Head and neck cancer: oral care during radiotherapy

For patients with head and neck cancer who are compromised by the side-effects of radiotherapy, effective mouth care is essential. This article describes the detrimental effects of radiotherapy to the oral cavity and provides a practical guide to oral cleansing.     

P53 overexpression in head and neck carcinoma and radiotherapy results

PURPOSE: P53 gene mutations are the common genetic changes encountered in human cancers, and there is extensive evidence that the P53 status may determine tumor response to therapy. This study was carried out to investigate whether there is any correlation between accumulation (overexpression) of P53 protein and poor prognosis in patients with head and neck carcinomas treated with radical radiotherapy. METHODS AND MATERIALS: Seventy-nine patients with head and neck carcinomas who were diagnosed and treated in 1989-90 with curative radiotherapy were studied retrospectively. Paraffin sections from archival material were studied using immunohistochemical staining (IHC) with mouse monoclonal antibodies (D0-7) to human P53 protein. Univariate and multivariate analysis of loco-regional tumor control and patient survival were performed on possible prognostic factors. RESULTS: Forty-two (53%) patients showed positive IHC staining in their tumors. Fifty-three percent of the laryngeal, 64% of the oropharyngeal, and 43% of the oral cavity carcinomas showed P53 overexpression. All tumor specimens with vascular, lymphatic, and/or sarcolemmal invasion showed P53 overexpression. The proportion of tumor-stained nuclei was higher in the poorly differentiated than in the well and moderately differentiated tumors (p < 0.05), but there was no correlation with the patient overall or disease-free 5-year actuarial survival. There was no difference in the 5-year actuarial survival and disease-free survival between patients with P53 immunostaining in their tumors and those with no immunostaining (59% vs. 65% and 57% vs. 51%, respectively). The TNM tumor stage was the most significant prognostic factor with 5-year actuarial survival of 87% for early and 14% for late stages (p < 0.0001). There was a significant correlation between immunostaining and history of smoking (p = 0.02). CONCLUSION: The data demonstrate that the P53 accumulation as detected by immunohistochemical staining in a group of head and neck carcinomas was not predictive of patient's poor survival or disease-free survival. Multivariate statistical analysis showed that the TNM tumor stage was the only significant prognostic factor. There was a significant association between P53 accumulation and smoking.     

Variations in tumour oxygen tension (pO2) during accelerated radiotherapy of head and neck carcinoma

The study was performed to assess the effect of accelerated radiotherapy on oxygenation of primary tumours and metastatic nodes in patients with advanced head and neck tumours. In 14 patients with head and neck tumour, oxygen tension (pO2) was evaluated in normal tissues and tumours (primary tumour or metastatic neck node) before (0 Gy) and after 2 weeks (32 Gy) of accelerated radiotherapy (70 Gy in 3.5 weeks, with three daily fractions). Radiotherapy was combined with carbogen breathing in 5 patients. pO2 was measured using a polarographic technique. For pooled normal tissues, median pO2 was 38 mmHg before treatment and 46 mmHg after 2 weeks. For tumours, very low values (< 2 mmHg) represented 20% of the recorded values before treatment and 10% after 2 weeks. The relative increase in tumour oxygenation was more pronounced for primary tumours (median pO2 12 mmHg before treatment versus 26 mmHg after 2 weeks, P < 0.05) than for metastatic nodes (respectively, 20 and 27 mmHg P = 0.1). For the 5 patients who breathed carbogen during accelerated radiotherapy, the median pO2 was 44 mmHg at 2 weeks, compared with 13.5 mmHg before treatment (P = 0.05). Very low pO2 values, corresponding to tumour hypoxia, were found in the tumours (primary and metastatic neck nodes) prior to accelerated treatment. During the first 2 weeks of accelerated treatment, an increase in median pO2 was found in nine of the 14 tumours, together with a decrease in the frequency of very low values.     

Prognostic factors in oral, head, and neck cancer

Screening tests on mice with the use of a model of neurogenic damage to the stomach revealed antiulcerative activity in extracts of Amoor cork tree, Pacific Bergenia, Lespedeza dichromatic, Leuzea carthamoides, sea-buckthorn, common aspen, Manchurian nuts, Serratula coronarius, and Scutellaria baicalensis. It was proved that an extract of aspen cork produces a marked antiulcerative effect on being administered to animals with "acute" ulcers and in treatment of chronic peptic ulcer. The study of various drug forms of Serratula coronarius extracts (prepared from the bark and the bark and shoots) in experiments on mice (neurogenic ulcer) and rats (Aspirin ulcer) revealed the most marked gastroprotective effect of oil extracts of bark and shoots. A high antiulcerogenic activity of extracts prepared from grass and roots of Scutellaria baicalensis was demonstrated.     

