Unknown Primary Squamous Cell Carcinoma Research Articles

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

Patients 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. To determine whether localization of occult oropharyngeal cancers with transoral robotic surgery (TORS) combined with reduced pharyngeal and neck RT volumes provides acceptable disease control. This 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. Diagnostic- (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. Out-of-radiation treatment volume failure (<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. The 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%). These findings indicate that TORS for p16-positive CUP allows RT volume deintensification with excellent outcomes and support future investigation in randomized clinical trials. ClinicalTrials.gov Identifier: NCT03281499.

Head and Neck Squamous Cell Carcinoma of Unknown Primary: A Diagnostic Work-Up.

The current work-up of the primary tumor site of a head and neck squamous cell carcinoma of unknown primary is not standardized and results in several time-consuming procedures that delay treatment initiation. This article seeks to consolidate contemporary strategies used to identify the primary tumor site of an unknown primary head and neck squamous cell carcinoma and offer recommendations based on current literature review.

A comparison between p16-positive head and neck cancer of unknown primary (HPV-HNCUP) and oropharyngeal squamous cell carcinoma (HPV-OPSCC): are they the same disease?

IntroductionThe following study aimed to answer the question if HPV-HNCUP and HPV-OPSCC are the same disease. Propensity score matching (PSM) was used to compare the oncological outcomes of both groups, in particular the 5-year overall survival rate (OS), the 5-year disease specific survival rate (DSS) and the 5-year progression free survival rate (PFS).Materials and methodsFirstly, between January 1st, 2007, and March 31st, 2020 a total of 131 patients were treated with HNCUP at our Department. Out of these, 21 patients with a confirmed positive p16 status were referred to surgery followed by adjuvant therapy. Secondly, between January 1st, 2000, and January 31st, 2017, a total of 1596 patients were treated with an OPSSC at our Department. Out of these, 126 patients with a confirmed positive p16 status were referred to surgery followed by adjuvant therapy. After PSM, 84 patients with HPV-OPSCC and 21 HPV-HNCUP remained in the study for further comparison.ResultsThe OS was 63.5% (95% CI 39.4–87.6) for HPV-HNCUP and 88.9% (95% CI 90.4–100.0) for HPV-OPSCC patients and therefore, significantly lower for the first mentioned (p = 0.013). The DSS was also significantly impaired for HPV-HNCUP (71.0%, 95% CI 46.3–95.7), in comparison with HPV-OPSCC patients (95.5%, 95% CI 90.4–100.0; p = 0.002). The PFS for HPV-HNCUP patients was lower (75.6%, 95% CI 54.0–97.2) yet not significantly different to HPV-OPSCC (90.4%, 95% CI 83.5–97.3; p = 0.067).ConclusionsThe results presented demonstrate a significant reduced OS and DSS for HPV-HNCUP patients. Accordingly, in our study HPV-HNCUP and HPV-OPSCC are two different entities with a different oncological outcome.

Transoral Laser Resection of the Tongue Base in the Workup of Unknown Primary Head and Neck Squamous Cell Carcinoma.

Objective Failure to localize the primary tumor site in head and neck carcinoma of unknown origin after imaging and endoscopic evaluation leads to increased treatment-related morbidity. The use of transoral laser microsurgery to improve the detection of unknown primary carcinoma site identification is described in this article. Methods A retrospective cohort of 71 consecutive cases of cervical carcinoma of an unknown primary source from 2006 until 2012 from a single academic institution was analyzed. Of these, 10 patients were excluded based on our exclusion criteria. All patients underwent endoscopy with biopsies performed by fellowship-trained head and neck cancer surgeons. Results The primary detection rate was 76% for patients who underwent laser tongue base resection versus 34% for traditional operative examination. There were no complications or prolonged recovery times in either group. Operative time was increased by the addition of the transoral base of tongue resection by 30 minutes. Conclusions Laser tongue base excision offers improved sensitivity in primary site detection without a significant increase in morbidity and only a modest increase in operative time.

