Artificial neural networks allow response prediction in squamous cell carcinoma of the scalp treated with radiotherapy.

BACKGROUND: Epithelial neoplasms of the scalp account for approximately 2% of all skin cancers and for about 10-20% of the tumours affecting the head and neck area. Radiotherapy is suggested for localized cutaneous squamous cell carcinomas (cSCC) without lymph node involvement, multiple or extensive lesions, for patients refusing surgery, for patients with a poor general medical status, as adjuvant for incompletely excised lesions and/or as a palliative treatment. To date, prognostic risk factors in scalp cSCC patients are poorly characterized. OBJECTIVE: To identify patterns of patients with higher risk of postradiotherapy recurrence. METHODS: A retrospective observational study was performed on scalp cSCC patients with histological diagnosis who underwent conventional radiotherapy (50-120 kV) (between 1996 and 2008, follow-up from 1 to 140 months, median 14 months). Out of the 79 enrolled patients, 22 (27.8%) had previously undergone a surgery. Two months after radiotherapy, 66 (83.5%) patients achieved a complete remission, 6 (7.6%) a partial remission, whereas 2 (2.5%) proved non-responsive to the treatment and 5 cases were lost to follow-up. Demographical and clinical data were preliminarily analysed with classical descriptive statistics and with principal component analysis. All data were then re-evaluated with a machine learning-based approach using a 4th generation artificial neural networks (ANNs)-based algorithm. RESULTS: Artificial neural networks analysis revealed four scalp cSCC profiles among radiotherapy responsive patients, not previously described: namely, (i) stage T2 cSCC type, aged 70-80 years; (ii) frontal cSCC type, aged <70 years; (iii) non-recurrent nodular or nodulo-ulcerated, stage T3 cSCC type, of the vertex and treated with >60 Grays (Gy); and (iv) flat, occipital, stage T1 cSCC type, treated with 50-59 Gy. The model uncovering these four predictive profiles displayed 85.7% sensitivity, 97.6% specificity and 91.7% overall accuracy. CONCLUSIONS: Patient profiling/phenotyping with machine learning may be a new, helpful method to stratify patients with scalp cSCCs who may benefit from a RT-treatment.

Dermatologic radiotherapy in the treatment of extensive basal cell carcinomas: a retrospective study.

BACKGROUND: The increase of the number of new cases for year of basal cell carcinoma (BCC) has brought also an increase of BCC difficult to treat (extensive, locally advanced and high risk forms). OBJECTIVE: To evaluate retrospectively the results obtained with dermatologic radiotherapy (RT) for better defining the indications respect to new emerging treatments. METHODS: A series of extensive 115 BCC treated with RT from 1977 to 2014 were selected for the study, since endowed with histological diagnosis on the amount of 181 extensive BCC. RT was performed with conventional energies (50-160 kV) administering a total dose ranging from 47 to 85 Gy (median 55 Gy). The mean follow up was 40.66 months (median 21 months). A statistical evaluation was performed with chi-square test to analyse the possible correlations among therapeutic and cosmetic results and size, localisation and clinical type of the lesions. RESULTS: A complete remission (CR) was obtained in 70.43%, a partial remission (PR) in 20% of the lesions treated, while in 9.56% a no response (NR) or not evaluable response (NER) was registered. In 19% of the lesions a relapse was observed, with a five-year cure-rate of 55.13%. Cosmetic results were good in 28%, acceptable in 50% and not acceptable in 22% of the lesions in CR. In six lesions, localised at the trunk region, a chronic radiodermatitis developed. A statistically significative correlation was observed between therapeutic results and size, between cosmetic results and size and between therapeutic results and clinical type of BCC. CONCLUSION: The treatment of extensive BCC is still a challenge and radiotherapy is one of the possible choices, preferred in the elderly, in relapsing cases, after incomplete excision, and in difficult localisations of the face. Radiotherapy might be included in sequential schedules of treatment to improve final results.

Localized conventional radiotherapy in the treatment of Mycosis Fungoides: our experience in 100 patients.

