Patterns of prescription and adherence to European Association of Urology guidelines on androgen deprivation therapy in prostate cancer: an Italian multicentre cross-sectional analysis from the Choosing Treatment for Prostate Cancer (CHOICE) study.

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.

Can automation in radiotherapy reduce costs?

BACKGROUND: Computerized automation is likely to play an increasingly important role in radiotherapy. The objective of this study was to report the results of the first part of a program to implement a model for economical evaluation based on micro-costing method. To test the efficacy of the model, the financial impact of the introduction of an automation tool was estimated. A single- and multi-center validation of the model by a prospective collection of data is planned as the second step of the program. MATERIAL AND METHODS: The model was implemented by using an interactive spreadsheet (Microsoft Excel, 2010). The variables to be included were identified across three components: productivity, staff, and equipment. To calculate staff requirements, the workflow of Gemelli ART center was mapped out and relevant workload measures were defined. Profit and loss, productivity and staffing were identified as significant outcomes. Results were presented in terms of earnings before interest and taxes (EBIT). Three different scenarios were hypothesized: baseline situation at Gemelli ART (scenario 1); reduction by 2 minutes of the average duration of treatment fractions (scenario 2); and increased incidence of advanced treatment modalities (scenario 3). By using the model, predicted EBIT values for each scenario were calculated across a period of eight years (from 2015 to 2022). RESULTS: For both scenarios 2 and 3 costs are expected to slightly increase as compared to baseline situation that is particularly due to a little increase in clinical personnel costs. However, in both cases EBIT values are more favorable than baseline situation (EBIT values: scenario 1, 27%, scenario 2, 30%, scenario 3, 28% of revenues). CONCLUSION: A model based on a micro-costing method was able to estimate the financial consequences of the introduction of an automation tool in our radiotherapy department. A prospective collection of data at Gemelli ART and in a consortium of centers is currently under way to prospectively validate the model.

Adaptive optimization by 6 DOF robotic couch in prostate volumetric IMRT treatment: rototranslational shift and dosimetric consequences.

The purpose of this study was to investigate the magnitude and dosimetric relevance of translational and rotational shifts on IGRT prostate volumetric-modulated arc therapy (VMAT) using Protura six degrees of freedom (DOF) Robotic Patient Positioning System. Patients with cT3aN0M0 prostate cancer, treated with VMAT simultaneous integrated boost (VMAT-SIB), were enrolled. PTV2 was obtained adding 0.7 cm margin to seminal vesicles base (CTV2), while PTV1 adding to prostate (CTV1) 0.7 cm margin in all directions, except 1.2 cm, as caudal margin. A daily CBCT was acquired before dose delivery. The translational and rotational displacements were corrected through Protura Robotic Couch, collected and applied to the simulation CT to obtain a translated CT (tCT) and a rototranslated CT (rtCT) on which we recalculated the initial treatment plan (TP). We analyzed the correlation between dosimetric coverage, organs at risk (OAR) sparing, and translational or rotational displacements. The dosimetric impact of a rototranslational correction was calculated. From October 2012 to September 2013, a total of 263 CBCT scans from 12 patients were collected. Translational shifts were < 5 mm in 81% of patients and the rotational shifts were < 2° in 93% of patient scans. The dosimetric analysis was performed on 172 CBCT scans and calculating 344 VMAT-TP. Two significant linear correlations were observed between yaw and the V20 femoral heads and between pitch rotation and V50 rectum (p < 0.001); rototranslational correction seems to impact more on PTV2 than on PTV1, especially when margins are reduced. Rotational errors are of dosimetric significance in sparing OAR and in target coverage. This is relevant for femoral heads and rectum because of major distance from isocenter, and for seminal vesicles because of irregular shape. No correlation was observed between translational and rotational errors. A study considering the intrafractional error and the deformable registration is ongoing.

Impact of radiotherapy on pain relief and recalcification in plasma cell neoplasms: long-term experience.

