Development and validation of a new set-up simulator dedicated to ocular proton therapy at CNAO.

An Eye Tracking System (ETS) is used at CNAO for providing a stable and reproducible ocular proton therapy (OPT) set-up, featuring a fixation light (FL) and monitoring stereo-cameras embedded in a rigid case. The aim of this work is to propose an ETS set-up simulation algorithm, that automatically provides the FL positioning in space, according to patient-specific gaze direction and avoiding interferences with patient, beam and collimator. Two configurations are provided: one in the CT room for acquiring images required for treatment planning with the patient lying on a couch, and one related to the treatment room with the patient sitting in front of the beam. Algorithm validation was performed reproducing ETS simulation (CT) and treatment (room) set-up for 30 patients previously treated at CNAO. The positioning accuracy of the device was quantified through a set of 14 control points applied to the ETS case and localizable both in the CT volume and in room X-ray images. Differences between the position of ETS reference points estimated by the algorithm and those measured by imaging systems are reported. The corresponding gaze direction deviation is on average 0.2° polar and 0.3° azimuth for positioning in CT room and 0.1° polar and 0.4° azimuth in the treatment room. The simulation algorithm was embedded in a clinically usable software application, which we assessed as capable of ensuring ETS positioning with an average accuracy of 2 mm in CT room and 1.5 mm in treatment room, corresponding to gaze direction deviations consistently lower than 1°.

Reirradiation of salivary gland tumors with carbon ion radiotherapy at CNAO.

AIMS: To report oncologic and functional outcomes in terms of tumor control and toxicity of carbon ion radiotherapy (CIRT) in reirradiation setting for recurrent salivary gland tumors at CNAO. METHODS: From November 2013 to September 2016, 51 consecutive patients with inoperable recurrent salivary gland tumors were retreated with CIRT in the frame of the phase II protocol CNAO S14/2012C for recurrent head and neck tumors. RESULTS: Majority of pts (74.5%) had adenoid cystic carcinoma, mainly rcT4a (51%) and rcT4b (37%). Median dose of prior photon based radiotherapy was 60 Gy. Median dose of CIRT was 60 Gy [RBE] at a mean of 3 Gy [RBE] per fraction. During reirradiation, 19 patients (37.3%) experienced grade G1 toxicity, 19 pts (37.3%) had G2 and 2 pts (3.9%) had G3. Median follow up time was 19 months. Twenty one (41.2%) patients had stable disease and 30 (58.8%) tumor progression at the time of last follow up. Furthermore, 9 (18%) patients had G1 late toxicity, 19 (37%) had G2 and 9 (17. 5%) had G3. Using the Kaplan Meier method, progression free survival (actuarial) at one and two years were 71.7% and 52.2% respectively. Estimated overall survival (actuarial) at one and two years were 90.2% and 64%, respectively. CONCLUSIONS: CIRT is a good option for retreatment of inoperable recurrent salivary gland tumors with acceptable rates of acute and late toxicity. Longer follow up time is needed to assess the effectiveness of CIRT in reirradiation setting of salivary gland tumors.

A novel framework for spatial normalization of dose distributions in voxel-based analyses of brain irradiation outcomes.

PURPOSE: To devise a novel Spatial Normalization framework for Voxel-based analysis (VBA) in brain radiotherapy. VBAs rely on accurate spatial normalization of different patients' planning CTs on a common coordinate system (CCS). The cerebral anatomy, well characterized by MRI, shows instead poor contrast in CT, resulting in potential inaccuracies in VBAs based on CT alone. METHODS: We analyzed 50 meningioma patients treated with proton-therapy, undergoing planning CT and T1-weighted (T1w) MRI. The spatial normalization pipeline based on MR and CT images consisted in: intra-patient registration of CT to T1w, inter-patient registration of T1w to MNI space chosen as CCS, doses propagation to MNI. The registration quality was compared with that obtained by Statistical Parametric Mapping software (SPM), used as benchmark. To evaluate the accuracy of dose normalization, the dose organ overlap (DOO) score was computed on gray matter, white matter and cerebrospinal fluid before and after normalization. In addition, the trends in the DOOs distribution were investigated by means of cluster analysis. RESULTS: The registration quality was higher for the proposed method compared to SPM (p < 0.001). The DOO scores showed a significant improvement after normalization (p < 0.001). The cluster analysis highlighted 2 clusters, with one of them including the majority of data and exhibiting acceptable DOOs. CONCLUSIONS: Our study presents a robust tool for spatial normalization, specifically tailored for brain dose VBAs. Furthermore, the cluster analysis provides a formal criterion for patient exclusion in case of non-acceptable normalization results. The implemented framework lays the groundwork for future reliable VBAs in brain irradiation studies.

