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.

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.

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.

Feasibility and Acceptability of Office-Based Polypectomy With a 16F Mini-Resectoscope: A Multicenter Clinical Study.

STUDY OBJECTIVE: To investigate the feasibility and acceptability of office hysteroscopic polypectomy using a novel continuous-flow operative 16F mini-resectoscope. DESIGN: Multicenter prospective case series (Canadian Task Force classification III). SETTING: "SS Antonio e Biagio" Hospital, Alessandria, and University "Federico II" of Naples. PATIENTS: One hundred eighty-two patients with endometrial polyps. INTERVENTIONS: Hysteroscopic polypectomy performed with 16F mini-resectoscope in an office setting, without analgesia and/or anesthesia. MEASUREMENTS AND MAIN RESULTS: Polypectomy was successfully performed in 175 patients in a single surgical step (96.15%), with only 1 patient (.54%) requiring a second office surgical step to complete the surgery. Seven patients (3.84%) were excluded from the analysis of operative parameters because of severe pelvic pain during the office procedure, which required a second inpatient surgical step. No major complications were recorded. CONCLUSION: Our findings demonstrate that removal of endometrial polyps using the 16F mini-resectoscope in an office setting is a feasible and safe surgical option. Outpatient see-and-treat polypectomy is an acceptable and effective alternative to inpatient resectoscopic polypectomy.

A safe method of vaginal longitudinal morcellation of bulky uterus with endometrial cancer in a bag at laparoscopy.

BACKGROUND: Total laparoscopic hysterectomy (TLH) is becoming an increasingly popular treatment in endometrial cancer. Intra-abdominal or vaginal uterus morcellation are well described and routinely practiced techniques in removing a benign bulky uterus but contraindicated in endometrial cancer. In malignancy, the uterus needs to be removed intact to avoid intraperitoneal spillage of the endometrial cancer cells, and a uterine size of 12 gestational weeks (g.w.) or larger has been considered a contraindication for the laparoscopic approach. The aim of our study was to evaluate the feasibility and safety of a sealed vaginal morcellation technique in a bag for endometrial cancer laparoscopic treatment. METHODS: We prospectively scheduled 12 patients affected by endometrial cancer with uterus bigger than 12 g.w. for endometrial cancer laparoscopic treatment. After performing TLH, a sterile plastic wrapping bag was inserted by a 12 mm camera port by rolling it onto the blunt probe. The uterus was covered from the fundus to the cervix, placing the free edges of the bag down into the manipulator cup with two blunt graspers. The specimen completely covered by the bag was then pushed down under direct laparoscopic vision through colpotomy and pulled out from the vagina. The uterus was morcellated by the vaginal route. RESULTS: All patients underwent laparoscopic treatment with vaginal uterine morcellation. The mean uterus weight was 290.8 ± 79.7 g with a mean morcellation operative time of 12.1 min. All vaginal morcellations were completed successfully. All patients were without evidence of local or distant recurrence at the median follow-up time of 18 months. CONCLUSIONS: This technique allows the surgeon to morcellate a bulky uterus in cases of endometrial cancer and reduces the chance of neoplastic cell spillage during debulking at TLH. Vaginal morcellation following oncologic rules permits a rapid uterine extraction and may avoid a number of unnecessary laparotomies.

Primary Malignant Melanoma of The Endocervix Uteri and Outpatient Hysteroscopy as a Diagnostic Tool: Case Report and Literature Overview.

Mucosal malignant melanoma has a low incidence and only 2% are diagnosed in the gynecological tract. Diagnosis of primary cervical malignant melanoma is often challenging. The clinical presentation mimics other malignant cervical tumors, usually with abnormal bleeding or discharge. Cervical screening tests, such as cytology, often fail to detect malignant melanomas because of the rarity of the disorder, and histological evaluation of lesions is of paramount importance. The treatment is often based on regimens used for cutaneous malignant melanoma. We present the first case in the literature of primary malignant melanoma of the endocervix diagnosed by outpatient hysteroscopy and we have performed a narrative review of the literature on PubMed, Scopus and Web of Science from 1980 to December 2023, identifying 137 cases. The most common initial symptom was vaginal bleeding in 82.8% of cases, and 84.8% of patients were menopausal at the time of diagnosis. The first diagnostic modality was biopsy in 67.7%; 90% of patients underwent surgery and 64.5% of the deaths occurred within the first 12 months after diagnosis. Primary malignant melanoma of the cervix is extremely rare and difficult to diagnose at an early stage which is due to the aggressiveness of the disease and the non-specificity of the symptoms. To improve survival, early diagnosis is essential and hysteroscopy could be a useful tool in achieving it. It is crucial to increase the attention of gynecologists on primary malignant melanoma of the cervix to also perform a diagnostic hysteroscopy in case of doubtful symptoms.