Comparison of PD-L1 expression in squamous cell cancer of unknown primary and oropharyngeal squamous cell carcinoma

PurposeThe tumorigenesis of squamous cell cancer of unknown primary (SCCUP) in the head and neck area has not been decoded so far, while poor survival rates and limited therapeutic options pose a serious challenge. The aim of this project was to investigate immunological characteristics of SCCUPs and compare them to oropharyngeal squamous cell carcinoma (OPSCC).MethodsPD-L1 expression (TC) was examined by immunohistochemistry in 50 lymph node metastases of SCCUP and 47 primaries of OPSCC. CD3 + and CD8 + lymphocytic infiltration was measured in 5 high power fields. Expression of p16 and HPV ISH were assessed.ResultsSCCUP demonstrated a significantly higher expression of PD-L1 than OPSCC. In p16-negative SCCUPs PD-L1 proved to be an independent prognostic factor to prioritize high-risk patients.ConclusionsImmunologic differences between SCCUP and OPSCC were detected. A higher PD-L1 expression in SCCUP could potentially facilitate further evaluation of checkpoint inhibitor therapy.

Transoral robotic surgery (TORS)-guided radiotherapy (RT) volume de-intensification in p16-positive unknown primary squamous cell carcinoma (SCC) of the neck: A phase 2 trial (FIND).

6067 Background: TORS has improved the likelihood of identifying an oropharyngeal cancer for patients presenting with unknown primary. We evaluate the oncologic and functional outcomes after reduction of RT volumes based on TORS findings. Methods: Patients with p16-positive, neck SCC (cN1-N3) with no primary on examination and CT/MRI were included between 08/2017 and 12/2019. All patients underwent PET-CT, surgical evaluation with either therapeutic intent including neck dissection for cN1 without extranodal extension (Group 1, n=9) or diagnostic intent (Group 2, n=13). Patients underwent excision of palatine tonsil (PT) followed by lingual tonsil (LT), if the PT was negative, or excision of PET-CT avid regions. Pharyngeal-sparing radiotherapy (PSRT) was given when no primary was found (pT0) and for primaries completely excised (margins &gt;= 3mm). Unilateral neck radiotherapy (UNRT) was given for lateralized (&gt;1 cm from midline) primaries or pT0 with unilateral disease. The primary outcome was 2-year out-of-treated volume failures (OTVF). Swallowing-related quality of life (SR-QOL) was measured using MD Anderson Dysphagia Inventory (MDADI) composite score. A sample size of 22 was required assuming OTVF cannot exceed 15% (vs. 1% historical), power of 0.8, alpha of 0.05 (one-sided), and loss to follow-up of 10%. Results: All 22 patients [median age 60 (46-68); 86% male; 86% N1, 9% N2, 5% N3] underwent surgical evaluation. PET-CT showed suspicious findings in 12 (55%) [sensitivity = 0.44, specificity = 0.29]. Excision of PT and LT were performed in 14 (64%) and 14 (64%) patients respectively; and 8 (36%) had previous PT. Oropharyngeal primaries were found in 17 patients (77%) [14 (64%) single primary, 3 (13%) two primaries]. RT volume de-intensification was achieved in 11 patients (50%) who had PSRT and 10 (45%) who had UNRT. In Group 1, adjuvant RT was given to 6 (67%) and CRT to 1 (11%). In group 2, 8 (62%) had RT and 5 (38%) had CRT. There were no OTVF, local, or regional failures [median follow-up 29 months]. Two-year OS, DFS, and LRC were 100%, 95%, and 100%. SR-QOL showed good recovery (Table). Grade III/IV surgical as well as acute and late toxicities occurred in 2 (9%), 5 (23%), and 1 (5%) respectively. Conclusions: TORS evaluation for p16-positive unknown primary SCC allowed RT volume de-intensification with excellent disease control and quality of life. Future randomized trials can compare transoral surgery versus existing diagnostic approaches. MDADI composite scores. Clinical trial information: NCT03281499. [Table: see text]

The usefulness of FDG-PET/CT in the diagnosis of head and neck squamous cell carcinoma (HNSCC) of unknown primary with cervical lymph node metastasis

