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Purpose Helical tomotherapy (HT) has been recently introduced in the neoadjuvant treatment of locally advanced rectal cancer. Aim of this study is to report the toxicity and local control rates of a large series of locally advanced rectal cancer patients treated with neoadjuvant chemotherapy and HT under daily image guidance followed by surgery. Methods Data from 117 locally advanced rectal cancer patients treated at two Swiss Radiotherapy departments were collected and analyzed. Radiotherapy consisted of 45 Gy (1.8 Gy/fraction, 5 fractions/week delivered in 5 weeks) to the regional pelvic lymph nodes. Seventy patients also received a simultaneous integrated boost (SIB) up to 50 Gy to the tumor and involved nodes (2 Gy/fraction, 5 fractions/week delivered in 5 weeks). Chemotherapy consisted of capecitabine 825 mg/m2, twice daily, during the irradiation days. After a median interval of 59 days [95% confidence interval (CI) 53–65 days), all patients underwent surgery. Results Median follow-up was 45 months (range 4–90 months). The overall rate of acute grade 2–4 toxicity was 18.8% (n = 22). Four patients (3.4%) presented a grade 3 dermatitis (n = 1) or diarrhea (n = 3), and 1 (0.8%) demonstrated grade 4 rectal toxicity. No patients presented with grade ≥ 3 hematologic toxicity. Six patients (5.1%) had late grade 3 gastrointestinal toxicity. The 4-year local control rate was 88.4% (95% CI 87.5–88.5%). Conclusions Neoadjuvant chemoradiotherapy delivered with HT under daily image guidance is well tolerated and shows a high 4-year local control rates.

Objective Primary uterine leiomyosarcomas (ULMS) are rare, and the optimal treatment is controversial. We aimed to assess the outcome and prognostic factors in a multicenter population of women treated for primary ULMS. Methods We retrospectively collected data of 110 women treated in 19 institutions of the Rare Cancer Network (RCN). Inclusion criteria consisted of a pathology report confirming the diagnosis of ULMS, aged 18-80 years, complete International Federation of Gynecology and Obstetrics (FIGO) stage information, complete information on treatment, and a minimum follow-up of 6 months. Local control (LC) and locoregional control (LRC), overall survival (OS) and disease-free survival (DFS) rates were computed using the Kaplan-Meier method. Univariate analysis was implemented using the log rank test, and multivariate analysis using the Cox model. Results All patients underwent surgery. Seventy-five patients (68%) received adjuvant radiotherapy (RT), including brachytherapy in 18 (16%). Seventeen patients (15%) received adjuvant chemotherapy. Median follow-up was 58 (range, 6-240) months. Five-year OS and DFS rates were 50% and 34%, and LC and LRC rates were 88% and 72%, respectively. On multivariate analysis, independent favorable prognostic factors were younger age, FIGO stage I, small tumor size, previous uterine disease, and no vascular invasion for OS and DFS. FIGO stage was the only favorable factor influencing LRC. Adjuvant local or systemic treatments did not improve the outcomes. Eight patients treated with RT presented a grade 3 acute toxicity, and only one patient with grade 3 late toxicity. Conclusions In this large population of primary ULMS patients, we found good results in terms of LC and LRC. Nevertheless, OS remains poor, mainly due to the occurrence of distant metastases. An early diagnosis seemed to improve the prognosis of the patients. Adjuvant local or systemic treatments, or more aggressive surgical procedures such as the Wertheim procedure, did not seem to impact the outcome.

We report the first known instance of the clinical use of 99mTc-mebrofenin hepatobiliary scintigraphy (HBS) for the optimization of radiotherapy treatment planning and for the follow-up of acute toxicity in a patient undergoing stereotactic body radiation therapy for hepatocellular carcinoma. In our experience, HBS allowed the identification and the sparing of more functioning liver areas, thus potentially reducing the risk of radiation-induced liver toxicity.

New imaging modalities may be useful to identify prostate cancer patients with small volume, limited nodal relapse ("oligo-recurrent") potentially amenable to local treatments (radiotherapy, surgery) with the aim of long-term control of the disease, even in a condition traditionally considered prognostically unfavorable. This report reviews the new diagnostic tools and the main published data about the role of surgery and radiation therapy in this particular subgroup of patients. © 2013 Elsevier Ireland Ltd.

