The effect of tumor volume on radiotherapy outcome and correlation with other prognostic factors in patients with T2 supraglottic cancer.

The retrospective chart review of 110 patients with T2 supraglottic cancer who underwent radiotherapy was performed to correlate tumor volume with other prognostic factors and to analyze its impact on treatment results. Patients with involved nodes, poor histopathological tumor differentiation, or hemoglobin concentration ≤ 14.3 g/dl had significantly larger tumors. Patients with large tumors had significantly lower 5-year local control rate, overall survival rate and presented significantly higher risk of nodal involvement and the ratio of poor histopathological differentiation of the tumor. Tumor volume significantly impacts radiotherapy outcome and should be considered to optimize treatment strategy for patients with T2 supraglottic cancer.

Intraoperative radiotherapy (IORT) with low-energy photons as a boost in patients with early-stage oral cancer with the indications for postoperative radiotherapy : treatment feasibility and preliminary results.

PURPOSE: To evaluate the feasibility and preliminary results of intraoperative radiotherapy (IORT) with low-energy photons as a boost in patients with early-stage oral cancer with the indications for postoperative radiotherapy. PATIENTS AND METHODS: Between 2003 and 2006, 16 patients with early-stage cancer of mobile tongue (n = 10 [63%]) or floor of the mouth (n = 6 [37%]) treated at Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland, were evaluated for IORT boost with the INTRABEAM®System (Carl Zeiss Surgical GmbH; IORT-PRS) because of the high risk of local recurrence due to positive margins on frozen pathologic section. After tumor resection, the applicator was positioned in the tumor bed. The applicator's diameter (range: 1.5-5 cm) was selected to encompass high-risk area of tumor recurrence. The dose (5 Gy, 7 Gy, or 7.5 Gy) was applied according to tumor volume and bone proximity. External-beam radiotherapy (EBRT) was provided to the tumor bed in all patients (50 Gy) and to the nodal area, when needed. Toxicity and local tumor control were assessed. RESULTS: Median follow-up was 36 months. IORT did not increase acute mucosal reaction. Local tumor control was found in all cases. Early mucosal reaction did not exceed 3 according to the RTOG scale and healed in median time of 35 days after completion of EBRT. No late adverse effects were observed. CONCLUSION: This preliminary report has demonstrated the feasibility of IORT-PRS for patients with early oral cancer with the indications for postoperative radiotherapy. This method may be considered an alternative boost technique, although additional studies are needed to establish long-term results in a larger group of patients.

[Comparison of quantitative computerized angiography and intravascular ultrasound in assessment of renal artery stenosis in patients with renovascular hypertension treated with percutaneous transluminal angioplasty with concomitant intravascular brachytherapy]. / Porównanie ilosciowej angiografii i ultrasonografii wewnatrznaczyniowej w ocenie zwezenia resztkowego i restenozy u chorych z nadcisnieniem naczyniowo- nerkowym leczonych metoda przezskórnej angioplastyki tetnicy nerkowej i brachyterapii sródnaczyniowej.

UNLABELLED: Renal Angiography and IntraVascular UltraSonography (IVUS), are valuable diagnosis methods for assessment of renovascular hypertension (RVH). Endovascular techniques employing percutaneous transluminal renal angioplasty (PTRA) are effective for therapy of ischaemic nephropathy in patients with RVH. Success of PTRA is limited by a significant rate of restenosis. THE AIM OF STUDY was to compare the assessment of residual stenosis and restenosis with angiography and IVUS. MATERIAL AND METHODS: Residual stenosis after PTRA (combine with intravascular brachyterapy in 33 patients--group I) were assessed in 62 RVH patients with angiography and IVUS techniques. Both baseline and 9-month follow-up quantitative computerized angiography (QCA) and intravascular ultrasound (IVUS) analysis were performed to assess restenosis. RESULTS: Residual stenosis after PTRA of atherosclerotic lesions was slightly lower with QCA than IVUS (in group I 15.49 +/- 4.69% and 18.81 +/- 4.81% and in group II 15.36 +/- 4.68% and 18.43 +/- 4.69%, respectively). The loss of lumen area in QCA assessment was slightly greater than in IVUS measurement (1.2 +/- 0.7 mm vs. 0.9 +/- 0.8 mm in group I i 1.7 +/- 0.7 mm vs. 1.5 +/- 0.8 mm in group II). The angiographic measurements of late lumen loss, diameter stenosis, and minimal lumen diameter correlated well with IVUS measurements (r = 0.81, r = 0.89 and r = 0.89 respectively). CONCLUSIONS: Angiography and IVUS are equally effective methods for diagnosis and assessment of residual stenosis and restenosis after endovascular renal artery revascularisation.

