Publications by authors named "Giovanna Mantini"

61 Publications

Predicting Radiotherapy Impact on Late Bladder Toxicity in Prostate Cancer Patients: An Observational Study.

Cancers (Basel) 2021 Jan 6;13(2). Epub 2021 Jan 6.

UOC Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia,Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Largo Agostino Gemelli 8, 00168 Roma, Italy.

Background And Purpose: The aim of our study was to elaborate a suitable model on bladder late toxicity in prostate cancer (PC) patients treated by radiotherapy with volumetric technique.

Materials And Methods: PC patients treated between September 2010 and April 2017 were included in the analysis. An observational study was performed collecting late toxicity data of any grade, according to RTOG and CTCAE 4.03 scales, cumulative dose volumes histograms were exported for each patient. Vdose, the value of dose to a specific volume of organ at risk (OAR), impact was analyzed through the Mann-Whitney rank-sum test. Logistic regression was used as the final model. The model performance was estimated by taking 1000 samples with replacement from the original dataset and calculating the AUC average. In addition, the calibration plot (Hosmer-Lemeshow goodness-of-fit test) was used to evaluate the performance of internal validation. RStudio Software version 3.3.1 and an in house developed software package "Moddicom" were used.

Results: Data from 175 patients were collected. The median follow-up was 39 months (min-max 3.00-113.00). We performed Mann-Whitney rank-sum test with continuity correction in the subset of patients with late bladder toxicity grade ≥ 2: a statistically significant -value with a Vdose of 51.43 Gy by applying a logistic regression model (coefficient 4.3, value 0.025) for the prediction of the development of late G ≥ 2 GU toxicity was observed. The performance for the model's internal validation was evaluated, with an AUC equal to 0.626. Accuracy was estimated through the elaboration of a calibration plot.

Conclusions: Our preliminary results could help to optimize treatment planning procedures and customize treatments.
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January 2021

Effectiveness of abiraterone acetate plus prednisone in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer in a large prospective real-world cohort: the ABItude study.

Ther Adv Med Oncol 2020 29;12:1758835920968725. Epub 2020 Oct 29.

Department of Medical Oncology, University Campus Biomedico, Rome, Italy.

Background: Real-world data on chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone plus prednisone are limited, largely deriving from small retrospective studies.

Methods: ABitude is an Italian, observational, prospective, multicenter study of mCRPC patients receiving abiraterone plus prednisone in clinical practice. Chemotherapy-naïve mCRPC patients were consecutively enrolled at abiraterone start (February 2016 to June 2017) and are being followed for 3 years, with evaluation approximately every 6 months. Several clinical and patients reported outcomes were examined.

Results: In this second interim analysis, among 481 enrolled patients, 453 were evaluable for analyses. At baseline, the median age was 77 years and ~69% of patients had comorbidities (mainly cardiovascular diseases). Metastases were located mainly at bones and lymph nodes; 8.4% of patients had visceral metastases. During a median follow-up of 18 months, 1- and 2-year probability of radiographic progression-free survival were 73.9% and 56.2%, respectively; the corresponding rates for overall survival were 87.3% and 70.4%. In multivariable analyses, the number of bone metastases significantly affected radiographic progression-free survival and overall survival. During abiraterone plus prednisone treatment, 65% of patients had a ⩾50% prostate-specific antigen decline, and quality of life remained appreciably high. Among symptomatic patients according to the Brief Pain Inventory) (32%), scores significantly declined after 6 months of treatment. Overall, eight patients (1.7%) had serious adverse reactions to abiraterone.

Conclusions: Abiraterone plus prednisone is effective and safe for chemotherapy-naïve mCRPC patients in clinical practice.
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October 2020

Simultaneous Integrated Radiotherapy Boost to the Dominant Intraprostatic Lesion: Final Results of a Phase I/II Trial.

Anticancer Res 2020 Nov;40(11):6499-6503

Radiotherapy Unit, Gemelli Molise Hospital, Campobasso, Italy.

Background/aim: Late toxicity and long-term outcomes of a phase I-II trial on patients with prostate cancer treated with an integrated boost to the dominant intraprostatic lesion (DIL) are reported.

Patients And Methods: Patients were treated using intensity-modulated radiotherapy, with a simultaneous integrated boost to the DIL, defined on staging magnetic resonance imaging, delivering 72 Gy in 1.8 Gy/fraction to prostate/seminal vesicles and 80 Gy in 2 Gy/fraction to the DIL. The primary endpoint was acute toxicity and secondary endpoints were late toxicity and biochemical disease-free survival.

Results: Forty-four patients were enrolled. The median follow-up was 120 (range=25-150) months. Five-year rates of grade 3 late gastrointestinal and genitourinary toxicity were 2.3% and 4.5%, respectively; only one grade 4 late genitourinary toxicity was recorded. Five-year biochemical relapse-free and overall survival rates were 95.3% and 95.5%, respectively.

Conclusion: The treatment was well tolerated and achieved excellent results in terms of outcome in patients with low-intermediate Gleason's score and low risk of nodal metastasis.
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November 2020

Oncotype DX Predictive Nomogram for Recurrence Score Output: The Novel System ADAPTED01 Based on Quantitative Immunochemistry Analysis.

Clin Breast Cancer 2020 10 5;20(5):e600-e611. Epub 2020 May 5.

UOC di Radioterapia Oncologica, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Dipartimento di Scienze della Salute della Donna e del Bambino e di Sanità Pubblica, Rome, Italy; Università Cattolica del Sacro Cuore, Istituto di Radiologia, Rome, Italy.

Purpose: Oncotype DX (ODX) predicts breast cancer recurrence risk, guiding the choice of adjuvant treatment. In many countries, access to the test is not always available. We used correlation between phenotypical tumor characteristics, quantitative classical immunohistochemistry (IHC), and recurrence score (RS) assessed by ODX to develop a decision supporting system for clinical use.

Patients And Methods: Breast cancer patients who underwent ODX testing between 2014 and 2018 were retrospectively included in the study. The data selected for analysis were age, menopausal status, and pathologic and IHC features. IHC was performed with standardized quantitative methods. The data set was split into two subsets: 70% for the training set and 30% for the internal validation set. Statistically significant features were included in logistic models to predict RS ≤ 25 or ≤ 20. Another set was used for external validation to test reproducibility of prediction models.

Results: The internal set included 407 patients. Mean (range) age was 53.7 (31-80) years, and 222 patients (54.55%) were > 50 years old. ODX results showed 67 patients (16.6%) had RS between 0 and 10, 272 patients between 11 and 25 (66.8%), and 68 patients > 26 (16.6%). Logistic regression analysis showed that RS score (for threshold ≤ 25) was significantly associated with estrogen receptor (P = .004), progesterone receptor (P < .0001), and Ki-67 (P < .0001). Generalized linear regression resulted in a model that had an area under the receiver operating characteristic curve (AUC) of 92.2 (sensitivity 84.2%, specificity 80.1%) and that was well calibrated. The external validation set (183 patients) analysis confirmed the model performance, with an AUC of 82.3 and a positive predictive value of 91%. A nomogram was generated for further prospective evaluation to predict RS ≤ 25.

