T3 Laryngeal cancer: a retrospective study of the Dutch Head and Neck Oncology Cooperative Group: study design and general results

511 Patients with T₃ N_0-3M ₀ squamous cell carcinoma of the larynx, treated in the Netherlands from 1975 until 1984, were retrospectively analysed. Four different treatment policies were followed: primary surgery, planned combination of radiotherapy and surgery, primary radical radiotherapy, and selective radiotherapy. General results are presented. Local control rate was 72%. Regional control rate was 90% for clinically N₀ patients and 78% for clinically N₊ patients. Salvage therapy was overall successful in 38%. Surgical salvage for local radiation failures (with regional relapse) was successful in 69%, and for regional failures (without local relapse) in 46%. Ultimate locoregional control was 78% and, due to 8% distant metastases, 5-year actuarial corrected survival was 70%. Prognosis did not improve over the years. Corrected survival was independently correlated with tumour extension, involvement of neck nodes and treatment strategy. Corrected survival was similar for primary radiotherapy and primary surgery, but significantly better for planned combined therapy. Multiple primary tumours occurred significantly more often in male (19.5%) than in female patients (7.3%) (P = 0.05), the bronchus being most commonly affected. Cumulative actuarial risk for metachronous tumour was 15% after 5 years and 30% after 10 years so prevention and early detection of these second tumours may play the most important role in improving overall survival rates in the future.     

Carcinoma of the soft palate and uvula. An analysis of the results and the reasons for failures. A study of 76 cases

The treatment of carcinomas of the soft palate most often involves radiotherapy. In order to assess the value of irradiation, notably in the treatment of limited T1 or T2 tumours, a retrospective study was carried out of 76 case records suitable for analysis of patients treated in our hospital for this type of tumour between 1974 and 1987. There were 70 men and 6 women. The mean age was 54 years. Fifty-four patients had limited T1 or T2 tumours (including 40 without lymphadenopathy). Treatment methods varied but 48/76 were treated by radiotherapy only (transcutaneous irradiation and/or local interstitial implant). Local tumour control was obtained in 87% of patients with T1 tumours, in 77% with T2 and in 50% with T3 tumours. Lymph node control was obtained in 68% of patients. None of the patients initially classified NO showed any subsequent lymph node involvement. The actuarial five-year survival rate was 67% for T1, 38% for T2 and 22% for T3. Lymph node involvement was the only other prognostic factor. Fourteen patients developed distant metastases and 13% had at least one other tumour site. Radiotherapy as tumour treatment is thus felt to be the method most widely used apart from tumours strictly limited to the uvula, where surgery is preferred. Cervical lymph nodes are treated surgically when there is a palpable lymphadenopathy and by radiotherapy for N0 patients. Induction chemotherapy before radiotherapy is used in addition at stages T3 and T4.     

Radiation therapy in early glottic cancer. Analysis of 177 consecutive cases

Early vocal cord carcinomas (TiS or T1) in a consecutive series of 177 patients treated by primary radiotherapy over a 10-year period 1970-79 at the Department of General Oncology, Radiumhemmet, Karolinska Sjukhuset, were analysed regarding treatment results. In 137 cases the tumours were invasive (T1N0M0) and in 40 cases carcinoma of in situ type (TiS). Patient were treated with cobalt 60 gamma irradiation in fractions of 2 Gy up to a total dose of 64 Gy delivered as split course (CRE=17.8). Minimum follow-up time was 5 years. Tumour recurred in 21 cases (12%). All but 4 patients were rescued by subsequent surgery, giving 98% total survival. Treatment failures after primary radiotherapy were analysed in detail. Failures could not be attributed to treatment irregularities. No difference in pretreatment tumour size was detected when cured patients were compared with patients who relapsed. Biological factors that cause a relative radioresistance are considered to be the main reason for radiotherapy failures in early glottic cancer.     

