Increasing toxicity during neoadjuvant radiochemotherapy as positive prognostic factor for patients with esophageal carcinoma.

The aim of this study was to correlate acute organ toxicity during preoperative radiochemotherapy with overall survival and tumor regression for patients with primarily operable esophageal carcinoma. From 1995 to 2002, 60 patients with primarily operable esophageal carcinoma were treated in a preoperative setting at our department. Thirty-three percent of the patients had International Union against Cancer (UICC)-stage II tumors, 62% had UICC-stage III tumors, and 5% had UICC-stage IVA tumors. All patients received irradiation (40 Gy at 2 Gy/fraction). Chemotherapy for all patients with adenocarcinoma and, from 2001, also for patients with squamous cell carcinoma consisted of two cycles, 5-fluorouracil and cisplatinum; between 1995 and 2001, patients with squamous cell carcinoma received three courses of chemotherapy (folinic acid, etoposide, 5-fluorouracil, and cisplatinum every 3 weeks) before and further cisplatinum and etoposide during radiotherapy. We found a significant correlation between acute organ toxicity and histopathological tumor regression, as well as overall survival. The probability to achieve tumor regression grade 1 after radiochemotherapy was nearly four times higher for patients with worsening of odynophagia than for those without an increase (odds ratio: 3.97). Patients with worsening of odynophagia had a 5-year overall-survival rate of 66% compared with 39% in patients without (P = 0.048). Our data indicate that normal tissue and tumor tissue may behave similar with respect to treatment response, as acute organ toxicity showed to be an independent prognostic marker in our patient population. The hypothesis should be further analyzed on biomolecular and clinical level in future clinical trials.

Fractionated external beam radiotherapy of skull base metastases with cranial nerve involvement.

BACKGROUND AND PURPOSE: Skull base metastases frequently appear in a late stage of various tumor entities and cause pain and neurological disorders which strongly impair patient quality of life. This study retrospectively analyzed fractionated external beam radiotherapy (EBRT) as a palliative treatment approach with special respect to neurological outcome, feasibility and acute toxicity. PATIENTS AND METHODS: A total of 30 patients with skull base metastases and cranial nerve disorders underwent EBRT with a mean total dose of 31.6 Gy. Neurological status was assessed before radiotherapy, during radiotherapy and 2 weeks afterwards categorizing orbital, parasellar, middle fossa, jugular foramen and occipital condyle involvement and associated clinical syndromes. Neurological outcome was scored as persistence of symptoms, partial response, good response and complete remission. Treatment-related toxicity and overall survival were assessed. RESULTS: Before EBRT 37 skull base involvement syndromes were determined with 4 patients showing more than 1 syndrome. Of the patients 81.1 % responded to radiotherapy with 10.8 % in complete remission, 48.6 % with good response and 21.6 % with partial response. Grade 1 toxicity of the skin occurred in two patients and grade 1 hematological toxicity in 1 patient under concurrent chemoradiotherapy. Median overall survival was 3.9 months with a median follow-up of 45 months. CONCLUSION: The use of EBRT for skull base metastases with symptomatic involvement of cranial nerves is marked by good therapeutic success in terms of neurological outcome, high feasibility and low toxicity rates. These findings underline EBRT as the standard therapeutic approach in the palliative setting.

Second primary malignancies in head and neck cancer patients: high prevalence of curable-stage disease.

BACKGROUND AND PURPOSE: Patients treated for squamous cell carcinoma of the head and neck (HNSCC) carry a high risk of second primary malignancies (SPM). Recently, computed tomography (CT) of the chest was shown to significantly decrease the risk of death due to bronchial carcinoma (BC) in a cohort of smokers whose risk of BC is increased but might be lower than that of patients previously treated for HNSCC. Thus, the present study evaluated the potential benefit of CT and other examinations in the detection of SPM in HNSCC patients. PATIENTS AND METHODS: Between July 2008 and November 2011, 118 participants underwent a prospective, systematic examination for SPM (13 women, 105 men, median age 62 years). All patients had been previously treated for HNSCC and showed no recurrence or distant metastases at the time of the study start. CT scans, ear-nose-throat endoscopy, and endoscopy of the esophagus and stomach were performed. RESULTS: Overall, 33 suspicious findings were clarified by additional investigations. In all, 26 SPM were confirmed in 21 of 118 patients (18%; 10 lung, 7 HNSCC, 3 gastrointestinal, 1 renal). Eighteen of these 21 patients (86%) underwent therapy with curative intent. CONCLUSION: The examinations revealed a high prevalence of curable stage SPM in HNSCC patients. Adapting a surveillance scheme including a chest CT is recommended.

