Nadia Pasinetti

Cetuximab and Radiotherapy Versus Cisplatin and Radiotherapy for Locally Advanced Head and Neck Cancer: A Randomized Phase II Trial

PURPOSE No randomized trials have been conducted to directly compare radiotherapy (RT) with concomitant cisplatin (CDDP) versus concomitant cetuximab (CTX) as first-line treatment of locally advanced squamous cell carcinoma of the head and neck. In this randomized trial, we compared these two treatment regimens in terms of compliance, toxicity, and efficacy. PATIENTS AND METHODS Eligible patients were randomly assigned in a 1:1 ratio to receive either CDDP 40 mg/m(2) once per week or CTX 400 mg/m(2) as loading dose followed by CTX 250 mg/m(2) once per week concomitant to radical RT. For primary end points, compliance to treatment was defined as number of days of treatment discontinuation and drug dosage reduction. The acute toxicity rate was defined according to the National Cancer Institute Common Toxicity Criteria. Efficacy end points were local recurrence-free survival, metastasis-free survival, cancer-specific survival, and overall survival. RESULTS The study was discontinued early because of slow accrual after the enrollment of 70 patients. RT discontinuation for more than 10 days occurred in 13% of patients given CTX and 0% given CDDP (P = .05). Drug dosage reduction occurred in 34% given CTX and 53% given CDDP (difference not significant). Toxicity profiles differed between the two arms, with hematologic, renal, and GI toxicities more frequent in the CDDP arm, and cutaneous toxicity and the need for nutritional support more frequent in the CTX arm. Serious adverse events related to treatment, including four versus one toxic deaths, were higher in the CTX arm (19% v 3%, P = .044). Locoregional control, patterns of failure, and survivals were similar between the treatment arms. CONCLUSION CTX concomitant to RT lowered compliance and increased acute toxicity rates. Efficacy outcomes were similar in both arms. These results raise the issue of appropriately selecting patients with head and neck cancer who can benefit from CTX in combination with RT.

Circulating Tumour Cells in locally advanced head and neck cancer: Preliminary report about their possible role in predicting response to non-surgical treatment and survival

BACKGROUND AND PURPOSE The mechanism of dissemination of locally advanced head and neck cancer (LAHNC) is far to be resolved. Circulating tumour cells (CTC) have been identified as a prognostic factor in metastatic breast and prostate cancer. This prospective multi-centric analysis studied the possible role of CTC identification in LAHNC. MATERIALS AND METHODS CTC were searched in 73 patients with LAHNC (oropharynx, n=39; nasopharynx, n=10; larynx, n=10; paranasal sinuses, n=6, of whom 3 with sinonasal undifferentiated carcinoma, SNUC; hypopharynx, n=5; oral cavity, n=3). All of them (apart from SNUC) had squamous cell cancers. The relationship between CTC positivity and other clinical prognostic factors has been investigated. Response to treatment and survival has been related with changes in CTC number during the treatment. RESULTS CTC were frequently identified in oro- and hypopharyngeal cancer and in SNUC. They were more frequent in stage IV than in stages I-III disease (18% versus 6%, p=NS (not significant)). Partial or complete response (CR) was related with the absence or disappearance of CTC during treatment (p=0.017). A decrease in the CTC number or their absence throughout the treatment seems also related with non-progressive disease, after both complete or incomplete remission and with the proportion of patients alive and NED (no evidence of disease) (p=0.009). CONCLUSIONS These preliminary data suggest a possible role of CTC determination in head and neck cancer. Additional and longer follow up data need to be collected to confirm these findings.

Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study

Background:The aim of the present study is to evaluate the impact of metastases-directed stereotactic body radiotherapy in two groups of oligometastatic prostate cancer (PC) patients: oligorecurrent PC and oligoprogressive castration-resistant PC (oligo-CRPC).Methods:Inclusion criteria of the present multicentre retrospective analysis were: (1) oligorecurrent PC, defined as the presence of 1–3 lesions (bone or nodes) detected with choline positron emission tomography or CT plus bone scan following biochemical recurrence; (2) oligo-CRPC, defined as metastases (bone or nodes) detected after a prostatic-specific antigen rise during androgen deprivation therapy (ADT). Primary end points were: distant progression-free survival (DPFS) and ADT-free survival in oligorecurrent PC patients; DPFS and second-line systemic treatment-free survival in oligo-CRPC patients.Results:About 100 patients with oligorecurrent PC (139 lesions) and 41 with oligo-CRPC (70 lesions), treated between March 2010 and April 2016, were analysed. After a median follow-up of 20.4 months, in the oligorecurrent group 1- and 2-year DPFS were 64.4 and 43%. The rate of LC was 92.8% at 2 years. At a median follow-up of 23.4 months, in the oligo-CRPC group 1- and 2-year DPFS were 43.2 and 21.6%. Limitations include the retrospective design.Conclusions:Stereotactic body radiotherapy seems to be a useful treatment both for oligorecurrent and oligo-CRPC.

Radiotherapy for adult medulloblastoma: Long term result from a single institution. A review of prognostic factors and why we do need a multi-institutional cooperative program

AIM We retrospectively analyzed our Institution experience with these patients. The endpoints of the analysis were overall survival (OS), disease-free survival (DFS), local control (LC), metastasis free survival (MFS); results were compared with the literature. BACKGROUND Medulloblastoma in adult patients is a very rare disease; the 5 and 10-year overall survival rates range between 33-78% and 27-56%, respectively. The collection of more clinical data is strongly needed. MATERIALS AND METHODS From September 1975 to October 2006, we treated 16 adult patients (9 males and 7 females) with a histological diagnosis of medulloblastoma. Acute and late toxicities were scored according to RTOG toxicity scale. Karnofski performance status (KPS) and neurological performance status (NPS) pre- and post-RT were reported. Median age was 27 years (range 18-53 years). All the patients received cranio-spinal irradiation, two patients were also given chemotherapy. Median follow-up period was 121.5 months. RESULTS In January 2014, 10/16 patients were alive without evidence of disease, 6/16 died with progressive disease (1 local and spinal, 3 spinal and 2 extraneural). Ten-year LC, OS, DFS, MFS were, respectively, 84%, 67%, 60% and 59%. Univariate analysis shows that gross total resection is associated with better survival. No acute or late G3-G4 toxicity was observed. CONCLUSIONS This experience and the analysis of the literature confirm the efficacy of postoperative RT but also the need of large datasets to better define prognostic factors and the possible role of the association of chemotherapy.

The impact of tumour histology and recursive partitioning analysis classification on the prognosis of patients treated with whole-brain hypofractionated radiotherapy for brain metastases: analysis of 382 patients

