Quality of Life Longitudinal Evaluation in Prostate Cancer Patients from Radiotherapy Start to 5 Years after IMRT-IGRT.

PURPOSE: The purpose of this study is to study the evolution of quality of life (QoL) in the first 5 years following Intensity-modulated radiation therapy (IMRT) for prostate cancer (PCa) and to determine possible associations with clinical/treatment data. MATERIAL AND METHODS: Patients were enrolled in a prospective multicentre observational trial in 2010-2014 and treated with conventional (74-80 Gy, 1.8-2 Gy/fr) or moderately hypofractionated IMRT (65-75.2 Gy, 2.2-2.7 Gy/fr). QoL was evaluated by means of EORTC QLQ-C30 at baseline, at radiation therapy (RT) end, and every 6 months up to 5 years after IMRT end. Fourteen QoL dimensions were investigated separately. The longitudinal evaluation of QoL was analysed by means of Analysis of variances (ANOVA) for multiple measures. RESULTS: A total of 391 patients with complete sets of questionnaires across 5 years were available. The longitudinal analysis showed a trend toward the significant worsening of QoL at RT end for global health, physical and role functioning, fatigue, appetite loss, diarrhoea, and pain. QoL worsening was recovered within 6 months from RT end, with the only exception being physical functioning. Based on ANOVA, the most impaired time point was RT end. QoL dimension analysis at this time indicated that acute Grade ≥ 2 gastrointestinal (GI) toxicity significantly impacted global health, physical and role functioning, fatigue, appetite loss, diarrhoea, and pain. Acute Grade ≥ 2 genitourinary (GU) toxicity resulted in lower role functioning and higher pain. Prophylactic lymph-nodal irradiation (WPRT) resulted in significantly lower QoL for global health, fatigue, appetite loss, and diarrhoea; lower pain with the use of neoadjuvant/concomitant hormonal therapy; and lower fatigue with the use of an anti-androgen. CONCLUSIONS: In this prospective, longitudinal, observational study, high radiation IMRT doses delivered for PCa led to a temporary worsening of QoL, which tended to be completely resolved at six months. Such transient worsening was mostly associated with acute GI/GU toxicity, WPRT, and higher prescription doses.

Worsening of 2-year patient-reported intestinal functionality after radiotherapy for prostate cancer including pelvic node irradiation.

BACKGROUND AND PURPOSE: To quantify patient-reported 2-year intestinal toxicity (IT) from pelvic nodal irradiation (PNI) for prostate cancer. The association between baseline/acute symptoms and 2-year worsening was investigated. MATERIALS AND METHODS: Patient-reported IT was prospectively assessed through the Inflammatory Bowel Disease Questionnaire (IBDQ), filled in at baseline, radiotherapy mid-point and end, at 3 and 6 months and every 6 months until 5 years. Two-year deterioration of IBDQ scores relative to the Bowel Domain was investigated for 400 patients with no severe baseline symptoms and with questionnaires available at baseline, 2 years, RT mid-point and/or end and at least three follow-ups between 3 and 18 months. The significance of the 2-year differences from baseline was tested. The association between baseline values and ΔAcute (the worst decline between baseline and RT mid-point/end) was investigated. RESULTS: In the IBDQ lower scores indicate worse symptoms. A significant (p < 0.0001) 2-year mean worsening, mostly in the range of -0.2/-0.4 points on a 1-7 scale, emerged excepting one question (IBDQ29, "nausea/feeling sick"). This decline was independent of treatment intent while baseline values were associated with 2-year absolute scores. The ΔAcute largely modulated 2-year worsening: patients with ΔAcute greater than the first quartile (Q1) and ΔAcute less or equal than Q1 showed no/minimal and highly significant (p < 0.0001) deterioration, respectively. Rectal incontinence, urgency, frequency and abdominal pain showed the largest mean changes (-0.5/-1): risk of severe worsening (deemed to be of clinical significance if ≤ 2) was 3-5 fold higher in the ΔAcute ≤ Q1 vs ΔAcute > Q1 group (p < 0.0001). CONCLUSION: A modest but significant deterioration of two-year patient-reported intestinal symptoms from PNI compared to baseline was found. Patients experiencing more severe acute symptoms are at higher risk of symptom persistence at 2 years, with a much larger prevalence of clinically significant symptoms.

