The Radiation Therapy Technology Evidence Matrix: a framework to visualize evidence development for innovations in radiation therapy.

Clinical evidence is crucial in enabling the judicious adoption of technological innovations in radiation therapy (RT). Pharmaceutical evidence development frameworks are not useful for understanding how technical advances are maturing. In this paper, we introduce a new framework, the Radiation Therapy Technology Evidence Matrix (rtTEM), that helps visualize how the clinical evidence supporting new technologies is developing. The matrix is a unique 2D model based on the R-IDEAL clinical evaluation framework. It can be applied to clinical hypothesis testing trials, as well as publications reporting clinical treatment. We present the rtTEM and illustrate its application, using emerging and mature RT technologies as examples. The model breaks down the type of claim along the vertical axis and the strength of the evidence for that claim on the horizontal axis, both of which are inherent in clinical hypothesis testing. This simplified view allows for stakeholders to understand where the evidence is and where it is heading. Ultimately, the value of an innovation is typically demonstrated through superiority studies, which we have divided into three key categories - administrative, toxicity and control, to enable more detailed visibility of evidence development in that claim area. We propose the rtTEM can be used to track evidence development for new interventions in RT. We believe it will enable researchers and sponsors to identify gaps in evidence and to further direct evidence development. Thus, by highlighting evidence looked for by key policy decision makers, the rtTEM will support wider, timely patient access to high value technological advances.

Local Control Following Stereotactic Body Radiation Therapy for Liver Oligometastases: Lessons from a Quarter Century.

The utilization of stereotactic body radiation therapy for the treatment of liver metastasis has been widely studied and has demonstrated favorable local control outcomes. However, several predictive factors play a crucial role in the efficacy of stereotactic body radiation therapy, such as the number and size (volume) of metastatic liver lesions, the primary tumor site (histology), molecular biomarkers (e.g., KRAS and TP53 mutation), the use of systemic therapy prior to SBRT, the radiation dose, and the use of advanced technology and organ motion management during SBRT. These prognostic factors need to be considered when clinical trials are designed to evaluate the efficacy of SBRT for liver metastases.

Structure of the Motor Descending Pathways Correlates with the Temporal Kinematics of Hand Movements.

The projection system, a complex organization of ascending and descending white matter pathways, is the principal system for conveying sensory and motor information, connecting frontal and sensorimotor regions with ventral regions of the central nervous system. The corticospinal tract (CST), one of the principal projection pathways, carries distal movement-related information from the cortex to the spinal cord, and whether its microstructure is linked to the kinematics of hand movements is still an open question. The aim of the present study was to explore how microstructure of descending branches of the projection system, namely the hand motor tract (HMT), the corticospinal tract (CST) and its sector within the internal capsule (IC), can relate to the temporal profile of reaching and reach-to-grasp movements. Projection pathways of 31 healthy subjects were virtually dissected by means of diffusion tractography and the kinematics of reaching and reach-to-grasp movements were also analyzed. A positive association between Hindrance Modulated Orientation Anisotropy (HMOA) and kinematics was observed, suggesting that anisotropy of the considered tract can influence the temporal unfolding of motor performance. We highlight, for the first time, that hand kinematics and the visuomotor transformation processes underlying reaching and reach-to-grasp movements relate to the microstructure of specific projection fibers subserving these movements.

Brain metastases from primary colorectal cancer: is radiosurgery an effective treatment approach? Results of a multicenter study of the radiation and clinical oncology Italian association (AIRO).

