Topical ivermectin ointment treatment of Demodex blepharitis: a 6-year retrospective study.

BACKGROUND: To evaluate the efficacy of topical ivermectin 1% ointment, for the treatment of Demodex blepharitis. METHODS: A retrospective study was designed to review electronic medical records of patients seen between January 2017 and December 2022, who had a diagnosis of Demodex blepharitis, treated with topical ivermectin 1% with at least 6 months of follow-up (Centro de Ojos Quilmes, Buenos Aires, Argentina). The presence of collarettes was graded from 0 to 4. An imaging system (Keratograph) was used, to evaluate tear meniscus height (TMH), non-invasive tear break-up time (NIKBUT), and degree of conjunctival redness. In addition, the ocular surface disease index (OSDI) test was performed. Results were compared before and after ivermectin treatment, which was performed once a day for 2 months. RESULTS: A total of 2157 patients (4314 eyes) were included. The mean age was 50.43 ± 15.3 years, and the follow-up time was 26.1 ± 8.5 months. No one discontinued treatment due to intolerance, although 14 cases (0.6 %) reported occasional discomfort. The grade of collarettes decreased with statistical significance, from 3.37 ± 0.7 to 0.1 ± 0.3 (p < 0.01), as well as conjunctival redness from 1.32 ± 0.3 to 0.94 ± 0.4 (p < 0.01) and OSDI score from 58.74 ± 17.9 to 17.1 ± 10.5 (p = 0.02). TMH and NIKBUT improved without statistical difference. CONCLUSION: Treatment with ivermectin 1% topical ointment, once daily for 2 months, was effective in reducing the presence of collarettes and in improving symptoms in patients with Demodex blepharitis.

An empirical approach to the definition of the target margins in eye radiosurgery.

INTRODUCTION: A system for stabilizing and monitoring eye movements during LINAC-based photon beam one single fraction stereotactic radiotherapy was developed at our Institution. This study aimed to describe the feasibility and the efficacy of our noninvasive optical localization system that was developed, tested, and applied in 20 patients treated for uveal melanoma. METHODS: Our system consisted of a customized thermoplastic mask to immobilize the head, a gaze fixation LED, and a digital micro-camera. The localization procedure, which required the active collaboration of the patient, served to monitor the eye movements during all phases of the treatment, starting from the planning computed tomography up to the administration of radiotherapy, and allowed the operators to suspend the procedure and to interact with the patient in case of large movements of the pupil. RESULTS: Twenty patients were treated with stereotactic radiosurgery (27 Gy in one fraction) for primary uveal melanoma. All patients showed a good tolerance to the treatment; until now, all patients were in local control during the follow up and one died for distant progression 6 months after radiosurgery. CONCLUSIONS: This study showed that this noninvasive technique, based on eye position control, is appropriate and can contribute to the success of LINAC-based stereotactic radiotherapy. A millimetric safety margin to the clinical target volume was adequate to take account for the organ movement. All patients treated till now showed a good local control; failures in the disease control were due to metastatic spread.

Success rate in micropulse diode laser treatment with regard to lens status, refractive errors, and glaucoma subtypes.

PURPOSE: To evaluate the efficacy of micropulse transscleral cyclophotocoagulation (MP-TSCPC) considering different characteristics: glaucoma subtypes and lens status. METHODS: A retrospective case-series study was designed to evaluate intraocular pressure (IOP), and the number of IOP-lowering medications, used by glaucoma patients treated with MP-TSCPC between 2016 and 2019. Cases had a follow-up period of 12 months. Achieving an IOP reduction higher than 20%, or the decrease of at least one IOP-lowering medication, was considered a successful outcome. The same population was analyzed by classifying them in two groups as: glaucoma subtypes and lens status. The baseline spherical equivalent (SE) was also calculated for considering association with the achieved IOP. RESULTS: A total of 86 eyes were included. In most cases, IOP and IOP-lowering medications were decreased with a statistically significant difference (p < 0.0001), and all of them had a successful outcome. The percentage of IOP drop oscillated between 25.9% (open-angle glaucoma sub-group) and 37.5% (pseudoexfoliative glaucoma sub-group), 12 months after surgery. The difference between the groups was not statistically significant (p 0.20 and 0.32 for glaucoma subtypes and lens status, respectively). The Pearson's coefficient obtained was low for the SE and IOP association, at the 12 -month postoperative mark (- 0.009; p < 0.001). CONCLUSIONS: The MP-TSCPC treatment was successful in decreasing IOP and IOP-lowering medications, in different glaucoma subtypes. Differences between groups (glaucoma subtypes, phakic and pseudophakic eyes) were not statistically significant. No association was found between the SE and the IOP achieved value after MS-TSCPC treatment.

