Results of a phase II pilot study of moderate dose radiotherapy for inoperable desmoid-type fibromatosis--an EORTC STBSG and ROG study (EORTC 62991-22998).

BACKGROUND: To determine the activity of radiotherapy in patients with inoperable desmoid-type fibromatosis (DF) a multicenter prospective phase II trial was carried out. MATERIALS AND METHODS: Patients with inoperable progressive disease of primary, recurrent or incompletely resected lesions received a dose of 56 Gy in 28 fractions. Follow-up MRI studies were carried out every 3 months for 2 years and thereafter every 6 months. The primary end point was local control rate at 3 years, estimated by a nonparametric method for interval-censored survival data. Secondary end points were objective tumor response, acute and late toxic effect. RESULTS: Forty-four patients (27 F/17 M) were enrolled from 2001 to 2008. Median age was 39.5 years. Main tumor sites included trunk 15 (34.1%) and extremities 27 (61.3%). Median follow-up was 4.8 years. The 3-year local control rate was 81.5% (90% one-sided confidence interval 74% to 100%). Best overall response during the first 3 years was complete response (CR) 6 (13.6%), partial response (PR) 16 (36.4%), stable disease 18 (40.9%), progressive disease 3 (6.8%) and nonassessable 1 (2.3%). Five patients developed new lesions. After 3 years, the response further improved in three patients: (CR 2, PR 1). Acute grade 3 side-effects were limited to skin, mucosal membranes and pain. Late toxic effect consisted of mild edema in 10 patients. CONCLUSIONS: Moderate dose radiotherapy is an effective treatment of patients with DF. Response after radiation therapy is slow with continuing regression seen even after 3 years.

Are risks and benefits of oncological research protocols both incommensurable and incompensable?

Institutional review boards (IRBs) are legally required to determine whether the balance between the risks and benefits (the risk-benefit ratio or RBR) of a proposed study is "reasonable" or "proportional". This obligation flows from their duty to protect the interests of research subjects. It has been argued that it is difficult, perhaps even impossible for IRBs to determine the RBR of studies, because the risks and benefits are not only heterogeneous, but also incommensurable. After arguing that the relevant meaning of incommensurability is incomparability, we discuss whether the risks of participating in a trial and the benefits are comparable. We conclude that at least the risks and the benefits to participants are comparable. In the last section we show that the main problem of RBR analyses is that of interpersonal incompensability. IRBs have to assume that risks to research subjects be compensated by benefits to others. The question is: To what extent? When does it become unreasonable to ask that patients accept the risks of participating in a trial for the benefit of science and/or future patients?

The evaluation of the risks and benefits of phase II cancer clinical trials by institutional review board (IRB) members: a case study.

OBJECTIVES: There are indications that institutional review board (IRB) members do not find it easy to assess the risks and benefits in medical experiments, although this is their principal duty. This study examined how IRB members assessed the risk/benefit ratio (RBR) of a specific phase II breast cancer clinical trial. PARTICIPANTS AND METHODS: The trial was evaluated by means of a questionnaire administered to 43 members of IRBs at six academic hospitals and specialised cancer centres in the Netherlands. The questionnaire addressed: identification and estimation of inconvenience, toxicity, psychosocial distress, and benefits of trial participation to patients; identification and estimation of benefits to future patients and medical science; assessment of the trial's RBR; and assessment of its ethical acceptability. RESULTS: Most IRB members expected trial participation to involve fairly or very serious inconvenience, fairly severe to sometimes life-threatening toxicity, and serious psychological and social consequences. Conversely, the perceived likelihood of benefits to patients was modest. Most regarded the study as important, and the balance between risks and benefits to be favourable, and believed that the protocol should be approved. The IRB members' final judgement on the trial's ethical acceptability was significantly correlated with their RBR assessment of the protocol. CONCLUSIONS: Because most patients who participate in clinical trials hope this will prolong their lives, it is suggested that patient information should better describe the anticipated benefits-for example, the likelihood of prolonging life. This would allow patients to make decisions regarding participation based on realistic expectations.

[The practice guideline 'Carcinoma of the oral cavity and oropharynx']. / Richtlijn 'Mondholte-en orofarynxcarcinoom'.