Conclusion: RS was related to quantitative IHC in patients with RS ≤ 25, with a good performance of the statistical model in both internal and external validation. A nomogram for enhancing clinical approach in a cost-effective manner was developed. Prospective studies must test this application in clinical practice.
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October 2020

BIT-ART: Multicentric Comparison of HDR-brachytherapy, Intensity-modulated Radiotherapy and Tomotherapy for Advanced Radiotherapy in Prostate Cancer.

In Vivo 2020 May-Jun;34(3):1297-1305

Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.

Background/aim: The aim of the study was to evaluate acute and late genitourinary (GU) and gastrointestinal (GI) toxicity in patients with high- or intermediate-risk prostate cancer.

Patients And Methods: We evaluated data of patients from three Radiation Oncology Departments (Rome, Lübeck and Perugia). Patients treated in Rome underwent exclusive intensity-modulated-radiotherapy (IMRT) or IMRT plus high-dose-rate interventional radiotherapy (HDR-IRT). IMRT plus two fractions HDR-IRT was performed in Lübeck, while in Perugia Helical Tomotherapy was performed. The Common Toxicity Criteria for Adverse Event (Version 4.03) scale was used to describe acute and late toxicity.

Results: At a median follow-up of 28 months, all 51 patients were alive and disease-free. Patients treated by HDR-IRT plus VMAT showed only G1-2 genitourinary- gastrointestinal (GU-GI) acute and late toxicity. Univariate analysis showed a lower risk of acute GU toxicity (p=0.048) in IMRT+HDR-IRT.

Conclusion: Low grade and less acute GU toxicity was observed in patients undergoing HDR-IRT boost.
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February 2021

Radiotherapy Plus GnRH Analogue High Dose Bicalutamide: A Case Control Study.

Anticancer Res 2019 Nov;39(11):6373-6378

Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine - DIMES, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.

Background/aim: Radiotherapy (RT) with adjuvant hormone therapy (HT) improves prognosis in prostate cancer (PC) patients. Gonadotrophin-releasing hormone agonist (GnRHa) with luteinizing hormone-releasing hormone (LH-RH) analogues is the standard HT. High-dose antiandrogen therapy also improves survival in patients with locally advanced PC. The aim of this study was to compare the results of patients treated with RT plus GnRHa and patients treated with RT plus bicalutamide.

Patients And Methods: Our institutional PC database was used to identify patients treated with definitive or postoperative RT +/- HT which were included in this study.

Results: Three hundred and eighteen patients were retrospectively reviewed (median follow-up=56 months). Five-year biochemical relapse-free survival was 85.5% and 88.3% in patients treated with GnRHa and bicalutamide, respectively (p=0.712).

Conclusion: Bicalutamide may be offered as an adjuvant treatment to RT in patients who refuse GnRHa because of related side effects. Furthermore, our study justifies randomized trials comparing RT plus GnRHa and RT plus bicalutamide.
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November 2019

MR-guided radiotherapy in rectal cancer: First clinical experience of an innovative technology.

Clin Transl Radiat Oncol 2019 Sep 12;18:80-86. Epub 2019 Apr 12.

Fondazione Policlinico Universitario "A. Gemelli" IRCCS, UOC di Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Roma, Italy.

•This study represents one of the first reports of online MRgRT.•Integrated Low-field MR provides better anatomical visualization than CBCT or MVCT.•Better visualization of the target can help to reduce the margins from CTV to PTV.•MRgRT appears a feasible option in rectal cancer treatment offering potential benefits.•MRgRT represents a promising technology for rectal cancer management.
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September 2019

Shoulder girdle impairment in breast cancer survivors: the role of range of motion as predictive factor for dose distribution and clinical outcome.

Tumori 2019 Aug 1;105(4):319-330. Epub 2019 Apr 1.

1 Fondazione Policlinico Universitario "A. Gemelli" IRCCS, UOC di Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Roma, Italia.

Background: Pain and functional impairment of the ipsilateral shoulder girdle in patients who underwent surgery and radiotherapy for breast cancer (BC) is a late complication reported in the literature. We analyze a correlation with dosimetric parameters and propose an algorithm for sparing strategies.

Methods: A total of 111 patients treated for BC were included in this observational analysis during follow-up protocol visits. Exclusion criteria were the presence of moderate or severe arthrosis history and/or rheumatologic diseases. All the patients had complete physical and multidimensional examinations during joint (physiatrist and radiotherapy oncology) follow-up visits. A scapula-humeral articulation (SHA) standardized contouring was performed retrospectively on Eclipse® treatment plans. A possible correlation between patients' characteristics, radiotherapy, and dosimetry analysis and functional impairment was investigated at statistical analysis. Results of analysis were summarized into a proposal of algorithm for sparing SHA.

Results: A total of 111 patients were selected during follow-up visits. Mean age of patients was 60 years (range 41-85 years). A total of 103 patients (93%) underwent conservative surgery, with 110 patients (99%) undergoing axilla surgery as well. Fifty-two patients (46.8%) presented a reduction of range of motion (ROM) abduction on the treated side at the observational analysis. Mean ROM abduction reduction was 13°06' (range 0°-100°). Disability of the Arm, Shoulder and Hand questionnaire (DASH) score results were excellent in 79 patients (71.2%), discrete in 15 patients (13.5%), good in 15 patients (13.5%), and sufficient in 2 patients (1.8%). Median EQD D at SHA was 18 Gy (range 0.22-51.9 Gy) and median EQD mean dose at SHA was 2 Gy (range 0.04-24.32 Gy). Univariate analysis showed a linear correlation between DASH score and ROM of abduction of treated side (ρ=-0.7), ROM of abduction and ROM of flexion in ipsilateral arm (ρ=0.8), or ROM of abduction and ROM of flexion in contralateral arm (ρ=0.8). A statistically significant difference in ROM abduction between the 2 arms was found at χ test (<0.05 at χ confidence interval = 95%). Cox linear regression analysis showed ROM abduction on treated arm as a predictive factor of DASH score (<0.0001). Age (<0.05), DASH score (=0.006), and ROM abduction on treated arm (=0.005) were found as independent predictive factors of mean dose at multivariate analysis. A mean dose higher than 7 Gy and ROM abduction reduction more than 30° were related to DASH score level reduction.

Conclusions: This hypothesis-generating study introduces an algorithm to be validated for management of sparing SHA and improving quality of survivorship. ROM evaluation after surgery, early physiotherapy, standard contouring, and planning adaptation represent possible indications to preserve shoulder impairment. Further prospective studies are needed to discriminate impairment of surgery and radiotherapy in order to personalized therapeutic plan programs.
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August 2019

Tailored postoperative treatment of prostate cancer: final results of a phase I/II trial.

