated with increased rate of grade 2+ GU toxicity (odds ratio, 3.19; P = .024). Furthermore, PV (analyzed as a continuous variable) did not have an effect on toxicity, quality of life, or oncologic outcomes. CONCLUSIONS: With early FU, ultra large prostate glands do not portend increased risk of high-grade toxicity after SBRT but likely carry an elevated risk of low-grade GU toxicity.