Difference In 5-year Disease-free Survival Research Articles

Adjuvant chemotherapy with S-1 after curative treatment in patients with head and neck cancer (ACTS-HNC).

6004 Background: To establish the efficacy of adjuvant chemotherapy with S-1 (tegafur gimeracil oteracil potassium) after curative treatment in patients with advanced squamous cell carcinoma of the head and neck (SCCHN), we conducted a randomized phase III study to investigate whether S-1 is superior to UFT (uracil/tegafur). Methods: Patients with SCCHN who had received curative treatment and were confirmed to be tumor-free were randomly assigned to receive UFT (300 or 400 mg/day for 1 year) or S-1 (80, 100, or 120 mg/day for 1 year). The primary end point was disease-free survival (DFS). Secondary end points were overall survival (OS), relapse-free survival (RFS), and safety. We estimated that 500 patients were needed to establish the primary end point. Results: From April 2006 through November 2008, a total of 526 patients (262 assigned to UFT; 264 assigned to S-1) were enrolled. The 3-year DFS rate was 66.0% in the UFT group and 64.1% in the S-1 group (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.66 to 1.16; [log-rank], P = .34). The 3-year OS rate was 75% in the UFT group and 82.9% in the S-1 group (HR, 0.64; 95% CI, 0.44 to 0.94; [log-rank], P = .022). The 3-year RFS rate was 63.6% in the UFT group and 68.2% in the S-1 group (HR, 0.81; 95% CI, 0.60 to 1.09; [log-rank], P = .16). There were no significant differences in 3-year DFS or RFS; however, the 3-year OS was significantly better in the S-1 group. The incidence of the following grade 3 or 4 events was significantly higher in the S-1 group: oral mucositis/stomatitis (2.4%), leukopenia (5.2%), neutropenia (3.6%), and thrombocytopenia (5.0%). Conclusions: S-1 was not demonstrated to be superior to UFT in terms of 3-year DFS; however, 3-year OS was significantly better with S-1 than with UFT. Clinical trial information: NCT00336947.

Carcinoma of the ampulla of Vater: Patterns of failure after resection and benefit of adjuvant radiotherapy.

254 Background: Ampullary carcinoma is a rare malignancy. Despite radical resection, survival rates remain low with high rates of local failure. To define the role of radiation therapy and chemotherapy with surgery, we performed a single institution analysis of treatment- related outcomes. Methods: A retrospective analysis was performed of all patients undergoing potentially curative therapy for adenocarcinoma of the ampulla of Vater at Duke University Hospitals between 1975 and 2009. Local control (LC), overall survival (OS), disease-free survival (DFS), and metastases-free survival (MFS) were estimated using the Kaplan-Meier Method. Results: One hundred thirty-seven patients with ampullary carcinoma underwent potentially curative pancreaticoduodenectomy. Sixty-one patients undergoing resection received adjuvant (n= 43) or neoadjuvant (n=18) radiation therapy with concurrent chemotherapy (CRT). Patients receiving radiotherapy were more likely to have poorly differentiated tumors. Median radiation dose was 50 Gy. Median follow up was 8.8 years. Of patients receiving neoadjuvant therapy, 67% were downstaged on final pathology with 28% achieving pathologic complete response. Three-year local control was significantly improved in patients receiving CRT (88% vs. 55% p= 0.001) with trend toward a 3-year OS benefit in patients receiving CRT (62% vs. 46% p=0.074). Despite this, there was no significant difference in 3-year DFS (66% CRT vs 48% surgery alone p=0.09) or MFS (69% CRT vs 63% surgery alone p=0.337). Conclusions: Long term survival rates are low. Local failure rates are high following radical resection alone and improved with CRT. Despite more adverse pathologic features in patients receiving CRT, survival outcomes were at least equivalent with a trend toward statistical significance. Given the patterns of relapse with surgery alone and local control benefit in patients receiving CRT, the use of chemoradiotherapy in selected patients should be considered. No significant financial relationships to disclose.

