Sara Falivene

Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapy.

Cancer radiotherapy (RT) may induce what is referred to as the “abscopal effect,” a regression of non-irradiated metastatic lesions distant from the primary tumor site directly subject to irradiation. This clinical response is rare, but has been surmised to be an immune-mediated phenomenon, suggesting that immunotherapy and RT could potentially synergize. Here, we report the outcome of patients with advanced melanoma treated with the immune checkpoint blockade monoclonal antibody antagonist, ipilimumab followed by RT. Patients were selected for enrollment at the National Cancer Institute “Fondazione G.Pascale” through the expanded access program in Italy. Those who experienced disease progression after ipilimumab thus received subsequent RT and were selected for analysis. Among 21 patients, 13 patients (62%) received RT to treat metastases in the brain and 8 received RT directed at extracranial sites. An abscopal response was observed in 11 patients (52%), 9 of whom had partial responses (43%) and 2 had stable disease (10%). The median time from RT to an abscopal response was 1 month (range 1–4). Median overall survival (OS) for all 21 patients was 13 months (range 6–26). Median OS for patients with abscopal responses was extended to 22.4 months (range 2.5–50.3) vs. 8.3 months (range 7.6–9.0) without. A local response to RT was detected in 13 patients (62%) and, of these, 11 patients (85%) had an abscopal response and abscopal effects were only observed among patients exhibiting a local response. These results suggest RT after ipilimumab may lead to abscopal responses in some patients with advanced melanoma correlating with prolonged OS. Our data also suggest that local responses to RT may be predictive of abscopal responses. Further research in larger randomized trials is needed to validate these results.

Preventing the acute skin side effects in patients treated with radiotherapy for breast cancer: the use of corneometry in order to evaluate the protective effect of moisturizing creams

Background and purposeThe purpose of this study was to add, to the objective evaluation, an instrumental assessment of the skin damage induced by radiation therapy.Materials and methodsA group of 100 patients affected by breast cancer was recruited in the study over one year. Patients were divided into five groups of 20 patients. For each group it was prescribed a different topical treatment. The following products were used: Betaglucan, sodium hyaluronate (Neoviderm®), Vitis vinifera A. s-I-M.t-O.dij (Ixoderm®), Alga Atlantica plus Ethylbisiminomethylguaicolo and Manganese Cloruro (Radioskin1®) and Metal Esculetina plus Ginko Biloba and Aloe vera (Radioskin 2®); Natural triglycerides-fitosterols (Xderit®); Selectiose plus thermal water of Avene (Trixera+®). All hydrating creams were applied twice a day starting 15 days before and one month after treatment with radiations. Before and during treatment patients underwent weekly skin assessments and corneometry to evaluate the symptoms related to skin toxicity and state of hydration. Evaluation of acute cutaneous toxicity was defined according to the RTOG scale.ResultsAll patients completed radiotherapy; 72% of patients presented a G1 cutaneous toxicity, 18% developed a G2 cutaneous toxicity, 10% developed a G3 toxicity, no one presented G4 toxicity. The corneometry study confirmed the protective role of effective creams used in radiation therapy of breast cancer and showed its usefulness to identify radiation-induced dermatitis in a very early stage.ConclusionsThe preventive use of topic products reduces the incidence of skin side effects in patients treated with radiotherapy for breast cancer. An instrumental evaluation of skin hydration can help the radiation oncologist to use strategies that prevent the onset of toxicity of high degree. All moisturizing creams used in this study were equally valid in the treatment of skin damage induced by radiotherapy.

Rectal/urinary toxicity after hypofractionated vs conventional radiotherapy in low/intermediate risk localized prostate cancer: Systematic review and meta analysis

Purpose The aim of this review was to compare radiation toxicity in Localized Prostate Cancer (LPC) patients who underwent conventional fractionation (CV), hypofractionated (HYPO) or extreme hypofractionated (eHYPO) radiotherapy. We analyzed the impact of technological innovation on the management of prostate cancer, attempting to make a meta-analysis of randomized trials. Methods PubMed database has been explored for studies concerning acute and late urinary/gastrointestinal toxicity in low/intermediate risk LPC patients after receiving radiotherapy. Studies were then gathered into 5 groups: detected acute and chronic toxicity data from phase II non randomized trials were analyzed and Odds Ratio (OR) was calculated by comparing the number of patients with G0-1 toxicity and those with toxicity > G2 in the studied groups. A meta-analysis of prospective randomized trials was also carried out. Results The initial search yielded 575 results, but only 32 manuscripts met all eligibility requirements: in terms of radiation-induced side effects, such as gastrointestinal and genitourinary acute and late toxicity, hypofractionated 3DCRT seemed to be more advantageous than 3DCRT with conventional fractionation as well as IMRT with conventional fractionation compared to 3DCRT with conventional fractionation; furthermore, IMRT hypofractionated technique appeared more advantageous than IMRT with conventional fractionation in late toxicities. Randomized trials meta-analysis disclosed an advantage in terms of acute gastrointestinal and late genitourinary toxicity for Hypofractionated schemes. Conclusions Although our analysis pointed out a more favorable toxicity profile in terms of gastrointestinal acute side effects of conventional radiotherapy schemes compared to hypofractionated ones, prospective randomized trials are needed to better understand the real incidence of rectal and urinary toxicity in patients receiving radiotherapy for localized prostate cancer.

