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With this review, we aimed to describe the role of adjuvant radiotherapy in the therapeutic management of metastatic inflammatory breast cancer, a rare and aggressive disease historically characterized by high rates of recurrence and poor prognosis. In the context of a multimodality approach, Post-Mastectomy Radiotherapy (PMRT) affirms its role as an appriopriate treatment strategy to improve loco-regional tumor control in selected patients. Further validation in prospective trials is required to better define a standardized therapeutic management of this disease.

Purpose: Prostate motion during the radiotherapy course is an important issue. This study investigated the inter-fraction prostate motion in controlled rectal filling condition. Methods: 10 prostate cancer patients underwent image-guided radiotherapy (IGRT) using a cone-beam computed tomography (CBCT) system, after the insertion of fiducial markers (FMs). The planning CT was the reference CT (CTref) used to estimate the reference intermarker distances, and CBCTs were used for off-line comparison with CTref. We evaluated the influence of rectal and bladder volume on prostate shifts. We calculated the required planning target volume (PTV) margins in this patient population. Results: 120 CBCTs were analyzed. Mean prostate displacements (± SD) along the 3 axes (x, y, z) averaged over the 10 patients, were: 0.90 ± 0.84 mm in x, 0.00 ± 2.07 mm in y, -0.80 ± 1.28 mm in z. There is a statistically significant anti-correlation between prostate displacements and: bladder volume variations (P < 0.001) in the y-axis, and rectal volume variations (P < 0.05) in the z-axis. PTV margins obtained for the directions x, y and z are respectively 2.5, 5.6 and 3.9 mm. Conclusion: IGRT in reproducible empty rectum condition allow a high reduction of daily treatment uncertainties.

This review analyzes the experience and trends in external beam radiotherapy for delivering a boost in locally advanced cervical cancer, identifying whether radiation therapy modalities impact clinical outcomes with the ultimate aim of evaluating alternatives to brachytherapy. Three independent Italian radiation oncologists conducted a literature search on different external beam radiotherapy boost modalities in locally advanced cervical cancer. The search yielded 30 studies. Eight dosimetric studies, evaluating target coverage and dose to organs at risk, and nine clinical investigations, reporting clinical outcomes, were analyzed. Dosimetric studies comparing external beam radiotherapy boost with brachytherapy produced divergent results, while clinical studies were limited by their retrospective nature, heterogeneous doses, radiation schedules, volumes and techniques, diverse follow-up times, and small cohorts of patients. Evidence emerged that high-tech external beam radiotherapy seemed no better than image-guided brachytherapy for delivering a boost in locally advanced cervical cancer. Prospective clinical studies comparing high-tech external beam radiotherapy and image-guided brachytherapy should be encouraged.

Elderly breast cancer patients are frequently affected by significant comorbidities that make sophisticated radiotherapy treatments particularly challenging. We dosimetrically analyzed two different simple free-breathing external beam radiotherapy (EBRT) techniques for the hypofractionated treatment of the left breast in elderly patients with a low compliance, to compare target coverage, and heart and left anterior descending coronary artery (LADCA) sparing. We developed radiation plans for 24 elderly patients using 3D conformal (3DCRT) field-in-field tangential technique and intensity-modulated (IMRT) tangential beam technique. Dose-Volume-Histograms (DVHs) were used to provide a quantitative comparison between plans. The median breast volume was 645 cm3. IMRT and 3DCRT plans comparison demonstrated no significant differences in terms of organ sparing for the heart. Regarding LADCA, mean dose (10.3 ± 9.5 Gy vs 11.9 ± 9.6 Gy, p = 0.0003), maximum dose (26.1 ± 16.1 Gy vs 29.1 ± 16.1 Gy, p = 0.004) and V17 Gy (21.5% ± 26.9% vs 25.0% ± 27.2%, p = 0.002) significantly decreased using IMRT compared with 3DCRT. IMRT plans showed a better target coverage compared with 3DCRT (0.91 ± 0.05 vs 0.93 ± 0.04, p = 0.05). Comparing the two different EBRT techniques, we demonstrated few, although substantial, dosimetric differences in terms of doses to the organs at risk characterized by a statistically significant dose reduction of LADCA in the IMRT plans. Elderly patients with a low compliance to treatment might benefit from 3DCRT with field-in-field tangential arrangement or from a simple IMRT approach. IMRT should be preferred.

Papillary tumor of the pineal region (PTPR) is a recently defined tumor entity. Its clinical course is characterized by frequent local recurrence, and patients may experience the burden of symptoms due to the anatomical location of the growing mass. Guidelines for treatment protocols, and the role of radiotherapy are still being investigated.We report the case of a 27-year old woman who was referred to our department after she was diagnosed with PTPR and had undergone multiple surgical interventions. We delivered adjuvant conformal radiotherapy on the gross residual tumor to a total dose of 59.4 Gy (33 × 1.8 Gy).After a follow-up period of 41 months, we obtained a complete response to the treatment, according to the Response evaluation criteria in solid tumors criteria (RECIST). Radiation treatment was well tolerated, and the patient did not develop acute and late side effects. The neurological symptoms, which were documented at the diagnosis and after the surgical procedure, have not been recorded at last follow-up.Formal consensus for managing patients with a diagnosis of PTPR are nonexistent. Despite surgery, this tumor has a tendency to recur. Radiotherapy could have a role in the adjuvant setting and needs to be investigated in a multicenter setting with a long follow-up.Key words: radiotherapy - neurosurgery - magnetic resonance - pineal region - brain tumor.

