Transoral tongue base mucosectomy for the identification of the primary site in the work-up of cancers of unknown origin: Systematic review and meta-analysis

Farooq, Salman; Khandavilli, Sunil; Dretzke, Janine; Moore, David; Nankivell, Paul; Sharma, Neil; Almeida, John R. de; Winter, Stuart C; Simon, Christian; Paleri, Vinidh; De, Mriganka; Siddiq, Somiah; Holsinger, Christopher; Ferris, Robert L.; Mehanna, Hisham

doi:10.1016/j.oraloncology.2019.02.018

Cited by 66 publications

(67 citation statements)

References 35 publications

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“…Transoral Laser Microsurgery (TOLM) is an alternative to TORS with comparable results (primary identification rate for TOLM 91% (85%-98%; 95% CI); however, the most recent meta-analysis of transoral tongue base mucosectomy for HNCUP only demonstrated 17% of patients undergoing TOLM compared to 83% undergoing TORS. 1 Therefore, more data are required in order to fully evaluate the two methods. There are also reported advantages of TORS over TOLM in the literature which includes 3D panoramic vision, improved range of motion, better optics, hand tremor filtration and easier en bloc resection.…”

Section: Discussionmentioning

confidence: 99%

“…Head and neck cancer of unknown primary (HNCUP) accounts for approximately 1-5% of all head and neck cancers and is a genuine diagnostic and therapeutic dilemma. 1 The typical presentation of HNCUP is a patient with a suspicious neck lump that demonstrates metastatic carcinoma on fine needle aspiration cytology (FNAC), but no apparent primary tumour on clinical examination of the mucosal surfaces of the upper aerodigestive tract (UADT) can be found. Despite rigorous investigations in accordance with the British Association of Head and Neck Oncologists (BAHNO) (including Magnetic Resonance Imaging (MRI), Computed Tomography (CT) and Positron Emission Tomography-Computed Tomography (PET-CT)), the primary site remains unknown in approximately 40% of cases.…”

Section: Introductionmentioning

confidence: 99%

“…Despite rigorous investigations in accordance with the British Association of Head and Neck Oncologists (BAHNO) (including Magnetic Resonance Imaging (MRI), Computed Tomography (CT) and Positron Emission Tomography-Computed Tomography (PET-CT)), the primary site remains unknown in approximately 40% of cases. 1,2 Identification of the primary tumour is key to reducing morbidity from wide-field radiation effects whilst also increasing overall and disease-free survival. 3,4 When a primary lesion is identified in these patients, it is commonly located in the tonsils (44.7%) or base of tongue (BOT) (43.9%).…”

Section: Introductionmentioning

confidence: 99%

“…Consequently, a recent meta-analysis credited TORS with an overall oropharyngeal primary diagnostic yield of 74%, whilst specifically for the BOT, a diagnostic yield of 53% in patients where all previous imaging has returned negative. 1 As reflected in the American Joint Committee on Cancer 8th edition of tumour staging, there is currently significant debate as to the role of high-risk human papilloma virus (HPV) status in the stratification of head and neck cancer patients. 5 p16 is used commonly as a surrogate marker of HPV infection status, and although sensitivity is approximately 80%, it is the most widely reported tool for HPV infection status.…”

Section: Introductionmentioning

confidence: 99%

“…5 p16 is used commonly as a surrogate marker of HPV infection status, and although sensitivity is approximately 80%, it is the most widely reported tool for HPV infection status. 1,6 As demonstrated by the adapted and simplified Table 1, current literature has demonstrated HPV-positive and HPV-negative head and neck cancer patients differ in multiple aspects. 7 With the separate staging system comes opportunities for further research into the treatment of oropharyngeal squamous cell carcinoma (SCC) patients as separate entities, reflected by ongoing trials into de-escalation therapy such as Postoperative Adjuvant Treatment for HPV-positive Tumours (PATHOS).…”

