Enzo Banelli

PROGNOSTIC IMPLICATION OF CLINICAL AND PATHOLOGIC FEATURES IN PATIENTS WITH GLIOBLASTOMA MULTIFORME TREATED WITH CONCOMITANT RADIATION PLUS TEMOZOLOMIDE

Aims and background Glioblastoma multiforme is the most common and most malignant primary brain tumor in adults. The current standard of care for glioblastoma is surgical resection to the extent feasible, followed by adjuvant radiotherapy plus temozolomide, given concomitantly with and after radiotherapy. This report is a prospective observational study of 43 cases treated in the Department of Radiotherapy, University of Rome La Sapienza, Italy. We examine the relationship between pathologic features and objective response rate in adult patients treated with concomitant radiation plus temozolomide to identify clinical, neuroradiologic, pathologic, and molecular factors with prognostic significance. Methods Forty-three consecutive patients (24 males and 19 females), ages 15-77 years (median, 57) with newly diagnosed glioblastoma multiforme, were included in this trial between 2002 and 2004 at our department. All patients were treated with surgery (complete resection in 81%, incomplete in 19%) followed by concurrent temozolomide (75 mg/m2/day) and radiotherapy (median tumor dose, 60 Gy), followed by temozolomide, 200 mg/m2/day for 5 consecutive days every 28 days. Neurologic evaluations were performed monthly and cranial magnetic resonance bimonthly. We analyzed age, clinical manifestations at diagnosis, seizures, Karnofsky performance score, tumor location, extent of resection, proliferation index (Ki-67 expression), p53, platelet-derived growth factor and epidermal growth factor receptor immunohistochemical expression as prognostic factors in the patients. The Kaplan-Meier statistical method and logrank test were used to assess correlation with survival. Results Fourteen patients (32%) manifested clinical and neuroradiographic evidence of tumor progression within 6 months of surgery. In contrast, 5 patients (12%) showed no disease progression for 18 months from the beginning of treatment. Median overall survival was 19 months. Multivariate analysis revealed that an age of 60 years or older (P <0.03), a postoperative performance score ≤70 (P = 0.04), the nontotal tumor resection (P = 0.03), tumor size >4 cm (P = 0.01) and proliferation index overexpression (P = 0.001) were associated with the worst prognosis. p53, PDGF and EGFR overexpression were not significant prognostic factors associated with survival. Conclusions The results suggest that analysis of prognostic markers in glioblastoma multiforme is complex. In addition to previously recognized prognostic variables such as age and Karnofsky performance score, tumor size, total resection and proliferation index overexpression were identified as predictors of survival in a series of patients with glioblastoma multiforme.

RADIOTHERAPY FOR T1 CARCINOMA OF THE GLOTTIS

Aims and background The management of patients with T1 carcinoma of the glottic larynx is controversial, because surgery and radiation therapy are reported to be effective treatments. Several studies have shown radiotherapy to be safe and effective, with a high percentage of voice preservation and minimal complications, but most Italian physicians prefer to surgically treat such patients. Methods From 1980 to 1990, 36 patients with stage I squamous cell glottic carcinoma were treated with radiotherapy alone at the Institute of Radiology of University of Rome “La Sapienza”. In all patients the irradiation fields were limited to the larynx, with field size ranging from 4 × 4 cm to 7 × 7 cm. Total tumor doses ranged between 51 and 70 Gy (median 60 Gy) with a mean number of 30 fractions of 2 to 3 Gy per fraction (3 or 5 fractions per week). Results After a median follow-up of 98 months, we observed an overall survival rate at 5 years of 91.4% and actuarial 10-year survival of 85.7%. Local control was achieved in 97.1% of cases, with an event-free survival of 94.2% at 5 and 10 years. No major complications like necrosis or persistent edema of the larynx were observed. Minor complications like dysphonia (8%) and dysphagia (5.5%) were temporary; laryngeal function was completely preserved at the end of therapy. Final voice quality ranged from good to excellent. Conclusions Our series confirms that radiation therapy has a major role in the management of early glottic cancer, with results comparable to surgical approaches and with better voice preservation.

Hodgkin's disease stage I and II with exclusive subdiaphragmatic presentation. The experience of the Departments of Radiation Oncology and Hematology, University "La Sapienza" of Rome.

During the period 1978 to 1994, 1054 patients with Hodgkins disease were evaluated and treated at the Departments of Radiation Oncology and Hematology, University “La Sapienza”, Rome. A total of 549 patients presented with clinical or pathological stage I and II; 37 of these had Hodgkins disease below the diaphragm (BDHD), and 512 above the diaphragm (ADHD). A comparison of patients with BDHD versus those with ADHD showed that the first group had a higher male to female ratio. A comparison of cases with stage II BDHD versus those with stage II ADHD showed that patients with BDHD were older (48 years vs 28 years), had different histologic features and a higher incidence of systemic symptoms (67% vs 33%). Stage II BDHD patients had a worse prognosis; in fact, there were significant differences in the overall survival and relapse-free-survival rates for cases with stage II BDHD versus those with stage II ADHD (overall survival, 46% vs 80%, P<0.001; relapse-free survival, 44% vs 69%, P<0.005). Stage was found to be the most important prognostic factor for BDHD cases without systemic symptoms treated with radiation therapy alone. The type of infradiaphragmatic presentation (intra-abdominal vs peripheral disease) did not influence outcome, probably due to the more aggressive therapy received by the intra-adbominal group. Treatment recommendations for BDHD cases should be tailored to the stage and the presence or absence of intra-abdominal localization. For patients with stage IA extended fields, irradiation (inverted Y) is sufficent. However, combined modality therapy should be the treatment of choice for stage II cases, particularly in the presence of intra-abdominal disease. Patients with systemic symptoms also require combined modalities.