With a total incidence of ca. 800 per year, oral cavity or oropharyngeal carcinoma represents only a small fraction of the total number of cases of cancer in The Netherlands. In order to achieve as much nationwide uniformity as possible in its diagnosis, treatment, after-care and follow-up, a practice guideline has now been developed. The diagnosis of the primary tumour and the neck, careful clinical examination is complemented by echography, often combined with a biopsy, MRI and CT, while technetium scintigraphy in combination with an orthopantomogram is used to detect invasion of the mandible. The smaller oropharyngeal carcinomas (T1 and T2), surgery and radiotherapy (external therapy or brachytherapy) are equally useful, but for the larger carcinomas (T3 and T4) in patients in good general condition, surgery in combination with radiotherapy is preferred. When radiotherapy is chosen, then brachytherapy is preferred for the smaller tumours of the tongue and the floor of the mouth. In patients without demonstrable metastases to the lymph nodes, just as in the case oforopharyngeal carcinomas, the decision whether or not to treat the neck depends on the chances that cervical lymph node metastases are present: when the risk is smaller than 20% (as with smaller tumours), then a wait-and-see policy is justified, but if the risk is greater than 20% (as with larger tumours or very thick rumours), then the neck should be treated, either surgically or by radiotherapy. The practice guideline also contains information regarding decision making, information and communication, palliative therapy and symptomatic treatment, psychosocial assistance, prosthetic reconstruction, physiotherapy, oral hygiene, nutrition and dietetics, swallowing and speech rehabilitation, and the policy with regard to smoking and alcohol consumption.

Treatment results of regional metastasis from cutaneous head and neck squamous cell carcinoma.

AIMS: To investigate the results of our treatment policy, we present our institutional experience in the management of regional neck node metastases of cutaneous head and neck squamous cell carcinoma (CHNSCC). METHODS: Between 1977 and 1997, 343 patients presented with CHNSCC, of whom 41 were treated for regional metastases, with parotidectomy and/or (selective) neck dissection. Histological analysis was performed on all operation specimens. Patients with multiple nodes and/or extra capsular rupture, at risk for recurrence, received adjuvant radiotherapy. RESULTS: Seventy-six percent of the regional metastases occurred within the first 2 years, but a delay of more than 5 years was also observed. Parotid gland (56%), neck levels II (39%) and V (22%) were most frequently involved. Twenty-four percent of patients treated with curative intent failed at the regional site. Five years overall survival was 46%, with a median survival of 49 months. No survival differences emerged between patients treated by surgery alone and patients receiving adjuvant radiotherapy (P=0.14). Five patients died of disease, of whom three with distant metastases. CONCLUSION: Regionally metastasized CHNSCC is a serious disease with a high risk of regional recurrence, calling for combined surgery and adjuvant radiotherapy. A small subset of patients with a long interval between completion of primary treatment and presence of regional nodes justifies a long follow-up.

Assessment of the risk/benefit ratio of phase II cancer clinical trials by Institutional Review Board (IRB) members.

BACKGROUND: This study examined the assessment of risk/benefit ratios for phase II cancer clinical trials by Institutional Review Board (IRB) members. PATIENTS AND METHODS: Semi-structured interviews were conducted with 53 IRB members from six research hospitals and specialized cancer centers in The Netherlands. RESULTS: While the toxicity and side-effects of treatment were most often identified as risks associated with participating in a phase II trial, approximately two-thirds of IRB members also cited psychosocial and/or quality-of-life risks. Conversely, 68% of the respondents identified psychosocial benefits of trial participation, while 25% cited treatment effectiveness as a possible benefit. Between one-quarter and two-thirds of respondents indicated that trial protocols provide insufficient information regarding the likelihood, magnitude and duration of both risks and benefits. Between 15% and 34% of IRB members reported feeling less than fully competent at evaluating various aspects of phase II protocols (e.g. originality and feasibility of the study, adequacy of the methods and analysis procedures, etc.). This was particularly the case for non-physician IRB members. Few IRB members reported weighing risks and benefits in a systematic manner, but rather relied on global impressions or preferred to leave such matters to the IRB as a whole or to their patients. CONCLUSIONS: A substantial minority of IRB members believes that trial protocols provide too little information relevant to evaluating various cost/benefit and scientific issues, and feels less than fully competent in carrying out such evaluations. IRB members are more likely to identify psychosocial benefits than physical health benefits that may accrue to patients participating in phase II trials.