OBJECTIVES: The prognosis of brain metastatic colorectal cancer patients (BMCRC) is poor. Several local treatments have been used, but the optimal treatment choice remains an unresolved issue. We evaluated the clinical outcomes of a large series of BMCRC patients treated in several Italian centers using stereotactic radiosurgery (SRS). METHODS: 185 BMCRC patients for a total of 262 lesions treated were evaluated. Treatments included surgery followed by post-operative SRS to the resection cavity, and SRS, either single-fraction, then hypofractionated SRS (HSRS). Outcomes was measured in terms of local control (LC), toxicities, brain distant failure (BDF), and overall survival (OS). Prognostic factors influencing survival were assed too. RESULTS: The median follow-up time was 33 months (range 3-183 months). Surgery plus SRS have been performed in 28 (10.7%) cases, SRS in 141 (53.8%), and HSRS in 93 (35.5%). 77 (41.6%) patients received systemic therapy. The main total dose and fractionation used were 24 Gy in single fraction or 24 Gy in three daily fractions. Local recurrence occurred in 32 (17.3%) patients. Median, 6 months,1-year-LC were 86 months (95%CI 36-86), 87.2% ± 2.8, 77.8% ± 4.1. Median,6 months,1-year-BDF were 23 months (95%CI 9-44), 66.4% ± 3.9, 55.3% ± 4.5. Median,6 months,1-year-OS were 7 months (95% CI 6-9), 52.7% ± 3.6, 33% ± 3.5. No severe neurological toxicity occurred. Stage at diagnosis, Karnofsky Performance Status (KPS), presence and number of extracranial metastases, and disease-specific-graded-prognostic-assessment (DS-GPA) score were observed as conditioning survival. CONCLUSION: SRS/HSRS have proven to be an effective local treatment for BMCRC. A careful evaluation of prognostic factors as well as a multidisciplinary evaluation is a valid aid to manage the optimal therapeutic strategy for CTC patients with BMs. ADVANCES IN KNOWLEDGE: The prognosis of BMCRC is poor. Several local treatments was used, but optimal treatment choice remains undefined. Radiosurgery has proven to be an effective local treatment for BMCRC. A careful evaluation of prognostic factors and a multidisciplinary evaluation needed.

Cisplatin plus capecitabine concomitant with intensity-modulated radiation therapy in non-metastatic anal squamous cell carcinoma: the experience of a single research cancer center.

BACKGROUND AND AIMS: The standard treatment of non-metastatic anal squamous cell carcinoma (ASCC) consists of chemotherapy with mitomycin (MMC) plus 5-fluorouracil (5FU) for 1-2 cycles concomitant with pelvic radiotherapy. Subsequent studies introduced cisplatin (CDDP) combined with 5FU, with unclear results. We evaluated the doublet capecitabine (C) and CDDP as a possible alternative to MMC-5FU regimen concomitant with intensity-modulated radiation therapy (IMRT). PATIENTS AND METHODS: We carried out a retrospective study on 67 patients affected by stage I-III ASCC, treated with CDDP (60-70 mg/m2 every 21 days for two courses) plus C (825 mg/m2 twice daily for 5 days/week) chemotherapy concomitant with IMRT for curative intent. RESULTS: At a median follow up of 41 months, the clinical complete response calculated at the 6-month time-point (6-moCR), the 6-month objective response rate and the 6-month disease control rate were 93%, 94%, and 99%, respectively.Disease-free survival rates at 1, 2, and 3 years were 89%, 87%, and 85%, while the overall survival rates at 1 and 2 years were 100% and 95%. The colostomy-free survival rates were 90% at 1 year and 88% at 2 years. Grade 3-4 acute adverse events were reported in 61% of patients; predominantly skin toxicity (46%) and limited hematological toxicity (12%). CONCLUSION: In this retrospective study, chemotherapy with C plus CDDP concomitant with IMRT proved safe and effective, and may represent a possible alternative option to standard MMC-containing regimen for curative intent.

Intensity-modulated radiotherapy (IMRT) in the treatment of squamous cell anal canal cancer: acute and early-late toxicity, outcome, and efficacy.

