Lars Vendelbo Johansen

Cervical lymph node metastases from unknown primary tumours Results from a national survey by the Danish Society for Head and Neck Oncology

BACKGROUND AND PURPOSE The management of patients with cervical lymph node metastases from unknown primary tumours is a major challenge in oncology. This study presents data collected from all five oncology centres in Denmark. MATERIAL AND METHODS Of the 352 consecutive patients with squamous cell or undifferentiated tumours seen from 1975 to 1995, a total of 277 (79%) were treated with radical intent. The general treatment policy at all centres during the entire study period has been to treat all suitable candidates with radiotherapy to both sides of the neck and include elective irradiation of the mucosal sites in nasopharynx, and larynx, hypopharynx and larynx (81%). Irradiation of the ipsilateral neck only was done in 26 patients (10%). Radical surgery was the only treatment in 23 N1-N2 patients (9%). RESULTS The 5-year estimates of neck control, disease-specific survival and overall survival for radically treated patients were 51, 48 and 36%, respectively. The emergence of the occult primary was observed in 66 patients (19%). About half of the emerging primaries were within the head and neck region with oropharynx, hypopharynx and oral cavity being the most common sites. Emerging primaries outside the head and neck region were primarily located in the lung (19 patients) and oesophagus (five patients). The frequency of emerging primary in the head and neck was significantly higher in patients treated with surgery alone, the actuarial risks at 5-year being 54+/-1% (no RT) vs. 15+/-3% (with RT), P<0.0001. The most important factor for neck control was nodal stage (5-year estimates 69% (N1), 58% (N2) and 30% (N3)). Other important parameters for neck control and disease-specific survival included haemoglobin, gender and overall treatment time. Patients treated with ipsilateral radiotherapy had a relative risk of recurrence in the head and neck region of 1.9 compared with patients treated to both neck and mucosa. At 5 years, the estimated control rates were 27% (ipsilateral) and 51% (bilateral; P=0.05). The 5-year disease-specific survival estimates were 28 and 45%, respectively (P=0.10). CONCLUSIONS This study has confirmed that patients with neck node metastases from occult head and neck cancer have clinical features and prognosis similar to other head and neck malignancies. Extensive irradiation to both sides of the neck and the mucosa in the entire pharyngeal axis and larynx resulted in significantly less loco-regional failures compared with patients treated with ipsilateral techniques, but only a trend towards better survival. A prospective randomized trial is required to determine the optimal strategy in terms of locoregional control, survival and morbidity.

CLINICAL RADIOBIOLOGY OF SQUAMOUS CELL CARCINOMA OF THE OROPHARYNX

Local tumor control is analyzed in a series of 181 patients treated with definitive megavoltage radiotherapy (RT) for histologically proven squamous cell carcinoma of the oropharynx. Considerable variation in treatment time stemmed from the general use of a split-course technique in 49 patients treated from 1978 to 1985. Incomplete follow-up, in those patients alive and well at the termination of the study or who have died from metastases or intercurrent disease before developing a local recurrence, was allowed for by using a multi-variate mixture model. The tumor control probability (TCP) after radiotherapy showed a significant dependence on the following tumor and treatment characteristics: (a) tumor size: the number of tumor target cells increases approximately as the fourth root of estimated tumor volume; (b) sex: the estimated TCP in males is lower than in females with the same characteristics; (c) histopathological differentiation: well-differentiated tumors have a lower TCP than poorly and intermediately differentiated; (d) hemoglobin concentration: patients in the upper normal range have a significantly higher TCP than others; (e) total dose: there is a significant dose-response relationship; and (f) overall treatment time: TCP decreased with increasing overall time, the dose equivalent of proliferation with 2 Gy per fraction was 0.68 Gy/day with 95% confidence limits [0.05, 1.3] Gy/day. The TCP did not depend significantly on subsite within the oropharynx or nodal disease at presentation. The data were consistent with an alpha/beta ratio of the linear-quadratic model of 10 Gy.

Pharyngo-cutaneous fistulae after laryngectomy. Influence of previous radiotherapy and prophylactic metronidazole.

