Prognostic factors and a survival score for patients with metastatic spinal cord compression from colorectal cancer.

BACKGROUND: This study aimed to identify independent prognostic factors and to create a survival score for patients with metastatic spinal cord compression (MSCC) from colorectal cancer (CRC). PATIENTS AND METHODS: Data from 121 patients irradiated for MSCC from CRC were retrospectively analyzed. Eleven potential prognostic factors were investigated including tumor type, age, gender, Eastern Cooperative Oncology Group performance status score (ECOG-PS), number of involved vertebrae, ambulatory status prior to radiotherapy (RT), other bone metastases, visceral metastases, interval from cancer diagnosis to RT of MSCC, time of developing motor deficits prior to RT, and the RT schedule. RESULTS: On multivariate analysis, improved motor function was significantly associated with an ECOG-PS of 1-2 (p = 0.011) and a slower development of motor deficits (p < 0.001). Improved local control was significantly associated with absence of visceral metastases (p = 0.043) and longer-course RT (p = 0.008). Improved survival was significantly associated with an ECOG-PS of 1-2 (p < 0.001), ambulatory status (p < 0.001), absence of visceral metastases (p < 0.001), and a slower development of motor deficits (p = 0.047). These four prognostic factors were included in a survival score. The score for each factor was determined by dividing the 6-month survival rate by 10. The prognostic score represented the sum of the factor scores. Four prognostic groups were designed; the 6-month survival rates were 0% for 8-12 points, 26% for 13-18 points, 62% for 20-23 points, and 100% for 24-27 points (p < 0.001). CONCLUSION: This study identified several independent prognostic factors for treatment outcomes in patients irradiated for MSCC from CRC. The survival prognosis of these patients can be estimated with a new score.

Impact of zoledronic acid on control of metastatic spinal cord compression.

BACKGROUND: Zoledronic acid was demonstrated to reduce the rate of skeletal-related events, a hypernym including various outcomes, in patients with bone metastases. In contrast to other studies, this matched-pair analysis focused solely on the impact of zoledronic acid on metastatic spinal cord compression (MSCC). PATIENTS AND METHODS: Data from 98 patients with MSCC receiving radiotherapy plus zoledronic acid were matched 1:2 to 196 patients receiving radiotherapy alone for ten potential prognostic factors. Both groups were compared for local control of MSCC within the irradiated region, overall control of MSCC (local and distant MSCC control), and survival. RESULTS: The 1-year local control rates were 90% after radiotherapy plus zoledronic acid and 81%, after radiotherapy alone (p = 0.042). The 1-year overall control rates were 87% and 75%, respectively (p = 0.016), and the 1-year survival rates were 60% and 52%, respectively (p = 0.17). Results were significant in the Cox proportional hazards model regarding local control (p = 0.024) and overall control (p = 0.008). CONCLUSION: According to the results of this study, zoledronic acid was associated with improved control of MSCC in irradiated patients.

Prognostic factors for local control and survival in patients with spinal cord compression from myeloma.

BACKGROUND: This retrospective study aimed to identify prognostic factors for local control and survival in 214 patients irradiated for spinal cord compression (SCC) from myeloma. PATIENTS AND METHODS: Ten potential prognostic factors were investigated including age, gender, Eastern Cooperative Oncology Group performance score (ECOG-PS), number of involved vertebrae, ambulatory status, other osseous lesions, extraosseous lesions, interval from first diagnosis of myeloma to SCC, time developing motor deficits before radiotherapy (RT), and the RT schedule (short-course vs. long-course RT). RESULTS: On univariate analysis, no factor was associated with local control of SCC. Survival was associated with ECOG-PS (p < 0.001), ambulatory status (p < 0.001), other osseous lesions (p < 0.001), and extraosseous lesions (p < 0.001). On multivariate analysis, these prognostic factors maintained significance. CONCLUSION: New independent prognostic factors were identified for survival after RT of SCC from myeloma. These factors can help tailor treatment to the individual patient.

Prognostic factors in a series of 504 breast cancer patients with metastatic spinal cord compression.

