Papers by Maria grazia Fabrini
International Journal of Radiation Oncology Biology Physics, Nov 1, 2015
concurrent chemoradiation therapy for locally advanced non-small cell lung cancer (NSCLC). Materi... more concurrent chemoradiation therapy for locally advanced non-small cell lung cancer (NSCLC). Materials/Methods: Eighty-four patients with stage III NSCLC from a prospective clinical trial were evaluated by FDG PET before, during (after delivery of 40-50 Gy), and after chemoradiation therapy. PET/CT images were analyzed with microRNA target detection software and the following FDG uptake variables generated: maximum standardized uptake value [SUVmax], SUVmean, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Percent changes in these variables from before to during or after treatment were also analyzed. Both the absolute values and changes in these variables were added to a clinical model (which included age, sex, race, tumor size, histology, disease stage, smoking history, receipt of induction chemotherapy, radiation technique, and total delivered dose) to assess added prediction power. Endpoints were recurrence within the planning target volume (PTV) and times to distant metastasis, disease-free survival, and OS, assessed by Cox regression analysis. Results: Median time to recurrence within the PTV was 12 months; time to distant metastasis, 9 months; disease-free survival, 9 months; and OS, 24 months. On the pretreatment PET/CT scans, SUVmax (hazard ratio [HR] 0.938, 95% confidence interval [CI] 0.887-0.991, PZ0.023) and SUVpeak (HR 0.927, 95% CI 0.870-0.988, PZ0.019) of the primary tumor correlated with distant metastasis in univariate analysis but not after adjustment for clinical factors in multivariate analysis (SUVmax: HR 0.954, 95% CI, 0.899-1.012, PZ0.117; SUVpeak: HR 0.944, 95% CI 0.881-0.987, PZ0.106). On the mid-treatment scans, MTV and TLG of lymph nodes were associated with time to local recurrence in both univariate and multivariate analyses after adjustment for clinical factors (MTV: HR 1.027, 95% CI 1.008-1.046, PZ0.005; TLG: HR 1.008, 95% CI 1.003-1.012, P<0.001). On the post-treatment PET/CT scans, no variables for primary tumor or lymph nodes, whether absolute values or percent changes were associated with clinical outcomes. Conclusion: Our results suggest that MTV and TLG in lymph nodes during chemoradiation therapy predicted local recurrence after concurrent chemoradiation therapy for locally advanced NSCLC. This information may help clinicians to modify treatment accordingly.
PubMed, Apr 1, 2016
Aim: To assess the outcome of 35 patients with vaginal carcinoma treated with different radiother... more Aim: To assess the outcome of 35 patients with vaginal carcinoma treated with different radiotherapy modalities. Materials and methods: Thirty-one patients received external-beam irradiation (EBRT) to the entire vagina, para-vaginal area and pelvic nodes (total dose=45-50.4 Gy). Concomitant chemotherapy was used in 22 patients. Nineteen patients received additional 15-25 Gy high-dose-rate brachytherapy (BT) boost and eight received additional EBRT boost to the primary tumor site. Four women received exclusive 30-40 Gy high-dose-rate BT. Results: Median progression-free survival and median overall survival were 22 months and 89 months, respectively. Age <70 years, use of EBRT plus BT, and concomitant chemotherapy were associated with better progression-free (p=0.002, p=0.007, and p=0.02) and overall (p=0.01, p=0.009, p=0.009) survival. Conclusion: Concomitant EBRT and chemotherapy followed by BT is the best treatment for vaginal carcinoma.
Anticancer Research, Oct 1, 2018
Background/Aim: In patients with recurrent glioblastoma, the best timing to administer bevacizuma... more Background/Aim: In patients with recurrent glioblastoma, the best timing to administer bevacizumab is not well addressed yet. In this study, we reported the results of a monocentric experience comparing the early use of bevacizumab (following the first GBM recurrence) with the delayed administration (following the second or even further GBM recurrences). Materials and Methods: This analysis included 129 glioblastoma patients with a median follow-up of 22.4 months (range=5.26-192 months). Results: The median time lapse from diagnosis of glioblastoma to disease recurrence was 11.6 months; 13.1 for patients treated with deferred administration of bevacizumab and 9.9 for patients with early administration (p=0.047). Bevacizumab progression-free survival with early and delayed use was 3.45 and 2.92 months, respectively (p=0.504). Survival time from the start of bevacizumab was 6.18 months in patients with early administration, and 6.47 in the delayed administration one (p=0.318). Conclusion: Delayed administration of bevacizumab can be considered in selected patients with less aggressive recurrent glioblastoma.
