The Use of Methotrexate and Mifepristone for Treatment of Interstitial Pregnancies: An Overview of Effectiveness and Complications.

Interstitial pregnancy is an unusual and potentially life-threatening form of ectopic pregnancy, accounting for approximately 1-6% of all ectopic pregnancies, with a maternal mortality rate of 2-2.5%. Implantation happens in the proximal portion of the fallopian tube as it passes through the myometrium. The resolution of interstitial pregnancy after medical treatment should be assessed by a decline in serum ß-hCG, which occurs in about 85-90% of cases. Nonetheless, its effectiveness and consequences have been presented through case reports and case series. However, few cases of interstitial pregnancies treated totally medically with the use of methotrexate and mifepristone have been presented in the literature. Complications of this medical treatments have also never been reviewed before. In the present manuscript, we present a case of interstitial pregnancy treated with methotrexate and mifepristone. The patient after treatment developed a uterine arteriovenous malformation, treated with uterine artery embolization. Furthermore, we performed a systematic review of the literature using Scopus, PubMed and Google Scholar. A total of 186 papers were found, and 7 papers which included 10 cases were assessed for eligibility. The systemic medical treatment with the use of methotrexate and mifepristone was effective in 7 of the 10 cases. Two cases of hemoperitoneum following combined methotrexate and mifepristone treatment were reported. The applicability of this medical conservative treatment should be tailored to the patient, taking into account their obstetric history, gestational age at diagnosis and desire for future pregnancies. Complete resolution after this treatment was achieved in most of the cases reported without major complications. The appearance of uterine arteriovenous malformation can be managed conservatively, and we propose uterine artery embolization as an effective treatment of this rare complication.

IROCA-TES: Improving Quality in Radiation Oncology through Clinical Audits - Training and Education for Standardization.

Background: Clinical audits are an important tool to objectively assess clinical protocols, procedures, and processes and to detect deviations from good clinical practice. The main aim of this project is to determine adherence to a core set of consensus- based quality indicators and then to compare the institutions in order to identify best practices. Materials and methods: We conduct a multicentre, international clinical audit of six comprehensive cancer centres in Poland, Spain, Italy, Portugal, France, and Romania as a part of the project, known as IROCATES (Improving Quality in Radiation Oncology through Clinical Audits - Training and Education for Standardization). Results: Radiotherapy practice varies from country to country, in part due to historical, economic, linguistic, and cultural differences. The institutions developed their own processes to suit their existing clinical practice. Conclusions: We believe that this study will contribute to establishing the value of routinely performing multi-institutional clinical audits and will lead to improvement of radiotherapy practice at the participating centres.

Urinary toxicity in patients treated with radical EBRT for prostate cancer: Analysis of predictive factors in an historical series.

AIM AND BACKGROUND: The present study aims to identify predictive factors for urinary toxicity and self-reported symptoms after external beam radiotherapy (EBRT) for prostate cancer. METHODS: Two-hundred and eighty patients treated with EBRT for prostate cancer were included in the present study. Toxicity was scored following the grading system based on Radiation Therapy Oncology Group (RTOG) scale. International Prostatic Symptom Score (IPSS) and Consultation on Incontinence Questionnaires - Short Form (ICIQ-SF) were used to analyse self-reported symptoms. Acute and late urinary toxicities were correlated to clinical and treatment parameters, radiation dosimetry data, IPSS and ICIQ-SF. RESULTS: Median patient age was 74 years (range, 64-83). Thirty-one percent experienced acute G1 urinary toxicity, 24% G2 and 3% G3. Fourteen percent experienced G1 late urinary toxicity and 3% G2. Bladder volume<200 cc was associated with acute urinary toxicity (P=0.014); use of MRI for treatment planning allowed a lower incidence of late toxicity (P=0.062) and use of IMRT allowed for reduced incidence in late toxicity (P=0.038). Maximum bladder dose correlated with late urinary toxicity (P=0.014). The analysis of self-reported symptoms showed a significant correlation between IPSS baseline values (P=0.009), presence of nocturia (P=0.002), bladder urgency (P=0.024) and incontinence (P=0.024) and development of acute urinary toxicity at univariate analysis. At multivariate logistic regression analysis, bladder filling, IPSS value, nocturia, and urinary incontinence retained significant correlation with acute toxicity (P=0.0003). DISCUSSION: Significant independent predictors for acute urinary toxicity grade≥2 were bladder filling, IPSS value, nocturia, and urinary incontinence at baseline assessment.