BACKGROUND: This study was performed to identify new significant prognostic factors in breast cancer patients irradiated for metastatic spinal cord compression (MSCC). PATIENTS AND METHODS: The data of 504 patients with breast cancer patients with MSCC were retrospectively analyzed with respect to posttreatment motor function, local control of MSCC, and survival. The investigated potential prognostic factors included age, Eastern Cooperative Oncology Group (ECOG) performance score, number of involved vertebrae, other bone metastases, visceral metastases, pretreatment ambulatory status, interval from cancer diagnosis to radiotherapy of MSCC, time developing motor deficits before radiotherapy, and the radiation schedule. RESULTS: On multivariate analysis, better functional outcome was associated with ambulatory status prior to RT (estimate - 1.29, p < 0.001), no visceral metastases (estimate - 0.52, p = 0.020), and slower development of motor deficits (estimate + 2.47, p < 0.001). Improved local control was significantly associated with no other bone metastases (risk ratio (RR) 4.33, 95% confidence interval (CI) 1.36-14.02, p = 0.013) and no visceral metastases (RR 3.02, 95% CI 1.42-6.40, p = 0.005). Improved survival was significantly associated with involvement of only 1-2 vertebrae (RR 1.27, 95% CI 1.01-1.60, p = 0.044), ambulatory status before radiotherapy (RR 1.75, 95% CI 1.23-2.50, p = 0.002), no other bone metastases (RR 1.93, 95% CI 1.18-3.13, p = 0.009), no visceral metastases (RR 7.60, 95% CI 5.39-10.84, p < 0.001), and time developing motor deficits before radiotherapy (RR 1.55, 95% CI 1.30-1.86, p < 0.001). CONCLUSION: Several new independent prognostic factors were identified for treatment outcomes. These prognostic factors should be considered in future trials and may be used to develop prognostic scores for breast cancer patients with MSCC.

Metastatic spinal cord compression in non-small cell lung cancer patients. Prognostic factors in a series of 356 patients.

BACKGROUND: Patients with metastatic spinal cord compression (MSCC) from non-small cell lung cancer (NSCLC) have an unfavorable prognosis compared to most other MSCC patients. This study was performed to identify prognostic factors for functional outcome and survival in these patients after radiotherapy (RT) alone. PATIENTS AND METHODS: Data of 356 patients irradiated for MSCC from NSCLC were retrospectively analyzed. Ten potential prognostic factors were investigated including age, gender, Eastern cooperative Oncology Group performance score (ECOG-PS), number of involved vertebrae, pre-RT ambulatory status, other bone metastases, visceral metastases, interval from cancer diagnosis to RT of MSCC, time developing motor deficits before RT, and the radiation schedule. RESULTS: On multivariate analysis, better functional outcome was associated with pre-RT ambulatory status (estimate: - 0.84, p = 0.022), no visceral metastases (estimate: - 1.15, p < 0.001), interval from cancer diagnosis to RT of > 15 months (estimate: + 0.48, p = 0.019), and slower (> 7 days) development of motor deficits (estimate: + 1.56, p < 0.001). On multivariate analysis, improved survival was significantly associated with female gender (risk ratio (RR) 1.32, p = 0.043), ECOG-PS 1-2 (RR 1.45, p = 0.034), pre-RT ambulatory status (RR 0.58, p < 0.001), no other bone metastases (RR 1.38, p = 0.010), no visceral metastases (RR 2.87, p < 0.001), interval from cancer diagnosis to RT of > 15 months (RR 0.84, p = 0.035), and slower (> 7 days) development of motor deficits (RR 0.78, p < 0.001). CONCLUSION: This study identified additional independent prognostic factors for outcomes after radiotherapy of MSCC from NSCLC. These prognostic factors can be used for stratification in future trials and can help develop prognostic scores for MSCC from NSCLC.

A survival score for patients with metastatic spinal cord compression from prostate cancer.

BACKGROUND: This study aimed to develop and validate a survival scoring system for patients with metastatic spinal cord compression (MSCC) from prostate cancer. PATIENTS AND METHODS: Of 436 patients, 218 patients were assigned to the test group and 218 patients to the validation group. Eight potential prognostic factors (age, performance status, number of involved vertebrae, ambulatory status, other bone metastases, visceral metastases, interval from cancer diagnosis to radiotherapy of MSCC, time developing motor deficits) plus the fractionation regimen were retrospectively investigated for associations with survival. Factors significant in the multivariate analysis were included in the survival score. The score for each significant prognostic factor was determined by dividing the 6-month survival rate (%) by 10. The total score represented the sum of the scores for each factor. The prognostic groups of the test group were compared to the validation group. RESULTS: In the multivariate analysis of the test group, performance status, ambulatory status, other bone metastases, visceral metastases, and interval from cancer diagnosis to radiotherapy were significantly associated with survival. Total scores including these factors were 20, 21, 22, 24, 26, 28, 29, 30, 31, 32, 33, 35, 37, or 39 points. In the test group, the 6-month survival rates were 6.5% for 20-24 points, 44.6% for 26-33 points, and 95.8% for 35-39 points (p < 0.0001). In the validation group, the 6-month survival rates were 7.4%, 45.4%, and 94.7%, respectively (p < 0.0001). CONCLUSIONS: Because the survival rates of the validation group were almost identical to the test group, this score can be considered valid and reproducible.

