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Background: The evolution of therapeutic landscape of human epidermal growth factor receptor-2 (HER2)-positive breast cancer (BC) has led to an unprecedented outcome improvement, even if the optimal sequence strategy is still debated. To address this issue and to provide a picture of the advancement of anti-HER2 treatments, we performed a large, multicenter, retrospective study of HER2-positive BC patients. Methods: The observational PANHER study included 1,328 HER2-positive advanced BC patients treated with HER2 blocking agents since June 2000 throughout July 2020. Endpoints of efficacy were progression-free survival (PFS) and overall survival (OS). Results: Patients who received a first-line pertuzumab-based regimen showed better PFS ( p < 0.0001) and OS ( p = 0.004) than those receiving other treatments. Median PFS and mOS from second-line starting were 8 and 28 months, without significant differences among various regimens. Pertuzumab-pretreated patients showed a mPFS and a mOS from second-line starting not significantly affected by type of second line, that is, T-DM1 or lapatinib/capecitabine ( p = 0.80 and p = 0.45, respectively). Conversely, pertuzumab-naïve patients receiving second-line T-DM1 showed a significantly higher mPFS compared with that of patients treated with lapatinib/capecitabine ( p = 0.004). Median OS from metastatic disease diagnosis was higher in patients treated with trastuzumab-based first line followed by second-line T-DM1 in comparison to pertuzumab-based first-line and second-line T-DM1 ( p = 0.003), although these data might be partially influenced by more favorable prognostic characteristics of patients in the pre-pertuzumab era. No significant differences emerged when comparing patients treated with ‘old’ or ‘new’ drugs ( p = 0.43), even though differences in the length of the follow-up between the two cohorts should be taken into account. Conclusion: Our results confirmed a relevant impact of first-line pertuzumab-based treatment and showed lower efficacy of second-line T-DM1 in trastuzumab/pertuzumab pretreated, as compared with pertuzumab-naïve patients. Our findings may help delineate a more appropriate therapeutic strategy in HER2-positive metastatic BC. Prospective randomized trials addressing this topic are awaited.

A radiological or nuclear attack could involve such a large number of subjects as to overwhelm the emergency facilities in charge. Resources should therefore be focused on those subjects needing immediate medical attention and care. In such a scenario, for the triage management by first responders, it is necessary to count on efficient biological dosimetry tools capable of early detection of the absorbed dose. At present the validated assays for measuring the absorbed dose are dicentric chromosomes and micronuclei counts, which require more than 2–3 days to obtain results. To overcome this limitation the NATO SPS Programme funded an Italian–Egyptian collaborative project aimed at validating a fast, accurate and feasible tool for assessing the absorbed dose early after radiation exposure. Biomarkers as complete blood cell counts, DNA breaks and radio-inducible proteins were investigated on blood samples collected before and 3 h after the first fraction of radiotherapy in patients treated in specific target areas with doses/fraction of about: 2, 3.5 or > 5 Gy and compared with the reference micronuclei count. Based on univariate and multivariate multiple linear regression correlation, our results identify five early biomarkers potentially useful for detecting the extent of the absorbed dose 3 h after the exposure.

Purpose/Objective(s) Post-operative loco-regional (LR) hypofractionated radiotherapy (Hypo-RT) is an attractive approach in locally advanced breast cancer (LABC). The aim of this study is to report the preliminary results of a 10 fraction hypofractionated schedule in patients (pts) with resected LABC. Materials/Methods The present is a single arm phase II study assessing toxicity outcomes after 34 Gy/10 fxs/2 wks to the whole breast/chest wall and to the draining lymph nodes; an optional single fraction 8 Gy boost was administered with electrons to the tumor bed in patients who had undergone conservative surgery. Both acute (CTCAE v4.0) and late (LENT/SOMA) toxicities were collected. All pts but those who underwent mastectomy without reconstruction or with temporary expander were also asked to rate their cosmetic outcome according to the Harvard scale. Toxicity was assessed weekly during RT and then at each follow-up examination (1, 3, 6 months and then yearly). Results From February 2015 to March 2019, 59 women (median age 60 yrs, IQR: 48.3-68.8 yrs) with stage II to IIIA breast cancer who underwent axillary dissection and conservative surgery (83%) or mastectomy (17%) entered the study. One patient refused follow up immediately after the end of RT. Of the 58 evaluable pts, 56 underwent neo-adjuvant (41%) or adjuvant (59%) chemotherapy. Trastuzumab was administered concomitant with RT in all HER2 positive pts (25%). RT was delivered initially with a conformal 3D-CRT (32.8%) and then with an optimized IMRT (67.2%) technique to improve the dose distribution. A deep inspiration breath hold technique was used in compliant left-sided LABC pts (48.4%). All ptscompleted treatment as planned. At a median follow up of 42.3 months (IQR 31.4-57.2 mths), no locoregional failures have been observed. Peak acute toxicity was as follows: grade 0, 30 pts (51.7%); grade 1, 25 pts (43.1%); grade 2, 3 pts (5.2%); no grade > 2 toxicity was recorded. Regarding late toxicity, peak 2 events were found for fibrosis (1 pt, 1.7%), telangiectasia (1 pts, 1.7%); lymphedema (1 pt, 1.7%). One patient (1.7%) experienced grade 3 breast retraction. No other grade 2+ events were reported. Of eligible patients (N = 51) patient-reported cosmetic outcome was excellent, good, fair and poor in 59%, 23.5%, 11.7% and 5.8%, respectively. Conclusion These preliminary data support the feasibility and tolerability of our 10-fraction fractionation schedule targeting the primary site as well as the draining lymph node stations after surgery for LABC.

Background There is no widely accepted intervention in the prevention of acute mucositis during chemoradiotherapy for head and neck carcinoma. In the present double-blind study, we tested 4 natural agents, propolis, aloe vera, calendula, and chamomile versus placebo. Methods Patients undergoing concomitant chemo-intensity-modulated radiotherapy (IMRT) were given natural agent or matched placebo; grade 3 mucositis on physical examination according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was the primary endpoint. Various covariates were tested at logistic regression, including the individual amount of mucosa receiving at least 9.5 Gy per week (V9.5w). Results One hundred seven patients were randomized from January 2011 to July 2014, and 104 were assessable (51%-49% were assigned to the placebo group and 53%-51% were assigned to the natural agent). Overall, 61 patients developed peak grade 3 mucositis with no difference between arms (P = .65). Conversely, V9.5w (P = .007) and primary site (P = .037) were independent predictors. Conclusion The selected natural agents do not prevent mucositis, whereas the role of V9.5w is confirmed.