Effect of the structural features of biobased linear polyester plasticizers on the crystallization of polylactides.

This work presents, for the first time, a detailed report on how the nucleation and crystallization of polylactide (PLLA) are affected by biobased aliphatic polyesters plasticizers. Three biobased polyesters were synthesized via solvent-free two-stage melt polycondensation of adipic acid (AdA) with three different biobased aliphatic diols and used as plasticizers for poly (L-lactic acid) (PLLA). The molecular structure of the synthesized polyesters was proved using 1H NMR, 13C NMR and Fourier transform infrared (FTIR) spectroscopy. PLLA/AdA-based blends containing 10 wt% of the polyester plasticizers were studied by tensile tests, dynamic mechanical analysis (DMA), wide-angle x-ray scattering (WAXS), differential scanning calorimetry (DSC) and polarized light optical microscopy (PLOM). Adding the plasticizers to PLLA decreased Tg by up to 11 °C and significantly increased the elongation at break by about 8 times compared with neat PLLA. The addition of 10 wt% of any AdA-based plasticizer to PLLA increases the nucleation rate from the glassy state by around 50-110 % depending on the plasticizer. The overall crystallization rate from the glassy state was 2-3 times faster for the plasticized PLLAs than neat PLLA. These results are a consequence of the lower energy barrier for both nucleation and growth processes. The incorporation of AdA-based linear polyesters had an incremental impact on the crystal growth rate (or secondary nucleation) of PLLA spherulites from the melt and glassy states. In conclusion, the AdA-based aliphatic polyesters allowed to enhance PLLA crystallization rates and showed interesting potential for the formulation of fully biobased PLLA blends.

Variation in Body Mass and Skeletal Muscle Indices in Head and Neck Cancer Patients Undergoing (Chemo)Radiotherapy and Nutritional Intervention.

The aim of this study was to analyze variation in body mass index (BMI) and skeletal muscle index (SMI) in head and neck squamous cell carcinoma (HNSCC) patients who underwent exclusive radiotherapy (RT) or concurrent chemo-radiotherapy (RT-CHT). We enrolled 73 HNSCC pts treated with definitive or post-operative RT (14 pts) or RT-CHT (59 pts). At the time of diagnosis (t0) and 3 months after treatment completion (t3), CT scans were retrieved to measure skeletal muscle at the level of the C3 vertebra. Median follow-up was 16 months. Nine disease progressions with distant metastases and eleven local relapses were observed. Fifty-three pts were free from progression at 1 year. At t0, average BMI was 25.8 (SD 4.1), while at t3 it was 24.5, with no reduction in 54 pts. A BMI decrease of −1.3 (p-value < 0.0001) between t0 and t3 was found with the Wilcoxon signed-rank test. SMI was 57.1 and 59.2 at t0 and t3, respectively (p-value = 0.005). According to our analysis, SMI variation seems to reflect the effect of an appropriate nutritional intervention and may represent a reliable, simple tool for muscle mass analysis.

Targeted Next-Generation Sequencing for the Identification of Genetic Predictors of Radiation-Induced Late Skin Toxicity in Breast Cancer Patients: A Preliminary Study.

Normal tissue radiosensitivity is thought to be influenced by an individual's genetic background. However, the specific genetic variants underlying the risk of late skin reactions following radiotherapy for breast cancer remain elusive. To unravel the genetic basis for radiation-induced late skin toxicity, we carried out targeted next-generation sequencing of germline DNA samples from 48 breast cancer patients with extreme late skin toxicity phenotypes, consisting of 24 cases with grade 2-3 subcutaneous fibrosis and/or grade 2-3 telangiectasia (LENT-SOMA scales) and 24 controls with grade 0 fibrosis and grade 0 telangiectasia. In this exploratory study, a total of five single-nucleotide variants (SNVs) located in three genes (TP53, ERCC2, and LIG1) reached nominal levels of statistical significance (p < 0.05). In the replication study, which consisted of an additional 45 cases and 192 controls, none of the SNVs identified by targeted NGS achieved nominal replication. Nevertheless, TP53 rs1042522 (G > C, Pro72Arg) in the replication cohort had an effect (OR per C allele: 1.52, 95%CI: 0.82-2.83, p = 0.186) in the same direction as in the exploratory cohort (OR per C allele: 4.70, 95%CI: 1.51-14.6, p = 0.007) and was found be nominally associated to the risk of radiation-induced late skin toxicity in the overall combined cohort (OR per C allele: 1.79, 95%CI: 1.06-3.02, p = 0.028). These results raise the possibility of an association between TP53 rs1042522 and risk of radiation-induced late skin toxicity in breast cancer patients; however, large replication studies are warranted for conclusive evidence.