Clinical and volumetric predictors of local control after robotic stereotactic radiosurgery for cerebral metastases: active systemic disease may affect local control in the brain.

BACKGROUND: The aim of the study was to assess the association between physical and biological dose normalized to volume of the metastatic tumor as well as clinical factors with local control in patients with brain metastases who underwent robotic stereotactic radiosurgery. PATIENTS AND METHODS: A cohort of 69 patients consecutively treated with robotic radiosurgery between 2011 and 2016 was analyzed. The patients were treated with either single fraction radiosurgery or hypofractionated regimens. Biologically effective dose (BED) was calculated assuming alpha/beta value = 10 and both physical dose and BED were normalized to the tumor volume to allow dose-volume effect evaluation. Moreover, clinical and treatment-related variables were evaluated to asses association with local control. RESULTS: A total of 133 tumors were irradiated and their volumes ranged between 0.001 and 46.99 cm3. Presence of extracranial progression was associated with worse local control whereas higher total dose, BED10 > 59 Gy and single metastasis predicted statistically significantly better local outcome. BED10/cm3 > 36 Gy, and BED2 > 60 Gy negatively affected local control in univariate analysis. In multivariate analysis performed on all these variables, presence of a single metastasis, BED10 > 59 Gy and extracranial progression retained their significance. Excluding a priori the BED2/ cm3 parameter resulted with a Cox model confirming significance of all remaining variables. CONCLUSIONS: Hypofractionated treatment schemes have similar efficiency to single fraction treatment in terms of local control and the effect depends on BED irrespective of fractionation schedule. Effective control of extracranial sites of the disease is associated with higher probability of local control in the brain which in turn is consistently lower in patients with multiple lesions.

Randomised clinical trial on 7-days-a-week postoperative radiotherapy vs. concurrent postoperative radio-chemotherapy in locally advanced cancer of the oral cavity/oropharynx.

OBJECTIVE: To compare the efficacy and tolerance of 7-days-a-week accelerated postoperative radiotherapy (p-CAIR) vs postoperative radio-chemotherapy (p-RTCT). METHODS: Between September 2007 and October 2013, 111 patients were enrolled and randomly assigned to receive 63 Gy in 1.8 Gy fractions 7-days-a-week (n = 57, p-CAIR) or 63 Gy in 1.8 Gy fractions 5-days-a-week with concurrent cisplatin 80-100 mg per square meter of body-surface area on days 1, 22 and 43 of the radiotherapy course (p-RTCT). It represents approximately 40% of the intended trial size, that was closed prematurely due to slowing accrual. Only high-risk patients with squamous cell cancer of the oropharynx/oral cavity, considered fit for concurrent treatment were enrolled. RESULTS: The rate of locoregional control (LRC) did not differ significantly between treatment arms (p = 0.18, HR = 0.56), 5 year LRC tended, however, to favour p-RTCT (81%) vs p-CAIR (62%). There was no difference in overall survival between treatment arms (p = 0.90, HR = 1.03).The incidence and severity of acute mucosal reactions and late reactions did not differ significantly between treatment arms. Haematological toxicity of p-RTCT was, however, considerably increased compared to p-CAIR. CONCLUSION: Concurrent postoperative RTCT tended to improve locoregional control rate as compared to p-CAIR. This, however, did not transferred into improved overall survival. Postoperative RTCT was associated with a substantial increase in haematological toxicity that negatively affected treatment compliance in this arm. ADVANCES IN KNOWLEDGE: To our knowledge, this is the first trial that compares accelerated radiotherapy and radio-chemotherapy in postoperative treatment for oralcavity/oropharyngeal cancer.

Randomized clinical trial on 7-days-a-week postoperative radiotherapy for high-risk squamous cell head and neck cancer.