Patient-reported persistent symptoms after radiotherapy and association with quality of life for prostate cancer survivors.

PURPOSE: To evaluate the persistence of symptoms after radiotherapy (RT) for localised prostate cancer (PCa) and the association with quality of life (QOL). MATERIALS AND METHODS: Prospective patient-reported outcome (PRO) from a multi-institutional study on PCa treated with radical RT (2010-2014) was analysed. Data was collected at baseline (BL) and follow-ups (FUPs) up to 5 years. Patients with BL and ≥3 late FUPs (≥6 months) were analysed. PRO was scored by means of the IPSS and ICIQ-SF (urinary), LENT-SOMA (gastrointestinal [GI]), and EORTC-C30 (pain, insomnia, fatigue, and QOL) questionnaires. Symptoms were defined 'persistent' if the median score over FUPs was ≥3 (urinary) or ≥2 (GI, pain, insomnia, and fatigue), and worse than BL. Different thresholds were chosen to have enough events for each symptom. QOL was linearly transformed on a continuous scale (0-100). Linear-mixed models were used to identify significant differences between groups with and without persistent symptoms including age, smoking status, previous abdominal surgery, and diabetes as confounders. Mean QOL differences between groups were evaluated longitudinally over FUPs. RESULTS: The analysis included 293 patients. Persistent urinary symptoms ranged from 2% (straining) to 12% (weak stream, and nocturia). Gastrointestinal symptoms ranged from 7% (rectal pain, and incontinence) to 30% (urgency). Proportions of pain, insomnia, and fatigue were 6, 13, and 18%. Significant QOL differences of small-to-medium clinical relevance were found for urinary incontinence, frequency, urgency, and nocturia. Among GI symptoms, rectal pain and incontinence showed small-to-medium differences. Fatigue was associated with the largest differences. CONCLUSIONS: The analysis showed that symptoms after RT for PCa occur with different persistence and their association with QOL varies in magnitude. A number of persistent urinary and GI symptoms showed differences in a comparable range. Urinary incontinence and frequency, rectal pain, and faecal incontinence more often had significant associations. Fatigue was also prevalent and associated with largely deteriorated QOL.

Use of Nitric Oxide Donor-Loaded Microbubble Destruction by Ultrasound in Thrombus Treatment.

In the presence of a vascular thrombus, the recovery of blood flow and vascular recanalization are very important to prevent tissue damage. An alternative procedure to thrombolysis is required for patients who are unable to receive surgery or thrombolytic drugs due to other physical conditions. Recently, the performance of thrombolysis combined with microbubbles has become an attractive and effective therapeutic procedure. Indeed, in a recent study, we demonstrated that, upon exposure to ultrasound, liposomes loaded with nitric oxide release agonists conjugated to microbubbles; therefore, there is potential to release the agonist in a controlled manner into specific tissues. This means that the effect of the agonist is potentiated, decreasing interactions with other tissues, and reducing the dose required to induce nitric-oxide-dependent vasodilation. In the present study, we hypothesized that a liposome microbubble delivery system can be used as a hydrophilic agonist carrier for the nitric oxide donor spermine NONOate, to elicit femoral vasodilation and clot degradation. Therefore, we used spermine-NONOate-loaded microbubbles to evaluate the effect of ultrasound-mediated microbubble disruption (UMMD) on thromboembolic femoral artery recanalization. We prepared spermine NONOate-loaded microbubbles and tested their effect on ex vivo preparations, hypothesizing that ultrasound-induced microbubble disruption is associated with the vasorelaxation of aortic rings. Thrombolysis was demonstrated in aorta blood-flow recovery after disruption by spermine NONOate-loaded microbubbles via ultrasound application in the region where the thrombus is located. Our study provides an option for the clinical translation of NO donors to therapeutic applications.