PURPOSE: To retrospectively review our experience on 84 patients with squamous cell anal canal cancer (SCAC) within 12 months after combined treatment with intensity-modulated RT (IMRT), in terms of acute and early-late toxicity, overall treatment time and interruptions, colostomy-free survival (CFS), and tumor response. METHODS: Acute gastrointestinal (GI), genitourinary (GU), and cutaneous (CU) toxicities were assessed according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03. Early-late toxicity was scored using the Radiation Therapy Oncology Group (RTOG) late radiation morbidity scoring system. Tumor response was evaluated with response evaluation criteria in solid tumors (RECIST) v1.1. RESULTS: Acute toxicity for 84 subjects (100%): severe (≥ G3) GI and skin toxicity was observed in 4 (5%) and 19 patients (23%), respectively. Early-late toxicity for 73 subjects (87%): severe (≥ G3) GI and vulvo-vaginal toxicity was observed in 2 (3%) and 2 (3%) patients, respectively. No acute or early-late severe GU toxicity was reported. A treatment interruption occurred in 65 patients (77%). CFS was 96% (95% CI 89-99) at 6 months and 92% (95% CI 83-96) at 12 months. At 6 months complete response (CR), partial response (PR) and progressive disease (PD) was observed in 70 (83%), 3 (4%), and 7 patients (8%), respectively. At 12 months, CR was observed in 60 patients (81%); eleven patients (15%) experienced PD. CONCLUSION: Our study showed an excellent clinical result and very low acute toxicity rates, confirming the IMRT as standard of care for curative treatment of anal cancer patients. The current trial was registered with the number IEO N87/11.

Long-Term Results and Reconstruction Failure in Patients Receiving Postmastectomy Radiation Therapy with a Temporary Expander or Permanent Implant in Place.

BACKGROUND: This study investigated the risk of reconstruction failure after mastectomy, immediate breast reconstruction, and radiotherapy to either a temporary tissue expander or permanent implant. METHODS: Records of women treated at a single institution between June of 1997 and December of 2011 were reviewed. Two patient groups were identified based on type of immediate breast reconstruction: tissue expander followed by exchange with a permanent implant and permanent implant. The study endpoint was rate of reconstruction failure, defined as a replacement, loss of the implant, or conversion to flap. RESULTS: The tissue expander/permanent implant and the permanent implant groups consisted of 63 and 75 patients, respectively. The groups were well balanced for clinical and treatment characteristics. With a median follow-up of 116 months, eight implant losses, 50 implant replacements, and four flap conversions were recorded. Reconstruction failure occurred in 22 of 63 patients in the expander/implant group and in 40 of 75 patients in the permanent implant group. A traditional proportional hazards model showed a higher risk of reconstruction failure for the expander/implant group (hazard ratio, 2.01) and a significantly shorter time to reconstruction failure compared with the permanent implant group (109.2 months versus 157.7 months; p = 0.03); however, according to a competing risk model, the between-groups cumulative incidences were not significantly different (hazard ratio, 1.09). CONCLUSIONS: Radiotherapy to either a tissue expander or a permanent implant presented a fairly large risk of reconstruction failure over time. The expander/implant group was not more likely to develop reconstruction failure compared to permanent implant group, but the timing of onset was shorter. More complex techniques should be investigated to lower the risk of reconstruction failure. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Intra- and inter-observer variability in breast tumour bed contouring and the controversial role of surgical clips.

The purpose of this study was to evaluate whether the visualization of surgical clips (SCs) on the same set of planning computed tomography (CT) of breast cancer (BC) patients influences agreement on tumour bed (TB) delineation. Planning CT (CTorig) of 47 BC patients with SCs to visualize the TB was processed in order to blur SCs and create a virtual CT (CTmod). Four radiation oncologists (ROs, 2 juniors and 2 seniors) contoured TB on both the CT sets. Centre of mass distance (CMD), percentage overlap as Dice similarity coefficient (DSC), surface distance as average Hausdorff distance (AHD) and TB volume size were analysed. The intra-observer variability when contouring TB with and without SCs was statistically significant (p-values = 0.016, 0.0002 and ≪ 0.001 for CMD, AHD and DSC, respectively). Junior ROs showed worse reproducibility compared to seniors. The median DSC was < 0.7. The inter-observer variability with and without SCs was statistically significant (p < 0.001) for all metrics, with an increase of 48.7% in DSC and decrease of 50.7% and 57.1% in CMD and AHD, respectively, as relative median values, when SCs were visible. Regarding TB volumes, when SCs were visible, the intra-observer analysis revealed that 3/4 ROs delineated larger volumes, especially juniors. The inter-observer analysis showed that, in presence of visible SCs, the difference in TB volume among all the ROs fell from statistically significant to borderline significance (p = 0.052). TB contouring is confirmed to be an observer-dependent task. SCs decreased the intra and inter-observer variability but the overall agreement between ROs remained low.

