Postoperative radiation for squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site: outcomes and patterns of failure

BACKGROUND: This retrospective study assesses the outcomes and patterns of failure in patients with squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site treated with combined surgery and postoperative radiotherapy. METHODS: One hundred thirty-six patients with squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary source were treated postoperatively with radiotherapy at the University of Texas M. D. Anderson Cancer Center between the years 1968 and 1992. Stage distribution was: N1, 31 patients; N2a, 49; N2b, 25; N2c, 3; N3, 18; and Nx, 10. Thirty-nine patients had excisional biopsies only, 64 patients underwent modified neck dissections, and 33 had radical neck dissections. Extracapsular extension was present in 87 cases. Fifty-nine patients had multiple nodes involved. The median duration of follow-up for surviving patients was 8.7 years. RESULTS: Twelve patients, all with extracapsular nodal disease, developed regional relapse. The 5-year actuarial rates of regional relapse in patients with and without extracapsular nodal disease were 16% and 0%, respectively (p = .004). Nine patients (22%) with extracapsular disease and multiple nodes relapsed compared with three patients (7%) with extracapsular disease and a solitary node (p = .02). None of the patients treated with excisional biopsy and radiotherapy relapsed regionally. No statistically significant relationship between dose, treatment duration, time interval between surgery, and the start of radiotherapy and relapse was detected. The 2-, 5-, and 10-year actuarial disease-specific survival rates were 82%, 74%, and 68%, respectively. Fourteen patients developed cancers in head and neck mucosal sites; six of these cancers were located in unirradiated tissues. CONCLUSIONS: Relapse occurred infrequently in patients treated with excisional biopsies and postoperative radiotherapy. Extracapsular extension and multiple nodes were associated with worse regional control and disease-specific survival. These results appear consistent with those expected for patients with advanced neck disease and a known primary site, and the absence of a primary site should not exclude patients from studies aiming to improve outcomes in patients with extensive neck disease from a head and neck squamous cell cancer. We continue to recommend radiation to the necks and pharyngeal axis for patients suspected of having residual microscopic disease following surgery for squamous cell carcinoma metastatic to the neck from an unknown primary site.     

Postoperative radiotherapy with concurrent cisplatin appears to improve locoregional control of advanced, resectable head and neck cancers: RTOG 88-24

PURPOSE: Despite aggressive surgery and postoperative radiation therapy, only 30% of patients who have advanced, potentially resectable carcinomas of the head and neck survive for 5 years. In the hope of improving this situation we studied the effect of postoperative radiotherapy delivered concurrently with cisplatin. METHODS AND MATERIALS: Patients who had Stage IV tumors and/or involved surgical margins received 60 Gy in 30 fractions over 6 weeks plus 100 mg/m2 of cisplatin on radiotherapy days 1, 23 and 43. Fifty-two patients participated in this trial and 51 were evaluated. Forty-three (84%) patients had pathologic T3 or T4 disease, 43 (84%) had Stage IV disease, and 27 (53%) had histologically involved surgical margins. RESULTS: Severe and life-threatening toxicities occurred in 20% and 12% of patients, respectively; the most common drug-related toxicities were leukopenia, anemia, nausea, and vomiting. Seventeen patients (43%) remain alive with no evidence of disease. Four patients (8%) died with no evidence of neoplastic disease, and one patient has died of a second independent malignancy. By actuarial analysis at 3 years, 48% of patients are alive, 81% have locoregional control of disease, and 57% are free of distant metastases. CONCLUSIONS: Based on comparison with similar patients treated in a prior Radiation Therapy Oncology Group/Intergroup trial (RTOG), we conclude that postoperative radiotherapy with concurrent cisplatin may improve locoregional control rates and should be prospectively tested.     

