Publications by authors named "Giuseppe Fanetti"

35 Publications

Prognostic Nutritional Index Predicts Toxicity in Head and Neck Cancer Patients Treated with Definitive Radiotherapy in Association with Chemotherapy.

Nutrients 2021 Apr 13;13(4). Epub 2021 Apr 13.

Division of Radiotherapy, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy.

Background: The Prognostic Nutritional Index (PNI) is a parameter of nutritional and inflammation status related to toxicity in cancer treatment. Since data for head and neck cancer are scanty, this study aims to investigate the association between PNI and acute and late toxicity for this malignancy.

Methods: A retrospective cohort of 179 head and neck cancer patients treated with definitive radiotherapy with induction/concurrent chemotherapy was followed-up (median follow-up: 38 months) for toxicity and vital status between 2010 and 2017. PNI was calculated according to Onodera formula and low/high PNI levels were defined according to median value. Odds ratio (OR) for acute toxicity were calculated through logistic regression model; hazard ratios (HR) for late toxicity and survival were calculated through the Cox proportional hazards model.

Results: median PNI was 50.0 (interquartile range: 45.5-53.5). Low PNI was associated with higher risk of weight loss > 10% during treatment (OR = 4.84, 95% CI: 1.73-13.53 for PNI < 50 versus PNI ≥ 50), which was in turn significantly associated with worse overall survival, and higher risk of late mucositis (HR = 1.84; 95% CI:1.09-3.12). PNI predicts acute weight loss >10% and late mucositis.

Conclusions: PNI could help clinicians to identify patients undergoing radiotherapy who are at high risk of acute and late toxicity.
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http://dx.doi.org/10.3390/nu13041277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070136PMC
April 2021

Distant metastasis time to event analysis with CNNs in independent head and neck cancer cohorts.

Sci Rep 2021 Mar 19;11(1):6418. Epub 2021 Mar 19.

Department of Radiation Oncology, University Hospital, LMU Munich, Munich, 81377, Germany.

Deep learning models based on medical images play an increasingly important role for cancer outcome prediction. The standard approach involves usage of convolutional neural networks (CNNs) to automatically extract relevant features from the patient's image and perform a binary classification of the occurrence of a given clinical endpoint. In this work, a 2D-CNN and a 3D-CNN for the binary classification of distant metastasis (DM) occurrence in head and neck cancer patients were extended to perform time-to-event analysis. The newly built CNNs incorporate censoring information and output DM-free probability curves as a function of time for every patient. In total, 1037 patients were used to build and assess the performance of the time-to-event model. Training and validation was based on 294 patients also used in a previous benchmark classification study while for testing 743 patients from three independent cohorts were used. The best network could reproduce the good results from 3-fold cross validation [Harrell's concordance indices (HCIs) of 0.78, 0.74 and 0.80] in two out of three testing cohorts (HCIs of 0.88, 0.67 and 0.77). Additionally, the capability of the models for patient stratification into high and low-risk groups was investigated, the CNNs being able to significantly stratify all three testing cohorts. Results suggest that image-based deep learning models show good reliability for DM time-to-event analysis and could be used for treatment personalisation.
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http://dx.doi.org/10.1038/s41598-021-85671-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979766PMC
March 2021

Adjuvant radiotherapy and radioiodine treatment for locally advanced differentiated thyroid cancer: systematic review and meta-analysis.

Tumori 2021 Mar 16:300891621996817. Epub 2021 Mar 16.

Radiation Oncology, Department of Biomedicine and Prevention, University of Rome "Tor Vergata," Rome, Italy.

Background: Treatment for locally advanced differentiated thyroid cancer is surgery followed by radioiodine while the role of adjuvant external beam radiotherapy (EBRT) is debated.

Methods: The panel of the Italian Association of Radiotherapy and Clinical Oncology developed a clinical recommendation on the addition of EBRT to radioiodine after surgery for locally advanced differentiated thyroid cancer by using the Grades of Recommendation, Assessment, Development, and Evaluation methodology and the Evidence to Decision framework. A systematic review with meta-analysis about this topic was conducted with a focus on outcome of benefits and toxicity.

Results: Locoregional control was improved by EBRT while no considerable toxicity impact was reported.

Conclusion: The panel judged uncertain the benefit/harms balance; final recommendation was conditional both for EBRT + radioiodine and radioiodine alone in the adjuvant setting.
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http://dx.doi.org/10.1177/0300891621996817DOI Listing
March 2021

Does an immobilization mask have added value during planning magnetic resonance imaging for stereotactic radiotherapy of brain tumours?

Phys Imaging Radiat Oncol 2020 Jan 6;13:7-13. Epub 2020 Mar 6.

UMC Utrecht, Department of Radiation Oncology, Utrecht, The Netherlands.

Background And Purpose: When using an immobilization mask, a magnetic resonance imaging (MRI) head receive coil cannot be used and patients may experience discomfort during the examination. We therefore wish to assess the added value of an immobilization mask during all MRI scans intended for cranial stereotactic radiotherapy (SRT) planning.

Materials And Methods: An MRI was acquired with and without a thermoplastic immobilization mask in ten patients eligible for SRT. A planning computed tomography (CT) scan was also made, to which the two MRIs were independently registered. Additionally, the MRI without immobilization was registered to the MRI in mask. On each sequence, gross tumour volume (GTV), the right eye, brain stem and chiasm were delineated. The absolute differences in centre-of-gravity coordinates and Dice coefficients of the volumes of the delineated structures between the two MRIs were compared.

Results: Differences in GTV volume between the two MRIs were low, with median Dice coefficients between 0.88 and 0.91. Similarly, the median absolute differences in centre-of-gravity coordinates between the GTVs, organs at risk and landmarks delineated on the two MRIs were within 0.5 mm. The 95% confidence intervals of the median absolute differences in the three GTV coordinates was within 1 mm, which corresponds to the target volume safety margin used to account for possible errors during the SRT treatment chain.

Conclusions: The effect of scanning a patient without the immobilization mask falls within acceptable bounds of error for the geometrical accuracy of the SRT treatment chain. Consequently, placing the head in treatment position during all MRI scans for patients undergoing radiotherapy of brain metastasis is deemed unnecessary.
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http://dx.doi.org/10.1016/j.phro.2020.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807597PMC
January 2020

A pre-operative prognostic score for the selection of patients for salvage surgery after recurrent head and neck squamous cell carcinomas.

Sci Rep 2021 Jan 12;11(1):502. Epub 2021 Jan 12.

