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The purpose of the study was to evaluate the outcomes of stereotactic radiation therapy for primary and secondary liver tumours in Jean-Perrin cancer centre (Clermont-Ferrand, France) in terms of efficacy and safety.Between December 2013 and June 2016, 25 patients were included. Treatment was performed on a linear accelerator Novalis TXMedian follow-up was 10.5 months. Treatment tolerance was good with few side effects grade 3 or above, no acute toxicity and only one late toxicity. We have highlighted that hepatic artery haemorrhage was associated with the presence of a biliary prosthesis in contact with the artery (P=0.006) and in the irradiation field. There was no correlation with the dose delivered to the artery and hepatic artery haemorrhage.Stereotactic radiation therapy for liver tumours allows a good local control with few secondary effects. Caution should be exercised when treating patients with biliary prostheses in the vicinity of the target volume because there is a risk of haemorrhage of the hepatic artery in contact with the prosthesis.

Stereotactic radiotherapy is a major issue in the management of brain metastases. Radionecrosis is a major concern, especially for large lesions. Optimizing dosimetric parameters is essential to allow optimal local control rate while minimizing potential toxicity. We report the case of a 30-mm brain metastases treated with stereotactic radiotherapy after initial whole brain radiotherapy, complicated with symptomatic radionecrosis. A dose of 24Gy in three fractions on the 80% isodose were delivered using a dynamic conformal arc technique (Novalis TX

Purpose The objective of this randomised phase II study was to evaluate the impact in terms of response and toxicities of induction or consolidation chemotherapy respectively before or after concurrent chemoradiotherapy in unresectable stage III non-small-cell lung cancer. Patients and methods In the induction arm, patients received induction chemotherapy with cisplatin (80 mg/m 2 ) and paclitaxel (200 mg/m 2 ) on days 1 and 29 followed by a concurrent chemoradiotherapy (66 Gy in 33 fractions, cisplatin 80 mg/m 2 days 1, 29 and 57, vinorelbine 15 mg/m 2 days 1, 8, 29, 36, 57 and 64). In consolidation arm, the same concurrent chemoradiotherapy began on day 1 followed by two cycles of cisplatin and paclitaxel. Results One hundred twenty seven patients were randomised. The intent to treat response rates in induction and consolidation arms were 58% and 56% respectively. Median survival was 19.6 months in induction arm and 16.3 months in consolidation arm and 4-year survival rates were 21% and 30% respectively. Haematologic and non-haematologic toxicities were similar in both arms, except grade 3/4 oesophagitis, more frequent in consolidation arm than in induction arm (17% versus 10%). Conclusion Cisplatin-based chemotherapy as induction or consolidation with concurrent chemoradiotherapy can be administrated safely. Response rates were similar in both arms with a trend in favour for consolidation arm for long-term survival.

Conventional treatment of high-grade glioma includes maximal surgical resection followed by external radiation therapy. Despite this treatment, the prognosis for patients is poor. High doses of chemotherapy might be another way to increase the response rate and median survival. Increasing doses of BCNU might be more effective, but also provokes unacceptable myelotoxicity. This dose-limiting toxicity can be circumvented by using autologous blood stem cell rescue. We report our experience of high-dose BCNU followed by transplantation of autologous hematopoietic stem cells in 114 patients with high-grade gliomas. Of the 114 gliomas, 78 were glioblastoma multiforme (GM) (68%), 24 anaplastic astrocytomas (AA) (21%), and 12 anaplastic oligodendrogliomas (OD) (11%). Complete surgical resection was performed for 22 patients (18 GM and 4 AA). The median age was 44 years (range 17-65). A total of 84 patients received autologous hematopoietic stem cells from bone marrow harvest, while 30 patients received granulocyte colony-stimulating factor followed by apheresis and received peripheral blood progenitor cells (PBPC). High dose of BCNU (800 mg/m(2)) was given at least 1 month after neurosurgery. Bone marrow or PBPC was transplanted 48-72 h after chemotherapy. Radiotherapy was started approximately 40 days after transplantation to a total of 60 Gy. Median follow-up was 89 months (19-163). The overall survival (OS) was, respectively, 12 months for GM, 37 months for OD and 81 months for AA. Histological type appeared to be the main discriminating factor, with a worse prognosis for GM. Within the GM population, age, completeness of surgery, and response appeared to be one important prognostic factors. The AA and OD populations were small to reliably assess prognostic factors. On multivariate analysis, the main prognostic factors were histologic type, quality of surgery, and age (P

In the treatment of brain metastases, whole brain radiotherapy can be carried out according two distinct methods: one using multileaf collimator for field shaping and protection of organs at risk, and a second one is to make a rotation of the field to avoid the eyes. The aim of the study was to compare for 10 patients the dose distributions at organs at risk for each method. Patients received 30 Gy in 10 fractions. Except for parotid glands, the dose received by organs at risk and the planning target volume was the same with each method. For whole brain radiotherapy, excluding the cisterna cerebellomedullaris, the mean parotid dose was 9.63 Gy using the multileaf collimator versus 12.32 Gy using the field rotation (P=0.04). For whole brain radiotherapy including the cisterna cerebellomedullaris, the mean parotid dose was 11.12 Gy using the multileaf collimator versus 20.06 Gy using field rotation (P0.001). Using the multileaf collimator seems recommended for whole brain radiotherapy, to reduce the dose to the parotids.

