Barbara A Jereczek-Fossa

IEO - Istituto Europeo di Oncologia, Milano, Lombardy, Italy

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Publications (124)332.33 Total impact

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    ABSTRACT: To compare our standard technique for postprostatectomy radiotherapy of prostate cancer, i.e. using two lateral conformal dynamic arcs with volumetric-modulated arc therapy (VMAT) performed with the RapidArc(®) (Varian Medical Systems, Palo Alto, CA, USA). The plans were referred to as DA and RA, respectively. The treatment plans of 44 patients receiving adjuvant/salvage radiotherapy in the first months of 2010 were compared. In all cases, the prescribed total dose was 66-68.2 Gy (2.2 Gy per fraction). Both DA and RA plans were optimized in terms of dose coverage and constraints. Small differences between the techniques were observed for planning target volume (PTV) dose distribution, whereas significant differences in sparing of organs at risk (OARs) were recorded (p < 0.0001). The OAR values (median; 95 % confidence interval, CI) were: rectum: D30 % = 60.7 Gy (59.40-62.04 Gy) and 48.2 Gy (46.40-52.72 Gy), D60 % = 34.1 Gy (28.50-38.92 Gy) and 27.7 Gy (21.80-31.51 Gy); bladder: D30 % = 57.3 Gy (45.83-64.53 Gy) and 46.4 Gy (33.23-61.48 Gy), D50 % = 16.4 Gy (11.89-42.38 Gy) and 17.2 Gy (10.97-27.90 Gy), for DA and RA, respectively. Treatment times were very similar, whereas the monitor units (MU) were 550 ± 29 versus 277 ± 3 for RA and DA, respectively. Dose-volume histograms (DVHs) show improvements in OAR sparing with RA. However, the RA technique is associated with almost double the number of MUs compared to DA. Regarding the PTV, DA is slightly superior in terms of D2 % and dose homogeneity. On the whole, the results suggest that RA be the favorable technique.
    Strahlentherapie und Onkologie 02/2014; · 4.16 Impact Factor
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    ABSTRACT: to evaluate the role of 18F-fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) integrated with computer tomography (CT) scan [(18)F]FDG-PET/CT in the staging and target volume definition in Intensity Modulated RapidarcTM Delivery (RA-IMRT) in cervical cancer. From June 2010 to December 2011, 66 patients affected by cervical cancer, candidates for definitive or adjuvant radiochemotherapy, underwent standard staging with CT and magnetic resonance imaging (MRI). All patients underwent [(18)F]FDG-PET/CT in order to exclude distant metastases and to define gross tumor volume (GTV). 40 and 26 patients received exclusive and adjuvant radiotherapy, respectively. RA-IMRT with simultaneous integrated boost (SIB) to the positive disease technique was employed. [(18)F]FDG-PET/CT has changed the stage, and radiotherapy treatment planning was modified in 25% and 7.7 % of patients that received definitive and adjuvant radiotherapy, respectively. Particularly [(18)F]FDG-PET/CT imaging showed metabolically active tumor in lymph nodes area, therefore the stage and the treatment planning changed for these patients. [(18)F]FDG-PET/CT leads to a better staging and definition of disease and has the potential of showing lymph-node metastasis not only within the pelvis but also in the para-aortic area. In addition, [(18)F]FDG-PET/CT is useful for better definition of the target volume and to produce a 'dose painted' treatment. This might also open the field for escalation dose regimens.
    ecancermedicalscience 01/2014; 8:405.
