Publications by authors named "Marta Scorsetti"

240 Publications

Almost one year of COVID-19 pandemic: how radiotherapy centers have counteracted its impact on cancer treatment in Lombardy, Italy. CODRAL/AIRO-L study.

Tumori 2021 Apr 22:3008916211009974. Epub 2021 Apr 22.

IRCCS Humanitas Research Hospital, Radiotherapy and Radiosurgery Center, Rozzano, Milan, Italy.

Lombardy has represented the Italian and European epicenter of the coronavirus disease 2019 (COVID-19) pandemic. Although most clinical efforts within hospitals were diverted towards the care of virally infected patients, therapies for patients with cancer, including radiotherapy (RT), have continued. During both the first and second pandemic waves, several national and regional organizations provided Italian and Lombardian RT departments with detailed guidelines aimed at ensuring safe treatments during the pandemic. The spread of infection among patients and personnel was limited by adopting strict measures, including triage procedures, interpersonal distance, and adequate implementation of personal protective equipment (PPE). Screening procedures addressed to both the healthcare workforce and patients, such as periodic nasopharyngeal swabs, have allowed the early identification of asymptomatic or pauci-symptomatic COVID-19 cases, thus reducing the spread of the infection. Prevention of infection was deemed of paramount importance to protect both patients and personnel and to ensure the availability of a minimum number of staff members to maintain clinical activity. The choice of treating COVID-19-positive patients has represented a matter of debate, and the risk of oncologic progression has been weighted against the risk of infection of personnel and other patients. Such risk was minimized by creating dedicated paths, reserving time slots, applying intensified cleaning procedures, and supplying personnel and staff with appropriate PPE. Remote working of research staff, medical physicists, and, in some cases, radiation oncologists has prevented overcrowding of shared spaces, reducing infection spread.
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http://dx.doi.org/10.1177/03008916211009974DOI Listing
April 2021

Nonmyeloablative Conditioning Regimen Including Low-Dose Total Marrow/Lymphoid Irradiation Before Haploidentical Transplantation with Post-Transplantation Cyclophosphamide in Patients with Advanced Lymphoproliferative Diseases.

Transplant Cell Ther 2021 Mar 15. Epub 2021 Mar 15.

BMT Unit, Humanitas Clinical and Research Center-IRCCS, Humanitas Cancer Center, Milan, Italy. Electronic address:

Low-dose total body irradiation (TBI) has long been used in nonmyeloablative conditioning (NMAC) regimens before allogeneic stem cell transplantation from haploidentical donors (haplo-SCT). More recently, the use of total marrow lymphoid irradiation (TMLI) instead of TBI in conditioning is increasing. This study aimed to evaluate outcomes in a cohort of patients treated with low-dose TMLI in terms of engraftment, full donor chimerism status, graft-versus-host disease (GVHD), and extrahematologic toxicities, and to compare these outcomes with those in a cohort of patients receiving conventional TBI-containing conditioning. This retrospective single-center study included 100 patients with advanced hematologic malignancies who underwent haplo-SCT. Between 2009 and 2011, the NMAC regimen consisted of cyclophosphamide, fludarabine, and low-dose TBI (2 Gy), and after 2011, TBI was replaced with TMLI (2 Gy). Patients received post-transplantation cyclophosphamide, calcineurin inhibitor, and mycophenolate mofetil as GVHD prophylaxis. For all patients, the median time to absolute neutrophil count (ANC) recovery to >0.5 × 10/L was 21 days (range, 15 to 49 days), the 30-day incidence of ANC recovery was 97% (95% confidence interval [CI], 89% to 99%), the median time to achieve an unsupported platelet count >20 × 10/L was 26 days (range, 12 to 67 days), and the 60-day rate of platelet engraftment was 99% (95% CI, 89% to 100%). Cumulative incidence of full donor chimerism by day 100 was 88% (95% CI 79-90). Grade II-IV acute GVHD occurred in 35% of the patients (95% CI, 26% to 45%) at a median of 40 days (range, 23 to 166 days). The incidence of moderate to severe chronic GVHD was 5% (95% CI, 2% to 10%). No differences between the TBI and TMLI cohorts were seen in terms of engraftment, full donor chimerism, and GVHD. No organ toxicity was observed in the first months after transplantation in either cohort. The overall 2-year OS and PFS rates were 63%, and 54%, respectively, and were comparable in the 2 groups (P = .548). The strongest finding was that TBI can be safely replaced by TMLI in terms of engraftment, achievement of full donor chimerism status, GVHD incidence, and extrahematologic toxicities.
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http://dx.doi.org/10.1016/j.jtct.2021.03.013DOI Listing
March 2021

Charlson comorbidity index and G8 in older old adult(≥80 years) hepatocellular carcinoma patients treated with stereotactic body radiotherapy.

J Geriatr Oncol 2021 Jan 15. Epub 2021 Jan 15.

Humanitas Clinical and Research Center, IRCSS, Radiotherapy and Radiosurgery Department, Rozzano, Italy; Radiotherapy Department, University of Florence, Florence, Italy.

Introduction: Hepatocellular Carcinoma (HCC) is characterized, in Western countries, by higher incidence and mortality rates in the older adult population. In frail patients, limited therapeutic resources are available due to limited expected benefit concerning the risk of treatment-related toxicity. The aim of our study is to evaluate the role of Stereotactic Body Radiotherapy (SBRT) in the clinical management of older old adults (age ≥ 80 years) HCC patients and to identify predictors of efficacy and toxicity.

Material And Methods: Clinical and treatment-related data of older old adults HCC patients treated with SBRT at our institution were retrospectively reviewed. Statistical analysis was carried out to identify variables correlated with impaired outcome and toxicity.

Results: Forty-two patients were included, accounting for 63 treated tumors. Median age was 85 (range 80-91) years. Median Charlson Comorbidity Index (CCI) and G8 scores were 10 (range 7-16) and 11 (range 8-14), respectively. SBRT was administered to a median BED10 of 103 Gy10. Median follow-up interval was 11 (range 3-40) months. Two years Local Control (LC), Progression-Free Survival (PFS), and Overall Survival (OS) were 93%, 31%, and 43%, respectively. Acute toxicity occurred in 28% (n = 13) of treatments. A G8 score > 10 was associated with improved survival (p = 0.045), while a CCI ≥10 was correlated with increased acute toxicity (p = 0.021).

Conclusions: SBRT is a safe and effective option in older old adults HCC patients. A comprehensive geriatric assessment (CGA) is advised before treatment decisions to select optimal candidates for SBRT.
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http://dx.doi.org/10.1016/j.jgo.2021.01.001DOI Listing
January 2021

Comparing hypofractionated and conventionally fractionated whole breast irradiation for patients with ductal carcinoma in situ after breast conservation: a propensity score-matched analysis from a national multicenter cohort (COBCG-02 study).

J Cancer Res Clin Oncol 2021 Jan 2. Epub 2021 Jan 2.

Radiotherapy and Radiosurgery Department, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milano, Italy.