Stage as major long term outcome predictor in minor salivary gland carcinoma.

BACKGROUND: The myriad of histologic types and anatomic sites of occurrence make minor salivary gland carcinomas the most heterogeneous group of carcinomas of the upper aerodigestive tract. Many publications addressing this group consider different subsections, making it hard to get a clear picture of long term treatment results and of modifying prognostic factors. METHODS: Overall survival, disease specific survival, and percentage rates for no recurrence in all 55 patients with a minor salivary gland carcinoma, treated at the Netherlands Cancer Institute from 1973 to 1994, were calculated and compared to the results in major salivary gland carcinoma patients. Major prognostic factors were univariately analyzed. The median period of follow-up time for patients alive at the end of follow-up was 134 months. RESULTS: The overall 5- and 10-year survival rates were 66% and 57%, respectively. The 5- and 10-year disease specific survival rates (DSS) were 76% and 74%, respectively; and the 5- and 10-year recurrence-free rates were 63% and 60%, respectively. Prognostic for overall survival were age (P = 0.0005), site of occurrence (P = 0.0001), and the International Union Against Cancer/American Joint Committee on Cancer (UICC/AJCC) Tumor, Node, and Metastases (TNM) classification and stage regrouping system (P = 0.0001). Factors predicting DSS were site of occurrence (P < 0.0001) and the UICC/AJCC TNM classification and stage regrouping (P < 0.0001). In surgical patients, histologic evidence for metastatic lymph nodes (P = 0.0037) and vascular invasion (P = 0.0051) conferred a lower DSS. Tumor recurrence was predicted by the UICC/AJCC TNM classification and stage regrouping (P = 0.0001). In surgical patients, soft tissue invasion (P = 0. 0085) predicted tumor recurrence. CONCLUSIONS: Sixty percent of patients treated for minor salivary gland carcinoma were free of tumor ten years later. This equals the result in major salivary gland carcinoma patients. The recent UICC/AJCC TNM classification and stage regrouping are confirmed as major predictors of outcome.

Does the combination of radiotherapy and debulking surgery favor survival in paranasal sinus carcinoma?

PURPOSE: To determine the contribution of debulking surgery on local control and survival in paranasal sinus tumors. As most patients present with locally advanced disease, the possibility of radical surgery is limited. Consequently, radiotherapy is often needed as monotherapy or as an adjunct to surgery. METHODS AND MATERIALS: Between 1977 and 1996, 73 patients (50 male: 23 female) with a paranasal sinus carcinoma were treated. The histology distribution was as follows: squamous cell carcinoma, 55%; adenocarcinoma, 19%; adenoid cystic carcinoma, 11%; and undifferentiated carcinoma, 15%. The clinical T classification was (UICC/TNM 1997): T2 14%, T3 27%, and T4 59%. Pathological neck nodes were found in 11% of patients. Treatment consisted of surgery only in 3, chemotherapy only in 1, radiotherapy only in 18, both surgery and radiotherapy in 50 patients. One patient did not receive any treatment at all. Three patients had concurrent chemotherapy. Median follow-up was 66 months (range, 1-213 months). RESULTS: Five-year local control (LC) was 65% with combination of radiotherapy and debulking surgery in comparison with 47% with radiotherapy alone, but this difference was not statistically significant (p = 0.58). However, combination treatment gave significantly better 5-year overall survival (OS) (60% vs. 9%; p = 0.001) and 5-year disease-free survival (DFS) (53% vs. 6%; p < 0. 0001). Cox-regression analysis showed that pathologic N status (p = 0.04), palliative intention of treatment (p = 0.018), clinical orbital invasion (p = 0.003), and orbital wall invasion (p = 0.003) were parameters significantly associated with poor local control. Total radiation dose of greater than 65 Gy (p = 0.05) and treatment consisting of radiotherapy alone (p = 0.002) were associated with worse overall survival; for disease-free survival clinical orbital invasion (p = 0.0005), age of greater than 65 years (p = 0.013) and pathologic T4 classification (p = 0.002) were significant factors for an unfavorable outcome. In 19 of 73 patients, 26 serious (mainly ophthalmological) complications were reported; in the majority of these, the visual tract was (partly) included in the treatment fields because of tumor extension. To analyze on which basis patients were selected for the combination therapy, a logistic regression was performed, concluding that clinical T4 classification (p = 0.05), radiological evidence of skull base invasion (p = 0.005), age of greater than 65 years (p = 0.026), radiological evidence of nasopharynx invasion (p = 0.02), clinical suspicion of palate invasion (p = 0.02), and radiological evidence of skin invasion (p = 0.009) were associated with choosing radiotherapy alone. CONCLUSION: Debulking surgery of paranasal sinus malignancies followed by high-dose radiotherapy to the involved sites was associated with better survival and (although not statistically significant) local control. Patient selection, based on clinical and radiological impression of tumor extension, was the main factor explaining these favorable results. We favor this combination regimen because the surgery gives quick relief of complaints and, at the same time, offers an excellent histologically proven staging method, enabling radiotherapy to be adjusted to the involved sites, thereby decreasing the risk of complications. This can all be achieved with a very low orbital exenteration rate.