Late-onset distal-apical intracorneal ring-segments keratopathy: an analysis of a large sample in a multicenter study.

PURPOSE: To review the prevalence and describe the characteristics, of cases with late-onset intracorneal ring segments (ICRS) keratopathy in a multicenter study. METHODS: A retrospective multicentric case-series study was performed in a specialized keratoconus service, from Buenos Aires, Argentina. An electronic clinical chart from patients with ICRS keratopathy between January 1999 and January 2019 was reviewed. We included cases with late-onset distal-apical ICRS keratopathy, which was defined as a persistent corneal lesion developed 12 months or later after implantation, located over, around, or closer to the ICRS. All the surgeries were performed by a manual corneal tunnel creation technique. Samples were taken to rule out infectious etiology. RESULTS: From 5217 eyes that underwent ICRS implantation, 13 cases (0.24%) were detected. The keratopathy onset was 72 ± 42.98 months (29-133) after ICRS implantation. Cultures were negative in all cases. An ICRS exchange was made for five cases in stage I and four in stage II. Four cases presented with partial ICRS extrusion in stage III. ICRS exchange was possible in two of them and a penetration keratoplasty was necessary for the rest. All cases remained stable 1 year after surgical procedures. CONCLUSIONS: A late-onset distal-apical ICRS keratopathy was detected with low prevalence (0.24%) in a large sample. It was classified into three stages according to its severity. Different treatments were selected for each stage, obtaining stable results 1 year after treatment.

Photon-based high-dose single-fraction radiosurgery, an effective treatment modality for recurrent uveal melanoma.

Introduction: To evaluate and report the outcome of a patient with locally recurrent uveal melanoma (UM) previously treated with brachytherapy (BT), using a second personalized globe-sparing radiotherapy approach. Material and methods: In June 2020, a 78-year-old man arrived at our institution with diplopia and suspected uveal melanoma. At the ophthalmological evaluation (B-scan and A-scan ultrasonography) a lesion in the right eye at 6-7 hours of about 5 mm thickness, with internal lacunar areas, approximately 7 mm away from the limbus, was observed. The patient underwent ruthenium plaque BT at a total dose of 110 Gy prescribed to the apex of the tumour. At the follow-up, the lesion was under control until September 2021, but it recurred with a satellite exudative detachment in the lower and temporal sectors 7-10 hours. At the B-scan the lesion had a maximum thickness of 4.6 mm. Subsequently, in a multidisciplinary discussion, one single fraction stereotactic radiosurgery was scheduled. The prescribed dose was 27 Gy in the de-novo lesion and 24 Gy in the previously irradiated site. Stereotactic radiosurgery was performed in October 2021. Results: The time interval between the 2 treatments was 15 months. Twenty months after recurrence, local tumour control was observed, and no metastases were detected on follow-up examinations. No severe acute or late toxicity was observed due to the retreatment. Conclusions: Photon stereotactic radiotherapy is a feasible, acceptably tolerated modality, and it represents an eye-preserving treatment also for patients with recurrent UM unfit for BT.

High-dose-rate brachytherapy for non-melanoma skin cancer using tailored custom moulds - a single-centre experience.

