Abstract: Fluconazole is recommended in the prophylaxis of oropharyngeal candidiasis (OPC) in patients undergoing radiotherapy for head-neck tumours; however, the actual effectiveness of fluconazole in this setting remains unclear. Adult patients with cervico-cephalic carcinoma submitted to radical or adjuvant radiotherapy were randomized to 100 mg fluconazole (n = 138) or matched placebo (n = 132) oral suspension once daily from the sixth session of radiotherapy up to the end of treatment. The final analysis of the investigation showed a higher rate of the OPC outbreak-free survival in the fluconazole compared with placebo (P = 0.008 in the log-rank test). The mean time (95% CI) to OPC outbreak was 56 (53-59) days in the fluconazole group and 47 (43-51) days with placebo. The mean duration of radiotherapy was 43.5 and 39.9 days, respectively in the two groups (P = 0.027). Adverse effects were reported in 70.3% of patients in the fluconazole group and in 67.4% with placebo. The results showed prophylaxis with fluconazole given in irradiated patients with head-neck tumours significantly reduces the rate and the time to development of OPC compared with placebo.
Abstract: BACKGROUND: Local therapy for early rectal cancer is a valid alternative to the classical radical operation, which has a higher morbidity and mortality rate. The use of high-dose preoperative radiation appears to enhance the options for sphincter-saving surgery even for T2-T3 rectal cancer patients with effective local control. The authors report their experience with transanal endoscopic microsurgery (TEM) used to manage selected cases of distal rectal cancer without evidence of nodal or distant metastasis (N0-M0). METHODS: The study enrolled 196 patients with rectal cancer (51 T1, 84 T2, and 61 T3). All the patients staged preoperatively as T2 and T3 underwent preoperative high-dose radiotherapy, and since 1997, patients younger than 70 years in good general condition also have undergone preoperative chemotherapy. RESULTS: Minor complications were observed in 17 patients (8.6%) and major complications in only 3 patients (1.5%). The definitive histology was 33 pT0 (17%), 73 pT1 (37%), 66 pT2 (34%), and 24 pT3 (12%). Eight patients (5 pT2 and 3 pT3) experienced local recurrence (4.1%). The rectal cancer-specific survival rate at the end of the follow-up period was 100% for pT1, 90% for pT2, and 77% for pT3 patients. CONCLUSIONS: Patients with T1 cancer and favorable histologic features may undergo local excision alone, whereas those with T2 and T3 rectal cancer require preoperative radiochemotherapy. The results in the authors' experience after TEM appear not to be substantially different in terms of local recurrence and survival rate from those described for conventional surgery.
Abstract: PURPOSE: The aim of this study was to evaluate downstaging as primary end point, and progression-free survival and overall survival as secondary end points, in rectal adenocarcinoma patients treated with preoperative chemoradiation. METHODS: One hundred and thirty-six extraperitoneal adenocarcinoma patients (33 low rectum T2, 74 T3, 29 T4 [without sacral invasion], 25 with mucinous subtype) were treated with posterior pelvis preoperative radiotherapy (5040 cGy total dose, 180 cGy/fr, 5 fr/w, 10-15 MV linac X-rays) and concomitant 5-fluorouracil-based chemotherapy. After 6 to 8 weeks patients underwent surgery and prechemoradiation clinical stage was compared with pathologic stage to evaluate downstaging in each patient. Seventy-four patients received adjuvant chemotherapy. Median follow-up was 39 months (4-84). RESULTS: Forty-four patients had macroscopic complete response, 52 patients had partial response, 37 patients showed no change and 3 patients had progression. At multivariate analysis only histotype showed correlation with downstaging (hazard ratio = 0.350 and 0.138 - 0.885 95 percent confidence interval) because of the evidence for poor downstaging in mucinous subtype. There were no significant differences in overall survival and progression-free survival between adenocarcinoma and mucinous subtype. CONCLUSIONS: The main finding is that mucinous histology is associated with poor downstaging after preoperative chemoradiation but this poor response was not associated with worse outcome in this small study. The good outcome for mucinous histology is at odds with other reports in the literature and requires further study.