Severe asthma and COVID-19: lessons from the first wave.

OBJECTIVE: Severe asthma is considered a risk factor for SARS-Coronavirus 2 (SARS-CoV-2) infection but scientific evidences are lacking. METHODS: we performed a literature search and review based on PubMed database national, international recommendations as well as papers on severe asthmatic patients and their management during SARS-CoV-2 pandemic. RESULTS: the majority of international recommendations, expert panels and editorials provide indications about management of severe asthmatic patients. No published studies evaluated the effects of biologic agents on severe asthmatic patients during SARS-CoV-2 pandemic. CONCLUSIONS: the relationship between SARS-CoV-2 and asthma is variable worldwide and severe asthmatic patients were seldom reported in published cohorts. International recommendations suggest maintaining asthma under control to limit exacerbations occurrence, by using all available treatment. The minimum steroid dosage effective to control symptoms should be maintained to avoid exacerbations; biologic agents administration should be regularly scheduled encouraging patient support programmes.

Erratum to "IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper" [World Allergy Organ J 13/2 (2020) 100080].

[This corrects the article DOI: 10.1016/j.waojou.2019.100080.].

Predictors of Patient-Reported Incontinence at Adjuvant/Salvage Radiotherapy after Prostatectomy: Impact of Time between Surgery and Radiotherapy.

BACKGROUND: Baseline urinary incontinence (UI) strongly modulates UI recovery after adjuvant/salvage radiotherapy (ART/SRT), inducing clinicians to postpone it "as much as possible", maximizing UI recovery but possibly reducing efficacy. This series aims to analyze the trend of UI recovery and its predictors at radiotherapy start. METHODS: A population of 408 patients treated with ART/SRT enrolled in a cohort study (ClinicalTrials.gov #NCT02803086) aimed at developing predictive models of radiation-induced toxicities. Self-reported UI and personality traits, evaluated by means of the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-SF) and Eysenck Personality Questionnaire - Revised (EPQ-R) questionnaires, were assessed at ART/SRT start. Several endpoints based on baseline ICIQ-SF were investigated: frequency and amount of urine loss (ICIQ3 and ICIQ4, respectively), "objective" UI (ICIQ3 + 4), "subjective" UI (ICIQ5), and "TOTAL" UI (ICIQ3 +4 + 5). The relationship between each endpoint and time from prostatectomy to radiotherapy (TTRT) was investigated. The association between clinical and personality variables and each endpoint was tested by uni- and multivariable logistic regression. RESULTS: TTRT was the strongest predictor for all endpoints (p-values ≤ 0.001); all scores improved between 4 and 8 months after prostatectomy, without any additional long-term recovery. Neuroticism independently predicted subjective UI, TOTAL UI, and daily frequency. CONCLUSIONS: Early UI recovery mostly depends on TTRT with no further improvement after 8 months from prostatectomy. Higher levels of neuroticism may overestimate UI.

Acute patient-reported intestinal toxicity in whole pelvis IMRT for prostate cancer: Bowel dose-volume effect quantification in a multicentric cohort study.