To compare long-term late local toxicity after either concomitant or sequential chemoradiation therapy after breast-conserving surgery.From 1997 to 2002, women aged 18 to 75 years who underwent breast-conserving surgery and axillary dissection for early breast cancer and in whom CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) chemotherapy was planned were randomized between concomitant and sequential radiation therapy. Radiation therapy was delivered to the whole breast through tangential fields to 50 Gy in 20 fractions over a period of 4 weeks, followed by an electron boost. Surviving patients were tentatively contacted and examined between March and September 2014. Patients in whom progressive disease had developed or who had undergone further breast surgery were excluded. Local toxicity (fibrosis, telangiectasia, and breast atrophy or retraction) was scored blindly to the treatment received. A logistic regression was run to investigate the effect of treatment sequence after correction for several patient-, treatment-, and tumor-related covariates on selected endpoints. The median time to cross-sectional analysis was 15.7 years (range, 12.0-17.8 years).Of 206 patients randomized, 154 (74.8%) were potentially eligible. Of these, 43 (27.9%) refused participation and 4 (2.6%) had been lost to follow-up, and for 5 (3.2%), we could not restore planning data; thus, the final number of analyzed patients was 102. No grade 4 toxicity had been observed, whereas the number of grade 3 toxicity events was low (8%) for each item, allowing pooling of grade 2 and 3 events for further analysis. Treatment sequence (concomitant vs sequential) was an independent predictor of grade 2 or 3 fibrosis according to both the National Cancer Institute Common Terminology Criteria for Adverse Events (odds ratio [OR], 4.05; 95% confidence interval [CI], 1.34-12.2; P=.013) and the SOMA (Subjective, Objective, Management and Analytic) scale (OR, 3.75; 95% CI, 1.19-11.79; P=.018), as well as grade 2 or 3 breast atrophy or retraction (OR, 3.87; 95% CI, 1.42-10.56; P=.008). No effect on telangiectasia was detected.At long-term follow-up, concomitant chemoradiation therapy has a detrimental effect on both fibrosis and retraction with an approximately 4-fold increase in the odds of grade 2 or 3 toxicity.

Background Variant ATM heterozygotes have an increased risk of developing cancer, cardiovascular diseases, and diabetes. Costs and time of sequencing and ATM variant complexity make large-scale, general population screenings not cost-effective yet. Recently, we developed a straightforward, rapid, and inexpensive test based on p53 mitotic centrosomal localization (p53-MCL) in peripheral blood mononuclear cells (PBMCs) that diagnoses mutant ATM zygosity and recognizes tumor-associated ATM polymorphisms. Methods Fresh PBMCs from 496 cancer patients were analyzed by p53-MCL: 90 cases with familial BRCA1/2-positive and -negative breast and/or ovarian cancer, 337 with sporadic cancers (ovarian, lung, colon, and post-menopausal breast cancers), and 69 with breast/thyroid cancer. Variants were confirmed by ATM sequencing. Results A total of seven individuals with ATM variants were identified, 5/65 (7.7 %) in breast cancer cases of familial breast and/or ovarian cancer and 2/69 (2.9 %) in breast/thyroid cancer. No variant ATM carriers were found among the other cancer cases. Excluding a single case in which both BRCA1 and ATM were mutated, no p53-MCL alterations were observed in BRCA1/2-positive cases. Conclusions These data validate p53-MCL as reliable and specific test for germline ATM variants, confirm ATM as breast cancer susceptibility gene, and highlight a possible association with breast/thyroid cancers. Electronic supplementary material The online version of this article (doi:10.1186/s13046-016-0410-3) contains supplementary material, which is available to authorized users.

Purpose: The aim of this study was to design and build a prototype beam shaper to be used on a dedicated mobile accelerator that protects organs at risk within the radiation field and conforms the beam to the target geometry during intraoperative electron radiotherapy (IOERT). A dosimetric characterization of the beam shaper device was performed based on Monte Carlo(MC) simulations, as well as experimental data, at different energies, field sizes, and source to skin distances. Methods: A mobile light intraoperative accelerator (LIAC®, Sordina, Italy) was used. The design of the beam shaper prototype was based on MC simulations (BEAMnrc/OMEGA and DOSXYZnrc code) for a selection of materials and thicknesses, as well as for dosimetric characterization. Percentage depth dose (PDD) and profile measurements were performed using a p-type silicon diode and a commercial water phantom, while output factors were measured using a PinPoint ion chamber in a PMMA phantom. Planar doses in planes of interest were carried out using radiochromic films (GafchromicTM EBT and EBT2) in PMMA and in a Solid Water® phantom. Several experimental set-ups were investigated with the beam shaper device fixed on the top of the phantom, varying both the short side of the rectangular field and the air gap between the device and the phantom surface, simulating the clinical situation. The output factors (OFs) were determined using different geometrical set-ups and energies. Results: The beam shaper prototype consists of four blades sliding alongside each other and mounted on a special support at the end of the 10 cm diameter PMMA circular applicator. Each blade is made of an upper layer of 2.6 cm of Teflon ® and a lower layer of 8 mm of stainless steel. All rectangles inscribed in a 5 cm diameter can be achieved in addition to any “squircle-shaped” field. When one side of the rectangular field is held constant and the second side is reduced, both R 50 and R max move towards the phantom surface. Comparing the PDDs obtained with the 5 cm circular applicator and with a 4.4 × 4.4 cm2 square field (that is the equivalent square of the 5 cm circular field) obtained with the beam shaper, a different behavior was observed in the region extending from the surface to a depth of 50% of the maximum dose. Isodoses measured for rectangular fields used for clinical cases (i.e., 4 × 9 cm2 8 MeV) are shown, with different air gaps. For each energy investigated, the normalized OFs slowly increase, when the length of the side decreases down to about 4 cm, and then rapidly decreases for smaller field widths. MC simulation showed an excellent agreement with experimental data (

Purpose One of the worst radiation-induced acute effects in treating head-and-neck (HN) cancer is grade 3 or higher acute (oral and pharyngeal) mucosal toxicity (AMT), caused by the killing/depletion of mucosa cells. Here we aim to testing a predictive model of the AMT in HN cancer patients receiving different radiotherapy schedules. Methods and Materials Various radiotherapeutic schedules have been reviewed and classified as tolerable or intolerable based on AMT severity. A modified normal tissue complication probability (NTCP) model has been investigated to describe AMT data in radiotherapy regimens, both conventional and altered in dose and overall treatment time (OTT). We tested the hypothesis that such a model could also be applied to identify intolerable treatment and to predict AMT. This AMT NTCP model has been compared with other published predictive models to identify schedules that are either tolerable or intolerable. The area under the curve (AUC) was calculated for all models, assuming treatment tolerance as the gold standard. The correlation between AMT and the predicted toxicity rate was assessed by a Pearson correlation test. Results The AMT NTCP model was able to distinguish between acceptable and intolerable schedules among the data available for the study (AUC = 0.84, 95% confidence interval=0.75-0.92). In the equivalent dose at 2 Gy/fraction (EQD2) vs OTT space, the proposed model shows a trend similar to that of models proposed by other authors, but was superior in detecting some intolerable schedules. Moreover, it was able to predict the incidence of ≥G3 AMT. Conclusion The proposed model is able to predict ≥G3 AMT after HN cancer radiotherapy, and could be useful for designing altered/hypofractionated schedules to reduce the incidence of AMT.

