Autologous freeze-treated bone for mandibular reconstruction after malignant tumor resection: a study of 72 patients.

OBJECTIVE: The aim of the study was to assess the possibility of mandibular reconstruction with autologous freeze-treated bone after mandibular resection for malignant tumors. PATIENTS: The medical records of 72 consecutive patients surgically treated with segmental mandibular resection and reconstruction with autologous freeze-treated mandible were reviewed. RESULTS: All tumors were in stage T4a for deep infiltration of the mandible. Soft tissues were reconstructed with a direct mucosal closure (4 cases), with a pedicled pectoralis flap (17 cases), and with a forearm fasciocutaneous free flap without or with radial periosteum (18 and 33 cases). Four patients presented with a recurrence after previous surgery and radiotherapy, and 26 patients underwent postoperative radiotherapy. We resected the mental arch in 35 cases and the lateral mandible in 37 cases. Forty-one patients (56.9%) retained their autologous mandibular graft. In 31 cases, the bone graft was removed for mucosal dehiscence and bone infection. Lateral resections achieved a better success rate than anterior resections (75.7% vs 37.1%). The pedicled pectoralis flap achieved the worse success rate (35.3%) in comparison with forearm fasciocutaneous flap (66.7%). Postoperative radiotherapy decreased the success rate (40.0% vs 69.1%). CONCLUSIONS: Mandibular reconstruction with autologous frozen bone is an interesting alternative to more sophisticated methods for patients with oral cancer involving the bone. It is time and cost sparing in comparison to fibula or iliac crest flaps. However, in spite of any intraoral reconstruction, the success rate is not stirring. In our opinion, this type of mandibular reconstruction must be reserved to patients with lateral tumors, with poor prognosis, or severe comorbidities not allowing more complex bone reconstruction.

Lymph node metastases in malignant tumors of the paranasal sinuses: prognostic value and treatment.

OBJECTIVE: To assess the frequency of nodal involvement and its prognostic value in malignant tumors of the paranasal sinuses, particularly in maxillary sinus squamous cell carcinoma. DESIGN: Retrospective review. SETTING: Tertiary cancer center. PATIENTS: The medical records of 704 consecutive patients surgically treated for malignant tumors of the paranasal sinuses from January 1968 to March 2003 were reviewed. The tumors were staged according to American Joint Committee on Cancer-International Union Against Cancer 2002 classification. Only patients with clinically positive nodes underwent a neck dissection. MAIN OUTCOME MEASURES: Lymph node metastases (at presentation or during follow-up, occurring alone, or with concurrent local recurrence and/or distant metastasis). Also analyzed were local recurrence (occurring alone or with concurrent distant metastasis), distant metastasis (occurring alone), and overall survival. RESULTS: The tumor site was the ethmoid sinus in 305 cases and maxillary sinus in 399 cases. At baseline, 5 patients (1.6%) in the ethmoid sinus group and 33 (8.3%) in the maxillary sinus group presented with positive nodes (P < .001); during follow-up, nodal recurrences (alone or simultaneous with T and/or M recurrence) occurred in 15 and 51 patients, respectively, and the corresponding 5-year incidence estimates were 4.3% and 12.5% (P = .001). The highest incidence of node metastases was found in maxillary sinus squamous cell carcinoma, particularly in T2 tumors. Five-year overall survival estimates were 45.3% for patients with N0 tumors and 0% for those with N+ (N1, N2, or N3) ethmoid sinus tumors, and 50.6% and 16.8%, respectively, for patients with maxillary sinus tumors. CONCLUSIONS: Lymph node metastases are a poor prognostic factor for patients with malignant tumors of the paranasal sinuses. The incidence of these metastases is low, particularly in ethmoid sinus tumors. A prophylactic treatment of the neck in patients with N0 tumors (surgery or radiotherapy) might be considered in T2 squamous cell carcinoma of the maxillary sinus and in undifferentiated carcinoma of the ethmoid sinus.

Molecular and cytogenetic subgroups of oropharyngeal squamous cell carcinoma.