A pivotal role for glutamate in the pathogenesis of schizophrenia, and its cognitive dysfunction

PURPOSE: To compare the outcome for patients with squamous cell carcinoma of cervical lymph nodes metastatic from an unknown primary site who were irradiated to both sides of the neck and potential mucosal sites with opposed photon beams, and for those irradiated to the ipsilateral side of the neck alone with an electron beam. METHODS AND MATERIALS: Fifty-two patients with squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site were irradiated by two different methods. Thirty-six were irradiated with a bilateral technique (BT), i.e., to both sides of the neck, including the naso-oro-hypopharyngeal mucosa, and 16 were irradiated with an electron beam (EB) to the ipsilateral side of the neck alone. Twenty patients of the BT group and 11 of the EB group had cervical lymph node dissections, and the remaining 21 patients had lymph node biopsies, prior to radiotherapy. RESULTS: Tumor control in the ipsilateral side of the neck did not differ for either radiation technique, but was significantly higher after lymph node dissection than after biopsy (90 vs. 48%; p = 0.0004). Control of subclinical metastases in the contralateral cervical lymph nodes was higher for patients irradiated with BT than for patients irradiated with EB (86 vs. 56%; p = 0.03). The occult primary was later discovered in 8% of the patients in the BT group and 44% of the EB group (p = 0.0005). The disease-free survival rate at 5 years for patients who had lymph node dissection prior to irradiation was 61%, and was 37% for those who had biopsy (p = 0.05). Only 20% of patients who subsequently developed an occult primary were salvaged and survived for 5 years after salvage treatment. CONCLUSION: Bilateral neck and mucosal irradiation is superior to ipsilateral neck irradiation in preventing contralateral cervical lymph node metastases and the subsequent appearance of an occult primary cancer. Both techniques combined with cervical lymph node dissection were equally effective in controlling the ipsilateral neck disease.     

Nodal disease in purely glottic carcinoma: is elective neck treatment worthwhile?

OBJECTIVE: Although there is a generalized understanding of the relatively low overall incidence of nodal disease from purely glottic carcinoma, the exact role for elective neck treatment in the management of this disease remains controversial. The purpose of this study was to identify the incidence of occult nodal disease (including paratracheal) in patients who have glottic carcinoma without significant extraglottic extension and to identify which patients are at risk for this. A retrospective chart review of 92 such patients who had either undergone neck dissection or been observed for a minimum of 2 years was performed. RESULTS: For the 92 patients, neck treatment consisted of observation in 68 patients, paratracheal node dissection in four, unilateral neck dissection in four, unilateral neck dissection and excision of paratracheal nodes in 14, and bilateral neck dissection with paratracheal node excision in two. Of the 24 nodal dissections performed, four were positive for occult metastatic disease. No patient in the observation group developed nodal disease. CONCLUSION: The incidence of occult nodal disease in NO glottic carcinoma is low, 0% in early stage disease (T1-T2) and 19% in late stage disease (T3-T4). Nodes at highest risk included only the paratracheal, level II, and level III. Elective neck treatment should only be undertaken for advanced (T3-T4) disease and even then is of questionable benefit. If undertaken, it should have a low potential morbidity, such as selective neck dissection or radiation. Computed tomography was not useful in staging the neck for this subset of patients.     

Phase II trial of cisplatin and gemcitabine in advanced squamous-cell carcinoma of the head and neck

BACKGROUND: To evaluate the toxicity profile and efficacy of cisplatin combined with gemcitabine in patients with irresectable locally recurrent or metastatic squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: Gemcitabine was given at a dose of 800 mg/m2 on days 1, 8 and 15, plus cisplatin at a dose of 50 mg/m2 on days 1 and 8; every four weeks. RESULTS: Twenty-four patients with a median age of 59 years (range 42-74) were included. All patients were evaluable for toxicity and 22 patients were assessable for response. Eleven cases had advanced recurrent locoregional disease while 13 patients had metastatic disease. One CR (4.7%) and four PR (18%) were observed, for an overall response rate of 22.7% (95% CI: 8%-42%). The main toxicity was hematological: neutropenia grade 3-4 in 28% of the cycles and thrombocytopenia grade 3-4 in 16%. The most significant non-hematological toxicity was asthenia grade 2-3 in 24% of the cycles. CONCLUSIONS: This cisplatin plus gemcitabine combination schedule has a favourable toxicity profile with a discrete activity in patients with locally recurrent or metastatic squamous-cell carcinoma of the head and neck.     