Concurrent Taxol and split-course accelerated radiotherapy for advanced head and neck cancer

AIM: The aim of this study was to investigate feasibility and toxicity of fractionated paclitaxel administration concurrently with accelerated radiotherapy in the treatment of advanced head and neck cancer. PATIENTS AND METHODS: Patients with a proven histology of inoperable head and neck carcinoma were eligible for this study. Between July 1994 and August 1995, 12 patients with stage IV (UICC) tumors were treated. Patients were required to have normal end-organ function. Exclusion criteria included: age > 70 years, metastatic disease, performance status (Karnofsky < 70), major intercurrent medical disorders, and previous chemotherapy. External radiation was delivered twice a day at 1.5 Gy per fraction, specified to the reference point (ICRU 50), with a minimum interfraction interval of 6 hours. The accelerated scheme was split into 2 courses by a rest period of 9 days (including weekends) after administration of 30 Gy within 2 weeks. After 39 days a total dose of 72 Gy was reached. Paclitaxel (30 mg/m2/d) was administered as a continuous intravenous infusion over a period of 3 hours on days 1 to 5 and 29 to 33 of radiation therapy. All patients received premedication to avoid allergic reactions and circulatory monitoring was used routinely. RESULTS: Radiochemotherapy was completed in 10 patients with 8 complete and 2 partial remissions. Most important toxicity was a short period of neutropenia, which occurred 3 to 6 days after chemotherapy and was associated with fever in 9 cases. During paclitaxel infusion there was a significant but clinically not relevant increase in blood pressure and a decrease in heart rate. No acute cardiac effects occurred and no hypersensitivity reaction was seen. CONCLUSIONS: This regimen demonstrates a high activity in locally advanced head and neck cancer. Neutropenia associated with fever was the major dose limiting toxicity.     

Intraoperative electron beam radiotherapy for previously irradiated advanced head and neck malignancies

In patients with malignant astrocytomas or metastatic brain disease treated with high-dose radiotherapy, conventional imaging methods may not adequately distinguish recurrent tumor from radiation change. We used a fast spoiled gradient refocusing technique in the open-configuration intraoperative MR system to assess the rate of regional enhancement of the treated tumor bed and to localize specific sites for pathologic sampling to determine whether gadolinium uptake correlated with histologic data. Twenty-four patients were studied. Fourteen of 15 patients with areas of early enhancement had recurrent tumor present in histologic samples, and 8 of the remaining 9 patients had only reactive changes. Dynamic MRI was predictive of recurrent tumor (P < .0005, Fisher exact test and P < .002, Student t test). We conclude that dynamic MRI in the open-bore magnet is a promising method for localizing potential sites of active tumor growth in patients treated for malignant astrocytomas and metastatic brain lesions.     

Neoadjuvant chemotherapy and radiotherapy for inoperable head and neck cancer: the LSU-Shreveport experience

A retrospective review of 8 years of treatment in 2 hospitals in Shreveport showed that neoadjuvant chemotherapy with radiotherapy was performed in 39 patients with inoperable, locally advanced head and neck cancer. Twenty-two individuals treated by definitive radiotherapy alone served as historical controls. The cumulative survival rate at 4 years was 34% in patients managed by neoadjuvant chemotherapy with radiotherapy and 7% in patients treated by radiotherapy only. With the exception of greater acute toxicity seen in patients receiving neoadjuvant chemotherapy with radiotherapy, differences in locoregional failure, distant metastasis, and late complication rates were not observed between the patient groups.     