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    ABSTRACT: Purpose We report the experience of the Radiation Oncology Department of the European Institute of Oncology in Milan, Italy, on the adjuvant low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy. Brachytherapy might be useful to improve keloids recurrence rate or reduce keloids treatment side effects instead of external beam radiotherapy. Methods and Materials Data on 70 consecutive patients treated after complete keloid surgical excision were retrospectively analyzed. First 38 patients and 46 keloids were treated with adjuvant LDR brachytherapy and the following 39 patients and 50 keloids underwent HDR treatment. Median delivered dose of LDR therapy was 16 Gy; HDR median dose was 12 Gy. Sixty-four keloids (66.7%) were symptomatic at diagnosis with pain, itching, or stress. Results Fourteen relapses over 46 treated keloids (30.4%) were observed in the LDR group and 19 of 50 keloids (38%) in the HDR group (p = 0.521). Recurrence rate was significantly higher in males (p = 0.009), in patients younger than 44 years (p < 0.0001), for arms, neck, and chest wall anatomic sites (p = 0.0001) and for symptomatic keloids (p = 0.017). Aesthetic outcome was better in case of larger keloids (>8 cm) (p = 0.064). Symptomatic relief was achieved in 92% of HDR patients and only 68% of LDR patients (p = 0.032). Conclusions Postoperative brachytherapy is an effective treatment for keloids. In our study, LDR and HDR treatments resulted in similar recurrence rate. Better symptomatic relief was reported in case of HDR treatment compared with the LDR regimen.
    Brachytherapy 01/2014; · 1.22 Impact Factor
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    ABSTRACT: New imaging modalities may be useful to identify prostate cancer patients with small volume, limited nodal relapse ("oligo-recurrent") potentially amenable to local treatments (radiotherapy, surgery) with the aim of long-term control of the disease, even in a condition traditionally considered prognostically unfavorable. This report reviews the new diagnostic tools and the main published data about the role of surgery and radiation therapy in this particular subgroup of patients.
    Critical reviews in oncology/hematology 11/2013; · 5.27 Impact Factor
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    ABSTRACT: The purpose of our study was to analyze the role of [(11)C]choline-positron emission tomography/computed tomography (cho-PET/CT) in the management of patients with prostate cancer referred for radiotherapy. Inclusion criteria for this retrospective study were (1) presence of prostate cancer, (2) referral for first radiotherapy course (for primary or recurrent tumor) between February 2007 and July 2010, and (3) performance of cho-PET/CT. All cho-PET/CT scans were classified according to whether they were positive in the prostate/prostate bed (T), pelvic lymph nodes (N), and distant metastases (M) or negative. Therapeutic strategy based on the cho-PET/CT evaluation was compared with the strategy that would have been proposed had cho-PET/CT imaging not been available, following international and national prostate cancer guidelines. Eighty-two cho-PET/CT scans performed in 74 patients were analyzed. Cho-PET/CT was positive in 49 studies (60%): T only in 22 (45% of all positive studies); N only in 4 (8%); T in combination with N in 3 (6%); and M in combination with T or N, or both, in 16 (33%). Treatment after positive cho-PET/CT examination included radiotherapy ± androgen deprivation (29 patients), surgery ± radiotherapy (6 patients), androgen deprivation only (8 patients), and other treatment (6 patients). In 22 cases, cho-PET/CT (27%) altered the treatment approach compared with the treatment that would have been adopted in the absence of cho-PET/CT analysis. Cho-PET/CT is valuable in defining the extent of disease and supporting therapeutic decisions in the management of prostate cancer. The therapeutic strategy turned out to be influenced by cho-PET/CT imaging in about one third of the patients included in this study.
    Clinical Genitourinary Cancer 11/2013; · 1.43 Impact Factor
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    ABSTRACT: To check the interobserver agreement between radiation oncologists and therapists (RTT) using an on- and off-line cone-beam computer tomography (CBCT) protocol for setup verification in the radiotherapy of prostate cancer. The CBCT data from six prostate cancer patients treated with hypofractionated intensity-modulated radiotherapy (IMRT) were independently reviewed off-line by four observers (one radiation oncologist, one junior and two senior RTTs) and benchmarked with on-line CBCT positioning performed by a radiation oncologist immediately prior to treatment. CBCT positioning was based on manual soft-tissue registration. Agreement between observers was evaluated using weighted Cohen's kappa statistics. In total, 152 CBCT-based prostate positioning procedures were reviewed by each observer. The mean (± standard deviation) of the differences between off- and on-line CBCT-simCT registration translations along the three directions (antero-posterior, latero-lateral and cranio-caudal) and rotation around the antero-posterior axis were - 0.7 (3.6) mm, 1.9 (2.7) mm, 0.9 (3.6) mm and - 1.8 (5.0) degrees, respectively. Satisfactory interobserver agreement was found, being substantial (weighted kappa > 0.6) in 10 of 16 comparisons and moderate (0.41-0.60) in the remaining six comparisons. CBCT interpretation performed by RTTs is comparable to that of radiation oncologists. Our study might be helpful in the quality assurance of radiotherapy and the optimization of competencies. Further investigation should include larger sample sizes, a greater number of observers and validated methodology in order to assess interobserver variability and its impact on high-precision prostate cancer IGRT. In the future, it should enable the wider implementation of complex and evolving radiotherapy technologies.
