Postoperative prognostic factors for carcinoma of the thoracic esophagus

To evaluate significant postoperative prognostic factors for esophageal carcinoma, clinicopathological findings and several markers for biological malignant potential were studied, including cell nuclear DNA contents, EGF receptor, p53 protein, MMP-2, Ki-67 positive cell rate, and tumors infiltrating Leu 7 cells. The subjects of this study were 96 patients with thoracic esophageal carcinoma, who underwent radical surgery with extended lymphadenectomy. In the pathological findings, the postoperative survival rate significantly correlated with depth of invasion (pT1(-2) vs. pT3, p = 0.003), lymph node involvement (pNo vs. pN1, p = 0.0002), vascular invasion (-vs. +, p = 0.0003), stage (pSt. 1-2A vs. 3, p = 0.0018), and the number of node involvements (1-3 vs. more than 4, p = 0.025). Analyzing the markers for the malignancy, a significant difference in postoperative mortality due to the relapse was recognized with p value of 0.0009 between Ki-67 positive (under 1%) and Ki-67 negative (over 1%) tumor. Ki-67 positive tumor significantly correlated with the mortality in both cases with pNo (p = 0.024) and pN1 (p = 0.020). Low-grade tumor infiltrating Leu 7 cells significantly correlated with the mortality (Grade 1+ vs. 2+, p = 0.013; Grade 1+ vs. 3+, p = 0.008). These results suggest that Ki-67 study is a useful prognostic factor after radical surgery for thoracic esophageal carcinoma.     

Late follow-up results of operative ankle arthroscopy in patients under local anaesthesia

The clinical diagnoses of nodal status (N) and tumor invasion (T) were performed intraoperatively during 1499 consecutive operations for gastric carcinoma and compared with subsequent pathologic diagnoses. An accurate macroscopic diagnosis of N stage was difficult; overall accuracy was only 56.6%. Intraoperative assessment of T stage (particularly of serosal invasion) was correct for 93.2% of early stages of the disease with invasion confined to the mucosa or submucosa (pT1) when the pathologist assessed the T stage in the resected specimen, for 95.6% of advanced tumors invading the serosa (pT3), but for tumors of an intermediate stage with invasion involving the muscularis propria or the subserosa (pT2) in only 41.9% of cases. Macroscopic overestimation occurred in 58.1% of cases with pT2 tumors, which were characterized by carcinomas in the upper third of the stomach, tumors larger than 5 cm, carcinomas of the ulcerating type, differentiated adenocarcinomas, tumors invading the subserosa, and those accompanied by lymph node metastasis or liver metastasis. The overestimated group had a significantly poorer prognosis than the correctly assessed cases (P < 0.05). Since multivariate logistic regression analysis showed that the significant risk factor related to the inaccurate intraoperative assessment of T stage was tumor size, the error in diagnosis may correlate with a greater degree of tumor spread. Surgeons should decide their therapeutic approach at the time of surgery on the basis of their intraoperative assessment of tumor spread. We recommend extensive surgery followed by adequate chemotherapy when serosal invasion is suspected at surgery.     

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.     

Combined-modality therapy for squamous carcinoma of the buccal mucosa: treatment results and prognostic factors

BACKGROUND: Reports on locoregional control and survival of squamous cell carcinoma of buccal mucosa are scarce in literature. In this study, a single institutions's experience of combined surgery and postoperative radiotherapy (RT) for buccal mucosal malignancy with favorable results was analyzed and presented. The prognostic factors on locoregional control were also discussed. METHODS: From January 1988 to July 1994, 57 patients with squamous cell carcinoma of buccal mucosa treated by surgery and RT were reviewed. The distributions according to American Joint Committee on Cancer (AJCC) staging were: stage II, 6; stage III, 21; and stage IV, 30 patients. Total dose of RT at the buccal area ranged from 45 Gy to 68.4 Gy, median 61.2 Gy. Tumor-related factors (AJCC stage, T stage, histologic grading, pathologic tumor invasion to skin of cheek, adjacent bony structures, and regional lymph nodes) and treatment-related factors (surgical margin, radiation dose, and the time interval between operation and RT) were analyzed to determine their influence on locoregional control. RESULTS: Three-year actuarial locoregional control rate, overall survival rate, and disease-specific survival rates were 64%, 55%, and 62%, respectively. Ten of these 22 patients (45%) with recurrent tumors were reoperated, but only 2 patients were successfully salvaged. Positive surgical margin and tumor invasion to skin of cheek were significantly poor prognostic factors on locoregional control by univariate analysis. In multivariate analysis, tumor invasion to skin of cheek was the only prognostic factor (p = .0014). CONCLUSIONS: Locoregional failure was the major cause of death for squamous buccal mucosa cancers managed with surgery and RT. Few recurrences could be detected early and successfully salvaged. Skin of cheek involvement is an important prognostic factor for buccal mucosa cancers.     

