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Giuseppe Sanguineti

Publications and source records attributed to Giuseppe Sanguineti.

At least 19 recordsLinked to original sources
PubMed2006

Is there a "mucosa-sparing" benefit of IMRT for head-and-neck cancer?

PURPOSE: To investigate whether intensity-modulated radiation therapy (IMRT) allows more mucosal sparing than standard three-field technique (3FT) radiotherapy for early oropharyngeal cancer. METHODS AND MATERIALS: Whole-field IMRT plans were generated for 5 patients with early-stage oropharyngeal cancer according to Radiation Therapy Oncology Group 0022 (66 Gy/30 fractions/6 weeks) guidelines with and without a dose objective on the portion of mucosa not overlapping any PTV. 3FT plans were also generated for the same 5 patients with two fractionation schedules: conventional fractionation (CF) to 70 Gy/35 fractions/7 weeks and concomitant boost (CB) to 72 Gy/40 fractions/6 weeks. Cumulative dose volume histograms (DVHs) of the overall mucosal volume (as per in-house definition) from all trials were compared after transformation into the linear quadratic equivalent dose at 2 Gy per fraction with a time factor correction. RESULTS: Compared with IMRT without dose objective on the mucosa, a 30-Gy maximum dose objective on the mucosa allows approximately 20% and approximately 12% mean absolute reduction in the percentage of mucosa volume exposed to a dose equivalent to 30 Gy (p < 0.01) and 70 Gy (p < 0.01) at 2 Gy in 3 and 7 weeks, respectively, without detrimental effect on the coverage of other regions of interest. Without mucosal dose objective, IMRT is associated with a larger amount of mucosa exposed to clinically relevant doses compared with both concomitant boost and conventional fractionation; however, if a dose objective is placed, the reverse is true, with up to approximately 30% reduction in the volume of the mucosa in the high-dose region compared with both concomitant boost and conventional fractionation (p < 0.01). CONCLUSIONS: Intensity-modulated radiation therapy can be potentially provide more mucosal sparing than traditional approaches.

Carcinoma, Squamous Cell↗
PubMed2006

Does treatment of the pelvic nodes with IMRT increase late rectal toxicity over conformal prostate-only radiotherapy to 76 Gy?

PURPOSE: To compare late rectal toxicity rates after three-dimensional conformal radiotherapy to the prostate alone (P-3D-CRT) and whole-pelvis intensity-modulated radiotherapy along with a prostate boost (WP-IMRT/PB) to the same nominal total dose to the prostate. PATIENTS AND METHODS: 68 patients treated with conformal radiotherapy to the prostate only to 76 Gy at the National Institute for Cancer Research, Genoa, Italy, represented the first group (P-3D-CRT). The second group consisted of 45 patients treated at the University of Texas Medical Branch (UTMB), Galveston, TX, USA, with IMRT covering the pelvic nodes and seminal vesicles to 54 Gy at 1.8 Gy per fraction and the prostate to 60 Gy in the same 30 fractions. A separate phase boosted the prostate to 76 Gy (WP-IMRT/PB). Major aspects of planning were remarkably similar at both institutions leaving the inclusion or not of pelvic nodes as the main treatment-related difference between the two groups. Late rectal toxicity was prospectively scored according to the RTOG scale. All patients have a 12-month minimum follow-up, and mean follow-up, similar in both groups, is 25.9 months (SD [standard deviation]: 8.4 months). RESULTS: At 2 years, the estimated cumulative incidence of grade 2 late rectal toxicity is 6%+/-4% for WP-IMRT/PB and 21.2%+/-6% for P-3D-CRT (p=0.06). The difference became significant (HR [hazard ratio]=0.1, 95% CI [confidence interval]: 0.0-0.6; p=0.01) at multivariate analysis. None of the patients developed grade 3+ toxicity. CONCLUSION: Despite the larger treated volume, WP-IMRT/PB allows more rectal sparing than P-3D-CRT.

Actuarial Analysis↗
PubMed2005

Is IMRT needed to spare the rectum when pelvic lymph nodes are part of the initial treatment volume for prostate cancer?