BACKGROUND AND PURPOSE: To assess bowel dose-volume relationships for acute patient-reported intestinal symptoms of patients treated with whole-pelvis intensity-modulated radiotherapy (WPRT) for prostate cancer. MATERIALS AND METHODS: Complete data of 415 patients enrolled in a multi institute, prospective trial (#NCT02803086) treated with radical (31%), adjuvant (33%) and salvage (36%) intent at a median dose to pelvic nodes/lymph-nodal area of 53 Gy were available. The most severe changes between baseline and radiotherapy mid-point/end toxicity assessed by Inflammatory Bowel Disease Questionnaire (only Bowel Domain) were considered (ΔIBDQ). The 25th percentile values of these score variations were set as endpoints. DVHs of bowel loops for patients with/without toxicity were compared for each endpoint, having excluded patients with baseline scores <5 (rate ranging between 2% and 7% according to the endpoint): the resulting best dosimetric predictors were combined with selected clinical parameters through multivariate logistic regression (MVA) to derive predictive models. RESULTS: ΔIBDQ ranged between 0.2-1.5 points considering separately each IBDQ symptom. Only four symptoms (IBDQ1 = frequency, IBDQ5 = diarrhea, IBDQ17 = gas passage, IBDQ24 = urgency) showed a median worsening ≥ 1; DVH predicted the risk of worse symptoms for IBDQ5, IBDQ24 and overall Bowel Domain. At multivariable analysis DVHs (best cut-off: V46Gy ≥80 cc) and baseline scores (Odd-Ratio:0.35-0.65) were independently associated to the three end-points. The resulting models were reliable (H&L test: 0.453-0.956), well calibrated (calibration plot: slope = 0.922-1.069, R2 = 0.725-0.875) and moderately discriminative (Area Under the Curve:0.628-0.669). A bootstrap-based validation confirmed their robustness. CONCLUSION: Constraining the bowel loops (V46 < 80 cc) may reduce the risk of several moderate intestinal symptoms, with a much greater impact for patients with lower IBDQ baseline scores.

Salvage radiotherapy for oligo-progressive malignant pleural mesothelioma.

OBJECTIVES: No standard treatment option is available for patients with unresectable malignant pleural mesothelioma (MPM) progressing after upfront chemotherapy. We aimed to explore the role of focal radiotherapy (FRT) as a treatment modality for oligo-progressive MPM. MATERIALS AND METHODS: In this retrospective study, consecutive patients pretreated with ≥1 lines of chemotherapy were included. Oligo-progressive MPM was defined as an unresectable disease with radiological progression at ≤3 sites according to a chest-abdominal contrast-enhanced computed tomography. Patients were treated with either stereotactic body radiotherapy (SBRT, ≥5 Gy per fraction) or hypo-fractionated radiotherapy (hypoRT, <5 Gy per fraction). Time to further systemic therapy (TFST) and local control (LC) after FRT were the primary endpoints. Biologically effective dose (BED) was calculated using three different alpha/beta models (1.5 Gy, 3 Gy and 10 Gy). RESULTS: From April 2006 to March 2019, 37 patients were treated on 43 pleural lesions; 16/37 (43 %) had undergone upfront multimodality treatment (MMT) including surgery. FRT was given in 22/37 (59.5 %) after one line of chemotherapy. SBRT was delivered for 26/43 lesions (60.5 %), hypoRT for 17/43 (39.5 %). Median TFST was 6 months (95 % CI 4.9-7.1). LC at 6 months and 1 year was 84 % and 76 %, respectively. Median TFST was longer in patients treated after 1 vs >1 line of chemotherapy (9 vs 4 months, p = 0.001) and in patients pretreated with MMT (6 vs 3 months, p = 0.021). Six-month LC was better in patients treated with a BED > 100 using alpha/beta 1.5 and 3. No ≥ G3 acute or late toxicities were reported. CONCLUSION: FRT was feasible in selected patients with oligo-progressive MPM, allowing delay of further systemic therapies, with no severe toxicity. FRT was more effective when performed at progression after one line of systemic therapy. Our results suggest a radio-resistant behavior of MPM.

Predictors of 2-Year Incidence of Patient-Reported Urinary Incontinence After Post-prostatectomy Radiotherapy: Evidence of Dose and Fractionation Effects.