AIM OF THE STUDY: The aim of this retrospective study was to analyse tumour control, toxicity, and aesthetic outcome of patients affected by non-melanoma skin cancer (NMSC) treated with 192 Ir high-dose-rate (HDR)-brachytherapy (BT) at the Division of Radiotherapy, University of Pisa. MATERIAL AND METHODS: From January 2014 to December 2019 we treated 37 patients (median age 79 years; range 31-91 years) affected by NMSC, with the following histological subtypes: 62.2% basal cell carcinoma and 37.8% squamous cell carcinoma. We analysed 40 lesions with a depth ≤ 5 mm, located in 40.0% scalp, 17.5% nose, 25.0% face, and 17.5% ear, all treated with 192 Ir-based HDR-BT, using tailored custom moulds, with a median of 5 catheters (range, 1-9) spaced 1 cm apart. The most common fractionation scheme was 40 Gy in 8 daily fractions; the biological effective dose was 60 Gy. RESULTS: The median follow-up was 25 months (range, 3-70 months). The 2-year local control rate was 90%. Common terminology criteria for adverse event (CTCAE vs. 5.0) G1 toxicities were dermatitis (52%), pain (25%), and ulceration (22%). The only G2 acute toxicities were dermatitis and ulceration. The most common G1 late toxicities were fibrosis (17%), atrophy (15%), and hypopigmentation (12%). No G3 or higher acute or late toxicity was reported. Excellent cosmetic results were observed in 65.0% of the lesions; only 1 case (2.5%) reported a poor cosmetic result. CONCLUSIONS: Surface mould HDR-BT is a safe, effective, and well tolerated treatment modality for NMSC and can be considered a good alternative, especially for elderly patients who are often unfit for surgery.

Clinical trials and drug cost savings for Italian health service.

BACKGROUND: The cost of anticancer drugs is constantly growing. The aim of this study was determine the impact in terms of cost reduction for anticancer drug in the Italian Health Service due to patient participation in clinical trials. METHODS: We evaluated the cost of drugs administered to patients treated in clinical trials at the National Cancer Institute of Naples in a four-week time period. Patients with a diagnosis of different cancers were considered, including adjuvant therapy and treatment for advanced disease, pharma sponsored and investigator initiated phase I, II and III clinical studies. We defined the expected standard treatment for each patient and we calculated the cost of the standard antineoplastic drugs that should be administered in clinical practice outside clinical trials. We used the market price of drugs to determine the cost savings value. Costs other than drugs were not included in the cost saving calculation. RESULTS: From 23.10.2017 to 17.11.2017, 126 patients were treated in 34 pharma sponsored and investigator initiated clinical trials, using experimental drugs provided free of charge by the sponsors, for an overall number of 152 cycles of therapy. If these patients were treated with conventional therapies in clinical practice the cost of antineoplastic drugs would account for 517,658 Euros, with an average of 5487 Euros saved per patients for a period of 4 weeks. CONCLUSIONS: Clinical trials with investigational antineoplastic drugs provided free of charge by Sponsors render considerable cost savings, with a tangible benefit in clinical and administrative strategies to reduce drug expenditures.

Iodine Plaque Brachytherapy a Customized Conservative Approach to the Management of Medium/Large-sized Uveal Melanoma.

BACKGROUND/AIM: The objective of this study was to assess the role of iodine (125I) plaque brachytherapy in the management of uveal melanoma. PATIENTS AND METHODS: This is a retrospective study of 50 patients (median age 67 years; range=33-86 years) with uveal melanoma, treated with 125I plaque brachytherapy at the University Hospital of Pisa. Uveal melanoma was diagnosed with A-scan and B-scan standardized echography, fluorescein angiography, indocyanine green-angiography, optical coherence tomography, and/or magnetic resonance imaging. The primary outcomes assessed were local control, overall survival, disease progression, globe preservation, and metastases. Secondary outcomes were acute and late radiation adverse effects. RESULTS: Inclusion criteria comprised Eastern Cooperative Oncology Group performance status ≤2, life expectancy >6 months, and tumor thickness ≤10 mm and\or diameter ≤20 mm. All the patients were treated with 125I plaque brachytherapy, with a prescription dose of 85 Gy to the tumor apex. The 5-year rate of local control, progression-free survival, metastasis-free survival, enucleation-free survival, and overall survival were 83.0%, 81.4%, 90.3%, 83.1%, and 92.1% respectively. Twenty-four patients (48.0%) had one or more acute and late toxicities. The most common acute adverse events (CTCAE vs. 5.0) grade 1-3 were conjunctivitis and eye pain (6.0%). Regarding late events, radiation retinopathy grade 1-3 occurred in 18.0% of cases, while grade 1-3 vitreous hemorrhage in 2.5%. CONCLUSION: 125I plaque brachytherapy offers an effective and safe approach for selected cases of uveal melanoma, due to the reported satisfactory results in terms of local control, eye conservation and survival.