Division of Otolaryngology, General Hospital "Santa Maria Degli Angeli", Pordenone, Italy.

Salvage surgery in recurrent head and neck squamous cell carcinoma has a poor outcome, both in terms of survival and quality of life. Therefore, the identification of pre-operative prognostic factors to improve the selection of patients who could benefit the most from salvage surgery is clinically relevant. The present study is a single-center retrospective analysis of 164 patients treated with salvage surgery after recurrence of head and neck cancer. Progression free survival and overall survival were calculated through Kaplan-Meier method. Hazard risk (HR) and corresponding confidence intervals (CI) were estimated through Cox proportional hazard model, adjusting for potential confounders. Significant predictors were combined into a prognostic score, attributing one point to each factor. Progression-free survival and overall survival were respectively 50.3% and 56.5% at 2 years, and 36.6% and 44.2% at 5 years. Four pre-operative factors were independently associated with poor prognosis: age > 70 years (HR = 2.18; 95% CI 1.27-3.73), initial stage IV (HR = 2.37; 95% CI 1.18-4.76), disease free interval < 12 months (HR = 1.72; 95% CI 1.01-2.94), and loco-regional recurrence (HR = 2.22; 95% CI 1.22-4.04). No post operative factor was associated with oncologic outcomes. Patients with 3-4 unfavorable factors showed a 5-year overall survival of 0.0% compared to 65.7% in those with 0-1 unfavorable factors (HR = 5.61; 95% CI 2.89-10.92). Despite the low number of patients, 3-4 unfavorable factors were associated to worse prognosis in all sub-sites. In conclusion, age > 70 years, initial stage IV, disease-free interval < 12 months, and loco-regional recurrence are strong independent pre-operative predictors of poor outcome in patients undergoing salvage surgery. Patients with two or more of these factors should be informed about the low success rate after salvage surgery and alternative treatments should be considered.
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http://dx.doi.org/10.1038/s41598-020-79759-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804332PMC
January 2021

Radical Hemithoracic Radiotherapy Versus Palliative Radiotherapy in Non-metastatic Malignant Pleural Mesothelioma: Results from a Phase 3 Randomized Clinical Trial.

Int J Radiat Oncol Biol Phys 2021 Apr 28;109(5):1368-1376. Epub 2020 Nov 28.

Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.

Purpose: We conducted a phase 3 randomized clinical trial to assess whether radical hemithoracic radiation therapy (RHR) compared with palliative radiation therapy (PR) can achieve overall survival (OS) advantages in patients with malignant pleural mesothelioma (MPM).

Methods And Materials: From August 2014 to May 2018, patients with histologically diagnosed nonmetastatic MPM, who underwent nonradical lung-sparing surgery and chemotherapy (CHT), were randomly assigned (1:1) to receive RHR or PR. RHR total dose to the involved pleural cavity was 50 Gy in 25 fractions, and the gross residual disease received a simultaneous integrated boost of 60 Gy. The primary endpoint was OS. Secondary endpoints were local control, distant metastasis-free survival, progression-free survival, and acute and late toxicity rates. A sample size of 108 patients considering a type I error (α) of 0.05 and a statistical power of 80% was calculated to prove that RHR could improve the 2-year OS. OS was estimated with the Kaplan-Meier method and the log-rank test (2-sided) tested differences between arms. The univariate and multivariate analyses were performed using Cox proportional hazard model. Possible prognostic factors investigated: age, sex, performance status, lung surgery, gross residual disease, and histology.

Results: One hundred eight patients were randomized: 53 to the PR arm and 55 to the RHR arm. Median follow-up was 14.6 months. The 2-year OS rate was 58% in the RHR arm versus 28% in the PR arm (hazard ratio, 0.54; 95% confidence interval, 0.31-0.95; P = .031). In the RHR arm: 11 patients experienced acute toxicity grade ≥3, 17 patients had grade 3 to 4 late toxicity. Nine patients experience a grade ≥2 pneumonitis, including 1 patient with grade 5.

Conclusions: RHR significantly improves survival in patients with MPM treated with nonradical lung-sparing surgery and CHT compared with palliative treatments, although it is associated with a nonnegligible toxicity profile.
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http://dx.doi.org/10.1016/j.ijrobp.2020.11.057DOI Listing
April 2021

Partial prostate re-irradiation for the treatment of isolated local recurrence of prostate cancer in patients previously treated with primary external beam radiotherapy: short-term results of a monocentric study.

Neoplasma 2021 Jan 7;68(1):216-226. Epub 2020 Oct 7.

Department of Radiation Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.

Many different therapeutic options are available for locally recurrent prostate cancer (PCa). However, standard treatment has not yet been established. We conducted a partial prostate re-irradiation (PPR) program for the treatment of isolated and limited-size intraprostatic recurrences, in patients who previously underwent external beam radiation therapy (EBRT) as primary treatment for prostatic cancer (PCa). The analysis of this experience in terms of feasibility, toxicity, and efficacy is reported. The inclusion criteria of this retrospective analysis were: previous definitive EBRT, evidence of biochemical recurrence, radiological detection of isolated local relapse, and PPR as local salvage therapy. Gastrointestinal (GI) and genitourinary (GU) toxicities were registered according to the RTOG/EORTC criteria. Between July 2012 and May 2019, 44 patients were treated with PPR. All patients completed the planned treatment. The median follow-up was 25.4 months. Tumor progression was observed in 18 patients (40.9%). Two-year local control, biochemical failure-, and clinical relapse-free survival rates were 90.1%, 58.3%, and 67.9%, respectively. The occurrence of biochemical failure after PPR is lower for patients with the time interval between the primary EBRT and first biochemical failure >4 years; local control results strongly associated with a biologically effective dose (BED) at first EBRT >177 Gy. No acute grade 3 or greater toxic events were observed. Two late grade 3 GU toxicities were reported. Although retrospective in design, our study indicates that PPR appears as a feasible, well-tolerated, and effective salvage treatment for isolated local PCa recurrence. Long term data are required in order to confirm these results.
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http://dx.doi.org/10.4149/neo_2020_200622N651DOI Listing
January 2021

A snapshot on radiotherapy for head and neck cancer patients during the COVID-19 pandemic: a survey of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) head and neck working group.

Radiol Med 2021 Feb 6;126(2):343-347. Epub 2020 Oct 6.

National Center of Oncological Hadrontherapy (Fondazione CNAO), Strada Campeggi, 53, 27100, Pavia, Italy.