[Diagnosis and treatment of 39 patients with cervical lymph node metastases of squamous cell carcinoma of unknown primary origin, referred to Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, 1979-98]. / Diagnostiek en behandeling van 39 patiënten met halskliermetastasen van plaveiselcelcarcinoom van onbekende primaire origine, verwezen naar het Nederlands Kanker Instituut/Antoni van Leeuwenhoek Ziekenhuis, 1979/'98.

OBJECTIVE: Evaluation of diagnostic procedures and treatment results in patients with lymph node metastases of squamous cell carcinoma in the head and neck region with an unknown primary. DESIGN: Retrospective, descriptive. PATIENTS AND METHODS: In 1979-98, 39 patients (30 male, 9 female; mean age 59 years; range: 39-88) were treated for cervical lymph node metastases of squamous cell carcinoma with an unknown primary. According to protocol, all patients underwent ENT examination, radiodiagnostic procedures and, if possible, examination under general anaesthesia of the upper respiratory and digestive tracts. Most patients were treated by neck dissection followed by bilateral radiotherapy to the neck and to mucosal sites of suspected origin. The data were collected from medical records. The number of patients who had had no local or regional recurrence and were still alive after 5 years were calculated by the Kaplan-Meier method. RESULTS: There was a median interval of three months (3-100 weeks) between the first symptoms and presentation in our clinic. During this period an extensive search for a primary tumour was performed. Most lymph nodes metastases (37/44; 84%) were found at level II and III. The N-stage was as follows: N1 (6), N2 (14), N3 (19). In two patients a primary tumour was diagnosed 20 and 37 months after treatment, respectively, both at mucosal sites which were not irradiated. A five-year locoregional recurrence-free interval was seen in 66%. The five-year overall survival rate was 52% and was significantly related to the extent of the cervical lymph node metastases. CONCLUSION: Early treatment of patients with cervical lymph node metastases from an unknown primary tumour improves survival rates. Radiation therapy of the laryngo-pharyngeal axis seems effective in preventing outgrowth of an occult primary.

Consequences of voice impairment in daily life for patients following radiotherapy for early glottic cancer: voice quality, vocal function, and vocal performance.

PURPOSE: To assess consequences of voice impairment in daily life for patients following radiotherapy for early glottic cancer, by means of a multidimensional analysis protocol including voice quality, vocal function, and vocal performance measures. METHODS AND MATERIALS: A total of 60 men treated with radiotherapy (66 Gy/33 fractions, 60 Gy/30 fractions, 60 Gy/25 fractions) for early T1 glottic cancer and 20 matched control speakers filled in questionnaires on vocal performance. Furthermore, perceptual analyses of voice quality and stroboscopic measures of vocal function were performed. There was a longitudinal group of 10 patients from whom data were collected before, as well as 6 months and 2 years after, radiation. Furthermore, data were collected on 5 separate groups of 10 patients each: before, 6 months after, 2 years after, 3-7 years after, and 7-10 years after radiation. RESULTS: High correlations were found between self-ratings of vocal performance and several voice measures. Patients before radiotherapy experienced poor voice characteristics that improved 6 months to 10 years after treatment, and became comparable to vocal performance of control speakers in 50% of the patients. Following radiotherapy, deviant voice characteristics and consequences in daily life occurred significantly more often for patients in whom initial diagnosis consisted of stripping the vocal cord instead of biopsies and for patients who continued smoking after treatment. CONCLUSION: Voice characteristics of patients diagnosed with early glottic cancer improved after radiotherapy, and became normal in half of our patients. Stripping the vocal cord for initial diagnosis and continued smoking after treatment decreased deviant voice characteristics.