HALFMOON TomoTherapy (Helical ALtered Fractionation for iMplant partial OmissiON): implant-sparing post-mastectomy radiotherapy reshaping the clinical target volume in the reconstructed breast.

PURPOSE: To report the dosimetric feasibility of the radiation technique HALFMOON (Helical ALtered Fractionation for iMplant partial OmissiON) for post-mastectomy radiation therapy (PMRT) in intermediate-high-risk breast cancer patients with implant-based immediate breast reconstruction, where the clinical target volume (CTV) does not include the whole implant (implant-sparing approach). METHODS: In the HALFMOON technique, the CTV consisted of skin, subcutaneous tissues, and pectoralis major muscle, excluding the implant, chest wall muscles, and rib plane. The HALFMOON plans were compared with conventionally contoured CTV plans, in which the whole implant, chest wall muscles, and ribs plane were included in the CTV, in a ratio 1:3. All patients underwent hypofractionated treatment of 40.05 Gy/15 fractions, using helical Tomotherapy®. RESULTS: Eighteen patients undergoing HALFMOON technique were compared to 54 subjects treated with conventionally contoured CTV plans. No difference was found in the planning target volume coverage between the two groups. Conversely, a statistically relevant dose reduction in HALFMOON patients was observed for ipsilateral lung (D15%, p < 0.0001; D20%, p < 0.0001; D35%, p = 0.003), contralateral lung (D20%, p = 0.048), contralateral breast (D15%, p = 0.031; D20%, p = 0.047), and stomach (Dmean, p = 0.011). Regarding the implant, V90% and D50% decreased by 46% and 8%, respectively, in the HALFMOON plans (p < 0.0001). CONCLUSION: The HALFMOON approach is technically feasible and resulted in high-dose conformity of the target with a significant reduction of radiation dose delivered to implant and other organs. A clinical study is needed to assess the impact on reconstruction cosmetic outcome and local control.

Immune inflammation indicators in anal cancer patients treated with concurrent chemoradiation: training and validation cohort with online calculator (ARC: Anal Cancer Response Classifier).

Background: In anal cancer, there are no markers nor other laboratory indexes that can predict prognosis and guide clinical practice for patients treated with concurrent chemoradiation. In this study, we retrospectively investigated the influence of immune inflammation indicators on treatment outcome of anal cancer patients undergoing concurrent chemoradiotherapy. Methods: All patients had a histologically proven diagnosis of squamous cell carcinoma of the anal canal/margin treated with chemoradiotherapy according to the Nigro's regimen. Impact on prognosis of pre-treatment systemic index of inflammation (SII) (platelet x neutrophil/lymphocyte), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were analyzed. Results: A total of 161 consecutive patients were available for the analysis. Response to treatment was the single most important factor for progression-free survival (PFS) and overall survival (OS). At univariate analysis, higher SII level was significantly correlated to lower PFS (p<0.01) and OS (p=0.046). NLR level was significantly correlated to PFS (p=0.05), but not to OS (p=0.06). PLR level significantly affected both PFS (p<0.01) and OS (p=0.02). On multivariate analysis pre-treatment, SII level was significantly correlated to PFS (p=0.0079), but not to OS (p=0.15). We developed and externally validated on a cohort of 147 patients a logistic nomogram using SII, nodal status and pre-treatment Hb levels. Results showed a good predictive ability with C-index of 0.74. An online available calculator has also been developed. Conclusion: The low cost and easy profile in terms of determination and reproducibility make SII a promising tool for prognostic assessment in this oncological setting.

Ductal carcinoma in situ and intraoperative partial breast irradiation: Who are the best candidates? Long-term outcome of a single institution series.