Treatment of the regional lymph nodes in squamous carcinoma of the penis

OBJECTIVES: We evaluated the management of the regional lymph nodes to determine the appropriate treatment for carcinoma of the penis. METHODS: The records of 36 patients with carcinoma of the penis were reviewed. Lymphadenectomy was performed in 18 patients, 17 were managed conservatively (watchful waiting) and 1 patient had a biopsy and received radiotherapy. RESULTS: Positive nodes were found in 2 of 2 pT4, 2 of 3 pT3, 8 of 13 pT2 and 2 of 12 pT1 patients submitted to lymphadenectomy. Concerning the histological grade, positive nodes were found in all of the 4 G3, 5 of 12 G2 and 3 of 20 G1 patients. The survival rate was 100% for the patients with negative lymph nodes (pNO = 6) or a single positive inguinal lymph node (pN1 = 5). A correlation was found between the T and the histological grade and the likelihood of lymph node invasion. CONCLUSIONS: The T and the histological grade of the primary lesion must be considered when deciding the approach in the management of the lymph nodes as unnecessary lymphadenectomy can be avoided and those at high risk of lymph node invasion can be treated radically and timely.     

Combined surgery and postoperative radiotherapy for carcinoma of the base of radiotherapy for carcinoma of the base of tongue: analysis of treatment outcome and prognostic value of margin status

BACKGROUND: Choice of treatment for base of tongue carcinoma is controversial, with options including surgery alone, radiotherapy alone, or multimodality treatment. Given the highly aggressive nature of these tumors, it has been our institutional policy to manage this disease with combined partial glossectomy (with attempt to avoid laryngectomy if possible) with planned postoperative radiotherapy (RT). We reported on our institutional experience with this approach. METHODS: A retrospective review of the charts of 17 patients with primary base of tongue squamous cell carcinoma treated with surgery and postoperative RT was performed. Patients treated with chemotherapy as part of their management were excluded. All patients underwent partial, hemi-, or subtotal glossectomy; 15/17 patients underwent ipsilateral radical or modified radical neck dissection. All patients received comprehensive postoperative RT (median dose 6000 cGy; range 5040-6920 cGy). Stage distribution was as follows: stage I, 2; stage II, 3; stage III, 2; stage IV, 10. Positive margins for invasive carcinoma were found in 9/17 patients. Median follow-up of surviving patients is 46 months; median follow-up for all patients is 31 months. RESULTS: For the entire group of patients, the actuarial 3-year local-regional control rate was 68%. The actuarial 3-year overall survival rate was 46%. The local-regional control rate was 83% for patients with stage I-III disease versus 50% for stage IV disease. There were no local failures among eight patients with negative margins (local control 100%) compared with an actuarial local control rate of 36% among patients with positive margins (p = .03). Survival, disease-specific survival, and locoregional control were also highly correlated with margin status (p = .003). Late major complications included 5/17 patients requiring permanent G-tubes and/or tracheostomy to prevent aspiration. CONCLUSIONS: Surgery plus postoperative RT is an intensive treatment for carcinoma of the base of tongue which offers high locoregional control in patients in whom negative margins are achieved. Positive margins indicate a high risk of locoregional and systemic failure, and these patients should be considered for innovative clinical trials after surgery.     

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.     

Comprehensive analysis of results of surgical treatment of oral tongue carcinoma in Hong Kong

OBJECTIVE: To evaluate the results of primary surgical treatment of carcinoma of oral tongue in Hong Kong. METHODS: Patients who had undergone primary surgical treatment of oral tongue carcinoma in Queen Mary Hospital were reviewed. RESULTS: There were 112 patients in this study. The first sites of tumor recurrence were 10 (9%) local, 25 (22%) nodal, 3 (3%) locoregional, 5 (5%) distant, 1 (1%) local and distant, 3 (3%) nodal and distant, and 1 (1%) neck extranodal site. Of the 63 T1-2 N0 M0 patients, the regional recurrence rate was 9% for elective neck dissection compared with 47% for "watchful waiting" (Chi-square test, P = 0.0008). The regional recurrence related mortality was 3% for elective neck dissection compared with 23% for "watchful waiting" (Fisher's test, P = 0.02). The 5-year actuarial survival rate was 86% for elective neck dissection compared with 55% for "watchful waiting" (Wilcoxon, P = 0.01). CONCLUSIONS: Local and regional recurrences were the main sites of treatment failure. Elective neck dissection has significant benefits in the reduction of regional failure and improvement of survival. Elective selective I-III neck dissection have to be considered in patients with stage I and stage II oral tongue carcinoma.     