    Strahlentherapie und Onkologie 08/2013; · 4.16 Impact Factor
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    ABSTRACT: Radical external-beam radiotherapy (EBRT) is a standard treatment for prostate cancer (PC) patients. Despite this, the rate of intraprostatic relapses after primary EBRT is still not negligible. There is no consensus on the most appropriate management of these patients after EBRT failure. Treatment strategies after PC relapse are strongly influenced by the effective site of the tumor recurrence, and thus the instrumental evaluation with different imaging techniques becomes crucial. In cases of demonstrated intraprostatic failure, several systemic (androgen deprivation therapy) or local (salvage prostatectomy, cryotherapy, high-intensity focused ultrasound, brachytherapy, stereotactic EBRT) treatment options could be proposed and are currently delivered by clinicians with a variety of results. In this review we analyze the correct definition of intraprostatic relapse after radiotherapy, focusing on the recent developments in imaging to detect intraprostatic recurrence. Furthermore, all available salvage treatment options after a radiation therapy local failure are presented and thoroughly discussed.
    Critical reviews in oncology/hematology 08/2013; · 5.27 Impact Factor
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    ABSTRACT: Purpose. Radiotherapy (RT) has an established role in the treatment of prostate cancer patients. Despite the large number of patients treated with RT, some issues about optimal techniques, doses, volumes, timing, and association with androgen deprivation are still subject of debate. The aim of this survey was to determine the patterns of choice of Italian radiation oncologists in two different clinical cases of prostate cancer patients treated with radical RT. Study design. During the 2010 Italian Association of Radiation Oncology (AIRO) National congress, four different clinical cases were presented to attending radiation oncologists. Two of them were prostate cancer cases that could be treated by RT +/- hormonal therapy (HT), different for T stage of primary tumour according to TNM, preoperative diagnostic procedures for staging, initial prostate specific antigen (iPSA), and Gleason Score sum of biopsy. For each clinical case, radiation oncologists were asked to: (a) give indication to pretreatment procedures for staging; (b) give indication to treatment; (c) define specifically, where indicated, total dose, type of fractionation, volumes of treatment, type of technique type of image-guided setup control; (d) indicate if HT should be prescribed; (e) define criteria that particularly influenced prescription. A descriptive statistical analysis was performed. Results. Three hundred questionnaires were given to radiation oncologists attending the congress, 128 questionnaires were completed and considered for this analysis (41%). Some important differences were shown in prescribing and delivering RT, particularly with regards to treatment volumes and fractionation. Conclusions. Despite the results of clinical trials, several differences still exist among Italian radiation oncologists in the treatment of prostate cancer patients. These patients probably deserve a more uniform approach, based on upto- date, detailed, and evidence-based recommendations.