Results of the IROCA international clinical audit in prostate cancer radiotherapy at six comprehensive cancer centres.

To assess adherence to standard clinical practice for the diagnosis and treatment of patients undergoing prostate cancer (PCa) radiotherapy in four European countries using clinical audits as part of the international IROCA project. Multi-institutional, retrospective cohort study of 240 randomly-selected patients treated for PCa (n = 40/centre) in the year 2015 at six European hospitals. Clinical indicators applicable to general and PCa-specific radiotherapy processes were evaluated. All data were obtained directly from medical records. The audits were performed in the year 2017. Adherence to clinical protocols and practices was satisfactory, but with substantial inter-centre variability in numerous variables, as follows: staging MRI (range 27.5-87.5% of cases); presentation to multidisciplinary tumour board (2.5-100%); time elapsed between initial visit to the radiation oncology department and treatment initiation (42-102.5 days); number of treatment interruptions ≥ 1 day (7.5-97.5%). The most common deviation from standard clinical practice was inconsistent data registration, mainly failure to report data related to diagnosis, treatment, and/or adverse events. This clinical audit detected substantial inter-centre variability in adherence to standard clinical practice, most notably inconsistent record keeping. These findings confirm the value of performing clinical audits to detect deviations from standard clinical practices and procedures.

A randomized clinical study on the impact of Comprehensive Geriatric Assessment (CGA) based interventions on the quality of life of elderly, frail, onco-hematologic patients candidate to anticancer therapy: protocol of the ONCO-Aging study.

BACKGROUND: Age is considered as one of the most important risk-factor for many types of solid and hematological cancers, as their incidence increases with age in parallel to the ever-growing elderly population. Moreover, cancer incidence is constantly increasing as a consequence of the increase in life expectancy that favors the process of cellular senescence. Geriatric assessment has been increasingly recognized as predictive and prognostic instrument to detect frailty in older adults with cancer. In particular, the G8 score is a simple and reproducible instrument to identify elderly patients who should undergo full geriatric evaluation. Due to their frailty, elderly patients may be often under-treated and a therapeutic choice based also on a comprehensive geriatric assessment (CGA) is recommended. With these premises, we aim to test the impact of the CGA based interventions on the quality of life (QoL) of frail elderly onco-hematological patients, identified by the G8 screening, candidate for innovative target directed drugs or treatments including the combination of radiotherapy and chemotherapy (RT + CT). METHODS: Patients aged > 65 years, candidate to target directed agents or to RT + CT treatments are screened for frailty by the G8 test; those patients classified as frail (G8 ≤ 14) are randomized to receive a CGA at baseline or to conventional care. The primary endpoint is QoL, assessed by EORTC QLQ-C30C. As collateral biological study, the potential prognostic/predictive role of T-cell senescence and myeloid derived suppressor cells (MDSC) are evaluated on plasma samples. DISCUSSION: This trial will contribute to define the impact of CGA on the management of frail elderly onco-hematologic patients candidate to innovative biological drugs or to integrated schedules with the association of RT + CT. Furthermore, the use of plasma samples to assess the potential prognostic value of imbalance of immune-competent cells is expected to contribute to the individualized care of elderly patients, resulting into a fine tuning of the therapeutic strategies. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04478916 . registered July 21, 2020 - retrospectively registered.

Multicentre clinical radiotherapy audit in rectal cancer: results of the IROCA project.