New mini-resectoscope: analysis of preliminary quality results in outpatient hysteroscopic polypectomy.

PURPOSE: We investigated the feasibility and acceptability of office hysteroscopic polypectomy using a new continuous-flow operative 16 Fr Gubbini's mini-resectoscope. This is a prospective clinical study (Canadian Task Force classification III). METHODS: The office hysteroscopic polypectomy was performed with a mini-resectoscope without analgesia or anesthesia. We evaluated the polyp size and the number, the effectiveness of resection, the operating time, the pelvic pain and complications. RESULTS: The office hysteroscopic polypectomy was successfully performed in all 33 patients. The polyps ranged in size from 5 to 50 mm with a mean of 18.15 ± 11.45 mm. We analyzed the operating time with a mean of 11.45 ± 4.71 min: 29 procedures took less than 15 min from the start of vaginoscopy to the end of surgery. Overall mean visual analog scale (VAS) calculated was 2.48 ± 1.37 (range 0-6). The correlation between the size of the polyps and operating time was statistically significant (p < 0.001). No major complications were recorded. CONCLUSION: Our preliminary data demonstrated that can be possible to remove endometrial polyps by hysteroscopy, using the mini-resectoscope, in an office setting. All procedures were completed successfully and well tolerated with a little discomfort permitting the removal also of big sized polyps without a statistical correlation between VAS and size of polyps or operating time. The outpatient polypectomy is a less-costing procedure and represents an acceptable and effective alternative to inpatient resectoscopic polypectomy, leading to a complete polyp excision in nearly all patients.

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.

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.

DTI and PWI analysis of peri-enhancing tumoral brain tissue in patients treated for glioblastoma.

To analyse the role of MR diffusion-tensor imaging (DTI) and perfusion-weighted imaging (PWI) in characterising tumour boundaries in patients with glioblastoma multiforme. Seventeen patients with surgically treated WHO IV grade gliomas who were candidates for adjuvant chemo-radiotherapy were enrolled. Before (T0) and after radiation treatment (T1), they underwent DTI and PWI, and the apparent diffusion coefficient (ADC), fractional anisotropy (FA) and relative cerebral blood volume (rCBV) in the enhancing tumour, the hyperintense tissue adjacent to the enhancing tumour, and the normal-appearing white matter (NAWM) adjacent to the hyperintense areas were analysed. The enhancing tissue at T1 was retrospectively divided on the basis of whether or not it was also enhancing at T0. The controls were the corresponding contralateral areas, on which we normalized the rCBV values, calculating the rCBV ratio. In NAWM, we did not find any significant differences in FA, ADC or rCBV. In the hyperintense perilesional regions, FA was significantly lower and ADC significantly higher than in the unaffected contralateral tissue; there were no significant differences in the rCBV maps. The values of FA, ADC and rCBV in enhancing neoplastic tissue were all significantly different from those observed in the contralateral tissue. There was no significant difference in rCBV values between the areas enhancing at T0 and those not enhancing at T0 but enhancing at T1, which may indicate the neoplastic transformation of apparently normal brain tissue. DTI metrics identify ultrastructural changes in hyperintense perilesional areas, but these are not specific for neoplastic tissue. rCBV seemed to reflect an ultrastructural alteration that was not visible at T0, but became visible (as neoplastic progression) on conventional MR images at T1. These findings could help identify tissue at risk of tumour infiltration.

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.

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.

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.

Psychosexual well-being in women using oral contraceptives containing drospirenone.

Considerable advances have been made in hormonal contraception in recent years, geared at maximizing compliance and minimizing discontinuation. In oral contraceptive (OC) formulations, the estrogenic component, generally ethinyl estradiol (EE), has been reduced significantly and newer progestins like dienogest and drospirenone (DRSP), compounds with different molecular structures, have been introduced; in addition, new regimens (extended, flexible, 24/4 formats instead of the standard 21/7 format) and innovative delivery systems (vaginal rings, transdermal patches, subcutaneous implants and intrauterine devices) are available. The multitude of choices allows hormonal contraception to be tailored to the individual woman in order to obtain non-contraceptive benefits, without significant side effects, and also a favorable risk/benefit profile for her general and reproductive health. Over the past few years, new OC formulations combining DRSP (3 mg), a unique progestin with both antimineralocorticoid and antiandrogenic activities, with estrogen (30 mcg or 20 mcg EE), in two regimens (24/4 and 21/7) of active pills in a 28-day cycle, have shown positive effects on water retention-related weight gain and physical, emotional and psychosexual well-being. It seems likely that the use of a low-dose, well-balanced OC and the shorter 4-day hormone-free interval may minimize the side effects that can impair quality of life and thus increase women's compliance with hormonal contraception therapy.

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.