Multi-omics staging of locally advanced rectal cancer predicts treatment response: a pilot study.

Treatment response assessment of rectal cancer patients is a critical component of personalized cancer care and it allows to identify suitable candidates for organ-preserving strategies. This pilot study employed a novel multi-omics approach combining MRI-based radiomic features and untargeted metabolomics to infer treatment response at staging. The metabolic signature highlighted how tumor cell viability is predictively down-regulated, while the response to oxidative stress was up-regulated in responder patients, showing significantly reduced oxoproline values at baseline compared to non-responder patients (p-value < 10-4). Tumors with a high degree of texture homogeneity, as assessed by radiomics, were more likely to achieve a major pathological response (p-value < 10-3). A machine learning classifier was implemented to summarize the multi-omics information and discriminate responders and non-responders. Combining all available radiomic and metabolomic features, the classifier delivered an AUC of 0.864 (± 0.083, p-value < 10-3) with a best-point sensitivity of 90.9% and a specificity of 81.8%. Our results suggest that a multi-omics approach, integrating radiomics and metabolomic data, can enhance the predictive value of standard MRI and could help to avoid unnecessary surgical treatments and their associated long-term complications.

Neuromuscular Electrical Stimulation for Intermittent Claudication (NESIC): multicentre, randomized controlled trial.

METHODS: This was an open, multicentre, randomized controlled trial. Patients with intermittent claudication attending vascular surgery outpatient clinics were randomized (1:1) to receive either neuromuscular electrical stimulation (NMES) or not in addition to local standard care available at study centres (best medical therapy alone or plus supervised exercise therapy (SET)). The objective of this trial was to investigate the clinical efficacy of an NMES device in addition to local standard care in improving walking distances in patients with claudication. The primary outcome was change in absolute walking distance, measured by a standardized treadmill test at 3 months. Secondary outcomes included intermittent claudication (IC) distance, adherence, quality of life, and haemodynamic changes. RESULTS: Of 200 participants randomized, 160 were included in the primary analysis (intention to treat, Tobit regression model). The square root of absolute walking distance was analysed (due to a right-skewed distribution) and, although adjunctive NMES improved it at 3 months, no statistically significant effect was observed. SET as local standard care seemed to improve distance compared to best medical therapy at 3 months (3.29 units; 95 per cent c.i., 1.77 to 4.82; P < 0.001). Adjunctive NMES improved distance in mild claudication (2.88 units; 95 per cent c.i., 0.51 to 5.25; P = 0.02) compared to local standard care at 3 months. No serious adverse events relating to the device were reported. CONCLUSION: Supervised exercise therapy is effective and NMES may provide further benefit in mild IC.This trial was supported by a grant from the Efficacy and Mechanism Evaluation Program, a Medical Research Council and National Institute for Health and Care Research partnership. Trial registration: ISRCTN18242823.

Patients with intermittent claudication experience pain in their legs during walking or exercise which ends with rest. This severely impairs physical activity and quality of life. Treatment for such patients typically involves best medical therapy, which includes exercise advice. This study aimed to determine whether a neuromuscular electrical stimulation device improved the walking distance of patients with intermittent claudication compared to local standard care available (which may include supervised exercise therapy) in a trial. Supervised exercise improved walking distances but there was no difference in those that received a device in this patient group.

Whole breast radiotherapy in cN0 early breast cancer patients with pathological sentinel lymph nodes (pN1mic, pN1a) without axillary dissection: preliminary results of the observational LISEN trial.

