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International Journal of Radiation Oncology Biology Physics | 1998

Preoperative Chemoradiation for Extraperitoneal T3 Rectal Cancer: Acute Toxicity, Tumor Response, and Sphincter Preservation

Vincenzo Valentini; Claudio Coco; Numa Cellini; Aurelio Picciocchi; D. Genovesi; Giovanna Mantini; Brunella Barbaro; Santa Cogliandolo; Claudio Mattana; Fabrizio Ambesi-Impiombato; Manfredo Tedesco; Maurizio Cosimelli

PURPOSE To evaluate whether or not an intermediate dose of preoperative external radiation therapy intensified by systemic chemotherapy could improve the tumor response, sphincter preservation, and tumor control. METHODS AND MATERIALS Between March 1990 and December 1995, 83 consecutive patients with resectable extraperitoneal adenocarcinoma of the rectum were treated with preoperative chemoradiation: bolus i.v. mitomycin C (MMC), 10 mg/m2, Day 1 plus 24-h continuous infusion i.v. 5-fluorouracil (5FU) 1000 mg/m2, Days 1-4, and concurrent external beam radiotherapy (37.8 Gy). All but 2 patients had T3 disease. Surgery was performed 4-6 weeks after the end of chemoradiation. RESULTS Total Grade 3-4 acute toxicity during chemoradiation was observed in 11 (13%) patients: hematological Grade 3 toxicity was recorded in 8 (10%) patients, and Grade 4 toxicity was recorded in 2 (2%) patients. Grade 3 diarrhea was seen in 2 (2%) patients. No patient had major skin or urological acute toxicity. Two patients had no surgery: 1 died before surgery from septic complications after Grade 4 hematological toxicity; 1 refused surgery and is still alive after 6 years. There was no postoperative mortality and the overall perioperative morbidity rate was 25%. The analysis of tumor response involved 81 patients. Overall, 9% (7) of 81 patients had a complete pathologic response. Comparing the stage at the diagnostic workup with the pathologic stage, tumor downstaging was observed in 46 (57%) patients. We had 7 (9%) pT0, 5 (6%) pT1, 33 (41%) pT2, and 36 (44%) pT3. Nodal status downstaging was detected in 46 patients (57%). No evidence of nodal involvement was observed in 59 patients (73%). The incidence of tumor response was affected significantly by the number of quarters of rectal circumference involved (p = 0.03) and, marginally, by the length of the tumor (p = 0.09). The distance between the lower pole of the tumor and the anorectal ring had no influence. Of the patients, 63 (78%) had a sphincter-saving surgical procedure. In 12 (44%) of 27 patients candidate for an APR, the sphincter was preserved, as it was in 19 (95%) of 20 probable candidates. Lengthening of the distance between the anorectal ring and the lower pole of the tumor > 20 mm was observed in 21 patients (26%). Of 63 patients, 4 (6%) had moderate soilage after the sphincter-saving procedure. CONCLUSION Preoperative combined modality therapy seems to afford some potential advantages in nonrandomized trials: patients are able to tolerate higher chemotherapy doses and they experience a lower acute toxicity. Tumor downstaging and resectability rates are high; sphincter preservation is feasible. Larger T3 tumors remained less influenced by this treatment; thus, taking into account the low toxicity rate recorded, a more aggressive schedule should be applied in these resectable tumors.