PURPOSE: To perform a clinical audit to assess adherence to standard clinical practice for the diagnosis, treatment, and follow-up of patients undergoing radiotherapy for rectal cancer treatment in four European countries. MATERIALS AND METHODS: Multi-institutional, retrospective cohort study of 221 patients treated for rectal cancer in 2015 at six European cancer centres. Clinical indicators applicable to general radiotherapy processes were evaluated. All data were obtained from electronic medical records. RESULTS: The audits were performed in the year 2017. We found substantial inter-centre variability in adherence to standard clinical practices: 1) presentation of cases at departmental clinical sessions (range, 0-100%) or multidisciplinary tumour board (50-95%); 2) pretreatment MRI (61.5-100%) and thoracoabdominal CT (15.0-100%). Large inter-centre differences were observed in the mean interval between biopsy and first visit to the radiotherapy department (range, 21.6-58.6 days) and between the first visit and start of treatment (15.1-38.8 days). Treatment interruptions ≥ 1 day occurred in 43.9% (2.5-90%) of cases overall. Treatment compensation was performed in 2.1% of cases. Treatment was completed in the prescribed time in 55.7% of cases. CONCLUSIONS: This multi-institutional clinical audit revealed that most centres adhered to standard clinical practices for most of the radiotherapy processes-related variables assessed. However, the audit revealed marked inter-centre variability for certain quality indicators, particularly inconsistent record keeping. Multiple targets for improvement and/or harmonisation were identified, confirming the value of routine clinical audits to detect potential deviations from standard clinical practice.

Automatic genetic planning for volumetric modulated arc therapy: A large multi-centre validation for prostate cancer.

PURPOSE: The first clinical genetic autoplanning algorithm (Genetic Planning Solution, GPS) was validated in ten radiotherapy centres for prostate cancer VMAT by comparison with manual planning (Manual). METHODS: Although there were large differences among centres in planning protocol, GPS was tuned with the data of a single centre and then applied everywhere without any centre-specific fine-tuning. For each centre, ten Manual plans were compared with autoGPS plans, considering dosimetric plan parameters and the Clinical Blind Score (CBS) resulting from blind clinician plan comparisons. AutoGPS plans were used as is, i.e. there was no patient-specific fine-tuning. RESULTS: For nine centres, all ten plans were clinically acceptable. In the remaining centre, only one plan was acceptable. For the 91% acceptable plans, differences between Manual and AutoGPS in target coverage were negligible. OAR doses were significantly lower in AutoGPS plans (p < 0.05); rectum D15% and Dmean were reduced by 8.1% and 17.9%, bladder D25% and Dmean by 5.9% and 10.3%. According to clinicians, 69% of the acceptable AutoGPS plans were superior to the corresponding Manual plan. In case of preferred Manual plans (31%), perceived advantages compared to autoGPS were minor. QA measurements demonstrated that autoGPS plans were deliverable. A quick configuration adjustment in the centre with unacceptable plans rendered 100% of plans acceptable. CONCLUSION: A novel, clinically applied genetic autoplanning algorithm was validated in 10 centres for in total 100 prostate cancer patients. High quality plans could be generated at different centres without centre-specific algorithm tuning.

Apoptotic and predictive factors by Bax, Caspases 3/9, Bcl-2, p53 and Ki-67 in prostate cancer after 12 Gy single-dose.