A multicenter phase II study for assessing the efficacy and the toxicity of hypofractionated radiotherapy with SIB plus temozolomide in patients with glioblastoma was carried out by the Brain Study Group of the Italian Association of Radiation Oncology. Twenty-four patients with newly diagnosed glioblastoma belonging to Recursive Partitioning Analysis classes III and IV were enrolled. The prescribed dose was 52.5 Gy in 15 fractions of 3.5 Gy and 67.5 in 15 fractions of 4.5 Gy to the SIB volume. Dose constraints for the hypofractionated schedule were provided. Radiotherapy was associated with concomitant and sequential temozolomide. Median overall survival (OS) was 15.1 months, while median progression-free survival (PFS) was 8.6 months. Actuarial OS at 12 months was 65.6% ± 0.09, whereas actuarial PFS at 12 months was 41.2% ± 0.10. Status of methylation of MGMT promoter resulted to be a significant prognostic factor for OS. Radiotherapy-related acute toxicity was not relevant. Three patients (12.5%) had G3 myelotoxicity that required temozolomide temporary interruption or dose reduction during the chemotherapy. However, chemotherapy was not definitely discontinued for toxicity in any case. One patient out of 24 (4.2%) developed radionecrosis that required surgical resection with no evidence of disease in the surgical specimen. This trial confirms that hypofractionated radiotherapy with SIB and association with temozolomide may be a reasonable and feasible option for good prognosis patients with GBM.

Magnetic resonance imaging (MRI) has been proposed as a staging tool for bladder cancer (BC), but its use has been limited by its high costs and limited availability. Microultrasound (mUS) is a novel technology capable of providing high-resolution images of the prostate.To test the feasibility of high-resolution mUS in patients diagnosed with BC and its ability to differentiate between non-muscle-invasive BC (NMIBC) and muscle-invasive BC (MIBC).This is an observational prospective study performed in 23 patients with a diagnosis of primary BC scheduled for an endoscopic treatment.Micro-US was performed before transurethral resection of bladder tumor using the ExactVu system with an EV29L 29-MHz side-fire transducer (Exact Imaging, Markham, Canada).The endpoints were to test the feasibility, describe the normal bladder wall anatomy, identify the lesions, and compare the mUS findings with the histopathological results.Micro-US was accurate in differentiating the three layers of the bladder wall in all cases. Bladder cancers were clearly identified as heterogeneous structures protruding from the normal bladder wall. In 14 cases the lesions appeared confined to the lamina propria, and in all cases NMIBC was confirmed by the final pathological report. In the other patients, the lesions seemed to extend into the muscular layer, but MIBC was confirmed in five out of seven cases (71.4%) from the pathologist. The small sample size was the main limitation of the current study.Our findings showed that mUS is able to differentiate the bladder wall layers and identify the bladder cancer stage. Further studies with a larger population and imaging correlation with MRI are warranted before its introduction in clinical practice.In this report, a new imaging technique was tested for the characterization of bladder cancer. Microultrasound appears to be feasible and capable of discriminating between superficial and invasive tumors.

Large heterogeneity in therapeutic approaches to cervical cancer (CC) patients has been registered worldwide; a national survey exploring practice settings and equipments in CC treatment was distributed to radiation oncologists. Questionnaires were compiled in 90 of 194 Centers (compliance: 46.3 %). Most of respondents reported the presence of multidisciplinary tumor board, and modern equipments/techniques; 55.5 % of centers reported >1 brachytherapy (BT) equipment, thus implying the need to refer their patients outside for the remaining centers. Post-surgery radiotherapy was performed in 96.7 % of early CC (ECC) cases with pathological high risk factors. Exclusive chemoradiation with concomitant platinum schedules was referred to be used by 84.4 % of centers in locally advanced CC. Alternative options were reported with a range between 4.4 and 28.9 %. The present survey reports a broad spectrum of therapeutic options for CC in Italy. Availability and use of modern techniques is quite diffuse, but the distribution of BT resources and skills remains a challenge.

In RPA V-VI glioblastoma patients both hypofractionated radiotherapy and exclusive temozolomide can be used; the purpose of this trial is to compare these treatment regimens in terms of survival and quality of life. Patients with histologic diagnosis of glioblastoma were randomized to hypofractionated radiotherapy (RT–30 Gy in 6 fractions) and exclusive chemotherapy (CHT–emozolomide 200 mg/m2/day 5 days every 28 days). Overall (OS) and progression free survival (PFS) were evaluated with Kaplan Maier curves and correlated with prognostic factors. Quality- adjusted survival (QaS) was evaluated according to the Murray model (Neurological Sign and Symptoms–NSS) From 2010 to 2015, 31 pts were enrolled (CHT: 17 pts; RT: 14pts). Four pts were excluded from the analysis. RPA VI (p = 0.048) and absence of MGMT methylation (p = 0.001) worsened OS significantly. Biopsy (p = 0.048), RPA class VI (p = 0.04) and chemotherapy (p = 0.007) worsened PFS. In the two arms the initial NSS scores were overlapping (CHT: 12.23 and RT: 12.30) and progressively decreased in both group and became significantly worse after 5 months in CHT arm (p = 0.05). Median QaS was 104 days and was significantly better in RT arm (p = 0.01). The data obtained are limited by the poor accrual. Both treatments were well tolerated. Patients in RT arm have a better PFS and QaS, without significant differences in OS. The deterioration of the NSS score would seem an important parameter and coincide with disease progression rather than with the toxicity of the treatment.

The aim of this review is to present the available radiobiological, technical and clinical data about extreme hypofractionation in primary prostate cancer radiotherapy. The interest in this technique is based on the favourable radiobiological characteristics of prostate cancer and supported by advantageous logistic aspects deriving from short overall treatment time. The clinical validity of short-term treatment schedule is proven by a body of non-randomised studies, using both isocentric (LINAC-based) or non-isocentric (CyberKnife®-based) stereotactic body irradiation techniques. Twenty clinical studies, each enrolling more than 40 patients for a total of 1874 treated patients, were revised in terms of technological setting, toxicity, outcome and quality of life assessment. The implemented strategies for the tracking of the prostate and the sparing of the rectal wall have been investigated with particular attention. The urinary toxicity after prostate stereotactic body irradiation seems slightly more pronounced as compared to rectal adverse events, and this is more evident for late occurring events, but no worse as respect to conventional fractionation schemes. As far as the rate of severe acute toxicity is concerned, in all the available studies the treatment was globally well tolerated. While awaiting long-term data on efficacy and toxicity, the analysed studies suggest that the outcome profile of this approach, alongside the patient convenience and reduced costs, is promising. Forty-eight ongoing clinical trials are also presented as a preview of the expectation from the near future.

