Biomedical subjects

V Rudat

Publications and source records attributed to V Rudat.

At least 19 recordsLinked to original sources

PubMed2004

[Diagnosis with (18)F-FDG PET scan after larynx preservation by primary radiochemotherapy].

PATIENTS AND METHODS: In a group of 20 patients undergoing chemoradiation for larynx organ preservation after diagnosis of laryngeal and hypopharyngeal carcinoma, (18)F-fluordeoxyglucose positron emission tomography ((18)F-FDG-PET) was performed before the start of therapy. After i.v. application of 240 MBq FDG, a dynamic PET in 3-D-mode was performed over 90 min (Siemens CTI ECAT EXACT HR(+)). Analysis was done visually and semiquantitatively (60-90 min p.i.) following iterative reconstruction. Additional (18)F-FDG-PET investigations were done and correlated with the clinical outcome in 16/20 patients at 3 months and in 14/20 patients at 6 months after the end of therapy. RESULTS: In 17/20 patients (85%), the preclinical (18)F-FDG-PET correlated well with the histologically confirmed primary tumor. Three cases were false negatives. In one case this was due to an increased glucose value (203 mg%). After 3 months, 8/13 (62%) patients showed a positive correlation between clinical and PET results (sensitivity 100%, specificity 70%). After 6 months, 9/11 (82%) patients presented clinically normal PET results. PET results were false negative in one case (sensitivity 67%, specificity 88%). CONCLUSION: The data of our trial slightly reduce the enthusiasm of early (18)F-FDG-PET detection of residual disease after chemoradiation in resectable laryngeal or hypopharyngeal cancer. Further trials should optimize the calculation integrating the exact quantification of glucose metabolism with the aim of improving sensitivity and specificity.

Aged↗

PubMed2004

Prognostic impact of EBV-related LMP-1, histologic type, and environmental factors in nasopharyngeal carcinoma in a German population.

INTRODUCTION: This retrospective study addressed the possible involvement of latent Epstein-Barr virus (EBV) infection, in particular LMP-1 expression, and further exogenous factors, i.e. tobacco, alcohol and occupational hazardous substances, in nasopharyngeal carcinoma (NPC) in a German population. PATIENTS AND METHODS: From 1980 to 2000, 44 patients suffering from histologically confirmed NPC were entered into the study. 33 specimens were available for immunostaining (IHC) to analyze LMP-1 expression. Information about environmental exposures were obtained employing a detailed standardized questionnaire. RESULTS: Outcome of patients with squamous cell NPC (SC-NPC) was significant worse than that of those with non-keratinizing NPC (NK-NPC). Age and tumor size correlated with response to therapy. The group with negative conventional LMP-1 staining showed better overall survival after 5 years compared to the group with positive or marginally positive LMP-1 detection (not significant). Nevertheless, after staining by tyramid-augmented IHC (TSA-IHC), nearly all specimens with negative LMP-1-staining in conventional IHC were found to be clearly positive. All patients with SC-NPC were smokers. The distribution of smokers and non-smokers in the group of NK-NPC was balanced. Comparable to the tobacco observation, there was also a correlation between high alcohol consumption and SC-NPC. CONCLUSION: Prognosis of NPC is mainly dependent on histologic type. Prognostic impact of LMP-1 is still unclear since LMP-1 was detected in all specimens using TSA-IHC. Therefore, TSA-IHC-LMP-1 detection might be interesting for diagnostic specification and development of new therapeutic strategies in NPC.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Approaches to preserve larynx function in locally advanced laryngeal and hypopharyngeal cancer.

Randomized controlled studies have shown that preservation of the larynx function in patients with advanced resectable laryngeal and hypopharyngeal cancer is possible without compromising survival compared to total laryngectomy (TL). Options for preserving the larynx include function-sparing surgery, radiotherapy alone, induction chemotherapy followed by radiotherapy of responders, and concomitant radiochemotherapy. The current data suggest that induction chemotherapy followed by radiotherapy of responders is an acceptable alternative to TL for patients desiring larynx preservation. Concomitant radiochemotherapy (platinum/5-FU) leads to superior local control and larynx preservation rates compared to induction chemotherapy followed by radiation. The optimal treatment sequence for newer cytotoxic agents is, however, unclear. Such cytotoxic agents and more effective fractionation regimens as well as more advanced surgical techniques are currently evaluated. Predictive tests to successfully stratify patients for the optimal treatment option and more effective systemic therapy are needed to improve therapeutic possibilities and survival.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

[Immunohistochemical determination of cell cycle regulatory proteins. No prognostic significance in advanced squamous epithelial carcinomas of the head-neck area].

