Cyberknife stereotactic radiosurgery for the re-irradiation of brain lesions: a single-centre experience.

PURPOSE: The aim of our study was to retrospectively evaluate the feasibility and clinical benefit of cyberknife stereotactic radiosurgery (CSRS) in patients treated at Florence University for recurrent, pre-irradiated brain lesions. MATERIALS AND METHODS: Thirteen patients were retreated with cyberknife. Mean age was 47.1 years (range 33-77 years). Karnofsky performance status ranged from 60 to 100 (median 80). Eleven (84.6%) out of 13 patients had metastatic lesions: four (36.4%) had primary lung, three (27.2%) had primary breast cancer and four (36.4%) other types of solid malignancies. Two (15.4%) out of 13 patients had recurrent of glioblastoma. RESULTS: In terms of compliance with CSRS, the majority of patients did not develop any acute side effects. However, two (15.4%) out of 13 patients developed acute grade 2 toxicity requiring an increase of steroid medication. At the time of the last follow-up, response rates were as follows: complete response in one case (16.6%), partial response in three (50%) and stable disease in two (33.4%). CONCLUSIONS: Re-irradiation with CSRS is a feasible and effective option for pre-irradiated, recurrent brain lesions to obtain clinical benefit without excessive acute toxicity.

Late treatment-related complications in 214 patients with extremity soft-tissue sarcoma treated by surgery and postoperative radiation therapy.

BACKGROUND: We assessed the occurrence of long-bone fracture and other side effects in a group of 214 consecutive patients who underwent radical excision for soft-tissue sarcoma of the limb followed by postoperative irradiation. METHODS: Two hundred fourteen patients underwent postoperative irradiation after radical excision of soft-tissue sarcoma of the limb; 156 (73%) received postoperative brachytherapy (BRT) plus external-beam radiation therapy (EBRT), and 58 (27%) underwent postoperative EBRT only. All patients were followed-up for a median time of 4.5 years (range 3 months to 10 years). RESULTS: Seven patients developed bone fracture, which is considered severe morbidity; time between surgery and occurrence of fracture ranged between 10 and 72 months (average 31). Severe sclerosis with impairment of limb function was diagnosed in 5 and peripheral nerve damage in 3 patients. Wound complications were detected in 8 patients. CONCLUSIONS: In our series, no statistically significant correlation between bone fracture and clinical features or "technical" parameters was found, but all of the patients who experienced bone fracture (7 of 7) were postmenopausal women >55 years old.

Radical radiotherapy for early glottic cancer: Results in a series of 1087 patients from two Italian radiation oncology centers. II. The case of T2N0 disease.

PURPOSE: To retrospectively evaluate local control rates, late damage incidence, functional results, and second-tumor occurrence according to the different patient, tumor, and treatment features in a large bi-institutional series of T2 glottic cancer. METHODS AND MATERIALS: A total of 256 T2 glottic cancer cases treated consecutively with radical intent at the Florence University Radiation Oncology Department (FLO) and at the Radiation Oncology Department of the University of Brescia, Istituto del Radio "O. Alberti" (BS) were studied. Cumulative probability of local control (LC), disease-specific survival (DSS), and overall survival (OS) rates were calculated and compared in the different clinical and therapeutic subgroups by both univariate and multivariate analysis. Types of relapse and their surgical salvage were evaluated, along with the functional results of treatment. Late-damage incidence and second-tumor cumulative probability (STP) were also calculated. RESULTS: In the entire series, 3-year, 5-year, and 10-year OS rates were, respectively, 73%, 59%, and 37%. Corresponding values for cumulative LC probability were 73%, 73%, and 70% and for DSS, 89%, 86%, and 85%, taking into account surgical salvage of relapsed cases. Seventy-three percent of the patients were cured with function preserved. Main determinants of a worse LC at univariate analysis were larger tumor extent and impaired cord mobility. At multivariate analysis, the same factors retained statistical significance. Twenty-year STP was 23%, with second-tumor deaths less frequent than larynx cancer deaths (20 of 256 vs. 30 of 256). Incidence of late damage was higher in the first decade of accrual (22%) than in the last decade (10%, p = 0.03); the same was true for severe late damage (9% vs. 1.8%). CONCLUSION: Present-day radical radiotherapy can be considered a standard treatment for T2 glottic cancer. Better results are obtained in patients with less extended disease. Late damage is relatively infrequent, but a careful follow-up is warranted for early detection not only of relapses (because salvage surgery is feasible) but also of second malignant tumors, which constitute a relevant but not the leading cause of death in these patients and are potentially curable.