Timing and duration of postoperative radiotherapy in patients with laryngeal cancer

Aim of this was an evaluation of the impact of prolongation of combined treatment time on the local-regional control laryngeal cancer patients treated with surgery and postoperative radiotherapy. Study was based on retrospective analysis of 254 patients with T3/T4 and N0-N2 laryngeal cancer who were treated between January 1993 and December 1996 with surgery and postoperative radiotherapy (RT). Median age of investigated group was 56.3 years. Surgery consisted of total laryngectomy in all cases and with selective neck dissection. RT began 22 to 78 days postoperatively (median 45 days) and continued for a median of 47 days (range, 40-74 days). The primary tumor bed and all lymph neck nodes were treated in all patients. The total dose to the primary tumor bed was about 60 Gy, fraction dose was 2 Gy. All lymph nodes were irradiated with a dose of 50 Gy. The factors studied for prognostic importance for a local-regional failure included: overall combined treatment time, interval between surgery and the start of radiotherapy, radiotherapy treatment time, age, sex, T and N categories. The 5-year actuarial disease-free local-regional survival was 50%. On univariate analysis, using log rank test, only N status, sex were predicted for the locoregional control of postoperative radiotherapy. Overall treatment time longer than 90 days and especially 100 days was correlated with worse locoregional results of combined treatment respectively (p = 0.003 and p = 0.0007). Also prolongation of interval time between surgery and postoperative radiotherapy beyond 50 days was connected with higher rate of failures (p = 0.02). The same trend was observed when time of irradiation was longer than 47 days (p = 0.01). This analysis indicated that the prolongation of the overall treatment time of combined modality, the the time between surgery, and radiotherapy and time of postoperative radiotherapy were correlated with increased of local regional failures.     

Squamous cell carcinoma of the oral cavity. A review of 176 cases with application of malignancy grading and DNA measurements

This retrospective study comprised 176 patients with squamous cell carcinoma of the oral cavity treated at The Link?ping University Hospital over a 19-year period. Clinical parameters, microscopic malignancy grading (according to Jakobsson et al. and Glanz and Eichhorn), DNA cytofluorometry, analysis of therapeutic modalities and statistics regarding survival and prognosis are reported. The mean age was 70 years with a male: female ratio of 1.3:1 One hundred and four patients had T1 or T2 tumours and 109 an N0 neck. Cervical lymph node metastases were more frequent in patients with larger tumours (T3 + T4) than in those with smaller (T1 + T2) (P less than 0.01), in tumours with a high malignancy grading compared to those with a low (P less than 0.05) and in DNA non-diploid tumours compared to diploid ones (P less than 0.001). The aneuploid tumours responded better to preoperative radiotherapy than did diploid (P less than 0.01) or polyploid (P less than 0.05) tumours. Eighty-nine per cent of the recurrences occurred within 1 year of initial therapy. Secondary treatment was successful in 15 of 37 (41%) patients in whom the tumour recurred either at the primary site or in regional lymph nodes, but only in 1 of 8 (12%) with recurrences in both locations. Surgery alone or combined with radiotherapy resulted in equivalent survival rates for tumours in stages I and II. In advanced stages combined radiotherapy and surgery gave better survival figures than either modality alone (P less than 0.01; Kaplan-Meier). The presence of lymph node metastases (P less than 0.001), tumour size (P less than 0.01) and tumour ploidy (P less than 0.005) were the only clinical and histological parameters that significantly influenced survival (Cox regression analysis). Twenty-four patients developed a secondary primary malignancy; 21 of these were located in the aerodigestive tract.     

Prognostic factors for hypopharyngeal cancer: a univariate and multivariate study of 142 cases

CONCLUSIONS: Reduction of distant metastases is essential for better survival. Effective adjuvant chemotherapy should be developed for patients with advanced primary disease (T>2) as well as for patients with advanced nodal status (N>0 or PLN>2). OBJECTIVES: The aim of this study was to identify prognostic factors for hypopharyngeal cancer. PATIENTS AND METHODS: In all, 142 previously untreated patients were analyzed retrospectively; 75% of the cases were stage III or IV. Surgical resection was administered as primary treatment to 116 of the patients (82%), while 26 patients (18%) underwent primary radiotherapy. RESULTS: The cause-specific 5-year actuarial survival was 46.3%. Distant metastases were the most frequent (23%) cause of failure, followed by local recurrence (15%), and regional recurrence (13%). Cox's regression analysis showed that the significant factors affecting cause-specific survival were N classification, T classification, number of pathological lymph node metastases (PLN), lymphatic invasion, and positive surgical margin. Similarly, T classification and PLN affected distant metastases.     