Between 1971 and 1989, 59 patients received external radiation therapy with a curative intent. There were 25 females and 34 males, ranging in age from 19 to 87. No patients had distant metastasis at the onset of treatment. The majority of patients had a total thyroidectomy ( 55 59 ), generally combined with neck dissection. Residual tumour was left in 11 cases, and 44 patients had positive cervical nodes. Using megavoltage radiotherapy, the whole neck and the upper mediastinum area were most often irradiated through a large anterior Y-shaped field without laryngeal shielding. The mean dose to the tumoural bed was 54 Gy. Dysphagia was observed in 32 patients (11, 17 and 5 scores were grade 1, 2 and 3, respectively). Dyspnea occurred in five cases and in two of these cases, it was considered to be severe. Local recurrences were noted in 18 (30%) patients, most of them occurring within the fields of irradiation. Parameters such as age, sex, total dose, irradiated volumes or cervical node enlargement did not modify the local control rate. The same conclusions can be drawn for distant failures. Thirty five patients are still alive and among them, 24 have no evidence of disease. The average length of survival is 70.5 months and is shortened by the occurrence of distant failures except in patients with bone metastases.

Objectives. To see if a past history of radiation therapy is a risk factor for septic arthritis. Methods. We retrospectively searched our records of 282 patients with septic arthritis and found 10 cases of septic arthritis post-radiotherapy, all in females. We analysed our group, correlating them with the literature. We also compared our patients with a group of septic arthritis patients without radiation therapy. Results. Nine had had radiation therapy for carcinoma of the breast. The shoulder joint was involved in six and the sternoclavicular joint in three. The tenth patient had had brachytherapy and radiation for carcinoma of the cervix and presented with septic arthritis of the hip. The mean age of the patients was 69 yr (49-82 yr). The mean time elapsed since radiation was 16yr (3-34yr). Twenty-three cases of shoulder septic arthritis in patients without past radiation therapy were selected for comparison. The five patients with past radiation therapy had fever less often and a longer time lapse before diagnosis. They required longer antibiotherapy. However, this prevented neither bone destruction nor relapse. Conclusions. In our study, a past history of radiation therapy was observed in 6/50 infections of the shoulder, 3/5 infections of the sternoclavicular joint, 6/23 cases of septic arthritis of the shoulder and all cases of septic arthritis of the sternoclavicular joint for females. Radiation therapy seems to be a risk factor for septic arthritis. Diagnosis would be aided by a greater awareness of the clinical and radiological features of this septic arthritis.

We have evaluated CYFRA 21-1 serum level variations as an indicator of tumor response and survival in 44 consecutive patients with locally advanced non-small cell lung cancer (NSCLC) treated with induction chemotherapy (IC). Irrespective of the initial CYFRA 21-1 serum concentration, a more than 65% decrease in the serum level after the first chemotherapy course was significantly predictive of an objective tumor response (p=0.0022). In addition, a more than 80% decrease in this level significantly predicted a better disease-free survival (p=0.039). In patients with initial CYFRA 21-1 serum levels >3.3 ng/mL (n=29), a more than 80% decrease after the first IC course was the most significant predictor of overall survival (p=0.025) in a Cox analysis including initial staging, tumor response and surgery. We conclude that early monitoring of CYFRA 21-1 serum levels may be a useful prognostic tool for tumor response and survival in stage III NSCLC patients treated by induction chemotherapy.

Repair of cytotoxic DNA damage by O(6)-methylguanine-DNA methyltransferase (MGMT) is a potentially important factor of chemoresistance to chloroethylnitrosoureas (CENUs), commonly used in the treatment of glioblastoma multiforme (GBM). The value of p53 as a prognostic factor in GBMs remains unclear, but a possible relationship between MGMT gene expression and p53 has been suggested. To further examine these GBM characteristics in vivo, we assessed MGMT gene expression using semi-quantitative RT-PCR and p53 alteration by immuno-histochemistry on a series of 39 GBMs. MGMT gene expression was inversely correlated with age (p0.03), consistent with the results of others. Interestingly, tumors from male patients had higher MGMT mRNA amounts than tumors from female patients (p0.03). No prognostic implication was observed either for MGMT gene expression or for p53 accumulation. However, MGMT gene expression was significantly lower in p53-altered GBM, regardless of the percentage of positive cells (p0.01). Our observation suggests that in human glial tumors, a low level of MGMT gene expression might promote p53 alteration, probably via mutation of its gene. Int. J. Cancer (Pred. Oncol.) 84:416-420, 1999.