Introduction: Carcinoma of unknown primary is uncommon, estimated to represent only 3–5% of all head and neck cancers. Aim: The aim of our study was to estimate the role of FDG-PET/CT in the detection of the occult primary tumor in patients with histologically proven squamous cell carcinoma and cervical lymph node metastasis. Materials and Methods : We retrospectively reviewed a total of 18 patients with unknown primary and head and neck squamous cell carcinoma (HNSCC) presented as cervical lymph node metastasis. They were referred to the Department of Nuclear Medicine in the period 2015–2017. All patients presented fine-needle biopsy proven squamous cell carcinoma metastasis of the neck lymph nodes. The patients underwent PET/CT for detection of unknown primary head and neck cancer after endoscopic/physical examination and computer imaging (contrast-enhanced CT of neck, thorax/abdomen). The final results were obtained from the histopathologic reports of tissue samples from anatomical regions suspected for primary tumor, additional imaging exams and clinical follow-up data. Results : There were FDG-PET/CT identified sites suggestive of primary tumor location in 12 patients. Subsequent directed biopsy of these sites yielded positive results in 11 cases (61%): hypopharynx—1 (9%), nasopharynx—3 (27%), oropharynx—5 (42%), larynx—1 (9%), skin of the face—1 (9%). Тhere was 1 false positive result (5.5%). Six out of 18 patients (33%) remained without evidence of a primary tumor. In 1 case (5.5%) we did not reveal any pathology within the localizations indicated by FDG-ET/CT on directed biopsy. In 1 case (5.5%) we obtained histological confirmation of neoplasm despite the negative results of the PET/CT scan. FDG-PET/CT had a sensitivity of 92%, a specificity of 83%, a positive predictive value of 92%, a negative predictive value of 83%, and accuracy of 89% in the identification of head and neck squamous cell carcinoma of unknown primary with cervical lymph node metastasis. Conclusion: Non-invasive FDG-PET/CT offers a great likelihood of successfully identifying the location of head and neck squamous cell carcinoma of unknown primary with cervical lymph node metastasis.

Approach to the Patient with Unknown Primary Squamous Cell Carcinoma of the Head and Neck.

Head and neck cancer of unknown primary (HNCUP) is increasingly encountered in both community otolaryngology practice and the academic head and neck cancer program. A stepwise diagnostic evaluation will identify many primary sites. However, true HNCUP remains common in high-volume practices after appropriate examination, imaging, and biopsies. The prognosis for the majority of the patients is good, owing to the common association with high-risk HPV, and putative oropharyngeal primary origin. With high oncologic control rates, judicious treatment selection is essential to optimize functional outcomes.

Narrowband Imaging for p16+ Unknown Primary Squamous Cell Carcinoma Prior to Transoral Robotic Surgery.

Our purpose was to assess the potential utility of narrowband imaging (NBI) as a tool in diagnosing and treating unknown primary oropharyngeal squamous cell carcinoma (OPSCC) in patients prior to diagnostic resection with transoral robotic surgery (TORS). Between 2016 and March 2019, 29 patients with carcinoma of unknown primary meeting inclusion criteria were identified and treated with TORS. NBI was used preoperatively in 9 of 29 patients. A suspected tumor site was delineated by NBI in 8 of 9 patients (89%). Of the patients imaged with NBI, 8 of 9 (89%) patients had a pathologically confirmed tumor following TORS, corresponding to the same 8 suspected tumor sites identified with NBI. In contrast, a primary tumor was localized following TORS in 15 of 20 (75%) patients not evaluated with NBI. Thus, we see NBI as a potentially useful tool for the diagnosis and management of p16+ carcinoma of unknown primary.Level of Evidence: IIb.

Intraoperative Primary Tumor Identification and Margin Assessment in Head and Neck Unknown Primary Tumors

Surgical management of the unknown primary head and neck squamous cell carcinoma (UP HNSCC) remains controversial due to challenging clinical diagnosis. This study compares positron emission tomography-computed tomography (PET-CT) findings with intraoperative identification of primary tumors and compares intraoperative frozen-section margins to final histopathology. In addition, adjuvant therapy indications are provided. Prospective cohort study. Academic university hospital. Sixty-one patients with UP HNSCC were included. Patients received PET-CT, followed by oropharyngeal transoral laser microsurgery (TLM). Margins were assessed intraoperatively using frozen sections and afterward by final histopathology. Adjuvant treatment was based on final histopathology. The sensitivity of localizing the primary tumor with PET-CT was 50.9% with a specificity of 82.5%. The primary tumor was found intraoperatively on frozen sections in 82% (n = 50) of patients. Five more tumors were identified on final histopathology, leading to a total of 90% (n = 55). Of the 50 intraoperatively found tumors, 98% (n = 49) had negative margins on frozen sections, and 90% (n = 45) were truly negative on final histopathology. Eighteen patients (29.5%) avoided adjuvant treatment. PET-CT localized the primary tumor in fewer than half the cases. This protocol identified 90% of primary tumors. Intraoperative frozen-section margin assessment has shown potential with a specificity of 92% compared to final histopathology. As a result, adjuvant therapy was avoided in almost one-third of our patients.