Prostate Cancer Prostatic Dis 2018 11 23;21(4):564-572. Epub 2018 Jul 23.

Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine - DIMES, University of Bologna, S. Orsola-Malpighi Hospital, 40138, Bologna, Italy.

Backgroud: The European Organization for Research and Treatment of Cancer (EORTC) trial 22,911 reported 74% 5-year biochemical disease-free survival (bDFS) in patients with prostate carcinoma treated with radical prostatectomy (RP) followed by postoperative radiotherapy (RT). This study aimed to improve these outcomes by using a combined-intensified-modulated-adjuvant treatment, including RT and hormone therapy (HT) after RP.

Materials And Methods: This phase I/II trial treatment was designed to improve 5-year bDFS from ~ 75 to 90%. Patients were consecutively enrolled using the following inclusion criteria: age < 80 years, histological diagnosis of prostate adenocarcinoma without known metastases, stage pT2-4N0-1, and Eastern Cooperative Oncology Group performance status of 0-2. All patients had at least one of these pathologic features: capsular perforation, positive surgical margins, seminal vesicle invasion, and pelvic lymph nodes involvement. A minimum dose of 64.8 Gy to the tumor bed was delivered in all patients. Depending on tumor characteristics at diagnosis, patients received a higher dose (70.2 Gy; 85.4%) and/or prophylactic pelvic lymph nodes irradiation (57.7%) and/or HT (69.1%). Biochemical relapse was defined as two consecutive rising prostate-specific antigen (PSA) values > 0.2 ng/ml.

Results: A total of 123 patients were enrolled in the study and completed the scheduled treatment. Median preoperative and postoperative PSA were: 8.8 and 0.06 ng/mL, respectively. The percentages of patients with pathologically involved nodes and positive resection margins were: 14.6% and 58.5%, respectively. With a median follow-up of 67 months (range: 37-120 months), the actuarial 5-year bDFS, local control, metastasis-free survival, and overall survival (OS) were: 92.9%, 98.7%, 96.1%, and 95.1%, respectively.

Conclusion: A higher 5-year bDFS (92.9%) was recorded compared to studies based on standard adjuvant RT, even though patients with nodal disease and detectable postoperative PSA were enrolled. Clinical end points, as long-term disease-free survival and OS, will require further assessments. ( NCT03169933).
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November 2018

Predictive Factors of Late-onset Rectal Mucosal Changes After Radiotherapy of Prostate Cancer.

In Vivo 2017 Sep-Oct;31(5):961-966

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.

Background/aim: The Vienna Rectoscopy Score (VRS; from 0, absence of rectal mucosal changes, to 5) assessed 1 year after radiotherapy is a surrogate end-point of late rectal toxicity. The aim of this study was to investigate the association between treatment-related factors and 1-year VRS.

Patients And Methods: We performed a retrospective analysis of prospectively collected data. Patients with prostate adenocarcinoma treated with definitive or postoperative radiotherapy (RT) underwent endoscopy 1 year after RT. Relationships between VRS of 2 or more and treatment parameters were investigated by univariate and multivariate logistic analyses.

Results: One hundred and ninety-five patients (mean age=69 years; range=43-81 years) were considered eligible for the study. At univariate analysis, patients treated with hypofractionation plus radiosurgery boost (p<0.001) and an equivalent dose in 2 Gy per fraction (EQD2) (α/β=3) ≥75 Gy (p<0.001) was associated with a significantly higher incidence of VRS ≥2 after 1 year of follow-up. At multivariate analysis, radiosurgery boost was an independent risk factor for developing rectal mucosal lesions (VRS ≥2), yielding an odds ratio (OR) of 4.14 (95% confidence interval (CI)=1.2-13.8), while pelvic surgery was inversely associated with VRS ≥2 (OR=0.39; 95% CI=0.17-0.94).

Conclusion: Hypofractionation followed by radiosurgery boost significantly increased the risk of developing late-onset rectal mucosal changes. Therefore, special care and preventative treatment strategies are needed when using radiosurgery boost after hypofractionated RT.
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May 2018

Beyond geometrical overlap: a Dosimetrical Evaluation of automated volumes Adaptation (DEA) in head and neck replanning.

Tech Innov Patient Support Radiat Oncol 2017 Sep-Dec;3-4:1-6. Epub 2017 Jul 21.

Gemelli Advanced Radiation Therapy Center, Fondazione Policlinico Universitario "A. Gemelli", Università Cattolica del Sacro Cuore, Rome, Italy.

Introduction: Automated target volumes adaptation could be useful in H&N replanning, but its dosimetric impact has not been analyzed.Primary aim of this investigation is dose coverage assessment in fully automated and edited PTV adaptation settings, compared to manual benchmark.

Materials And Methods: Ten IMRT patients were selected and replanning CTs were acquired.A deformable registration with PTV adaptation was performed defining PTVA.PTV B was obtained through manual editing and a benchmark PTV C was manually segmented by a delineation team.The Dice Similarity Index (DSI) and the mean Hausdorff Distance (mHD) were calculated between PTV A and PTV C, and between PTV B and PTV C.One IMRT plan was realized for each PTV: the plans optimized on PTV A and PTV B were proposed on PTV C to evaluate their dosimetric reliability compared to the benchmark plan in terms of PTV V95% dose coverage.

Results: The comparisons between PTV A with PTV C and PTV B with PTV C showed that the better DSI (high) and mHD values (low) are, the smaller difference when compared to PTV C V95% is described.Evaluating plan A and B, PTV C V95% reduced by 6.1 ± 3.0% and by 4.1 ± 2.3% respectively when compared to plan C PTV C V95%.PTV B reaches acceptable dose coverage values (PTV V95% >95%) when DSI is >0.91 and a mHD < 0.17 mm and it has better results when compared to PTV A in 70%.

Discussion: The results show a correlation between the DSI-mHD and the PTV V95% variation, in the comparisons PTV A and PTV B vs PTV C.Furthermore, we observed that PTV V95% coverage is higher in PTV B than in PTV A: the use of automated propagation may not be definitive and requires manual correction.
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July 2017

The predictive value of F-FDG PET-CT for assessing the clinical outcomes in locally advanced NSCLC patients after a new induction treatment: low-dose fractionated radiotherapy with concurrent chemotherapy.

Radiat Oncol 2017 Jan 5;12(1). Epub 2017 Jan 5.

Institute of Nuclear Medicine, Fondazione Policlinico Universitario Agostino Gemelli, Università Cattolica del Sacro Cuore, Largo A. Gemelli, 8, 00168, Rome, Italy.

Background: Patients with locally advanced non-small-cell lung cancer (LA-NSCLC) have poor prognosis despite several multimodal approaches. Recently, low-dose fractionated radiotherapy concurrent to the induction chemotherapy (IC-LDRT) has been proposed to further improve the effects of chemotherapy and prognosis. Until now, the predictive value of metabolic response after IC-LDRT has not yet been investigated.