Journal of Clinical Oncology, May 20, 2009
2012 Background: Bevacizumab (BV) has shown a promising activity in recurrent malignant gliomas (... more 2012 Background: Bevacizumab (BV) has shown a promising activity in recurrent malignant gliomas (MG) in combination with irinotecan. Few data are available on the combination of bevacizumab and nitrosoureas, that represent the standard cytotoxic option at recurrence. Methods: In this ongoing phase II study patients with MG recurrent after surgery, radiation therapy, and temozolomide are eligible. The treatment consists of an induction phase with BV at 10 mg/kg intravenously on day 1 and 15 and fotemustine (FTM) (a nitrosourea with elevated lipophilic properties) at 75 mg/m2 intravenously on day 1 and 8, followed after a 3-week interval by a maintenance phase with BV at 10 mg/kg i.v. and FTM 75 mg/m2 i.v. every 3 weeks until tumor progression or unacceptable toxicity. Patients undergo clinical and MRI assessment 1 month after the start of treatment and thereafter every 2 months. Monitoring of CBV with perfusion MRI is performed in selected centers. The co-primary endpoints are objective response rate (ORR), based on Mc Donald's criteria (CR + PR) and progression-free survival at 6 months (PFS6), with secondary endpoints of safety time to tumor progression (TTP) and overall survival. Results: From April 2008 to December 2008, 34 patients were enrolled and 31 (22 glioblastomas and 9 anaplastic gliomas) are evaluable for response. Overall response rate (2 CR and 9 PR) was 35% (glioblastomas 33%, anaplastic gliomas 41.5%). Median time to maximal response was 1 month. Steroids were reduced in 50% of patients. Sixteen of 31 patients progressed with a TTP of 2.6 months (1–8.5). Patterns of progression were local in 10/16, local + leptomeningeal spread in 3/16 and gliomatosis in 3/16. Fifteen patients are free of tumor progression (from 2 to 8 months). Toxicities included grade III-IV neutropenia in three patients, grade III-IV piastrinopenia in five, and grade III thrombosis in two. Seventeen patients developed mild to moderate fatigue, six arterial hypertension, and three grade I intratumoral haemorrhage. Conclusions: Combination of bevacizumab and fotemustine in recurrent malignant gliomas is safe and promising. Updated results, monitoring of CBV with perfusion MRI, and correlations between MGMT promoter methylation and response/outcome will be presented. No significant financial relationships to disclose.
PubMed, 2010
The aim of this retrospective investigation was to assess the prognostic relevance of some pre-tr... more The aim of this retrospective investigation was to assess the prognostic relevance of some pre-treatment clinical variables and histological findings assessed on the surgical samples of 46 patients with stage Ib(2)-IIb cervical cancer treated with cisplatin-based neoadjuvant chemotherapy followed by radical hysterectomy. Seven patients achieved a pathologically documented complete response, 6 had an optimal partial response, 29 had a suboptimal partial response, and 4 had stable disease. As for histological findings on surgical samples, 7 (15.2%) patients had positive lymph nodes, 10 (21.7%) had lymph-vascular space involvement, and 10 (21.7%) had positive parametria and/ or surgical margins. After surgery, 38 patients received further treatment with chemotherapy and/or irradiation. The median follow-up of survivors was 53 months (range, 4-167 months).Thirteen (28.3%) patients developed recurrent tumour, 11 (23.9%) patients died of tumour and one patient died of ictus with no clinical evidence of tumour. Recurrence-free and overall survival were significantly related to tumour stage (Ib(2)-IIa versus IIb, p=0.01 and p=0.02, respectively), pathologically assessed lymph node status (negative versus positive, p=0.0009 and p=0.007), lymph-vascular space status (negative versus positive, p=0.01 and p=0.009), parametrial and/or surgical margin status (negative versus positive, p=0.0001 and p=0.0005), but not to haemoglobin level before chemotherapy, patient age, tumour grade or chemotherapy regimen. A platelet count before chemotherapy above the median value of 272,000/microl was associated with a trend for a shorter recurrence-free survival (p=0.06) and with a significantly shorter overall survival (p=0.04) when compared with a lower platelet count. In conclusion, FIGO stage, lymph node status, lymph-vascular space status, parametrial and/or surgical margin status and pre-treatment platelet count are predictors of clinical outcome in patients with FIGO stage Ib(2)-IIb cervical cancer undergoing cisplatin-based neoadjuvant chemotherapy followed by radical hysterectomy. A multivariate analysis on a larger series of homogeneously treated patients is warranted to better define the clinicopathological risk factors useful to adequately plan the therapeutic strategy.