PURPOSE: Axillary management remains unclear when sentinel lymph node (SLN) results are positive in cN0 patients with breast cancer (BC). The trial ACOSOG Z0011 represented a revolution with axillary lymph node dissection (ALND) omission in SLN+ patients, despite critiques regarding non-uniformity of radiation fields. We conducted an observational study (LISEN) where whole breast radiotherapy (WBRT) was planned with tangential fields without nodal irradiation in patients eligible for the Z0011 trial. METHODS: Inclusion criteria were female patients with histologically proven BC, cT1-2cN0, planned conservative surgery, no neoadjuvant therapy. Patients were stratified into two groups: micrometastatic (pN1mic, group 1) and macrometastatic (pN1a, group 2) lymph nodes. Tangential field WBRT was mandatory. Clinical outcomes were analysed, measured from surgery until the first event. RESULTS: In all, 199 patients underwent conservative surgery and SLN biopsy; 133 patients meeting criteria were analysed: 41 patients (30.8%) pN1mic and 92 (69.2%) pN1a. The 5­year disease-free survival (DFS) was 95.0% (85.9-100%) in group 1 and 93.0% (86.3-100.0%) in group 2 (p = 0.78). Overall survival (OS) was 100% (100-100%) in group 1 and 97.4% (92.4-100%) in group 2 (p = 0.74). For the whole cohort DFS and OS were 93.6% (88.2-99.4%) and 96.9% (91.5-100.0%), respectively. For groups 1 and 2, the 5­year outcomes were 5.0% (0.0-14.4%) and 2.3% (0.0-6.1%) for local recurrence (p = 0.51), and 6.2% (0.0-17.4%) and 7.0% (0.0-13.7%) for distant metastasis (p = 0.61), respectively. In group 1, regional recurrence (RR) and local regional recurrence (LRR) were 5.0% (0.0-14.1%; p = 0.13). In group 2, RR and LRR were 0.0% (0.0-0.0%). CONCLUSION: Our results showed good regional control in patients who met the Z0011 trial criteria. WBRT, without nodal surgery or RT, avoiding axillary morbidity, seems to be a good choice.

May Measurement Month 2019: an analysis of blood pressure screening results from Nigeria.

The aim of this study is to estimate the frequency of undetected hypertension across the six geopolitical zones of Nigeria. We conducted an opportunistic screening of adults aged at least 18 years in the month of May 2019. Participants were recruited by trained volunteers using the May Measurement Month protocol. Blood pressure (BP) was measured using validated digital and mercury sphygmomanometers. We defined hypertension as BP ≥140/90 mmHg or the use of BP-lowering medication. A total of 3646 participants (52.8% females) with a mean age of 44.5 ± 15.7 years were screened. Hypertension was present in 39.2% of the participants but only 55. 4% of these were on antihypertensive medications. Only 46.8% hypertensives who were on medications had their BP controlled (<140/90 mmHg). Previous history of hypertension in pregnancy, alcohol intake and smoking were associated with increased mean systolic and diastolic BPs. The frequency of Nigerians with hypertension is high while only about half of those on antihypertensive medications are controlled. A multi-pronged approach to reduce the burden of hypertension is needed.

Cone-beam computed tomography for organ motion evaluation in locally advanced rectal cancer patients.

PURPOSE: Due to a reported dose-response relationship in rectal cancer radiotherapy, a greater interest in dose intensification on small boost volume arises. Considering the need of an appropriate target movements evaluation, this retrospective study aimed to use cone-beam computed tomography (CBCT) for GTV and mesorectum organ motion (OM) evaluation, in locally advanced rectal cancer (LARC) patients treated with neoadjuvant chemo-radiotherapy, in prone and supine position. METHODS: Thirty-two LARC patients were analyzed. GTV and mesorectum were delineated on MRI co-registrated with CT simulation. GTV and mesorectum OM was estimated on all CBCTs, performed during treatment, co-registrated with CT simulation. OM evaluation was obtained, as mean shift in left and right (L-R), postero-anterior (P-A) and cranio-caudal (Cr-C) directions. Volumes variability was calculated by DICE index. RESULTS: A total of 296 CBCTs were analyzed. Mean shifts of the GTV and mesorectum in prone position were - 0.16 cm and 0.15 cm in L-R direction, 0.28 cm and - 0.40 cm in P-A direction, and 0.14 cm and - 0.21 cm, in Cr-C direction; for supine position the mean shifts of the GTV were - 0.10 cm and 0.17 cm in R-L direction, 0.26 cm and - 0.23 cm in A-P direction, 0.09 cm and - 0.11 cm in Cr-C direction. Mean DICE index for GTV and mesorectum was 0.74 and 0.86, in prone position, and 0.78 and 0.89 in supine position, respectively. CONCLUSION: GTV and mesorectum OM was less than 4 mm in all directions in both positions, with a 1 mm less deviation in supine position. CBCTs resulted effective for OM assessment, and it could be an appropriate method for the implementation on an intensification treatment.

