Cesare Grandi

Salivary duct carcinoma : Clinical characteristics and treatment strategies

Salivary duct carcinoma (SDC) is a highly malignant tumor of the salivary gland.

Cancer of the oropharynx

Oropharyngeal cancer is a rare tumour. Tobacco use and alcohol consumption are recognised as major risk factors. Several carcinogens, occupational exposures and vitamin deficiencies represent the most significant predisposing factors. A varying host susceptibility to carcinogens can be inferred. Carcinoma of the oropharynx has to be suspected whenever sore throat, odynophagia, and ear-ache are described by the patient. Biopsy is mandatory for the definitive diagnosis. TNM classification is crucial for treatment decision-making, while stage grouping is less important. Prognostic factors are treatment-related. Standard treatment of T1-T2 tumours is radiation therapy, for T3 and T4 tumour treatment options are controversial. More advanced tumours can be treated either with surgery followed by conventional radiotherapy or by combined chemo-radiation. Non-conventional fractionation radiotherapy in combination with chemotherapy may represent a third option. Acute toxicity needs to be managed promptly. Late sequelae are less known. Treatment of such tumours requires a multidisciplinary approach within experienced centres.

Sentinel European Node Trial (SENT): 3-year results of sentinel node biopsy in oral cancer

PURPOSE Optimum management of the N0 neck is unresolved in oral cancer. Sentinel node biopsy (SNB) can reliably detect microscopic lymph node metastasis. The object of this study was to establish whether the technique was both reliable in staging the N0 neck and a safe oncological procedure in patients with early-stage oral squamous cell carcinoma. METHODS An European Organisation for Research and Treatment of Cancer-approved prospective, observational study commenced in 2005. Fourteen European centres recruited 415 patients with radiologically staged T1-T2N0 squamous cell carcinoma. SNB was undertaken with an average of 3.2 nodes removed per patient. Patients were excluded if the sentinel node (SN) could not be identified. A positive SN led to a neck dissection within 3 weeks. Analysis was performed at 3-year follow-up. RESULTS An SN was found in 99.5% of cases. Positive SNs were found in 23% (94 in 415). A false-negative result occurred in 14% (15 in 109) of patients, of whom eight were subsequently rescued by salvage therapy. Recurrence after a positive SNB and subsequent neck dissection occurred in 22 patients, of which 16 (73%) were in the neck and just six patients were rescued. Only minor complications (3%) were reported following SNB. Disease-specific survival was 94%. The sensitivity of SNB was 86% and the negative predictive value 95%. CONCLUSION These data show that SNB is a reliable and safe oncological technique for staging the clinically N0 neck in patients with T1 and T2 oral cancer. EORTC Protocol 24021: Sentinel Node Biopsy in the Management of Oral and Oropharyngeal Squamous Cell Carcinoma.

Cancer of the nasopharynx

Nasopharyngeal cancer (NPC) is quite rare throughout Europe, accounting for an annual incidence rate below 1 per 100.000, whereas the highest risk area is South East Asia. A predominant occurrence in males is to be noted. NPC is an etiologically multifactorial disease, most probably involving viral, genetic and environmental factors. Carcinomas of the nasopharynx can be divided into two major histotypes: keratinizing squamous cell carcinomas (WHO-type 1) and non-keratinizing carcinomas (WHO-type 2). The histological type is a prognostic factor and it has a clear impact on the outcome of treatment. Standard therapeutic option for early stages of NPC is radiation, while an integration of radiation therapy and chemotherapy is indicated in more advanced stages.

Biological markers as indicators of pathological response to primary chemotherapy in oral-cavity cancers.

The predictive role in terms of pathological response and prognostic role of biomarkers such as GST‐π, p53, bcl‐2 and bax expression, immuno‐histochemically detected, and of the S‐phase cell fraction, autoradiographically determined as thymidine labeling index (TLI), were investigated within a prospective randomized phase III clinical trial on squamous‐cell carcinoma of the oral cavity, including surgery or primary chemotherapy (PCT), which foresaw the prospective determination of biological markers. Pathological response was defined as the achievement after PCT of a pathological complete remission or the presence of microresidual disease. The study was performed on tumors obtained from a series of 100 previously untreated patients with resectable T2–4N0–2M0 carcinoma. All biomarkers were unrelated, except for an inverse relation between TLI and GST‐π and a direct relation between bcl‐2 and bax expression. In patients treated with surgery alone, 3‐year disease‐free survival (DFS) appeared to be weakly, but not significantly, related only to GST‐π and p53 expression. In patients treated with PCT, pathological response and DFS were independent of p53 expression and cell proliferation. Conversely, low GST‐π and bax expression were indicative of pathological response but lost relevance as predictors of DFS, whereas absence of bcl‐2 was associated with high probability of 3‐year DFS in the overall series as well as in non‐responding patients. Within this latter sub‐set, all patients with bcl‐2‐positive tumors relapsed within 1 year of surgery, whereas a 60% probability of 3‐year DFS was observed for patients with bcl‐2‐negative tumors (p= 0.02). This interim analysis appears to indicate that some biofunctional markers can provide information on pathological response to PCT and could help in understanding treatment efficacy at a cellular level. Int. J. Cancer (Pred. Oncol.) 79:619–623, 1998.