Objective: To investigate predictors of patient-reported urinary incontinence (PRUI) in the first 2 years after post-prostatectomy radiotherapy (PORT) with particular emphasis on possible dose-effect relationships. Patients and Methods: Two-hundred-thirteen patients, whose clinical and dosimetric data were prospectively collected within a registered multi-institutional cohort study, underwent PORT with adjuvant (n = 106) or salvage (n = 107) intent with conventional (n = 123, prescribed dose to the prostatic bed: 66.6-79.8Gy in 1.8-2.0Gy/fr) or moderately hypo- (n = 90, 65.8-76.8Gy in 2.1-2.7Gy/fr) fractionation during the period 2011-2017. PRUI was evaluated through the ICIQ-SF questionnaire filled in at baseline and every 6 months thereafter. The analysis focused on three ICIQ-based clinically relevant endpoints: (a) very frequent leakage (FREQUENCY, ICIQ3 score >3), (b) moderate to severe amount of urine loss (AMOUNT, ICIQ4>2) (c) objective severe symptoms (OBJECTIVE, ICIQ3+4>5). Predictors of the incidence within 2 years for the three endpoints were investigated focusing only on patients without endpoint symptoms at baseline. A uni-variable logistic regression analysis was performed in order to determine the best dose metrics describing PRUI risk in terms of 2-Gy equivalent dose (EQD2) calculated with different α/ß values reported in the literature (0.8, 3, 5Gy), and to identify the most significant clinical variables. Variables showing p < 0.20 at uni-variable analysis were entered into a backward stepwise multi-variable logistic regression analysis. Lastly, the goodness of fit and model calibration were evaluated and internally validated. Results: Patients without symptoms at baseline experienced (a), (b), and/or (c) within 2 years in 41/130 (32%), 40/192 (21%), and 41/129 (32%) of the cases, respectively. EQD2 for α/ß = 0.8Gy was the best dose metric associated with PRUI. Multi-variable analysis identified baseline incontinence levels as the strongest predictor for all endpoints (p < 0.006). Both FREQUENCY and OBJECTIVE were significantly influenced also by EQD2(α/ß = 0.8Gy). The goodness of fit was excellent, as was the calibration; internal calibration confirmed apparent performance. Conclusion: Baseline mild urinary incontinence symptoms strongly modulate the 2-year risk of PRUI. In addition, FREQUENCY is characterized by a marked dose-effect relationship also influencing the trend of OBJECTIVE, with results more reliable than AMOUNT as an objective index. A strong impact of fractionation on severe PRUI after post-prostatectomy radiotherapy also emerged.

IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper.

Currently, testing for immunoglobulin E (IgE) sensitization is the cornerstone of diagnostic evaluation in suspected allergic conditions. This review provides a thorough and updated critical appraisal of the most frequently used diagnostic tests, both in vivo and in vitro. It discusses skin tests, challenges, and serological and cellular in vitro tests, and provides an overview of indications, advantages and disadvantages of each in conditions such as respiratory, food, venom, drug, and occupational allergy. Skin prick testing remains the first line approach in most instances; the added value of serum specific IgE to whole allergen extracts or components, as well as the role of basophil activation tests, is evaluated. Unproven, non-validated, diagnostic tests are also discussed. Throughout the review, the reader must bear in mind the relevance of differentiating between sensitization and allergy; the latter entails not only allergic sensitization, but also clinically relevant symptoms triggered by the culprit allergen.

Follow-up of elderly patients with urogenital cancers: Evaluation of geriatric care needs and related actions.

