Purpose. 5-Fluorouracil (5-FU) has shown radiosensitizing properties in vitro. This paper reports the effects of radiotherapy and concomitant intravenous 5-FU radiosensitization in the treatment of advanced bone sarcomas.Subjects/methods. Four patients with large inoperable bone sarcomas (three chondrosarcomas and one fibrosarcoma) were treated with hypofractionated radiotherapy and concomitant 5-FU bolus injection (300 mg m(-2)) before each fraction of radiotherapy. A radiation fraction of 5 Gy was given twice a week to a normalized total dose (alpha/beta=4 Gy) of 75 Gy.Results. The regimen was well tolerated, the main toxicity being grade I/II diarrhoea in two cases with pelvic irradiation. Treatment interruption for 1 week was necessary in two cases with pelvic disease but not in two patients treated for sarcoma of the extremities. A complete symptomatic relief was obtained in all cases immediately after the third to the fifth fraction and the median duration was 10 months. Computed tomography scan documented a partial response in 2/4 cases.Discussion. Hypofractionated radiotherapy combined with potential lethal damage inhibitors for bone sarcomas requires further investigation.
Hypoxia inducible factor 1a and 2a (HIF-1a and HIF-2a) are key proteins regulating cellular response to hypoxia. Because the efficacy of photodynamic therapy (PDT) is dependent on the presence of oxygen, the assessment of HIF-1a and HIF-2a expression may be of value in predicting clinical response to PDT. Using recently produced MoAbs, we examined the expression of HIF1a and HIF2a in a series of 37 early-stage esophageal cancers treated with PDT and with additional radiotherapy in case of incomplete response after PDT. Strong expression of the HIF1a and of HIF2a proteins in all optical fields examined was noted in 51% and in 13% of cases, respectively. High expression was associated with a low complete response (CR) rate and with the absence of bcl-2 protein expression. On the contrary, bcl-2 expression was associated with a high CR rate. Combined analysis of HIF1a and bcl-2 protein expression revealed that of 16 cases with high HIF1a expression and the absence of bcl-2 reactivity, only 1 (7%) responded completely to PDT (P = 0.007). Bivariate analysis showed that HIF1a expression was independently related to response to PDT (P = 0.04; t ratio = 2.8), whereas bcl-2 approached significance (P = 0.07; t-ratio = 1.8). The final response to radiotherapy was high (70%) and independent of the HIF and bcl-2 status, which may be a result of reoxygenation after cellular depletion mediated by PDT. The present study suggests that assessment of HIF and of bcl-2 expression are important predictors of in vivo sensitivity to PDT. Modulation of PDT response with bioreductive drugs and/or drugs targeting bcl-2 (i.e., taxanes) may prove of significant therapeutic importance in a subgroup of patients with high HIF expression.
Introduction ECT is based on the local delivery of electric pulses that causes transient permeabilisation of the cell membrane, facilitating the intracellular delivery of chemotherapeutic drugs, otherwise not permitted by the integrity of the membrane. ECT was first introduced at the Institute Gustave Roussy in France (1990 - with bleomycin) and at the Institute of Oncology, Ljubljana, Slovenia (1994 - with cisplatin). Today we find more than 300 records in PubMed search for more than 1000 patients treated all over the world, Greece included. Methods In the framework of the ESOPE-EU project, the standard operational procedures are well defined and certified with the participation of four leading European Cancer Centers. Results The aim of this presentation is to focus on the ECT Treatment clinical experience gathered from 44 patients treated and 64 applications performed by the Hellenic Group of ECT (HeGECT). Conclusion Electrochemotherapy (ECT) is a highly efficient and safe new anticancer therapeutic modality, useful predominantly in cutaneous and subcutaneous tumor nodules of multiple origins and histological types.