BACKGROUND: In recent years, a number of molecular markers have been tested for their potential to predict the outcome after radiotherapy or radiochemotherapy in patients with advanced head and neck squamous cell carcinomas (HNSCC). These studies have produced controversial results. PATIENTS AND METHODS: The expression patterns of the proteins p53, pRb, cyclinD1, cdk4, p21(CIP1/WAF1), p16(INK4a), bcl-2, and mib-1/ki-67 were analyzed in pretreatment tumor biopsies of 53 patients with advanced nonresectable head and neck squamous cell carcinomas (mainly UICC IV). The patterns obtained were compared with clinical outcome after accelerated radiochemotherapy with carboplatin and 5-fluorouracil or accelerated fractionated radiotherapy alone, respectively. RESULTS: The expression patterns of the proteins examined did not correlate with response to therapy or with further clinical course. CONCLUSION: In patients with advanced head and neck squamous cell carcinomas, the prognostic relevance of pretreatment expression patterns of the proteins investigated in this study, particularly p53, cyclinD1, and cdk4, has to be questioned.

Adult↗

PubMed2002

[Organ preservation in advanced laryngeal and hypopharyngeal carcinoma by primary radiochemotherapy. Results of a multicenter phase II study].

INTRODUCTION: Regarding the promising results of international trials we conducted the first German prospective multicentre phase II trial for organ preservation with primary simultaneous chemoradiation in advanced laryngeal and hypopharyngeal cancer. PATIENTS AND METHODS: 28 of 30 recruited patients suffering from stage II and III (UICC) laryngeal and hypopharyngeal cancer were treated with primary simultaneous chemoradiation within an organ preservation program and monitored in follow-up of one year. Exclusion criteria included tumor infiltration of the laryngeal cartilage, bilateral neck nodes (N2c) and need for flap reconstruction in case of laryngectomy. The protocol included an accelerated concomitant boost chemoradiation (66 Gy) with Carboplatinum (70 mg/m2 1st and 5th week) and a restaging procedure one month after therapy. In case of residual disease, salvage laryngectomy and/or neck dissection were performed. RESULTS: After follow-up of one year 20 of 28 patients (71%) were presented with stable complete remission and functionally preserved larynx. Of these 20 patients 3 developed pulmonary metastases, 1 secondary primary carcinoma of the lung and 3 neck metastases which needed neck dissections. The other patients showed in 4 cases relapsing tumor which was indicated for laryngectomy. One patient needed tracheotomy because of persisting edema and 2 patients died due to tumor progress. One patient died after complications due to salvage surgery. CONCLUSION: The organ preservation protocol was feasible with well tolerated early toxicity. Problems of screening for recurrent disease, salvage surgery and late toxicity should be noted and pronounced in patient information. Further studies should focus on the improvement of patient selection which could be realized by induction Chemotherapy (using new components like taxan) and/or use of prediction factors such as tumor volume and hemoglobin levels.

Adult↗

PubMed2002

[Prospective phase II study of neoadjuvant radiochemotherapy in advanced operable carcinoma of the mouth cavity. 3-year outcome].