PURPOSE: To evaluate the impact of radiotherapy on pain relief and on recalcification in patients with osteolytic lesions due to plasma cell neoplasm. PATIENTS AND METHODS: Pain relief was evaluated according to a 0-10 verbal numerical rating scale (NRS) and recalcification was measured using radiological imaging. RESULTS: From 1996-2007, 52 patients were treated (Table 1). Median total dose was 38 Gy (range, 16-50 Gy). Pain be-fore radiotherapy was reported by 45 of 52 (86.5%) patients (Table 2) as being severe (8 ≤ NRS ≤ 10) in 5 (11%), moderate (5 ≤ NRS ≤ 7) in 27 (60%), and mild in 13 (29%). Pain relief was achieved in 41 of 45 patients (91%): complete relief was obtained in 21 (51.2%) and partial relief in 20 patients (48.8%); patients with severe pain experienced resolution and none present-ed an increase of pain. Drugs reduction/suspension was achieved in 7 of the 21 patients with complete response. Of 42 patients evaluable for recalcification (Table 3), 21 (50%) presented a radiological response, which was identified as complete in 16 (38%). CONCLUSION: Our data confirm the effectiveness of radiotherapy for pain relief, including a reduction in drug intake, and on recalcification, thus, supporting its use in a multidisciplinary approach.

Whole-brain radiotherapy combined with surgery or stereotactic radiotherapy in patients with brain oligometastases: long-term analysis.

OBJECTIVE: To verify whether the treatment of brain oligometastases with whole-brain radiotherapy (WBRT) plus stereotactic radiotherapy (SRT) or surgical resection results in different outcomes. METHODS: Files of patients affected by brain metastases submitted to surgical resection followed by WBRT (group A) or WBRT + SRT (group B) were retrospectively selected for this study. The two treatment groups were matched for the following potential prognostic factors: WBRT schedule, age, gender, performance status, tumor type, number of brain metastases, extra-cerebral metastases, and recursive partitioning analysis class (RPA). The outcomes of patients in both groups were evaluated in terms of toxicity, local control, and overall survival. RESULTS: Total of 97 patients were selected (56 male; 42 female) who were respectively submitted to surgical resection followed by WBRT (group A, n = 50 patients) or WBRT + SRT (Group B, n = 47 patients). Median follow-up was 95 months (range, 8-171 months). The 1-year local control rates were 46.0% and 69.0% respectively. No significant difference in local tumor control was observed between group A and B (p = 0.10). Median overall survival was 15 and 19 months in group A and B, respectively. One-year survival was 56.0% and 62%, respectively. No difference was observed in the two groups (p = 0.40). CONCLUSION: Surgery remains the main therapeutic approach in symptomatic patients; nevertheless, our data support the use of WBRT plus SRT in one or two brain metastases smaller than 3 cm.

Predicting Radiotherapy Impact on Late Bladder Toxicity in Prostate Cancer Patients: An Observational Study.

BACKGROUND AND PURPOSE: The aim of our study was to elaborate a suitable model on bladder late toxicity in prostate cancer (PC) patients treated by radiotherapy with volumetric technique. MATERIALS AND METHODS: PC patients treated between September 2010 and April 2017 were included in the analysis. An observational study was performed collecting late toxicity data of any grade, according to RTOG and CTCAE 4.03 scales, cumulative dose volumes histograms were exported for each patient. Vdose, the value of dose to a specific volume of organ at risk (OAR), impact was analyzed through the Mann-Whitney rank-sum test. Logistic regression was used as the final model. The model performance was estimated by taking 1000 samples with replacement from the original dataset and calculating the AUC average. In addition, the calibration plot (Hosmer-Lemeshow goodness-of-fit test) was used to evaluate the performance of internal validation. RStudio Software version 3.3.1 and an in house developed software package "Moddicom" were used. RESULTS: Data from 175 patients were collected. The median follow-up was 39 months (min-max 3.00-113.00). We performed Mann-Whitney rank-sum test with continuity correction in the subset of patients with late bladder toxicity grade ≥ 2: a statistically significant p-value with a Vdose of 51.43 Gy by applying a logistic regression model (coefficient 4.3, p value 0.025) for the prediction of the development of late G ≥ 2 GU toxicity was observed. The performance for the model's internal validation was evaluated, with an AUC equal to 0.626. Accuracy was estimated through the elaboration of a calibration plot. CONCLUSIONS: Our preliminary results could help to optimize treatment planning procedures and customize treatments.

