Concetta Laliscia

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.

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.

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.

Clinical Outcomes of Stereotactic Body Radiotherapy in Oligometastatic Gynecological Cancer.

OBJECTIVE The objective of this study was to assess the role of stereotactic body radiotherapy (SBRT) in the treatment of distantly recurrent, oligometastatic gynecological cancer. METHODS The hospital records of 45 patients with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography positive, distantly recurrent, oligometastatic gynecological cancer were reviewed. All these patients had a number of target lesions less than 5, with largest diameter less than 6 cm. The treatment was delivered with a TrueBeam LINAC and RapidArc technique, using 10 or 6 MV FFF beams. A total of 70 lesions were treated, and lymph nodes represented the most common site of metastases, followed by lung, liver, and soft tissues. Twenty lesions were treated with one single fraction of 24 Gy and 5 lesions received 27 Gy delivered in 3 fractions, depending on the ability to fulfill adequate target coverage and safe dose/volume constraints for the organ at risk with either regimen. RESULTS Positron emission tomography scan 3 months after SBRT showed a complete response (CR) in 45 lesions (64.3%), a partial response in 14 (20.0%), a stable disease in 5 (7.1%), and a progressive disease in 6 (8.6%). No lesions in CR after SBRT subsequently progressed. Overall acute toxicity occurred in 13 (28.9%) patients. The most common grade 1 to 2 adverse event was pain (n = 9, 20.0%), followed by nausea and vomiting (n = 5, 11.1%). No grade 3 to 4 acute toxicities occurred, and no late toxicities were observed. Patients who failed to achieve a CR had a 2.37-fold higher risk of progression and a 3.60-fold higher risk of death compared with complete responders (P = 0.04 and P = 0.03, respectively). CONCLUSIONS Stereotactic body radiotherapy offers an effective and safe approach for selected cases of oligometastatic gynecological cancer.Objective The objective of this study was to assess the role of stereotactic body radiotherapy (SBRT) in the treatment of distantly recurrent, oligometastatic gynecological cancer. Methods The hospital records of 45 patients with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography positive, distantly recurrent, oligometastatic gynecological cancer were reviewed. All these patients had a number of target lesions less than 5, with largest diameter less than 6 cm. The treatment was delivered with a TrueBeam LINAC and RapidArc technique, using 10 or 6 MV FFF beams. A total of 70 lesions were treated, and lymph nodes represented the most common site of metastases, followed by lung, liver, and soft tissues. Twenty lesions were treated with one single fraction of 24 Gy and 5 lesions received 27 Gy delivered in 3 fractions, depending on the ability to fulfill adequate target coverage and safe dose/volume constraints for the organ at risk with either regimen. Results Positron emission tomography scan 3 months after SBRT showed a complete response (CR) in 45 lesions (64.3%), a partial response in 14 (20.0%), a stable disease in 5 (7.1%), and a progressive disease in 6 (8.6%). No lesions in CR after SBRT subsequently progressed. Overall acute toxicity occurred in 13 (28.9%) patients. The most common grade 1 to 2 adverse event was pain (n = 9, 20.0%), followed by nausea and vomiting (n = 5, 11.1%). No grade 3 to 4 acute toxicities occurred, and no late toxicities were observed. Patients who failed to achieve a CR had a 2.37-fold higher risk of progression and a 3.60-fold higher risk of death compared with complete responders (P = 0.04 and P = 0.03, respectively). Conclusions Stereotactic body radiotherapy offers an effective and safe approach for selected cases of oligometastatic gynecological cancer.

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 corticos-teroid 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 non-small 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.