Radiotherapy and Oncology | 2002

Adjuvant radiotherapy in non-small cell lung cancer with pathological stage I: definitive results of a phase III randomized trial

Lucio Trodella; Pierluigi Granone; Salvatore Valente; Vincenzo Valentini; M. Balducci; Giovanna Mantini; Adriana Turriziani; Stefano Margaritora; Alfredo Cesario; Sara Ramella; Giuseppe Maria Corbo; Rolando Maria D'Angelillo; Antonella Fontana; Domenico Galetta; Numa Cellini

BACKGROUND AND PURPOSE To evaluate the benefits and the drawbacks of post-operative radiotherapy in completely resected Stage I (a and b) non-small cell lung cancer (NSCLC). MATERIALS AND METHODS Patients with pathological Stages Ia and Ib NSCLC have been randomized into two groups: Group 1 (G1) received adjuvant radiotherapy, Group 0 (G0) the control group did not receive any adjuvant therapy. Local control, toxicity and survival have been evaluated. RESULTS Between July 1989 and June 1997, 104 patients with pathological stage I NSCLC have been enrolled in this study. Fifty-one patients were randomized to G1 and 53 to G0. Six patients have been excluded from the study due to incomplete follow-up data. Regarding local control, one patient in the G1 group had a local recurrence (2.2%) while in the G0 12 local recurrences have been observed (23%). Seventy-one percent of patients are disease-free at 5 years in G1 and 60% in G0 (P=0.039). Overall 5-year survival (Kaplan-Meier) showed a positive trend in the treated group: 67 versus 58% (P=0.048). Regarding toxicity in G1, six patients experienced a grade 1 acute toxicity. Radiological evidence of long-term lung toxicity, with no significant impairment of the respiratory function, has been detected in 18 of the 19 patients who have been diagnosed as having a post-radiation lung fibrosis. CONCLUSIONS Adjuvant radiotherapy gave good results in terms of local control in patients with completely resected NSCLC with pathological Stage I. Overall 5-year survival and disease-free survival showed a promising trend. Treatment-related toxicity is acceptable.


International Journal of Radiation Oncology Biology Physics | 2001

Ten years of preoperative chemoradiation for extraperitoneal T3 rectal cancer : Acute toxicity, tumor response, and sphincter preservation in three consecutive studies

Vincenzo Valentini; Claudio Coco; Numa Cellini; Aurelio Picciocchi; M.Claudia Fares; Maria Elena Rosetto; Giovanna Mantini; A.G. Morganti; Brunella Barbaro; Santa Cogliandolo; Gennaro Nuzzo; Manfredo Tedesco; Fabrizio Ambesi-Impiombato; Maurizio Cosimelli; Marvin Rotman