Radio-induced apoptosis is mediated by the activation of tumor protein p53, Bax and caspases. The purpose of this study was to investigate the early activation of this pathway in men receiving in vivo irradiation immediately before radical prostatectomy for locally advanced prostate cancer. We also investigated cell proliferation index (Ki-67), proto-oncogene (p53) and anti-apoptotic protein (Bcl-2) levels as potential predictive factors. We selected a homogeneous sample of 20 patients with locally advanced prostate cancer and candidate to radical prostatectomy. To assess the apoptotic pathways, Bax, is studied through immunofluorescence assay, before and after 12 Gy single dose intraoperative radiotherapy (IORT) to the prostate, on bioptic samples and on surgical specimens. Moreover, before and after IORT, Bcl-2, p53, and Ki-67 were also detected through immunohistochemistry. A count of positive Bax spots for immunofluorescence was performed on tumor cells, prostatic intraepithelial neoplasia (PIN), and healthy tissue areas before and after IORT. We also analyzed Caspases 3 and 9 expressions after IORT. Before IORT, Bcl-2 mean value in neoplastic cells was 2.23% ± 1.95, mean Ki-67 in neoplastic area was 4.5% ± 3.8, and p53 was 22.5% ± 6.8. After IORT, Bcl-2 mean value in neoplastic cells was 8.85 ± 8.92%, Ki-67 in neoplastic area was 7.8 ± 6.09%, and p53 was 24.9 ± 26.4%. After the irradiation, healthy areas expressed significantly lower levels of Bax (2.81 ± 1.69%) with respect to neoplastic cells (p < 0.0001), while in PIN areas, Bax positive cells were significantly more present than in neoplastic areas (p = 0.0001). At statistical analysis, it was observed that cancer cells with Ki-67 ≥ 8% had a trend toward greater expression of Bax (p = 0.0641). We observed an increase of Bcl-2 expression after IORT in neoplastic areas (p = 0.0041). Biopsy specimens with p53 ≥ 18% and Ki-67 ≥ 8% had worse post-operative staging with extracapsular invasion (p = 0.04 for both parameters) and nodal positivity (p = 0.04 for p53 and p = 0.0001 at pathology for ki-67). No correlation between IORT and Caspases activation was noted. In conclusion, after 12 Gy IORT, Bax was overexpressed in tumor and PIN cells. Pre-operative Ki-67 and p53 definition could be used in future studies to predict patients with worse pathological stage, while Bcl-2 activation after IORT might be a predictive factor for loco-regional failure.

Impact of ATM rs1801516 on late skin reactions of radiotherapy for breast cancer: Evidences from a cohort study and a trial sequential meta-analysis.

The relationship between the ataxia-telangiectasia mutated (ATM) rs1801516 gene polymorphism and risk of radiation-induced late skin side effects remains a highly debated issue. In the present study, we assessed the role of ATM rs1801516 as risk factor for radiation-induced fibrosis and telangiectasia, using the LENT-SOMA scoring scale in 285 breast cancer patients who received radiotherapy after breast conserving surgery. A systematic review with meta-analysis and trial sequential analysis (TSA) was then conducted to assess reliability of the accumulated evidence in breast cancer patients. In our cohort study, no association was found between ATM rs1801516 and grade ≥ 2 telangiectasia (GA+AA vs GG, HRadjusted: 0.699; 95%CI: 0.273-1.792, P = 0.459) or grade ≥ 2 fibrosis (GA+AA vs GG, HRadjusted: 1.175; 95%CI: 0.641-2.154, P = 0.604). Twelve independent cohorts of breast cancer patients were identified through the systematic review, of which 11 and 9 cohorts focused respectively on the association with radiation-induced fibrosis and radiation-induced telangiectasia. Pooled analyses of 10 (n = 2928 patients) and 12 (n = 2783) cohorts revealed, respectively, no association of ATM rs1801516 with radiation-induced telangiectasia (OR: 1.14; 95%CI: 0.88-1.48, P = 0.316) and a significant correlation with radiation-induced fibrosis (OR: 1.23; 95%CI: 1.00-1.51, P = 0.049), which however did not remain significant after TSA adjustment (TSA-adjusted 95%CI: 0.85-1.78). These results do not support an impact of ATM rs1801516 on late skin reactions of radiotherapy for breast cancer, nevertheless further large studies are still required for conclusive evidences.

Outcomes of music therapy interventions in cancer patients-A review of the literature.

BACKGROUND: Effectiveness of music-based interventions (MI) on cancer patients' anxiety, depression, pain and quality of life (QoL) is a current research theme. MI are highly variable, making it challenging to compare studies. OBJECTIVE AND METHODS: To summarize the evidence on MI in cancer patients, 40 studies were reviewed following the PRISMA statement. Studies were included if assessing at least one outcome among anxiety, depression, QoL and pain in patients aged ≥ 18, with an active oncological/onco-haematological diagnosis, participating to any kind of Music Therapy (MT), during/after surgery, chemotherapy or radiotherapy. RESULTS: A positive effect of MI on the outcomes measured was supported. Greater reductions of anxiety and depression were observed in breast cancer patients. MI involving patients admitted to a hospital ward were less effective on QoL. CONCLUSION: The increasing evidence about MI effectiveness, tolerability, feasibility and appreciation, supports the need of MI implementation in Oncology, Radiotherapy and Surgery wards, and promotion of knowledge among health operators.