AIMS: To report the long-term outcome of a single institution series of pure ductal carcinoma in situ (DCIS) treated with accelerated partial irradiation using intraoperative electrons (IOERT). METHODS: From 2000 to 2010, 180 DCIS patients, treated with quadrantectomy and 21 Gy IOERT, were analyzed in terms of ipsilateral breast recurrences (IBRs) and survival outcomes by stratification in two subgroups. The low-risk group included patients who fulfilled the suitable definition according to American Society of Radiation Oncology (ASTRO) Guidelines (size ≤2.5 cm, grade 1-2 and surgical margins ≥3 mm) (Suitable), while the remaining ones formed the high-risk group (Non-Suitable). RESULTS: Eighty-four and 96 patients formed the Suitable and Non-Suitable groups, respectively. In the whole population, the cumulative incidence of IBR at 5, 7 and 10 years was 19%, 21%, and 25%, respectively. In the Suitable group, the cumulative incidence of IBR remained constant at 11% throughout the years, while in the Non-Suitable group increased from 26% at 5 years to 36% at 10 years (p < 0.0001). When hormonal positivity and HER2 absence of expression were added to the selection of the Suitable group, the cumulative incidence of IBR dropped and stabilized at 4% at 10 years. None died of breast cancer. In the whole population, 5-year and 10-year overall survival rate was 98% and 96.5%, respectively, without any difference between the two groups. CONCLUSIONS: The overall and by group IBR rates were high and stricter criteria are required for acceptable local control for Suitable DCIS. Because of the concerns raised, IOERT should not be used in clinical practice.

Evaluation of supportive and barrier-protective skin care products in the daily prevention and treatment of cutaneous toxicity during systemic chemotherapy.

INTRODUCTION: The purpose of this multicenter, prospective, observational, open-label study was to evaluate the use and tolerability of dermo-cosmetic products in preventing skin reactions associated with cancer treatments. PATIENTS AND METHODS: A 12-product kit was supplied to patients before chemotherapy began and was to be used throughout the treatment phase. Cutaneous adverse events were evaluated at each treatment session. Physicians evaluated skin reactions (edema, erythema, dryness, desquamation, pigmentation disorders, and cracks) and gave their opinion on the skin benefit for patients at the end of the study. Patients also evaluated the product benefit using the Patient Benefit Index (PBI) questionnaire. Results were analyzed by subgroups of casual and regular users, based on number and frequency of products used. RESULTS: A total of 147 patients were enrolled in cancer services in Germany, France, Italy, Spain, and Canada. Mean age was 59 years with 71% being female. Product tolerance on whole body was rated good to excellent for at least 89% of the patients for each product. Aggravated skin reactions during the study were reported more frequently by casual users than regular users (39.5% versus 22%; p=0.029). Similarly, casual users reported more erythema aggravation (p=0.02) and desquamation (p=0.03) than regular users. PBI >1 was reported for 95.5% of patients and regular users had significantly higher scores than casual users (p=0.049). DISCUSSION: Overall, the 12-product kit was very well tolerated, with regular users reporting benefits more frequently than casual users. Results support international recommendations to use appropriate skin care products to minimize the impact of cutaneous reactions associated with chemotherapy.

Second pelvic recurrence of rectal cancer successfully treated with a re-reirradiation (3rd radiation course).

INTRODUCTION: In case of pelvic recurrence of colorectal cancer, reirradiation of previously irradiated patients may increase the rate of salvage radical resection. Due to the high cumulative dose, one of the main concerns is radiation-induced lumbosacral plexopathy. This report describes multiple irradiations of a lesion adjacent to the lumbosacral plexus, using a highly selective technique, which allows optimal sparing of such a critical structure. CASE DESCRIPTION: A 53-year-old woman treated in 2008 for a locally advanced rectal adenocarcinoma with preoperative pelvic irradiation and concomitant chemotherapy followed by surgery had disease recurrence in 2011 and underwent a second course of pelvic radiotherapy. In December 2015, magnetic resonance imaging showed a single local recurrence infiltrating the muscle next to the right lumbosacral plexus and close to the cauda equina. Repeat reirradiation was planned. The total dose deriving from the previous treatment plans was assessed by nonrigid image registration using the dedicated tool implemented in MIM 6.1.7 (MIMvista Corp., Cleveland, OH). The treatment was performed with Cyberknife (Accuray, Sunnyvale, CA) with a schedule of 20 Gy in 5 fractions (4 Gy per fraction). The dose was prescribed to 70% isodose and target coverage was 97%. Two months after the treatment, magnetic resonance imaging showed a decreased signal and stable disease with no change in tumor size. CONCLUSIONS: This case report suggests that pelvic re-reirradiation might be a possibility in very carefully selected cases of rectal cancer, using high-precision radiation modalities.