Abstract: BACKGROUND: We hypothesized that anemia could represent one of the major factors influencing the outcome of patients undergoing neo-adjuvant treatment of rectal cancer. PATIENTS AND METHODS: This analysis included all the consecutive patients who underwent neo-adjuvant treatment (chemotherapy and/or radiotherapy) before surgery for rectal cancer in three oncology/radiotherapy departments from June 1996 to December 2003. RESULTS: Three hundred and seventeen patients were eligible for our analysis. Median age at diagnosis was 64 years (range 26-88 years); male/female ratio was 184/133. Two hundred and eighty-five patients (89.9%) were diagnosed with adenocarcinoma, while 32/317 (10.1%) with mucinous adenocarcinoma. Neo-adjuvant treatments carried out were as follows: radiotherapy alone in 75/317 patients (23.7%), radiotherapy plus chemotherapy in 242/317 patients (76.3%). At univariate and multivariate analysis, only the hemoglobin (Hb) level (group 1: < or=12 g/dl versus group 2: >12 g/dl) resulted in a significant factor for disease-free survival. The role of the Hb level seemed to be confirmed further by the clinical downstaging obtained in approximately 55% of patients in group 2, in comparison with 35% of the patients achieving a significant downstaging in group 1. CONCLUSION: Our results indicated that anemia could represent an important parameter able to influence the outcome in patients receiving neo-adjuvant treatment of rectal cancer.
Abstract: In the present study, we report results of 28 rectal cancer patients, aged 70 years and older, treated with preoperative radiotherapy and 5FU concomitant chemotherapy. Twenty-eight out of 136 patients treated in our Department between 1997 and 2004 aged > or = 70 years, mean 73 (range 70-81); 3 T2, 18 T3, 7 T4; 15 N0, 5N1, 8 N2; Radiotherapy (5040 cGy, 28 fractions) was delivered combined with 5FU - based concomitant chemotherapy. Compliance to chemoradiotherapy was excellent. Major acute toxicity (> or = G3) evaluation showed haematological Grade 3 only in 2 patients. No severe acute Gastrointestinal toxicity was observed. All patients underwent surgery without severe perioperative complications. Complete pathological response pT0 was found in 3 patients (11%). Overall T downstaging occurred in 61% of the cases. Mean follow up was 34 months (range 4- 84). Kaplan Meier Overall Survival and Disease Free Survival at 5 years were 74% (95% CI 54 -95) and 65% (95% CI 38-93), respectively. Only 1 patient showed G3 diarrhea according to CTCAE that interfered with his Quality of Life and required hospitalization. In conclusion, concomitant radiochemotherapy 5FU based is safe in rectal cancer patients aged > or = 70 with a good tumour downstaging (61% of patients) and excellent feasibility. No treatment related death was observed.
Abstract: The problem of radiotherapy treatment interruptions has been addressed taking into account the linear quadratic model. Simple treatment interruption recovery is possible by using the Biological Effective Dose equivalence between the initially planned total dose and the increased actual total dose. The supplement dose necessary to compensate for tissue proliferation during interruption, is to be considered. This is possible only for acute responding tissue with large alfa/beta ratio as tumors, epithelium, mucosa. However, a higher total dose planned for treatment interruption recovery may overcome late responding vascular and connective tissue or spinal cord tolerance where tissue proliferation is stimulated only after very long latent periods, well beyond the end of even prolonged treatments. Models of dose fractionation or hyperfractionation for recovery of tumor effect not exceeding the late responding tissue tolerance, can be devised by compromising between the planned and modified Biological Effective Dose both in acute and late response tissue.