Journal of Contemporary Brachytherapy, 2016
Purpose: The incidence of non-melanoma skin cancer (NMSC) has been increasing over the past 30 ye... more Purpose: The incidence of non-melanoma skin cancer (NMSC) has been increasing over the past 30 years. There are different treatment options and surgical excision is the most frequent treatment due to its low rates of recurrence. Radiotherapy is an effective alternative of surgery, and brachytherapy (BT) might be a better therapeutic option due to high radiation dose concentration to the tumor with rapid dose fall-off resulting in normal tissues sparing. The aim of this review was to evaluate the local control, toxicity, and cosmetic outcomes in NMSC treated with high-dose-rate BT (HDR-BT). Material and methods: In May 2016, a systematic search of bibliographic database of PubMed, Web of Science, Scopus, and Cochrane Library with a combination of key words of "skin cancer", "high dose rate brachytherapy", "squamous cell carcinoma", "basal cell carcinoma", and "non melanoma skin cancer" was performed. In this systematic review, we included randomized trials, non-randomized trials, prospective and retrospective studies in patients affected by NMSC treated with HDR-BT. Results: Our searches generated a total of 85 results, and through a process of screening, 10 publications were selected for the review. Brachytherapy was well tolerated with acceptable toxicity and high local control rates (median: 97%). Cosmetic outcome was reported in seven study and consisted in an excellent and good cosmetic results in 94.8% of cases. Conclusions: Based on the review data, we can conclude that the treatment of NMSC with HDR-BT is effective with excellent and good cosmetics results, even in elderly patients. The hypofractionated course appears effective with very good local disease control. More data with large-scale randomized controlled trials are needed to assess the efficacy and safety of brachytherapy.
Radiotherapy and Oncology, Apr 1, 2015
European Journal of Cancer, Feb 1, 2017
The median age at the time of diagnosis was 82.7 (range 77 to 88). The median follow up was 42 mo... more The median age at the time of diagnosis was 82.7 (range 77 to 88). The median follow up was 42 months. Fifty five patients (65%) received partial mastectomy and 30 patients (35%) total mastectomy (MT). Fifty four patients (63%) received whole breast or chest wall irradiation, while 31 patients (37%) received locorregional irradiation. Five patients presented cutaneous toxicity grade 3. Overall survival was 70% at 5 years and breast cancer specific survival (BCSS) was 94% at 5 years. Four patients (4.2%) died of cardiovascular disease. In the univariate analysis clinical preoperative nodal stage, clinical and pathological tumour size, locorregional irradiation and pathologic tumor stage were significant variables for worst overall survival (Table 1). No other examined factor was significantly related. Conclusion: Patients older than 80 treated by Stage I−III breast cancer have long survival after treatment. OS and BCSS is high at five years. Patients with locally advanced preoperative disease, pathologic tumor size and locorregional irradiation contributed negatively to survival. No conflict of interest. 214 POSTER The role of post-mastectomy radiotherapy (PMRT) and prognostic factors of locoregional recurrence
Radiotherapy and Oncology, Apr 1, 2015
S704 3rd ESTRO Forum 2015 treatment. Image matching was performed initially using the auto match ... more S704 3rd ESTRO Forum 2015 treatment. Image matching was performed initially using the auto match feature on the TomoTherapy platform and positioning was then refined by the treating radiographers. In addition to the initial radiographer who performed matching at time of treatment, a further two radiographers repeated the image matching process in order to provide information about inter-observer variability. Results: The results of intra-fraction motion include components both of positional change and also residual error in inter-observer image matching. The inter-observer variation had a standard deviation of 0.6mm left-right (LR), 0.3mm anterior-posterior (AP) and 0.9mm cranio-caudal (CC). Intra-fraction motion had a mean positional change approximately 0 in LR and AP and 0.6mm CC. The standard deviations were 0.7, 0.6 and 1.0mm in LR, AP and CC directions. Using the standard van Herk PTV margin recipe 1 , the margin required to allow for these two components of uncertainty is 2.3mm LR, 1.7mm AP and 3.4 mm CC. Conclusions: The PTV margin component attributable to intra-fraction motion and inter-observer matching is bigger than expected, and bigger than used. When using high dose single fraction radiosurgery, the standard PTV margin recipe may be unnecessarily generous. Work is ongoing to resolve the difference between the 'ideal' PTV margin and the 'clinically practical' margin currently in use. References: 1. Van Herk et al. The probability of correct target dosage: dose-population histograms for deriving treatment margins in radiotherapy IJROBP 47: 1121-1135, 2000.