PURPOSE: The purpose of simultaneous chemoradiotherapy is to increase local-regional control and to decrease the incidence of distant metastases. Regimens containing cisplatin/5-FU chemotherapy are widely accepted as standard treatment in advanced head and neck cancer. Most studies reported promising response and survival data, but also severe mucosal toxicity. In recent years the newly developed drug Taxol demonstrated interesting activity in head and neck cancer as a single agent as well as in combination drug regimens. In the present outpatient phase II trial, we investigated the combination of Taxol/carboplatin with 40 Gy radiotherapy in a neoadjuvant setting of operable stage III/IV squamous cell carcinoma of the oral cavity and oropharynx. PATIENTS AND METHODS: Fifty-three patients were enrolled in this trial during the period from May 1998 to October 2000 and received five cycles weekly of Taxol (40 mg/m2) and carboplatin (AUC 1.5) with conventional radiotherapy (40 Gy). Within 3-4 weeks after chemoradiotherapy resection of the primary tumor and the regional neck nodes was performed. RESULTS: Fifty-two patients were evaluable for toxicity and response. Complete response was observed in 31 of 52 patients (CR 60%), and partial remission was seen in 21 of 52 patients (PR 40%). In 30 of 52 patients complete pathologic response (pCR 58%) was documented in the resection specimens. The 1-, 2-, and 3-year overall survival rate was calculated as 84%. CONCLUSION: Our present results demonstrated impressive clinical and pathological response rates of concurrent Taxol/carboplatin and radiotherapy as a preoperative treatment modality in advanced oral and oropharyngeal cancer.

Adult↗

PubMed2001

Alteration of radiation-induced hematotoxicity by amifostine.

PURPOSE: To investigate whether amifostine can reduce radiation hematotoxicity. PATIENTS AND METHODS: Seventy-three patients undergoing radiotherapy for squamous cell carcinoma of the head and neck at the university clinics of Freiburg, Heidelberg, and Erlangen were evaluated. All received 60 Gy (50-70 Gy) at 5 x 2 Gy fractions per week employing standard techniques. Thirty-five were randomized to receive 200 mg/m(2) amifostine i.v. 30 min before radiation; 38 served as control patients. Blood counts (total n = 501) were determined before, during, and while completing radiotherapy. Changes of leukocyte, platelet, and hemoglobin levels were determined and compared using the t test. RESULTS: The blood hemoglobin level and the platelet count were not affected by irradiation, for either the amifostine-treated or control patients. Similarly, the leukocyte counts of amifostine-treated patients did not change during irradiation. However, control patients experienced a decrease in leukocyte count from 8.1 x 10(3)/mm(3) to 5.8 x 10(3)/mm(3) (difference: 2.3 x 10(3)/mm(3)). This seems to be line specific: Whereas amifostine does not affect lymphocyte count, a radiation-induced decrease of neutrophil granulocytes seems to be prevented. CONCLUSION: Amifostine protects from radiation hematotoxicity, particularly affecting the granulocytopoiesis. These data confirm results from our former study.

Amifostine↗

PubMed2001

Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy--results of a multicentric randomized German trial in advanced head-and-neck cancer.

PURPOSE: To demonstrate the efficacy of radiochemotherapy (RCT) as the first choice of treatment for advanced unresectable head-and-neck cancer. To prove an expected benefit of simultaneously given chemotherapy, a two-arm randomized study with hyperfractionated accelerated radiochemotherapy (HF-ACC-RCT) vs. hyperfractionated accelerated radiotherapy (HF-ACC-RT) was initiated. The primary endpoint was 1-year survival with local control (SLC). METHODS AND MATERIALS: Patients with Stage III and IV (UICC) unresectable oro- and hypopharyngeal carcinomas were randomized for HF-ACC-RCT with 2 cycles of 5-FU (600 mg/m(2)/day)/carboplatinum (70 mg/m(2)) on days 1--5 and 29--33 (arm A) or HF-ACC-RT alone (arm B). In both arms, there was a second randomization for testing the effect of prophylactically given G-CSF (263 microg, days 15--19) on mucosal toxicity. Total RT dose in both arms was 69.9 Gy in 38 days, with a concomitant boost regimen (weeks 1--3: 1.8 Gy/day, weeks 4 and 5: b.i.d. RT with 1.8 Gy/1.5 Gy). Between July 1995 and May 1999, 263 patients were randomized (median age 56 years; 96% Stage IV tumors, 4% Stage III tumors). RESULTS: This analysis is based on 240 patients: 113 patients with RCT and 127 patients with RT, qualified for protocol and starting treatment. There were 178 oropharyngeal and 62 hypopharyngeal carcinomas. Treatment was tolerable in both arms, with a higher mucosal toxicity after RCT. Restaging showed comparable nonsignificant different CR + PR rates of 92.4% after RCT and 87.9% after RT (p = 0.29). After a median observed time of 22.3 months, l- and 2-year local-regional control (LRC) rates were 69% and 51% after RCT and 58% and 45% after RT (p = 0.14). There was a significantly better 1-year SLC after RCT (58%) compared with RT (44%, p = 0.05). Patients with oropharyngeal carcinomas showed significantly better SLC after RCT (60%) vs. RT (40%, p = 0.01); the smaller group of hypopharyngeal carcinomas had no statistical benefit of RCT (p = 0.84). For both tumor locations, prophylactically given G-CSF was a poor prognostic factor (Cox regression), and resulted in reduced LRC (log-rank test: +/- G-CSF, p = 0.0072). CONCLUSION: With accelerated radiotherapy, the efficiency of simultaneously given chemotherapy may be not as high as expected when compared to standard fractionated RT. Oropharyngeal carcinomas showed better LRC after HF-ACC-RCT vs. HF-ACC-RT; hypopharyngeal carcinomas did not. Prophylactic G-CSF resulted in an unexpected reduced local control and should be given in radiotherapy regimen only with strong hematologic indication.