Testicular radiation dose after multimodal curative therapy for locally advanced rectal cancer. Influence on hormone levels, quality of life, and sexual functioning.

PURPOSE: The purpose of the current work was to prospectively measure the influence of testicular radiation dose on hormone levels, quality of life (QoL), and sexual functioning following multimodal therapy (neoadjuvant radiochemotherapy, surgery, and adjuvant chemotherapy) for rectal cancer. PATIENTS AND METHODS: From November 2007 to November 2009, 83 male patients were treated at the University of Goettingen with radiochemotherapy (RCT) for locally advanced rectal cancer [total dose 50.4 Gy, concomitant chemotherapy with two cycles of 5-fluorouracil (FU) or 5-FU and oxaliplatin]. Testicular radiation doses were analyzed and correlated with hormone levels [luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone and free androgen index (FAI) serum levels], QoL, and sexual functioning, which were determined before and up to 1 year after RCT. RESULTS: Mean dose at the testes was 3.9 Gy (range 0.28-11.98 Gy). It was higher for tumors located < 6 cm from the anocutaneous line (p < 0.05). One year after therapy, testosterone, the testosterone/LH ratio, and the FAI/LH ratio were significantly decreased (3.5-3.0 µg/l, 0.9-0.4, 7.9-4.5, respectively) while LH and FSH (4.2-8.5 IU/l, 6.0-21.9 IU/l) were increased. QoL and sexual functioning were significantly impaired. However, there was no statistical correlation between testicular radiation dose and changes in hormone levels, QoL, or sexual functioning. CONCLUSION: Multimodal treatment for rectal cancer including RCT leads to hormone level changes and to impaired QoL and sexual functioning. However, because there was no apparent correlation between the analyzed parameters, QoL is probably also influenced by other factors, e.g., psychosocial aspects.

Mediastinal radiotherapy after multidrug chemotherapy and prophylactic cranial irradiation in patients with SCLC--treatment results after long-term follow-up and literature overview.

INTRODUCTION: Curative therapy for patients with small-cell lung cancer (SCLC) is based on multidrug chemotherapy combinations and radiotherapy. After a long time follow-up, the aim of the study was to evaluate the efficacy and toxicity of sequential chemo-radiotherapy and the effect of prophylactic cranial irradiation (PCI). METHODS: From 1995-2005, 96 patients with SCLC (64 limited-disease [LD], 32 extensive-disease [ED]; median age 61 years [range 39-79]) were treated at our department with varying chemotherapy regimens and sequential mediastinal radiotherapy (50 Gy + 10 Gy boost in case of residual disease after chemotherapy). Afterwards, 15 patients with LD, good general condition and at least partial response after local treatment received PCI (30 Gy). RESULTS: After a median follow-up of 78.6 months, 20 patients remained alive (20.8%, median survival time 18.2 months). The 2-/5-year overall survival rates were 33.8% and 12.6%, the 2-/5-year loco-regional control rates were 30.3% and 24.5%, respectively. Distant metastases occurred in 43 patients (24 cerebral). Cerebral metastasis occurred in 6.7% and 27.2% of the patients with PCI and without PCI respectively. Only tumor stage showed a statistically significant impact on overall survival and loco-regional control in multivariate analysis. Radiotherapy was well tolerated. Grade 3/4 toxicity occurred in seven patients. Prognosis of patients with SCLC remains poor. Administration of PCI in selected patients bears a decrease in the incidence of cerebral metastases. Alternative chemotherapy schemes as well as irradiation schemes and techniques should be the substance of future randomized trials.

Chemoradioimmunotherapy with 5-fluorouracil, cisplatin and interferon-alpha in pancreatic and periampullary cancer: results of a feasibility study.