Fractionated total body irradiation in allogeneic bone marrow transplantation in leukemia patients: analysis of prognostic factors and results in 136 patients

BACKGROUND AND PURPOSE The results of a single-institution series of patients with chronic and acute leukemias are analyzed with regard to literature-reported predictor variables. MATERIALS AND METHODS Between 1985 and 1994, 136 patients, 82 patients with chronic myeloid leukemia (CML) and 54 with acute leukemia (AL), received a uniform preparatory regimen of fractionated total body irradiation (TBI; 12 Gy in 3 days) plus different chemotherapy regimens before bone marrow transplantation. Eighty-six patients were considered to be in early phase of disease (CML in chronic phase or AL in first complete remission) and 50 in advanced phase (all those beyond first remission or first chronic phase). Ninety-five patients received unmanipulated allogeneic BM, and 41 T-lymphocyte-depleted BM. RESULTS The 5-year overall survival (OS) and disease-free survival (DFS) of the whole series were 43% and 31%, and median survival was 43 and 10 months, respectively. A Cox proportional hazard model identified variables related to overall and disease-free survival. For OS, graft versus host disease (GVHD) was the first independent variable (P < 0.0001), followed by age (P < 0.001), T-depletion (P < 0.01), disease status (P < 0.05) and type of leukemia (P < 0.05). With regard to DFS, only T-depletion (P < 0.0001), disease status (P < 0.01) and GVHD (P < 0.01) resulted predictor factors. Early complications after BMT were reported in 59 patients, TBI-induced delayed toxicity in 9 patients, and 16 patients suffered late complications. CONCLUSIONS Our results confirm the curability of early phase leukemias with standard fractionated TBI-induced Allogeneic bone marrow transplantation (ABMT). With an homogeneous fractionated TBI schedule as employed in our series, T-cell depletion negatively affected the outcome.

Radiation Treatment of Testicular Relapse in Acute Lymphoblastic Leukemia

Ten patients with testicular relapse among 128 cases of acute lymphoblastic leukemia are reported. At the time of the initial diagnosis of leukemia all patients with later testicular relapse showed one or more risk factors as predictive for leukemic infiltration of the testicles. All patients except one, who underwent orchiectomy and died 11 weeks after surgical intervention, received radiation therapy with doses ranging from 12 to 20 Gy and chemotherapy. The local control was excellent. Average survival time from testicular relapse to death was 68 weeks in 8 of 9 patients treated by irradiation and chemotherapy. One patient is still alive without signs of disease after 6 years.

Comparison between intensified neoadjuvant treatment and standard preoperative chemoradiation for rectal cancer.

Objectives The aim of the current study was to compare a neoadjuvant regimen containing oxaliplatin with standard preoperative treatment for rectal cancer. Methods From December 2006 to December 2007, 20 patients with rectal cancer were treated at our Institution with the weekly addition of oxaliplatin (50 mg/m2) to radiotherapy (50.4–54.0 Gy in 28–30 daily fractions) and continuous infusion of 5-fluorouracil (200 mg/m2). The results of the regimen were compared with a historical control group including 21 consecutive patients previously treated with standard 5-fluorouracil treatment from December 2004 to October 2006. Results Both the rate of sphincter preservation in low rectal cancer (91.7% vs 36.4%, P = 0.009) and the rate of downstaging (84.2% vs 47.6%, P = 0.023) were higher in the oxaliplatin group than in the control group. Pathological complete response was achieved in 8 patients (42.1%) in the oxaliplatin group and in 4 patients (19.0%) in the control group (P = 0.172). When ypT0-pT1 stages were analyzed together, the P value was 0.051. Acute toxicity was increased in the oxaliplatin group, with a higher incidence of G3 diarrhea and pelvic pain than in the control group (30.0% vs 14.3%, P = NS). Conclusions Our data seem to correlate the addition of oxaliplatin to the standard treatment for rectal cancer with higher rates of sphincter preservation, down-staging and complete response. Toxicity is increased and requires careful monitoring. However, our results refer to a retrospective comparison of a small series of patients and need to be validated by the large, phase III randomized trial currently ongoing.

Pre-operative Radio-Chemotherapy of Rectal Cancer: Toxicity and Preliminary Results with the Addition of Weekly Oxaliplatin

The standard pre-operative treatment of rectal cancer consists of radiotherapy combined with continuous infusion of fluorouracil (FU) at a dose of 200 mg/m2/day. Platinum compounds can increase the anti-tumour activity of radiotherapy and are suitable agents to be combined with FU. We report our experience with the addition of oxaliplatin to radiotherapy and FU in the pre-operative treatment of patients with rectal cancer.

The Role of Restaging Laparotomy in Hodgkin'S Disease

The role of restaging laparotomy (RL) in Hodgkins disease was studied in 41 patients. Two patients were in clinical stage I, 16 in clinical stage II, 13 in clinical stage III and 10 in clinical stage IV. Eight cases had previously received radiation therapy alone, 26 chemotherapy and 7 combined chemo-, and radiotherapy. The patients were divided into 2 groups, depending on the results of the preoperative clinical reevaluation. Group 1 included 20 patients with suspicion of persistent disease; in 6 (30%) RL was positive. Group 2 consisted of 21 cases with clinical appearance of complete response; RL was positive in one case (4.7%). The results of the comparison confirm the high rate of false positive findings in CT and lymphography. RL appears as a valuable procedure in patients with positive or doubtful clinical findings at reevaluation after radical therapy, in order to reduce the risk of unnecessary treatment.