Role of upper abdominal reirradiation for gastrointestinal malignancies: a systematic review of cumulative dose, toxicity, and outcomes on behalf of the Re-Irradiation Working Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

PURPOSE: Abdominal recurrences of gastrointestinal malignancies are common. Evidence in clinical studies has shown that re-irradiation (Re-I) is tolerable and efficient in different tumor locations. In contrast, little clinical data are available on normal long-term Re­I tolerance doses. A systematic review of upper abdominal Re­I was performed with the aim of exploring the cumulative dose, toxicity, and outcomes. METHODS: A computerized search was undertaken in MEDLINE, EMBASE, OVID, and the Cochrane database. Only studies reporting toxicity and/or outcomes were taken into consideration. To improve the comparability of the different Re­I regimens and assess the relationship between Radiotherapy (RT) dose and toxicity, the equivalent dose in 2­Gy fractions was calculated according to the linear quadratic model. RESULTS: Sixteen studies met the inclusion criteria, with the total patients numbering 408. Median follow-up Re­I ranged from 5.9 to 45 months. The median time elapsed since previous RT treatment was 15 months (2-162 months). Re­I prescription doses were variable (22.5 Gy in 3 fractions to 126.5 Gy with 125I). Cumulative doses calculated for acute- and late-responding tissues ranged from 67.25 to 136 Gy and 30.3 to 188.38 Gy, respectively. Comprehensively, the pooled ≥G3 toxicity was 12% (95%CI: 7.6-19%). The overall 1­year survival and local recurrence-free survival rates were 53.7% (95%CI: 45.6-63.2%) and 66.5% (95% CI: 58.7-75.4%), respectively. Pain improvement was reported in 66.9% of patients. CONCLUSION: Due to limited evidence as a result of the retrospective design of the majority of the studies, our review suggests that upper abdominal Re­I is effective in terms of local control and palliation, with a moderate rate of severe toxicities.

Effects of high-energy photon beam radiation therapy on Jarvik 2000 LVAD: in vitro evaluation.

PURPOSE: Left ventricular assist device (LVAD) is considered a standard care for patients with advanced heart failure. The aim of this work was to study in vitro the effects of direct exposure of the Jarvik 2000 LVAD to 10-MV photon beams. METHODS: Jarvik 2000 pump was immersed in a siliconized box filled with deionized water. A 30 × 30 × 15 cm RW3 slabs were added forth and back to the box. A treatment plan consisting of a single direct 10 × 10 cm2 field size beam was used to deliver 1000 MU at the center of the pump. During irradiation, the external Flow Maker controller and the lithium battery were positioned away from the beam. Pump parameter data (included voltage, current and frequency) were measured, recorded and analyzed for changes in pump function among baseline, pre-irradiation, during irradiation, post-irradiation and after 6 months. The whole session lasted 6 months. The Mann-Whitney U test was used to compare the repeated measurements. X-ray radiation attenuation was also studied. RESULTS: The parameters investigated remained stable over the 6 months; that is, no pump stops, alarms, events, operational changes or abnormalities during the discharge rate of the connected power sources, were encountered, confirmed by the Mann-Whitney U test applied to all sessions (p > 0.1). The measured X-ray attenuation differed from the calculated one by TPS by 34%. CONCLUSION: The Jarvik 2000 resulted stable under direct X-ray beam of 10-MV energy. Its strong attenuation, however, can affect dose deposition in the pump in TPS, and it must be taken into account.

Magnetic resonance imaging (MRI) compared with computed tomography (CT) for interobserver agreement of gross tumor volume delineation in pancreatic cancer: a multi-institutional contouring study on behalf of the AIRO group for gastrointestinal cancers.

