Stefano Ursino

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.

Adjuvant radiotherapy on older and oldest breast cancer patients after conservative surgery: A retrospective analysis

Purpose of this study was to evaluate the impact of adjuvant radiotherapy, in terms of feasibility and activity, in women aged ≥ 75 years with early (stage) breast cancer. From January 2000 to December 2007, 131 consecutive patients aged 75 years or older received adjuvant radiotherapy after breast conserving surgery. Eighty-two patients received radiotherapy in combination with 5 years of hormone therapy with tamoxifen or aromatase inhibitor. Thirty out of 131 received chemotherapy. Variables considered were age, stage, co-morbidity, performance status, radiation dose (boost), hormone therapy and chemotherapy. The mean age was 78.3 years (range 75-88 years). A total of 19.1% of the patients had no co-morbidity, 57.38% mild, 19.8% moderate, and 3.8% had severe co-morbidities. All patients but one completed the planned radiation schedule. At a median follow-up of 56 months, the 5-year overall survival rate was 78.8%. There was a better survival for patients with no or mild co-morbidities (p<0.0001). The disease-free survival at 5 years was 89.6%. No difference in acute and late toxicity rates was found between patients with different ACE-27 (Adult Comorbidity Evaluation-27) indexes and for different age. We conclude that compliance with adjuvant radiotherapy is good and rate of toxicity is acceptable in elderly patients. Patients with no or mild co-morbidities have a significantly better survival. Increasing severity of co-morbidity may sufficiently shorten remaining life expectancy to cancel gains with adjuvant radiotherapy. Further prospective trials are needed to confirm these results.

How does radiotherapy impact swallowing function in nasopharynx and oropharynx cancer? Short-term results of a prospective study

SUMMARY The objective of this study is to report the initial results of a prospective trial assessing instrumental deglutition function in nasopharynx and oropharynx cancers after radio or chemoradiotherapy using intensity-modulated radiotherapy (IMRT). IMRT was delivered aiming to spare the swallowing organ at risk (SWOARs) for Stage II-IV naso- and oropharynx cancer. Objective instrumental assessment included videofluoroscopy (VFS), fiberoptic endoscopic evaluation of swallowing (FEES) and oro-pharyngeal-oesophageal scintigraphy (OPES) at baseline and at 1 month after radiotherapy. Dysphagia parameter scores were calculated at each exam after liquid (L) and semi-liquid (SL) bolus intake: pre-deglutition penetration, aspiration, pharyngeal transit time (PTT) and hypopharyngeal retention index (HPRI). Overall, 20 patients (6 nasophaynx and 14 oropharynx) completed treatment and instrumental assessment after 1 month. Comparison between pre- and post-treatment HPRI score values showed a significant worsening in both FEES-L (p = 0.021) and SL (p = 0.02) and at VFS-L (p = 0.008) and SL (p = 0.005). Moreover, a relationship between HPRI worsening at FEES-L and FEES-SL (p = 0.005) as well as at VFS-L and VFS-SL (p < 0.001) was observed. PTT was not significantly affected by radiotherapy (p > 0.2). Only a few patients experienced pre-deglutition penetration (1 patient with base of tongue cancer at FEES-L and SL) and aspiration (1 patient with nasopharynx cancer at OPES-L and FEES-SL) after radiotherapy. Our early results showed that IMRT-SWOARs sparing caused a significant increase in the post-deglutition HPRI score. Longer follow-up will be necessary to evaluate if the increase of HPRI is related to a high risk of developing late aspiration.

Stereotactic body radiotherapy of bone metastases in oligometastatic disease: prognostic factors of oncologic outcomes.

Background To evaluate the safety of stereotactic body radiotherapy (SBRT) of bone metastases in oligometastatic disease and to investigate prognostic factors of local control (LC), progression/disease-free survival (PDFS), and overall survival (OS). Methods Eligibility criteria were number of metastates ≤5, controlled primary tumor without evidence of progression under systemic therapy, exclusion of surgery, and no previous radiotherapy of the lesion of interest. Oligometastatic status was classified into only bone (BOD) and outside bone disease (OBOD), whereas SBRT was delivered to bone lesions using 2 different schedules: 24 Gy/1 fraction or 27 Gy/3 fractions. A positron emission tomography study of the lesion of interest was performed at baseline and at 3 months after SBRT to evaluate metabolic response according to European Organization for Research and Treatment of Cancer (EORTC) criteria. A Cox regression model was used for univariate and multivariate analysis. Results Between January 2010 and December 2013, 40 patients were enrolled. Only 1 patient experienced severe late toxicity (radiation-related fracture). Local control was longer among responders’ than nonresponders’ lesions (94.2% and 91.2% versus 63% and 35% at 1 and 2 years, respectively) (p = 0.004; hazard ratio = 9.958). The multivariate analysis of PDFS showed a significant correlation with planning target volume (PTV) size (p = 0.003) and oligometastatic status (p = 0.002). The multivariate analysis of OS confirmed a statistically significant value of the oligometastatic status (p = 0.002) and a significant trend for PTV size (p = 0.065). Conclusions Stereotactic body radiotherapy is safe with a low incidence of severe toxicity. Positron emission tomography response was a strong prognostic factor of LC whereas BOD status and small PTV size could identify a subset of oligometastatic patients at better prognosis.