Single-arm phase II study of conformal radiation therapy and temozolomide plus fractionated stereotactic conformal boost in high-grade gliomas: final report.

PURPOSE: To assess survival, local control and toxicity using fractionated stereotactic conformal radiotherapy (FSCRT) boost and temozolomide in high-grade gliomas (HGGs). PATIENTS AND METHODS: Patients affected by HGG, with a CTV(1)(clinical target volume, representing tumor bed ± residual tumor + a margin of 5 mm) ≤ 8 cm were enrolled into this phase II study. Radiotherapy (RT, total dose 6,940 cGy) was administered using a combination of two different techniques: three-dimensional conformal radiotherapy (3D-CRT, to achieve a dose of 5,040 or 5,940 cGy) and FSCRT boost (19 or 10 Gy) tailored by CTV(1)diameter (≤ 6 cm and > 6 cm, respectively). Temozolomide (75 mg/m(2)) was administered during the first 2 or 4 weeks of RT. After the end of RT, temozolomide (150-200 mg/m(2)) was administered for at least six cycles. The sample size of 41 patients was assessed by the single proportion-powered analysis. RESULTS: 41 patients (36 with glioblastoma multiforme [GBM] and five with anaplastic astrocytoma [AA]) were enrolled; RTOG neurological toxicities G1-2 and G3 were 12% and 3%, respectively. Two cases of radionecrosis were observed. At a median follow-up of 44 months (range 6-56 months), global and GBM median overall survival (OS) were 30 and 28 months. The 2-year survival rate was significantly better compared to the standard treatment (63% vs. 26.5%; p < 0.00001). Median progression-free survival (PFS) was 11 months, in GBM patients 10 months. CONCLUSION: FSCRT boost plus temozolomide is well tolerated and seems to increase survival compared to the standard treatment in patients with HGG.

Radiotherapy and concomitant temozolomide during the first and last weeks in high grade gliomas: long-term analysis of a phase II study.

We tested the efficacy and safety of temozolomide (TMZ) when given concomitantly to radiotherapy only in the first and last weeks of treatment to patients affected by high grade gliomas. Conformal radiotherapy (CTV1: tumor bed + residual tumor if present + 1.5 cm, 5,940 cGy, 180 cGy/day; CTV2: oedema, 3,960 cGy, 180 cGy/day) was associated with TMZ, 75 mg/m(2) x 5 days, the first and last weeks of radiotherapy. Adjuvant chemotherapy with TMZ (150 mg/mq daily x 5 days, q28 on the first cycle, 200 mg/mq daily x 5 days, q28 for the following cycles) was given, after chemoradiation, until disease progression or up to 6 cycles. From October 2000 to December 2003, 29 patients (25 GBL, 86.2%; 4 AA, 13.8%) were enrolled in this study. Twenty-two patients (75.8%) received a median 6 cycles of adjuvant chemotherapy with TMZ (range 1-20). Hematological toxicity was absent during concomitant chemoradiation and mild in adjuvant therapy, while neurological toxicity (seizures) was observed only in one case. At a median follow-up of 66 months (range 3-96), median progression-free survival (PFS) was 8 months, with a 1- and 2-year PFS of 46.7 and 28.7%, respectively; median overall survival (OS) time was 21 months, with a 1- and 2-year OS of 69.2 and 42.3%, respectively. In our experience, TMZ proved to be effective even when given only during the first and the last week of radiotherapy, with lower hematological toxicity.

Simultaneous Integrated Radiotherapy Boost to the Dominant Intraprostatic Lesion: Final Results of a Phase I/II Trial.