PURPOSE To compare acute toxicity, tumor response, and sphincter preservation in three schedules of concurrent chemoradiation in resectable transmural and/or node-positive extraperitoneal rectal cancer. PATIENTS AND METHODS Between 1990 and 1999, 163 consecutive patients were treated according to the following combined modalities: FUMIR: between 1990 and 1995, 83 patients were treated with bolus i.v. mitomycin C (MMC), 10 mg/m(2) day 1, plus 24-h continuous infusion i.v. 5-fluorouracil (5-FU) 1,000 mg/m(2) days 1-4, and concurrent external beam radiotherapy (37.8 Gy). PLAFUR-4: between 1995 and 1998, 40 patients were treated with cisplatin (c-DDP) 60 mg/m(2) given as slow infusion (1-4 h) on days 1 and 29, plus 24-h continuous infusion i.v. 5-FU 1,000 mg/m(2), days 1-4 and 29-32 with concurrent external-beam radiotherapy (50.4 Gy). PLAFUR-5: between 1998 and 1999, 40 patients were treated with c-DDP 60 mg/m(2) given as slow infusion (during 1-4 h) on days 1 and 29, plus 24-h continuous infusion i.v. 5-FU 1,000 mg/m(2), days 1-5 and 29-33 with concurrent external-beam radiotherapy (50.4 Gy). RESULTS Grade > or = 3 acute toxicity occurred in 14%, 5%, and 17% of patients treated in the FUMIR, PLAFUR-4, and PLAFUR-5 studies, respectively (p = 0.201). In the FUMIR, PLAFUR-4, and PLAFUR-5 studies, clinical response rate was 77%, 70%, and 83%, respectively. Tumor downstaging occurred in 57%, 68%, and 58% of patients, respectively. Pathologic complete response was recorded in 9% (FUMIR), 23% (PLAFUR-4), and 20% (PLAFUR-5) of patients. Sphincter-preserving surgery was feasible in 44% (FUMIR), 40% (PLAFUR-4), and 61% (PLAFUR-5) of patients having a distance between the anal-rectal ring and the lower pole of the tumor of 0-30 mm, and in 95%, 100%, and 100%, respectively, in those having a distance of 31-50 mm. Comparing FUMIR vs. PLAFUR, the clinical response rate was similar in the two series: a partial response was observed in 62/81 (77%) patients with FUMIR treatment, and in 61/80 (76%) patients with PLAFUR treatment. Tumor downstaging was observed in 46/81 (57%) patients and in 50/80 (68%) patients, respectively. The pathologic complete response rate was statistically higher in the PLAFUR series: 7/81 (9%) patients with FUMIR treatment and 17/80 (21%) patients with PLAFUR treatment (p = 0.04). Major downstaging (pT0+ pTmic+ pT1) in the FUMIR group was reported in 12/81 (15%) patients versus 31/80 (39%) patients in the PLAFUR group (p = 0.0006). The anal sphincter was preserved in 63/81 (78%) patients with FUMIR treatment and in 69/80 (86%) patients with PLAFUR treatment. The perioperative morbidity was statistically lower with PLAFUR: a perioperative morbidity was experienced by 20/81 (25%) patients with FUMIR treatment and by 9/80 (11%) patients with PLAFUR treatment (p = 0.042). CONCLUSION In our experience, higher radiation dose (50.4 Gy vs. 37.8 Gy), a second course of concurrent 5-FU, and the use of c-DDP instead of MMC improved the pathologic response rate without increasing acute toxicity and perioperative morbidity. The use of 5-FU 5-day infusion (PLAFUR-5) resulted in higher toxicity with a similar response rate compared to 4-day infusion (PLAFUR-4).


International Journal of Radiation Oncology Biology Physics | 1999

Preoperative chemoradiation with cisplatin and 5-fluorouracil for extraperitoneal T3 rectal cancer: acute toxicity, tumor response, sphincter preservation ☆

Vincenzo Valentini; Claudio Coco; Numa Cellini; Aurelio Picciocchi; Maria Elena Rosetto; Giovanna Mantini; Luca Marmiroli; Brunella Barbaro; Santa Cogliandolo; Gennaro Nuzzo; Manfredo Tedesco; Fabrizio Ambesi-Impiombato; Maurizio Cosimelli; Marvin Rotman

PURPOSE To evaluate the impact of preoperative external radiation therapy intensified by systemic chemotherapy including bolus cisplatin (c-DDP) and 4-day infusional 5-fluorouracil (PLAFUR-4) on tumor response and sphincter preservation in patients with extraperitoneal T3 rectal cancer with acceptable toxicity, and to compare the results to our previous experience with bolus mitomycin c (MMC) and 4-day infusion 5-FU (FUMIR). METHODS AND MATERIALS Between October 1995 and March 1998, 40 consecutive patients with resectable extraperitoneal adenocarcinoma of the rectum were treated with preoperative chemoradiation: slow infusion i.v. c-DDP, 60 mg/m2, day 1 and 29 plus 24-h continuous infusion i.v. 5-fluorouracil (5-FU) 1000 mg/m2, days 1-4 and 29-32, and concurrent external beam radiotherapy (45 Gy whole pelvis followed by 5.4 Gy boost). All but 3 patients had T3 disease. Surgery was performed 6-8 weeks after the end of chemoradiation. RESULTS No patient had Grade 4 acute toxicity. Grade 3 hematological toxicity was observed only in 2 (5%) patients. No patient had major gastrointestinal, skin, or urological acute toxicity. All patients had radical surgery. There was no perioperative mortality; perioperative morbidity rate was 12%. Overall, 23% (9 of 40) of patients had a complete pathological response and 10% (4 of 40) of patients had rare isolated residual cancer cells (Tmic). Comparing the stage at the diagnostic workup with the pathological stage, tumor downstaging was observed in 27 (68%) patients; nodal status downstaging was detected in 24 (60%) patients. Thirty-four (85%) patients had a sphincter-saving surgical procedure. In 4 of 10 (40%) patients who were definitive candidates for an abdominoperineal resection (APR), the sphincter was preserved, as it was in 13 of 13 (100%) probable candidates. Lengthening of the distance between the anorectal ring and the lower pole of the tumor > or =20 mm was observed in 9 (23%) patients. None of the patients had soilage after the sphincter-saving procedure. In our previous experience with FUMIR the complete pathological response was 9%, the sphincter-saving surgical procedure was performed in 66% cases, and the Grade 3+ toxicity was observed in 13% of patients. CONCLUSIONS The addition of c-DDP to 5-FU (PLAFUR-4) in a neoadjuvant radiochemotherapy schedule improved the pathological response rate in comparison with our previous experience. Toxicity was low indeed, thus we commenced another study adding one more day of 5-FU infusion (PLAFUR-5) to further improve our results.