An online gene expression assay for determining adjuvant therapy eligibility in patients with stage 2 or 3 colon cancer

Background:The decision whether to treat patients with non-metastatic colon cancer with adjuvant chemotherapy is determined by clinical staging, frequently resulting in over or undertreatment.Methods:Gene expression data and clinical information from 232 stage 1–4 colon cancer patients were analysed to identify expression patterns predictive of recurrence. The signature was evaluated on an independent series of 60 stage 2 and 3 patients. Multivariate analyses were performed to assess the clinical utility of the assay.Results:A 163-probe signature was able to stratify patients into high- and low-risk groups for disease-free survival (DFS) in both the training and validation series (stage 2: P⩽0.031, stage 3: P⩽0.057) and for disease-specific survival in the training series (stage 2: P=0.01, stage 3: P=0.0017). Multivariate analysis showed the classifier to be associated with approximately three- to fourfold increased risk of recurrence.Conclusions:The prognostic gene expression signature is able to stratify stage 2 and 3 colon cancer patients into groups with significant differences in 5-year DFS, information that may ultimately reduce deaths from colon cancer. Further validation work is required and at this stage the assay is available for evaluation at www.ChipDX.com.

Adjuvant chemoradiation versus chemotherapy in completely resected advanced gastric cancer with D2 nodal dissection

Adjuvant chemoradiation has become a standard of care in the USA. We evaluated the efficacy and toxicity of adjuvant chemoradiation versus chemotherapy in completely resected locally advanced gastric cancer. Patients with stage IIIA, IIIB and IV (without metastasis) gastric cancer were treated with chemoradiation and 5-fluorouracil/cisplatin (FP) (arm A) or FP (arm B). Arm A consisted of one cycle of FP followed by 4500 cGY to radiation field with capecitabine. One month after completion of radiotherapy, patients received three additional cycles of FP every 3 weeks. Arm B consisted of six cycles of FP. A total of 61 patients were enrolled, of whom 31 were placed in arm A and 30 in arm B. The median follow-up duration was 77.2 months (range 24-92.8 months). We did not find any difference in 3-year disease-free survival between arm A and B (80.0 vs 75.2%, respectively; P = 0.887). There was no significant difference between the arms in 5-year disease-free survival (76.7 vs 59.1%, respectively; P = 0.222) or overall survival (70.1 vs 70.0%, respectively; P = 0.814). Seven patients (22.6%) relapsed in arm A and 12 patients (40%) relapsed in arm B. Grade 3/4 neutropenia occurred in 48.5% of patients in arm A and 22.9% in arm B. Grade 3 nausea or vomiting occurred in 6% in arm A and 14.6% in arm B. We could not make any conclusion about the benefit of adding radiation to adjuvant chemotherapy.

Local excision after neoadjuvant chemoradiation for rectal cancer: Is it an acceptable treatment option?

3646 Background: Neoadjuvant concurrent chemoradiation (CCRT) followed by radical surgery is standard in patients (pts) with locally advanced rectal cancer (LARC). Nevertheless, some pts undergo local excision (LE) only, for various reasons. The role of LE in this setting is currently unclear; the main concern regarding LE is the possible neglectance of involved regional lymph nodes (LNs). We therefore evaluated the correlation between pathologic T stage and LN involvement following CCRT and the outcome of pts with good histologic response, i.e. pathological complete response (pCR), undergoing LE. Methods: 340 eligible pts, who underwent neoadjuvant CCRT followed by surgery for LARC between 1/1997 and 12/2007, were included in the study. LARC was defined as T3-4Nx, TxN+ or distal (≤ 6 cm from the anus) T2N0. Radiotherapy was standard (50.4-54 Gy in fractions of 1.8 Gy) and chemotherapy consisted of several common fluoropyrimidine-based regimens. Results: The median age of the whole group was 67 years, 50% were males and 52% had distal tumors. 309 pts (91%) underwent radical surgery, 22 (6%) had LE only and 9 (3%) did not have surgery following CCRT. Of the 22 pts who had LE only, 15 had pT0, 3- microscopic residual disease (mRd), 3-pT1 and 1-pT2. With a median follow-up of 34 month, two pts died, one with mRd and one with T1. We compared the outcome of pT0 pts (n = 37) who underwent radical surgery (group I) with that of pT0 pts (n = 15) who had LE only (group II). With a median follow-up of 48 month, 4 pts in group I had a recurrence (3-local, 1-distant) and none in group II; one pt died in group I and none in group II. There was no significant difference in 5-year disease-free survival (88% vs. 100%), pelvic recurrence-free survival (92% vs. 100%) and overall survival (97% vs. 100%) between the groups. Conclusions: In this small cohort, pts who underwent LE following neoadjuvant CCRT had a relatively good outcome. In pts with pCR, radical surgery did not result in an improved outcome. Therefore, LE may be an acceptable option, at least for pts with mural pCR. No significant financial relationships to disclose.