Aim: to evaluate whether the early metabolic response, assessed by F-fluoro-deoxyglucose positron emission-computed tomography (F-FDG PET-CT), could predict the prognosis in LA-NSCLC patients treated with a multimodal approach, including IC-LDRT.

Methods: Forty-four consecutive patients (35males, mean age: 66 ± 7.8 years) with stage IIIA/IIIB NSCLC were retrospectively evaluated. Forty-four patients underwent IC-LDRT (2 cycles of chemotherapy, 40 cGy twice daily), 26/44 neo-adjuvant chemo-radiotherapy (CCRT: 50.4Gy), and 20/44 surgery. F-FDG PET-CT was performed before (baseline), after IC-LDRT (early) and after CCRT (final), applying PET response criteria in solid tumours (PERCIST). Patients with complete/partial metabolic response were classified as responders; patients with stable/progressive disease as non-responders. Progression free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meyer analysis; the relationship between clinical factors and survivals were assessed using uni-multivariate regression analysis.

Results: Forty-four out of 44, 42/44 and 23/42 patients underwent baseline, early and final PET-CT, respectively. SUL of primary tumour and lymph-node significantly (p = 0.004, p = 0.0002, respectively) decreased after IC-LDRT with a further reduction after CCRT (p = 0.0006, p = 0.02, respectively). At early PET-CT, 20/42 (47.6%) patients were classified as responders, 22/42 (52.3%) as non-responders. At final PET-CT, 19/23 patients were classified as responders (12 responders and 7 non-responders at early PET-CT), and 4/23 as non-responders (all non-responders at early PET-CT). Early responders had better PFS and OS than early non-responders (p ≤ 0.01). Early metabolic response was predictive factor for loco-regional, distant and global PFS (p = 0.02, p = 0.01, p = 0.005, respectively); surgery for loco-regional and global PFS (p = 0.03, p = 0.009, respectively).

Conclusions: In LA-NSCLC patients, F-FDG metabolic response assessed after only two cycles of IC-LDRT predicts the prognosis. The early evaluation of metabolic changes could allow to personalize therapy. This multimodality approach, including both low-dose radiotherapy that increases the effects of induction chemotherapy, and surgery that removes the disease, improved clinical outcomes. Further prospective investigation of this new induction approach is warranted.
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January 2017

Prevalence of Cardiovascular Disease and Osteoporosis During Androgen Deprivation Therapy Prescription Discordant to EAU Guidelines: Results From a Multicenter, Cross-sectional Analysis From the CHOsIng Treatment for Prostate canCEr (CHOICE) Study.

Urology 2016 Oct 8;96:165-170. Epub 2016 Jul 8.

Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy.

Objective: To analyze the prevalence of cardiovascular disease (CVD) and osteoporosis in patients treated with androgen deprivation therapy (ADT) for prostate cancer (PCa) but not adherent to European Association of Urology (EAU) guidelines.

Materials And Methods: The CHOosIng Treatment for Prostate CanCEr (CHOICE) study was an Italian multicenter, cross-sectional study conducted from December 2010 to January 2012. A total of 1386 patients treated with ADT for PCa (first prescription or renewal of ADT) were selected. According to EAU guidelines, the cohort was categorized in discordant ADT (Group A) and concordant ADT (Group B). The prevalence of CVD and osteoporosis after ADT was recorded.

Results: The final cohort included 1075 patients. According to EAU guidelines adherence, 285 (26.51%) and 790 (73.49%) were considered discordant and concordant, respectively. The proportion of men with Charlson Comorbidity Index  > 2 at baseline was statistically similar in Group A (81.8%) compared to Group B (80.8%) (P = .96). The number of complications reported at enrollment was as follows: cardiovascular in 351 (32.7%), endocrine in 166 (15.4%), sexual in 498 (46.3%), osteoporosis in 181 (16.8%), and gynecomastia in 274 (25.5%) subjects. At the multivariate logistic regression analysis adjusted for confounding factors, discordant ADT was associated with greater risk of cardiovascular complications (odds ratio: 2.07; P < .01) and osteoporosis (odds ratio: 1.75; P = .04).

Conclusion: About one-third of patients with PCa received inappropriate ADT and showed a greater risk of CVD and osteoporosis. These results could be useful for setting better policy strategies to limit the inappropriateness of ADT prescription.
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October 2016

Radiochemotherapy with Gemcitabine in Unresectable Extrahepatic Cholangiocarcinoma: Long-term Results of a Phase II Study.

Anticancer Res 2016 Feb;36(2):737-40

Institute of Radiotherapy, Università Cattolica del Sacro Cuore, Rome, Italy.

Purpose: To evaluate the outcome of patients affected by unresectable extrahepatic cholangiocarcinoma treated with radiotherapy (ERT) and concurrent gemcitabine-based chemotherapy with or without intraluminal brachytherapy (BT).

Patients And Methods: Twenty-seven patients underwent weekly gemcitabine (100 mg/m(2)) as a 24-h infusion during the course of three-dimensional radiotherapy (50.4 Gy to the tumor and 39.6 Gy to the nodes). Among them, certain patients received a boost of intraluminal high-dose rate (HDR) brachytherapy with 192 Ir. The outcome of patients was evaluated in terms of response to therapy, local control (LC), overall survival (OS) and toxicity.

Results: We analyzed a total of 27 patients with the diagnosis of unresectable, non-metastatic adenocarcinoma of the extrahepatic biliary ducts, treated with radiochemotherapy with gemcitabine. After a dose of 50 Gy, a boost of HDR intraluminal brachytherapy was administered in 6 patients (22%): 4 patients received 15 Gy and 2 patients 20 Gy. With a median follow-up of 16 months (range=3-52 months), for the entire group, 2-year LC was 29% (median=12 months), 2-year MFS was 36% (median 16 months). Two-year and three-year OS were 27% and 7% respectively, with a median of 14 months. Toxicities were acceptable. Median OS in patients treated with brachytherapy boost was 21 months versus 14 months for the group treated with gemcitabine-based radiochemotherapy only; 2-year LC was 53% versus 25%, respectively.

Conclusion: Gemcitabine appears to be a potent radiation sensitizer, and when combined with radiation therapy, it shows encouraging tumor response. Moreover, patients treated with a boost of brachytherapy after radiochemotherapy seem to have a better local control with an acceptable toxicity. Further investigation is warranted to confirm these data and define the optimal combined treatments.
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February 2016

Adaptive optimization by 6 DOF robotic couch in prostate volumetric IMRT treatment: rototranslational shift and dosimetric consequences.

J Appl Clin Med Phys 2015 09 8;16(5):35-45. Epub 2015 Sep 8.

Università Cattolica del Sacro Cuore.