Implications of a positive sentinel node in oral squamous cell carcinoma.

The role of sentinel node biopsy in head and neck cancer is currently being explored. Patients with positive sentinel nodes were investigated to establish if additional metastases were present in the neck, their distribution, and their impact on outcome.

Sentinel node in oral cancer: the nuclear medicine aspects. A survey from the sentinel european node trial

Purpose Nuclear imaging plays a crucial role in lymphatic mapping of oral cancer. This evaluation represents a subanalysis of the original multicenter SENT trial data set, involving 434 patients with T1-T2, N0, and M0 oral squamous cell carcinoma. The impact of acquisition techniques, tracer injection timing relative to surgery, and causes of false-negative rate were assessed. Methods Three to 24 hours before surgery, all patients received a dose of 99mTc-nanocolloid (10–175 MBq), followed by lymphoscintigraphy. According to institutional protocols, all patients underwent preoperative dynamic/static scan and/or SPECT/CT. Results Lymphoscintigraphy identified 723 lymphatic basins. 1398 sentinel lymph nodes (SNs) were biopsied (3.2 SN per patient; range, 1–10). Dynamic scan allowed the differentiation of sentinel nodes from second tier lymph nodes. SPECT/CT allowed more accurate anatomical localization and estimated SN depth more efficiently. After pathological examination, 9.9% of the SN excised (138 of 1398 SNs) showed metastases. The first neck level (NL) containing SN+ was NL I in 28.6%, NL IIa in 44.8%, NL IIb in 2.8%, NL III in 17.1%, and NL IV in 6.7% of positive patients. Approximately 96% of positive SNs were localized in the first and second lymphatic basin visualized using lymphoscintigraphy. After neck dissection, the SN+ was the only lymph node containing metastasis in approximately 80% of patients. Conclusions Best results were observed using a dynamic scan in combination with SPECT/CT. A shorter interval between tracer injection, imaging, and surgery resulted in a lower false-negative rate. At least 2 NLs have to be harvested, as this may increase the detection of lymphatic metastases.

Effectiveness of selective neck dissection in head and neck cancer: The experience of two Italian centers

The aim of this study was to evaluate the oncologic outcomes after a selective neck dissection (SND), both in elective and therapeutic settings, with particular regard to regional recurrence rate.

Unresectable Ameloblastoma Successfully Treated with Definitive Proton Therapy

We report the case of an 87-year-old man affected by an unresectable ameloblastoma of the right jaw that was successfully treated by definitive proton therapy up to a dose of 66 Gy in 33 fractions. Treatment was well tolerated, and there were no interruptions due to toxicity. At follow-up visits, the patient experienced complete response to treatment with no evidence of disease and complete recovery from acute side effects. In this report, we discuss the potential and possible pitfalls of proton therapy in the treatment of specific settings.

OP188: Selective neck dissection: A multicenter study

Purpose to evaluate the efficacy of Selective Neck Dissections (SNDs) in different clinical settings examining a large series and verifying the prognosticators of regional recurrence. Patients and methods from 1999 to 2011, 827 patients (pts) with squamous cell carcinoma of the oral cavity (39.9%), oropharynx (25.5%), hypopharynx (10.8%) and larynx (23.8%), had SND. Fifty-six point 6% of pts were class N0, 18.0% N1, 6.7% N2a, 11.8% N2b, 6.9% N2c or N3. The main characteristics are reported as regards class of T, grading, angiolymphatic and perineural invasion, type of SND, class of pN, number of examined nodes, previous or adjuvant treatments, complications, outcome. Results Only 2.7% had recurrence in the neck side treated by SND (more often within the dissected levels). The main clinical and pathologic characteristics, significantly different in relationship with initial or salvage-planned-other T treatment and with elective or therapeutic treatment are reported. The main prognosticators for the regional recurrence of SND were the class of pN and the number on nodal metastases without Extra-Capsular Spread (ECS), the prognosticators for the recurrences elsewhere (T, contralateral neck, M) were the class of N and pN, angiolymphatic invasion, number of nodal metastases with ECS. The survival curves according to the main characteristics are reported. Conclusions the SNDs are reliable and allow for a low percentage of regional recurrences either as elective or therapeutic treatment, either in neck already treated by radiotherapy or not; the postoperative adjuvant treatments allow to compensate the unfavourable prognostic significance of the negative pathologic factors.