外放疗联合碘-125粒子植入治疗头颈癌的临床应用

目的:初步评价外放疗联合碘-125(125I)粒子植入治疗头颈癌患者的局部控制率和放射性损伤的有关结果.方法:选择2008年2月至2010年7月在北京大学口腔医院口腔颌面外科就诊的头颈痛患者10例,其中鳞状细胞癌8例,低分化腺癌2例,均因全身疾病或局部晚期而不能手术治疗.所有患者均先接受常规分割外放疗,然后再行125I粒子植入增量放疗.外放疗总照射剂量(total dose,Dt)为50 Gy(鳞癌)或70 Gy(低分化腺癌);125I粒子植入治疗的匹配周缘剂量(matched peripheral dose,MPD)为60 Gy(TNM分期为Ⅰ～Ⅱ)或80 Gy(TNM分期为Ⅲ～Ⅳ).125I粒子活度为25.9～29.6 MBq/个.对患者进行随访,分析急性放射性损伤、晚期放射性损伤、局部控制和生存情况.结果:平均随访12个月(2～28个月),有1例出现软组织坏死,1例出现吞咽困难和局部大出血,余末见其他严重副作用.所有病灶均在6个月内完全消退,1例出现颈淋巴结转移,1例出现远处转移,余未见复发和转移.10例患者中有7例存活.结论:外放疗联合125I粒子植入是治疗不能根治手术头颈癌患者的一种安全、有效的选择方法.     

Continuous hyperfractionated accelerated radiotherapy with/without mitomycin C in head and neck cancer

PURPOSE: To evaluate the effect of mitomycin C to an accelerated hyperfractionated radiation therapy. The aim was to test a very short schedule with/without mitomycin C (MMC) with conventional fractionation in histologically verified squamous cell carcinoma of the head and neck region. METHODS AND MATERIALS: From October 1990 to December 1996, 188 patients entered the trial. Tumors originated in the oral cavity in 54, oropharynx in 82, larynx in 20, and hypopharynx in 32 cases, respectively. Patients' stages were predominantly T3 and T4 (158/188, 84%) and most patients had lymph node metastases (144/188, 77%) at diagnosis. Only 22 patients were female, 166 were male, the median age of patients was 57 years (range 34 to 76 years). Patients were randomized to one of the following three treatment options: conventional fractionation (CF) consisting of 70 Gy in 35 fractions over 7 weeks (65 patients) or continuous hyperfractionated accelerated radiation therapy (V-CHART; 62 patients) or continuous hyperfractionated accelerated radiation therapy with 20 mg/sqm MMC on day 5 (V-CHART + MMC; 61 patients). By the accelerated regimens, the total dose of 55.3 Gy was delivered within 17 consecutive days, by 33 fractions. On day 1, a single dose of 2.5 Gy was given, from day 2 to 17 a dose of 1.65 Gy was delivered twice: the interfraction interval was 6 hours or more. RESULTS: Mucositis was very intense after accelerated therapy, most patients experiencing a grade III/IV reaction. The mucosal reaction did not differ whether MMC was administered or not. Patients treated by accelerated fractionation experienced a confluent mucosal reaction 12-14 days following start of therapy and recovered (no reaction) within 6 weeks. The skin reaction was not considered different in the three treatment groups. Those patients treated with additional chemotherapy experienced a grade III/IV hematologic toxicity in 12/61 patients. Initial complete response (CR) was recorded in 43% following CF, 58% after V-CHART, and 67% after V-CHART + MMC, respectively (p < 0.05). Actuarial survival (Kaplan-Meier) was significantly improved in the combined treated patients. Local tumor control was 28%, 32%, and 56% following CF, V-CHART, and V-CHART + MMC, respectively (p < 0.05). CONCLUSION: We conclude that our continuous hyperfractionated accelerated radiation therapy regimen is equal to conventional fractionation, suggesting that by shortening the overall treatment time from 7 weeks to 17 days a reduction in dose from 70 Gy to 55.3 Gy is possible, with maintenance of local tumor control rates. The administration of MMC to the accelerated regimen is tolerable and improves the outcome for patients significantly.     

Concomitant radiotherapy with mitomycin C and bleomycin compared with radiotherapy alone in inoperable head and neck cancer: final report