Radical radiotherapy for early glottic cancer: Results in a series of 1087 patients from two Italian radiation oncology centers. I. The case of T1N0 disease.

PURPOSE: To retrospectively evaluate local control rates, late damage incidence, functional results, and second tumor occurrence according to the different patient, tumor, and treatment features in a large bi-institutional series of T1 glottic cancer. METHODS AND MATERIALS: A total of 831 T1 glottic cancer cases treated consecutively with radical intent at the Florence University Radiation Oncology Department (FLO) and at the Radiation Oncology Department of the University of Brescia-Istituto del Radio "O. Alberti" (BS) were studied. Actuarial cumulative local control probability (LC), disease-specific (DSS), and overall survival (OS) rates have been calculated and compared in the different clinical and therapeutic subgroups with both univariate and multivariate analysis. Types of relapse and their surgical salvage have been evaluated, along with the functional results of treatment. Late damage incidence and second tumor cumulative probability (STP) have been also calculated. RESULTS: In the entire series, 3-, 5-, and 10-year OS was equal to 86%, 77%, and 57%, respectively. Corresponding values for LC were 86%, 84%, and 83% and for DSS 96%, 95%, and 93%, taking into account surgical salvage of relapsed cases. Eighty-seven percent of the patients were cured with function preserved. Main determinants of a worse LC at univariate analysis were: male gender, earlier treatment period, larger tumor extent, anterior commissure involvement, and the use of Cobalt 60. At multivariate analysis, only gender, tumor extent, anterior commissure involvement, and beam type retained statistical significance. Higher total doses and larger field sizes are significantly related (logistic regression) with a higher late damage incidence. Scatterplot analysis of various combinations of field dimensions and total dose showed that field dimensions >35 and <49 cm2, together with doses of >65 Gy, offer the best local control results together with an acceptably low late damage incidence. Twenty-year STP was equal to 23%, with second tumor deaths being more frequent than larynx cancer deaths (67 of 831 vs. 46/831). CONCLUSION: The results of this study support the opinion, suggested by some international guidelines, that radiotherapy is standard treatment for T1 glottic cancer. Better results are obtained in patients with less extended disease and with 4-6 MV photon beams. The use of doses in excess of 65 Gy and of field sizes of 36-49 cm2 is probably the best technical choice available. Late damage is infrequent, but careful follow-up is warranted to detect early not only relapses (because conservative salvage surgery is feasible), but also second malignant tumors, which constitute the main cause of death in these patients and are potentially curable.

Treatment of uterine sarcoma at the University of Florence from 1980-2001.

PURPOSE: To correlate the treatment used in uterine sarcoma with outcome. The prognostic importance of pathology, clinical parameters and treatment are analyzed. PATIENTS AND METHODS: Forty patients (median age, 59 years; range, 37-85) with histologically verified uterine sarcoma were identified from a database compiled at the University of Florence from 1980 to 2001. Patients were followed for a median of 54 months (range, 3 months to 10 years). Twenty-four patients had leiomyosarcoma, 12 patients had mixed mullerian tumors, and 3 patients had endometrial stromal sarcoma. Stage I, II, III and IV tumors were identified in 22, 2, 9 and 7 patients, respectively. High, intermediate, low and unspecified grade sarcoma occurred in 9, 4, 5 and 22 patients, respectively. RESULTS: At the time of analysis, 58% of patients had died and 42% were alive, with a median survival of 2 years from the initial diagnosis. Cause-specific survival for the entire group was 81%, 41% and 25% at 1, 3 and 5 years, respectively. In our series, univariate analysis for cause-specific survival did not demonstrate statistical significance for histology, grade, stage or age. There appeared to be a significant impact for postoperative radiotherapy in reducing local recurrence with a total dose higher than 50 Gy. CONCLUSIONS: Our data favor treatment for uterine sarcoma with radical surgery plus irradiation, even in elderly patients.

Accelerated intensity-modulated external radiotherapy as a new technical approach to treat the index quadrant after conserving surgery in early breast cancer: a preliminary study.