    La radiologia medica 06/2013; · 1.46 Impact Factor
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    ABSTRACT: PURPOSE: To evaluate the outcome of robotic CyberKnife (Accuray Inc. Sunnyvale, USA)-based stereotactic radiotherapy (CBK-SRT) for oligometastic cancer patients. PATIENTS AND METHODS: Between May 2007 and December 2009, 95 patients with a total of 118 lesions underwent CBK-SRT (median dose 24 Gy in 3 fractions). Inclusion criteria: adult patients with limited volume cancer; suitability for SRT but not for other local therapies. Primary diagnoses included breast, lung, head and neck, gastrointestinal and other malignancies. Prostate cancer patients were excluded. Concomitant systemic therapy was given in 40 % of cases and median follow-up was 12 months. Toxicity and tumor response were evaluated using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) Scale and Response Evaluation Criteria in Solid Tumors RECIST. RESULTS: Toxicity was rare and observed mainly in patients with comorbidities or uncontrolled cancer. Out of 87 evaluable lesions, complete radiological response, partial response, stabilization and progressive disease were observed in 15 (17 %), 25 (29 %), 34 (39 %) and 13 (15 %) lesions, respectively. Upon restricting the analysis to lesions treated with CBK-SRT alone (no concomitant therapy), response- and local control (LC) rates remained similar. Actuarial 3-year in-field progression-free survival- (i.e. LC), progression-free survival- (PFS) and overall-survival (OS) rates were 67.6, 18.4, and 31.2 %, respectively. LC was reduced in cases of early recurrence. OS- and cause-specific survival (CSS) rates were significantly lower in patients treated for visceral lesions. Failures were predominantly out-field. CONCLUSION: CBK-SRT is a feasible therapeutic approach for oligometastastic cancer patients that provides long-term in-field tumor control with a low toxicity profile. Further investigations should focus on dose escalation and optimization of the combination with systemic therapies.
    Strahlentherapie und Onkologie 04/2013; · 4.16 Impact Factor
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    ABSTRACT: Electronic portal imaging (EPI) is commonly used to identify and correct for inter-fraction variability in tangential breast irradiation. Based on the institutional policy, EPI registration is performed by either radiation oncologist or therapist. Little data is available on the inter-observer agreement in EPI registration among different health practitioners. The aim of our study was to analyze inter-observer agreement among radiation oncologists and therapists in the evaluation of EPI for breast cancer radiotherapy verification. EPI data of 40 patients treated with tangential fields were independently reviewed by a radiation oncologist (on-line, just before treatment) and off-line by junior and senior therapists. Displacement of each EPI image with respect to the digital reconstructed radiographs (DRRs) was quantified using manual EPI registration based on bony marks with the corresponding DRRs. Agreement between observers was evaluated using weighted Cohen's Kappa statistics. In 95% out of 720 EPI-DRR comparisons, the EPI-DRR misalignment was < 5 mm. The difference between observers was < 2 mm in 666 (92.5%) out of all 720 delta values. High inter-observer agreement was found, with weighted Cohen's Kappa values attesting evaluation overlaps ranging from moderate (among therapists) to almost perfect (among radiation oncologist and therapists). The high agreement among the observers demonstrated the precision of breast localization using EPI. These findings suggest that routine EPI-based patient set-up verification in breast cancer radiotherapy can be safely entrusted to trained therapists (supervision should be assured based on the local tasks definition). Our study might be useful in quality assurance and in the optimization of workload in the radiotherapy departments. They might allow for wider implementation of complex and evolving radiotherapy technologies. Keywords:
    Neoplasma 02/2013; · 1.57 Impact Factor
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    ABSTRACT: PURPOSE: Radiotherapy (RT) has an established role in the postoperative treatment of prostate cancer patients with extracapsular extension, positive surgical margins or a detectable post-operative prostate-specific antigen (PSA). Despite the large number of patients treated with postoperative RT, some issues about optimal technique, doses, volumes, timing and association with androgen deprivation are still subject of debate. The aim of this survey was to determine the patterns of choice of Italian radiation oncologists in two different clinical cases of postoperative prostate cancer patients. STUDY DESIGN: During the 2010 National Congress of the Italian Association of Radiation Oncology (AIRO), four clinical cases were presented to the attending radiation oncologists. Two of them were cases of postoperative prostate cancer, differing in T stage of the primary tumour according to the TNM classification, preoperative staging procedures, preoperative PSA (iPSA), Gleason score of biopsies and definitive pathological specimen after surgery and postoperative PSA. For each clinical case, the radiation oncologists were asked to: (a) give indication to new pre-treatment procedures for staging; b) give indication to postoperative treatment; (c) to define specifically, where indicated, the total dose, type of fractionation, treatment volumes, type of technique, type of image-guided setup control; (d) indicate whether adjuvant hormonal therapy should be prescribed; (e) define criteria that mostly influenced the prescription. A descriptive statistical analysis was then performed. RESULTS: A total of 300 questionnaires were distributed amongst radiation oncologists attending the congress; 128 were completed and considered for this analysis (41%). Some important differences were shown in prescribing and performing postoperative radiotherapy, and some significant differences with international guidelines and data available from the literature were also reviewed and discussed. CONCLUSIONS: Despite the results of clinical trials, significant differences still exist among Italian radiation oncologists in deciding postoperative treatment in prostate cancer patients. These patients probably deserve a more uniform approach based on updated, detailed and evidencebased recommendations.