Stereotactic body radiotherapy (SBRT) is emerging as a treatment option in oligometastatic cancer patients. This retrospective study aimed to analyze local control, biochemical progression-free survival (b-PFS), and toxicity in patients affected by isolated prostate cancer lymph node metastases. Finally, we evaluated androgen deprivation therapy-free survival (ADT-FS).Forty patients with 47 isolated lymph nodes of recurrent prostate cancer were treated with SBRT. Mostly, two different fractionation schemes were used: 5 × 7 Gy in 23 (48.9 %) lesions and 5 × 8 Gy in 13 (27.7 %) lesions. Response to treatment was assessed with periodical PSA evaluation. Toxicity was registered according to RTOG/EORTC criteria.With a mean follow-up of 30.18 months, local control was achieved in 98 % of the cases, with a median b-PFS of 24 months. We obtained a 2-year b-PFS of 44 % with 40 % of the patients ADT-free at last follow-up (mean value 26.18 months; range 3.96-59.46), whereas 12.5 % had a mean ADT-FS of 13.58 months (range 2.06-37.13). Late toxicity was observed in one (2.5 %) patient who manifested a grade 3 gastrointestinal toxicity 11.76 months after the end of SBRT.Our study demonstrates that SBRT is safe, effective, and minimally invasive in the eradication of limited nodal metastases, yielding an important delay in prescribing ADT.

Aim To provide a literature review on risk factors and strategies to prevent acute carotid blowout (CBO) syndrome in patients who underwent reirradiation (reRT) for recurrent head and neck (HN) malignancies. Patients and Methods Inclusion criteria were: 1) CBO following reRT in the HN region, 2) description on patient-, tumor- or treatment-related risk factors, 3) clinical or radiological signs of threatened or impending CBO, and 4) CBO prevention strategies. Results Thirty-five studies were selected for the analysis from five hundred seventy-seven records. Results provided indications on clinical, radiological and dosimetric parameters possibly associated with higher risk of CBO. Endovascular procedures (artery occlusion and stenting) to prevent acute massive hemorrhage in high risk patients were discussed. Conclusion Literature data are still scarce with a low level of evidence. Nevertheless, the present work provides a comprehensive review useful for clinicians as a multidisciplinary pragmatic tool in their clinical practice.

A platinum salt (oxaliplatin or cisplatin) is widely used to enhance chemoradation (CRT) response. The potential of cisplatin in neoadjuvant CRT for locally advanced rectal cancer (LARC) has not been fully investigated. Consecutive patients with histologically confirmed LARC were treated with standard pelvic radiotherapy and concurrent cisplatin plus capecitabine (CisCape CRT). Surgery and eight cycles of adjuvant FOLFOX4 were offered to all patients after CRT. Common biochemical variables and key germline genetic polymorphisms were analyzed as predictors of pathological complete response (pCR). Fifty-one patients were enrolled. pCR (regression AJCC grade 0) was documented in 7 patients (14%), nearly complete response (AJCC grade 1) in 10 pts. There was a strong association between disease-free survival and AJCC grade (p 0.0047). Grade 3-4 toxicities (mainly diarrhea) was observed in 41% of patients. Among all analyzed variables, baseline hemoglobin (Hb) was significantly associated with AJCC grade 0-1 response (p 0.027). As for the pharmacogenetic analysis, XRCC1 rs25487 polymorphism was significantly associated with AJCC grade 0-1, Odds Ratio 25.8, p 0.049. AJCC grade 0-1 response rate for patients with high Hb and/or XRCC1 rs25487 G/G genotype was as high as 57%. Baseline Hb and XRCC1 polymorphisms are valuable selection criteria for the CisCape CRT regimen, given its otherwise meaningful toxicity.

Background The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. Methods One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). Results At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Conclusions Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care.

AIM: To identify factors influencing toxicity in patients affected by localized prostate cancer treated with conformal image-guided radiotherapy. BACKGROUND: Image guidance in combination with conformal techniques is the standard of care in localized prostate cancer, but factors affecting toxicity are still under investigation. MATERIALS AND METHODS: 294 patients were analyzed. Median age at diagnosis was 71 year. 76 Gy (38 × 2 Gy) were delivered to the target volume. We used the χ(2) test to analyse associations between toxicity and dosimetric and clinical parameters. Multivariate analysis was performed using binary logistic regression. Kaplan–Meier method was used for survival analysis. RESULTS: Median follow-up was 62.9 months. Acute grade ≥2 gastro-intestinal toxicity (GI) was 12.1%. Acute genito-urinary (GU) toxicity of grade ≥2 was 33.9%. Actuarial 4 and 5 years late grade ≥2 GI was 3% and 4%, respectively. Four and 5-year late grade ≥2 GU toxicity was 6% and 10%. At multivariate analysis for acute toxicity rectal V(70) was correlated with GI toxicity (p = 0.01, HR 2.73 CI 1.19–6.26), and smoking habit with GU toxicity (p

Background The tumors of many patients with prostate cancer eventually become refractory to androgen deprivation therapy with progression to metastatic castration-resistant disease. Significant advances in the treatment of metastatic castration-resistant prostate cancer (mCRPC) have been made in recent years, and new treatment strategies have recently been made available. The aim of this report was to schematically review all the approved pharmacologic treatment options for patients with mCRPC through 2018, analyzing the efficacy and possible side effects of each therapy to assist clinicians in reaching an appropriate treatment decision. New biomarkers potentially of aid in the choice of treatment in this setting are also briefly reviewed. Methods We performed a literature search of clinical trials of new drugs and treatments for patients diagnosed with mCRPC published through 2018. Results Two new hormonal drugs, abiraterone acetate and enzalutamide have been approved by FDA in 2011 and 2012, respectively for the treatment of patients with mCRPC and have undergone extensive testing. While these treatments have shown a benefit in progression-free and overall survival, the appropriate sequencing must still be determined so that treatment decisions can be made based on their specific clinical profile. Cabazitaxel has been shown to be an efficient therapeutic option in a postdocetaxel setting, while its role in chemotherapy-naive patients must still be determined. Sipuleucel-T and radium-223 have been studied in patients without visceral metastases and have achieved overall survival benefits with good safety profiles. The feasibility and efficacy of combinations of new treatments with other known therapies such as chemotherapy are currently under investigation. Conclusions Drug development efforts continue to attempt to prolong survival and improve quality of life in the mCRPC setting, with several therapeutic options available. Ongoing and future trials are needed to further assess the efficacy and safety of these new drugs and their interactions, along with the most appropriate sequencing.