PURPOSE: We present a novel technical approach to treat the index quadrant after conserving surgery in patients with early breast cancer and study its clinical feasibility. METHODS AND MATERIAL: Patients selected for the study, after breast conserving surgery with histologically verified breast carcinoma, signed a full informed consent to intensity-modulated external radiotherapy of the partial breast. Treatment was performed with the 6 MV beam from one of the Elekta Precise LINAC units installed in our Department. The prescribed dose was 30 Gy in 5 fractions in 10 days. RESULTS: Acute toxicity was minimal. No skin changes were noted during treatment or during the first 6 months after radiotherapy treatment. CONCLUSIONS: Accelerated partial breast irradiation using intensity-modulated external radiotherapy is technically feasible. We think the approach will give good results in terms of local control, toxicity and quality of life, at the same time sparing resources for the patient and health care system.

Practice patterns for prostate cancer in nine central and northern Italy radiation oncology centers: a survey including 1759 patients treated during two decades (1980-1998).

PURPOSE: Prostate cancer patients in Italy are offered the choice of the full spectrum of possible treatment options for their disease, but the diffusion of the more recent technological refinements among the Radiation Oncology centers is not homogeneous and there is a need to establish a reference "historical" data source. This retrospective study describes the changing patterns in prostate cancer patient practice and the therapeutic results obtained in nine Radiation Oncology centers of Northern and Central Italy (five in Northern Italy and four in Central Italy). METHODS AND MATERIALS: A total of 1759 prostate cancer patients, radically treated in the nine radiotherapy (RT) centers between 1980 and 1998, made up the study population. Data collected for each patient included clinical, pathologic, therapeutic features, and toxicity. The overall survival, disease-specific survival (DSS), and clinical relapse-free survival (RFS) were calculated for the whole series and for the subsets of patients defined by different clinical, pathologic, and therapeutic features, according to three accrual periods (A, 1980-1990; B, 1991-1994; and C, 1995-1998). Univariate and multivariate analyses were performed to identify prognostic factors related to survival and late adverse effects (cystitis and proctitis) probability. RESULTS: Patient accrual increased markedly during the 2 decades considered, and the percentage of cases with Stage C or D disease dropped from 49% (period A) to 43% (period B) to 37% (period C) (p < 0.0001, chi-square). The baseline prostate-specific antigen value was available for 10%, 76%, and 95% of the cases treated in the three different periods. The major changes in the therapeutic options were an increase in dose to the prostate (>66 Gy in 44%, 84%, and 93% of the patients treated in period A, B, and C, respectively); a reduction in treated volumes, including pelvic lymphatic drainage (56-39% before 1995, 22% thereafter); and an increase in cases treated in association with hormonal therapy (50% before 1991, 80% thereafter). Lower energy (<10 MV) photon beams were progressively abandoned (12% before 1990 vs. 6-7% thereafter), along with an increase in the use of blocks (60% in the last 4 years of the study vs. about 30-40% before 1995) and "conformal" RT (applied in 41% of cases treated after 1994). The actuarial RFS, DSS, and overall survival rate at 5 years was, respectively, 60% +/- 2%, 75% +/- 2%, 66% +/- 2% for period A; 74% +/- 2%, 90% +/- 1%, 83% +/- 2%, for period B; and 67% +/- 5%, 90% +/- 2%, 79% +/- 5% for period C. The actuarial overall survival, DSS, and RFS rate for the whole series of 1759 patients was 77% +/- 1%, 86% +/- 1%, and 68% +/- 1% at 5 years, respectively. Multivariate analysis showed that only American Urologic Association stage, grade, dose to the prostate, accrual period, association with hormonal treatment after (or both after and before) RT (only in terms of DSS and RFS), and baseline prostate-specific antigen value (only for RFS) retained prognostic significance in the final Cox model. CONCLUSION: The increase in the accrual of prostate cancer patients radically treated with RT has been accompanied by considerable changes in the clinical features at presentation, as well as in the staging and treatment procedures. Patients treated more recently had better survival results. An earlier stage and more favorable grade were linked with better overall, DSS, and RFS at multivariate analysis. Lower prostate-specific antigen baseline values were also related to better RFS. Better results were obtained with higher radiation doses, and the dose to tumor seemed the most important treatment-related prognostic factor. The toxicity (cystitis and proctitis, every Radiation Therapy Oncology Group grade) was substantially the same in the different accrual periods, but larger treated volumes and higher doses appeared to increase the incidence of late effects.