BACKGROUND: Recent studies give rise to the hypothesis, that adjuvant chemoradioimmunotherapy with 5-fluorouracil (5-FU), cisplatin and interferon-alpha (IFN-alpha) might be a possible new treatment of pancreatic cancer in resected patients. We report the up-to-now experience at our institution. PATIENTS AND METHODS: Eleven patients with histological diagnosis of localized carcinoma of the pancreas (n=7) or periampullary (n=4) were prospectively analyzed. Four patients were deemed unresectable because of local invasion of adjacent organs (neoadjuvant setting) and seven patients underwent curative resection (adjuvant setting). Eight patients were classified as T3 carcinomas and three T4 carcinomas. Fifty-five per cent (6/11) of the patients presented with positive lymph node involvement. One histological Grade I, six Grade II and three Grade III were detected. External conformal irradiation to a total dose of 50.4 Gy with 1.8 Gy per day was delivered. All patients received a concomitant chemotherapy with continuous 5-FU 200 mg/m2 per day on 28 treatment days and intravenous bolus cisplatin 30 mg/m2 per week (Day 2, 9, 16, 23, 30). A recombinant r-IFN-alpha was administered on three days weekly during Week one to five of the radiotherapy course as subcutanous injections with 3*3 Mio. I.U. weekly. RESULTS: The four-year overall survival rate for all patients was 55%. In the neoadjuvant group, three of four patients died due to progressive disease; in the adjuvant group, combined chemoradioimmunotherapy lead to controlled disease in five of seven patients. The overall toxicity was well-managed. CONCLUSION: Our data strengthens the hypothesis of concomitant chemoradioimmunotherapy with 5-FU, IFN-alpha and cisplatin as a possible new treatment of pancreatic cancer in resected patients.

Irradiation leads to apoptosis of Kupffer cells by a Hsp27-dependant pathway followed by release of TNF-alpha.

In a previous publication, we were able to show that irradiation of Kupffer cells, the liver resident macrophages, leads to an increased TNF-alpha concentration in the culture medium. The pathomechanisms underlying this phenomenon, however, remained to be elucidated. Here, we show that following irradiation of Kupffer cells, the apoptosis rate increased drastically within 48 h. At the same time, the total TNF-alpha concentration in cell lysates of Kupffer cells attached to the culture plate decreased. However, normalization of the TNF-alpha concentration with respect to cell number revealed that TNF-alpha concentration per attached cell remained constant during the observation period. Western blot analysis showed that heat shock protein 27 (Hsp27) is strongly downregulated and bax is upregulated in irradiated Kupffer cells as compared to sham-irradiated cells. Overexpression of Hsp27 in Kupffer cells was shown to prevent the effect of irradiation on bax expression, apoptosis and, at the same time, on increase of TNF-alpha concentration in the Kupffer cell medium. We conclude that irradiation of Kupffer cells leads to apoptosis because of downregulation of Hsp27 and consecutive upregulation of bax expression. Furthermore, we suggest that apoptosis of Kupffer cells leads to an increase of TNF-alpha concentration in the culture medium which may be due to cell death rather than active release or synthesis.

A comparison of three-field and four-field techniques in different clinical target volumes in prostate cancer irradiation using dose volume histograms: a prospective three-dimensional analysis.

The purpose of the current study was to quantitatively assess differences between irradiation techniques on normal tissue exposure in different clinical target volumes (CTVs) in irradiation of prostate cancer. 14 patients with prostate cancer undergoing external beam radiotherapy were investigated. The prostate and prostate + proximal/entire seminal vesicles were delineated as CTVs. A three-field and two different four-field plans were generated and compared concerning rectum, bladder and femoral head dose-volume histograms (DVHs). The exposure of the rectum exposed to 40-60 Gy was significantly lower for all CTVs with the three-field technique compared with both four-field techniques. The exposure of the rectum to 70 Gy was significantly lower for all CTVs with the weighted four-field technique compared with the unweighted four-field and three-field techniques. The weighted four-field technique was worst in bladder dose sparing for the three CTVs. Comparing the three-field and the unweighted four-field technique for irradiation of the prostate and prostate + entire seminal vesicles, no technique provided a clear advantage or disadvantage in bladder dose sparing. For irradiation of the prostate + proximal seminal vesicles the unweighted four-field technique provided the best bladder dose sparing. Concerning the exposure of the femoral heads, the three-field technique was significantly worse for the three CTVs compared with both four-field techniques. No difference was found between the unweighted and the weighted four-field techniques. In conclusion, none of the studied techniques consistently proved superior in different CTVs in prostate cancer irradiation with respect to sparing all organs at risk. The absolute differences between the three techniques were small and the clinical relevance of these findings is uncertain.