Section: Introductionmentioning

confidence: 99%

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Royal Society of Medicine Surgical Innovation Day Adrian Tanner Prize Winner 2019: Multidisciplinary care and surgical innovation for the benefit of the patient with head and neck cancer of unknown primary

Mistry

Walker

et al. 2020

JRSM Open

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Head and neck carcinoma of unknown primary accounts for approximately 1–5% of all head and neck cancers and presents a genuine diagnostic and therapeutic dilemma. Despite advanced investigations, the primary tumour location remains unknown in up to 40% of these cases. Transoral robotic surgery presents a viable diagnostic and therapeutic option in these patients. This surgical innovation alongside advances in the understanding of head and neck cancer biology means that a multidisciplinary approach in the management of these complex patients is of utmost importance to ensure optimal therapeutic outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Royal Society of Medicine Surgical Innovation Day Adrian Tanner Prize Winner 2019: Multidisciplinary care and surgical innovation for the benefit of the patient with head and neck cancer of unknown primary

Mistry

Walker

et al. 2020

JRSM Open

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Step Serial Sectioning in Head and Neck Squamous Cell Carcinoma of Unknown Primary

Hardman,

Harrington,

O’Leary

et al. 2024

JAMA Otolaryngol Head Neck Surg

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ImportancePatients with suspected head and neck squamous cell carcinoma of unknown primary (HNSCCUP) may undergo tonsillectomy and tongue base mucosectomy (TBM) to help identify clinicoradiologically occult primary disease. It is hypothesized that when these diagnostic specimens are analyzed, conventional histopathological (CH) techniques risk missing small primary tumors that may be hidden in the tissue blocks.ObjectiveTo establish the outcomes of a step serial sectioning (SSS) histopathological technique vs CH when analyzing diagnostic tissue specimens from TBM and tonsillectomy performed for HNSCCUP.Design, Setting, and ParticipantsThe MOSES prospective multicenter noninterventional cohort study was conducted over a 25-month period from November 2019 at secondary and tertiary care ear, nose, and throat departments in the United Kingdom and included adults with clinicoradiologically occult HNSCCUP who were undergoing TBM.InterventionConventional histopathological techniques performed on TBM and tonsillectomy specimens at participating centers, followed by SSS performed at the central laboratory.Main OutcomeIdentification of cancer on central histopathological review of TBM and tonsillectomy specimens.ResultsTissue from 58 eligible patients was analyzed (median [range] age, 58 [47-82] years; 10 women [17%]), with 20 480 sections cut in the laboratory and 4096 sections directly examined by a pathologist (median [range], 64 [28-135] per patient). The overall identification rate for TBM following SSS according to study protocol was 50.0% (95% CI, 37.5%-62.5%) and by subgroups was 42.9% (95% CI, 21.4%-67.4%) when performed following a negative bilateral tonsillectomy, 46.7% (95% CI, 24.8%-69.9%) at the same time as bilateral tonsillectomy, and 57.1% (95% CI, 36.5%-75.5%) following historic tonsillectomy. Conventional histopathological techniques at central review identified 2 undiagnosed primary tumors and revised the diagnosis of 2 other cases (1 nonmalignant and another down staged). Step serial sectioning identified a single additional tumor: an ipsilateral synchronous tongue base tumor for which a contralateral tumor had been identified on CH. Multifocal disease was seen in 5 (8.6%); all were human papillomavirus–related and in the tongue base.Conclusions and RelevanceIn this multicenter cohort study of patients undergoing TBM for HNSCCUP, SSS was associated with added considerable histopathological workload with minimal additional diagnostic benefit. A second opinion for conventional histological techniques may be more beneficial. Synchronous primary disease should be considered when planning diagnostic oropharyngeal surgery for these patients.

