Evaluation of cervical nodal necrosis in nasopharyngeal carcinoma by computed tomography: incidence and prognostic significance

PURPOSE: The purpose was to study the prognostic value of contrast-enhanced computed tomography (CT) nodal necrosis in nasopharyngeal carcinoma. PATIENTS AND METHODS: One hundred sixty-one patients with newly diagnosed nasopharyngeal carcinoma and nodal metastases were reviewed. Forty patients also received cisplatin-based neoadjuvant chemotherapy in addition to radiotherapy. Nodal necrosis was defined as presence of hypodense areas in more than 33% of the node. Nodal response rate to chemotherapy, overall nodal control rate, local control rate, distant failure rate, overall relapse-free survival rate, and overall and cause-specific survival rates were compared between patients with and without nodal necrosis. Multivariate analysis was also performed. RESULTS: The incidence of nodal necrosis was 22.9%. Overall nodal response rates to chemotherapy were 88.9% (8/9) in patients with nodal necrosis and 74.2% (23/31) in those without. No significant differences in nodal control rate, local control rate, distant failure rate, and overall and cause-specific survival rates were found. Five-year overall relapse-free survival rate was lower in patients with cervical nodal necrosis (36%) as compared with those without (53%, p = .04). Multivariate analysis, however, did not confirm cervical nodal necrosis to be an independent prognostic factor. CONCLUSIONS: Presence of nodal necrosis in nasopharyngeal carcinoma does not affect nodal response to chemotherapy and nodal control by radiotherapy with or without chemotherapy. Cervical nodal necrosis does not appear to be an independent factor in predicting treatment outcome. Further studies to correlate nodal density with oxygenation status as well as tumor cell kinetics are warranted.     

Complications of endonasal paranasal sinus surgery--diagnostic and therapeutic consequences

BACKGROUND: Functional endoscopic sinus surgery has been proven the therapeutic method of choice in surgical therapy of chronic sinusitis. On the other hand, endonasal sinus surgery may cause severe complications even when performed by a skilled surgeon. This is easily explained by the close vicinity of many functionally important structures to the operative site. CASE REPORTS: Three histories are reported that involve possible complications even in apparently simple cases. Diagnostic and therapeutic consequences are discussed. In a case previously diagnosed histologically as chronic unspecific sinusitis, an endonasal biopsy resulted in endocranial bleeding requiring neurosurgical intervention. Midline granuloma was found to be the correct diagnosis. Another patient was seen with a normal X-ray of the sinuses and solitary polypoid structure in his left nose. Polypectomy was planned and a CT scan was performed, which demonstrated a meningocele. Transfacial surgery was then performed to remove the meningocele. Another patient presented with a traumatic impression of the frontal sinus, and open reposition by transfacial surgery of the frontal and ethmoid sinus was planned. When CT scans revealed an uncovered optic nerve in the sphenoid sinus of the fractured side, we abandoned ethmodectomy and performed reposition of the frontal sinus as the only surgical procedure. RESULTS AND CONCLUSIONS: In this paper, we show typical complications of endonasal sinus surgery and strategies for avoiding them. If any complication occur, prompt treatment is required. Three groups of complications can be defined: perforation of frontobasal dura resulting in cerebrospinal fluid (CSF) fistula, severe bleeding, and orbital or optic nerve injury. When the surgeon discovers an intraoperative complication, possible consequences must be considered immediately to minimize side effects for the patient. A CSF fistula should be closed in the same procedure, and transfacial surgery may be necessary. Hemorrhage resulting from an ethmoidal artery may require frontoorbital surgery and ligation of this vessel. If retrobulbar hemorrhage caused by retraction of an ethmoid artery occurs, immediate intervention is necessary. Usually a transfacial approach, resection of the medial orbital wall and retrobulbar decompression are performed. In some cases lateral canthotomy may be the best way to drain haematoma and decompress the optic nerve. Subsequently, orbital revision and ligation of the retracted artery must be performed. Any delay can result in persistent visual loss. We conclude that the extranasal frontoorbital approach should be part of the residency training program in ENT departments. Any surgeon performing endonasal sinus surgery must be trained in transfacial emergency procedures, which should be part of anatomic preparations in teaching courses, thus avoiding severe damage in case of intraoperative complication.     

