Filippo Bertoni

Prognostic value of Dworak grade of regression (GR) in patients with rectal carcinoma treated with preoperative radiochemotherapy

Background and aimPreoperative radiochemotherapy improves local control in locally advanced rectal cancer; however, its role in prolonging survival is still controversial. In order to better define the subset in patients who might benefit from this multimodal treatment, we have evaluated the correlation between grade of regression (GR) to preoperative treatment and disease-free survival (DFS).MethodsWe reviewed retrospectively the surgical specimens of 106 patients with locally advanced T3/T4 N0/ M0 rectal cancer. All patients were treated preoperatively with radiotherapy and 5-fluorouracil-based regimen chemotherapy. We evaluated ypTNM stage, and tumor regression was graded using the Dworak system that varies from GR 0 (absence of regression) to GR 4 (complete regression).ResultsGR was as follows: GR 4, 16 patients (15%); GR 3, 25 patients (23.6%), GR 2, 30 patients (28.4%), GR 1, 32 patients (30.2%) and GR 0, 3 patients (2.8%). A significant correlation was found between GR and DFS. Three-year DFS was 100, 85, 82, 66 and 33% in GR 4, 3, 2, 1 and 0, respectively (p=0.01). DFS was significantly lower in patients with advanced stages at diagnosis and in patients without down-staging. Moreover, in postoperative stage II and III cases, GR 3 correlated with a better DFS than GR 2–0 (p=0.2 and p=0.4, respectively).ConclusionsThe GR was a significant prognostic factor in locally advanced rectal carcinoma treated with preoperative chemoradiotherapy. The pathological stage and down-staging also have prognostic value. The use of a standardized system to evaluate GR in rectal cancer can allow for comparisons between different institutions and can identify patients at worse prognosis to be treated with adjuvant therapy.

Patterns of care and survival in a retrospective analysis of 1059 patients with glioblastoma multiforme treated between 2002 and 2007: a multicenter study by the Central Nervous System Study Group of Airo (italian Association of Radiation Oncology).

OBJECTIVETo investigate the pattern of care and outcomes for newly diagnosed glioblastoma in Italy and compare our results with the previous Italian Patterns of Care study to determine whether significant changes occurred in clinical practice during the past 10 years. METHODSClinical, pathological, therapeutic, and survival data regarding 1059 patients treated in 18 radiotherapy centers between 2002 and 2007 were collected and retrospectively reviewed. RESULTSMost patients underwent both computed tomography and magnetic resonance imaging either preoperatively (62.7%) or postoperatively (35.5%). Only 123 patients (11.6%) underwent a biopsy. Radiochemotherapy with temozolomide was the most frequent adjuvant treatment (70.7%). Most patients (88.2%) received 3-dimensional conformal radiotherapy. Median survival was 9.5 months. Two- and 5-year survival rates were 24.8% and 3.9%, respectively. Multivariate analysis showed the statistical significance of age, postoperative Karnofsky Performance Status scale score, surgical extent, use of 3-dimensional conformal radiotherapy, and use of chemotherapy. Use of a more aggressive approach was associated with longer survival in elderly patients. Comparing our results with those of the subgroup of patients included in our previous study who were treated between 1997 and 2001, relevant differences were found: more frequent use of magnetic resonance imaging, surgical removal more common than biopsy, and widespread use of 3-dimensional conformal radiotherapy + temozolomide. Furthermore, a significant improvement in terms of survival was noted (P < .001). CONCLUSIONChanges in the care of glioblastoma over the past few years are documented. Prognosis of glioblastoma patients has slightly but significantly improved with a small but noteworthy number of relatively long-term survivors.

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.

Radiotherapy and temozolomide in anaplastic astrocytoma: a retrospective multicenter study by the Central Nervous System Study Group of AIRO (Italian Association of Radiation Oncology).

