Matthias Kreppel

Impact of podoplanin expression in oral squamous cell carcinoma: clinical and histopathologic correlations

Cervical lymph node metastases reduce the overall survival of patients with oral squamous cell carcinoma (OSCC) and require a neck dissection. However, elective management of a clinical N0 neck remains a controversial topic, as there are no reliable factors available predicting cervical lymph node metastases. Recent studies suggest an impact of podoplanin expression on metastatic spread to the cervical lymph nodes. Our aim was to investigate the influence of podoplanin expression on prognosis and metastatic lymphatic spread. In our retrospective study, podoplanin expression was examined in a set of 80 patients with OSCC by immunhistochemistry. We analysed associations between the level of podoplanin expression and various clinicopathologic parameters. In 67 patients (84%), podoplanin was expressed on the tumour cells. Nineteen patients (24%) showed high levels of expression. The 5-year overall survival (31%) for patients with high levels of podoplanin expression was significantly lower (p < 0.001) than for patients with low and moderate expression of podoplanin (93% and 65%, respectively). There was an association between podoplanin expression and the frequency of cervical lymph node metastases. Cervical lymph node metastases were found in 79% of the patients with high podoplanin expression, while patients with weak podoplanin expression had metastases in only 22% (p < 0.001). None of the 13 patients without podoplanin expression had cervical lymph node metastases. We concluded that podoplanin is expressed frequently in OSCC and that podoplanin expression correlates with cervical lymph node metastases and clinical outcome.

Lymph node density in oral cavity cancer: results of the International Consortium for Outcomes Research

Background:Lymph node density (LND) has previously been reported to reliably predict recurrence risk and survival in oral cavity squamous cell carcinoma (OSCC). This multicenter international study was designed to validate the concept of LND in OSCC.Methods:The study included 4254 patients diagnosed as having OSCC. The median follow-up was 41 months. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control and distant metastasis rates were calculated using the Kaplan–Meier method. Lymph node density (number of positive lymph nodes/total number of excised lymph nodes) was subjected to multivariate analysis.Results:The OS was 49% for patients with LND⩽0.07 compared with 35% for patients with LND>0.07 (P<0.001). Similarly, the DSS was 60% for patients with LND⩽0.07 compared with 41% for those with LND>0.07 (P<0.001). Lymph node density reliably stratified patients according to their risk of failure within the individual N subgroups (P=0.03). A modified TNM staging system based on LND ratio was consistently superior to the traditional system in estimating survival measures.Conclusion:This multi-institutional study validates the reliability and applicability of LND as a predictor of outcomes in OSCC. Lymph node density can potentially assist in identifying patients with poor outcomes and therefore for whom more aggressive adjuvant treatment is needed.

Primary Tumor Staging for Oral Cancer and a Proposed Modification Incorporating Depth of Invasion: An International Multicenter Retrospective Study

IMPORTANCE The current American Joint Committee on Cancer (AJCC) staging system for oral cancer demonstrates wide prognostic variability within each primary tumor stage and provides suboptimal staging and prognostic information for some patients. OBJECTIVE To determine if a modified staging system for oral cancer that integrates depth of invasion (DOI) into the T categories improves prognostic performance compared with the current AJCC T staging. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of 3149 patients with oral squamous cell carcinoma treated with curative intent at 11 comprehensive cancer centers worldwide between 1990 and 2011 with surgery ± adjuvant therapy, with a median follow-up of 40 months. MAIN OUTCOMES AND MEASURES We assessed the impact of DOI on disease-specific and overall survival in multivariable Cox proportional hazard models and investigated for institutional heterogeneity using 2-stage random effects meta-analyses. Candidate staging systems were developed after identification of optimal DOI cutpoints within each AJCC T category using the Akaike information criterion (AIC) and likelihood ratio tests. Staging systems were evaluated using the Harrel concordance index (C-index), AIC, and visual inspection for stratification into distinct prognostic categories, with internal validation using bootstrapping techniques. RESULTS The mean and median DOI were 12.9 mm and 10.0 mm, respectively. On multivariable analysis, DOI was a significantly associated with disease-specific survival (P < .001), demonstrated no institutional prognostic heterogeneity (I² = 6.3%; P = .38), and resulted in improved model fit compared with T category alone (lower AIC, P < .001). Optimal cutpoints of 5 mm in T1 and 10 mm in T2-4 category disease were used to develop a modified T staging system that was preferred to the AJCC system on the basis of lower AIC, visual inspection of Kaplan-Meier curves, and significant improvement in bootstrapped C-index. CONCLUSIONS AND RELEVANCE We propose an improved oral cancer T staging system based on incorporation of DOI that should be considered in future versions of the AJCC staging system after external validation.