PURPOSE: The aim of this study was to acquire further insights into the pathogenetic pathways of head and neck squamous cell carcinomas (HNSCC) that may be useful for identifying new biomarkers instrumental in developing more specific treatment approaches. EXPERIMENTAL DESIGN: Cell cycle regulators and epidermal growth factor receptor (EGFR) and BRAF genes were analyzed in a series of 90 oropharyngeal SCCs of a cohort of surgically treated patients from a single institution, and the results were matched with the presence of high-risk human papillomavirus (HR-HPV) DNA and the TP53 status. RESULTS: At least four distinct groups of tumors were identified sharing a common histology but displaying different molecular/cytogenetic patterns: (a) 19% were HPV-positive SCCs whose lack of alterations of the investigated genes could explain their particular natural history, which requires less aggressive treatment; (b) 37% were HPV-negative SCCs carrying TP53 mutations, which may be more effectively treated by drugs acting through p53-independent apoptosis; (c) 34% were HPV-negative SCCs carrying wild-type TP53 and loss of 9p21 (p16INK4a and p15INK4b) and/or cyclin D1 overexpression that justify treatment with DNA-damaging drugs followed by cell cycle inhibitors; and (d) 10% were HPV-negative lacking tumor suppressor genes and cell cycle alterations. The second, third, and fourth groups also showed an increased copy number of EGFR and chromosome 7 (43%) that might justify the additional or alternative use of EGFR inhibitors. CONCLUSIONS: Our findings suggest that assessing HPV, TP53, 9p21, and EGFR status may be crucial to finding more tailored and beneficial treatments for oropharyngeal SCCs.

Lip-splitting in transmandibular resections: is it really necessary?

Mandibular resection approach (Commando or Composite resection) is one of the fundamental techniques for oral and oropharyngeal large tumour resection. We reviewed the charts of patients who underwent a transmandibular resection for an oral and/or oropharyngeal cancer between 1980 and 2002. Of 700 patients who underwent a mandibular resection for cancer, 332 had been operated without lower lip splitting. A mono or bilateral en-block neck dissection was always performed, except in cases of relapses after a prior surgical treatment with neck dissection. We repaired 307 patients with flaps (pedicled or free flaps, with or without bone). Unsplitting of the lip never complicated resection and reconstruction. Furthermore the procedure was time sparing, as we avoided haemostasis and suture of the lip. The cosmetic results were better than those obtained by traditional technique. We used a non-lip-splitting technique also for pull-through, marginal mandibulectomy and, sometimes, for mandibular-swing approaches. In the latter case, the technique has some advantages and disadvantages and must be applied according to circumstances. We can conclude that lip-splitting in transmandibular resection for oral and oropharyngeal tumours is not necessary.

Locoregionally advanced carcinoma of the oropharynx: conventional radiotherapy vs. accelerated hyperfractionated radiotherapy vs. concomitant radiotherapy and chemotherapy--a multicenter randomized trial.