The development of a pharyngocutaneous fistulae is a major complication after total laryngectomy. In Denmark radiotherapy is the primary treatment for all laryngeal carcinomas. Based on the experience with conventional daily irradiation, a split‐course radiation schedule was introduced in 1978. The charts of 106 consecutive patients laryngectomized for recurrence in the years 1975 to 1984 were examined. Thirty‐four patients developed a fistula. An evaluation of the different radiotherapy schedules used during this period allowed a dose‐response curve to be constructed. It showed a pronounced increase of fistulae with high doses of radiotherapy. Split‐course radiotherapy caused a rise in late complications and did not improve tumor control. Large field sizes increased the number of fistulae. High‐dose fractions showed a surprisingly high incidence of late complications. Prophylactic metronidazole (introduced in 1980) resulted in a highly significant decrease in the frequency of postoperative fistulae. Patients in whom fistula formed were hospitalized for an average of 54 days, patients without, for 22 days.

Salvage laryngectomy and pharyngocutaneous fistulae after primary radiotherapy for head and neck cancer: a national survey from DAHANCA

In 1998, the Danish Society for Head and Neck Oncology decided to conduct a nationwide survey at the five head and neck oncology centers with the aim of evaluating the surgical outcome of salvage laryngectomy after radiotherapy with special emphasis on identifying factors that could contribute to the development of pharyngocutaneous fistulae.

Primary radiotherapy of T1 squamous cell carcinoma of the larynx: Analysis of 478 patients treated from 1963 to 1985

Radiotherapy was administered to 478 consecutively treated patients with laryngeal T1 squamous cell carcinoma between 1963-1985. One hundred and seventeen had a supraglottic, 358 a glottic, and 3 a subglottic tumor. Supraglottis: 71% males; 49% T1a; 14 patients with nodes. Glottis: 90% males; 82% T1a; 1 patient with node. The 10-year value for local control in the supraglottic group was 55% and in the glottic group 81%. No difference was observed between T1a and T1b. Regional nodes and distant metastases were seldom seen in the glottic, but frequently observed in the supraglottic group. The treatment results appeared to be most favorable in women. The 10-year corrected survival for supraglottic and glottic tumors demonstrated a highly significant difference, 67% compared to 94%. There was a significantly increasing incidence of events with lower tumor differentiation. Split-course and conventional radiotherapy gave equal treatment results, but late complications were significantly more common with the former. A major problem was new primary cancers, which within 20 years occurred in 34% of patients surviving a supraglottic tumor and in 23% of the glottic patients. The predominant new site was the lung (23% and 13%, respectively). Thus, in the glottic group more patients died from the new cancer than from the glottic carcinoma.

Hypopharyngeal squamous cell carcinoma : Treatment results in 138 consecutively admitted patients

The aim of this study was to evaluate the results of the initial and salvage treatment for hypopharyngeal carcinoma. The study was conducted in 1963 to 1991and included 138 patients (38 females (28%) and 100 males (73%)). Most of the tumours originated in the piriform sinus (86%). Tumour stage distribution was T1: 20%, T2: 27%, T3: 37% and T4: 17% and nodal stage distribution was N0: 45%, N1: 25%, N2: 10%, and N3: 20%. Primary treatment was delivered with curative intent in 124 out of 138 cases (90%). Treatment failure was noted in 98 patients, with 55% recurrence in T-position, 39% in N-position, and 14% at distant metastases sites. Salvage surgery was successful in 9 out of 32 patients. The overall 5-year locoregional tumour control, cause-specific and overall survival rates were 20%, 25% and 19%, respectively. Univariate actuarial analysis showed that T- and N-stage, clinical stage, tumour size and well-differentiated tumours were significant prognostic parameters. A Cox multivariate analysis showed that only the T- and N-stages were independent prognostic factors. In conclusion, the prognosis for advanced hypopharyngeal carcinoma is extremely poor and the meagre results with conventional radiotherapy alone indicate that other treatment modalities should be introduced in the management of this disease.The aim of this study was to evaluate the results of the initial and salvage treatment for hypopharyngeal carcinoma. The study was conducted in 1963 to 1991 and included 138 patients (38 females (28%) and 100 males (73%)). Most of the tumours originated in the piriform sinus (86%). Tumour stage distribution was T1: 20%, T2: 27%, T3: 37% and T4: 17% and nodal stage distribution was N0: 45%, N1: 25%, N2: 10%, and N3: 20%. Primary treatment was delivered with curative intent in 124 out of 138 cases (90%). Treatment failure was noted in 98 patients, with 55% recurrence in T-position, 39% in N-position, and 14% at distant metastases sites. Salvage surgery was successful in 9 out of 32 patients. The overall 5-year locoregional tumour control, cause-specific and overall survival rates were 20%, 25% and 19%, respectively. Univariate actuarial analysis showed that T- and N-stage, clinical stage, tumour size and well-differentiated tumours were significant prognostic parameters. A Cox multivariate analysis showed that only the T- and N-stages were independent prognostic factors. In conclusion, the prognosis for advanced hypopharyngeal carcinoma is extremely poor and the meagre results with conventional radiotherapy alone indicate that other treatment modalities should be introduced in the management of this disease.