The purpose of this study was to investigate the magnitude and dosimetric relevance of translational and rotational shifts on IGRT prostate volumetric-modulated arc therapy (VMAT) using Protura six degrees of freedom (DOF) Robotic Patient Positioning System. Patients with cT3aN0M0 prostate cancer, treated with VMAT simultaneous integrated boost (VMAT-SIB), were enrolled. PTV2 was obtained adding 0.7 cm margin to seminal vesicles base (CTV2), while PTV1 adding to prostate (CTV1) 0.7 cm margin in all directions, except 1.2 cm, as caudal margin. A daily CBCT was acquired before dose delivery. The translational and rotational displacements were corrected through Protura Robotic Couch, collected and applied to the simulation CT to obtain a translated CT (tCT) and a rototranslated CT (rtCT) on which we recalculated the initial treatment plan (TP). We analyzed the correlation between dosimetric coverage, organs at risk (OAR) sparing, and translational or rotational displacements. The dosimetric impact of a rototranslational correction was calculated. From October 2012 to September 2013, a total of 263 CBCT scans from 12 patients were collected. Translational shifts were < 5 mm in 81% of patients and the rotational shifts were < 2° in 93% of patient scans. The dosimetric analysis was performed on 172 CBCT scans and calculating 344 VMAT-TP. Two significant linear correlations were observed between yaw and the V20 femoral heads and between pitch rotation and V50 rectum (p < 0.001); rototranslational correction seems to impact more on PTV2 than on PTV1, especially when margins are reduced. Rotational errors are of dosimetric significance in sparing OAR and in target coverage. This is relevant for femoral heads and rectum because of major distance from isocenter, and for seminal vesicles because of irregular shape. No correlation was observed between translational and rotational errors. A study considering the intrafractional error and the deformable registration is ongoing.
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September 2015

MITHRA - multiparametric MR/CT image adapted brachytherapy (MR/CT-IABT) in anal canal cancer: a feasibility study.

J Contemp Brachytherapy 2015 Oct 19;7(5):336-45. Epub 2015 Oct 19.

Radiation Oncology Department, Gemelli-ART, Università Cattolica del Sacro Cuore, Rome, Italy.

Purpose: The aim of this study is to test a novel multiparametric imaging guided procedure for high-dose-rate brachytherapy in anal canal cancer, in order to evaluate the feasibility and safety.

Material And Methods: For this analysis, we considered all consecutive patients who underwent magnetic resonance/computed tomography image adapted brachytherapy (MR/CT-IABT) treated from February 2012 to July 2014. To conduct this project, we formed a working group that established the procedure and identified the indicators and benchmarks to evaluate the feasibility and safety. We considered the procedure acceptable if 90% of the indicators were consistent with the benchmarks. Magnetic resonance imaging with contrast and diffusion weighted imaging were performed with an MRI-compatible dummy applicator in the anus to define the position of the clinical target volume disease and biological information. A pre-implantation treatment planning was created in order to get information on the optimal position of the needles. Afterwards, the patient underwent a simulation CT and the definite post-implantation treatment planning was created.

Results: We treated 11 patients (4 men and 7 women) with MR/CT-IABT and we performed a total of 13 procedures. The analysis of indicators for procedure evaluation showed that all indicators were in agreement with the benchmark. The dosimetric analysis resulted in a median of V200, V150, V100, V90, V85, respectively of 24.6%, 53.4%, 93.5%, 97.6%, and 98.7%. The median coverage index (CI) was 0.94, the median dose homogeneity index (DHI) was 0.43, the median dose non-uniformity ratio (DNR) resulted 0.56, the median overdose volume index (ODI) was 0.27. We observed no episodes of common severe acute toxicities.

Conclusions: Brachytherapy is a possible option in anal cancer radiotherapy to perform the boost to complete external beam radiotherapy (EBRT). Magnetic resonance can also have biological advantages compared to the US. Our results suggest that the multiparametric MR/CT-IABT for anal cancer is feasible and safe. This new approach paves the way to prospective comparison studies between MRI and ultrasound-guided brachytherapy (USBT) in anal canal cancer.
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October 2015

Can automation in radiotherapy reduce costs?

Acta Oncol 2015 23;54(9):1282-8. Epub 2015 Sep 23.

a Radiation Oncology Department, Gemelli-ART , Università Cattolica S. Cuore , Rome.

Background: Computerized automation is likely to play an increasingly important role in radiotherapy. The objective of this study was to report the results of the first part of a program to implement a model for economical evaluation based on micro-costing method. To test the efficacy of the model, the financial impact of the introduction of an automation tool was estimated. A single- and multi-center validation of the model by a prospective collection of data is planned as the second step of the program.

Material And Methods: The model was implemented by using an interactive spreadsheet (Microsoft Excel, 2010). The variables to be included were identified across three components: productivity, staff, and equipment. To calculate staff requirements, the workflow of Gemelli ART center was mapped out and relevant workload measures were defined. Profit and loss, productivity and staffing were identified as significant outcomes. Results were presented in terms of earnings before interest and taxes (EBIT). Three different scenarios were hypothesized: baseline situation at Gemelli ART (scenario 1); reduction by 2 minutes of the average duration of treatment fractions (scenario 2); and increased incidence of advanced treatment modalities (scenario 3). By using the model, predicted EBIT values for each scenario were calculated across a period of eight years (from 2015 to 2022).

Results: For both scenarios 2 and 3 costs are expected to slightly increase as compared to baseline situation that is particularly due to a little increase in clinical personnel costs. However, in both cases EBIT values are more favorable than baseline situation (EBIT values: scenario 1, 27%, scenario 2, 30%, scenario 3, 28% of revenues).

Conclusion: A model based on a micro-costing method was able to estimate the financial consequences of the introduction of an automation tool in our radiotherapy department. A prospective collection of data at Gemelli ART and in a consortium of centers is currently under way to prospectively validate the model.
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August 2016

Reducing heart dose during left breast cancer radiotherapy: comparison among 3 radiation techniques.

Tumori 2016 Mar-Apr;102(2):184-9. Epub 2015 Sep 5.

Department of Radiation Oncology, Catholic University of the Sacred Heart, Rome - Italy.

Purpose: Breast cancer survivors have a high risk of cardiac death as a consequence of heart irradiation during left breast tangential radiotherapy (RT). This study compares the cardiac dose delivered by standard 3D conformal tangential RT (CRT) to that delivered by prospective-gating RT (PGRT) or 5-field intensity-modulated RT (IMRT).

Methods: Patients with early left breast cancer, referred for adjuvant RT to our institution, were enrolled in this study. For each patient, 2 simulation computed tomography scans were acquired: the first during free breathing, and the second on prospective gating during deep inspiration breath-hold. The scans were monitored by the Varian RPM™ respiratory gating system. For each patient, 3 treatment plans were performed: a 3D-CRT and an IMRT plan, each based on the free-breathing scan, and a PGRT plan, based on the deep inspiration breath-hold scan. Dose-volume histograms were compared by means of the Friedman test.

