The Role of Radiotherapy in Extramammary Paget Disease: A Systematic Review.

OBJECTIVE/PURPOSE: Extramammary Paget disease (EMPD) is a rare neoplasm of the skin generally affecting the anogenital area. Because of the low-frequency of the disease, no specific guidelines about the treatment strategy are available. Surgery is the recommended therapy for resectable and localized disease, but several other local treatments have been reported such as radiotherapy (RT). Most articles report small retrospective studies, referring to patients treated decades ago with large heterogeneity in terms of RT dose and technique. The aim of this study was to systematically review the main experiences in RT for the treatment of EMPD in the past 30 years. MATERIALS AND METHODS: A systematic search of the bibliographic databases PubMed and Scopus from January 1986 to January 2017 was performed including studies published in English, Italian, Spanish, French, and German language. RESULTS: According to the search strategy, 19 full-text articles, published from 1991 to 2015, fulfilled inclusion criteria and were included in the final review. All articles were retrospective analyses with no randomized controlled trials. These studies evaluated 195 EMPD patients treated with RT, delivered in several settings. A large variability in terms of RT doses, fractionation, clinical setting, and techniques was found.Radiotherapy was administered as definitive treatment for primary or recurrent disease after surgery in 18 studies with doses ranging from 30 to 80.2 Gy delivered in 3 to 43 fractions. Radiotherapy was administered as postoperative adjuvant treatment in 9 articles with doses ranging between 32 and 64.8 Gy in 20 to 30 fractions. Two studies reported the RT use in preoperative neoadjuvant setting with doses ranging between 40 and 43.30 Gy, and 2 experiences reported the RT treatment for in situ EMPD, using 39.6 to 40 Gy. Adverse events were reported in almost all but 2 articles and were grade 2 or lower.The 18 studies evaluating RT as definitive treatment for primary or recurrent disease after surgery reported a complete response rate ranging from 50% to 100%, with a variable rate of local relapse or persistent disease ranging from 0% to 80% of cases. The 9 studies evaluating RT as postoperative adjuvant treatment reported a local relapse or persistent disease rate of 0% to 62.5%. A dose-response relationship was reported suggesting doses greater than or equal to 60 Gy for gross tumor volume treatment. Local control, disease-free survival, and overall survival at 12, 20, and 60 months have been retrieved for available data, respectively.In patients with EMPD and concurrent underlying internal malignancy, the prognosis was often worsened by the latter. In this setting, literature analysis showed a potential RT palliative role for symptoms control or local control maintenance.Derma tumor invasion greater than 1 mm and lymph node metastases were reported to be important prognostic factors for distant metastases or death. CONCLUSIONS: To date, literature highlights the role of RT in the management of EMPD, but with low level of evidences.

Impact of residual disease after "unplanned excision" of primary localized adult soft tissue sarcoma of the extremities: evaluation of 452 cases at a single Institution.

BACKGROUND: Soft tissue sarcomas are often inappropriately excised; it is, however, still a matter of debate whether the presence of residual disease in the re-excision specimen can affect patients' prognosis. The aim of this study is to investigate the impact of re-excision after unplanned surgery of primary soft tissue sarcomas (STS) of the extremities. PATIENTS AND METHODS: We retrospectively evaluated 452 adults with grade 2-3, localized STS (349 primary and 103 unplanned excisions). RESULTS: In the re-excision group, a full 43% of the patients had residual tumor. The re-excision group achieved a significantly better outcome in terms of sarcoma-specific survival (SS) (p = 0.002), local recurrence (LR) (p = 0.004) and distant metastasis (DM) (p = 0.028). Residual tumor was associated with a higher risk of DM (p = 0.005). CONCLUSION: We confirm that unplanned surgery does not compromise patients' prognosis; scar re-excision guarantees at least the same SS, LR and DM rates compared to STS primarily treated in a referral center. Routine use of radiation therapy after re-excision could improve local control. Distant metastases seem to be negatively affected by the presence of residual tumor, and therefore, the use of CT in deep and large STS is suggested. The main goal is to avoid unplanned surgery by referring suspected lumps (especially deep, large, increasing in size) to a specialist center.

Radiation-induced apoptosis in relation to acute impairment of rat salivary gland function.

PURPOSE: To find an answer to the question: Are the acute radiation effects on salivary gland function, as seen in earlier studies, causally related to radiation-induced apoptosis? MATERIALS AND METHODS: Rat parotid and submandibular glands were X-irradiated with doses up to 25 Gy and morphological damage assayed up to 6 days after irradiation. Damage to the different cell types in the glands was assessed after H & E staining. Apoptotic appearance was judged by compacted chromatin and fragmentation of cells into lobulated masses. RESULTS: In about 3% of the cells aberrant nuclei were observed after doses as low as 2 Gy and around 7.5 and 24 h after irradiation. About half of these aberrant nuclei had an apoptotic appearance. After a dose of about 5 Gy no dose-response for apoptotic cells was found, as evidenced by a plateau in the dose-effect curve. At 6 days after 2 Gy, no signs of radiation-induced apoptosis was apparent and for most cell types a value close to zero was observed. CONCLUSIONS: Radiation studies on salivary function in the rat show the typical response with respect to dose (5-15 Gy) and time (1-3 days). This differs from reported findings with light microscopy. Therefore, the extent of apoptosis induced by radiation cannot explain the observed gland malfunction. Alternative mechanisms are proposed.

Determinants of non-attendance to mammographic screening. Analysis of a population sample of the screening program in the District of Florence.

The characteristics associated with non-attendance to mammographic breast cancer screening were studied by interviewing a random sample (213 attenders, 121 non-attenders in the 1989 screening) of residents in one of the municipalities of the Florence District Program, where screening has been ongoing since 1970. The overall attendance rate was 60%, and it was dependent on age (40-49 years, 66.5%; 50-59 years, 62.5%; 60-70 years, 55.5%), whereas a significant association with socio-economic status, educational level and health-behavior reported in other programs was not confirmed in the study. This finding suggests that determinants of non-attendance may vary and should be evaluated in each local setting. The belief that screening is useless, fear of cancer being detected, postponement and laziness were the most common motivations of refusal stated by non-attenders, and such a negative attitude towards screening was rather strong since most non-attenders stated they would not like to be informed or stimulated to attend future screenings. Rapid improvement of attendance rates in such a context might be achieved only by putting special pressure on women aimed to change their negative attitude towards screening and their opinion about the benefits of early breast cancer detection. This might be regarded as unacceptable and however would involve high costs and a major organization effort.