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Because of its anti-inflammatory, anti-fibrotic, anti-apoptotic and anti-neoplastic properties, the PPAR-γ agonist rosiglitazone is an interesting drug for investigating for use in the prevention and treatment of radiation-induced intestinal damage. We aimed to evaluate the radioprotective effect of rosiglitazone in a murine model of acute intestinal damage, assessing whether radioprotection is selective for normal tissues or also occurs in tumour cells.Mice were total-body irradiated (12 Gy), with or without rosiglitazone (5 mg/kg/day). After 24 and 72 hours, mice were sacrificed and the jejunum was collected. HT-29 human colon cancer cells were irradiated with a single dose of 2 (1000 cells), 4 (1500 cells) or 6 (2000 cells) Gy, with or without adding rosiglitazone (20 µM) 1 hour before irradiation. HT-29-xenografted CD1 mice were irradiated (16 Gy) with or without rosiglitazone; tumour volumes were measured for 33 days.Rosiglitazone markedly reduced histological signs of altered bowel structures, that is, villi shortening, submucosal thickening, necrotic changes in crypts, oedema, apoptosis, and inflammatory infiltrate induced by irradiation. Rosiglitazone significantly decreased p-NF-kB p65 phosphorylation and TGFβ protein expression at 24 and 72 hours post-irradiation and significantly decreased gene expression ofRosiglitazone exerts a protective effect on normal tissues and reduces alterations in bowel structures and inflammation in a radiation-induced bowel toxicity model, without interfering with the radiation effect on HT-29 cancer cells. PPAR-γ agonists should be further investigated for their application in abdominal and pelvic irradiation.

To conduct a survey among Sicilian centers of radiation oncology belonging to Associazione Italiana di Radioterapia ed Oncologia Clinica (AIRO), to record the different methods of integration of radio-chemotherapy both in neoadjuvant and adjuvant settings, to evaluate surgical procedures in relation to the sphincter preservation and to report the different toxicity profiles of the treatment strategies. A questionnaire was sent at the end of 2017 to all the radiation oncology centers of Sicily region in order to collect the data from individual centers and the treatment characteristics retrospectively over the previous 5 years, from 2012 to 2016. The required data were collected from 13 centers out of 17 which, in relation to the single catchment areas, correspond to approximately 85% of the Sicilian population. The requested data concerned the type of integrated treatment (neoadjuvant vs adjuvant vs radical), combination with chemotherapy (induction, concomitant, adjuvant), type of surgical intervention (sphincter-saving vs abdomino-perineal resection), disease stage, schedule and radiotherapy technique adopted, as well as toxicity detected over the treatment period. A total of 784 pts (M/F: 509/275) were treated between 2012 and 2016, with a median age of 67 years (range 25–92). The majority of patients was treated in the neoadjuvant phase (62% of the total) compared to the adjuvant phase (31%) and to those treated radically (7%). Twenty-five percent of patients did not receive combination chemotherapy mainly for cardiovascular problems. Chemotherapy used concomitantly to radiotherapy was single-agent capecitabine (73% of patients) or 5-fluorouracil (27%). The use of chemotherapy alone before concomitant treatment is more common for patients treated in the adjuvant phase (64% of this subgroup), while 14% of patients treated in the neoadjuvant phase received induction chemotherapy before the concomitant phase; in both cases of chemotherapy alone, the majority of patients (91%) received oxaliplatin-based protocols (FOLFOX/XELOX/CAPOX). Few patients (3%) received chemotherapy alone after the concomitant phase. Information on the surgical treatment received is available for 88% of the sample. Of these, 93% received a surgical treatment. The overall rate of sphincter-saving surgery (anterior resection) was 72%, but the contribution of neoadjuvant treatment allowed to reach a rate of 83% in this subgroup (against 65% found in the subgroup of patients treated in adjuvant phase). Traditional radiotherapy schedule (45–50 Gy in 25–28 fractions) was used in 90% of patients, of which an intensified treatment in neoadjuvant phase (45 Gy + boost of 9–10 Gy) was used in 11% of patients. A short-course regimen (25 Gy in 5 fraction) in neoadjuvant setting was opted rarely (7%). Three-dimensional conformal technique was preferred over intensity-modulated ones (73% vs 27%). Toxicity was mainly of grade I–II CTCAE (skin 23%, gastrointestinal 39%, genitourinary 14%) compared to grade III (gastrointestinal 4%, genitourinary and hematological

Background Oral mucositis is a side effect of treatment regimens containing 5-fluorouracil (5-FU). The purpose of this study was to present our evaluation to see if rosiglitazone (RGZ) protected normal tissues from chemotherapy-induced oral mucositis. Methods C57BL/6J mice were treated with 5-FU for 5 days, with or without RGZ. Mice were euthanized after 5, 8, 11, or 15 days, and mucosal segments were collected. Results The RGZ did not affect the 5-FU-induced decrease in mouse body weight. The 5-FU caused loss of epithelial architecture, collagen fiber impairment, and inflammatory infiltration. The RGZ reduced leukocyte infiltration, preserved tissue structure, and dampened the 5-FU-induced expression of p53 and matrix metalloproteinase (Mmp)-2 after 5 days, and of Mmp-2 and interleukin (Il-1β after 15 days. The RGZ inhibited the 5-FU-induced increase of transforming growth factor-beta (TGF-β) and nuclear factor-kappa B (NF-κB) proteins and restored collagen protein levels. Conclusion The RGZ had a protective effect on oral mucosa damaged by chemotherapy. These data encourage the further study of RGZ for the prevention of 5-FU-induced mucositis in patients with cancer.

Aim To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin ® SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Methods Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. Results In the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. Conclusion SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC.

Meningiomas account for up to 20 % of all primary intracranial neoplasms; although the majority of these have a benign course, as many as 5–10 % can display more aggressive behavior and a higher incidence of disease progression. The benefit of immediate adjuvant radiotherapy is still being debated for atypical and malignant meningiomas. This study aimed to retrospectively assess prognostic factors and outcome in 68 patients with atypical and malignant meningiomas. Sixty-eight meningioma patients were treated with radiotherapy after initial resection or for recurrence, between January 1993 and December 2011. Surgery was macroscopically complete in 80 % of the patients; histology was atypical and malignant in 51 patients and 17 patients, respectively. Mean dose of radiotherapy was 54.6 Gy. Fifty-six percent of all patients received radiotherapy after surgical resection, 26 % at the first relapse, and 18 % at the second relapse. Median follow-up was 6.7 years, (range 1.5–19.9 years). The 5- and 10-year actuarial overall survival (OS) rates were 74.1 and 45.6 %, respectively. At univariate analysis age >60 years, radiotherapy dose >52 Gy showed statistical significance, (p = 0.04 and p = 0.03, respectively). At the multivariate analysis radiotherapy dose >52 Gy maintained the statistical significance, (p = 0.037). OS of patients treated with radiotherapy at diagnosis was longer than the survival of patients treated with salvage radiotherapy; however this difference did not reach statistical significance when tested for the entire series or for the subgroups of grade 2 and grade 3 patients. The 5- and 10-year disease-free survival (DFS) rates were 76.5 and 69.5 %, respectively, and were significantly influenced by size >5 cm (p = 0.04) and grading (p = 0.003) on univariate analysis. At multivariate analysis, size and grading both remained significant prognostic factors, p = 0.044 and p = 0.0006, respectively. Grade ≤ 2 acute side effects were seen during radiotherapy treatment in 16 % of the patients, with no ≥ grade 3 acute toxicity, based on the Common Terminology Criteria for Adverse Events. In this mono-institutional retrospective study, age and radiotherapy dose were associated with a longer OS, while preoperative size and grading of the tumor influenced DFS. Although there were some advantages in terms of OS for patients treated with postoperative radiotherapy, the benefit did not reach the significance. Multicenter prospective studies are necessary to clarify the management and the correct timing of radiotherapy in such a rare disease.