BACKGROUND: Due to the high soft tissue resolution, magnetic resonance imaging (MRI) could improve the accuracy of pancreatic tumor delineation in radiation treatment planning. A multi-institutional study was proposed to evaluate the impact of MRI on inter-observer agreement in gross tumor volume (GTV) and duodenum delineation for pancreatic cancer compared with computer tomography (CT). MATERIAL AND METHODS: Two clinical cases of borderline resectable (Case 1) and unresectable (Case 2) pancreatic cancer were selected. In two sequential steps, diagnostic contrast-enhanced CT scan and MRI sequences were sent to the participating centers. CT-GTVs were contoured while blinded to MRI data sets. DICE index was used to evaluate the spatial overlap accuracy. RESULTS: Thirty-one radiation oncologists from different Institutions submitted the delineated volumes. CT- and MRI-GTV mean volumes were 21.6 ± 9.0 cm3 and 17.2 ± 6.0 cm3, respectively for Case 1, and 31.3 ± 15.6 cm3 and 33.2 ± 20.2 cm3, respectively for Case 2. Resulting MRI-GTV mean volume was significantly smaller than CT-GTV in the borderline resectable case (p < .05). A substantial agreement was shown by the median DICE index for CT- and MRI-GTV resulting as 0.74 (IQR: 0.67-0.75) and 0.61 (IQR: 0.57-0.67) for Case 1; a moderate agreement was instead reported for Case 2: 0.59 (IQR:0.52-0.66) and 0.53 (IQR:0.42-0.62) for CT- and MRI-GTV, respectively. CONCLUSION: Diagnostic MRI resulted in smaller GTV in borderline resectable case with a substantial agreement between observers, and was comparable to CT scan in interobserver variability, in both cases. The greater variability in the unresectable case underlines the critical issues related to the outlining when vascular structures are more involved. The integration of MRI with contrast-enhancement CT, thanks to its high definition of tumor relationship with neighboring vessels, could offer a greater accuracy of target delineation.

Advances in Lipidomics for Cancer Biomarkers Discovery.

Lipids play critical functions in cellular survival, proliferation, interaction and death, since they are involved in chemical-energy storage, cellular signaling, cell membranes, and cell-cell interactions. These cellular processes are strongly related to carcinogenesis pathways, particularly to transformation, progression, and metastasis, suggesting the bioactive lipids are mediators of a number of oncogenic processes. The current review gives a synopsis of a lipidomic approach in tumor characterization; we provide an overview on potential lipid biomarkers in the oncology field and on the principal lipidomic methodologies applied. The novel lipidomic biomarkers are reviewed in an effort to underline their role in diagnosis, in prognostic characterization and in prediction of therapeutic outcomes. A lipidomic investigation through mass spectrometry highlights new insights on molecular mechanisms underlying cancer disease. This new understanding will promote clinical applications in drug discovery and personalized therapy.

DWI-MR and PET-CT Functional Imaging for Boost Tumor Volume Delineation in Neoadjuvant Rectal Cancer Treatment.

BACKGROUND/AIM: T2 weighted magnetic resonance (MR) imaging is the gold standard for locally advanced rectal cancer (LARC) staging. The potential benefit of functional imaging, as diffusion-weighted MR (DWI) and positron emission tomography-computed tomography (PET-CT), could be considered for treatment intensification strategies. Dose intensification resulted in better pathological complete response (pCR) rates. This study evaluated the inter-observer agreement between two radiation oncologists, and the difference in gross tumor volume (GTV) delineation in simulation-CT, T2-MR, DWI-MR, and PET-CT in patients with LARC. PATIENTS AND METHODS: Two radiation oncologists prospectively delineated GTVs of 24 patients on simul-CT (CTGTV), T2-weighted MR (T2GTV), echo planar b1000 DWI (DWIGTV) and PET-CT (PETGTV). Observers' agreement was assessed using Dice index. Kruskal-Wallis test assessed differences between methods. RESULTS: Mean CTGTV, T2GTV, DWIGTV, and PETGTV were 41.3±26.9 cc, 25.9±15.2 cc, 21±14.8 cc, and 37.7±27.7 cc for the first observer, and 42.2±27.9 cc, 27.6±16.9 cc, 19.9±14.9cc, and 34.8±24.3 cc for the second observer, respectively. Mean Dice index was 0.85 for CTGTV, 0.84 for T2GTV, 0.82 for DWIGTV, and 0.89 for PETGTV, representative of almost perfect agreement. Kruskal-Wallis test showed a statistically significant difference between methods (p=0.009). Dunn test showed there were differences between DWIGTV vs. PETGTV (p=0.040) and DWIGTV vs. CTGTV (p=0.008). CONCLUSION: DWI resulted in smaller volume delineation compared to CT, T2-MR, and PET-CT functional images. Almost perfect agreements were reported for each imaging modality between two observers. DWI-MR seems to remain the optimal strategy for boost volume delineation for dose escalation in patients with LARC.