BACKGROUND/AIM: Late toxicity and long-term outcomes of a phase I-II trial on patients with prostate cancer treated with an integrated boost to the dominant intraprostatic lesion (DIL) are reported. PATIENTS AND METHODS: Patients were treated using intensity-modulated radiotherapy, with a simultaneous integrated boost to the DIL, defined on staging magnetic resonance imaging, delivering 72 Gy in 1.8 Gy/fraction to prostate/seminal vesicles and 80 Gy in 2 Gy/fraction to the DIL. The primary endpoint was acute toxicity and secondary endpoints were late toxicity and biochemical disease-free survival. RESULTS: Forty-four patients were enrolled. The median follow-up was 120 (range=25-150) months. Five-year rates of grade 3 late gastrointestinal and genitourinary toxicity were 2.3% and 4.5%, respectively; only one grade 4 late genitourinary toxicity was recorded. Five-year biochemical relapse-free and overall survival rates were 95.3% and 95.5%, respectively. CONCLUSION: The treatment was well tolerated and achieved excellent results in terms of outcome in patients with low-intermediate Gleason's score and low risk of nodal metastasis.

BIT-ART: Multicentric Comparison of HDR-brachytherapy, Intensity-modulated Radiotherapy and Tomotherapy for Advanced Radiotherapy in Prostate Cancer.

BACKGROUND/AIM: The aim of the study was to evaluate acute and late genitourinary (GU) and gastrointestinal (GI) toxicity in patients with high- or intermediate-risk prostate cancer. PATIENTS AND METHODS: We evaluated data of patients from three Radiation Oncology Departments (Rome, Lübeck and Perugia). Patients treated in Rome underwent exclusive intensity-modulated-radiotherapy (IMRT) or IMRT plus high-dose-rate interventional radiotherapy (HDR-IRT). IMRT plus two fractions HDR-IRT was performed in Lübeck, while in Perugia Helical Tomotherapy was performed. The Common Toxicity Criteria for Adverse Event (Version 4.03) scale was used to describe acute and late toxicity. RESULTS: At a median follow-up of 28 months, all 51 patients were alive and disease-free. Patients treated by HDR-IRT plus VMAT showed only G1-2 genitourinary- gastrointestinal (GU-GI) acute and late toxicity. Univariate analysis showed a lower risk of acute GU toxicity (p=0.048) in IMRT+HDR-IRT. CONCLUSION: Low grade and less acute GU toxicity was observed in patients undergoing HDR-IRT boost.

Oncotype DX Predictive Nomogram for Recurrence Score Output: The Novel System ADAPTED01 Based on Quantitative Immunochemistry Analysis.

PURPOSE: Oncotype DX (ODX) predicts breast cancer recurrence risk, guiding the choice of adjuvant treatment. In many countries, access to the test is not always available. We used correlation between phenotypical tumor characteristics, quantitative classical immunohistochemistry (IHC), and recurrence score (RS) assessed by ODX to develop a decision supporting system for clinical use. PATIENTS AND METHODS: Breast cancer patients who underwent ODX testing between 2014 and 2018 were retrospectively included in the study. The data selected for analysis were age, menopausal status, and pathologic and IHC features. IHC was performed with standardized quantitative methods. The data set was split into two subsets: 70% for the training set and 30% for the internal validation set. Statistically significant features were included in logistic models to predict RS ≤ 25 or ≤ 20. Another set was used for external validation to test reproducibility of prediction models. RESULTS: The internal set included 407 patients. Mean (range) age was 53.7 (31-80) years, and 222 patients (54.55%) were > 50 years old. ODX results showed 67 patients (16.6%) had RS between 0 and 10, 272 patients between 11 and 25 (66.8%), and 68 patients > 26 (16.6%). Logistic regression analysis showed that RS score (for threshold ≤ 25) was significantly associated with estrogen receptor (P = .004), progesterone receptor (P < .0001), and Ki-67 (P < .0001). Generalized linear regression resulted in a model that had an area under the receiver operating characteristic curve (AUC) of 92.2 (sensitivity 84.2%, specificity 80.1%) and that was well calibrated. The external validation set (183 patients) analysis confirmed the model performance, with an AUC of 82.3 and a positive predictive value of 91%. A nomogram was generated for further prospective evaluation to predict RS ≤ 25. CONCLUSION: RS was related to quantitative IHC in patients with RS ≤ 25, with a good performance of the statistical model in both internal and external validation. A nomogram for enhancing clinical approach in a cost-effective manner was developed. Prospective studies must test this application in clinical practice.