Background And Purpose: Randomized trials confirmed the efficacy and the safety of hypofractionated whole breast irradiation (HF-WBI) in patients with early-stage breast cancer. However, the role of HF-WBI in patients with DCIS after breast conserving surgery has not yet been clearly established in prospective randomized trials. The aim of this study was to evaluate if HF-WBI can be considered comparable to conventionally fractionated (CF)-WBI in DCIS patients.

Materials And Methods: The analysis included DCIS patients from four Italian centers treated with CF-WBI 50 Gy/25 fractions or HFRT 40.5 Gy/15 fractions, without tumor bed boost. A propensity score matching (PSM) analysis was performed using a logistic regression that considered age, grading, presence of necrosis, resection margin status and adjuvant endocrine therapy.

Results: Five hundred twenty-seven patients was included (367 in the CF-WBI-group and 160 in the HR-WBI group). After 1:1 matching, 101 patients were allocated to the CF-WBI-group and 104 to the HF-WBI group. No correlation was observed between the type of RT schedule and LRFS (HR 1.68, 95% CI 0.82-3.45; p = 0.152). After PSM, no statistical difference was observed between the two RT group (HR 1.11, 95% CI 0.40-3.04; p = 0.833), with 3- and 5-years LRFS rates of 100% and 97.9% for CF-WBI and 95.6% and 94% for HF-WBI.

Conclusion: A short course of radiation therapy seems to be comparable to CF-WBI in terms of clinical outcomes. These data support the use of hypofractionated schedules in DCIS patients, but considering the remaining uncertainties.
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http://dx.doi.org/10.1007/s00432-020-03483-5DOI Listing
January 2021

The Multicenter, Randomized, Phase 2 PEACE V-STORM Trial: Defining the Best Salvage Treatment for Oligorecurrent Nodal Prostate Cancer Metastases.

Eur Urol Focus 2021 Mar 29;7(2):241-244. Epub 2020 Dec 29.

Department of Radiation Oncology and Experimental Cancer Research, Ghent University Hospital, Ghent, Belgium. Electronic address:

Optimal local treatment for nodal oligorecurrent prostate cancer is unknown. The randomized phase 2 PEACE V-STORM trial will explore the best treatment approach in this setting. Early results on the acute toxicity profile are projected to be published in quarter 3, 2021.
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http://dx.doi.org/10.1016/j.euf.2020.12.010DOI Listing
March 2021

Metastatic salivary gland carcinoma: A role for stereotactic body radiation therapy? A study of AIRO-Head and Neck working group.

Oral Dis 2020 Dec 15. Epub 2020 Dec 15.

Radiation Oncology Unit 2, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.

Objectives: The role of radiotherapy (RT) for oligometastases is currently established in different oncological settings but data on salivary gland cancer (SGC) are lacking. We evaluated the role of RT in oligometastatic SGC patients, focusing on stereotactic body radiation therapy (SBRT).

Materials And Methods: We performed a retrospective, multicentric study of oligometastatic SGC treated with palliative RT or SBRT. Endpoints included response evaluation and local control (LC).

Results: Between 2006 and 2016, 64 patients were collected from 9 Italian Cancer Centers, on behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) Head and Neck Working Group. 37 patients (57.8%) were suffering from adenoid cystic carcinoma (ACC) and 27 patients (42.2%) had non-ACC. Thirty-four patients underwent palliative RT (53,1%), and 30 received SBRT (46,9%). Most common metastatic sites were bone for palliative RT and lung for SBRT. Among patients treated with SBRT, an objective response or a stability was observed in all treated lesions. After a median follow-up of 29.2 months (range 2.3-117.1), LC at 12 months was 57.5% for patients treated with SBRT and was higher in ACC subgroup.

Conclusion: We confirmed the potential role of SBRT in the management of oligometastatic SGC patients to control limited burden of disease considering the absence of effective systemic therapies.
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http://dx.doi.org/10.1111/odi.13755DOI Listing
December 2020

Salvage radiotherapy for oligo-progressive malignant pleural mesothelioma.

Lung Cancer 2021 02 26;152:1-6. Epub 2020 Nov 26.

Department of Medical Oncology, Cliniche Humanitas Gavazzeni, Via Gavazzeni 21, 24125 Bergamo, Italy. Electronic address:

Objectives: No standard treatment option is available for patients with unresectable malignant pleural mesothelioma (MPM) progressing after upfront chemotherapy. We aimed to explore the role of focal radiotherapy (FRT) as a treatment modality for oligo-progressive MPM.

Materials And Methods: In this retrospective study, consecutive patients pretreated with ≥1 lines of chemotherapy were included. Oligo-progressive MPM was defined as an unresectable disease with radiological progression at ≤3 sites according to a chest-abdominal contrast-enhanced computed tomography. Patients were treated with either stereotactic body radiotherapy (SBRT, ≥5 Gy per fraction) or hypo-fractionated radiotherapy (hypoRT, <5 Gy per fraction). Time to further systemic therapy (TFST) and local control (LC) after FRT were the primary endpoints. Biologically effective dose (BED) was calculated using three different alpha/beta models (1.5 Gy, 3 Gy and 10 Gy).

Results: From April 2006 to March 2019, 37 patients were treated on 43 pleural lesions; 16/37 (43 %) had undergone upfront multimodality treatment (MMT) including surgery. FRT was given in 22/37 (59.5 %) after one line of chemotherapy. SBRT was delivered for 26/43 lesions (60.5 %), hypoRT for 17/43 (39.5 %). Median TFST was 6 months (95 % CI 4.9-7.1). LC at 6 months and 1 year was 84 % and 76 %, respectively. Median TFST was longer in patients treated after 1 vs >1 line of chemotherapy (9 vs 4 months, p = 0.001) and in patients pretreated with MMT (6 vs 3 months, p = 0.021). Six-month LC was better in patients treated with a BED > 100 using alpha/beta 1.5 and 3. No ≥ G3 acute or late toxicities were reported.

Conclusion: FRT was feasible in selected patients with oligo-progressive MPM, allowing delay of further systemic therapies, with no severe toxicity. FRT was more effective when performed at progression after one line of systemic therapy. Our results suggest a radio-resistant behavior of MPM.
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http://dx.doi.org/10.1016/j.lungcan.2020.11.022DOI Listing
February 2021

The Potential Role of Intensity-Modulated Proton Therapy in Hepatic Carcinoma in Mitigating the Risk of Dose De-Escalation.

Technol Cancer Res Treat 2020 Jan-Dec;19:1533033820980412

Radiotherapy and Radiosurgery Department, Humanitas Clinical and Research Center, IRCSS, Milan-Rozzano, Italy.

Purpose: To investigate the role of intensity-modulated proton therapy (IMPT) for hepatocellular carcinoma (HCC) patients to be treated with stereotactic body radiation therapy (SBRT) in a risk-adapted dose prescription regimen.

Methods: A cohort of 30 patients was retrospectively selected as "at-risk" of dose de-escalation due to the proximity of the target volumes to dose-limiting healthy structures. IMPT plans were compared to volumetric modulated arc therapy (VMAT) RapidArc (RA) plans. The maximum dose prescription foreseen was 75 Gy in 3 fractions. The dosimetric analysis was performed on several quantitative metrics on the target volumes and organs at risk to identify the relative improvement of IMPT over VMAT and to determine if IMPT could mitigate the need of dose reduction and quantify the consequent potential patient accrual rate for protons.