Surgery in the management of small cell lung cancer

OBJECTIVE: We analyzed our experience in the period January 1975-December 1995 aiming to confirm the role of surgery in the multimodality treatment of small cell lung cancer (SCLC). METHODS: 127 patients (5.28% of the overall lung resections for carcinoma) underwent surgery for SCLC. The median age was 60 years (range 34-73). In 87 patients (68.5%) a pre-operative tissue diagnosis was effected and those patients underwent a complete staging procedure. Fifteen patients received up to six complete courses of neoadjuvant and adjuvant chemotherapy. The surgical procedures included: 50 pneumonectomies, 71 lobectomies and six wedge resections. Two patients experienced a local recurrence and a completion pneumonectomy was performed. RESULTS: The median follow-up is 66 months (range 6-214). The 5-year actuarial survival rate is 22.6% (median 18 months). Twenty-three patients are still alive, 21 of them being disease-free. Considering the most conspicuous group of patients (n = 92) treated by surgery and adjuvant chemotherapy, the survival data were 47.2, 14.8 and 14.4% for Stage I, II and III, respectively (P = 0.001). NO patients had a significantly better survival than N1 and N2 patients (P = 0.035). CONCLUSIONS: Surgery and adjuvant chemotherapy might represent an effective form of treatment of limited SCLC without lymph-node involvement. The role of surgery is yet to be verified as regards N1 and N2 status, where even neoadjuvant chemotherapy has not achieved the hoped-for results (no patient reaching a 2-year survival).     

Anastomotic leakage: impact on local recurrence and survival in surgery of colorectal cancer

Anastomotic leakage is a serious complication in colorectal surgery, especially in the treatment of adenocarcinoma located in the left-sided colon and rectum. It is controversial whether anastomotic leakage is a prognostic factor for local recurrence and/or survival in this disease. To evaluate the impact of anastomotic dehiscence on the outcome of surgery we reviewed data on 467 consecutive patients with adenocarcinoma of the left colon and rectum treated between 1985 and 1995 in our Department. Of these, 41 (8.8%) developed anastomotic leakage. The overall-survival differed nonsignificantly (P = 0.57) between leakage and nonleakage groups. Of 331 patients with curative resection 29 showed an anastomotic leakage. There were 46 R0-resected patients who died under disease-related conditions: 7 patients in the leakage group (24.1%) and 39 in the nonleakage group (12.9%; P = 0.045). In the curatively resected group 5 of 29 patients developed local recurrence in the leakage group (17.2%) but only 26 of 302 patients in the nonleakage group (8.6%; P = 0.0357). Multivariate analysis showed only the factors of age, stage of resection, staging of lymph nodes, and tumor staging as independent prognostic factors for overall survival. For local recurrence the multivariate analysis revealed tumor staging and anastomotic leakage as independently significant. Anastomotic leakage thus appears to be a prognostic factor for local tumor recurrence of colorectal cancer. In addition, disease-related survival is considerably decreased under leakage conditions. Anastomotic leakage was not shown in this study to be an independent prognostic factor for overall survival due to the lack of statistical significance.     

Implementation of guidelines for No-CPR orders by a general medicine unit in a teaching hospital

Improvements in reconstruction of the skull base have made craniofacial surgery safe. Reconstruction of the anterior skull base must provide a seal between the cranial cavity and upper respiratory tract, as well as offer structural support for the brain. A wide variety of local flaps have been designed. The choice of flap in individual cases depends on the location and size of the defect. We report a reconstructive technique for the anterior skull base with vertical median forehead flaps which we used to treat two patients, one patient with adenocarcinoma and the other with leiomyosarcoma. Both were lesions of the ethmoid sinuses and nasal cavity.     

