Induction chemotherapy in head and neck cancer patients followed by concomitant docetaxel-based radiochemotherapy.

Concurrent chemoradiotherapy has become the standard of care for patients with inoperable squamous cell head and neck carcinoma. More recently, induction chemotherapy has been adopted as an approach in the management of these patients. We report the results of a phase II trial associating induction chemotherapy and concomitant chemoradiotherapy in a series of patients with inoperable squamous cell head and neck cancer. Twenty-nine patients with advanced squamous cell carcinoma ineligible for surgery were enrolled. Induction chemotherapy with docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) every 21 days was administered for two cycles. Radiotherapy followed the induction phase. During radiotherapy, docetaxel was administered weekly at the dose of 33 mg/m(2) . Primary end point of the study was feasibility of treatment. Six (18%) patients failed to conclude the treatment schedule. Although response rates in evaluable patients were very high (disease control rate >90%), toxicities were a matter of concern. The reported treatment schedule proved infeasible. However, some modifications in ancillary therapies aimed at exploiting its efficacy could make it practicable.

Effects of fluconazole in the prophylaxis of oropharyngeal candidiasis in patients undergoing radiotherapy for head and neck tumour: results from a double-blind placebo-controlled trial.

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.

Anemia may influence the outcome of patients undergoing neo-adjuvant treatment of rectal cancer.

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.

Feasibility of preoperative chemoradiation in rectal cancer patients aged 70 and older.

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.

[The Monte Carlo method and parallel estimation in the drawing up of radiosurgery treatment plans]. / Metodo Monte Carlo e calcolo parallelo nella stesura dei piani di trattamento radiochirurgici.

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.

Halo ring supporting the Brown-Roberts-Wells stereotactic frame for fractionated radiotherapy.

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.

[The mammographic images of the irradiated breast after conservative therapy for carcinoma]. / Quadri mammografici della mammella irradiata dopo terapia conservativa per carcinoma.

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.

[Comparison of acceptance tests of 5 linear electron accelerators for radiotherapy]. / Confronto tra i test di accettazione di cinque acceleratori lineari di elettroni per radioterapia.

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.

[Preliminary evaluation of the clinical use of a system for intraoperative radiotherapy with electrons (IORT)]. / Valutazioni preliminari all'impiego clinico di un sistema dedicato per radioterapia intraoperatoria con elettroni (IORT).

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.

[Physico-technical aspects of total skin irradiation with high-intensity-dose electrons]. / Aspetti fisico-tecnici nell'irradiazione cutanea totale con elettroni in alta intensità di dose.

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.

[Postoperative radiotherapy in the treatment of soft-tissue sarcomas of the limbs: 63 consecutive cases]. / Radioterapia post-operatoria nel trattamento dei sarcomi delle parti molli degli arti: sessantatré casi consecutivi.

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.

[Radiotherapy of recurrences of adenocarcinoma of the rectum after radical surgery: Galliera Hospitals (1976-1985)]. / La radioterapia delle recidive di adenocarcinoma del retto operato radicalmente: Ospedali Galliera (1976-1985).

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.

[High-dose gynecologic endocavitary brachytherapy. Technical and dosimetric aspects]. / Brachiterapia endocavitaria ginecologica ad alta intensità di dose. Aspetti tecnici e dosimetrici.

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.