PurposeRecursive partitioning analysis (RPA) is a prognostic index capable of predicting survival in patients with brain metastases. Histology of the primary tumour has only recently been introduced among the factors that could potentially affect the prognosis of these patients. The main purpose of this study was to analyse the impact of RPA in correlation with histology of the primary tumour in patients with brain metastases treated with hypofractionated radiotherapy.Materials and methodsA total of 382 patients were treated at the Department of Radiotherapy of Brescia University, and RPA classes were retrospectively assigned to all patients. Univariate and multivariate analyses were then performed to verify the role of the single prognostic variables, for the entire group and for each prognostic class, as well as in correlation with histology of the primary tumour.ResultsMost patients were classified as RPA prognostic class 2 (48%). The majority of patients was treated with a total dose of 30 Gy delivered in ten fractions, whereas the dose of 20 Gy in four or five fractions was primarily used in patients classified as RPA class 3. At univariate analysis, the main variable correlating with overall survival (OS) was RPA class (p=0.000). Uni- and multivariate analysis performed on RPA class 1 patients only confirmed the role of general performance status, number of metastases and total radiotherapy dose for predicting OS. In the group with the worst prognosis (RPA class 3), none of the variables had a statistically significant role in improving OS. Tumour histology and radiotherapy dose influence OS, even in RPA class 1 and 2 patients.ConclusionsThis analysis confirms that RPA prognostic class is the factor that most predicts survival. Primary tumour histology helps determine prognosis, especially in RPA prognostic classes 1 and 2. As regards RPA class 3, no factor influences survival prognosis.RiassuntoObiettivoLa recursive partitioning analysis (RPA) è un indice prognostico capace di predire la sopravvivenza in pazienti affetti da metastasi cerebrali. L’istologia della malattia primitiva è stata solo di recente inserita in maniera organica tra i fattori che potenzialmente potrebbero influenzare la prognosi di questi pazienti. L’obiettivo primario di questo studio è quello di analizzare l’impatto della RPA correlato con l’istologia del tumore primitivo in pazienti con metastasi cerebrali, trattati con radioterapia ipofrazionata.Materiali e metodiTrecentoottantadue pazienti sono stati trattati presso la Cattedra di Radioterapia di Brescia. La classe RPA è stata attribuita retrospettivamente a tutti i pazienti. È stata quindi eseguita l’analisi univariata e multivariata per verificare il ruolo delle singole variabili prognostiche, nell’intero gruppo e nelle singole classi prognostiche, anche in correlazione con l’istologia del tumore primitivo.RisultatiLa maggior parte dei pazienti è stata classificata nella classe prognostica RPA 2 (48%). La maggior parte dei pazienti è stata trattata con una dose totale di 30 Gy erogati in 10 frazioni, la dose di 20 Gy in 4 o 5 frazioni è stata utilizzata per lo più in pazienti classificati in classe RPA 3. All’analisi univariata la variabile principale correlata alla sopravvivenza globale (OS) è la classe RPA (p=0,000). L’analisi uni- e multivariata eseguita limitatamente ai pazienti in classe prognostica RPA 1 conferma il ruolo del performance status generale, del numero di metastasi e della dose totale di radioterapia nel predire la OS. Nel gruppo prognosticamente peggiore (RPA 3) nessuna variabile ha un ruolo statisticamente significativo nel migliorare la OS. L’istologia della malattia e la dose di radioterapia influiscono sulla OS, anche in pazienti con classi RPA 1 e 2.ConclusioniQuesta analisi conferma che le classi prognostiche RPA sono il fattore che principalmente influisce sulla sopravvivenza. L’istologia della neoplasia primitiva influisce sulla prognosi specialmente nelle classi prognostiche RPA 1 e 2. Per la classe prognostica RPA 3 nessun fattore influisce sulla sopravvivenza.

Three-dimensional conformal radiotherapy, static intensity-modulated and helical intensity-modulated radiotherapy in glioblastoma. Dosimetric comparison in patients with overlap between target volumes and organs at risk

Aims and Background Radiotherapy is the standard treatment of glioblastoma. Three-dimensional conformal radiotherapy is the standard technique to treat glioblastoma. Intensity-modulated radiotherapy and helical intensity-modulated radiotherapy (tomotherapy) are becoming widely used. The present study compared three-dimensional conformal radiotherapy, intensity-modulated radiotherapy and tomotherapy in terms of target coverage and preservation of organs at risk. Methods Ten patients treated with three-dimensional conformal radiotherapy, with a target volume close to or superimposed to the organs at risk, were retrospectively selected. The plans were re-planned with step-and-shoot 3/5 fields intensity-modulated radiotherapy and tomotherapy. Target coverage and sparing of organs at risk were statistically compared. Results Mean planning target volume V95% improved with sophisticated techniques (87.2%, 93.2%, 97.6% with three-dimensional conformal radiotherapy, intensity-modulated radiotherapy and tomotherapy, respectively). The comparison of three-dimensional conformal radiotherapy and intensity-modulated radiotherapy did not show significant differences, whereas differences were significant when three-dimensional conformal radiotherapy and tomotherapy as well as intensity-modulated radiotherapy and tomotherapy were compared. Mean planning target volume/clinical target volume D99-D98-D95 were not different between three-dimensional conformal radiotherapy and intensity-modulated radiotherapy, but they were different between tomotherapy and three-dimensional conformal radiotherapy and intensity-modulated radiotherapy, with better clinical target volume/and planning target volume coverage with the tomotherapy plans. Brain D33/66 were 31.1/11.8 Gy, 37.5/18.3 Gy and 28.5/14.7 Gy with three-dimensional conformal radiotherapy, intensity-modulated radiotherapy and tomotherapy, respectively. Mean brainstem, optic nerves and chiasma Dmax were always within the defined constraints. The homogeneity index improved with intensity-modulated radiotherapy/tomotherapy compared to three-dimensional conformal radiotherapy. Tomotherapy was better than intensity-modulated radiotherapy in all patients. Conclusions In this selected group of patients, a significant dosimetric advantage was evident for tomotherapy compared with three-dimensional conformal radiotherapy and intensity-modulated radiotherapy. Significant advantages were evident in terms of panning target volume coverage (V95), D99, D98 and D95. The clinical significance of the results should be defined.