PURPOSE: To assess whether a 4-field box technique (4FBT), along with its technical refinements, is an adequate approach in terms of rectal sparing and target coverage for patients with localized prostate cancer undergoing whole-pelvic radiotherapy followed by a prostate boost and whether or not intensity-modulated radiotherapy (IMRT) is needed. METHODS AND MATERIALS: For 8 patients, 31 plans were generated, each of them differing in one or more features, including prescription (dose/volume) and/or technical factors. For the latter, several "solutions" to try to reduce the amount of irradiated rectal volume were addressed, including modifications of the 4FBT and the use of sequential IMRT. We constructed a database with 248 plans that were tested for their ability to meet a series of rectal dose-volume constraints at V50, V60, V65, V70, V75, and V75.6. Multivariate logistic regression was used to identify factors independently associated with the end point. Successful solutions were also compared in terms of coverage of both pelvic node and prostate planning target volume (PTV) by isodose 95%. RESULTS: At multivariate logistic regression, both rectal blocking and IMRT were independent predictors of the probability of meeting rectal dose-volume constraints during the pelvic and boost phases of treatment with close relative risks. However, on average, partial rectal blocking on lateral fields of 4FBT during whole-pelvic radiotherapy resulted in about 3% of pelvic node PTV being outside isodose 95%; only 2 of 8 patients had the pelvic nodal PTV covered similarly to what was achieved by whole-pelvis IMRT. Conversely, blocking the rectum during the last 3 fractions of the conformal boost showed a dosimetric coverage of prostate PTV similar to that achieved by IMRT boost. Interestingly, patient anatomic configuration was the strongest predictor of rectal sparing. Finally, the size of prostate margins to generate PTV was also independently associated with the probability of meeting rectal dose-volume constraints. CONCLUSION: In the dose range of 70-76 Gy to the prostate, IMRT and standard techniques are equally effective in meeting rectal dose-volume constraints. However, whole-pelvis IMRT might be preferable to standard techniques for its slightly superior PTV coverage.

Chi-Square Distribution↗
PubMed2005

Accelerated versus conventional fractionated postoperative radiotherapy for advanced head and neck cancer: results of a multicenter Phase III study.

PURPOSE: To determine whether, in the postoperative setting, accelerated fractionation (AF) radiotherapy (RT) yields a superior locoregional control rate compared with conventional fractionation (CF) RT in locally advanced squamous cell carcinomas of the oral cavity, oropharynx, larynx, or hypopharynx. METHODS AND MATERIALS: Patients from four institutions with one or more high-risk features (pT4, positive resection margins, pN >1, perineural/lymphovascular invasion, extracapsular extension, subglottic extension) after surgery were randomly assigned to either RT with one daily session of 2 Gy up to 60 Gy in 6 weeks or AF. Accelerated fractionation consisted of a "biphasic concomitant boost" schedule, with the boost delivered during the first and last weeks of treatment, to deliver 64 Gy in 5 weeks. Informed consent was obtained. The primary endpoint of the study was locoregional control. Analysis was on an intention-to-treat basis. RESULTS: From March 1994 to August 2000, 226 patients were randomized. At a median follow-up of 30.6 months (range, 0-110 months), 2-year locoregional control estimates were 80% +/- 4% for CF and 78% +/- 5% for AF (p = 0.52), and 2-year overall survival estimates were 67% +/- 5% for CF and 64% +/- 5% for AF (p = 0.84). The lack of difference in outcome between the two treatment arms was confirmed by multivariate analysis. However, interaction analysis with median values as cut-offs showed a trend for improved locoregional control for those patients who had a delay in starting RT and who were treated with AF compared with those with a similar delay but who were treated with CF (hazard ratio = 0.5, 95% confidence interval 0.2-1.1). Fifty percent of patients treated with AF developed confluent mucositis, compared with only 27% of those treated with CF (p = 0.006). However, mucositis duration was not different between arms. Although preliminary, actuarial Grade 3+ late toxicity estimates at 2 years were 18% +/- 4% and 27% +/- 6% for CF and AF, respectively (p = 0.10). CONCLUSION: Accelerated fractionation does not seem to be worthwhile for squamous cell carcinoma of the head and neck after resection; however, AF might be an option for patients who delay starting RT.

Adult↗
PubMed2005

IMRT to escalate the dose to the prostate while treating the pelvic nodes.

