Stefano Zurrida

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

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Publications (205)969.03 Total impact

  • Annals of surgery 10/2015; DOI:10.1097/SLA.0000000000001397 · 8.33 Impact Factor
  • Roberto Orecchia · Piero Fossati · Stefano Zurrida · Marco Krengli ·
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    ABSTRACT: Purpose of review: The aim of this article is to review published data on proton therapy in the multimodality treatment of breast cancer so as to provide an overview of the advantages and critical issues relating to this irradiation modality. Recent findings: In-silico studies show a clear advantage in terms of dose homogeneity to the target and dose reduction to the non-target structures including heart, lungs, and healthy breast tissues. Clinical studies have shown the feasibility of proton therapy in breast cancer and allowed optimizing the technique by using multiple beams and intensity modulation. Summary: Proton therapy is able to optimize the dose to the target and to reduce the irradiation of the healthy tissues. Clinical studies are expected to show a decreased risk of late side effects with potential improvement of the quality of life of breast cancer patients.
    Current opinion in oncology 09/2015; 27(6). DOI:10.1097/CCO.0000000000000228 · 4.47 Impact Factor
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    Stefano Zurrida · Umberto Veronesi ·
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    ABSTRACT: Modern treatment started in the 1880s with Halsted's mastectomy. The next milestone—a century later—was breast-conserving surgery, with equivalent survival but better esthetic outcomes than mastectomy. Sentinel node biopsy, introduced in the 1990s, was a milestone that permitted avoidance of axillary dissection if the sentinel node was disease-free. Chemotherapy was established for early breast cancer in the 1980s and its efficacy continues to improve; however side effects remain a concern, particularly since chemotherapy does not benefit most patients. External whole breast irradiation was introduced with conservative surgery, as it reduces recurrences. By the 2000s, 3-week regimens had been shown equivalent to standard 6-week regimens—easing pressure on patients and radiation centers. Intraoperative partial breast irradiation is potentially more beneficial as it permits complete local treatment in a single session; however, trials show that patients must be very carefully selected. From the 1990s irradiation technology was combined with imaging and computer technologies to produce equipment that directs radiation to more precisely defined target volumes, allowing increased dose to the target and markedly reduced dose to nearby tissues. Irradiation systems are evolving rapidly but are being implemented without data on long-term morbidity or efficacy, while costs rise steeply. The first targeted treatment was tamoxifen, a selective estrogen receptor inhibitor. Since its widespread use starting in the 1980s, tamoxifen has saved the lives or prolonged the survival of millions with estrogen-positive disease; it is cheap and has limited (but not negligible) side effects. The same cannot be said of newer targeted treatments like trastuzumab and pertuzumab, which, although effective against human epidermal growth factor receptor 2-positive cancer, come with important side effects and huge costs. Breast cancer mortality is declining in rich countries, but treatments have become more demanding and more expensive, so the outlook for the increasing numbers of women worldwide who develop the disease is uncertain.
    The Breast Journal 12/2014; 21(1). DOI:10.1111/tbj.12361 · 1.41 Impact Factor

