Trans-Frontal Five-Fluorouracil (TraFFF): a novel technique for the application of adjuvant topical chemotherapeutic agents in sinonasal adenocarcinoma.

Sinonasal adenocarcinoma has traditionally been treated with surgery (craniofacial or endoscopic) and adjuvant radiotherapy. Two large series have demonstrated favourable 5-year survival using surgery with adjuvant topical chemotherapy applied repeatedly over several weeks. The authors describe a novel, transnasal application of topical 5-fluorouracil. However, complete coverage of the frontal region of the anterior skull base can be difficult to achieve with a purely transnasal approach in an outpatient setting. We present a novel adjunct method of delivering chemotherapeutic agents into this key area used in a 37-year-old man with T2N0M0 ethmoid adenocarcinoma. The procedure was well tolerated in an outpatient setting and remains disease free at 3 years postoperatively. We suggest that frontal trephination is a useful adjunct to aid accurate placement of adjuvant topical chemotherapeutic agents in the treatment of sinonasal adenocarcinoma.

Induction chemotherapy in head and neck squamous cell carcinoma of the paranasal sinus and nasal cavity: a role in organ preservation.

BACKGROUND/AIMS: The role of induction chemotherapy (IC) for eyeball preservation has not been established in head and neck squamous cell carcinoma (HNSCC) of the paranasal sinus and nasal cavity (PNSNC). Periorbital involvement frequently leads to eyeball exenteration with a margin of safety. We evaluated the treatment outcomes, including survival and eyeball preservation, of patients who received IC for HNSCC of the PNSNC. METHODS: We reviewed 21 patients diagnosed with HNSCC of the PNSNC who were treated with IC. We analyzed response, eyeball preservation rate, and overall survival. RESULTS: Tumors were located in the paranasal sinus (n = 14) or nasal cavity (n = 7). Most patients had stage T4a (n = 10) or T4b (n = 7) disease. More than half of the patients received a chemotherapy regimen of docetaxel, fluorouracil, and cisplatin (n = 11). Thirteen patients (61.9%) achieved a partial response after IC and 15 patients (71.4%) achieved T down-staging. Among 17 patients with stage T4 disease, which confers a high risk of orbital exenteration, 14 (82.4%) achieved preservation of the involved eye. The 3-year overall survival (OS) rate of patients who achieved a partial response to IC was 84.6%. The 3-year OS rate of patients with stable disease or disease progression after IC was 25.0% (p = 0.038). CONCLUSIONS: IC could be considered for down-staging patients with advanced T-stage disease. It could also be a reasonable option for eyeball preservation in locally advanced HNSCC of the PNSNC.

[Influence of chemotherapy regimen on antioxidant level in patients with locally-advanced tumors of the maxilla, nasal and paranasal sinuses].

The study dealt with effect of chemoradiotherapy on the oxidant/antioxidant system in 57 patients with locally-advanced tumors (stage III-IV) of the maxilla, nasal and paranasal sinuses. Therapy modalities ranged from systemic chemoradiotherapy (22), intraarterial chemoradiotherapy + UHF-hyperthermia (20) and intraarterial chemotherapy + radiotherapy (15). The most frequent regimen of chemotherapy involved cisplatin 15 mg/ m2, total dose of 100 mg; fluorouracil 600 mg/m2, total dose of 2,000-3,000 mg, and doxorubicin 15 mg/m2, total dose of 40-60 mg. As far as telegammatherapy is concerned, all patients received STD of 3 Gy and TTD of 40-60 Gy. Unlike systemic chemoradiotherapy, continuous intraarterial chemoradiotherapy with UHF-hyperthermia or without it was followed by lower incidence of enhanced oxidative reaction response and tumor-related endotoxicosis.

The efficacy and safety of concurrent chemoradiotherapy for maxillary sinus squamous cell carcinoma patients.