Improving radiation oncology through clinical audits: Introducing the IROCA project.

As radiotherapy practice and processes become more complex, the need to assure quality control becomes ever greater. At present, no international consensus exists with regards to the optimal quality control indicators for radiotherapy; moreover, few clinical audits have been conducted in the field of radiotherapy. The present article describes the aims and current status of the international IROCA "Improving Radiation Oncology Through Clinical Audits" project. The project has several important aims, including the selection of key quality indicators, the design and implementation of an international audit, and the harmonization of key aspects of radiotherapy processes among participating institutions. The primary aim is to improve the processes that directly impact clinical outcomes for patients. The experience gained from this initiative may serve as the basis for an internationally accepted clinical audit model for radiotherapy.

Intraoperative radiotherapy in gynaecological and genito-urinary malignancies: focus on endometrial, cervical, renal, bladder and prostate cancers.

Intraoperative radiotherapy (IORT) refers to the delivery of a single radiation dose to a limited volume of tissue during a surgical procedure. A literature review was performed to analyze the role of IORT in gynaecological and genito-urinary cancer including endometrial, cervical, renal, bladder and prostate cancers.Literature search was performed by Pubmed and Scopus, using the words "intraoperative radiotherapy/IORT", "gynaecological cancer", "uterine/endometrial cancer", "cervical/cervix cancer", "renal/kidney cancer", "bladder cancer" and "prostate cancer". Forty-seven articles were selected from the search databases, analyzed and briefly described.Literature data show that IORT has been used to optimize local control rate in genito-urinary tumours mainly in retrospective studies. The results suggest that IORT could be advantageous in the setting of locally advanced and recurrent disease although further prospective trials are needed to confirm this findings.

DNA Methyltransferase Gene Polymorphisms for Prediction of Radiation-Induced Skin Fibrosis after Treatment of Breast Cancer: A Multifactorial Genetic Approach.

PURPOSE: This study was conducted to investigate the role of four polymorphic variants of DNA methyltransferase genes as risk factors for radiation-induced fibrosis in breast cancer patients. We also assessed their ability to improve prediction accuracy when combined with mitochondrial haplogroup H, which we previously found to be independently associated with a lower hazard of radiation-induced fibrosis. MATERIALS AND METHODS: DNMT1 rs2228611,DNMT3A rs1550117,DNMT3A rs7581217, and DNMT3B rs2424908 were genotyped by real-time polymerase chain reaction in 286 Italian breast cancer patients who received radiotherapy after breast conserving surgery. Subcutaneous fibrosis was scored according to the Late Effects of Normal Tissue-Subjective Objective Management Analytical (LENT-SOMA) scale. The discriminative accuracy of genetic models was assessed by the area under the receiver operating characteristic curves (AUC). RESULTS: Kaplan-Meier curves showed significant differences among DNMT1 rs2228611 genotypes in the cumulative incidence of grade ≥ 2 subcutaneous fibrosis (log-rank test p-value= 0.018). Multivariate Cox regression analysis revealed DNMT1 rs2228611 as an independent protective factor for moderate to severe radiation-induced fibrosis (GG vs. AA; hazard ratio, 0.26; 95% confidence interval [CI], 0.10 to 0.71; p=0.009). Adding DNMT1 rs2228611 to haplogroup H increased the discrimination accuracy (AUC) of the model from 0.595 (95% CI, 0.536 to 0.653) to 0.655 (95% CI, 0.597 to 0.710). CONCLUSION: DNMT1 rs2228611 may represent a determinant of radiation-induced fibrosis in breast cancer patients with promise for clinical usefulness in genetic-based predictive models.

Three-dimensional surface and ultrasound imaging for daily IGRT of prostate cancer.