  • The Breast Journal 05/2014; 20(4). DOI:10.1111/tbj.12295 · 1.41 Impact Factor
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    ABSTRACT: Locally advanced breast cancer (LABC) should be taken into decision making when planning breast conservative surgery, but this procedure should be done on the principle of oncologic safety in order to achieve negative surgical margin and maintain aesthetic result. This procedure should be offered as the choice of treatment in selected patients.
    02/2014; 3(1):22-7. DOI:10.3978/j.issn.2227-684X.2014.01.01
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    ABSTRACT: Intraoperative radiotherapy with electrons allows the substitution of conventional postoperative whole breast irradiation with one session of radiotherapy with the same equivalent dose during surgery. However, its ability to control for recurrence of local disease required confirmation in a randomised controlled trial. This study was done at the European Institute of Oncology (Milan, Italy). Women aged 48-75 years with early breast cancer, a maximum tumour diameter of up to 2·5 cm, and suitable for breast-conserving surgery were randomly assigned in a 1:1 ratio (using a random permuted block design, stratified for clinical tumour size [<1·0 cm vs 1·0-1·4 cm vs ≥1·5 cm]) to receive either whole-breast external radiotherapy or intraoperative radiotherapy with electrons. Study coordinators, clinicians, and patients were aware of the assignment. Patients in the intraoperative radiotherapy group received one dose of 21 Gy to the tumour bed during surgery. Those in the external radiotherapy group received 50 Gy in 25 fractions of 2 Gy, followed by a boost of 10 Gy in five fractions. This was an equivalence trial; the prespecified equivalence margin was local recurrence of 7·5% in the intraoperative radiotherapy group. The primary endpoint was occurrence of ipsilateral breast tumour recurrences (IBTR); overall survival was a secondary outcome. The main analysis was by intention to treat. This trial is registered with, number NCT01849133. 1305 patients were randomised (654 to external radiotherapy and 651 to intraoperative radiotherapy) between Nov 20, 2000, and Dec 27, 2007. After a medium follow-up of 5·8 years (IQR 4·1-7·7), 35 patients in the intraoperative radiotherapy group and four patients in the external radiotherapy group had had an IBTR (p<0·0001). The 5-year event rate for IBRT was 4·4% (95% CI 2·7-6·1) in the intraoperative radiotherapy group and 0·4% (0·0-1·0) in the external radiotherapy group (hazard ratio 9·3 [95% CI 3·3-26·3]). During the same period, 34 women allocated to intraoperative radiotherapy and 31 to external radiotherapy died (p=0·59). 5-year overall survival was 96·8% (95% CI 95·3-98·3) in the intraoperative radiotherapy group and 96·9% (95·5-98·3) in the external radiotherapy group. In patients with data available (n=464 for intraoperative radiotherapy; n=412 for external radiotherapy) we noted significantly fewer skin side-effects in women in the intraoperative radiotherapy group than in those in the external radiotherapy group (p=0·0002). Although the rate of IBTR in the intraoperative radiotherapy group was within the prespecified equivalence margin, the rate was significantly greater than with external radiotherapy, and overall survival did not differ between groups. Improved selection of patients could reduce the rate of IBTR with intraoperative radiotherapy with electrons. Italian Association for Cancer Research, Jacqueline Seroussi Memorial Foundation for Cancer Research, and Umberto Veronesi Foundation.
    The Lancet Oncology 11/2013; 14(13). DOI:10.1016/S1470-2045(13)70497-2 · 24.69 Impact Factor
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    ABSTRACT: Complete surgical resection is the standard treatment for localized breast phyllodes tumors. Post-surgical treatments are still a matter of debate. We carried out an overview of the literature to investigate the clinical outcome of patients with phyllodes tumor. A retrospective analysis of mono-institutional series has been included as well. We reviewed all the retrospective series reported from 1951 until April 2012. We analyzed cases treated at our institution from 1999 to 2010. Eighty-three articles (5530 patients; 1956 malignant tumors) were reviewed. Local recurrences were independent of histology. Distant recurrences were more frequent in the malignant tumors (22%). A total of 172 phyllodes tumors were included in the retrospective analysis. Prognosis of phyllodes tumors is excellent. There are no convincing data to recommend any adjuvant treatment after surgery. Molecular characterization may well provide new clues to permit identification of active treatments for the rare poor prognosis cases.
    Critical reviews in oncology/hematology 07/2013; 88(2). DOI:10.1016/j.critrevonc.2013.06.005 · 4.03 Impact Factor
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    ABSTRACT: Aim: Axillary dissection is increasingly forgone in early breast cancer patients with a clinically negative axilla. The GRISO 053 randomised trial recruited 435 patients of age over 45 years, tumour ≤1.4 cm and clinically negative axilla, to assess the importance of axillary radiotherapy versus no axillary radiotherapy in patients not given axillary dissection. In the present study on a subgroup GRISO cases our aim was to assess the prognostic importance of tumour biological factors after more than 10 years of follow-up. Methods: We retrospectively assessed biological factors in a subgroup of 285 GRISO cases (145 given axillary radiotherapy; 140 not given axillary radiotherapy) with complete biologic, therapeutic and follow-up information, using multivariable Cox proportional hazards regression modelling. Results: Only 10-year cumulative incidence of distant metastasis was lower in the axillary radiotherapy (1%) than no axillary radiotherapy arm (7%) (p=0.037). Irrespective of study arm, hormone receptor positivity had significantly favourable effects on 10-year disease-free survival (DFS) and overall survival. human epidermal growth factor receptor 2 (HER2)-positive and triple-negative subtypes were associated with lower 10-year DFS (60% and 76%, respectively) than luminal A (96%) and B (91%) (p=0.001). Ten-year DFS for high (≥14%) Ki67 cancers was lower than for low Ki67 cancers (p=0.027); however, this effect was mainly confined to the no axillary radiotherapy arm. Concluding statement: For patients with clinically node-negative small breast cancer not given axillary dissection, 10-year DFS is worsened by HER2 positivity, triple-negative phenotype and high Ki67. Axillary radiotherapy counteracts the negative prognostic effect of high Ki67 in patients not receiving axillary dissection.
    European journal of cancer (Oxford, England: 1990) 06/2013; 49(15). DOI:10.1016/j.ejca.2013.05.007 · 5.42 Impact Factor
  • V Galimberti · B. F. Cole · S. Zurrida ·