Results: IMPT and VMAT plans resulted in equivalent target dose distributions: both could ensure the required coverage for CTV and PTV. Systematic and significant improvements were observed with IMPT for all organs at risk and metrics. An average gain of 9.0 ± 11.6, 8.5 ± 7.7, 5.9 ± 7.1, 4.2 ± 6.4, 8.9 ± 7.1, 6.7 ± 7.5 Gy was found in the near-to-maximum doses for the ribs, chest wall, heart, duodenum, stomach and bowel bag respectively. Twenty patients violated one or more binding constraints with RA, while only 2 with IMPT. For all these patients, some dose de-intensification would have been required to respect the constraints. For photons, the maximum allowed dose ranged from 15.0 to 20.63 Gy per fraction while for the 2 proton cases it would have been 18.75 or 20.63 Gy.

Conclusion: The results of this in-silico planning study suggests that IMPT might result in advantages compared to photon-based VMAT for HCC patients to be treated with ablative SBRT. In particular, the dosimetric characteristics of protons may avoid the need for dose de-escalation in a risk-adapted prescription regimen for those patients with lesions located in proximity of dose-limiting healthy structures. Depending on the selection thresholds, the number of patients eligible for treatment at the full dose can be significantly increased with protons.
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http://dx.doi.org/10.1177/1533033820980412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727039PMC
December 2020

Bilateral radiation recall pneumonitis during immunotherapy for an advanced renal cell carcinoma: A challenging case enhances the need for a multidisciplinary approach.

Eur J Cancer 2021 01 7;143:75-77. Epub 2020 Dec 7.

Department of Specialized, Experimental and Diagnostic Medicine, S.Orsola-Malpighi University Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy.

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http://dx.doi.org/10.1016/j.ejca.2020.10.024DOI Listing
January 2021

Treatment of patients with glioma during the COVID-19 pandemic: what we learned and what we take home for the future.

Neurosurg Focus 2020 12;49(6):E10

2Radiotherapy and Radiosurgery.

Objective: Coronavirus disease 2019 (COVID-19) has changed the way in which cancer is treated. Patients with high-grade glioma (HGG) are believed to be in a vulnerable category. The aim of this study was to describe the experience of a hub cancer center and the measures that were put in place for treatment of patients with newly diagnosed and recurrent glioma.

Methods: To prevent in-hospital contagion and preserve the safety of health professionals and patients, specific protocols and strict regulations were introduced. Physical distancing, use of surgical masks, and diligent hand hygiene were adopted. Each case was discussed in a multidisciplinary board meeting before treatment. All patient candidates for surgical procedures were tested for SARS-CoV-2 with a nasopharyngeal swab and a chest CT scan. Indications for surgery were the radiological suspicion of HGG in patients with a good performance status and/or the rapid and progressive occurrence of neurological deficits. Adjuvant treatments were performed only in cases of HGG. This therapy consisted of conventional fractional radiotherapy (RT; 60 Gy/30 fractions) with concomitant and adjuvant temozolomide chemotherapy (TMZCHT) in younger patients; in elderly patients, a short course of RT was employed (40.5 Gy/15 fractions). For recurrent HGG, treatments were assessed after a careful evaluation of the patient's general condition, neurological status, and risk of early impairment in neurological status if not treated. During simulation CT for the RT plan, each patient underwent a chest CT study. In cases in which an imaging study was suspicious for COVID-19 pneumonia, the patient was immediately isolated and rapidly underwent nasopharyngeal swab testing.

Results: Between March 1 and April 30, 2020, 23 HGGs were treated, and these cases are included in the present evaluation. Fifteen patients harboring newly diagnosed glioblastoma (GBM) underwent resection followed by a regimen of chemotherapy and RT, and 3 patients with newly diagnosed anaplastic oligodendroglioma underwent surgery followed by adjuvant RT. Five patients were treated for recurrent GBM, and they received surgery plus adjuvant RT. One patient in whom the simulation CT study was suspicious for COVID pneumonia was tested with a nasopharyngeal swab, which proved positive for SARS-CoV-2 infection. No patients contracted COVID-19 during hospitalization for surgery or during RT treatment. Corticosteroid therapy was administered to all patients beginning on the 1st day of RT.

Conclusions: The authors' experience during the COVID-19 pandemic showed that patients with HGG can be treated in the most effective manner without a compromise in safety. Careful selection criteria and a multidisciplinary evaluation are pivotal to assessing the optimal therapeutic strategy.
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http://dx.doi.org/10.3171/2020.9.FOCUS20704DOI Listing
December 2020

The 70-year-old newly diagnosed glioblastoma patients are older than the 65-year-old? Outcome evaluation of the two categories in a matched case control study with propensity score balancing.

Radiother Oncol 2021 03 25;156:49-55. Epub 2020 Nov 25.

Radiotherapy and Radiosurgery Department, Humanitas Clinical and Research Center-IRCCS, Rozzano (MI), Italy; Humanitas University, Department of Biomedical Sciences, Pieve Emanuele-Milan, Italy.

Background: The standard of care for elderly, newly-diagnosed glioblastoma patients consists, if feasible, of surgical resection followed by a short course of radiation therapy (RT) with concomitant and adjuvant temozolomide chemotherapy (TMZCHT). To date, the literature lacks of consistence in the definition of elderly, if older than 65 years, or 70 years. Aim of this study was to explore whether differences exist between these two cohorts, comparing outcomes using a propensity score matched analysis (PSM).

Materials And Methods: Two hundred twenty-one elderly newly diagnosed glioblastoma patients were included. All patients received surgery followed by RT with concurrent and adjuvant TMZCHT. The RT dose prescribed was 60 Gy/30 fractions for patients 65-69-year-old or 40.5 Gy/15 fractions for ≥70-year-old. After 1:1 matching there were 86 patients in each group. Distribution of covariates was adequately balanced in the matched data set.

Results: After PSM median PFS time, 1,2,3-year PFS rates were 10 months, 33.3%, 13.1%, and 6.6% for the 65-69-year group, 9 months, 34.7%, 11% and 4.8% for the ≥70-year group (p = 0.530). Median OS time, and 1,2,3-year OS rates were 14 months, 54.1%, 23.4%, 13.9% for the 65-69-year old group, and 12 months, 49.3%, 21.5%, 10% for the ≥70-year group (p = 0.357). No differences were recorded in relation to different groups of age.

Conclusions: The PSM analyses showed a similar outcome in 65-69-year old patients compared to older ones notwithstanding a more burdensome RT schedule. Hypofractionated RT treatment has to be considered also in this group of younger elderly, newly-diagnosed GBM patients.
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http://dx.doi.org/10.1016/j.radonc.2020.11.022DOI Listing
March 2021

Prognostic relevance of temporal muscle thickness as a marker of sarcopenia in patients with glioblastoma at diagnosis.

Eur Radiol 2020 Nov 17. Epub 2020 Nov 17.

Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090, Milan, Italy.

Objectives: Temporal muscle thickness (TMT) is a surrogate marker of sarcopenia, correlated with survival expectancy in patients suffering from brain metastases and recurrent or treated glioblastoma. We evaluated the prognostic relevance of TMT measured on brain MRIs acquired at diagnosis in patients affected by glioblastoma.