Management of thyroid carcinoma invading the aerodigestive tract

OBJECTIVES: To evaluate approaches to thyroid carcinoma invading the aerodigestive tract, with particular attention to well-differentiated carcinomas. STUDY DESIGN: Retrospective review of experience with thyroid carcinoma invading the aerodigestive tract over a 20-year period at a tertiary referral hospital. METHODS: The medical records of all patients with a diagnosis of thyroid cancer treated at Emory University Hospital, Atlanta, Georgia, from 1977 through 1997 were reviewed. Multiple clinical variables were analyzed including treatment, development of recurrence, and survival. Survival and time to local recurrence were determined by Kaplan-Meier analysis, and statistical comparisons were made using log-rank analysis. RESULTS: Five hundred thirty-six cases were identified; 28 patients (5.2%) were identified with invasive disease involving the aerodigestive tract. Histologic findings at the time of invasion included 15 well-differentiated (WD) carcinomas and 13 poorly differentiated (PD) carcinomas. Eight of the 28 patients (5 WD, 3 PD) underwent surgical resection of some portion of the aerodigestive tract with curative intent. Ten patients (8 WD, 2 PD) underwent incomplete resection with tumor left adjacent to aerodigestive tract structures. All patients undergoing incomplete resection developed local recurrence. Six required salvage resection, as opposed to no recurrences in WD carcinomas following complete resection (P = .01). Survival at 5 years for WD carcinomas undergoing complete resection versus initial incomplete resection was 100% versus 50%, respectively (P = .27). CONCLUSION: Review of our experience shows that complete resection of thyroid carcinoma invading the aerodigestive tract can offer prolonged palliation, improved local control, and the opportunity for cure in selected patients.     

Unusual approaches to hypophyseal adenomas

For pituitary adenomas surgery, rhinoseptal transsphenoidal approach is used in 98 to 99% of the cases. Although this approach is fitting for microadenomas and the majority of macroadenomas, some of them develop extensions in the nasal fossas, the posterior cranial fossa, the suprasellar region, or into the cavernous sinus and will require other approaches. For the superior routes, the frontopterional approach gives good control of the suprasellar region, the anterior and middle base of the skull. The tumor dissection is performed inside the concavity of the chiasm and between the internal carotid artery and the optic nerve (optico-carotid approach). The frontopterional approach is used for superolateral extensions, especially in the lateral fissure. The bifrontal basal inter hemispheric approach, through a medial frontal bone flap tangential to the base, gives a good route to the suprasellar region and behind the dorsum, and also for tumors extended in the third ventricle in case of prefixed chiasm. For the inferior routes, the participation of ENT or craniofacial surgeons is a great help. The transfacial or transethmoidal approach performs a hollowing of the nasal fossas and gives a large interorbital tunnel adapted for tumors extended in the rhinopharynx and the ethmoid. The Le Fort I maxillary osteotomy offers also a large approach for adenomas extending in the rhinopharynx. The transcavernous approach from Dolenc, for adenomas progressing in the cavernous sinus requires a long and difficult procedure. The progression of some adenomas in many directions may require a combined approach in one or two procedures.     

Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer

BACKGROUND: We performed a multi-institutional randomized trial comparing preoperative chemotherapy followed by surgery with surgery alone for patients with local and operable esophageal cancer. METHODS: Preoperative chemotherapy for patients randomly assigned to the chemotherapy group included three cycles of cisplatin and fluorouracil. Surgery was performed two to four weeks after the completion of the third cycle; patients also received two additional cycles of chemotherapy after the operation. Patients randomly assigned to the immediate-surgery group underwent the same surgical procedure. The main end point was overall survival. RESULTS: Of the 440 eligible patients with adequate data , 213 were assigned to receive preoperative chemotherapy and 227 to undergo immediate surgery. After a median possible study time of 55.4 months, there were no significant differences between the two groups in median survival: 14.9 months for the patients who received preoperative chemotherapy and 16.1 months for those who underwent immediate surgery (P=0.53). At one year, the survival rate was 59 percent for those who received chemotherapy and 60 percent for those who had surgery alone; at two years, survival was 35 percent and 37 percent, respectively. The toxic effects of chemotherapy were tolerable, and the addition of chemotherapy did not appear to increase the morbidity or mortality associated with surgery. There were no differences in survival between patients with squamous-cell carcinoma and those with adenocarcinoma. Weight loss was a significant predictor of poor outcome (P=0.03). With the addition of chemotherapy, there was no change in the rate of recurrence at locoregional or distant sites. CONCLUSIONS: Preoperative chemotherapy with a combination of cisplatin and fluorouracil did not improve overall survival among patients with epidermoid cancer or adenocarcinoma of the esophagus.     