We evaluated the efficiency of two different treatment procedures with continuous positive airway pressure (CPAP) on sleep, nocturnal breathing characteristics and daytime vigilance in 18 newly diagnosed patients with untreated sleep apnoea/hypopnoea syndrome (SAHS) randomly allocated to two different groups. In group I, the positive pressure (PP) level was set to suppress flow limitation (PFL), while in group II the PP was set at a level that eliminated only apnoea/hypopnoea and snoring (PAHS). At the end of a 3 week period of home CPAP therapy, a follow-up sleep study, vigilance and cognitive tests were made. Overall, PFL was significantly higher than PAHS values (PFL: 10.42.6 cmH2O; PAHS: 8.9+/-2.6 cmH2O; p<0.01, mean+/-SD). We found no difference in sleep quality, nocturnal saturation and apnoea/hypopnoea index, or in daytime vigilance tests between the two groups at the end of the treatment period. However, there was a significantly greater scattering in the changes of sleep latency in group II than in group I. This was associated with a significant difference in the daily duration of nasal CPAP use between the two groups (group I: 7.29+/-0.95 h x day(-1); group II: 6.01+/-0.94 h x day(-1); p=0.01) and with a positive correlation between final maintenance of wakefulness test values and the duration of CPAP use (p<0.05; r=0.55). These results tend to show that correcting flow limitation is associated with a higher observance and a more important efficiency in normalizing daytime vigilance than with conventional nasal continuous positive airway pressure.     

Vascular endothelial growth factor expression in head and neck squamous cell carcinoma

BACKGROUND: Angiogenesis is an essential process required for growth and metastasis in cancer. In breast, gastric, and prostate cancer, vascular endothelial growth factor (VEGF) has been implicated in angiogenesis; however, little is known about VEGF in HNSCC. In this study, we hypothesize that VEGF is present in elevated levels in HNSCC and may therefore play a role in promoting angiogenesis. METHODS: We obtained tumor tissue from 63 HNSCC patients undergoing primary resection. All tissue samples were analyzed by immunohistochemistry (IHC) techniques for the presence and localization of VEGF; however, only 36 had sufficient amounts of tissue for quantitative analysis of VEGF by ELISA. Nine control specimens taken from patients undergoing uvulopalatopharyngoplasty were also analyzed. RESULTS: In all 63 of our patient samples we found VEGF to be present and localized to the cancer cells and endothelial cells. The poorly differentiated cancer cells stained more intensely in comparison with the well-differentiated ones. There was a 20-fold increase in the patient levels when compared with controls levels (P > or =0.05). Analysis by enzyme-linked immunosorbent assay revealed elevated mean levels of VEGF (241 +/- 326 pg/mg total protein [TP]) with a range of 2 to 1484 pg/mg TP. The control specimens had mean levels of 13 +/- 11 pg/mg TP and a range of 1 to 78 pg/mg TP. Patients who exhibited higher levels of VEGF tended to have a higher rate of disease recurrence (P < or =0.048) and shorter disease-free interval (P < or =0.05). CONCLUSIONS: The expression of VEGF in elevated levels in the HNSCC tumor microenvironment appears to be associated with more aggressive disease. Based on our results, VEGF may be an important angiogenic factor associated with cancer cells and endothelial cells in HNSCC. Further studies are needed to better define the role of VEGF in HNSCC and its role as a potential target for therapeutic intervention.     

Comparison between radiation-induced cell cycle delay in lymphocytes and radiotherapy response in head and neck cancer

Two experiments examined the frequency specificity of habituation of the acoustic startle response in the rat. Following the long-term habituation of startle to one of two pure tone stimuli in Experiment 1, animals were presented with the other stimulus. Startle response asymptotes were unaffected by this change in stimulus frequency. Short-term habituation of startle also was insensitive to stimulus frequency. In Experiment 2, pure tone stimuli were used to provoke both a startle response and the interruption of drinking. Long-term habituation of startle to either stimulus was unaffected by a change in frequency. Animals that received the two stimuli on alternating days showed as rapid a habituation as did the groups receiving only one stimulus frequency during acquisition. Conversely, the lick suppression measure was found to be frequency specific. Lick suppression durations rose to pre-habituation levels when the frequency of the stimulus was changed. Animals that received the two stimuli on alternating days showed retarded habituation compared to those groups presented with only one stimulus frequency during acquisition. Although long-term habituation of startle is not stimulus specific, it is mediated by central processes and thus remains a valuable model in the study of neurophysiological mechanisms of behavioral change.     

