Objective
Intra‐operative stimulated Raman histology (SRH) is a novel technology that uses laser spectroscopy and color‐matching algorithms to create images similar to the formalin‐fixed ...paraffin‐embedded (FFPE) section. We aim to assess the accuracy of SRH in a novel range of sinonasal and skull base tumors.
Methods
Select patients undergoing sinonasal and skull base surgery using the Invenio Imaging™ Nio™ Laser Imaging SRH system between June 2020 and September 2021 were assessed. The SRH images were reviewed for pathologic features similar to frozen section (FS) and FFPE. Time taken for results and diagnostic concordance was assessed.
Results
Sixty‐seven SRH images from 7 tumor types in 12 patients were assessed. Pathologies included squamous cell carcinoma, rhabdomyosarcoma, inverted papilloma, adenoid cystic carcinoma, SMARCB1‐deficient sinonasal carcinoma, mucosal melanoma, metastatic colonic adenocarcinoma, and meningioma. Tumor was identified in 100% of lesional specimens, with characteristic diagnostic features readily appreciable on SRH. Median time for diagnosis was significantly faster for SRH (4.3 min) versus FS (44.5 min; p = <.0001). Where SRH sample site matched precisely to FS (n = 32/67, 47.8%), the same diagnosis was confirmed in 93.8%. Sensitivity, specificity, precision, and overall accuracy of SRH were 93.3%, 94.1%, 93.8%, and 93.3%, respectively. Near‐perfect concordance was seen between SRH and FS (Cohen's kappa κ = 0.89).
Conclusion
Stimulated Raman histology can rapidly produce images similar to FFPE H&E in sinonasal and skull base tumors. This technology has the potential to act as an adjunct or alternative to standard FS.
Level of Evidence
4 Laryngoscope, 132:2142–2147, 2022
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Methods of assessing final margin status in patients undergoing surgery for oral cavity squamous cell carcinoma, such as intraoperative frozen section histopathology (IFSH) taken from the tumor bed, ...may have limitations in accuracy.
To evaluate the accuracy and implications of using IFSH samples to assess tumor bed margins in patients undergoing surgery for oral cavity squamous cell carcinoma (SCC).
This cross-sectional study included 1257 patients who underwent surgery for oral cavity SCC between January 1, 2000, and December 31, 2015, at an academic cancer center. A total of 4821 IFSH samples were examined from 1104 patients (87.8%) who had at least 1 IFSH sample. Institutional practice is to harvest margins for IFSH from the tumor bed. Statistical analysis was performed from August 1, 2021, to April 4, 2022.
Sensitivity and specificity were calculated for IFSH samples of margins compared with the permanent pathology samples of the same tissue and for IFSH compared with the final tumor specimen histopathology (FTSH). Results were classified using a binary method, with histopathologic reports interpreted as either negative (including negative or atypia or dysplasia) or positive (including carcinoma in situ, suspicious, or positive).
A total of 1257 patients met the inclusion criteria, including 709 men (56.4%), with a median age of 62 years (IQR, 52-73 years); 1104 patients (627 men 56.8%; median age, 62 years IQR, 52-72 years) had IFHS samples. For IFSH relative to permanent sections of the IFSH tissue, sensitivity and specificity of IFSH were high (sensitivity, 76.5% 95% CI, 67.5%-85.5%; specificity, 99.9% 95% CI, 99.8%-100%), with discordant results in 24 of 4821 total specimens (0.5%). Final specimen margins were positive in 11.7% of patients (147 of 1257). Compared with FTSH, the sensitivity of IFSH for defining margin status was 10.8% (95% CI, 5.8%-15.8%), and the specificity was 99.1% (95% CI, 98.8%-99.4%). The rate of discordance was 4.0% (171 of 4284 specimens) between IFSH and FTSH.
The findings of this cross-sectional study suggest that IFSH is accurate compared with permanent pathologic characteristics of the same tissue, but less reliable at assessing final margin status on the tumor specimen. Despite a high specificity, the sensitivity of IFSH compared with FTSH is low, which may be associated with the inherent inability of tumor bed IFSH margin analysis to accurately account for the 3-dimensional association of tumor margins with the periphery of the specimen and the overall low rate of positive final tumor margins. Although tumor bed IFSH is widely used in the management of oral cavity cancer, this study suggests that there are limitations of this modality in assessing the final surgical margin status.