OBJECTIVES: To investigate a comprehensive geriatric assessment (CGA) with subsequent investigation of healthcare patterns in older patients with urological cancers undergoing initial surgery or radiotherapy, to verify the usefulness of the incorporation of geriatric principles in future care plans. MATERIAL AND METHODS: This is a prospective cohort study. From November 2011 to March 2015, CGA was offered to all patients aged 70+ years treated with radiotherapy or surgery at seven tertiary centers. Patients were classified as fit, vulnerable, or frail according to Balducci's definition. CGA and follow-up data were collected by two trained evaluators at 6 and 12months. The information collected was not available to the caring physicians during follow-up. RESULTS: CGA was performed in 453 patients with prostate cancer (295), bladder cancer (126), or kidney cancer (32). 40% of patients with prostate cancer were fit, 47% vulnerable, and 13% frail. The corresponding values for renal cancer were 25%, 40%, and 34%, and for bladder cancer, 21%, 42%, and 37%. During follow-up, 60% of patients with cardiac diseases, 42% of those with diabetes/other metabolic disorders, 35% of those with hypertension, and 35% of those with respiratory diseases were followed by a specialist (for these severe/extremely severe comorbidities). Of 16 patients with ADL impairment and 63 with IADL impairment, only 4 (25%) and 6 (10%), respectively, were referred to a rehabilitation service. Only one case was referred to a geriatrician. CONCLUSIONS: Appropriate clinical care patterns are advisable to improve quality of survivorship in older patients with urological cancers.

Electrochemical RNA genosensors for toxic algal species: enhancing selectivity and sensitivity.

Harmful algal blooms (HABs) are becoming more frequent as climate changes, with tropical species moving northward. Monitoring programs detecting the presence of toxic algae before they bloom are of paramount importance to protect aquatic ecosystems, aquaculture, human health and local economies. Rapid and reliable species identification methods using molecular barcodes coupled to biosensor detection tools have received increasing attention over the past decade as an alternative to the impractical standard microscopic counting-based techniques. This work reports on a PCR amplification-free electrochemical genosensor for the enhanced selective and sensitive detection of RNA from multiple Mediterranean toxic algal species. For a sandwich hybridization (SHA), we designed longer capture and signal probes for more specific target discrimination against a single base-pair mismatch from closely related species and for reproducible signals. We optimized experimental conditions, viz., minimal probe concentration in the SHA on a screen-printed gold electrode and selected the best electrochemical mediator. Probes from 13 Mediterranean dinoflagellate species were tested under optimized conditions and the format further tested for quantification of RNA from environmental samples. We not only enhanced the selectivity and sensitivity of the state-of-the-art toxic algal genosensors but also increased the repertoire of toxic algal biosensors in the Mediterranean, towards an integral and automatic monitoring system.

Phase II trial of hypofractionated VMAT-based treatment for early stage breast cancer: 2-year toxicity and clinical results.

BACKGROUND: To report toxicity and early clinical outcomes of hypofractionated simultaneous integrated boost (SIB) approach with Volumetric Modulated Arc Therapy (VMAT) as adjuvant treatment after breast-conserving surgery. METHODS: Patients presenting early-stage breast cancer were enrolled in a phase II trial. ELIGIBILITY CRITERIA: age > 18 years old, invasive cancer or ductal carcinoma in situ (DCIS), Stage I-II (T < 3 cm and N ≤ 3), breast-conserving surgery without oncoplastic reconstruction. Any systemic therapy was allowed in neoadjuvant or adjuvant setting. All patients underwent VMAT-SIB technique to irradiate the whole breast and the tumor bed. Doses to whole breast and surgical bed were 40.5 Gy and 48 Gy, respectively, delivered in 15 fractions over 3 weeks. Acute and late skin toxicities were recorded. Cosmetic outcome was assessed as excellent/good or fair/poor. RESULTS: The present study focused on results of a cohort of 144 patients with a minimum follow-up of 24 months (median 37, range 24-55 months). Median age was 62 years old (range 30-88). All patients had an invasive carcinoma (no patients with DCIS were present in this subset). At one year, the highest reported skin toxicity was G1, in 14 % of the patients; this data dropped to 4 % at the last follow-up, after more than 2 years. Breast pain was recorded in 21.6 % of the patients 6 months after treatment, while it was present in 3.5 % of the patients at the last follow-up, showing a significant improvement with time. Correlation between liponecrosis and boost target volume was found not significant. Breast pain was correlated with breast volume. No pulmonary or cardiological toxicities were recorded. After an early evaluation of clinical outcomes, only one case presented disease relapse, as liver metastases. CONCLUSIONS: The 3-week VMAT-SIB course as adjuvant treatment after breast-conserving surgery showed to be well tolerated and was associated with optimal local control. Long-term follow-up data are needed to assess late toxicity and clinical outcomes.

