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Riccardo Valdagni

Publications and source records attributed to Riccardo Valdagni.

10 recordsLinked to original sources
PubMed2006

Vaccination therapy in prostate cancer.

Radical prostatectomy and radiation therapy provide excellent localized prostate cancer (PC) control. Although the majority of prostate carcinoma is nowadays diagnosed at early stages with favourable risk features, in patients up to 30-40% it recurs within 10 years. Furthermore, the lack of effective therapies, once prostate carcinoma becomes refractory to androgen deprivation, mandates the development of alternative therapeutic options. There is a growing interest in harnessing the potency and specificity of anti-tumour immunity through the generation of fully competent dendritic cells and tumour reactive effector lymphocytes. Several strategies to treat or prevent the development of metastatic PC have been explored in clinical trials and are summarized in this review, considering also the feasibility and safety of these approaches. In some cases clinical responses were achieved showing that vaccine-primed T cells induced anti-tumour activity in vivo. The present findings and perspectives of the immunologic interventions in PC patients will be discussed.

Cancer Vaccines↗
PubMed2006

Emptying the rectum before treatment delivery limits the variations of rectal dose - volume parameters during 3DCRT of prostate cancer.

PURPOSE: To investigate the impact of rectum motion on dose - volume histograms of the rectum including filling and of the wall (DVH and DWH, respectively), during 3D-conformal radiotherapy (3DCRT) for localized prostate cancer. MATERIALS AND METHODS: Ten patients received a planning CT scan (CT(0)) and 11-14 CT during 3DCRT for prostate cancer (total CT scans=126). CT images were 3D matched using bony anatomy. A single observer drew the external contours of rectum and rectum wall and the CTV (prostate + seminal vesicles) on CT(0). Patients were asked to empty their rectum before every CT, as generally performed at the Institute for Cancer Research and Treatment (IRCC) before treatment delivery. Bladder was kept full by drinking 500 cm(3) of water 60 min before the scan, according to our protocol. A 4-field box 3DCRT technique was planned and dose statistics/dose - volume histograms of the rectum were calculated for each contour referred to CT(0),CT(1),...,CT(n) for each patient. Average DVHs during treatment were calculated along with their standard deviation (SD(rand)) and compared to the planned DVH. The analyses on the patient population included the assessment of systematic deviation (average difference and SD, named SD(sys)) as well as the average SD(rand) value expressing the random component of organ motion. Rectum shifts were also assessed by anterior and lateral BEV projections. RESULTS: As to the rectum, 8/10 patients showed a "better" average DVH than DVH on CT(0). Wilcoxon test showed a statistically significant reduction when correlating the difference Delta between the average DVH during therapy and planning DVH at CT(0): for instance V(70)Delta = -3.6% and p = 0.022, V(50)Delta = -5.5% and p = 0.022, D(med)Delta = -3.2 Gy and p = 0.007. Average values of DVH systematic difference (average difference between planning scan and treatment), standard deviations (SD(sys)) and average standard deviations of the random fluctuation (SD(random)) were -4.0%, 4.7% and 6.6%, respectively. Whilst the fluctuation results were slightly smaller for DWH. Volume analysis showed a slight systematic variation of the rectal volume between planning and treatment BEV. The average rectal volume during therapy was larger than at the planning CT in 8/10 patients. The systematic shifts of the rectal wall between the planning phase and the treatment were rather small, both below and above the flexure. The larger random fluctuation of the rectum shape was found to be in the cranial half (1 SD=4.4 mm). CONCLUSIONS: The practice of carefully emptying the rectum during simulation and therapy for prostate cancer, which is a safe and simple procedure, reduces the impact of organ motion on dose - volume parameters of the rectum.

Dose-Response Relationship, Radiation↗
PubMed2005

Is the alpha-beta ratio of prostate cancer really low? A prospective, non-randomized trial comparing standard and hyperfractionated conformal radiation therapy.

BACKGROUND AND PURPOSE: The objectives of the current study were to compare genito-urinary (GU) and gastro-intestinal (GI) toxicities as well as biochemical control (bRFS) in prostate cancer, utilizing conventional (2.0 Gy daily) (STD) or hyperfractionated (HFX) conformal irradiation (CRT). HFX (1.2 Gy BID) was chosen as a radiobiological method to try to reduce long term sequelae without compromising local control. PATIENTS AND METHODS: Three-hundred-and-seventy consecutive patients (pts) entered this prospective, non-randomized trial in the period January 1993-January 2003; 209 were treated with STD and 161 with HFX CRT. All were evaluable for acute toxicity analysis, 179 (STD) and 151 pts (HFX) being evaluable for late sequelae and bRFS analyses. Pt characteristics were not statistically different in the two groups. CRT consisted of a 4-field technique for prostate and/or pelvic nodes and a 5-field boost with rectal shielding. Median doses were 74 and 79.2 Gy for STD and HFX patients respectively, the latter dose being isoeffective for tumour control assuming alpha/beta=10 (EQD(2)=73.9 Gy). Median follow-up was 29.4 months (25.2 mos for STD; 37.7 mos for HFX; P<0.01). The two regimens were compared in terms of acute and late GU and GI toxicities and 5-year bRFS by univariate and multivariate analyses. RESULTS: Acute grade> or =2 GU toxicity was higher in the STD group (48.6% versus 37.3% in HFX, P=0.03), while no significant difference was found for acute GI toxicity. Late grade> or =2 GU and GI toxicities were lower in the HFX group (5-year actuarial rate: GU: 10.1% versus 20.3%, P=0.05; GI: 6.0% versus 10.6%, P=0.18). Five-year bRFS were 70% (+/-13.8%, 95% CI) and 82.6% (+/-7.2%) for STD and HFX, respectively (P=0.44); a trend favouring HFX was found in the subgroup of pts who did not receive hormonal therapy (5-year bRFS: 85.9%+/-12.4% versus 63.9%+/-23.8%, P=0.15). Multivariate analysis revealed only risk groups and age statistically related to bRFS but not fractionation regimen. Using the Nahum-Chapman TLCP model and prostate parameter set, which includes hypoxia, the TLCPs are approximately equal for the two regimens, whereas assuming alpha/beta=1.5 and no hypoxia we obtain 73% for the STD group but only 36% for the HFX group. CONCLUSIONS: As expected from radiobiological considerations, HFX reduces GI and GU late toxicities. Concerning early bRFS, our clinical findings suggest that HFX is no less effective than STD when delivering an isoeffective (alpha/beta=10) dose. Despite the relatively short follow-up, this result appears to be inconsistent with a low alpha/beta ratio for prostate cancer.