    La radiologia medica 01/2013; · 1.46 Impact Factor
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    ABSTRACT: PURPOSE: To prospectively analyse quality of life (QoL) in a cohort of prostate cancer patients undergoing treatment with a course of hypofractionated image-guided radiotherapy (hypo-IGRT). MATERIAL AND METHODS: Between 8/2006 and 1/2011, 337 cT1-T2N0M0 prostate cancer patients (median age 73 years) were eligible for this prospective longitudinal study on hypo-IGRT (70.2Gy/26 fractions), employing one out of 3 IGRT modalities (transabdominal ultrasound, X-Ray, cone-beam computed tomography) available at our Radiation Oncology Department. Patients filled in 4 questionnaires before treatment, and at 6, 12 and 24 months afterwards: the International Index of Erectile Function-5 (IIEF-5), the International Prostate Symptom Score (IPSS), the European Organization for Research and Treatment of Cancer (EORTC) prostate-cancer-specific QLQ-PR25 and QLQ-C30. RESULTS: Patients follow-up was updated to at least last questionnaire time point (median follow-up 19 months). Significant deterioration in erectile function (IIEF-5) was registered over time only in the patients without androgen deprivation (p=0.0002). No change over time was observed in urinary symptoms-related QoL at the QLQ-PR25 and IPSS questionnaires. Slight deterioration in the QLQ-PR25 bowel symptoms-related QoL was observed (p=0.02). Overall, the QLQ-C30 Global Health Status was found to be improved over time (p=0.03) and significantly correlated at univariate analysis to the maximum RTOG/EORTC urinary and bowel late toxicity score after radiotherapy. CONCLUSIONS: The regimen of hypo-IGRT with multiple imaging modalities adopted in our Radiation Oncology Department for localised prostate cancer might be a successful strategy for dose escalation with limited impact on different aspects of QoL over time.
    The Journal of urology 01/2013; · 4.02 Impact Factor
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    ABSTRACT: New imaging modalities may be useful to identify prostate cancer patients with small volume, limited nodal relapse (“oligo-recurrent”) potentially amenable to local treatments (radiotherapy, surgery) with the aim of long-term control of the disease, even in a condition traditionally considered prognostically unfavorable. This report reviews the new diagnostic tools and the main published data about the role of surgery and radiation therapy in this particular subgroup of patients.
    Critical Reviews in Oncology/Hematology. 01/2013;
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    ABSTRACT: Aims and background. To calculate peripheral radiation dose to the second primary site in patients who have developed a second malignancy after breast cancer radiotherapy (index cases) and to compare it with dose in the analogous anatomical site in radiotherapy-treated breast cancer patients who did not experience a second malignancy (controls). To evaluate the feasibility of Peridose-software peripheral dose calculation in retrospective case-control studies. Material and study design. A case-control study on 12,630 patients who underwent adjuvant breast radiotherapy was performed. Minimum 5-year follow-up was required. Each index case was matched with 5 controls by 1) year of birth, 2) year of radiotherapy and 3) follow-up duration. Peridose-software was used to calculate peripheral dose. Results. 195 second cancers were registered (0.019% of all patients treated with adjuvant irradiation). Several methodological limitations of the Peridose calculation were encountered including impossibility to calculate the peripheral dose in the patients treated with intraoperative or external electron beam radiotherapy, in case of second tumors located at <15 cm from the radiotherapy field etc. Moreover, Peridose requires full radiotherapy data and the distance between radiotherapy field and second primary site. Due to these intrinsic limitations, only 6 index cases were eligible for dose calculation. Calculated doses at the second cancer site in index cases and in an analogous site in controls ranged between 7.5 and 145 cGy. The mean index-control dose difference was -3.15 cGy (range, -15.8 cGy and +2.7 cGy).Conclusions. The calculated peripheral doses were low and the index-control differences were small. However, the small number of eligible patients precludes a reliable analysis of a potential dose-response relationship. Large patient series followed for a long period and further improvement in the methodology of the peripheral dose calculation are necessary in order to overcome the methodological challenges of the study.