Objectives: The objective of the paper was to assess real-life experience in the management of head and neck cancer (HNC) patients during the COVID-19 pandemic in radiotherapy departments and to evaluate the variability in terms of adherence to American Society of Radiation Oncology (ASTRO) and European Society for Radiotherapy and Oncology (ESTRO) recommendations.

Materials And Methods: In May 2020, an anonymous 30-question online survey, comparing acute phase of outbreak and pre-COVID-19 period, was conducted. Two sections exploited changes in general management of HNC patients and different HNC primary tumors, addressing specific statements from ASTRO ESTRO consensus statement as well.

Results: Eighty-eight questionnaires were included in the demographic/clinical workflow analysis, and 64 were analyzed for treatment management. Forty-eight percent of radiotherapy departments became part of oncologic hubs. First consultations reduced, and patients were addressed to other centers in 33.8 and 18.3% of cases, respectively. Telematic consultations were used in 50% of follow-up visits and 73.9% of multidisciplinary tumor board discussions. There were no practical changes in the management of patients affected by different primitive HNCs. Hypofractionation was not favored over conventional schedules.

Conclusions: Compared to pre-COVID era, the clinical workflow was highly re-organized, whereas there were no consistent changes in RT indications and schedules.
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http://dx.doi.org/10.1007/s11547-020-01296-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538045PMC
February 2021

IMRT versus 2D/3D conformal RT in oropharyngeal cancer: A review of the literature and meta-analysis.

Oral Dis 2020 Aug 18. Epub 2020 Aug 18.

Division of Radiotherapy, IEO, European Institute of Oncology IRCCS, Milan, Italy.

Based on literature, intensity-modulated radiation therapy (IMRT) provides less related toxicity compared with conventional 2D/3D-RT with no impact on oncological outcomes for oropharyngeal cancer. The aim of this systematic review and meta-analysis is to assess whether IMRT might provide similar clinical outcomes with reduced related toxicity in comparison with conventional 2D/3D RT in patients treated for clinically advanced oropharyngeal cancer (OPC). Inclusion criteria for paper selection included: squamous OPC patients, treatment performed by concomitant CRT or RT alone, four treatment performed for curative intent, and presence of clinical outcome of interest, namely, overall survival (OS) and disease-free survival (DFS) and full paper available in English. Acute and late toxicities were retrieved together with OS and DFS. Crude relative risk estimates of relapse and death comparing 2D/3D-RT versus IMRT were calculated from tabular data, extracting events at 2-3 years of follow-up. Eight studies were selected. Six of them were included in the meta-analysis considering summary relative risk. Considering both acute and late toxicities, the considered studies evidenced advantages for IMRT populations, with the 2D/3D-RT population showing higher frequencies than the IMRT one. No statistical difference between IMRT and 2D/3D-RT in terms of death (SRR = 0.93, 95% CI: 0.83-1.04 with no heterogeneity I  = 0%) and relapse (SRR = 0.92, 95% CI: 0.83-1.03, with no heterogeneity I  = 0%) was found. Results of our study suggest the improvement in the therapeutic index with IMRT with evidenced reduced toxicity without any worsening in clinical outcome when compared to 2D/3DCRT.
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http://dx.doi.org/10.1111/odi.13599DOI Listing
August 2020

Head and neck radiotherapy amid the COVID-19 pandemic: practice recommendations of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

Med Oncol 2020 Aug 17;37(10):85. Epub 2020 Aug 17.

Department of Radiotherapy, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy.

Management of patients with head and neck cancers (HNCs) is challenging for the Radiation Oncologist, especially in the COVID-19 era. The Italian Society of Radiotherapy and Clinical Oncology (AIRO) identified the need of practice recommendations on logistic issues, treatment delivery and healthcare personnel's protection in a time of limited resources. A panel of 15 national experts on HNCs completed a modified Delphi process. A five-point Likert scale was used; the chosen cut-offs for strong agreement and agreement were 75% and 66%, respectively. Items were organized into two sections: (1) general recommendations (10 items) and (2) special recommendations (45 items), detailing a set of procedures to be applied to all specific phases of the Radiation Oncology workflow. The distribution of facilities across the country was as follows: 47% Northern, 33% Central and 20% Southern regions. There was agreement or strong agreement across the majority (93%) of proposed items including treatment strategies, use of personal protection devices, set-up modifications and follow-up re-scheduling. Guaranteeing treatment delivery for HNC patients is well-recognized in Radiation Oncology. Our recommendations provide a flexible tool for management both in the pandemic and post-pandemic phase of the COVID-19 outbreak.
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http://dx.doi.org/10.1007/s12032-020-01409-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430932PMC
August 2020

Beyond MicroRNAs: Emerging Role of Other Non-Coding RNAs in HPV-Driven Cancers.

Cancers (Basel) 2020 May 15;12(5). Epub 2020 May 15.

Division of Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, 33081 Aviano (PN), Italy.

Persistent infection with high-risk Human Papilloma Virus (HPV) leads to the development of several tumors, including cervical, oropharyngeal, and anogenital squamous cell carcinoma. In the last years, the use of high-throughput sequencing technologies has revealed a number of non-coding RNA (ncRNAs), distinct from micro RNAs (miRNAs), that are deregulated in HPV-driven cancers, thus suggesting that HPV infection may affect their expression. However, since the knowledge of ncRNAs is still limited, a better understanding of ncRNAs biology, biogenesis, and function may be challenging for improving the diagnosis of HPV infection or progression, and for monitoring the response to therapy of patients affected by HPV-driven tumors. In addition, to establish a ncRNAs expression profile may be instrumental for developing more effective therapeutic strategies for the treatment of HPV-associated lesions and cancers. Therefore, this review will address novel classes of ncRNAs that have recently started to draw increasing attention in HPV-driven tumors, with a particular focus on ncRNAs that have been identified as a direct target of HPV oncoproteins.
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http://dx.doi.org/10.3390/cancers12051246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281476PMC
May 2020

Prognostic significance of neutrophil-to-lymphocyte ratio in HPV status era for oropharyngeal cancer.

Oral Dis 2020 Oct 13;26(7):1384-1392. Epub 2020 May 13.

Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy.

Aim: To evaluate the role of baseline neutrophil-to-lymphocyte ratio (NLR) as prognostic marker in squamous cell carcinoma of the oropharynx (OPC) treated with definitive chemoradiotherapy (CRT) in the era of HPV status.