Abstract: AIMS: To compare preoperative down-staging, toxicity and sphincter-saving procedures obtained with preoperative radiotherapy and two different concomitant chemotherapy schedules. METHODS: From February 1997 to August 2001, 68 consecutive patients were treated with external radiotherapy (5040 cGy in 28 fractions) and concomitant chemotherapy: group a) 36 patients (10 T2, 19 T3, 7 T4, 25 adenocarcinoma and 11 mucinous histology) were treated with cis-diamminedichloroplatinum bolus + 5-fluorouracil continuous infusion; group b) 32 patients (14 T2, 18 T3, 27 adenocarcinoma and 5 mucinous histology) were treated with 5-fluorouracil bolus +/- mitomycin C. The interval between the end of radiotherapy and surgery ranged from 4 to 9 weeks. RESULTS: Group a) Overall down-staging was 63.9%. Longitudinal shrinkage of the neoplasm allowed conservative surgery in 6 of 11 patients with a pre-chemoradiation tumor location < or = 3 cm from the external anal ring. When patients with adenocarcinoma (25/36) were studied separately from patients with mucinous histology, 7/25 patients (28%) were found to have no microscopic evidence of residual tumor (pT0); 8/25 (32%) were found to have only rare isolated cancer cells (pTmic); only 7/25 patients (28%) were found to have no change. Overall, 72% patients had down-staging. In contrast, only 5/11 (45.5%) of mucinous tumors had partial down-staging and 6/11 (54.5%) no down-staging at all. Group b) Overall down-staging was 46.9%. When patients with adenocarcinoma (27/32) were studied separately, 7/27 (26%) were found to have pT0, 3/27 (11.1%) pTmic, and 13/27 (48.1%) no change. Only 1/5 (20%) of mucinous tumors had down-staging and 4/5 (80%) had no down-staging at all. Overall toxicity was comparable among groups a and b, except for lower hematologic and gastrointestinal G3-4 toxicity observed in group a. CONCLUSIONS: The overall response allowed conservative surgery in 56 (82.3%) of the 68 patients. Continuous infusion of 5-fluorouracil and diamminedichloroplatinum as a radiosensitizer determined better results in group a than group b (63.9% down-staging vs 46.9% even with a higher incidence of mucinous histology). Mucinous histology, for a definitely lower response rate, could benefit from an even more aggressive approach.
Abstract: Transanal endoscopic microsurgery (TEM), associated with preoperative radiotherapy in selected groups, allows minimally invasive full thickness local excision of rectal tumors with perirectal fat dissection. In our experience, 95 patients with extraperitoneal rectal carcinoma underwent TEM resection for T1 (21 cases), T2 (48 cases) and T3 (15 cases) lesions. In eleven patients the pathologist did not find cancer cells in the specimen (pT0) after full dose of radiotherapy and TEM. The postoperative results were as follows: 11 minor complications (11.6%), 7 leaking sutures, 3 stool incontinence and 1 rectal haemorrhage, that resolved with medical therapy and two major complications (2.1%), one rectovaginal fistula that required reoperation and one rectourethral fistula treated by conservative therapy. No perioperative mortality was observed. Mean follow up was 40 months (range 2-96 months) with 7 (7.4%) local recurrences. Of those, 5 patients were successfully retreated and 2 high risk patients underwent postoperative radiotherapy. The overall survival in T0 and T1 patients was 100%. The overall survival in T2 and T3 patients was 81% and 62.1% respectively. This study reports the application of TEM combined with radiotherapy in the treatment of rectal cancer in selected patients. This approach is feasible, safe, and appears to be effective at the present follow up, with preservation of normal sphincter function.
Abstract: PURPOSE: We investigated the practical application of a calculation algorithm based on the Monte Carlo method to stereotactic radiosurgery treatment planning. In radiosurgery, high dose gradients and the lack of electronic disequilibrium make high resolution matrices and high computing power and speed necessary to obtain accurate dose distribution. To date, the main obstacle to the wider-spread use of the Monte Carlo method has been the huge computing time necessary to obtain a dose distribution on current hardware. MATERIAL AND METHODS: In this project, developed within the ESPRIT program, funded by the European Union, a Parsytec CC (Cognitive Computing) computer was used with 9 processors (Power PC 604, 133 Mhz, RAM 64 Mb) with IBM AIX/EPX OS and availability for Fortran parallel codes compilation, connected to a PC for data input, results rendering, and dose distribution calculation with a conventional algorithm for comparison with the Monte Carlo code (an EGS4 user code). The module named Rapt Region Extractor performs data compression with an octree method without decreasing resolution, for RAM and computing time requirements to remain acceptable. A model of the 6 MV photon beam from Clinac 2100C Varian linear accelerator was devised, based on incident photon energy spectrum and, for each collimator dimension, on bidimensional dose distribution orthogonal to beam direction measured at SSd = SAD = 100 cm. RESULTS: Parallelization was carried out on event numbers, allowing a simulation speed to number of processor ratio close to unity. A new random number generator was used, capable of correctly running on the parallel architecture. The simulation procedure includes: 1) CT acquisition in DICOM 3.0 format, Analyze or with scanner; 2) Target delineation, treatment arc definition. 3) Dose calculation, with both conventional and Monte Carlo methods. 4) Dose distribution rendering on every transverse, sagittal or coronal planes overlapped in color wash on anatomical representation. Comparison between conventional and Monte Carlo algorithms were carried out on an anthropomorphic phantom and 10 real patients, with 2.5 mm anatomical resolution and standard deviation never exceeding 2%. A simulation with 10,000,000 events and 1% maximum variance can be run in 43'. When PTV is an homogeneous areas the differences between the two methods are around 5%, while when PTV is localized in dishomogeneous areas discrepancies reach 20% in the bone. CONCLUSIONS: In conclusion, the feasibility of direct simulation with the Monte Carlo method in radiosurgery has been demonstrated within time and hardware costs compatible with clinical practice.