Variations in tumour oxygen tension (pO2) during accelerated radiotherapy of head and neck carcinoma

The study was performed to assess the effect of accelerated radiotherapy on oxygenation of primary tumours and metastatic nodes in patients with advanced head and neck tumours. In 14 patients with head and neck tumour, oxygen tension (pO2) was evaluated in normal tissues and tumours (primary tumour or metastatic neck node) before (0 Gy) and after 2 weeks (32 Gy) of accelerated radiotherapy (70 Gy in 3.5 weeks, with three daily fractions). Radiotherapy was combined with carbogen breathing in 5 patients. pO2 was measured using a polarographic technique. For pooled normal tissues, median pO2 was 38 mmHg before treatment and 46 mmHg after 2 weeks. For tumours, very low values (< 2 mmHg) represented 20% of the recorded values before treatment and 10% after 2 weeks. The relative increase in tumour oxygenation was more pronounced for primary tumours (median pO2 12 mmHg before treatment versus 26 mmHg after 2 weeks, P < 0.05) than for metastatic nodes (respectively, 20 and 27 mmHg P = 0.1). For the 5 patients who breathed carbogen during accelerated radiotherapy, the median pO2 was 44 mmHg at 2 weeks, compared with 13.5 mmHg before treatment (P = 0.05). Very low pO2 values, corresponding to tumour hypoxia, were found in the tumours (primary and metastatic neck nodes) prior to accelerated treatment. During the first 2 weeks of accelerated treatment, an increase in median pO2 was found in nine of the 14 tumours, together with a decrease in the frequency of very low values.     

Final report of a phase II study of chemotherapy with bleomycin, epirubicin, and cisplatin for locally advanced and metastatic/recurrent undifferentiated carcinoma of the nasopharyngeal type

PURPOSE: This article presents an assessment of the combination of bleomycin, epirubicin, and cisplatin as induction chemotherapy before radiotherapy in the treatment of undifferentiated carcinoma of the nasopharyngeal type in patients with recurrent/metastatic disease (group A), and in previously untreated patients with locoregionally advanced disease (UICC-AJCC 87, N2-3, M0) (group B) in terms of toxicity, antitumoral activity, and therapeutic efficacy. PATIENTS AND METHODS: From January 1987 to September 1990, 111 consecutive patients with histologically proven UCNT were treated with six cycles of intravenous cisplatin (100 mg/m2 day 1) epirubicin (80 mg/m2 day 1), and bleomycin (15 mg bolus day 1), followed by 16 mg/m2/day continuous infusion for 5 days, repeated every 21 days for three cycles. Three further cycles without bleomycin were given to 44 patients in group A. In group B (67 patients), only three cycles of the same protocol were given, with a slightly lower dose of epirubicin (70 mg/m2), followed by conventional radiotherapy (70 Gy/7 weeks). RESULTS: Of 44 patients entered in group A, 38 were evaluable for response. We observed 9 (20%) complete responses and 11 (25%) partial responses, for a 45% overall response rate. In 12 patients not previously given chemotherapy, there were 4 complete responses, compared to 5 complete responses in 32 patients previously treated with chemotherapy. Four patients are alive with no evidence of disease after 53+, 60+, 61+, and 72+ months. In group B the overall response rate to chemotherapy was 98% with 42 complete (62%) and 24 partial responses (36%). Three months after the end of radiotherapy, the overall complete response rate was 94% (63 patients). After a median follow-up time of 77 months (range, 53-94), the 4-year overall survival and disease-free survival rates for this group are 66% and 60%, respectively. The median disease-free survival has not been reached at 90 months. CONCLUSION: The results of the BEC combination trial are very encouraging in metastatic and recurrrent UCNT, with durable remissions in this poor-prognosis population. The results in patients with locally advanced disease have motivated prospective phase III testing of the neoadjuvant chemotherapy approach to evaluate its impact on locoregionally advanced disease (> or =N2MO UICC-AJCC 87).     

The impact of initial surgical management on outcome in young patients with differentiated thyroid cancer