Improvement in survival of patients with oral cavity squamous cell carcinoma: An international collaborative study

An association between the survival of patients with oral cavity squamous cell carcinoma (OCSCC) and advancements in diagnosis and therapy has not been established.

Prognostic value of the sixth edition of the UICC's TNM classification and stage grouping for oral cancer.

Carcinoma of the oral cavity is classified according to the TNM staging system of the UICC. The staging system is under continuous revision. The aim of our study was to assess the prognostic value of the UICC sixth edition for oral cancer, which was established in 2003.

The role of clinical versus histopathological staging in patients with advanced oral squamous cell carcinoma treated with neoadjuvant radiochemotherapy followed by radical surgery

INTRODUCTION Several studies have questioned the prognostic accuracy of the TNM system for oral cancer since neither patients comorbidity, specific tumor related factors nor multimodal treatment regimens such as preoperative radiochemotherapy (RCT) are incorporated. The present study was performed in order to evaluate the prognostic impact of cTNM and ypTNM in oral cancer patients treated with preoperative RCT and resection. METHODS In this retrospective analysis a total of 139 patients (103 male, 36 female, average age 56.8 years) with oral squamous cell carcinoma (UICC II-IVb) were included. Treatment consisted of concomitant RCT with 39.6 Gy radiations and Carboplatin (cumulative dose 300 mg/m(2)) during the first week of radiation, as well as surgical tumor resection and neck dissection. RESULTS During the mean follow up of 88.9 months 86 patients (61.9%) died. Locoregional recurrences occurred in 41 patients (29.5%). The 5 years overall survival rate was 45.5%. In univariate analysis margin status, ypT, ypN and ypUICC as well as complete pathological response revealed statistical significance on overall survival. In multivariate analysis ypT, ypN and margin status showed independent prognostic impact in our cohort. Neither cT nor cN provided statistical association with overall survival. CONCLUSION Results indicate that the clinical staging status of advanced oral cancer prior to preoperative RCT and resection should be interpreted with caution in terms of prognosis.

Podoplanin expression predicts prognosis in patients with oral squamous cell carcinoma treated with neoadjuvant radiochemotherapy.

Despite new therapeutic approaches patients with advanced oral squamous cell carcinoma still have a dismal prognosis. The main factor contributing to this problem is locoregional failure due to a lack of response to treatment. Several trials have proven the effect of neoadjuvant radiochemotherapy followed by radical surgery in comparison to primary surgery followed by adjuvant radiochemotherapy. No reliable parameters have been identified so far to predict response to radiochemotherapy. The aim of our study was to assess whether podoplanin expression in pretreatment biopsies could serve as a biomarker to predict the host response to neoadjuvant radiochemotherapy. In this retrospective study, podoplanin expression was examined in a set of 63 patients with oral squamous cell carcinoma by immunohistochemistry. We analyzed associations between the level of podoplanin expression and various clinicopathologic parameters, including response to radiochemotherapy, clinical and histological N-status. Furthermore we evaluated the effects of these parameters on overall survival and on locoregional control in univariate and multivariate analysis. The χ(2)-test revealed that high expression of podoplanin in pretreatment biopsy material was associated with non-regression of the tumor (p=0.013) and poor overall survival (p<0.001). Five-year survival rates of 92.9% for patients with weak expression and 15.0% for high expression were revealed. Podoplanin expression was also significantly associated with ypN status (p=0.004) and ypUICC status (p<0.001). We concluded that podoplanin might serve as a factor to predict treatment response in oral squamous cell carcinoma treated with neoadjuvant platin-based radiochemotherapy as well as a prognostic factor for overall survival and locoregional control.

Prognostic impact of different TNM-based stage groupings for oral squamous cell carcinoma

The purpose of this study was to evaluate the prognostic significance of different TNM‐based stage groupings proposed in the literature.