BACKGROUND AND PURPOSE: To assess and quantify the benefit of introducing intensity-modulated radiotherapy (IMRT) over conventional approaches to cover the pelvic nodes while escalating the dose to the prostate gland. MATERIAL AND METHODS: The pelvic lymphatics were planned to receive 50 Gy at 2 Gy per fraction by four-field box (4FB) technique and standard field blocks drawn on digitally reconstructed radiographs (DRR), 4FB with field blocks according to the position of pelvic nodes as contoured on serial planning CT slices, or IMRT. The lateral fields included three different variations of field blocks to assess the role of various degrees of rectal shielding. The boost consisted in 26 Gy in 13 fractions delivered via six-field three-dimensional conformal radiotherapy (3DCRT) or IMRT. By the combination of a pelvic treatment and boost, several plans were obtained for each patient, all normalized to be isoeffective with regard to prostate-planning target volume (PTV-P) coverage. Plans were compared with respect to dose-volume histogram (DVH) of pelvic nodes/seminal vesicles-PTV (PTV-PN/SV), rectum, bladder and intestinal cavity. Reported are the results obtained in eight patients. RESULTS: Pelvic IMRT with a conformal boost provided superior sparing of both bladder and rectum over any of the 4FB plans with the same boost. For the rectum the advantage was around 10% at V70 and even larger for lower doses. Coverage of the pelvic nodes was adequate with initial IMRT with about 98% of the volume receiving 100% of the prescribed dose. An IMRT boost provided a gain in rectal sparing as compared to a conformal boost. However, the benefit was always greater with pelvic IMRT followed by a conformal boost as compared to 4FB with IMRT boost. Finally, the effect of utilizing an IMRT boost with initial pelvic IMRT was greater for the bladder than for the rectum (at V70, about 9% and 3% for the bladder and rectum, respectively). CONCLUSION: IMRT to pelvic nodes with a conformal boost allows dose escalation to the prostate while respecting current dose objectives in the majority of patients and it is dosimetrically superior to 4FB. An IMRT boost should be considered for patients who fail to meet bladder dose objectives.

Computer Simulation↗
PubMed2004

Rectal and bladder motion during conformal radiotherapy after radical prostatectomy.

BACKGROUND AND PURPOSE: To investigate the extent and the impact of rectum and bladder motion during adjuvant conformal radiotherapy (3DCRT) after radical prostatectomy (RP). MATERIALS AND METHODS: Nine patients previously operated with RP and treated with early adjuvant 3DCRT were considered for this investigation. Weekly CT scans were collected during treatment (CT1-CTn, n=4-6) and were 3D matched using bony anatomy with the planning CT (CT0). A single observer drew the contours of rectum and bladder on all CTs. The CTV (prostate+/-seminal vesicles surgical bed) was contoured on CT0 by a single observer and a 4-field 3DCRT technique was planned: dose statistics/dose-volume histograms (DVH) of the rectum and bladder were calculated for each contour referred to CT0, CT1...CTn. Average DVHs during the treatment were then calculated and compared with the planned DVH. Cranial, caudal, anterior and posterior shifts of rectum and bladder were also assessed by lateral BEV projections. NTCP values for the rectum were also calculated using the Lyman-Kutcher model. RESULTS: Random variations of volume and DVHs due to variable filling content were found for the bladder; a trend of the bladder to be more empty during therapy with respect to CT0 was also found (median values: 45 cm3 vs. 79 cm3, P=0.02). Regarding the rectum, 6/9 patients showed an average DVH 'worse' than the planned one (up to 10-20%). BEV and volume analyses showed that the rectal volume decreased in 3/9 patients after the first week. In 6/9 patients a systematic anterior shift of the cranial half of the rectum was detected and found to be correlated with a corresponding shift of the posterior border of CTV contoured by five different observers. The average rectal NTCP during therapy was systematically higher than the NTCP referred to CT0 (average increase 1.2%; range 0.0-3.7%, for a 70 Gy ICRU dose, P=0.01). CONCLUSIONS: The impact of systematic uncertainty due to rectal wall motion seems to be relatively high for patients treated with adjuvant 3DCRT after RP. The detected trend of the rectum in migrating anteriorly during therapy is consistent with post-surgery settlement effects and/or some modification of rectum mobility due to irradiation. Rectal motion (and consequent shifts of CTV) was large at the half cranial portion of the rectum while it was very small below the flexure.

Aged↗
PubMed2004

Are neck nodal volumes drawn on CT slices covered by standard three-field technique?