BACKGROUND/PURPOSE: It is generally believed that differentiated thyroid cancer (DTC) in young patients has an excellent prognosis. This calls into question the need for more extensive surgical ablation of the thyroid gland with attendant risks of surgical complications. The purpose of this report was to investigate both the incidence of surgical morbidity and the impact of surgery on locoregional recurrence of disease. METHODS: The authors reviewed the clinical course of patients under 22 years of age treated for DTC within Department of Defense hospitals since 1950. Data were available for determination of surgical morbidity in 126 and for outcome in 105. RESULTS: The incidence of postoperative hypocalcemia was 17% and of recurrent laryngeal nerve injury 3%. Factors predictive of morbidity were (1) more extensive thyroid surgery (P = .023), and (2) the presence of gross tumor invasion (P = .022). The incidence of neck recurrence was analyzed among a cohort of 90 patients. A total of 19 (21%) patients had a local recurrence. The median time to recurrence was 24 months. The factor predictive of recurrence was the presence of gross invasion (P = .0001). A strong trend toward locoregional recurrence was found among patients with metastatic disease to more than five cervical nodes (P < .08). The primary operations on the thyroid and regional nodes were not significant predictors of neck recurrence. Among these 19 patients there have been no deaths, but 25% had persistent disease at a mean follow-up of 12.6 years. CONCLUSIONS: The incidence of surgical morbidity does increase with more extensive surgery. Outcome is predicted primarily by the initial extent of disease.     

Herpes simplex type 1 encephalitis in acquired immunodeficiency syndrome

PURPOSE: The judiciousness of open biopsy of lymph node mestastases in the neck is controversial. A retrospective review of treatment results at the University of Florida in patients who underwent excisional biopsy of a solitary metastatic neck node followed by radiotherapy was undertaken to determine whether the approach resulted in increased rates of regional and distant recurrence or wound complications. METHODS AND MATERIALS: Between October 1964 and September 1987, 41 patients were referred for radiotherapy after excisional biopsy of a solitary cervical node containing metastatic squamous cell carcinoma from a known mucosal site (19 patients) or unknown primary (22 patients) in the head and neck. None had known gross residual neck disease. The neck stage (based on N stage before surgery or size of the excised node) was unknown in seven patients, N1 in 15 patients, N2A in 18 patients, and N3A in one patient. All patients received radiotherapy to the neck and two had a planned neck dissection after radiotherapy. Doses to the nodal bed ranged from 5485 cGy to 8100 cGy (median, 6675 cGy). RESULTS: The probability of control of neck disease was 95% at both 5 and 10 years. Five-year probability of disease control above the clavicles was 90%. Distant metastasis occurred in 0 of 36 patients whose disease was controlled above the clavicles vs. 3 of 5 patients who suffered failure above the clavicles. CONCLUSION: Excisional biopsy of a solitary neck node followed by radiotherapy produced excellent regional control and no apparent increased rate of distant metastasis.     

Results of postoperative radiotherapy of cervix carcinoma after radical versus non radical hysterectomy

We studied the outcome of our 68 cervix carcinoma patients treated either with: 1) radical surgery and postoperative 192Ir high-dose rate afterloading brachytherapy or postoperative radiotherapy to the whole pelvis or with 2) standard hysterectomy and postoperative radiotherapy to the whole pelvis. Forty-eight women were treated by radical hysterectomy from 1988 to 1992 and--due to risk factors--by postoperative radiotherapy (Group 1), 20 other patients (Group 2) pretreated with standard hysterectomy were admitted to the university hospital for postoperative radiotherapy of the whole pelvis. Postoperative radiotherapy consisted of 39.6 Gy total dose using the box technique, plus two afterloading applications with a single dose of 7.5 Gy and 6 Gy external beam therapy to the pelvic lymph nodes sparing the midline. Comparing the Kaplan-Meier plots of both groups, the tumor related survival curve, the locoregional control and the rates of metastatic disease were nearly identical. But in the analysis of special subgroups, patients with positive lymph nodes after standard hysterectomy and postoperative radiotherapy had a worse prognosis (75% three years' survival rate) than patients after radical surgery (86% three years' survival rate). Lymphangiosis was a negative prognostic factor for the patients pretreated with standard hysterectomy (60% versus 80% three years' survival rate), but not for patients after radical surgery (80% three years' survival rate), despite the same radiotherapy in both groups. CONCLUSION: Standard hysterectomy fails to be an adequate treatment for early cervix carcinoma because moderately dosed postoperative radiotherapy cannot achieve complete locoregional control in all cases of positive lymph nodes or invasion of lymph vessels. However, based on the empirical results of many authors and our own results, postoperative radiotherapy is further indicated in high risk cases of cervix carcinoma after radical surgery.     