Podoplanin expression in cutaneous head and neck squamous cell carcinoma—prognostic value and clinicopathologic implications

Although most patients are cured by local treatment from cutaneous head and neck squamous cell carcinoma (cHNSCC), a significant number of patients develops metastases to the regional lymph nodes. Recent studies suggest an influence of podoplanin expression on regional lymph node metastases in other head and neck squamous cell carcinoma. The aim of our study was to assess the impact of podoplanin expression on regional lymph node metastasis, locoregional recurrence, and prognosis.

Combined-modality treatment in advanced oral squamous cell carcinoma: Primary surgery followed by adjuvant concomitant radiochemotherapy.

AbstractBackgroundThe efficacy of adjuvant radiochemotherapy (RCT) in patients with advanced stage head and neck carcinoma has been proven in prospective randomized trials. However, these trials focused on different head and neck sites. Specific analyses for treatment effects in squamous cell carcinoma of the oral cavity (OSCC) are missing. We evaluated our experiences with adjuvant concomitant RCT in advanced OSCC to compare the results with other treatment schemes using adjuvant RCT.Patients and MethodsA total of 183 patients with OSCC of UICC stages II–IVb were reviewed retrospectively. All patients were treated with radical surgery followed by adjuvant, conventional fractionated concomitant RCT using carboplatin. Overall survival was plotted by Kaplan–Meier analysis. Prognostic factors were identified through univariate and multivariate analysis.ResultsUnivariate analysis showed a significant impact of T, N, and UICC stage, histopathologic grading, surgical margins, extracaspular spread (ECS), and lymphangiosis carcinomatosa on overall survival (Table 3). Patients with stage IVa had a higher 5-year overall survival rate (42.8%) than patients with stage IVb (25.0%) (Figure 1). The differences were significant in multivariate analysis (p = 0.033) (Table 4).ConclusionAdjuvant concomitant RCT is an effective treatment in patients with advanced stage OSCC. However, it remains unclear, which patients should be treated with adjuvant RCT. For patients with stage IVb, adjuvant RCT yields poor results. Prospective randomized trials are needed to confirm which patients should be treated with adjuvant RCT.ZusammenfassungHintergrundDie Wirksamkeit der adjuvanten Radiochemotherapie bei fortgeschrittenen Kopf-Hals-Karzinomen wurde in prospektiven randomisierten Studien nachgewiesen. Jedoch bezogen sich diese Untersuchungen auf alle Regionen des Kopf-Hals-Bereiches. Spezielle Untersuchungen zur Wirksamkeit bei Plattenepithelkarzinomen der Mundhöhle fehlen. Wir haben unsere Erfahrungen mit adjuvanter Radiochemotherapie bei oralen Plattenepithelkarzinomen ausgewertet und mit anderen Behandlungsprotokollen mit adjuvanter Radiochemotherapie verglichen.Methoden183 Patienten mit oralen Plattenepithelkarzinomen der Stadien II–IVb wurden retrospektiv ausgewertet. Alle Patienten wurden mit einer radikalen Resektion, gefolgt von einer konventionell fraktionierten simultanen Radiochemotherapie mit Carboplatin behandelt. Das Gesamtüberleben wurde mit dem Kaplan-Meier-Verfahren ermittelt. Prognostische Faktoren wurden univariat und multivariat analysiert.ErgebnisseUnivariat zeigte sich ein signifikanter Einfluss von T-, N- und UICC-Klassifikation, von histopathologischen Gradings, Resektionsrändern, von extrakapsulärem Wachstum und Lymphangiosis carcinomatosa auf das Gesamtüberleben (Tabelle 3). Patienten im Stadium IVa hatten eine höhere 5-Jahres-Überlebensrate (42,8%) als Patienten im Stadium IVb (25,0%) (Abbildung 1). Die Unterschiede waren multivariat signifikant (p = 0,003) (Tabelle 4).SchlussfolgerungAdjuvante Radiochemotherapie ist eine effektive Behandlungsmethode bei fortgeschrittenen oralen Platten epithelkarzinomen. Es ist jedoch nicht klar, welche Patienten eine adjuvante Radiochemotherapie erhalten sollen. Für Patienten im Stadium IVb zeigten sich schlechte Ergebnisse. Prospektive randomisierte Studien werden benötigt, um zu identifizieren, welche Patienten mit einer adjuvanten Radiochemotherapie behandelt werden sollen.