Background Hormone therapy is the most prescribed systemic therapy for patients with breast cancer (BC). Some patients fail to respond to tamoxifen; one pathway seems to involve human epidermal growth factor receptor 2 (HER2) overexpression. To better understand this matter, we reviewed our single-center experience of premenopausal patients who were chemotherapy naive and treated with 5 years of tamoxifen for early-stage BC by focusing on estrogen receptor (ER), progesterone receptor, HER2 status, and Ki-67 proliferative index. Patients and Methods We reviewed 425 patients treated with tamoxifen for early-stage BC. Previous solid tumors, age less than 18 years, BC recurrences or contralateral tumor, tamoxifen discontinuation, adjuvant chemotherapy, and a follow-up shorter than 6 months were considered exclusions criteria of the study. Results At a mean follow-up of 8.1 years, the mean (SD) time to local relapse was 6.7 ± 3.6 years; range, 2.0-10.7 years), whereas the mean (SD) time to distant metastases was 4.7 ± 2.3 years; range, 2.2-8.8 years). HER2 status did not influence local relapse–free survival (log-rank test, 0.40), distant metastases–free survival (log-rank test, 0.72), and overall survival rate (log-rank test, 0.87). Conclusions Resistance to tamoxifen is a complex trait, and its pathway is still unclear; in patients with BC, a multidisciplinary approach is highly recommended. In our experience, we did not find a statistically significant difference in tamoxifen treatment efficacy according to HER2 status.

Background Due to its anti-inflammatory, antifibrotic and antineoplastic properties, the PPAR gamma agonist rosiglitazone is of interest in prevention and therapy of radiation-induced toxicities. We aimed to evaluate the radioprotective effect of rosiglitazone in a mouse model of radiation-induced oral mucositis. Material and methods Oral mucositis was obtained by irradiation of the oral region of C57BL/6J mice, pretreated or not with rosiglitazone. Mucositis was assessed by macroscopic scoring, histology and molecular analysis. Tumor xenograft was obtained by s.c. injection of Hep-2 cells in CD1 mice. Tumor volume was measured twice a week to evaluate effect of rosiglitazone alone and combined with radiotherapy. Results Irradiated mice showed typical features of oral mucositis, such as oedema and reddening, reaching the peak of damage after 12–15 days. Rosiglitazone markedly reduced visible signs of mucositis and significantly reduced the peak. Histological analysis showed the presence of an inflammatory cell infiltrate after irradiation; the association with rosiglitazone noticeably reduced infiltration. Rosiglitazone significantly inhibited radiation-induced tnfα, Il-6 and Il-1β gene expression. Rosiglitazone controlled the increase of TGF-β and NF-kB p65 subunit proteins induced by irradiation, and enhanced the expression of catalase. Irradiation and rosiglitazone significantly reduced tumor volume as compared to control. Rosiglitazone did not protect tumor from the therapeutic effect of radiation. Conclusion Rosiglitazone exerted a protective action on normal tissues in radiation-induced mucositis. Moreover, it showed antineoplastic properties on head-neck carcinoma xenograft model and selective protection of normal tissues. Thus, PPAR gamma agonists should be further investigated as radioprotective agents in head and neck cancer.

The purpose of this study was to evaluate the potential usefulness of [18F]-Choline PET/CT in the restaging of prostate cancer patients, who presented a rising PSA.We evaluated 170 prostate cancer patients, previously radically treated, that were referred for restaging with [18F]-Choline PET/CT.A total of 129 patients (median PSA 4.29 ng/ml at relapse) showed one or more areas of high uptake on PET/CT scan, while 41 patients with a median PSA of 1.07 ng/ml at relapse showed negative PET/CT scans. No false negative was found, while 31 patients were identified as false positive. Specificity of Choline PET/CT in our series was 56.9 %, while sensibility was 100 %. At the time of restaging, a PSA value superior or equal to 1 ng/ml was found to be a statistically significant predictive factor of PET positivity, either at the univariate (p0.0001) and at the multivariate analysis (p0.0001).Based on our findings, [18F]-Choline PET/CT is confirmed as a useful diagnostic tool to detect early recurrence, in patients with increasing PSA after primary treatment. However, in case of a mild increase in PSA, positive results must be validated with other techniques, as specificity and positive predictive value of [18F]-Choline PET/CT decrease with the lower values of PSA.

In men with adverse pathology after radical prostatectomy, the most appropriate timing to administer radiotherapy (RT) remains a topic of debate. We analyzed in terms of efficacy, prognostic factors and toxicity the two therapeutic strategies: immediate postoperative radiotherapy (PORT) and salvage radiotherapy (SART). Between January 1995 and November 2010, 307 patients underwent adjuvant or salvage radiotherapy, after prostatectomy. In the PORT group, 42 patients (20.7 %) had biochemical failure, with a median time to biochemical failure of 1.8 years; two parameters (age at diagnosis and PSA pre-RT) resulted to be significant at the survival analysis for overall survival (p = 0.003 and p = 0.046, respectively). In the SART group, 33 patients (31.7 %) had biochemical relapse; sixteen patients died of prostate cancer; postoperative hormones therapy, conformal radiotherapy and level of PSA pre-RT >1.0 ng/ml resulted to be significant at the survival analysis, p = 0.009, p = 0.039 and p = 0.002, respectively. Our study is limited by its retrospective and nonrandomized design. As such, decisions to treat with adjuvant or salvage radiotherapy and the time to initiate therapy were based on patient preference and physician counseling. Our recommendation is to suggest adjuvant radiotherapy for all patients with adverse prognostic factors and to reserve salvage radiotherapy for low-risk patients, when the biochemical recurrence occurs.

The 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.A 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.At 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.Results 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).