Effectiveness of abiraterone acetate plus prednisone in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer in a large prospective real-world cohort: the ABItude study.

BACKGROUND: Real-world data on chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone plus prednisone are limited, largely deriving from small retrospective studies. METHODS: ABitude is an Italian, observational, prospective, multicenter study of mCRPC patients receiving abiraterone plus prednisone in clinical practice. Chemotherapy-naïve mCRPC patients were consecutively enrolled at abiraterone start (February 2016 to June 2017) and are being followed for 3 years, with evaluation approximately every 6 months. Several clinical and patients reported outcomes were examined. RESULTS: In this second interim analysis, among 481 enrolled patients, 453 were evaluable for analyses. At baseline, the median age was 77 years and ~69% of patients had comorbidities (mainly cardiovascular diseases). Metastases were located mainly at bones and lymph nodes; 8.4% of patients had visceral metastases. During a median follow-up of 18 months, 1- and 2-year probability of radiographic progression-free survival were 73.9% and 56.2%, respectively; the corresponding rates for overall survival were 87.3% and 70.4%. In multivariable analyses, the number of bone metastases significantly affected radiographic progression-free survival and overall survival. During abiraterone plus prednisone treatment, 65% of patients had a ⩾50% prostate-specific antigen decline, and quality of life remained appreciably high. Among symptomatic patients according to the Brief Pain Inventory) (32%), scores significantly declined after 6 months of treatment. Overall, eight patients (1.7%) had serious adverse reactions to abiraterone. CONCLUSIONS: Abiraterone plus prednisone is effective and safe for chemotherapy-naïve mCRPC patients in clinical practice.

Radiotherapy Plus GnRH Analogue Versus High Dose Bicalutamide: A Case Control Study.

BACKGROUND/AIM: Radiotherapy (RT) with adjuvant hormone therapy (HT) improves prognosis in prostate cancer (PC) patients. Gonadotrophin-releasing hormone agonist (GnRHa) with luteinizing hormone-releasing hormone (LH-RH) analogues is the standard HT. High-dose antiandrogen therapy also improves survival in patients with locally advanced PC. The aim of this study was to compare the results of patients treated with RT plus GnRHa and patients treated with RT plus bicalutamide. PATIENTS AND METHODS: Our institutional PC database was used to identify patients treated with definitive or postoperative RT +/- HT which were included in this study. RESULTS: Three hundred and eighteen patients were retrospectively reviewed (median follow-up=56 months). Five-year biochemical relapse-free survival was 85.5% and 88.3% in patients treated with GnRHa and bicalutamide, respectively (p=0.712). CONCLUSION: Bicalutamide may be offered as an adjuvant treatment to RT in patients who refuse GnRHa because of related side effects. Furthermore, our study justifies randomized trials comparing RT plus GnRHa and RT plus bicalutamide.

MR-guided radiotherapy in rectal cancer: First clinical experience of an innovative technology.

•This study represents one of the first reports of online MRgRT.•Integrated Low-field MR provides better anatomical visualization than CBCT or MVCT.•Better visualization of the target can help to reduce the margins from CTV to PTV.•MRgRT appears a feasible option in rectal cancer treatment offering potential benefits.•MRgRT represents a promising technology for rectal cancer management.

Shoulder girdle impairment in breast cancer survivors: the role of range of motion as predictive factor for dose distribution and clinical outcome.