Although the evidence for the benefit of adding temozolomide (TMZ) to radiotherapy (RT) is limited to glioblastoma patients, there is currently a trend toward treating anaplastic astrocytomas (AAs) with combined RT + TMZ. The aim of the present study was to describe the patterns of care of patients affected by AA and, particularly, to compare the outcome of patients treated exclusively with RT with those treated with RT + TMZ. Data of 295 newly diagnosed AAs treated with postoperative RT ± TMZ in the period from 2002 to 2007 were reviewed. More than 75% of patients underwent a surgical removal. All the patients had postoperative RT; 86.1% of them were treated with 3D-conformal RT (3D-CRT). Sixty-seven percent of the entire group received postoperative chemotherapy with TMZ (n = 198). One-hundred sixty-six patients received both concomitant and sequential TMZ. Prescription of postoperative TMZ increased in the most recent period (2005-2007). One- and 4-year survival rates were 70.2% and 28.6%, respectively. No statistically significant improvement in survival was observed with the addition of TMZ to RT (P = .59). Multivariate analysis showed the statistical significance of age, presence of seizures, Recursive Partitioning Analysis classes I-III, extent of surgical removal, and 3D-CRT. Changes in the care of AA over the past years are documented. Currently there is not evidence to justify the addition of TMZ to postoperative RT for patients with newly diagnosed AA outside a clinical trial. Results of prospective and randomized trials are needed.

Are international guidelines for the prescription of adjuvant treatment for early breast cancer followed in clinical practice? Results of a population-based study on 1547 patients.

Aims and background The results of several randomized trials and meta-analyses have been reported on adjuvant treatment for early breast cancer and treatment guidelines have been defined accordingly, but detailed data are lacking on the appropriateness of treatment prescription in clinical practice. Methods We performed a prospective, observational, multicenter study to monitor the prescription, delivery and effectiveness of radiotherapy following conservative surgery for early breast cancer; 1610 patients treated with postoperative radiation to the breast in 1997 were entered by 12 centers in Lombardy, Italy. Here we report the results of a secondary analysis focused on the prescription of medical adjuvant treatment (1547 eligible patients). Results Chemotherapy only was prescribed to 526 patients (33%), hormonal therapy only to 539 (33%), and both treatments to 85 patients (5%); 460 women (29%) received no medical adjuvant treatment. We compared the collected data with guidelines defined in 1995 by the St Gallen Consensus Conference. Undertreatment was most frequent in node-negative patients at intermediate/high risk, no treatment (instead of tamoxifen or chemotherapy) being prescribed in 21–45% of cases. Node-negative patients at low risk, on the other hand, were overtreated with tamoxifen in 31% of cases. In node-positive, premenopausal women compliance with guidelines was far better, with a 91–96% rate of chemotherapy prescription. In node-positive, postmenopausal, estrogen receptor-positive patients chemotherapy was unduly prescribed in as many as 56% of cases. Comparison of clinical practice with the next version of the guidelines (1998) showed a somewhat better compliance. Conclusions Despite the availability of official and authoritative guidelines, adjuvant treatment prescription for early breast cancer in Lombardy in 1997 was suboptimal, especially in well-defined subgroups of patients.

Double-blind randomized study of lonidamine and radiotherapy in head and neck cancer

PURPOSE Preclinical studies showed lonidamine to potentiate the effects of x-irradiation by inhibiting the repair of potentially lethal damage. This Phase III double blind, placebo-controlled study was performed to evaluate whether lonidamine can increase the tumor control of radiotherapy in the treatment of advanced head and neck cancer without any synergistic toxic effects on the exposed normal tissues. METHODS AND MATERIALS Ninety-seven patients with Stages II-IV squamous cell carcinoma of the head and neck were enrolled. Separate analyses were done on the 96 eligible patients and the 90 patients who completed the prescribed treatment regimen. Patients received radiotherapy up to a planned total of 60-66 Gy, in 2 daily fractions of 1.5 Gy each and either lonidamine (450 mg p.o. in three divided daily doses) or placebo, given continuously for 3 months or up to 1 month after the end of radiotherapy. RESULTS The rate of tumor clearance was 66% (32/48) in the lonidamine group and 65% (31/48) in the placebo group, while the subsequent failure rate was 50% and 77%, respectively (p < 0.05). The 3 and 5 year locoregional control rates in the adequately treated patients achieving complete tumor clearance were 66% and 63% for lonidamine vs. 41% and 37% for placebo. The disease-free survival in adequately treated patients was significantly better in the lonidamine group (p < 0.03), with 3 and 5 year rates of 44% and 40%, respectively, vs. 23% and 19% in the placebo group. The overall survival rate for all eligible patients at both 3 and 5 years was 44% in the lonidamine group and 44% and 31%, respectively, in the placebo group. Both acute and late radiation reactions were similar in the two groups. Myalgia and testicular pain were the most frequent side effects of lonidamine with an incidence of 8.5% and 4.2%, respectively. CONCLUSION The addition of lonidamine to hyperfractionated radiotherapy was correlated with a statistically and clinically significant proportion of long-term disease-free patients. The toxicity of radiotherapy was not aggravated by the drug and the overall tolerance of the combined regimen was acceptable.

