Comparative effectiveness trial of transoral head and neck surgery followed by adjuvant radio(chemo)therapy versus primary radiochemotherapy for oropharyngeal cancer (TopROC)

Abstract

Background For loco-regionally advanced, but transorally resectable oropharyngeal cancer (OPSCC), the current standard of care includes surgical resection and risk-adapted adjuvant (chemo) radiotherapy, or definite chemoradiation with or without salvage surgery. While transoral surgery for OPSCC has increased over the last decade for example in the United States due to transoral robotic surgery, this treatment approach has a long history in Germany. In contrast to Anglo-Saxon countries, transoral surgical approaches have been used frequently in Germany to treat patients with oro-, hypopharyngeal and laryngeal cancer. Transoral laser microsurgery (TLM) has had a long tradition since its introduction in the early 70s. To date, the different therapeutic approaches to transorally resectable OPSCC have not been directly compared to each other in a randomized trial concerning disease control and survival. The goal of this study is to compare initial transoral surgery to definitive chemoradiation for resectable OPSCC, especially with regards to local and regional control. Methods TopROC is a prospective, two-arm, open label, multicenter, randomized, and controlled comparative effectiveness study. Eligible patients are ≥18 years old with treatment-naïve, histologically proven OPSCC (T1, N2a-c, M0; T2, N1–2c, M0; T3, N0-2c, M0 UICC vers. 7) which are amenable to transoral resection. Two hundred eighty patients will be randomly assigned (1:1) to surgical treatment (arm A) or chemoradiation (arm B). Standard of care treatment will be performed according to daily routine practice. Arm A consists of transoral surgical resection with neck dissection followed by risk-adapted adjuvant therapy. Patients treated in arm B receive standard chemoradiation, residual tumor may be subject to salvage surgery. Follow-up visits for 3 years are planned. Primary endpoint is time to local or locoregional failure (LRF). Secondary endpoints include overall and disease free survival, toxicity, and patient reported outcomes. Approximately 20 centers will be involved in Germany. This trial is supported by the German Cancer Aid and accompanied by a scientific support program. Discussion This study will shed light on an urgently-needed randomized comparison of the strategy of primary chemoradiation vs. primary surgical approach. As a comparative effectiveness trial, it is designed to provide data based on two established regimens in daily clinical routine. Trial registration NCT03691441 Registered 1 October 2018 - Retrospectively registered.

Detection of stage I HPV-driven oropharyngeal cancer in asymptomatic individuals in the Hamburg City Health Study using HPV16 E6 serology – A proof-of-concept study

“…All underwent treatment, currently undergo post-treatment surveillance and are currently free of recurrence. 21 Clinical diagnosis and treatment are described in detail in the supplement (Supplementary Table 6 and Supplementary Figure 1). In essence, one male participant was diagnosed at his first study visit with a prevalent tumor showing signs of advanced disease (i.e., extracapsular extension, ECE); the other male participant had an incident diagnosis of an ECE-positive tumor at his third study visit; and the female participant presented with an incident diagnosis of a small tumor without lymph node involvement at her third study visit.…”

Eugenol as a potential adjuvant therapy for gingival squamous cell carcinoma

“…This was to be expected as tongue carcinoma is generally regarded as a more aggressive and a highly metastatic entity as opposed to other oral subsites 45 . For instance, cervical lymph node metastasis, greatly correlated with tongue tumors, is known to reduce survival chances half 6,8,46 . In the present study, we focused on eugenol effectiveness against a less aggressive form occurring in the gingival tissue.…”

“…Despite proximity, the affected oral cavity subsite is also to be considered when planning therapy due to distinct anatomical features. In general, the standard oncologic control procedure consists of primary surgical resection 8 . According to tumor size and location, invasive approaches become necessary and involve a multidisciplinary team of experts to ensure favorable outcomes through reconstruction of surgical defects together with speech, swallowing and behavioral rehabilitation.…”

Strahlentherapie oder Operation bei HPV-positiven Oropharynxkarzinomen? Die ORATOR2-Studie – ein Vergleich von Birnen und Äpfeln

“…Die ORATOR-Studien sind aktuell die einzigen randomisierten Studien, die bereits – mit o. g. Einschränkungen – Ergebnisse zur Frage liefern, ob Oropharynxkarzinome primär operiert oder radio-(chemo)therapiert werden sollten. Die TopROC-Studie, eine IIT in Deutschland zu dieser Fragestellung, musste aufgrund der schleppenden Rekrutierung frühzeitig geschlossen werden, und die Ergebnisse der eingeschlossenen Patienten stehen bislang aus 36 . Die „Best-of Studie“ EORTC-1420 zählt aktuell über 50 eingeschlossene HPV-positive/negative Patienten und rekrutiert aktuell weiterhin im europäischen Raum zu dieser Fragestellung 37 .…”