PURPOSE: To compare conventional fractionation radiation therapy (RT), Arm A, vs. split-course accelerated hyperfractionated RT (S-AHF), Arm B, vs. conventional fractionation RT plus concomitant chemotherapy (CT), Arm C, in terms of survival and toxicity for advanced, unresectable epidermoid tumors of oropharynx. METHODS AND MATERIALS: Between January 1993 and June 1998, 192 previously untreated patients affected with Stage III and IV oropharyngeal carcinoma (excluding T1N1 and T2N1) were accrued in a multicenter, randomized Phase III trial (ORO 93-01). For Arms A and C, 66-70 Gy in 33-35 fractions, 5 days a week, were administered in 6.5-7 weeks to tumor and positive nodes. In Arm B, the dose delivered to tumor and involved nodes was 64-67.2 Gy, giving 2 fractions of 1.6 Gy every day with an interfraction interval of at least 4 h and preferably 6 h, 5 days a week. At 38.4 Gy, a 2-week split was planned; after the split, RT was resumed with the same modality. In Arm C, CT regimen consisted of carboplatin and 5-fluorouracil (CBDCA 75 mg/m(2), Days 1-4; 5-FU 1,000 mg/m(2) i.v. over 96 h, Days 1-4, recycling every 28 days (at 1st, 5th, and 9th week). RESULTS: No statistically significant difference was detected in overall survival (p = 0.129): 40% Arm A vs. 37% Arm B vs. 51% Arm C were alive at 24 months. Similarly, there was no statistically significant difference in terms of event-free survival (p = 0.196): 20% for Arm A, 19% for Arm B, and 37% for Arm C were event free at 24 months. On the contrary, the 2-year disease-free survival was significantly different among the three arms (p = 0.022), with a superiority for Arm C. At 24 months, the proportion of patients without relapse was 42% for Arm C vs. 23% for Arm A and 20% for Arm B. Patients in Arm A less frequently developed G3+ acute mucositis than their counterparts in Arm B or C (14.7% vs. 40.3% vs. 44%). Regarding the CT-related acute toxicity, apart from 1 case of fatal nephrotoxicity, only hematologic G3+ (Grade 3 or higher) acute sequelae were observed (World Health Organization scale), most commonly leukopenia (22.7%). Arm C showed slightly more G3+ skin, s.c. tissue, and mucosal late side effects (RTOG scale), although significant sequelae were relatively uncommon, and mucosal sequelae were most commonly transient. The occurrence of persistent G3 xerostomia was comparable in all three treatment arms. CONCLUSIONS: The combination of simultaneous CT and RT with the regimen of this trial is better than RT alone in advanced oropharyngeal squamous-cell carcinomas, by increasing disease-free survival. This improvement, however, did not translate into an overall survival improvement, and was associated with a higher incidence of acute morbidity.

Craniofacial resection for malignant tumours involving the anterior skull base.

Ethmoid malignant tumours are rare, but nearly all at least approach or involve the lamina cribrosa. An anterior craniofacial resection is almost always mandatory for a radical resection. While almost everything has been written about technical details, few studies reported meaningful analysis about prognostic factors and long-term results, for a series of reasons: the infrequency of these tumours, the variety of histologies, small patients cohorts presented by each author, a medley of untreated and pre-treated patients, the lack of a universally accepted classification. We perform a review of the literature in the light of our experience of 330 anterior craniofacial resections for ethmoid malignant tumours. We present our classification of ethmoid malignant tumours (called INT, Istituto Nazionale Tumori). It turned out to be more prognostic than AJCC-UICC classification.

High-risk human papillomavirus affects prognosis in patients with surgically treated oropharyngeal squamous cell carcinoma.

PURPOSE: Human papillomavirus (HPV) DNA tumors actively integrating the E6 and E7 oncogenes have a distinct biologic behavior resulting in a more favorable prognosis. To which extent the viral integration by itself, and/or the associated wild-type (wt) TP53 status, and/or a functional p16 contribute to prognosis is unclear. PATIENTS AND METHODS: To clarify how the presence of high-risk (HR) -HPV, TP53, and p16INK4a status interact with clinical outcome, we considered a retrospective series of 90 consecutive oropharyngeal cancer patients treated primarily with surgery. RESULTS: Seventeen (19%) patients showed integrated HPV 16 DNA (HPV positive), wt TP53 in all but two patients, normal p16INK4a in 15 assessable patients, and p16 expression in all 17 patients. Thirty-five patients (39%), two of whom were HPV positive, harbored TP53 mutations. p16INK4a deletion and p16 null immunophenotype occurred in 28 and 58 patients, respectively, and was similarly distributed in both patients with mutated TP53 (48% and 82%, respectively) and in patients with wt TP53 (46% and 77%, respectively). Statistical analysis showed that HPV-positive status significantly affects all investigated end points: overall survival (P = .0018), incidence of tumor relapse (P = .0371), and second tumor (P = .0152), whereas TP53 and p16INK4a status and p16 expression were not prognostic by themselves. CONCLUSION: Our molecular and clinical results are in agreement with previous findings but provide additional information into the biologic mechanisms involved in HR-HPV oropharyngeal cancer in comparison to HPV-negative tumors. According to the reduced risk of relapse and second tumors associated with HR-HPV positivity of oropharyngeal cancer, the therapeutic strategy and follow-up procedures should be reviewed.