Sandro Tonoli

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.

Adjuvant radiotherapy after extrapleural pneumonectomy for mesothelioma. Prospective analysis of a multi-institutional series

BACKGROUND AND PURPOSE To evaluate survival, locoregional control and toxicity in a series of 56 mesothelioma patients treated from May 2005 to May 2010 with post-operative radiotherapy after extrapleural pneumonectomy (EPP) in three Italian Institutions (Brescia, Florence, and Modena). MATERIAL AND METHODS Fifty-six patients treated with adjuvant radiotherapy (RT) after EPP were analyzed. Four patients were treated with 3DCRT, 50 with IMRT and two with helical tomotherapy. Forty-five to 50 Gy in 25 fractions were given to the affected hemithorax and to ipsilateral mediastinum, with a simultaneous integrated boost to the sites of microscopically involved margins up to 60 Gy in 20/56 cases. RESULTS Three year locoregional control (LRC), distant metastasis free (DMF), disease free (DF), disease specific (DSS) and overall survival (OS) rates are 90%, 66%, 57%, 62%, and 60%, respectively. CONCLUSION Postoperative RT with modern techniques is an effective method to obtain excellent local control and cure rates in mesothelioma patients submitted to EPP.

Expert opinions of the first Italian Consensus Conference on the management of malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a very important public health issue. A large amount of data indicates a relationship between mesothelioma and asbestos exposure. The incidence has both considerably and constantly increased over the past 2 decades in the industrialized countries and is expected to peak in 2010–2020. In Italy, a standardized-rate incidence in 2002 among men was 2.98 per 100,000 and 0.98 per 100,000 among women, with wide differences from one region to another. Stage diagnosis and definition may be difficult. Management of patients with MPM remains complex, so an optimal treatment strategy has not yet been clearly defined. The First Italian Consensus Conference on Malignant Pleural Mesothelioma was held Bologna (Italy) in May 20, 2008. The Consensus Conference was given the patronage of the Italian scientific societies AIOM, AIRO, AIPO, SIC, SICO, SICT, SIAPEC-IAP, AIOT, GOAM, and GIME. This Consensus did not answer all of the unresolved questions in MPM management, but the Expert Opinions have nonetheless provided recommendations, presented in this report, on MPM management for clinicians and patients.

Hypnosis instead of general anaesthesia in paediatric radiotherapy: report of three cases.

PURPOSE This report proposes hypnosis as a valid alternative to general anaesthesia for immobilisation and set-up in certain cases in paediatric radiotherapy. METHODS We report three cases of children who underwent radiotherapy in 1994 and were treated using hypnosis for set-up during irradiation. The first and the second were two cases of macroscopic resection of cerebellar medulloblastoma in which craniospinal irradiation was necessary, while the third patient suffered of an endorbitary relapse of retinoblastoma previously treated with bilateral enucleation, radiotherapy and chemotherapy; in this last situation the child needed radiation as palliative therapy. Hypnosis was used during treatment to obtain the indispensable immobility. Hypnotic conditioning was obtained by our expert psychotherapist while the induction during every single treatment was made by the clinician, whose voice was presented to the children during the conditioning. RESULTS Every single fraction of the radiation therapy was delivered in hypnosis and without the need for narcosis. CONCLUSIONS Hypnosis may be useful in particular situations to prepare paediatric cancer patients during irradiation, when lack of child collaboration might necessitate the use of general anaesthesia and when anaesthesia itself is not possible.

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.

Postoperative radiotherapy after radical prostatectomy for prostate carcinoma: the experience of the Brescia Radium Institute