Efficacy and safety of second-line fotemustine in elderly patients with recurrent glioblastoma.

Fotemustine (FTM) is a common treatment option for glioblastoma patients refractory to temozolomide (TMZ). Although elderly patients represent a large component of glioblastoma population, the feasibility and the efficacy of second-line FTM are not available in those patients.We retrospectively analyzed the records of glioblastoma patients older than 65 years, receiving FTM at a dose of 70-100 mg/m(2) of FTM every week for 3 consecutive weeks (induction phase) and then every 3 weeks (70-100 mg/m(2)), as second-line treatment.Between January 2004 and December 2011, 65 glioblastoma patients (median age, 70 years; range, 65-79 years) were eligible for this analysis. Sixty-five patients received a total of 364 FTM cycles, with a median of 4 cycles for each patient. After induction, we observed 1 complete response (1.5 %), 12 partial responses (18.5 %), 18 stable diseases (27.7 %), and 34 patients' progressions (47.7 %). Disease control rate was 43.1 %. Median survival from the beginning of FTM therapy was 7.1 months, while the median progression-free survival was 4.2 months, and the 6-months progression free survival rate was 35.4 %. The most relevant grade 3-4 toxicity events were thrombocytopenia (15.3 %) and neutropenia (9.2 %). In the univariate and multivariate analysis, time from radiotherapy to FTM, number of TMZ and FTM cycles and disease control resulted independent prognostic factors.This study showed that FTM is a valuable therapeutic option for elderly glioblastoma patients, with a safe toxicity profile.

Lymph-vascular Space Involvement and/or p53 Overexpression Correlated With the Clinical Outcome of Early-stage Endometrial Cancer Patients Treated With Adjuvant Vaginal Brachytherapy.

BACKGROUND/AIM: The majority of patients with endometrial cancer (EC) are diagnosed at an early stage and undergo primary surgery, followed by observation or adjuvant therapy according to risk factors on surgical samples. The objective of this study was to assess the correlation between a risk profile represented by the presence of substantial lymph-vascular space involvement (LVSI) and/or p53 overexpression and the clinical outcome of patients with early-stage endometrial cancer (EC) who received adjuvant vaginal brachytherapy (BT). PATIENTS AND METHODS: This investigation assessed 79 patients who underwent hysterectomy, bilateral salpingo-oophorectomy, and pelvic and/o aortic lymphadenectomy or sentinel lymph node biopsy followed by hypofractionated (HDR)-vaginal BT, using 192Ir source, for stage I-II endometrioid (n=70) or non-endometrioid (n=9) EC. Thirty-four patients (43.0%) were considered to have an unfavorable risk profile defined by the presence of substantial LVSI and /or p53 overexpression. RESULTS: Five-year disease-free survival (DFS) and five-year overall survival (OS) were 93.7% and 95%, respectively. There was a significant correlation between unfavorable risk-profile and pelvic recurrence rate (p=0.002) and distant recurrence rate (p=0.017). Patients with abnormal p53 had a higher risk of local relapse (p=0.041). Substantial LVSI was strongly associated with pelvic recurrence (p=0.001) and distant metastasis (p<0.001). CONCLUSION: The presence of substantial LVSI and/or p53 overexpression strictly correlated with poor outcome of patients with early-stage EC and should be taken into consideration for better planning adjuvant treatment in this clinical setting.

A retrospective pooled analysis of response patterns and risk factors in recurrent malignant glioma patients receiving a nitrosourea-based chemotherapy.