The development of a prognostic score for patients with parotid carcinoma.

BACKGROUND: Understanding of prognostic factors in parotid carcinoma has grown considerably. In particular, clinical tumor staging and histologic classification have been found to be prognostically important. Univariate and multivariate analyses have indicated that other variables, such as age, pain, skin invasion, and facial nerve impairment, are important predictors as well. In an actual patient, some of these factors are present and others are absent. However, a clinical tool incorporating this information, resulting in an individualized prognosis based on the combined effects of present adverse prognostic factors, has never been devised. METHODS: Of a cohort of 168 patients, 151 were evaluated to assess the prognostic value of clinical and pathologic factors in a multivariate proportional hazards analysis. Follow-up ranged from 1 to 278 months (median, 37 months). The end point was tumor recurrence. Identified prognostic factors and their hazard ratios were combined into prognostic scores. RESULTS: Clinical T classification, clinical N classification, pain, age at diagnosis, skin invasion, facial nerve dysfunction, perineural growth, and positive surgical margins acted as major factors predicting recurrence. A prognostic score (PS), generated by the weighted combination of the factors present in the individual patient, placed the patient in one of four subgroups with markedly different prognoses. In the subgroups based on the preoperative prognostic score, 5-year recurrence free percentages ranged from 92% (in the group PS1=1) to 23% (in PS1=4). In the subgroups based on the postoperative prognostic score, which took into account the histologic details of the resected specimen, 5-year recurrence free percentages ranged from 95% (in the group PS2=1) to 42% (in PS2=4). CONCLUSIONS: The proposed subgrouping, which is based on the combined effects of key prognostic preoperative and postoperative factors, provides a practical prognostic grouping system for the clinician treating patients with parotid carcinoma.

Prognostic factors for long term results of the treatment of patients with malignant submandibular gland tumors.

BACKGROUND: Concerning malignant submandibular gland tumors, a rare disease entity, there are few recent reports of long term treatment results and of prognostic factors modifying these results. METHODS: The clinical data of 43 patients with malignant submandibular gland tumors who were treated at the Netherlands Cancer Institute between 1973 and 1994 were reviewed to evaluate treatment results and to control described prognostic factors. The median follow-up for patients alive at the end of follow-up was 143 months. Only univariate analyses were performed. RESULTS: The crude 5- and 10-year survival rates were 50% and 36%, respectively; the 5- and 10-year disease specific survival (DSS) rates were 61% and 51%, respectively; and the 5- and 10-year recurrence free percentages were 57% and 52%, respectively. Factors predicting crude survival were age at diagnosis (P = 0.0006), International Union Against Cancer/American Joint Committee on Cancer (UICC/ AJCC) TNM classification and its regrouping into tumor stage (P = 0.001), and clinical skin invasion (P = 0.005). In surgically treated patients, soft tissue invasion (P = 0.005), metastatic lymph nodes (P = 0.006), and perineural growth (P = 0.01) were prognostic for survival. Factors predicting DSS were the UICC/AJCC TNM classification and regrouping into tumor stage (P = 0.002). In surgical patients, perineural growth (P = 0.0008) conferred a lower DSS. Factors predicting tumor recurrence were the UICC/AJCC TNM classification and its regrouping into tumor stage (P = 0.009). In surgical patients, perineural growth (P = 0.003) predicts tumor recurrence. CONCLUSIONS: Of patients with submandibular gland carcinoma treated according to a stable treatment protocol in a European tertiary referral center, 52% were tumor free 10 years later. Patients exhibiting the described adverse prognostic factors are likely to benefit from added radiotherapy.

Multidimensional assessment of voice characteristics after radiotherapy for early glottic cancer.