Aims To quantify the changes in dose as well as in the prediction of parotid gland toxicity due to anatomical changes during therapy of head and neck cancer patients. Materials and methods Fifteen patients with advanced locoregional head and neck cancer, with no evidence of distant metastasis, were enrolled in a prospective study. All patients were treated with intensity-modulated radiotherapy. Multiple computed tomography scans were repeated at the end of each treatment week. The original treatment plans were copied to the per-treatment scans to create hybrid plans. The normal tissue complication probability (NTCP) was calculated assuming the end point to be grade ≥3 xerostomia according to the Radiation Therapy Oncology Group late toxicity scale. Results The gross tumour volume dose coverage was slightly affected by the anatomical changes, whereas the mean dose (D mean ) to the parotids changed from 26.1 ± 6.0 to 27.4 ± 7.4 Gy, with a mean increase of 0.22 Gy/treatment week. Consequently, the mean NTCP increased from 0.15 ± 0.06 to 0.18 ± 0.10, primarily due to a few patients exhibiting a marked increase. The absolute gross tumour volume shrinkage and the percentage parotids shrinkage were the best independent predictors for the NTCP variations. Conclusions On average, the increase in the parotids D mean as well as in NTCP during treatment is limited, and the observed variations were strongly patient-dependent.

Background: Do ATM heterozygous (ATM-htz) carriers have an increased risk of developing breast cancer? Do they have an increased sensitivity to ionizing radiation (IR)? Definitive information does not yet exist to answer these questions. Case-control studies have suggested a link between single copy ATM gene mutation and increased breast cancer risk. Lymphoblasts and skin fibroblasts from ATM-htz carriers are less sensitive to IR than cells from Ataxia Telangiectasia (AT) patients, but more sensitive than cells from the general population. Because of the clinical and environmental implication of these aspects, large studies are in progress to better understand the interaction between ATM-htz and increased breast cancer risk or radio-sensitivity. However, to be performed on the general population rather than on the obligate ATM-htz carriers, i.e., the rare parents of children affected by AT, these studies must relay on the expensive sequencing of the entire ATM gene (approximately 160Kb of genomic DNA, a 13Kb transcript of 66 exons, and more than 400 unique mutations that extend across the full length of the gene). Materials and Methods: Based on a serendipitous discovery, we have development of a new, non-invasive, easy, quick, and inexpensive test to identify AT patients and, more interestingly, the ATM-htz carriers. In particular, we found that, in mitosis, p53 localizes at centrosomes, the cytoplasmic organelles that organize the interphase cytoskeleton and contribute to bipolar spindle formation during mitotic cell division. In addition, we demonstrated that ATM is required for p53 localization at centrosome. These findings allowed us to identify a particular phenotype of peripheral blood lymphocytes (PBL) from AT patients or their parents, the obligate ATM-htz that should allow to easily discriminate the ATM-htz carries in the general population with a very high statistical significance (P Discussion: Beside an accurate assessment of the relative contribution of ATM heterozygosity to tumor susceptibility, this study will open the possibility of performing large screening for ATM-htz carries in the general population for different clinical aspects, such as IR sensitivity, genetic counseling, cancer predisposition, or selection for specific targeted therapies. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-06-01.

Objective To evaluate both the patterns of prescription of androgen deprivation therapy (ADT) in patients with prostate cancer (PCa) and the adherence to European Association of Urology (EAU) guidelines for ADT prescription. Methods The Choosing Treatment for Prostate Cancer (CHOICE) study was an Italian multicentre cross-sectional study conducted between December 2010 and January 2012. A total of 1 386 patients, treated with ADT for PCa (first prescription or renewal of ADT), were selected. With regard to the EAU guidelines on ADT, the cohort was categorized into discordant ADT (Group A) and concordant ADT (Group B). Results The final cohort included 1 075 patients with a geographical distribution including North Italy (n = 627, 58.3%), Central Italy (n = 233, 21.7%) and South Italy (n = 215, 20.0%). In the category of patients treated with primary ADT, a total of 125 patients (56.3%) were classified as low risk according to D'Amico classification. With regard to the EAU guidelines, 285 (26.51%) and 790 patients (73.49%) were classified as discordant (Group A) and concordant (Group B), respectively. In Group A, patients were more likely to receive primary ADT (57.5%, 164/285 patients) than radical prostatectomy (RP; 30.9%, 88/285 patients), radiation therapy (RT; 6.7%, 19/285 patients) or RP + RT (17.7%, 14/285 patients; P < 0.01). Multivariate logistic regression analysis, adjusted for clinical and pathological variables, showed that patients from Central Italy (odds ratio [OR] 2.86; P < 0.05) and South Italy (OR 2.65; P < 0.05) were more likely to receive discordant ADT. Conclusion EAU guideline adherence for ADT was low in Italy and was influenced by geographic area. Healthcare providers and urologists should consider these results in order to quantify the inadequate use of ADT and to set policy strategies to overcome this risk.

We aimed at developing a more detailed understanding of cyclin D1 in early stage human breast cancer and defining the biologic profiles with different prognostic value correlating cyclin D1 gene amplification and chromosome 11 aneusomy with bio-pathologic variables of known clinical importance. Cyclin D1 gene amplification and chromosome 11 aneusomy were investigated using fluorescence in situ hybridization whereas cyclin D1, PgR, HER-2, Bcl2, p53, and Ki-67 expressions were analyzed by immunohistochemistry in 121 stage I or II breast cancer patients uniformly treated with cyclophosphamide/metotrexate/5-fluorouracil-based chemotherapy. Cyclin D1 was amplified in 6.6% and overexpressed in 32.2% of cases. Amplification was not associated with any selected bio-pathologic variables, whereas the chromosome 11 aneusomy level significantly increased in tumors with higher histologic grade (P0.01), higher tumor size (P0.003), p53 nuclear accumulation (P0.04), and ERalpha negativity (P0.049). Multiple correspondence analysis showed 4 different biologic tumor profiles. The first, characterized by high Ki-67 score, p53+, cyclin D1+, HER-2+, aneusomy level30%, ratio (cyclin D1 gene/CEP11)2, was associated with tumor relapse defining the most unfavorable biologic profile. Kaplan-Meier's method showed significantly shorter disease-free survival in patients with at least 3 variables positive out of the 6 detected by multiple correspondence analysis. In multivariate analysis, the identified biologic profile emerged as the only significant prognostic indicator. Our findings are of particular clinical interest for early stage breast cancer patients, because the assessment of biologic factors predictive of tumor aggressiveness may influence postoperative therapeutic strategies.

