Biomedical subjects
Publications and source records attributed to L Licitra.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
PURPOSE: To assess the role of TP53 status in predicting pathologic complete remission after primary chemotherapy in patients with ethmoidal intestinal-type adenocarcinoma (ITAC). PATIENTS AND METHODS: Thirty patients with ethmoidal ITAC enrolled onto a phase II study received chemotherapy with cisplatin, fluorouracil, and leucovorin (PFL) followed by surgery and radiation. On surgical specimens, absence of viable tumor cells was defined as pathologic complete remission (pCR). TP53 status/p53 function, analyzed on pretreatment biopsies, were retrospectively correlated with pathologic results and patient outcome. RESULTS: Twelve patients achieved a pCR; 18 patients did not (overall response rate, 40%). In patients with wild-type (wt) TP53 or functional p53 protein, the pCRs were 83% and 80%, respectively; in patients with mutated TP53 or impaired p53 protein, pCRs were 11% and 0%, respectively (P < or = .0001). At a median 55-month follow-up, all pCR patients were disease-free; 44% of nonresponding patients experienced relapse (P = .0061). CONCLUSION: The results indicate the existence of two genetic ITAC subgroups, defined by differences in TP53 mutational status or protein functionality, that strongly influence pathologic response to primary chemotherapy and, ultimately, prognosis. PFL seems to be highly effective in terms of pCR and disease-free survival in the presence of a wt or a still-efficient p53 protein, even when encoded by a mutated TP53 gene (eg, early-stop codon mutation), but ineffective in ITACs carrying a disabled p53 protein. Whether this model is extensible to other head and neck cancers needs appropriate investigation.
After approximately 20 years of conflicting results from chemotherapy in randomized trials in advanced head and neck cancer, three meta-analyses reviewed its use. All three concluded that chemotherapy was associated with a statistically significant advantage in survival, but that this was low (4% absolute benefit at 2 and 5 years). The improvement in survival was mainly based on the more robust improvement obtained with the concomitant use of chemotherapy and radiotherapy. Induction chemotherapy, in particular, was not associated with any relevant survival advantage. This article reviews current indications for neoadjuvant chemotherapy in advanced head and neck cancer. Implications for current and future research are discussed.
Explore the source record for details and available documents.
Sinonasal tumours, particularly those of ethmoidal origin, are rare neoplasms, of which adenocarcinoma is the most frequent histotype in Europe. The association between sinonasal malignancies and exposure to wood or leather dusts has been widely documented, however, the precise tumour site and histology has seldom been reported. In the present study, exposure to wood or leather dusts was investigated in 499 patients diagnosed with sinonasal tumours, who were treated at the Head and Neck Surgery Department of the National Cancer Institute of Milan, Italy, between 1987 and 2001. The original tumour site and histology were carefully assessed. Of the 499 patients evaluated, 249 had ethmoidal tumours; 124 of which adenocarcinomas, affecting 115 males; 9 females. Of the males with adenocarcinoma, 90.4% had been exposed to wood or leather dusts; 16.3% of these had only been exposed for a short time and long before onset of the disease (median exposure 11 years; median latency 31 years). Of the remaining 125 patients with ethmoidal tumours other than adenocarcinomas, only 2 (1.6%) had ever been exposed to these dusts. Non-ethmoidal sinonasal tumours were seen in 250 cases; 17 of these (6.8%) were adenocarcinomas; no exposure to wood or leather dusts was reported in any of these patients. Ethmoid proved to be the sinonasal site affected by adenocarcinomas induced by exposure to wood or leather dusts. Even brief exposure, which may have occurred a very long time before onset of the disease, seems to be sufficient to increase the incidence of this tumour type. No significant correlation was observed between exposure and either non-ethmoidal sinonasal neoplasms or ethmoidal tumours other than adenocarcinomas.