    Tumori. 11/2012; 98(6):715-21.
  • European Urology Supplements 11/2012; 11(5):214. · 2.16 Impact Factor
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    ABSTRACT: OBJECTIVES:: To evaluate stereotactic body radiotherapy (SBRT) for single abdominal lymph node cancer recurrence. METHODS:: Inclusion criteria for this retrospective study were as follows: adult oligometastatic cancer patients with single abdominal lymph node recurrence that underwent SBRT but not other local therapy, written informed consent for treatment. Previous radiotherapy or concomitant systemic therapy were allowed. Toxicity and tumor response were evaluated using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Scale and Response Evaluation Criteria in Solid Tumors. RESULTS:: Sixty-nine patients (94 lesions) underwent SBRT (median 24 Gy/3 fractions). Primary diagnosis included urological, gastrointestinal, gynecologic, and other malignancies. Concomitant systemic therapy was performed in 35 cases. Median follow-up was 20 months. Two grade 3 acute and 1 grade 4 late toxicity events were registered. Complete radiologic response, partial response, stabilization, and progressive disease were observed in 36 (44%), 21 (26%), 20 (25%), and 4 (5%) lesions, respectively, out of 81 evaluable lesions. Response rates were similar when analysis was restricted to lesions treated with exclusive SBRT (no concomitant therapy). Actuarial 3-year in-field progression-free interval, progression-free survival and overall-survival rates were 64.3%, 11.7%, and 49.9%, respectively. Overall-survival rates were significantly higher in favorable histology cases (prostate and kidney tumors). Pattern of failure was predominantly out-field. CONCLUSIONS:: SBRT is a feasible approach for single abdominal lymph node recurrence, offering excellent in-field tumor control with low-toxicity profile. Future studies are warranted to identify the patients that benefit most from this treatment. The optimal combination with systemic treatment should also be defined.
    American journal of clinical oncology 09/2012; · 2.21 Impact Factor
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    ABSTRACT: Correction After publication of this work [1], we noted that we inadvertently failed to include the complete list of all coauthors. The full list of authors has now been added and the Authors' contributions and Competing interests section modified accordingly. Competing interests The authors declare they have no competing interests. Authors' contributions PP developed the model and designed the study. BAJ, LS, BV, DA, MC, FB, GI and AF checked the appropriateness of the study from oncology, radiotherapy and mathematical points of view. PP, RC, MC and LS compiled the manuscript and produced the graphical illustrations. AN, GS, MB, RO and VF supervised the manuscript from radiobiological and clinical point of view. All co-authors approved the manuscript. References 1. Pedicini P, Caivano R, Jereczek-Fossa BA, Strigari L, Vischioni B, Alterio D, Cremonesi M, Botta F, Nappi A, Improta G, Storto G, Benassi M, Orecchia R and Fusco V: Modelling the correlation between EGFr expression and tumour cell radiosensitivity, and combined treatments of radiation and monoclonal antibody EGFr inhibitors. Theor Biol Med Model 2012, 9:23.