OBJECTIVES/HYPOTHESIS: To assess voice characteristics of patients following radiotherapy for early glottic cancer through a multidimensional analysis protocol including vocal function and voice quality measures. METHODS: Voice analyses were performed for 60 patients treated with radiotherapy (66 Gy/33 fractions, 60 Gy/30 fractions, or 60 Gy/25 fractions) for early T1 glottic cancer and 20 matched control speakers. There was a longitudinal group of 10 patients for whom data were collected before as well as 6 months and 2 years after radiation. Furthermore, data were collected for five separate groups of 10 patients each, before, 6 months after, 2 years after, 3 to 7 years after, and 7 to 10 years after radiation. Vocal function was investigated by means of videolaryngostroboscopy, phonetography, maximum phonation time, and phonation quotient measures. Voice quality was assessed by means of objective acoustical analysis and subjective perceptual ratings by trained raters. RESULTS: Voice characteristics of patients were decreased before radiotherapy, improved after treatment, and became comparable to the voice characteristics of control speakers in at least 55% of the patients. Following radiotherapy, deviant voice quality was mainly negatively affected by increased age and stripping the vocal cord for initial diagnosis. Stroboscopy revealed that next to increasing age and stripping the vocal cord, continued smoking after treatment decreased vocal function following radiotherapy. CONCLUSION: Voices of patients diagnosed with early glottic cancer improved but did not normalize fully after radiotherapy. Stripping the vocal cord for initial diagnosis and continued smoking after treatment decreased voice characteristics. A multidimensional analysis protocol including perceptual and acoustical analysis of voice quality and stroboscopic analysis of vocal function is recommended to investigate voice characteristics following treatment for early glottic cancer.

Metastasizing pleomorphic adenoma: a report of three cases.

Three cases of metastasizing pleomorphic adenoma are described. All three had a history of incomplete surgery of the primary tumour and several surgical procedures for local recurrences before systemic metastases became apparent. The histology of the primary tumour, recurrences and metastases were typical of pleomorphic adenoma. In view of the lack of information in the literature, it is concluded that inadequate surgical procedures, such as incomplete surgery or enucleation, leading to multiple recurrences, appear to be a prerequisite for the development of systemic disease.

The impact of treatment time and smoking on local control and complications in T1 glottic cancer.

PURPOSE: To define the optimal treatment regimen, patients with T1N0M0 glottic larynx carcinoma were treated with six different radiotherapy (RT) schedules. To assess the influence of patient characteristics, complication rates, and to evaluate the overall larynx preservation. METHODS AND MATERIALS: Out of a consecutive series of 383 patients treated for T1N0M0 glottic larynx carcinoma between 1965 and 1992, 352 evaluable patients were treated with six different "standard" fractionation schedules: 65 Gy (20 x 3.25 Gy), 62 Gy (20 x 3.1 Gy), 61.6 Gy (22 x 2.8 Gy), 60 Gy (25 x 2.4 Gy), 66 Gy (33 x 2 Gy) and 60 Gy (30 x 2 Gy). The median follow-up of all patients was 89 months. Patient factors analyzed included: age, sex, concurrent illness, smoking habits, tumor localization and extension, tumor differentiation, the effect of tumor biopsy or stripping of the vocal cord, and the presence of visible tumor at the start of radiotherapy. Treatment parameters evaluated were: year of treatment, beam energy, treatment planning, field size, fractionation schedule, fraction size, number of fractions, total dose, treatment time and treatment gap, the use of wedges, and neck diameter. RESULTS: The overall 5-year actuarial locoregional control was 89%, varying between 83 and 93% for the different schedules. Univariately, local control decreased with increasing treatment time. This could not be explained by the confounding variables sex, tumor extension, and field length (p = 0.0065). Adjusted for these variables, 5-year local control percentage decreased from 95% (SE 2%) for 22-29 days to 79% (SE 6%) for treatment time > or = 40 days. The overall complication rate (grade I-IV) at 5 years was 15.3%, and varied between the different schedules, from 7 to 17%. No relation was found between complications and treatment factors. Patients who continued smoking had a higher complication rate than those who never smoked or stopped smoking, univariately as well as adjusted for tumor extension, macroscopic tumor, and neck diameter (p = 0.0038). Twenty-eight percent (SE 6%) of the patients who continued smoking had complications at 10 years, compared to about 13% (SE 4%) of those who stopped before or after RT. No evidence was found for any other relation between complications and patient or tumor factors. Severe edema and necrosis (grade III and IV) were not observed in the 2 Gy fraction schedules. A laryngectomy was performed in 36 patients: 30 for recurrence, 3 for complications (at 40, 161, and 272 months), and 3 for a second primary. The overall larynx preservation was 90% at 10 years, and for the different schedules it was 20 x 3.25 Gy: 97%; 20 x 3.1 Gy: 96%; 22 x 2.8 Gy: 92%; 25 x 2.4 Gy: 89%; 33 x 2 Gy: 78%; and 30 x 2 Gy: 80%. CONCLUSION: Overall treatment time is the most significant factor for locoregional control of T1 glottic cancer. A schedule of 25 x 2.4 Gy appeared to be the optimal treatment schedule considering both tumor control and long term toxicity. The complication rate was increased in patients who continued smoking.