Efficacy of radiotherapy in patients on progression after treatment with ipilimumab 3 mg/kg

Background Ipilimumab, a fully human monoclonal antibody (IgG1) that promote antitumor immunity by blocking CTLA4, was the first agent which showed a long-term survival benefit, about the 20% of patients, for the treatment of metastatic melanoma. The combination of ipilimumab with other therapies might improve its efficacy. The term “abscopal effect” refers to a regression of metastatic lesions distant from the primary site of radiotherapy (RT). This new phenomenon represent the systemic response observed in patients who received ipilimumab. Here we reported the outcomes from patients treated in the ipilimumab Italian expanded access program (EAP) who received RT after ipilimumab progression. Patients and methods Patients with advanced melanoma after ipilimumab progression were selected for analysis. Patients, who failed ipilimumab therapy and for whom no other therapeutic options were available, were elegible for radiotherapy. Results

Radiosurgery and Stereotactic Radiotherapy for Brain MetastasesAccording the New Prognostic Indexes: our Preliminary Experience

Purpose: This work is a retrospective analysis of our experience in the treatment of patients with BMs using SRS or SRT with Cyberknife ® (CK) system (Accuray Inc., Sunnyvale, California, USA). The aim is to evaluate the local control of disease and overall survival according to modern prognostic indices. Material and methods: From November 2012 to March 2014, we treated 116 patients, (178 brain metastases), with CK system, an image-guided frameless robotic SRS/SRT. We stratified the patients according to the Diagnosis- Specific GPA (DS-GPA) and we treated patients with a single fraction (10-24 Gy) in 72%, with two fractions (18-21 Gy) in 3%, with three fractions (18-24 Gy) in 23%, with five fractions (20-25Gy) in 2%. The dose was prescribed to 80% isodose line. All patients were evaluated with clinical and radiological follow-up using MRI every 2 months. We calculated the local tumor control rate according with RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Results: Percentage of complete remission, partial remission, stable disease, was: 38% in NSCLC (Non-smallcell lung carcinoma) (16% in classes with best score), 28% in Melanoma (all in classes with best score), 52% in breast (43% in classes with best score). We noted a similar result for partial remission and stable disease, particularly in Melanoma and Breast cancer, who have a higher percentage of PR (partial response) and SD (stable disease) of 33- 23%, and in Melanoma of 40-50% in classes with higher scores. Conclusions: we confirm the precious contribution of the DS-GPA in correct selection of patients with brain metastases, and encourage the use of special technologies in properly selected patients.

The abscopal effect: efficacy of radiotherapy in patients on progression after treatment with ipilimumab 3 mg/kg

Meeting abstracts After more than 30 years, Ipilimumab was the first agent which showed a survival benefit for the treatment of metastatic melanoma. However, only about the 20% of patients have a long-term survival benefit. The combination of ipilimumab with other therapies might improve its

Short-course radiotherapy in elderly women with breast cancer: Comparison by age, comorbidity index and toxicity

BACKGROUND Breast cancer is the most common malignancy amongst elderly women. It represents the main cause of mortality for those women and it is steadily increasing. The primary therapeutic approach remains surgery, as in other age groups. The role of radiotherapy following surgery is still debated. The use of hypofractionated schedules is challenging the standard fractionation and has now been considered an advantageous option within this subgroup of patients. Results from randomized controlled trials have not been shown to be inferior to standard fractionation in terms of local recurrence, disease-free survival and overall survival. Acute and late side effects were not increased by hypofractionated regimens. PATIENTS AND METHODS 60 elderly women treated by hypofractionated radiotherapy after breast conserving surgery were stratified by age. Comorbidities associated compliance and toxicity correlation to age were the first endpoints of the study. Comorbidity associated compliance was calculated by Cumulative Illness Rating Scale Geriatric. RESULTS At a median follow-up of 15 months overall survival was 100%, without severe late toxicity. No statistical significant differences were found between Cumulative Illness Rating Scale-Geriatric, systemic therapy and toxicity. CONCLUSION In our experience hypofractioned regimens seem to be safe and reliable in the elderly setting, although longer follow up is needed.