International Journal of Radiation Oncology Biology Physics | 2008

Infusional 5-fluorouracil and ZD1839 (Gefitinib-Iressa) in combination with preoperative radiotherapy in patients with locally advanced rectal cancer: a phase I and II Trial (1839IL/0092)

Vincenzo Valentini; Antonino De Paoli; Maria Antonietta Gambacorta; Giovanna Mantini; Carlo Ratto; Fabio Maria Vecchio; Brunella Barbaro; R. Innocente; Carlo Riccardo Rossi; G. Boz; M.C. Barba; Alessandro Frattegiani; Marco Lupattelli; Giovan Battista Doglietto

PURPOSE To report the final data of a Phase I and II study (1839IL/0092) on the combination of an anti-epidermal growth factor receptor drug (gefitinib), infusional 5-fluorouracil, and preoperative radiotherapy in locally advanced, resectable rectal cancer. METHODS AND MATERIALS Patients received 45 Gy in the posterior pelvis plus a boost of 5.4 Gy on the tumor and corresponding mesorectum. Infusional 5-fluorouracil (5-FU) and gefitinib (250 and 500 mg/day) were delivered during all radiotherapy course. An IORT boost of 10 Gy was allowed. The main endpoints of the study were to establish dose-limiting toxicity (DLT) and to evaluate the rate of pathologic response according to the tumor regression grade (TRG) Mandard score. RESULTS A total of 41 patients were enrolled. The DLT was not reached in the 6 patients enrolled in the dose-escalation part of the study. Of the 33 patients in the Phase II, TRG 1 was recorded in 10 patients (30.3%) and TRG 2 in 7 patients (21.2 %); overall 17 of 33 patients (51.5%) had a favorable endpoint. Overall, Grade 3+ toxicity was recorded in 16 patients (41%); these included Grade 3+ gastrointestinal toxicity in 8 patients (20.5%), Grade 3+ skin toxicity in 6 (15.3%), and Grade 3+ genitourinary toxicity in 4 (10.2%). A dose reduction of gefitinib was necessary in 24 patients (61.5%). CONCLUSIONS Gefitinib can be associated with 5-FU-based preoperative chemoradiation at the dose of 500 mg without any life-threatening toxicity and with a high pCR (30.3%). The relevant rate of Grade 3 gastrointestinal toxicity suggests that 250 mg would be more tolerable dose in a neaoadjuvant approach with radiotherapy and infusional 5-FU.