BACKGROUND: Pain and functional impairment of the ipsilateral shoulder girdle in patients who underwent surgery and radiotherapy for breast cancer (BC) is a late complication reported in the literature. We analyze a correlation with dosimetric parameters and propose an algorithm for sparing strategies. METHODS: A total of 111 patients treated for BC were included in this observational analysis during follow-up protocol visits. Exclusion criteria were the presence of moderate or severe arthrosis history and/or rheumatologic diseases. All the patients had complete physical and multidimensional examinations during joint (physiatrist and radiotherapy oncology) follow-up visits. A scapula-humeral articulation (SHA) standardized contouring was performed retrospectively on Eclipse® treatment plans. A possible correlation between patients' characteristics, radiotherapy, and dosimetry analysis and functional impairment was investigated at statistical analysis. Results of analysis were summarized into a proposal of algorithm for sparing SHA. RESULTS: A total of 111 patients were selected during follow-up visits. Mean age of patients was 60 years (range 41-85 years). A total of 103 patients (93%) underwent conservative surgery, with 110 patients (99%) undergoing axilla surgery as well. Fifty-two patients (46.8%) presented a reduction of range of motion (ROM) abduction on the treated side at the observational analysis. Mean ROM abduction reduction was 13°06' (range 0°-100°). Disability of the Arm, Shoulder and Hand questionnaire (DASH) score results were excellent in 79 patients (71.2%), discrete in 15 patients (13.5%), good in 15 patients (13.5%), and sufficient in 2 patients (1.8%). Median EQD2 Dmax at SHA was 18 Gy (range 0.22-51.9 Gy) and median EQD2 mean dose at SHA was 2 Gy (range 0.04-24.32 Gy). Univariate analysis showed a linear correlation between DASH score and ROM of abduction of treated side (ρ=-0.7), ROM of abduction and ROM of flexion in ipsilateral arm (ρ=0.8), or ROM of abduction and ROM of flexion in contralateral arm (ρ=0.8). A statistically significant difference in ROM abduction between the 2 arms was found at χ2 test (P<0.05 at χ2 confidence interval = 95%). Cox linear regression analysis showed ROM abduction on treated arm as a predictive factor of DASH score (P<0.0001). Age (P<0.05), DASH score (P=0.006), and ROM abduction on treated arm (P=0.005) were found as independent predictive factors of mean dose at multivariate analysis. A mean dose higher than 7 Gy and ROM abduction reduction more than 30° were related to DASH score level reduction. CONCLUSIONS: This hypothesis-generating study introduces an algorithm to be validated for management of sparing SHA and improving quality of survivorship. ROM evaluation after surgery, early physiotherapy, standard contouring, and planning adaptation represent possible indications to preserve shoulder impairment. Further prospective studies are needed to discriminate impairment of surgery and radiotherapy in order to personalized therapeutic plan programs.

Intraoperative radiation therapy in resected pancreatic carcinoma: long-term analysis.

PURPOSE: The combination of external radiotherapy (RT) plus intraoperative radiotherapy (IORT) in patients with pancreatic cancer is still debated. This study presents long-term results (minimum follow-up, 102 months) for 26 patients undergoing integrated adjuvant RT (external RT+IORT). METHODS AND MATERIALS: From 1990 to 1995, a total of 17 patients with pancreatic cancer underwent IORT (10 Gy) and postoperative external RT (50.4 Gy). Preoperative "flash" RT was included for the last 9 patients. The liver and pancreatic head received 5 Gy (two 2.5-Gy fractions) the day before surgery. In the subsequent period (1996-1998), 9 patients underwent preoperative concomitant chemoradiation (39.6 Gy) with 5-fluorouracil, IORT (10 Gy), and adjuvant chemotherapy. RESULTS: Preoperative chemoradiation was completed in all patients, whereas postoperative therapy was completed in 13 of 17 patients. All 26 patients underwent pancreatectomy (25 R0 and one R1 resections). One patient died of postoperative complications (3.8%) not related to IORT. The 9 patients undergoing concomitant chemoradiation were candidates for adjuvant chemotherapy; however, only 4 of 9 underwent adjuvant chemotherapy. At last follow-up, 4 patients (15.4%) were alive and disease free. Disease recurrence was documented in 20 patients (76.9%). Sixteen patients (61.5%) showed distant metastasis, and 5 patients (19.2%) showed local recurrence. The incidence of local recurrence in R0 patients was 4 of 25 (16.0%). The overall 5-year survival rate was 15.4%. There was significant correlation with overall survival of tumor diameter (p=0.019). CONCLUSIONS: The incidence of local recurrence in this long follow-up series (19.2%) was definitely less than that reported in other studies of adjuvant RT (approximately 50%), suggesting a positive impact on local control of integrated adjuvant RT (IORT+external RT).