BACKGROUND: The objective of this study was to evaluate prognostic factors of local and distant recurrence in patients diagnosed with T1a and T1b, lymph node-negative breast carcinoma (BC) with emphasis on human epidermal growth factor receptor 2 (HER2) status. METHODS: The authors reviewed 704 women with T1aT1bN0M0 BC who received treatment at the Radiation-Oncology Center of Florence University between November 2002 and December 2008. Patients with ductal carcinoma in situ or recurrent BC at presentation and patients who received adjuvant chemotherapy were excluded from the analysis. RESULTS: In total, 75 patients had HER2-positive BC (10.7%). At a mean follow-up of 4.9 years (standard deviation, 2.6 years; range, 0.5-10.8 years), 19 events were identified, including 10 distant recurrences. Patients with HER2-positive BC had worse distant recurrence-free survival (DRFS) than patients with HER2-negative BC (hazard ratio, 3.66; 95% confidence interval, 0.94-14.69; P = .045). Negative hormone receptor (HR) status was associated significantly with worse DRFS (hazard ratio, 0.26; 95% confidence interval, 0.07-0.93; P = .026). In multivariate analysis, younger age was the only significant risk factor for an event of recurrence (hazard ratio, 0.61;95% confidence interval, 0.20-1.82; P = .029). CONCLUSIONS: The current results indicated that patients with T1a/T1b, lymph node-negative BC have a low risk of distant and local recurrence, but younger age is a significant risk factor for events occurrence. Young women with HER2-positive and HR-negative status have a significant risk of distant recurrence and should be considered for future clinical trials with anti-HER2 adjuvant therapy. Cancer 2011. © 2011 American Cancer Society.

Purpose Clinical radiosensitivity varies considerably among patients, and radiation-induced side effects developing in normal tissue can be therapy limiting. Some single nucleotide polymorphisms (SNPs) have been shown to correlate with hypersensitivity to radiotherapy. We conducted a prospective study of 87 female patients with breast cancer who received radiotherapy after breast surgery. We evaluated the association between acute skin reaction following radiotherapy and 11 genetic polymorphisms in DNA repair genes: XRCC1 (Arg399Gln and Arg194Trp), XRCC3 (Thr241Met), XPD (Asp312Asn and Lys751Gln), MSH2 (gIVS12-6T>C), MLH1 (Ile219Val), MSH3 (Ala1045Thr), MGMT (Leu84Phe), and in damage-detoxification GSTM1 and GSTT1 genes (allele deletion). Methods and Materials Individual genetic polymorphisms were determined by polymerase chain reaction and single nucleotide primer extension for single nucleotide polymorphisms or by a multiplex polymerase chain reaction assay for deletion polymorphisms. The development of severe acute skin reaction (moist desquamation or interruption of radiotherapy due to toxicity) associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for cumulative biologically effective radiation dose. Results Radiosensitivity developed in eight patients and was increased in carriers of variants XRCC3-241Met allele (hazard ratio [HR] unquantifiably high), MSH2 gIVS12-6nt-C allele (HR = 53.36; 95% confidence intervals [95% CI], 3.56–798.98), and MSH3-1045Ala allele (HR unquantifiably high). Carriers of XRCC1-Arg194Trp variant allele in combination with XRCC1-Arg399Gln wild-type allele had a significant risk of radiosensitivity (HR = 38.26; 95% CI, 1.19–1232.52). Conclusions To our knowledge, this is the first report to find an association between MSH2 and MSH3 genetic variants and the development of radiosensitivity in breast cancer patients. Our findings suggest the hypothesis that mismatch repair mechanisms may be involved in cellular response to radiotherapy. Genetic polymorphisms may be promising candidates for predicting acute radiosensitivity, but further studies are necessary to confirm our findings.

Purpose Individual variability in radiosensitivity is large in cancer patients. Single nucleotide polymorphisms (SNPs) in genes involved in DNA repair and in protection against reactive oxygen species (ROS) could be responsible for such cases of radiosensitivity. We investigated the association between the occurrence of acute reactions in 101 patients with squamous cell carcinoma of the head and neck (SCCHN) after radiotherapy (RT) and five genetic polymorphisms: XRCC1 c.1196A > G, XRCC3 c.722C > T, RAD51 (c.-3429G > C, c.-3392G > T), and GSTP1 c.313A > G. Materials and methods Genetic polymorphisms were detected by high resolution melting analysis (HRMA). The development of acute reactions (oral mucositis, skin erythema and dysphagia) associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for biologically effective dose (BED). Results Development of grade ⩾2 mucositis was increased in all patients (chemo-radiotherapy and radiotherapy alone) with XRCC1-399Gln allele (HR = 1.72). The likelihood of developing grade ⩾2 dysphagia was higher in carriers of RAD51 c.-3429 CC/GC genotypes (HR = 4.00). The presence of at least one SNP or the co-presence of both SNPs in XRCC1 p.Gln399Arg /RAD51 c.-3429 G > C status were associated to higher likelihood of occurrence of acute toxicities (HR = 2.03). Conclusions Our findings showed an association between genetic polymorphisms, XRCC1 c.1196A > G and RAD51 c.-3429 G > C, and the development of radiation-induced toxicities in SCCHN patients.

The aim of this study was to review the treatment, toxicity, and outcomes in patients with stage I seminoma after orchidectomy.A retrospective chart review of all patients with stage I seminoma referred for initial treatment during the last 49 years was performed. Initial treatment approaches, toxicity, and outcomes were analyzed.A total of 320 patients were seen between 1960 and 2009. Median age at diagnosis was 37 years (range: 20-72), with a median follow-up of 22.7 years (range: 1-48). All patients but 12 were treated with adjuvant radiotherapy. Acute toxicity was mainly gastrointestinal, with 7.6% classified as grade 2. The 10-year disease-specific survival and relapse-free survival were 97.7 and 97.6%, respectively. 8 patients (2.7%) developed a relapse and were managed with chemotherapy. 10 patients died, 6 of the disease and 4 from other causes (disease-free at time of death).In the management of stage I seminoma, 3 treatment options are available; currently in the European Consensus, surveillance is the first choice, considering the overall comparable outcome and the low acute and late toxicity. Adjuvant radiotherapy and adjuvant chemotherapy should be considered as alternative options only if the patient declines the surveillance strategy.

Purpose To evaluate with a randomized clinical trial the possibility of treating the index quadrant with external intensity-modulated radiotherapy (IMRT) in a selected group of patients with early-stage breast cancer and to analyze the acute toxicity. Methods and Materials From September 2005, a randomized Phase III clinical trial has been conducted to compare conventional (tangential field) fractionated whole breast treatment (Arm A) with accelerated partial breast irradiation plus intensity-modulated radiotherapy (Arm B). For intensity-modulated radiotherapy, the clinical target volume was drawn with a uniform 1-cm margin around the surgical clips in three dimensions. The ipsilateral and contralateral breast, ipsilateral and contralateral lung, heart, and spinal cord were contoured as organs at risk. All the regions of interest were contoured according to the International Commission on Radiation Units and Measurements reports 50 and 62 recommendations. Results In September 2008, 259 patients were randomized and treated. The mean clinical target volume in Arm B was 44 cm 3 and the mean planning target volume was 123 cm 3 . The mean value of the ratio between the planning target volume and the ipsilateral breast volume was 21%. The rate of Grade 1 and Grade 2 acute skin toxicity was 22% and 19% in Arm A (Radiation Therapy Oncology Group scale), respectively. The tolerance in Arm B was excellent with only 5% Grade 1 and 0.8% Grade 2 acute skin toxicity. The planning constraints were fully satisfied in most patients. In a very few cases, this was not possible because of very unfavorable anatomy. Quality assurance procedures were performed according to our internal quality assurance protocol, with excellent results. Conclusion In the present preliminary analysis, we have demonstrated that accelerated partial breast irradiation is feasible, with very low acute toxicity.

