Simone Marnitz

Role of Surgical Versus Clinical Staging in Chemoradiated FIGO Stage IIB-IVA Cervical Cancer Patients—Acute Toxicity and Treatment Quality of the Uterus-11 Multicenter Phase III Intergroup Trial of the German Radiation Oncology Group and the Gynecologic Cancer Group

PURPOSE The Uterus-11 trial was designed to evaluate the role of surgical staging in patients with cervical cancer before primary chemoradiation therapy (CRT). The present report provides the toxicity data stratified by the treatment arm and technique. METHODS AND MATERIALS A total of 255 patients with carcinoma of the uterine cervix (International Federation of Gynecology and Obstetrics stage IIB-IVA) were randomized to either surgical staging followed by CRT (arm A) or clinical staging followed by CRT (arm B). Patients with para-aortic metastases underwent extended field radiation therapy (RT). Brachytherapy was mandatory. The present report presents the acute therapy-related toxicities stratified by treatment arm and radiation technique. RESULTS A total of 240 patients were eligible (n=121 in arm A; n=119 in arm B). Of the 240 patients, 236 (98.3%) underwent external beam RT with a median total dose of 50.4 Gy. The mean treatment duration was 53 days. Of the patients, 60% underwent intensity modulated RT (IMRT). A total of 234 patients (97.5%) underwent chemotherapy, and 231 (96.3%) underwent brachytherapy, with a median single dose of 6 Gy covering the tumor to a median nominal total dose of 28 Gy. Treatment was well tolerated, with 0% grade ≥3 genitourinary and gastrointestinal toxicity, 6% grade 3 nausea, 3% grade 3 vomiting, and <2% grade 3 diarrhea. More patients after surgical staging experienced grade 2 anemia (54.3% in arm A vs 45.3% in arm B; P=.074) and grade 2 leukocytopenia (41.4% vs 31.6%; P=.56). Of the patients who received IMRT versus a 3-dimensional technique, 65.3% versus 33.7% presented with grade 2 anemia. Grade 3 gastrointestinal and grade 2 bladder toxicity were significantly reduced with the use of IMRT. CONCLUSIONS The incidence and severity of acute therapy-related toxicity compared favorably with those from other randomized trials. Excellent adherence to treatment and treatment quality was achieved compared with patterns of care analyses. Surgical staging led to a doubled number of patients treated with extended field RT. The question of whether surgical staging is beneficial in the context of primary CRT requires further study.

Molecular Diagnosis for Nodal Metastasis in Endoscopically Managed Cervical Cancer: The Accuracy of the APTIMA Test to Detect High-risk Human Papillomavirus Messenger RNA in Sentinel Lymph Nodes.

STUDY OBJECTIVE To evaluate the feasibility and accuracy of a commercially available test to detect E6/E7 mRNA of 14 subtypes of high-risk HPVs (APTIMA; Hologic, Bedford, MA) in the sentinel lymph nodes of CC patients laparoscopically operated. DESIGN Prospective pilot study. SETTING The study was conducted in the Department of Advanced Operative and Oncologic Gynecology, Asklepios Hospital, Hamburg, Germany. PATIENTS 54 women with HPV-positive CC submitted to laparoscopic sentinel node biopsy alone or sentinel node biopsy followed by systematic pelvic and/or para-aortic endoscopic lymphadenectomy. INTERVENTIONS All removed sentinel lymph nodes (SLNs) underwent sample collection by cytobrush for the APTIMA assay before frozen section. MEASUREMENTS Results obtained with the HPV mRNA test were compared with the definitive histopathological analysis of the SLNs and additional lymph nodes removed. RESULTS A total of 125 SLNs (119 pelvic and 6 paraaortic) were excised with a mean number of 2.3 SLNs per patient. Final histopathologic analysis confirmed nodal metastases in 10 SLNs from 10 different patients (18%). All the histologically confirmed metastatic lymph nodes were also HPV E6/E7 mRNA positive, resulting in a sensitivity of 100%. Four histologically free sentinel nodes were positive for HPV E6/E7 mRNA, resulting in a specificity of 96.4%. CONCLUSION The HPV E6/E7 mRNA assay in the SLNs of patients with CC is feasible and highly accurate. The detection of HPV mRNA in 4 women with negative SLNs might denote a shift from microscopic identification of metastasis to the molecular level. The prognostic value of this findings awaits further verification.

Neoadjuvante Chemotherapie vor radikaler Hysterektomie beim Zervixkarzinom – Response ist nicht Überleben

Hintergrund Obwohl zunehmend außerhalb klinischer Studien eingesetzt, war und ist die Evidenz für einen Vorteil durch eine neoadjuvante Chemotherapie (NACT) bei den hier untersuchten Stadien des Zervixkarzinoms mehr als dürftig [2, 3]. Trotzdem fand und findet, mit Verweis auf beeindruckende Responseraten, der Einsatz der NACT viele Befürworter und Anwender. Diese Kenntnislücke wollten die Autoren mit einer randomisierten Phase-III-Studie an einem großen Patientengut schließen [1].

The relevance of the lymph node ratio as predictor of prognosis is higher in HPV-negative than in HPV-positive oropharyngeal squamous cell carcinoma

Lymph node ratio (LNR) is an established predictor in different entities of carcinoma, including head and neck malignancies. In oropharyngeal squamous cell carcinoma (OPSCC), lymph node involvement differs between human papilloma virus (HPV)‐positive and HPV‐negative tumours. Herein, we evaluate the impact of HPV association on the concept of LNR.

Substantieller Vorteil durch CT-geplante HDR-Brachytherapie bei Zervixkarzinompatientinnen im Vergleich zu historischen Serien bezüglich lokaler Kontrolle und Toxizität?

Hintergrund und Zielsetzung Die primäre Radiochemotherapie (RCT) ist die Standardbehandlung für Patientinnen mit nodal positiven und/oder lokal fortgeschrittenen Zervixkarzinomen. Die Therapie besteht aus perkutaner Strahlentherapie (EBRT), simultaner Chemotherapie mit Cisplatin und einer intrazervikalen Brachytherapie (BT). Der Einsatz der hoch standardisierten BT aufMRT-Basis konnte die lokale Kontrolle deutlich verbessern und auch die Toxizität unter definierten Kriterien wesentlich absenken [1].