Rossella Di Franco

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.

Skin toxicity from external beam radiation therapy in breast cancer patients: Protective effects of Resveratrol, Lycopene, Vitamin C and anthocianin (Ixor ®)

IntroductionThis is an observational study and the aim is to evaluate the effect of dietary supplements based on Resveratrol, Lycopene, Vitamin C and Anthocyanins (Ixor®) in reducing skin toxicity due to external beam radiotherapy in patients affected by breast cancer.Materials and methods71 patients were enrolled and they were divided in two different groups: a control group (CG) of 41 patients treated with prophylactic topical therapy based on hyaluronic acid and topical steroid therapy in case of occurrence of radiodermatitis, and a Ixor-Group (IG) of 30 patients treated also with an oral therapy based on Resveratrol, Lycopene, Vitamin C and Anthocyanin (Ixor®) at a dose of 2 tablets/day, starting from 10 days before the radiation treatment until 10 days after the end of treatment. Skin toxicity has been related to PTV, to breast volume that received a radiation dose equal or lower than 107%, included between 107% and 110%, or greater than 110% of the prescribed dose. Moreover its been studied the relationship between skin toxicity and the chemotherapy schedule used before treatment. We calculated in both groups the percentage of patients who had a skin toxicity of grade 2 or 3 (according to RTOG scale). Absolute risk reduction (ARR), relative risk (RR) and odds ratio (OR) have been calculated for each relationship.ResultsControl Group (CG) patients with a PTV > 500 ml presented skin toxicity G2 + G3 in 30% of cases, versus 25% of Ixor-Group (IG) [OR 0.77]. In patients with a PTV < 500 ml G2 + G3 toxicity was 0% in the IG compared to 18% in CG (OR 0.23). When Dmax was less than or equal to 107% of the prescribed dose skin toxicity was G2 + G3 in 12.5% in CG, versus 0% in IG (OR 0.73), instead when Dmax was included between 107 and 110% of the prescribed dose, G2 + G3 skin toxicity was 35% in CG and 21% in IG (OR 0.50). In patients undergoing chemotherapy with anthracyclines and taxanes, G2 + G3 toxicity was 27% in CG, against 20% in IG (OR 0.68).ConclusionsThe protective effect of Resveratrol, Lycopene, Vitamin C and Anthocyanin (Ixor®) is more detected in patients with PTV < 500 ml, when Dmax reaches values lower or equal to 107%, but not exceeding 110% of the prescribed dose, and in patients undergoing adjuvant chemotherapy with anthracyclines and taxanes.

Epithelial-mesenchymal transition in prostate cancer: An overview

Prostate cancer is a main urological disease associated with significant morbidity and mortality. Radical prostatectomy and radiotherapy are potentially curative for localized prostate cancer, while androgen deprivation therapy is the initial systemic therapy for metastatic prostate disease. However, despite temporary response, most patients relapse and evolve into castration resistant cancer. Epithelial-mesenchymal transition (EMT) is a complex gradual process that occurs during embryonic development and/or tumor progression. During this process, cells lose their epithelial characteristics and acquire mesenchymal features. Increasing evidences indicate that EMT promotes prostate cancer metastatic progression and it is closely correlated with increased stemness and drug resistance. In this review, we discuss the main molecular events that directly or indirectly govern the EMT program in prostate cancer, in order to better define the role and the mechanisms underlying this process in prostate cancer progression and therapeutic resistance.

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.

Prevention of cutaneous damages induced by radiotherapy in breast cancer: an institutional experience.

BACKGROUND AND AIMS A minimal part of patients treated with radiotherapy on the entire breast may present an acute, subacute or chronic cutaneous damage of the healthy tissues involved in the radiation fields. The aim of this retrospective study was to evaluate the most efficient topical hydrating treatment in the prevention of cutaneous radio-induced acute effects in breast cancer. MATERIAL AND METHODS From February 2009 to March 2010, 100 patients affected by breast cancer have been recruited, all of the female sex and with an average age of 47 years. The following topical treatments were compared: Pure vitamin E (Vea lipogel®), Omega-3,6,9 (Quinovit®), Betaglucan, sodium hyaluronate (Neoviderm®), Vitis vinifera A.s-I-M.t-O.dij, (Ixoderm®), natural triglycerides-fitosterols (Xderit®). All enrolled patients were subjected to breast conservative treatment (quadrantectomy with or without homolateral axillary dissection) and without prosthesis positioning, in combination or not with hormonal treatment. Evaluation of the cutaneous acute toxicity was defined according to the RTOG scale either during radiotherapy and during follow-up (3 months after radiation treatment). RESULTS All patients completed the radiotherapy; 62% of patients presented G0-G1 cutaneous toxicity, 28% have developed G2 cutaneous toxicity, 10% have developed G3 toxicity; no patient presented G4 toxicity. Analysis of the data revealed a correlation between the topical treatment used and the incidence of cutaneous toxicity. CONCLUSIONS Of the patients who used the cutaneous hydrating creams--betaglucan, sodium hyaluronate (Neoviderm®) and Vitis vinifera A.s-I-M.t-O.dij (Ixoderm®)--during the radiation treatment, 80% developed G0-G1 toxicity and 20% G2 toxicity. The patients who used the other hydrating creams tested in the study manifested not only G1-G2 toxicity but also some G3 toxicity. Chemotherapeutic treatment with taxanes and/or anthracyclines did not result in an increased breast cutaneous toxicity induced by radiotherapy. The hormone therapy given to patients undergoing radiotherapy did not result in increased breast cutaneous toxicity. Further analysis on a larger number of patients is necessary for definitive results.