Impact of mucinous histology on prognosis for patients with radically resected stage Dukes B2 and C colon cancer: Preliminary results

4126 Background: Previous reports have suggested that mucinous colorectal adenocarcinomas have a poorer prognosis than nonmucinous colorectal adenocarcinomas. This retrospective analysis was conducted to explore whether mucinous carcinoma (MC) is associated with a worse prognosis than nonmucinous carcinoma (NMC) for patients with Dukes B2 and C radically resected colon cancer. Methods: We investigated 1,006 unselected patients who underwent curative surgery for sporadic colon cancer and followed up at six Oncology Department between 1998 and 2006. Univariate and multivariate analyses were performed to determine prognostic factors of survival. Results: MC accounted for 17.9% (n=180) of all colon carcinomas. Patient characteristics were as follows. MC: M/F 104/76; median age, 68 (range, 28–97); pT1/2/3/4, 1/4/153/22; Dukes B2/C 98/82; invasion 26 (14%); ≥12 examined lymph nodes, 115 (64%); adjuvant chemotherapy, 110 (61%). NMC: M/F 445/381; median age, 68 (range, 29–95); pT1/2/3/4, 9/51/715/51; Dukes B2/C 384/442; invasion 199 (24%); ≥12 examined lymph nodes, 499 (60%); adjuvant chemotherapy, 545 (66%). MC were more frequently located in the proximal colon (54.4% versus 34.6% for NMC; p<0.001). No difference between MC and NMC in disease-free survival (hazard ratio, HR 1.01; 95% CI, 0.76–1.36; p=0.92) and overall survival (HR 1.05; 95% CI, 0.74–1.49; p=0.78) was found. After stratification by stage of disease, MC and NMC had no statistically significant difference in 5-year disease-free survival (Dukes B2: 79.1% and 78.1%, respectively, p=0.86; Dukes C: 53.8% and 56.2%, respectively, p=0.58) and overall survival (Dukes B2: 84.2% and 85.5%, respectively, p=0.80; Dukes C: 68.0% and 67.3% p=0.52). Multivariate analysis using the Cox proportional hazards model showed that the clinically significant prognostic factors were stage at diagnosis (p<0.0001), grading (p<0.0001), and number of lymph node examined (p=0.0002) in the specimen. Conclusions: In this preliminary analysis, patients with mucinous histology who underwent surgery with curative intent for stage Dukes B2 and C colon cancer had similar prognosis compared to NMC. No significant financial relationships to disclose.

A study of lymph node ratio as a prognostic marker in colon cancer

Aim The aim of this study was to evaluate and describe the lymph node ratio (LNR) as a prognostic parameter for patients with colon cancer. As lymphatic involvement is the key, focus was set at stage III disease. Interest was directed at the possibility of identifying high-risk groups and the clinical implementation and consequence. Method The study was retrospective using a database of clinical data of all cancer patients treated at our unit. It has been continuous in registration, inclusion and update since 1999 including survival and clinical features. All patients ( n = 265) diagnosed with stage III colon cancer during 1999–2003 were included for the study. LNR was calculated and quartile groups were created. LNR and associated parameters were analysed towards 3-year disease-free survival (DFS). Basic patient data as well as surgery, pathology and postoperative treatment were taken into consideration. Results Significant differences in disease-free survival were found for TNM N-status, tumour differentiation grade and LNR quartile group. There was a difference in 3-year DFS from 80% in LNR group 1 compared with less than 30% in group 4. These results were of prognostic interest both independently and in interaction with each other. High-risk groups could be identified and in the worst prognosis LNR group we also found a tendency towards more side effects with adjuvant chemotherapy. Conclusion The lymph node ratio, the quota between the number of lymph node metastasis and assessed lymph nodes, is a highly significant ( p < 0.001) prognostic factor in stage III colon cancer. It can be an aid in identifying risk groups that could benefit from a more intense postoperative surveillance and possibly bring changes in adjuvant treatment strategy. More studies of clinical data, genetic and biochemical markers are needed in this patient group to understand the possible difference in tumour behaviour and tailor the treatment.