    The Lancet Oncology 06/2013; 14(7):E254-E254. · 24.69 Impact Factor
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    ABSTRACT: BACKGROUND: For patients with breast cancer and metastases in the sentinel nodes, axillary dissection has been standard treatment. However, for patients with limited sentinel-node involvement, axillary dissection might be overtreatment. We designed IBCSG trial 23-01 to determine whether no axillary dissection was non-inferior to axillary dissection in patients with one or more micrometastatic (≤2 mm) sentinel nodes and tumour of maximum 5 cm. METHODS: In this multicentre, randomised, non-inferiority, phase 3 trial, patients were eligible if they had clinically non-palpable axillary lymph node(s) and a primary tumour of 5 cm or less and who, after sentinel-node biopsy, had one or more micrometastatic (≤2 mm) sentinel lymph nodes with no extracapsular extension. Patients were randomly assigned (in a 1:1 ratio) to either undergo axillary dissection or not to undergo axillary dissection. Randomisation was stratified by centre and menopausal status. Treatment assignment was not masked. The primary endpoint was disease-free survival. Non-inferiority was defined as a hazard ratio (HR) of less than 1·25 for no axillary dissection versus axillary dissection. The analysis was by intention to treat. Per protocol, disease and survival information continues to be collected yearly. This trial is registered with, NCT00072293. FINDINGS: Between April 1, 2001, and Feb 28, 2010, 465 patients were randomly assigned to axillary dissection and 469 to no axillary dissection. After the exclusion of three patients, 464 patients were in the axillary dissection group and 467 patients were in the no axillary dissection group. After a median follow-up of 5·0 (IQR 3·6-7·3) years, we recorded 69 disease-free survival events in the axillary dissection group and 55 events in the no axillary dissection group. Breast-cancer-related events were recorded in 48 patients in the axillary dissection group and 47 in the no axillary dissection group (ten local recurrences in the axillary dissection group and eight in the no axillary dissection group; three and nine contralateral breast cancers; one and nine regional recurrences; and 34 and 25 distant relapses). Other non-breast cancer events were recorded in 21 patients in the axillary dissection group and eight in the no axillary dissection group (20 and six second non-breast malignancies; and one and two deaths not due to a cancer event). 5-year disease-free survival was 87·8% (95% CI 84·4-91·2) in the group without axillary dissection and 84·4% (80·7-88·1) in the group with axillary dissection (log-rank p=0·16; HR for no axillary dissection vs axillary dissection was 0·78, 95% CI 0·55-1·11, non-inferiority p=0·0042). Patients with reported long-term surgical events (grade 3-4) included one sensory neuropathy (grade 3), three lymphoedema (two grade 3 and one grade 4), and three motor neuropathy (grade 3), all in the group that underwent axillary dissection, and one grade 3 motor neuropathy in the group without axillary dissection. One serious adverse event was reported, a postoperative infection in the axilla in the group with axillary dissection. INTERPRETATION: Axillary dissection could be avoided in patients with early breast cancer and limited sentinel-node involvement, thus eliminating complications of axillary surgery with no adverse effect on survival. FUNDING: None.
    The Lancet Oncology 03/2013; 14(4). DOI:10.1016/S1470-2045(13)70035-4 · 24.69 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; 60(3). DOI:10.4149/neo_2013_040 · 1.87 Impact Factor