Feasibility and outcome of a progressively accelerated concomitant boost radiotherapy schedule for head and neck carcinomas

PURPOSE: To evaluate toxicity and treatment outcome in patients with head and neck carcinomas treated with a modified bifractionated concomitant boost radiotherapy schedule. METHODS AND MATERIALS: Eighty-five patients were treated from February 1991 to October 1995. According to clinical TN stage 23 tumors were T1, 33 T2, 20 T3, 9 T4, 44 N0, and 41 N1-N3. The primary tumor was located in the oral cavity in 6 patients, oropharynx in 36, larynx in 19, hypopharynx in 17, and nasopharynx in 7. The basic treatment delivered 50.4 Gy in 28 fractions, once a day, to the primary site and both sides of the neck. During the last 3.5 weeks, a boost to the initial gross disease was delivered in 13 fractions of 1.5 Gy each as a second daily fraction in a progressively accelerated schedule (total dose 69.9 Gy). Eighteen patients had a uni- or bilateral neck dissection, and 2 an adenectomy before radiotherapy. The median follow-up for the surviving patients was 28 months (range: 3-61 months). RESULTS: All the patients completed the planned radiotherapy schedule. According to the RTOG scoring system, 57 patients (67%) presented with Grade 3-4 acute toxicity. Grade 3 dysphagia was observed in 20 patients (23.5%). Three patients died during the 3 months following the treatment. Among 73 patients evaluable for late effects, five developed Grade 3-4 complications. At 3 years actuarial loco-regional control was 67% and overall survival was 62%. CONCLUSIONS: Although longer follow-up is needed to evaluate the definitive results, we conclude that this particular concomitant boost schedule is feasible and appears to be effective. While acute toxicity was greater than in monofractionated schedules, it was manageable, provided that supportive care measures were implemented in a timely fashion.     

Lymphocyte response in patients with head and neck cancer: effect of clinical stage and radiotherapy

Ffty-three patients with head and neck cancer tested before radiation treatment to determine numbers of blood lymphocytes and immunologic responses to mitogens of lymphocytes in whole-blood cultures had mean values that were 19% to 26% less than values for healthy individuals. Thirty patients whose disease was in stages III or IV had values similar to those in 23 patients whose disease was in stages I or II. Values for 45 patients tested at end of radiotherapy decreased to about 50% of pretreatment values; however, patients with advanced lesions experienced greater decreases (to 24% to 50%) than patients with localized lesions (to 71% to 84%). Patients with advanced lesions usually received radiation to larger areas than patients with localized lesions; therefore, the extent of decline in laboratory values was most likely dependent on volume of tissue treated.     

Simultaneous radiochemotherapy versus radiotherapy alone in advanced head and neck cancer: a randomized multicenter study

PURPOSE: A prospective randomized multicenter trial was performed to evaluate the contribution of simultaneously administered chemotherapy (CT) and radiotherapy (RT) in previously untreated patients with unresectable stage III/IV head and neck cancer. PATIENTS AND METHODS: Patients with locoregionally advanced head and neck cancer were treated either with RT alone (arm A) or simultaneous RT plus CT (RCT; arm B). RT was identical in both arms and administered in three courses with 13 fractions of 1.8 Gy each twice daily. During one course, from day 3 to 11, 23.4 Gy was delivered. In arm B, cisplatin (CDDP) 60 mg/m2, fluorouracil (5-FU) 350 mg/m2 by intravenous (i.v.) bolus, and leucovorin (LV) 50 mg/m2 by i.v. bolus were given on day 2, and 5-FU 350 mg/m2/24 hour by continuous infusion and LV 100 mg/m2/24 hours by continuous infusion were given from day 2 to 5. Treatment was repeated on days 22 and 44; a total RT dose of 70.2 Gy was administered. Treatment breaks were scheduled from days 12 to 21 and days 34 to 43. RESULTS: From 1989 to 1993, 298 patients were enrolled and 270 patients were assessable. Acute mucositis grade 3 or 4 was more frequent in arm B (38%) than in arm A (16%) (P < .001). Total treatment time was significantly longer in arm B than in arm A (P < .001) due to prolonged breaks. According to hematologic toxicity, scheduled drug doses were given in 74% of patients for the second course and 46% for the third course. The 3-year overall survival rate was 24% in arm A and 48% in arm B (P < .0003). The 3-year locoregional control rate was 17% in arm A and 36% in arm B (P < .004). Both arms showed similar distant failure patterns (arm A, 13 of 140; arm B, 12 of 130). Serious late side effects were not significantly different between treatment arms (arm A, 6.4%; arm B, 10%; not significant). CONCLUSION: Concomitant CT offered improved disease control and survival in advanced head and neck cancer patients. Due to increased acute toxicity, more supportive care is demanded when CT is given simultaneously. Increased total treatment time does not exert a negative impact on outcome in this combined modality regimen.     