Finding/identifying primaries with neck disease (FIND) clinical trial protocol: a study integrating transoral robotic surgery, histopathological localisation and tailored deintensification of radiotherapy for unknown primary and small oropharyngeal head and neck squamous cell carcinoma

IntroductionCarcinomas of unknown primary site (CUP) of the head and neck have historically been worked up and managed heterogeneously. Failure to identify a primary site may result in large radiotherapy...

Roles of Ki-67 and p16 as biomarkers for unknown primary head and neck squamous cell carcinoma

Treatment guidelines have not been established for unknown primary head and neck squamous cell carcinoma (SCC). For these patients, chemoradiotherapy (CRT) can provide a better prognosis than that for patients with other head and neck cancers. The presence of HPV in the tumor is associated with a better outcome. However, not all patients with HPV-positive unknown primary head and neck SCC experience good treatment outcomes in actual clinical settings. We thus retrospectively determined the Ki-67 proliferation index and p16 expression status to assess the associations of these parameters with treatment outcomes of patients with unknown primary head and neck SCC. The subjects were 13 patients who underwent CRT after surgery or excision biopsy between 1999 and 2016. The 2- and 5-year overall survival (OS) rate was 76.9% and 68.4%, respectively. The prognostic factor was age. There was no significant difference in survival between patients with a high Ki-67 vs. low Ki-67 or between patients with p16-positive vs. p16-negative metastases OS. However, all p16-positive patients with low Ki-67 showed good locoregional control. The combination of ki67 expression and p16 expression status may allow prediction of local control more accurately than p16 expression status alone.

Treatment outcomes of unknown primary squamous cell carcinoma of the head and neck.

BackgroundTreatment modality of unknown primary squamous cell carcinoma of the head and neck (SCCHN) remains controversial.ObjectivesTo evaluate the treatment outcomes and prognostic factors of unknown primary SCCHN.Materials and methodsPatients with unknown primary SCCHN from April 1995 to March 2013 were recruited retrospectively.ResultsSixty-nine patients were enrolled. The median time of follow-up was 55.5 months. The 2-year loco-regional control rate of all the patients was 60.4%. Multivariate Cox regression analysis revealed that N3 stage, extracapsular spread, distant metastasis, and treatment modality were significantly associated with neck recurrence. The actuarial 5-year disease-specific survival rates of neck dissection, neck dissection plus adjuvant therapy, radiotherapy alone, and combined therapy were 80.0%, 61.7%, 33.3%, and 68.8%, respectively (p = 0.046). The 5-year disease-specific survival rates of N1/N2a, N2b/N2c, and N3 stage were 83.9%, 64.3%, and 36.7%, respectively (p = 0.013). Univariate regression analysis revealed that neck recurrence, supraclavicular node involvement, distant metastasis, N3 stage, and unhealthy lifestyle habits were correlated with disease-specific mortality, especially the first three parameters. Patient’s occupation and comorbidity were not significantly correlated with survival.ConclusionsComposite therapy is mandatory for advanced unknown primary SCCHN. Supraclavicular node involvement and unhealthy lifestyle habits, such as betel nut chewing, indicate a poor prognosis.

Combination of panendoscopy and positron emission tomography/computed tomography increases detection of unknown primary head and neck carcinoma.