Adult↗

PubMed2001

Predictive value of the tumor oxygenation by means of pO2 histography in patients with advanced head and neck cancer.

PURPOSE: The purpose of this analysis was to evaluate the potential of the tumor oxygenation by means of Eppendorf pO2 histography as a predictive test to select patients for treatment alternatives. PATIENTS AND METHODS: Pretreatment tumor pO2 histographies of locoregional lymph node metastases were assessed in 194 patients with squamous cell carcinoma of the head and neck. Included in the analysis were 134 patients who received a primary radio- or radiochemotherapy with a radiation dose of > or = 60 Gy, and who had no distant metastasis at beginning of the therapy. RESULTS: The Cox regression analysis revealed the fraction of pO2 values < or = 2.5 mm Hg (p = 0.004), age (p = 0.04) and radiotherapy/radiochemotherapy (p = 0.03) as significant independent prognostic factors for the survival. The positive and negative predictive values were calculated using different cut-off values of the fraction of pO2 values < or = 2.5 mm Hg and the survival status at 1 or 2 years after beginning of the therapy as endpoint. The highest positive and negative predictive values of all cut-off values were 0.50 and 0.41 at 1 year, and 0.81 and 0.26 at 2 years. CONCLUSIONS: Our data confirm the influence of the tumor oxygenation on the prognosis of patients with squamous cell carcinoma of the head and neck after radiotherapy. However, the calculated positive and negative predictive values suggest that the pO2 histography alone is not sufficient to be used as a predictive test to successfully select patients for treatment alternatives.

Adult↗

PubMed2001

Overexpression of the DNA-binding domain of poly(ADP-ribose) polymerase inhibits rejoining of ionizing radiation-induced DNA double-strand breaks.

PURPOSE: To assess the influence of trans-dominant inhibition of poly(ADP-ribosyl)ation on the rejoining kinetics of radiation-induced DNA double-strand breaks (DSB). MATERIALS AND METHODS: Stable transfectants of the SV40-transformed hamster cell line CO60 were used: COM3 cells contain a construct to overexpress the poly(ADP-ribose) polymerase (PARP-1) DNA-binding domain (DBD) when induced by dexamethasone, as well as a construct for the constitutive overexpression of the human glucocorticoid receptor (Hg0). COR3 are control cells containing only the Hg0 plasmid. DSB induction and rejoining in X-irradiated cells was assessed by DNA pulsed-field electrophoresis. RESULTS: DSB induction was identical in both cell lines and independent of the presence of dexamethasone. DSB rejoining kinetics was independent of dexamethasone in COR3 cells and identical to COM3 cells without dexamethasone. However, in COM3 cells treated with dexamethasone to induce PARP-1 DBD overexpression, the fast component of the rejoining kinetic was largely reduced, and residual fragmentation increased concomitant with the increased damage fraction in slow rejoining. CONCLUSIONS: The results indicate that inhibition of cellular PARP-1 does not affect the rate-limiting step of either fast or slow DSB rejoining. Rather, it appears that absence of poly(ADP-ribosyl)ation due to dominant negative PARP-1 expression induces a shift from rapid to slow DSB rejoining and by this mechanism PARP inhibition may increase the risk of repair failures.