OBJECTIVE: Combined treatment modality, e.g., definitive surgery followed by radiotherapy (RT) and definitive RT with concurrent chemotherapy, has been applied for advanced maxillary sinus squamous cell carcinoma (MSSCC) patients to obtain a better survival with organ preservation in Japan. METHODS: The outcome of 40 patients with MSSCC between 1991 and 2007 in our institute was analyzed retrospectively. There were 36 males and 4 females, the average age being 59.5 years (ranging from 34 to 81 years). The median follow-up time was 66.1 months. All the patients had received a combined treatment consisting of definitive surgery, RT, and intra-arterial or systemic chemotherapy. The chemotherapeutic regimen was different depending on the performance status and/or complications of the patients. Since 1998, concurrent chemoradiotherapy with cisplatin, 5-fluorouracil, methotrexate and leucovorin regimen (CCRT-PFML) instead of neo-adjuvant chemotherapy has been applied. RESULTS: The overall 5-year survival rate was 59.2%, the 5-year disease-specific survival rate was 71.7%, and the 5-year organ preservation survival rate was 42.4%. In the group receiving CCRT-PFML, the overall 5-year survival rate was 60.0%, the 5-year disease-specific survival rate was 76.0%, and the 5-year organ preservation survival rate was 60.3%. CONCLUSION: CCRT-PFML for advanced MSSCC patients is feasible to preserve the organs without reducing the survival rate.

Is surgical debridement and topical 5 fluorouracil the optimum treatment for woodworkers' adenocarcinoma of the ethmoid sinuses? A case-controlled study of a 20-year experience.

OBJECTIVES: Woodworkers' adenocarcinoma of the ethmoid sinuses is an extremely rare occupational malignancy with a locally aggressive course. Treatment with surgical exenteration and topical 5 fluorouracil (5FU) packs has become standard treatment over the last 10 years in this ENT unit. This study presents level 2 evidence that 5FU provides improved survival over previous management with primary radiotherapy and salvage craniofacial resection. DESIGN: Retrospective case series with historical control group. SETTING: District General Hospital. PARTICIPANTS: The records of 31 consecutive patients with the disease were analysed. Five patients died prior to treatment. One patient was treated with surgery alone and therefore excluded. Twenty-five patients were included in the analysis. Fourteen were treated with primary radiotherapy and 11 with surgery and topical 5FU. OUTCOME MEASURES: Disease free survival was measured using Kaplan-Meier survival analysis. RESULTS: Five-year disease free survival improved from 50% with primary radiotherapy to 86% with surgery and 5FU. This improvement is statistically significant (P = 0.03). CONCLUSION: Topical 5FU treatment improves survival of Woodworker's adenocarcinoma of the ethmoid sinuses. This finding may be useful in the treatment of other locally aggressive sinonasal malignancies.

Adenocarcinoma of the ethmoid sinuses: a case of two primary tumours.

The authors present a case report of a retired furniture worker who initially presented with a mucin-secreting adenocarcinoma of the right ethmoid sinus. He underwent surgical resection, leaving the nasal septum intact, and topical treatment with 5-fluorouracil. He remained disease free. Three years after his initial presentation he was found to have a left nasal polyp on routine examination. This subsequently proved to be a second primary adenocarcinoma. A review of the literature has not shown any other cases of a second primary adenocarcinoma of the ethmoid sinuses.

An alternative therapeutic procedure for sinonasal undifferentiated carcinoma.

We describe two cases of sinonasal undifferentiated carcinoma, a rare and highly aggressive neoplasm of the paranasal sinuses. Case 1 had first been diagnosed as esthesioneuroblastoma, and intra-arterial and systemic chemotherapy and radiotherapy were performed. The tumor became smaller but did not disappear, and the patient died 2 months later. Case 2 received systemic chemotherapy and chemoradiotherapy, with daily venous administration of cisplatin during radiotherapy. The tumor became much smaller but also remained, and the patient died a month later. Although the therapy failed, chemoradiotherapy has some possibility of controlling the disease.

[Cancer of the ethmoid sinus]. / Cancer de l'ethmoïde.

Ethmoid sinuses are located at the level of the anterior skull base. Seventy to 80% of the ethmoid sinus malignant tumors are adenocarcinomas. Wood dust exposure is a carcinogen agent to ethmoid adenocarcinoma. More than 90% of patients with ethmoid adenocarcinoma are woodworkers. Craniofacial computed tomography scan and magnetic resonance imaging are always performed before treatment. It is always a multidisciplinary treatment including surgical resection followed by external radiation therapy. Some authors recommend a neoadjuvant chemotherapy. A total ethmoidectomy including the cribriform plate through a transcranial subfrontal approach is the best surgical technique. Local recurrence is the most frequent cause of failure; 5-year survival of patients with ethmoid adenocarcinoma is around 50%. A regular follow-up including clinical and radiological examination is always required.

Carboxypeptidase G2 rescue in a 79 year-old patient with cranial lymphoma after high-dose methotrexate induced acute renal failure.