The advent of effective chemo-radiotherapy has made Hodgkin Disease (HD) a highly curable malignancy, but the great improvement in survival rates allowed the observation in long-term survivors of several treatment complications. Secondary malignancies are the most serious complications and breast cancer (BC) represents the most common solid tumor among female survivors. The aim of our analysis is to describe the clinico-pathological characteristics and management of BC occurred after HD treatment. Between 1960 and 2003, 2,039 patients were treated for HD at the Department of Radiotherapy-Oncology of the Florence University. In this study we considered 1,538 patients on whom a minimum follow up of 6 months had been obtained. Of these, 725 were women. The most represented histological subtype was nodular sclerosis (50.6%). Supradiaphragmatic alone or with subdiaphragmatic complementary extended field radiotherapy was delivered to 83.1% of patients while supradiaphragmatic involved field radiotherapy was delivered to 10.7% of patients. Concerning the characteristics and incidence of BC, we focused our analysis exclusively on the female group. We found that BC occurred in 39, with an overall incidence of 5.4%. The mean interval after Hodgkin treatment was 19.5 years (SD +/- 9.0). The median age of BC diagnosis was 50.8 years (SD +/- 13.3) while the median age of Hodgkin diagnosis was 31.2 years (SD +/- 14.5). Thirty-seven women received mediastinal irradiation. We observed a decreasing trend of the secondary BC incidence with increasing age of Hodgkin treatment with the maximum incidence registered in women treated at age 20 or younger. In Our Institute we perform a whole life follow up and recommend that annual mammography begins 10 years after HD treatment or, in any case, not later than age 40.

To determine whether a boost to the tumor bed after breast-conserving surgery (BCS) and radiotherapy (RT) to the whole breast affects local control and disease-free survival.A total of 1,138 patients with pT1 to pT2 breast cancer underwent adjuvant RT at the University of Florence. We analyzed only patients with a minimum follow-up of 1 year (range, 1-20 years), with negative surgical margins. The median age of the patient population was 52.0 years (+/-7.9 years). The breast cancer relapse incidence probability was estimated by the Kaplan-Meier method, and differences between patient subgroups were compared by the log rank test. Cox regression models were used to evaluate the risk of breast cancer relapse.On univariate survival analysis, boost to the tumor bed reduced breast cancer recurrence (p0.0001). Age and tamoxifen also significantly reduced breast cancer relapse (p = 0.01 and p = 0.014, respectively). On multivariate analysis, the boost and the medium age (45-60 years) were found to be inversely related to breast cancer relapse (hazard ratio [HR], 0.27; 95% confidence interval [95% CI], 0.14-0.52, and HR 0.61; 95% CI, 0.37-0.99, respectively). The effect of the boost was more evident in younger patients (HR, 0.15 and 95% CI, 0.03-0.66 for patients45 years of age; and HR, 0.31 and 95% CI, 0.13-0.71 for patients 45-60 years) on multivariate analyses stratified by age, although it was not a significant predictor in women older than 60 years.Our results suggest that boost to the tumor bed reduces breast cancer relapse and is more effective in younger patients.

Objectives To review the treatment, toxicity, and outcomes in patients with Stage II seminoma after orchidectomy. Materials and methods A retrospective chart review of all patients with Stage II seminoma referred for initial treatment, from 1965 to 2005, was performed. Treatment approaches, toxicity, and outcomes were analyzed. Results A total of 106 patients (83 with Stage IIA, 19 with Stage IIB, and 4 with Stage IIC) were seen between 1965 and 2005. Median age at diagnosis was 36 years (range: 19–71). Median follow-up was 21 years (range: 1.2–42). Eighty-nine patients were treated with adjuvant radiotherapy alone; 13 patients received a combined treatment modality with chemotherapy and radiotherapy after orchidectomy, 4 patients were treated with chemotherapy alone. Generally the treatment was well tolerated, with the main toxicity occurring in patients treated with extended-field radiotherapy. The 5-year disease-specific survival was 96% for the entire group. The 5-year relapse-free survivals for Stages IIA, IIB, and IIC disease were 94%, 72.5%, and 75%, respectively. Fifteen patients developed a relapse and were managed by chemotherapy; 5 of them achieved complete remission and remain free from further recurrence at last follow-up, while 10 died of the disease. Second malignancies were diagnosed in 4 (3.7%) patients during the follow-up. Conclusions In Stage IIA seminoma, radiotherapy continues to provide excellent results, as the majority of patients will be cured with this treatment alone. Radiotherapy or chemotherapy should be offered as an alternative to Stage IIB patients. Chemotherapy remains the treatment of choice for Stage IIC seminoma.

Aims and Background Analysis of patients with late relapse of testicular germ cell tumors (GCTs) with reports on clinicopathological features and outcomes. Methods We identified all patients diagnosed with testicular GCTs at our Institute between 1988 and 2004 who developed relapse ≥24 months after completion of primary therapy. A retrospective case-note review was performed to extract clinical, pathological, treatment and outcome data. Results Six patients (1.25%) developed late relapse. All patients presented with stage I disease and were classified as “good risk” according to the International Germ Cell Consensus Classification. Mean time to late relapse was 48 months. Markers at late relapse were normal in all patients. Relapse was confined to retroperitoneal sites in five patients and located in the mediastinum in one patient. Five patients were managed by chemotherapy alone while one underwent combined treatment with surgery followed by chemotherapy. All patients obtained a complete response and all remained free from recurrence with a mean follow-up of 115 months. Conclusions The incidence of late relapse in this small series is low. Chemonaive patients with late relapse were successfully salvaged with chemotherapy alone or surgical excision followed by cisplatin-based chemotherapy. The optimal duration of follow-up in patients with testicular GCTs is not known and practice varies widely. At our Institute we advise lifelong follow-up of all patients with malignant GCTs of the testis.

