The strategy to anticipate radiotherapy (RT) before surgery, for breast cancer (BC) treatment, has recently generated a renewed interest. Historically, preoperative RT has remained confined either to ...highly selected patients, in the context of personalized therapy, or to clinical research protocols. Nevertheless, in the recent years, thanks to technological advances and increased tumor biology understanding, RT has undergone great changes that have also impacted the preoperative settings, embracing the modern approach to breast cancer. In particular, the reappraisal of preoperative RT can be viewed within the broader view of personalized and tailored medicine. In fact, preoperative accelerated partial breast irradiation (APBI) allows a more precise target delineation, with less variability in contouring among radiation oncologists, and a smaller treatment volume, possibly leading to lower toxicity and to dose escalation programs. The aim of the present review, which represents a benchmark study for the AIRC IG-23118, is to report available data on different technical aspects of preoperative RT including dosimetric studies, patient’s selection and set-up, constraints, target delineation and clinical results. These data, along with the ones that will become available from ongoing studies, may inform the design of the future trials and representing a step toward a tailored APBI approach with the potential to challenge the current treatment paradigm in early-stage BC.
Trial registration:
The study is registered at clinicaltrials.gov (NCT04679454).
Several progressively refined percutaneous devices for patent foramen ovale (PFO) closure have been recently developed. We describe our single-center experience with the new Gore septal occluder ...(GSO).
Between January 2012 and May 2013, all consecutive patients with a PFO and previous cerebral thromboembolic events underwent percutaneous closure with the GSO system. Device implantation was performed under local anesthesia with combined fluoroscopic and intracardiac echographic monitoring. Follow-up schedule was: transthoracic echo at day 1 and day 30, as well as transcranial Doppler at 6 months and 12 months, all with clinical concomitant evaluation.
Twenty-two patients (11 males and 11 females) with a mean age of 51.2 ± 13.9 years (range, 40-74 years) had PFO closure. At baseline, 4 and 18 subjects had medium-grade and large-grade right to left permanent shunt, respectively; isolated PFO was present in 13 patients and PFO with atrial septal aneurysm was present in 9 patients. Device placement was successful in all patients. Median procedural and fluoroscopic times were 40.5 minutes (range, 22-92 minutes) and 6.5 minutes (range, 3-16 minutes), respectively. Clinical and instrumental follow-up data were obtained at 12 months in 22 patients (100%). A low-grade (<5 microbubbles) permanent residual shunt was registered in 5 patients at 6 months and in 2 patients (during Valsalva only) at 12-month follow-up. Functional PFO occlusion was thus obtained in all patients.
This single-center initial experience suggests that the GSO is a safe and effective closure device, straightforward to implant with quick deployment and minimal imaging, and suitable for a range of atrial septal anatomies. Incidence and entity of residual shunts at follow-up were consistent with functional PFO occlusion in all patients.
: Although androgen deprivation therapy (ADT) is widely recognized as a mainstay in the treatment of recurrent prostate cancer (PCa), newer data suggest that focal approaches (e.g. radiotherapy (RT), ...or high intensity focused ultrasound) may be considered in adequately selected patients. The aim of the current study was to present the technical feasibility and clinical outcomes of multiple external beam RT(EBRT) for low-burden locally recurrent PCa on a series of patients treated at a tertiary care center Retrospective analysis of an updated series of patients who received multiple (>3 EBRT courses to prostate/prostate bed) re-EBRT with stereotactic image-guided technique and hypofractionated RT. Eight patients received three EBRT courses, 2 of them were candidates to subsequent forth EBRT following further local recurrence. No alternative focal approaches were considered. Two patients received surgery as a primary treatment modality; 6 were treated withEBRT +/- ADT. Local relapse was assessed by multiparametric magnetic resonance imaging (MRI) and/or choline positron emission tomography (PET). The presence of local