With positron emission tomography/computed tomography (PET/CT) now commonplace as a diagnostic tool, new questions have arisen regarding the utility and cost-effectiveness of panendoscopy. In this retrospective review of a large cohort of head and neck squamous cell carcinoma of unknown primary (HNSCC-UP), we describe the enduring utility of panendoscopy in the detection of the primary site of mucosal disease even when PET/CT is negative. Retrospective cohort study. A retrospective analysis of patients presenting to the senior author (y.d.) from July 1 1997 to July 1 2017 with fine-needle aspiration-proven metastatic squamous cell carcinoma to the neck. All patients underwent formal panendoscopy (direct laryngoscopy, bronchoscopy, and rigid esophagoscopy). Presence of squamous cell carcinoma on final pathology was examined. A total of 190 patients had HNSCC-UP, with 87 positive and 103 negative on PET/CT. Of the PET/CT-negative patients, 71 patients retained the HNSCC-UP designation after panendoscopy. Eighteen patients (56% of cases) were found to have primary tonsillar squamous cell carcinoma. Eight of 32 primary sites were found in the base of tongue (25%), with HPV positivity in two of these patients. The sensitivity and negative predictive value of PET/CT in detecting the primary site in unknown primary head and neck squamous cell carcinoma in the total study population were 73.1% and 68.9%, respectively. Surgical panendoscopy has an important role in the workup of patients with unknown primary head and neck squamous cell carcinoma. There is a high rate of cancer diagnosis, even in PET/CT negative patients. 4 Laryngoscope, 2573-2575, 2018.

Effectiveness of primary surgery versus primary radiotherapy on unknown primary head and neck squamous cell carcinoma: a systematic review protocol.

The review question is: what is the effectiveness of primary surgery versus primary radiotherapy on disease-free survival and quality of life in adults with an unknown primary, head and neck squamous cell carcinoma?

Unknown primary squamous cell carcinoma of the head and neck: retrospective analysis of 80 cases

Objectives: The management of patients with cervical metastasis in head and neck cancer of unknown primary (HNCUP) remains controversial. This current multicenter retrospective study investigated the treatment outcomes of patients with HNCUP.Methods: The study included patients who were treated curatively at 12 institutions in Japan from January 2006 to December 2015.Results: Eighty patients with HNCUP were included. The median follow-up period was 34 months. The three-year overall survival (OS), disease-specific survival (DSS), regional relapse-free survival (RRFS), local progression-free survival (LPFS), and distant metastasis-free survival (DMFS) rates were 72.5%, 80.3%, 74.0%, 89.7%, and 86.9%, respectively. Nodal status was a significant factor for OS, DSS, RRFS, and DMFS; and extracapsular extension (ECE) was significant for OS and DSS. There was a distinct difference between the survival rates of patients with N1–2a and N2b–3 disease. RT was a significant positive factor for LPFS (3-year LPFS, RT 93.0% vs. no RT 83.0%, p = .043).Conclusions: For N2a as well as N1 disease without ECE, a single treatment modality, including ND or RT alone is acceptable. When ND alone is performed, thorough monitoring should be continued during follow-up to identify the emergence of the primary lesion.

Post-operative therapy following transoral robotic surgery for unknown primary cancers of the head and neck

ObjectivesOur primary objective is to describe the post- operative management in patients with an unknown primary squamous cell carcinoma of the head and neck (HNSCC) treated with trans-oral robotic surgery (TORS). Materials & MethodsWe conducted a retrospective multi-institutional case series including all patients diagnosed with an unknown primary HNSCC who underwent TORS to identify the primary site from January 1, 2010 to June 30, 2016. We excluded those with recurrent disease, ≤6months of follow up from TORS, previous history of radiation therapy (RT) to the head and neck, or evidence of primary tumor site based on previous biopsies. Our main outcome measure was receipt of post-operative therapy. ResultsThe tumor was identified in 26/35 (74.3%) subjects. Post-TORS, 2 subjects did not receive adjuvant therapy due to favorable pathology. Volume reduction of RT mucosal site coverage was achieved in 12/26 (46.1%) subjects who had lateralizing tumors, ie. those confined to the palatine tonsil or glossotonsillar sulcus. In addition, for 8/26 (30.1%), the contralateral neck RT was also avoided. In 9 subjects, no primary was identified (pT0); four of these received RT to the involved ipsilateral neck nodal basin only without pharyngeal mucosal irradiation. ConclusionSurgical management of an unknown primary with TORS can lead to deintensification of adjuvant therapy including avoidance of chemotherapy and reduction in RT doses and volume. There was no increase in short term treatment failures. Treatment after TORS can vary significantly, thus we advocate adherence to NCCN guideline therapy post-TORS to avoid treatment-associated variability.