Purpose/objective(s) Due to its anti-inflammatory, antifibrotic and antineoplastic properties, the PPAR-γ agonist rosiglitazone is of interest in the prevention and therapy of radiation-induced pulmonary injury. We evaluated the radioprotective effects of rosiglitazone in a murine model of pulmonary damage to determine whether radioprotection was selective for normal and tumor tissues. Methods Lungs in C57BL/6J mice were irradiated (19 Gy) with or without rosiglitazone (RGZ, 5 mg/kg/day for 16 weeks, oral gavage). Computed tomography (CT) was performed and Hounsfield Units (HU) were determined during the observation period. Histological analysis and evaluation of fibrosis/inflammatory markers by western blot were performed at 16 weeks. A549 tumor-bearing CD1 mice were irradiated (16 Gy) with or without RGZ, and tumor volumes were measured at 35 days. Results Rosiglitazone reduced radiologic and histologic signs of fibrosis, inflammatory infiltrate, alterations to alveolar structures, and HU lung density that was increased due to irradiation. RGZ treatment also significantly decreased Col1, NF-kB and TGF-β expression and increased Bcl-2 protein expression compared to the irradiation group and reduced A549 clonogenic survival and xenograft tumor growth. Conclusions Rosiglitazone exerted a protective effect on normal tissues in radiation-induced pulmonary injury, while irradiated lung cancer cells were not protected in vivo and in vitro. Thus, rosiglitazone could be proposed as a radioprotective agent in the treatment of lung cancer.

This study was undertaken to evaluate the association of individual parameters and outcome in patients with unresectable locally advanced head and neck cancer treated with radiochemotherapy.We retrospectively reviewed data from 126 patients treated in our Institution between 1998 and 2010 for a locally advanced head and neck cancer. Sixteen individual parameters were evaluated for association with specific outcomes such as overall survival, persistence of disease, disease-specific survival and disease-free survival.Six factors influenced overall survival on Kaplan-Meier survival analysis and on univariate Cox regression analysis: smoking, body mass index, site, haemoglobin (Hb) nadir, total dose of radiotherapy and comorbidities. On a multivariate logistic model with stepwise selection, comorbidities, body mass index, total dose and site maintained significance. A significant association for persistence of disease was found with smoking, Hb nadir and site of cancer on univariate and multivariate analysis. Disease-free survival was correlated with performance status, Hb nadir and comorbidities using Kaplan-Meier survival analysis and on univariate Cox regression analysis. Only performance status maintained the significance on multivariate analysis. Disease-specific survival was correlated with five parameters: body mass index, site, Hb nadir, therapy interruption and total dose; on multivariate analysis, Hb nadir, therapy interruption and site maintained a statistically significant association.Hb nadir during treatment, body mass index, smoking, stage, comorbidities and performance status are prognostic factors of outcome and response to radical treatment with radiochemotherapy.

Purpose: A correlation of treatment for uterine sarcoma with outcome, prognostic importance of pathology, and clinical parameters. Patients and Methods: One hundred forty-one patients (median age: 56 years, range: 19 - 85 years) with a histologically verified uterine sarcoma were identified from a database compiled at the Royal Marsden Hospital and the University of Florence between 1974 and 2001. Seventy-two patients had leiomyosarcoma, 42 had mixed mullerian tumors, 22 had endometrial stromal sarcoma, 1 hemangiopericytoma, 1 rhabdomyosarcoma, and 3 patients had unspecified sarcoma. According to FIGO classification, Stage I, II, III, and IV tumors were identified in 71, 13, 31, and 26 patients, respectively. Results: At the time of analysis, 73.7% of patients were dead, and 26.3% were alive with a median survival of 2 years from initial diagnosis. Univariate analysis for cause-specific survival demonstrated statistical significance for histology (p 0.02), grade (p 0.003), stage (p 0.007), and age (p 0.02). Multivariate analysis demonstrated significant prognostic values for stage ( p 0.02) and histology (p 0.05) only. Postoperative radiotherapy with a total dose higher than 50 Gy seems to be significant ( p 0.001) in reducing local recurrence. Conclusions: Our data favor treatment for Stages I, II, and III of uterine sarcoma with radical surgery plus radical dose irradiation comprising both external beam radiotherapy and brachytherapy. © 2003 Elsevier Inc. Brachytherapy, Radiotherapy, Uterine sarcoma.

Small cell lung cancer is an aggressive histologic subtype of lung cancer in which the role of chemotherapy and radiotherapy has been well established in limited-stage disease. We retrospectively reviewed a series of limited-stage small cell lung cancers treated with chemotherapy and thoracic and brain radiotherapy.A total of 124 patients affected by limited-stage small cell lung cancer has been treated over 10 years in our Institute. Fifty-three patients (42.8%) had concomitant radio-chemotherapy treatment and 71 patients (57.2%) a sequential treatment. Eighty-eight patients (70.9%) underwent an association of a platinum-derived drug (cisplatinum or carboplatinum) and etoposide. Prophylactic cranial irradiation was planned in all patients with histologically proven complete response to primary radio-chemotherapy.With a mean follow-up of 2.2 years, complete response was obtained in 50.8% of cases. We found a significant difference between different radio-chemotherapy association approaches (P = 0.007): percentages of overall survival were respectively 10.0%, 12.9% and 5.6% in early, late concomitant and sequential radio-chemotherapy timing. Cranial prophylaxis did not seem to influence overall survival (P = 0.21) or disease-free survival for local relapse (P = 0.34).Concomitant radio-chemotherapy is the best approach according to our experience. Our results show a benefit of prophylactic cranial irradiation in distant metastasis-free survival.

We report the toxicity and preliminary clinical outcome in patients affected by locally recurrent head and neck cancer treated with stereotactic re-irradiation.Between February 2012 and August 2013, 17 patients were treated with CyberKnife as stereotactic re-irradiation for locally recurrent head and neck cancer. All patients had previously received a full dose radiation treatment with radical intent, with a median total dose of 66 Gy (range, 50-70) delivered with standard fractionation. The median interval between the primary radiotherapy and re-irradiation was 24 months (range, 10-168).All patients completed the prescribed treatment, which was delivered in 5 fractions. The median tumor dose administered was 30 Gy (range, 25-35) prescribed to the 80% isodose line. Treatment sites were as follows: neck lymph nodes in 5 patients, paranasal sinuses in 5, oropharynx in 2, nasopharynx, and larynx, oral cavity, nasal fossa and parotid gland each in 1 patient. The median target volume treated was 58.7 cm3 (range, 8.5-211.3). Sixteen patients (94%) were evaluated for response. At a median follow-up of 7.5 months (range, 2-17), 4 patients achieved complete response (25%), 5 had partial response (31%) and 7 showed stable disease (44%). No patient showed in-field progression after re-irradiation. Grade 3 acute toxicity was noted in one patient only; no late side effect was observed during the follow-up.Stereotactic re-irradiation with CyberKnife is an appealing non-surgical salvage treatment for selected patients with local-regionally recurrent head and neck cancer.

We report the case of a 48-year-old woman affected by inoperable primary angiosarcoma of the right atrium who was treated with 4 cycles of induction chemotherapy and radical radiotherapy. We present the application and the result of helical tomotherapy for this patient. We also describe the technical aspects of the simulation, planning, setup and delivery of radiotherapy. At 16 months after the diagnosis the patient is still in good condition without any symptoms and with a partial response of the lesion. This case shows the feasibility of treatment with high doses of radiation for a primary unresectable cardiac sarcoma.