Salivary gland cancers (SGCs) are rare, aggressive cancers without effective treatments when metastasized. We conducted a phase 2 trial evaluating nivolumab (nivo, anti-PD-1) and ipilimumab (ipi, ...anti-CTLA-4) in 64 patients with metastatic SGC enrolled in two histology-based cohorts (32 patients each): adenoid cystic carcinoma (ACC; cohort 1) and other SGCs (cohort 2). The primary efficacy endpoint (≥4 objective responses) was met in cohort 2 (5/32, 16%) but not in cohort 1 (2/32, 6%). Treatment safety/tolerability and progression-free survival (PFS) were secondary endpoints. Treatment-related adverse events grade ≥3 occurred in 24 of 64 (38%) patients across both cohorts, and median PFS was 4.4 months (95% confidence interval (CI): 2.4, 8.3) and 2.2 months (95% CI: 1.8, 5.3) for cohorts 1 and 2, respectively. We present whole-exome, RNA and T cell receptor (TCR) sequencing data from pre-treatment and on-treatment tumors and immune cell flow cytometry and TCR sequencing from peripheral blood at serial timepoints. Responding tumors universally demonstrated clonal expansion of pre-existing T cells and mutational contraction. Responding ACCs harbored neoantigens, including fusion-derived neoepitopes, that induced T cell responses ex vivo. This study shows that nivo+ipi has limited efficacy in ACC, albeit with infrequent, exceptional responses, and that it could be promising for non-ACC SGCs, particularly salivary duct carcinomas. ClinicalTrials.gov identifier: NCT03172624 .
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Background
Diffuse sclerosing papillary thyroid carcinoma (DSPTC) is an aggressive histopathologic subtype of papillary thyroid carcinoma. Correlation between genotype and phenotype has not been ...comprehensively described. This study aimed to describe the genomic landscape of DSPTC comprehensively using next-generation sequencing (NGS), analyze the prognostic implications of different mutations, and identify potential molecular treatment targets.
Methods
Tumor tissue was available for 41 DSPTC patients treated at Memorial Sloan Kettering Cancer Center between 2004 and 2021. After DNA extraction, NGS was performed using the Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets platform, which sequences 505 critical cancer genes. Clinicopathologic characteristics were compared using the chi-square test. The Kaplan-Meier method and log-rank statistics were used to compare outcomes.
Results
The most common mutation was
RET
fusion, occurring in 32% (13/41) of the patients. Other oncologic drivers occurred in 68% (28/41) of the patients, including 8
BRAF
V600E
mutations (20%) and 4
USP8
mutations (10%), which have not been described in thyroid malignancy previously. Patients experienced
RET
fusion-positive tumors at a younger age than other drivers, with more aggressive histopathologic features and more advanced T stage (
p
= 0.019). Patients who were
RET
fusion-positive had a significantly poorer 5-year recurrence-free survival probability than those with other drivers (46% vs 84%;
p
= 0.003; median follow-up period, 45 months). In multivariable analysis,
RET
fusion was the only independent risk factor for recurrence (hazard ratio HR, 7.69;
p
= 0.017).