Objective The study objective was to evaluate the efficacy of salvage stereotactic body radiation therapy (SBRT) as a treatment modality in patients with oligometastatic prostate cancer. Methods A total of 16 patients with 18 isolated lymph nodes with recurrent prostate cancer were treated between 2008 and 2013. All patients underwent [11C] choline-positron emission tomography/computed tomography before SBRT. Two patients were treated in different sessions for metachronous metastases. Ten patients received androgen deprivation therapy concomitant to SBRT (total dose range, 12-35 Gy, delivered in 1-5 daily fractions). Results The mean and median follow-up periods were 29.35 and 29.38 months, respectively (range, 6.3-68.8 months). Local disease control and a decrease in serum prostate-specific antigen were obtained in 15 of 16 patients (94%); only 1 patient had an in-field progression. In the 6 patients without androgen deprivation therapy at the time of SBRT, the mean time of deferment of palliative androgen deprivation therapy was 23.7 months (range, 2.5-51 months). At last follow-up, 8 patients had active prostate cancer disease; biochemical progression was observed after a mean time of 7.9 months from the completion of SBRT. One patient died of disease. Overall survival was 94%. The 2-year biochemical relapse-free survival was 44%. Late toxicity (gastrointestinal) was observed in 1 patient who had a G3 toxicity. Conclusions SBRT seems to be safe, effective, and minimally invasive in the eradication of limited nodal recurrence from oligometastatic prostate cancer. SBRT is well tolerated by patients with low toxicity and yielded a local control of the disease.

To retrospectively evaluate the outcome of stereotactic body radiation therapy (SBRT) in the treatment of elderly patients affected by isolated body metastasis from different primitive tumors. 70 patients with isolated body metastasis were treated. Median age at diagnosis was 75 years (IQR 69–80). The most common SBRT fractionation scheme was 5 × 7 Gy (total dose 35 Gy). The primary endpoints were Local Control (LC) and Toxicity. Secondary endpoints were Overall Survival (OS) and Disease-Specific Survival (DSS). Response to radiotherapy was assessed according to RECIST criteria v1.1. Toxicity was registered according to Common Terminology Criteria for Adverse Events (CTCAE) v 4.0. We performed survival analysis with the Kaplan–Meier method. The correlation between time actuarial incidence and clinical parameters was studied. Median follow-up was 26.5 months. 44 patients (62.8%) were alive at the time of analysis, while 22 (31.4%) died because of the disease. Local control at 2 and 3 years was 87%. The 2-year OS and DSS were 84 and 71%, respectively, while the 3-year values were 57 and 62%. PFS at 2 and 3 years was 41 and 25%, respectively. On univariate analysis, KPS ≥ 90 is statistically correlated with improved OS and DSS (p

Background/aim This multicenter, retrospective, 'field-practice' study investigated treatment outcomes of ongoing abiraterone therapy with the addition of radiotherapy (RT) - initiated for oligoprogression or with a palliative intent. Patients and methods Consecutive patients affected by metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate were considered if they had received RT after the initiation of abiraterone treatment. Results A total of 32 patients were enrolled in the study. Median duration of abiraterone treatment was 13.0 months (range=3.8-40.9 months). Median duration of abiraterone treatment before RT was 5.9 months (range=0.4-40.0 months), and 7.2 months after RT (range=0.1-29.7 months). Median progression-free survival (PFS) was 12.6 months (95%CI=10.5-14.7) from the initiation of abiraterone treatment. From RT administration, PFS was 9.6 months (95%CI=6.4-12.9). Median overall survival (OS) since abiraterone initiation was 18.9 months (95%CI=4.7-33.0). Conclusion RT prolongs abiraterone treatment in mCRPC patients leading to better clinical outcomes with this molecule.

To evaluate the outcome of patients affected by a single isolated body metastasis treated with stereotactic body radiotherapy (SBRT).Seven-eight patients were treated with SBRT for isolated body metastasis. The most frequent primary tumor was prostate cancer (28.2%), followed by colorectal cancer (23.1%) and lung cancer (20.5%). Median age at diagnosis of oligometastatic disease was 70 years (range 47-88). Median Karnofsky Performance Status (KPS) was 90 (range 70-100). The most common SBRT fractionation scheme was 5 × 7 Gy (total dose 35 Gy). Response to radiotherapy was determined according to RECIST criteria v1.1. Toxicity was registered according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. The survival analysis was performed with the Kaplan-Meier method. The correlation between time actuarial incidence and clinical parameters was studied, and the Kaplan-Meier method of log-rank test was applied.With a median follow-up of 22.68 months, local control was achieved in 89.7% of the cases. The two-year overall survival (OS) and progression-free survival (PFS) were 68% and 42%, respectively. On univariate analysis, KPS ≥80 is predictive for improved OS (p = .001) and PFS (p = .001). Acute toxicity of grade ≥2 occurred in eight (10.2%) patients and late grade ≥2 toxicity in five (6.4%) patients.Ablative radiotherapy in 'early oligometastatic state' is a safe, effective and minimally invasive treatment modality. A good performance status (KPS ≥80) seems to influence the clinical outcome.