Metastatic squamous cell carcinoma in cervical lymph nodes from an unknown primary tumour: prognostic factors

The aim of this retrospective review is the study of the prognostic factors related to cervical metastases of squamous cell carcinoma from an unknown primary tumour. Sixty-seven patients were selected and surgery and postoperative radiotherapy was the treatment used. Nineteen tumours were subsequently found (27%). The 5-year actuarial survival rate of all patients was 22%. Survival rates were significantly related to lymph node stages and to the histological degree of differentiation. Nevertheless, actuarial survival rates were not related to the appearance of the primary tumour (P = 0.07). In our series, the single most important prognostic factor was the neck stage. The value close to statistical significance observed when the primary tumour subsequently appeared (P = 0.07), suggests that this could worsen the prognosis.     

Post-operative radiotherapy in advanced laryngeal cancer: effect on local and regional recurrence, distant metastases and second primaries

This was a retrospective study of patients who did or did not receive post-operative radiotherapy for squamous cell carcinoma of the larynx.The rates of local and regional recurrences, distant metastases and second primaries were evaluated in 236 patients who received radiotherapy following surgery. These rates were evaluated and compared with those from 294 patients treated with surgery alone. Multivariate analysis of irradiated patients revealed that local and regional recurrences were determined independently by tumour (T) and pathologic node (pN) stages (p < 0.05). The distant metastasis rate significantly depended on N stage (p < 0.05). Multiple primary tumours were not significantly affected by any of the factors studied (p > 0.05). Analysis of both irradiated and non-irradiated patients revealed that local and regional recurrence was determined independently by pathologic T (pT) stage, tumour localization, radiation status and pN stages (p < 0.05). The distant metastasis rate significantly depended on N stage and tumour localization (p < 0.05) and the rate of formation of multiple primary tumours was significantly affected by the patient's age and radiation status (p < 0.05). In conclusion irradiation of laryngeal cancer patients independently increases the risk of local and regional recurrence, and also increases the risk of multiple primary tumours while not significantly influencing the risk of distant metastasis. The risk of distant metastasis is affected by determinants of advanced lesions and tumour localization.     

Primary and recovery transmaxillar buccopharyngectomy in buccopharyngeal cancers

From january 1976 to december 1986, 78 patients were treated surgically for squamous cell carcinoma of the lateral buccopharyngeal junction without chemotherapy at first. 36 patients were treated by primary surgery with post-operative radiotherapy and 31 patients were treated by recovery surgery. Post-operative course was uncomplicated in 41% of cases (39% in primary surgery, 43% in recovery surgery); in 14% of cases serious local complications were observed (11% in primary surgery, 17% in recovery surgery). Carcinological failures appeared in 46% of cases in primary surgery and in 70% of cases in recovery surgery. Three years and five years actuarial survival rate were 45% and 39% respectively in recovery surgery. Prognostic factors are studied: resection quality, histological metastasis in lymph nodes. The authors emphasize on the best control of the big tumors in primary surgery and on the best results with small ulcerated infiltrant carcinoma.     

Ploidy in head and neck cancer: a review and meta-analysis

A review is presented of all the series reporting ploidy in squamous cell carcinoma of the head and neck. A total of 1984 patients have been reported in 26 different series: 37% of tumours were diploid, 54% aneuploid and 11 % polyploid. Thus 64% of tumours were non-diploid. The mean age of patients with diploid and aneuploid tumours was very similar (60.9 and 60.3 years respectively) but patients with polyploid tumours had a mean age of 54 years. Although men were 5% more likely than women to have a non-diploid tumour the difference was not significant. Data relating ploidy to performance status are not available. The incidence of non-diploid tumours did not vary between sites, nor with stage grouping, but non-diploid tumours increased in frequency with diminishing degree of differentiation and with the presence of lymph node metastases. There was no difference in ploidy pattern between the primary tumour and node metastases. In the entire series the survival was better for diploid tumours than for non-diploid tumours. Subgroup analysis showed this effect to be due to mouth cancers, whereas ploidy did not affect the outcome in laryngeal cancer. Also, recurrence was more likely in non-diploid tumours. Patients with end-stage cancer treated by chemotherapy had a better survival if their tumour was non-diploid. Ploidy did not influence response to radiotherapy. When a tumour recurred after radiotherapy it was more likely to be diploid than a previously treated tumour. Non-diploid tumours had a greater S-phase fraction and a greater growth fraction than diploid tumours.     

