R. Frakulli

Palliative electro-chemotherapy in elderly patients with vulvar cancer: A phase II trial.

The primary endpoint of this trial was to assess clinical response (cCR) of squamocellular vulvar cancer (V‐SCC) in elderly patients treated with electro‐chemotherapy (ECT). Secondary endpoints were symptoms relief and local tumor control.

Adjuvant radiotherapy with brachytherapy boost in soft tissue sarcomas

Purpose The standard primary treatment for soft tissue sarcoma (STS) is a wide surgical resection, preceded or followed by radiotherapy. Purpose of this retrospective study was to assess the efficacy of perioperative brachytherapy (BRT) plus postoperative external beam radiation therapy (EBRT) in patients with intermediate-high risk STS. Material and methods BRT delivered dose was 20 Gy. External beam radiation therapy was delivered with 3D-technique using multiple beams. The prescribed dose was 46 Gy to the PTV. Neoadjuvant and adjuvant chemotherapy (CHT) was used in patients with potentially chemosensitive histological subtypes. The primary aim of the study was to analyze overall survival (OS) and local control (LC) in a large patient population treated with surgery, perioperative BRT, and adjuvant EBRT ± CHT. Secondary objective was to identify prognostic factors for patients outcome in terms of LC, disease-free survival (DFS), and OS. Results From 2000 to 2011, 107 patients presenting 2-3 grade (FNLCC) primary or recurrent STS were treated with surgery, perioperative BRT, and adjuvant EBRT ± CHT. Five-year LC and OS were 80.9% and 87.4%, respectively. At univariate analysis, a higher LC was recorded in primary vs. recurrent tumors (p = 0.015), and in lower limb tumors vs. other sites (p = 0.027). An improved DFS was recorded in patients with lower limb tumors vs. other sites (p = 0.034). Conclusions The combination of BRT and EBRT was able to achieve satisfactory results even in a patients population with intermediate-high risk STS. Patients with recurrent or other than lower limb sited tumors show a worse LC.

Brachytherapy in non melanoma skin cancer of eyelid: a systematic review.

Purpose Non melanoma skin cancers (NMSC) of eyelid are uncommon. Many treatments approach are available with surgery being considered as the gold standard. Radiotherapy is an effective alternative in patients unfit for surgery. Brachytherapy (BT) might be a better therapeutic option due high radiation dose concentration to the tumor and rapid dose fall-off resulting in normal tissues sparing. The aim of this review is to evaluate local control, toxicity, and functional cosmetic outcome of BT in NMSC of eyelid. Material and methods A systematic search of the bibliographic databases PubMed, Scopus, and Cochrane Library from the earliest possible date through October 2015 was performed. Only studies published in English were included. Results Six articles fulfilled the selection criteria and were included in our review. Due to high risk of bias, all studies were classified to provide a low level of evidence (according to Scottish Intercollegiate Guidelines Network Classification). No randomized controlled trials or case control studies were founded. Brachytherapy was well tolerated with acceptable toxicity and high local control rates (median: 95.2%). Functional and cosmetic outcome were reported in five study as acceptable good functional-cosmetic outcome (median: 100%). Conclusions To date, few evidences are available on the role of BT in eyelid NMSC, and they show satisfactory results in terms of local control and functional cosmetic outcome. Therefore, prospective controlled trials are justified.

Feasibility of 2D‑conformal radiotherapy for pancreatic carcinoma

The purpose of the present study was to propose an optimized 2D technique (2D-conformal) for radiotherapy (RT) of pancreatic cancer (CaP). This technique is based on double simulation which resolves the problems of radiographic image distortion. Five patients with locally advanced CaP were identified and enrolled. Treatment planning was simulated in 3 different ways: Two dimensional-standard (2D-SRT), 2D-conformal (2D-CRT), and three dimensional-conformal (3D-CRT) techniques for 10 MV LINAC. Simulation for a cobalt machine was also performed using only the 2D techniques. 2D-SRT technique was planned with fields definition based on anatomical landmarks (bone and duodenum). 3D-CRT was planned with standard virtual simulation technique, and 3D dose evaluation and optimization. 2D-CRT technique was based on manual information transfer from a diagnostic CT-scan to simulation radiograms. To eliminate the X-ray image distortion, a double simulation was employed and the profile of the GTV was delineated on radiographs bearing the simulator isocenter into the target center. Concerning target irradiation of either LINAC (10 MV) or cobalt source, the PTV constraints (ICRU 62) were met in all patients (Dmin >95%, Dmax <107%) with all techniques (2D-SRT, 3D-CRT, 2D-CRT). For organs at risk irradiation, in terms of Dmax to both duodenum and spinal cord, similar results were recorded with all techniques using the LINAC (10 MV). Liver and kidneys Dmean gradually improved from 2D-SRT to 2D-CRT and 3D-CRT. The 2D-CRT compared to 2D-SRT technique, halved the average dose to the liver and reduced to about 1/3 the average dose to the kidneys. With the cobalt source, using the 2D-CRT produced a reduction of Dmean to the kidneys (median from 30.7 to 16.9%) and liver (median from 33.4 to 22.3%) compared to 2D-SRT. This analysis showed better planning results in RT treatment of CaP while using a 2D-CRT compared to 2D-SRT technique and therefore presents an example for optimized 2D RT use.