A prospective randomized trial comparing 5-fluorouracil (5-FU), mitomycin-C (MMC), and polysaccharide-K (PSK) versus UFT and PSK as adjuvant chemoimmunotherapy (CITX) for patients with locally advanced gastric cancer with curative resection

15074 Background: Adjuvant chemotherapy has demonstrated small but significant survival benefit in locally advanced gastric cancer in several meta-analyses, while adjuvant CITX showed improved outcome of patients (pts) compared to chemotherapy alone in a few trials. However, optimal chemotherapy regimen remains to be determined. We conducted a randomized trial comparing oral (PO) CITX with intravenous (IV) CITX in gastric cancer pts with curative resection. Methods: All enrolled pts underwent radical surgery with at least D2 dissection. After stratification for pathologic stage (IB or II vs. III) and primary tumor size (=5 cm vs. &gt;5 cm), pts were randomized to IV CITX (5-FU 500 mg/m2 weekly for 24 weeks, MMC 8 mg/m2 every 6 weeks x 4) or PO CITX (UFT 400–600 mg/day for 12 months). Pts in both arms received PSK 3 g/day PO for 4 months. The planned target number of pts was 368 to prove the non-inferiority of PO CITX compared to IV CITX in overall survival. Results: A total of 82 pts (stage IB: 6, II: 29, IIIA: 30, IIIB: 17; 44 in IV arm, 38 in PO arm) were enrolled between May 2002 and October 2005, when the trial was closed due to poor accrual. Pts characteristics were well balanced. With a median follow-up of 39 months (14–55 months) in survivors, there were no significant differences in 3-year disease-free survival (82% vs. 61%, p=0.302) and overall survival (84% vs. 79%, p=0.838) between IV and PO arms. No grade 4 toxicity was observed in both arms. IV arm demonstrated higher incidence of grade 2 or 3 neutropenia (79% vs. 52%, p=0.025), thrombocytopenia (19% vs. 0%, p=0.008), and vomiting (36% vs. 9%, p=0.013). Conclusions: Although accrual was well below that planned, the results of this trial suggest that PO CITX with UFT might have similar efficacy with lower toxicity profile compared with 5-FU and MMC CITX in adjuvant treatment for gastric cancer. No significant financial relationships to disclose.

Pelvic Exenteration Affords Safe and Durable Treatment for Locally Advanced Rectal Carcinoma

Treatment of locally advanced rectal carcinoma (LARC) often involves exenterative surgery, which can be associated with high perioperative morbidity and mortality. To assist in patient selection for radical surgery, we sought to determine clinicopathologic factors influencing recurrence and disease-free survival (DFS) of LARC. Consecutive patients with LARC undergoing exenterative surgery were retrospectively identified in our institutional database. Factors evaluated included age, sex, primary versus recurrent tumors, neoadjuvant or adjuvant chemoradiotherapy, resection margin status, recurrence, time to recurrence, and survival. The primary outcome was DFS. Secondary outcomes were overall survival and perioperative morbidity. A total of 72 patients were identified; median age was 52 years, and median follow-up time was 30 months. The overall complication rate was 43%; rates were similar among the patients with primary (47%) or recurrent (37%) LARC. Primary or recurrent tumor status was the only factor significantly predictive of outcome after exenteration. Local recurrence rates were lower in the primary group (primary 22%, recurrent 52%, P = .05). A significant difference in 5-year DFS was found between primary and recurrent tumor (52% vs. 13%; P < .01). The median time to recurrence was longer in the patients with primary LARC (17 months vs. 8 months; P < .01). The complication rates for pelvic exenteration remain high, but the morbidity can typically be managed without a clinically important increase in hospitalization. In primary LARC, an aggressive surgical approach provides most patients 5-year DFS. Select patients with recurrent LARC will also benefit from pelvic exenteration.

DOES THE HISTOLOGY OF NODAL METASTASIS PREDICT SYSTEMIC RELAPSE AFTER RETROPERITONEAL LYMPH NODE DISSECTION IN PATHOLOGICAL STAGE B1 GERM CELL TUMORS?