Patients And Methods: A retrospective analysis of 125 patients (pts) affected with locally advanced OPC was performed. Inclusion criteria were age >18 years, stage III or IV (TNM 7th ed.) and definitive CRT. Haematological marker for their independent role as prognostic biomarkers for progression-free survival (PFS) and overall survival (OS). Logistic models were used to assess the association with downstage in TNM 8th ed.

Results: Seventy-seven (61.6%) pts had HPV/p16 + related OPC. Therapeutic choice consisted in sequential and concurrent CRT. Median follow-up was 50 months. A value of NLR ≥3 was associated with poorer OS. Two-year OS was 91% and 81% in pts with NLR <3 and ≥3, respectively.

Conclusion: A baseline NLR ≥ 3 at treatment initiation represented a negative prognostic marker for OPC treated with definitive CRT. These results are in line with literature data, and prognostic value of NLR has been confirmed restaging our cohort with new TNM staging (8th ed.). Therefore, NLR could be considered a valuable biomarker for risk stratification in pts with OPC.
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http://dx.doi.org/10.1111/odi.13366DOI Listing
October 2020

Intra- and inter-observer variability in breast tumour bed contouring and the controversial role of surgical clips.

Med Oncol 2019 Apr 29;36(6):51. Epub 2019 Apr 29.

Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy.

The purpose of this study was to evaluate whether the visualization of surgical clips (SCs) on the same set of planning computed tomography (CT) of breast cancer (BC) patients influences agreement on tumour bed (TB) delineation. Planning CT (CT) of 47 BC patients with SCs to visualize the TB was processed in order to blur SCs and create a virtual CT (CT). Four radiation oncologists (ROs, 2 juniors and 2 seniors) contoured TB on both the CT sets. Centre of mass distance (CMD), percentage overlap as Dice similarity coefficient (DSC), surface distance as average Hausdorff distance (AHD) and TB volume size were analysed. The intra-observer variability when contouring TB with and without SCs was statistically significant (p-values = 0.016, 0.0002 and ≪ 0.001 for CMD, AHD and DSC, respectively). Junior ROs showed worse reproducibility compared to seniors. The median DSC was < 0.7. The inter-observer variability with and without SCs was statistically significant (p < 0.001) for all metrics, with an increase of 48.7% in DSC and decrease of 50.7% and 57.1% in CMD and AHD, respectively, as relative median values, when SCs were visible. Regarding TB volumes, when SCs were visible, the intra-observer analysis revealed that 3/4 ROs delineated larger volumes, especially juniors. The inter-observer analysis showed that, in presence of visible SCs, the difference in TB volume among all the ROs fell from statistically significant to borderline significance (p = 0.052). TB contouring is confirmed to be an observer-dependent task. SCs decreased the intra and inter-observer variability but the overall agreement between ROs remained low.
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http://dx.doi.org/10.1007/s12032-019-1273-1DOI Listing
April 2019

Metastasis-directed stereotactic radiotherapy for oligoprogressive castration-resistant prostate cancer: a multicenter study.

World J Urol 2019 Dec 11;37(12):2631-2637. Epub 2019 Mar 11.

Radiation Oncology Department, University and Spedali Civili Hospital, Brescia, Italy.

Purpose: Herein, we report the clinical outcomes of a multicenter study evaluating the role of SBRT in a cohort of patients affected by oligoprogressive castration-resistant prostate cancer (CRPC).

Materials And Methods: This is a retrospective multicenter observational study including eleven centers. Inclusion criteria of the current study were: (a) Karnofsky performance status > 80, (b) histologically proven diagnosis of PC, (c) 1-5 oligoprogressive metastases, defined as progressive disease at bone or nodes levels (detected by means of choline PET/CT or CT plus bone scan) during ADT, (d) serum testosterone level under 50 ng/ml during ADT, (e) controlled primary tumor, (f) patients treated with SBRT with a dose of at least 5 Gy per fraction to a biologically effective dose (BED) of at least 80 Gy using an alpha-to-beta ratio of 3 Gy, (g) at least 6 months of follow-up post-SBRT.

Results: Eighty-six patients for a total of 117 lesions were treated with SBRT. The median follow-up was 30.7 months (range 4-91 months). The median new metastasis-free survival after SBRT was 12.3 months (95% CI 5.5-19.1 months). One- and two-year distant progression-free survival was 52.3% and 33.7%, respectively. Twenty-six out of 86 patients underwent a second course of SBRT due to further oligoprogressive disease: This resulted in a median systemic treatment-free survival of 21.8 months (95% CI 17.8-25.8 months). One-year systemic treatment-free survival was 72.1%.

Conclusion: SBRT appears to be a promising approach in oligoprogressive castration-resistant prostate cancer. Further investigations are warranted.
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http://dx.doi.org/10.1007/s00345-019-02717-7DOI Listing
December 2019

Direct health-care cost of head and neck cancers: a population-based study in north-eastern Italy.

Med Oncol 2019 Feb 28;36(4):31. Epub 2019 Feb 28.

Unit of Radiatherapic Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, via Gallini 2, 33081, Aviano, PN, Italy.

Improvements in prognosis of head-and-neck squamous cell carcinoma (HNSCC) have paralleled with an increase in health-care costs, so that an economic evaluation is of growing importance. Presently, most of the evidence is from insurance-based studies in the USA. Between 2007 and 2010, 879 HNSCC patients were identified through the population-based cancer registry of the Friuli Venezia Giulia region, including 266 oral, 187 oropharyngeal, 136 hypopharyngeal, and 290 laryngeal cancers. Health-care costs from diagnosis to treatment initiation and in the following 2 years were retrieved through a record linkage with the regional health data warehouse. This database collected comprehensive health information on all resident citizens. Generalized linear models with a gamma distribution and log-link function were applied to model costs. The average health-care cost from diagnosis up to 2 years after treatment initiation was €20,184 (95% confidence interval: €19,634 - 20,733). Heterogeneity emerged according to cancer site, elective treatment, and retreatment for cancer persistence/recurrence (no: €13,896; yes: €24,599; p < 0.001). An advanced stage was associated with increased costs stage (I: €12,969; II: €18,276; III: €26,229; IV: €25,574; p < 0.001) as the result of treatment complexity and elevated frequency of patients retreatment due to recurrence. These findings further support strategies to diagnose patients at an earlier cancer stage and the accurate definition of diagnostic and treatment pathways, to start treating patients when radical unimodal approach is still feasible. Besides the advantage in prognosis due to timely curative treatments, this would reduce the economic burden of cancer treatment.
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http://dx.doi.org/10.1007/s12032-019-1256-2DOI Listing
February 2019

Reirradiation for isolated local recurrence of prostate cancer: Mono-institutional series of 64 patients treated with salvage stereotactic body radiotherapy (SBRT).