    Theoretical Biology and Medical Modelling 08/2012; 9:37. · 1.46 Impact Factor
  • The Lancet Oncology 07/2012; 13(7):e280-1; author reply e284. · 25.12 Impact Factor
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    ABSTRACT: Aims and background. To evaluate clinical outcome and toxicity using high-dose-rate brachytherapy as monotherapy in head and neck carcinomas. Methods Between September 2004 and April 2010, a series of 12 patients with lip (7 patients) or buccal mucosa (5 patients) cancers were treated by exclusive interstitial high-dose-rate brachytherapy. The median age of the patients was 71.5 years (range, 47-87). Stages were T1N0M0 and T2N0M0 in 6 and 6 patients, respectively. A dose of 27 to 54 Gy in 9 to 16 fractions, 3 to 4.5 Gy per fraction, 2 fractions per day with a minimal gap of 6 h in between was delivered. Results. After a median follow-up of 46 months (range, 10-85), the disease-free and overall survival was 83% (10 of 12 patients) and 50% (6 of 12 patients), respectively. The crude local control in the lip cancer patients was 100% and in the buccal mucosa cancer patients was 60%. No severe toxicity was registered. Conclusions. High-dose-rate brachytherapy is feasible and safe and offers the possibility to treat patients in an outpatient regimen.
    Tumori. 07/2012; 98(4):471-7.
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    ABSTRACT: Purpose To estimate the effects of heterogeneity on tumour cell sensitivity to radiotherapy combined with radiosensitizing agents attributable to differences in expression levels of Epidermal Growth Factor Receptor (EGFr). Materials and methods Differences in radiosensitivity are not limited to cells of different cancer histotypes but also occur within the same cancer, or appear during radiotherapy if radiosensitizing drugs are combined with ionizing radiation. A modified biologically effective dose (MBED), has been introduced to account for changes in radiosensitivity parameters (alpha and alpha/beta) rather than changes in dose/fraction or total dose as normally done with standard biologically effective dose (BED). The MBED approach was applied to cases of EGFr over-expression and cases where EGFr inhibitors were combined with radiation. Representative examples in clinical practice were considered. RESULTS: Assuming membrane EGFr over-expression corresponds to reduced radiosensitivity (alphaH = 0.15 Gy-1 and alphaH/betaH = 7.5 Gy) relative to normal radiosensitivity (alpha = 0.2 Gy-1 and alpha/beta = 10 Gy), an increased dose per fraction of 2.42 Gy was obtained through the application of MBED, which is equivalent to the effect of a reference schedule with 30 fractions of 2 Gy. An equivalent hypo-fractionated regime with a dose per fraction of 2.80 Gy is obtained if 25 fractions are set. Dose fractionations modulated according to drug pharmacokinetics are estimated for combined treatments with biological drugs. Soft and strong modulated equivalent hypo-fractionations result from subtraction of 5 or 10 fractions, respectively. CONCLUSIONS: During this computational study, a new radiobiological tool has been introduced. The MBED allows the required dose per fraction to be estimated when tumour radiosensitivity is reduced because EGFr is over-expressed. If radiotherapy treatment is combined with EGFr inhibitors, MBED suggests new treatment strategies, with schedules modulated according to drug pharmacokinetics.
    Theoretical Biology and Medical Modelling 06/2012; 9(1):23. · 1.46 Impact Factor

Publication Stats

1k Citations
332.33 Total Impact Points

Institutions

  • 1999–2014
    • IEO - Istituto Europeo di Oncologia
      • Division of Radiotherapy
      Milano, Lombardy, Italy
  • 2013
    • Università degli Studi di Brescia
      Brescia, Lombardy, Italy
  • 2007–2013
    • University of Milan
      • Faculty of Medicine
      Milano, Lombardy, Italy
  • 2011
    • Politecnico di Milano
      • Department of Bioengineering
      Milano, Lombardy, Italy
    • Azienda Ospedaliero Universitaria Maggiore della Carità
      • Department of Radiotherapy
      Novara, Piedmont, Italy
  • 2008
    • Amedeo Avogadro University of Eastern Piedmont
      Novara, Piedmont, Italy
  • 1998–2003
    • Medical University of Gdansk
      • Department of Oncology and Radiotherapy
      Gdańsk, Pomeranian Voivodeship, Poland