Trends in combined radio-chemotherapy for locally advanced rectal cancer: a survey among radiation oncology centers of Sicily region on behalf of AIRO.

AIM: 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. METHODS: 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. RESULTS: 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 < 1%). Interestingly, the toxicity rates were significantly higher in the adjuvant group compared to the neoadjuvant (GI: 58% vs 31%, GU: 21% vs 10%). CONCLUSION: The present survey shows that in the Sicily region integrated therapies for rectal cancer have allowed a neoadjuvant approach in the majority of patients, thus resulting in a greater use of sphincter conservative surgery. The toxicity has also been reported to be significantly less in this treatment setting.

Peroxisome proliferator activated receptor-gamma stimulation for prevention of 5-fluorouracil-induced oral mucositis in mice.

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-1ß after 15 days. The RGZ inhibited the 5-FU-induced increase of transforming growth factor-beta (TGF-ß) 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.

A PPAR-gamma agonist protects from radiation-induced intestinal toxicity.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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 TGFß protein expression at 24 and 72 hours post-irradiation and significantly decreased gene expression of Collagen1, Mmp13, Tnfα and Bax at 24 hours and p53 at 72 hours post-irradiation. Rosiglitazone reduced HT-29 clonogenic survival, but only produced a slight reduction of xenograft tumour growth. CONCLUSION: Rosiglitazone 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.

A PPAR gamma agonist protects against oral mucositis induced by irradiation in a murine model.

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 12-15days. 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-1ß gene expression. Rosiglitazone controlled the increase of TGF-ß 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.

Prognostic factors in patients with locally advanced head and neck cancer treated with concurrent radiochemotherapy.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A PPAR-gamma agonist attenuates pulmonary injury induced by irradiation in a murine model.

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, 5mg/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-ß 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.

Salvage stereotactic re-irradiation with CyberKnife for locally recurrent head and neck cancer: a single center experience.

AIMS AND BACKGROUND: We report the toxicity and preliminary clinical outcome in patients affected by locally recurrent head and neck cancer treated with stereotactic re-irradiation. METHODS: 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). RESULTS: 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. CONCLUSIONS: Stereotactic re-irradiation with CyberKnife is an appealing non-surgical salvage treatment for selected patients with local-regionally recurrent head and neck cancer.

Radiotherapy timing in the treatment of limited-stage small cell lung cancer: the impact of thoracic and brain irradiation on survival.

AIMS AND BACKGROUND: 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. METHODS AND STUDY DESIGN: 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. RESULTS: 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). CONCLUSIONS: 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.

Comparison of stereotactic plans for brain tumors with two different multileaf collimating systems.

Linac-based stereotactic radiosurgery (SRS) has been widely used for treating small intracranial lesions. This technique allows conforming the dose distribution to the planning target volume (PTV), providing a steep dose gradient with the surrounding normal tissues. This is realized through dedicated collimation systems. The present study aims to compare SRS plans with two collimating systems: the beam modulator (BM) of the Elekta Synergy linac and the DirexGroup micromultileaf collimator (µMLC). Seventeen patients (25 PTVs) were planned both with BM and µMLC (mounted on an Elekta Precise linac) using the Odyssey (PerMedics) treatment planning system (TPS). Plans were compared in terms of dose-volume histograms (DVH), minimum dose to the PTV, conformity index (CI), and homogeneity index (HI), as defined by the TPS, and doses to relevant organs at risk (OAR). The mean difference between the µMLC and the BM plans in minimum PTV dose was 5.7% ± 4.2% in favor of the µMLC plans. No statistically significant difference was found between the distributions of the CI values for the two planning modalities (p = 0.54), while the difference between the distributions of the HI values was statistically significant (p = 0.018). For both BM and µMLC plans, no differences were observed in CI and HI, depending on lesion size and shape. The PTV homogeneity achieved by BM plans was 15.1% ± 6.8% compared to 10.4% ± 6.6% with µMLC. Higher maximum and mean doses to OAR were observed in the BM plans; however, for both plans, dose constraints were respected. The comparison between the two collimating systems showed no substantial differences in terms of PTV coverage or OAR sparing. The improvements obtained by using µMLC are relatively small, and both systems turned out to be adequate for SRS treatments.

Neoadjuvant treatment of soft tissue sarcoma.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Clinical outcome of stereotactic body radiotherapy for abdominal lymph node metastases.

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.

Application of helical tomotherapy for the treatment of a right atrium angiosarcoma: a case report.

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.

Atypical and malignant meningioma: outcome and prognostic factors in 68 irradiated patients.

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.

Simultaneous integrated boost-intensity-modulated radiotherapy in head and neck cancer.

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.

Stereotactic body radiotherapy for cardiac and paracardiac metastases: University of Florence experience.

PURPOSE: 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. MATERIALS AND METHODS: 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). RESULTS: 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. CONCLUSIONS: Results of our retrospective study indicate that SBRT represents a safe and effective treatment option for patients with cardiac and paracardiac metastases.

Prognostic role of human epidermal growth factor receptor 2 status in premenopausal early breast cancer treated with adjuvant tamoxifen.

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.

Radiotherapy boost dose-escalation for invasive breast cancer after breast-conserving surgery: 2093 patients treated with a prospective margin-directed policy.

PURPOSE: 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). METHODS AND MATERIALS: A total of 2093 patients were treated between 2000 and 2008. 10 Gy boost was prescribed in case of FMS>5mm; 16 Gy boost with FMS between 2 and 5mm; 20 Gy boost in case of FMS<2mm or positive. RESULTS: 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 test <0.05). FMS, that directed the RT boost dose, did not have significant impact on LRFS (p=0.46). LR rates were 2.3% for FMS<2mm, 2.6% for 2-5mm FMS and 1.8% for FMS>5mm. 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. CONCLUSIONS: 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.

Accuracy of a 3D laser∕camera surface imaging system for setup verification of the pelvic and thoracic regions in radiotherapy treatments.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adjuvant and salvage radiotherapy after prostatectomy: outcome analysis of 307 patients with prostate cancer.

AIM: 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). MATERIALS AND METHODS: Between January 1995 and November 2010, 307 patients underwent adjuvant or salvage radiotherapy, after prostatectomy. RESULTS: 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. CONCLUSION: 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.

Management of inflammatory breast cancer: focus on radiotherapy with an evidence-based approach.

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.