Br J Radiol 2019 Feb 9;92(1094):20180494. Epub 2018 Nov 9.

1 Division of Radiation Oncology, European Institute of Oncology IRCCS , Milan , Italy.

Objective:: To evaluate high-precision external beam reirradiation (re-EBRT) for local relapse of prostate cancer (PCa) after radiotherapy.

Methods:: This retrospective study included patients with biochemical failure and evidence of isolated local recurrence of PCa after radical/salvage EBRT or brachytherapy that received salvage stereotactic body radiation therapy (SBRT, re-EBRT). Biopsy was not mandatory if all diagnostic elements were univocal (prostate specific antigen evolution, choline-positron emission tomography or magnetic resonance imaging). Salvage SBRT (re-EBRT) was delivered with image-guided radiation therapy (RapidArc®, VERO® and CyberKnife®).

Results:: Data of 64 patients were included, median age at salvage SBRT was 73.2 years, median pre-salvage SBRT prostate specific antigen was 3.89  ng ml . Median total dose was 30  Gy in five fractions, biologically effective dose (BED) of 150  Gy. One acute G3 genitourinary event and one late G3 genitourinary event were observed. No G ≥ 3 bowel toxicity was registered. At the median follow-up of 26.1 months, tumor progression was observed in 41 patients (64%). 18 patients (28%) experienced local relapse. 2-year local control, biochemical and clinical relapse free survival rates were 75, 40 and 53%, respectively. With BED ≥130  Gy 1-year biochemical and clinical progression-free survival rate were 85 and 90%, respectively.

Conclusions:: Salvage SBRT (re-EBRT) for isolated local PCa recurrence is a safe, feasible and noninvasive salvage treatment. Further investigation is warranted to define the optimal patient selection, dose and volume parameters.

Advances In Knowledge:: Salvage SBRT reirradiation for the locally recurrent PCa offer a satisfactory tumor control and excellent toxicity profile, if BED ≥130 Gy is administered.
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http://dx.doi.org/10.1259/bjr.20180494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404844PMC
February 2019

Nutritional Intervention for Nonsurgical Head and Neck Cancer Patients Treated with Radiation Therapy: Results from a Prospective Stepped-Wedge Clinical Protocol.

Nutr Cancer 2018 10 1;70(7):1051-1059. Epub 2018 Oct 1.

a Department of Radiotherapy , European Institute of Oncology , Milan, Italy.

Aim: To evaluate the impact on weight loss (WL) of a standardized nutritional stepped-wedge protocol on consecutive head and neck cancer (HNC) patients treated with curative radiotherapy (RT).

Methods: We prospectively collected data of patients followed by a trained dietitian and treated according to a pre-defined stepped-wedge protocol. Patients with swallowing defect at the baseline and WL >10% 3 months prior to the beginning of RT were excluded from the analysis. Nutritional status was assessed at the baseline and weekly during the course of RT. Fluid and caloric intake were assessed through a 24-h recall.

Results: Between May 2010 and March 2011, 42 patients treated were evaluated. Median overall treatment time was 52.5 days. WL per CTCAE 4.03 was G0, G1 and G2 in 23 (55%), 14 (33%) and 5 (12%) patients, respectively. Thirty-five (83%) patients did not require enteral nutrition. About 90% of patients completed RT without interruption of oral feeding.

Conclusions: Despite the high toxicity profile of curative RT in HN, we proposed a standardized stepped-wedge protocol allowing to prevent severe WL in most of our patients. Further larger prospective studies are warranted to validate our approach and to achieve consensus on nutritional intervention in this subset of patients.
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http://dx.doi.org/10.1080/01635581.2018.1497187DOI Listing
October 2018

Late toxicity of image-guided hypofractionated radiotherapy for prostate: non-randomized comparison with conventional fractionation.

Radiol Med 2019 Jan 15;124(1):65-78. Epub 2018 Sep 15.

Scientific Directorate, European Institute of Oncology, Milan, Italy.

Purpose: To evaluate the incidence and predictors for late toxicity and tumor outcome after hypofractionated radiotherapy using three different image-guided radiotherapy (IGRT) systems (hypo-IGRT) compared with conventional fractionation without image guidance (non-IGRT).

Methods And Materials: We compared the late rectal and urinary toxicity and outcome in 179 prostate cancer patients treated with hypo-IGRT (70.2 Gy/26 fractions) and 174 non-IGRT patients (80 Gy/40 fractions). Multivariate analysis was performed to define predictors for late toxicity. 5- and 8-year recurrence-free survival (RFS) and overall survival (OS) were analyzed.

Results: Mean follow-up was 81 months for hypo-IGRT and 90 months for non-IGRT group. Mainly mild late toxicity was observed: Hypo-IGRT group experienced 65 rectal (30.9% G1/G2; 6.3% G3/G4) and 105 urinary events (56% G1/G2; 4% G3/G4). 5- and 8-year RFS rates were 87.5% and 86.8% (hypo-IGRT) versus 80.4% and 66.8% (non-IGRT). 5- and 8-year OS rates were 91.3% and 82.7% in hypo-IGRT and 92.2% and 84% in non-IGRT group. Multivariate analysis showed that hypo-IGRT is a predictor for late genitourinary toxicity, whereas hypo-IGRT, acute urinary toxicity and androgen deprivation therapy are predictors for late rectal toxicity. Advanced T stage and higher Gleason score (GS) were correlated with worse RFS.

Conclusions: A small increase in mild late toxicity, but not statistically significant increase in severe late toxicity in the hypo-IGRT group when compared with conventional non-IGRT group was observed. Our study confirmed that IGRT allows for safe moderate hypofractionation, offering a shorter overall treatment time, a good impact in terms of RFS and providing potentially more economic health care.
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http://dx.doi.org/10.1007/s11547-018-0937-9DOI Listing
January 2019

Stereotactic body radiotherapy for castration-sensitive prostate cancer bone oligometastases.

Med Oncol 2018 Apr 18;35(5):75. Epub 2018 Apr 18.

Division of Radiotherapy, European Institute of Oncology, Ripamonti 435, 20141, Milan, Italy.