PURPOSE: Several definitions have been proposed in the past few years on how to contour the various neck nodal levels on CT slices. However, whether the resulting nodal volumes would have been covered by standard techniques is unknown. The purpose of this study was to clarify this issue. METHODS AND MATERIALS: Eight patients (N0-N1) with head-and-neck cancer from various primary sites referred to us for definitive radiotherapy were included in this study. Two observers contoured the level Ib-V neck nodal volumes on planning CT according to seven reported definitions. Each observer also drew blocks on digitally reconstructed radiographs for the initial (on-cord) phase of a standard three-field technique (parallel opposed lateral fields and AP supraclavicular field) for three different clinical settings: "medium" larynx (to cover upper, mid, and low jugular nodes), "big" larynx (same as for medium, plus posterior cervical nodes), and "tonsil" (same as for big plus retropharyngeal nodes). Fields blocks were concentrically reduced 5 mm in all directions as a surrogate for the clinical target volume to planning target volume expansion. A plan was created for each of the clinical settings, delivering 2 Gy to the International Commission on Radiation Units and Measurements reference point. The coverage of the nodal levels according to the various definitions was investigated throughout the analysis of the volume receiving 50%, 80%, and 95% of the prescribed dose (V(50), V(80), and V(95), respectively) and dose covering at least 95% of the volume (D(95)) values extracted from their cumulative dose-volume histograms in the three clinical settings. RESULTS: The V(50) coverage of levels III and IV was adequate for all definitions and trials. For level V, about 3-5% of the volume was outside the 50% isodose of those trials that targeted the posterior cervical chain. Coverage of level Ib was highly dependent on the definition, with up to 21% of the volume outside the standard tonsillar fields. For level II, although the 50% isodose from the tonsillar fields seemed to encompass all definitions, this was not the case for the laryngeal trials. Overall, we found 20-30% of the volumes to be outside the 95% isodose, with larger percentages for levels II and V. Similarly the D(95) results showed all volumes to be underdosed; only about 45% and 65% of levels II and V, on average, received 95% of the prescription dose. CONCLUSION: Within three different clinical settings, we showed that the current definitions provide nodal neck volumes that often fall outside the 50% and 95% isodose lines of the standard three-field technique. Because these volumes are routinely used to define nodal neck volumes for intensity-modulated radiotherapy, the dose-volume objectives of intensity-modulated radiotherapy may not be consistent with those traditionally achieved by the standard three-field technique.

Carcinoma, Squamous Cell↗
PubMed2004

A case of radiation recall mucositis associated with docetaxel.

BACKGROUND: Radiation recall reactions, in particular dermatitis, are well documented in the literature. However, radiation recall mucositis is a rare clinical phenomenon. METHODS: We report a case of a 45-year-old man diagnosed with squamous cell carcinoma of the base of tongue. He was treated with surgery followed by chemotherapy and radiation therapy. Several months after completing treatment, he had a recurrence develop outside of the previously irradiated field. He was offered radiation therapy concurrent with docetaxel as salvage therapy. RESULTS: During salvage therapy, acute recall mucositis developed corresponding to his previously irradiated fields. His chemotherapy with docetaxel was withheld, and his symptoms rapidly improved. CONCLUSIONS: This case describes radiation recall mucositis associated with docetaxel, a rare but potentially serious clinical situation. Given the potential severity of the reaction and increasing use of docetaxel as second-line treatment of recurrent head and neck cancers, it is important to be aware of this phenomenon.

Antineoplastic Agents, Phytogenic↗
PubMed2004

Anatomic variations due to radical prostatectomy. Impact on target volume definition and dose-volume parameters of rectum and bladder.

BACKGROUND AND PURPOSE: A quantitative estimate of the impact of prostatectomy on pelvic anatomy is unavailable, even if it would be an important prerequisite for a precise definition of clinical target volume (CTV) in post-prostatectomy radiotherapy. The purpose of this study was to investigate the impact of prostatectomy on the definition of CTV, on the position of bladder and rectum and their implications for three-dimensional conformal radiotherapy (3-D CRT). PATIENTS AND METHODS: Six patients eligible for radical retropubic prostatectomy were considered. Each patient underwent a planning CT between 1 week and 1 month before surgery (CTpre), and then CT was repeated in the same positioning 1-2 months after surgery (CTpost). For each patient the CT(pre/post) scans were matched; rectum, bladder and CTV were contoured on both CT scans for each patient by one observer. Two different CTVs were contoured: CTV1: prostate + seminal vesicles in CTpre; prostate + seminal vesicles surgical bed in CTpost; CTV2: prostate in CTpre; prostate surgical bed in CT(post). After image registration, the contours of rectum, bladder and CTV1/2 drawn on CTpost were transferred on CTpre. The corresponding planning target volumes (PTVs) were generated, and for each PTV, a conformal four field technique using 18-MV X-rays was planned. The volumes of CTV1, CTV2, PTV1, PTV2, rectum and bladder pre- and post-surgery were compared. Differences in 3-D position of these structures before and after surgery were analyzed by beam's eye view (BEV) images. Pre- and post-surgery dose-volume histograms (DVHs) of rectum and bladder were compared together with the fraction of rectum/bladder receiving at least 95% of the ICRU dose (V95), the treated volume (TV, body included in the 95% isodose) and the irradiated volume (IV, body included in the 50% isodose). RESULTS: For both CTV1 and CTV2, the volumes were significantly reduced after prostatectomy (average reduction around 30 cm3 for both; range 0-60 cm3). This reduction was mainly due to a more caudal definition of the cranial edge of CTV after prostatectomy (average difference for CTV2: 1.5 cm; range 0-2.5 cm). Concerning the bladder, a systematic posterior shift of the bladder base (average: 1.5 cm) was found and was correlated with a significant reduction of V95 for bladder (around 10 cm3; p = 0.03). V95 of the rectum, TV and IV also resulted to be significantly lower after surgery. The average reduction of V95 for the rectum was relatively small (2.5 cm3 of rectal wall). CONCLUSION: The impact of prostatectomy on CTV definition is high. A significant reduction of CTV, PTV, TV and IV may be expected after surgery with a consequent reduction of the portions of rectum/bladder irradiated with adjuvant radiotherapy.