Methods: We retrospectively enrolled 51 patients in our Institution affected by methylated MGMT promoter, IDH1-2 wild-type glioblastoma, who underwent complete surgical resection and subsequent radiotherapy with concomitant and maintenance temozolomide, from January 1, 2015, to April 30, 2017. The last clinical/radiological follow-up date was set to September 3, 2019. TMT was measured bilaterally on reformatted post-contrast 3D MPRAGE images, acquired on our 3-T scanner no more than 2 days before surgery. The median, 25th, and 75th percentile TMT values were identified and population was subdivided accordingly; afterwards, statistical analyses were performed to verify the association among overall survival (OS) and TMT, sex, age, and ECOG performance status.

Results: In our cohort, the median OS was 20 months (range 3-51). Patients with a TMT ≥ 8.4 mm (median value) did not show a statistically significant increase in OS (Cox regression model: HR 1.34, 95% CI 0.68-2.63, p = 0.403). Similarly, patients with a TMT ≥ 9.85 mm (fourth quartile) did not differ in OS compared to those with TMT ≤ 7 mm (first quartile). The statistical analyses confirmed a significant association among TMT and sex (p = 0.0186), but none for age (p = 0.642) and performance status (p = 0.3982).

Conclusions: In our homogeneous cohort of patients with glioblastoma at diagnosis, TMT was not associated with prognosis, age, or ECOG performance status.

Key Points: • Temporal muscle thickness (TMT) is a surrogate marker of sarcopenia and has been correlated with survival expectancy in patients suffering from brain metastases and recurrent or treated glioblastoma. • We appraised the correlation among TMT and survival, sex, age at surgery, and performance status, measured on brain MRIs of patients affected by glioblastoma at diagnosis. • TMT did not show any significant correlation with prognosis, age at surgery, or performance status, and its usefulness might be restricted only to patients with brain metastases and recurrent or treated glioblastoma.
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http://dx.doi.org/10.1007/s00330-020-07471-8DOI Listing
November 2020

Critical Re-Evaluation of a Failure Mode Effect Analysis in a Radiation Therapy Department After 10 Years.

Pract Radiat Oncol 2021 May-Jun;11(3):e329-e338. Epub 2020 Nov 13.

Radiotherapy and Radiosurgery Department, Humanitas Clinical and Research Center-IRCCS, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy.

Purpose: Failure mode effect analysis (FMEA) is a proactive methodology that allows one to analyze a process, regardless of whether an adverse event occurs. In our radiation therapy (RT) department, a first FMEA was performed in 2009. In this paper we critically re-evaluate the RT process after 10 years and present it in terms of a lesson learned.

Methods And Materials: A working group (WG), led by a qualified clinical risk engineer, which included radiation oncologists, physicists, a radiation therapist, and a nurse, evaluated the possible failure modes (FMs) of the RT process. For each FM, the estimated frequency of occurrence (O, range 1-4), the expected severity of the damage (S, range 1-5), and the detectability lack (D, range 1-4) were scored. A risk priority number (RPN) was obtained as RPN = OxSxD. The data were compared with the 2009 edition.

Results: In the 2020 analysis, 67 FMs were identified (27 in the 2009 series). The absolute risk values of the previous 3 highest FMs were generally reduced. The patient identification risk (highest value in the 2009 analysis) was reduced from 48.0 to 6.9, becoming the 51st RPN score, thanks to a patient barcode recognition within the bunker. The 2020 highest risk values regarded: (i-2020) the patient's inadequate recollection and reporting of his/her medical history (ie, anamnesis) during the first medical examination and (ii-2020) the incorrect interpretation of tumor and normal tissue in computed tomography images. The WG proposed corrective actions.

Conclusions: In this single institution experience, the 10-year FMEA analysis showed a reduction in the previous higher RPN values thanks to the corrective actions taken. The new FMs and subsequent RPNs reveal the need for a continuous iterative improvement process.
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http://dx.doi.org/10.1016/j.prro.2020.11.002DOI Listing
November 2020

Knowledge-based intensity-modulated proton planning for gastroesophageal carcinoma.

Acta Oncol 2021 Mar 10;60(3):285-292. Epub 2020 Nov 10.

Radiotherapy and Radiosurgery Department, IRCSS, Humanitas Clinical and Research Center, Milan-Rozzano, Italy.

Purpose: To investigate the performance of a narrow-scope knowledge-based RapidPlan (RP) model, for optimisation of intensity-modulated proton therapy (IMPT) plans applied to patients with locally advanced carcinoma in the gastroesophageal junction.

Methods: A cohort of 60 patients was retrospectively selected; 45 were used to 'train' a dose-volume histogram predictive model; the remaining 15 provided independent validation. The performance of the RP model was benchmarked against manual optimisation. Quantitative assessment was based on several dose-volume metrics.

Results: Manual and RP-optimised IMPT plans resulted dosimetrically similar, and the planning dose-volume objectives were met for all structures. Concerning the validation set, the comparison of the manual vs RP-based plans, respectively, showed for the target (PTV): the homogeneity index was 6.3 ± 2.2 vs 5.9 ± 1.2, and V98% was 89.3 ± 2.9 vs 91.4 ± 2.2% (this was 97.2 ± 1.9 vs 98.8 ± 1.1 for the CTV). Regarding the organs at risk, no significant differences were reported for the combined lungs, the whole heart, the left anterior descending artery, the kidneys, the spleen and the spinal canal. The D for the left ventricle resulted in 40.3 ± 3.4 vs 39.7 ± 4.3 Gy(RBE). The mean dose to the liver was 3.4 ± 1.3 vs 3.6 ± 1.5 Gy(RBE).

Conclusion: A narrow-scope knowledge-based RP model was trained and validated for IMPT delivery in locally advanced cancer of the gastroesophageal junction. The results demonstrate that RP can create models for effective IMPT. Furthermore, the equivalence between manual interactive and unattended RP-based optimisation could be displayed. The data also showed a high correlation between predicted and achieved doses in support of the valuable predictive power of the RP method.
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http://dx.doi.org/10.1080/0284186X.2020.1845396DOI Listing
March 2021

Back to (new) normality-A CODRAL/AIRO-L survey on cancer radiotherapy in Lombardy during Italian COVID-19 phase 2.

Med Oncol 2020 Nov 4;37(11):108. Epub 2020 Nov 4.

Radiation Oncology Centre, Ospedale Sant'Anna, ASST Lariana, Como, Italy.

Background: Italy experienced one of the world's severest COVID-19 outbreak, with Lombardy being the most afflicted region. However, the imposed safety measures allowed to flatten the epidemic curve and hence to ease the restrictions and inaugurate, on the 4th of May 2020, the Italian phase (P) 2 of the pandemic. The present survey study, endorsed by CODRAL and AIRO-L, aimed to assess how radiotherapy (RT) departments in Lombardy have dealt with the recovery.

Materials And Methods: A questionnaire dealing with the management of pandemic was developed online and sent to all CODRAL Directors on the 10th of June 2020. Answers were collected in full anonymity one week after.