Strahlentherapie Und Onkologie | 2010

Single-Arm Phase II Study of Conformal Radiation Therapy and Temozolomide plus Fractionated Stereotactic Conformal Boost in High-Grade Gliomas

M. Balducci; Giuseppina Apicella; S. Manfrida; Annunziato Mangiola; Alba Fiorentino; L. Azario; Giuseppe Roberto D’Agostino; V. Frascino; N. Dinapoli; Giovanna Mantini; Alessio Albanese; Pasquale De Bonis; S. Chiesa; Vincenzo Valentini; Carmelo Anile; Numa Cellini

Purpose:To assess survival, local control and toxicity using fractionated stereotactic conformal radiotherapy (FSCRT) boost and temozolomide in high-grade gliomas (HGGs).Patients and Methods:Patients affected by HGG, with a CTV1(clinical target volume, representing tumor bed ± residual tumor + a margin of 5 mm) ≤ 8 cm were enrolled into this phase II study. Radiotherapy (RT, total dose 6,940 cGy) was administered using a combination of two different techniques: three-dimensional conformal radiotherapy (3D-CRT, to achieve a dose of 5,040 or 5,940 cGy) and FSCRT boost (19 or 10 Gy) tailored by CTV1diameter (≤ 6 cm and > 6 cm, respectively). Temozolomide (75 mg/m2) was administered during the first 2 or 4 weeks of RT. After the end of RT, temozolomide (150–200 mg/m2) was administered for at least six cycles. The sample size of 41 patients was assessed by the single proportion–powered analysis.Results:41 patients (36 with glioblastoma multiforme [GBM] and five with anaplastic astrocytoma [AA]) were enrolled; RTOG neurological toxicities G1–2 and G3 were 12% and 3%, respectively. Two cases of radionecrosis were observed. At a median follow-up of 44 months (range 6–56 months), global and GBM median overall survival (OS) were 30 and 28 months. The 2-year survival rate was significantly better compared to the standard treatment (63% vs. 26.5%; p < 0.00001). Median progression-free survival (PFS) was 11 months, in GBM patients 10 months.Conclusion:FSCRT boost plus temozolomide is well tolerated and seems to increase survival compared to the standard treatment in patients with HGG.ZusammenfassungZiel:Untersuchung von Uberleben, lokaler Tumorkontrolle und Toxizitat einer fraktionierten stereotaktischen konformalen Strahlentherapie (FSCRT) mit Boostbestrahlung in Kombination mit Temozolomid bei hochmalignen Gliomen (HMG).Patienten und Methodik:Patienten mit HMG und einem CTV1(klinisches Zielvolumen, d. h. Tumorbett ± Resttumor + einem Sicherheitsabstand von 5 mm) ≤ 8 cm wurden in diese Phase-II-Studie eingeschlossen. Die Strahlentherapie (Gesamtdosis 6 940 cGy) wurde als Kombination aus zwei unterschiedlichen Techniken appliziert: dreidimensionale konformale Strahlentherapie (3D-CRT, um eine Strahlendosis von 5 040 oder 5 940 cGy zu erreichen) und lokale Dosisaufsattigung mit FSCRT-Boost (19 oder 10 Gy), die auf den CTV1-Durchmesser (≤ 6 cm bzw. > 6 cm) zugeschnitten war. Temozolomid (75 mg/m2) wurde wahrend der ersten 2 oder 4 Wochen der Strahlentherapie verabreicht. Nach dem Ende der Strahlentherapie erhielten die Patienten Temozolomid (150–200 mg/m2) fur wenigstens sechs Zyklen. Die Fallzahl wurde mit Hilfe eines einfach-proportionalen Testverfahrens („single proportion-powered analysis“) bei 41 Patienten bestimmt.Ergebnisse:41 Patienten (36 mit Glioblastoma multiforme [GBM] und funf mit anaplastischem Astrozytom [AA]) wurden behandelt; Neurotoxizitat gemas RTOG-Skala G1–2 bzw. G3 wurde in 12% bzw. 3% der Patienten beobachtet. Zwei Falle von Radionekrose traten auf. Bei einer mittleren Beobachtungszeit von 44 Monaten (Range 6–56 Monate) lagen die mittlere Gesamt- und die GBM-spezifische Uberlebenszeit (OS) bei 30 und 28 Monaten. Die 2-Jahres-Uberlebensrate war signifikant besser im Vergleich zur Standardbehandlung (63% vs. 26,5%; p < 0.00001). Die mittlere progressionsfreie Uberlebenszeit (PFS) betrug 11 Monate, bei GBM-Patienten 10 Monate.Schlussfolgerung:FSCRT-Boostbestrahlung plus Temozolomid wird gut toleriert und scheint im Vergleich zur Standardbehandlung die Uberlebenszeit von Patienten mit HMG zu verbessern.