AIMS: Predictors of outcome after radiotherapy alone for nasopharyngeal carcinoma (NPC) are now available from several retrospective studies. On the basis of these, it is theoretically possible to separate patients at risk of local failure from patients at risk of distant metastases (DM). According to classical principles of chemoradiotherapy timing, patients at risk of local failure would benefit mostly from concomitant chemoradiotherapy, whereas patients at risk distantly would benefit from sequential combinations. MATERIALS AND METHODS: We reviewed the literature on combined chemoradiotherapy treatment for nasopharyngeal carcinoma to assess whether timing of combined treatment matches pattern of failure. RESULTS: Available data show a significant overlap of activity, sequential treatments reducing local failure and concomitant treatments reducing DM. Therefore, in the individual patient, the strict adoption of traditional risk profiles in therapeutic decision-making may not fully exploit all the potential therapeutic effects derived from the maximal association of both sequential and concomitant therapies. CONCLUSION: Whether such combination is clinically worthwhile in every patient with locoregionally advanced nasopharyngeal carcinoma needs prospective validation, because of the high toxicity of this modality.
BACKGROUND: To study prospectively the activity of primary chemotherapy with cisplatin, fluorouracil and leucovorin (PFL) in patients with paranasal cancer receiving surgery and postoperative radiotherapy. PATIENTS AND METHODS: Forty-nine patients, previously untreated, with resectable paranasal carcinoma were enrolled. PFL (leucovorin 250 mg/m2/day for 5 days as a 120 h continuous infusion (c.i.), 5-fluorouracil 800 mg/m2/day from day 2 as a 96 h c.i. and cisplatin 100 mg/m2 day 2 q 3 weeks) was planned for five courses. RESULTS: Thirty-two patients (65%) completed three or more chemotherapy courses. Two deaths from thrombotic events were observed after the first cycle. Eight cardiac toxicities were recorded during chemotherapy causing treatment discontinuation. Objective response to PFL was observed in 21 patients [43%; 95% confidence interval (CI) 29% to 58%], including four complete responses (CRs) (8%; 95% CI 2% to 20%) and 17 partial responses (PRs) (35%). Pathological complete remission (pCR) was achieved in eight of 49 patients (16%). At 3 years, overall survival was 69% and event-free survival 57%. Overall and event-free survival in patients achieving pCR is 100%. CONCLUSIONS: PFL is active in paranasal cancer. Patients who attain a pathological complete remission have a favorable prognosis. Cardiovascular complications represent the limiting toxicity. Primary chemotherapy combined with surgery-sparing treatment approaches deserves further investigation.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The purpose of this article is to review the most significant results of the clinical studies conducted in the past two decades by the EORTC Head and Neck Cancer Group (HNCG). As for phase III trials, the HNCG investigated, besides the efficacy of chemopreventive drugs, the impact of cytostatic agents on various therapeutic targets, in combination or not with surgery and chemotherapy. These targets were: (a) chemo-prevention in curatively treated early stage disease; (b) organ preservation programmes in patients with operable tumour, comparing immediate surgery versus first-line chemotherapy; (c) postoperative management of locally advanced tumours, comparing radio-chemotherapy versus radiotherapy alone. Other phase II and phase III studies were also completed to investigate drug activity in advanced and/or recurrent head and neck squamous cell and adenoid cystic carcinomas. The present article will also analyse the strategies developed within the Group in the field of translational research.
Mucoepidermoid carcinoma (MEC) represents 15% of all salivary glands malignancies. Metastatic disease at diagnosis is observed in less than 5% of the cases. The lung is the most commonly involved site. This is the first reported case of high-grade MEC of the salivary gland with skin metastases at diagnosis. This feature was associated with a chemoresistant and aggressive behaviour. Differential diagnosis between metastatic MEC and primary skin MEC is essential for therapeutic management and prognosis.
Explore the source record for details and available documents.