Results: The median mean heart dose was 3 Gy (range 0.9-7.3 Gy) in the CRT plans, 1.9 Gy (range 0.5-3.6 Gy) in the PGRT plans, and 4.5 Gy (range 1.1-10.5 Gy) in the IMRT plans (p = 0.001). The mean heart V25 was 1.2% (range 0%-9.7%), 0% (range 0%-2.0%), and 0.2% (range 0%-7.3%) for CRT, PGRT, and IMRT plans, respectively (p<0.001).

Conclusions: Prospective-gating RT to the left breast offered the best protection of heart and lung, as well as a lower irradiation of the contralateral breast, compared to CRT or IMRT.
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September 2016

Patterns of prescription and adherence to European Association of Urology guidelines on androgen deprivation therapy in prostate cancer: an Italian multicentre cross-sectional analysis from the Choosing Treatment for Prostate Cancer (CHOICE) study.

BJU Int 2016 06 23;117(6):867-73. Epub 2015 Sep 23.

Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy.

Objective: To evaluate both the patterns of prescription of androgen deprivation therapy (ADT) in patients with prostate cancer (PCa) and the adherence to European Association of Urology (EAU) guidelines for ADT prescription.

Methods: The Choosing Treatment for Prostate Cancer (CHOICE) study was an Italian multicentre cross-sectional study conducted between December 2010 and January 2012. A total of 1 386 patients, treated with ADT for PCa (first prescription or renewal of ADT), were selected. With regard to the EAU guidelines on ADT, the cohort was categorized into discordant ADT (Group A) and concordant ADT (Group B).

Results: The final cohort included 1 075 patients with a geographical distribution including North Italy (n = 627, 58.3%), Central Italy (n = 233, 21.7%) and South Italy (n = 215, 20.0%). In the category of patients treated with primary ADT, a total of 125 patients (56.3%) were classified as low risk according to D'Amico classification. With regard to the EAU guidelines, 285 (26.51%) and 790 patients (73.49%) were classified as discordant (Group A) and concordant (Group B), respectively. In Group A, patients were more likely to receive primary ADT (57.5%, 164/285 patients) than radical prostatectomy (RP; 30.9%, 88/285 patients), radiation therapy (RT; 6.7%, 19/285 patients) or RP + RT (17.7%, 14/285 patients; P < 0.01). Multivariate logistic regression analysis, adjusted for clinical and pathological variables, showed that patients from Central Italy (odds ratio [OR] 2.86; P < 0.05) and South Italy (OR 2.65; P < 0.05) were more likely to receive discordant ADT.

Conclusion: EAU guideline adherence for ADT was low in Italy and was influenced by geographic area. Healthcare providers and urologists should consider these results in order to quantify the inadequate use of ADT and to set policy strategies to overcome this risk.
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June 2016

Breakthrough pain management in patients undergoing radiotherapy: a national survey on behalf of the Palliative and Supportive Care Study Group.

Tumori 2015 Nov-Dec;101(6):603-8. Epub 2015 May 16.

Department of Bioimaging and Radiological Sciences, Unit of Radiation Oncology, Catholic University of the Sacred Heart, Rome - Italy.

Aims: To assess the contribution of radiation oncologists in Italy in current management of breakthrough pain (BtP).

Methods: In 2012, the Palliative and Supportive Care Study Group of the Italian Association of Radiation Oncology (AIRO) proposed a survey. All Italian radiation oncologists were individually invited to complete an online questionnaire regarding their management of BtP in patients undergoing radiotherapy treatment.

Results: A total of 303 Italian radiation oncologists (of 330 who had access to the Web site) completed the questionnaire over an 8-month period. Some important differences were shown in pain intensity assessment by validated measurement scales, as well as in setting and prescribing analgesic therapy to prevent procedural pain. These differences were also reviewed and discussed related to international guidelines and data available from the literature.

Conclusions: Compared to other medical professionals, the involvement of radiation oncologists in cancer pain management remains marginal, at least in Italy. More than 70% of radiation oncologists directly optimized the analgesic therapy during the treatment course and more than 50% implemented specific treatment for BtP. However, the ability of the radiation oncologist to manage BtP could be improved. In order to increase the consciousness of systematic symptom measurement and to spread the knowledge of the best type of analgesic drugs to be used, training events promoted by national associations, such as AIRO, and a collaborative multidisciplinary approach of the management of cancer pain will be promoted.
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March 2016

A Phase I study of high-dose-rate intraluminal brachytherapy as palliative treatment in extrahepatic biliary tract cancer.

Brachytherapy 2015 May-Jun;14(3):401-4. Epub 2015 Jan 13.

Department of Radiation Oncology, Catholic University of the Sacred Heart, Campobasso, Italy.

Purpose: To determine the recommended dose of endoscopically assisted high-dose-rate intraluminal brachytherapy (HDR-192Ir-ILBT) as a palliative treatment of extrahepatic biliary tract cancer.

Methods And Materials: Patients with non-metastatic extrahepatic biliary cancer with age <80 years, unsuitable for surgical resection or radiochemotherapy for comorbidities or Eastern Cooperative Oncology Group (ECOG) ≥2 or patients with age ≥80 years were included. They were undergone to implantation of metal stents by endoscopic retrograde cholangiopancreatography followed by HDR-192Ir-ILBT. The initial dose of HDR-192-Ir-ILBT was 15 Gy. Three levels of dose were planned. At each dose level almost three patients were treated, and if no Grade 3-4 toxicity (considering as dose-limiting toxicity) was recorded, dose escalation was applied with 5 Gy increments until the maximum tolerated dose was established. A high dose Iridium-192 after loading system was used (Nucletron Microselectron HDR).

Results: From May 2007 to January 2010, 18 patients underwent HDR-192Ir-ILBT, with one catheter in 12 patients and two catheters in six patients. Three levels of dose were planned: 15 Gy in three patients, 20 Gy in nine patients, and 25 Gy in six patients with daily dose of 500 cGy per fraction. One patient at Dose Level II experienced acute toxicity (cholangitis) related to brachytherapy procedure, so the cohort was expanded. No patient of Level III had a dose-limiting toxicity and we stopped at this dose level waiting to assess the late toxicity that has not yet appeared at the time of the analysis. Six months and 1 year overall survival was 77% and 59%, respectively, with a median of 12 months.

Conclusions: The recommended dose was defined as 25 Gy in five fractions. It will be used in a Phase II study to better evaluate tumor and symptom control in patients with extrahepatic biliary tract cancer.
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December 2015

Intensified adjuvant treatment of prostate carcinoma: feasibility analysis of a phase I/II trial.

Biomed Res Int 2014 30;2014:480725. Epub 2014 Jun 30.

Unità Operativa di Radioterapia, Dipartimento di Bio-Immagini e Scienze Radiologiche, Università Cattolica del Sacro Cuore, Policlinico Gemelli, Largo A. Gemelli 8, 00168 Roma, Italy.