Could Machine Learning Improve the Prediction of Pelvic Nodal Status of Prostate Cancer Patients? Preliminary Results of a Pilot Study

ABSTRACT We tested and compared performances of Roach formula, Partin tables and of three Machine Learning (ML) based algorithms based on decision trees in identifying N+ prostate cancer (PC). 1,555 cN0 and 50 cN+ PC were analyzed. Results were also verified on an independent population of 204 operated cN0 patients, with a known pN status (187 pN0, 17 pN1 patients). ML performed better, also when tested on the surgical population, with accuracy, specificity, and sensitivity ranging between 48–86%, 35–91%, and 17–79%, respectively. ML potentially allows better prediction of the nodal status of PC, potentially allowing a better tailoring of pelvic irradiation.

A benchmark study on 883 nasopharyngeal cancer patients treated in two Italian Centres from 1977 to 2000. Part I: evolving technical choices and survival

PurposeThe authors sought to define treatment results according to the different accrual periods and clinical-therapeutic features in a large series of nasopharyngeal cancer (NPC) patients treated in two Italian centres over more than two decades.Materials and methodsA total of 883 patients consecutively treated with radiotherapy between 1977 and 2000 at the Florence (FLO) and Brescia (IRA) Radiation Oncology centres were studied. Five-year overall (OS) and disease-specific (DSS) actuarial survival rates in the different pathological, clinical and therapeutic subgroups were calculated, along with the actuarial local-regional control (LRC) probability.ResultsAt univariate analysis, survival and local control rates were significantly better in the more recent accrual periods and in the more favourable disease presentations; treatment-related parameters mainly affect LRC. At multivariate analysis, patient- and disease-related factors had a more evident prognostic effect than did therapeutic factors, although dose to the nasopharynx and treatment technique had a marginally significant impact on DSS and OS.ConclusionsResults of this benchmark study may be useful for understanding the development of new radio-therapy techniques for NPC, such as three-dimensional conformal radiotherapy (3D-CRT) and particularly intensity-modulated radiotherapy (IMRT).RiassuntoObiettivoL’obiettivo primario di questo studio è di definire i risultati del trattamento di una vasta serie di pazienti affetti da neoplasie della rinofaringe (NPC), trattati in due centri italiani per oltre un ventennio, secondo i diversi periodi di reclutamento e le caratteristiche cliniche dei pazienti.Materiali e metodiSono stati studiati 883 pazienti consecutivamente trattati con radioterapia dal 1977 al 2000 a Firenze (FLO, Florence) e Brescia (IRA, Istituto del Radio Alberti). Sono stati calcolati, nei diversi sottogruppi patologici, clinici e terapeutici, i valori attuariali a 5 anni della sopravvivenza globale (OS), della sopravvivenza specifica per malattia (DSS) e del controllo loco-regionale (LCR).RisultatiAll’analisi univariata, la sopravvivenza globale e il controllo locale sono risultati significativamente migliori nei periodi più recenti e nelle presentazioni di malattia più favorevoli; i parametri legati al trattamento influenzano prevalentemente il LCR. All’analisi multivariata, i fattori legati al paziente e alla malattia hanno un effetto prognostico più evidente rispetto a quelli legati al trattamento, benché la dose alla rinofaringe e la tecnica di trattamento abbiano un impatto marginale anche sulla DSS e sull’OS.ConclusioniI risultati di questo studio di riferimento potrebbero essere utili per la comprensione dell’evoluzione di nuove tecniche radioterapiche per il trattamento dei tumori della rinofaringe, come la radioterapia tridimensionale conformazionale (3DCRT) e specialmente la radioterapia a modulazione d’intensità (IMRT).