Purpose.The purpose of this study was to evaluate the efficacy of postoperative radiotherapy in reducing the incidence of prostate carcinoma (PCa) recurrences after radical prostatectomy (RP), define the importance of the time interval between surgery and radiotherapy for prognosis and the toxicity of the treatment in comparison with radiotherapy or surgery alone.Materials and methods.We examined 97 patients who consecutively underwent postoperative radiotherapy after RP between 1980 and 2003. The treatment was considered “adjuvant” if was conducted less than 6 months after RP, if there was no macroscopic residual disease and if there was no progressive increase in serum prostate–specific antigen (PSA) and “salvage” if performed more than 6 months after RP, for the presence of macroscopic recurrence or with rising PSA. Radiotherapy was salvage in 56 patients and adjuvant in 41. Age range was 60–70 years in 80% of patients, and the Karnofsky index was over 80 in 78% of cases. Histology revealed extracapsular spread in 60% of patients. Preradiotherapy PSA was higher than 1 ng/ml in 36%. Radiotherapy was performed on the surgical bed only in 80%, and the total dose was 70 Gy in 62% of cases.Results.Recurrence–free survival (RFS) at 5 years and 10 years was 53±8% and 32±14.2%, respectively, for the whole sample; 76±9% and 38±2.7% for patients treated with adjuvant radiotherapy and 36±10% and 28±10% for those treated with salvage radiotherapy (p<0.01). Moreover, the 5–year RFS was better in the group treated with adjuvant radiotherapy and PSA less than or equal to 1 ng/ml (p<0.05). Treatment toxicity was acceptable.Conclusions.Postoperative radiotherapy improves RFS and reduces the risk of local recurrence. The best results are obtained with early postoperative treatment (“adjuvant”); adjuvant radiotherapy of high–risk forms yields better results if performed with PSA less than or equal to 1 ng/ml.

Open-source, low-cost, high-reliability solutions for digital imaging systems: example of a "dicom router".

PurposeThe purpose of this article is to illustrate a case where acquisition of digital imaging know-how by a modern radiotherapy division has helped to solve a technical problem while allowing substantial savings through the use of free and open-source resources. The problem was related to the necessity to route, with complex policies, the images produced by different digital imaging and communications in medicine (DICOM) sources within the department or in other divisions and/or hospitals.Materials and methodsThe problem was solved by using completely free, well-tested and stable technologies (PHP, Apache, MySQL, DCMTK OFFIS, Red Hat Linux 9A and Linux Fedora Core 4) and low-cost hardware to contain costs. In the development, we also considered integration of the routed images with the existing electronic clinical records.ResultsThe system developed, called the dicom router, implemented two kinds of routing: manual and automatic, both oriented to link the images acquired with the existing electronic clinical records. System stability was enhanced in a second phase by using a low-cost hardware redundancy solution. The system has now been operating for 1 year and has proved the value of the technologies used.ConclusionsThe need to operate with more than one provider creates a series of integration issues, so that it becomes economically appealing to acquire internally the knowledge needed to interact more precisely with providers of big information technology (IT) solutions. This need is well catered for by open-source technologies, which are well documented and available to everyone. By using them, in-house IT technicians are able to implement valuable technical solutions for small-to medium-sized informatization problems, which would otherwise remain unsolved except with great economic efforts.RiassuntoObiettivoScopo di questo lavoro è presentare un caso in cui l’acquisizione in seno ad un moderno reparto di radioterapia del “know how” relativo all’imaging digitale ha consentito di risolvere un problema con un cospicuo risparmio economico grazie all’utilizzo di risorse free ed open source. Il problema risolto è relativo alla necessità di instradare in maniera complessa immagini prodotte da differenti sorgenti DICOM provenienti dal reparto e da altri reparti e/o ospedali.Materiali e metodiIl problema è stato affrontato usando tecnologie gratuite (PHP, Apache, MySQL, DCMTK OFFIS, Linux Red Hat 9A e Linux Fedora Core 4), collaudate e stabili e sfruttando hardware di basso costo al fine di contenere le spese. Nella realizzazione si è inoltre considerato il problema dell’integrazione delle immagini acquisite nel sistema di cartelle cliniche informatizzate in uso nel reparto.RisultatiÈ stato realizzato un dispositivo, detto dicom router, che implementa due tipologie di instradamento: automatica e manuale, entrambe orientate all’integrazione delle immagini acquisite con il sistema di cartelle cliniche informatizzate. L’aspetto legato all’instabilità dell’hardware è stato poi risolto con una tecnica di ridondanza dei dispositivi. Il sistema così prodotto, già operante da più di un anno presso il nostro reparto, ha avuto modo di provare la validità delle scelte tecnologiche.ConclusioniLa necessità di operare con più fornitori crea una serie di problemi di integrazione per cui spesso diventa economicamente accattivante l’idea di acquisire in seno al reparto il “know how” per dialogare in maniera più precisa e disambigua con i fornitori di grandi soluzioni informatiche. Questa necessità ben si sposa con le possibilità offerte da tecnologie software open source ben documentate ed accessibili a tutti. Infatti, con l’uso di queste, il personale tecnico informatico in seno al reparto può implementare valide soluzioni per i piccoli/medi problemi di informatizzazione che, altrimenti, resterebbero insormontabili o economicamente molto impegnativi.