Purpose: To perform a preliminary feasibility acute and late toxicity evaluation of an intensified and modulated adjuvant treatment in prostate cancer (PCa) patients after radical prostatectomy.

Material And Methods: A phase I/II has been designed. Eligible patients were 79 years old or younger, with an ECOG of 0-2, previously untreated, histologically proven prostate adenocarcinoma with no distant metastases, pT2-4 N0-1, and with at least one of the following risk factors: capsular perforation, positive surgical margins, and seminal vesicle invasion. All patients received a minimum dose on tumor bed of 64.8 Gy, or higher dose (70.2 Gy; 85.4%), according to the pathological stage, pelvic lymph nodes irradiation (57.7%), and/or hormonal therapy (69.1%).

Results: 123 patients were enrolled and completed the planned treatment, with good tolerance. Median follow-up was 50.6 months. Grade 3 acute toxicity was only 2.4% and 3.3% for genitourinary (GU) and gastrointestinal (GI) tract, respectively. No patient had late grade 3 GI toxicity, and the GU grade 3 toxicity incidence was 5.8% at 5 years. 5-year BDSF was 90.2%.

Conclusions: A modulated and intensified adjuvant treatment in PCa was feasible in this trial. A further period of observation can provide a complete assessment of late toxicity and confirm the BDSF positive results.
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March 2015

[Radiotherapy in men with prostate cancer: indications, evolutions and integrated approaches].

Urologia 2013 Jul-Sep;80(3):188-201

Prostate cancer is a heterogeneous, indolent or sometimes aggressive tumor. Treatment options are various and without proved superiority. Radiotherapy (RT) plays a key role in the disease history. Technological evolution with Intensity Modulate Radiation Therapy (IMRT) and Image Guided Radiation Therapy (IGRT) allowed improvement, with significant results on local control and survival. Hypofractionation, Stereotactic Body RT (SBRT) and new brachytherapy approachs are still under investigation, with promising opportunities. Adjuvant vs salvage postoperative RT, hormone association, prophylactic pelvic irradiation are still under debate, but guidelines express overlapping indications.
Multidisciplinary managements will be the future for care optimization, providing the best tool for 
holistic and informed patients’ choice.
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April 2015

Low-dose radiotherapy as a chemo-potentiator of a chemotherapy regimen with pemetrexed for recurrent non-small-cell lung cancer: a prospective phase II study.

Radiother Oncol 2012 Nov 12;105(2):161-6. Epub 2012 Oct 12.

Department of Radiation Oncology, Catholic University, Rome, Italy.

Purpose: Low-dose radiotherapy (LDR) (<50 cGy) induces enhanced cell killing in vitro via the hyper-radiation sensitivity phenomenon. Aim of this study was to evaluate the safety and efficacy of a palliative regimen combining pemetrexed and LDR (as a chemopotentiator) on patients affected by recurrent non-small-cell lung cancer (NSCLC).

Methods And Materials: Eligible patients had an ECOG performance status ≤2, one prior chemotherapy regimen for advanced NSCLC, adequate organ function, measurable lesions. Patients received pemetrexed (500 mg/m(2) IV) and concurrent LDR (40 cGy bid on days 1 and 2) delivered to target pulmonary or metastatic disease. This cycle was repeated fourfold every 21 days. The accrual was determined by the single proportion powered analysis (α=0.05, power=0.8) with H0 ("bad" response probability, 9% according to literature) and H1 ("good" response probability, 35% ongoing study); 19 is the number required.

Results: Nineteen patients with stage III and IV disease were enrolled. Only one patient experienced neutropenia grade 4. All patients are evaluable for clinical response of irradiated lesion: overall response rate was 42%.

Conclusions: Low-dose radiotherapy combined with pemetrexed has a similar toxicity profile to chemotherapy alone. The response rate of this novel approach is encouraging, since it was higher than what was reported for pemetrexed alone (42% versus 9.1%). Additional scientific investigation of this new treatment paradigm is warranted.
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November 2012

Impact of age and co-morbidities in patients with newly diagnosed glioblastoma: a pooled data analysis of three prospective mono-institutional phase II studies.

Med Oncol 2012 Dec 7;29(5):3478-83. Epub 2012 Jun 7.

Department of Radiation Oncology, Catholic University of Sacred Heart, Largo A. Gemelli, 00135, Rome, Italy.

To analyse the impact of age and co-morbidities on compliance and outcomes in GBM patients enrolled in three prospective phase II trials. GBM patients (≥ 18 years) were treated with radiotherapy (60 Gy) or enrolled in a Fractionated Stereotactic Conformal-Radiotherapy Phase II trial (69.4 Gy). Concomitant and adjuvant chemotherapy with Temozolomide (TMZ) was administered. Charlson Index Co-morbidity (CCI) was used to assess co-morbidity. Toxicity was evaluated according to RTOG score. Survival analysis was performed by the Kaplan-Maier. Influence of age and co-morbidity was evaluated using log-rank test. From 2001 to 2008, 146 patients were enrolled: 56 (38.4 %) aged over 65 and 90 under 65. CCI ≥ 1 was observed in 41 % of elderly and 22 % of young group. Patients' compliance was 97.9 % for radio-chemotherapy. Acute toxicity was mild with no difference between the groups. Global median progression-free survival (PFS) and overall survival (OS) were 12 and 18 months, respectively. Age, surgery and radiation dose correlated with survival (p = 0.01, p = 0.04 and p = 0.03). CCI ≤ 2 did not show any influence on OS. Our data show that elderly with a good performance status and few co-morbidity may be treated as younger patients; moreover, age confirms a negative impact on survival while CCI ≤ 2 did not correlated with OS.
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December 2012

A feasibility study of neo-adjuvant low-dose fractionated radiotherapy with two different concurrent anthracycline-docetaxel schedules in stage IIA/B-IIIA breast cancer.

Tumori 2012 Jan-Feb;98(1):79-85

Radiotherapy Department, Policlinico Universitario A. Gemelli, Catholic University, Rome, Italy.

Aims And Background: The aim of the study was to evaluate the feasibility of neoadjuvant low-dose fractionated radiotherapy, in combination with two anthracycline-docetaxel regimens, in breast cancer treatment.

Materials And Methods: Women with stage IIA/B-IIIA breast cancer were assigned to receive the treatment of low-dose fractionated radiotherapy (0.4 Gy/per fraction, 2 fractions per day, for 2 days, every 21 days for 8-6 cycles) with concomitant neoadjuvant chemotherapy with non-pegylated liposomal doxorubicin and docetaxel. Two chemotherapy schedules were planned to be combined with low-dose fractionated radiotherapy. The first schedule consisted of four cycles of non-pegylated liposomal doxorubicin sequentially followed by four cycles of docetaxel, and the second schedule consisted of six cycles of non-pegylated liposomal doxorubicin plus concomitant docetaxel. Acute toxicity was evaluated according to the Radiation Therapy Oncology Group score system. Pathological response was evaluated by the Mandard score and expressed as tumor regression grade.