A 79 year-old female patient presented with immunoblastic B-cell lymphoma of the ethmoidal sinuses and destruction of the anterior cranial fossa. After 3 cycles of high-dose methorexate (HD-MTX) MTX serum level remained elevated and creatinine serum levels raised. The patient received Carboxypeptidase G2 (CPG2) intravenously. Within one hour the MTX serum level decreased to <1 micromol/l as determined by high pressure liquid chromatography (HPLC). The patient recovered without significant toxicity and attained a long lasting ongoing (>14 months) complete remission. In this case we were able to demonstrate that rescue from HD-MT nephrotoxicity by CPG2 is also safe and effective in patients with advanced age with impaired renal function. With the help of CPG2, sufficient and potentially curative therapy with HD-MTX may also be provided to patients with a high risk of renal failure.

Cisplatin-based neoadjuvant chemotherapy and combined resection for ethmoid sinus adenocarcinoma reaching and/or invading the skull base.

OBJECTIVE: To review our experience with cisplatin-based neoadjuvant chemotherapy before en bloc resection via a combined neurosurgical and transfacial approach for ethmoid sinus adenocarcinoma reaching and/or invading the skull base. DESIGN: Case series. SETTING: A tertiary care center and university teaching hospital. PATIENTS: Twenty-two patients with primary untreated ethmoid sinus adenocarcinoma reaching and/or invading the skull base consecutively treated between 1984 and 1992 with cisplatin-based neoadjuvant chemotherapy and combined neurosurgical and transfacial approach. MAIN OUTCOME MEASURES: Statistical analysis of survival, local control, nodal recurrence, distant metastasis, and metachronous second primary tumor incidence based on the Kaplan-Meier actuarial method. Univariate analysis was performed to analyze the relationships between various factors, survival, and local recurrence. Clinical response, histological response, toxic effects of chemotherapy, and postoperative course were also reported. RESULTS: The Kaplan-Meier 3-year survival, local control, nodal recurrence, and distant metastasis estimates were 68.1%, 65.7%, 5.3%, and 10%, respectively. Metachronous second primary tumor was not encountered in our series. Survival was statistically more likely to be reduced in patients with intrasphenoidal tumor extent (P = .04) and local recurrence (P = .01). Local recurrence was statistically more likely in patients with intrasphenoidal tumor extent (P = .002) and no response to cisplatin-based neoadjuvant chemotherapy (P = .03). CONCLUSIONS: The results achieved suggest that cisplatin-based neoadjuvant chemotherapy before combined neurosurgical and transfacial approach should be further investigated for the treatment of ethmoid sinus adenocarcinoma reaching and/or invading the skull base.

Ethmoid sinus carcinomas: results and prognosis after neoadjuvant chemotherapy and combined surgery--a 10-year experience.

From June 1982 to June 1992, 144 ethmoido-sphenoido-orbital tumors have been referred to the neurosurgical department of Ste Anne Hospital. One hundred five of them were malignant lesions, among which 83 were included into our therapeutic protocol (1) neo-adjuvant chemotherapy (CDDP + 5-FU), (2) combined surgical procedure (subfrontal and transfacial), (3) postoperative radiotherapy. Fifty nine percent of the patients had no response to chemotherapy; 19% had a partial response (reduction of the tumoral volume > 50% and < 100%), 22% had a complete response. One patient had an immediate and transient postoperative rhinorrhea responsible for meningitis (acinetobacter) that was cured after a 3-day treatment. Four patients had postoperative meningitis without any cerebrospinal fluid leakage; they were also cured. Five patients had a local suppuration that was treated by subcutaneous drainage (n = 1) or the removal of the cranial basis graft (n = 4). Oncologic results are presented for only adenocarcinomas (n = 63) because they represent the only population of this series large enough to assure significant statistical figures. The global actuarial survival rate was 53% at 3 years and 42.5% at 5 years. The 5-year actuarial survival rate was 80% for T1 tumors, 60% for T2, 40% for T3, and 25% for T4. Patients with an intracranial extension had a 3-year survival rate of 19%; none survived after 4-year follow-up. Neo-adjuvant chemotherapy seemed to influence the survival: 100% survival rate at 5 and 10 years for the complete responders. We discuss the opportunity of intraorbital exenteration, the indications, and the limits of combined surgery. We emphasize the importance of neo-adjuvant chemotherapy and of combined surgical procedures, even when the patients are complete responders to chemotherapy: complete responders who had only a transfacial approach have a 5-year actuarial survival rate of 80% (instead of 100% when a combined procedure was performed). Those who were not operated primarily recurred within 3 years and then had to be operated. We propose to follow such a combined surgery for all large ethmoidal cancers (T3 and T4) and for small tumors (T1 and T2) developed superiorly and posteriorly. Anterior T1 and T2 tumors should be operated through a single transfacial route.