Do elderly patients benefit from surgery in addition to radiotherapy for treatment of metastatic spinal cord compression?

BACKGROUND: Treatment of elderly cancer patients has gained importance. One question regarding the treatment of metastatic spinal cord compression (MSCC) is whether elderly patients benefit from surgery in addition to radiotherapy? In attempting to answer this question, we performed a matched-pair analysis comparing surgery followed by radiotherapy to radiotherapy alone. PATIENTS AND METHODS: Data from 42 elderly (age > 65 years) patients receiving surgery plus radiotherapy (S + RT) were matched to 84 patients (1:2) receiving radiotherapy alone (RT). Groups were matched for ten potential prognostic factors and compared regarding motor function, local control, and survival. Additional matched-pair analyses were performed for the subgroups of patients receiving direct decompressive surgery plus stabilization of involved vertebrae (DDSS, n = 81) and receiving laminectomy (LE, n = 45). RESULTS: Improvement of motor function occurred in 21% after S + RT and 24% after RT (p = 0.39). The 1-year local control rates were 81% and 91% (p = 0.44), while the 1-year survival rates were 46% and 39% (p = 0.71). In the matched-pair analysis of patients receiving DDSS, improvement of motor function occurred in 22% after DDSS + RT and 24% after RT alone (p = 0.92). The 1-year local control rates were 95% and 89% (p = 0.62), and the 1-year survival rates were 54% and 43% (p = 0.30). In the matched-pair analysis of patients receiving LE, improvement of motor function occurred in 20% after LE + RT and 23% after RT alone (p = 0.06). The 1-year local control rates were 50% and 92% (p = 0.33). The 1-year survival rates were 32% and 32% (p = 0.55). CONCLUSION: Elderly patients with MSCC did not benefit from surgery in addition to radiotherapy regarding functional outcome, local control of MSCC, or survival.

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.

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.

MRI and Ultrasonography for assessing multifocal disease and tumor size in breast cancer: Comparison with histopathological results.

UNLABELLED: The purpose of the study was to compare the accuracy of breast MRI and ultrasonography in assessing the tumor focality and tumor size of newly diagnosed non-high risk breast cancer patients. METHODS: The tumor focality status and the maximal tumor diameter by MRI and ultrasonography were retrospectively compared with the corresponding histopathological findings as reference. Test characteristics concerning the tumor focality status were calculated. Bland-Altman plots were generated to evaluate the agreement of the tumor size measurements by imaging and histopathology. The t-test for dependent samples and the Fisher exact test were used to test differences between groups for statistical significance. The Pearson correlation coefficient r was calculated to measure the degree of association between the tumor diameter by imaging and histopathology. RESULTS: Sixty-four patient diagnosed between 2011 and 2013 were analyzed. MRI showed a good sensitivity of 83% for detecting multifocal disease (ultrasonography, 75%). The positive predictive value was 67% and the ratio of true-positive to false-positive findings 2.0. MRI showed better limits of agreement (-21 to 26 mm versus -29 to 26 mm) and a better correlation (r=0.77 versus r=0.66) with the histopathological tumor diameter compared to ultrasonography. The mean differences between the tumor diameter by MRI and histopathology and ultrasonography and histopathology were not significantly different (p=0.09). The T classification (T1a, T1b, T1c, T2, T3) was correctly estimated by MRI in 43 patients (67.2%) and by ultrasonography in 39 patients (60.9%) (p=0.58). CONCLUSION: In our patient cohort only a modest diagnostic advantage of MRI compared to ultrasonography could be detected.

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.

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.

Predictive value of the flow cytometric PCNA assay (proliferating cell nuclear antigen) in head and neck tumors after accelerated-hyperfractionated radiochemotherapy.