Stereotactic body radiation therapy: A promising chance for oligometastatic breast cancer.

BACKGROUND: Multidisciplinary management of oligometastatic breast cancer with local therapy could improve disease control. The aim of our study is the assessment of safety and efficacy of Stereotactic Body Radiation Therapy (SBRT) in selected subset of patients. PATIENTS AND METHODS: Oligometastastic patients from breast cancer were treated with SBRT for 1-3 lung and liver lesions, in an observational study. Inclusion criteria were: age >18 years, ECOG 0-2, diagnosis of breast cancer, no extrapulmonary and/or extrahepatic disease, other metastatic sites stable or responding after chemotherapy were allowed, no life threatening conditions, less than 5 lung and liver lesions (with maximum diameter <5 cm), chemotherapy completed at least 3 weeks before treatment, written informed consent. Prescription dose ranged between 48 and 75 Gy in 3 or 4 consecutive fractions. Primary end-point was local control (LC). Secondary end-points were toxicity, overall survival (OS) and progression-free survival (PFS). RESULTS: From April 2010 to June 2014, 33 patients for a total number of 43 lesions were irradiated. Median follow up was 24 months (range 3-59). Actuarial LC rates were 98% at 1 year and 90% at 2 and 3 years. Complete response, partial response and progressive disease were detected in 25 (53.2%), 16 (34%), and 6 (12.8%) lesions, respectively. Median OS was 48 months. Actuarial OS rates at 1 and 2 years were 93% and 66% respectively. Median PFS was 11 months, with a PFS rate at 1 and 2 years of 48% and 27%, respectively. At univariate analysis DFI >12 months, hormonal receptor positivity, medical therapies after SBRT showed a significant impact on OS. Treatment was well tolerated, with no G3-4 toxicities. CONCLUSIONS: SBRT is a safe and feasible alternative treatment of liver and lung oligometastases from breast cancer, in selected patients not amenable to surgery, with good local control and survival rate.

Hypofractionated Stereotactic Radiation Therapy in Recurrent High-Grade Glioma: A New Challenge.

PURPOSE: The aim of this study was to evaluate outcomes of hypofractionated stereotactic radiation therapy (HSRT) in patients re-treated for recurrent high-grade glioma. MATERIALS AND METHODS: From January 2006 to September 2013, 25 patients were treated. Six patients underwent radiation therapy alone, while 19 underwent combined treatment with surgery and/or chemotherapy. Only patients with Karnofsky Performance Status (KPS) > 70 and time from previous radiotherapy greater than 6 months were re-irradiated. The mean recurrent tumor volume was 35 cm(3) (range, 2.46 to 116.7 cm(3)), and most of the patients (84%) were treated with a total dose of 25 Gy in five fractions (range, 20 to 50 Gy in 5-10 fractions). RESULTS: The median follow-up was 18 months (range, 4 to 36 months). The progression-free survival (PFS) at 1 and 2 years was 72% and 34% and the overall survival (OS) 76% and 50%, respectively. No severe toxicity was recorded. In univariate and multivariate analysis extent of resection at diagnosis significantly influenced PFS and OS (p < 0.01). Patients with smaller recurren tumor volume treated had better local control and survival. Indeed, the 2-year PFS was 40% (≤ 50 cm(3)) versus 11% (p=0.1) and the 2-year OS 56% versus 33% (> 50 cm(3)), respectively (p=0.26). CONCLUSION: In our experience, HSRT could be a safe and feasible therapeutic option for recurrent high grade glioma even in patients with larger tumors. We believe that a multidisciplinary evaluation is mandatory to assure the best treatment for selected patients. Local treatment should also be considered as part of an integrated approach.

