Colorectal cancer remains a leading source of cancer mortality worldwide. Initial response is often followed by emergent resistance that is poorly responsive to targeted therapies, reflecting currently undruggable cancer drivers such as KRAS and overall genomic complexity. Here, we report a novel approach to developing a personalized therapy for a patient with treatment-resistant metastatic KRAS-mutant colorectal cancer. An extensive genomic analysis of the tumor’s genomic landscape identified nine key drivers. A transgenic model that altered orthologs of these nine genes in the Drosophila hindgut was developed; a robotics-based screen using this platform identified trametinib plus zoledronate as a candidate treatment combination. Treating the patient led to a significant response: Target and nontarget lesions displayed a strong partial response and remained stable for 11 months. By addressing a disease’s genomic complexity, this personalized approach may provide an alternative treatment option for recalcitrant disease such as KRAS-mutant colorectal cancer.

Summary Adenoid cystic carcinoma (ACC) is a rare cancer type that originates in the salivary glands. Tumors commonly invade along nerve tracks in the head and neck, making surgery challenging. Follow-up treatments for recurrence or metastasis including chemotherapy and targeted therapies have shown limited efficacy, emphasizing the need for new therapies. Here, we report a Drosophila-based therapeutic approach for a patient with advanced ACC disease. A patient-specific Drosophila transgenic line was developed to model the five major variants associated with the patient's disease. Robotics-based screening identified a three-drug cocktail—vorinostat, pindolol, tofacitinib—that rescued transgene-mediated lethality in the Drosophila patient-specific line. Patient treatment led to a sustained stabilization and a partial metabolic response of 12 months. Subsequent resistance was associated with new genomic amplifications and deletions. Given the lack of options for patients with ACC, our data suggest that this approach may prove useful for identifying novel therapeutic candidates.

ObjectivesTo assess the outcomes of abdominal dermal‐fat grafting following superficial and total parotidectomy.MethodsA retrospective chart review of parotidectomy patients was performed. Patients were divided into four groups based on surgical extent and grafting status: superficial parotidectomy (SP), superficial parotidectomy with grafting (SPg), total parotidectomy (TP), and total parotidectomy with grafting (TPg). Complication rates and operative times were then compared between surgically matched groups (SP vs. SPg, TP vs. TPg). Complications included graft necrosis, gustatory sweating, first‐bite syndrome, infection, hematoma, sialocele, and seroma. Data was analyzed via chi‐square and two‐sample t testing, logistic regression, and one‐way analysis of variance.ResultsThe cohort consisted of 330 patients: 106 SP (32.12%), 61 SPg (18.48%), 82 TP (24.85%), and 81 TPg (24.55%). No donor site complications occurred. TPg resulted in seven graft necroses (8.64%), and 22 reported gustatory sweating (27.20% vs. 10 TP patients (12.2%), P = 0.016); SPg resulted in two necroses (3.28%). There were no other statistically significant differences in complication rates. Graft recipients receiving adjuvant radiation were more likely to develop necrosis (odds ratio [OR] 4.60, 95% confidence interval [CI], 1.16–18.27, P = .0194). Patients who developed gustatory sweating were 8.38 years younger (95% CI 2.66–14.10, P = 0.002, follow‐up time > 48 days). Grafting did not increase operative times (TP/TPg: mean = 275.91/263.65 minutes, standard error of the mean = 41.96/33.75, P = 0.822).ConclusionAn abdominal dermal‐fat graft is an excellent reconstructive choice for a parotidectomy defect and is not associated with increased complication rates or prolonged operative time.Level of Evidence4 Laryngoscope, 130:2144–2147, 2020