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.

Patterns of postoperative radiotherapy for head and neck cancer in Italy: a prospective, observational study by the Head and Neck group of the Italian Association for Radiation Oncology (AIRO)

AIMS AND BACKGROUND Our previous survey showed that the patterns of postoperative radiotherapy (PORT) for head and neck cancer (HNC) in Italy might be suboptimal. A prospective observational study was therefore designed to evaluate this issue in greater detail. METHODS All radiotherapy centers involved in the HNC Working Group of the Italian Radiation Oncology Association were asked to enter into the study all patients treated with PORT during a 6-month period. RESULTS A total of 200 patients were accrued by 24 centers from December 2008 to May 2009. Larynx (38%) and oral cavity (34%) were the most common primary sites. The median time between surgery and the start of radiotherapy was 69 days (range, 25-215 days). Seventy-nine percent of cases with no evidence of risk factors for local recurrence were treated with high-dose radiotherapy to the primary site. In about 75% of cases the pN0 neck was included in the target volume. Concomitant chemotherapy was delivered to about 60% of patients with major risk factors and 21% of patients with no risk factors. CONCLUSIONS Three issues emerged from our study as potential targets for future investigations: the impact on clinical outcome of the interval between surgery and the start of PORT; factors driving radiation oncologists to overtreat volumes at low risk of recurrence; and problems associated with the delivery of concomitant chemotherapy.

Set-up errors in head and neck cancer treated with IMRT technique assessed by cone-beam computed tomography: a feasible protocol

Purpose To investigate set-up errors, suggest the adequate planning target volume (PTV) margin and image-guided radiotherapy frequency in head and neck (H&N) cancer treated with intensity-modulated radiotherapy (IMRT) assessed by kV cone-beam computed tomography (CBCT). Methods We analyzed 360 CBCTs in 60 patients with H&N cancer treated with IMRT. The target delineation was contoured according to ICRU62. PTVs were generated by adding a 3–5 mm margin in all directions to the respective clinical target volumes. The kV CBCT images were obtained at first three days of irradiation and weekly thereafter. The overall mean displacement, range, systematic (∑) and random (σ) errors were calculated. Adequate PTV margins were calculated according to the van Herk formula (2.5∑ + 0.7r). Results The mean of set-up errors was less than 2 mm in any direction. The overall frequency of set-up displacements greater than 3 mm was 3.9% in medial-lateral (ML) direction, 8% in superior-inferior (SI) direction, and 15.5% in anterior-posterior (AP) direction. The range of translations shifts was 0–9 mm in ML direction, 0–5 mm in SI direction and 0–10 mm in AP direction, respectively. After systematic set-up errors correction, the adequate margin to overcome the problem of set-up errors was found to be less than 3 mm. Conclusion Image-guided kV CBCT was effective for the evaluation of set-up accuracy in H&N cancer. The kV CBCT at first three fractions and followed-by weekly appears adequate for reducing significantly set-up errors in H&N cancer treated with IMRT technique. Finally, 3–5 mm PTV margins appear adequate and safe to overcome the problem of set-up errors.

Re-irradiation with curative intent in patients with squamous cell carcinoma of the head and neck: a national survey of usual practice on behalf of the Italian Association of Radiation Oncology (AIRO)

AbstractObjectiveTo report the results of a national survey investigating the pattern of practice of curative re-irradiation (ReRT) for recurrent squamous cell carcinoma of the head and neck.MethodsIn March 2016, a 22-item, 4-section questionnaire was sent to all Italian Radiation Oncology centers. Sections were focused on assessing the expertise level of each center and collecting specific information on reRT prescription modalities in the adjuvant and definitive settings.ResultsOverall, 77 centers completed the survey. The majority (50/77, 64.9%) of participating radiation oncologists were senior consultants (> 10 years of experience). Of the responding centers, 63 (81.8%) performed curative ReRT, while 14 (18.1%) did not, mainly (5/14, 35.7%) due to the avoidance of severe toxicity. The use of adjuvant ReRT was reported by less than half of the interviewed radiation oncologists (36/77, 46.7%). In case of unresectable local recurrence, definitive ReRT was claimed to be adopted in 55/77 (71.4%) for non-nasopharyngeal and 47/77 (61%) for nasopharyngeal cancer. The preferred treatment technique was Intensity Modulated Radiation Therapy (IMRT) followed by Stereotactic Body Radiation Therapy (SBRT). When IMRT was applied, the most common (19/55 responders, 34.5%) selection of treatment volume consisted of the Gross Tumor Volume (GTV) + 0.5 cm margin to account for microscopic disease.ConclusionDespite the absence of definitive evidence-based recommendations, a possible consideration for ReRT in case of unresectable recurrent head and neck cancer was reported by over 80% of radiation oncologists taking part in the national survey.

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.