Variability in axillary lymph node delineation for breast cancer radiotherapy in presence of guidelines on a multi-institutional platform

Abstract Aim: To quantify the variability between radiation oncologists (ROs) when outlining axillary nodes in breast cancer. Material and methods: For each participating center, three ROs with different levels of expertise, i.e., junior (J), senior (S) and expert (E), contoured axillary nodal levels (L1, L2, L3 and L4) on the CT images of three different patients (P) of an increasing degree of anatomical complexity (from P1 to P2 to P3), according to contouring guidelines. Consensus contours were generated using the simultaneous truth and performance level estimation (STAPLE) method. Results: Fifteen centers and 42 ROs participated. Overall, the median Dice similarity coefficient was 0.66. Statistically significant differences were observed according to the level of expertise (better agreement for J and E, worse for S); the axillary level (better agreement for L1 and L4, worse for L3); the patient (better agreement for P1, worse for P3). Statistically significant differences in contouring were found in 18% of the inter-center comparison. Less than a half of the centers could claim to have a good agreement between the internal ROs. Conclusions: The overall intra-institute and inter-institute agreement was moderate. Central lymph-node levels were the most critical and variability increased as the complexity of the patient’s anatomy increased. These findings might have an effect on the interpretation of results from multicenter and even mono-institute studies.

Adjuvant treatment in patients at high risk of recurrence of thymoma: efficacy and safety of a three-dimensional conformal radiation therapy regimen.

Background The clinical benefits of postoperative radiation therapy (PORT) for patients with thymoma are still controversial. In the absence of defined guidelines, prognostic factors such as stage, status of surgical margins, and histology are often considered to guide the choice of adjuvant treatment (radiotherapy and/or chemotherapy). In this study, we describe our single-institution experience of three-dimensional conformal PORT administered as adjuvant treatment to patients with thymoma. Methods Twenty-two consecutive thymoma patients (eleven male and eleven female) with a median age of 52 years and treated at our institution by PORT were analyzed. The patients were considered at high risk of recurrence, having at least one of the following features: stage IIB or III, involved resection margins, or thymic carcinoma histology. Three-dimensional conformal PORT with a median total dose on clinical target volume of 50 (range 44–60) Gy was delivered to the tumor bed by 6–20 MV X-ray of the linear accelerator. Follow-up after radiotherapy was done by computed tomography scan every 6 months for 2 years and yearly thereafter. Results Two of the 22 patients developed local recurrence and four developed distant metastases. Median overall survival was 100 months, and the 3-year and 5-year survival rates were 83% and 74%, respectively. Median disease-free survival was 90 months, and the 5-year recurrence rate was 32%. On univariate analysis, pathologic stage III and presence of positive surgical margins had a significant impact on patient prognosis. Radiation toxicity was mild in most patients and no severe toxicity was registered. Conclusion Adjuvant radiotherapy achieved good local control and showed an acceptable toxicity profile in patients with high-risk thymoma.

Treatment of cutaneous angiosarcoma of the face: efficacy of combined chemotherapy and radiotherapy.

INTRODUCTION Cutaneous angiosarcoma (AS) is a rare form of soft tissue sarcoma. It is aggressive and has a poor prognosis. The aim of our report is to show that with combined chemotherapy and radiotherapy it is possible to obtain good results in terms of local control, complete response, and aesthetic outcome. CASE REPORT We present the case of a 60-year-old man affected by AS covering the entire surface of the nose. Surgery, although indicated, was excluded because it was considered mutilating and would give a poor cosmetic result. The patient was treated with chemotherapy consisting of paclitaxel 80 mg/m2 for 6 cycles followed by radiotherapy at a dose of 50 Gy. Then 3 additional cycles of chemotherapy were administered according to the same scheme. A complete response was obtained. At 40 months after treatment, the patient did not show any signs of late toxicity, all lesions had disappeared, and all laboratory tests were negative. CONCLUSIONS Our experience shows that concomitant chemoradiotherapy can be delivered safely and can be tolerated with low toxicity and good results in terms of local control and complete response. We obtained an excellent aesthetic result with improvement of the patients quality of life.