Radiotherapy (RT) has an established role in the postoperative treatment of prostate cancer patients with extracapsular extension, positive surgical margins or a detectable post-operative prostate-specific antigen (PSA). Despite the large number of patients treated with postoperative RT, some issues about optimal technique, doses, volumes, timing and association with androgen deprivation are still subject of debate. The aim of this survey was to determine the patterns of choice of Italian radiation oncologists in two different clinical cases of postoperative prostate cancer patients.During the 2010 National Congress of the Italian Association of Radiation Oncology (AIRO), four clinical cases were presented to the attending radiation oncologists. Two of them were cases of postoperative prostate cancer, differing in T stage of the primary tumour according to the TNM classification, preoperative staging procedures, preoperative PSA (iPSA), Gleason score of biopsies and definitive pathological specimen after surgery and postoperative PSA. For each clinical case, the radiation oncologists were asked to: (a) give indication to new pre-treatment procedures for staging; b) give indication to postoperative treatment; (c) to define specifically, where indicated, the total dose, type of fractionation, treatment volumes, type of technique, type of image-guided setup control; (d) indicate whether adjuvant hormonal therapy should be prescribed; (e) define criteria that mostly influenced the prescription. A descriptive statistical analysis was then performed.A total of 300 questionnaires were distributed amongst radiation oncologists attending the congress; 128 were completed and considered for this analysis (41%). Some important differences were shown in prescribing and performing postoperative radiotherapy, and some significant differences with international guidelines and data available from the literature were also reviewed and discussed.Despite the results of clinical trials, significant differences still exist among Italian radiation oncologists in deciding postoperative treatment in prostate cancer patients. These patients probably deserve a more uniform approach based on updated, detailed and evidence-based recommendations.

Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. Background: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. Objective: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. Design: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. Setting: Online Delphi survey and consensus conference. Participants: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. Outcome measurements and statistical analysis: Statements were ranked by experts according to their level of agreement: 1–3 (disagree), 4–6 (equivocal), 7–9 (agree). A priori (level 1) consensus was defined as 70% agreement and 15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). Results and limitations: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. Conclusions: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach, The authors would like to thank Peter E. Clark from Atrium Health, Levine Cancer Institute, Charlotte, NC, USA, for his contribution to the Delphi survey. Angela Corstorphine of Kstorfin Medical Communications Ltd provided medical writing support with the preparation of this manuscript; this support was funded jointly by EAU and ESMO.

Introduction: Stereotactic ablative radiotherapy (SABR) has been shown to increase survival in oligometastatic disease, but local control of colorectal metastases remains poor. We aimed to identify potential predictive factors of SBRT response through a multicenter large retrospective database and to investigate the progression to the polymetastatic disease (PMD). Material and methods: The study involved 23 centers, and was approved by the Ethical Committee (Prot. Negrar 2019-ZT). 1033 lung metastases were reported. Clinical and biological parameters were evaluated as predictive for freedom from local progression-free survival (FLP). Secondary end-point was the time to the polymetastatic conversion (tPMC). Results: Two-year FLP was 75.4%. Two-year FLP for lesions treated with a BED < 00 Gy, 100–124 Gy, and ≥125 Gy was 76.1%, 70.6%, and 94% (p = 0.000). Two-year FLP for lesion measuring ≤10 mm, 10–20 mm, and >20 mm was 79.7%, 77.1%, and 66.6% (p = 0.027). At the multivariate analysis a BED ≥125 Gy significantly reduced the risk of local progression (HR 0.24, 95%CI 0.11–0.51; p = 0.000). Median tPMC was 26.8 months. Lesions treated with BED ≥125 Gy reported a significantly longer tPMC as compared to lower BED. The median tPMC for patients treated to 1, 2–3 or 4–5 simultaneous oligometastases was 28.5, 25.4, and 9.8 months (p = 0.035). Conclusion: The present is the largest series of lung colorectal metastases treated with SABR. The results support the use of SBRT in lung oligometastatic colorectal cancer patients as it might delay the transition to PMD or offer relatively long disease-free period in selected cases. Predictive factors were identified for treatment personalization.