Definitive Radiotherapy for Primary Squamous Cell Carcinoma of the Vagina: Are High-Dose External Beam Radiotherapy and High-Dose-Rate Brachytherapy Boost the Best Treatment? Experience of Two Italian Institutes

Introduction: We assessed the clinical outcome and survival of 70 patients with primary vaginal squamous cell carcinoma undergoing radiotherapy (RT) at the Divisions of Radiotherapy, University of Pisa and ASST Cremona between January 1995 and June 2016. Methods: 58 patients received external beam RT (EBRT) to the entire vagina, para-vaginal area and pelvic nodes (total dose: 45-50.4 Gy). 29 patients (41.4%) received concomitant weekly cisplatin 40 mg/m2. 35 patients received an additional (15-36 Gy) high-dose-rate (HDR) brachytherapy (BT) boost and 13 received an additional (9-25 Gy) EBRT boost to the primary tumor site. 12 women exclusively received HDR-BT up to a total dose of (30-58 Gy). Results: Median overall survival (OS) was 85 months. A total RT dose of > 60 Gy was significantly associated with a better OS (p = 0.015). There was a trend for a better OS for patients aged < 70 years and for those undergoing EBRT to the entire vagina and pelvis plus BT boost. The most common grade 1-2 acute toxicities were diarrhea (24.1%) and cystitis (20.7%); grade 3 cystitis only occurred in 2 patients (3.4%). Conclusions: EBRT followed by BT boost seems to be the best treatment for vaginal carcinoma. The total dose of RT should be > 60 Gy.

Adjuvant Radiotherapy in High-Risk Squamous Cell Carcinoma of the Vulva: A Two-Institutional Italian Experience

Background: The aim of this study was to assess the treatment benefit and patterns of recurrence for patients with high-risk vulvar squamous cell carcinoma treated with surgery followed by adjuvant radiotherapy (RT). Patients and Methods: From January 1999 to June 2016, 51 patients underwent total or partial deep vulvectomy with inguinofemoral lymphadenectomy followed by adjuvant RT with 45-50 Gy in 25 fractions +/- a 4-10 Gy boost. 17 (33.3%) women received concomitant chemotherapy. Results: Median overall survival was 81 months. The 5-year disease-free survival and overall survival rates were 52 and 63%, respectively. In univariate and multivariate analysis, patients aged ≤ 76 years and those receiving an RT total dose of > 54 Gy had a significantly lower risk of progression (p = 0.044 and 0.045; p = 0.012 and 0.018, respectively) and death (p = 0.015 and 0.011; p = 0.015 and 0.026, respectively). There was a trend towards a lower risk of progression for patients with tumor size ≤ 4 (p = 0.098) and negative lymphovascular space involvement (p = 0.080). Also, there was a trend towards a higher risk of death (p = 0.075) for grade 3 tumors. Concomitant chemotherapy provided no significant benefit. Conclusion: Only age and RT total dose are significant prognostic variables for squamous cell carcinoma of the vulva treated with primary surgery and adjuvant RT to improve local and locoregional control.

Induction treatment with FOLFOXIRI + bevacizumab (BV) followed by chemo-radiotherapy (CRT) + BV and surgery in locally advanced rectal carcinoma (LARC): The phase II TRUST trial.

673 Background: Induction chemotherapy (CT) is a promising option in LARC. FOLFOXIRI + BV is an effective treatment in metastatic colorectal cancer. Methods: Patients (pts) with LARC at < 12 cm from the anal verge, N+ or cT4 or high risk cT3 (MRI criteria) underwent 6 cycles of FOLFOXIRI + BV followed by CRT (50.4 Gy + 5FU 225 mg/m2/day or capecitabine 800 mg/m2/bid 5 days/week + BV 5 mg/kg on days 1, 15, 28). Surgery was planned 8 weeks after CRT. Primary endpoint is 2-year disease-free survival (DFS). Results: From April 2012 to April 2015 48 pts were enrolled. At now, 46 pts completed induction CT, 43 completed CRT and 39 underwent surgery (5 pts ongoing). Pts characteristics were: median age, 53 years (range 30-74); cT2/cT3/cT4, 4%/60%/36%; cN0/N+, 4%/96%. Main grade (G) 3/4 toxicities during induction were neutropenia (42%), febrile neutropenia (4.2%), diarrhea (12.5. Two pts did not complete induction: one died due to bowel perforation and sepsis and one discontinued CT after acute kidney injury. Re...