Concurrent low-dose cisplatin and thoracic radiotherapy in patients with inoperable stage III non-small cell lung cancer: a phase II trial with special reference to the hemoglobin level as prognostic parameter.

PURPOSE: To evaluate the efficacy of concurrent radiochemotherapy in patients with stage III non-small cell lung cancer (NSCLC), and to examine the effect of hemoglobin levels on survival of those patients. The negative impact of anemia on survival has been noticed for other cancer sites including the head and neck, and the uterine cervix, but it has been rarely described in NSCLC cancer patients treated with radiotherapy. METHODS: From April 1995 through March 2002, 56 patients with inoperable stage III non-small lung cancer were treated with radiotherapy consisting of 60 Gy (50 Gy+10 Gy boost) given in 30 fractions of 2 Gy daily, 5 days a week, over a period of 6 weeks, and concurrent low-dose daily chemotherapy (CHT) consisting of 6 mg/m(2) of cisplatin given Mondays-Fridays during weeks 1-2 and 5-6. All patients had stage III disease and ages ranged from 39 to 81 years old (median 63.9 years). RESULTS: The 2-year and 3-year survival rates were 34% and 16%, respectively. Patients with a pretreatment hemoglobin level superior or equal to 11.6 g/dl had a 2-year survival rate of 52% as compared to 15.5% for patients with a pretreatment hemoglobin level inferior to 11.6 g/dl (p=0.0075). Patients with higher KI (>70%) showed better survival rates than those with lower KI. Surprisingly, patients in stage IIIA did not survive significantly longer than those in stage IIIB. Hematological toxicity (grade > or =2) prevailed (25%), followed by esophageal (5.4%) and bronchopulmonary (2%) toxicity. Only three patients experienced acute grade 3 hematological toxicity. Because of acute toxic effects, irradiation was interrupted in 8 patients (14.3%) for 7-13 days (median 7.5 days). Late high-grade (> or =3) toxicity was not found. No grade 4 toxicity or treatment-related deaths were observed during this study. CONCLUSION: Our data show that concurrent radiotherapy with daily low dose cisplatin is well tolerated, and shows survival rates comparable to more aggressive treatment regimens. A combination of this chemotherapy with accelerated hyperfractionated radiotherapy might improve the results in the future. Furthermore, we could show that the hemoglobin levels prior to therapy have an influence on the prognosis, where lower levels were associated with worse outcome. Further trials should consider supplementation with erythropoietin.

Interactions between radiation and endocrine therapy in breast cancer.

Adjuvant radiotherapy and adjuvant endocrine therapy are commonly given to patients with invasive breast cancer or with ductal carcinoma in situ (DCIS). Although both therapies have been well established through a number of randomized studies, little is known about a possible interaction of both treatment modalities if they are given simultaneously. A number of in vitro studies have indicated that tamoxifen treatment might reduce the intrinsic radiosensitivity of MCF-7 breast cancer cells. Conversely, estradiol treatment increases the intrinsic radiosensitivity of MCF-7 cells. In one available animal study, an antagonistic effect of tamoxifen and ionizing radiation (XRT) could not be observed. Retrospective analyses of randomized clinical studies have not indicated an antagonistic effect of tamoxifen on the effectiveness of XRT, since local control has been consistently higher when XRT was combined with tamoxifen, compared with treatment with XRT alone, regardless of whether tamoxifen was started simultaneously with radiotherapy or after completion of radiotherapy. Currently there are no clinical data available that would suggest an adverse effect of adjuvant tamoxifen treatment started prior to or simultaneously with radiotherapy in breast cancer or DCIS. However, since an antagonistic effect of tamoxifen and simultaneous chemotherapy has been reported recently, the issue of simultaneous versus sequential radiation and tamoxifen treatment in breast cancer should be addressed in further studies.