Results: All the 33 contacted RT facilities (100%) responded to the survey. Despite the scale of the pandemic, during P1 14 (42.4%) centres managed to safely continue the activity (≤ 10% reduction). During P2, 10 (30.3%) centres fully recovered and 14 (42.4%) reported an increase. Nonetheless, 6 (18.2%) declared no changes and, interestingly, 3 (9.1%) reduced activities. Overall, 21 centres (63.6%) reported suspected or positive cases within healthcare workforce since the beginning of the pandemic. Staff units were quarantined in 19 (57.6%) and 6 (18.2%) centres throughout P1 and P2, respectively. In the two phases, about two thirds centres registered positive or suspected cases amongst patients.

Conclusion: The study revealed a particular attention to anti-contagion measures and a return to normal or even higher clinical workload in most RT centres in Lombardy, necessary to carry out current and previously deferred treatments.
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http://dx.doi.org/10.1007/s12032-020-01434-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641253PMC
November 2020

Preliminary Results of a Randomized Study on Postmenopausal Women With Early Stage Breast Cancer: Adjuvant Hypofractionated Whole Breast Irradiation Versus Accelerated Partial Breast Irradiation (HYPAB Trial).

Clin Breast Cancer 2020 Sep 9. Epub 2020 Sep 9.

Radiotherapy and Radiosurgery Department, Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy; Humanitas University, Department of Biomedical Sciences, Milan, Italy.

Background: The purpose of this study was to report preliminary data of a randomized phase III trial comparing hypofractionated whole breast irradiation (HWBI) and accelerated partial breast irradiation (APBI) using volumetric modulated arc therapy (VMAT).

Material And Methods: The HYPAB trial enrolled postmenopausal women with biopsy-proven infiltrating breast cancer, clinically negative axilla, single T1 to T2 tumors, who were treated with breast-conserving surgery. Patients were randomized 1:1 after surgery to HWBI (40.5 Gy whole breast, 48.0 Gy to surgical bed, 15 fractions over 3 weeks) or APBI (30 Gy delivered in 5 fractions of 6 Gy given on alternate days on the surgical bed). Cosmetic outcome was the primary end point of the study.

Results: A total of 172 patients were enrolled. After a median follow-up of 36 months, 5 local failures and 3 locoregional failures were recorded, with no difference between the 2 treatment arms. Use of HWBI as compared with APBI was significantly correlated with increased incidence of overall (62% vs. 14%; P < .001) and grade 2 (18% vs. 1%; P < .001) acute skin toxicity. APBI was correlated with a lower incidence of overall late toxicity as compared with HWBI (18% vs. 41%; P = .001), but no significant difference was found in term of occurrence of grade 2 events (1% vs. 4%; P = NS). At comparative assessment between baseline and post-radiotherapy evaluation, impairment in cosmetic outcome was reported in 19 (11%) patients. Owing to premature closure of the study, no per-protocol comparison between the treatment arms was performed.

Conclusion: APBI with the VMAT technique is safe and feasible, with lower acute toxicity when compared with HWBI.
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http://dx.doi.org/10.1016/j.clbc.2020.09.004DOI Listing
September 2020

Brain metastases from primary colorectal cancer: is radiosurgery an effective treatment approach? Results of a multicenter study of the radiation and clinical oncology Italian association (AIRO).

Br J Radiol 2020 Dec 22;93(1116):20200951. Epub 2020 Oct 22.

Radiotherapy and Radiosurgery Department, Humanitas Clinical and Research Hospital-IRCCS, Rozzano (MI), Italy.

Objectives: The prognosis of brain metastatic colorectal cancer patients (BMCRC) is poor. Several local treatments have been used, but the optimal treatment choice remains an unresolved issue. We evaluated the clinical outcomes of a large series of BMCRC patients treated in several Italian centers using stereotactic radiosurgery (SRS).

Methods: 185 BMCRC patients for a total of 262 lesions treated were evaluated. Treatments included surgery followed by post-operative SRS to the resection cavity, and SRS, either single-fraction, then hypofractionated SRS (HSRS). Outcomes was measured in terms of local control (LC), toxicities, brain distant failure (BDF), and overall survival (OS). Prognostic factors influencing survival were assed too.

Results: The median follow-up time was 33 months (range 3-183 months). Surgery plus SRS have been performed in 28 (10.7%) cases, SRS in 141 (53.8%), and HSRS in 93 (35.5%). 77 (41.6%) patients received systemic therapy. The main total dose and fractionation used were 24 Gy in single fraction or 24 Gy in three daily fractions. Local recurrence occurred in 32 (17.3%) patients. Median, 6 months,1-year-LC were 86 months (95%CI 36-86), 87.2% ± 2.8, 77.8% ± 4.1. Median,6 months,1-year-BDF were 23 months (95%CI 9-44), 66.4% ± 3.9, 55.3% ± 4.5. Median,6 months,1-year-OS were 7 months (95% CI 6-9), 52.7% ± 3.6, 33% ± 3.5. No severe neurological toxicity occurred. Stage at diagnosis, Karnofsky Performance Status (KPS), presence and number of extracranial metastases, and disease-specific-graded-prognostic-assessment (DS-GPA) score were observed as conditioning survival.

Conclusion: SRS/HSRS have proven to be an effective local treatment for BMCRC. A careful evaluation of prognostic factors as well as a multidisciplinary evaluation is a valid aid to manage the optimal therapeutic strategy for CTC patients with BMs.

Advances In Knowledge: The prognosis of BMCRC is poor. Several local treatments was used, but optimal treatment choice remains undefined. Radiosurgery has proven to be an effective local treatment for BMCRC. A careful evaluation of prognostic factors and a multidisciplinary evaluation needed.
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http://dx.doi.org/10.1259/bjr.20200951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716018PMC
December 2020

Moderate hypofractionated radiotherapy for post-operative treatment of prostate cancer: long-term outcome and pattern of toxicity.

Strahlenther Onkol 2021 Feb 1;197(2):133-140. Epub 2020 Oct 1.

Humanitas Clinical and Research Center-IRCCS, Radiotherapy and Radiosurgery Dept., via Manzoni 56, 20089, Rozzano, Mi, Italy.

Objective: Postoperative radiotherapy (RT) is an established treatment for prostate cancer (PC). Though hypofractionation is commonly used for radical treatments, open issues still remain in the postoperative setting due to the lack of long-term data. Aim of this study was to evaluate long-term results of postoperative moderately hypofractionated RT (MHRT).

Methods: We conducted a retrospective analysis including PC patients treated with prostatectomy and postoperative MHRT delivered with volumetric modulated arc therapy (VMAT). Endpoints of the analysis included biochemical relapse-free survival (BRFS), distant metastases free-survival (DMFS), overall survival (OS), and pattern of acute and late toxicity.