Cone-beam CT-based inter-fraction localization errors for tumors in the pelvic region.

PURPOSE: To evaluate inter-fraction tumor localization errors (TE) in the RapidArc® treatment of pelvic cancers based on CBCT. Appropriate CTV-to PTV margins in a non-IGRT scenario have been proposed. METHODS: Data of 928 patients with prostate, gynecological, and rectum/anal canal cancers were retrospectively analyzed to determine systematic and random localization errors. Two protocols were used: daily online IGRT (d-IGRT) and weekly IGRT. The latter consisted in acquiring a CBCT for the first 3 fractions and subsequently once a week. TE for patients who underwent d-IGRT protocol were calculated using either all CBCTs or the first 3. RESULTS: The systematic (and random) TE in the AP, LL, and SI direction were: for prostate bed 2.7(3.2), 2.3(2.8) and 1.9(2.2) mm; for prostate 4.2(3.1), 2.9(2.8) and 2.3(2.2) mm; for gynecological 3.0(3.6), 2.4(2.7) and 2.3(2.5) mm; for rectum 2.8(2.8), 2.4(2.8) and 2.3(2.5) mm; for anal canal 3.1(3.3), 2.1(2.5) and 2.2(2.7) mm. CTV-to-PTV margins determined from all CBCTs were 14 mm in the AP, 10 mm in the LL and 9-9.5 mm in the SI directions for the prostate and the gynecological groups and 9.5-10.5 mm in AP, 9 mm in LL and 8-10 mm in the SI direction for the prostate bed and the rectum/anal canal groups. If assessed on the basis of the first 3 CBCTs, the calculated CTV-to-PTV margins were slightly larger. CONCLUSIONS: without IGRT, large CTV-to-PTV margins up to 15 mm are required to account for inter-fraction tumor localization errors. Daily IGRT should be used for all hypo-fractionated treatments to reduce margins and avoid increased toxicity to critical organs.

Hypofractionated postmastectomy radiotherapy with helical tomotherapy in patients with immediate breast reconstruction: dosimetric results and acute/intermediate toxicity evaluation.

The aim of this study was to evaluate the dosimetry and toxicity of hypofractionation in postmastectomy radiotherapy (PMRT) with intensity-modulated radiotherapy (IMRT) in breast cancer (BC) patients. Stage II-III BC patients with implant-based immediate breast reconstruction received PMRT to the chest wall (CW) and to the infra/supraclavicular nodal region (NR) using a 15-fraction schedule (2.67 Gy/fraction) and helical IMRT (Tomotherapy® System, Accuray Incorporated, Sunnyvale, CA). A score was assigned to each treatment plan in terms of planning target volume (PTV) coverage of CW and NR and the sparing of the organs at risk (OARs). The total score for each plan was calculated. Toxicity was prospectively assessed according to validated scales. Data from 120 consecutive patients treated in the period 2012-2015 were analysed with a median follow-up from the end of radiotherapy of 13.2 months (range 0.0-35 months). 70.8% (85/120) of the plans had high total scores as a result of an optimal coverage of both CW and RN and optimal sparing of all OARs. The maximum acute toxicity was of grade 2 in 36.7% of the cases. Early late toxicity was mild in the majority of cases. In the study population, helical tomotherapy-based IMRT produced optimal treatment plans in most cases. Acute and late toxicity was mild/moderate. Hypofractionated helical IMRT appears to be safe and feasible in the moderate term for PMRT.

Atlas-based segmentation in breast cancer radiotherapy: Evaluation of specific and generic-purpose atlases.