BACKGROUND: Image guided radiotherapy (IGRT) is an essential pre-requisite for delivering high precision radiotherapy. We compared daily variation detected by two non-ionizing imaging modalities (surface imaging and trans-abdominal ultrasound, US) to verify prostate patient setup and internal organ variations. METHODS: Forty patients with organ confined prostate cancer and candidates to curative radiotherapy were enrolled in this prospective study. At each treatment session, after laser alignment, all patients received imaging by a 3D-surface and a 3D-US system. The shifts along the three directions (anterior-posterior AP, cranial-caudal CC, and later-lateral LL) were measured in terms of systematic and random errors. Then, we performed statistical analysis on the differences and the possible correlations between the two modalities. RESULTS: For both IGRT modalities, surface imaging and US, 1318 acquisitions were collected. According with Shapiro Wilk test, the positioning error distributions were not Gaussian for both modalities. The differences between the systematic errors detected by the two modalities were statistically significant only in LL direction (p < 0.05), while the differences between the random errors were not statistically significant in any directions. The 95% confidence interval of the residual errors obtained by subtracting the random errors detected with surface images to those detected with US was included in the range from -7 mm to 7 mm corresponding to the minimum PTV margin adopted in AP direction in our clinical routine. CONCLUSIONS: From our data, it emerges that setup misalignments measured by surface imaging can be predictive of US displacements after the adjustment for systematic errors. Moreover, surface imaging can detect setup errors predictive of registration errors measured by US. This data suggest that the two IGRT modalities could be considered as complementary to each other and could represent a daily "low-cost" and non-invasive IGRT modality in prostate cancer patients.

Patient selection for partial breast irradiation by intraoperative radiation therapy: can magnetic resonance imaging be useful?-perspective from radiation oncology point of view.

The guidelines of the European and American Societies of Radiation Oncology (GEC-ESTRO and ASTRO) defined the selection criteria to offer partial breast irradiation (PBI) after lumpectomy in patients with low risk breast cancer regardless pre-operative staging. A recent publication by Tallet et al. explored the impact of preoperative magnetic resonance imaging (MRI) on patient eligibility for PBI. From their study, an ipsilateral BC was detected in 4% of patients, excluding these patients from intraoperative radiotherapy (IORT). The authors suggested that preoperative MRI should be used routinely for patient's candidate to IORT, because of the rate of ipsilateral breast cancer detected. In view of Tallet's article, we analyzed some aspects of this issue in order to envisage some possible perspective on how to better identify those patients who could benefit from PBI, especially using IORT. From historical studies, the risk of breast cancer recurrence outside index quadrant without irradiation is in the range of 1.5-3.5%. MRI sensitivity for detection of invasive cancer is reported up to 100%, and it is particularly useful in dense breast. Other imaging technique did not achieve the same sensibility and specificity as conventional MRI. Of note, none of randomized trials published and ongoing on PBI included preoperative MRI as part of staging. To perform a preoperative MRI in PBI setting is an interesting issue, but the available data suggest that this issue should be preferably studied in the setting of prospective clinical trials to clarify the role of MRI and the clinical meaning of the discovered additional foci.

Hypofractionated radiation therapy for breast cancer: long-term results in a series of 85 patients.

PURPOSE: Whole-breast irradiation after conservative surgery is the standard treatment for early breast cancer. The purpose of this study is to report the late toxicity, cosmetic result, and disease control in a group of patients treated with hypofractionated radiotherapy (RT) comparing results with retrospective data of a control group who underwent conventional RT. METHODS: From 2006 to 2008, 85 patients were treated with hypofractionated schedule to dose of 45 Gy, 2.25 Gy/fr, followed by a boost. We evaluated late toxicity, cosmetic result, and disease control. The data were compared to a control group of 70 patients who underwent conventional RT before 2006. RESULTS: At 8 years of follow-up, the cumulative incidence of late skin toxicity was 6.2 in the hypofractionated RT group and 7.5 in the standard RT group (p = 0.94). The cumulative incidence of late subcutaneous tissue toxicity was 11.6 in the hypofractionated RT group and 18.7 in the standard RT group (p = 0.23). Cosmetic outcome was rated as excellent or good in 84/85 patients of the hypofractionated RT group and in 68/70 patients of the conventional RT group (p = 0.7). No statistically significant differences were found in terms of local control (p = 0.05), disease-free survival (p = 0.06), or overall survival (p = 0.17) between the 2 groups. CONCLUSIONS: The present analysis, focused on long-term effects, disease control, and survival, confirms, in a daily practice setting, the low incidence of skin atrophy and fibrosis, the satisfactory cosmetic outcome, and the high grade of local and distant disease control with hypofractionated schedule.