Cricohyoidopexy in selected infrahyoid epiglottic carcinomas presenting with pathological preepiglottic space invasion

Nineteen patients who presented with infrahyoid epiglottic squamous cell carcinoma with gross pathological preepiglottic space invasion, not amenable to a partial horizontal supraglottic laryngectomy, were offered a supracricoid partial laryngectomy with a cricohyoidopexy technique; this was an attempt to preserve physiological phonation, respiration, and deglutition while achieving the same local control rate as with a total laryngectomy. Preoperative chemotherapy and bilateral jugulocarotid lymph node dissection were performed in all cases. Patients were monitored for at least 5 years or until death. No patients were unavailable for follow-up. The 5-year actuarial survival (Kaplan-Meier method) was 84.2%. Local recurrence, nodal recurrence, and distant metastasis occurred once in our series, while six patients presented with a second primary tumor. We present, analyze, and compare functional results with those of the previously reported series. Our experience with the supracricoid partial laryngectomy with a cricohyoidopexy, in the face of selected infrahyoid epiglottic squamous cell carcinoma invading the preepiglottic space, not amenable to a partial horizontal supraglottic laryngectomy, suggested that a total laryngectomy might be avoided without decreasing the cure rate.     

Residual metastatic axillary lymph nodes following neoadjuvant chemotherapy predict disease-free survival in patients with locally advanced breast cancer

BACKGROUND: This study was performed to validate the prognostic significance of residual axillary lymph node metastases in patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy and to analyze other clinicopathologic factors that might be independent predictors of disease-free survival (DFS) in an attempt to identify patients in whom axillary dissection might be omitted. METHODS: One hundred sixty-five assessable patients with LABC were treated in a prospective trial of neoadjuvant chemotherapy utilizing four cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide. Responding patients were treated with segmental mastectomy and axillary dissection or modified radical mastectomy. Patients subsequently received additional chemotherapy followed by irradiation of the breast or chest wall and draining lymphatics. The median follow-up was 35 months. RESULTS: Clinical tumor response to neoadjuvant chemotherapy (P = 0.046) and the number of residual metastatic axillary lymph nodes found at axillary dissection (P = 0.05) were the only independent predictors of DFS. Patients with a complete clinical response had a predictably excellent DFS and those with no change or progressive disease had a poor DFS. In patients with a partial response, the number of residual metastatic lymph nodes further stratified patients with respect to DFS (P = 0.006). CONCLUSIONS: Clinical response and residual metastatic axillary lymph nodes following neoadjuvant chemotherapy are important predictors of DFS. Patients with a clinically positive axilla following neoadjuvant chemotherapy should undergo axillary dissection to ensure local control. However, the benefit of axillary dissection in patients with a clinically negative axilla may be minimal if the axilla will be irradiated, and histologic staging does not affect subsequent systemic treatment. A prospective randomized trial of axillary dissection versus axillary radiotherapy in patients with a clinically negative axilla following neoadjuvant chemotherapy is presently under way to evaluate this hypothesis.     

Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer

BACKGROUND: The B-20 study of the National Surgical Adjuvant Breast and Bowel Project (NSABP) was conducted to determine whether chemotherapy plus tamoxifen would be of greater benefit than tamoxifen alone in the treatment of patients with axillary lymph node-negative, estrogen receptor-positive breast cancer. METHODS: Eligible patients (n = 2306) were randomly assigned to one of three treatment groups following surgery. A total of 771 patients with follow-up data received tamoxifen alone; 767 received methotrexate, fluorouracil, and tamoxifen (MFT); and 768 received cyclophosphamide, methotrexate, fluorouracil, and tamoxifen (CMFT). The Kaplan-Meier method was used to estimate disease-free survival, distant disease-free survival, and survival. Reported P values are two-sided. RESULTS: Through 5 years of follow-up, chemotherapy plus tamoxifen resulted in significantly better disease-free survival than tamoxifen alone (90% for MFT versus 85% for tamoxifen [P = .01]; 89% for CMFT versus 85% for tamoxifen [P = .001]). A similar benefit was observed in both distant disease-free survival (92% for MFT versus 87% for tamoxifen [P = .008]; 91% for CMFT versus 87% for tamoxifen [P = .006]) and survival (97% for MFT versus 94% for tamoxifen [P = .05]; 96% for CMFT versus 94% for tamoxifen [P = .03]). Compared with tamoxifen alone, MFT and CMFT reduced the risk of ipsilateral breast tumor recurrence after lumpectomy and the risk of recurrence at other local, regional, and distant sites. Risk of treatment failure was reduced after both types of chemotherapy, regardless of tumor size, tumor estrogen or progesterone receptor level, or patient age; however, the reduction was greatest in patients aged 49 years or less. No subgroup of patients evaluated in this study failed to benefit from chemotherapy. CONCLUSIONS: Findings from this and other NSABP studies indicate that patients with breast cancer who meet NSABP protocol criteria, regardless of age, lymph node status, tumor size, or estrogen receptor status, are candidates for chemotherapy.     

The activated clotting time loading dose response ratio (ACTLORR) as an indicator of heparin demand during cardiopulmonary bypass

PURPOSE: To develop a new technique, intraoperative high dose rate brachytherapy (IOHDR), to deliver localized radiation therapy intraoperatively to head and neck tumors at sites inaccessible to intraoperative electron beam radiotherapy (IOEBRT) in the skull base region. METHODS: After maximal surgical resection, afterloading catheters spaced 1 cm apart embedded in custom surface applicators made of foam or silicone were placed on resected tumor beds. IOHDR was delivered in a shielded operating room using preplanned dosimetry with a nominal 10 Ci iridium-192 source in an HDR micro-Selectron afterloader. Twenty-nine patients (20 males, 9 females) ranging in age from 9 to 80 years (median = 61) were irradiated intraoperatively for advanced head and neck tumors at sites inaccessible to IOEBRT. Six patients who had previously received external beam radiation (EBRT) ranging from 50 to 75 Gy, were given 15 Gy of IOHDR only. Twenty-three patients who had no prior radiation received 7.5 to 12.5 Gy IOHDR, and 45 to 50 Gy EBRT was planned post-operatively; however, six of these patients did not complete the planned EBRT. Doses to normal tissues were reduced whenever possible by shielding with lead or by displacement with gauze or retractors. Treatment time ranged from 3.8 to 23 min (median = 6.5 min). Five patients received concurrent cis-platinum based chemotherapy. RESULTS: Twenty-nine patients treated to 30 sites had local tumor control of 67% and crade survival of 72%, with the follow-up ranging from 3 to 33 months (median = 21 months). In the group of 17 previously unirradiated patients who had completed full treatment (IOHDR and EBRT) to 18 sites, the local tumor control was 89%, and all of these patients survived. Tumor control in the six previously unirradiated patients who did not complete EBRT was 50% with a crude survival of 50%. In the group of six previously irradiated patients treated by IOHDR only, the local tumor control was 17% with a crude survival of 17%. No intraoperative complications were noted. The delayed morbidity included cerebrospinal fluid (CSF) leak with bone exposure (1), chronic subdural hematoma (1), septicemia (1), otitis media (1), and severe xerostomia (1). We cannot comment on long-term morbidity due to the relatively short follow-up period of 21 months. CONCLUSIONS: It is feasible to deliver IOHDR, with acceptable toxicity, to skull base tumors at sites inaccessible to IOEBRT. The use of IOHDR as a pre-radiotherapy boost produced excellent local control and survival in the selected group of patients who had no previous radiation therapy. The use of exclusive IOHDR in the previously irradiated group resulted in poor outcome, possibly due to the limitations on re-irradiation doses and/or volumes determined by normal tissue tolerance or because these patients have inherently radioresistant tumors. Higher IOHDR doses, additional EBRT, and/or chemotherapy should be considered for this group. The use of IOHDR as a pre-EBRT boost to maximize local control has a promising future in the treatment of carefully selected patients with advanced skull base tumor.     