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).

Di riferimento su 883 pazienti affetti da neoplasia della rinofaringe trattati in due Centri italiani dal 1977 al 2000. Parte II: evoluzione delle scelte tecniche e tossicità

PurposeThe authors sought to define toxicity patterns 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 from 1977 to 2000 at the Florence (FLO) and Brescia (IRA) radiation oncology centres were studied. The crude incidence of late treatment toxicity in the different subgroups of patients was calculated and compared.ResultsHigher total and fractional doses and the “older” treatment techniques were related with an increased incidence of the main late effects of treatment. More recently treated patients experienced less treatment-related complications.ConclusionsResults of this benchmark study may have implications for understanding and developing new radiotherapy techniques, such as three-dimensional conformal radiotherapy (3D-CRT) and, in particular, intensity-modulated radiotherapy (IMRT) for NPC patients.RiassuntoObiettivoLo scopo di questo studio è definire i modelli di tossicità 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 2000 a Firenze (FLO, Florence) e Brescia (IRA, Istituto del Radio Alberti). La incidenza assoluta dei danni tardivi da trattamento è stata calcolata e confrontata per i vari sottogruppi di pazienti.RisultatiDosi totali e per frazione più elevate e le tecniche di trattamento più datate sono correlate ad un aumento dell’incidenza dei principali effetti tardivi del trattamento radioterapico. I pazienti trattati più recentemente hanno manifestato meno complicazioni legate al trattamento.ConclusioniI risultati di questo studio di riferimento potrebbero avere implicazioni anche per la comprensione e lo sviluppo delle nuove tecniche radioterapiche, come la radioterapia tridimensionale conformazionale (3DCRT) e specialmente la radioterapia a modulazione d’intensità (IMRT).

WHICH ROLE FOR RADIATION THERAPY IN ETHMOID CANCER? A RETROSPECTIVE ANALYSIS OF 84 CASES FROM A SINGLE INSTITUTION

Purpose To define the results of radiotherapy for the treatment of ethmoid carcinoma in a large, retrospective, substantially unselected series from a single institution. Methods and Materials A relatively large series of 84 consecutive patients treated at our Institution over a 30-year period (1970-2000) was retrospectively analyzed. Sixteen more patients treated in the same period were affected by a relapse of disease at presentation and were therefore excluded from the analysis. Most of the patients had T3 or T4 disease (76%), and half of them had undifferentiated (G3-G4) tumors. Radical surgery preceded radiotherapy in 60 patients, the remaining had only biopsy or incomplete surgery. Average ICRU dose varied according to the extent of postsurgical residual disease. Results The 5-year actuarial overall survival of the entire series was 48.6%, 5-year disease-specific survival 58%, and 5-year relapse-free survival 54.6%. Overall, disease-specific and relapse-free survival were significantly better (logrank test) for early stage patients (T1-T2) and for those with low-grade disease; relapse-free and disease-specific survival were also significantly (or almost significantly) better for patients who had radical surgery and for those with less extended postsurgical residue. Patients treated with radiotherapy after biopsy only or grossly incomplete surgery had 5-year relapse-free, disease-specific and overall survival of 22%, 42% and 37%, respectively. Higher cumulative doses (>60 Gy) were related to a not significantly lower recurrence probability in patients with micro- or macroscopic residual disease after surgery (54% vs 62%). Multivariate analysis (Cox model) showed that only T stage and grading were independent prognostic factors for overall and disease-specific survival, whereas the prognostic impact of radical surgery was limited to relapse-free survival. Conclusions Radical radiation therapy alone is able to cure about 25% of the unfavorably selected cases, after biopsy only or partial surgery. Radical surgery is associated with better relapse-free survival rates, but the contribution of postoperative radiotherapy to the primary treatment of these patients cannot be eliminated.