PURPOSE: To evaluate the normal tissue reactions and loco-regional control rates (LRC) in patients treated with 7-days-a-week postoperative continuous irradiation (p-CAIR) compared to conventionally fractionated 5-days-a-week postoperative radiotherapy (CF). MATERIALS/METHODS: Between 2001 and 2004, 279 patients with high-risk squamous cell cancer of the larynx (158 pts.) or cancer of the oral cavity/oropharynx (121 pts.) were enrolled. They were stratified according to the primary cancer site (larynx vs. others) and the treating center and randomized to receive 63 Gy in fractions of 1.8 Gy given 5-days-a-week (140 pts: CF) or 7-days-a-week (139 pts: p-CAIR). RESULTS: The acute and late toxicity was considered acceptable, although the proportion of patients with confluent mucositis was higher in p-CAIR compared to CF (60.0 vs. 33.3%). The actuarial 3-year LRC were 64 vs. 70% for CF and p-CAIR, respectively, p=0.32. A statistically significant improvement in 3-year LRC in p-CAIR arm appeared in a subset of the patients with cancer of the oropharynx/oral cavity (74% p-CAIR vs. 53% CF, p=0.02). By contrast, there was no improvement in LRC in a subset of the patients with cancer of the larynx (p=0.46). CONCLUSION: An improvement in LRC attributable to acceleration of postoperative radiotherapy appeared restricted to the patients with cancer of the oropharynx/oral cavity. In patients with cancer of the larynx acceleration of postoperative radiotherapy did not have any beneficial effect.

Angiographic and intravascular ultrasound assessment of immediate and 9-month efficacy of percutaneous transluminal renal artery balloon angioplasty with subsequent brachytherapy in patients with renovascular hypertension.

BACKGROUND/AIM: Scarce data exist concerning the long-term effect of renal balloon angioplasty (PTRA) enhanced by intravascular gamma-brachytherapy (IVBT) in patients with renovascular hypertension. The aim of this randomized study was to evaluate long-term outcome after PTRA with IVBT in patients with renal artery stenosis. PATIENTS AND METHODS: 71 patients with renovascular hypertension were randomized into group I (PTRA + IVBT) or group II (PTRA). 9 patients who required stent implantation were excluded. Both baseline and 9-month follow-up quantitative computerized angiography and intravascular ultrasound (IVUS) analysis were performed to assess restenosis. During the 9-month follow-up, 3 patients died - 2 from group I and 1 from group II. RESULTS: The restenosis rate was 16.1% in group I and 32.1% in group II. The 9-month lumen loss in angiography was 1.2 +/- 0.7 and 1.7 +/- 0.7 mm (p = 0.004) and the area loss (IVUS) was 6.5 +/- 4.8 and 10.1 +/- 5.6 mm(2) in groups I and II, respectively (p = 0.01). eGFR increased both in group I (from 75 +/- 22 to 84 +/- 31 ml/min/1.73 m(2); p < 0.001) and in group II (from 74 +/- 23 to 77 +/- 23 ml/min/1.73 m(2); p = 0.04). Only the diastolic blood pressure in group I decreased significantly (65 +/- 17 and 77 +/- 18 mm Hg; p = 0.048). The rate of blood pressure normalization was low in both groups (6.1 and 6.9%). CONCLUSIONS: IVBT after PTRA with a self-centering source is a safe and effective method for prevention of restenosis in patients with renovascular hypertension.

Methylation of the MGMT and p16 genes in sporadic colorectal carcinoma and corresponding normal colonic mucosa.

BACKGROUND: Colorectal cancer, one of the most aggressive cancers, occurs with a high incidence in most countries. The usual treatment is surgery and subsequent chemotherapy and radiotherapy. Cancer development and progression is dictated by series of alterations in genes such as tumor suppressor genes, DNA repair genes, oncogenes and others. In colorectal carcinogenesis disturbances different from mutations called an epigenetic regulation are also taken into consideration. Epigenetics is defined as a modifications of the genome, heritable during cell division, which do not involve a change in the DNA sequence. In our study we analyzed methylation of CpG islands in the MGMT and p16 genes in sporadic colorectal cancers and normal corresponding colonic mucosa. MATERIAL/METHODS: Fresh tissue samples were obtained from 68 patients (age of 23 to 81 years) with primary colorectal adenocarcinoma and corresponding normal tissues. We used methylation-specific polymerase chain reaction (MSP) for analysis of the methylation status of MGMT and p16. RESULTS: Methylation of MGMT and p16 was detected in 59% and 53% of tumors, respectively. In corresponding normal colonic mucosa methylation of MGMT was detected in 20% and p16 in 18%. The normal colon mucosa obtained from younger patients (age of <65 years) showed less methylation frequency as compared with the normal mucosa from the older ones (age of >65 years). CONCLUSIONS: The older age and female gender are generally associated with higher methylation levels for most CpG islands in normal colonic mucosa. These results indicate that MGMT and/or p16 aberrant methylation may play an important role in colorectal cancer.