Background In the last several decades, combined radiotherapy (RT) and chemotherapy (CT) have been recognized as feasible in locally-advanced-squamous-cell-carcinoma of the head-and-neck (LA-HNSCC). Several meta-analyses identified concurrent RT + CT (CRT) most likely effective approach respect to RT-alone. However, radiobiological models comparing different chemotherapeutic schedules against delivered RT fractionation schedule for overall survival and toxicity are still needed. Methods and materials Based on 9 randomized trials (2785 patients), radiobiological models and multivariate logistic regression model were used to derive dose-response curves and estimate the 5-year-overall survival (OS) and ≥G3 acute mucositis rate of CRT or RT-alone. Results Equivalent dose at 2 Gy/fraction (EQD2) was calculated using the linear quadratic model. The effect of CRT schedules, considering the CT type and its administration schedule and the HPV status of tumors were estimated using the univariate/multivariate logistic regression. The multivariate logistic regression model for 5y-OS indicated EQD2 and the type of CT, the chemo-sensitization fraction and the HPV status significant prognostic factors, while for toxicity both EQD2 and the concomitant administration of 5-fluorouracil (5Fu) resulted as significant prognostic factors. Combined schedules cisplatin (DDP)+/−5Fu + RT produced the higher OS compared with combined carboplatin+/−5Fu + RT or RT-alone. The concomitant administration of Fu and schedule with high EQD2 increase the rate of observed ≥G3 acute mucositis. Conclusion Multivariate logistic regression models can be used to predict CRT effect in terms of OS and ≥G3-mucositis, contributing to the identification of novel treatment schedules.

Purpose: To compare two different timings of radiation treatment in patients with breast cancer who underwent conservative surgery and were candidates to receive adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy. Methods and Materials: A total of 206 patients who had quadrantectomy and axillary dissection for breast cancer and were planned to receive adjuvant CMF chemotherapy were randomized to concurrent or sequential radiotherapy. Radiotherapy was delivered only to the whole breast through tangential fields to a dose of 50 Gy in 20 fractions over 4 weeks, followed by an electron boost of 10–15 Gy in 4–6 fractions to the tumor bed. Results: No differences in 5-year breast recurrence-free, metastasis-free, disease-free, and overall survival were observed in the two treatment groups. All patients completed the planned radiotherapy. No evidence of an increased risk of toxicity was observed between the two arms. No difference in radiotherapy and in the chemotherapy dose intensity was observed in the two groups. Conclusions: In patients with negative surgical margins receiving adjuvant chemotherapy, radiotherapy can be delayed to up to 7 months. Concurrent administration of CMF chemotherapy and radiotherapy is safe and might be reserved for patients at high risk of local recurrence, such as those with positive surgical margins or larger tumor diameters.

The aim of the study was to report the clinical results in patients with high-risk prostate cancer treated with pelvic intensity-modulated radiation therapy (IMRT) and simultaneous integrated boost (SIB) to the prostate area. A total of 110 patients entered our study, 37 patients presented with localized prostate cancer and radiological evidence of node metastases or ≥15% estimated risk of lymph node (LN) involvement, while 73 patients underwent postoperative adjuvant or salvage irradiation for biochemical or residual/recurrent disease, LN metastases, or high risk of harboring nodal metastases. All patients received androgen deprivation therapy (ADT) for 2 years. The median follow-up was 56.5 months. For the whole patient group, the 3- and 5-year freedom from biochemical failure were 82.6% and 74.6%, respectively, with a better outcome in patients treated with radical approach. The 3- and 5-year freedom from local failure were 94.4% and 90.2%, respectively, while the 3- and 5-year distant metastasis-free survival were 87.8% and 81.7%, respectively. For all study patients, the rate of freedom from G2 acute rectal, intestinal, and urinary toxicities was 60%, 77%, and 61%, respectively. There was no G3 acute toxicity, ≥G2 late intestinal toxicity, or G3 late urinary or rectal toxicity. The 3- and 5-year ≥G2 freedom from late rectal toxicity rate were 98% and 95%, respectively, while the 3- and 5-year ≥G2 freedom from late urinary toxicity rate were 95% and 88%, respectively. The study concludes that pelvic IMRT and SIB to the prostatic area in association with 2-year ADT was a well-tolerated technique, providing high disease control in patients with prostate cancer requiring LN treatment.

Background To investigate the potential dosimetric and clinical benefits of Deep Inspiration Breath-Hold (DIBH) technique during radiotherapy of breast cancer compared with Free Breathing (FB). Methods Eight left-sided breast cancer patients underwent a supervised breath hold during treatment. For each patient, two CT scans were acquired with and without breath hold, and virtual simulation was performed for conventional tangential fields, utilizing 6 or 15 MV photon fields. The resulting dose–volume histograms were calculated, and the volumes of heart/lung irradiated to given doses were assessed. The left anterior descending coronary artery (LAD) mean and maximum doses were calculated, together with tumour control probability (TCP) and normal tissue complication probabilities (NTCP) for lung and heart. Results For all patients a reduction of at least 16% in lung mean dose and at least 20% in irradiated pulmonary volumes was observed when DIBH was applied. Heart and LAD maximum doses were decreased by more than 78% with DIBH. The NTCP values for pneumonitis and long term cardiac mortality were also reduced by about 11% with DIBH. The NTCP values for pericarditis were zero for both DIBH and FB. Conclusion Delivering radiation in DIBH conditions the dose to the surrounding normal structures could be reduced, in particular heart, LAD and lung, due to increased distance between target and heart, and to reduced lung density.

In this article we report on the current role of radiotherapy in the management of non-muscle invasive as well as in muscle invasive bladder cancer. Radiotherapy seems to have no role in non-muscle invasive bladder cancer. In muscle invasive bladder tumors, the role of radiotherapy is under investigation in view of new radiotherapy techniques and novel cytotoxic and biological agents.