Osteosarcoma of the jaw bones. Long-term follow up of 48 cases.

To evaluate the incidence and treatment results of osteosarcoma of the jaw (OSJ) in the Netherlands, data from 48 patients with a histologically proven diagnosis of osteogenic sarcoma of the maxilla or mandible were retrospectively analysed. Patient files, covering the period from 1964 to 1992, were obtained from all university hospitals in the Netherlands and the Netherlands Cancer Institute. The incidence of OSJ in the Netherlands is estimated to be at least 0.14 per 1,000,000. The overall 10-year survival was 59%. Distant metastasis occurred in 21% and local recurrences in 31% of the cases. Survival was significantly better in case of radical surgery and small tumours. Long-term survival after treatment of OSJ was good if complete surgical excision was achieved. Radiotherapy should only be considered to prevent local recurrence if surgery is not complete. The possible benefit of current chemotherapy in preventing metastatic disease is still questionable. Since other malignant neoplasms associated with OSJ occurred in 17% of the cases, lifelong follow up is mandatory for the detection of these second primary malignancies.

Complications of combined radiotherapy and isolated limb perfusion with tumor necrosis factor alpha +/- interferon gamma and melphalan in patients with irresectable soft tissue tumors.

BACKGROUND: Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF alpha) +/-interferon gamma (IFN gamma) and melphalan in patients with primarily irresectable soft tissue sarcoma is promising in terms of tumor regression and limb salvage. However, the feasibility of radiotherapy in combination with this treatment modality has not been established. METHODS: Fifteen patients with irresectable soft tissue tumors of the limb underwent ILP with TNF alpha, +/-IFN gamma, and melphalan. Three groups could be distinguished with respect to the role of radiotherapy. In nine patients, the residual tumor could be resected after ILP, and this was followed by radiotherapy with a total dose of 50-70 Gy (2 Gy/day). In one patient with aggressive fibromatosis, ILP was followed by radiotherapy without tumor resection (Group I). In two patients who underwent ILP for recurrent sarcoma, the primary tumor had been treated before by resection and radiotherapy (60 Gy) (Group II). In three patients whose tumors remained irresectable after ILP, radiotherapy was applied later in the course of disease for local palliation (Group III). RESULTS: In Group I, healing of the resection wound was markedly delayed in four patients, with soft tissue necrosis and infection necessitating amputation in two of them. Following completion of radiotherapy, persistent lymphoceles were encountered in two patients. Radiotherapy-induced fibrosis was encountered in five patients, resulting in a mild limb malfunction in two. Three-patients developed mild edema during radiotherapy. Tumor-associated neuropathy was aggravated by ILP in three patients causing severely disabling motor deficits and limb contractures in two of them. In Group II, ILP did not cause any local problem in the heavily irradiated areas. In Group III, pre-existing limb edema was increased after a total palliative dose of 20 Gy in one patient. Another patient, who had been re-operated for arterial thrombosis immediately after ILP, developed occlusion of the brachial artery 4 months after completion of palliative radiotherapy (36 Gy in 6 Gy fractions). CONCLUSIONS: In patients with irresectable soft tissue tumors, multimodality treatment using ILP with TNF alpha +/- IFN gamma and melphalan, tumor resection, and postoperative high-dose radiotherapy is associated with a considerable risk of tissue necrosis and impaired healing. This risk should be weighed against a possible benefit from radiotherapy in local tumor control.