Neck dissection for unknown cancer of the head and neck in the era of chemoradiation

PurposeTo report outcomes for patients with cervical lymph node metastases from an unknown primary site of the head and neck treated with either non-operative therapy or neck dissection followed by adjuvant therapy. Materials and MethodsAll patients with squamous cell carcinoma of an unknown primary site of the head or neck seen between 2003 and 2013 were reviewed. The Kaplan-Meier method was used to estimate overall survival, local recurrence free survival, loco-regional recurrence free survival, and progression free survival. The log-rank test and proportional hazards regression were used to analyze factors influencing outcomes. ResultsOf 2258 patients with a new diagnosis of head and neck cancer, no primary site was identified in 66 patients. Twenty-nine patients were treated with definitive non-operative therapy (15 with chemoradiation and 14 with radiation alone). Thirty-seven patients received an upfront neck dissection followed by adjuvant radiation or chemoradiation. Three-year loco-regional recurrence free survival, progression free survival, and overall survival were 55.9%, 55.4%, and 69.4% respectively. Patients treated with preoperative neck dissection had improved local recurrence free survival (96.7% vs 54.1%, p=0.003) and loco-regional recurrence free survival (82.2% vs 46.4%, p=0.068) compared to patients treated with definitive chemoradiation with no difference in overall survival (p=0.641). ConclusionsNeck dissection improved local and regional control but not overall survival in patients with unknown primary squamous cell carcinoma of the head and neck over non-operative therapy alone.

Unknown primary head and neck squamous cell carcinoma in the era of fluorodeoxyglucose-positron emission tomography/CT and intensity-modulated radiotherapy.

The diagnosis and treatment of head and neck carcinoma of unknown primary (CUP) have changed with the introduction of fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT and intensity-modulated radiotherapy (IMRT), with potential implications for outcome. We conducted a retrospective analysis of 80 patients with head and neck CUP who were PET-staged and treated with curative intention using IMRT between 2006 and 2016 in the Netherlands Cancer Institute. Patient, tumor, and treatment demographics were recorded and oncologic outcomes were analyzed. Local control was 100% in mucosal irradiated patients. Regional control was 90%. Ten patients developed distant metastases, which were associated with N3, extracapsular extension (ECE) and lower neck positive lymph nodes. Overall survival (OS) at 5 years was 62% and disease-specific survival was 78%. ECE, N3 neck, multiple levels of positive lymph nodes, and positive lymph nodes in the lower neck were associated with worse prognosis. Locoregional outcome of head and neck CUP managed with modern techniques is good. Future research needs to focus on reducing toxicity and patients prone for distant metastasis.

Transoral robotic surgery for management of cervical unknown primary squamous cell carcinoma: Updates on efficacy, surgical technique and margin status

ImportanceManagement of cervical unknown primary squamous cell carcinoma (CUP) has evolved with the introduction of transoral robotic surgery (TORS). Objectives1. To describe the efficacy of TORS lingual and palatine tonsillectomy in identifying the primary site of malignancy. 2. To explore how the extent of surgery affects diagnostic yield. 3. To report margin status of TORS resections. Design, setting and participantsA retrospective, single-center cohort study utilizing a prospectively collected database of CUP patients in a high-volume tertiary referral center. Patient underwent operative laryngoscopy plus TORS as clinically indicated. Main outcomes and measuresPrimary end point was successful identification of the primary. The extent of surgery and margin status were also examined. ResultsFrom 2010–2016, 64 patients with CUP were treated. The primary tumor was found in 51 patients (80%). Fourteen patients (22%) were identified with operative laryngoscopy alone. Fifty patients underwent TORS lingual tonsillectomy ± palatine tonsillectomy with 37 primary tumors identified (74%). The primary was located in the lingual tonsil in 32 patients (86%) and palatine tonsil in 5 patients (10%, p<0.001). Negative margins were achieved in 19 patients (51%). The deep margin was the most commonly positive margin (47%, p=0.049). Conclusion and relevanceOperative laryngoscopy with TORS is efficacious, localizing the primary in 80% of patients. If a margin was positive, it was most commonly the deep margin. This study provides valuable information that can help standardize surgical technique, further increasing the diagnostic yield and decreasing the negative margin rate of TORS for CUP.