BACKGROUND: Radiotherapy (RT) is one of the treatments of choice as skin-directed therapy in Mycosis Fungoides (MF), both in first stages of the disease as total skin electron beam irradiation and in tumoural stage as localized treatment with conventional energies or electrons. OBJECTIVE: Through a retrospective study, to evaluate the results of localized superficial RT in a series of 100 patients affected by MF. METHODS: All the patients, after diagnosis supported by histological and immunophenotyping investigations, have been treated with conventional RT (range 50-150 kV) and a total dose ranging from 9 to 40 Gy. RESULTS: Complete remission of the irradiated lesion has been observed in 88%, partial remission in 6% and non-response in 2%. Four patients were lost to follow-up. Local relapse has been observed in 13 lesions, with a local control rate of 85% after 5 years from the end of RT. Cosmetic results have been good and acceptable in 93% of cases. The treatment has been always well tolerated. The results confirm to be dose dependent, and show that better response is found in the range of higher energies. CONCLUSION: Localized RT is an effective and safe tool in the care and palliation of MF.

Radiotherapy of morphea-type basal cell carcinoma: results in 127 cases.

BACKGROUND: The morphea-type basal cell carcinoma (MBCC) is a rare form of basal cell carcinoma (BCC) with lower response to treatments than other types of BCC.Objective To evaluate the role of radiotherapy (RT) in the therapeutic strategy of MBCC. METHODS: A retrospective study was performed on 127 patients affected with MBCC, who underwent RT in the period 1982-2013. RT was delivered with conventional energies ranging from 50 to 120 kV and the administration of a total dose ranging from 40 to 70 Gy (mean 56.17 Gy). The irradiated fields included a margin of 1.5 cm around the lesion. RESULTS: The median follow-up time was 29 months (range 1-324 months). Complete remission was observed in 122 patients (96.06%), partial remission in one (0.78%). Three cases were non-responsive (2.36%). In one case (0.78%), the lesion failed to heal after RT, since the onset of radiodermatitis histologically ascertained. The cure rate was 81.08% after 5 years and 78.02% after 10 years from the end of RT. Twelve cases relapsed (10.2%). CONCLUSION: Because of the frequent diagnostic delay and its ill-defined margins, MBCC is difficult to cure. Our results after 5 years from RT (cure rate 81.08%) are more satisfactory respect to the others reported in the literature (69% and 72.3%), but less good than those obtained in other forms of primary malignant neoplasms of the skin (92.43%). Nevertheless,we consider that RT plays an important role in the therapeutic strategy of MBCCs. In fact, it can be applied easily in elderly patients, and in peculiar localization of the disease (eyelid, nose and ear), without being invasive.

Relevance of dermatologic radiotherapy in the therapeutic strategy of skin epithelial neoplasms: excellent results in the treatment of lesions localized on eyelids and skin overlying the cartilage of the nose.

AIM: Epithelial cancer of the skin is the most common human neoplasm. In spite of the multiple modalities of treatment available, about 10 % of these tumours results resistant to them. Therefore, improving the therapeutic strategies is mandatory. METHODS: A retrospective study has been carried out on 905 patients affected by 986 basal and squamous cell carcinoma, histologically ascertained, localized on eyelids and on skin overlying the cartilages of the nose treated with conventional radiotherapy. All the lesions were classified according to TNM classification. RESULTS: Follow-up ranged from 1 to 425 months. The five-year cure-rate was 96.38% for eyelids neoplasms and 92.43% for those localized on skin covering nose cartilages, respectively. The percentage of relapse was 5.47%.The graphic representation shows how the risk of relapse remains high for the first five years. On the whole cosmetic and functional outcomes were good. CONCLUSION: Our results confirm dermatologic radiotherapy as a treatment proper to afford very high cure-rates, and support the importance of a correct follow-up. The knowledge of these data and the possibility to compare them with others obtained by different therapies and endowed with histopathologic investigation, TNM classification, adequate follow-up and significant clinical series would result in improvement of the management of skin epithelial neoplasms.

Oral polypodium leucotomos extract photoprotective activity in 57 patients with idiopathic photodermatoses.

AIM: Idiopathic photodermatoses (IP) are a recurrent, acquired sunlight-induced rash of delayed onset, appearing after exposure to ultraviolet radiation in susceptible individuals. The aim of this study was to assess the photoprotective activity of polypodium leucotomos (PL) in IP. METHODS: Fifty-seven patients affected by IP were recruited for the study (53 with polymorphic light eruption and 4 with solar urticaria). The use of UV protection filters or other drugs that could in some way interfere with exposure to light were excluded. All patients exposed themselves to sunlight while consuming 480 mg/day of PL extract orally. A statistical evaluation of the basal clinical conditions compared to those after sunlight exposure with PL was performed. RESULTS: About 73.68% of the patients had a benefit from the administered PL, with a significant reduction of skin reaction and subjective symptoms. No side effects were observed. Results were statistically significant (P<0.05). CONCLUSION: PL complete absence of toxicity combined with its multifactorial protection, makes it an effective and safe treatment for photoprotection in IP.