Objectives/Hypothesis To review toxicity and outcomes in patients with head and neck cancer treated with simultaneous integrated boost–intensity-modulated radiotherapy (SIB-IMRT). Study Design Review of experience with the SIB-IMRT technique. Methods Fifty patients were treated with the SIB-IMRT technique. Two possible schedules of radiation therapy (RT) were used: SIB 70 (70/60/54 in 33 fractions) and SIB 66 (66/60/54 in 33 fractions). Forty-one patients also received chemotherapy. Results All but two patients completed treatment as prescribed. No G4 acute toxicity has been reported in our series. We did not observe any G3 to G4 chronic toxicity, apart from one case of cutaneous necrosis. After a median follow-up of 23.3 months (range, 1–60 months), 41 patients (82%) were alive and negative for disease, and one patient (2%) was alive with distant metastases. Eight patients (16%) died, seven because of progressive disease and one for other causes. Conclusions SIB-IMRT is a highly effective and safe technique of RT in the treatment of head and neck cancer. Level of Evidence 4 Laryngoscope, 123:E97–E103, 2013

Aims and background To report the clinical outcome of linac-based or robotic, image-guided stereotactic body radiotherapy in patients affected by abdominal lymph node metastases from different primary cancers. Methods and Methods Twenty-six patients with 32 abdominal lymph node metastases were consecutively treated at the University of Florence between April 2011 and May 2012. The mean follow-up was 4.6 months (SD, 3.9; range, 0.3–13). The dose prescription ranged between 24 Gy and 36 Gy delivered in 1–5 fractions. Results In terms of local control, complete response to stereotactic body radiotherapy was obtained in 18 cases (66.7%), partial response in 7 (25.9%), and stable disease in 2 (7.4%). At the Cox univariate regression analysis, an increased risk of partial response or absence of local response to radiotherapy was found for subjects of the female sex (P = 0.036), age less than 50 years (P = 0.022), primary tumor of the genital tract (P = 0.007), and previous chemotherapy (P = 0.057). An excellent local control rate (90.9%) was obtained in patients affected by abdominal lymph node metastases of prostatic origin. Conclusions Stereotactic body radiotherapy for abdominal lymph node metastases is a safe and effective treatment in terms of high rates of local control, especially in a subset of patients affected by prostate cancer.

The aim of this paper is to investigate the accuracy of a laser∕camera surface imaging system (Sentinel) when used on patients treated in the thorax or pelvic regions and to evaluate system employment conditions and patient setup procedures that provide more accurate results.The system was tested on two groups of patients for whom different patient setup procedures and Sentinel employment conditions were considered. For the first group of 33 patients (FG) no changes to the usual setup procedures were made and a surface extension limited to the treated region was considered. For the second group of 14 patients (SG) the reproducibility of external body surfaces, including body parts not in close proximity to the treatment site, was optimized and a wider surface was captured. In all cases the system accuracy was evaluated comparing registration results from concurrent Sentinel and cone beam CT (CBCT) acquisitions for a total of 192 occasions. External body surfaces, extracted from planning CT studies, were used as reference in both cases, but for SG also surface data captured by Sentinel system at the first treatment were employed.In the 90th percentile of the distributions reporting CBCT and Sentinel registration parameters, absolute differences for FG were less than 6.4 mm and 3.8°. Better performances were observed for SG (≤5.7 mm and 2°). Mean absolute differences between three translation and three rotation parameters of CBCT and Sentinel were: less than 3.5 mm and 2.1° and 3.7 mm and 1.3° in FG for thorax and pelvis, respectively, and less than 2.8 mm and 1° and 2.7 mm and 0.9° for pelvis and thorax, respectively, in SG. No advantage in considering surface data captured by Sentinel as a reference instead of the surface extracted from the planning CT was observed.The accuracy of Sentinel system in detecting errors is influenced by the extension and reliability of the surface used. When the reproducibility of external body surfaces was optimized differences between CBCT and Sentinel registration parameters resulted less than 5.7 mm and 2° in the 90% of the pelvis and thorax considered cases. No advantage in considering a Sentinel acquisition as reference was observed.

Percutaneous fine-needle aspiration biopsy (FNAB) is a well-established and useful procedure in the diagnosis of lung squamous cell carcinoma (LSCC). Tumor seeding has been shown to be a potential risk. We report the case and management of a 78-year-old patient affected by LSCC who developed a chest wall metastasis in a straight line from the primary lesion along the FNAB needle track. Although tumor seeding after FNAB is a rare but possible complication, we suggest that careful examination for implantation (with periodical CT scans) should be performed for at least three years after FNAB.

The aim of this study was to evaluate disease-free survival (DFS), overall survival and toxicity of patients who underwent preoperative therapy for soft tissue sarcoma. The data of 38 consecutive patients affected by soft tissue sarcoma were retrospectively analysed. Six (15.8 %) patients were treated only with neoadjuvant radiotherapy, and 32 (84.2 %) with neoadjuvant chemo-radiation therapy. Surgery was performed within 4–6 weeks after the completion of neoadjuvant treatment. Median follow-up was 4.9 years (range 1–13.7 years). All patients received preoperative external beam radiotherapy (RT). Most patients (84.2 %) underwent neoadjuvant chemotherapy treatment associated with radiotherapy. After neoadjuvant treatment, the majority of patients underwent wide excision (32 out of 38) and five patients had marginal surgery; only one patient underwent amputation. Local recurrence was observed in only two patients (5.2 %). Fourteen (36.8 %) patients experienced metastatic relapse. At the time of our analysis 13 patients (34.2 %) had died due to metastatic spread of the disease. In our series, DFS in relation to distant metastases (DM) showed a significant result for lower limb involvement (p = 0.038) and marginal excision (p = 0.024), both predictors of a worse DFS, histology was statistically significant although it was not possible to evaluate the risk for specific histology due to the small number of events in the different subtypes. The results obtained from our study are encouraging with regard to the feasibility and efficacy of preoperative RT in the treatment of soft tissue sarcoma in view of the results obtained in terms of local control, limb sparing and safety.

Background: Combined-modality therapy is a promising approach to improve the therapeutic index of radiotherapy. However, these improvements could come at the cost of increased toxicities. Clinical trials evaluating anti-tumour efficacy of bevacizumab combined with radiotherapy have encountered unexpected side effects. This study is the first systematic evaluation of normal tissue toxicity triggered by anti-angiogenic agents combined with radiation therapy in mice. Methods: Effect of a mouse anti-VEGF antibody was monitored on acute toxicity studying radiation-induced intestinal ulceration (12 Gy TBI); on subacute toxicity using a model of oral mucositis (16.5 Gy); on late radiation injuries by monitoring lung fibrosis (bleomycin and 19 Gy). Results: Combination of irradiation with anti-VEGF antibody enhanced intestinal damages with severe epithelial ulcerations, had no adverse impact on oral mucositis and dramatically worsened the fibrotic picture induced by bleomycin and irradiation to the lung. Interpretation: These reports bring to light the important questions about safety and underscore the need for appropriate preclinical modelling of the impact on normal tissues of novel drug–radiation regimens. Our findings also highlight the complexity of anti-VEGF action, which could in defined conditions exert tissue-specific protection. The findings indicate that the combination of targeted drugs with radiotherapy should be approached with caution.