Supratentorial malignant gliomas in childhood: a single institution perspective

BACKGROUND: A retrospective study evaluated the clinical characteristics, prognostic factors, and outcome of patients with newly diagnosed supratentorial malignant gliomas treated with preirradiation chemotherapy. METHODS: Of 41 patients with supratentorial malignant gliomas accrued between 1984-1994, all had neuroimaging documentation of the extent of resection and 37 had complete neuraxis staging prior to treatment; 80% were treated with one of a variety of neoadjuvant chemotherapy regimens. RESULTS: Thirteen patients had anaplastic astrocytoma (AA), 25 had glioblastoma multiforme (GBM), and 3 had anaplastic oligodendroglioma. Gross total resection (GTR) was performed in 10 patients, subtotal resection (STR) in 22 patients, and biopsy (Bx) alone in 9 patients. For the entire group the 3-year overall and progression free survivals were 35 +/- 8% and 18 +/- 6%, respectively. Tumor recurrence was dominantly local. However, 9 patients with initially local disease failed at a distant neuraxis site, giving a 26 +/- 7% actuarial risk of dissemination at 3 years. The only significant prognostic factor was extent of tumor resection: patients who underwent GTR survived longer than those who underwent STR or Bx (P = 0.004). Histology (GBM vs. AA), age, and the use of enhanced local dose radiation therapy (brachytherapy or stereotactic irradiation) did not affect survival. CONCLUSIONS: Neoadjuvant chemotherapy was not associated with a survival rate significantly different from that observed in adjuvant chemotherapy studies. Systematic neuraxis staging at diagnosis and recurrence revealed a rate of neuraxis dissemination as a component of recurrence that was higher than previously reported; the utility of craniospinal irradiation in preventing isolated dissemination remains uncertain.     

The role of neoadjuvant therapy in surgically resectable esophageal cancer

OBJECTIVE: To determine the effect of neoadjuvant therapy (NT) (preoperative chemotherapy, radiation therapy, or both) in surgically resectable esophageal cancer. DESIGN: A retrospective review over a 20-year period. SETTING: A tertiary academic medical center. PARTICIPANTS: All patients undergoing surgical resection for esophageal cancer (N = 316) over this time period. MAIN OUTCOME MEASURES: Perioperative morbidity and mortality, local and distant recurrences, and overall survival. RESULTS: Patients undergoing NT (n = 106) had prognostic factors similar to those treated with surgery alone (n = 210). No increase was noted in surgical morbidity with NT (anastomotic leaks, reoperation rates, complications, or extended hospital stays). Overall survival was not improved by NT (median survival, 14 months) except in the subset of patients (11/83) who responded completely (100% histological necrosis) to preoperative chemotherapy (median survival, 79.2 months; P < .02). Complete response to radiation therapy alone was not associated with improved survival. Partial necrosis of the primary tumor was seen in 13 (15%) of 83 patients but conferred no survival advantage. Complete response to preoperative chemotherapy was associated with squamous cell pathological features and excellent performance status as measured by preanesthesia evaluation. CONCLUSIONS: The addition of NT did not increase perioperative morbidity or mortality. Only the subset of patients who had a complete response to preoperative chemotherapy showed a survival advantage. Excellent performance status and squamous cell pathological features were associated with an increased chance of complete pathological response following preoperative chemotherapy.     