A new conditioning regimen involving total marrow irradiation, busulfan and cyclophosphamide followed by autologous PBSCT in patients with advanced multiple myeloma.

The overall survival of patients with advanced multiple myeloma (MM) undergoing high-dose chemotherapy and autologous stem cell transplantation (SCT) depends mainly on the quality of response. Thus, to improve the response rate, a new intensified high-dose chemoradiotherapy was evaluated in a phase I/II study. After induction chemotherapy, 89 patients (median age 51 years, range 32-60 years) with MM stage II/III received a conditioning regimen with total marrow irradiation (9 Gy), busulfan (12 mg/kg) and cyclophosphamide (120 mg/kg) followed by SCT. Regimen-related toxicity according to WHO criteria and response rates defined by EBMT/IBMTR were analyzed. The main toxicity was mucositis grade III/IV in 76%, and fever grade >I in 75% of patients. Three patients developed reversible veno-occlusive disease. Transplant-related mortality was 2%. Among patients with de novo and pretreated MM, a CR rate of 48 and 41%, respectively, was documented. With a median follow-up of 45 months, the actuarial median durations of event-free survival (EFS) and overall survival (OS) after transplant were 29 and 61 months for the whole group, 36 and 85 months for patients with de novo MM, respectively. Thus, administration of this intensified conditioning regimen was associated with tolerable toxicity, a high response rate and long EFS and OS.

Lack of interferon beta-induced radiosensitization in four out of five human glioblastoma cell lines.

PURPOSE: To investigate the potential of interferon beta to enhance the cytotoxic activity of ionizing irradiation against glioma cells, and to elucidate the possible mechanisms responsible for conflicting clinical results. METHODS AND MATERIALS: Five glioblastoma cell lines (U87MG, U118MG, U373MG, MO59K, MO59J) with different radiosensitivity and genetic background were used. Experiments were performed in exponentially growing cultures, and cell survival was measured by a colony-forming assay. Cells were incubated with natural interferon beta (n-IFN-beta; 30-3000 IU/mL) for 24 h followed by single dose irradiation with 1 to 6 Gy of gamma-rays. RESULTS: Significant differences in n-IFN-beta sensitivity were found. The cell lines also differed in their radiation sensitivity, and there was no correlation between the n-IFN-beta and the radiation sensitivity. In three of five cell lines, the interaction of n-IFN-beta and irradiation was infra-additive; in one cell line, it was additive. For MO59J cells only, which are NHEJ-deficient, supra-additivity was observed. CONCLUSION: Our results confirm the remarkable heterogeneity that is characteristic of malignant glioma. The combined effect of n-IFN-beta and radiation was mostly infra-additive or additive; synergistic interaction might occur in tumor cells that already have acquired repair deficiencies because of their genetic instability, as shown for the MO59J cell line.

Effect of keratinocyte growth factor on the proliferation, clonogenic capacity and colony size of human epithelial tumour cells in vitro.

PURPOSE: The effect of recombinant human keratinocyte growth factor (rHuKGF) on the proliferation, clonogenic capacity and colony size of low-passage human epithelial tumour cells was tested in vitro. MATERIALS AND METHODS: Five tumour cell cultures derived from head and neck squamous cell carcinomas, three cultures derived from pleural effusions of carcinomas of different origin and normal human nasal epithelial cells were analysed in passages 2-4. Expression of FGF7 and its receptor (FGFR2) were determined by the RNase protection assay. Cells were incubated with rHuKGF (10-200 ng ml(-1)) 3 days before or immediately after plating for clonal growth in serum-depleted media. To determine cellular radiosensitivity, single doses of 1-8 Gy X-rays were applied. Colony formation as well as colony size, reflecting the number of cell divisions, was determined after 10-15 days of growth in rHuKGF-treated and control cells. RESULTS: Normal nasal epithelial cells showed a two- to threefold increase in the number of cell divisions due to rHuKGF-treatment. In tumour cell cultures, significant stimulation of proliferation occurred in only one of eight samples. Tumour cells expressed FGF7 mRNA and protein, and low levels of FGFR2 mRNA. The addition of rHuKGF to the medium of the tumour cell cultures influenced neither radiation-induced impairment of proliferation nor clonogenic cell survival. CONCLUSION: rHuKGF has been shown to ameliorate the radiation tolerance of normal epithelia. The minimum in vitro tumour cell response to rHuKGF compared with normal epithelial cells suggests a potential for selective protection of normal epithelia during radiotherapy. The low FGFR2 expression as well as the FGF7 expression in the tumour cells may contribute to their resistance to rHuKGF treatment.