BACKGROUND: At recurrence the use of nitrosoureas is widely-used as a therapeutic option for glioblastoma (GBM) patients. The efficacy of fotemustine (FTM) has been demonstrated in phase II clinical trials; however, these papers report a wide range of progression-free-survival (PFS-6 m) rates, ranging from 21% to 52%. We investigated whether FTM could have a different response pattern in respect to time to adjuvant temozolomide failure, or whether specific independent risk factors could be responsible for the wide range of response rates observed. METHODS: Recurrent GBM patients have been treated with fotemustine 75-100 mg/sqm at day 1, 8, 15 and after 4/5 weeks of rest with 100 mg/sqm every 21 days. Patients were stratified in 4 groups according to time to temozolomide failure: before starting (B0), during the first 6 months (B1), after more than 6 months of therapy (B2), and after a treatment-free interval (B3). Primary endpoint was PFS-6 m. A multivariable analysis was performed to identify whether gender, time after radiotherapy, second surgery and number of TMZ cycles could be independent predictors of the clinical benefit to FTM treatment. RESULTS: 163 recurrent GBM patients were included in the analysis. PFS-6 m rates for the B0, B1, B2 and B3 groups were 25%, 28%, 31.1% and 43.8%, respectively. The probability of disease control was higher in patients with a longer time after radiotherapy (p = 0.0161) and in those who had undergone a second surgery (p = 0.0306). CONCLUSIONS: FTM is confirmed as a valuable therapeutic option for patients with recurrent GBM and was active in all study patient groups. Time after the completion of radiotherapy and second surgery are independent treatment-related risk factors that were predictive of clinical benefit.

Photon-based High-dose Single-fraction Radiosurgery, an Effective Treatment Modality for Large and Posterior Uveal Melanoma.

BACKGROUND/AIM: Uveal melanoma (UM) is the most common primary intraocular malignant tumor. This malignancy is frequently treated using brachytherapy, stereotactic radiotherapy, or proton therapy. The objective of this study was to assess the role of stereotactic radiosurgery in the treatment of large and posterior UM. PATIENTS AND METHODS: From January 2014 to July 2021, we treated 65 patients (median age=71 years; range=31-89 years) affected by UM. Inclusion criteria were Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2, life expectancy >6 months, tumor thickness >10 mm, diameter >16 mm or posterior UM. The treatment was delivered with a True Beam™ LINAC with arc modulation technique. All patients received 27 Gy in one fraction (biological effective dose ≈100 Gy, assuming an α/ß of 10). RESULTS: The median follow-up was 36 (range=3-90) months. Acute toxicities were reported in 14 patients, whereas late toxicity occurred in 45 (69.2%). Fifteen patients (23.0%) underwent enucleation: eight (12.3%) for failure of local control and seven (10.7%) for late treatment co-morbidities. The 5-year local control, and progression-free, metastasis-free, enucleation-free, and overall survival rates were 80%, 43%, 62%, 65% and 56%, respectively. In multivariate analysis, tumor dimensions significantly influenced survival [larger basal diameter: progression-free [hazard ratio (HR)=2.42] and overall (HR=2.61) survival; greater thickness: overall survival (HR=2.36)]. In multivariate analysis, patients without local control had a higher risk of distant metastasis (HR=3.25). CONCLUSION: Stereotactic radiosurgery offers an effective and safe approach for selected cases of UM due to the satisfactory results in terms of local control, eye conservation and survival.

Two different sizes of Valencia applicators in non-melanoma skin cancer treatment with iridium-192 high-dose-rate brachytherapy.