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Transoral Robotic Surgery and Radiation Volume Deintensification in Unknown Primary Squamous Cell Carcinoma of the Neck

de Almeida,

Martino,

Hosni

et al. 2024

JAMA Otolaryngol Head Neck Surg

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ImportancePatients with unknown primary squamous cell carcinoma (CUP) with cervical metastases typically receive comprehensive radiotherapy (RT) of the pharynx and bilateral neck. Typically, these patients receive comprehensive RT of the pharynx and bilateral neck that may produce treatment-related toxic effects.ObjectiveTo determine whether localization of occult oropharyngeal cancers with transoral robotic surgery (TORS) combined with reduced pharyngeal and neck RT volumes provides acceptable disease control.Design, Setting, and ParticipantsThis phase 2, single-group nonrandomized controlled trial at a single institution accrued 32 prospective participants with p16-positive CUP without a primary squamous cell carcinoma on examination and imaging from 2017 to 2019, and 24-month follow-up. The data analysis was conducted from January 2021 to June 2022.InterventionDiagnostic- (n = 13) or therapeutic-intent (n = 9) TORS, with pharyngeal-sparing radiotherapy (PSRT) prescribed for negative margins or pT0, and unilateral neck RT (UNRT) prescribed for unilateral lymphadenopathy with lateralized primary tumor or pT0.Main Outcomes and MeasuresOut-of-radiation treatment volume failure (&lt;15% was hypothesized to be acceptable) and reports of local and regional recurrence, overall survival, toxic effects, swallowing outcomes (per the MD Anderson Dysphagia Inventory), and videofluoroscopic swallow (per Dynamic Imaging Grade of Swallowing Toxic Effects [DIGEST]) ratings.ResultsThe study sample comprised 22 patients (mean [SD] age, 59.1 [5.7] years; 3 [14%] females and 19 [86%] male) with CUP. Of these, 19 patients (86%) had tumor stage cN1; 2 (9%), cN2; and 1 (5%), cN3. Five patients (23%), 14 patients (64%), and 3 patients (13%) had 0, 1, or 2 primary tumors, respectively. Twenty patients received RT; of these, 9 patients (45%) underwent PSRT and 10 patients (50%), UNRT. In the diagnostic-intent group, 8 patients (62%) and 5 patients (38%) underwent RT and RT-concurrent chemotherapy, respectively. In the therapeutic-intent group, 6 patients (67%) and 1 patient (11%) received adjuvant RT-concurrent chemotherapy, respectively; 2 patients declined RT. Two-year out-of-radiation treatment volume failure, locoregional control, distant metastasis control, and overall survival were 0%, 100%, 95%, and 100%, respectively. Grade 3 or 4 surgical, acute, and late toxic effects occurred in 2 (9%), 5 (23%), and 1 (5%) patients, respectively. PSRT was associated with lower RT dose to superior constrictors (37 vs 53 Gy; mean difference, 16 Gy; 95% CI, 6.4, 24.9), smaller decline in swallowing scores during treatment (19.3 vs 39.7; mean difference, −20.4; 95% CI, −34.1 to −6.1), and fewer patients with worsening DIGEST grade on findings of videofluoroscopic swallow studies at 2 years (0% vs 60%; difference, 60%; 95% CI, 30% to 90%).Conclusions and RelevanceThese findings indicate that TORS for p16-positive CUP allows RT volume deintensification with excellent outcomes and support future investigation in randomized clinical trials.Trial RegistrationClinicalTrials.gov Identifier: NCT03281499

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Transoral tongue base mucosectomy for the identification of the primary site in the work-up of cancers of unknown origin: Systematic review and meta-analysis

Cited by 66 publications

References 35 publications

Royal Society of Medicine Surgical Innovation Day Adrian Tanner Prize Winner 2019: Multidisciplinary care and surgical innovation for the benefit of the patient with head and neck cancer of unknown primary

Royal Society of Medicine Surgical Innovation Day Adrian Tanner Prize Winner 2019: Multidisciplinary care and surgical innovation for the benefit of the patient with head and neck cancer of unknown primary

Step Serial Sectioning in Head and Neck Squamous Cell Carcinoma of Unknown Primary

Transoral Robotic Surgery and Radiation Volume Deintensification in Unknown Primary Squamous Cell Carcinoma of the Neck

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