Background: The aim of the present study is to evaluate the impact of metastases-directed stereotactic body radiotherapy in two groups of oligometastatic prostate cancer (PC) patients: oligorecurrent PC and oligoprogressive castration-resistant PC (oligo-CRPC). Methods: Inclusion criteria of the present multicentre retrospective analysis were: (1) oligorecurrent PC, defined as the presence of 1–3 lesions (bone or nodes) detected with choline positron emission tomography or CT plus bone scan following biochemical recurrence; (2) oligo-CRPC, defined as metastases (bone or nodes) detected after a prostatic-specific antigen rise during androgen deprivation therapy (ADT). Primary end points were: distant progression-free survival (DPFS) and ADT-free survival in oligorecurrent PC patients; DPFS and second-line systemic treatment-free survival in oligo-CRPC patients. Results: About 100 patients with oligorecurrent PC (139 lesions) and 41 with oligo-CRPC (70 lesions), treated between March 2010 and April 2016, were analysed. After a median follow-up of 20.4 months, in the oligorecurrent group 1- and 2-year DPFS were 64.4 and 43%. The rate of LC was 92.8% at 2 years. At a median follow-up of 23.4 months, in the oligo-CRPC group 1- and 2-year DPFS were 43.2 and 21.6%. Limitations include the retrospective design. Conclusions: Stereotactic body radiotherapy seems to be a useful treatment both for oligorecurrent and oligo-CRPC.

Aim To evaluate toxicity of high conformal image-guided radiotherapy of the prostate bed. Background Radiotherapy of the prostate bed has a pivotal role in the post-operative and salvage settings, but few clinical data are available on the use of daily image guidance in combination with highly conformal techniques, and data on long-term results are lacking. Materials and methods We analyzed 118 patients irradiated on the prostate bed using conformal plans processed with a micro-multileaf collimator, and daily checking treatment set-up with a cone-beam CT system. Correlation between toxicity and clinical-dosimetric parameters was assessed by the Cox regression model and log-rank test. Survival analyses were performed with the Kaplan–Meier method. Results Median follow-up was 54.08 months. Late grade ≥2 gastro-intestinal (GI) and genito-urinary (GU) toxicity were 3.4% and 4.2%, respectively. Actuarial 4-year late grade ≥2 GI and GU toxicities were 4% and 6%, respectively. Four-year relapse-free survival was 87%. At log-rank test, acute grade ≥2 GI toxicity is associated with the use of antihypertensives (p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.03), and there is a trend toward significance between the use of anticoagulants and late grade ≥2 GI toxicity (p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.07). At Cox analysis, acute grade ≥2 GU toxicity is correlated with the percentage of bladder volume receiving more than 65[[ce:hsp sp="0.25"/]]Gy (p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.02, HR 1.87 CI 1.25–2.8), and the maximal dose to the rectum is correlated to the development of late grade ≥2 GI toxicity (p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.03, HR 2.75 CI 1.10–6.9). Conclusions Conformal volumetric image-guided radiotherapy of the prostate bed leads to low toxicity rates.

We evaluated the clinical impact of a high definition micro-multileaf collimator and a linac-integrated cone-beam computed tomography in 142 patients treated with conformal radiotherapy for localized prostate cancer to a total dose of 76 Gy. Details on treatment toxicity and tumour control were collected. The 3 years biochemical relapse-free survival was 90%. Acute and late gastrointestinal toxicities were low (3-year actuarial late toxicity of 11.2%). Acute genitourinary toxicity was relatively high, the 3-year actuarial genitourinary late toxicity was 12%. Conformal image-guided radiotherapy for localized prostate cancer leads to low rates of late toxicity with a high rate of tumor control.

The purpose of this study is to analyze the dosimetric effect of Elekta Beam Modulator in 3-dimensional conformal radiation therapy (3DCRT) and in intensity-modulated radiation therapy (IMRT) for localized prostate cancer. We compared treatment plans developed with 2 different Elekta multileaf collimators (MLC): Beam Modulator micro-MLC (mMLC) (4-mm leaf width at the isocenter) and standard MLC (10-mm leaf width at the isocenter). The comparison was performed for 15 patients with localized prostate cancer in 3DCRT and IMRT delivery; a total of 60 treatment plans were processed. The dose-volume histograms were used to provide the quantitative comparison between plans. In particular, we analyzed differences between rectum and bladder sparing in terms of a set of appropriate Vx (percentage of organ at risk [OAR] volume receiving the x dose) and differences between target conformity and coverage in terms of coverage factor and conformation number. Our analysis demonstrates that in 3DCRT there is an advantage in the use of Elekta Beam Modulator mMLC in terms of organ sparing; in particular, a significant decrease in rectal V60 and V50 (p = 0.001) and in bladder V70 and V65 (p = 0.007 and 0.002, respectively) was found. Moreover, a better target dose conformity was obtained (p = 0.002). IMRT plans comparison demonstrated no significant differences between the use of the 4 or 10-mm MLCs. Our analysis shows that in 3DCRT the use of the Elekta Beam Modulator mMLC gives a gain in target conformity and in OARs dose sparing whereas in IMRT plans there is no advantage.

Purpose: To evaluate the performance of a rectum model in predicting late rectal toxicity of prostate patients undergoing 3D conformal radiation therapy while following a dietary protocol combined with image guidance. Methods: A linear accelerator equipped with a Cone Beam Computed Tomography (CBCT) system was used to treat 20 patients who were following a dietary protocol. The set-up was verified by co-registering CBCT scans with the planning CT scan (pCT). A mean dose volume histogram () as the arithmetical mean of the rectum DVHs from each CBCT scan was obtained. A suitably defined 3D rectum model (Average Rectum, AR) was defined and its DVH (DVHAR) was calculated. DVHs were also evaluated for the first five CBCT scans using both methods (5 > and DVHAR5). The Lyman-Kutcher-Burman NTCP model with QUANTEC parameters was used to compare the calculated DVHs. The QUANTEC dose values were used to describe the time behaviour of the relative volumes using the Gamma Distribution for the frequency of the relative rectum volumes at each QUANTEC dose value. Results: No statistically significant differences between NTCPAR5 and NTCPAR and between NTCP and NTCP were found. The best agreement with the observed toxicity rate (0%) was obtained form DVHAR. The Gamma Distributions of the rectum volumes at the QUANTEC dose levels were found to be highly variable among the patients. Conclusions: Both dietary protocol and image guidance were found effective in limiting late rectal toxicity. AR was a better predictor for late rectal toxicity and better described the rectum volume during the treatment course. Finally, from the Gamma distributions, and from our toxicity data, we can suggest V75 as the best predictor of late rectal toxicity.