Results: 181 patients were included. Pathological stage was classified as pT3a in 33.6% and pT3b in 30%. Median PSA value before RT was 0.23 ng/ml and median RT total dose was 70 Gy (65-74.2 Gy) in 25/28 fractions. With a median follow-up of 54.5 months, rates of BRFS at 3 and 5 years were 80.7 and 72.3%. ISUP grade group (HR 1.44, p = 0.015), pathological T stage (HR 2.03; p = 0.009), and pre-RT PSA >0.2 ng/ml (HR 2.64; p = 0.015) were correlated with BRFS. Three and 5‑year DMFS were 87.4 and 80.8%. ISUP grade group (HR 1.50; p = 0.011) and pre-RT PSA (HR 5.34; p = 0.001) were correlated with DMFS. Five (2.7%) and 3 (1.6%) patients reported late grade 3 GU and GI toxicity, respectively.

Conclusion: Our results confirm the long-term safety and efficacy of postoperative MHRT for PC.

Advances In Knowledge: The present paper demonstrates the long-term safety and efficacy of MHRT for postoperative prostate cancer. Reduction of treatment time in long-course radiotherapy has advantages in terms of both patients' quality of life and departmental organization.
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http://dx.doi.org/10.1007/s00066-020-01691-zDOI Listing
February 2021

Total marrow and total lymphoid irradiation in bone marrow transplantation for acute leukaemia.

Lancet Oncol 2020 10;21(10):e477-e487

Department of Radiotherapy and Radiosurgery, Humanitas Clinical and Research Hospital-IRCCS, Rozzano, Milan, Italy.

The use of total body irradiation as part of conditioning regimens for acute leukaemia is progressively declining because of concerns of late toxic effects and the introduction of radiation-free regimens. Total marrow irradiation and total marrow and lymphoid irradiation represent more targeted forms of radiotherapy compared with total body irradiation that have the potential to decrease toxicity and escalate the dose to the bone marrow for high-risk patients. We review the technological basis and the clinical development of total marrow irradiation and total marrow and lymphoid irradiation, highlighting both the possible advantages as well as the current roadblocks for widespread implementation among transplantation units. The exact role of total marrow irradiation or total marrow and lymphoid irradiation in new conditioning regimens seems dependent on its technological implementation, aiming to make the whole procedure less time consuming, more streamlined, and easier to integrate into the clinical workflow. We also foresee a role for computer-assisted planning, as a way to improve planning and delivery and to incorporate total marrow irradiation and total marrow and lymphoid irradiation in multi-centric phase 2-3 trials.
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http://dx.doi.org/10.1016/S1470-2045(20)30342-9DOI Listing
October 2020

Dose coverage impacts local control in ultra-central lung oligometastases treated with stereotactic radiotherapy.

Strahlenther Onkol 2021 May 24;197(5):396-404. Epub 2020 Sep 24.

Radiotherapy and Radiosurgery Department, Humanitas Clinical and Research Center, IRCSS, Via Manzoni 56, Rozzano, 20089, Italy.

Introduction: The use of Stereotactic Body Radiotherapy (SBRT) is controversial in Ultra-Central lung tumors, a subset of central lung tumors characterized by proximity to critical mediastinal structures. This is of interest in oligometastatic (≤3 metastases) patients, who can yield survival benefit from local treatments. The aim of our study is to assess the determinants of efficacy and toxicity in this setting.

Materials And Methods: Clinical and dosimetric parameters were reviewed in a cohort of oligometastatic patients treated with SBRT for ultra-central tumors. Local control rate (LC) and toxicity were assessed. Statistical Analysis was carried out to assess the impact of those predictors on local recurrence and adverse events.

Results: One-hundred-nine consecutive patients were included. A median Biologic Effective Dose (BED) of 105 (75-132) Gy10 was prescribed. At a median follow-up of 17 (range 3-78) months, 2-year LC was 87%. Improved LC was correlated to Planning Treatment Volume (PTV) covered by 95% of the prescription dose (V95% PTV) > 85% (HR 0.15, 95%CI 0.05-0.49, p = 0.0017) and to Gross Tumor Volume (GTV) < 90 cm (HR 0.2, 95%CI 0.07-0.56, p = 0.0021). Overall and grade ≥ 3 toxicity incidence was 20% and 5%, respectively. Patients experiencing acute and late toxicities received significantly higher dose to 1 cm (D1cm) of esophagus and lung volume receiving ≥5 Gy (V5Gy) (p = 0.016 and p = 0.013), and higher dose to 0.1 cm (D0.1cm) of heart (p = 0.036), respectively.

Conclusion: V95% PTV > 85% and GTV < 90 cm are independent predictors of LC. Dose to esophagus, lung and heart should be carefully assessed to minimize treatment-related toxicities.
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http://dx.doi.org/10.1007/s00066-020-01687-9DOI Listing
May 2021

Stereotactic body radiotherapy in hepatocellular carcinoma: patient selection and predictors of outcome and toxicity.

J Cancer Res Clin Oncol 2021 Mar 18;147(3):927-936. Epub 2020 Sep 18.

Radiotherapy and Radiosurgery Department, Humanitas Clinical and Research Center, IRCSS, Via Manzoni 56, 20089, Rozzano, Milan, Italy.

Introduction: Stereotactic Body Radiotherapy (SBRT) emerged as a valuable option in early to advanced-stage Hepatocellular Carcinoma (HCC) as defined by Barcelona Clinic Liver Cancer (BCLC) system. The aim of our study is to evaluate SBRT in HCC patients and to identify predictors of outcome and toxicity.

Materials And Methods: A retrospective review of HCC patients treated at our Institution between November 2011 and December 2018 was carried out. SBRT was delivered in 3-10 fractions to a median Biologically Effective Dose (BED) of 103 Gy.

Results: SBRT was performed in 128 patients to 217 HCC localizations, accounting for 142 treatment courses. BCLC stage was A, B, C in, respectively, 40 (31%), 72 (56%) and 16 (13%) patients. Local Control (LC), Progression Free Survival (PFS) and Overall Survival (OS) at 2 years were, respectively: 78%, 15% and 58%. LC was influenced by BED10 > 120 Gy (Hazard Ratio, HR: 0.08, 95% CI 0.01-0.59; p = 0.013) and size ≥ 3 cm (HR: 2.71, 95% CI 1.10-6.66; p = 0.03). BCLC stage was correlated to PFS (median 14 vs 12 vs 5 months, p = 0.012). In BCLC stage A-B disease (n = 112), LC was associated with improved survival (median 30 months vs not reached, p = 0.036). Acute and late toxicity rate was 26% (n = 37) and 8% (n = 11). Patients with BCLC B-C stage disease showed increased acute toxicity (HR: 2.9, 95% CI 1.10-7.65; p = 0.032).

Conclusion: Delivery of ablative doses > 120 Gy and tumor size are determinants of LC. Prolonged PFS and improved OS can be obtained in BCLC A-B patients. Grade 3 liver dysfunction is infrequent.
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http://dx.doi.org/10.1007/s00432-020-03389-2DOI Listing
March 2021

Stereotactic Body Radiation Therapy for Intermediate-risk Prostate Cancer With VMAT and Real-time Electromagnetic Tracking: A Phase II Study.

Am J Clin Oncol 2020 09;43(9):628-635

Departments of Radiotherapy and Radiosurgery.

Objectives: Stereotactic body radiation treatment represents an intriguing therapeutic option for patients with early-stage prostate cancer. In this phase II study, stereotactic body radiation treatment was delivered by volumetric modulated arc therapy with flattening filter free beams and was gated using real-time electromagnetic transponder system to maximize precision of radiotherapy and, potentially, to reduce toxicities.