To evaluate outcome in patients treated with stereotactic body radiotherapy (SBRT) on bone oligometastases from castration-sensitive prostate cancer after primary treatment. We retrospectively collected data of patients with less than five lesions at time of SBRT and hormone-naïve disease at the first extra-regional localization, treated between 03/2012 and 11/2016. Prostate-specific antigen (PSA) was measured every 3 months after SBRT. Imaging was performed in case of progression. Survival analysis was performed with Kaplan-Meier (log-rank test) approach. Fifty-five patients were treated on 77 bone oligometastases. Median age, initial PSA and pre-SBRT PSA were 72 years, 9.12 and 3.5 ng/mL, respectively. Twenty-five patients (45%) received SBRT alone while the remaining 30 patients (55%) received concomitant ADT. Median follow-up was 24.6 months (range 3.0-67.2 months). No acute or late toxicity of grade > 1 was reported. Clinical progression was observed in 38 (69%) patients. 1-year biochemical progression-free survival (b-PFS), clinical progression-free survival (c-PFS), prostate-specific survival (PCSS) and local control (LC) rates were 51, 56, 100 and 83%, respectively. Comparing patients treated with SBRT alone and with concomitant ADT, no significant differences were found for those outcomes. SBRT is safe and allows high 1-year LC rate (83%) with low toxicity profile. No significant improvement in outcomes was registered with the addition of ADT to SBRT.
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http://dx.doi.org/10.1007/s12032-018-1137-0DOI Listing
April 2018

Cone-beam CT-based inter-fraction localization errors for tumors in the pelvic region.

Phys Med 2018 Feb;46:59-66

Division of Radiation Oncology, European Institute of Oncology, Milano, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milano, Italy.

Purpose: To evaluate inter-fraction tumor localization errors (TE) in the RapidArc® treatment of pelvic cancers based on CBCT. Appropriate CTV-to PTV margins in a non-IGRT scenario have been proposed.

Methods: Data of 928 patients with prostate, gynecological, and rectum/anal canal cancers were retrospectively analyzed to determine systematic and random localization errors. Two protocols were used: daily online IGRT (d-IGRT) and weekly IGRT. The latter consisted in acquiring a CBCT for the first 3 fractions and subsequently once a week. TE for patients who underwent d-IGRT protocol were calculated using either all CBCTs or the first 3.

Results: The systematic (and random) TE in the AP, LL, and SI direction were: for prostate bed 2.7(3.2), 2.3(2.8) and 1.9(2.2) mm; for prostate 4.2(3.1), 2.9(2.8) and 2.3(2.2) mm; for gynecological 3.0(3.6), 2.4(2.7) and 2.3(2.5) mm; for rectum 2.8(2.8), 2.4(2.8) and 2.3(2.5) mm; for anal canal 3.1(3.3), 2.1(2.5) and 2.2(2.7) mm. CTV-to-PTV margins determined from all CBCTs were 14 mm in the AP, 10 mm in the LL and 9-9.5 mm in the SI directions for the prostate and the gynecological groups and 9.5-10.5 mm in AP, 9 mm in LL and 8-10 mm in the SI direction for the prostate bed and the rectum/anal canal groups. If assessed on the basis of the first 3 CBCTs, the calculated CTV-to-PTV margins were slightly larger.

Conclusions: without IGRT, large CTV-to-PTV margins up to 15 mm are required to account for inter-fraction tumor localization errors. Daily IGRT should be used for all hypo-fractionated treatments to reduce margins and avoid increased toxicity to critical organs.
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http://dx.doi.org/10.1016/j.ejmp.2018.01.011DOI Listing
February 2018

Comparison of Treatment Outcome Between Invasive Lobular and Ductal Carcinomas in Patients Receiving Partial Breast Irradiation With Intraoperative Electrons.

Int J Radiat Oncol Biol Phys 2017 09 4;99(1):173-181. Epub 2017 May 4.

Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy; Department of Medical Imaging and Radiation Sciences, European Institute of Oncology, Milan, Italy.

Purpose: To investigate the local outcome of patients after accelerated partial breast irradiation with intraoperative electrons (IORT) for invasive lobular carcinoma (ILC) compared with invasive ductal carcinoma (IDC).

Methods And Materials: From 1999 to 2007, 2173 patients were treated with breast-conserving surgery and IORT (21 Gy/1 fraction) as the sole local treatment: 252 patients with ILC (11.6%) were compared with 1921 patients with IDC in terms of local control.

Results: Compared with the IDC subgroup, patients with ILC had a low-risk profile and were more hormone responsive. The 5- and 10-year in-breast tumor reappearance (IBTR) rates were 5.5% and 14.4%, respectively, for the IDC group and 7.5% and 21.8%, respectively, for the ILC group (log-rank P=.03). The excess risk of IBTR associated with ILC was particularly high for small tumors (≤1 cm: hazard ratio [HR], 2.24; 95% confidence interval [CI], 1.03-4.85), elderly patients (60-69 years: HR, 2.27; 95% CI, 1.11-4.63; ≥70 years: HR, 3.28; 95% CI, 1.08-10.0), low-grade tumors (grade 1: HR, 3.50; 95% CI, 1.05-11.7), and luminal A molecular subtype (HR, 3.18; 95% CI, 1.49-6.77). Among the ILC histologic variants, no difference between classic and nonclassic subgroups was observed, although the signet ring cell and solid variants had the worst local control.

Conclusions: Despite a favorable tumor profile, accelerated partial breast irradiation with IORT led to a higher incidence of IBTRs in patients with ILC compared with those with IDC. Our institutional experience emphasized the importance of the size of the irradiation field, pointing to the use of larger collimators, even when dealing with small tumors, to improve local control.
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http://dx.doi.org/10.1016/j.ijrobp.2017.04.033DOI Listing
September 2017

Salvage Stereotactic Body Radiotherapy for Isolated Lymph Node Recurrent Prostate Cancer: Single Institution Series of 94 Consecutive Patients and 124 Lymph Nodes.

Clin Genitourin Cancer 2017 08 11;15(4):e623-e632. Epub 2017 Jan 11.

Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy; Scientific Directorate, European Institute of Oncology, Milan, Italy.

Background: The purpose of the study was to evaluate the prostate serum antigen (PSA) response, local control, progression-free survival (PFS), and toxicity of stereotactic body radiotherapy (SBRT) for lymph node (LN) oligorecurrent prostate cancer.