recurrence was confirmed histologically in 4 cases (in other cases with univocal PET, MRI and PSA findings, all suggestive of recurrence, biopsy was not required). All patients had been evaluated for toxicity from previous EBRT per Radiation Therapy Oncology Group (RTOG)/ European Organization for Research and Treatment of Cancer (EORTC) criteria. Biochemical control was assessed according to 2006 Phoenixdefinition. Dosimetric constraints were based on previously published institutional experience on PCa re-RT. Previous treatment plans were retrieved for each patient. Computed tomography (CT) simulation EBRT sessions were performed with full bladder and empty rectum, according to oral and written instructions handed over during the first visit (water intake of 500 ml 30 minutes before CT scan and treatment; enema the day before CT simulation and low-fiber diet during radiation treatment). Gross tumor volumes (GTVs) were limited to the site of relapse; planning target volume margins were achieved expanding the GTVs of 3 mm posteriorly, and of 5 mm in any other direction. Clinical data and radiologicalof the primary and recurrent tumor were retrospectively collected from electronic medical records; treatment plans were retrieved for each patient using iPlan Net 3.0.0 (Brainlab, Munich, Germany) and Cyberknife MultiPlan® System for treatment planning (Accuray, Sunnyvale, CA, USA). Mean age at second re-EBRT was 68 years standard deviation (SD)=7.2 years; all patients had a good performance status according to Karnofsky and Eastern Cooperative Oncology Group scoring system. At diagnosis, 4 cases were classified as high-risk PCa, 3 as intermediate and 1 as low per National Comprehensive Cancer Network 2017. Median follow-up time from diagnosis was 168.5 months interquartile range (IQR)=144.2-203.1 months for the whole cohort. In the nonsurgical scenario (6 patients), mean PSA at the time of first and second relapse was 5.2 ng/ml (SD=3.7) and 5.3 ng/ml (SD=4.4), respectively. Median follow-up time from the third RT was 12 months (IQR=3.1-42.5); follow-up time from the forth RT course were 17 and 6 months. Biochemical progression-free intervals after the first and the second EBRT-course were 74 months (IQR=59.3-133.6) and 33 months (IQR=20.8-53.1), respectively. Biochemical and radiological response was registered in all patients; at present, 7/8 patients are free of disease. Overall toxicity profile was good; no severe acute or late genitourinary or gastrointestinal events were recorded. Conclusion: Multiple-course re-EBRT with high precision technology and image guidance can be proposed as a possible salvage therapy for locally recurrent,low-burden PCa recurrence in adequately selected patients. Some room for further dose escalation is suggested. Additionally, re-EBRT may be regarded as an option for avoiding/deferring ADT in carefully selected patients. Larger series and longer follow-up are warranted to assess the potential of multiple re-RT in the setting of local salvage therapies for PCa.
ABSTRACT
Introduction. The role of phosphodiesterase type 5 inhibitors in the treatment of post‐radiotherapy erectile dysfunction (ED) has not been extensively investigated.
Aim. To compare the ...efficacy and safety of on‐demand 20‐mg tadalafil (arm A) with the newly released tadalafil 5‐mg once‐a‐day dosing (arm B) in patients with ED following radiotherapy for prostate cancer (PC).
Methods. Randomized study to receive on‐demand 20‐mg or once‐a‐day 5‐mg tadalafil for 12 weeks.
Main Outcome Measures. Changes in the International Index of Erectile Function (IIEF) domain scores and Sexual Encounter Profile (SEP) question 2 and 3 positive response rates.
Results. Fifty‐two out of 86 screened patients were randomized. Forty‐four patients were evaluable for efficacy. A significant improvement in all domains of the IIEF was observed in both arms (P = 0.0001) with mean erectile function domain scores values of 25 and 27.1 for the 20‐mg and 5‐mg tadalafil, respectively (P = 0.19). SEP 2 and 3 positive response rates increased from 0% in both arms at baseline to 81% and 70% in the 20‐mg arm and 90% and 73% in the 5‐mg arm, respectively, at the end of treatment (P = 0.27). End of treatment global efficacy question positive answers were 86% in the 20‐mg arm and 95% in the 5‐mg arm (P = 0.27). Higher treatment compliance was shown in arm B (100%) as compared with arm A (86%). There was a nonstatistically significant trend toward fewer side effects in favor of the 5‐mg daily dose arm.