PURPOSE/OBJECTIVE(S): stereotactic ablative radiotherapy (SABR) has been shown to increase survival rates in oligometastatic disease (OMD), but local control of colorectal metastases still remains poor. We aimed to identify potential predictive factors of SBRT response through a multicenter large retrospective database and to investigate how lung SBRT can impact on the progression to the polymetastatic disease (PMD). MATERIALS/METHODS: the study involved 22 centers, and was approved by the Ethical Committee (Prot. Negrar 2019-ZT). 1023 lung metastases treated with SBRT in 622 patients were reported. The median BED was 105 Gy10. Lesion diameter GTV, PTV volume, dose, fractionations, and site of primary tumor were evaluated as potential predictive marker for SBRT response for the primary end-point local progression-free survival (LPFS). EGFR, KRAS, NRAS, BRAF, and MSI were also evaluated. Secondary end-point was the time to the polymetastatic conversion (ttPMC). RESULTS: the median follow-up was 26 months (range 3-117 months). The median lesion diameter was 13 mm (range 4-58 mm). The 2- and 3-year LPFS were 75.6% and 71%, respectively. At the univariate analysis, BED ≥125Gy10 was associated with improved LPFS (2-year: 94.1% versus 72.6%; P = < 0.0001), single fraction SBRT correlated with better LPFS in the overall population (2-year: 80.6% versus 73.7%; P = 0.03), but no significant difference was observed when considering the population treated with BED > 100 Gy10. Lesion diameter ≤19 mm correlated with improved LPFS (2-year 80% versus 60%; P = < 0.0001). The median ttPMC was 26 months, and the 2-year ttPMC was 54.5%. The median PFS was 11.3 months. After SABR, 36% patients had polymetastatic relapse, 39.5% patients had an oligometastatic relapse, and 24.5% patients had no further relapse. CONCLUSION: the present is the largest series of lung colorectal metastases treated with SABR. The results support the use of SBRT in lung oligometastatic colorectal cancer patients as it might delay the transition to PMD or offer relatively long disease-free period in selected cases. Several biological and clinical predictive factors were identified to assure the highest local control, on the basis of which a decisional algorithm will be derived.

Anal squamous cell carcinoma (SCC) is a rare tumor, and bio-humoral predictors of response to chemo-radiation (CT-RT) are lacking. We developed a prognostic score system based on laboratory inflammation parameters. We investigated the correlation between baseline clinical and laboratory variables and disease-free (DFS) and overall (OS) survival in anal SCC patients treated with CT-RT in five institutions. The bio-humoral parameters of significance were included in a new scoring system, which was tested with other significant variables in a Cox’s proportional hazard model. A total of 308 patients was included. We devised a prognostic model by combining baseline hemoglobin level, SII, and eosinophil count: the Hemo-Eosinophils Inflammation (HEI) Index. We stratified patients according to the HEI index into low- and high-risk groups. Median DFS for low-risk patients was not reached, and it was found to be 79.5 months for high-risk cases (Hazard Ratio 3.22, 95% CI: 2.04–5.10, p &lt, 0.0001). Following adjustment for clinical covariates found significant at univariate analysis, multivariate analysis confirmed the HEI index as an independent prognostic factor for DFS and OS. The HEI index was shown to be a prognostic parameter for DFS and OS in anal cancer patients treated with CT-RT. An external validation of the HEI index is mandatory for its use in clinical practice.

The European SocieTy for Radiation and Oncology -Advisory Committee on Radiation Oncology Practice (ESTRO-ACROP) endorsed a project to provide guidelines (GL) for the identification and delineation of clinically negative lymph-nodal stations (LNs) involved in upper gastrointestinal clinical scenarios. The presented GL is focused on preoperative (or definitive) setting. The project aim is to improve the consistency of clinical target volume (CTV) delineation by providing: a description of the anatomical boundaries of the LNs; a radiological computed tomography-based atlas depicting the LNs areas; a free, web-based, interactive example case for independent training of radiation oncologists on LNs delineation according to the presented GL, by both qualitative and quantitative analysis (through the FALCON EduCase platform). This project was carried out with the intention to facilitate and improve uniformity of future upper gastrointestinal guidelines on nodal CTV delineation. We report methodology and results from the collaboration of a working group panel selected by the ESTRO-ACROP. ispartof: RADIOTHERAPY AND ONCOLOGY vol:164 pages:92-97 ispartof: location:Ireland status: published

The authors regret that a co-author was mistakenly missed from the authorship. The following co-author should have been included in the authorship: Peter-Paul M. Willemse Department of Oncological Urology, University Medical Center, Utrecht Cancer Center, Utrecht, The Netherlands

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.