Glottic carcinoma – patterns of failure and salvage treatment after curative radiotherapy in 861 consecutive patients

BACKGROUND AND PURPOSE The aim of this study was to evaluate the patterns of failure and the treatment of recurrences, in a series of primary irradiated patients with squamous cell carcinoma of the glottic larynx. MATERIALS AND METHODS Eight hundred and sixty-one consecutive patients were included in this study from 1963 to 1991, out of which 74 were females and 787 males. The stages were: I 56, II 26, III 15, and IV 3%. In 847 of 861 cases (98%) the primary treatment was delivered with curative intent, and out of these 834 patients received primary radical radiotherapy. RESULTS With a minimum follow up of 5 years, 274/861(32%) patients had persistent or recurrent disease; in 91% of these the persistent or recurrent disease was in the T-position, 15% in the N-position, and 5% developed distant metastases. Curative salvage attempt was possible in 207 patients, and 145 were subsequently controlled. A total of 718 (83%) patients obtained ultimate tumour control, 584 (68%) without a laryngectomy (134 of the controlled had a laryngectomy, 109 had a total laryngectomy and 25 had a partial laryngectomy). In the patients treated with curative intent, the overall 5-year local tumour control, loco-regional tumour control, disease specific survival rate and overall survival rate was 72, 70, 86 and 66%, respectively. For patients with small tumours the disease specific survival for T1a, T1b and T2 was 95, 93 and 83%, respectively. In the 718 patients cured for their glottic carcinoma, 204 new primary malignant tumours were detected. CONCLUSIONS The study shows that laryngeal glottic carcinoma can be effectively managed by primary radiotherapy and surgery salvage. The control is obtained with a high proportion of laryngeal preservation (68%). Recurrences treated with surgical salvage have a success rate of 70%. New primaries are a major problem.

Squamous Cell Carcinoma of the Oropharynx-An Analysis of Treatment Results in 289 Consecutive Patients

In this retrospective study the results of primary and salvage treatment of oropharyngeal carcinoma were evaluated. A total of 289 consecutive patients (103 females and 186 males) were included in the study. Most tumours originated in the tonsil area (58%) and comprised stages I 8%, II 19%, III 46% and IV 28%. The primary treatment was delivered with curative intent in 276 cases (96%). Of these, 266 received primary radiotherapy. The median radiation dose was 62 Gy, given as laterally opposed fields to the primary tumour and bilateral neck. Eight patients were treated with primary surgery and two with chemotherapy as part of a curatively intended treatment programme including radiotherapy. Six patients received palliative treatment, and seven were not treated at all. Out of 276 tumours treated with curative intent, 173 reappeared; 72% recurred in T position, 38% in N position, and 12% at distant metastatic sites, some in combination. Salvage surgery was possible in 52 patients, and 24 treatments were successful. Salvage radiotherapy or cryotherapy was used in 22 patients and 4 were controlled. For the entire group, the 5-year locoregional tumour control, disease-specific survival and overall survival rates were 38%, 44% and 31%, respectively. For patients treated with curative intent, clinical T- and N-stage, stage, tumour size, gender, age, and pretreatment haemoglobin were significant prognostic parameters in a univariate analysis. The Cox multivariate analysis showed that T-stage, N-stage and gender were independent prognostic factors. It is concluded that T-stage, N-stage and gender are significant independent prognostic factors. The primary control of the carcinoma in the T-position is crucial for overall success, but salvage surgery is found to have a favourable success rate in patients suitable for relapse treatment.In this retrospective study the results of primary and salvage treatment of oropharyngeal carcinoma were evaluated. A total of 289 consecutive patients (103 females and 186 males) were included in the study. Most tumours originated in the tonsil area (58%) and comprised stages I 8%, II 19%, III 46% and IV 28%. The primary treatment was delivered with curative intent in 276 cases (96%). Of these, 266 received primary radiotherapy. The median radiation dose was 62 Gy, given as laterally opposed fields to the primary tumour and bilateral neck. Eight patients were treated with primary surgery and two with chemotherapy as part of a curatively intended treatment programme including radiotherapy. Six patients received palliative treatment, and seven were not treated at all. Out of 276 tumours treated with curative intent, 173 reappeared; 72% recurred in T position, 38% in N position, and 12% at distant metastatic sites, some in combination. Salvage surgery was possible in 52 patients, and 24 treatments were successful. Salvage radiotherapy or cryotherapy was used in 22 patients and 4 were controlled. For the entire group, the 5-year locoregional tumour control, disease-specific survival and overall survival rates were 38%, 44% and 31%, respectively. For patients treated with curative intent, clinical T- and N-stage, stage, tumour size, gender, age, and pretreatment haemoglobin were significant prognostic parameters in a univariate analysis. The Cox multivariate analysis showed that T-stage, N-stage and gender were independent prognostic factors. It is concluded that T-stage, N-stage and gender are significant independent prognostic factors. The primary control of the carcinoma in the T-position is crucial for overall success, but salvage surgery is found to have a favourable success rate in patients suitable for relapse treatment.