Novel prognostic groups in thymic epithelial tumors: assessment of risk and therapeutic strategy selection.

PURPOSE: To assess the role of multimodality treatment on patients with thymic epithelial tumors (TETs) (i.e., thymomas and thymic squamous cell carcinoma) and to define the prognostic classes according to the Masaoka and World Health Organization histologic classification systems. METHODS AND MATERIALS: Primary surgery was the mainstay of therapy. Extended thymectomy was performed in all cases. The cases were primarily staged according to the Masaoka system. Adjuvant radiotherapy was given to patients diagnosed with Masaoka Stage II, III, and IVA TET. Adjuvant chemotherapy was administered in selected cases. RESULTS: We reviewed the records of 120 patients with TETs, with a mean follow-up of 13.8 years. Of the 120 patients, 98 (81.6%) received adjuvant radiotherapy. Of these 98 patients, Grade 1-2 pulmonary or esophageal toxicity was acute in 12 (12.2%) and late in 8 (8.2%). The median overall survival was 21.6 years. Of the 120 patients, 106 were rediagnosed and reclassified according to the World Health Organization system, and the survival rate was correlated with it. Three different prognostic classes were defined: favorable, Masaoka Stage I and histologic grade A, AB, B1, B2 or Masaoka Stage II and histologic grade A, AB, B1; unfavorable, Stage IV disease or histologic grade C or Stage III and histologic grade B3; intermediate, all other combinations. The 10- and 20-year survival rate was 95% and 81% for the favorable group, 90% and 65% for the intermediate group, and 50% and 0% for the unfavorable group, respectively. Local recurrence, distant recurrence, and tumor-related deaths were also evaluated. CONCLUSION: The analysis of our experience singled out three novel prognostic classes and the assessment of risk identified treatment selection criteria.

Tailored postoperative treatment of prostate cancer: final results of a phase I/II trial.

BACKGROUD: The European Organization for Research and Treatment of Cancer (EORTC) trial 22,911 reported 74% 5-year biochemical disease-free survival (bDFS) in patients with prostate carcinoma treated with radical prostatectomy (RP) followed by postoperative radiotherapy (RT). This study aimed to improve these outcomes by using a combined-intensified-modulated-adjuvant treatment, including RT and hormone therapy (HT) after RP. MATERIALS AND METHODS: This phase I/II trial treatment was designed to improve 5-year bDFS from ~ 75 to 90%. Patients were consecutively enrolled using the following inclusion criteria: age < 80 years, histological diagnosis of prostate adenocarcinoma without known metastases, stage pT2-4N0-1, and Eastern Cooperative Oncology Group performance status of 0-2. All patients had at least one of these pathologic features: capsular perforation, positive surgical margins, seminal vesicle invasion, and pelvic lymph nodes involvement. A minimum dose of 64.8 Gy to the tumor bed was delivered in all patients. Depending on tumor characteristics at diagnosis, patients received a higher dose (70.2 Gy; 85.4%) and/or prophylactic pelvic lymph nodes irradiation (57.7%) and/or HT (69.1%). Biochemical relapse was defined as two consecutive rising prostate-specific antigen (PSA) values > 0.2 ng/ml. RESULTS: A total of 123 patients were enrolled in the study and completed the scheduled treatment. Median preoperative and postoperative PSA were: 8.8 and 0.06 ng/mL, respectively. The percentages of patients with pathologically involved nodes and positive resection margins were: 14.6% and 58.5%, respectively. With a median follow-up of 67 months (range: 37-120 months), the actuarial 5-year bDFS, local control, metastasis-free survival, and overall survival (OS) were: 92.9%, 98.7%, 96.1%, and 95.1%, respectively. CONCLUSION: A higher 5-year bDFS (92.9%) was recorded compared to studies based on standard adjuvant RT, even though patients with nodal disease and detectable postoperative PSA were enrolled. Clinical end points, as long-term disease-free survival and OS, will require further assessments. (ClinicalTrials.gov: NCT03169933).