  • 11/2012; 1(3):151-5. DOI:10.3978/j.issn.2227-684X.2012.10.09
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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 (19% [corrected] 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.
    11/2012; 98(6):715-21. DOI:10.1700/1217.13494
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    ABSTRACT: Sentinel node (SN) biopsy may predict axillary status in breast cancer. We retrospectively analyzed more than 500 SN cases, to suggest more precise indications for the technique. 99mTc-labeled colloid was injected close to the tumor; lymphoscintigraphy was then performed to reveal the SN. The next day, during surgery, the SN was removed by using a gamma probe. Complete axillary dissection followed, except in later cases recruited to a randomized trial. The SN was examined intraoperatively by conventional frozen section, in later cases by sampling the entire node and using immunocytochemistry. In the first series, the SN was identified in 98.7% of cases; in 6.7%, the SN was negative but other axillary nodes were positive; in 32.1%, the SN was negative by intraoperative frozen section but metastatic by definitive histology, prompting introduction of the exhaustive method. In the randomized trial, the SN was identified in all cases so far, the false-negative rate is approximately 6.5%, and in 15 cases, internal mammary chain nodes were biopsied. SN biopsy can reliably assess axillary status in selected patients. The problems are the SN detection rate, false negatives, and the intraoperative examination, which can miss 30% of SN metastases. Our exhaustive method overcomes the latter problem, but it is time consuming.
    Annals of Surgical Oncology 04/2012; 7(1):28-31. DOI:10.1007/s10434-000-0028-7 · 3.93 Impact Factor

  • European Journal of Cancer 03/2012; 48:S179-S180. DOI:10.1016/S0959-8049(12)70521-X · 5.42 Impact Factor