Conclusions. In the study population, both tadalafil formulations generated significantly high response rates according to the outcome measures and were well tolerated. The once‐a‐day 5‐mg dosing showed higher compliance and marginally reduced side effects, thus making it an attractive alternative to on‐demand therapy for ED in post‐radiotherapy PC patients. Ricardi U, Gontero P, Ciammella P, Badellino S, Valentino F, Munoz F, Guarneri A, Rondi N, Moretto F, Filippi AR, Ragona R, and Tizzani A. Efficacy and safety of tadalafil 20 mg on demand vs. tadalafil 5 mg once‐a‐day in the treatment of post‐radiotherapy erectile dysfunction in prostate cancer men: A randomized phase II trial. J Sex Med 2010;7:2851–2859.
Background
While a systematic approach to weaning reduces the rate of extubation failure in intubated brain-injured patients, no data are available on the weaning outcome of these patients after ...tracheotomy. We aimed to assess whether a systematic approach to disconnect tracheotomized neurological and neurosurgical patients off the ventilator (intervention) is superior to the sole physician’s judgment (control). Based on previous work in intubated patients, we hypothesized a reduction of the rate of failure within 48 h from 15 to 5 %. Secondary endpoints were duration of mechanical ventilation, ICU length of stay and mortality.
Methods
We designed a single center randomized controlled study. Since no data are available on tracheotomized patients, we based our a priori power analysis on results derived from intubated patients and calculated an overall sample size of 280 patients.
Results
After inclusion of 168 consecutive patients, the trial was interrupted because the attending physicians judged the observed rate of reconnection to be much greater than expected. The overall rate of failure was 29 %, confirming the physicians’ judgment. Twenty-one patients (24 %) in the intervention group and 27 (33 %) controls were reconnected to the ventilator within 48 h (p = 0.222). The main reasons for failure were respiratory distress (80 and 88 % in the treatment and control group, respectively), hemodynamic impairment (15 and 4 % in the treatment and control group, respectively), neurological deterioration (4 % in the control group only). The duration of mechanical ventilation was of 412 ± 202 h and 402 ± 189 h, in the control and intervention group, respectively. ICU length of stay was on average of 23 days for both groups. ICU mortality was 6 % in the control and 2 % in the intervention group without significant differences.
Conclusion
We found no difference between the two groups under evaluation, with a rate of failure much higher than expected. Consequent to the early interruption, our study results to be underpowered. Based on the results of the present study, a further trial should overall enroll 790 patients.
Trial registration: ACTRN12612000372886
Background and purpose: To check the dose delivered to patients during intraoperative electron beam radiation therapy (IOERT) for early breast cancer and also to define appropriate action levels.
...Patients and methods: Between December 2000 and June 2001, 54 patients affected by early-stage breast cancer underwent exclusive IOERT to the tumour bed using a Novac7 mobile linac, after quadrantectomy. Electron beams (5, 7, 9
MeV) at high dose per pulse values (0.02–0.09
Gy/pulse) were used. The prescribed single dose was 21
Gy at the depth of 90% isodose (14–22 mm). In 35 cases, in vivo dosimetry was performed. The entrance dose was derived from the surface dose measured with thin and calibrated MD-55-2 radiochromic films, wrapped in sterile envelopes. Films were analysed 24–72 h after the irradiation using a charge-coupled-device imaging system. Field disturbance caused by the film envelope was negligible.
Results: The mean deviation between measured and expected doses was 1.8%, with one SD equal to 4.7%. Deviations larger than 7% were found in 23% of cases, never consecutively, not correlated with beam energy or field size and with no evidence of linac daily output variation or serious malfunctioning or human mistake. The estimated overall uncertainty of dose measurement was about 4%. In vivo dosimetry appeared both reliable and feasible. Two action levels, for unexplained observed deviations larger than 7 and 10%, were preliminary defined.
Conclusions: Satisfactory agreement between measured and expected doses was found. The implementation of in vivo dosimetry in IOERT is suggested, particularly for patients enrolled in a clinical trial.
The role of phosphodiesterase type 5 inhibitors in the treatment of post-radiotherapy erectile dysfunction (ED) has not been extensively investigated.
To compare the efficacy and safety of on-demand ...20-mg tadalafil (arm A) with the newly released tadalafil 5-mg once-a-day dosing (arm B) in patients with ED following radiotherapy for prostate cancer (PC).