Salvage CyberKnife-Based Reirradiation of Patients With Recurrent Prostate Cancer: The Single-Center Experience.

The aim of this study was to evaluate CyberKnife-based radioablation as a salvage treatment for prostate cancer postirradiation relapses based on a group of patients disqualified from available conventional methods of salvage treatment. Thirty-eight patients were treated with a fraction dose varying from 5.5 to 10 Gy (median 7.35) to a total dose of 18 to 36.25 Gy (median 36.25). In all, 55.3% of patients had androgen deprivation therapy during this time. Nine patients had oligometastases in the salvage time. The follow-up varied from 1.6 to 46.4 months (mean 19.7, median 14.4). In all, 92.6% to 97.4% of patients had no gastrointestinal acute adverse effects; no effects higher than G1 were noted. There were particular (up to 4.8%) G2 late gastrointestinal effects. The percentage without genitourinary acute effects varied from 59.1% to 78.9%; 3.7% had G3 toxicity. G3 late genitourinary toxicity appeared 3 times, the maximal percentage being 12.5% (24 months after salvage treatment). The nadir of prostate-specific antigen median was 0.24 ng/mL (9 months after treatment). Twelve (31.6%) patients failed in the timeline of 6 to 42 months after salvage treatment (mean 18.7, median 16.5)-5 due to dissemination. In 2 cases, progression in existing metastases was identified. Five (13.2%) patients had biochemical failure without additional metastases (local relapses); hence, local control was 86.8%. The failure risk is strongly influenced by initial disease stage and presalvage prostate-specific antigen concentration. The obtained results permit us to conclude that such a treatment could be an effective and safe option for prostate cancer postirradiation relapse salvage treatment.

Continuous accelerated 7-days-a-week radiotherapy for head-and-neck cancer: long-term results of phase III clinical trial.

PURPOSE: To update 5-year results of a previously published study on special 7-days-a-week fractionation continuous accelerated irradiation (CAIR) for head-and-neck cancer patients. METHODS AND MATERIALS: One hundred patients with squamous cell carcinoma of head and neck in Stage T(2-4)N(0-1)M(0) were randomized between two definitive radiation treatments: accelerated fractionation 7 days a week including weekends (CAIR) and conventional 5 days a week (control). Hence the overall treatment time was 2 weeks shorter in CAIR. RESULTS: Five-year local tumor control was 75% in the CAIR group and 33% in the control arm (p < 0.00004). Tumor-cure benefit corresponded with significant improvement in disease-free survival and overall survival rates. Confluent mucositis was the main acute toxicity, with the incidence significantly higher in CAIR patients than in control (respectively, 94% vs. 53%). When 2.0-Gy fractions were used, radiation necrosis developed in 5 patients (22%) in the CAIR group as a consequential late effect (CLE), but when fraction size was reduced to 1.8 Gy no more CLE occurred. Actuarial 5-year morbidity-free survival rate was similar for both treatments. CONCLUSIONS: Selected head-and-neck cancer patients could be treated very effectively with 7-days-a-week radiation schedule with no compromise of total dose and with slight 10% reduction of fraction dose (2 Gy-1.8 Gy), which article gives 1 week reduction of overall treatment time compared with standard 70 Gy in 35 fractions over 47-49 days. Although this report is based on the relatively small group of patients, its results have encouraged us to use CAIR fractionation in a standard radiation treatment for moderately advanced head-and-neck cancer patients.

Randomized clinical trial on continuous 7-days-a-week postoperative radiotherapy for high-risk squamous cell head-and-neck cancer: a report on acute normal tissue reactions.