Monte Carlo simulation tool for online treatment monitoring in hadrontherapy with in-beam PET: A patient study.

Hadrontherapy is a method for treating cancer with very targeted dose distributions and enhanced radiobiological effects. To fully exploit these advantages, in vivo range monitoring systems are required. These devices measure, preferably during the treatment, the secondary radiation generated by the beam-tissue interactions. However, since correlation of the secondary radiation distribution with the dose is not straightforward, Monte Carlo (MC) simulations are very important for treatment quality assessment. The INSIDE project constructed an in-beam PET scanner to detect signals generated by the positron-emitting isotopes resulting from projectile-target fragmentation. In addition, a FLUKA-based simulation tool was developed to predict the corresponding reference PET images using a detailed scanner model. The INSIDE in-beam PET was used to monitor two consecutive proton treatment sessions on a patient at the Italian Center for Oncological Hadrontherapy (CNAO). The reconstructed PET images were updated every 10 s providing a near real-time quality assessment. By half-way through the treatment, the statistics of the measured PET images were already significant enough to be compared with the simulations with average differences in the activity range less than 2.5 mm along the beam direction. Without taking into account any preferential direction, differences within 1 mm were found. In this paper, the INSIDE MC simulation tool is described and the results of the first in vivo agreement evaluation are reported. These results have justified a clinical trial, in which the MC simulation tool will be used on a daily basis to study the compliance tolerances between the measured and simulated PET images.

Dosimetric characterization of carbon fiber stabilization devices for post-operative particle therapy.

PURPOSE: The aim of this study was to evaluate the dosimetric impact caused by recently introduced carbon fiber reinforced polyetheretherketone (CF/PEEK) stabilization devices, in comparison with conventional titanium (Ti) implants, for post-operative particle therapy (PT). METHODS: As a first step, protons and carbon ions Spread-Out Bragg Peaks (SOBPs) were delivered to CF/PEEK and Ti screws. Transversal dose profiles were acquired with EBT3 films to evaluate beam perturbation. Effects on image quality and reconstruction artifacts were then investigated. CT scans of CF/PEEK and Ti implants were acquired according to our clinical protocol and Hounsfield Unit (HU) mean values were evaluated in three regions of interest. Implants and artifacts were then contoured in the sample CT scans, together with a target volume to simulate a spine tumor. Dose calculation accuracy was assessed by comparing optimized dose distributions with Monte Carlo simulations. In the end, the treatment plans of nine real patients (seven with CF/PEEK and two with Ti stabilization devices) were retrospectively analyzed to evaluate the dosimetric impact potentially occurring if improper management of the spine implant was carried out. RESULTS: As expected, CF/PEEK screw caused a very slight beam perturbation in comparison with Ti ones, leading to a lower degree of dose degradation in case of contouring and/or set-up uncertainties. Furthermore, CF/PEEK devices did not determine appreciable HU artifacts on CT images thus improving image quality and, as a final result, dose calculation accuracy. CONCLUSIONS: CF/PEEK spinal fixation devices resulted dosimetrically more suitable than commonly-used Ti implants for post-operative PT.

Dosimetric accuracy of a treatment planning system for actively scanned proton beams and small target volumes: Monte Carlo and experimental validation.

This study was performed to evaluate the accuracy of a commercial treatment planning system (TPS), in optimising proton pencil beam dose distributions for small targets of different sizes (5-30 mm side) located at increasing depths in water. The TPS analytical algorithm was benchmarked against experimental data and the FLUKA Monte Carlo (MC) code, previously validated for the selected beam-line. We tested the Siemens syngo(®) TPS plan optimisation module for water cubes fixing the configurable parameters at clinical standards, with homogeneous target coverage to a 2 Gy (RBE) dose prescription as unique goal. Plans were delivered and the dose at each volume centre was measured in water with a calibrated PTW Advanced Markus(®) chamber. An EBT3(®) film was also positioned at the phantom entrance window for the acquisition of 2D dose maps. Discrepancies between TPS calculated and MC simulated values were mainly due to the different lateral spread modeling and resulted in being related to the field-to-spot size ratio. The accuracy of the TPS was proved to be clinically acceptable in all cases but very small and shallow volumes. In this contest, the use of MC to validate TPS results proved to be a reliable procedure for pre-treatment plan verification.