Abstract: The authors describe a new instrumentation for repositioning of the Brown-Roberts-Wells (BRW) stereotaxic system, useful for precise fractionated radiotherapy. A lucite ring is fixed to the patient's skull with four screws. Another ring, partially open, is then firmly connected co-axially to the lower part of the first one with four spacer-bars. The fixture permits an exact repositioning of the B.R.W. stereotaxic system, placing the target point in the linear accelerator isocenter. The preliminary technical results obtained in five children are reported and the fixture performance, advantages, and perspectives are discussed.
Abstract: The mammographic patterns of the patients treated with conservative surgery (quadrantectomy) plus radiotherapy for early breast carcinoma were evaluated to assess treatment-induced changes over time and to improve the differential diagnosis between postirradiation effects and possible tumor recurrences. The mammographic examinations of 79 patients who had undergone quadrantectomy and radiotherapy for breast carcinoma (stage T1-T2) were examined. Skin thickening, edema, fibrosis, distortion and calcifications were considered and classified by comparing the radiographic patterns of the treated breast with those of the contralateral and untreated one. Pattern changes over time were also evaluated and quantified by comparing serial follow-up examinations of the same breast. The percentage of patients with irradiation-induced skin thickening steadily reduced from 100% at 6 months to just above 50% at 4 years. The number of patients showing diffuse irradiation-induced edema decreased from 56% at 6 months to 15% at 1 year and to 0% at 2 years, while the number of cases with localized edema decreased more slowly. The incidence of localized postirradiation breast fibrosis increased to 74% at 4 years, while diffuse fibrosis stabilized around 14%. The patients with no postoperative breast distortion accounted for nearly 33% of the examined cases, while those with minimal distortion approximated 58% and those with gross distortion 9%. In conclusion, the overall results confirmed the value of mammography in the follow-up of the patients treated with QUART.
Abstract: The acceptance tests of five electron linear accelerators have been analyzed to compare their completeness, the standards specified by the manufacturers and the measured deviations. Involved tests were relative to geometrical and mechanical parameters, photon and electron beam characteristics, dose monitoring systems, treatment table and safety systems. The comparison of acceptance tests has shown a significant nonuniformity, also due to the absence of a specific legislation; anyway, the measured deviations generally appeared to be within internationally recommended values.
Abstract: The authors have addressed the physical and technical problems involved in the total skin irradiation with a linear accelerator Varian Clinac 2100 C expressly preset for this modality with electrons of 6 MeV nominal energy and dose rate of about 2500 UM/min at the isocenter. The six dual field technique has been implemented and the effect of interposed degrading filters has been evaluated with film dosimetry on an anthropomorphic phantom. It was verified that the total skin electron irradiation expressly offered by the manufacturer as an established treatment option on the Clinac 2100 C with high performance ionizing chambers and high dose rate makes the all procedure safer and simpler.
Abstract: The preliminary evaluation of the dosimetric characteristics of a dedicated intraoperative electron beam therapy system is described (Bionix Corporation). The linear accelerator is the Varian 2100 C with electron beam energies of 6, 9, 12, 16 e 20 MeV. The isodose distribution for each of 15 available applicators (5 plane and 10 beveled) has been studied with a water phantom. The problems of the homogeneity of dose distribution, scattered and leakage radiation outside the applicators and X-ray contamination of the electron beams have been addressed, at the nominal 20 MeV energy for exemplification. The accurate knowledge of such physical and dosimetric properties are necessary for the implementation of the IORT techniques in terms of choice of the applicator size and electron beam energy for tumor coverage and dose sparing of critical organs.