High-energy electron beams generated by linear accelerators, typically in the range 6 to 20 MeV, are used in small field sizes for radiotherapy of localized superficial tumors. Unshielded silicon diodes (Si-D) are commonly considered suitable detectors for relative dose measurements in small electron fields due to their high spatial resolution. Recently, a novel synthetic single crystal diamond diode (SCDD) showed suitable properties for standard electron beams and small photon beams dosimetry. The aim of the present study is twofold: to characterize 6 to 15 MeV small electron beams shaped by using commercial tubular applicators with 2, 3, 4 and 5 cm diameter and to assess the dosimetric performance under such irradiation conditions of the novel SCDD dosimeter by comparison with commercially available dosimeters, namely a Si-D and a plane-parallel ionization chamber. Percentage depth dose curves, beam profiles and output factors (OFs) were measured. A good agreement among the dosimeters was observed in all of the performed measurements. As for the tubular applicators, two main effects were evidenced: (i) OFs larger than unity were measured for a number of field sizes and energies, with values up to about 1.3, that is an output 30% greater than that obtained at the 10 × 10 cm 2 reference field; (ii) for each diameter of the tubular applicator a noticeable increase of the OF values was observed with increasing beam energy, up to about 100% in the case of the smaller applicator. This OF behavior is remarkably different from what typically observed for small blocked fields having the same size and energy as those used in this study. OFs for tubular applicators depend considerably on the field size, so interpolation is unadvisable to predict the linear accelerator output for such applicators whereas reliable high-resolution detectors, as the silicon and diamond diodes used in this work allow OF measurements with uncertainties of about 1%. © 2013 Institute of Physics and Engineering in Medicine. Printed in the UK & the USA.

The identification of predictive biomarkers for neoadjuvant chemoradiation therapy (CRT) is a current clinical need. The heterodimer Ku70/80 plays a critical role in DNA repair and cell death induction after damage. The aberrant expression and localization of these proteins fail to control DNA repair and apoptosis. sClusterin is the Ku70 partner that sterically inhibits Bax-dependent cell death after damage in some pathologic conditions. This study sought to evaluate the molecular relevance of Ku70-Ku80-Clu as a molecular cluster predicting the response to neoadjuvant CRT in patients with locally advanced rectal cancer (LARC).Patients enrolled in this study underwent preoperative CRT followed by surgical excision. A retrospective study based on individual response, evaluated by computed tomography and diffusion-weighted magnetic resonance imaging, identified responder (56%) and no-responder patients (44%). Ku70/80 and Clu expression were observed in biopsy specimens obtained before and after treatment with neoadjuvant CRT from the same LARC patients. In vitro studies before and after irradiation were also performed on radioresistant (SW480) and radiosensitive (SW620) colorectal cancer cell lines, mimicking sensitive or resistant tumor behavior.We found a conventional nuclear localization of Ku70/80 in pretherapeutic tumor biopsies of responder patients, in agreement with their role in DNA repair and regulating apoptosis. By contrast, in the no-responder population we observed an unconventional overexpression of Ku70 in the cytoplasm (P.001). In this context we also overexpression of sClu in the cytoplasm, which accorded with its role in stabilizing of Bax-Ku70 complex, inhibiting Bax-dependent apoptosis. Strikingly, Ku80 in these tumor tissues was lost (P.005). In vitro testing of colon cancer cells finally confirmed the results observed in tumor biopsy specimens, proving that Ku70/80-Clu deregulation is extensively involved in the resistance mechanism.These results strongly suggest a potential role of these proteins as a new prognostic tool to predict the response to chemoradiation in LARC.

Low-dose-rate brachytherapy (LDR-BT) in localized prostate cancer is available since 15 years in Italy. We realized the first national multicentre and multidisciplinary data collection to evaluate LDR-BT practice, given as monotherapy, and outcome in terms of biochemical failure.Between May 1998 and December 2011, 2237 patients with early-stage prostate cancer from 11 Italian community and academic hospitals were treated with iodine-125 ((125)I) or palladium-103 LDR-BT as monotherapy and followed up for at least 2 years. (125)I seeds were implanted in 97.7% of the patients: the mean dose received by 90% of target volume was 145 Gy; the mean target volume receiving 100% of prescribed dose (V100) was 91.1%. Biochemical failure-free survival (BFFS), disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan-Meier method. Log-rank test and multivariable Cox regression were used to evaluate the relationship of covariates with outcomes.Median follow-up time was 65 months. 5- and 7-year DSS, OS and BFFS were 99 and 98%, 94 and 89%, and 92 and 88%, respectively. At multivariate analysis, the National Comprehensive Cancer Network score (p 0.0001) and V100 (p = 0.09) were correlated with BFFS, with V100 effect significantly different between patients at low risk and those at intermediate/high risk (p = 0.04). Short follow-up and lack of toxicity data represent the main limitations for a global evaluation of LDR-BT.This first multicentre Italian report confirms LDR-BT as an excellent curative modality for low-/intermediate-risk prostate cancer.Multidisciplinary teams may help to select adequately patients to be treated with brachytherapy, with a direct impact on the implant quality and, possibly, on outcome.

To the Editor, External beam radiotherapy is a therapeutic option for the radical treatment of localized prostate cancer [1]. High-dose conformal radiotherapy with conventional 2 Gy daily fractions...

An overview of the clinical series assessing the efficacy of the most important targeted agents when used together with radiotherapy against glioblastoma is herein provided.