  • Cancer Research 02/2012; 71(24 Supplement):S3-1-S3-1. DOI:10.1158/0008-5472.SABCS11-S3-1 · 9.33 Impact Factor
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    ABSTRACT: Wide tumor resection plus postoperative whole breast irradiation is standard treatment for early breast cancer. Irradiation decreases recurrence rates, but may cause poor cosmesis, breast pain, and cardiac and lung toxicity. Accelerated partial breast irradiation is increasingly used in the hope of increasing convenience, decreasing sequelae and maintaining cure rates. Intraoperative radiotherapy with electrons is an attractive accelerated partial breast irradiation technique because collimator placement is under the direct control of the surgeon who removes the tumor, the skin is spared, shielding protects the chest wall and complete irradiation can be given in a single intraoperative session (avoiding 5-7 weeks of whole breast irradiation). Intraoperative radiotherapy with electrons seems as safe as whole breast irradiation; however, long-term results on local control and survival are not available yet.
    Women s Health 01/2012; 8(1):89-98. DOI:10.2217/whe.11.86
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    ABSTRACT: Breast cancer is the most frequent secondary tumor in young women previously treated with mantle radiation for Hodgkin's disease. Prior therapeutic radiation to the breast region is considered an absolute contraindication to breast conservative surgery, and mastectomy is considered the treatment of choice. We performed a retrospective review to assess the potential of performing breast conservative surgery and intraoperative radiotherapy with electrons (ELIOT), in these patients. Forty-three patients affected by early breast cancer, previously treated with mantle radiation for malignant lymphoma, who underwent breast conservative surgery and ELIOT, were identified in our institution. Median age at diagnosis of lymphoma was 26 years (49% were less than 25). Median interval between lymphoma and breast cancer occurrence was 19 years. A total dose of 21 Gy (prescribed at 90% isodose) in 39 patients (91%), of 17 Gy (prescribed at 100% isodose) in 1 patient and 18 Gy (prescribed at 90% isodose), was delivered. ELIOT was well tolerated in all patients without any unusual acute or late reactions. After a median follow-up of 52 months, local recurrence occurred in 9% of the patients and metastases in 7% patients. In patients previously treated for lymphoma, partial breast irradiation, and in particular ELIOT, permits breast conservative surgery without acute local complications, decreasing the number of avoidable mastectomies.
    Breast (Edinburgh, Scotland) 10/2011; 20 Suppl 3:S99-103. DOI:10.1016/S0960-9776(11)70304-6 · 2.38 Impact Factor
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    ABSTRACT: The management of ductal intraepithelial neoplasia (DIN) has substantially changed over the past 30 years, as its incidence has increased (from 2-3% to more than 20%), mainly due to the widespread use of mammography screening. This article describes not only the more widespread theoretical concepts on DIN but also the differences in the practical applications of the theory between different countries, different oncology specialists, and different cancer centers. Papers related to the international multicentre-randomized trials and retrospective studies were analyzed. We include articles and papers published between 1993 and 2010 related to patients with DIN, and abstracts and reports from MEDLINE and other sources were indentified. The standard of care for DIN consists of (a) breast conservative surgery (mastectomy is still indicated in large lesions--masses or microcalcifications--in about 30% of cases); (b) radiotherapy (RT) after conservative surgery, and (c) medical treatment in estrogen receptors-positive patients. However, most studies have shown significant differences between theory and practical application. Moreover, there are differences regarding (a) the indications of sentinel lymph node biopsy, (b) the definition and identification of low-risk DIN subgroups that can avoid RT and tamoxifen, and (c) the research into new alternative drugs in adjuvant medical therapy. A general agreement on the best management of DIN does not exist as yet. New large trials are needed in order to define the best management of DIN patients which is (in most respects) still complex and controversial.
    Breast Cancer Research and Treatment 07/2011; 128(2):369-78. DOI:10.1007/s10549-010-1124-4 · 3.94 Impact Factor
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    ABSTRACT: Breast cancer is the most common cancer in women. Primary treatment is surgery, with mastectomy as the main treatment for most of the twentieth century. However, over that time, the extent of the procedure varied, and less extensive mastectomies are employed today compared to those used in the past, as excessively mutilating procedures did not improve survival. Today, many women receive breast-conserving surgery, usually with radiotherapy to the residual breast, instead of mastectomy, as it has been shown to be as effective as mastectomy in early disease. The relatively new skin-sparing mastectomy, often with immediate breast reconstruction, improves aesthetic outcomes and is oncologically safe. Nipple-sparing mastectomy is newer and used increasingly, with better acceptance by patients, and again appears to be oncologically safe. Breast reconstruction is an important adjunct to mastectomy, as it has a positive psychological impact on the patient, contributing to improved quality of life.
    International Journal of Surgical Oncology 06/2011; 2011(5):980158. DOI:10.1155/2011/980158

Publication Stats

10k Citations
969.03 Total Impact Points


  • 1995-2015
    • IEO - Istituto Europeo di Oncologia
      • Division of Breast Cancer Surgery
      Milano, Lombardy, Italy
  • 1992-2014
    • University of Milan
      Milano, Lombardy, Italy
  • 2009
    • Università degli Studi di Milano-Bicocca
      • Department of Statistics and Quantitative Methods
      Milano, Lombardy, Italy
  • 2002
    • European School of Oncology
      Milano, Lombardy, Italy
  • 2001-2002
    • Memorial Sloan-Kettering Cancer Center
      • Department of Surgery
      New York City, NY, United States
  • 1991-1996
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
      Meldola, Emilia-Romagna, Italy
  • 1990-1995
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
      • s.c. Medicina Nucleare
      Milano, Lombardy, Italy
  • 1994
    • Universität Ulm
      Ulm, Baden-Württemberg, Germany
  • 1992-1993
    • CRO Centro di Riferimento Oncologico di Aviano
      • Division of Surgical Oncology
      Aviano, Friuli Venezia Giulia, Italy