An Alternating Regimen of Irinotecan/ 5-Fluorouracil/Folinic Acid and Oxaliplatin/ 5-Fluorouracil/Folinic Acid in Metastatic Colorectal Cancer: A Phase II Trial

Objective: To assess the feasibility and activity of a combination schedule with irinotecan (CPT-11), oxaliplatin (L-OHP), brief infusional fluorouracil (5-FU) and folinic acid (FA) as first-line treatment in metastatic colorectal cancer (MCC) patients. Methods: Fifty consecutive patients were treated with CPT-11 125 mg/m2 as a 90-min intravenous infusion, followed by FA 20 mg/m2 as an intravenous bolus, and 5-FU 500 mg/m2 over a 2-hour intravenous infusion on days 1 and 8. L-OHP was administered at 85 mg/m2 over 2 h on day 15, in combination with a FA 60 mg/m2 intravenous bolus and 5-FU 600 mg/m2 as a 2-hour intravenous infusion on days 15–16. The treatment was repeated every 4 weeks for a maximum of 9 cycles. Results: Twenty-five of 50 assessable patients achieved a complete (n = 5) or partial (n = 20) response, leading to a response rate of 50% (95% CI 35–64%). Eighteen (36%) patients showed stable disease. The median time to tumor progression was 10.3 months (95% CI 9.6–10.9 months). After a median follow-up of 16.4 months, the median survival was not reached. Grade 3 neutropenia (8%), grade 3 nausea/vomiting (6%) and grade 3 diarrhea (2%) were the major adverse events. Conclusion: This alternating three-drug regimen is very well tolerated, manageable and effective in terms of activity and time to progression.

Primary cutaneous non-Hodgkin lymphoma: results of a retrospective analysis in the light of the recent ILROG guidelines

Purpose: To analyze clinical outcome, local response, survival and toxicity in patients with primary cutaneous lymphoma (PCL) treated with radiotherapy. Methods: From 1995 to 2014, 112 patients were treated. B-cell lymphomas (CBCLs; n = 86) and T-cell lymphomas (CTCLs; n = 23) were analyzed separately. Clinical and therapeutic characteristics (age, sex, histology, primary treatment and radiotherapy modality) were related to response to treatment, survival and toxicity. Results: CBCLs were divided into 4 subgroups: marginal-zone lymphoma (n = 20), follicle center lymphoma (n = 32), diffuse large-cell lymphoma (DLBCL; n = 22) and DLBCL-leg type (n = 12). No significant correlation was found between doses and systemic treatments, extent of biopsy and number of lesions. DLBCL-leg type patients were older (p = 0.05), had disseminated disease (p = 0.034), and more frequently had local (p = 0.01) or systemic recurrence (p = 0.05). CTCLs were divided into 4 subgroups: α/β CTCL (n = 3), nasal type CTCL (n = 0), γ/δ CTCL (n = 10) and mycosis fungoides (n = 10). Longer disease-free survival was observed in patients obtaining complete remission (p<0.001). Conclusions: Radiotherapy is feasible, safe and effective for localized PCLs. The choice of dose is related to histological subgroups and the related prognoses. Survival results are very good also in relapsing disease. In advanced cutaneous lymphoma radiotherapy alone has mainly a role in symptom palliation.