Purpose: To report long-term results and patterns of failure after conventional and hypofractionated radiation therapy in high-risk prostate cancer. Methods and Materials: This randomized phase III trial compared conventional fractionation (80 Gy at 2 Gy per fraction in 8 weeks) vs hypofractionation (62 Gy at 3.1 Gy per fraction in 5 weeks) in combination with 9-month androgen deprivation therapy in 168 patients with high-risk prostate cancer. Freedom from biochemical failure (FFBF), freedom from local failure (FFLF), and freedom from distant failure (FFDF) were analyzed. Results: In a median follow-up of 70 months, biochemical failure (BF) occurred in 35 of the 168 patients (21%) in the study. Among these 35 patients, local failure (LF) only was detected in 11 (31%), distant failure (DF) only in 16 (46%), and both LF and DF in 6 (17%). In 2 patients (6%) BF has not yet been clinically detected. The risk reduction by hypofractionation was significant in BF (10.3%) but not in LF and DF. We found that hypofractionation, with respect to conventional fractionation, determined only an insignificant increase in the actuarial FFBF but no difference in FFLF and FFDF, when considering the entire group of patients. However, an increase in the 5-year rates in all 3 endpoints - FFBF, FFLF, and FFDF - was observed in the subgroup of patients with a pretreatment prostate-specific antigen (iPSA) level of 20 ng/mL or less. On multivariate analysis, the type of fractionation, iPSA level, Gleason score of 4+3 or higher, and T stage of 2c or higher have been confirmed as independent prognostic factors for BF. High iPSA levels and Gleason score of 4+3 or higher were also significantly associated with an increased risk of DF, whereas T stage of 2c or higher was the only independent variable for LF. Conclusion: Our results confirm the isoeffectiveness of the 2 fractionation schedules used in this study, although a benefit in favor of hypofractionation cannot be excluded in the subgroup of patients with an iPSA level of 20 ng/mL or less. The α/β ratio might be more appropriately evaluated by FFLF than FFBF results, at least in high-risk disease

Background The aim of this study was to evaluate the potential association between single nucleotide polymorphisms related response to radiotherapy injury, such as genes related to DNA repair or enzymes involved in anti-oxidative activities. The paper aims to identify marker genes able to predict an increased risk of late toxicity studying our group of patients who underwent a Single Shot 3D-CRT PBI (SSPBI) after BCS (breast conserving surgery). Methods A total of 57 breast cancer patients who underwent SSPBI were genotyped for SNPs (single nucleotide polymorphisms) in XRCC1, XRCC3, GST and RAD51 by Pyrosequencing technology. Univariate analysis (ORs and 95% CI) was performed to correlate SNPs with the risk of developing ≥ G2 fibrosis or fat necrosis. Results A higher significant risk of developing ≥ G2 fibrosis or fat necrosis in patients with: polymorphic variant GSTP1 (Ile105Val) (OR = 2.9; 95%CI, 0.88-10.14, p = 0.047). Conclusions The presence of some SNPs involved in DNA repair or response to oxidative stress seem to be able to predict late toxicity. Trial Registration ClinicalTrials.gov: NCT01316328

Background To evaluate the association between polymorphisms involved in DNA repair and oxidative stress genes and mean dose to whole breast on acute skin reactions (erythema) in breast cancer (BC) patients following single shot partial breast irradiation (SSPBI) after breast conservative surgery. Materials and Methods Acute toxicity was assessed using vers.3 criteria. single nucleotides polymorphisms(SNPs) in genes: XRCC1(Arg399Gln/Arg194Trp), XRCC3 (A4541G-5'UTR/Thr241Met), GSTP1(Ile105Val), GSTA1 and RAD51(untranslated region). SNPs were determined in 57 BC patients by the Pyrosequencing analysis. Univariate(ORs and 95% CI) and logistic multivariate analyses (MVA) were performed to correlate polymorphic genes with the risk of developing acute skin reactions to radiotherapy. Results After SSPBI on the tumour bed following conservative surgery, grade 1 or 2 acute erythema was observed in 19 pts(33%). Univariate analysis indicated a higher significant risk of developing erythema in patients with polymorphic variant wt XRCC1Arg194Trp, mut/het XRCC3Thr241Met, wt/het XRCC3A4541G-5'UTR. Similarly a higher erythema rate was also found in the presence of mut/het of XRCC1Arg194Trp or wt of GSTA1. Whereas, a lower erythema rate was observed in patients with mut/het of XRCC1Arg194Trp or wt of XRCC1Arg399Gln. The mean dose to whole breast(p = 0.002), the presence of either mut/het XRCC1Arg194Trp or wt XRCC3Thr241Met (p = 0.006) and the presence of either mut/het XRCC1Arg194Trp or wt GSTA1(p = 0.031) were confirmed as predictors of radiotherapy-induced erythema by MVA. Conclusions The Whole breast mean dose together with the presence of some polymorphic genes involved in DNA repair or oxidative stress could explain the erythema observed after SSPBI, but further studies are needed to confirm these results in a larger cohort. Trial Registration ClinicalTrials.gov Identifier: NCT01316328

Background To report the clinical outcome after a Single Shot 3D-CRT PBI (SSPBI) in breast cancer patients after conservative surgery (ClinicalTrials.gov Identifier: NCT01316328). Methods A dose of 18Gy (in the first 4 patients) and 21Gy (in the remaining 60 patients) was prescribed in a single session and delivered to the index area (i.e. the area of breast including the primary tumor bed and the surrounding tissue) using 3D-CRT with patients in prone position. Acute and late toxicity was assessed using the National Cancer Institute's CTC for Adverse Events. Cosmesis was defined based on modified Harvard criteria. Differences between dosimetric or clinical parameters of patients with/without G2 or more late toxicity or unsatisfactory (poor or fair) cosmetic outcome were evaluated with the Mann-Whitney test. Odds ratios and 95% confidence interval were calculated for cosmesis and fibrosis. Univariate and multivariate analyses(UVA/MVA) were used to determine covariates associated with an increase in fibrosis or fat necrosis rate. Results Sixty four patients were enrolled. With a median follow-up of 3 years, G2 and G3 subcutaneous fibrosis was detected in 20(31%) and in 8(13%) patients, and ≥G2 fat necrosis was observed in 2(3%) patients. Good to excellent, fair and poor cosmesis was observed in 38(59%), 23(36%) and 3(5%) patients, respectively. Based on UVA, the breast volume receiving more than 21Gy (V21Gy) was found to be a predictor of the ≥G1 or ≥G2 fibrosis/fat necrosis. Based on MVA, V21Gy was confirmed as a predictor for ≥G1 fibrosis/fat necrosis, the results correlated as a trend for ≥G2. Cosmesis was correlated with whole breast (WB) mean dose (p = 0.030). Conclusion Our choice of a single dose of 21Gy significantly increased the treatment related toxicity. However, this should not discourage novel SSPBI approaches with lower equivalent doses.