Statistical methods for handling compliance in randomized controlled trials of device interventions: a systematic review.

OBJECTIVES: We aimed to review the extent to which analysis of randomized controlled trials (RCTs) of device interventions includes methods to handle compliance to the study intervention as described in the protocol. STUDY DESIGN AND SETTING: We conducted a systematic review of the statistical methods used to handle compliance to a device intervention when estimating the effect of the device compared to another intervention in RCTs. We searched Embase, MEDLINE, PsychInfo, and the Cochrane Central Register of Controlled Trials. We sought to evaluate what methods were used and how using these methods impacted the estimate of the effect size. RESULTS: One hundred fifty eight RCTs were identified for inclusion, of which only 21 (13%) described using a method to account for compliance to the device intervention, consisting of alternative analysis populations such as per-protocol, modified intention-to-treat, or as-treated, alongside a primary intention-to-treat analysis. No causal inference methods were used. Fourteen (9%) studies included compliance as a factor in the analysis and investigated its effect on outcomes. CONCLUSION: Although some studies consider methods to handle compliance, causal inference methods have not been well adopted in the analysis of device trials. An increased awareness of the applications of statistical methods to adjust for compliance is needed.

DICE: Dual mTorc Inhibition in advanCed/recurrent Epithelial ovarian cancer resistant to standard treatment-a study protocol for a randomised trial investigating a novel therapy called TAK228.

BACKGROUND: The standard initial treatment for ovarian cancer is surgery and platinum-based chemotherapy and potentially maintenance therapy with avastin or inhibitors of poly-ADP ribose polymerase (PARP). While a proportion of women are cured by this approach, the vast majority will relapse and become resistant to platinum chemotherapy either initially or on subsequent treatment. There is an unmet need to improve response to treatment and quality of life in these women. TAK228 is a novel therapy that can be added to standard treatment in the participant population and the aim of the DICE trial is to assess its effectiveness. Laboratory and clinical research has shown that these ovarian cancers may respond to the molecular target of a drug such as TAK228, and there have been studies using it in other advanced solid tumours including endometrial cancer. METHODS: One hundred twenty-four eligible women will be recruited from participating research sites in the United Kingdom (UK) and Germany. Randomised participants will receive either weekly paclitaxel alone (standard treatment, n = 62) or TAK228 plus weekly paclitaxel (n = 62) until the cancer significantly worsens; there are significant adverse events or any other protocol-defined stopping criteria. Participants will be monitored for response to treatment (using radiological imaging), adverse events and quality of life during both randomised treatment and subsequent follow-up. DISCUSSION: The primary objective/endpoint of the study is to compare the two treatments in terms of progression-free survival, or the length of time that each participant is alive without the cancer significantly worsening according to defined assessment criteria. If the addition of TAK228 to weekly paclitaxel chemotherapy is shown to significantly improve this statistically, and adverse events and quality of life are not significantly worse than standard treatment, then TAK228 plus weekly paclitaxel could potentially be taken forward within the context of a larger phase III trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT03648489 . Registered on 27 August 2018.

Lower Bladder Toxicity of Salvage Versus Adjuvant Modern Radiotherapy for Prostate Cancer Patients.

BACKGROUND/AIM: In prostate cancer, postoperative radiotherapy timing is debated to avoid overtreatments and toxicities. This study compared acute and late rectal and bladder toxicities in the adjuvant and salvage setting. PATIENTS AND METHODS: In total, 129 patients were analyzed in two groups: adjuvant radiotherapy (aRT) and salvage radiotherapy (sRT). RESULTS: In aRT and sRT, grade 1 (G1) acute bladder toxicities were detected in 40 and 30 patients, and grade 2 (G2) in 1 and 6; G1 late bladder toxicities were described in 30 and 20, and G2 in 6 and 2, respectively. In aRT and sRT, acute G1 rectal toxicities were reported in 18 and 27 patients, and G2 in 5 and 4, respectively. Late rectal G1 toxicities were observed in 10 patients, G2 in 6 and G3 in 1 in the aRT. In sRT, 8 patients and 1 developed G1 and G2 toxicities, respectively. Regarding bladder toxicity, a higher incidence occurred in aRT; late toxicity was lower in sRT. CONCLUSION: Adjuvant and salvage RT in prostate cancer treatment resulted in acceptable toxicities.

