Bevacizumab for the Treatment of Radiation-Induced Cerebral Necrosis: A Systematic Review of the Literature

Radiation necrosis (RN) of brain tissue is a serious late complication of brain irradiation and recently bevacizumab has been suggested as treatment option of RN. There is a lack of data in the literature regarding the effectiveness of bevacizumab for the treatment of RN. The purpose of this review was to perform a comprehensive analysis of all reported cases using bevacizumab for the treatment of brain RN. In September 2016, we performed a comprehensive literature search of the following electronic databases: PubMed, Web of Science, Scopus and Cochrane Library. The research for the review was conducted using a combination of the keywords “radiation necrosis”, “radiotherapy” and “bevacizumab” alongside the fields comprising article title, abstract and keywords. Randomized trials, non-randomized trials, prospective studies, retrospective studies and single case reports were included in the review. Our research generated 21 studies and 125 cases where bevacizumab had been used for the treatment of RN. The median follow-up was 8 months and the most frequent bevacizumab dose used was 7.5 mg/kg for 2 weeks with a median of four cycles. Low-dose bevacizumab resulted in effectiveness with improvement in both clinical and radiographic response. The median decrease in T1 contrast enhancement and in T2/FLAIR signal abnormality was 64% and 60%, respectively. A reduction in steroidal therapy was observed in majority of patients treated. Based on the data of our review, bevacizumab appears to be a promising agent for the treatment of brain RN. Future prospective studies are required to evaluate the role of bevacizumab in RN and to define the optimal scheduling, dosage and duration of therapy

The effectiveness of bevacizumab in radionecrosis after radiosurgery of a single brain metastasis

Radionecrosis (RN) of brain tissue is a serious late complication of brain irradiation and historically has been treated with corticosteroid therapy and alternatively surgical decompression. Recently, bevacizumab has been suggested for treatment of cerebral radiation necrosis. We present a case of a 73- years-old women affected by a primary nonsmall cell lung cancer with a single brain metastasis treated with radiosurgery. Two years after radiosurgery the patient referred neurological symptoms and a brain magnetic resonance confirmed the presence of RN. The patient refused surgical decompression so underwent at the treatment with bevacizumab 7.5 mg/kg/2 weeks for a total of 4 cycles. After two months of treatment the patient reported strumental and clinical improvement. Ten months after bevacizumab discontinuation the patient experienced a recurrence of RN with evident clinical manifestation and confirmed by radiological imaging. A new treatment with bevacizumab was not performed due to the systemic progression disease and the worsening of clinical status. Despite limited to only one clinical case, our study suggests the efficacy of bevacizumab to treat RN. Future studies are needed to confirm its mechanism and to properly define the optimal scheduling, dosage and duration of therapy

Non-melanoma skin cancer treated with high-doserate 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

A multimodal approach to the treatment of bilateral choroidal metastases from thyroid carcinoma

A 58-year old man, affected by metastatic thyroid carcinoma, experienced a progressive bilateral visual impairment. Ophthalmic examination revealed the presence of a choroidal mass with an associated exudative retinal detachment in both eyes. Twelve years before, a diagnosis of metastatic thyroid carcinoma had been established and the patient had been subject to several therapeutic procedures

Non-melanoma skin cancer treated with high-dose-rate brachytherapy: a review of literature

Purpose: The incidence of non-melanoma skin cancer (NMSC) has been increasing over the past 30 years. There are different treatment options and surgical excision is the most frequent treatment due to its low rates of recurrence. Radiotherapy is an effective alternative of surgery, and brachytherapy (BT) might be a better therapeutic option due to high radiation dose concentration to the tumor with rapid dose fall-off resulting in normal tissues sparing. The aim of this review was to evaluate the local control, toxicity, and cosmetic outcomes in NMSC treated with high-dose-rate BT (HDR-BT). Material and methods: In May 2016, a systematic search of bibliographic database of PubMed, Web of Science, Scopus, and Cochrane Library with a combination of key words of “skin cancer”, “high dose rate brachytherapy”,“squamous cell carcinoma”, “basal cell carcinoma”, and “non melanoma skin cancer“ was performed. In this systematic review, we included randomized trials, non-randomized trials, prospective and retrospective studies in patients affected by NMSC treated with HDR-BT. Results: Our searches generated a total of 85 results, and through a process of screening, 10 publications were selected for the review. Brachytherapy was well tolerated with acceptable toxicity and high local control rates (median: 97%). Cosmetic outcome was reported in seven study and consisted in an excellent and good cosmetic results in 94.8% of cases. Conclusions: Based on the review data, we can conclude that the treatment of NMSC with HDR-BT is effective with excellent and good cosmetics results, even in elderly patients. The hypofractionated course appears effective with very good local disease control. More data with large-scale randomized controlled trials are needed to assess the efficacy and safety of brachytherapy