BACKGROUND AND PURPOSE: To analyse acute mucosal reactions in patients treated with continuous accelerated postoperative irradiation (p-CAIR) compared to conventionally fractionated postoperative radiotherapy (p-CF). PATIENTS AND METHODS: The patients were randomly assigned to receive 63 Gy in 1.8 Gy fractions 7-days-a-week given over a period of 5 weeks (n=88), or 63 Gy in 1.8 Gy fractions given 5-days-a-week over 7 weeks (n=87). It represents 65% of an overall trial size. Acute mucosal reactions were scored using modified Dische system. Polychotomous logistic regression was used to estimate the influence of the selected variables on maximum grade of mucositis, and percent of the body weight loss during radiotherapy. RESULTS: The average maximum Dische score and percent of the patients with confluent mucositis were higher in patients treated with p-CAIR, compared to p-CF (13.3 vs. 10.8 and 54 vs. 27%). Polychotomous logistic regression analysis revealed that fractionation scheme and tumour site have significantly influenced maximum Dische score. Tumour site (laryngeal vs. other) had even stronger influence on maximum Dische score than fractionation scheme. The average residual Dische score 8 weeks after radiotherapy was higher in p-CAIR compared to p-CF (2.1 vs. 1.4), and was, most frequently, related to persistent mucosal erythema (70 vs. 57% of pts.). No severe consequential toxicity of radiotherapy was observed, so far, in the trial. CONCLUSIONS: While the incidence, intensity and duration of mucosal reactions was higher in p-CAIR than in p-CF the accelerated treatment can be considered tolerable with respect to acute toxicity. In both arms of the trial slight or moderate mucosal erythema was the most frequent acute side effect, which did not completely subside within 8 weeks after irradiation.

[Evaluation of tolerance and efficacy of postoperative combined radiotherapy and chemotherapy in locally advanced gastric cancer]. / Ocena tolerancji i skutecznosci pooperacyjnej radiochemioterapii u chorych na zaawansowanego miejscowo raka zoladka.

PURPOSE: To assess the toxicity and the efficacy of adjuvant radio-chemotherapy in patients with high-risk gastric cancer. METHODS AND MATERIALS: Patients with adenocarcinoma of the stomach were enrolled into the study from April 1999 to December 2000. There were 15 females and 27 males, 33 to 69 years old (median 52). There were following inclusion criteria: tumor stages T1-2 N1-3 or T3-4 N0-3, no distant metastases (except resected metastases to sac or spleen). All patients had lymph node and/or serosal involvement. Radiation dose of 42.5 Gy in 1.7 Gy per fraction was delivered to the tumor bed and regional lymph nodes over 5 weeks. In 4 cases of nonradical surgery a boost dose of 8.5 Gy was given. Chemotherapy consisted of 5-Fu 325 mg/m2/day, given on day 1-3 and 29-31 of radiotherapy. RESULTS: All patients completed radiotherapy as planned. Mild nausea/vomiting in 43% of pts., leucopenia WHO 1 and 2 in 43% of pts. as well as WHO 3 in 5% of pts. and diarrhea WHO 1 and 2 in 21% of pts. were the most frequent toxicities. Three year relapse-free survival and overall survival rates were 29% and 31%, respectively (median 12 and 18 months). Three year survival rates in stage II, III and IV were 67%, 24% and 17% respectively. CONCLUSION: Postoperative radio-chemotherapy in patients with locally advanced gastric cancer was safe and well tolerated. The results obtained in this study and from literature suggest that adjuvant radio-chemotherapy may improve 3-year survival rates by 10-15% compared to historical controls treated with surgery alone.

[Assessment of radiation injuries to the salivary glands after treatment of head and neck cancers]. / Ocena wystepowania póznego odczynu popromiennego w obrebie slinianek po napromienianiu nowotworów glowy i szyi.

PURPOSE: The purpose of this investigation was to evaluate the quality of life, measured in LENT-SOMA and DISCHE scale, of patients with xerostomia as late irradiation injury. MATERIALS AND METHODS: 45 head and neck cancer patients were radically irradiated receiving doses from 48 Gy to 76.8 Gy (mean: 65.1 Gy) on PTV. Patients received doses from 48 to 76 Gy on salivary gland (mean: 63.8 Gy, SD: 8). The irradiation injury of the oral cavity was assessed using DISCHE scale at the end of radiotherapy and late radiation sequels of salivary gland was assessed in 6 and 7 month after radiotherapy using DISCHE and LENT-SOMA scale. The average follow-up for this group of patients was 8 months. RESULTS: All patients with 6 and more points of acute reactions assessed in DISCHE scale at the end of radiotherapy have had xerostomia in follow-up period. Results measured by LENT-SOMA scale was similar to DISCHE scale. CONCLUSIONS: Dose escalation of radiotherapy increases number of xerostomia as late irradiation injury. Both scales (LENT-SOMA and DISCHE) are similar in qualifying and quantifying of salivary gland radiation injury. Minimal therapeutic dosage prescribed on salivary gland after which irradiation injury occurred was 63 Gy.