Gangliogliomas with anaplastic features are classified as grade III tumors by the World Health Organization. The clinical course and optimal treatment of anaplastic gangliogliomas have not been well understood to date. We report a case of a primary pure anaplastic ganglioglioma in a 14-year-old male treated with surgery and radiotherapy, who is disease-free 6 years after the diagnosis. A review of primary pure anaplastic gangliogliomas in children (between 3 and 21 years of age) is presented. Gross total removal and focal radiotherapy with a total dose of 54 Gy are recommended. The addition of chemotherapy should be evaluated. Prospective studies are needed to identify an appropriate chemotherapy schedule and to define biological factors in order to select those patients with a poor prognosis, who are to be treated with a more aggressive therapy.

To investigate the outcome of invasive early breast cancer patients that underwent breast-conserving surgery and adjuvant radiotherapy (RT), treated with a prospective margin-directed institutional policy for RT boost dose, based on final margins status (FMS).A total of 2093 patients were treated between 2000 and 2008. 10 Gy boost was prescribed in case of FMS5mm; 16 Gy boost with FMS between 2 and 5mm; 20 Gy boost in case of FMS2mm or positive.After a median follow up of 5.2 years, we recorded 41 local relapse (LR, 2%). Concerning LR free survival, age at diagnosis, nuclear grade, hormonal status, T-stage, adjuvant hormonal therapy and adjuvant chemotherapy emerged as significant parameters (p-values from log rank test0.05). FMS, that directed the RT boost dose, did not have significant impact on LRFS (p=0.46). LR rates were 2.3% for FMS2mm, 2.6% for 2-5mm FMS and 1.8% for FMS5mm. At multivariate analysis, higher nuclear grade (p=0.045), triple negative subtype (p=0.036) and higher T-stage (p=0.02) resulted as the independent predictors of LR occurrence.Our experience showed that a margin-directed policy of RT boost dose-escalation seems to reduce the negative impact of FMS on LR, but it is not able to overcome the unfavorable effect of higher nuclear grade, higher T stage and triple negative subtype.

Inflammatory breast cancer represents a rare and extremely aggressive subtype of breast cancer. Due to its rarity, prospective studies are a difficult goal to obtain in this field. Nowadays a multimodal approach seems to be the standard approach. Role and timing of surgery, radiotherapy and chemotherapy are still debated issues. In this scenario interest is rising in molecular and target therapies. We performed a review analyzing the management of this unfavorable disease focusing on the role of radiotherapy, with particular emphasis on levels of evidence.

This study sought to evaluate acute toxicity and local control in patients who underwent extracranial stereotactic body radiation therapy (SBRT) for paracardiac and cardiac metastatic lesions, defined as such when located at a maximum distance of 1 cm from the heart or inside its parenchyma.Between January 2009 and May 2011, 16 patients with paracardiac and cardiac lesions were treated with SBRT. For dose specification, in 15 of 16 patients, the prescription dosage was 36 Gy in three fractions (70% isodose). In one patient, the target lesion was inside the heart, and the prescription dosage was 30 Gy in three fractions (70% isodose).Regarding response to stereotactic radiotherapy, we recorded one (6%) complete response (CR), six (37%) partial responses (PR), five (32%) stable disease (SD) and four (25%) local failures. Median interval to local failure was 5.2 (range, 3-12) months. The cause of death was distant progression of disease in all four patients. Compliance to treatment was excellent; no patient developed cardiological symptoms or electrocardiographic abnormalities, even months after SBRT.Results of our retrospective study indicate that SBRT represents a safe and effective treatment option for patients with cardiac and paracardiac metastases.

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.

Meningeal carcinomatosis (MC) is a rare complication in breast cancer (BC) with no efficient modality of treatment yet found; overall survival (OS) generally did not exceed six months. We reviewed the experience of the University of Florence focusing on prognostic factors and MC survival.We analyzed 33 patients treated for MC from BC between 2002 and 2010.Mean OS from MC diagnosis was 4.9 months. At survival analysis clinical stage emerged as the only statistical significant parameter (P = 0.009) among BC diagnosis features. Among MC diagnosis parameters, more than three metastases at diagnosis (P = 0.037), multimodality treatment (P = 0.014) and poor performance status (P = 0.003) reached the statistical significance. At multivariate analysis only performance status at MC diagnosis maintained the statistical significance (P = 0.0047; HR: 3.34; CI 95% 1.45-7.73).Our experience confirms that performance status is probably the most important prognostic factor in these patients. Multimodality approach is probably the best option.

Nasopharyngeal carcinoma (NPC) is a unique malignant head and neck cancer with clinical, demographic, and geographic features distinct from other head and neck epithelial malignancies. Non-keratinizing, poorly differentiated, and undifferentiated WHO types 2 and 3 is the most common subtypes of NPC. NPC is also characterized by its relatively high sensitivity to radiation, so that in the last decades radiotherapy (RT) has been the cornerstone of treatment. However, in the majority of cases NPC is discovered at locally advanced stage. The results are disappointing when RT alone is offered. The 5-year survival rates have been reported to be about 34-52%. The poor prognosis for advanced NPC led to increasing interests in exploring the use of chemotherapy (CT). NPC has been considered to be not only radiosensitive but also chemo-sensitive and has shown high response rate to various chemotherapeutic agents. Certainly, the treatment strategies for NPC will continue to change and evolve as a better understanding is gained of the molecular and immune mechanisms that drive this disease. We reviewed the current literature focusing on the role of CT and new-targeted agents.

Renal transplant recipients are a population usually considered at a higher risk of malignancies, mostly skin cancer and lymphoproliferative disorder. In recent years, prostate cancer in renal transplant recipients has been becoming more frequent. This is probably due to the growing age and the longer survival of the transplanted patients. We report the case of a 50-year-old man with prostate cancer and renal allograft, who received radiotherapy after prostatectomy at the Institute of Radiotherapy of the University of Florence. Radiotherapy is part of the standard treatment for many cases of prostate cancer. According to the few series reported in the literature and also to our experience, radiation therapy is feasible also in renal transplant recipients with accurate treatment planning.

This review aims to summarize what is currently known about neurocognitive outcome and quality of life in patients with brain tumors treated with radiotherapy. Whether potential tumor-controlling benefits of radiotherapy outweigh its potential toxicity in the natural history of brain tumors is a matter of debate. This review focuses on some of the adult main brain tumors, for which the issue of neurocognitive decline has been thoroughly studied: low-grade gliomas, brain metastases, and primary central nervous system lymphomas. The aims of this review are: (1) the analysis of existing data regarding the relationship between radiotherapy and neurocognitive outcome; (2) the identification of strategies to minimize radiotherapy-related neurotoxicity by reducing the dose or the volume; (3) the evidence-based data concerning radiotherapy withdrawal; and (4) the definition of patients subgroups that could benefit from immediate radiotherapy. For high grade gliomas, the main findings from literature are summarized and some strategies to reduce the neurotoxicity of the treatment are presented. Although further prospective studies with adequate neuropsychological follow-up are needed, this article suggests that cognitive deficits in patients with brain tumor have a multifactorial genesis: radiotherapy may contribute to the neurocognitive deterioration, but the causes of this decline include the tumor itself, disease progression, other treatment modalities and comorbidities. Treatment variables, such as total and fractional dose, target volume, and irradiation technique can dramatically affect the safety of radiotherapy: optimizing radiation parameters could be an excellent approach to improve outcome and to reduce neurotoxicity. At the same time, delayed radiotherapy could be a valid option for highly selected patients.

