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The aim of the study was to model acute hematologic toxicity (HT) and dose to pelvic osseous structures in anal cancer patients treated with definitive chemo-radiation (CT-RT). A total of 53 patients receiving CT-RT were analyzed. Pelvic bone marrow and corresponding subsites were contoured: ilium, lower pelvis and lumbosacral spine (LSBM). Dose-volume histograms points and mean doses were collected. Logistic regression was performed to correlate dosimetric parameters and ≥G3 HT as endpoint. Normal tissue complication probability (NTCP) was evaluated with the Lyman-Kutcher-Burman (LKB) model. Logistic regression showed a significant correlation between LSBM-mean dose and ≥G3 leukopenia ( β coefficient 0.122; p = 0.030; 95% CI 0.012-0.233). According to NTCP modeling, the predicted HT probability had the following parameters: TD: 37.5 Gy, γ : 1.15, m: 0.347. For node positive patients, TD: 35.2 Gy, γ : 2.27, m: 0.176 were found. Node positive patients had significantly higher PBM-V (Mean 81.1 vs. 86.7%; p = 0.04), -V (Mean 72.7 vs. 79.9%; p = 0.01) and V (Mean 50.2 vs. 57.3%; p = 0.03). Patients with a mean LSBM dose >32 Gy had a 1.81 (95% CI 0.81-4.0) relative risk to develop ≥G3 leukopenia. For node positive patients, those risks were 2.67 (95% CI 0.71-10). LKB modeling seems to suggest that LSBM-mean dose should be kept below 32 Gy to minimize ≥G3 HT in anal cancer patients treated with IMRT and concurrent chemotherapy. The contribution of LSBM dose in the development of HT above 25 Gy seems steeper in node positive patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate local control, survival and toxicity profile of a consecutive cohort of early-stage breast cancer (EBC) patients treated with adjuvant hypofractionated radiotherapy (HF) with no boost delivered to the lumpectomy cavity, after breast-conserving surgery (BCS). Between 2005 and 2015, a total of 493 women affected with EBC were treated with HF (46 Gy/20 fractions or 40.05 Gy/15 fractions) to the whole breast without boost to tumor bed, because of age and/or favorable tumor characteristics. The primary endpoint was 5-year actuarial local control (LC); secondary endpoints included survival, toxicity profile and cosmesis. Median follow-up was 57 months (range 6-124). Actuarial 5-year overall, cancer-specific, disease-free survival and LC were 96.3, 98.9, 97.8 and 98.6 %, respectively. On multivariate analysis, tumor stage (T1 vs. T2) and hormonal status (positive vs. negative estrogen receptors) were significantly correlated with LC. Only 2 % of patients experienced ≥G3 acute skin toxicity. Late toxicity was mild with only 1 case of G3 fibrosis. Most of the patients (95 %) had good-excellent cosmetic results. HF to the whole breast with no boost delivered to the tumor bed is a safe and effective option for a population of low-risk breast cancer patients after BCS, with excellent 5-year LC, mild toxicity profile and promising cosmetic outcome. A subgroup of patients with larger tumors and/or with no estrogen receptor expression may potentially benefit from treatment intensification with a boost dose to the lumpectomy cavity. [ABSTRACT FROM AUTHOR]

Stereotactic ablative radiotherapy (SABR) is a safe treatment approach for hepatocellular carcinoma (HCC) with comparable results to other local therapies. For lesions larger than 3 cm, no definitive standard treatment is present and several options are available. We retrospectively review local control (LC) and survival results of SABR in patients with HCC lesions >3 cm. Between 2012 and 2015, we treated 29 patients (39 lesions) having histological or radiological diagnosis of HCC and at least one lesion sized >3 cm. Patients were prescribed 36-48 Gy in 3-5 fractions (mainly 16 Gy × 3 fractions or 8 Gy × 5 fractions), in 3-5 consecutive days. A total of 15 lesions (52 %) had complete, while 10 (34 %) had partial remission; 3 (11 %) had a stable disease. Mean time for CR achievement was 5.8 months (range 1-17). One- and two-year actuarial LC was 100 %. Moreover, 1- and 2-year progression-free (PFS), cancer-specific and overall survival were 57.9 % [standard error (SE) 0.09; 95 % CI 36.9-74.2] and 41.2 % (SE 0.12; 95 % CI 17.7-63.5), 80.7 % (SE 0.08; 95 % CI 59.6-91.5) and 63.3 % (SE 0.11; 95 % CI 38.4-80.3), 71.7 % (SE 0.08; 95 % CI 51.2-84.7) and 56.2 % (SE 0.10; 95 % CI 33.8-73.6). On multivariate analysis, achieving a CR within the target lesion had a borderline significance with respect to PFS (HR 0.83; SE = 0.014; z −1.15; p = 0.095; 95 % CI 0.71-7.45). Time between HCC diagnosis and SABR delivery ( < vs >12 months) was significantly correlated with OS (HR 16.5; SE 21.5; z = 2.14; p = 0.032; 95 % CI 1.27-213.3) as CLIP score (score: 0-1 vs 2) (HR 5.6; SE 4.6; z = 2.10; p = 0.036; 95 % CI 1.11-27.8). A total of 6 major toxic events (G3-G4) were recorded (20 %). In 2 patients (6 %), a radiation-induced liver disease was seen. In conclusion, SABR provided LC and survival rates comparable to other local therapies for patients with HCC lesion sized >3 cm, with acceptable toxicity profile. [ABSTRACT FROM AUTHOR]