1H-MR spectroscopy of normal brain tissue before and after postoperative radiotherapy because of primary brain tumors.

PURPOSE: Brain metabolism after surgery and postoperative radiotherapy (pRT) because of primary brain tumors was assessed by proton magnetic resonance spectroscopy ((1)H-MRS) in vivo. The study was designed to reveal the impact of pRT on normal brain tissue metabolism, which may potentially help in delineating the target volumes for reirradiated patients. METHODS AND MATERIALS: Spectra of 43 patients ages 16-63 years treated with pRT for primary glial tumors in the Center of Oncology Maria Curie Memorial Institute Branch in Gliwice were analyzed. The control group consisted of spectra acquired for 30 healthy volunteers. All patients were treated with 3D conformal techniques using 6-20 MV photons to total doses of 60 Gy. Spectra were acquired from the control region before pRT and from three uninvolved regions 9-12 months after the end of pRT. Voxels were located in the region of low (<6 Gy), medium (29-39 Gy), and high radiation dose ( approximately 60 Gy). Relative intensities of the signals relating to N-acetyl-aspartate (NAA), choline-based compounds, creatine and phosphocreatine (Cr), mio-Inositol, lactate, and lipids were obtained. RESULTS: The spectra of "normal brain" taken 9 months after pRT are significantly different from those obtained for control volunteers and from the spectra acquired before radiotherapy. The lactate and lipids signals are very strong; however, they are not correlated with absorbed dose. NAA/Cr ratios are significantly lower than before radiotherapy even for the low-dose regions. Differences increase with radiation dose: the NAA/Cr ratio is significantly lower for the regions of brain receiving a high dose of radiation than for the low-dose areas. CONCLUSION: Combined treatment of primary brain tumors (surgery + postoperative radiotherapy) causes alteration of brain metabolism, even in regions of the brain far from the postoperative tumor bed and receiving relatively low total doses of radiation. Single voxel MRS spectroscopy in vivo cannot help in delineating target volumes for secondary irradiation.

Clinical radiobiology of stage T2-T3 bladder cancer.

PURPOSE: To evaluate the relationship between total radiation dose and overall treatment time (OTT) with the treatment outcome, with adjustment for selected clinical factors, in patients with Stage T2-T3 bladder cancer treated with curative radiotherapy (RT). METHODS AND MATERIALS: The analysis was based on 480 patients with Stage T2-T3 bladder cancer who were treated at the Center of Oncology in Gliwice between 1975 and 1995. The mean total radiation dose was 65.5 Gy, and the mean OTT was 51 days. In 261 patients (54%), planned and unplanned gaps occurred during RT. Four fractionation schedules were used: (1) conventional fractionation (once daily, 1.8-2.5 Gy/fraction); (2) protracted fractionation (pelvic RT, once daily, 1.6-1.7 Gy/fraction, boost RT, once daily, 2.0 Gy/fraction); (3) accelerated hyperfractionated boost (pelvic RT, once daily, 2.0 Gy/fraction; boost RT, twice daily, 1.3-1.4 Gy/fraction); and (4) accelerated hyperfractionation (pelvic and boost RT, twice daily, 1.2-1.5 Gy/fraction). In all fractionation schedules, the total radiation dose was similar (average 65.5 Gy), but the OTT was different (mean 53 days for conventional fractionation, 62 days for protracted fractionation, 45 days for accelerated hyperfractionated boost, and 41 days for accelerated hyperfractionation). A Cox proportional hazard model and maximum likelihood logistic model were used to evaluate the relationship between the treatment-related parameters (total radiation dose, dose per fraction, and OTT) and clinical factors (clinical T stage, hemoglobin level and bladder capacity before RT) and treatment outcome. RESULTS: With a median follow-up of 76 months, the actuarial 5-year local control rate was 47%, and the overall survival rate was 40%. The logistic analysis, which included the total dose, OTT, and T stage, revealed that all of these factors were significantly related to tumor control probability (p = 0.021 for total radiation dose, p = 0.038 for OTT, and p = 0.00068 for T stage). A multivariate Cox model, which included the treatment-related parameters and other clinical factors, revealed that the hemoglobin level and bladder capacity before RT and T-stage were statistically significant factors determining local control and overall survival. The total radiation dose was of borderline statistical significance for overall survival (p = 0.087), and OTT did not reach statistical significance. CONCLUSION: The results of our study showed that the treatment outcome after RT for bladder cancer depends mainly on clinical factors: hemoglobin level and bladder capacity before RT, and clinical T stage. An increase in the total radiation dose seemed to be associated with a better treatment outcome. The effect of the OTT was difficult to define, because it was influenced by other prognostic factors.