Stereotactic radiotherapy of pancreatic cancer: a systematic review on pain relief.

Locally advanced pancreatic carcinoma (LAPC) has a poor prognosis and the purpose of treatment is survival prolongation and symptom palliation. Radiotherapy has been reported to reduce pain in LAPC. Stereotactic RT (SBRT) is considered as an emerging radiotherapy technique able to achieve high local control rates with acceptable toxicity. However, its role in pain palliation is not clear. To review the impact on pain relief with SBRT in LAPC patients, a literature search was performed on PubMed, Scopus, and Embase (January 2000–December 2017) for prospective and retrospective articles published in English. Fourteen studies (479 patients) reporting the effect of SBRT on pain relief were finally included in this analysis. SBRT was delivered with both standard and/or robotic linear accelerators. The median prescribed SBRT doses ranged from 16.5 to 45 Gy (median: 27.8 Gy), and the number of fractions ranged from 1 to 6 (median: 3.5). Twelve of the 14 studies reported the percentage of pain relief (in patients with pain at presentation) with a global overall response rate (complete and partial response) of 84.9% (95% CI, 75.8%–91.5%), with high heterogeneity (Q2 test: P<0.001; I2=83.63%). All studies reported toxicity data. Acute and late toxicity (grade ≥3) rates were 3.3%–18.0% and 6.0%–8.2%, respectively. Reported gastrointestinal side effects were duodenal obstruction/ulcer, small bowel obstruction, duodenal bleeding, hemorrhage, and gastric perforation. SBRT achieves pain relief in most patients with pancreatic cancer with an acceptable gastrointestinal toxicity rate. Further prospective studies are needed to define optimal dose/fractionation and the best systemic therapies modality integration to reduce toxicity and improve the palliative outcome. Finally, the quality of life and, particularly, pain control should be considered as an endpoint in all future trials on this emerging treatment technique.

Radiotherapy of pancreatic cancer in older patients: A systematic review

Pancreatic cancer (PaC) will soon be one of the main causes of cancer mortality. Furthermore, its incidence is higher in the older population and radiotherapy (RT) represents a treatment option. The aim of this review was to evaluate feasibility and outcome of RT in older patients with PaC. A systematic literature review of patients aged ≥65 years with PaC treated with RT was performed using the PRISMA methodology. Eleven papers (1830 patients) fulfilled our inclusion criteria and were analyzed. RT was prescribed either alone or as an adjuvant treatment. Prescribed RT dose ranged from 22.0 to 70.0 Gy with conventional fractionation or hypo-fractionated schedule and delivered by three-dimensional conformal RT, intensity modulated RT or stereotactic body RT. Grade ≥ 3 acute and grade ≥ 2 late toxicity rates ranged between 0.0% and 52.6% (median: 0.5%) and between 0.0% and 15.0% (median: 0%), respectively. Median overall survival and two-year survival rate were 11.3 months (range: 6.4-69.0 months) and 49.0% (range 6.6-75.5%), respectively. RT in older patients seems to be tolerable and safe particularly in terms of late toxicity irrespective of the treatment settings. Therefore, RT can represent a treatment option in PaC even in an older population. Further analyses and prospective trials enrolling older patients are needed to better define the risk/benefit ratio in different treatment settings.

Brachytherapy boost after chemoradiation in anal cancer: a systematic review

Radio-chemotherapy (RCT) is the primary treatment of anal cancer (AC). However, the role and the optimal total dose of a radiation boost is still unclear. No randomized controlled trials nor systematic reviews have been performed to analyze the efficacy of brachytherapy (BRT) as boost in AC. Therefore, we performed this systematic review based on PRISMA methodology to establish the role of BRT boost in AC. A systematic search of the bibliographic databases: PubMed, Scopus, and Cochrane library from the earliest possible date through January 31, 2018 was performed. At least one of the following outcomes: local control (LC), loco-regional control (LRC), overall survival (OS), disease-free survival (DFS), or colostomy-free survival (CFS) had to be present for inclusion in this systematic review in patients receiving a BRT boost. Data about toxicity and sphincter function were also included. Ten articles fulfilled the inclusion criteria. All the studies had retrospective study design. All studies were classified to provide a level of evidence graded as 3 according to SIGN classification. Median 5-year LC/LRC, CFS, DFS, and OS were: 78.6% (range, 70.7-92.0%), 76.1% (range, 61.4-86.4%), 75.8% (range, 65.9-85.7%), and 69.4% (63.4-82.0%), respectively. The reported toxicities were acceptable. RCT is the treatment cornerstone in AC. High-level evidences from studies on BRT boost in AC are lacking. Further studies should investigate: efficacy of BRT boost in comparison to no boost and to external beam boost, patients who can benefit from this treatment intensification, and optimal radiation dose.

