Standardized Diagnostics Including PET-CT Imaging, Bilateral Tonsillectomy and Neck Dissection Followed by Risk-Adapted Post-Operative Treatment Favoring Radio-Chemotherapy Improve Survival of Neck Squamous Cell Carcinoma of Unknown Primary Patients

Abstract

BackgroundAbout five to 10% of cancers in the head and neck region are neck squamous cell carcinoma of unknown primary (NSCCUP). Their diagnosis and treatment are challenging given the risk of missing occult tumors and potential relapse. Recently, we described human papillomavirus (HPV)-related NSCCUP-patients (NSCCUP-P) as a subgroup with superior survival. However, standardized diagnostic workup, novel diagnostic procedures, decision-making in the multidisciplinary tumor board (MDTB) and multimodal therapy including surgery and post-operative radio-chemotherapy (PORCT) may also improve survival.MethodsFor assessing the impact of standardized diagnostic processes simultaneously established with the MDTB on outcome, we split our sample of 115 NSCCUP-P into two cohorts treated with curative intent from 1988 to 2006 (cohort 1; n = 53) and 2007 to 2018 (cohort 2; n = 62). We compared diagnostic processes and utilized treatment modalities applying Chi-square tests, and outcome by Kaplan–Meier plots and Cox regression.ResultsIn cohort 2, the standardized processes (regular use of [18F]-FDG-PET-CT imaging followed by examination under anesthesia, EUA, bilateral tonsillectomy and neck dissection, ND, at least of the affected site) improved detection of primaries (P = 0.026) mostly located in the oropharynx (P = 0.001). From 66.0 to 87.1% increased ND frequency (P = 0.007) increased the detection of extracapsular extension of neck nodes (ECE+) forcing risk factor-adapted treatment by increased utilization of cisplatin-based PORCT that improved 5-years progression-free and overall survival from 60.4 and 45.3 to 67.7% (P = 0.411) and 66.1% (P = 0.025).ConclusionsStandardized diagnostic workup followed by ND and risk-factor adapted therapy improves survival of NSCCUP-P.

Standardized Diagnostic Workup and Patient-Centered Decision Making for Surgery and Neck Dissection Followed by Risk-Factor Adapted Adjuvant Therapy Improve Loco-Regional Control in Local Advanced Oral Squamous Cell Carcinoma

“…Despite significantly improved LC and LRC, the DC appeared to be reduced (p=0.0033). A reduced DC/DMFS was also reported for neck squamous cell carcinoma of unknown primary tumors (8). Impaired DC in our sample was found to be significantly associated with N3 category (p=2.97•10 -4 ), localization in the tongue (C02; p=0.049), ECE+ (p=3.16•10 -5 ), and history of tobacco smoking (≤40 vs. >40 pack years, p=0.044).…”

“…This change is attributable to the adherence and better implementation of the guidelines linked to decision-making and quality control of results in the MDTB. The benefit of an elective neck dissection for survival was demonstrated in cN0 oral cancer in several studies (5,8,10,17). The mean number of assessed lymph nodes (nodal yield) increased from 10.1 before 2006 to 26.9 after 2006, respectively, suggesting the quality of neck dissection during the study period.…”

“…In cohort 2, the LAOSCC-P with ND and detection of only unilateral N+ (N2b) without risk factors present (up to 2 N+ <6 cm, no ECE, R0/no incision biopsy) received PORT of 60 Gy ipsilateral and 50 Gy contralateral, independent from ND also of the unaffected site or not. Irradiation after resection of a single node without risk factors (<6 cm, no ECE, R0/no incision biopsy) was unilateral 60 Gy ( 8 , 9 ). Whenever risk factors for local recurrence (bilateral N+, i.e.…”

“…N2c, or one node ≥6 cm, i.e. N3, or ECE+, R1) were detected, bilateral irradiation with 64 Gy was accompanied by concomitant cisplatin ( 8 , 9 ). Cisplatin was given either in up to 3 cycles of single infusions (100 mg/m 2 at days 1, 22, and 43) or fractionated in five daily doses of 20 mg/m 2 (days 1-5, 22-26, and 43-47) ( 8 , 9 ).…”

“…The general use of computed tomography (CT) imaging, in selected cases combined with positron-emission tomography (PET-CT) ( 1 ) together with standardized staging procedures ( 2 ) and presentation of LAOSCC patients in multidisciplinary tumor boards (MDTB) before treatment ( 3 , 4 ) as well as utilization of elective neck dissection (ND) even in absence of suspect neck nodes (radiologic N0 category) are shown to improve outcome ( 5 ). The implementation of evidence-based decision-making for particular diagnostic and therapy according to institutional guidelines by adhering to NCCN ( 6 ) and ASCO guidelines ( 7 ) and the discussion of the individual case in the light of results obtained with the modern diagnostic and therapeutic procedures should improve survival rates especially in LAOSCC, as we recently demonstrated improved outcome since 2007 for neck squamous cell carcinoma of unknown primary ( 8 ). However, the now more patient-centered decision-making processes that consider individual preferences of the patient as well as more intense counselling of the patient that includes offering to get second opinion from another health care provider, sometimes associated with a delay in starting the treatment, and other factors may lead to increased heterogeneity in treatment applied and the individual clinical course of the patient and hence also influence the outcome.…”