Effect of anordrin on the development of mouse preimplantation embryos in vitro

The aim of this study was to establish the feasibility, evaluate the response rate, and assess the impact on local control and survival in locally advanced (bulky nodal) squamous cell carcinoma of the head and neck (SCCHN) patients treated with neoadjuvant chemotherapy consisting of cisplatin followed by continuous infusion of vindesine and fluorouracil with intermittent i.v. folinic acid. Eligibility criteria included histologically proven SCCHN, previously untreated locally advanced stage III-IV with measurable or evaluable disease, no distant metastases, an Eastern Cooperative Oncology Group (ECOG) performance status of less than 2, patient age of at least 18 years, and adequate bone marrow, hepatic, and renal functions. The protocol consisted of three cycles (day 1, day 21, day 42) of Cisplatin (CDDP) 100 mg/m2/day i.v. on day 1 immediately followed by 4 days (96 h) of continuous infusion of vindesine 0.8 mg/m2/day and 5-fluorouracil (5-FU) 600-700 mg/m2/day with folinic acid 150 mg/m2 i.v. every 6 h x 16 doses before locoregional treatment with radiotherapy preceded by radical surgery when appropriate. Twenty-nine patients were enrolled in this study, and 28 were evaluable for activity; an objective response rate of 55% (four complete responses, 12 partial responses) was achieved. Leukopenia and mucositis were the most frequent and severe toxicities. The addition of vindesine did not improve the activity of the CDDP-FU-folinic acid combination, but this may be partly because of the particularly poor prognosis of the present patient population, with 75% of stage IV bulky nodal disease (N2c-N3).     

Induction chemotherapy is associated with an increase in the incidence of locoregional recurrence in patients with carcinoma of the oral cavity: results from a single institution

BACKGROUND: This study was conducted to determine long term survival rates and the pattern of failure in patients with carcinoma of the oral cavity treated with induction chemotherapy or preoperative radiotherapy followed by surgery. METHODS: A retrospective analysis was performed of 141 eligible patients with Stage II-IV International Union Against Cancer (UICC) staging system squamous cell carcinoma of the oral cavity at the study department between 1985 and 1994. These patients received one of three treatments: surgery with or without peplomycin chemotherapy (Group A; n = 49); preoperative radiotherapy with or without concomitant peplomycin chemotherapy followed by surgery (Group B; n = 59); and induction chemotherapy followed by surgery (Group C; n = 33). Induction chemotherapy was comprised of two cycles of cisplatin, vincristine, peplomycin, with or without mitomycin C. RESULTS: When all 141 patients were analyzed, there was no significant difference in overall survival or disease free survival. However, a statistically significant increase in the incidence of neck recurrence in Group C was observed compared with Group A (P = 0.002). Within 79 patients with N0 disease, a statistically significant disadvantage was detected for Group C in terms of disease free survival compared with Group A (P = 0.038). In patients with Stage II disease (50 patients), there was a significant difference in disease free survival, with Group C inferior to both Group A (P = 0.04) and Group B (P = 0.066). CONCLUSIONS: Induction chemotherapy was associated with a significant increase in regional failure for patients with carcinoma of the oral cavity with N0 disease and those with Stage II disease.     

Carcinoma of the tonsillar fossa: prognostic factors and long-term therapy outcome