Diseases of The Colon & Rectum | 2006

Long-Term Results After Neoadjuvant Radiochemotherapy for Locally Advanced Resectable Extraperitoneal Rectal Cancer

Claudio Coco; Vincenzo Valentini; Alberto Manno; Claudio Mattana; Alessandro Verbo; Numa Cellini; Maria Antonietta Gambacorta; Marcello Covino; Giovanna Mantini; Francesco Miccichè; Giorgio Pedretti; Luigi Petito; Gianluca Rizzo; Maurizio Cosimelli; Fabrizio Ambesi Impiombato; Aurelio Picciocchi

PurposeThis study was designed to evaluate long-term outcome in locally advanced resectable extraperitoneal rectal cancer treated by preoperative radiochemotherapy.MethodsEighty-three consecutive patients who developed locally advanced resectable extraperitoneal rectal cancer underwent preoperative concomitant radiochemotherapy followed by surgery, including total mesorectal excision.ResultsMedian follow-up was 108 (range, 10–169) months. The living patients underwent complete follow-up of, at least, nine years. Fourteen patients developed local recurrence. The time to detection was longer than two years in eight cases and longer than five years in four. Twenty-one patients developed metastases, 19 within the first five years from surgery. At the univariate analysis, clinical stage at presentation, lymph node involvement at clinical restaging after neoadjuvant therapy, and pTand pN stage were found positively correlated to the incidence of metastases. At the multivariate analysis, the only factors which confirmed a positive correlation were pT stage and pN stage. The actuarial overall survival at five, seven, and ten years was 75.5, 67.8, and 60.4 percent, respectively. The same figures for cancer-related survival were 77.9, 70, and 65.8 percent. At the univariate analysis, factors directly correlated with worse survival were: TNM stage at clinical restaging after neoadjuvant therapy (in particular lymph node involvement) pTNM, pT, and pN. At the multivariate analysis the only factors that confirmed a correlation with worse survival were pTNM, pT, and pN.ConclusionsLong- term follow-up allows to individuate 28 percent of all local relapses after the first five years from surgery. Postoperative stage is highly predictive of prognosis.


American Journal of Clinical Oncology | 2012

Intensity-modulated radiotherapy with simultaneous integrated boost to dominant intraprostatic lesion: preliminary report on toxicity.

Edy Ippolito; Giovanna Mantini; Alessio Giuseppe Morganti; Ercole Mazzeo; Gilbert D.A. Padula; C. Digesù; Savino Cilla; V. Frascino; Stefano Luzi; Mariangela Massaccesi; G. Macchia; F. Deodato; Gian Carlo Mattiucci; Angelo Piermattei; Numa Cellini