Testicular cancer from diagnosis to epigenetic factors

Testicular cancer (TC) is one of the most common neoplasms that occurs in male and includes germ cell tumors (GCT), sex cord-gonadal stromal tumors and secondary testicular tumors. Diagnosis of TC involves the evaluation of serum tumor markers alpha-fetoprotein, human chorionic gonadotropin and lactate dehydrogenase, but clinically several types of immunohistochemical markers are more useful and more sensitive in GCT, but not in teratoma. These new biomarkers are genes expressed in primordial germ cells/gonocytes and embryonic pluripotency-related cells but not in normal adult germ cells and they include PLAP, OCT3/4 (POU5F1), NANOG, SOX2, REX1, AP-2γ (TFAP2C) and LIN28. Gene expression in GCT is regulated, at least in part, by DNA and histone modifications, and the epigenetic profile of these tumours is characterised by genome-wide demethylation. There are different epigenetic modifications in TG-subtypes that reflect the normal developmental switch in primordial germ cells from an under- to normally methylated genome. The main purpose of this review is to illustrate the findings of recent investigations in the classification of male genital organs, the discoveries in the use of prognostic and diagnostic markers and the epigenetic aberrations mainly affecting the patterns of DNA methylation/histone modifications of genes (especially tumor suppressors) and microRNAs (miRNAs).

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.

Assessing Response to Radiation Therapy Treatment of Bone Metastases: Short-Term Followup of Radiation Therapy Treatment of Bone Metastases with Diffusion-Weighted Magnetic Resonance Imaging

This study examined the usefulness of diffusion-weighted (DW) Magnetic Resonance Imaging (MRI) in monitoring bone metastases response to radiation therapy in 15 oligometastatic patients. For each metastasis, both mean apparent diffusion coefficient (ADC) changes and high b-value DW metastasis/muscle signal intensity ratio (SIR) variations were evaluated at 30 ± 5 days and 60 ± 7 days after the end of treatment. On baseline DW-MRI, all bone metastases were hyperintense and had signal intensities higher than normal bone marrow on calculated ADC maps. At follow-up evaluations, 4 patterns of response were identified: (I) decreased high b-value DW SIR associated with increased mean ADC (83.3% of cases); (II) increased mean ADC with no change of high b-value DW SIR (10% of cases); (III) decreased both high b-value DW SIR and mean ADC (3.3% of cases); (IV) a reduction in mean ADC associated with an increase in high b-value DW SIR compared to pretreatment values (3.3% of cases). Patterns (I) and (II) suggested a good response to therapy; pattern (III) was classified as indeterminate, while pattern (IV) was suggestive of disease progression. This pattern approach may represent a useful tool in the differentiation between treatment-induced necrosis and highly cellular residual tumor.

Management of breast cancer in elderly patients

Even if there is not a general consensus, we consider elderly patients of 65 years old or more. The degree of aging is extremely variable so that we can individuate different groups of patients that are different one from the other in relation with Performance Status, the presence of other pathology, and of eventual social discomfort. Breast Cancer is the most common Tumor in elderly woman and it represent the first death cause The 45% of Breast Cancer arise in women more than 65 years old and the 33% arise in women of more than 70 years old. Despite these data elderly women are often excluded from screening schedules, moreover despite there is no evidence that breast cancer is less aggressive in elderly patient they are generally non considered in trial studies so that they are under treated if compared to young patients thats why we cannot observe a decrease of mortality such as in younger patients Relative survival between 5 and 10 years in patients more than 75 years old its lesser than the one observed in younger patients (between 45 and 70 years old) maybe thats because of the incongruity in the access to sanitary structures and because of the social and economic discomfort. When we speak about Breast Cancer we cannot be able to leave a multidisciplinary approach out of consideration. Patients evaluation must be done by a group of dedicated specialists that are: Radiologist, Pathologist, Surgeon, Radiotherapist and Oncologist. The team need to analyze all data to improve treatment and obtain a better cosmetic result [4]. Complex cases must be discussed collectively before surgery to obtain the best therapeutic strategy. Moreover its strictly important patients involvement in treatment selection. Consensus is mandatory and it can be obtained only if the patient is well informed about treatment phases, adverse effects, and results.

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.