OBJECTIVES: Atlas-based automatic segmentation (ABAS) addresses the challenges of accuracy and reliability in manual segmentation. We aim to evaluate the contribution of specific-purpose in ABAS of breast cancer (BC) patients with respect to generic-purpose libraries. MATERIALS AND METHODS: One generic-purpose and 9 specific-purpose libraries, stratified according to type of surgery and size of thorax circumference, were obtained from the computed tomography of 200 BC patients. Keywords about contralateral breast volume and presence of breast expander/prostheses were recorded. ABAS was validated on 47 independent patients, considering manual segmentation from scratch as reference. Five ABAS datasets were obtained, testing single-ABAS and multi-ABAS with simultaneous truth and performance level estimation (STAPLE). Center of mass distance (CMD), average Hausdorff distance (AHD) and Dice similarity coefficient (DSC) between corresponding ABAS and manual structures were evaluated and statistically significant differences between different surgeries, structures and ABAS strategies were investigated. RESULTS: Statistically significant differences between patients who underwent different surgery were found, with superior results for conservative-surgery group, and between different structures were observed: ABAS of heart, lungs, kidneys and liver was satisfactory (median values: CMD<2 mm, DSC≥0.80, AHD<1.5 mm), whereas chest wall, breast and spinal cord obtained moderate performance (median values: 2 mm ≤ CMD<5 mm, 0.60 ≤ DSC<0.80, 1.5 mm ≤ AHD<4 mm) and esophagus, stomach, brachial plexus and supraclavicular nodes obtained poor performance (median CMD≥5 mm, DSC<0.60, AHD≥4 mm). The application of STAPLE algorithm generally yields higher performance and the use of keywords improves results for breast ABAS. CONCLUSION: The homogeneity in the selection of atlases based on multiple anatomical and clinical features and the use of specific-purpose libraries can improve ABAS performance with respect to generic-purpose libraries.

From technological advances to biological understanding: The main steps toward high-precision RT in breast cancer.

Radiotherapy improves local control in breast cancer (BC) patients which increases overall survival in the long term. Improvements in treatment planning and delivery and a greater understanding of BC behaviour have laid the groundwork for high-precision radiotherapy, which is bound to further improve the therapeutic index. Precise identification of target volumes, better coverage and dose homogeneity have had a positive impact on toxicity and local control. The conformity of treatment dose due to three-dimensional radiotherapy and new techniques such as intensity modulated radiotherapy makes it possible to spare surrounding normal tissue. The widespread use of dose-volume constraints and histograms have increased awareness of toxicity. Real time image guidance has improved geometric precision and accuracy, together with the implementation of quality assurance programs. Advances in the precision of radiotherapy is also based on the choice of the appropriate fractionation and approach. Adaptive radiotherapy is not only a technical concept, but is also a biological concept based on the knowledge that different types of BC have distinctive patterns of locoregional spread. A greater understanding of cancer biology helps in choosing the treatment best suited to a particular situation. Biomarkers predictive of response play a crucial role. The combination of radiotherapy with molecular targeted therapies may enhance radiosensitivity, thus increasing the cytotoxic effects and improving treatment response. The appropriateness of an alternative fractionation, partial breast irradiation, dose escalating/de-escalating approaches, the extent of nodal irradiation have been examined for all the BC subtypes. The broadened concept of adaptive radiotherapy is vital to high-precision treatments.

Radiotherapy in the multidisciplinary treatment of liver cancer: a survey on behalf of the Italian Association of Radiation Oncology.

PURPOSE: To report the results of the first Italian survey investigating the role of liver-directed radiotherapy in the multidisciplinary approach of primary and metastatic liver cancer. MATERIALS AND METHODS: A 21-item, two-section questionnaire was sent to all Italian radiotherapy centers on June 2014. The two sections aimed at: (1) evaluating the presence of a multidisciplinary liver tumor board and describing the role of radiation oncologists within the latter, (2) analyzing Radiotherapy treatment details and differences between centers. RESULTS: A total of 37 centers completed the survey. A multidisciplinary liver tumor board was available in most centers (73 %), with a radiation oncologist routinely attending the latter in the majority of cases (85 %). Most of the respondents considered liver-directed Radiotherapy as the third line choice when other therapies were not indicated or technically suitable. 18 centers reported the use of liver-directed radiotherapy. The majority of centers started liver irradiation after 2010. The most adopted motion management strategy was abdominal compression. The most adopted GTV-CTV expansion was 0 and 5 mm for metastases and hepatocellular carcinoma, respectively. Stereotactic body radiotherapy was the technique of choice; several treatment schedules were registered, being 45 Gy in three fractions the most reported fractionation scheme. Dose was prescribed at the PTV margin in most cases. CONCLUSION: Liver-directed radiotherapy represents a new field of interest which is currently adopted by 10 % of all Italian Centers. The technical equipment seems adequate. The variations observed in the treatment regimens reflect the lack of a well-established standard schedule.