Toxicity profile and early clinical outcome for advanced head and neck cancer patients treated with simultaneous integrated boost and volumetric modulated arc therapy.

BACKGROUND: Shortening the overall treatment time without increasing acute reactions is one of the major aims in radiotherapy for head and neck cancer (HNC). Volumetric modulated arc therapy (VMAT) with Simultaneous Integrated Boost (SIB) showed improvements in outcome and pattern of toxicity. Patients with stage III-IV HNC treated with VMAT-SIB have been analysed, and doses were correlated to limiting structures and toxicity. METHODS: One hundred two patients treated from December 2008 to August 2014 were analysed. Patients were treated with VMAT (RapidArc) and SIB in 33 fractions for a total dose of 69.96 and 54.45Gy, respectively. For organs at risk, D1/3 V, D1/2 V, D2/3 V, the mean dose, VD with D = 10,20,30,40,50,70 Gy were analysed. For targets, D98%, D2%, and V95%, V107%, conformity and homogeneity indexes were calculated. Toxicity was graded according to CTCAE3. RESULTS: Oral cavity V30Gy, V40Gy, and V70Gy, were found correlated with mucosal toxicity grading. Concerning salivary glands, significant was only D2/3V for one of the two parotids. Almost all analysed parameters of the inferior constrictor muscle were significant while no correlations were found for middle and superior constrictors. With median follow-up of 19 months, Overall Survival (OS) at 3 and 5 years was 83 % ± 4 % and 73 % ± 10 %. Mean OS was 51 ± 3 months. Disease Free Survival (DFS) at 3 and 5 years was 71 % ± 7 %, and 34 % ± 16 %. Mean DFS was 43 ± 3 months. CONCLUSIONS: RapidArc technology and SIB with 1.65 and 2.12Gy/fraction for 33 fractions showed a good toxicity profile and encouraging trend for OS and DFS for patients with stage III-IV HNC.

The role of stereotactic body radiation therapy (SBRT) in the treatment of oligometastatic disease in the elderly.

OBJECTIVE: To report about clinical outcome of stereotactic body radiation therapy (SBRT) in the treatment of oligometastatic disease in elderly patients. METHODS: Patients with 1-4 inoperable metastases were treated with SBRT. Dose prescription ranged from 40 to 75 Gy in 3-8 fractions. SBRT was delivered using the volumetric modulated arc therapy technique with flattening filter-free photon beams. The primary end points were in-field local control (LC) and toxicity. Secondary end points were overall survival (OS) and disease-specific survival (DSS). RESULTS: 82 patients with 111 total metastases were treated. Median age was 79 years. 64 patients (78%) had a single lesion; the remaining patients had 2-4 lesions. 16 (14.4%) lesions were localized in the abdomen, 50 (45.0%) in the liver and 45 (40.5%) in the lungs. Local response was observed for 87 lesions (78.4%) while local progression was observed in 24 lesions (21.6%). Actuarial 1-year LC was 86.8% ± 3.3%. Actuarial 1-year OS was 93.6% ± 2.7%. 2-year findings were 76.3% ± 4.4% and 72.0% ± 5.6%, respectively. Actuarial 1- and 2-year DSS results were 97.5% ± 2.0% and 81.6% ± 4.9%, respectively. Treatment-related Grade 2-3 toxicity was observed in five patients (4.2%); Grade 1 toxicity in seven patients (5.9%) and no toxicity was observed in 85.4% of the cases. CONCLUSION: SBRT is a safe and effective therapeutic option for the treatment of oligometastatic disease in the elderly with acceptable rates of LC and low treatment-related toxicity. ADVANCES IN KNOWLEDGE: The use of SBRT for oligometastatic disease in the elderly can be considered as a valuable approach, particularly for patients with fragile status or refusing other approaches.