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Paola Franzone

Publications and source records attributed to Paola Franzone.

9 recordsLinked to original sources

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↗

Review of the role of radiotherapy in craniopharyngiomas: how does patient age influence management decisions?

Craniopharyngioma is a brain tumor that can affect children and adults. Although histologically benign, if untreated it can enlarge and lead to serious morbidity and even death, because of its close proximity to critical structures in the parasellar region, including the pituitary, hypothalamus, optic chiasm, carotid arteries and third ventricle. Surgically, two main approaches are currently pursued: macroscopic complete excision or a primarily conservative approach. Another question is the role of radiotherapy in the postoperative setting. Because the associated morbidities with aggressive surgery or radiotherapy can be particularly pronounced in children, the most appropriate management of craniopharyngiomas in this age group remains controversial.

Aging↗

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.

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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↗

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.

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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↗

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.

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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↗

Italian survey in postoperative radiation therapy for prostate carcinoma by the AIRO National Working Group on Prostate Radiotherapy: definitive results.

AIMS AND BACKGROUND: The National Working Group on Prostate Radiotherapy of AIRO (Associazione Italiana Radioterapia Oncologica, Italian Association of Radiotherapeutic Oncology) was established in March 2001. A retrospective multi-center survey was performed to analyze the patterns of care for prostate cancer patients treated with postoperative radiotherapy following radical prostatectomy in Italy with regard to the year 2000. MATERIALS AND METHODS: A structured questionnaire was mailed to 47 Italian radiotherapy centers to assess patient accrual in the postoperative setting in the interval comprised between period January-December 2000. Numbers of patients treated for different stages, specific prognostic factors indicating the need for adjuvant radiotherapy, fractionation schedules and prescription doses were acquired as well as other clinically important factors such as radiotherapy timing and the use of hormone therapy. More technical features of the treatment, such as patient positioning, mode of simulation, typical field setup and dose prescription criteria were also included in the questionnaire. RESULTS: The questionnaire was returned by 24 radiotherapy Institutions (51%) with a total number of 470 patients treated postoperatively in the year 2000. An average of about 20 patients were enrolled by each radiotherapy center. The age range was 45-81 years. Radiotherapy was delivered within 6 months of radical prostatectomy in 297 patients (65.4%) (mean, 3.4 months). In 157 (34.6%), the treatment was delivered as a salvage approach for biochemical or micro-macroscopic recurrence. Most of patients had locally advanced stage disease (pT3-pT4) (76%). Unfavorable prognostic factors, such as positive margins, capsular invasion, Gleason pattern score > 7 were present in about 50% of patients. CONCLUSIONS: The study confirmed that important risk factors for recurrences are present in a significant percentage of patients treated by radical prostatectomy. The number of patients that would benefit from adjuvant radiotherapy is therefore potentially very large. Future prospective studies should be conducted to assess and to clarify the respective roles of adjuvant and salvage radiotherapy in prostate cancer patients.

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