OBJECTIVE A prospective, phase III randomized study was undertaken to compare the outcomes of 2 different radiotherapy and chemotherapy sequences in conservatively treated patients with breast cancer. METHODS Between January 1997 and November 2002, 206 patients operated of quadrantectomy and axillary dissection for breast cancer, candidates to receive adjuvant CMF chemotherapy (cyclophosphamide, methotrexate, and fluorouracil) were assigned to concurrent or sequential radiation treatment by using a balanced randomization method. Before randomization patients were stratified by tumor diameter, age, and lymph node status. The primary end point was the freedom from breast recurrence, and secondary end points were overall and disease-free survival. Overall outcomes were analyzed according to the intention-to-treat principle. RESULTS All 206 patients enrolled and randomized in the trial were analyzed. The median follow-up was 111 months, with no patient lost for follow-up. No difference in 10-years breast recurrence-free, disease-free, metastasis-free, and overall survival rates was observed in the 2 treatment sequence groups. The Hazard Ratios, calculated for each prognostic factor, showed no difference in all outcomes between the 2 treatment sequences. CONCLUSIONS No influence of the treatment sequence on long-term outcomes was observed in this trial. This finding suggests that to avoid an increased risk of distant recurrence or an excessive toxicity, radiation therapy may be delayed until after the end of the more, recently used, anthracycline-based chemotherapy without increasing the risk of breast recurrences, thus allowing the delivery of full-dose chemotherapy in patients at risk for systemic disease spread.

Background The purpose of this study was to compare 5-field and 7-field intensity-modulated radiation therapy (IMRT) techniques in terms of xerostomia and related quality of life in patients with nasopharyngeal cancer. Methods Eight and 23 patients were treated with 5-field (group I) and 7-field (group II) techniques, respectively. The xerostomia was evaluated using the Radiation Therapy Oncology Group (RTOG) scale, stimulated and unstimulated salivary flow (SSF/USF), and xerostomia-related questionnaires (XQs). The assessments were done before and at 3, 6, 12, 18, and 24 months after radiotherapy. Results The mean parotid dose was 45.7 Gy and 29.9 Gy and the ≥G3 toxicity at 24 months was 25% and 19% in group I and II, respectively. Sixty-three percent and 93% of patients recovered at least 25% of SSF pretherapy values. The XQ scores of both groups improved over time but more so in group II. Conclusion The 7-field technique decreases the mean parotid dose, reducing xerostomia assessed by the RTOG/XQ score. © 2011 Wiley Periodicals, Inc. Head Neck, 2012

Background Accelerated hypofractionation is an attractive approach for adjuvant whole breast radiotherapy. In this study we evaluated the adverse effects at least 3 years post an accelerated hypofractionated whole breast radiotherapy schedule. Methods From October 2004 to March 2006, 39 consecutive patients aged over 18 years with pTis, pT1-2, pN0-1 breast adenocarcinoma who underwent conservative surgery were treated with an adjuvant accelerated hypofractionated radiotherapy schedule consisting of 34 Gy in 10 daily fractions over 2 weeks to the whole breast, followed after 1 week by an electron boost dose of 8 Gy in a single fraction to the tumour bed. Skin and lung radiation toxicity was evaluated daily during therapy, once a week for one month after radiotherapy completion, every 3 months for the first year and from then on every six months. In particular lung toxicity was investigated in terms of CT density evaluation, pulmonary functional tests, and clinical and radiological scoring. Paired t-test, Chi-square test and non-parametric Wilcoxon test were performed. Results After a median follow-up of 43 months (range 36-52 months), all the patients are alive and disease-free. None of the patients showed any clinical signs of lung toxicity, no CT-lung toxicity was denoted by radiologist on CT lung images acquired about 1 year post-radiotherapy, no variation of pulmonary density evaluated in terms of normalised Hounsfield numbers was evident. Barely palpable increased density of the treated breast was noted in 9 out of 39 patients (in 2 patients this toxicity was limited to the boost area) and teleangectasia (2) limited to the boost area was evident in 2 out of 39 patients. The compliance with the treatment was excellent (100%). Conclusion The radiotherapy schedule investigated in this study (i.e 34 Gy in 3.4 Gy/fr plus boost dose of 8 Gy in single fraction) is a feasible and safe treatment and does not lead to adjunctive acute and late toxicities. A longer follow up is necessary to confirm these favourable results.

BACKGROUND: To quantify the magnitude of benefit of the addition of hormone treatment (HT) to exclusive radiotherapy for locally advanced prostate cancer, a literature-based meta-analysis was conducted. METHODS: Event-based relative risks (RR) with 95% confidence intervals (CIs) were derived through a random-effect model. Differences in primary (biochemical failure and clinical progression-free survival) and secondary outcomes (cancer-specific survival, overall survival [OS], recurrence patterns, and toxicity) were explored. Absolute differences and numbers of patients needed to treat (NNT) were calculated. A heterogeneity test, a metaregression analysis with clinical predictors of outcome, and a correlation analysis for surrogate endpoints were also performed. RESULTS: Seven trials (4387 patients) were gathered. Hormone suppression significantly decreased both biochemical failure (RR, 0.76; 95% CI, 0.70-0.82; P < .0001) and clinical progression-free survival (RR, 0.81; 95% CI 0.71-0.93; P = .002), with absolute differences of 10% and 7.7%, respectively, which translates into 10 and 13 NNT. cancer-specific survival (RR, 0.76; 95% CI, 0.69-0.83; P < .0001) and OS (RR, 0.86; 95% CI, 0.80-0.93; P < .0001) were also significantly improved by the addition of HT, without significant heterogeneity, with absolute differences of 5.5% and 4.9%, respectively, which translates into 18 and 20 NNT. Local and distant relapse were significantly decreased by HT, by 36% and 28%, respectively, and no significant differences in toxicity were found. Primary and secondary efficacy outcomes were significantly correlated. CONCLUSIONS: Hormone suppression plus radiotherapy significantly decreases recurrence and mortality of patients with localized prostate cancer, without affecting toxicity. Cancer 2009. © 2009 American Cancer Society.