Radiological differential diagnosis between fibrosis and recurrence after stereotactic body radiation therapy (SBRT) in early stage non-small cell lung cancer (NSCLC)

Background Parenchymal changes after stereotactic body radiation therapy (SBRT) make differential diagnosis between treatment outcomes and disease recurrence often difficult. The purpose of our study was to identify the radiographic features detectable at computed tomography (CT) scan [high-risk features (HRFs)] that allow enough specificity and sensitivity for early detection of recurrence. Methods We retrospectively evaluated patients who underwent SBRT for inoperable early stage non-small cell lung cancer (NSCLC). The median delivered dose performed was 50 Gy in 5 fractions prescribed to 80% isodose. All patients underwent chest CT scan before SBRT and at 3, 6, 12, 18, 24 months after, and then annually. Each CT scan was evaluated and benign and HRFs were recorded. 18F-fluorodeoxyglucose-CT was not used routinely. Results Forty-five patients were included (34 males, 11 females; median age: 77 years; stage IA: 77.8%, stage IB: 22.2%; median follow-up: 21.7 months). Two year and actuarial local control was 77%. HRFs were identified in 20 patients. The most significant predictor of relapse was an enlarging opacity at 12 months (P<0.001) with 84.6% sensitivity and 71.8% specificity. The presence of ≥2 HRFs demonstrated a high sensibility (92.3%) and specificity (71.9%) (P<0.0001). Conclusions Detection of HRFs is predictive of relapse with a sensibility that increases with the number of HRFs observed. This observation may allow to better define the diagnostic follow algorithm up suggesting to performing further exams only in patients with >2 HRFs.

Predictive factors of late-onset rectal mucosal changes after radiotherapy of prostate cancer

BACKGROUND/AIM The Vienna Rectoscopy Score (VRS; from 0, absence of rectal mucosal changes, to 5) assessed 1 year after radiotherapy is a surrogate end-point of late rectal toxicity. The aim of this study was to investigate the association between treatment-related factors and 1-year VRS. PATIENTS AND METHODS We performed a retrospective analysis of prospectively collected data. Patients with prostate adenocarcinoma treated with definitive or postoperative radiotherapy (RT) underwent endoscopy 1 year after RT. Relationships between VRS of 2 or more and treatment parameters were investigated by univariate and multivariate logistic analyses. RESULTS One hundred and ninety-five patients (mean age=69 years; range=43-81 years) were considered eligible for the study. At univariate analysis, patients treated with hypofractionation plus radiosurgery boost (p<0.001) and an equivalent dose in 2 Gy per fraction (EQD2) (α/β=3) ≥75 Gy (p<0.001) was associated with a significantly higher incidence of VRS ≥2 after 1 year of follow-up. At multivariate analysis, radiosurgery boost was an independent risk factor for developing rectal mucosal lesions (VRS ≥2), yielding an odds ratio (OR) of 4.14 (95% confidence interval (CI)=1.2-13.8), while pelvic surgery was inversely associated with VRS ≥2 (OR=0.39; 95% CI=0.17-0.94). CONCLUSION Hypofractionation followed by radiosurgery boost significantly increased the risk of developing late-onset rectal mucosal changes. Therefore, special care and preventative treatment strategies are needed when using radiosurgery boost after hypofractionated RT.

Unusual case of spindle cell sarcoma metastases to right ventricle: a case report and a literature review

Cardiac metastases from sarcoma are uncommon. Due to their rarity there is not a standard of care. However, complete cardiac metastases resection is the best option but most of patients has widespread disease. In these patients palliative radiotherapy (RT) might improve symptoms and prevent further cardiac function decline. Here we present the case of a symptomatic 30-year-old woman with spindle cell sarcoma metastasis of right ventriculum and widespread disease. The patient received radiotherapy to the heart with palliative intent. Cardiac metastases represent a challenging clinic problem. Treatment should be individualized in a multidisciplinary setting, when possible surgery seems to be the best options. However, radiotherapy even in case of widespread disease can improve clinical control symptoms by reducing the mass effect.