Image guided particle therapy in CNAO room 2: implementation and clinical validation.

In this contribution we describe the implementation of a novel solution for image guided particle therapy, designed to ensure the maximal accuracy in patient setup. The presented system is installed in the central treatment room at Centro Nazionale di Adroterapia Oncologica (CNAO, Italy), featuring two fixed beam lines (horizontal and vertical) for proton and carbon ion therapy. Treatment geometry verification is based on robotic in-room imaging acquisitions, allowing for 2D/3D registration from double planar kV-images or 3D/3D alignment from cone beam image reconstruction. The calculated six degrees-of-freedom correction vector is transferred to the robotic patient positioning system, thus yielding automated setup error compensation. Sub-millimetre scale residual errors were measured in absolute positioning of rigid phantoms, in agreement with optical- and laser-based assessment. Sub-millimetre and sub-degree positioning accuracy was achieved when simulating setup errors with anthropomorphic head, thorax and pelvis phantoms. The in-house design and development allowed a high level of system customization, capable of replicating the clinical performance of commercially available products, as reported with preliminary clinical results in 10 patients.

Capecitabine chemoradiation for rectal cancer after curative surgery.

This study reports the tolerability and feasibility of capecitabine, an oral fluoropyrimidine, chemoradiation as postoperative treatment. Stage II-III rectal cancer patients received 2 cycles of bolus 5-FU (425 mg/m2) and leucovorin (LV) (20 mg/m2) on days 1-5 q3w followed by oral capecitabine (800 mg/m2 bid) continuously during pelvic radiotherapy (total 50.4 Gy). Two additional cycles of 5-FU/LV were finally administered. Forty-one radically resected patients (median age: 61 years) were enrolled. All patients were evaluable for safety. Grade 3 adverse events included: proctitis (n = 3, 7%), diarrhea (n = 5, 12%), and leukopenia (n = 1, 2%). The overall rate of grade 3 diarrhea and leukopenia was 15% (95% confidence interval, 5-29%). Capecitabine chemoradiation in the adjuvant setting is well tolerated and is convenient to administer. These results support the use and further study of capecitabine chemoradiation in radically resected rectal cancer patients.

Adenocarcinoma of the lower third of the rectum surgically treated with a <10-MM distal clearance: preliminary results in 35 N0 patients.

BACKGROUND: Recent reports suggest that a distal clearance (DC) of 10 mm at the lower surgical margin may be considered adequate in the surgical treatment of rectal cancer, but there are no data on the possible adequacy of a < 10-mm DC in N0 patients in whom a good prognosis can otherwise be expected, that is, those with negative surgical margins and negative lymph nodes. METHODS: Between November 1991 and December 1998, 154 consecutive patients with adenocarcinoma of the lower third of the rectum had a total rectal resection with total mesorectal excision and coloendoanal anastomosis. Among 76 N0 patients, there were 35 with <10-mm DC and 41 with > or =10-mm DC. Each group was divided into two subgroups depending on whether the surgical margins were involved or not, and the rate of local recurrence in the various categories was compared. All B2 Astler-Coller stage patients in the series received postsurgical chemoradiotherapy. RESULTS: The local recurrence rate in the 35 patients with DC < 10 mm was 11.4% and that of the 41 patients with DC > or =10 mm was 7.3%. When only patients with negative surgical margins were considered, the local recurrence rate was 3.4% for those with < 10-mm DC and 5.1% for those with > or =10-mm DC. CONCLUSIONS: Our results suggest that a radical surgery with <10-mm DC followed by chemoradiotherapy may be adequate in N0 patients, provided that a careful pathologic examination of the surgical specimen excludes the presence of lymph node metastases and that the distal rectal and mesorectal resection margins fall in healthy tissue.

[Simultaneous radiochemotherapy in rectal tumors]. / La radiochemioterapia concomitante nei tumori del retto.