Conclusion
Gene-sequencing should be strongly considered for recurrent DSPTC due to significant prognostic and treatment implications of
RET
fusion identification. The novel finding of
USP8
mutation in DSPTC requires further investigation into its potential as a driver mutation.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Defects in pathways governing genomic fidelity have been linked to improved response to immune checkpoint blockade therapy (ICB). Pathogenic POLE/POLD1 mutations can cause hypermutation, yet how ...diverse mutations in POLE/POLD1 influence antitumor immunity following ICB is unclear. Here, we comprehensively determined the effect of POLE/POLD1 mutations in ICB and elucidated the mechanistic impact of these mutations on tumor immunity. Murine syngeneic tumors harboring Pole/Pold1 functional mutations displayed enhanced antitumor immunity and were sensitive to ICB. Patients with POLE/POLD1 mutated tumors harboring telltale mutational signatures respond better to ICB than patients harboring wild-type or signature-negative tumors. A mutant POLE/D1 function-associated signature-based model outperformed several traditional approaches for identifying POLE/POLD1 mutated patients that benefit from ICB. Strikingly, the spectrum of mutational signatures correlates with the biochemical features of neoantigens. Alterations that cause POLE/POLD1 function-associated signatures generate T cell receptor (TCR)-contact residues with increased hydrophobicity, potentially facilitating T cell recognition. Altogether, the functional landscapes of POLE/POLD1 mutations shape immunotherapy efficacy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Sinonasal and skull base tumors comprise a heterogeneous group of malignancies with a significant rate of distant recurrence (DR). The aim of this study was to analyze tumor and host factors, ...including pretreatment neutrophil-to-lymphocyte ratio (NLR), that predict DR in these patients.
We retrospectively reviewed sinonasal tumors and/or tumors involving the skull base treated with surgery between 1973 and 2015 (n = 473). We stratified NLR using the top 5 percentile as cutoff. Factors predictive of outcome were determined by Cox proportional hazards model.
Most tumors were primary (81%) and 67% had skull base resection. The most common site was the nasal cavity (37%) and the most common histology was squamous cell carcinoma (34%). Most patients presented with advanced primary tumor stage (pT3/T4; 80%) and most had no regional neck disease (pNx/N0; 93%). A total of 104 patients developed DR. The 5-year overall and disease-specific survival for patients who developed DR were 36.4% and 35.8%, compared to 69.0% and 74.9% for patients who did not. Patients with DR had a higher percentage of NLR-high patients compared patients without DR (11% vs 3%, p = .006). In a multivariable analysis, melanoma histology (HR = 5.469, 95% CI 3.171–9.433), pT3/T4 (HR = 2.686, 95% CI 1.150–6.275), pN+ (HR = 6.864, 95% CI 3.450–13.653), and NLR-high (HR = 3.489, 95% CI 1.593–7.639) were independent predictors of DR.
Melanoma histology, pT, pN, and high NLR predict DR, suggesting that both tumor and host factors need to be considered. NLR may act as a surrogate marker of the host́s immune system.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This review explores how human papillomavirus‐related oropharyngeal cancer affects health‐related quality of life (HR‐QoL) and the role patient‐reported outcomes (PROs) can play in optimizing ...treatment. PRO measures (PROMs) are comprehensive, subjective assessments of patients’ day‐to‐day HR‐QoL. Developed through a scientifically robust, multistage process, PROMs offer insight into patients’ symptoms, function, and satisfaction with care. The use of PROMs can increase symptom awareness, stimulate discussion, and enhance shared decision‐making between patients and healthcare providers.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The epidemiology and management of oral cavity cancer have changed considerably in recent decades. This study examines epidemiological and management trends in oral cavity squamous cell carcinoma ...(OCSCC).
A retrospective cohort study of data from the National Cancer Registry of Ireland between 1994 and 2014.
A total of 2725 patients were identified. The most common subsites were the tongue (34 %, n = 1025), lip (19 %, n = 575), floor of mouth (FOM) (18 %, n = 550), and retromolar trigone (RMT) (6 %, n = 189). The incidence of OCSCC remained largely unchanged (3.14 cases/100000/year) during the study period. 5-year disease-specific survival (DSS) was 58.6 % overall, varying between subsites (lip 85 %, RMT 62.9 %, tongue 54.7 %, and FOM 47.3 %). DSS improved over the study period (p = 0.03), in particular for tongue primaries (p = 0.007). Primary surgery significantly improved DSS versus radiotherapy (HR 0.28, p < 0.0001). Survival of T4 disease managed surgically was superior to that of T1 disease managed with radiotherapy. In node positive patients, chemotherapy improved overall survival (HR 0.8 p = 0.038) but not DSS (HR 0.87 p = 0.215).
Primary surgery remains the standard of care in the management of OCSCC. Prognosis has improved in line with an increase in the use of primary surgery in the same time frame, though the incidence remains unchanged.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