Aged↗
PubMed2004

Is there a "curative" role of radiotherapy for clinically localized hormone refractory prostate cancer?

Whether definitive radiotherapy (RT) is still an option for patients with clinically prostate-confined prostate cancer treated with androgen deprivation (AD) alone who develop a rising prostate-specific antigen (PSA) is not clear. In this retrospective series, we report the outcome of 29 such patients treated with "curative" radiotherapy at our institution between 1991 and 2000. At initial diagnosis, all patients had evidence of prostate-confined disease and for several reasons underwent AD alone. Afterward all patients developed rising PSA, but again, without clinical evidence of distant/pelvic node disease. All underwent RT with curative intent up to 70 Gy (66 to 76 Gy). Median follow-up after radiotherapy is 33.1 month (range: 7-134.2 months). For living patients, minimum and median follow-ups are 30.4 and 55.4 months, respectively. Twenty-three patients (79%) developed overt clinical disease, most of which (19/23, 83%) involved distant sites, whereas isolated locoregional failure was observed in only 4 patients (4/23, 17%). The estimates of locoregional control rate (LRC), actuarial incidence of distant metastases, and overall survival at 5 years are 89 +/- 7%, 68 +/- 9%, and 28 +/- 9%, respectively. Although we were unable to find any predictor of LRC at univariate analysis, patients with low Gleason score at diagnosis, lower PSA at RT, lower risk category and advanced age were less likely to develop distant disease. RT has a palliative role, because most patients with still presumed localized hormone refractory prostate cancer will develop distant metastases. A subset of patients, those with more differentiated tumor at diagnosis and with pre-RT PSA less than 20 ng/mL, might be considered for a more aggressive locoregional approach.

Aged↗
PubMed2003

Rectal dose-volume constraints in high-dose radiotherapy of localized prostate cancer.

PURPOSE: To investigate the relationship between rectal bleeding and dosimetric-clinical parameters in patients receiving three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer. METHODS: In a retrospective national study (AIROPROS01-01, AIRO: Associazione Italiana Radioterapia Oncologica), planning/clinical data for 245 consecutive patients with stage T1-4N0-x prostate carcinoma who underwent 3D-CRT to 70-78 Gy (ICRU point) were pooled from four Italian institutions. The correlation between late rectal bleeding and rectal dose-volume data (the percentage of rectum receiving more than 50, 55, 60, 65, 70, and 75 Gy [V(50-70)]) and other dosimetric and clinical parameters were investigated in univariate (log-rank) and multivariate (Cox regression model) analyses. Median follow-up was 2 years. RESULTS: Twenty-three patients were scored as late bleeders according to a modified RTOG definition (Grade 2: 16; Grade 3: 7); the actuarial 2-year rate was 9.2%. Excepting V75, all median and third quartile V(50-70) values were found to be significantly correlated with late bleeding at univariate analysis. The smallest p value was seen for V(50) below/above the third quartile value (66%). The V70 (cut-off value: 30%) was found to be also predictive for late bleeding. In the high-dose subgroup (74-78 Gy), Grade 3 bleeding was highly correlated with this constraint. The predictive value of both V(50) and V(70) was confirmed by multivariate analyses. CONCLUSIONS: The present article provides evidence for correlation between rectal DVH parameters and late rectal bleeding in patients treated with curative intent with 3D-CRT. To keep the rate of moderate/severe rectal bleeding below 5-10%, it seems advisable to limit V(50) to 60-65%, V(60) to 45-50%, and V70 to 25-30%.

Aged↗
PubMed2003

Sucralfate versus mesalazine versus hydrocortisone in the prevention of acute radiation proctitis during conformal radiotherapy for prostate carcinoma. A randomized study.