Patients And Methods: Between May 2012 and October 2015, 124 lesions were treated in 94 patients with a median dose of 24 Gy in 3 fractions. Seventy patients were treated for a single lesion and 25 for > 1 lesion. In 34 patients androgen deprivation (AD) was combined with SBRT. We evaluated biochemical response according to PSA level every 3 months after SBRT: a 3-month PSA decrease from pre-SBRT PSA of more than 10% identified responder patients. In case of PSA level increase, imaging was performed to evaluate clinical progression. Toxicity was assessed every 6 to 9 months after SBRT.

Results: Median follow-up was 18.5 months. In 13 patients (14%) Grade 1 to 2 toxicity was reported without any Grade 3 to 4 toxicity. Biochemical response, stabilization, and progression were observed in 64 (68%), 10 (11%), and 20 (21%) of 94 evaluable patients. Clinical progression was observed in 31 patients (33%) after a median time of 8.1 months. In-field progression occurred in 12 lesions (9.7%). Two-year local control and PFS rates were 84% and 30%, respectively. Age older than 75 years correlated with better biochemical response rate. Age older than 75 years, concomitant AD administered up to 12 months, and pelvic LN involvement correlated with longer PFS.

Conclusion: SBRT is safe and offers good in-field control. At 2 years after SBRT, 1 of 3 patients is progression-free. Further investigation is warranted to identify patients who benefit most from SBRT and to define the optimal combination with AD.
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http://dx.doi.org/10.1016/j.clgc.2017.01.004DOI Listing
August 2017

No increase in toxicity of pelvic irradiation when intensity modulation is employed: clinical and dosimetric data of 208 patients treated with post-prostatectomy radiotherapy.

Br J Radiol 2016 Jul 25;89(1063):20150985. Epub 2016 Apr 25.

1 Division of Radiation Oncology, European Institute of Oncology, Milan, Italy.

Objective: To compare the toxicity of image-guided intensity-modulated radiotherapy (IG-IMRT) to the pelvis or prostate bed (PB) only. To test the hypothesis that the potentially injurious effect of pelvic irradiation can be counterbalanced by reduced irradiated normal tissue volume using IG-IMRT.

Methods: Between February 2010 and February 2012, 208 patients with prostate cancer were treated with adjuvant or salvage IG-IMRT to the PB (102 patients, Group PB) or the pelvis and prostate bed (P) (106 patients, Group P). The Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria were used to evaluate toxicity.

Results: Median follow-up was 27 months. Toxicity G ≥ 2 in Group PB: in the bowel acute and late toxicities were 11.8% and 10%, respectively; urinary acute and late toxicities were 10.8% and 15%, respectively. Toxicity G ≥ 2 in Group P: in the bowel acute and late toxicities were both 13.2%; urinary acute and late toxicities were 13.2% and 15.1%, respectively. No statistical difference in acute or late toxicity between the groups was found (bowel: p = 0.23 and p = 0.89 for acute and late toxicity, respectively; urinary: p = 0.39 and p = 0.66 for acute and late toxicity, respectively). Of the clinical variables, only previous abdominal surgery was correlated with acute bowel toxicity. Dosimetric parameters that correlated with bowel toxicity were identified.

Conclusion: The toxicity rates were low and similar in both groups, suggesting that IG-IMRT allows for a safe post-operative irradiation of larger volumes. Further investigation is warranted to exclude bias owing to non-randomized character of the study.

Advances In Knowledge: Our report shows that modern radiotherapy technology and careful planning allow maintaining the toxicity of pelvic lymph node treatment at the acceptable level, as it is in the case of PB radiotherapy.
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http://dx.doi.org/10.1259/bjr.20150985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5257309PMC
July 2016

Pathological response after neoadjuvant bevacizumab- or cetuximab-based chemotherapy in resected colorectal cancer liver metastases.

Med Oncol 2015 Jul 24;32(7):182. Epub 2015 May 24.

Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori (National Cancer Institute), Via Venezian, 1, 20133, Milan, Italy,

Neoadjuvant chemotherapy (NACT) prior to liver resection is advantageous for patients with colorectal cancer liver metastases (CLM). Bevacizumab- or cetuximab-based NACT may affect patient outcome and curative resection rate, but comparative studies on differential tumour regression grade (TRG) associated with distinct antibodies-associated regimens are lacking. Ninety-three consecutive patients received NACT plus bevacizumab (n = 46) or cetuximab (n = 47) followed by CLM resection. Pathological response was determined in each resected metastasis as TRG rated from 1 (complete) to 5 (no response). Except for KRAS mutations prevailing in bevacizumab versus cetuximab (57 vs. 21 %, p = 0.001), patients characteristics were well balanced. Median follow-up was 31 months (IQR 17-48). Bevacizumab induced significantly better pathological response rates (TRG1-3: 78 vs. 34 %, p < 0.001) as well as complete responses (TRG1: 13 vs. 0 %, p = 0.012) with respect to cetuximab. Three-year progression-free survival (PFS) and overall survival (OS) were not significantly different in the two cohorts. At multivariable analysis, significant association with pathological response was found for number of resected metastases (p = 0.015) and bevacizumab allocation (p < 0.001), while KRAS mutation showed only a trend. Significant association with poorer PFS and OS was found for low grades of pathological response (p = 0.009 and p < 0.001, respectively), R2 resection or presence of extrahepatic disease (both p < 0.001) and presence of KRAS mutation (p = 0.007 and p < 0.001, respectively). Bevacizumab-based regimens, although influenced by the number of metastases and KRAS status, improve significantly pathological response if compared to cetuximab-based NACT. Possible differential impact among regimens on patient outcome has still to be elucidated.
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http://dx.doi.org/10.1007/s12032-015-0638-3DOI Listing
July 2015

Role of MGMT as biomarker in colorectal cancer.

World J Clin Cases 2014 Dec;2(12):835-9

Alessandro Inno, Stefania Gori, Massimo Cirillo, Medical Oncology Department, Ospedale Sacro Cuore Don Calabria, Negrar, 37100 Verona, Italy.

O(6)-methylguanine DNA methyltransferase (MGMT) gene promoter methylation plays an important role in colorectal carcinogenesis, occurring in about 30%-40% of metastatic colorectal cancer. Its prognostic role has not been defined yet, but loss of expression of MGMT, which is secondary to gene promoter methylation, results in an interesting high response to alkylating agents such as dacarbazine and temozolomide. In a phase 2 study on heavily pre-treated patients with MGMT methylated metastatic colorectal cancer, temozolomide achieved about 30% of disease control rate. Activating mutations of RAS or BRAF genes as well as mismatch repair deficiency may represent mechanisms of resistance to alkylating agents, but a dose-dense schedule of temozolomide may potentially restore sensitivity in RAS-mutant patients. Further development of temozolomide in MGMT methylated colorectal cancer includes investigation of synergic combinations with other agents such as fluoropyrimidines and research for additional biomarkers, in order to better define the role of temozolomide in the treatment of individual patients.
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http://dx.doi.org/10.12998/wjcc.v2.i12.835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266830PMC
December 2014

FOLFOX-4 chemotherapy for patients with unresectable or relapsed peritoneal pseudomyxoma.