Animals↗

PubMed2000

Protective effect of amifostine on dental health after radiotherapy of the head and neck.

PURPOSE: The cytoprotective agent amifostine has been shown to reduce the radiation-induced acute and chronic xerostomia in head and neck cancer patients. The purpose of this study was to evaluate whether or not amifostine also reduces the incidence of dental caries associated with the radiation-induced xerostomia. METHODS AND MATERIALS: The dental status before and 1 year after radiotherapy was retrospectively compared in 35 unselected patients treated as part of the prospective randomized and multicenter open-label Phase III study (WR-38) at the University Hospitals of Heidelberg, Freiburg, and Erlangen. The WR-38 study compared radiotherapy in head and neck cancer with and without concomitant administration of amifostine. RESULTS: Patient and treatment characteristics (particularly the radiation dose and percentage of parotids included in the treatment volume) were equally distributed between the patients who received (n = 17) or did not receive (n = 18) amifostine. Fifteen patients of the amifostine group showed no deterioration of the dental status 1 year after radiotherapy as compared to 7 patients who did not receive the cytoprotector (p = 0. 015, two-tailed Fisher exact test). CONCLUSION: Our data suggest a protective effect of amifostine on the dental health after radiotherapy of the head and neck. The dental status should be used as a primary endpoint in future studies on amifostine.

Adult↗

PubMed2000

Phase III randomized trial of amifostine as a radioprotector in head and neck cancer.

PURPOSE: Radiotherapy for head and neck cancer causes acute and chronic xerostomia and acute mucositis. Amifositine and its active metabolite, WR-1065, accumulate with high concentrations in the salivary glands. This randomized trial evaluated whether amifostine could ameliorate these side effects without compromising the effectiveness of radiotherapy in these patients. PATIENTS AND METHODS: Patients with previously untreated head and neck squamous cell carcinoma were eligible. Primary end points included the incidence of grade > or =2 acute xerostomia, grade > or =3 acute mucositis, and grade > or =2 late xerostomia and were based on the worst toxicity reported. Amifostine was administered (200 mg/m(2) intravenous) daily 15 to 30 minutes before irradiation. Radiotherapy was given once daily (1.8 to 2.0 Gy) to doses of 50 to 70 Gy. Whole saliva production was quantitated preradiotherapy and regularly during follow-up. Patients evaluated their symptoms through a questionnaire during and after treatment. Local-regional control was the primary antitumor efficacy end point. RESULTS: Nausea, vomiting, hypotension, and allergic reactions were the most common side effects. Fifty-three percent of the patients receiving amifostine had at least one episode of nausea and/or vomiting, but it only occurred with 233 (5%) of 4,314 doses. Amifostine reduced grade > or =2 acute xerostomia from 78% to 51% (P<.0001) and chronic xerostomia grade > or = 2 from 57% to 34% (P=.002). Median saliva production was greater with amifostine (0.26 g v 0.10 g, P=.04). Amifostine did not reduce mucositis. With and without amifostine, 2-year local-regional control, disease-free survival, and overall survival were 58% versus 63%, 53% versus 57%, and 71% versus 66%, respectively. CONCLUSION: Amifostine reduced acute and chronic xerostomia. Antitumor treatment efficacy was preserved.

Adult↗

PubMed2000

Prognostic relevance of serum levels of the angiogenic peptide bFGF in advanced carcinoma of the head and neck treated by primary radiochemotherapy.

BACKGROUND: The objective of this trial was to analyze the prognostic relevance of the angiogenic peptides basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-2 (MMP-2) in the serum of patients with advanced carcinoma of the head and neck treated by primary radiochemotherapy. METHODS: From 1992 to 1995, 26 patients with advanced head and neck cancer (25 stage IV, 1 stage III UICC) were treated according to the protocol of radiochemotherapy with carboplatin. The pretreatment serum levels VEGF, bFGF, and MMP-2 were measured by ELISA, and data were correlated with tumor characteristics and followed up (median time of follow up, 60 months). RESULTS: An increase in bFGF serum level above the upper limit of normal controls showed a significant correlation with shorter time the of locoregional control (p =.036). In covariant analysis bFGF serum concentration proved to be independent of other prognostic factors like tumor site, age, total tumor volume, and response to therapy. No prognostic relevance of VEGF and MMP-2 serum levels could be determined. CONCLUSIONS: The results of this pilot study indicate that the serum concentration of bFGF has prognostic relevance for advanced head and neck cancer.