PURPOSE: To assess whether the topical use of steroids or 5-aminosalicylic acid (5-ASA) is superior to sucralfate in preventing acute rectal toxicity during three-dimensional conformal radiotherapy (3DCRT) to 76 Gy. PATIENTS AND METHODS: Patients undergoing 3DCRT for prostate carcinoma at our institution were offered to be randomized to sucralfate 3 g in 15 ml suspension enema (Antepsin, mesalazine 4 g gel enema (Enterasyn, or hydrocortisone 100 mg foam enema (Colifoam. Randomization was blind to the treating physician but not to the patient. Sucralfate was chosen as control arm. Topical treatment had to be performed once daily, starting on day 1 of 3DCRT. Acute rectal toxicity was scored weekly according to RTOG criteria. Time to occurrence of grade 2+ acute rectal toxicity was taken as endpoint. RESULTS: The trial was opened in August 1999, and after the first 24 patients had been treated, arm 2 was discontinued because of eight patients receiving mesalazine, seven actually developed acute rectal toxicity (five patients grade 3 and two patients grade 2). Until May 2001, 134 consecutive patients were randomly assigned to sucralfate (63 patients), mesalazine (eight patients) or hydrocortisone (63 patients). The cumulative incidence of acute rectal toxicity at the end of treatment by arm is 61.9 +/- 6.1%, 87.5 +/- 11.7%, and 52.4 +/- 6.2% for arms 1, 2, and 3, respectively. The difference between the mesalazine group and the sucralfate group is highly significant (hazard ratio [HR] 2.5, 95% confidence interval [CI] 1.1-5.7; p = 0.03). At both uni- and multivariate analysis taking into account several patients and treatment covariates, the difference between hydrocortisone and sucralfate is not significant (HR 0.7, 95% CI 0.5-1.2; p = 0.2). CONCLUSION: Topical mesalazine is contraindicated during radiotherapy. Hydrocortisone enema is not superior to sucralfate in preventing acute rectal toxicity.

Acute Disease↗
PubMed2003

Neoadjuvant androgen deprivation and prostate gland shrinkage during conformal radiotherapy.

PURPOSE: The shrinking effect of 3-month neoadjuvant androgen deprivation (NAD) on preradiotherapy prostate gland volume is well documented. However, recently, it has been shown that the cancerous prostate gland keeps shrinking up to 12 months after NAD start. Thus, if such a reduction is not taken into account, a larger than planned portion of the surrounding normal tissues might shift in the high-dose region during conformal radiotherapy (3DCRT) course. The present study was undertaken to quantify this issue. MATERIALS AND METHODS: Prostate gland volume reduction between planning CT (plCT) and the last week of 3DCRT (tmtCT) was prospectively assessed in 33 consecutive patients with localized prostate carcinoma. The median time interval between plCT and tmtCT was 2.5 months (2.1-2.7 months). A single observer was asked to draw on each slice prostate gland volume as appropriate. The observer was 'blind' to the timing of CT (plCT vs. tmtCT). In order to estimate intra-observer variability, prostate gland delineation was repeated twice for each data set. Mean prostate gland change, plCT and tmtCT cumulative dose volume histogram (DVH) calculations for the rectum were analyzed for each patient. Results were correlated to AD status and its duration before plCT. Means were compared by non-parametric rank tests. RESULTS: Based on an internal protocol, 14 patients (42%) did not receive AD, while 19 patients (58%) had undergone neoadjuvant and concomitant AD. The median duration of AD before plCT ranged from 0.2 to 6 months (median: 2.9 months). Although individual data were highly variable, compared to plCT volume, mean prostate gland volume change at the end of 3DCRT was similar for patients receiving (-7.3%) or not (-7%) androgen deprivation (P=0.77). However, within the group of patients treated with hormones, patients starting AD within 3 months from plCT had a significantly larger reduction in prostate volume (-14.2%) than patients with longer NAD duration (-1.1%, P=0.03). At tmtCT, on average, patients undergoing 3DCRT within 3 months from AD start showed an increase of the amount of rectum receiving 40-75 Gy compared to plCT values. At 40 Gy (V40) the mean difference between tmtCT and plCT was +7.5%. In the other two groups, average variations of V40-70 were within +/-2% of plCT values. However, these differences are not significant. CONCLUSION: For patients who undergo plCT and 3DCRT shortly after AD start, prostate gland shrinkage may be substantial. In some of these patients, this might lead to an unexpected increase of the percentage of rectal wall exposed to intermediate doses.

Aged↗
PubMed2002

Rectum contouring variability in patients treated for prostate cancer: impact on rectum dose-volume histograms and normal tissue complication probability.

