Loredana Costa

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.

Breast conserving treatment (BCT) for stage I-II breast cancer in elderly women: analysis of 927 cases.

INTRODUCTION Few breast conserving treatment (BCT) data include women older than 70. MATERIAL 910 women older than 70 were treated by BCT for stage I-II BC, with 670 pT(1) (72.3%), 245 pT(2) (26.4%) and 12 pT(x) (1.3%). Axillary nodal involvement occurred in 30.7% of cases. ER and PgR were positive in 85% and 71% of cases. Radiotherapy (RT) was delivered in all patients, tamoxifen in 55.8% and chemotherapy in 4.8%. RESULTS With a 65-month median follow-up, 28 (3%) local recurrences (LR) and 83 (9.1%) metastases occurred. Second cancer occurred in 51 (5.6%) patients. The 8-year overall survival (OS) and disease-specific survival (DSS) rates were 74% and 90%. The 8-year OS and DSS rates were 77% and 92% versus 65% and 84% in pT(1) versus pT(2) patients (p=0.01). 676 patients were in complete remission (74.3%); 22 were evolutive (2.4%). 206 patients died (22.6%). CONCLUSION Our study confirms the excellent local control in elderly patients treated by BCT with RT and identifies subgroups at high risk of distant relapse that should be treated more aggressively.

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.

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).

Optimizing Radiation Treatment Decisions for Patients Who Receive Neoadjuvant Chemotherapy

The indications for postoperative radiotherapy after surgery following neoadjuvant systemic therapy for breast cancer are reviewed and the controversial issues summarized. Current standards and areas of future development are delineated. The need of collecting data on radiotherapy characteristics and results, according to different clinical and biological parameters, in the framework of perspective clinical studies, is underlined.