The objective of this study was to evaluate prognostic factors of local and distant recurrence in patients diagnosed with T1a and T1b, lymph node-negative breast carcinoma (BC) with emphasis on human epidermal growth factor receptor 2 (HER2) status.The authors reviewed 704 women with T1aT1bN0M0 BC who received treatment at the Radiation-Oncology Center of Florence University between November 2002 and December 2008. Patients with ductal carcinoma in situ or recurrent BC at presentation and patients who received adjuvant chemotherapy were excluded from the analysis.In total, 75 patients had HER2-positive BC (10.7%). At a mean follow-up of 4.9 years (standard deviation, 2.6 years; range, 0.5-10.8 years), 19 events were identified, including 10 distant recurrences. Patients with HER2-positive BC had worse distant recurrence-free survival (DRFS) than patients with HER2-negative BC (hazard ratio, 3.66; 95% confidence interval, 0.94-14.69; P = .045). Negative hormone receptor (HR) status was associated significantly with worse DRFS (hazard ratio, 0.26; 95% confidence interval, 0.07-0.93; P = .026). In multivariate analysis, younger age was the only significant risk factor for an event of recurrence (hazard ratio, 0.61;95% confidence interval, 0.20-1.82; P = .029).The current results indicated that patients with T1a/T1b, lymph node-negative BC have a low risk of distant and local recurrence, but younger age is a significant risk factor for events occurrence. Young women with HER2-positive and HR-negative status have a significant risk of distant recurrence and should be considered for future clinical trials with anti-HER2 adjuvant therapy.

The efficacy of postoperative radiotherapy (RT) in the treatment of early-stage endometrial carcinoma (EC) is still under debate. This study was aimed to review the outcome and adverse effects in patients treated for EC with postoperative RT at a single center.A total of 883 patients with pathological stages I to II EC were retrospectively analyzed. Surgery consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy, or vaginal hysteroannessiectomy in 532 patients (60.2%) with pelvic lymphadenectomy in 351 patients (39.8%). Seven hundred forty-seven patients (84.6%) underwent whole pelvic RT (WPRT) and 136 (15.4%) combined WPRT and vaginal brachytherapy (BT) boost.At a median follow-up of 9 years (range, 1.2-27.6 years), we observed 10.6% disease relapse. Forty-seven patients experienced local recurrence (LR), and 38 patients experienced distant metastases (DMs). At univariate analysis, age at diagnosis (P0.0001), stage (P0.04), and histological subtype (P0.0001) resulted in significant prognostic factors. At multivariate analysis, histotype emerged as an independent relapse predictor (P = 0.0001). Acute WPRT-related toxicity was mild; diarrhea was the most common adverse effect (19.8%). We recorded long-term adverse effects in 7.8% of the patients.Our study showed that patients with early-stage EC have a good outcome in overall survival and disease-free survival. In our experience, standard surgery (including hysterectomy and bilateral salpingo-oophorectomy followed by WPRT with or without BT) showed an acceptable toxicity profile.

OBJECTIVE: To 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. METHODS: Clinical, pathological, therapeutic, and survival data regarding 1059 patients treated in 18 radiotherapy centers between 2002 and 2007 were collected and retrospectively reviewed. RESULTS:Most 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). CONCLUSION: Changes 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.

Aims and background Uterine serous cancer is associated with a poor outcome and poses a therapeutic challenge. We retrospectively evaluated the experience of the Radiotherapy Department of the University of Florence. Methods Forty-three patients with stage I-III uterine serous cancer underwent surgery with (18 patients, group 1) or without complete surgical staging (25 patients, group 2) followed by adjuvant whole pelvic radiotherapy alone or combined with vaginal brachytherapy (in 35 and 8 cases, respectively). The median dose delivered with whole pelvic radiotherapy was 50Gy (range, 45–56) and for brachytherapy was 20 Gy (range, 20–30). Results Actuarial overall survival and disease-free survival rates at 5 years were 62.5% and 61%, respectively. Local failure was observed in 17 patients (39.5%) and distant metastasis in 10 (23.2%). Nine patients had both local failure and distant metastasis, which had developed concurrently in 7 cases. Isolated abdominal failure occurred in 4 cases (9.3%). Local relapse was noted in 22.2% of patients in group 1 compared to 52% in group 2. A trend towards a better 5-year overall survival (67.2% vs 58%), disease-free survival (63% vs 59%) and local control (70% vs 59%) was observed in group 1 than group 2, although the difference between the two groups failed to reach statistical significance. Conclusions Given the patterns of failure of patients with uterine serous cancer, adjuvant whole pelvic radiotherapy may be a reasonable approach, although novel integrated strategies are needed because the results achieved remain disappointing. Adjuvant whole pelvic radiotherapy might improve overall survival, disease-free survival and local control in complete surgically staged patients, but further investigations are required.

The advent of effective chemo-radiotherapy has made Hodgkin Disease (HD) a highly curable malignancy, but the great improvement in survival rates allowed the observation in long-term survivors of several treatment complications. Secondary malignancies are the most serious complications and breast cancer (BC) represents the most common solid tumor among female survivors. The aim of our analysis is to describe the clinico-pathological characteristics and management of BC occurred after HD treatment. Between 1960 and 2003, 2,039 patients were treated for HD at the Department of Radiotherapy-Oncology of the Florence University. In this study we considered 1,538 patients on whom a minimum follow up of 6 months had been obtained. Of these, 725 were women. The most represented histological subtype was nodular sclerosis (50.6%). Supradiaphragmatic alone or with subdiaphragmatic complementary extended field radiotherapy was delivered to 83.1% of patients while supradiaphragmatic involved field radiotherapy was delivered to 10.7% of patients. Concerning the characteristics and incidence of BC, we focused our analysis exclusively on the female group. We found that BC occurred in 39, with an overall incidence of 5.4%. The mean interval after Hodgkin treatment was 19.5 years (SD +/- 9.0). The median age of BC diagnosis was 50.8 years (SD +/- 13.3) while the median age of Hodgkin diagnosis was 31.2 years (SD +/- 14.5). Thirty-seven women received mediastinal irradiation. We observed a decreasing trend of the secondary BC incidence with increasing age of Hodgkin treatment with the maximum incidence registered in women treated at age 20 or younger. In Our Institute we perform a whole life follow up and recommend that annual mammography begins 10 years after HD treatment or, in any case, not later than age 40.