Supraglottic carcinoma: patterns of failure and salvage treatment after curatively intended radiotherapy in 410 consecutive patients.

PURPOSE In a series of consecutive patients with squamous cell carcinoma of the supraglottic larynx, in which almost all were treated by primary radiotherapy, the study describes the path from diagnosis to cure or death, and evaluates the patterns of failure and the treatment of recurrences. METHODS AND MATERIALS The analysis included 410 patients, 104 females and 306 males, treated between 1963 and 1991. Most patients were in Stage I (33%), and the remaining were in Stage II (18%), III (23%), and IV (26%). Primary intended curative treatment was delivered in 398 (radiotherapy, 394; surgery, 4) of 410 cases (98%). RESULTS Initial radical treatment resulted in 173 cured patients and 225 patients with a recurrence. Curatively intended salvage could be applied in 158 patients: surgery in 154 patients (74 cured) and radiotherapy in 4 (none cured). Overall, 247 patients (60%) obtained tumor control, 179 (44%) without a laryngectomy. Sixty-three patients had a total laryngectomy, and five had a partial laryngectomy. The 5-year locoregional tumor control, disease-specific survival, and overall survival rates were 43%, 61%, and 47%, respectively. With a follow-up of 20 years posttreatment, 91 new primary malignant tumors were detected. CONCLUSIONS Radiotherapy is effective in the treatment of supraglottic laryngeal carcinoma, and the patients have a relatively good prognosis. Many patients retained their larynx intact. Recurrence after primary radiotherapy can be treated by surgery, with a high success rate even in advanced stages. Development of second primary cancer is a growing problem.

Post-operative problems and complications in 313 consecutive cochlear implantations

OBJECTIVE To describe problems and complications associated with cochlear implantation, and their management, in a Danish patient population comprising both paediatric and adult patients. DESIGN Retrospective chart review. SETTING Tertiary referral centre. SUBJECTS Three hundred and thirteen consecutive cochlear implantations were studied. The median age of the study population was 10 years. Sixty per cent of patients were children and 40 per cent were adult; 52 per cent were female and 48 per cent were male. INTERVENTION Two hundred and ninety-four patients received a Cochlear Nucleus implant. The remaining 19 received an Advanced Bionics implant. MAIN OUTCOME MEASURE Presence of problems and complications after cochlear implantation. RESULTS Post-operative complications were found in 15.7 per cent of patients. The majority of these complications (11.2 per cent) were minor; 4.5 per cent were major. The major complications included one patient with meningitis, one patient with multiple antibiotic resistant Staphylococcus aureus infection of a radical cavity, and one diabetic patient who developed a severe skin infection and whose implant became exposed. CONCLUSION Cochlear implantation is a safe procedure within the studied setting. However, it is essential that careful attention be paid to surgical planning and technique, and it is important that healthcare staff and patients be aware of the possible problems and complications.