PURPOSE: Proliferation of tumor cells during radiotherapy may limit tumor control, especially in rapidly proliferating tumors such as head and neck carcinomas. We present a flow cytometric method for detection of PCNA in solid head and neck tumors and how these data correlate with outcome. METHODS AND MATERIALS: Pretherapeutic biopsies of 20 inoperable patients with Stage IV squamous cell carcinoma were examined. Biparametric flow cytometry was done after anti-PCNA (PC10) and propidium iodine staining were performed. PCNA index (percentage PCNA positive cells), DNA index, and S phase fraction (SPF, euploid tumors only) were determined. The therapy consisted of an accelerated-hyperfractionated radiochemotherapy (66 Gy/5 weeks, concomitant boost of 1.6 Gy/day in weeks 4+5, Carboplatin 5 x 70 mg/m2 in weeks 1+5). The median follow-up time was 30 months. RESULTS: Fourteen patients suffered from disease progession and 12 died. Median actuarial, cause-specific survival, and disease-free survival (DFS) times were 17 and 9 months, respectively. PCNA indices ranged from 4 to 70% (median 9%); there were 7 aneuploid and 13 euploid tumors. SPF ranged from 4 to 14.5% (median 10.5%). Neither SPF nor ploidy had a significant influence on outcome. Patients were divided according to PCNA index in higher (n = 10) and lower (n = 10) than the median. Survival and DFS were 13 and 6 months for the group >9% and 20 and 15 months for the group <9%. The difference in DFS was significant (p = 0.03, log rank test). CONCLUSION: These results fall in line with other studies showing the influence of pretherapeutic proliferation on outcome after radiotherapy. Although the moderately accelerated therapy regimen certainly reduces the influence of proliferation on outcome, patients with faster proliferating tumors still have a worse outcome. DFS is the more relevant endpoint in this study because of effective salvage therapies, which influence survival.

Combined error of patient positioning variability and prostate motion uncertainty in 3D conformal radiotherapy of localized prostate cancer.

PURPOSE: To measure the patient positioning and prostate motion variability and to estimate its influence on the calculated 3D dose distribution in 3D conformal radiotherapy of patients with localized prostate carcinoma. METHODS AND MATERIALS: Patient positioning variability was determined retrospectively by comparing 54 orthogonal simulator films with 125 corresponding portal films from 27 patients. Prostate motion variability was determined by 107 computed tomography (CT) examinations with a CT simulator in 28 patients during radiotherapy. RESULTS: In each observed direction, the patient positioning variability and prostate motion showed a normal distribution. This observation enabled the calculation of a combined error of both components. The standard deviation (1 SD) of the patient positioning error in three directions ranged from 3.1 to 5.4 mm; the prostate motion variability was significantly greater in the anterior-posterior direction (1 SD = 2.8 mm) than in the mediolateral direction (1 SD = 1.4 mm). The 1 SD of the estimated combined error was in the anterior-posterior direction 6.1 mm and in mediolateral direction 3.6 mm. CONCLUSION: The range of patient positioning variability and prostate motion were statistically predictable under the patient setup conditions used. Dose-volume histograms demonstrating the influence of the combined error of both components on the calculated dose distribution are presented.

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.

Glucose uptake, perfusion, and cell proliferation in head and neck tumors: relation of positron emission tomography to flow cytometry.

The uptake of 18F-Deoxyglucose (FDG) was studied in vivo in relation to the proliferation rate of human head and neck tumors. Forty-two patients with histologically proven squamous-cell carcinoma of the head and neck and four patients with metastases of head and neck tumors were examined with PET and FDG prior to surgery. In 35 of these patients, a flow cytometric analysis of the DNA content and the proliferation rate was done using one-dimensional flow cytometry rate was done using one-dimensional flow cytometry (DAPI staining). In 17 cases, perfusion studies with 15O-labeled water were performed. Twenty-seven specimens were evaluable by flow cytometry. The analysis of the distribution of the FDG uptake revealed two groups, showing a high and a lower uptake pattern. In both groups the FDG uptake and the proliferation rate were correlated with an r-value of 0.64 and 0.8 respectively. However, the slope of the regression function was flat. No correlation was found between the perfusion and the proliferation rate. It is suggested that these differences in uptake in histologically identical tumor populations may correspond to differences at the molecular level, e.g., differences in the amount of the glucose carrier, perhaps caused by oncogenic transformation.