Materials And Methods: Patients affected by histologically proven prostate adenocarcinoma and National Comprehensive Cancer Network (NCCN) intermediate class of risk were enrolled in this phase II study. Beacon transponders were positioned transrectally within the prostate parenchyma 7 to 10 days before simulation computed tomography scan. The radiotherapy schedule was 38 Gy in 4 fractions delivered every other day. Toxicity assessment was performed according to Common Terminology Criteria for Adverse Events (CTCAE), v4.0.

Results: Thirty-six patients were enrolled in this study. Median initial prostate-specific antigen was 7.0 ng/mL (range: 2.3 to 14.0 ng/mL). Median nadir-prostate-specific antigen after treatment was 0.2 ng/mL (range: 0.006 to 4.8 ng/mL). A genitourinary acute toxicity was observed in 21 patients (dysuria grade [G] 1: 41.7%, G2: 16.7%). Gastrointestinal acute toxicity was found in 9 patients (proctitis G1: 19.4%, G2: 5.6%). Late toxicity was mild (genitourinary toxicity G1: 30.6%; G2: 8.3%; gastrointestinal toxicity G1: 13.9%; G2: 19.4%). At a median follow-up time of 41 months, 3 biochemical recurrences were observed (2 local recurrences, 1 distant metastasis). Three-year biochemical recurrence-free survival was 89.8% (International Society of Urologic Pathology Grade Group 2: 100%, Grade Group 3: 77.1%, P=0.042).

Conclusion: Ultrahypofractionated radiotherapy, delivered with flattening filter free-volumetric modulated arc therapy and gated by electromagnetic transponders, is a valid option for intermediate-risk prostate cancer.
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http://dx.doi.org/10.1097/COC.0000000000000721DOI Listing
September 2020

Is IDH status the only factor predicting prognosis in newly diagnosed anaplastic glioma patients? Outcome evaluation and prognostic factor analysis in a single-institution large series.

J Neurosurg 2020 Sep 4:1-14. Epub 2020 Sep 4.

Departments of1Radiotherapy and Radiosurgery.

Objective: Anaplastic gliomas (AGs) are an extremely heterogeneous group of primary brain tumors. More recently, new discoveries have indicated that isocitrate dehydrogenase (IDH) mutation status is the most important parameter predicting survival. The primary aim of the present analysis was to identify prognostic factors, other than IDH status, that eventually impact survival.

Methods: Patients with available clinical, imaging, and molecular profile data who were amenable to resection were evaluated. The extent of resection (EOR) was defined as gross-total resection (GTR), near-total resection (NTR), subtotal resection (STR), or partial resection (PR). Residual tumor volume (RTV) was quantified. Following surgery, patients received adjuvant chemotherapy alone, radiation therapy plus concomitant and adjuvant temozolomide (TMZ), or sequential radio-chemotherapy. Clinical outcome was evaluated by neurological examination and MRI 1 month after treatment and every 4 months thereafter. Tumor progression was defined according to the Response Assessment in Neuro-Oncology (RANO) working group.

Results: Among 402 patients referred to the authors' institution for AG, 142 were included in the present analysis. Eighty-eight (62%) were male and 54 (38%) were female, with a median age of 43 years (range 19-70 years). At admission, most patients had a Karnofsky Performance Scale score of 90-100 (84.5%) and were symptomatic (93.7%). Forty-eight (33.8%) patients had newly diagnosed anaplastic oligodendrogliomas (AOs), and 94 (66.2%) had anaplastic astrocytomas (AAs). Most of them had mutant IDH tumors (67.6%) and methylated O6-methylguanine-DNA-methyltransferase (MGMT) promoter status (71.8%). GTR was performed in more than half of the patients (56.3%). RTV was detected in 83 (58.5%) patients. Following surgery, 72 (50.7%) patients received radiotherapy with concomitant and adjuvant TMZ, 48 (33.8%) received sequential radio-chemotherapy, and 22 (15.5%) received adjuvant chemotherapy alone. The median follow-up time was 40 months (range 16-146 months). The median PFS time and the 1-, 3-, and 5-year PFS rates were 35 months (95% CI 27-76) and 78.9% ± 3.4%, 49.7% ± 4.6%, and 42.7% ± 5.4%, respectively. The median OS time and the 1-, 3-, and 5-year OS rates were 91 months (95% CI 66-95) and 90.1% ± 2.5%, 70.9% ± 4.2%, and 61.8% ± 4.9%, respectively. Prognostic factors predicting survival other than molecular profile were the EOR and the RTV (p < 0.0001). Sequential radio-chemotherapy was the more effective treatment administered.

Conclusions: In addition to IDH status, EOR and the RTV have proved to statistically impact survival. The pivotal role of adjuvant radiotherapy has been recorded in all AG patients, regardless of tumor features.
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http://dx.doi.org/10.3171/2020.5.JNS201116DOI Listing
September 2020

Hypofractionated Whole Breast Irradiation and Simultaneous Integrated Boost in Large-breasted Patients: Long-term Toxicity and Cosmesis.

Clin Breast Cancer 2020 12 20;20(6):527-533. Epub 2020 Jun 20.

Radiotherapy and Radiosurgery Department, Humanitas Clinical and Research Center IRCCS, Milan-Rozzano, Italy; Department of Biomedical Sciences, Humanitas University, Milan-Pieve Emanuele, Italy.

Introduction: The purpose of this study was to evaluate the impact of breast size on long-term toxicity and cosmesis in patients with breast cancer treated with hypofractionated simultaneous integrated boost (SIB) using volumetric modulated arc therapy (VMAT).

Patients And Methods: Patients with early stage breast cancer were treated with 3-week hypofractionated SIB-VMAT to the whole breast (40.5 Gy) and tumor bed (48 Gy). Two cohorts were identified: small/medium- (< 1000 cm) and large- (> 1000 cm) breasted patients. Acute and late (at 2 and 5 years) skin toxicity and cosmetic data were analyzed. Univariate and multivariate analysis evaluated associations between toxicity and dosimetric/anatomical variables.

Results: From August 2010 to March 2017, a total of 1160 patients were treated; 831 had at least 2 years of follow-up and were analyzed. Treated skin area (TSA) receiving at least 20 Gy > 400 cm and V > 5 cm were significant predictors for acute skin toxicity. Multivariate analysis at 2 years was significant for boost volume > 70 cm, TSA > 400 cm, and breast size > 1500 cm. At 5 year analysis (352 patients), none of the analyzed variables was significant. For cosmetic outcome, only the breast size (> 1000 cm) and the boost size > 70 cm at 2 and 5 years, respectively, confirmed significance.

Conclusions: The TSA > 400 cm resulted as a significant predictor of both acute and late skin toxicity at 2 years; however, at 5 years, no breast size or dosimetric parameter suggested indications for increased toxicity. A worse cosmetic outcome was recorded at the 2-year follow up for large breasts, but was not confirmed at the 5-year follow-up. These long-term data suggest that hypofractionated SIB-VMAT is a viable modality also in large-breasted patients.
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http://dx.doi.org/10.1016/j.clbc.2020.06.005DOI Listing
December 2020

Present and Future of De-intensification Strategies in the Treatment of Oropharyngeal Carcinoma.