Results: Between March 2008 and February 2009, 10 patients underwent low-dose fractionated radiotherapy and concomitant chemotherapy. No grade 3-4 breast toxicity was observed. Five patients had a clinical complete response. Seven patients underwent conservative surgery. Overall, tumor regression grade 1 (absence of residual cancer) was achieved in one patient (10%) and grade 2 (residual isolated cells scattered through the fibrosis) in 4 patients (40%). The pathologic major response rate (tumor regression grade 1 + 2) was 20% in patients receiving low-dose fractionated radiotherapy and sequential non-pegylated liposomal doxorubicin and docetaxel and 80% in the group receiving low-dose fractionated radiotherapy and concurrent non-pegylated liposomal doxorubicin and docetaxel treatment.

Conclusions: Concomitant low-dose fractionated radiotherapy combined with anthracycline and docetaxel is feasible. The toxicity profile of radio-chemotherapy was similar to that of chemotherapy alone: there was no acute skin or cardiac toxicity. The concurrent application of liposomal doxorubicin and docetaxel with low-dose fractionated radiation led to higher histological response rates compared to the sequential application of the same two drugs.
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July 2012

Locally advanced prostate cancer: three-dimensional magnetic resonance spectroscopy to monitor prostate response to therapy.

Int J Radiat Oncol Biol Phys 2012 Nov 19;84(3):719-24. Epub 2012 Mar 19.

Department of Bioimaging and Radiological Sciences, Section of Radiology, Università Cattolica del Sacro Cuore di Roma, Milan, Italy.

Purpose: To correlate results of three-dimensional magnetic resonance spectroscopic imaging (MRSI) with prostate-specific antigen (PSA) levels and time since external beam irradiation (EBRT) in patients treated with long-term hormone therapy (HT) and EBRT for locally advanced disease to verify successful treatment by documenting the achievement of metabolic atrophy (MA).

Methods And Materials: Between 2006 and 2008, 109 patients were consecutively enrolled. MA was assessed by choline and citrate peak area-to-noise-ratio <5:1. Cancerous metabolism (CM) was defined by choline-to-creatine ratio >1.5:1 or choline signal-to-noise-ratio >5:1. To test the strength of association between MRSI results and the time elapsed since EBRT (TEFRT), PSA levels, Gleason score (GS), and stage, logistic regression (LR) was performed. p value <0.05 was statistically significant. The patients' outcomes were verified in 2011.

Results: MRSI documented MA in 84 of 109 and CM in 25 of 109 cases. LR showed that age, GS, stage, and initial and recent PSA had no significant impact on MRSI results which were significantly related to PSA values at the time of MRSI and to TEFRT. Patients were divided into three groups according to TEFRT: <1 year, 1-2 years, and >2 years. MA was detected in 54.1% of patients of group 1, 88.9% of group 2, and in 94.5% of group 3 (100% when PSA nadir was reached). CM was detected in 50% of patients with reached PSA nadir in group 1. Local relapse was found in 3 patients previously showing CM at long TEFRT.

Conclusion: MA detection, indicative of successful treatment because growth of normal or abnormal cells cannot occur without metabolism, increases with decreasing PSA levels and increasing time on HT after EBRT. This supports long-term HT in advanced prostate cancer. Larger study series are needed to assess whether MRSI could predict local relapse by detecting CM at long TEFRT.
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November 2012

Early proctoscopy is a surrogate endpoint of late rectal toxicity in prostate cancer treated with radiotherapy.

Int J Radiat Oncol Biol Phys 2012 Jun 22;83(2):e191-5. Epub 2012 Feb 22.

Radiotherapy Unit, Fondazione di Ricerca e Cura Giovanni Paolo II, Università Cattolica del S Cuore, Campobasso, Italy.

Purpose: To predict the grade and incidence of late clinical rectal toxicity through short-term (1 year) mucosal alterations.

Methods And Materials: Patients with prostate adenocarcinoma treated with curative or adjuvant radiotherapy underwent proctoscopy a year after the course of radiotherapy. Mucosal changes were classified by the Vienna Rectoscopy Score (VRS). Late toxicity data were analyzed according to the Kaplan-Meier method. Comparison between prognosis groups was performed by log-rank analysis.

Results: After a median follow-up time of 45 months (range, 18-99), the 3-year incidence of grade ≥ 2 rectal late toxicity according to the criteria of the European Organization for Research and Treatment of Cancer and the Radiation Therapy Oncology Group was 24%, with all patients (24/24; 100%) experiencing rectal bleeding. The occurrence of grade ≥ 2 clinical rectal late toxicity was higher in patients with grade ≥ 2 (32% vs. 15 %, p = 0.02) or grade ≥ 3 VRS telangiectasia (47% vs. 17%, p ≤ 0.01) and an overall VRS score of ≥ 2 (31% vs. 16 %, p = 0.04) or ≥ 3 (48% vs. 17%, p = 0.01) at the 1-year proctoscopy.

Conclusions: Early proctoscopy (1 year) predicts late rectal bleeding and therefore can be used as a surrogate endpoint for late rectal toxicity in studies aimed at reducing this frequent complication.
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June 2012

Role of radiotherapy in the treatment of fibrosarcoma of the spermatic cord: a case report and review of the literature.

Tumori 2011 Nov-Dec;97(6):36e-8e

Radiation Oncology Service, Bioimages and Radiological Science Department, Catholic University, Rome, Italy.

Background: Spermatic cord sarcomas are rare. The therapeutic approach is based only on case reports and small series. The standard treatment is radical orchiectomy with wide local resection, while the role of adjuvant therapies is not clear. We present a case of fibrosarcoma of the spermatic cord treated with surgery and adjuvant radiotherapy. A review of the literature about the role of adjuvant treatments is also discussed.

Case Report: A 59-year-old man presented a right testicular mass of about 4 × 3 cm in size. Biopsy showed a high-grade polymorphous sarcoma, consistent with a diagnosis of poorly differentiated fibromyosarcoma. He underwent a right radical inguinal orchiectomy and adjuvant radiotherapy (total dose: 5940 cGy). During treatment the patient developed a G3 skin toxicity (RTOG score) in the inguinal fold. After a follow-up of 57 months, he is alive and without evidence of local or distant recurrence. No late toxicity was noted.

Conclusion: The optimal adjuvant management of spermatic cord sarcoma is still uncertain. Looking at the literature, it seems that adjuvant radiotherapy can improve locoregional control and disease-free survival without additional late toxicity.
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April 2012

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

Neuro Oncol 2012 Jan 12;14(1):79-86. Epub 2011 Oct 12.

Department of Radiotherapy, Catholic University of the Sacred Heart, Rome, Italy.

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.
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January 2012