PURPOSE: To identify prognostic parameters and evaluate the therapeutic outcomes for patients with carcinoma of the tonsillar fossa treated with three treatment modalities. METHODS AND MATERIALS: The results of therapy are reported in 384 patients with histologically proven epidermoid carcinoma of the tonsillar fossa; 154 were treated with irradiation alone (55-70 Gy), 144 with preoperative radiation therapy (20-40 Gy), and 86 with postoperative irradiation (50-60 Gy). The operation in all but four patients in the last two groups consisted of an en bloc radical tonsillectomy with ipsilateral lymph node dissection. RESULTS: Treatment modality and total irradiation doses had no impact on survival. Actuarial 10-year disease-free survival rates were 65% for patients with T1 tumors, 60% for T2, 60% for T3, and 30% for T4 disease. Patients with no cervical lymphadenopathy or with a small metastatic lymph node (N1) had better disease-free survival (60% and 70%, respectively) at 5 years than those with large or fixed lymph nodes (30%). Primary tumor recurrence (local, marginal) rates in the T1, T2, and T3 groups were 20-25% in patients treated with irradiation and surgery and 31% for those treated with irradiation alone (difference not statistically significant). In patients with T4 disease treated with surgery and postoperative irradiation, the local failure rate was 32% compared with 86% with low-dose preoperative irradiation and 47% with irradiation alone (p = 0.03). The overall recurrence rates in the neck were 10% for N0 patients, 25% for N1 and N2, and 35-40% for patients with N3 cervical lymph nodes, without significant differences among the various treatment groups. The incidence of contralateral neck recurrences was 8% with the various treatment modalities. On multivariate analysis the only significant factors for local tumor control and disease-free survival were T and N stage (p = 0.04-0.001). Fatal complications were noted in 7 of 144 (5%) patients treated with preoperative irradiation and surgery, 2 of 86 (2%) of those receiving postoperative irradiation, and 2 of 154 (1.3%) patients treated with radiation therapy alone. Other moderate or severe nonfatal sequelae were noted in 30% of the patients treated with preoperative irradiation and surgery, in 53% treated with postoperative irradiation, and in 19% receiving radiation therapy alone. CONCLUSION: Primary tumor and neck node stage are the only significant prognostic factors influencing locoregional tumor control and disease-free survival. Treatment modality had no significant impact on outcome. Radiation therapy remains the treatment of choice for patients with stage T1-T2 carcinoma of the tonsillar fossa. In patients with T3-T4 tumors and good general condition, combination surgery and postoperative irradiation offers better tumor control than single-modality and preoperative irradiation procedures, but with greater morbidity.     

Comparison of radiotherapy and surgical results of early stage glottic cancer: a retrospective analysis

From March 1977 to October 1989, 85 patients with early stage glottic cancer were treated with either radiotherapy or surgery at Chang Gung Memorial Hospital (CGMH). Patients were excluded from the analysis of local control if they died or remained disease-free with a follow-up period of less than two years. Of the 26 patients treated with definitive radiotherapy, initial control of the primary lesions was achieved in 100% of stage T1s, 76% of T1, and 57% of T2 patients. Surgical salvage of radiation failure was achieved in 83% of the patients, giving the ultimate local control of 100% for T1s, 94% for T1, 86% for T2 patients. Of the 44 patients treated with definitive surgery, initial control of the primary lesions was achieved in 100% for T1s, 95% for T1, and 78% for T2 patients. Salvage of the surgical failure was 50%, giving the ultimate control in this group of 100% for T1s, 95% for T1, 83% for T2. There was no difference in either initial or ultimate control of T1 and T2 lesions between patients treated with primary radiotherapy and primary surgery. Voice preservation rates were 73% and 34% in the radiotherapy and surgery group, respectively. When divided into two groups according to the times they were being treated, we found that surgery preserved a comparable number of larynges as radiotherapy did after 1988 (60% vs 77%, p = 0.33). It is concluded that radiotherapy and surgery could achieve the same good local control results and long-term survival and comparable functional results of early stage glottic cancer, if conservative surgery is carefully selected for each patient.(ABSTRACT TRUNCATED AT 250 WORDS)     

Calbistrins, novel antifungal agents produced by Penicillium restrictum. I. Production, taxonomy of the producing organism and biological activity

Over a 14-year period, from 1971 to 1985, there were 15 patients referred to the Princess Margaret Hospital in Toronto for postoperative radiotherapy to the cervical lymph nodes following radical neck surgery for metastatic cancer. An intensive investigation failed to yield a primary site in any patient. All of the patients had extensive neck disease with significant indications for postoperative radiotherapy (massive neck nodes, invasion of extra nodal structures or fixation to unresectable adjacent structures). Of this highly selected group of patients with advanced neck disease: 4/15 (27%) died within one year of uncontrolled local disease, a further 2/15 (13%) died within four years of metastatic/recurrent disease, 6/15 (33%) died of intercurrent disease and 3/15 (20%) were alive with at least four years follow-up. Although all patients presented with advanced disease, survival and significant palliation was possible in this select group of patients.     