Child abuse and neglect investigative process

To clarify the role of postoperative radiotherapy for adenoid cystic carcinoma of the tracheobronchial system (ACC), we analyzed patients treated at the National Cancer Center Hospital, Tokyo. Seven patients with ACC were treated with resective surgery and postoperative radiotherapy from 1962-1990. None of the primary lesions was completely surgically resected. Postoperative irradiation was delivered by standard fractionation at a dose range of 49.2-72 Gy. Four of seven patients lived more than 5 years, up to 21 years, without local recurrence. In contrast, three other patients who showed recurrence within 2 years died of disease before 5 years. Three of four patients who received postoperative irradiation of 60 Gy or more attained local control. One of three patients who received less than 60 Gy failed locally. A high dose of postoperative radiotherapy for patients with a positive surgical margin of ACC seems to improve local control and result in long-term survival.     

The type of local treatment conditions the prognosis in patients with nonmetastatic Ewing's sarcoma of the extremities treated with adjuvant chemotherapy

The results obtained in 172 cases of non metastatic Ewing's sarcoma of the extremities are reported. The patients were advised to undergo surgical treatment, followed by radiotherapy (40-45 Gy) in case of inadequate surgical margins. 48 patients who refused surgical treatment, were locally treated with radiotherapy alone (50-65 Gy). With a mean follow-up of 8 years (R. 3-15) 101 patients (58.7%) are free of disease and 68 relapsed with metastases and/or local recurrence. A radio-induced bone sarcoma developed in two patients, one patient died of ADM cardiomyopathy. No differences in terms of risk factors were observed between patients who were or were not treated with surgery. A better DFS was observed in the patients treated with surgery (66.9%) in comparison with those treated with radiotherapy alone. The higher percentage of local recurrences observed in patients treated with radiotherapy alone seems to be responsible for the worse prognosis observed in these patients. The authors' conclusion is that the local control in patients with non metastatic Ewing's sarcoma should always be achieved by means of surgery.     

The epidemiology of Langerhans cell histiocytosis

PURPOSE: During recent years, more intensified systemic and local treatment regimens have increased the 5-year survival figures in localized Ewing's sarcoma to more than 60%. There is, however, concern about the risk of second malignancies (SM) in long-term survivors. We have analyzed the second malignancies in patients treated in the German Ewing's Sarcoma Studies CESS 81 and CESS 86. MATERIALS AND METHODS: From January 1981 through June 1991, 674 patients were registered in the two sequential multicentric Ewing's sarcoma trials CESS 81 (recruitment period 1981-1985) and CESS 86 (1986-1991). The systemic treatment in both studies consisted of a four-drug-regimen (VACA = vincristine, actinomycin D, cyclophosphamide, and adriamycin; or VAIA = vincristine, actinomycin D, ifosfamide, and adriamycin) and a total number of four courses, each lasting nine weeks, was recommended by the protocol. Local therapy in curative patients was either complete surgery (n = 162), surgery plus postoperative radiotherapy with 36-46Gy (n = 274), or definitive radiotherapy with 46-60Gy (n = 212). The median follow-up at the time of this analysis was 5.1 years, the maximum follow-up 16.5 years. RESULTS: The overall survival of all patients including metastatic patients was 55% after 5 years, 48% after 10 years, and 37% after 15 years. Eight out of 674 patients (1.2%) developed a SM. Five of these were acute myelogenic leukemias (n = 4) or MDS (n = 1), and three were sarcomas. The interval between diagnosis of Ewing's sarcoma and the diagnosis of the SM was 17-78 months for the four AMLs, 96 months for the MDS and 82-136 months for the three sarcomas. The cumulative risk of an SM was 0.7% after 5 years, 2.9% after 10 years, and 4.7% after 15 years. Out of five patients with AML/MDS, three died of rapid AML-progression, and two are living with disease. Local therapy (surgery vs. surgery plus postoperative irradiation vs. definitive radiotherapy) had no impact on the frequency of AML/MDS, but local therapy did influence the risk of secondary sarcomas. All three patients with secondary sarcomas had received radiotherapy; however, all three sarcomas were salvaged by subsequent treatment and are in clinical remission with a follow-up of 1 month, 4.3 years, and 7.5 years after the diagnosis of the secondary sarcoma. Thus far, SM contributed to less than 1 % (3/328) of all deaths in the CESS-studies. CONCLUSIONS: The risk of leukemia after treatment for Ewing's sarcoma is probably in the range of 2%. The risk of solid tumors also seems to be low within the first 10 years after treatment and remains in the range of 5 % after 15 years. In the CESS-studies, less than 1% of all deaths within the first 10 years after diagnosis were caused by SM. Effective salvage therapy for secondary sarcomas is feasible.     