Objectives/Hypothesis Use validated eye‐tracking technology to objectively measure 1) the attentional distraction of facial contour defects after superficial and total parotidectomy and 2) changes in attentional distraction with abdominal dermal fat graft reconstruction. Methods Standardized frontal and oblique facial images of 16 patients who had undergone superficial or total parotidectomy with or without fat graft reconstruction; four normal controls were obtained. One hundred casual observers were recruited to view these images, and gaze data were collected using a Tobii Pro eye‐tracking system. Gaze durations for predefined facial areas of interest were analyzed using mixed‐effects linear regression to test study hypotheses. Results For frontal images, total parotidectomy increased gaze to the operated parotid area compared to the contralateral nonoperated parotid area (92 milliseconds, 95% confidence interval [CI]: 48‐138 milliseconds, P < .001). Fat grafting normalized the attentional distraction, with no difference in gaze time on the operated parotid region compared to normal control faces (P = .414). For oblique images, total parotidectomy increased gaze to the operated parotid area compared to the contralateral nonoperated parotid area (658 milliseconds, 95% CI: 463‐854 milliseconds, P < .001). Fat grafting normalized this attentional distraction, with no difference in gaze time on the operated parotid region compared to normal control faces (P = .504). In both views, superficial parotidectomy demonstrated no significant attentional distractions, with or without fat grafting. Conclusions This eye‐tracking study objectively demonstrates that total parotidectomy results in a facial contour deformity that is distracting to observers, whereas superficial parotidectomy does not. For total parotidectomy, this attentional distraction can be normalized with dermal fat graft reconstruction. Level of Evidence 3b Laryngoscope, 131:E124–E131, 2021

Objective To identify social determinants of health care that are associated with poorer pediatric well-differentiated thyroid cancer (WDTC) outcomes and increased stage at presentation. Study Design Using the SEER database (Surveillance, Epidemiology, and End Results), we retrospectively gathered data on pediatric WDTC across the United States between 1973 and 2015. Setting All patients between 0 and 19 years old with a diagnosis of WDTC were included. Methods Patient variables were analyzed for relationships to AJCC stage at presentation (American Joint Committee on Cancer), overall survival, and disease-specific survival. Results Among 3913 patients with pediatric thyroid cancer, 3185 were female (81.4%), 3366 had papillary thyroid cancer (85.3%), and 367 had follicular thyroid cancer (9.4%). Two- and 5-year overall and disease-specific survival approached 100%. However, when outcomes were analyzed by specific populations, male sex, non-Caucasian race, poverty, and language isolation were linked to worse overall survival. Male sex and poverty were associated with poorer disease-specific survival. Regarding overall AJCC stage at presentation, male sex and Black race were related to higher overall presenting AJCC stage. Later AJCC T stage at presentation was seen in male, Hispanic, Asian, and Black patients. There were no variables significantly related to following through with recommended surgery. Conclusion Pediatric WDTC continues to carry an excellent prognosis in the United States. However, when we consider specific populations, the social determinants of health care affect survival and disease burden at presentation: male sex, poverty, language isolation, and race affected survival and/or AJCC stage at presentation in pediatric WDTC.

Objective The objective of this study is to describe the clinical presentation, tumor characteristics, natural history, and treatment patterns of sinonasal osteosarcoma. Methods Fourteen patients who had been treated for osteosarcoma of the nasal cavity and paranasal sinuses at a tertiary care center were reviewed. In addition, a systematic review of the literature for osteosarcoma of the sinonasal cavity was performed. Results In a systematic review, including 14 patients from the authors' institution, 53 total studies including 88 patients were assessed. Median follow-up was 18 months (interquartile range: 8–39 months). The most common presenting symptoms were facial mass or swelling (34%), and nasal obstruction (30%). The most common paranasal sinus involved by tumor was the maxillary sinus (64%), followed by the ethmoid sinuses (52%). The orbit (33%), dura (13%) and infratemporal fossa (10%) were the most common sites of local invasion. The majority of patients underwent surgery followed by adjuvant therapy (52.4%). Increasing age was associated with decreased overall survival rate (unit risk ratio [95% confidence interval (CI)] = 1.02 [1.003–1.043]; p = 0.0216) and T4 disease was associated with decreased disease-specific survival rate (hazard ratio [HR] = 2.87; p = 0.0495). The 2- and 5-year overall survival rates were 68 and 40%, respectively, while 2- and 5-year disease-specific survival rates were 71% and 44%, respectively. Conclusions Sinonasal osteosarcomas are uncommon tumors and can pose a significant therapeutic challenge. Increasing age and T4 disease are associated with worse prognosis. This disease usually warrants consultation by a multidisciplinary team and consideration of multimodality therapy.