BACKGROUND: Recent investigations showed some correlation between three-dimensional (3D) treatment planning dose-volume data (dose-volume histograms: DVH, dose statistics) and rectal toxicity for patients treated for prostate cancer. However, no data are available about the possible impact of inter-institute variability in contouring the rectum, so that the possibility of reliably using information from single-centre studies remains doubtful. PURPOSE: Within a retrospective three-institutes study on correlation between dose-volume treatment planning data and rectum bleeding in patients treated for prostate cancer, an investigation about the impact of inter- and intra-observer variability in contouring the rectum was performed. MATERIALS AND METHODS: Ten patients were considered for a dummy run exercise and three observers (one per Institute) contoured the rectum (including filling). An anatomically based definition of rectum extension was previously accepted by the three observers. Six of the ten patients were randomly chosen in the subgroup of patients (large spacing, LS) with a distance between computed tomography (CT) slices (outside the prostate region) equal to 10 mm; for the remaining four patients the distance between CT slices was 5 mm over the whole rectum volume (small spacing, SS). The original 3D treatment planning was recovered on the Cadplan treatment planning system for each patient and rectum dose statistics (mean, median and maximum rectum dose), volume, DVH and NTCP values were calculated for each observer. For DVH analysis, the values of V(50), V(55), V(60), V(65) and V(70) (defined as the % of rectum volume receiving at least 50, 55, 60, 65, 70 Gy) were considered. Normal tissue complication probabilities (NTCPs) were calculated for the original ICRU dose and for a 75.6 Gy ICRU dose (NTCP and NTCP(75.6), respectively). Intra-observer variability was investigated by asking the observers to redraw the same rectum contours 6 months later and comparing the two contouring sessions. RESULTS: In general, a good agreement was found for most patients and, in particular, for all SS patients. The impact of inter-observer variability was quite significant on dose statistics and DVH in two of six LS patients. Looking at the patient population, some systematic deviations, even if quite small, were demonstrated between institute B and institute C (volume, P = 0.02) and between institute A and institute B (mean/median dose, V(50)-V(65), NTCP(75.6); P < 0.05). Four of six LS patients (0/4 in the SS group) presented a maximum difference among observers at the cranial and/or caudal limit of the rectum equal to 1 cm. For these patients, inter-observer variability was significantly higher than for the others (P < 0.03). When inter-observer variability was expressed in terms of standard deviations (SD), values around 2-3 Gy and 0.5 Gy for LS and SS patients, respectively, were found for mean/median dose; values around 3-4% and 0.5-2% for LS and SS patients, respectively, were found for V(50)-V(70). The average SD for NTCP and NTCP(75.6) were 0.4 and 0.6%, respectively (0.5 and 0.9% for LS patients; 0.2 and 0.3% for SS patients). Intra-observer variability was found to be lower than inter-observer variability even if the impact on dose statistics and DVH was visible. CONCLUSIONS: Once a robust definition of rectum is assessed, inter- and intra-institute variability in contouring the rectum appear relatively modest. However, the results suggest that the number of LS patients in DVH correlation studies should be as low as possible; the low number of these patients in the multi-centric trial involving our institutions should not have significant impact on the results of the study.

Hemorrhage↗
PubMed2002

Relationships between DVHs and late rectal bleeding after radiotherapy for prostate cancer: analysis of a large group of patients pooled from three institutions.