We evaluated the prognostic significance of the histology of metastatic lymph nodes to predict postoperative relapse in pathological stage B1 nonseminomatous germ cell tumor (NSGCT). A retrospective review of the testicular cancer database was performed to identify all patients with clinical stage A NSGCT who underwent primary retroperitoneal lymph node dissection and were found to have pathological stage B1 disease. No patient received adjuvant chemotherapy and minimal followup was 24 months. A total of 118 patients were identified with a 5-year disease-free survival (DFS) of 68% and a median followup of 43 months. Embryonal cell carcinoma was identified in 92 of 118 (77%) surgical specimens, which was significantly greater than the presence of teratoma (22%), seminoma (16%) and yolk sac (14.4%, p < or = 0.001) with no difference in 5-year DFS comparing the presence or absence of each histology. Solitary histology was noted in 88 of 118 patients (74.5%). Embryonal cell carcinoma was the most common single histology identified at surgery at 64 of 88 (73%), with the incidence of seminoma, teratoma and yolk sac being 12.5%, 9.0% and 5.5%, respectively (p < or = 0.001). There was no statistical difference in DFS for each of the solitary histological subtypes (p=0.67). Recurrence rates were similar for pure embryonal cell carcinoma (69%), mixed embryonal cell carcinoma (63%) and no embryonal cell carcinoma (73%) in the retroperitoneum (p=0.63). Retroperitoneal histology does not appear to predict outcome in patients with pathological stage B1 NSGCT.

Expression of the double-strand RNA activated protein kinase (PKR) and its prognostic significance in patients with locally advanced rectal cancer

3643 Background: The interferon induced, dsRNA-activated, protein kinase, PKR is a key regulator of translational initiation, playing an important role in the regulation of cell proliferation, apoptosis, and transformation. Increased expression of PKR has been shown to correlate with better patient prognosis in head and neck cancer ( Haines et al. Arch. Otolaryngol. Head Neck Surg. 1993). The aim of this study is to identify the prognostic significance of PKR in locally advanced rectal cancer. Methods: One hundred nine patients had potentially curative surgical resection and were treated with chemoradiation therapy followed by 5-fluorouracil based chemotherapy. Paraffin embedded tumor tissue was collected and evaluated in 92 patients. Samples were immunohistochemically stained with the monoclonal antibody TJ4C4. Overall scores for PKR expression were calculated based on staining intensity and percentage of immunoreactive tumor cells. Clinical information including tumor grade, stage, carcinoembryonic antigen (CEA), disease-free survival (DFS), and overall survival (OS) was evaluated and compared by PKR expression. Results: The median follow-up duration was 30 months. The PKR score was not related to the tumor grade, stage, CEA level. The relapse rate was lower in high PKR score group (>7.0) than low PKR score group, though statistically insignificant (27.5% vs. 41.5% p=0.158). There was no significant difference in 5-year DFS (70.2% vs. 47.1%, p=0.3575) and 5- year OS (74.3% vs. 53.9%, p=0.9283) between the two groups. Cox regression multivariate analyses showed that new AJCC stage and tumor differentiation were significant independent prognostic factors in both DFS and OS. Conclusions: The levels of PKR expression were not associated with clinical outcome in locally advanced rectal cancer patients. No significant financial relationships to disclose.

Stage IC adenocarcinoma of the endometrium: survival comparisons of surgically staged patients with and without adjuvant radiation therapy

Objective The goal of this study was to determine the outcomes of stage IC endometrial carcinoma patients who are managed with and without adjuvant radiation therapy after comprehensive surgical staging. Methods Patients with FIGO stage IC adenocarcinoma of the endometrium diagnosed from 1988 to 1999 were identified from tumor registry databases at four institutions. A retrospective chart review identified 220 women who underwent comprehensive surgical staging including a total hysterectomy, bilateral salpingo-oophorectomy, pelvic/paraaortic lymphadenectomy, and peritoneal cytology. Results Of the 220 stage IC patients, 56 (25%) patients received adjuvant brachytherapy (BT), 19 (9%) received whole-pelvis radiation (WPRT), and 24 (11%) received both WPRT and BT. One hundred twenty-one patients (55%) did not receive adjuvant radiation. There were 6 recurrences (6%) in the radiated group and 14 (12%) in the observation group ( P = 0.20). Seven of fourteen recurrences in the observation group were local, and all local recurrences were salvaged with radiation therapy. Two of seven distant recurrences in this group were also salvaged with surgery and chemotherapy. The overall salvage rate for the observation group was 64%. There was a statistical difference in 5-year disease-free survival between the radiated and observation groups (93% vs 75%, P = 0.013). However, the 5-year overall survival was similar in the two groups (92% vs 90%, P = 0.717). Conclusion Adjuvant radiation therapy improves disease-free survival in surgical stage IC patients; however, overall survival is not improved with adjuvant radiation therapy since the majority of local recurrences in conservatively managed patients can be salvaged with radiation therapy.