Circulating tumor cells in patients with recurrent or metastatic head and neck carcinoma: prognostic and predictive significance.

INTRODUCTION: We investigated the frequency of detection and the prognostic and predictive significance of circulating tumor cells (CTCs) in patients with recurrent/metastatic (R/M) head and neck carcinoma (HNC) before starting systemic therapy. PATIENTS AND METHODS: Using the CellSearch technology, CTCs were assessed prospectively in peripheral blood of 53 R/M-HNC patients. We performed spiking experiments to test the diagnostic performance of the CellSearch platform in identifying squamous carcinoma cells. RESULTS: CTCs were identified in 14 (26%) and 22 (41%) patients at baseline and at any time point, respectively. In univariate analysis ≥2 CTCs had a poorer prognostic role than 0-1 CTC. In multivariate analysis, the presence of one CTC or more was associated with a poor prognosis both in terms of progression-free survival (PFS) [Hazard Ratio (HR): 3.068, 95% confidence interval (CI): 1.53-6.13, p 0.002] and overall survival (OS) [HR: 3.0, 95% CI: 1.48-6.0, p 0.002]. A disease control after systemic therapy was obtained in 8% of CTC-positive patients as opposed to 45% in CTC-negative ones (p 0.03). The epidermal growth factor receptor (EGFR) expression was identified in 45% of CTC-positive patients. DISCUSSION: In conclusion, CTCs are detected in one out of three patients with RM-HNC. CTC detection is a strong prognostic parameter and may be predictive of treatment efficacy. The frequency of EGFR expression in CTCs seems to be lower than that expected in the primary tumor.

Paclitaxel and bevacizumab in first-line treatment for HER2-negative metastatic breast cancer: single-center experience.

The aim of our analysis was to report the outcome and safety of patients treated with bevacizumab and paclitaxel as first-line treatment for HER2-negative metastatic breast cancer. Between February 2009 and August 2011, 62 consecutive patients received paclitaxel 90 mg/m(2) on days 1, 8, and 15 and bevacizumab (BV) 10 mg/kg intravenously on days 1 and 15, every 28-day cycle. After 6 cycles of combined treatment, patients were given maintenance BV every 3 weeks (15 mg/kg) until progression disease or unacceptable toxicity. At time of analysis, median overall survival was 12.3 months (range 4.6-44.8 months), progression-free survival was 8.1 months (range 2.3-33.2 months), and time to treatment failure was 8.4 months (range 2.3-33.2 months). Our results confirmed the efficacy and the acceptable toxicity profile of bevacizumab plus paclitaxel as first-line regimen for metastatic breast cancer.

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 cancer in the elderly: treatment of 1500 patients.

There is a significant difference in the extent of treatment offered to the elderly with breast cancer; in the United States, while 98% of patients less than 65 years of age receive standard treatment, 81% of those older than 65 years were treated according to protocol. This study's goal was to evaluate disease-specific survival and local-regional recurrence in breast cancer patients more than 65 years of age at diagnosis. A total of 1500 patients with invasive breast carcinoma were treated consecutively from May 1971 to July 2002 at the University of Florence, Florence, Italy. All patients were more than 65 years of age. The median age was 70.6 years (range 65.1-87.3 years). The median follow-up was 8.7 years (range 1-30 years). The crude probability of survival (or relapse occurrence) was estimated using the Kaplan-Meier method and survival (or relapse occurrence) comparisons were carried out using Cox proportional hazard regression models. The Cox regression model by stepwise selection showed as independent prognostic factors for disease-specific survival (DSS), the occurrence of a local relapse (p < 0.0001), pN status (p < 0.0001), the type of surgery (p < 0.0001), and the use of radiotherapy (p < 0.0006) and chemotherapy (p = 0.01). For local disease-free survival (LDFS), the Cox regression model by stepwise selection showed that mastectomy (p < 0.0001), histotype (p < 0.0001), pN status (p < 0.0001), and pT status (p = 0.001) were the only independent prognostic factors. Age was not a prognostic factor for DSS nor LDFS. We suggest treating patients with appropriate treatment for their prognostic factors.