Adult↗

PubMed2000

[Prognostic value of hemoglobin level for primary radiochemotherapy of head-neck carcinomas].

The pretherapeutic hemoglobin level (Hb) has been postulated to constitute a prognostic marker for outcome after primary chemoradiation of patients with advanced cancer of the head and neck. However, this hypothesis has not been tested systematically in large study samples. In the years 1992-1997, 125 patients with advanced head and neck cancer (stages III/IV UICC) were treated with primary chemoradiation in two different prospective multicentric trials, 62 patients in trial A (phase II, 1992-1995), and 63 in trial B (phase III, 1995-1997). Beside initial Hb, other pretherapeutic parameters with potential prognostic relevance were assessed and correlated with clinical outcome after 43-months follow-up: total tumor volume (TTV; calculated in initial CT scans), tumor oxygenation (polarographic measurements with Eppendorf histography), TNM, tumor localization, age, and performance status. The evaluation of the clinical end points (progression-free and overall survival and local tumor control) revealed that Hb and TTV were independent parameters with strong predictive character of outcome after primary chemoradiation in both trials (n = 125). Bivariate analysis showed < median (13.5 g/dl) a hazard ratio of 2.1 (P = 0.002) for Hb; and > median (98 ml) a Hazard ratio of 2.0 (P = 0.006) for TTV. Severe anemia (Hb < 10 g/dl) was an adverse factor in three patients. Hypoxia was associated with poorer initial therapeutical response but was not predictive of clinical outcome. Furthermore, tumor oxygenation showed no correlation with Hb. The other parameters examined failed to show prognostic significance. Our results indicate a high prognostic value of initial Hb for outcome after primary chemoradiation in advanced head and neck cancer and imply a therapeutic benefit of Hb substitution or erythropoietin administration. We propose to test this in randomized clinical trials.

Adult↗

PubMed2000

Repeatability and prognostic impact of the pretreatment pO(2) histography in patients with advanced head and neck cancer.

PURPOSE: The purpose of this study was to evaluate the repeatability and the predictive relevance of the pretreatment pO(2) histography on the survival of patients with advanced head and neck cancer. PATIENTS AND METHODS: From July 1995 to August 1998, polarographic pO(2) measurements of lymph node metastases before therapy were performed in altogether 60 patients with histologically proven squamous cell carcinoma of the head and neck using the Eppendorf histograph. Forty-one of 60 patients were treated with an accelerated-hyperfractionated radiotherapy regimen with or without simultaneous chemotherapy as part of a multicenter phase III study. In 23 of 60 patients, two repeated independent measurements of the same tumor were performed with a time interval of approximately 24 h between the two measurements. RESULTS: The multivariate analysis revealed the fraction of pO(2) values </=2.5 mmHg as the only significant prognostic factor for the survival (P=0.05) in the 41 study patients. No correlation was found between tumour oxygenation and the volume of the measured lymph node metastases or the haemoglobin concentration. The coefficient of variation of the repeated measurements representing the assay variability was 57-68% of the total variation. CONCLUSION: Our data support the concept of the relevance of the pretreatment tumour hypoxia for the prognosis of patients with head and neck cancer after fractionated radiotherapy. Because of the relative poor repeatability of the pO(2) histography and the small patient number, further studies are required to confirm this finding and to evaluate the most relevant oxygenation parameter for clinical endpoints.

Adult↗

PubMed2000

Oxygenation of advanced head and neck cancer: prognostic marker for the response to primary radiochemotherapy.