Clinically significant, isolated metastatic disease to the thyroid gland

Despite being second only to the adrenal glands in terms of relative vascular perfusion, the thyroid gland is a rare site of metastatic disease; but when thyroid metastases occur, long-term survival has been reported to be dismal. To determine the incidence and management of isolated, metastatic disease to the thyroid, we reviewed our clinical experience. Between June 1986 and August 1994 ten patients underwent thyroidectomy for isolated, metastatic disease of nonthyroidal origin (mean +/- SD age 58 +/- 6 years, 30% female). The primary tumors were renal cell carcinomas (RCCs) (n = 5), esophageal adenocarcinoma (n = 1), pulmonary squamous cell carcinoma (n = 1), gastric leiomyosarcoma (n = 1), lingual squamous cell carcinoma (n = 1), and parotid gland carcinoma (n = 1). Three patients underwent preoperative fine-needle aspiration (FNA), all of which were suggestive of metastatic disease. The mean time from resection of the primary tumor to thyroid metastases was 3.5 +/- 6.0 years (range 0-19.5 years). Total thyroidectomy (n = 5) or lobectomy (n = 5) was performed without morbidity or mortality. After a median follow-up of 5.2 years six patients are alive and two are free of disease. Moreover, no patients have had recurrent disease in the neck. Thus carcinomas metastatic to the thyroid represent a rare cause of clinically significant thyroid disease, with RCCs comprising 50%. Most thyroid metastases (80%) present within 3 years of primary tumor resection, but with RCC they can occur as late as 19 years. The diagnosis of metastatic disease should be suspected in patients with even a remote history of cancer, especially RCC, and an FNA revealing clear cell or spindle cell carcinoma. Contrary to previous reports, long-term survival can be achieved after resection of the metastatic tumor. Furthermore, thyroidectomy may also palliate/prevent the potential morbidity of tumor recurrence in the neck.     

Results and prognostic factors in the retreatment of locally recurrent nasopharyngeal carcinoma

PURPOSE: To review the results and evaluate the prognostic factors in the retreatment of locally recurrent nasopharyngeal carcinoma. METHODS AND MATERIALS: We reviewed the records of 74 patients with locally recurrent nasopharyngeal carcinoma treated at the University of California, San Francisco between 1957 and 1995. The histologic types included squamous cell carcinoma in 6 (8.1%), nonkeratinizing carcinoma in 48 (64.9%), and undifferentiated carcinoma in 20 (27%) cases. The site of recurrence was in the primary in 46 (62.2%), in the neck nodes in 20 (27%), and in both sites in 8 (10.8%) patients. The recurrent disease was Stage I in 10 (13.5%), Stage II in 16 (21.6%), Stage III in 20 (27%), and Stage IV in 28 (37.9%) patients. Thirty-seven (50%) patients developed recurrence within 2 years and 58 (78.4%) within 5 years after initial treatment. Radiotherapeutic techniques used in the retreatment of primary recurrence consisted of external beam radiotherapy (EBRT), intracavitary brachytherapy, heavy-charged particle beam, and gamma knife, alone or in combination. Reirradiation doses ranged from 18 to 108 Gy, with a median dose of 60 Gy. Treatment of recurrent neck nodes consisted of radical neck dissection (RND) +/- intraoperative radiotherapy (IORT), or EBRT +/- hyperthermia, or chemotherapy +/- hyperthermia. Chemotherapy was used in 22 (30%) patients. Median follow-up was 20 months (range: 2 to 308 months). RESULTS: The 3-, 5-, and 10-year actuarial overall survival following retreatment were 49, 37, 18%, respectively. Thirty-six patients (49%) were free of further local-regional recurrence after retreatment. The 3-, 5-, and 10-year local-regional progression-free rates were 52, 40, and 38%, respectively. On univariate analysis, histologic type (p < 0.0001), interval to recurrence (p = 0.034), and treatment modality for early-stage disease (p = 0.01) were significant prognostic factors for overall survival, with age being marginally significant (p = 0.053). For local-regional progression-free rate, only histology was significant (p = 0.035). On multivariate analysis, age (p = 0.026), histology (p = 0.015), and interval to recurrence (p = 0.030) were significant for overall survival, and only histology (p = 0.002) and presence of complications (p = 0.016) were significant for local-regional progression-free rate. Of the 64 reirradiated patients, late complications were documented in 29 (45%) patients. The late complications were permanent in 21 (33%) and severe in 15 (23%) patients. CONCLUSION: Retreatment using radiotherapy alone or in combination with other treatment modalities can achieve long-term local-regional control and survival in a substantial proportion of patients with locally recurrent nasopharyngeal carcinoma. Age, histology, and interval to recurrence were independent prognostic factors for overall survival, but only histology and presence of complications were significant for local-regional progression-free rate.     