Statistical analysis plan for the Dual mTorc Inhibition in advanCed/recurrent Epithelial ovarian, fallopian tube or primary peritoneal cancer (of clear cell, endometrioid and high-grade serous type, and carcinosarcoma) trial (DICE).

BACKGROUND: Treatment for ovarian cancer includes platinum-based chemotherapy, but many women become resistant to chemotherapy, becoming platinum-resistant. Standard of care for these women is weekly paclitaxel chemotherapy, but cancers can often become paclitaxel resistant. TAK228, an investigational dual TORC1/2 inhibitor, is an oral therapy that can be added to standard treatment. The DICE trial is a phase II international multicentre, parallel-group, superiority clinical trial with 1:1, open label randomisation which has the aim of investigating the effectiveness of TAK228 plus weekly paclitaxel. The planned sample size is 124 women (62 per treatment arm) with platinum-resistant ovarian cancer. OBJECTIVE: To outline the planned analyses for DICE in a statistical analysis plan (SAP) before database hard lock and the start of analysis. This ensures that bias is minimised during the analysis phase. RESULTS: This SAP provides detailed descriptions of the analysis principles and statistical procedures for analysing primary and secondary outcomes of the trial. The primary outcome is overall progression-free survival (PFS). Secondary outcomes include progression-free survival (PFS) at 24 weeks, overall response rate (ORR), duration of response (DoR), time to progression (TTP), clinical benefit rate (CBR) at 4 months, Cancer Antigen 125 (CA125) response according to Gynaecological Cancer Intergroup (GCIG) criteria, overall survival (OS), safety and tolerability as assessed by adverse events and the quality-of-life questionnaires (EORTC QLQ-C30 and EORTC QLQ-OV28). This detailed description includes significance levels, sensitivity analyses and compliance analysis. DISCUSSION: The DICE trial will determine whether the addition of TAK228 to weekly paclitaxel chemotherapy shows a statistically significant improvement to participant's progression free and overall survival and that the adverse events (AEs) and quality of life (QoL) are not significantly worse than the standard treatment. The study commenced recruitment in September 2018. An interim analysis was performed in early 2021, the results of which advised continuation of the trial. The study recruitment is ongoing and is due to complete by the end of 2021. TRIAL REGISTRATION: ClinicalTrials.gov NCT03648489 . Registered on 27 August 2018.

Smile InTM Totems in Radiotherapy: Patients' Satisfaction with Limited Equipment and COVID-19.

BACKGROUND: We report a mono-institutional experience regarding patient-perceived quality regarding the Chieti Radiotherapy Department, through RAMSI (Radiotherapy Amica Mia-SmileINTM(SI)-My Friend RadiotherapySI) project, in critical scenarios of limited equipment and COVID-19. MATERIAL AND METHODS: Patient-reported experience measures (PREMs) were assessed as follows: Patient-centric welcome perception (PCWP), Comfort, Professional skills and Punctuality. Patients could give anonymous feedback using HappyOrNot technology through four totems located in strategic areas within the center. An internal benchmark was obtained using the feedback received after a preliminary observation period. The SI Experience Index was collected, analyzed and compared. Weekly and monthly reports were generated. RESULTS: From February 2019 to February 2022, 8924 patients accessed the department; 17,464 daily treatments were recorded and 5830 points of feedback were collected: 896, 1267, 1125 and 2542 for PCWP, Comfort, Professional skills and Punctuality, respectively. A LINAC decommissioning period was analyzed, with decreases in the SI-Index score and Smile-IN approved percentage and an improvement after this period. Additionally, the COVID-19 pandemic was analyzed with a mild evaluations decrease for PREM's Welcome, Comfort and Punctuality (Δ-value: -9%, -3% and -4%, respectively), while Professional skills were always optimal. CONCLUSION: The RAMSI project was effective for assessing treatment quality perception, allowing for improving clinical procedures with corrective actions. The RAMSI project is ongoing.