Small cell lung cancer (SCLC) is relative rare histology in lung cancer patients. The standard treatment, in patients with an intra-thoracic disease, is represented by the use of concurrent chemo-radiotherapy; while patients with early SCLC stage, surgical resection could be recommended. Stereotactic body radiotherapy (SBRT) is a recently introduced technique allowing the delivery of very high radiation doses to limited target volumes and it is considered the standard approach in the treatment of not operable stage I Non Small-Cell Lung Cancer (NSCLC). The successful role option of SBRT in early NSCLC in terms of local control and toxicity profile opened the issue in the use of this approach in early stage small cell lung cancer (SCLC). Aim of this review is to discuss the current literature in the safety and efficacy of SBRT in the treatment of patients with stage I SCLC.

Objective To perform a critical review focusing on the applicability in clinical daily practice of data from three randomized controlled trials (RCTs): SWOG 8794, EORTC 22911, and ARO/AUO 96-02. Methods and materials An analytical framework, based on the identified population, interventions, comparators, and outcomes (PICO) was used to refine the search of the evidence from the three large randomized trials regarding the use of radiation therapy after prostatectomy as adjuvant therapy (ART). Results With regard to the inclusion criteria: (1) Population: in the time since they were designed, in two among three trial (SWOG 8794 and EORTC 22911) patients had a detectable PSA at the time of randomization, thus representing de facto a substantial proportion of patients who eventually received salvage RT (SRT) at non-normalised PSA levels rather than ART. (2) Interventions: although all the trials showed the benefit of postoperative ART compared to a wait-and-see approach, the dose herein employed would be now considered inadequate; (3) Comparators: the comparison arm in all the 3 RCTs was an uncontrolled observation arm, where patients who subsequently developed biochemical failure were treated in various ways, with up to half of them receiving SRT at PSA well above 1 ng/mL, a level that would be now deemed inappropriate; (4) Outcomes: only in one trial (SWOG 8794) ART was found to significantly improve overall survival compared to observation, with a ten-year overall survival rate of 74% vs. 66%, although this might be partly the result of imbalanced risk factors due to competing event risk stratification. Conclusions ART has a high level of evidence due to three RCTs with at least 10-year follow-up recording a benefit in biochemical PFS, but its penetrance in present daily clinics should be reconsidered. While the benefit of ART or SRT is eagerly expected from ongoing randomized trials, a dynamic risk-stratified approach should drive the decisions making process.

Currently, androgen deprivation therapy (ADT) has a well-defined role when administered together with radiotherapy (RT): neo-adjuvant and concurrent combination for intermediate risk-disease and adjuvant therapy for high risk disease. Evidence of this association was generated by randomized trials designed and led approximately 30 years ago; thus the question which arises is how relevant and portable are these data in our current clinical practice? In the present review, we examine the pitfalls of these published randomized controlled trials, their relevance to present daily clinics, where high-dose external beam RT or brachytherapy is applied, as well as the adoption of ADT in patients with concomitant cardiovascular disorders. © 2014 Elsevier Ireland Ltd. All rights reserved.

In the last decades, new technologies have been introduced in the daily clinical practice of the radiation oncologist: 3D-Conformal radiotherapy (RT) became almost universally available, thereafter, intensity modulated RT (IMRT) gained large diffusion, due to its potential impact in improving the clinical outcomes, and more recently, helical and volumetric arc IMRT with image-guided RT are becoming more and more diffused and used for prostate cancer patients. The conventional dose-fractionation results to be the best compromise between the efficacy and the safety of the treatment, but combining new techniques, modern RT allows to overcame one of the major limits of the 'older' RT: the impossibility of delivering higher total doses and/or high dose/fraction. The evidences regarding radiobiology, clinical and technological evolution of RT in prostate cancer have been reported and discussed.