PurposeWe examined the influence of body mass index (BMI) and body fat distribution on rectal dose in patients treated with permanent seed brachytherapy for localized prostate cancer.Methods and materialsWe analyzed 213 patients treated with I125 seed brachytherapy for localized prostate cancer. BMI and rectal dosimetry data for all patients were available. Data on visceral and subcutaneous fat distribution at the level of the iliac crest (n = 140) as well as the distribution of periprostatic and subcutaneous fat at the symphysis pubis level were obtained (n = 117). Fat distribution was manually contoured on CT on day 30 after brachytherapy. The correlation between BMI, fat distribution and rectal dose (R100 (in cc), R150 (cc), D2 (Gy)) was analyzed using the Spearman correlation coefficient. Differences in rectal dose between tertiles of body fat distribution were calculated using nonparametric tests.ResultsPeriprostatic adipose was only weakly correlated with BMI (r = 0.0.245, p = 0.008) and only weakly correlated with the other fat measurements (r = 0.31-0.37, p < 0.001). On the other hand, BMI was correlated with all other fat measurements (≥0.58, p < 0.001). All the other fat measurements were strongly correlated with each other (r = 0.5-0.87, p < 0.001). Patients with an R100 of >1.3 cc (23% of patients) had less visceral fat (p = 0.004), less subcutaneous fat at the level of the iliac crest (p = 0.046) and a lower BMI (26.8 kg/m2 vs. 28.5 kg/m2, p = 0.02) than patients with an R100 of <1.3 cc. Results were very similar when comparing an R100 of >1.0 cc (34% of patients) across the tertiles. None of the tested linear regression models were predictive (max 12%) of dose to the rectum.ConclusionDose to the rectum is dependent on BMI and body fat distribution. Periprostatic fat does not influence rectal dose. Dose to the rectum remains difficult to predict and depends on many factors, one of which is body fat distribution.

Background In this study we aim to describe presenting characteristics and identify prognostic factors for disease resolution in patients with chronic rhinosinusitis (CRS) in the setting of eosinophilic granulomatosis with polyangiitis (EGPA). Methods Patients evaluated at a tertiary care center with diagnoses of EGPA and CRS were identified. Descriptive statistics were obtained. Univariate analysis was used to search for prognostic factors associated with higher Lund‐Mackay score at presentation and disease resolution. Results Forty‐four patients were included with a mean age of 52.7 (standard deviation, 14) years. Twenty‐one patients (47.7%) were female, all had a diagnosis of asthma, and 36 (83.7%) had eosinophils >10%. Common presenting symptoms for CRS included nasal discharge (87.9%) followed by nasal congestion (83.9%) and facial pain and pressure (83.8%). Medical management of CRS included systemic corticosteroids (93.2%) and systemic antibiotics (75%). Surgical intervention occurred in 29 patients (67%). Nine patients (20.5%) had resolution of sinus symptoms, including 4 with imaging confirmation. Fourteen patients (31.8%) had continued CRS, but with improved symptoms, whereas 9 patients (20.5%) had continued CRS with no improvement in symptoms. Eleven patients (25%) were lost to follow‐up and 4 (9.1%) died. Univariate analysis did not show antineutrophil cytoplasmic antibody positivity, presence of peripheral eosinophilia, gender, age, or absence of systemic therapy to be predictive of higher Lund‐Mackay score at presentation or predictive of disease resolution. Conclusion CRS in patients with EGPA is often refractory to medical and surgical management. Treatment of these patients should occur in a multidisciplinary setting.