Aged↗
PubMed2005

Cancer of the prostate.

Prostate carcinoma, with about 190,000 new cases occurring each year (15% of all cancers in men), is the most frequent cancer among men in northern and western Europe. Causes of the disease are essentially unknown, although hormonal factors are involved, and diet may exert an indirect influence; some genes, potentially involved in hereditary prostate cancer (HPC) have been identified. A suspect of prostate cancer may derive from elevated serum prostate-specific antigen (PSA) values and/or a suspicious digital rectal examination (DRE) finding. For a definitive diagnosis, however, a positive prostate biopsy is requested. Treatment strategy is defined according to initial PSA stage, and grade of the disease and age and general conditions of the patient. In localized disease, watchful waiting is indicated as primary option in patients with well or moderately differentiated tumours and a life expectancy <10 years, while radical prostatectomy and radiotherapy (with or without hormone-therapy) could be appropriate choices in the remaining cases. Hormone-therapy is the treatment of choice, combined with radiotherapy, for locally advanced or bulky disease and is effective, but not curative, in 80-85% of the cases of advanced disease. Patients who develop a hormone-refractory prostate cancer disease (HRPC) have to be evaluated for chemotherapy because of the recent demonstration of improved overall survival (2-2.5 months) and quality of life with docetaxel in more than 1,600 cases.

Antineoplastic Protocols↗
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

The impact of contouring uncertainty on rectal 3D dose-volume data: results of a dummy run in a multicenter trial (AIROPROS01-02).

PURPOSE: To estimate the impact of the uncertainty in contouring the rectum on rectal dose-volume parameters and normal tissue complication probability (NTCP) in a prospective (AIROPROS01-02) investigation about rectal toxicity. METHODS AND MATERIALS: The participants in a prospective trial (18 observers) were asked to draw the external contour of the rectum of 4 sample patients (3 patients undergoing radical conformal radiotherapy, 1 patient undergoing post-prostatectomy) on CT images (0.5 cm spacing) using a 3D treatment planning system. A previously accepted definition of cranial and caudal borders of the rectum was applied. For each patient, four- and six-field 3D-conformal techniques (70-76 Gy, ICRU dose) were planned and DVH/dose statistics of the rectum were calculated. The impact of interobserver variability on rectal volume, cranial and caudal borders, mean, maximum, and median rectal dose, percentage of rectum receiving more than 40, 45, 50, 55, 60, 65, 70, and 75 Gy (V(40)-V(75)), and NTCP were investigated. RESULTS: Concerning DVHs, 9/18 observers tended to have some systematic deviation. However, deviations from the mean values greater than 5% were found only in 1/9 because of a systematic discrepancy in the caudal limit assessment (mean deviation from the most frequently chosen slice: 8 mm). No other observers showed a mean deviation in the cranial or the caudal limit definition greater than 5.8 mm. For another observer, it was possible to clearly assess the cause of a relatively large systematic deviation for DVH parameters. In both cases, the observers were contacted to avoid these systematic deviations. When considering the remaining 16/18 observers, the average values of SD for V(40)-V(75) ranged between 1% and 4% and were found to be lower (<3%) for the 3 nonoperated patients. The average values of the SD were around 1.5-2 Gy and less than 1.5% for mean/median dose and NTCPs, respectively. CONCLUSIONS: Concerning the uncertainty in rectum definition, the collection of rectal dose-volume data in multicenter investigations seems to be feasible after a clear and previously accepted definition of rectum is assessed. However, even with a general agreement on rectum definition, contouring appears to be a quite significant source of uncertainty. A dummy run procedure is useful in identifying possible discrepancies among single observers and in assessing reliable confidence levels on dose-volume constraints because of contouring uncertainty, making the dummy run mandatory in multicenter trials evaluating 3D dose-volume data.

Humans↗
PubMed2003

Malignant melanoma.

In the European Community cutaneous melanoma accounts for 1 and 1.8% of cancers occurring in men and women, respectively. The incidence rate is increasing faster than that of any other tumour. Sun exposure, patient's phenotype, family history, and history of a previous melanoma are the major risk factors. The change over a period of months is the main sign of a skin lesion turned into a melanoma. The ABCDE scheme for early detection of melanoma is commonly accepted. A new staging classification will be published in the next AJCC/UICC Cancer Staging System Manual in 2002. The clinical course of melanoma is determined by its dissemination and depends on thickness, ulceration, localisation, gender and histology of the primary tumour. Tumour stage at diagnosis remains the major prognostic factor. Surgery is the standard treatment option for operable local-regional disease. Sentinel node biopsy represents a promising experimental approach in the clinical detection and early treatment of occult lymph node involvement. For metastatic inoperable patients systemic chemotherapy can be attempted, while radiation therapy has to be considered as palliative treatment. No studies concerning frequency of follow-up are currently available, but common procedures may be performed.

Female↗
PubMedDate not supplied

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.

Aged↗