ObjectivesTo evaluate the feasibility of intensity-modulated radiotherapy with simultaneous integrated boost to the dominant intraprostatic lesion for definitive treatment of prostate cancer. Materials and MethodsPatients were deemed eligible for the study if they had histologically proven stage cT2-T3 N0M0 prostate adenocarcinoma. In addition <20% risk of lymph nodal involvement according to Roach formula, was required for enrollment. Patients were treated with intensity-modulated radiotherapy with simultaneous integrated boost technique to the dominant intraprostatic lesion defined by magnetic resonance imaging. The prescribed dose to the prostate and seminal vesicles was 72 Gy (1.8 Gy per fraction). The dose delivered to the intraprostatic lesion received was 80 Gy (2 Gy per fraction). Acute gastrointestinal (GI) and genitourinary (GU) toxicity was evaluated weekly during treatment, and at 1 and 3 months thereafter. Late GI and GU toxicity was evaluated by Kaplan Meier method. ResultsForty patients were deemed evaluable. Acute and late GI and GU toxicity were evaluated in all patients. Two patients (5%) developed acute grade 3 GI toxicity and 1 patient (2.5%) developed acute grade 3 GU toxicity. No grade 4 acute GI or GU toxicity occurred. With a median follow-up of 19 months (interquartile range, 15 to 26 mo), the 2-year actuarial cumulative incidence of grade ≥2 rectal toxicity was 9.5%. The 2-year actuarial cumulative incidence of grade ≥2 urinary toxicity was 13.3%. ConclusionsTreatment related acute toxicity was low in our cohort. Prolonged observation with a larger series of patients is necessary to evaluate late toxicity and local control.


Neuro-oncology | 2012

Low-dose fractionated radiotherapy and concomitant chemotherapy in glioblastoma multiforme with poor prognosis: a feasibility study

M. Balducci; S. Chiesa; B. Diletto; G.R. D'Agostino; Annunziato Mangiola; S. Manfrida; Giovanna Mantini; Alessio Albanese; Alba Fiorentino; V. Frascino; Berardino De Bari; Francesco Miccichè; Fiorenza De Rose; Alessio Giuseppe Morganti; Carmelo Anile; Vincenzo Valentini

We explored the feasibility of concurrent palliative chemotherapy and low-dose fractionated radiotherapy (LD-FRT) in glioblastoma multiforme (GBM). Patients with recurrent/progressive GBM at least 3 months after the end of primary radiotherapy received 0.3 Gy twice daily with cisplatin and fotemustine if progressing on temozolomide, or 0.4 Gy twice daily with temozolomide if recurrent 4-6 months later (retreatment group). Newly diagnosed GBM with gross residual mass received 30 Gy with concomitant and adjuvant temozolomide and 0.4 Gy twice daily from the second adjuvant cycle (naive group) for 2-4 cycles. Twenty-six patients were enrolled. In the retreatment group (n = 17; median LD-FRT total dose 7.2 Gy [range 2.4-11.6]), grade 3 or 4 hematological toxicity was observed in 5.9% of patients. Median follow-up time was 20 months (range 4-35). Median progression-free survival (PFS) and overall survival (OS) from the time of recurrence or progression were 4 and 8 months, respectively (OS at 6 months, 69%; at 12 months, 16.7%). In the naive group (n = 9; median LD-FRT total dose 8 Gy [range 3.2-16]), grade 3 or 4 hematological toxicity was observed in 11.1% of patients. Median follow-up time was 17 months (range 8-20)-median PFS was 9 months, with PFS at 6 months and at 1 year of 66.7% and 26.7%, respectively; and median OS was 12 months, with OS at 6 months and at 1 year of 77.8% and 34.6%, respectively. LD-FRT with concurrent chemotherapy was well tolerated.


Strahlentherapie Und Onkologie | 2011

Whole-brain radiotherapy combined with surgery or stereotactic radiotherapy in patients with brain oligometastases: Long-term analysis

G.R. D'Agostino; Rosa Autorino; Angelo Pompucci; Maria De Santis; S. Manfrida; Giuseppe Di Lella; Giovanna Mantini; V. Frascino; S. Chiesa; Alessio Albanese; N. Dinapoli; L. Azario; Alba Fiorentino; Vincenzo Valentini; Carmelo Anile; M. Balducci