Radiotherapy of carcinomas of the skin overlying the cartilage of the nose: our experience in 671 lesions.

BACKGROUND: The skin overlying the nose cartilage is a particularly frequent localization of skin carcinoma (about 25% of all carcinomas occurring on the head and neck). It is therefore of great practical interest to identify the best therapy, able to combine effectiveness with a good cosmetic and functional result. OBJECTIVE: To verify both the therapeutic effectiveness of dermatologic radiotherapy and its 'toxicity' in the treatment of a large number of skin carcinomas overlying the cartilage of the nose. METHODS: A retrospective study was done on 671 basal and squamous cell carcinomas treated by kilovoltage radiotherapy in the period 1972-2007. RESULTS: The mean follow-up time was 38.016 months (range, 1-351 months). The 5-year cure rate was 88.09%. Cosmetic results were evaluated as 'good' or 'acceptable' in 96.84% of the treated lesions in complete remission. So far, no complication or sequelae to the radiologic treatment have been observed. CONCLUSION: Dermatologic radiotherapy showed to be a safe, effective and non-invasive method, superior, on the basis of the literature data, to any other available therapeutic modality in the management of basal and squamous cell skin carcinomas localized over the nasal cartilages.

Radiotherapy of classic and human immunodeficiency virus-related Kaposi's sarcoma: results in 1482 lesions.

BACKGROUND: The lesions of the various forms of Kaposi's sarcoma (KS), which are relatively radiosensitive, have been treated with different modalities of radiotherapy, with heterogeneous aims and results. OBJECTIVE: To verify the effectiveness and safety of radiotherapy on a large number of lesions endowed (classic KS) with a prolonged follow-up. METHODS: A retrospective study was done on 711 lesions of classic KS and 771 lesions of human immunodeficiency virus (HIV)-related KS, treated with traditional X-ray therapy. RESULTS: In classic KS, a cure rate of 98.7% resulted after 13.5 years from the end of radiotherapy. In three lesions (0.42%) in the same patient, an acute radiodermatitis occurred after traumatic action. In HIV-related KS, a complete remission was obtained in 91.43% of the lesions, partial remission in 6.74% and non-response in 0.51% at 1 to 46 months from the end of radiotherapy. CONCLUSION: Radiotherapy showed to be a safe and effective method, with relevant importance in the therapeutic strategy of KS.

Photoprotective activity of oral polypodium leucotomos extract in 25 patients with idiopathic photodermatoses.

BACKGROUND: The incidences of idiopathic photodermatoses (IP) are increasing and the available therapeutic methods are often inadequate. AIM: To evaluate whether, in subjects affected by IP not responding to the usual available therapies, the oral administration of an extract of Polypodium leucotomos (PL) could provide an effective photoprotective activity. METHODS: 26 patients with polymorphic light eruption and two with solar urticaria were recruited to enter the study. The protocol excluded the use of ultraviolet protection filters or other drugs that could in some way interfere with exposure to light. All patients exposed themselves to sunlight while consuming 480 mg/day of PL orally. The response of the skin to sunlight exposure of 25 evaluable patients was compared with that occurring previously without administration of PL. RESULTS: With PL, we observed a relevant and statistically significant reduction of skin reaction and subjective symptoms. The tolerance of the drug has been excellent. CONCLUSION: PL extract administration has shown to be an effective and safe method, leading to a significant protection of skin in IP.

Radiotherapy of skin carcinomas of the pinna: a study of 115 lesions in 108 patients.