PURPOSE: The aim of this retrospective study was to analyze tumor control, toxicity, and aesthetic outcome of patients affected by non-melanoma skin cancer (NMSC) and treated with iridium-192 (192Ir) high-dose-rate (HDR) brachytherapy (BT) using Valencia applicators at the Division of Radiotherapy, University of Pisa. MATERIAL AND METHODS: From June 2015 to December 2020, 95 NMSC patients, including 61.5% basal cell carcinoma and 38.5% squamous cell carcinoma patients, with median age of 83 years (range, 32-96 years) were treated. In total, 182 lesions with a diameter ≤ 25 mm (median, 12 mm) and a depth ≤ 4 mm, located in scalp (19.2%), face (20.9%), chest (8.8%), nose (16.5%), ear (15.4%), and extremities (19.2%) were analyzed. All lesions were treated with 192Ir-based HDR afterloader using Valencia applicators. 105 lesions (57.7%) were treated with applicator of 20 mm and 77 lesions (42.3%) with applicator of 30 mm in diameter, depending on the size of lesions. Prescribed dose was 40 Gy in 8 fractions (5 Gy/fraction) delivered 2-3 times a week. Biological effective dose (BED) was ≈ 60 Gy. RESULTS: The median follow-up was 14 months (range, 3-59 months). The 2-year local control rate was 96%. According to common terminology criteria for adverse events (CTCAE v. 5.0), G1-G2 acute toxicities included dermatitis (22.0%) and pain (8.2%). The most common G1 late toxicities were hypopigmentation (27.5%) and fibrosis (8.2%), and G2 late toxicity included ulceration (0.5%). No G3 or higher acute or late toxicities were reported. Excellent cosmetic results were observed in 77.5% of the lesions, with one only (0.5%) reported as a poor cosmetic result (ulceration refractory to therapy). CONCLUSIONS: HDR-BT using Valencia applicators is a safe, effective, and well-tolerated treatment modality for NMSC, and can be considered a good alternative for treatment, especially in elderly patients who are often unfit for surgery.

Effect of Bevacizumab in Combination With Standard Oxaliplatin-Based Regimens in Patients With Metastatic Colorectal Cancer: A Randomized Clinical Trial.

Importance: Although bevacizumab is a standard of care in combination treatments for metastatic colorectal cancer (mCRC), its clinical benefit has been limited. Objective: To determine whether sequential scheduling of bevacizumab administration in combination with chemotherapy improves treatment efficacy in patients with mCRC, in keeping with the tumor vascular normalization hypothesis. Design, Setting, and Participants: This open-label, randomized clinical phase 3 trial was conducted from May 8, 2012, to December 9, 2015, at 3 Italian centers. Patients aged 18 to 75 years with unresectable, previously untreated, or single line-treated mCRC were recruited. Follow-up was completed December 31, 2019, and data were analyzed from February 26 to July 24, 2020. Interventions: Patients received 12 biweekly cycles of standard oxaliplatin-based regimens (modified FOLFOX-6 [levo-folinic acid, fluorouracil, and oxaliplatin]/modified CAPOX [capecitabine and oxaliplatin]) plus bevacizumab administered either on the same day as chemotherapy (standard arm) or 4 days before chemotherapy (experimental arm). Main Outcomes and Measures: The primary end point was the objective response rate (ORR) measured with Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included progression-free survival, overall survival, safety, and quality of life (QOL). Results: Overall, 230 patients (136 men [59.1%]; median age, 62.3 [interquartile range, 53.3-67.6] years) were randomly assigned to the standard arm (n = 115) or the experimental arm (n = 115). The median duration of follow-up was 68.3 (95% CI, 61.0-70.0) months. No difference in ORR (57.4% [95% CI, 47.8%-66.6%] in the standard arm and 56.5% [95% CI, 47.0-65.7] in the experimental arm; P = .89) or progression-free survival (10.5 [95% CI, 9.1-12.3] months in the standard arm and 11.7 [95% CI, 9.9-12.9] months in the experimental arm; P = .15) was observed. However, the median overall survival was 29.8 (95% CI, 22.5-41.1) months in the experimental arm compared with 24.1 (95% CI, 18.6-29.8) months in the standard arm (adjusted hazard ratio, 0.73; 95% CI, 0.54-0.99; P = .04). Moreover, the experimental arm was associated with a significant reduction in the rate of severe diarrhea (6 [5.3%] vs 19 [16.5%]; P = .006) and nausea (2 [1.8%] vs 8 [7.0%]; P = .05) and improved physical functioning (mean [SD] change from baseline, 0.65 [1.96] vs -7.41 [2.95] at 24 weeks; P = .02), and constipation scores (mean [SD] change from baseline, -17.2 [3.73] vs -0.62 [4.44]; P = .003). Conclusions and Relevance: In this randomized clinical trial, sequential administration of bevacizumab plus chemotherapy did not improve ORR, the primary end point. However, the overall survival advantage, fewer adverse effects, and better health-related QOL associated with sequential bevacizumab administration might provide the basis for exploring antiangiogenic combination treatments with innovative perspectives. Trial Registration: EudraCT Identifier: 2011-004997-27; ClinicalTrials.gov Identifier: NCT01718873.