Pre-operative radiochemotherapy is the most recent therapeutic option in the pre-operative downstaging of pancreatic cancer and in decreasing the rate of positive resection margins. The purpose of the study was to evaluate tolerance and efficacy of pre-operative radiochemotherapy in unresectable pancreatic cancers.This study included seven cases of pancreatic cancer considered unresectable. The patients received preoperatively 50 grays within a 5-week period associated with 5 FU and Platin during the 1st and 5th weeks.After radiochemotherapy, tomodensitometric evaluation showed a minor response in two cases. A pancreatico-duodenectomy could be performed in these two patients without any increase of pre- or post-operative morbidity or mortality.The results of the study suggest that preoperative radiochemotherapy may increase pancreatic cancer resectability. This hypothesis should be confirmed by a prospective randomised trial.

Fifty-seven uveal malignant melanomas (T2: 36.8%; T3: 49.1%) were treated between 1983 and 1989 with Cobalt 60 or/and Ruthenium 106 Rhodium 106 plaques. The mean follow-up was 32 months (from 6 to 69 months). A diminution of tumor size was observed in 88% of the cases, either rapid and marked (57%), or slower and more moderate (31%). A multivariate study showed the radiation dose administered to the tumor edge to be the most significant parameter associated with the tumor control. Seven patients developed metastases, and the probability of survival at 60 months was 83.3%. This probability was identical to that of 59 comparable patients treated, some years before, by enucleation. The most frequent complications were radiation retinopathy (28.1%) and retinal detachment (15.8%). The treated eye was retained in 86% of cases. In 57% of treated eyes, vision remained better or equal to 0.1. The predictive parameters of vision impairment after treatment seemed to be tumor size, tumor site near the macula and the optic nerve, and the radiation dose to the tumor base. The use of Ruthenium 106 Rhodium 106 appeared to be advantageous in controlling the disease as well as in reducing the incidence of complications.

ATM mutations predispose cells to malignancy by promoting chromosomal instability. We have identified a family with multiple cancers that segregates a mutant allele of ATM, IVS61+2insTA, which causes skipping of exon 61 in the mRNA, as well as a previously undescribed polymorphism, IVS61+104C(54):T(46). The mutation was inherited by two sisters, one who developed breast cancer at age 39 and the second at age 44, from their mother, who developed kidney cancer at age 67. Molecular studies were undertaken to determine the role of the ATM gene in the development of cancer in this family. Studies of irradiated lymphocytes from both sisters revealed elevated numbers of chromatid breaks, typical of A-T heterozygotes. Studies on lymphoblastoid cell lines established from these individuals revealed abnormal p53 induction and apoptosis after DNA damage. Loss of heterozygosity (LOH) in the ATM region of chromosome 11q23.1 showed that the normal ATM allele was lost in the breast tumor of the older sister. LOH was not seen at the BRCA1 or BRCA2 loci. BRCA2 is not likely to be a cancer-predisposing gene in this family because each sister inherited different chromosomes 13 from each parent. The sisters share their maternal BRCA1 allele, although no mutation in this gene was detected in the family. Our findings suggest that haploinsufficiency at ATM may promote tumorigenesis, even though LOH at the locus supports a more classic two-hit tumor suppressor gene model.

Rats bearing a transplanted nickel-induced rhabdomyosarcoma (RMS 9-4/0), treated with chlorozotocin (CZT), an alkylating agent, showed an amplified metastatic invasion of the lung (median of 165 lung tumour nodules, compared to 3 for untreated controls). A higher level of metastatic invasion (200 nodules) was reached spontaneously after the grafting of the S4T line, which was obtained by successive in vivo passages of RMS 9-4/0 cells in CZT treated rats. S4T tumour cells also invaded the liver and a considerable proportion of the lymph nodes. The NT4T line, obtained by successive in vivo passages in untreated rats, showed a lesser degree of enhancement of metastatic capacity (57 nodules). Both derived lines proved to be more aggressive than the parental, proliferated more rapidly, and were resistant to CZT toxicity. Only the non-treated lineage became more resistant to NK lysis. The S4T line lost its myogenic differentiation and was best described as a fibrohistiosarcoma, whereas NT4T did not. Chromosome analysis demonstrated a reduced range of chromosome number per cell in both lines. We conclude that both S4T and NT4T tumours became more metastatic than RMS 9-4/0 as the result of tumour progression through in vivo passages, and that in addition S4T acquired a spontaneously higher metastatic potential, similar to that which occurred in rats grafted with RMS 9-4/0 or NT4T tumours and treated by CZT. This suggests an inheritable mutation in the S4T line. Images Figure 3

A rat rhabdomyosarcoma clonal line RMS/8 was cotransfected with genomic DNA of procaryotic or eucaryotic origin and neomycin resistance plasmid pKOneo. The lung colonizing and metastatic capacity of transfected cells was evaluated. When col- meta- RMS/8 cells were transfected, an increase in lung colonizing but not in metastatic ability was observed. The DNA transfection of col+ meta- RMS/8 cells led to an enhancement of metastatic potential. These effects were independent of the origin of donor genomic DNA but were closely related to the transfection efficiency. It is suggested that DNA transfection destabilized the recipient genome, thus leading to an increased heterogeneity which potentially favours metastasis. The mock-transfected col+ meta- RMS/8 cells also exhibited an increased metastatic capacity. The non-specific effects of DNA transfection and of transfection procedure per se should therefore be taken into account in gene transfer studies of metastasis.