Can contrast enhanced MRI predict the response of Graves' ophthalmopathy to orbital radiotherapy?

The purpose of this study was to try to determine by means of contrast-enhanced MRI, a subset of patients with Graves' ophthalmopathy who will not respond to orbital radiotherapy. 54 patients with Graves' ophthalmopathy were treated with orbital radiotherapy (10 x 2 Gy) and symptom relief was recorded. MRI examinations prior to radiotherapy were retrospectively evaluated for enlargement, contrast enhancement and fibrotic changes in extraocular muscles and surrounding soft tissue. Imaging data were correlated with clinical features and response. Symptom relief was observed in 61% of patients but this could not be predicted by any of the MRI signs investigated. However, there is a trend for a better treatment reponse in patients who show contrast enhancement of extraocular muscles prior to orbital radiotherapy (p=0.08). MRI could not adequately predict the efficacy of orbital radiotherapy in this group of patients. Clinical assessment of disease activity is still the most reliable method.

Monitoring of therapy in head and neck patients during the radiotherapy by measurement of Cyfra 21-1.

PURPOSE: Cyfra 21-1, measuring serum fragments of cytokeratin 19, has been found to be related to tumour stage and tumour size in patients with cervical cancer. It could be a promising marker in squamous lung cancer. We evaluated this new marker with carcinoembryonic antigen, (CEA) and squamous cell carcinoma antigen (SCC-Ag) in the monitoring of 27 patients with head and neck cancer. PATIENTS AND METHODS: The retrospective study group consisted of 27 patients, 17 not suited for surgery and 10 after laser resection. Patients were clinically staged according to the TNM-classification. The mean age of the patients was 53 years (range 37-70 years). Serum levels of each marker were studied in relation to tumour stage and clinical status of the patients during radiotherapy and 6 weeks after the end of the treatment. The clinical performance of the various assays to separate those patients with complete remission from those patients with the presence of tumour was assessed. RESULTS: Pre-treatment serum Cyfra 21-1, CEA, and SCC-Ag levels were not related to stage of disease and were not found to be predictive of tumour response. The clinical performance of post-treatment serum SCC-Ag levels in predicting the presence of tumour was not better than the Cyfra 21-1 assays. CONCLUSION: We could not conclude from this study that Cyfra 21-1 marker is an additional parameter in identifying patients at risk of residual tumour after treatment, recurrent or progressive disease. An elevation of cyfra 21-1 marker was not detectable in 70% of the cases with macroscopic tumour. Therefore, Cyfra 21-1 is not a reliable parameter for the monitoring of patients with head and neck cancer during radiotherapy.

[The role of high-energy imaging in a radiotherapy service and its incorporation in a network]. / Apport de l'imagerie de haute énergie dans un service de radiothérapie et incorporation de celle-ci dans un système en réseau.

UNLABELLED: To directly compare the clinical efficacy of electronic to film portal images and the advantages of comparing directly on the monitor the simulation image and the portal image. MATERIAL AND METHODS: This study was designed to compare clinical efficacy of electronic to film portal images acquired using a liquid matrix ion-chamber electronic portal imaging device (EPID) and a conventional film system. Two radiation oncologists served as observers and evaluated a total of 30 sets of images for three different treatment sites: lung, pelvis, and head/neck. Each set of images included a simulation image, a portal film, a video paper print of electronic portal images, and a video prints of electronic portal images. Four to six anatomical landmarks were selected from each treatment site. Each observer was asked to rate each landmark in terms of its clinical visibility and to rate the ease of making the pertinent verification decision in the corresponding electronic and film portal images with the aid of the simulation image. The time needed to obtain and analyse a conventional portal image and an EPID would be analysed for the radiotherapist and the medical technicians. RESULTS: Ratings for the visibility of landmarks and for the verification decision of treatment ports were similar for electronic and film images for most landmarks. However, vertebral bodies and several landmarks in the pelvis such as the acetabulum and pubic symphysis were more visible in the electronic portal images than in the portal film images. For the medical technicians, the EPID is more comfortable, and they do not need to develop any images. CONCLUSION: The visibility of landmarks in electronic portal images is comparable to that in film portal images. Verification of treatment ports based only on electronic portal images acquired using an electronic portal imaging device is generally achievable. Thus the integration of the EPID and simulation image in a network provides more flexibility in the daily work of a medical radiotherapy team.