To test the hypothesis that irradiated volume of specific subregions of pelvic active bone marrow as detected by FDG-PET may be a predictor of decreased blood cells nadirs in anal cancer patients undergoing concurrent chemoradiation, we analyzed 44 patients submitted to IMRT and concurrent chemotherapy. Several bony structures were defined: pelvic and lumbar-sacral (LSBM), lower pelvis (LPBM) and iliac (IBM) bone marrow. Active BM was characterized employing FDG-PET and characterized in all subregions as the volume having standard uptake values (SUVs) higher than SUV. All other regions were defined as inactive BM. On dose-volume histograms, dosimetric parameters were taken. Endpoints included white blood cell count (WBC), absolute neutrophil count (ANC), hemoglobin (Hb) and platelet (Plt) nadirs. Generalized linear modeling was used to find correlations between dosimetric variables and blood cells nadirs. WBC nadir was significantly correlated with LSBM mean dose ( β = −1.852; 95 % CI −3.205/−0.500; p = 0.009), V ( β = −2.153; 95 % CI −4.263/−0.721; p = 0.002), V ( β = −2.081; 95 % CI −4.880/−0.112; p = 0.003), V ( β = −1.971; 95 % CI −4.748/−0.090; p = 0.023) and IBM V ( β = −0.073; 95 % CI −0.106/−0.023; p = 0.016). ANC nadir found to be significantly associated with LSBM V ( β = −1.878; 95 % CI −4.799/−0.643; p = 0.025), V ( β = −1.765; 95 % CI −4.050/−0.613; p = 0.030) and IBM V ( β = −0.039; 95 % CI −0.066/−0.010; p = 0.027). Borderline significance was found for correlation between Plt nadir and LSBM V ( β = −0.056; 95 % CI −2.748/−0.187; p = 0.060), V ( β = −0.059; 95 % CI −3.112/−0.150; p = 0.060) and IBM V ( β = −0.028; 95 % CI −0.074/−0.023; p = 0.056). No inactive BM subsites were found to be correlated with any blood cell nadir. FDG-PET is able to define active bone marrow within pelvic osseous structures. LSBM is the strongest predictor of decreased blood cells nadirs in anal cancer patients undergoing concurrent chemoradiation. [ABSTRACT FROM AUTHOR]

Purpose: Nasopharyngeal carcinoma represents a distinct entity as compared to other head and neck tumours. Radio-chemotherapy is the treatment of first choice in non-metastatic disease. Intensity-modulated radiation therapy (IMRT) allows the sparing of parotid glands, improving the toxicity profile. The aim of this study was to compare the results obtained with IMRT with those obtained with conventional 2D (2DRT) and 3D conformal radiation therapy (3DCRT) in terms of tumour control, survival, acute and late toxicity. Materials and methods: We reviewed the clinical records of 52 patients with histologically proven carcinoma of the nasopharynx (stage I-IVB according to the 2002 American Joint Committee on Cancer staging system) treated with curative intent between January 2003 and August 2011: 26 patients were treated with 2D or 3D technique (arm A) and 26 with IMRT technique (arm B) with simultaneous integrated boost. Fifty patients (96 %) received chemotherapy. Local control (LC), locoregional control (LRC), disease-free survival (DFS), overall survival (OS), acute and late toxicity were retrospectively evaluated. Results: After a median follow-up of 37.6 months (69 months in arm A and 23 months in arm B), 69 % of patients were alive and disease-free, 10 % were alive with disease and 21 % died of disease, with an OS of 81 % at 2 years and 79 % at 5 years, a LC rate of 88 % at 2 years and 78 % at 5 years, a LRC rate of 80 % at 2 years and 73 % at 5 years and a DFS of 74 % at 2 years and 65 % at 5 years, with no statistically significant differences between IMRT and 2DRT/3DCRT. In multivariate analysis, the TNM stage and the volume treated at high dose correlated with DFS. No factor was found to be related to OS. Chronic toxicity was not statistically different in the two study groups and in particular ≥G2 xerostomia rates were 67 and 41 % in arm A and B, respectively ( p = 0.10). Conclusions: The findings of this study confirm that IMRT associated with chemotherapy, even with moderately hypofractionated regimens, allows good disease control with better results in terms of late xerostomia, although without statistically significant differences compared to 2DRT and 3DCRT. The hypothesis of an impact of IMRT on survival has yet to be confirmed. [ABSTRACT FROM AUTHOR]