In vitro radiosensitivity of primary human fibroblasts. Lack of correlation with acute radiation toxicity in patients with head and neck cancer.

BACKGROUND AND PURPOSE: There is a considerable hope among clinicians and radiobiologists to detect genetically radiosensitive patients prior to radiotherapy. A predictive assay would enable adjustment of the total irradiation dose to the individual at a constant risk of normal tissue complications. In this prospective study, the clonogenic survival assay for primary human fibroblasts to determine radiosensitivity in vitro was evaluated and then correlated with clinically observed acute radiation reactions. MATERIALS AND METHODS: One hundred twenty-five independent survival experiments with primary fibroblasts derived from 63 biopsies from 55 cancer and non-cancer patients were performed. RESULTS: A wide variation of cell survival between biopsies was detected. Statistical analysis revealed a highly significantly larger interindividual than intraindividual variation of SF2 values. However, a considerable scatter of SF2 values in repeated experiments was observed in individual cases. Age, gender, disease status (cancer patient, non-cancer patient) and origin of fibroblasts (skin, periodontal tissue) were demonstrated not to be statistically significant confounding factors on the intrinsic radiosensitivity in vitro. In a prospective study, no correlation of the SF2 and acute reactions in 25 patients with head and neck cancer treated with a primary accelerated radiochemotherapy was detected. CONCLUSION: Our data show that the clonogenic assay is able to distinguish between intrinsic radiosensitivities of primary human fibroblasts if a statistical approach is used but does not predict acute radiation toxicity.

Influence of the positioning error on 3D conformal dose distributions during fractionated radiotherapy.

The influence of patient immobilization error on 3D planned conformal radiation therapy in tumors of the thorax and pelvis was studied. The mean positioning error in 43 patients with carcinomas of the thorax and pelvis undergoing 3D conformal radiotherapy (laser supported alignment, no immobilization device) was measured. A total of 194 portal films were superposed with the corresponding simulator radiographs according to anatomic landmarks and using a subtrascope. x-, y- and z-axis deviation was determined within a coordinate system. Using specialized software including Fourier transformation the mean positioning error was employed to recalculate the dose distributions of all cases under the influence of random (Gaussian) immobilization uncertainty. The mean two-dimensional positioning error using the data from all patients was 5.5 (+/- 3.7) mm. The distribution was Gaussian. Dose volume histograms (DVHs) of each patient with and without consideration of positioning uncertainty were compared on the base of tumor control probability estimations (TCP) using published DVH reduction and TCP algorithms. Inclusion of the positioning error resulted in a mean decrease in TCP (given as the difference between the TCP assuming no positioning error and the TCP modified by the positioning error) of 2% in a series of esophagus carcinomas and of 5% in the prostate carcinomas when looking at gross tumor volume (GTV), only. Planning target volume (PTV) exhibited a relative decrease in TCP of 5% and 11%, respectively.

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

Prognostic impact of total tumor volume and hemoglobin concentration on the outcome of patients with advanced head and neck cancer after concomitant boost radiochemotherapy.

PURPOSE: To identify prognostic clinical and treatment related factors for local control, distant metastasis-free survival, and survival by means of a multivariate analysis in patients with advanced squamous cell carcinoma of the head and neck after concomitant boost radiochemotherapy. PATIENTS AND METHODS: From 1992 to 1995, 68 patients with squamous cell cancer of the head and neck (93% stage IV disease) were treated with a simultaneous radiochemotherapy with Carboplatin using a concomitant boost technique. The total tumor volume (TTV) was quantitatively determined based on computed tomography scans in 56 patients. A Cox proportional hazards regression analysis was performed for each of the above endpoints and statistical significance of the Cox models was verified using the likelihood ratio test and Bonferroni correction for multiple testing. RESULTS: The survival and locoregional control rates at three years were 35 and 32%. The multivariate analysis revealed a significant association between the TTV and survival (P = 0.0008) and between the pretreatment serum hemoglobin concentration and locoregional control (P = 0.01) and survival (P = 0.05). The locoregional control was significantly associated with the N-stage (P = 0.007) and there was a good correlation between the N-stage and TTV in this study population. CONCLUSION: Our data corroborate the prognostic relevance of the tumor volume and hemoglobin concentration. In studies comparing the survival of patients with advanced cancer of the head and neck, the use of the TTV as a covariable may improve the statistical power.