Recent clinical studies suggest that the degree of tumor oxygenation may be predictive of the response of radiation therapy for cancer. In an exploratory investigation of cervical lymph node metastases in 27 patients with advanced squamous cell carcinoma of the oropharynx and hypopharynx, this relationship was investigated by means of oxygen measurements with an Eppendorf PO (2) histograph. The measurements were made before the start of radiation therapy and after the first week of therapy. Clinical response was evaluated 6 weeks after the completion of therapy. Before therapy, marked hypoxia was observed in the lymph node metastases, with a mean PO (2) value of 16.1 +/- 8.2 mm Hg and a hypoxic fraction (PO (2) < 10 mm Hg) of 56.4% +/- 20.0%. After the first week of radiation (9 Gy) there was a general reoxygenation (DeltaPO (2) = 5.0 +/- 10.1 mm Hg, P < 0.05; Deltahypoxic fraction = -11.3% +/- 31.3%, P = 0.11). A relationship between the degree of reoxygenation and tumor response was not observed. Patients without at least partial lymph node response (n = 8) showed poorer pretherapeutic oxygenation (PO (2) mean = 11.1 +/- 2.9 mm Hg) than those who responded to the therapy (n = 19, PO (2) mean = 18.2 +/- 8.8 mm Hg). In this investigation of a defined set of patients with advanced carcinoma of the oropharynx and hypopharynx, we found that pretherapeutic oxygenation data are predictive for the therapeutic response to radiation therapy or radiochemotherapy.

Adult↗

PubMed2000

Prognostic assessment of sonography and tumor volumetry in advanced cancer of the head and neck by use of doppler ultrasonography.

OBJECTIVE: The objective of this trial was to examine the degree of tumor vascularity in lymph node metastases as depicted by computer-assisted color Doppler sonography and the tumor volumes associated with prognosis in carcinomas of the oropharynx and hypopharynx after primary radiochemotherapy. PATIENTS AND METHODS: In a prospective trial, 25 patients with advanced squamous cell carcinomas of the oropharynx and hypopharynx (stage IV UICC 1997) were treated with radiochemotherapy. The color Doppler findings were quantified with a computer-assisted protocol that quantitatively describes color Doppler images by the relative color pixel density (CPD). As important prognostic cofactor, total tumor volume (TTV) was calculated from CT sections and related to the degree of vascularity. RESULTS: Low CPD in neck metastases showed a correlation with better overall survival. A high-CPD group and a high-TTV group (median survival 10.1 months) were determined and were compared with all other CPD/TTV combinations (median survival 28.4 months); the difference in survival was significant (P = 0.002). CONCLUSION: The results indicate that high tumor vascularity in combination with high TTV indicates a particularly bad prognosis in patients treated with primary radiochemotherapy for head and neck cancer.

Adult↗

PubMed1999

Alterations of intratumoral pharmacokinetics of 5-fluorouracil in head and neck carcinoma during simultaneous radiochemotherapy.

The kinetics of local drug uptake and metabolism of the anticancer drug 5-fluorouracil (5-FU) has been monitored by means of 19F nuclear magnetic resonance spectroscopy in 17 patients with neck tumors during concurrent radiochemotherapy. All of the patients underwent an accelerated hyperfractionated, concomitant-boost radiochemotherapy with 5-FU [600 or 1000 mg/m2 of body surface (b.s.)] and carboplatin (70 mg/m2 of b.s.). Serial 19F nuclear magnetic resonance spectra were obtained during and after the administration of 5-FU in a 15-T scanner with the use of a 5-cm diameter surface coil positioned on a cervical lymph node metastasis. Examinations were performed at day 1 of therapy and, in 13 patients, also after 43.5 Gy of irradiation at day 1 of the second chemotherapy cycle. Resonances of 5-FU and the catabolites 5,6-dihydro-5-fluorouracil (DHFU) and alpha-fluoro-beta-alanine (FBAL) were resolved in the tumor spectra. The median of the 5-FU and FBAL levels was significantly higher (more than 2-fold) at the second compared with the first examination, whereas the level of DHFU did not change. This effect could indicate an increased delivery of 5-FU into the interstitial space of the tumor in the course of the combined treatment, which would result in an enhanced exposure of the tumor cells to the drug. A potential mechanism for synergy between radio- and chemotherapy is discussed, but alternative mechanisms are also being considered. The findings indicate that a method is available to rationally address the design of dosing schedules in concurrent therapy regimens.

Adult↗