Primary osteogenic sarcoma of the breast: a clinicopathologic analysis of 50 cases

Extraskeletal osteosarcomas are rare. Few primary mammary osteosarcomas have been reported; many of these have been described in association with a biphasic tumor. Fifty pure osteosarcomas of the breast, diagnosed between 1957 and 1995, were reviewed after excluding those of biphasic origin. The absence of epithelial differentiation was confirmed using a panel of immunohistochemical markers in 32 cases and using ultrastructural evaluation in an additional four cases. Tumors occurred in 49 women and one man; age ranged from 27 to 89 years (median, 64.5 years). One patient received radiotherapy for ipsilateral breast carcinoma 9 years before presentation. Patients were treated by excisional biopsy (n = 13), tylectomy (n = 5) or mastectomy (n = 32). All axillary nodes, dissected in 20 patients, were free of tumor. One patient had extramammary spread at diagnosis. The neoplasms were 1.4 cm to 13.0 cm (mean, 4.6 cm), and 60% were grossly circumscribed. Tumors were classified as fibroblastic (n = 28), osteoclastic (n = 14), or osteoblastic (n = 8). Of 39 patients with available follow-up information, locally recurrent (n = 11) and metastatic (n = 15) disease developed in 23 (59%) at a mean of 10.5 and 14.5 months from diagnosis. Eight (73%) patients in whom local recurrence developed were treated with excisional biopsy or tylectomy; of these, seven had a positive margin. Sixteen (41%) patients died of disease at a mean of 17.1 months, within 20 months of onset of metastases, most commonly to the lung. Mammary osteosarcomas are aggressive tumors with a propensity for blood-borne rather than lymphatic spread. Total excision without axillary dissection is advised.     

Free revascularized jejunal loop repair following total pharyngolaryngectomy for carcinoma of the hypopharynx: report of 90 patients

Ninety patients with carcinoma of the hypopharynx underwent pharyngolaryngectomy and reconstruction with a jejunal free autograft. Fifty-five patients had primary surgery and 35 salvage surgery for recurrence after radiotherapy. Following primary surgery 28 patients had postoperative radiotherapy and 27 did not. Complications occurred in 51 per cent of patients, the most common being necrosis of the jejunal graft (19 per cent); 12 per cent developed significant stenosis and 4 per cent died in the perioperative period. Eleven per cent of patients developed a fistula. The total number of complications diminished as the experience of the unit increased. Median follow-up was 4.9 years. Of patients treated with primary surgery, 48 per cent developed primary site recurrence (at 3 years) and 53 per cent neck node recurrence (at 5 years). The tumour-specific 5-year survival rate for all patients was 42 per cent. Following primary surgery 28 per cent survived for 5 years and after salvage surgery the rate was 59 per cent. Positive resection margins and extensive neck disease adversely affected survival (P = 0.02 and P = 0.001 respectively). The free revascularized jejunal graft is a safe and predictable method of repair following total pharyngolaryngectomy.     