Oncologist 2014 Aug 20;19(8):845-50. Epub 2014 Jun 20.

Medical Oncology Department, Surgery Department, Pathology and Molecular Biology Department, Scientific Directorate, and Clinical Nutrition Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Purpose: The standard treatment of peritoneal pseudomyxoma is based on cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The establishment of newer systemic treatments is an unmet clinical need for unresectable or relapsed peritoneal pseudomyxoma. The aim of our study was to assess the activity of chemotherapy with 5-fluorouracil and oxaliplatin (FOLFOX-4 regimen) in terms of response rate in this subset of patients.

Materials And Methods: Patients were included in a single-center, observational study and treated with FOLFOX-4 administered every 2 weeks for up to 12 cycles or until progressive disease or unacceptable toxicity.

Results: Twenty consecutive patients were reviewed from July 2011 to September 2013. Only partial responses were observed, with an objective response rate of 20%. Median progression-free survival and overall survival were 8 months and 26 months, respectively. Two patients were able to undergo laparotomy with complete cytoreduction and HIPEC in one case. Safety data for FOLFOX-4 were consistent with the literature. By means of a mutant enriched polymerase chain reaction, KRAS mutation was found in 16 of 19 cases (84%), and MGMT promoter methylation was found in 8 (42%, all KRAS mutant).

Conclusion: FOLFOX-4 chemotherapy is tolerable and active in patients with peritoneal pseudomyxoma when disease is deemed unresectable or relapsed after peritonectomy and HIPEC. The identification of predictive biomarkers, such as KRAS for resistance to anti-epidermal growth factor receptor monoclonal antibodies and MGMT for response to temozolomide, is a priority for the development of evidence-based treatment strategies for peritoneal pseudomyxoma.
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http://dx.doi.org/10.1634/theoncologist.2014-0106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122474PMC
August 2014

Are antineoplastic drug acute hypersensitive reactions a submerged or an emergent problem? Experience of the Medical Day Hospital of the Fondazione IRCCS Istituto Nazionale Tumori.

Tumori 2014 Jan-Feb;100(1):9-14

Background: Acute hypersensitivity reactions are adverse events potentially associated with antineoplastic drug infusions. Their occurrence can be particularly relevant in an outpatient environment where time of administration and subsequent observation is limited to a short period of time. In addition, concern about the onset of more severe hypersensitivity reactions can limit subsequent use of crucial drugs.

Methods: During a 3-year observational period, we collected a total of 240 infusional acute hypersensitivity reactions out of 56,120 administrations performed, with an overall incidence of 0.4%.

Results: In order of frequency, platinum derivatives, taxanes and monoclonal antibodies accounted for the highest incidences. Their relative frequency was: oxaliplatin, 2.5%; carboplatin, 0.4%; paclitaxel, 1.2%; docetaxel, 1.2%; trastuzumab, 1.2%, and rituximab, 1.2%.

Conclusions: Since the number of chemotherapeutic agents is steadily increasing, much attention should be paid to such reactions, particularly when several administrations are performed daily, and where management of the potential risk associated with specific drugs is mandatory. Their occurrence represents an unpredictable, unexpected and often hard to manage contingency, and our opinion is that observation and consciousness of this issue are fundamental for its appropriate management. We describe our experience, emphasizing the role of this toxicity and explaining how this awareness allowed us to define some empirical rules to handle acute hypersensitivity reactions.
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http://dx.doi.org/10.1700/1430.15808DOI Listing
May 2014

Reversible bilateral blepharoptosis following oxaliplatin infusion: a case report and literature review.

Tumori 2013 Sep-Oct;99(5):e216-9

Oxaliplatin, a platinum analogue employed in the treatment of colorectal cancer and various other neoplasms, is characterized by a broad range of adverse events. Peripheral neuropathy is probably the most peculiar and clinically relevant toxicity associated with its use and can be distinguished into two types: acute and chronic neurotoxicity.We report a case of acute reversible bilateral palpebral ptosis and dyspnea without bronchospasm or laryngospasm which occurred at the end of the third administration of adjuvant oxaliplatin by infusion for stage III colon cancer in a 54-year-old woman. Chlorphenamine and hydrocortisone were administered with fast resolution of dyspnea and slight improvement of ptosis. Complete resolution with no sequelae occurred in one hour. No further recurrence of blepharoptosis was described during the following days. The subsequent cycles were prescribed at reduced dosage without acute complications.
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February 2014

Single agent panitumumab in KRAS wild-type metastatic colorectal cancer patients following cetuximab-based regimens: Clinical outcome and biomarkers of efficacy.

Cancer Biol Ther 2013 Dec 4;14(12):1098-103. Epub 2013 Sep 4.

Medical Oncology Department; Fondazione I.R.C.C.S. Istituto Nazionale Tumori; Milan, Italy.

Background: Few data are available outlining outcomes of panitumumab in advanced colorectal cancer patients benefiting from prior cetuximab-based regimens.

Patients And Methods: Thirty patients with KRAS wild type metastatic colorectal cancer with clinical benefit from prior cetuximab-based regimens between May 2004 and October 2011 were reviewed at nine Italian Institutions. Inclusion key criteria included interruption of cetuximab for reasons other than progressive disease. Patients were classified according to prior regimens (0 or ≥1), prior response or stabilization, surgery of metastases, and Köhne prognostic score. At the time of subsequent progression, patients were treated with single agent panitumumab until progressive disease, unacceptable toxicity, or consent withdrawal.

Results: Panitumumab obtained 67% disease control rate and 30% objective response rate, with median PFS of 4.2 and median OS of 9.6 mo. Patients with BRAF/NRAS/PI3KCA and KRAS (by mutant enriched technique) wild-type tumors had the best chance of response to panitumumab.

Conclusions: Single agent panitumumab provided significant clinical benefit in heavily pretreated patients without acquired resistance to prior cetuximab-based regimens.
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http://dx.doi.org/10.4161/cbt.26343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912032PMC
December 2013