Purpose: To retrospectively evaluate the role of high-dose salvage radiotherapy (SRT) alone with regard to biochemical and clinical outcomes in patients with biochemical failure (BF) after radical prostatectomy (RP). Methods: Between January 2003 and August 2011, 168 hormone-naïve localized prostate cancer patients received SRT alone for post-RP BF in a single institution and were retrospectively analyzed. Multivariate analysis was performed to determine the independent prognostic impact of clinical factors on biochemical and clinical outcomes [biochemical relapse-free survival (bRFS), clinical relapse-free survival (cRFS), cancer-specific survival (CSS) and overall survival (OS)]. Results: Median follow-up was 54 months. Actuarial bRFS, cRFS, CSS and OS at 5 years were, respectively, 64, 86.2, 94.5 and 96.3 %. On multivariate analysis, nadir PSA (nPSA) after SRT was significantly associated with bRFS (HR 15, p = 0.001) and cRFS (HR 9, p = 0.001), while CSS was associated with RT dose (≥70 Gy; HR 1.9 p = 0.023), pre-RT PSA (<1.5 vs. ≥1.5 ng/mL; HR 1.3, p = 0.008) and age (>75 years; HR 1.2, p = 0.05). OS was significantly correlated with pre-SRT PSA (linear correlation; HR 1.1, p = 0.023) and age (<75 vs. ≥ 75 years; HR 1.1, p = 0.026). Conclusions: Effective biochemical and clinical control rates may be safely achieved administering SRT with high doses (≥72 Gy) and using conformal techniques, especially in older patients presenting with lower pre-SRT PSA values. A lower nPSA after SRT predicts for better 5 years bRFS and cRFS rates. [ABSTRACT FROM AUTHOR]

Purpose: A proportion of patients with localized prostate cancer is still treated with primary androgen deprivation therapy (PADT) alone. Some of these patients may develop a PSA rising despite castration. The purpose of this study was to retrospectively evaluate the potential benefit of external beam radiotherapy (EBRT) in this cohort. Methods: Forty-two patients presenting a non-metastatic castration-resistant prostate cancer after PADT were referred to our institution and underwent RT between June 2003 and July 2011. Biochemical failure (BF) after EBRT was defined according to Phoenix criteria (nadir + 2 ng/mL 'at call'). Median RT dose was 78 Gy. Results: Median duration of PADT was 54 months (range 10.2-181 months). Median follow-up after EBRT was 53 months. Twenty-one patients had BF after EBRT (median time 27.4 months): 13 presented with loco-regional and/or distant metastases, while in 8 patients, a PSA rise only was observed. Ten patients died of prostate cancer (and no patient died of causes other than prostate cancer). Five-year biochemical disease-free survival (bDFS), distant metastases-free survival (DMFS) and cancer-specific survival (CSS) were, respectively, 39.4, 60 and 65 %. On multivariate analysis, GS, nadir PSA (nPSA) and a pre-EBRT PSA ≤5 ng/mL significantly affected bDFS, while Gleason score (GS) and T stage significantly affected distant metastases onset. No factors affected CSS at multivariate analysis. Conclusions: EBRT may be a suitable therapeutic option, able to provide an excellent loco-regional control and to obtain a systemic disease control in up to 60 % of patients at 5 years, especially in patients presenting with lower Gleason score and T stage at diagnosis and lower pre-RT PSA and nPSA post-RT. [ABSTRACT FROM AUTHOR]