After about 30 years from the first trials on concurrent chemoradiation in the treatment of rectal carcinoma, a large experience in this field has been shared, both in terms of laboratory and clinical data. The possibility of concurrent chemoradiation to improve the clinical outcome and sphincter preservation in low rectal tumors has been extensively demonstrated. Great attention should be paid to the quality of radiation treatment and drug administration, to minimize the risk of therapy-related toxicity. The impact of preoperative chemoradiation on tumor control will be further clarified by the ongoing randomized studies, in terms of comparison with radiation therapy alone (EORTC study), "Total mesorectal excision" (Duch Study), postoperative chemoradiation (German CAO/ARO/AIO 94) and the potential role of adjuvant chemotherapy (EORTC and Italian study). A series of phase II studies will probably clarify the role of unconventional fractionation modalities (hyperfractionation, accelerated treatments) and of new concomitant chemotherapy (new drugs, chronomodulation) in terms of organ and sphincter preservation. A close cooperation between radiation oncologists, medical oncologists and surgeons is required.

Total rectal resection and complete mesorectum excision followed by coloendoanal anastomosis as the optimal treatment for low rectal cancer: the experience of the National Cancer Institute of Milano.

BACKGROUND: At present, abdominoperineal resection remains the most diffuse method of treatment of very low rectal cancer. Today, we can avoid this method in some patients by using a sphincter-saving procedure. METHODS: From March 1990 to January 1999, 273 consecutive total rectal resections and coloendoanal anastomoses were performed at our Institute; this study concerns 141 consecutive patients treated for a primary adenocarcinoma of the distal rectum, from 3.5 to 8 cm from the anal verge. Patient stratification, based on definitive pathological report, was 31 Dukes' stage A (T2N0), 44 stage B (T3N0), and 66 stage C (T2N+-T3N+). RESULTS: Overall recurrence rate was 9.2%; postoperative morbidity attributable to the procedure was low. A perfect continence was documented in 61% of cases. The only pathological factor related to local recurrence rate is peritumoral lymphocytic reaction inside and around the tumor (P = .0005 and .031) independently from the number of metastatic lymph nodes, depth of fatty tissue infiltration, and lymphatic and venous neoplastic emboli. The minimum follow-up time is 12 months. CONCLUSIONS: Our data, in accordance with other authors, seem to highlight the relevant role that a well-practiced surgery, together with accurate information on the spreading of this disease, has in achieving an optimal local control of cancer.

Integrated treatment with doxifluridine and radiotherapy in recurrent or primary unresectable rectal cancer. A feasibility study.

AIMS AND BACKGROUND: When combined with radiotherapy, fluoropyrimidines have been shown to have synergistic effects on various tumor types. Doxifluridine (5-dFUR) is a 5-fluorouracil (5-FU) prodrug that is transformed into 5-FU in neoplastic tissue, which suggests that it may improve the activity of radiotherapy. The aims of this study were to evaluate the feasibility and efficacy of the combination of radiotherapy and oral 5-dFUR plus l-leucovorin in terms of pathologically complete remissions in locally advanced rectal cancer. METHODS: Eleven patients with locally recurrent (n = 7) or primary unresectable rectal cancer (n = 4) were treated with three cycles of oral l-leucovorin 25 mg/dose followed by 5-dFUR 750 mg/m2 twice daily for four days every 12, in combination with pelvic radiation at a standard dose of 45 Gy over five weeks. The tumor burden was assessed by means of CT and endoscopic ultrasound at baseline and at least four weeks after the end of the treatment and before surgery. RESULTS: Four patients achieved an objective response, 6 disease stabilization and 1 had progressive disease. After a median time of five weeks from the end of treatment 8 patients underwent radical resection and a pathologically complete remission was documented in 2. Seven of these patients are still alive and disease free after a median follow-up of 18 months. The major side effects were grade 3 diarrhea in one case, and grade 1-2 nausea and vomiting in three cases. No significant hematological toxicity was observed. CONCLUSIONS: This combination of radiation and 5-dFUR plus l-leucovorin led to an interesting rate of resectability, with pathological downstaging being documented in two cases. These preliminary results show an encouraging local control of an otherwise unresectable disease. Combined preoperative therapy with oral fluoropyrimidine plus l-leucovorin together with radiation may be an attractive approach in patients with operable rectal cancer.

Radio-chemotherapy of anal cancer.