Chemoradiotherapy as an alternative to radiotherapy alone in fast proliferating head and neck squamous cell carcinomas

The aim of this pilot study was to explore the prognostic relevance of cell kinetics parameters on the local control of patients affected by head and neck squamous cell carcinoma (HN-SCC), randomly assigned to receive either alternating chemoradiotherapy or partly accelerated radiotherapy. Between 1992 and 1995, 40 patients with HN-SCC at stages III and IV entered the study. Multiple primary tumor biopsies were obtained 6 h after in vivo infusion of bromodeoxyuridine, an analogue of thymidine that is incorporated in DNA-synthesizing cells. In vivo S-phase fraction labeling index (LI), duration of S-phase (TS), and potential doubling time (Tpot) were obtained by analysis of the flow cytometric content of bromodeoxyuridine and DNA. Twenty patients were treated by alternating chemotherapy and conventional radiotherapy (arm A), whereas 20 other matching patients received partly accelerated radiotherapy alone (arm B). Univariate local control analysis showed that LI, TS, and Tpot were not prognostically significant in either arm. However, local control probability at 2 years for fast growing tumors, characterized by a LI of 9%, was higher for patients treated with alternating chemoradiotherapy than it was for those treated with partly accelerated radiotherapy alone (68 versus 39%). Conversely, local control probabilities for slow proliferating tumors (LI, <9%) treated in the two arms were similar. These results suggest a potential role for alternating chemotherapy and radiotherapy in HN-SCC patients with fast growing tumors.     

Applying radiobiological principles to combined modality treatment of head and neck cancer--the time factor

Although gallbladder stasis exists in most patients with cholesterol gallstones, it is unknown whether stasis is a causative factor of gallstone disease or merely a consequence of it. We studied the impact of sustained gallbladder stasis induced by a cholecystokinin (CCK)-A receptor antagonist (MK-329) on gallstone formation in ground squirrels fed either a trace or a high-cholesterol diet. MK-329 markedly inhibited gallbladder contraction in vitro in response to CCK (at EC100, control: 3.6 +/- 0.5 vs. MK-329: 1.1 +/- 0.3 g; P < .05) and increased gallbladder fasting volume in vivo (control: 462 +/- 66 vs. MK-329: 1,004 +/- 121 microL; P < .05). Whereas the high-cholesterol diet alone (1%-cholesterol diet + placebo) increased the cholesterol saturation index (CSI) in control animals (trace-cholesterol diet + placebo), MK-329 significantly (P < .05) decreased the CSI in both hepatic and gallbladder bile in animals on the trace-(trace-cholesterol diet + MK-329) as well as on the high-cholesterol diets (1%-cholesterol diet + MK-329). The mucin content of the mucus layer on the epithelial surface of the gallbladder wall more than doubled (P < .05) with the high-cholesterol diet; adding MK-329 to the latter group produced a further 82% increase (P < .05). The cholesterol diet + MK-329 group had the highest (100%) incidence of cholesterol crystals that were evident in fresh gallbladder bile, coincident with a shortened nucleation time (2.5 +/- 0.6 days; P < .05 vs. the cholesterol diet + placebo group, 5.8 +/- 1.0 days or the other 2 groups, >21 days). Bile from animals on the trace-cholesterol diet, whether or not receiving MK-329, lacked crystals in bile and exhibited a normal nucleation time (>21 days). Thus, stasis per se may lower the CSI, but its detrimental effect on the gallbladder predominates locally, and so accelerates cholesterol crystal formation in this model.     

Basic fibroblast growth factor in serum and urine of patients with head and neck cancer

Between 1996 and 1997 serum and urine levels of basic fibroblast growth factor (b-FGF) in patients with head and neck cancer were measured to answer the following questions: i) Are increased levels of b-FGF in serum and urine detectable in patients with malignant head and neck tumors? ii) Do these parameters correlate with tumor stage and differentiation of tumors? iii) Is there an association between growth behaviour (local or metastatic growth) and b-FGF levels in serum and/or urine? Eighty-nine patients with head and neck cancer as well as 45 patients with diseases unrelated to cancer were investigated. Detectable levels of b-FGF were found in the serum and urine of patients with malignant head and neck tumors. In addition, there was a significant correlation between tumor size and b-FGF levels in either serum or urine. No association of b-FGF concentrations with degree of histologic differentiation and tumor growth behaviour was observed. The results of this study demonstrate that b-FGF levels are elevated in serum and urine of patients with head and neck cancer. These findings suggest an involvement of b-FGF in the formation of solid tumors.