Radiotherapy and Oncology, May 1, 2017
Annals of Oncology, Sep 1, 2012
efficacy benefit of adding docetaxel to CF (cisplatim + 5-fluorouracil) (DCF). DCF is associated ... more efficacy benefit of adding docetaxel to CF (cisplatim + 5-fluorouracil) (DCF). DCF is associated with significant toxicity, making it less tolerable to pts. We modified the original DCF regimen to reduce its toxicity without decreasing efficacy. Patients and methods: AGC pts received docetaxel 75 mg/m 2 and cisplatin 75 mg/ m 2 in day2 with leucovorin 50 mg and 5-fluorouracil 500 mg/m 2 (3-hour infusion) in day 1-3 every 3w (TPF) instead of original DCF (docetaxel 75 mg/m 2 , cisplatin 75 mg/m 2 in day 1 and fluorouracil 750 mg/m 2 in day 1-5 continuous infusion). Results: 39 CT-naïve pts with AGC were included in our study from Feb2008 to Dec2010 (20 female, 19 male). ECOG 0/1/2 were10/80/10% pts. ORR was 40% (16/39), SD-40% (16/39), PD-20% (7/39). Median PFS and median OS were evaluated in 38pts and were 5,4m and 9,5m, respectively. Toxicity was moderate. Grade 3 and 4 toxicities included leucopenia-32,5 and 7,5%, neutropenia-25 and 40%, thrombocytopenia-2,5 and 0% pts, febrile neutropenia-1pt (2,5%); asthenia-2,5 and 0%, stomatitis-2,5 and 0%, diarrhea-12,5 and 0%, vomiting-0 and 2,5% pts. We didn't use G-CSF prophylaxis. There were no deaths and treatment discontinuation due to toxicity. At present 5 pts are still alive, in three of them distant mts disappeared and operation became possible. Their survival is 28,5m (without PD), 32.9m with PD over 10m after surgery and 42m with PD over 12m after surgery. Conclusion: Our data suggest that TPF regimen has the similar efficacy and better tolerability than the standard DCF. TPF regimen can be safely given in an ambulant setting.
Investigative Ophthalmology & Visual Science, Sep 26, 2016
Annals of Oncology, Sep 1, 2012
efficacy benefit of adding docetaxel to CF (cisplatim + 5-fluorouracil) (DCF). DCF is associated ... more efficacy benefit of adding docetaxel to CF (cisplatim + 5-fluorouracil) (DCF). DCF is associated with significant toxicity, making it less tolerable to pts. We modified the original DCF regimen to reduce its toxicity without decreasing efficacy. Patients and methods: AGC pts received docetaxel 75 mg/m 2 and cisplatin 75 mg/ m 2 in day2 with leucovorin 50 mg and 5-fluorouracil 500 mg/m 2 (3-hour infusion) in day 1-3 every 3w (TPF) instead of original DCF (docetaxel 75 mg/m 2 , cisplatin 75 mg/m 2 in day 1 and fluorouracil 750 mg/m 2 in day 1-5 continuous infusion). Results: 39 CT-naïve pts with AGC were included in our study from Feb2008 to Dec2010 (20 female, 19 male). ECOG 0/1/2 were10/80/10% pts. ORR was 40% (16/39), SD-40% (16/39), PD-20% (7/39). Median PFS and median OS were evaluated in 38pts and were 5,4m and 9,5m, respectively. Toxicity was moderate. Grade 3 and 4 toxicities included leucopenia-32,5 and 7,5%, neutropenia-25 and 40%, thrombocytopenia-2,5 and 0% pts, febrile neutropenia-1pt (2,5%); asthenia-2,5 and 0%, stomatitis-2,5 and 0%, diarrhea-12,5 and 0%, vomiting-0 and 2,5% pts. We didn't use G-CSF prophylaxis. There were no deaths and treatment discontinuation due to toxicity. At present 5 pts are still alive, in three of them distant mts disappeared and operation became possible. Their survival is 28,5m (without PD), 32.9m with PD over 10m after surgery and 42m with PD over 12m after surgery. Conclusion: Our data suggest that TPF regimen has the similar efficacy and better tolerability than the standard DCF. TPF regimen can be safely given in an ambulant setting.