Preoperative chemoradiation and intra-operative radiotherapy for pancreatic carcinoma.

AIMS AND BACKGROUND: In recent years, preoperative chemoradiation has received growing interest for the treatment of locally advanced pancreatic cancer. In an attempt to improve resectability and disease control, we used preoperative radiation therapy and concomitant 5-fluorouracil in a combined modality therapy protocol. The aim of the study was to evaluate definitive results in terms of toxicity, response and clinical outcome. MATERIAL AND METHODS: Twenty-eight patients with unresectable (cT4, 19 patients) or resectable (cT3, 9 patients) nonmetastatic pancreatic tumors received radiotherapy (39.6 Gy) plus 5-fluorouracil (continuous infusion, days 1-4 at 1000 mg/m(2)/day). After 4 weeks, patients were evaluated for surgical resection. In 9 resected patients, electron-beam intra-operative radiotherapy (10 Gy) was given before reconstruction. Thereafter, in resected patients, adjuvant chemotherapy was prescribed. RESULTS: During chemoradiation, 1 patient (3.6%) developed grade 3 acute gastrointestinal toxicity and 2 patients (7.1%) developed grade 3 hematological toxicity. Three of 19 patients with unresectable tumors had tumor downstaging (15.8%). Two patients showed partial response (response rate, 7.1%; 95% CI, 0.2-25.3) and 4 patients (14.3%) had minimal tumor response. Four patients (14.3%) showed progressive disease after chemoradiation. One postoperative death was recorded. The median survival time was 11.3 months (20.5 and 9.0 months in resected and unresected patients, respectively). Only one local failure was recorded in 8 patients resected with negative margins. CONCLUSIONS: Although the response rate is still low, our preliminary results suggest that preoperative 5-fluorouracil chemoradiation is well tolerated and may result in tumor downstaging. Delivery of intra-operative radiotherapy seems to be associated with a low rate of local recurrences.

Sphincter preservation in four consecutive phase II studies of preoperative chemoradiation: analysis of 247 T3 rectal cancer patients.

AIMS AND BACKGROUND: To evaluate the impact of preoperative chemoradiation on sphincter preservation in patients with low-medium locally advanced resectable rectal cancer treated by four chemoradiation schedules. MATERIALS AND METHODS: Between 1990 and 2002, 247 patients were treated according to four schedules of chemoradiotherapy: FUMIR (5-fluorouracil, mitomycin, external beam radiotherapy 37.8 Gy), PLAFUR (cisplatinum, 5-fluorouracil, external beam radiotherapy 50.4 Gy),TOMRT (raltitrexed, external beam radiotherapy 50.4 Gy), and TOMOXRT (raltitrexed, oxaliplatin, external beam radiotherapy 50.4 Gy). Four to five weeks after chemoradiation, patients were restaged and surgery was performed 2-3 weeks later. RESULTS: Overall, the sphincter-saving surgery was performed in 82.5% of patients. In patients candidate to an abdominoperineal resection before chemoradiaton (distance tumor-anorectal ring, < 30 mm) a sphincter-saving surgery was possible in 58% of cases: 44% (FUMIR), 52% (PLAFUR), 63% (TOMRT), 76% (TOMOXRT) (P < 0.017). The involved surgeons kept the same surgical criteria in performing sphincter-saving surgery. After chemoradiation, patients with tumor location still between 0 and 30 mm received sphincter-saving surgery according to the protocols: 33% (FUMIR), 42% (PLAFUR), 50% (TOMRT), 64% (TOMOXRT) (P = 0.066). CONCLUSIONS: Even though the surgeons' skill in performing sphincter-saving surgery could be improved with time, the high rate of this procedure in the latest schedules suggests an impact of the new drugs in promoting tumor downsizing and therefore sphincter-saving surgery.