Conventional treatment of anal cancer has been the demolitive Miles operation for decades. Radiotherapy has been utilized in a limited number of centers for early cancers only. Radio-chemotherapy has become the treatment of choice for all stages of anal cancer after the first experiences by the group of Detroit and after the confirmation of successful results by many other centers. Infusional chemotherapy (5-FU and Mitomycin C or CDDP) and concurrent irradiation are able to achieve local control in more than 80% of patients. Surgery currently represents a rescue treatment for partial responders or in relapsing patients. A brief review of the literature and the experience at the Istituto Tumori in Milano are presented.

Radio-chemotherapy of vulvar cancer.

Surgery alone, more or less demolitive, is the treatment of choice of vulvar cancers. Cure rates are high for early cancers only, while locally advanced tumors with or without inguinal adenopathies and recurrences have a bad prognosis. The excellent results of concurrent chemo-radiotherapy of anal cancers suggested to adopt the same approach for locally advanced vulvar cancers. The shrinkage of the tumor allowed surgery, often less demolitive than usual, and the pathological examination demonstrated an overall complete response in 40% of cases. Survival has been improved through this multidisciplinary approach. Patients not suitable for surgery obtained important remissions and an improved quality of life. Clinical experience at the Istituto Tumori of Milano is presented.

Analysis of risk factors for mandibular bone radionecrosis after exclusive low dose-rate brachytherapy for oral cancer.

BACKGROUND: Brachytherapy is widely adopted as an exclusive treatment of T1/T2 oral cancer with a high probability of definitive cure. Therefore, any major complication, like mandibular bone necrosis, should be avoided. Many risk factors, either clinical or technical, have been considered in the literature. MATERIALS AND METHODS: One hundred consecutive interstitial iridium LDR treatments for early cancers of the tongue and floor of the mouth performed from January 1989 to November 1993 were reviewed. An analysis of some simple technical parameters (total dose, dose-rate, reference volume, linear activity, total reference kerma) was performed in order to identify the main physical risk factors. Moreover, total dose was recalculated as extrapolated responsive dose for normal tissue complications. RESULTS: Bone necrosis was observed in 10 out of 100 patients with a median follow-up of 38 months. No significant incidence of this complication was observed when tumor site (mobile tongue versus floor of the mouth), dental status or total physical dose were considered. A significant correlation between the incidence of bone necrosis and two main parameters was found, i.e. dose-rate (P < 0.02) and reference volume (P < 0.05). CONCLUSIONS: A threshold value may be suggested both for dose-rate (50 cGy/h) and reference volume (25,000 mm3). Bone necrosis is clearly related to both these parameters since most cases (i.e. 80%) were observed in the subgroup over the volume and dose-rate threshold.

Distal intramural spread in adenocarcinoma of the lower third of the rectum treated with total rectal resection and coloanal anastomosis.

PURPOSE: This study was designed to evaluate the frequency of microscopic distal intramural spread in rectal adenocarcinoma and its correlation to other histopathologic prognostic factors. METHODS: We examined 55 patients with adenocarcinomas of the lower one-third of the rectum and measured the extent of distal intramural spread in the submucosa and/or muscular layer in comparison with Dukes Stage, diameter of tumor, distance of distal margin of resection from tumor, depth of infiltration into perirectal adipose tissue, nodal status, neoplastic infiltration of lymphatic vessels, blood vessels, and nervous branches. RESULTS: Distal intramural spread was found in 40 percent of patients, 77 percent of whom had advanced tumors with nodal metastases. Distal intramural spread appeared to be strictly related to tumor size (superior to 40 mm), infiltration of the perirectal adipose tissue, multiple positive lymph nodes, presence of neoplastic emboli in the intramural lymphatic vessels, and neoplastic invasion of the nervous branches. Local recurrence occurred in one Dukes Stage B patient with a positive distal margin of resection and in four patients with a negative distal margin of resection: three Dukes Stage C and one Dukes Stage B patients with neoplastic involvement of the circumferential margin of resection of the mesorectum. CONCLUSION: These preliminary data suggest that distal intramural spread may carry little importance in determining local recurrence of rectal adenocarcinoma.

[Transcutaneous radiotherapy combined with low dose intraluminal brachytherapy in the treatment of non-operable neoplastic stenoses of the bile ducts]. / Radioterapia transcutanea associata a brachiterapia endoluminale con basso rateo di dolore nel trattamento delle stenosi neoplastiche inoperabili delle vie biliari.