Validity of the Cushing's Syndrome Severity Index in Patients with Iatrogenic Cushing's Syndrome. / Validación del índice de gravedad del síndrome de Cushing en pacientes con síndrome de Cushing iatrógénico.

INTRODUCTION: Currently there are no clinimetric instruments for the measurement of the severity of iatrogenic Cushing's syndrome (ICS). Sonino et al. created a clinical severity index of endogenous Cushing's disease (CSI) but it has not been applied to patients with ICS. OBJECTIVE: To validate and determine the utility of the CSI and its correlation with clinical variables in rheumatological patients with continuous use of glucocorticoids (GC). SUBJECTS AND METHODS: Patients with a history of continuous systemic GC use (for at least 4 weeks) indicated for treatment of rheumatological disease were included. All the patients filled out a questionnaire on sociodemographic data, characteristics of the CG used; the way of use and the presence or absence of adverse events. The CSI was applied by 2 observers independently. Consistency, interobserver concordance and principal component analysis were calculated. RESULTS: A total of 32 patients with an average age of 35.72±12.8 years were studied; 29 were women (90.6%). The average CSI score by the first observer was 3.50±2.02, and by the second observer was 2.31±1.75 (p=.004). The interobserver concordance was low in the items with imprecise definitions; for which modifications were made in the definitions to improve their performance. The CSI scores correlated with the presence of adverse effects and the type of dose used. CONCLUSIONS: The CSI has an adequate correlation with clinical manifestations in patients with chronic use of GC. The clinimetric characteristics of the questionnaire improved by standardising the definitions of subjective clinical variables.

Multimodal Evaluation of Voice Outcome in Early Glottic Cancers Treated With Definitive Radiotherapy.

Background/Aim: We employed a multimodal evaluation of voice outcome (MEVO) model to assess long-term voice outcome in early glottic cancer (EGC) patients treated with primary radiotherapy (RT). The model consisted of objective and subjective vocal evaluation during follow-up, by a dedicated Speech Pathologist and Speech Therapist. Patients and Methods: MEVO methodology includes Self-perception Voice Handicap Index (VHI-30), evaluation of parameters Grade (G), Roughness (R), Breathiness (B), Asthenia (A) and Strain (S) according to GRBAS scale, objective analysis and aerodynamics using the PRAAT software and laryngeal evaluation with videostroboscope (VS). Results: The MEVO methodology was described and tested on a sample of 10 EGCs submitted to definitive RT (total dose 66-70 Gy). Mean follow-up was 48.9 months (range=9-115). VHI was mild-moderate in 90% of patients; overall voice function (GRBAS) was normal-mildly impaired in 70% of patients; VS evaluation showed normal vocal cord motion in 90% of patients, but complete glottic closure in 60%. PRAAT scores confirmed these findings. Conclusion: A multidimensional voice evaluation is time consuming, but useful to objectify vocal impact of radiotherapy. The MEVO model allowed to quantify vocal dysfunction, showing a good objective vocal outcome.

Quality of Life in Early Breast Cancer Patients: A Prospective Observational Study Using the FACT-B Questionnaire.

BACKGROUND/AIM: Quality of life (QoL) in early breast cancer (BC) treatment may be affected by acute and late toxicities. This study evaluated the impact of radiotherapy (RT) schedules, treatment-related toxicities, hormone therapy (HT) and age on QoL. PATIENTS AND METHODS: Ninety-five patients answered the FACT-B 4.0 questionnaire. Acute or late toxicities were recorded at each follow-up visit. RESULTS: The median trend of the QoL subscales was stable during all questionnaires. HT negatively impacted on Functional Assessment of Cancer Therapy-General-Total, functional and emotional wellbeing. No difference was recorded between RT schedules and toxicity. No significant differences for age were detected in QoL. CONCLUSION: RT seems not to influence QoL of BC patients, in terms of fractionation regimen or RT-related side-effects. Moreover, women having systemic HT experienced a QoL worse than patients treated with RT only. Further and long-term protocols are needed to improve the validity of the tool.

