Cancers of the Major Salivary Gland

Son, Eugene L.; Panwar, Aru; Mosher, Charles H.; Lydiatt, Daniel D.

doi:10.1200/jop.2017.026856

Cited by 67 publications

(67 citation statements)

References 104 publications

(100 reference statements)

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“…Higher-grade histological subtypes were strongly associated with PNI and LVI, accounting for a poorer prognosis. In our study, contrary to others (7,10,11,16) , we did not find that pN classification, or the presence of ECS, affected survival. This could reflect the lower number of patients in these groups.…”

Section: Discussioncontrasting

confidence: 99%

Malignant Salivary Gland Tumours - a single centre experience

Malik

Devabalan

Bernstein

et al. 2020

Preprint

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Objectives: Salivary gland malignancies are an uncommon and heterogeneous group of cancers. We report our experience of clinicopathological variables that affect survival in patients treated by curative intent with surgery at a UK institution over a period of 15 years. Design: Retrospective cohort study Setting: Single centre study Participants We included 108 patients with malignant salivary gland tumours treated by curative intent with surgery from 2004 to 2019. Main outcome measures: The association between clinicopathological factors and their impact on overall survival (OS) and disease-free survival (DFS). Results: 77 (71.3%) presented with early pT classification and 81 (75%) of were node-negative. The parotid was the commonest site of malignancy (86, 79.6%). Perineural invasion (PNI) was present in 40 (37%) and lymphovascular invasion (LVI) was present in 20 (18.5%). 63 (58.3%) underwent adjuvant therapy. Median follow up was 36 months. Five-year OS and DFS were 81.7% and 71%. Age ?50, pT classification 3-4, high tumour grade, PNI, and advanced TNM stage were all associated with worse OS and DFS, and LVI with worse DFS. There was no survival difference between a close (1-<5 mm) or negative ([?]5 mm) resection margin. Conclusions: Age >50 years, advanced TNM stage, PNI and LVI are predictors of poor DFS. There was no difference in OS or DFS between patients with negative and close resection margins, indicating that close margins may be adequate for maintaining good oncologic outcomes in this group of patients.

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Section: Discussioncontrasting

confidence: 99%

Malignant Salivary Gland Tumours - a single centre experience

Malik

Devabalan

Bernstein

et al. 2020

Preprint

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“…High LMW-E expression is also an independent prognostic marker of poor RFS in MEC and AdCC and poor OS in the Aci subtype of patients, respectively, as indicated by our multivariable analysis. When presented as intermediate to high-grade tumors, both MEC and AdCC are aggressive subtypes, where patients present with a high rate of recurrence and distant metastases 2 . In the present study, 81% of MEC patients and 85% AdCC patients presented with intermediate to high-grade tumors.…”

Section: Discussionmentioning

confidence: 99%

“…Age and gender play major roles in the incidence of SGCs, with the male-to-female incidence ratio being 1.6:1 and an increased incidence of ~7 cases/100,000 individuals aged ≥70 years 1 . Although SGCs are listed as part of head and neck cancers (HNCCs) (~1-6% of all HNCCs), the etiology of SGCs is not linked to smoking, alcohol consumption, environmental, and genetic factors as seen in HNCC tumors 2 .…”

Section: Introductionmentioning

confidence: 99%

LMW cyclin E and its novel catalytic partner CDK5 are therapeutic targets and prognostic biomarkers in salivary gland cancers

et al. 2021

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Salivary gland cancers (SGCs) are rare yet aggressive malignancies with significant histological heterogeneity, which has made prediction of prognosis and development of targeted therapies challenging. In majority of patients, local recurrence and/or distant metastasis are common and systemic treatments have minimal impact on survival. Therefore, identification of novel targets for treatment that can also be used as predictors of recurrence for multiple histological subtypes of SGCs is an area of unmet need. In this study, we developed a novel transgenic mouse model of SGC, efficiently recapitulating the major histological subtype (adenocarcinomas of the parotid gland) of human SGC. CDK2 knock out (KO) mice crossed with MMTV-low molecular weight forms of cyclin E (LMW-E) mice generated the transgenic mouse models of SGC, which arise in the parotid region of the salivary gland, similar to the common site of origin seen in human SGCs. To identify the CDK2 independent catalytic partner(s) of LMW-E, we used LMW-E expressing cell lines in mass spectrometric analysis and subsequent biochemical validation in pull down assays. These studies revealed that in the absence of CDK2, LMW-E preferentially binds to CDK5. Molecular targeting of CDK5, using siRNA, resulted in inhibition of cell proliferation of human SGCs overexpressing LMW-E. We also provide clinical evidence of significant association of LMW-E/CDK5 co-expression and decreased recurrence free survival in human SGC. Immunohistochemical analysis of LMW-E and CDK5 in 424 patients representing each of the four major histological subtypes of human salivary cancers (Aci, AdCC, MEC, and SDC) revealed that LMW-E and CDK5 are concordantly (positive/positive or negative/negative) expressed in 70% of these patients. The co-expression of LMW-E/CDK5 (both positive) robustly predicts the likelihood of recurrence, regardless of the histological classification of these tumors. Collectively, our results suggest that CDK5 is a novel and targetable biomarker for the treatment of patients with SGC presenting with LMW-E overexpressing tumors.

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“…45,46 For instance, ACC's indolent behavior is explained by its scarce genetic instability whereas salivary duct carcinomas are characterized by a high mutation rate and the expression of androgen receptor. 45 Therefore, this latter type of PC has an aggressive clinical course yet promising trials are being conducted using androgendeprivation therapy. 36 Even more recently, it has been demonstrated how programmed death-1 ligand-1 (PD-L1) expression can significantly predict outcomes and the risk of developing DM.…”

Section: Discussionmentioning

confidence: 99%

A nomogram to estimate the risk of developing distant metastases in parotid cancer

et al. 2019

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Background Parotid cancer (PC) is a heterogeneous group of malignant tumors whose management mainly focuses on locoregional control. However, distant metastases (DM) can represent the most common cause of treatment failure. We have defined the predictors and developed a model that can predict a single patient's risk to develop DM. Methods We have analyzed our institutional database of 259 patients with PC and use it to develop a nomogram. C‐index and calibration curves were used to assess performance of our model. Results DM appeared in 18.9% of patients. Age, cT, pN, perineural invasion, and adenoid cystic carcinoma were significantly associated with distant failure. Conclusions We here present the first model to identify patients with PC at high risk of DM. Such tool can be of great value in managing these rare cancers in terms of a more precise prognosis and follow‐up while waiting for better systemic therapies to come in the future.

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Cancers of the Major Salivary Gland

Cited by 67 publications

References 104 publications

Malignant Salivary Gland Tumours - a single centre experience

Malignant Salivary Gland Tumours - a single centre experience

LMW cyclin E and its novel catalytic partner CDK5 are therapeutic targets and prognostic biomarkers in salivary gland cancers

A nomogram to estimate the risk of developing distant metastases in parotid cancer

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