CARCINOMA OF THE SOFT PALATE AND THE POSTERIOR OROPHARYNGEAL WALL

Between 1966 and 1984, 14 patients with carcinoma of the soft palate and eight patients with a posterior oropharyngeal wall carcinoma were treated at the Netherlands Cancer Institute. In the soft palate group, the majority of patients (10) had small tumours T₁-T₂; the median patient delay was 1 month (range 0-5). Eleven patients were treated with radiotherapy and three with surgery, as single treatment modalities. Tumour control was achieved in 10 patients following initial treatment. Five-year results for tumour control and overall survival were 67% and 41%, respectively. In the posterior wall group all patients had advanced tumours (T₃-T₄), after a median patient delay of 4 months (range 0-6). Six patients were treated with radiotherapy, one with surgery only and one with a combination of these. Following the initial treatment, tumour control was achieved in half of the patients. Five-year tumour control was 50%, and overall survival at 5 years was 38%. In conclusion, the tumours in these two sub-sites of the oropharynx differ significantly in the extent of the primary tumour (P < 0.01), posterior wall tumours being more advanced on admission, after a significantly longer history (P < 0.01).     

Squamous cell carcinoma of the nasal vestibule

Squamous cell carcinoma of the nasal vestibule is a rare disease. Most advocate radiotherapy as a primary treatment for early tumours, with surgery reserved for salvage. For advanced disease, combined therapy with surgery and postoperative radiotherapy is generally recommended. Fourteen patients with squamous cell carcinoma of the nasal vestibule were reviewed. A classification of early versus late lesions was used. We achieved a 78% local regional control rate (minimum follow-up 3 years) in patients with early disease, with either radiotherapy or surgery as a primary modality of treatment. All patients with late disease recurred, requiring further surgical and/or radiation treatment. Only 20% of these patients were disease free at 2 years. Recurrent disease in either group, whether local or regional, carried a grave prognosis, with a 25% disease-free survival at 3 years.     

The management of glomus jugulare tumours

The treatment details of 58 patients treated for glomus jugulare tumours in Newcastle upon Tyne are examined in the light of other studies reported in the literature. For the group of 55 patients treated by radiotherapy, the 20 year survival is 94% (determined actuarially). The 20 year disease-free survival (determined actuarially) is 77%. This is comparable with other series reported. As no glomus tympanicum tumour has recurred following surgery and there has been no morbidity due to these tumours they have not been included in the series. It is recommended that patients who are fit and have tumours confined to the tympanum should have primary surgical treatment. All other patients should be treated by accurately planned radiotherapy, using a dose of 50Gy in 5 weeks to the tumour volume. The morbidity of this treatment policy will be low.     

Clinically staged T3N0M0 laryngeal cancer: how is it best treated? Definitive radiotherapy with salvage surgery v/s combined surgery and radiotherapy

Controversy surrounds the optimum treatment of T3N0 cancer larynx. Curative radiotherapy with salvage surgery in reserve is an accepted methodology as is also a combined protocol of surgery and radiotherapy. A retrospective analysis of the survival results of 119 cases of clinically staged T3N0 cancer larynx treated over a 14-year period at a single centre with either of the above two modalities has been undertaken. The selection of the treatment modality for an individual patient was decided jointly by the patient and the clinicians at a combined cancer clinic. The combined surgery plus radiotherapy treatment group was comprised of a relatively greater number of transglottic tumours while the curative radiotherapy group had a higher proportion of glottic tumours. Actuarial four-year disease-free survival rates were significantly better with combined treatment (79.3 per cent) than with radical radiotherapy and surgical salvage (65.3 per cent)--p value = 0.024. In the radical radiotherapy group, failure was almost always at the primary site and the probability of surviving with an intact larynx was approximately half of the total survival. As per this study, a policy of radical radiotherapy (with salvage surgery for failure) for unselected clinically staged T3N0 cancer larynx, does not provide for comparable cure rates or for satisfactory laryngeal preservation.     