Nonrandomized comparison between concomitant and sequential chemoradiotherapy with anthracyclines in breast cancer.

PURPOSE: To evaluate the tolerance of concomitant administration of anthracycline-based chemotherapy (CHT) and 3-dimensional conformal radiotherapy (RT) after breast-conserving surgery. METHODS AND MATERIALS: Sixty-seven patients, treated with conservative surgery followed by 3-dimensional whole breast RT and concomitant CHT regimens including "Canadian modified" CEF (5-fluorouracil, epirubicin, cyclophosphamide) or AC (doxorubicin, cyclophosphamide) were evaluated for toxicity. They were compared in terms in compliance and acute toxicity with 67 patients irradiated sequentially after having received anthracyclines. RESULTS: Acute grade ≥2 skin toxicity was significantly higher in the concomitant group compared to the sequential group, although the incidence of Grade 3 desquamation showed no statistical difference (9% vs. 3%, p = 0.14). Haematological toxicity represented the main cause of treatment discontinuation, reporting higher rate of grade 3-4 leuco-neutropenia in the concomitant group (20.9% vs. 6%, p = 0.01). Mean RT duration was longer in the concomitant group (51 days vs. 45 days) owing to RT breaks. Late toxicity was acceptable. No symptomatic lung and heart events were reported. Radiological lung hyperdensity was detected in 27.7% of the patients in the concomitant group. Post-treatment left ventricular ejection fraction significantly decreased compared with baseline, but cardiac function remained within the normal range, without any difference between left or right-sided RT. CONCLUSIONS: Although there was more acute grade ≥2 skin toxicity in the concomitant group, the rate of grade 3 dermatitis was lower than expected, suggesting some advantages of 3-D CRT over older techniques. Haematological toxicity exerted a significant impact on both RT and CHT delivery.

Prognostic value of human papillomavirus in anal squamous cell carcinoma.

PURPOSE: Anal cancer is an uncommon malignancy, but its incidence is increasing worldwide. Chemoradiation is the standard primary treatment for patients with loco-regional limited disease. However, once patients develop metastatic spread, the prognosis is very poor. Human papillomavirus (HPV) is present in around 80 % of anal cancers, but its prognostic and/or predictive value is essentially unknown in this disease. METHODS: We retrospectively evaluated 50 patients with the diagnosis of anal squamous cell carcinoma treated at our institution with combined chemoradiotherapy for loco-regional limited disease. HPV status was evaluated from paraffin-embedded tumor tissues collected at the time of diagnosis by a polymerase chain reaction analysis. RESULTS: Among 50 patients, 42 (84 %) were HPV-positive. Thirty-two (64 %) patients were positive to genotype 16, two (4 %) to genotype 18, and three (6 %) to both 16 and 18. Lymph nodal involvement and clinical stage at diagnosis were more advanced for HPV-positive patients. After a median follow-up of 4 years (range 0.4-13.8), 46 (92 %) patients were alive. Overall, eight patients relapsed: One regional, one loco-regional, and six distant recurrences were observed. Four patients died of metastatic disease. Five-year disease-free survival (DFS) in HPV-positive and HPV-negative patients was 92.5 and 50.0 %, respectively (P < 0.01). In multivariate analysis, HPV-positivity was associated with a statistically significant better 5-year DFS (HR HPV+ vs HPV- 0.10; 95 % CI 0.02-0.50). Five-year overall survival in HPV-positive and HPV-negative patients was 93.3 and 66.7 %, respectively (P = 0.12). CONCLUSIONS: In our study, HPV-positive anal cancers had a statistically significant improved DFS compared to HPV-negative group.