Background and Purpose: Recent prospective studies have explored the partial breast irradiation (PBI) for patients with early-stage breast cancer using different technical approaches. The purpose of this study is to explore feasibility, tumor control and acute and late toxicity of a specific hypo-fractionated 3D-CRT when treating postmenopausal patients with early breast cancer with partial breast irradiation, using five fractions in five consecutive days. Materials and Methods: Ten patients, aged ≥ 70 underwent breast conservative surgery for invasive breast carcinoma with a complete microscopic resection; no lymphovascular invasion was found and negative axillary node status was assessed. Metal clips were positioned in the surgical bed at the time of surgery. All of the patients provided an informed consent for breast irradiation. Seven patients received Tamoxifen. Of the ten patients, five were treated for left breast disease, and five for right breast disease. The dose fractionation schedule was 3000 cGy delivered to the isocenter in 5 fractions (600 cGy/fr) using 6 MV photons. According to the linear quadratic model and an α/β ratio of 4 Gy this prescription is equivalent to 50 Gy in a standard 2-Gy fractionation schedule. Patients were treated in the supine position. A comercial breast board was used as immobilization device in order to keep the arms of the patient raised. The clinical target volume (CTV) was drawn with a uniform 1-cm three-dimensional margin around the surgical clips. The CTV was limited to 3 mm from the skin surface and 3 mm from the lung-chest wall interface. A three-dimensional margin was added to the CTV to obtain the planning target volume (PTV). The ipsilateral and controlateral breast, the ipsilateral and controlateral lung, heart and spinal cord were contoured as organs at risk (OAR). The treatment was developed using Precise Plan Treatment Planning System and four no-coplanar fields. The constraints used have been: uninvolved breast (ipsilateral breast-PTV): V15 ≤ 50%; heart: V3 ≤ 10%; ipsilateral lung: V10 ≤ 20%; controlateral lung: V5 ≤ 10% and controlateral breast: maximum dose ≤ 1 Gy. We required PTV coverage of ≥ 90%. Patient set-up was verified every day before treatment using portal images. No tumour bed boost was delivered. Clinical assessments of early normal tissue reaction were carried out every day during radiotherapy and 10 days after the end of the treatment. After radiotherapy, we visited all patients every 3 months during the first 2 years and every six month thereafter. Frontal and lateral pictures of the breast were taken on the first day of treatment (baseline), at the end of treatment, 10 days after the end of treatment and at the first follow-up. Any change in breast appearance compared with the baseline picture was scored on a four-point RTOG for acute and late radiation morbidity scoring scale. Results: No local or distant recurrences was observed and then confirmed by mammograms performed every year and breast ultrasound performed every six months. For acute and late toxicity, only 2 patients developed acute effects at the end of the treatment. Conclusion: The clinical outcomes observed in ten patients demonstrate a good feasibility of the schedule adopted both in terms of tumour control and acute and late toxicity, with good cosmetics results. Long term follow-up and a large number of patients will be needed for full evaluation.

This study aims at optimizing treatment planning in young patients affected by lymphoma (Stage II to III) by using an inclined board (IB) that allows reducing doses to the organs at risk. We evaluated 19 young patients affected by stage I to III lymphomas, referred to our Department for consolidation radiotherapy (RT) treatment on the mediastinum. Patients underwent 2 planning computed tomography (CT) scans performed in different positions: flat standard position and inclined position. A direct comparison between the different treatment plans was carried out analyzing dosimetric parameters obtained from dose-volume histograms generated for each plan. Comparison was performed to evaluate the sparing obtained on breast and heart. Dosimetric evaluation was performed for the following organs at risk (OARs): mammary glands, lungs, and heart. A statistically significant advantage was reported for V5, V20, and V30 for the breast when using the inclined board. A similar result was obtained for V5 and V10 on the heart. No advantage was observed in lung doses. The use of a simple device, such as an inclined board, allows the optimization of treatment plan, especially in young female patients, by ensuring a significant reduction of the dose delivered to breast and heart.

Purpose To investigate intraprostatic gold coils positional stability analyzing intermarker distance in on-board cone beam computed tomography (CBCT) scans acquired throughout the entire treatment course. Methods and materials A total of 29 fiducial markers (FMs) were implanted in 10 patients through the transperineal approach, under ultrasound guidance. After 2 weeks from the FM implantation, all the patients underwent CT and magnetic resonance imaging under radiation therapy–planning conditions. The planning CT was the reference CT (CTref) used to calculate the initial intermarker distances. For every patient, 8 CBCTi (i varying from 1 to 8) acquired once a week during the treatment course were selected to calculate intermarker distances and compared with CTref. Reconstructed images of CBCTi were exported to the treatment planning system, and every FM was contoured. A point of interest at the center of mass of each contoured FM was created. The mean coordinates obtained for point of interest at the center of mass of FMs were used to calculate relative marker distances on CTref and CBCTi. Results No patient developed postimplantation complications. A total of 224 marker distance variations (MDVs) were calculated for all 29 markers. The average directional variation of all MDVs (± standard deviation [SD]) was −0.14 ± 0.86 mm. The average absolute variations of all MDVs (± SD) were 0.71 ± 0.51 mm. The largest observed variation was 1.9 mm. All patients had not significant temporal trends in their marker distances. The SD of the MDVs was computed for each set of markers in all 10 patients. The SDs ranged between 0.4 and 1.1 mm in individual patients. The average of the mean SDs was 0.6 mm. Conclusions The three-dimensional definition of each fiducial marker volume, using on-board CBCT, demonstrated the stability of FMs position throughout the entire radiation therapy treatment course.

The purpose of this work has been to dosimetrically investigate four fluoroscopically guided interventions: the percutaneous vertebroplasty (PVP), the percutaneous disc decompression (PDD), the radiofrequency medial branch neurolysis (RF) (hereafter named spine procedures), and the endovascular treatment for the critical limb ischemia (CLI). The X‐ray equipment used was a Philips Integris Allura Xper FD20 imaging system provided with a dose‐area product (DAP) meter. The parameters investigated were: maximum skin dose (MSD), air kerma (Ka,r), DAP, and fluoroscopy time (FT). In order to measure the maximum skin dose, we employed a system based on MOSFET detectors. Before using the system on patients, a calibration factor Fc and correction factors for energy (CkV) and field size (CFD) dependence were determined. Ka,r, DAP, and FT were extrapolated from the X‐ray equipment. The analysis was carried out on 40 patients, 10 for each procedure. The average fluoroscopy time and DAP values were compared with the reference levels (RLs) proposed in literature. Finally, the correlations between MSD, FT, Ka,r, and DAP values, as well as between DAP and FT values, were studied in terms of Pearson's product‐moment coefficients for spine procedures only. An Fc value of 0.20 and a very low dependence of CFD on field size were found. A third‐order polynomial function was chosen for CkV. The mean values of MSD ranged from 2.3 to 10.8 cGy for CLI and PVP, respectively. For these procedures, the DAP and FT values were within the proposed RL values. The statistical analysis showed little correlation between the investigated parameters. The interventional procedures investigated were found to be both safe with regard to deterministic effects and optimized for stochastic ones. In the spine procedures, the observed correlations indicated that the estimation of MSD from Ka,r or DAP was not accurate and a direct measure of MSD is therefore recommended. PACS number: 87