Abstract: The technical and dosimetric aspects are presented of high-dose intracavitary brachytherapy in gynecology. Fifty-five patients (203 insertions) were examined over two years with a remote loading Selectron HDR 60Co unit installed in a dedicated bunker. The dose to the rectal and bladder markers on AP and LL films was calculated before every irradiation, in order to allow the necessary corrections to be made. Uniform irradiation conditions were obtained at each treatment set-up for both tumoral target and bladder and rectal doses. High-dose intracavitary brachytherapy proved to be a safe, reliable and versatile method from the technical and dosimetric point of view both in the treatment of unoperated gynecological malignancies and in postoperative therapy.
Abstract: Sixty-three patients with soft tissue sarcomas of the limbs received postoperative radiotherapy during the period from 1969 to 1985. The 5 years actuarial survival rate was 77% in 17 patients who underwent wide surgical operations + RT, 59% in 28 patients with marginal surgical excision + RT, 64% in 18 patients who received salvage RT after several recurrences. Locoregional control was higher in the patients with wide surgical operations + RT, while there were no significant differences in the disease free survival from lung metastasis among the three groups of patients.
Abstract: From 1976 through 1985, 68 patients were treated with radiation therapy at Ospedali Galliera, Genoa, Italy, for recurrence of radically-operated rectal adenocarcinomas, most of them in Dukes (Astler, Coller) B2, C1, and C2 stages. The average disease-free interval between surgery and recurrence was 12 months (range 2-144) in the whole group, versus only 6 months in stage C2 patients. Pain relief was obtained in 45 patients (66%), and reduction in recurrence size in 22 (32%), with the following global results: disease progression in 16 patients, no progression/regression in 26, partial regression in 19, complete response in 3, and not evaluable in 4. Twenty-one patients had many contemporaneous distant metastases (2 cases) or within a short period of time after the locoregional recurrence (19 cases). These results lead us to believe that radiation therapy should not be employed in so many cases of radical surgery for rectal adenocarcinoma as it is today, but only in case of locoregional recurrences, as an alternative to postoperative radiotherapy, combined, if needed, with adjuvant chemotherapy.
Abstract: Sixty-seven cases of brain metastases from breast carcinoma treated in the period from January 1969 to June 1986 with radiotherapy (high energies on homogeneous volume, 250-300 kV grid roentgenoherapy) have been evaluated retrospectively. Performance status improvement, evaluated according to Order's stages, with increased quality of life has been obtained in 66% of the patients. Results do not appear to be substantially affected from the different techniques and methods of irradiation. However the importance of implementing and performing the radiotherapy treatment in such a way to keep as high as possible the benefit/risk ratio is stressed, owing to the possibility to observe a few long survival patients after brain metastases occurrence.
Abstract: The ultrastructural appearances of preneoplastic liver nodules induced in male Wistar rats through sequential treatment with diethylnitrosamine (DENA) and 2-acetylaminofluorene (2-AAF) followed by partial hepatectomy were investigated. Although separately non-specific, the lesions reported represented altogether a fairly characteristic pattern consistent with previous observations in tumors and in preneoplastic nodules induced by long-term treatment with single carcinogens. Such data support the view that sequential treatment followed by partial hepatectomy is a reliable method to study early phenotypic changes in hepatocarcinogenesis. Such treatment is also advisable because it requires only a short period of latency in comparison to other in vivo screening tests of potential carcinogens.
Abstract: Contrast dependency in MR Tomography from several intrinsic and extrinsic parameters makes this technique versatile and sensitive; at the same time it makes more complex the image contrast evaluation and the optimized sequence choice. The approach to this problem from the viewpoint both of training and practical application becomes easier using the proposed personal computer program.
Abstract: DNA damage induced in mammalian cells (CHO-K1) by one hour treatment with several concentrations of N-diazoacetylglycine amide (DGA) was evaluated by the method of DNA denaturation in alkali and successive neutralization followed by separation of single from double stranded DNA with the recently described technique of hydroxylapatite chromatography performed in batch. This latter technique does not need complex apparatus and simplifies the simultaneous handling of large number of samples; it also appears as sensitive and reliable as the DNA alkaline elution on filter, to which it can be regarded as both alternative and complementary.