Reciprocal translocations in patients with testicular seminoma before and after radiotherapy.

PURPOSE: The evaluation of radiation-induced chromosomal translocations in peripheral lymphocytes using fluorescent in situ hybridization is a promising method for retrospective dosimetry after a radiation accident. We evaluated the genomic frequency of chromosomal translocations in patients with testicular seminoma who received adjuvant radiotherapy to the retroperitoneal lymph nodes, to evaluate the time-effect relationship of radiation-induced stable aberrations after partial body irradiation. METHODS: In 13 patients, peripheral lymphocytes could be evaluated before radiotherapy and at several time points after radiotherapy. In 17 additional patients, lymphocyte samples were obtained after radiotherapy. Thirteen healthy men served as age-matched controls for the aberration frequency before radiotherapy. Fluorescent in situ hybridization was performed using whole chromosome probes against chromosomes No. 4, No. 6, and No. 7. RESULTS: Nearly all patients displayed an increased spontaneous rate of genomic translocations (F(G)) before radiotherapy compared to age-matched, healthy men. The difference was significant in the paired ranks test (p < 0.0001). After adjuvant radiotherapy, the F(G) increased 2- to 8-fold in individual patients. Within 20 months after radiotherapy, the F(G) returned to pretherapeutic levels. CONCLUSIONS: The frequency of genomic translocations after partial body irradiation is time dependent. A persistence of chromosomal aberrations, which is to be expected after total body irradiation, could not be observed. It is likely that the dose and the volume of the irradiated bone marrow are playing a role in the persistence of stable chromosomal aberrations. Patients with testicular seminoma displayed an increased frequency of spontaneous genomic translocations before the initiation of radiotherapy. This chromosomal instability might be related to the known increased rate of secondary cancers in this patient group.

Radiotherapy combined with simultaneous chemotherapy with mitomycin-C and 5-fluorouracil for inoperable head and neck cancer.

The feasibility and effectiveness of a combined chemoradiotherapy treatment modality for locally advanced head and neck cancer was tested in a phase II trial. From March 1995 to June 1998, 35 patients with advanced squamous cell carcinoma of the head and neck were treated with a continuous intravenous infusion of 5-fluorouracil (600 mg m-2 24 h-1 for Days 1 to 5 (120 h)) and mitomycin-C (10 mg m-2 intravenously) on Day 5 during the first week of radiotherapy and on Day 36. 31 patients had stage IV disease; 4 patients had stage III; and 1 patient had stage II. Patient ages ranged from 42-69 years (median 56.7 years). The tumours involved were as follows: oral cavity (n = 11); oropharynx (n = 14); hypopharynx/larynx (n = 10). Radiotherapy was delivered to a total dose of 70 Gy with conventional fractionation (2 Gy per fraction, five times a week). Chemotherapy was well tolerated and all patients received the intended dose. Mild nausea occurred in five patients. After a mean follow-up of 21 months (range 10-44 months), 8 (23%) patients remain alive. A complete response was seen in 28 (80%) patients. When a recurrence appeared, it was within the first year after treatment. 1- and 2-year overall survival rates were 46% and 23%, respectively. Grade 3 mucositis occurred in 17% of patients. Grade 1-2 thrombopaenia occurred in 3 (9%) patients, grade > 2 leukopaenia in 4 (11%) patients, and grade > or = 2 anaemia in 3 (9%) patients. We observed a treatment interruption of maximum 1 week for six patients owing to mucositis. Febrile neutropaenia or aplasia were not observed. The concomitant use of 5-fluorouracil, mitomycin-C and radiotherapy in locally advanced head and neck carcinoma is well tolerated in this group of patients. This protocol showed good locoregional response with a very low toxicity profile.