Journal of Clinical Oncology, 2015
2054 Background: patients with glioblastoma failing radiotherapy plus temozolomide are treated in... more 2054 Background: patients with glioblastoma failing radiotherapy plus temozolomide are treated in Europe with nitrosourea-based regimens, but factors influencing survival are not entirely known.We investigated the factors influencing survival in a large cohort of Italian glioblastoma patients who received the nitrosourea fotemustine (FTM) at first relapse following the Stupp regimen. Methods: survival data and information on demographics, clinical, radiological, molecular and treatments factors were collected in 34 Italian Institutions. PFS and OS curves were constructed using the Kaplan-Meier method and both univariate and multivariate analysis were performed . Results: Since 2005, 921 (587 M 334 F, median age 56 yrs) patients were enrolled , and up to date 897 are evaluable. Median PFS following FTM was 103 days. Factors of prognostic significance in univariate analysis were: MGMT methylation (129 d methylated vs 90 d unmethylated tumors, p < 0.001) and association with bevacizumab (148 d the associatio...
Annals of Oncology, 2012
Background: TH-302 is a hypoxia targeted prodrug with a hypoxia-triggered 2-nitroimidazole compon... more Background: TH-302 is a hypoxia targeted prodrug with a hypoxia-triggered 2-nitroimidazole component designed to release the DNA alkylator, bromo-isophosphoramide mustard (Br-IPM), when reduced in severe hypoxia. A randomized Phase 2B study (NCT01144455) was conducted to assess the benefit of G + T to standard dose G as first-line therapy of PAC. Materials and methods: An open-label multi-center study of two dose levels of TH-302 (240 mg/m 2 or 340 mg/m 2) in combination with G versus G alone (randomized 1:1:1). G (1000 mg/m 2) and T were administered IV over 30-60 minutes on Days 1, 8 and 15 of a 28-day cycle. Patients on the G could crossover after progression and be randomized to a G + T arm. The primary efficacy endpoint was a comparison of progression-free survival (PFS) between the combination arms and G alone (80% power to detect 50% improvement in PFS with one-sided alpha of 10%). Summary PFS outcome has previously been reported; more detailed PFS as well as the initial overall survival (OS) data are presented. Results: 214 pts were treated; 164 (77%) Stage IV and 50 (23%) Stage IIIB. Median age 65 (range 29-86); 126 M/88 F; 40% ECOG 0/60% ECOG 1. Receiving 6 or more cycles: 32% G; 45% G + T240; 55% G + T340. Median PFS was 3.6 mo in G vs 5.5 mo in G + T240 (p = 0.031) and 6.0 mo in G + T340 (p = 0.008). Poorer prognostic factors (older age, poorer performance status, reduced albumin) were associated with larger treatment effect. Median OS was 7.0 mo in G vs 9.0 in G + T240 and 9.5 mo in G + T340. RECIST best response was 12% in G vs 17% in G + T240 and 27% in G + T340. CA19-9 decreases were significantly greater G + T340. A >50% CA19-9 decrease was 52% with G vs 50% with G + T240 and 70% with G + T340. AEs leading to discontinuation were: 16% G, 15% G + T240 and 11% G + T340. Rash (45% in G + T340) and stomatitis (36% in G + T340) were greater in combination, 4 pts Grade 3 rash. Grd 3/4 thrombocytopenia were 11% G, 39% G + T240 and 59% G + T340 and Grd 3/4 neutropenia were 28% G, 56% G + T240 and 59% G + T340. Conclusions: The combination of G plus TH-302 improved the efficacy of G. A TH-302 dose of 340 mg2 was identified for future studies. Skin and mucosal toxicity and myelosuppression were the most common TH-302 related AEs with no increase in treatment discontinuation.
Neuro-oncology, Sep 1, 2018
then remained stable until progression. CONCLUSION: The tests which showed to be more informative... more then remained stable until progression. CONCLUSION: The tests which showed to be more informative about the patients NPF were Token test, Object Naming test, Digit Memory Span, Corsi Block test, Semantic Fluency test. These tests showed a significant decline few weeks before tumor relapse/death.
European Journal of Cancer, 2017
method for evaluating LSIL and HSIL prognosis and individualization of treatment. Search for spec... more method for evaluating LSIL and HSIL prognosis and individualization of treatment. Search for specific changes of microRNAs opens possibility of developing new methods of screening and early diagnosis of cervical cancer, which enhance the efficiency of cervical cancer secondary prevention. No conflict of interest. 702A POSTER Comparison of MRI, PET-CT, and frozen biopsy in the evaluation of lymph node status before fertility-sparing radical trachelectomy in early stage cervical cancer
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Papers by Maria grazia Fabrini