Chemotherapy with methotrexate, vinblastine, epirubicin and carboplatin (Carbo-MVE) in transitional cell urothelial cancer. A Hellenic Co-Operative Oncology Group study

OBJECTIVES: We conducted a phase II study in order to assess the efficacy and toxicity of Carbo-MVE (carboplatin 250 mg/m2 i.v. day 1, methotrexate 25 mg/m2 i.v. days 1, 15 and 22, vinblastine 2.5 mg/m2 i.v. days 1, 15 and 22 and epirubicin 25 mg/m2 day 1). The regimen ws to be repeated every 28 days. METHODS: Forty-six patients with transitional cell carcinoma of the bladder entered the study. Patients with metastatic disease were treated for 6 cycles, while patients with locally advanced or locoregional disease had 4 cycles of induction chemotherapy followed by cystectomy or radiotherapy. RESULTS: Toxicity was generally mild and treatment well tolerated. The overall response rate was 54.4%, with 26% complete and 28.3% partial response rates. The median survival was 17.5 months with the complete responders to live significantly longer (64.82 months) than those who had a partial response (20.5 months), stable disease (15 months) or progressive disease (8.5 months). Survival was also significantly longer in patients with good performance status as well as in patients with locally advanced or locoregional disease. Finally, patients who had cystectomy as definitive treatment survived significantly longer (32 months) than those who had been irradiated (16 months). CONCLUSIONS: The Carbo-MVE regimen appears to be an effective and well-tolerated treatment in patients with transitional cell carcinoma of the bladder.     

Mammalian glial cells in culture synthesize acetylcholine

OBJECTIVE: To evaluate the postoperative outcome and long-term results of patients who underwent iterative and extended pulmonary resection leading to completion pneumonectomy for pulmonary metastases. METHODS: From January 1985 to December 1995, 12 patients (mean age 45 years) underwent completion pneumonectomy for pulmonary metastases. These patients represent 1.5% of all pulmonary metastases operated on. There were 5 sarcoma and 7 carcinoma patients. Before completion pneumonectomy, 8 patients had only one pulmonary resection (wedge resection, 2; segmentectomy, 2; lobectomy, 4), 3 patients had two operations and finally, 1 patient had multiple bilateral wedge resections and 1 lobectomy. The median interval time between the last pulmonary resection and completion pneumonectomy was 13.5 months (range 1-24 months). RESULTS: There were 10 left and two right completion pneumonectomies. Three patients had an extended resection (1 carina; 1 chest wall; 1 pleuropneumonectomy). Intrapericardial dissection was used in 3 patients. Two patients died within 30 days of the operation: 1 died of postoperative complications (8.3%) whereas the other died of rapidly evolving metastatic disease. The remaining 10 patients had an uneventful postoperative course. Only 1 patient is still alive and free of disease 69 months after completion pneumonectomy. One patient is alive with disease, another was lost to follow-up; 9 patients died of metastatic disease. The median survival time after completion pneumonectomy was 6 months (range 0-69 months). The estimated 5-year probability of survival was 10% (95% CI: 2-40%). CONCLUSIONS: Indications for both iterative and extended pulmonary resection for PM may be discussed only in highly young selected patients; the extremely poor outcome of our subgroup of patients should lead to even more restrictive indications of CP for pulmonary metastatic disease.     

Serum creatine kinase in fasciocutaneous and musculocutaneous flap surgery

BACKGROUND: Stage III and IV squamous cell cancers of the head and neck are often unresectable at presentation and are associated with poor disease-free and overall survival rates. A phase II study using concurrent cisplatin and radiotherapy in advanced head and neck cancer indicated impressive local-regional control and survival with organ preservation. METHODS: A multicentered phase II study was undertaken consisting of 1.8 Gy fraction radiotherapy for 2 weeks followed by 1.2 Gy BID hyperfractionation to 46.8 Gy. Continuous infusion cisplatin 20 mg/m2 was given on days 1 through 4 and 22 through 25. Biopsy of the primary tumor was done at this point, and patients with clinical and pathologic complete response continued with hyperfractionated radiotherapy to 75.6 Gy plus simultaneous carboplatin 25 mg/m2 BID for 12 consecutive days. Residual disease at 46.8 Gy required curative surgery. RESULTS: Seventy-four patients entered the study, and 73 completed their treatment. Twenty were stage III and 54 were stage IV. Fifty patients had involved regional lymph nodes. Treatment was well tolerated with only one grade IV hematologic toxicity. At 46.8 Gy, biopsy revealed a complete response in 75% of the primary sites and 47% of the nodes. Only 12 patients required resection of the primary lesion. At 4 years (median follow-up is 26 months), 29 patients have recurred. CONCLUSIONS: Accelerated hyperfractionated radiotherapy with concurrent chemotherapy in stage III and IV head and neck cancer yields excellent local-regional control with organ preservation. This protocol is intensive, and some patients have distant failures.