Purpose: Purpose of this study is to analyze outcomes and pre-treatment prognostic factors in high-risk prostate cancer patients with initial PSA ≥20 ng/mL, treated with high-dose external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT) in a single institution. Methods: Between March 2003 and December 2011, 155 consecutive high-risk prostate cancer patients (a) presenting with pre-treatment PSA level ≥20 ng/mL, (b) treated with definitive EBRT, and (c) with a minimum follow-up of 24 months were included in this retrospective analysis. Phoenix definition was used to define biochemical control. Primary endpoints were as follows: biochemical disease-free survival (bDFS), distant metastasis-free survival (DMFS), cancer-specific survival (CSS) and overall survival (OS). Multivariate analysis was performed to determine the independent prognostic impact of pre-treatment clinical factors [T stage, PSA, and Gleason score (GS)]. Results: At a median follow-up time of 62 months, actuarial bDFS, DMFS, CSS, and OS at 5 years were 64.8, 85.2, 95.8, and 94.4 %, respectively. On multivariate analysis, only GS was significantly associated with three clinical endpoints (bDFS: HR 1.6; p = 0.022, CSS: HR 4.27, p = 0.044, OS: HR 2.6; p = 0.038). Pre-treatment zenith PSA was associated only with bDFS (HR 1.87; p = 0.027). Conclusions: Patients with 'high' PSA levels (≥20 ng/mL) showed favorable clinical outcomes, supporting the role of local radiotherapy as primary therapy in combination with long-term ADT in patients with high PSA levels at diagnosis. A GS of 8-10 is the strongest predictor of outcome. [ABSTRACT FROM AUTHOR]

Purpose: To investigate a potential correlation between the achievement of a cut-off of nadir PSA (nPSA) after brachytherapy (BRT) with biochemical Disease-Free Survival (bDFS) and to define the rate of post-BRT PSA bounces. Methods: Retrospective analysis was carried out in 105 consecutive patients affected with early-stage prostate adenocarcinoma who underwent I BRT. Only patients with a minimum follow-up ≥24 months were included. Biochemical DFS was chosen as primary endpoint. Results: At a median follow-up of 51.2 months, 3- and 5-year bDFS were 96.8 and 91.2 %, respectively. Median time to biochemical failure (BF) was 54 months. By Kaplan-Meier analysis, patients achieving nPSA ≤ 0.35 ng/mL had significantly higher bDFS (3- and 5-year bDFS: 100 and 98.5 % vs 83.3 and 66.7 %, respectively; p = 0.001). Bounce PSA occurred in 28.6 % of patients, at a median time of 21.5 months. No BFs were observed in the bounce group. Achieving a nPSA ≤ 0.35 ng/mL was the only factor independently associated with long-term bDFS on both univariate ( p = 0.000) and multivariate analysis (HR 3.82; p = 0.003). Conclusions: Patients attaining a nPSA ≤ 0.35 ng/mL are significantly more likely to experience long-term freedom-from-biochemical failure. Bounce PSA occurs in approximately 30 % of patients. Time to onset of PSA increase seems the most reliable feature to distinguish bounce from failure. Tailored follow-up strategies are needed for patients at higher risk of recurrence, and caution is advised in interpreting an early increase in PSA levels in the first 24-30 months after BRT. [ABSTRACT FROM AUTHOR]

The aim of the study is to evaluate feasibility, safety, toxicity profile, and dosimetric results of volumetric modulated arc therapy (VMAT) to deliver definitive or pre-operative radiation in locally advanced esophageal cancer patients. A total of 68 patients were treated with VMAT between March 2014 and March 2018 (44% vs 56% for definitive and neoadjuvant settings, respectively). Dose prescription differed depending on the clinical scenario (54-60 Gy in 30 fractions for definitive treatments; 41.4/45 Gy in 23-25 fractions in the pre-operative setting). Most of the patients were given concurrent chemotherapy. Two coplanar and one non-coplanar arcs were employed for VMAT delivery. Treatment was generally well tolerated. Acute toxicity was generally mild. In patients treated with definitive intent, ≥ G3 toxicities were observed for esophagitis (30%), anorexia (26.7%), fatigue (26.7%), nausea (6.7%), and vomiting (3.3%). In patients treated within a neoadjuvant approach, ≥ G3 anorexia (21%), esophagitis (15.8%), fatigue (13.3%), nausea (5.3%), and vomiting (2.6%) were observed. Dosimetric results were consistent in term of both target coverage and normal tissue sparing. In conclusion, VMAT proved to be a feasible, safe, and effective strategy to deliver definitive or pre-operative radiation in locally advanced esophageal cancer patients. [ABSTRACT FROM AUTHOR]