Neoadjuvant chemotherapy has been reported to be extremely active in head and neck cancer but has failed to give a statistically significant improvement in survival.From 1981 to 1994, 33 operable patients with locally advanced oral cavity cancer received cisplatin-based chemotherapy before surgery. Postoperative radiotherapy was performed in high-risk patients.The overall clinical and pathologic complete response rates to neoadjuvant chemotherapy were 48% and 30%, respectively. At a median follow-up of 7.0 years (range, 0.3-15.3+ years), the 5-year and 10-year overall survival rates were 54.5% and 39.5%, and the disease-specific median survival was 6.6 years for all patients (8.3 and 2.3 years for stages III and IV, respectively). The univariate analysis showed a positive relationship between survival and male sex (p = .05), pathologic (p = .02), and clinical (p = .03) complete response. The Cox proportional hazard regression model confirmed the independent prognostic value of the clinical response with a 4.67 (95% CI, 1.70-12.86) hazard ratio. A second primary tumor occurred in six patients (18%), with a median of occurrence of 9 years (range, 7-11 years).This study confirms the prolonged survival expectancy largely exceeding 5 years for selected patients with stage IV and for most with stage III locally advanced oral cavity cancer achieving a clinical and/or pathologic complete response to chemotherapy.

BACKGROUND Single-modality radiotherapy is still considered standard treatment for patients with locally advanced unresectable cancer of the head and neck. As treatment outcome is poor, attempts to integrate chemotherapy into the overall management of these patients are ongoing. PATIENTS AND METHODS A randomized study was undertaken to compare a sequential with a simultaneous chemoradiotherapy program. Between February 1986 and February 1991, 93 eligible patients with locally advanced unresectable cancer of the head and neck were stratified by WHO PS, T and N class and primary site and then randomized to receive either three courses of neoadjuvant chemotherapy with cisplatin (100 mg/m2 i.v. d 1) and 5-fluorouracil 1000 mg/m2/days 1-5 by continuous i.v. infusion every 3 weeks prior to definitive conventional radiotherapy of 65-70 Gy (sequential treatment), or cisplatin 100 mg/m2 on days 1, 22, 43 given simultaneously for the duration of the same conventional radiotherapy (simultaneous treatment). RESULTS At the end of the entire treatment 18 complete responses (47%) in the sequential-treatment arm and 18 (41%) in the simultaneous treatment arm were obtained. No statistically significant differences in the 5-yr progression-free survival, in the median time to loco-regional and distant progression and in the 5-yr overall survival were observed. Leukopenia was more frequent in the simultaneous than in the sequential arm (p = 0.03), whereas alopecia (p = 0.008) and phlebitis (p < 0.0001) were more frequent in the sequential-treatment arm. A better compliance was associated with the concomitant treatment, with 87% of the patients completing the entire radiotherapy program versus 63% of those in the sequential arm (p = 0.01). CONCLUSIONS In the present study, the two treatment arms showed similar activity (complete response, progression-free and overall survival rates). Compliance to treatment was better in the concomitant arm. These data suggest that concomitant chemo-radiation therapy might be considered an option in unresectable locally advanced cancer of the head and neck. Phase III studies are needed in order to establish the superiority of this combination of cisplatin and radiotherapy versus radiotherapy alone.

Between May 1981 and December 1987, 152 consecutive patients with locally advanced and previously untreated head and neck squamous cell cancer (HNSCC) received two or three courses of neoadjuvant chemotherapy (NAC) prior to surgery and/or radiotherapy. Eighteen percent of patients achieved a complete response and 45% a partial response (PR), for an overall response rate of 63%. A variety of pretreatment patient and tumor characteristics were analyzed for both the tumor response to NAC and survival rate. Significantly higher CR rates were found in patients with a World Health Organization (WHO) performance status (PS) of 0 to 1 than in those patients with a PS of 2 (P = .03). Patients with stage III disease were significantly more likely to respond than those with stage IV (P = .006). Evaluation of all parameters through multivariate analysis identifies the tumor classification (P = .001) and the primary site (P = .006) as the most significant in predicting CR. The overall 5-year survival rate of the entire group of patients was 18% (median survival, 14.3 months). Analysis by PS (P = .001), stage (P = .002), and tumor (P = .001), and node (P = .01) classes showed significant differences. Patients achieving a CR after NAC had a significantly improved survival rate as compared with those with residual disease at assessment (P = .0003). With the multistep regression analysis, the tumor (P = .005) and node (P = .007) classifications, and the sex (P = .03) were significant factors, but CR (P = .0004) remained the most important and independent predictive factor. Randomized prospective trials are requested to clearly establish the role of NAC on survival rates.

The present retrospective study reports data regarding renal toxicity in 115 patients (63 males, 52 females; median age, 56 years) who received cumulative doses of cisplatin (DDP) ≥ 200 mg/m2. DDP was administered alone or in combination at a dose of 50-70 mg/m2 in 91 patients, and at a dose of 100 mg/m2 in 22 patients. Two patients after progression of ovarian carcinoma treated with conventional doses of DDP received 4 and 2 courses, respectively, of high-dose DDP (40 mg/m2 for 5 days) in hypertonic saline. The median number of DDP courses was 6 (range 2-14), and the median cumulative dose was 350 mg/m2 (range, 200-1200). Serum creatinine and urea nitrogen were determined before initiating the treatment and again 13-16 days after each administration. The incidence of azotemia (creatinina levels that exceeded 1.5 mg/dl) was similar before (7.8%) and after (6.1%) DDP doses of 200 mg/m2. Azotemia appears to be related to the association of DDP with other potentially nephrotoxic antineoplastic drugs (methotrexate) more than to the dose per course of DDP. Of 59 patients followed for 2 months or more after discontinuing the DDP treatment, 3 (5.1%) presented creatinine values higher than 1.5 mg/dl. The data deny that the incidence of nephrotoxicity is higher in patients receiving higher cumulative doses of DDP and confirm that increases in serum creatinine levels may occur some time after discontinuation of the drug.

In the present pilot study, two courses of CF and CABO combination chemotherapy were administered in an alternating manner to 27 patients affected with recurrent and metastatic squamous cell carcinoma of the head and neck. Of the 23 evaluable patients, 5 complete responses and 5 partial responses were observed; the overall response rate was 43.5%. Two out of five complete responders are still free of disease 30 and 65 weeks after the administration of CR. The toxicity of this program was tolerable and was carried out on an out-patient basis in all cases. The median survival of the entire group was 41 weeks (range 8-98.+). We conclude that these alternating regimens are not likely to produce better responses than other conventional cisplatin-including combinations, but they seem to significantly increase the duration of the response.