Randomized study to receive on-demand 20-mg or once-a-day 5-mg tadalafil for 12 weeks.
Changes in the International Index of Erectile Function (IIEF) domain scores and Sexual Encounter Profile (SEP) question 2 and 3 positive response rates.
Fifty-two out of 86 screened patients were randomized. Forty-four patients were evaluable for efficacy. A significant improvement in all domains of the IIEF was observed in both arms (P=0.0001) with mean erectile function domain scores values of 25 and 27.1 for the 20-mg and 5-mg tadalafil, respectively (P=0.19). SEP 2 and 3 positive response rates increased from 0% in both arms at baseline to 81% and 70% in the 20-mg arm and 90% and 73% in the 5-mg arm, respectively, at the end of treatment (P=0.27). End of treatment global efficacy question positive answers were 86% in the 20-mg arm and 95% in the 5-mg arm (P=0.27). Higher treatment compliance was shown in arm B (100%) as compared with arm A (86%). There was a nonstatistically significant trend toward fewer side effects in favor of the 5-mg daily dose arm.
In the study population, both tadalafil formulations generated significantly high response rates according to the outcome measures and were well tolerated. The once-a-day 5-mg dosing showed higher compliance and marginally reduced side effects, thus making it an attractive alternative to on-demand therapy for ED in post-radiotherapy PC patients. Ricardi U, Gontero P, Ciammella P, Badellino S, Valentino F, Munoz F, Guarneri A, Rondi N, Moretto F, Filippi AR, Ragona R, and Tizzani A. Efficacy and safety of tadalafil 20mg on demand vs. tadalafil 5mg once-a-day in the treatment of post-radiotherapy erectile dysfunction in prostate cancer men: A randomized phase II trial.
Aims and background
To calculate peripheral radiation dose to the second primary site in patients who have developed a second malignancy after breast cancer radiotherapy (index cases) and to compare ...it with dose in the analogous anatomical site in radiotherapy-treated breast cancer patients who did not experience a second malignancy (controls). To evaluate the feasibility of Peridose-software peripheral dose calculation in retrospective case-control studies.
Material and study design
A case-control study on 12,630 patients who underwent adjuvant breast radiotherapy was performed. Minimum 5-year follow-up was required. Each index case was matched with 5 controls by 1) year of birth, 2) year of radiotherapy and 3) follow-up duration. Peridose-software was used to calculate peripheral dose.
Results
195 second cancers were registered (0.019% of all patients treated with adjuvant irradiation). Several methodological limitations of the Peridose calculation were encountered including impossibility to calculate the peripheral dose in the patients treated with intraoperative or external electron beam radiotherapy, in case of second tumors located at <15 cm from the radiotherapy field etc. Moreover, Peridose requires full radiotherapy data and the distance between radiotherapy field and second primary site. Due to these intrinsic limitations, only 6 index cases were eligible for dose calculation. Calculated doses at the second cancer site in index cases and in an analogous site in controls ranged between 7.5 and 145 cGy. The mean index-control dose difference was −3.15 cGy (range, −15.8 cGy and +2.7 cGy).
Conclusions
The calculated peripheral doses were low and the index-control differences were small. However, the small number of eligible patients precludes a reliable analysis of a potential dose-response relationship. Large patient series followed for a long period and further improvement in the methodology of the peripheral dose calculation are necessary in order to overcome the methodological challenges of the study.
AMALFI MANIFESTO (Italy, 1967) Antonioni, Michelangelo; Bertolucci, Bernardo; Pasolini, Pier Paolo ...
Film Manifestos and Global Cinema Cultures,
04/2014
Book Chapter
Contemporary developments in theoretical studies on the sound film imply the need to take up a position at the outset against the systematic abuse of dubbing, which consistently compromises the ...expressive values of film. The actors themselves acquire from the habit of post-synchronisation (generally carried out with other people’s voices) an increasing detachment from the character they are playing. The techniques of dubbing and the use of stock sound-effects deprive films of the support, on the unitary plane of style, of elements which should be integral to them, and at the same time they subject the film to the manoeuvres
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