Percutaneous biliary drainage is an excellent method to relieve the acute symptoms related to neoplastic stenoses of extrahepatic bile ducts. However, survival rates are low and the quality of life of these patients is poor. High dose irradiation--combined with external beams (ERT) and intraluminal brachytherapy (BRT) through percutaneous drainage--allows effective disease control and, therefore, not only higher survival rates but also a much better quality of life when drainage can be removed after bile duct stenosis resolution. March, 1990, through March, 1993, eleven patients (8 with extrahepatic cholangiocarcinomas and 3 with extrinsic tumors) were treated with combined ERT (40-60 Gy, 6-15 MV X-rays) and intraluminal BRT (6-25 Gy, 192Ir wire, LDR). In 8 patients the biliary stenosis was resolved, completely (CR) in 5 and partially (PR) in 3, as shown by posttreatment cholangiography. In 5 patients biliary drainage could be removed for an average 9 months' period; 3 of 11 patients did not respond to treatment at all (NR). Average overall survival was 14 months: 11 months for NR patients and 16.5 months for CR+PR patients. Treatment complications were acceptable: in two patients only treatment had to be discontinued, both during BRT. Two cases of high grade postirradiation stenosis were observed, both resolved with percutaneous cholangioplasthy.

[Ileal obstruction following radiosurgical treatment for rectosigmoid neoplasm]. / Occlusione ileale dopo trattamento radiochirurgico per neoplasia rettosigmoidea.

A series of 191 patients submitted to adjuvant radiotherapy after surgery for rectal and rectosigmoid carcinoma from January, 1975, to December, 1990, has been analyzed to evaluate the incidence of high grade small bowel late toxicity (grades III/IV according to RTOG/EORTC scoring system). Surgical approach was abdominoperineal Miles resection in 92 patients, while a sphincter preserving bowel resection was performed in 99. The total radiation dose to the pelvis ranged from 40 to 60 Gy in 4 to 8 weeks, with conventional fractionation. Three different beams arrangements were used: two sagittal parallel opposite AP-PA fields in 106 patients, three fields (one posterior sagittal plus two parallel lateral fields) in 56, four fields (box technique) in 29. Fourteen patients (7.3%) developed sequelae grades III/IV: three of them died of toxicity. Average free interval between radiation and complication was 23 months (range: 4-87). The following risk factors were investigated: sex, age, type of surgery on primary rectosigmoid cancer, previous abdominal or pelvic surgery, radiation technique, treated volume, administered radiation dose. Dose was calculated as BED (time corrected biologically equivalent dose) according to the linear quadratic model. The only factors significantly related to late intestinal complications were the beam arrangement and, consequently, the treated volume. Detailed analysis showed that radiation sequelae developed in 12/106 (11.3%) patients treated with the two sagittal fields technique, while small bowel toxicity was observed in only 2/85 (2.3%) patients treated with the three--or four--fields technique. The difference is stastically significant (p < 0.05). Another significant correlation was the ratio between treated volume and late complications incidence observed.(ABSTRACT TRUNCATED AT 250 WORDS)

[The results of definitive transcutaneous radiotherapy in the treatment of oropharyngeal neoplasms]. / Risultati della radioterapia transcutanea esclusiva nel trattamento delle neoplasie dell'orofaringe.

From January 1976 to December 1986, 199 patients with oropharyngeal cancer were submitted to definitive radiotherapy. Survival and local control were analyzed and related to different parameters--i.e, T and N categories, histopathologic grading, tumor location, patients age, and radiation dose. Fifty-six per cent of patients (111/199) died from neoplastic disease within 5 years. Local progression, recurrence or metastases were observed in 149 cases (75%). Ninety-three per cent of first failures (138/149) were related to residual disease or to locoregional relapse while distant metastases occurred in 14 patients only. The majority of locoregional failures (94%) appeared within 2 years, with a mean disease-free interval of 8 months. Tumor recurrence in the primary location was observed to be the first cause of failure in 78% of relapsed patients; moreover, it was the sole cause of failure in half of the unfavorable events. On the contrary, nodal relapse appeared in 38% of treatment failures and in 12% only it was the sole cause of failure. Overall and disease-free survival were observed to depend mainly on T and N categories, while histopathologic grading was seen to affect only early response rate. No significant differences were observed depending on tumor site and patients age. Local control rates depended on total radiation dose, but the difference between low dose (NSD less than 1700) and high dose (NSD greater than 1700) was significant only for T1 and T2 patients.