BACKGROUND: The possibility of treating skin carcinomas of the pinna with radiotherapy is somewhat under discussion and scarcely known. Therefore the aim of the study was to evaluate the effectiveness and safety of dermatologic radiotherapy in a series of patients affected by basal or squamous cell carcinoma of the pinna. METHODS: A retrospective study was performed on 108 patients affected by 115 carcinomas of the pinna (99 basal cell carcinomas, 16 squamous cell carcinomas) without involvement of the external auditory canal. Radiotherapy was performed with kilovoltage techniques (55-120 kV) and the total doses administered ranged from 45 to 70 Gy (105 Gy in one case only), with different fractionations. RESULTS: The mean follow-up was 28.80 months. Complete remission was obtained in 111 lesions (96.52%) and partial remission in one (0.87%), as evaluated 1 month after the end of radiotherapy. No response was observed in two lesions (1.74%). The response was not evaluable in one lesion (0.87%). During follow up a relapse was observed in 12 lesions (all basal cell carcinomas): nine central and three marginal to the irradiation field. The 5-year cure-rate from the end of radiotherapy was 78%. The cosmetic results were evaluated as good or acceptable in 88.28% of lesions. No complications nor sequelae to the treatment were observed. CONCLUSIONS: The results obtained confirm the possibility of treating epithelial skin neoplasms of the pinna with dermatologic radiotherapy, which can afford high-remission percentages without damaging cartilaginous tissue.

[The role of aromatase inhibitors in the treatment of breast neoplasms. An evaluation of clinical efficacy and the tolerability profile]. / Il ruolo degli inibitori dell'aromatasi nel trattamento del tumore della mammella.

Constant acquisitions regarding endocrine pathogenesis and the biology of breast neoplasms have led to the evolution of hormone manipulation as a therapeutic option in patients suffering from this disease. There has been a shift from ablative surgical procedures to the use of drugs offering greater clinical efficacy and an improved tolerability profile. Since the late 1970s tamoxifen has been regarded as the gold standard for hormone treatment in hormone-responsive breast neoplasm, but promising new endocrine agents are now being compared in random trials. Of these, the latest generation of aromatase inhibitors appears to gather the widest consensus on the basis of the results published to date. This article aims to review this new category of drugs, illustrating their rationale of use, the results obtained in the treatment of breast neoplasm and the main studies in which they are currently being investigated.

[Expression and prognostic significance in epithelial ovarian cancer]. / Espressione e significato prognostico nel carcinoma ovarico epiteliale.

BACKGROUND: Insulin-like growth factor binding protein-3 (IGFBP-3) is a glycoprotein with specific binding affinity to peptide hormones insulin-like growth factors (IGFs) which are potent mitogens for a variety of cells. IGFBP-3 can inhibit the activities of IGFs by interfering with the interaction between IGFs and their receptor IGF-IR. Epithelial ovarian cancer (EOC) tissues express IGFBP-3, IGFs and IGF-IR. Moreover, high levels of IGF-I and IGF-IR have been shown in epithelial ovarian cancer, and IGF-I stimulates the growth of ovarian cancer. METHODS: We measured IGFBP-3 levels in ovarian cancer tissues of 147 consecutive patients and we examined its association with clinical and pathological features of the disease and patient survival. The average age of the patients in the study was 55 years and the median follow-up time was 37 months. IGFBP-3 levels were measured in the tissue extracts by a commercial ELISA kit and non-parametric statistics and the Cox regression survival analysis were used to determine the associations of IGFBP-3 with clinical and pathologic variables as well as with patient survival. RESULTS: High IGFBP-3 levels resulted significantly associated with some of the favorable prognostic features of the disease, including early clinical stage (p=0.048), small size of residual tumor (p=0.007), and optimal debulking result (p=0.007). High IGFBP-3 was also associated with a significantly reduced risk for disease progression (RR=0.52, p=0.034) and we showed an inverse dose-dependent relationship between IGFBP-3 and disease progression-free survival (p=0.033). However, the association with disease progression-free survival was no longer statistically significant in a multivariate analysis. An association between IGFBP-3 and overall survival was not shown. CONCLUSIONS: This study suggest that IGFBP-3 may play a role in the progression of epithelial ovarian cancer.

[Growth factors in epithelial ovarian cancer]. / Fattori di crescita e carcinoma epiteliale ovarico.

The aim of this study was to provide an up-to-date review of the knowledge on the role of the main growth factors involved in the onset and progression of epithelial ovarian cancer (Transforming Growth Factor a-TGFa, Trans-forming Growth Factor-TGFb, Epidermal Growth Factor-EGF, Insulin-Like Growth Factor-IGF, Vascular Endothelial Growth Factor-VEGF). Relevant articles published between 1991 and 2001 were identified using the Medline database. Publications identified by the search were reviewed and critically evaluated for their relevance to growth factors role in ovarian cancer. This review may be useful for clinicians wishing to study the biological mechanisms involved in epithelial ovarian neoplasms, in order to evaluate the possible value of Growth Factors as prognostic or predictive markers which could lead to novel therapeutic regimens, fitting individual needs based on single biological variations.