Reducing the unknowns: A systematic review &amp; meta-analysis of the effectiveness of trans-oral surgical techniques in identifying head and neck primary cancer in carcinoma unknown primary

Al-lami, Ali; Gao, Chuanyu; Saddiq, Muhammad; Zuhir, Naail Al; Simó, Ricard; Arora, Asit; Jeannon, Jean‐Pierre

doi:10.1016/j.oraloncology.2022.105748

Cited by 24 publications

(12 citation statements)

References 37 publications

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“…In the meta-analysis, the pooled proportion identified by TORS, based on 15 case-series, was 74% [95% confidence interval (CI) 68–79%], and by TLM (based on three studies) was 91% (95% CI 85–98%) [23]. Similar findings were reported by a smaller more recent meta-analysis [25 ▪▪ ].…”

Section: Some Outstanding Issuessupporting

confidence: 72%

“…This rose to 78% when there was a negative work-up even after palatine tonsillectomy [23]. Similar rates have been identified by other systematic reviews [24,25 ▪▪ ]. Detection rates are much lower in HPV-negative cases with a detection rate of only 13% reported in one recent study [26 ▪ ].…”

Section: Indications For Surgical Evaluationsupporting

confidence: 72%

“…Detection rates are much lower in HPV-negative cases with a detection rate of only 13% reported in one recent study [26 ▪ ]. This has been recently confirmed in a recent meta-analysis with detection rates of 82% in HPV-mediated CUP, compared with 12% in HPV-negative CUP cases [25 ▪▪ ].…”

Section: Indications For Surgical Evaluationmentioning

confidence: 84%

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The role of transoral surgery in the diagnosis of the carcinoma of unknown origin of the head and neck

Mehanna

2023

Current Opinion in Otolaryngology &Amp; Head &Amp; Neck Surgery

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Purpose of reviewThe aim of this article is to update readers on the most recent evidence on the role of trans oral surgery (TOS) in the diagnosis of carcinoma of the unknown primary of the head and neck. Recent findingsTongue base mucosectomy has an important role in identifying the primary in patients who have had negative imaging, PET CT scans and ipsilateral tonsillectomy. In patients with bilateral nodal disease, tongue base mucosectomy should precede tonsillectomy. There are several unanswered questions that remain regarding sequencing of operations and use of intraoperative frozen section.

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Section: Some Outstanding Issuessupporting

confidence: 72%

Section: Indications For Surgical Evaluationsupporting

confidence: 72%

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The role of transoral surgery in the diagnosis of the carcinoma of unknown origin of the head and neck

Mehanna

2023

Current Opinion in Otolaryngology &Amp; Head &Amp; Neck Surgery

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“…The MOSES study hypothesized that CH techniques may miss very small oropharyngeal tumors and sought to establish the true incidence of clinicoradiologically occult tumors in this population. Recently, Al-Lami et al 20 published their systematic review of histopathological detection of a primary tumor in HNSCCUP, which included more than 700 patients. 20 The focus was on comparing the effectiveness of different transoral surgical techniques.…”

Section: Tbm Identification Ratesmentioning

confidence: 99%

“…Recently, Al-Lami et al 20 published their systematic review of histopathological detection of a primary tumor in HNSCCUP, which included more than 700 patients. 20 The focus was on comparing the effectiveness of different transoral surgical techniques. The timing of palatine tonsillectomy was not considered.…”

Section: Tbm Identification Ratesmentioning

confidence: 99%

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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Reducing the unknowns: A systematic review & meta-analysis of the effectiveness of trans-oral surgical techniques in identifying head and neck primary cancer in carcinoma unknown primary

Cited by 24 publications

References 37 publications

The role of transoral surgery in the diagnosis of the carcinoma of unknown origin of the head and neck

The role of transoral surgery in the diagnosis of the carcinoma of unknown origin of the head and neck

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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