In vitro antiphagocytic effect of Melia azedarach leaf extracts on mouse peritoneal exudate cells

The first reported case of cerebellar metastasis from primary clear cell adenocarcinoma of the fallopian tube is presented. Initially diagnosed as stage Ia, the patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy, followed by cisplatin-based chemotherapy and whole pelvic irradiation. Thirty six months later multiple pulmonary metastases were detected that did not respond to chemotherapy. Later the patient presented with cerebellar metastasis. She received whole brain radiotherapy and steroids. The brain lesion partially responded and the patient's neurologic symptoms improved. Throughout there was no evidence of local recurrence. This case suggests that with the prolonged survival achieved by aggressive treatment occult brain metastases might become apparent.     

Normal regional anatomy of the shoulder

Transitional cell carcinoma of the bladder is associated with a high relapse rate, locally and systemically, particularly in patients with nodal or soft-tissue involvement, despite radical cystectomy. The responsiveness of the disease to chemotherapy in the metastatic setting has stimulated the use of systemic therapy in earlier stage disease, either before (neoadjuvant) or after (adjuvant) definitive local therapy. Interpretation of the data is hampered by low patient accrual to randomized trials, lack of standardization of local treatment modalities, and the use of a variety of chemotherapy agents and regimens pointing to the difficulty in reaching a consensus as to what constitutes standard therapy. In this article, we review the use of adjuvant and neoadjuvant chemotherapy, the advantages and disadvantages of both approaches, and the recommendations that can be made based on available data. New approaches to improving survival, potentially with organ preservation, include the development of more effective chemotherapy, and the identification of prognostic features-clinical or biologic-that might be a better guide to patient selection.     

Use of preoperative MR to predict dural, perineural, and venous sinus invasion of skull base tumors

PURPOSE: To assess the accuracy of MR imaging in predicting dural, venous sinus, and perineural invasion by skull base tumors. METHODS: The preoperative MR images of 22 patients who had resection of skull base neoplasms were evaluated for the following characteristics: dural enhancement, pial enhancement, local perineural invasion by adjacent tumor, and venous sinus invasion by tumor. The greatest width of dural enhancement was measured, and the character of dural enhancement was noted. The pathologic and surgical reports were reviewed retrospectively with specific attention to dural, venous, and local perineural invasion. RESULTS: Of the 22 patients studied, dural invasion by tumor was confirmed in eight patients, vascular invasion in six patients, and perineural invasion in four patients. The sensitivity of dural enhancement in predicting invasion was 88%, the specificity 50%, and the accuracy 64%. When enhancement and focal nodularity were present, the sensitivity remained at 88%; however, specificity was 100% and accuracy 95%. If the dural enhancement was more than 5 mm thick, sensitivity, specificity, and accuracy were 75%, 100%, and 91%, respectively. Predicting tumor invasion of the dura by the presence of pial enhancement was 50% sensitive and 100% specific. Venous sinus/jugular vein invasion was predicted with 100% sensitivity, 94% specificity, and 95% accuracy. Local perineural invasion was predicted with 100% sensitivity, 50% specificity, and 59% accuracy. CONCLUSIONS: The presence of pial enhancement, focal dural nodules, or dural thickening of more than 5 mm is highly accurate in predicting the presence of neoplastic dural invasion. Linear enhancement of dura does not imply dural infiltration by tumor. Venous invasion by tumor can be predicted accurately with preoperative MR imaging.     

The role of chemotherapy in the management of nasopharyngeal carcinoma

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a radiosensitive tumor for which there is a high local control rate after radical radiotherapy (RT). However, for patients with locoregionally advanced disease, the rate of distant metastasis is high and the 5-year overall survival rate is poor. METHODS: A review of retrospective and prospective clinical studies was performed to assess the role of chemotherapy in three settings: metastatic disease; neoadjuvant and/or adjuvant; and concurrent chemotherapy with radiotherapy. RESULTS: Cisplatin-based combination chemotherapy results in a high response rate in patients with metastatic NPC, and a subgroup may achieve long term disease free survival. The use of neoadjuvant and adjuvant chemotherapy to treat locoregionally advanced disease has resulted in consistently high response rates, but no randomized trial to date has demonstrated an improvement in overall survival. A recent Head and Neck Intergroup study randomized patients in the United States to receive concurrent chemotherapy (cisplatin) and radiotherapy or radiotherapy only. Although this approach demonstrated significant benefit in overall survival favoring the use of concurrent chemotherapy and radiotherapy, its applicability in geographic areas of high NPC incidence remains to be proven. CONCLUSIONS: NPC is a chemosensitive tumor, and patients with metastatic disease have a high response rate. Further prospective studies will define the standard approach to treating locoregionally advanced NPC, which is likely to incorporate into the primary treatment some form of systemic chemotherapy.     