T3N0M0 glottic carcinoma--a failure analysis

There is at present considerable controversy regarding the appropriate management of a patient who presents with a T3N0M0 glottic carcinoma. This paper presents the results for 141 patients presenting clinically with T3N0M0 glottic carcinoma between 1964 and 1981 and treated with primary radiotherapy reserving surgery for residual or recurrent disease. The actuarial survival for the entire group of patients was 50.5% at 5 yr; 28% of the patients died of glottic cancer. The local relapse-free rate achieved with radiotherapy was higher in female patients (68%) than male patients (41%) (P = 0.04); the local relapse-free rate was higher in males 60 yr of age or older (46%) than in males 59 yr of age or younger (31%) (P = 0.02). Involvement of all three laryngeal regions and initial tracheotomy were associated with a high primary failure rate. Fifty-nine per cent of patients alive at 5 yr retained and intact and functioning larynx. The time up until diagnosis of recurrence and the number of endoscopies required to establish recurrent or residual disease were all assessed with respect to their effects on survival and were shown to have no significant impact. Methods of improving the results of treatment for those patients with a high primary failure rate following radiotherapy are discussed.     

Treatment of neck nodes after induction chemotherapy in patients with primary advanced tumours

Responsiveness of neck nodes to induction chemotherapy often differs from that of the primary tumour. We have conducted a retrospective study to evaluate the results of treating the neck in a cohort of 350 patients with locally advanced (T3–4) head and neck carcinomas treated with radiation therapy at the primary location of the tumour after induction chemotherapy. One hundred and thirty-nine patients (40%) did not have neck nodes on diagnosis (N0). The treatment of the neck included surgery in 65 patients. Neck dissections were carried out before radiotherapy in 37 patients and after radiotherapy in 28 patients. The frequency of neck treatment failure was 24%. There was a tendency to better neck control when treatment included neck dissection, independently of the neck stage or response to chemotherapy. This tendency was statistically significant in patients with an advanced regional tumour (N2–3) who did not achieve a complete regional response after chemotherapy. In a multivariate analysis the variables that were related to the regional failure were the relapse of the tumour at the primary site, the neck stage (N), the type of treatment used in the neck, and the grade of regional response after induction chemotherapy. Our results lead us to suggest that after induction chemotherapy neck surgery is advisable in all cases with advanced regional disease (N2–3), independently of the grade of response achieved after induction chemotherapy, and is also advisable in N1 patients in whom induction chemotherapy does not achieve a complete response. Received: 27 December 1999 / Accepted: 6 June 2000     

Cervical lymph node metastases from occult squamous cell carcinoma: analysis of 82 cases

PURPOSE: The aim of this study was to analyze the prognostic value of some clinical factors and to compare the survival of different treatment plans in patients with cervical lymph node metastases from occult squamous cell carcinoma (SCC). METHODS: A retrospective review was conducted of patients who were diagnosed as having cervical lymph node metastases from occult SCC. Overall cumulative survival was analyzed using the standard Kaplan-Meier method. Tests of significance were based on log-rank statistics. RESULTS: The 82 patients in the study consisted of 69 males (84.2%) and 13 females (15.8%). The average age at diagnosis was 64.7 years. Fifty patients (60.9%) underwent surgical treatment of cervical metastasis. Radiotherapy was performed in 79 patients. Thirty-two patients (40.5%) received primary fractioned external beam radiotherapy; 47 patients (59.5%) received postoperative fractioned external beam radiotherapy. Ipsilateral radiotherapy was performed on 37 patients (46.8%), bilateral neck plus mucosal irradiation was performed in 42 patients (53.2%). Ten patients (12.2%) developed a primary tumor during the follow-up. The actuarial survival rates of all patients 2, 5 and 10 years after diagnosis were 50.9, 25.3 and 18.5%, respectively. Patients with nodal stage N2b, N2c and N3 had a significantly poorer prognosis than those with nodal stage N1 and N2a (p = 0.0239). The survival in patients with metastatic nodes in the supraclavicular region (level IV) was significantly poorer than that of patients with involvement of the upper-middle jugular lymph nodes (p = 0.0003). We observed a statistically significant better survival in patients receiving bilateral neck plus mucosal irradiation (p = 0.0003). CONCLUSIONS: Initial N-category and metastasis localization were the most important prognostic factors and nodal relapse the major cause of treatment failure, thus optimal management of cervical nodes appears crucial for the success of treatment. Patients receiving bilateral neck plus mucosal irradiation had a higher survival rate than those who received ipsilateral irradiation.     