Twenty-four patients receiving combination chemotherapy including cisplatin at a dosage of 50 mg/m2 were entered on this antiemetic randomized open cross-over study. High-dose dexamethasone (DXM) (regimen A) was compared with the combination of DXM and high doses of metoclopramide (MCP) (regimen B). Five patients (20%) treated with regimen A and 13 (54%) treated with regimen B suffered neither nausea nor vomiting (P less than 0.05). Regimen B was found to be significantly more effective than regimen A for all the parameters of evaluation considered. No severe side-effects were observed.

In two previous consecutive studies on antiemetic combination of metoclopramide and dexamethasone was found to be very active against nausea and vomiting induced by cisplatin (DDP; 50 mg/m2) alone or in combination with other cytotoxic emetogenic drugs. In the present study the activity of the same antiemetic combination has been followed in 18 patients during subsequent DDP courses. Twelve out of 18 patients (67%) had a complete control of the side effect after the first course of chemotherapy. No statistically significant differences were found as regards the intensity of nausea and vomiting, the patients' overall opinions and preference and the emesis duration. In conclusion this antiemetic combination can guarantee a high degree and long-term control of DDP-induced emesis at a dose of 50 mg/m2 given alone or in combination.

To establish the antiemetic activity of both dexamethasone (DXM) and metoclopramide (MCP) in patients receiving i.v. cyclophosphamide, methotrexate, and 5-fluorouracil (CMF), 25 women with stage II breast cancer were entered into this study. A randomized, double-blind, crossover design was employed to evaluate DXM (24 mg in 5 doses) versus MCP (1 mg/kg as a single dose) versus a combination of both drugs (as above) or placebo (PLC). The patients were requested to complete a questionnaire evaluating the antiemetic effect. All but one patient completed the planned antiemetic program during the first four CMF courses. As compared to PLC, both the DXM-MCP combination and DXM alone provided a higher complete antiemetic protection rate (p = 0.01 and p = 0.006, respectively). The DXM regimens were more effective than both PLC (p = 0.004 and p = 0.01) and MCP (p = 0.002 and p = 0.006) in reducing the prevalence of severe vomiting. As compared to MCP, the DXM regimens provided a better control of the nausea (p less than 0.04 and p less than 0.01) and reduced both the episodes and the duration of vomiting (p less than 0.02 and p less than 0.05). The DXM regimens were also associated with a better patient opinion than the PLC (p less than 0.002 and p less than 0.0002). No significant differences were found between MCP and PLC, nor between the DXM regimens. Except for two dystonic reactions, MCP-related toxicity was mild, whereas that induced by DXM was negligible in patients with no contraindications to corticosteroids. As employed in this study, DXM provided safe and effective antiemetic protection for patients receiving adjuvant i.v. CMF. Data available do not support the use of a short-course MCP, either alone or in combination with DXM. The search for better antiemetic treatments is mandatory, especially for patients receiving adjuvant chemotherapy. To date, we recommend the use of DXM as a standard regimen and as a control for further studies.

Between May 1981 and January 1986, 130 consecutive patients with advanced untreated head and neck squamous cell cancer (HNSCC) received neoadjuvant chemotherapy (NAC) with two or three courses of the CABO combination (methotrexate 40 mg/m2 intravenously (IV) on days 1 and 15; CDDP 50 mg/m2 IV on day 4; bleomycin 10 mg IV on days 1, 8, and 15; and vincristine 2 mg IV on days 1, 8, and 15 every 3 weeks) prior to surgery and/or radiotherapy. Of the 123 patients evaluable for response to chemotherapy, 19 (15.4%) had a complete remission and 59 (48%) a partial response, yielding a 63.4% overall response rate. Response rate was significantly correlated with the performance status (PS) (P = 0.001), the stage (P = 0.005), and the T class (P = 0.02); 107 patients completed subsequent local treatment (87 with radiotherapy and 20 with surgery +/- radiotherapy). The median survival of the 124 patients evaluable for survival was 14.7 months and the overall survival rate at 3 years was 24%. The median survival and the overall survival at 3 years for the surgical subgroup were 24.7 months and 38% and for the radiotherapy subgroup were 14.3 months and 22%. These results were compared with those obtained in a historical control group of 79 patients treated in our institute with short courses of chemotherapy regimens, which did not include cisplatin, followed by radiotherapy (29 patients) or local treatments alone (26 patients with radiotherapy and 24 patients with surgery +/- radiotherapy) between January 1976 and December 1980. Most of the patient characteristics were evenly distributed (age, sex, and primary sites) except that more advanced lesions were included in the NAC group (Stage IV: 85% versus 62%; T4: 65% versus 42%; N2-3: 48% versus 29%). The overall survival was significantly higher in patients receiving NAC than in the historical control group, comparing both the groups taken as a whole (P less than 0.05) and the surgery +/- radiotherapy (P less than 0.05) and the radiotherapy (P less than 0.02) subgroups. This experience suggests a positive role of NAC on survival. However, this improvement in outcome compared with a historical control group cannot be regarded as definitive evidence for benefit to patients. Randomized studies using active regimens are required to confirm these data.

e15038 Background: The addition of HT to RT significantly decreases recurrences and mortality of pts affected by LAPC eligible for exclusive RT. However, the value of adding RT to HT alone is still...

BackgroundHormone therapy plus radiotherapy significantly decreases recurrences and mortality of patients affected by locally advanced prostate cancer. In order to determine if difference exists according to the hormonal treatment duration, a literature-based meta-analysis was performed.MethodsRelative risks (RR) were derived through a random-effect model. Differences in primary (biochemical failure, BF; cancer-specific survival, CSS), and secondary outcomes (overall survival, OS; local or distant recurrence, LR/DM) were explored. Absolute differences (AD) and the number needed to treat (NNT) were calculated. Heterogeneity, a meta-regression for clinic-pathological predictors and a correlation test for surrogates were conducted.ResultsFive trials (3,424 patients) were included. Patient population ranged from 267 to 1,521 patients. The longer hormonal treatment significantly improves BF (with significant heterogeneity) with an absolute benefit of 10.1%, and a non significant trend in CSS. With regard to secondary end-points, the longer hormonal treatment significantly decrease both the LR and the DM with an absolute difference of 11.7% and 11.5%. Any significant difference in OS was observed. None of the three identified clinico-pathological predictors (median PSA, range 9.5-20.35, Gleason score 7-10, 27-55% patients/trial, and T3-4, 13-77% patients/trial), did significantly affect outcomes. At the meta-regression analysis a significant correlation between the overall treatment benefit in BF, CSS, OS, LR and DM, and the length of the treatment was found (p≤0.03).ConclusionsAlthough with significant heterogeneity (reflecting different patient' risk stratifications), a longer hormonal treatment duration significantly decreases biochemical, local and distant recurrences, with a trend for longer cancer specific survival.