Outcomes and toxicities of re-irradiation for prostate cancer: A systematic review on behalf of the Re-Irradiation Working Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

AIMS: The best therapeutic approach for local relapses of previously irradiated prostate cancer (PC) is still not defined. Re-irradiation (Re-I) could offer a chance of cure for highly selected patients, although high quality evidences are lacking. The aim of our study is to provide a literature review on efficacy and safety of Re-I. METHODS: Only studies where Re-I field overlaps with previous radiotherapy were considered. To determine 2 and 4 years overall mortality (OM), 2 and 4 years biochemical failure (BF) and pooled acute and late G ≥ 3 toxicities rate, a meta-analysis over single arm study was performed. RESULTS: Thirty-eight studies with 1194 patients were included. Median follow-up from Re-I was 30 months (10-94 months). Brachytherapy (BRT) was the most used Re-I technique (27 studies), followed by Stereotactic Body Radiotherapy (SBRT) (9) and External Beam Radiation Therapy (EBRT) (2). Re-I prescription doses ranged from 19 Gy in single HDR fraction to 145 Gy (interstitial BRT). The pooled 2 and 4 years OM rates were 2.1% (95%CI:1.1-3.7%, P < 0.001) and 12.5% (95%CI:8.1-19.5%; P < 0.001). The pooled 2 years BF rate was 24% (95% CI: 19.1-30.2%, P < 0.001). The pooled 4 years BF was 35.6% (95% CI: 28.7-44.3%, P < 0.001). The pooled result of G ≥ 3 acute toxicity was 1.4% (95%CI: 0.7-3%, P < 0.001). One hundred and three G ≥ 3 late adverse events were reported, with a pooled result of G ≥ 3 late toxicity of 8.7% (95%CI: 5.8-13%, P < 0.001). CONCLUSIONS: Re-I of local failures from PC showed promising OM and biochemical control rates with a safe toxicity profile.

Clinical outcomes in elderly rectal cancer patients treated with neoadjuvant chemoradiotherapy: impact of tumor regression grade : Tumor regression grade after neoadjuvant chemoradiotherapy in elderly rectal cancer patients.

PURPOSE: The effect of neoadjuvant chemoradiotherapy (CRT) and the relationship between pathological complete response (pCR) with clinical outcomes has been evaluated in elderly locally advanced rectal cancer (LARC) patients. METHODS: We retrospectively analyzed 117 LARC patients treated with conformal RT and concomitant fluoropirimidine-based chemotherapy. A dose of 4500 cGy, on the pelvis, up to 5500 cGy on the tumor was delivered. Multidisciplinary evaluation, including geriatric assessment, was previously performed to identify frail patients unsuitable for combined treatment. RESULTS: The median age was 75 (range 70-88 years), and 103 (88%) patients had ECOG Performance Status (PS) = 0. All patients except one completed CRT. Ten (8.5%) patients temporarily suspended CRT for acute severe hematologic complication, diarrhea and/or proctitis and hypokalemia. Of the 103 operated patients (88%), a pCR, according to Mandard tumor regression grade (TRG) score, was obtained in 28 patients (27.2%), with TRG1-2 rate of 43.7%. The 3- and 5-year overall survival (OS) rates were 80.2% ± 4.2% and 68.0% ± 5.2%, 72.4% ± 4.5% and 57.8% ± 5.2% for disease-free survival (DFS), and 92.2% ± 2.8% and 89.5% ± 3.9% for loco-regional control. Patients with TRG1-2 had 3- and 5-year OS rates of 84.1% ± 6.6% and 84.1% ± 6.6% compared with 82.8% ± 5.5% and 67.7% ± 7.2% for patients with TRG3-5 (p = 0.012). The 3- and 5-year DFS rates for patients with TRG1-2 were 77.6% ± 7.0% and 74.2% ± 7.5% compared with 70.9% ± 6.3% and 54.7% ± 7.3% for patients with TRG3-5 (p = 0.009). CONCLUSION: Our results reported good tolerability and clinical outcomes of neoadjuvant CRT, with a benefit in patients ≥ 70 years, confirming the prognostic role of pCR on clinical outcomes.