[18F]Choline PET/CT and stereotactic body radiotherapy on treatment decision making of oligometastatic prostate cancer patients: Preliminary results

Background: A new entity of patients with recurrent prostate cancer limited to a small number of active metastatic lesions is having growing interest: the oligometastatic patients. Patients with oligometastatic disease could eventually be managed by treating all the active lesions with local therapy, i.e. either surgery or ablative stereotactic body radiotherapy. This study aims to assess the impact of [18F]Choline ([18F]FMCH) PET/CT and the use stereotactic body radiotherapy (SBRT) in patients (pts) with oligometastatic prostate cancer (PCa). Methods: Twenty-nine pts with oligometastatic PCa (≤3 synchronous active lesions detected with [18F]FMCHPET/CT) were treated with repeated salvage SBRT until disease progression (development of > three active synchronous metastases). Primary endpoint was systemic therapy-free survival measured from the baseline [18F]FMCHPET/CT. Results: A total of 45 lesions were treated with SBRT. After a median follow-up of 11.5 months (range 3-40 months), 20 pts were still in the study and did not receive any systemic therapy. Nine pts started systemic therapy, and the median time of the primary endpoint was 39.7 months (CI 12.20-62.14 months). No grade 3 or 4 toxicity was recorded. Conclusions: Repeated salvage [18F]FMCHPET/CT-guided SBRT is well tolerated and could defer the beginning of systemic therapy in selected patients with oligometastatic PCa

Squamous cell carcinoma of the vagina: Natural history, treatment modalities and prognostic factors

Squamous cell carcinoma of the vagina accounts for less than 2% of all gynecologic malignancies. Surgery has a role in selected cases only. The standard treatment is radiotherapy, external beam radiation and/or brachytherapy, depending on the extent, thickness, location and morphology of the lesion. The role of chemotherapy is still under evaluation. Radiotherapy obtained 5-year overall survival rates ranged from 35% to 78%, with severe late complication rates of 9.4-23.1%. Tumor stage is the strongest prognostic factor. Tumor size >4. cm, tumor location outside the upper third of the vagina, and old age at presentation are additional predictors of poor survival in most papers, whereas the prognostic value of histological grade, prior hysterectomy, and hemoglobin levels is controversial. High-risk HPV DNA and low MIB-1 index are associated with better clinical outcome. Because of the rarity of this tumor, future multicenter studies would be strongly warrante

PET based target volume delineation in hypofractionated radiotherapy in locally advanced NSCLC: A single institution experience

Background: Chemo-radiotherapy is the standard of care of locally advanced (stage III) unresectable non-small cell lung cancers (NSCLC). Concomitant chemo-radiotherapy reduces local failure compared to sequential schedules but distant failures remain common (about 40%). Conventional radiotherapy is given in 2Gy fractions over 6−7 weeks of treatment (total dose 60−70Gy) conditioning the patent’s quality of life. Stereotactic body radiotherapy (SBRT) is effective for the treatment of early stage NSCLCs not eligible for surgical resection. The integration of positron emission tomography (PET) information for target volume delineation in radiation treatment planning is routine in many centers. We evaluated the feasibility of short course hypo fractionated radiotherapy with PET assisted visual-manual target delineation, given between chemotherapy cycles, in locally advanced NSCLCs. Methods: Patients, with a proven histological diagnosis of NSCLC, were enrolled if deem not resectable. Inclusion criteria were: maximum diameter of the primary tumor 1). All patient underwent 18FFDG PET-CT within 1 month from the beginning of the treatment and mean SUVmax was 12.6 (range 3.8–33.8). A total dose of 40 Gy was given in 5 fractions of 8Gy using volumetric modulated arch therapy and flattening filter free 6MV photon beams. Dose constraints from AAPM task group 101 were respected for organs at risk. Planning target volumes were delineated using the 18F-FDG uptake as reference and included the primary tumor and every clinically evident lymph node metastases. Platinum doublets were the preferred chemotherapy regimen (8 patients). Toxicity was evaluated according to CTCAE v4 and tumor response according to RECIST criteria 1.1 Results: From February 2014 to January 2015, 15 patients (11 males and 4 females) have been enrolled with a median age of 71 years (range 53−86). Performance status was 0 in 5 patients and 1 in the remaining. Eight were adenocarcinomas, 4 squamous cell carcinomas and 3 not otherwise specified NSCLCs. The median size of the primary tumor was 49mm (range 17−77; T1 13%, T2 13%, T3 27%, T4 47%). Five had N2, 3 N1 and 2 N3 lymph node metastases. Side effects were 7% of G1 esophagitis and 7% of G1 cough. Ten patients have been currently evaluated for response: partial responses 8 (80%) and stable disease 2 (20%), no local progression have been observed. Conclusions: Hypofractionated radiotherapy with PET-based target volume delineation is feasible with the current schedule in locally advanced NSCLCs with mediastinal spread and foresees promising results