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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Non-melanoma skin cancer treated with high-dose-rate brachytherapy and Valencia applicator in elderly patients: a retrospective case series.

PURPOSE: The incidence of non-melanoma skin cancer (NMSC) has been increasing over the past 30 years. Basal cell carcinoma and squamous cell carcinoma are the two most common subtypes of NMSC. The aim of this study was to estimate tumour control, toxicity, and aesthetic events in elderly patients treated with high-dose-rate (HDR) brachytherapy (BT) using Valencia applicator. MATERIAL AND METHODS: From January 2012 to May 2015, 57 lesions in 39 elderly eligible patients were enrolled. All the lesions had a diameter ≤ 25 mm (median: 12.5 mm) and a depth ≤ 4 mm. The appropriate Valencia applicator, 2 or 3 cm in diameter was used. The prescribed dose was 40 Gy in 8 fractions (5 Gy/fraction) in 48 lesions (group A), and 50 Gy in 10 fractions (5 Gy/fraction) in 9 lesions (group B), delivered 2/3 times a week. The biological effective dose (BED) was 60 Gy and 75 Gy, respectively. RESULTS: After median follow-up of 12 months, 96.25% lesions showed a complete response and only two cases presented partial remission. Radiation Therapy Oncology Group - European Organization for Research and Treatment of Cancer (RTOG/EORTC) G 1-2 acute toxicities were observed in 63.2% of the lesions: 56.3% in group A and 77.7% in group B. Late G1-G2 toxicities was observed in 19.3% of the lesions: 18.8% in group A and 22.2% in group B, respectively. No G3 or higher acute or late toxicities occurred. In 86% of the lesions, an excellent cosmetic result was observed (87.5% in group A and 77.8% in group B). Six lesions had a good cosmetic outcome and only 2.3% presented a fair cosmetic impact. CONCLUSIONS: The treatment of NMSC with HDR-BT using Valencia surface applicator is effective with excellent and good cosmetics results in elderly patients. The hypofractionated course appears effective and no statistical differences were observed between the two groups analysed.

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.

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.

Relationship between interval from surgery to radiotherapy and local recurrence rate in patients with endometrioid-type endometrial cancer: a retrospective mono-institutional Italian study.

AIM: To assess the relationship between the timing of radiotherapy and the risk of local failure in patients with endometrioid-type endometrial cancer who had undergone surgery and adjuvant external pelvic radiotherapy (with or without brachytherapy), but not chemotherapy. PATIENTS AND METHODS: One hundred and seventy seven patients were analyzed in this study. The median follow-up of the survivors was 72 months. RESULTS: Radiotherapy was delivered after a median time of 14.6 weeks from surgery and the median overall treatment time was 6.4 weeks. The tumor relapsed in 32 (18.1%) patients after a median time of 21 months. The local recurrence (vaginal or central pelvic) occurred in 11 patients. The local recurrence rate was associated with tumor grade (p=0.02), myometrial invasion (p=0.046), FIGO stage (p=0.003), pathological node status (p=0.037) and time interval from surgery to radiotherapy using 9 weeks as the cut-off value (p=0.046), but not with the overall treatment time. All the local relapses occurred in patients who received adjuvant irradiation after an interval from surgery >9 weeks. CONCLUSION: The time interval from surgery to radiotherapy might affect the local recurrence rate in patients not receiving chemotherapy. Every possible effort should be made to start radiotherapy within 9 weeks, when radiotherapy only is deemed necessary as adjuvant treatment.

Pattern of failures and clinical outcome of patients with locally advanced cervical cancer treated with a tailored integrated therapeutic approach.

AIM: To review a tailored treatment with concurrent chemoradiotherapy (CT/RT) or neoadjuvant chemotherapy (NACT) followed by radical hysterectomy in locally advanced cervical cancer. PATIENTS AND METHODS: One hundred and four patients were treated with a tailored therapeutic approach. CT/RT was the standard treatment for patients with stage Ib2-IIb disease aged more than 70 years, or with high surgical risk, as well as for those with stage III-IV disease. NACT followed by radical hysterectomy was the treatment of choice for patients with stage Ib(2)-IIb disease, maximum age of 70 years and good performance status. RESULTS: For the 61 women who underwent CT/RT, 5-year disease-free (DFS) survival and 5-year overall survival (OS) were 62% and 71%, respectively. Patient outcome was associated with the clinical response to CT/RT (complete responders versus others: 5-year DFS, 81% versus 19%, p<0.001; 5-year OS, 84% versus 37%, p=0.001). For the 43 women who underwent NACT, 5-year DFS and 5-year OS were 66% and 75%, respectively. Patient outcome was associated with the pathological response to chemotherapy (optimal responders versus others: 5-year DFS, 89% versus 62%, p=0.03; 5-year OS, 90% versus 72%, p=0.05). CONCLUSION: Tailored treatments obtained satisfactory clinical outcomes in locally advanced cervical cancer. Optimal pathological response to NACT has been found to be a surrogate endpoint of OS. The identification of biological variables able to predict response to NACT is strongly warranted for an accurate selection of patients who may really benefit from chemosurgical treatment.

Metronomic administration of zoledronic acid and taxotere combination in castration resistant prostate cancer patients: phase I ZANTE trial.

BACKGROUND: Docetaxel (DTX) and zoledronic acid (ZOL) are effective in patients with hormone resistant prostate cancer (HRPC) with bone metastases. A phase I clinical trial of metronomic administration of Zoledronic Acid AN d TaxoterE combination (ZANTE trial) in 2 different sequences was conducted in HRPC. RESULTS: The maximum tolerated dose was not achieved with sequence A. Two patients at third level of sequence B developed dose limiting toxicity. A disease control was obtained in six out of nine patients treated with sequence A, where a decrease of biological markers and PSA were also observed. No evidence of anti-tumor activity was observed in patients treated with sequence B. PATIENTS AND METHODS: Twenty-two patients enrolled into the study (median age: 73 years; range: 43-80) received one of three escalated doses of DTX (30, 40 and 50 mg/m(2)) in combination with a fixed dose of ZOL (2 mg), both administered every 14 days in two different sequences: DTX at the day 1 followed by ZOL at the day 2 (sequence A) or the reverse (sequence B). Patients were evaluated for adverse events and serum IL-8, MMP-2 and MMP-9 were evaluated prior and after therapy with the two sequences of administration of DTX and ZOL. CONCLUSIONS: The bi-weekly combination of DTX (50 mg/m(2)) followed by ZOL was feasible and show promising anti-tumor activity.