Although the subjective nature of quality of life is generally accepted, less attention has been paid to the procedure of selecting domains to be explored with questionnaires. To explore what contributes to cancer patients' quality of life, a survey was conducted with the aim of identifying contents of quality of life using cancer patients as 'experts'. A questionnaire with open-ended items aimed at exploring the meaning of quality of life and at determining the contents of health and not health related quality of life, was submitted to a sample of cancer patients stratified by residence, cancer site and stage of disease. The 248 questionnaires received were transcribed and broken down into phrases to allow coding. A content analysis was performed, using as a conceptual framework, the domains identified by the Italian Society of Psycho-Oncology. Overall, 43 domains and a list of symptoms were identified. The two most frequently reported symptoms were pain (21.4% patients) and fatigue (14.1% patients). Social relationships and psychological domains were heavily represented. Twenty sub-domains related to the domain 'psychological well-being'. This study suggests that information on the content of quality of life questionnaires to be submitted to people affected by a specific disease, should be derived by studying people suffering the specific disease. These results reinforce the criticism that available quality of life instruments are more likely to reflect the perspective of health professionals than patients.
OBJECTIVES: To propose our clinical classification of malignant ethmoid tumors and to compare it with the last American Joint Committee on Cancer (AJCC)-Union Internationale Contre le Cancer (UICC) classification, published in 1997. DESIGN: Retrospective review. SETTING: Tertiary cancer facility. PATIENTS: We evaluated 123 consecutive patients undergoing craniofacial resection for malignant ethmoid tumors involving the anterior skull base. The mean follow-up was 60 months. Fifty-nine patients (48%) presented with recurrent disease after prior therapy. We classified them with a new classification system (Istituto Nazionale per lo Studio e la Cura dei Tumori) based on the most commonly accepted unfavorable prognostic factors (involvement of dura mater; intradural extension; involvement of the orbit and, in particular, of its apex; invasion of maxillary, frontal, and/or sphenoid sinuses; and invasion of the infratemporal fossa and skin. We also classified patients with the AJCC classification published in 1997. MAIN OUTCOME MEASURES: Disease-free status and overall survival rate. To study a possible association with tumor stage, the Cox regression model was adopted. RESULTS: According to our classification, patient distribution by tumor type was T2, n = 46; T3, n = 29; and T4, n = 48 (no T1 tumors were present in the series). For previously untreated patients, 5-year disease-free survival estimates were T2, 57%; T3, 50%; and T4, 13%. For relapses, corresponding figures were T2, 31%; T3, 23%; and T4, 1%. The prognostic difference among stages was statistically significant (P<.001). Similar results were obtained for overall survival. In contrast, patient distribution among different AJCC stages was less balanced, and we failed to detect a significant association with the clinical outcome using this classification. CONCLUSION: We propose the use of our staging system by all those specialists in the field willing to validate the classification and possibly apply it for clinical and investigational purposes.
START ('State-of-the-Art Oncology in Europe'), a freely available resource on the Internet, is a European 'information base' of current clinical approaches to human tumours. Its aim is to help clinical oncologists make appropriate clinical decisions by providing them with updated information reflecting state-of-the-art cancer treatment as perceived by the European oncology community. It is based upon contributions from authors and internal reviewers from all over Europe as selected by START's editorial board under the supervision of an advisory board and a scientific committee. Close collaborations with the main European cancer societies are ongoing. An external feedback process augments the mechanisms for rendering START a truly European instrument. START is concerned with evidence-based cancer medicine, and the main clinical options are thus codified and their bases indicated in accord with a scale worked out from the perspective of clinical decision-making. Therapeutic options may be 'standard', 'investigational', or 'suitable for individual clinical use' (within the context of a decision made jointly by the patient and the physician). The goal of instruments such as START is to improve the quality of patient care. In addition, START hopes to make contributions to the methodology by which medical research is transformed into clinical decisions.
The predictive role in terms of pathological response and prognostic role of biomarkers such as GST-pi, 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-pi 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-pi and p53 expression. In patients treated with PCT, pathological response and DFS were independent of p53 expression and cell proliferation. Conversely, low GST-pi 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.