Curr Oncol Rep 2020 Jul 9;22(9):91. Epub 2020 Jul 9.

Department of Otorhinolaryngology, Humanitas Clinical and Research Center-IRCCS, Viale Manzoni 56, Rozzano, MI, Italy.

Purpose Of Review: The treatment of patients with squamous cell carcinoma of the oropharynx (OPSCC) remains controversial. HPV positivity is widely accepted as a favorable prognostic factor, and HPV+ OPSCC is considered a distinct pathological entity with dedicated NCCN guidelines and may deserve a more personalized therapeutic strategy. The possibility to reduce surgical invasiveness and acute and late toxicity of radiotherapy/chemotherapy has led to the new concept of de-escalation treatment strategies. In particular, several de-intensified approaches have been investigated with the aim to give patients less toxic treatments, while maintaining comparable results in terms of disease's control and survival. The aim of the present review is to systematically illustrate the current status of research in de-intensification surgical and non-surgical strategies in the treatment of the OPSCC.

Recent Findings: We categorized all completed and on-going trials on the basis of the specific de-escalated treatment protocol. Several de-intensified approaches have been investigated with the aim to give patients less toxic treatments, while maintaining comparable results in terms of disease's control and survival. Considering the conflicting results reported so far by preliminary studies, it is necessary to wait for the final results of the on-going trials to better clarify which is the best de-intensified strategy and which patients would really benefit from it.
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http://dx.doi.org/10.1007/s11912-020-00948-1DOI Listing
July 2020

Liver Metastases-directed Therapy in the Management of Oligometastatic Breast Cancer.

Clin Breast Cancer 2020 12 13;20(6):480-486. Epub 2020 May 13.

Department of Radiotherapy and Radiosurgery, Humanitas Clinical and Research Center - IRCCS, Rozzano, Milano, Italy; Department of Biomedical Sciences, Humanitas University, Rozzano (Milano), Italy.

Introduction: In the context of metastatic breast cancer, dissemination to the liver is a frequent occurrence. We aimed to evaluate the outcome and toxicity of metastatic breast cancer with liver oligometastases treated with metastases-directed therapies (MDTs), including surgery, stereotactic body radiation therapy, or thermal ablation (radiofrequency or microwaves).

Patients And Methods: We included patients with diagnosis of 1 to 5 liver metastases. Selection criteria included also age > 18 years; Eastern Cooperative Oncology Group performance status 0 to 2; absence of extra-hepatic disease or other controlled metastatic sites. Endpoints were liver progression-free survival (LPFS), progression-free survival (PFS), and overall survival.

Results: A total of 72 patients were included. Previous local treatments were performed in 13 (18.1%) patients, whereas systemic therapy was used in 81.9% of cases. Treatment of choice was stereotactic body radiation therapy in 54 (75%) patients followed by surgery (13 patients; 18%) and thermal ablation (5 patients; 7%). With a median follow-up of 26.2 months, LPFS at 1 and 2 years was 52.4% and 38.8%, respectively. The number of metastases predicted LPFS (hazard ratio [HR], 1.70; P = .004). Rates of PFS were 38.7% and 22% at 1 and 2 years, respectively. Systemic therapy before MDT (HR, 2.89; P = .016) was correlated with PFS. Overall survival at 1 and 2 years was 95.5% and 76.9%, respectively. Human epidermal growth factor receptor 2 status correlated with survival (HR, 1.82; P = .010).

Conclusion: Combination of systemic therapy with liver MDT in oligometastatic breast cancer results in durable disease control in a significant proportion of patients. Tumor biology, prior treatment, and extent of disease may be useful to guide the decision to add MDT to standard therapy.
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http://dx.doi.org/10.1016/j.clbc.2020.05.006DOI Listing
December 2020

Assessing the role of Stereotactic Body Radiation Therapy in a large cohort of patients with lymph node oligometastases: Does it affect systemic treatment's intensification?

Radiother Oncol 2020 09 25;150:184-190. Epub 2020 Jun 25.

Department of Radiotherapy and Radiosurgery, Humanitas Clinical and Research Center - IRCCS, Milano, Italy; Humanitas University, Department of Biomedical Sciences, Milano, Italy.

Background And Purpose: Lymph nodes (LN) are common site of oligometastases and stereotactic body radiation therapy (SBRT) represents an effective ablative treatment. Aim of this study was to analyze a large cohort of nodal oligometastases treated with SBRT to identify impact on systemic therapy intensification, pattern of recurrence, and predictive factors.

Materials And Methods: We included patients with a maximum of 5 oligometastases. Concomitant treatments were allowed. Patients were treated with Volumetric Modulated Arc Therapy (VMAT) and end points were local control of treated metastases (LC), locoregional nodal control (LRNC), distant nodal control (DNC), distant metastases free survival (DMFS), overall survival (OS) and freedom from treatment intensification (FFTI).

Results: 418 LN were treated in 278 patients with 327 SBRT treatments. Patients were more commonly affected by colorectal (20.9%) and prostate cancer (17.99%). Most represented schedule was 45 Gy in 6 fractions, with a median BED10 of 78.75 Gy. After median follow-up of 15.1 months, LC at 1 and 2 years were 87.2% and 76.8%, respectively. Prostate primary tumor, small volume, oligorecurrence, and BED10 ≥75 Gy were associated with higher LC. One and 2 years FFTI were 82.8% and 74.5%; in patients reporting intensification of systemic therapy, median time was 8.43 months, while for patients who repeated SBRT, median FFTI was 14.6 months. Rates of LRNC at 1 and 2 years were 70.9% and 57.6%, and DNC were 82.0% and 77.9%.

Conclusion: With the present analysis, we confirmed on a large cohort the benefit from SBRT on lymph node oligometastases in multidisciplinary management. Combination of SBRT with new systemic therapies, including immunotherapy and targeted therapy, should be investigated to reduce the risk of progression out of the field of irradiation.
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http://dx.doi.org/10.1016/j.radonc.2020.06.029DOI Listing
September 2020

Multimodality imaging of adult rhabdomyosarcoma: the added value of hybrid imaging.

Br J Radiol 2020 Aug 26;93(1112):20200250. Epub 2020 Jun 26.

Medical Oncology and Hematology Unit, Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy.

Rhabdomyosarcoma (RMS) represents more than 50% of paediatric soft tissue tumours. Conversely, it is extremely rare among adults, where it shows peculiar biological and clinical features that are still poorly investigated. RMS patients should be referred to a Sarcoma Centre, where the contribution of experienced radiologists plays a relevant role in the diagnostic assessment of the disease, including precise localisation, staging, image-guided biopsy, response evaluation after treatment and follow-up. Besides CT and MRI, hybrid imaging including positron emission tomography (PET)/CT and PET/MRI are giving an increasing contribution to provide functional insights about tumour biology and to improve the diagnostic accuracy of the imaging work-up. This review paper provides a revision of the pathology, clinical and radiological features of adult RMS, with a particular focus on the growing role of hybrid PET-based imaging.
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http://dx.doi.org/10.1259/bjr.20200250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446015PMC
August 2020