One hundred and fifty-three patients with inoperable non-small cell lung cancer (NSCLC) treated with radiotherapy alone have been retrospectively analysed. Normalized Total Dose (NTD) as defined by Macejewski, TN-stage (AJC-system) and histology have been examined with respect to 5-year disease-free survival (DFS) and the patterns of failure so as to identify subgroups of patients that routinely should be treated with radical intent. The 5-year DFS for T1, 2-N0, 1 and T3-N0, 1 staged patients was 30% (7/23) and 25% (4/16) respectively when the tumor NTD (a/b = 10 Gy) was 56–64 Gy vs. 12% (5/41) and 0% (0/10) when the NTD was 48–55 Gy. This difference was statistically significant for the squamous cell histology group. The higher doses significantly altered the patterns of death in N0, 1 staged squamous cell carcinoma and adenocarcinoma patients. Forty-five percent (22/55) and 41% (12/29) of squamous cell and adenocarcinoma patients respectively, died from local relapse without evidence of distant metastases when NTD less than 55 Gy were given vs. 21% (9/42) and 13% (2/15) when the NTD delivered was 56–64 Gy (p > 0.05). Although for N2, 3 staged patients or patients with direct extension of the tumor into the mediastinum death from local relapse occurred in 38% (10/26) of the high NTD treated patients vs. 51% (19/37) of the low-dose treated ones, the difference was not statistically significant. It is concluded that NSCLC patients should not à priori be considered as non-radiocurable. At least 30% of the patients with early local stages can be long-term disease-free survivors with radiation NTD up to 60 Gy and better results are to be expected with higher doses. Advanced T-stage without mediastinal involvement should be treated with radical intent since a high NTD could give cure rates of over 25%. The disappointing results for patients with mediastinal disease could perhaps be attributed to the low NTD delivered. For patients with good performance status, hyperfractionated regimens delivering high tumor doses should be tested and chemotherapy should be adapted to these radiation treatment schedules.
18531 Background: Anaemia is a poor prognostic factor for patients undergoing radiotherapy (XRT) and has been associated with decreased response to treatment. Darbepoetin alfa has been proven effective in treating anaemia and in improving QoL. The purpose of this study was to assess the efficacy, safety and the impact on QoL of darbepoetin alfa in these pts. Methods: Patients with Hb level 10–12 g/dl, PS ECOG <2, and life expectancy >6 mos were administered darbepoetin alfa SC 150 mcg once weekly during the 6 wk course of conventional XRT (2 Gy/5 days/week). All pts received iron supplem. Blood transfusion was given for Hb <9 g/dl. Complete blood counts, serum iron, folate, B12, ferritin, serum LDH, bilirubin and reticulocyte count were measured weekly. The primary study endpoints were changes in Hb level during XRT, number of transfusions and evaluation of QoL. Results: Between Mar 2002 and Feb 2004, 140 pts were entered, 116 were evaluable. Mean Hb at baseline was 10.95 ± 1.76. There was a significant increase (17.1%) in mean Hb levels from 2nd wks onwards with the peak value at wk 10 from XRT initiation. Hb significantly increased to 12.03 ± 2.39 (p < 0.001), 12.63 ± 2.10 (p < 0.001) and 12.96 ± 2.33 (p < 0.001) at 3,6 and 10 wks, respectively. Blood transfusion was necessary in 3 pts (2.6%). None of the pts experienced serious adverse events. There was a significant difference in physical well being score between Hb levels (p = .016) regardless the period of time (p = .17). Pts with high Hb levels had higher functional well being scores (p = .002) regardless time for the interaction (p = .24).There was a significant difference in mean fatigue score between Hb levels (p=.019) and a significant time by group interaction (p = .03).Pts with high Hb levels tend to have a higher social well being score than those with lower Hb (p = .08) while the differences were similar over time (p = .89).Those with Hb ≤ 12 g/dL had a tendency for increased emotional scores at 6 wks (p = .07) while the differences were similar over time (p = .138). Conclusion: Hb levels were significantly increased from baseline, irrespective of tumour localisation and stage. This increase reached the maximum value during wk 10 and remained significant 2 mos post XRT. QoL was significantly improved in these pts. No significant financial relationships to disclose.
The aim of this study is to present preliminary experience with 137Cs medium dose rate (MDR) afterloading transurethral radiotherapy for small-sized (< 2.5 cm) prostatic carcinomas. The phase II protocol comprises 46 Gy of external beam radiotherapy, followed by two insertions (1 week apart) of 137Cs MDR transurethral brachytherapy, each one delivering 8 Gy to a point 0.5 cm from the urethral walls. The treatment is completed with a 14-Gy boost to the prostatic area through lateral external beam fields. Up to now, 9 patients have been treated. The transurethral insertion is a simple procedure, requires no anesthesia and the ultrasonographic observation precisely and easily guided the positioning of the applicator. All 9 patients are alive and disease-free 12-36 months after the end of radiotherapy. One of them presented a mild degree of urethral stricture and none developed chronic proctitis or cystitis. Seven patients were sexually potent before radiotherapy and all of them maintained their potency. Transurethral radiotherapy for prostatic carcinoma requires further investigation. The radiation dose that the procedure delivers to the prostate is higher than the one prescribed for external beam irradiation regimens. Rectal and bladder dose is substantially reduced. Although the prostatic urethra receives a higher dose, the incidence of urethral stricture is low probably because of the small tissue volume (8 cm3) in the high radiation dose area.