Objective:To verify whether the treatment of brain oligometastases with whole-brain radiotherapy (WBRT) plus stereotactic radiotherapy (SRT) or surgical resection results in different outcomes.Methods:Files of patients affected by brain metastases submitted to surgical resection followed by WBRT (group A) or WBRT + SRT (group B) were retrospectively selected for this study. The two treatment groups were matched for the following potential prognostic factors: WBRT schedule, age, gender, performance status, tumor type, number of brain metastases, extra-cerebral metastases, and recursive partitioning analysis class (RPA). The outcomes of patients in both groups were evaluated in terms of toxicity, local control, and overall survival.Results:Total of 97 patients were selected (56 male; 42 female) who were respectively submitted to surgical resection followed by WBRT (group A, n = 50 patients) or WBRT + SRT (Group B, n = 47 patients). Median follow-up was 95 months (range, 8–171 months). The 1-year local control rates were 46.0% and 69.0% respectively. No significant difference in local tumor control was observed between group A and B (p = 0.10). Median overall survival was 15 and 19 months in group A and B, respectively. One-year survival was 56.0% and 62%, respectively. No difference was observed in the two groups (p = 0.40).Conclusion:Surgery remains the main therapeutic approach in symptomatic patients; nevertheless, our data support the use of WBRT plus SRT in one or two brain metastases smaller than 3 cm.Zielsetzung:Zu untersuchen, ob die Behandlung von Oligohirnmetastasen mit Ganzhirnbestrahlung (whole-brain radiotherapy, WBRT) plus stereotaktischer Radiotherapie (SRT) oder chirurgischer Resektion unterschiedliche Ergebnisse bringt.Methoden:Krankenakten von Patienten mit operativ entfernten Hirnmetastasen und anschließender WBRT (Gruppe A) oder WBRT + SRT (Gruppe B) wurden retrospektiv für diese Studie ausgewählt. Die zwei Beghandlungsarme wurden für folgende prognostische Parameter gematcht: WBRT-Schema. Alter, Geschlecht, Allgemeinzustand, Art des Primärtumors, Anzahl der Hirnmetastasen, extrazerebrale Metastasen, Recursive-Partioning-Analysis-(RPA-)Klasse. Das Behandlungsergebnis für beide Patientengruppen wurde im Hinblick auf Toxizität, lokale Tumorkontrolle und Gesamtüberleben bewertet.Ergebnisse:Insgesamt wurden 97 Patienten ausgewählt (56 m; 42 w), die entweder mit operativer Entfernung und anschließender WBRT (Gruppe A, n = 50 Pat.) oder mit WBRT + SRT (Gruppe B, n = 47 Pat.) behandelt wurden. Die mediane Beobachtungszeit betrug 95 Monate (Spanne 8–171). Die lokale Tumorkontrolle nach 1 Jahr betrug 46,0% (Gruppe A) und 69,0% (Gruppe B), ohne dass dieser Unterschied statistisch signifikant wäre (p = 0,10). Das mediane Gesamtüberleben betrug jeweils 15 und 19 Monate in Gruppe A and B. Die 1-Jahres-Überlebensrate betrug jeweils 56,0% and 62%. Es wurde kein Unterschied zwischen den beiden Gruppen gefunden (p = 0,40).Schlussfolgerung:Die chirurgische Entfernung bleibt die Behandlungsoption bei symptomatischen Patienten. Unsere Daten sprechen für eine Behandlung mit WBRT plus SRT bei Vorliegen von ein oder zwei Hirnmetastasen, die kleiner als 3 cm sind.

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Vincenzo Valentini

Catholic University of the Sacred Heart

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M. Balducci

Catholic University of the Sacred Heart

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V. Frascino

Catholic University of the Sacred Heart

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Numa Cellini

Catholic University of the Sacred Heart

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S. Chiesa

Catholic University of the Sacred Heart

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Gian Carlo Mattiucci

Catholic University of the Sacred Heart

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S. Manfrida

Catholic University of the Sacred Heart

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N. Dinapoli

Catholic University of the Sacred Heart

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Maria Antonietta Gambacorta

Catholic University of the Sacred Heart

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G.R. D'Agostino

Catholic University of the Sacred Heart

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