Time factor in postoperative radiotherapy: a multivariate locoregional control analysis in 868 patients.

PURPOSE: To study locoregional tumor control in postoperative radiotherapy (PRT) for head-and-neck cancer in relation to the position and duration of treatment gaps, duration of the interval surgery-radiotherapy, and to the other potentially prognostic variables. METHODS AND MATERIALS: The retrospective study included 868 patients with cancer of the larynx, oral cavity, oropharynx, and hypopharynx treated in Gliwice between 1980 and 1997. Mean total radiation dose, dose per fraction, overall radiation treatment time (OTT), and the interval surgery-PRT were 62.8 Gy, 2.1 Gy, 45 days, and 63 days, respectively. No interruptions during PRT (except for weekend breaks) appeared in 30% of patients, whereas 19% had more than 5 days of gap. The actuarial locoregional recurrence-free survival (RFS) has been examined using multivariate Cox regression model, and the ultimate locoregional tumor control probability using a logistic model. RESULTS: Increased duration of treatment gaps, positive resection margins, pathologically proven metastases to the neck nodes, and extralaryngeal site of cancer were significantly related to a decrease in RFS. The duration of time interval surgery-PRT appeared, by contrast, only borderline significant for RFS. The relative risk of locoregional recurrence was approximately the same for the gaps in days 1-21 as for the "late" gaps (days >21), except in a subgroup of patients with positive clinical margins. The logistic analysis revealed a significant time-related displacement of the dose-response curves for PRT. The detriment from the protraction of OTT appeared to be larger than the benefit from the equivalent shortening of OTT. CONCLUSIONS: Although the conclusions from this study must be regarded as only hypothesis-generating, we assume that a highly significant adverse influence of radiation treatment gaps on the rate of tumor control is consistent with rapid repopulation of cancer clonogenes during PRT. Lack of significant effect of the position of gaps on locoregional tumor control after radical surgery may suggest that a lag time for the onset of repopulation in PRT is short. A less likely explanation is that the total amount of regeneration during OTT is the same, regardless of the timing of the gap, even if all the repopulation occurred late. The magnitude of the detriment in tumor control from prolonged interval surgery-PRT indicates that repopulation of cancer cells between surgery and radiotherapy is not as fast as between the fractions of radiotherapy.

1H-MRS in vivo predicts the early treatment outcome of postoperative radiotherapy for malignant gliomas.

PURPOSE: To analyze prospectively the prognostic significance of 1H magnetic resonance spectroscopy (MRS) in vivo recorded from the tumor bed of patients after surgery for malignant glioma. METHODS AND MATERIALS: Fifty-one patients aged 20-68 years were examined using a MRI/MRS system (Elscint 2T Prestige). Of the 51 patients, 33 had Grade 3 gliomas and 18 had glioblastomas. MRI-localized 1HMR spectra were acquired using a single-voxel, double-spin-echo sequence. Relative intensities of the signals (choline, creatine [Cr] N-acetyl aspartate [NAA], myo-inositol, lactate, and lipids) were obtained by numeric integration of fitted signals. Two voxels were examined, one located at the tumor bed and the second distant to the tumor bed. All patients were irradiated to 60 Gy using three-dimensional conformal noncoplanar techniques to 60 Gy. RESULTS: MRS in vivo in patients after brain tumor surgery revealed a statistically significant decrease in the NAA/Cr ratio and increases in the choline/creatine (Cr), choline/NAA, and myo-inosytol/Cr ratios. The intensive signals of lactate and lipids appeared in spectrum. Survival correlated strongly with tumor grade and patient age but the strongest prognostic factor was the lactate/NAA ratio. For lactate/NAA values >2.0 (intensive lactate signal) the 1-year survival rate was 20%, and for lactate/NAA values <2.0, the 1-year survival rate was 85%. CONCLUSION: A new diagnostic tool demonstrated ability to distinguish between patients with a favorable prognosis and those who will die within 1 year.