BACKGROUND: Accurate modeling of late rectal reactions needs the collection of individual 3D dose-volume data (i.e. DVH) as well as clinical information of large cohorts of patients. The possibility of collecting a large number of patients with many different dose-volume combinations is very suitable for this purpose. PURPOSE: The purpose of the study is to search for significant correlation between dose-volume histograms/dose statistics of the rectum and late rectum bleeding. MATERIALS AND METHODS: Data from three institutions for 402 patients previously treated for prostate cancer with three to four field techniques, were retrospectively pooled and were collected with a number of clinical and physical parameters, including DVHs of the rectum (including filling). Patients with large air/fecal content in the rectum during planning computerized tomography (CT) scan were excluded from the analysis (n = 74). Out of 328 patients, 229 patients received an ICRU dose between 70 and 76Gy and the current analysis is referred to this subgroup of patients (median follow up: 30 months, range: 12-85 months). Out of these 229 patients, 189 patients were treated with conformal techniques. Rectum was contoured from the anal verge up to the sigmoid flessure by one observer for each institution. Dosimetric and contouring consistencies between the three institutions were previously investigated and the impact on DVHs was found to be quite modest for the purposes of the study. Median/quartile values of all parameters were considered as cut-off values for statistical analysis. We considered as bleeders those patients who experienced grades II-III late bleeding (modified RTOG scoring scale). RESULTS: Twenty two of 229 patients experienced > or =grade II late bleeding (30 months actuarial incidence: 10.7%). Significant correlation between a number of parameters and late bleeding was found (log-rank test). With regard to DVH, all median and third quartile values for V50-V70 were found to be significantly associated with an increased risk of rectal bleeding, if excepting the median value of V70. Based on the results of univariate analysis, the patients were divided into two groups: 'high risk', with at least one value above quartiles in the range V50-V60 (V50: 70%, V55: 64%, V60: 55%); 'low risk', the remaining patients. The 30 months actuarial rates of bleeding were 19.2 and 5.9% for the 'high' and the 'low' risk group, respectively (P = 0.0003 log-rank test). A multivariate analysis (Cox regression model) including 'DVH grouping' and the main remaining variables (age, previous prostatectomy, diabetes, hypertension, adjuvant hormonal therapy, rectum volume and ICRU dose) showed that 'DVH grouping' is the most predictive parameter (P = 0.005) together with adjuvant hormonal therapy (P = 0.025) and ICRU dose (P = 0.06). CONCLUSIONS: Our data confirm the role of the rectal DVH in separating groups of patients having prostate radiotherapy in low and high risk of developing late bleeding. Based on these results, V50 below 60-65% and V60 below 50-55% seem to be the robust cut-off values to keep the risk of developing late rectal bleeding reasonably low. However, due to the 'heterogeneity' of the considered population, the results found should be applied with caution in 'more homogeneous' groups of patients. The association of adjuvant hormone deprivation seems to be associated with an increased risk of rectal toxicity; the mechanism for this effect should be a focus of further research.

Actuarial Analysis↗
PubMedDate not supplied

Late local treatment morbidity after accelerated radiotherapy or alternating chemoradiotherapy for advanced head and neck carcinoma.

BACKGROUND: To report local long-term morbidity after concomitant boost radiotherapy (AFRT) or alternating chemoradiotherapy (CTRT), we analyzed the toxicity data recorded in 168 patients with advanced head and neck squamous cell carcinoma treated at our institution within phase II-III studies. PATIENTS AND METHODS: All patients enrolled in three consecutive phase II-III studies and followed for a minimum of three months after the end of treatment were included in the present analysis. Local late reactions were scored prospectively. The actuarial incidence of grade 2 or more (2-4) late local toxicity according to RTOG/EORTC was taken as endpoint. The median follow-up is 32.0 months (range, 3.3-138.1 months). For living patients the minimum and median follow-up are 12.1 and 69.3 months, respectively. RESULTS: The five-year actuarial incidence of grade 2+ and grade 3+ toxicity are 56.7 +/- 5% and 21 +/- 4%, respectively. At multivariate analysis, acute mucositis grade, complementary surgery, primary site and performance status proved to be independent predictive factors of grade 2+ late toxicity with P values of <0.001, 0.009, 0.022 and 0.033, respectively. No effect was found for treatment itself on the incidence of late toxicity, although patients treated with accelerated radiotherapy had a higher probability of confluent mucositis than patients treated with alternating chemoradiotherapy (68% vs 32%, P <0.01). CONCLUSIONS: A substantial proportion of surviving patients develops late complications, although severe irreversible reactions occur in a minority of patients. Acute local toxicity can be used to predict local late toxicity that arises within five years of the end of treatment.

Antineoplastic Agents↗
PubMedDate not supplied

Radiotherapy after prostatectomy.

AIMS AND BACKGROUND: The role of radiotherapy after prostatectomy is controversial. This paper tries to give some guidelines for everyday practice through an analysis of literature data. METHODS: The potential role of radiotherapy in the adjuvant and salvage setting is discussed. We also report and interpret available literature data for both settings. RESULTS: As regards an increase in or detectable prostate-specific antigen (PSA) after radical prostatectomy, about 40-50% of patients are rendered bNED with local salvage radiotherapy, but only 10-50% are long-term (5 years) biochemically controlled. A timely salvage treatment is crucial to optimize control probability. As regards adjuvant radiotherapy for undetectable postoperative PSA in patients at high risk of failure as judged on pathology, results are more encouraging. Recent data report bNED rates > 70% at 5 years. CONCLUSIONS: Although results are far from satisfactory, salvage radiotherapy should be considered for every patient with an increased or detectable PSA after surgery. Adjuvant radiotherapy seems preferable to salvage radiotherapy for patients at high (> 30%) risk of failure.

Humans↗