[Combined approach to malignant tumors of the ethmoid and other paranasal sinuses. Principles and results]. / Les abords combinés des tumeurs malignes de l'ethmoïde et autres sinus paranasaux Principes et résultats.

The authors present their experience concerning combined transfacial and neurosurgical procedures in the treatment of carcinomas of the ethmoid sinuses. 109 ethmoid-spheno-orbital tumors were treated at our department from 1982 to 1990: 85 were located into the ethmoidal and/or sphenoidal sinuses; 78 of these were malignant. Among the 65 ethmoidal carcinomas which were operated through a combined route, 48 underwent an induction chemotherapy and 19 a post-operative radiotherapy. The surgical technique is detailed, mostly the intra-cranial approach and the reconstruction of the cranial basis. Clinical results, and particularly the actuarial survival rates are discussed. The 5-year actuarial survival rate is 40% for all first hand ethmoidal adenocarcinomas. The figure reaches 52% for the patients without intra-cranial extension. At last, the 5-year actuarial survival rate is 100% for patients having a complete clinical response to induction chemotherapy.

Chemotherapy for paranasal sinus carcinoma. A 10-year experience at Wayne State University.

The role of chemotherapy in the management of patients with cancer of the paranasal sinus has not been defined. An analysis of 24 evaluable patients treated with chemotherapy as part of their overall therapy was performed. There were 16 male patients and eight female patients. Sixteen patients were previously untreated and eight had recurrent disease after surgery and/or radiotherapy. Six of the previously untreated patients had metastatic disease on presentation (four central nervous system (CNS) and two lung), and four recurrent patients had CNS involvement. The majority of patients (78%) had squamous cell carcinoma. The chemotherapy regimens included cisplatin (CDDP), vincristine (VCR), and bleomycin (COB), 5-fluorouracil (5-FU) infusion and CDDP, or 5-FU/CDDP and methotrexate (MTX). All patients had computed tomography (CT) measurable disease. Previously untreated patients underwent surgery and/or radiotherapy postchemotherapy. The overall response rate to chemotherapy for previously untreated patients was 82% (complete response [CR] 44%, partial response [PR] 38%) and for recurrent patients 88% (CR 38%, PR 50%). Predominant toxicities were nausea, vomiting, myelosuppression, mucositis, and renal impairment. The median survival of the previously untreated patients, based on response to chemotherapy, was as follows: CR 21+ months (range, 10+ to 81 months), PR 13.5 months (range, 2 to 21 months), and no response (NR) 3 months (range, 1 to 7 months). The median survival of patients with recurrent disease was as follows: CR 16 months, PR 13.5 months, and NR 5 months. We conclude that patients with paranasal cancers are responsive to CDDP-containing combinations. The role of adjuvant chemotherapy in previously untreated, locally advanced patients needs to be demonstrated by future randomized trials.

[Experiences with intratumor application of bleomycin-oil suspension (BOS) in cancers of the mouth, oropharynx and maxillary sinus]. / Erfahrungen mit intratumoraler Applikation von Bleomycin-Ol-Suspension (BOS) bei Karzinomen der Mundhöhle, des Oropharynx und Sinus maxillaris.

Bleomycin can be administered intravenously, intramuscularly and also locally into the tumor. Bleomycin in oil suspension (BOS) remains longer in the tumor-region with higher levels. In 6 patients with squamous cell carcinomas of the mouth, oropharynx and maxillary sinus, the intratumorous BOS-therapy was performed. The maximum dosage given was 180 mg. The results included: Progression (1), no-response (2), minor response (2), partial remission (1).

Effects of irradiation on the eye.

From 1954 through 1971, 47 patients with malignant tumors of the nasal cavity and paranasal sinuses were treated with an entire eye included in the tumor dose volume. All patients were treated with megavoltage radiation and received approximately 6,000 rads in 30 fractions in six weeks. Two thirds of the patients treated by irradiation alone had no problems with vision or difficulties related to treatment of the eye. When 5-fluorouracil (5-FU) was used in conjunction with high-dose radiotherapy, loss of vision was much more frequent and all patients had either visual loss or major clinical difficulties.