How fast is repopulation of tumor cells during the treatment gap?

PURPOSE/OBJECTIVE: Our goal was to analyze the repopulation of surviving tumor cells during a treatment gap in radiotherapy for head-and-neck cancer. METHODS AND MATERIALS: Clinical material is based on the records of 1502 patients treated by radiotherapy alone in Maria Sklodowska-Curie Memorial Institute in Gliwice during the period between1980 and 1989. All patients had histologically confirmed squamous cell carcinoma of the larynx or pharynx. The mean gap duration was 9 days. Only 10% of patients were treated without gaps. The dose per fraction was in the range of 1.5 to 2.5 Gy. Patient data were fitted directly to the mixed linear-quadratic model using maximum-likelihood estimation. Tumor stage or tumor localization was introduced into the equation as a categorical variable. Tumor proliferation was estimated by dividing the treatment gaps into three groups: the first 2 weeks, second 2 weeks, and the period after 4 weeks of irradiation. RESULTS: Tumor control probability was significantly correlated with radiation dose, tumor progression (according to TNM), overall treatment time, and gap duration. Laryngeal cancers had a better prognosis than cancers of the oro- and nasopharynx. Significant tumor repopulation was found after the first 2 weeks of radiotherapy. During the treatment gap, the proliferation rate was equal to 0.75 Gy/day. During the days with irradiation, repopulation was slower and equal to 0.2 Gy/day. CONCLUSION: The repopulation of tumor cells is faster during a gap than during the normal days of irradiation. Accelerated repopulation probably starts soon after 2 weeks of irradiation.

Training logbook for radiotherapy.

AIM: To develop a structured logbook for trainees in the medical specialty of radiotherapy with Europe that records the increasing experience throughout their training period. MATERIAL AND METHODS: A working party appointed by the European Board of Radiotherapy developed a draft version of a European logbook for trainees in radiotherapy. For development, the update European Core Curriculum for Radiotherapists (Radiation Oncologists) was taken into consideration. The logbook is composed of six sections: (1) biodata of the trainee, (2) scientific training documentation, (3) clinical training documentation, (4) record of formal presentations by the trainee, (5) publications, (6) training courses. Decisions were made to suggest that the clinical section of the logbook should: (a) only collect data that was essential for the purposes of appraisal, assessment and regulation, (b) be as user friendly as possible, (c) concentrate on quality of the data and not volume. The logbook was tested by trainees in several European training departments and adapted according to their suggestions. A final draft of the logbook was circulated among the national and professional societies for radiotherapy in Europe for review before a European consensus conference took place in Brussels in December 2002. RESULTS: The European training logbook for radiotherapy was endorsed by representatives of 35 European nations during the Brussels consensus conference on December 14, 2002. CONCLUSION: Keeping a training logbook is an essential feature of the record of training for all EU trainees who wish to retain an opportunity to spend part of their training time in another country of the Union, important for someone who seeks an appointment as a specialist in another country within a few years of achieving specialist accreditation, and good professional practice for all other trainees. The European training logbook for radiotherapy is a robust instrument that allows the systematic collection of the information that needs to be recorded to monitor the professional development of European trainees in Radiation Oncology.

Stereotactic methods in interdisciplinary diagnosis and treatment of posterior fossa tumours.

For over 2 years, we have had access to latest generation apparatus and software for planning and stereotactic treatment as well as for x-rays treatment. Until now, we have carried out over 100 procedures. These included 52 stereotactic biopsies of neoplasms, some of them located within the structures of the posterior fossa. In this report, we have discussed the possibilities and effectiveness of diagnosis and treatment of tumours located in different structures, including posterior cave. In the study, we used stereotactic methods. We have described biopsies of the following tumours: cerebellar hemisphere tumour (diagnosed as "metastatic atypic planoepitheliale carcinoma" in a patient with coexisting orbit lymphoma), a bifocal lesion (located in cerebellar hemisphere and cerebellar peduncle, diagnosed as pilocytic astrocytoma of WHO malignancy grade II/III), and lesion (located in the pons, diagnosed as pilocytic astrocytoma WHO grade II).