Determinative factors of biochemical cure after primary and reoperative surgery for sporadic medullary thyroid carcinoma

Normalization of calcitonin levels after surgery has been regarded as the most powerful prognostic factor for medullary thyroid carcinoma (MTC). Although the prognosis of patients with persistent hypercalcitoninemia may be acceptable, the biochemical cure rate can be improved by new microdissection techniques. This raises certain questions: Can extension of locoregional lymphadenectomy (LA) further improve biochemical cure and survival after primary or reoperative MTC surgery? Which factors concerning TNM categories are associated with the possibility of postoperative normalization of calcitonin levels? This study included 64 patients with sporadic MTC operated on from 1986 to 1997. Altogether 27 patients underwent primary surgery, and 37 patients were reoperated, performing a microdissection of all four locoregional compartments (four-compartment lymphadenectomy, or 4CLA). For primary MTC the biochemical cure rate was 100% in node-negative patients and 33% in node-positive patients; the latter could be improved to 45% after 4CLA. In contrast to reoperative MTC, the rate of lymph node metastases (LNMs) with primary MTC correlated with the pT category (pT1 33%, pT2 53%, pT3 100%, pT4 100%) but not with age or sex. Again in contrast to reoperative MTC, mediastinal LNMs in primary MTC were present only in patients with a pT4 tumor. At reoperation, 4CLA was able to cure 22% of node-positive patients, 28% without proved distant metastases. No patient with extrathyroidal tumor involvement or distant metastases was biochemically cured after either primary or reoperative surgery. For all node-positive MTC patients, in addition to cervicocentral LA at least a bilateral cervicolateral LA is recommended. Transsternal mediastinal lymph node dissection is indicated in patients with LNMs in the cervicomediastinal transition, facilitating biochemical cure in up to 45% after the first operation and 22% after reoperative surgery of sporadic MTC.     

Expression and function of a recombinant endothelial nitric oxide synthase gene in porcine coronary arteries

PURPOSE: To evaluate the influence of prognostic factors in postoperative radiotherapy of NSCLC with special emphasis on the time interval between surgery and start of radiotherapy. METHODS AND MATERIALS: Between January 1976 and December 1993, 340 cases were treated and retrospectively analyzed meeting the following criteria: complete follow-up; complete staging information including pathological confirmation of resection status; maximum interval between surgery (SX) and radiotherapy (RT) of 12 weeks (median 36 days, range 18 to 84 days); minimum dose of 50 Gy (R0), and maximum dose of 70 Gy (R2). Two hundred thirty patients (68%) had N2 disease; 228 patients were completely resected (R0). One hundred six (31%) had adenocarcinoma, 172 (51%) squamous cell carcinoma. RESULTS: In univariate analysis, Karnofsky performance status (90+ >60-80%; p = 0.019 log rank), resection status stratified for nodal disease (R+ 相似文献   

Selective approach to the treatment of oesophageal cancer

Between September 1985 and December 1994, 322 patients with oesophageal cancer were treated. Of the 190 patients who underwent operation, 173 had an oesophageal resection; in 124 this was performed as an abdominothoracic resection and in 49 by the transhiatal approach. The assessment of radicality after histological examination revealed a curative (R0) resection in 121 patients (70 per cent) and a palliative (R1-R2) resection in 52 (30 per cent). Prognosis was correlated with the extent of mediastinal lymph node dissection. In 77 patients with stage pT1-3 pN0-1 pM0 the 5-year survival rate was 40 per cent after abdominothoracic resection with two-field lymph node dissection and zero after transhiatal resection (P = 0.01). The authors propose a differentiated surgical approach involving abdominothoracic resection with two-field lymph node dissection for patients with limited tumours (pT1-3 pN0-1 M0) if the operative risk is tolerable. Transhiatal resection appears to be effective only in patients with early tumours (Union Internacional Contra la Cancrum stage 0).     