The treatment of early squamous cell carcinoma of the piriform fossa

The treatment of early piriform fossa cancer can be either primary radiotherapy with salvage surgery, if necessary, or with primary surgery. The present study investigates 65 patients with T₁, ≥₂ or T₃ stage disease with no cervical lymph node metastases at presentation. Of this group, 17 were treated by primary irradiation, 34 underwent primary surgery and 14 were unsuitable for any curative treatment. The adjusted actuarial 5-year survival rate for those patients receiving primary radiotherapy was 55% (95% CI 16–78%) and for the surgery group it was 44% (95% CI 18–67%). This difference was not significant (χ²₁= 1.29). The median survival for untreated patients was 7 months (4–12 months). There was no significant differences in the time to recurrence at the primary site or in the neck, or in survival after recurrence at these sites. Thirty-five per cent of patients treated by primary irradiation were controlled at the primary site compared with 68% in the surgical group. Failure in the neck was similar for the two groups at 12% and 15% respectively. Salvage surgery was effective for the radiotherapy group with eight out of 11 patients being suitable for treatment. In the final analysis in the radiotherapy group two patients were alive and with their larynx and two alive without their larynx, the remainder of patients having died from the original tumour, intercurrent disease or second primary tumours. The survival figures for the surgery group were proportionately similar except of course, that all patients had lost their larynx. Radiotherapy with salvage surgery for recurrence is a safe oncological treatment option. A high failure rate at the primary site is disappointing but if placed in perspective still allows half the survivors to retain their larynx.     

Survival in second primary malignancies of patients with head and neck cancer

Second primary tumours occur frequently in patients with a history of head and neck malignancies. Delays in making an early and correct diagnosis can seriously affect the therapy management and survival. This was a retrospective study of 120 patients with a history of head and neck cancer, presenting with a second primary tumour. Current follow-up strategies and the use of routine sonographic imaging of the head and neck regions were evaluated, and the impact that tumour chronology, the tumour site and the various treatment modalities have on the survival were assessed. Forty-two per cent of patients developed a metachronous second malignancy more than five years after diagnosis of the index tumour. The accuracy of colour-duplex sonography in detection of second primaries in the head and neck was 82.3 per cent. First and second primary tumours located in the larynx were observed to have the highest five-year survival rate. Patients who developed metachronous tumours had a five-year survival rate of 68.9 per cent for the index tumours, and a 26 per cent five-year survival rate with the occurrence of a second neoplasm. With synchronous tumours a mean survival time of 18 months and a five-year survival rate of 11.9 per cent was found (p < 0.0001). Where clinically appropriate an aggressive treatment strategy was employed and yielded the most favourable results with a five-year survival rate of 66.8 per cent and 35.9 per cent for index tumours and second primary malignancies, respectively. Since more than 40 per cent of the metachronous second primaries in patients with a history of head and neck malignancy occur beyond the five-year follow-up period, an extended protocol with individually adjusted close monitoring of high-risk patients seems appropriate. Colour-duplex sonography is a valuable screening investigation for the early detection of second primary tumours. The treatment of a second primary is often less successful than for the same malignancy occurring primarily. The prognosis of synchronous tumours is significantly lower when compared to malignancies of a metachronous nature, despite some encouraging individual results. Only the early implementation of aggressive treatment methods for second primaries is successful in terms of survival.     

Treatment failures of surgical and combined (surgery and radiotherapy) treatment in carcinoma of the larynx and hypopharynx--20 years experience of ENT Department, District Hospital in Kielce

The 280 cases (29.8%) of treatment failures after surgical and combined (surgery + rtg-therapy) treatment in 940 cases of carcinoma of larynx and hypopharynx has been taken into analysis. The recurrence within regional lymph nodes (11.9%), followed by local recurrences (11.5%) has dominated in this group. The distant metastases had been registered only in 2.6% of the whole treated group and the second primary tumours (included to the analysis of treatment failures) has been registered in 3.8%. The failures distribution has not been related to the sex and age of the patients, but significant dependence of failures rate to the general condition of the patient, the local and nodal advancement of the disease, and histological grade of tumour has been found. The highest rate of treatment failures was in hypopharynx localisation of primary tumour and the lowest in glottic region of the larynx. The results obtained in salvage treatment after failure of primary treatment has been unfavourable. In general, only 22.1% of patient with primary treatment failure has achieved 3-years survival, and 13.6% 5-years survival rate. In should be pointed out, that salvage treatment has been applied only to 40.8% of this group. The remaining patients received only symptomatic and palliative treatment.