Surgery or radiotherapy for early stages carcinomas of the glottic larynx.

The choice of treatment in limited squamous cell carcinoma of the glottic larynx often depends on individual and tumor factors. Data of the literature clearly show that surgery and radiotherapy tend to give identical results in terms of survival. We examined 196 cases of T1-T2/N0 cancers of the glottic larynx. We review the literature and discuss the indications and the efficacy of the various available treatments. 196 consecutive cases of T1-T2/N0 cancers of the glottic larynx were examined. In 54.5% the tumor was confined to the vocal cord; in 38.2% it extended to the anterior commissure, in 4.6% to the arytenoid cartilage and in 2.5% to the floor of the ventricle. We performed partial laryngeal surgery in 41.3% (81 cases). Radiotherapy alone was employed in 58.6% (115 cases). In T1a and T1b cases there was no statistically significant difference in 5-year disease-free survival. In T2 cases the NED survival of patients who underwent partial laryngectomies (90% of cases) was significantly better (P <0.05) than among patients given radiotherapy (73%). NED survival at 5 years in patients with the primary tumor on a vocal cord, ventricle or anterior commissure was 78%, 80% and 81%, respectively, with no statistically significant difference among the various sites. It is possible that involvement of the anterior commissure exposes patients to greater risk of recurrence when radiotherapy alone is used (5 out of 23 cases, 21.7%, compared to 3 out of 52 cases, 5.7%, among our surgically treated patients). When the tumor is confined to the vocal cord and mobility is not impaired (T1a), surgery and radiotherapy give comparable results, and the latter yields a better functional outcome. When the anterior commissure is involved, recurrences appear to be less likely after surgery. In T2 glottic carcinoma, surgery gives better results than radiotherapy alone. In any event, the choice of treatment should be patient-specific and based on a careful analysis of the factors involved in each case.

Improved survival of patients with chronic myelogenous leukemia undergoing allogeneic bone marrow transplantation.

A total of 28 patients with chronic myelogenous leukemia (CML) in chronic phase (CP) received bone marrow allografts from HLA-matched siblings at the University of Florida between August 1984-July 1992. The present study compares the disease-free survival (DFS) for those patients who were transplanted before or after August 1988 using the same conditioning regimen. The analysis shows significant difference in 3-year DFS for those patients transplanted post- vs. pre-August 1988 (69.6% vs. 20%, respectively; P = 0.006). A decrease in pneumonitis due to different etiologies from pre-August 1988 (6/13, 46%) to post-August 1988 (1/15, 7%) was statistically significant (P = 0.029). A decrease, although statistically insignificant, in the overall incidence and severity of acute and chronic graft vs. host disease (GVHD) after August 1988 was also noticed. This study indicates significantly improved outcome for patients with CML in CP who have been treated in the University of Florida after August 1988. Better supportive care and prophylaxis for GVHD most likely contributed to such improvement.

Definitive Irradiation of Nasopharyngeal Carcinoma Analysis of Results and Failures in 103 Cases

During the period 1975-1984, 103 patients were treated for nasopharyngeal carcinoma. Most of them presented with an advanced stage: 64 stage IV and 26 stage III. Sixty-one patients presented with neck nodes, which was the most frequent symptom of presentation. The histologic subtypes included 64 squamous cell carcinoma and 39 undifferentiated carcinoma. All patients were treated by high energy sources with portals encompassing the primary and the whole neck. Doses ranged from 50-55 Gy in T1 patients to 65-70 Gy in T4 patients. The mean survival was 58.5 months, and 31 patients were alive and disease free at 60 months from treatment. A clear difference in survival emerged among T1, T2-3, and T4 patients (p greater than 0.01), whereas there was no significant difference between T2 and T3 patients. Also, N0 and N1 showed no significant difference in 5-year disease-free survival (38% and 41%, respectively); only 20% of N2 and 7% of N3 patients survived for more than 5 years. As regards histology, 25% of patients with a squamous cell carcinoma and 36% of those with an undifferentiated carcinoma were alive at 5 years. The presence of distant metastases (in 20 patients) was not correlated with T stage but was strongly correlated with N stage; histology did not affect the development of metastases. There clearly was no correlation between T and N stage, a behavior which probably constitutes a characteristic of these tumors. From our analysis we can affirm that N stage has a greater influence on prognosis and final outcome than T stage, at least using the UICC staging criteria.