The role of preoperative adjuvant treatment in the management of esthesioneuroblastoma: the University of Virginia experience

OBJECTIVE: Multidisciplinary management of esthesioneuroblastoma has effected markedly increased survival during the past 20 years. The potential for radical craniofacial surgery for complete en bloc resection, the availability of advanced neuroimaging modalities, and the incorporation of neoadjuvant therapy into treatment strategies for tumor remission have all contributed to this accomplishment. However, a standard protocol for the management of these lesions has not been accepted; preoperative radiation and chemotherapy have been advocated, but neither radiographic nor clinical response has been quantified. METHODS: Thirty-four consecutive patients with biopsy-proven esthesioneuroblastoma treated at one institution from 1976 to 1994 were reviewed to determine the effects of preoperative radiation therapy, with or without chemotherapy, on tumor size and long-term survival. RESULTS: In a multivariate regression analysis, advanced age was predictive of decreased disease-free survival (P=0.008), whereas advanced Kadish stage was associated with a borderline higher rate of disease-related mortality (P=0.056). Two-thirds of the patients showed a significant reduction in tumor burden with adjuvant therapy. Patients with response to neoadjuvant therapy demonstrated a significantly lower rate of disease-related mortality (P=0.050). In this series, the overall 5- and 10-year survival rates were 81.0 and 54.5%, respectively. CONCLUSION: Preoperative neoadjuvant therapy provides a valuable complement to radical craniofacial resection, leading to reduction in tumor burden. Patients experiencing reduction in tumor volume by neoadjuvant therapy demonstrate an improved prognosis.     

Volumetric analysis of tumor extent in nasopharyngeal carcinoma and correlation with treatment outcome

PURPOSE: To investigate the variability of tumor volume in nasopharyngeal carcinoma using quantitative measurements of tumor bulk derived from computed tomography, and to study the prognostic value of tumor volume in comparison with other variables. METHODS AND MATERIALS: Two hundred ninety patients with newly diagnosed nasopharyngeal carcinoma were included in the study. The primary tumor volume (PTV) and nodal tumor volume (NTV) were obtained by outlining the tumor contour followed by summation of areas in sequential pretreatment computed tomography axial scans. Total tumor volume (TTV) was obtained by adding the PTV and NTV. All patients had radiotherapy as the primary treatment, 67 patients also received cisplatin-based neoadjuvant chemotheraphy. RESULTS: A large variation in tumor volume was observed, especially in advanced stage disease. The median PTV (cc) in Ho's T1, T2, and T3 disease were: 6.9 (range: 0.9-42.7), 18.8 (1.6-127.9), and 52.4 (3.3-166.8). The median TTV (cc) in Ho's stage I to IV disease were: 7.6 (range: 1.3-42.7), 19.8 (3.2-55.7), 40.7 (4.1-222.7), and 51.1 (3.1-274.7). Patients with a large PTV (>60 cc) were associated with significantly poorer local control (5-year local control rate: 56%) and disease-specific survival (5-year survival rate: 53%). In patients with a small PTV (< or =20 cc), there were no significant differences in local control among different T stages. Large NTV (>30 cc) was associated with significantly higher distant failure rate (5-year distant relapse-free survival rate: 54%) and lower disease-specific survival (5-year survival rate: 40%). In multivariate analysis, only PTV was found to be an independent factor in predicting local control. CONCLUSION: A large variation of tumor volume was present in different T stage disease of nasopharyngeal carcinoma, and PTV represents an independent prognostic factor of local control that appears to be more predictive than Ho's T stage classification.