CT colonography versus double-contrast barium enema for screening of colorectal cancer: comparison of radiation burden.

Our aim is to compare the radiation dose associated with a low-dose CT colonography (CTC) protocol for colorectal cancer screening with that delivered by double-contrast barium enema (DCBE). CTC of twenty asymptomatic individuals (M:F = 10:10) participating to a colorectal cancer screening program and DCBE of fifteen patients (M:F = 6:9) were evaluated. For CTC, absorbed dose was determined by calculating the dose-length product for each CTC examination from measurements on a CT dose phantom equipped with a CT ion chamber. For DCBE, the free-in-air Kerma at the patient's X-ray entry surface and the Kerma-area product during fluoroscopy and fluorography were measured with a Barracuda system, with fluoroscopy times being recorded blinded to the performing operator. Effective dose at CTC was 2.17 ± 0.12 mSv, with good and excellent image quality in 14/20 (70%) and 6/20 cases (30%), respectively. With DCBE, effective patient dose was 4.12 ± 0.17 mSv, 1.9 times greater than CTC (P < 0.0001). Our results show that effective dose from screening CTC is substantially lower than that from DCBE, suggesting that CTC is the radiological imaging technique of the large bowel with the lowest risk of stochastic radiation effects.

Perioperative high-dose-rate brachytherapy in the treatment of recurrent malignant gliomas.

PURPOSE: To assess the feasibility and effectiveness of perioperative high-dose-rate brachytherapy for recurrent malignant gliomas. PATIENTS AND METHODS: Between 2005 and 2008, 21 patients (14 males and seven females) with relapsed malignant glioma underwent a second surgery followed by a brachytherapy implant in the surgical cavity. Median age was 60 years, and median Karnofsky performance status 80. A single fraction of 18 Gy specified at 5 mm depth was administered perioperatively. Then, the applicator was removed nonsurgically. Mean postoperative hospitalization time was 3 days. RESULTS: At the time of analysis, 15 patients (71%) had died and six (29%) were alive. Median follow-up was 32.3 months. Median overall survival from diagnosis amounted to 21.7 months. Median survival after recurrence was 8.0 months, and 6-month progression-free survival 42%. Patients were stratified into classes according to the prognostic recursive partitioning analysis. CONCLUSION: Perioperative brachytherapy has proven to be safe and well tolerated in patients with recurrent malignant glioma. No severe toxicity was reported, and the treatment has proven to be effective in symptomatic recurrences of malignant gliomas.

High-dose-rate brachytherapy in a large squamous cell carcinoma of the hand.

PURPOSE: High-dose-rate (192)Ir-based brachytherapy can be used as an exclusive treatment of large skin tumors when teletherapy or surgery is not feasible. A case of an extended inoperable skin epithelioma of the hand is reported; the lesion involved the first finger, the tenar, the palm, and the back. METHODS AND MATERIALS: A detailed description of an individual case is reported. A customized mold was created for the patient, to administer a fractionated brachytherapy treatment in a reproducible way. RESULTS: A total dose of 50Gy was administered in 10 fractions, after a time schedule of three fractions per week. The treatment was well tolerated and the acute effects (mainly, epitheliolysis) were resolved completely within a month after the treatment. CONCLUSIONS: Nine months after the treatment, the malignant lesion completely disappeared and the cosmetic results are quite satisfactory. Therefore, we conclude that the treatment technique is well adaptable to any particular geometry and that the fractionation scheme has proven to be well tolerated and effective in tumor eradication.