Conservative treatment of breast ductal carcinoma in situ: results of an Italian multi-institutional retrospective study

BackgroundThe incidence of ductal carcinoma in situ (DCIS) has increased markedly in recent decades. In the past, mastectomy was the primary treatment for patients with DCIS, but as with invasive cancer, breast-conserving surgery followed by radiation therapy (RT) has become the standard approach. We present the final results of a multi-institutional retrospective study of an Italian Radiation Oncology Group for the study of conservative treatment of DCIS, characterized by a very long period of accrual, from February 1985 to March 2000, and a median follow-up longer than 11 years.MethodsA collaborative multi-institutional study was conducted in Italy in 10 Radiation Oncology Departments. A consecutive series of 586 women with DCIS histologically confirmed, treated between February 1985 and March 2000, was retrospectively evaluated. Median age at diagnosis was 55 years (range: 29–84); 32 patients were 40 years old or younger. All women underwent conservative surgery followed by whole breast RT. Irradiation was delivered to the entire breast, for a median total dose of 50 Gy; the tumour bed was boosted in 295 cases (50%) at a median dose of 10 Gy.ResultsAfter a median follow-up of 136 months (range: 16–292 months), 59/586 patients (10%) experienced a local recurrence: invasive in 37 cases, intraductal in 20 and not specified in two. Salvage mastectomy was the treatment of choice in 46 recurrent patients; conservative surgery in 10 and it was unknown in three patients. The incidence of local recurrence was significantly higher in women younger than 40 years (31.3%) (p= 0.0009). Five patients developed distant metastases. Furthermore 40 patients developed a contralateral breast cancer and 31 a second primary tumour in a different site. The 10-year actuarial overall survival (OS) was 95.5% and the 10-year actuarial disease-specific survival (DSS) was 99%.ConclusionsOur results are consistent with those reported in the literature. In particular it has been defined the importance of young age (40 years or less) as a relevant risk factor for local recurrence. This retrospective multi-institutional Italian study confirms the long term efficacy of breast conserving surgery with RT in women with DCIS.

A support vector machine tool for adaptive tomotherapy treatments: Prediction of head and neck patients criticalities

PURPOSE Adaptive radiation therapy (ART) is an advanced field of radiation oncology. Image-guided radiation therapy (IGRT) methods can support daily setup and assess anatomical variations during therapy, which could prevent incorrect dose distribution and unexpected toxicities. A re-planning to correct these anatomical variations should be done daily/weekly, but to be applicable to a large number of patients, still require time consumption and resources. Using unsupervised machine learning on retrospective data, we have developed a predictive network, to identify patients that would benefit of a re-planning. METHODS 1200 MVCT of 40 head and neck (H&N) cases were re-contoured, automatically, using deformable hybrid registration and structures mapping. Deformable algorithm and MATLAB(®) homemade machine learning process, developed, allow prediction of criticalities for Tomotherapy treatments. RESULTS Using retrospective analysis of H&N treatments, we have investigated and predicted tumor shrinkage and organ at risk (OAR) deformations. Support vector machine (SVM) and cluster analysis have identified cases or treatment sessions with potential criticalities, based on dose and volume discrepancies between fractions. During 1st weeks of treatment, 84% of patients shown an output comparable to average standard radiation treatment behavior. Starting from the 4th week, significant morpho-dosimetric changes affect 77% of patients, suggesting need for re-planning. The comparison of treatment delivered and ART simulation was carried out with receiver operating characteristic (ROC) curves, showing monotonous increase of ROC area. CONCLUSIONS Warping methods, supported by daily image analysis and predictive tools, can improve personalization and monitoring of each treatment, thereby minimizing anatomic and dosimetric divergences from initial constraints.

Vaginal molds for intracavitary curietherapy: a new method of preparation.

A new method of preparing vaginal molds for afterloading intracavitary brachytherapy is described. Our technique makes it possible to obtain the most accurate individualization of therapy as far as dose distribution is concerned by taking into account the patients anatomy and target volume.

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.