OBJECTIVE To analyse relapse patterns, toxicity and second malignancy in patients with stage I pure germ cell testicular tumours, treated in 1970–1999. PATIENTS AND METHODS In all, 487 patients received irradiation after surgery to the infra- (407, 83.5%) or infra- and supra-diaphragmatic volumes (80, 16.5%). Treatment-related toxicity was classified according to previous criteria and fertility investigated in 246 men. Second malignancies were identified by retrospective analysis of clinical records or telephone interviews in men who no longer needed a long-term follow-up. RESULTS The 10-year overall survival was 97% (98% and 96%, respectively, for the aortic nodes only, or aortic and iliac nodes, i.e. the ‘dog leg’ field) and disease-free survival was 94%. Twenty-one patients relapsed (five with a true ‘in-field’ recurrence, nine progressed to the mediastinum, and seven had disseminated disease). Acute toxicity was mainly gastrointestinal, with 7.6% classified as grade II. In all, 73 men achieved paternity after irradiation; nine did not but had normal sperm. Second malignancies were diagnosed in 16 (3.3%) men. CONCLUSION Para-aortic irradiation may be used safely in patients with stage I seminoma and undisturbed testicular drainage, with equivalent results to the ‘dog-leg’ group; these unrandomized data confirm the lower toxicity and equivalent survival rates of this treatment.

Purpose: To report a retro-orbital localization of Multiple Myeloma (MM) describing its treatment and clinical result. Case report: A 50-years-old male patient with Magnetic Resonance Imaging (MRI) evidence of a retro-orbital mass with exophthalmos, due to the pathological diagnosis of MM, was referred for Radiation Therapy (RT). Discussion: The orbital involvement in Multiple Myeloma is rare and few cases are reported in the literature. The treatment of choice is RT alone with a prescribed dose ranging between 40 Gy and 45 Gy. In our patient the retro-orbital lesion, measuring 26 × 16 mm, was treated with Intensity Modulated Radiotherapy Technique (IMRT) delivering 4400 cGy with conventional fractionation. The treatment was well tolerated, the patient experienced a complete regression of the exophthalmos without any significant side effect.

A patient with suprasellar and brain stem involvement in Erdheim Chester disease (ECD) underwent magnetic resonance (MR) imaging and proton MR spectroscopy (1H MRS) of the ventral pons before and 1, 4 and 18 months after external whole-brain (24 Gy) radiotherapy. By revealing a decrease of the N-acetyl-aspartate/choline ratio in the pons, 1H MR spectroscopy anticipated lesions growth on MR imaging. In line with the results in four patients reported in the literature, our observation indicates that external radiation therapy is not effective for intracranial involvement in ECD.

Purpose: To determine the temporal lobe (TL) damage rate in 96 patients treated with high-dose proton and photon irradiation for chordomas and chondrosarcomas of the base of the skull. Methods and Materials: The records of 96 consecutive patients treated at Massachusetts General Hospital (MGH) and Harvard Cyclotron Laboratory (HCL) between June 1984 and 1993, for chordomas and chondrosarcomas of the base of the skull were reviewed. All the patients had undergone some degree of resection of the tumor prior to radiation therapy. Seventy-five patients were classified as "primary tumors" and 21 as recurrent or regrowing tumors after one or more surgical procedures. All the patients were randomized to receive 66.6 or 72 cobalt Gray equivalent (CGE) on a prospective dose-searching study by proton and photon irradiation (Radiation Therapy Oncology Group #85-26) with conventional fractionation (1.8 CGE/day, 5 fractions/week). All treatments were planned using the three-dimensional (3D) planning system developed at the Massachusetts General Hospital, and the dose was delivered using opposed lateral fields for the photon component and a noncoplanar isocentric technique for the proton component. Clinical symptoms of TL damage were classified into 4 grades. Computerized tomography (CT) and magnetic resonance imaging (MRI) scans were evaluated for white matter changes. Abnormalities associated with persistent or recurrent tumor were distinguished from radiation-induced changes. TLs were delineated on the original scans of the 10 patients with damage and those of a group of 33 patients with no clinical or MRI evidence of injury. Dose distributions were calculated and dose–volume histograms were obtained for these patients. Results: Of the patients, 10 developed TL damage, with bilateral injury in 2 and unilateral injury in 8. The cumulative TL damage incidence at 2 and 5 years was 7.6 and 13.2%, respectively. The MRI areas suggestive of TL damage were always separated from the tumor bed. Symptoms were severe to moderate in 8 patients. Several baseline factors, tumor- or host-related, were analyzed to evaluate their predictivity for TL damage: age, gender, tumor site, histology, type of presentation, type and number of surgical procedures, primary tumor volume, prescribed dose, normal tissue involvement, and volume of TL receiving doses ranging between 10 and 50 CGE or more. Only gender, in a univariate analysis (log rank) was a significant predictor of damage (0.0155), with male patients being at significantly higher risk of TL injury. In a stepwise Cox regression that included gender as a variable, no other baseline variable improved the prediction of damage. Conclusions: The 2- and 5-year cumulative TL damage rates were 7.6 and 13.2%, respectively. Despite the different TL damage rates related to age, tumor volume, number of surgical procedures prior to radiation therapy, and prescribed doses to the tumor, only gender was a significant predictor of damage ( p = 0.0155) using a univariate (log rank) test. Chordomas and chondrosarcomas of the base of the skull may represent an interesting model to evaluate the TL damage rates because of their extradural origin, displacing the white matter instead of infiltrating it as gliomas do, because of their longer local recurrence-free survival other than gliomas and other brain tumors and because of the high doses of irradiation delivered to the target volume to obtain local control.