Delayed cytogenetics effects of chronic irradiation of South Ural population

The aim of this study was to assess the referral pattern and the impact on long-term survival of postoperative radiotherapy in patients with adenocarcinoma of the endometrium stage I. This was a retrospective study performed in a regional cancer registry which covers a population of approximately 1,000,000 persons. All 724 patients registered between 1975 and 1992 in the Comprehensive Cancer Centre South, Eastern Section, The Netherlands, were analysed. All patients had received surgery as primary treatment which was performed in one of the seven community hospitals of the region. Radiotherapy was given in one regional department. All pathology reports were checked for data on tumour differentiation and myometrial invasion. Almost half the patients (45%) were referred for postoperative radiotherapy. The depth of myometrial invasion and the degree of tumour differentiation were the main factors (P < 0.0001) influencing referral for postoperative radiotherapy. The referral pattern varied between the different hospitals, but became more similar during 1985-1988, to diverge again in recent years. In patients younger than 60 years, the depth of myometrial invasion was significantly (P = 0.01) correlated with survival. In patients older than 60 years, tumour differentiation (P = 0.05) and age (P < 0.001) were correlated with survival, but not the depth of myometrial invasion. After adjustment for known prognostic factors, a survival benefit of postoperative radiotherapy could not be established. The studied group had an excess death rate over the normal Dutch female population. This excess death rate did not decrease during follow-up, as even after 10 years an excess death rate was found. A prospective randomised trial is ongoing in The Netherlands.     

Strong prognostic impact of tumor-associated urokinase-type plasminogen activator in completely resected adenocarcinoma of the esophagus

The serine protease system has been shown to play an important role in the invasive potential of a variety of tumors. To date, however, there are little data about the expression of these proteases in esophageal carcinoma. To determine the level of expression and the significance of urokinase-type plasminogen activator (uPA) and its plasminogen activator inhibitor type 1 (PAI-1) in adenocarcinoma of the esophagus, we studied 54 tumor cases and a control group of normal gastric mucosa cases with ELISA using detergent-extracted samples. uPA and PAI-1 were significantly elevated as compared to control tissue by factors of 16 and 14, respectively. Median levels of both uPA and PAI-1 showed significant correlation with tumor pT, pN, and pM categories, whereas the presence of lymphatic invasion correlated only with the uPA content and tumor grade correlated only with PAI-1 content. Using maximally selected statistics, a cutoff value was found for uPA (2.85 ng/mg protein) but not for PAI-1, which divided the study group into significantly poorer and better survival subgroups. By univariate analysis, depth of tumor invasion (pT), lymph node involvement (pN), number of involved lymph nodes, lymph node ratio, distant nodal metastases [pM1(Iym)], lymphatic invasion, and uPA showed significant correlations with patient survival. By multivariate analysis, uPA (first rank), pN, and pM (lym) were identified as independent prognostic factors, with relative risks of 8.4, 4.1, and 4.3, respectively. In a second survival analysis method, a prognostic model was developed using classification and regression trees analysis, in which a significant difference among three patient survival groups was distinguished using the variables "number of involved lymph nodes" and "uPA content." In summary, tumor uPA content as determined by ELISA appears to be a powerful, independent prognostic factor for survival in adenocarcinoma of the esophagus.     

Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099

PURPOSE: The Southwest Oncology Group (SWOG) coordinated an Intergroup study with the participation of Radiation Therapy Oncology Group (RTOG), and Eastern Cooperative Oncology Group (ECOG). This randomized phase III trial compared chemoradiotherapy versus radiotherapy alone in patients with nasopharyngeal cancers. MATERIALS AND METHODS: Radiotherapy was administered in both arms: 1.8- to 2.0-Gy/d fractions Monday to Friday for 35 to 39 fractions for a total dose of 70 Gy. The investigational arm received chemotherapy with cisplatin 100 mg/m2 on days 1, 22, and 43 during radiotherapy; postradiotherapy, chemotherapy with cisplatin 80 mg/m2 on day 1 and fluorouracil 1,000 mg/m2/d on days 1 to 4 was administered every 4 weeks for three courses. Patients were stratified by tumor stage, nodal stage, performance status, and histology. RESULTS: Of 193 patients registered, 147 (69 radiotherapy and 78 chemoradiotherapy) were eligible for primary analysis for survival and toxicity. The median progression-free survival (PFS) time was 15 months for eligible patients on the radiotherapy arm and was not reached for the chemo-radiotherapy group. The 3-year PFS rate was 24% versus 69%, respectively (P < .001). The median survival time was 34 months for the radiotherapy group and not reached for the chemo-radiotherapy group, and the 3-year survival rate was 47% versus 78%, respectively (P = .005). One hundred eighty-five patients were included in a secondary analysis for survival. The 3-year survival rate for patients randomized to radiotherapy was 46%, and for the chemoradiotherapy group was 76% (P < .001). CONCLUSION: We conclude that chemoradiotherapy is superior to radiotherapy alone for patients with advanced nasopharyngeal cancers with respect to PFS and overall survival.