Acute and late vaginal toxicity after adjuvant high-dose-rate vaginal brachytherapy in patients with intermediate risk endometrial cancer: is local therapy with hyaluronic acid of clinical benefit?

PURPOSE: The aim of the present study was to evaluate the effectiveness of hyaluronic acid (HA) in the prevention of acute and late vaginal toxicities after high-dose-rate (HDR) vaginal brachytherapy (BT). MATERIAL AND METHODS: Between January 2011 and January 2015, we retrospectively analyzed 126 patients with endometrial cancer who underwent extrafascial hysterectomy with or without lymphadenectomy and adjuvant HDR-vaginal BT +/- adjuvant chemotherapy. The total dose prescription was 21 Gy in 3 fractions (one fraction for week). Vaginal ovules containing 5 mg of HA were given for whole duration of vaginal BT and for the two following weeks. Acute and late toxicities were evaluated according to CTCAE vs 4.02. RESULTS: According to the revised FIGO 2009 classification, most tumors were in stage IA (30.9%) and in stage IB (57.9%). Thirty-three patients (26.2%) received adjuvant chemotherapy before vaginal BT. Five-year disease-free survival (DFS) and five-year overall survival (OS) were 88% and 93%, respectively. The most common grade 1-2 acute toxicities were vaginal inflammation (18 patients, 14.3%) and dyspareunia (7 patients, 5.5%). Two patients (1.6%) had more than one toxicity. Late toxicity occurred in 20 patients (15.9%). Grade 1-2 late toxicities were fibrosis (14 patients, 11.1%) and telangiectasias (7 patients, 5.5%). Six patients (4.8%) had more than one late toxicity. No grade 3 or higher acute or late toxicities were observed. CONCLUSIONS: These results appear to suggest that the local therapy with HA is of clinical benefit for intermediate risk endometrial cancer patients who receive adjuvant HDR-vaginal BT after surgery. A randomized trial comparing HA treatment vs. no local treatment in this clinical setting is warranted to further evaluate the efficacy of HA in preventing vaginal BT-related vaginal toxicity.

Twenty-year results of the Naples GUN randomized trial: predictive factors of adjuvant tamoxifen efficacy in early breast cancer.

PURPOSE: Tamoxifen (TAM) is increasingly administered to new early breast cancer patients. Because it is not devoid of toxic effects, we studied factors potentially predictive of its efficacy. EXPERIMENTAL DESIGN: From 1978 to 1983, 433 patients were enrolled in the GUN randomized trial: 206 were assigned to TAM versus 227 controls (no-TAM). Premenopausal patients with axillary lymph node involvement (60 TAM versus 65 no-TAM) also received nine CMF cycles. Eight biological markers were retrospectively assayed for most patients: estrogen; progesterone; prolactin receptors (PrlRs); microvessel count (MVC); S-phase fraction; tumor ploidy; epidermal growth factor receptor (EGFR); and HER2. We performed a multivariate test of the TAM/covariate interactions to establish whether these variables predicted for TAM efficacy. Estimates of the TAM effect were expressed as hazard ratio (HR) of death of TAM over no-TAM patients with 95% confidence intervals (95% CIs). RESULTS: At a median follow-up of 15 years, PrlRs, MVC, S-phase fraction, ploidy, and EGFR did not influence TAM efficacy. Differently, HER2 had an overall significant predictive effect: HR = 0.59 (95% CI: 0.40-0.87) in HER2-negative subjects versus HR = 1.09 (95% CI: 0.63-1.87) in HER2-positive subjects (interaction test: P = 0.04). The predictive effect of HER2 was also evident in the subgroup of patients with steroid receptor-positive tumors (HER2 positive: HR = 1.33, 95% CI: 0.70-2.51; HER2 negative: HR = 0.73, 95% CI: 0.47-1.14). CONCLUSIONS: With the statistical power of the present randomized trial, S-phase, ploidy, EGFR, PrlR, and MVC do not seem to predict for TAM efficacy. Conversely, our data support the hypothesis that tumors overexpressing HER2 might not benefit from adjuvant TAM.