The recent paper by Gandaglia et al. evaluated the 8-year cancer specific mortality (CSM) associated with Intensity Modulated Radiation Therapy (IMRT) in 19064 patients with prostate cancer (PCa) [1]. Their complex and elegant matched pair analysis compares 9532 patients treated with IMRT and 9532 patients submitted to initial observation in the period 2001-2007. The authors conclude that IMRT is associated with lower CSM, but this gain is observed only in high risk group patients. These results are somewhat analogous to the effect seen for surgery over watchful waiting especially in non-low risk patients, recently reported by Bill-Axelsson et al [2]. The major interest of this article is that it is the first published study clearly showing better CSM for PCa patients treated with IMRT. The message brought to the scientific community via a highly accessed oncology journal sounds like a positive input in favour of the use of radiotherapy over observation in PCa patients, particularly if delivered with the modern technique of IMRT. Up to now, no randomized controlled phase III trials comparing IMRT against observation or older radiotherapy techniques are available. The absence of randomised data does not imply the absence of evidence: indeed other forms of comparative effectiveness research such as the proposed propensity-matched population-based analysis using SEER-Medicare database can inform clinical practice as well, provided that this methodology adhere to strict criteria. We believe that the comparisons herein discussed present some important limitations which might have affected the proposed title and conclusions. Firstly, the prescribed radiation dose was not reported and it was not included as covariate in statistical analysis. This information has always a crucial role in the interpretation of the results of studies concerning radiotherapy, in particular for high risk PCa, where higher doses are needed and recommended [3]. IMRT is a sophisticated technique allowing dose escalation, while maintaining equal (or reducing) toxicity, when compared to standard 3-dimensional conformal technique [4,5]. The absence of any information about dose prescription, when IMRT is the key point of the data interpretation, makes impossible to discern whether improved outcomes are related to IMRT by itself, rather than its inherently associated capability of allowing dose escalation. Secondly, 52.6% of the IMRT population also received androgen deprivation therapy (ADT, vs 26.4% in the observation group), but no further data as the duration time, the type of drug and the category risk of patients receiving it are reported. Moreover, ADT was not considered as covariate in statistical evaluation. ADT has already showed a major impact on the overall survival of intermediate and high risk PCa [3], and then it could potentially influence the results, in particular for the population that seem to benefit from IMRT. This is a crucial factor able to

Radical external-beam radiotherapy (EBRT) is a standard treatment for prostate cancer (PC) patients. Despite this, the rate of intraprostatic relapses after primary EBRT is still not negligible. There is no consensus on the most appropriate management of these patients after EBRT failure. Treatment strategies after PC relapse are strongly influenced by the effective site of the tumor recurrence, and thus the instrumental evaluation with different imaging techniques becomes crucial. In cases of demonstrated intraprostatic failure, several systemic (androgen deprivation therapy) or local (salvage prostatectomy, cryotherapy, high-intensity focused ultrasound, brachytherapy, stereotactic EBRT) treatment options could be proposed and are currently delivered by clinicians with a variety of results. In this review we analyze the correct definition of intraprostatic relapse after radiotherapy, focusing on the recent developments in imaging to detect intraprostatic recurrence. Furthermore, all available salvage treatment options after a radiation therapy local failure are presented and thoroughly discussed.

To analyse the impact of age and co-morbidities on compliance and outcomes in GBM patients enrolled in three prospective phase II trials. GBM patients (≥ 18 years) were treated with radiotherapy (60 Gy) or enrolled in a Fractionated Stereotactic Conformal-Radiotherapy Phase II trial (69.4 Gy). Concomitant and adjuvant chemotherapy with Temozolomide (TMZ) was administered. Charlson Index Co-morbidity (CCI) was used to assess co-morbidity. Toxicity was evaluated according to RTOG score. Survival analysis was performed by the Kaplan-Maier. Influence of age and co-morbidity was evaluated using log-rank test. From 2001 to 2008, 146 patients were enrolled: 56 (38.4 %) aged over 65 and 90 under 65. CCI ≥ 1 was observed in 41 % of elderly and 22 % of young group. Patients' compliance was 97.9 % for radio-chemotherapy. Acute toxicity was mild with no difference between the groups. Global median progression-free survival (PFS) and overall survival (OS) were 12 and 18 months, respectively. Age, surgery and radiation dose correlated with survival (p = 0.01, p = 0.04 and p = 0.03). CCI ≤ 2 did not show any influence on OS. Our data show that elderly with a good performance status and few co-morbidity may be treated as younger patients; moreover, age confirms a negative impact on survival while CCI ≤ 2 did not correlated with OS.