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Purpose: To assess the contribution of Italian radiation oncologists in the current management of recurrent high-grade gliomas (HGG), focusing on a reirradiation (reRT) approach. Methods: In 2015, the Reirradiation and the Central Nervous System Study Groups on behalf of the Italian Association of Radiation Oncology (AIRO) proposed a survey. All Italian radiation oncologists were individually invited to complete an online questionnaire regarding their clinical management of recurrent HGG, focusing on a reRT approach. Results: A total of 37 of 210 questionnaires were returned (18% of all centers): 16 (43%) from nonacademic hospitals, 14 (38%) from academic hospitals, 5 (13%) from private institutions, and 2 (6%) from hadron therapy centers. The majority of responding centers (59%) treated ≤5 cases per year. Performance status at the time of recurrence, along with a target diameter Conclusions: Although there were wide variations in the clinical practice of reRT across the 37 centers, the core activities were reasonably consistent. These findings provide a basis for encouraging a national collaborative study to develop, implement, and monitor the use of reRT in this challenging clinical setting.

The aim of this study was to determine whether parameters related to TBI impacted upon OS and relapse in patients with acute leukemia in CR who underwent haematopoietic SCT (HSCT) in 11 Italian Radiation Oncology Centres. Data were analysed from 507 patients (313 males; 194 females; median age 15 years; 318 with ALL; 188 with AML; 1 case not recorded). Besides 128 autologous transplants, donors included 192 matched siblings, 74 mismatched family members and 113 unrelated individuals. Autologous and allogeneic transplants were analysed separately. Median follow-up was 40.1 months. TBI schedules and HSCT type were closely related. Uni- and multi-variate analyses showed no parameter was significant for OS or relapse in autologous transplantation. Multivariate analysis showed type of transplant and disease impacted significantly on OS in allogeneic transplantation. Disease, GVHD and TBI dose were risk factors for relapse. This analysis illustrates that Italian Transplant Centre use of TBI is in line with international practice. Most Centres adopted a hyperfractionated schedule that is used worldwide (12 Gy in six fractions over 3 days), which appears to have become standard. TBI doses impacted significantly upon relapse rates.

To quantify radiation treatments for bone metastases from breast cancer in three Sicilian provinces (Messina, Catania, Ragusa) with respect to the general population and the incidence and prevalence of breast cancer in this macro-area in a 8-year period.All bone metastasis patients treated using radiotherapy in 8 radiation departments operating in the provinces of Messina, Catania and Ragusa were collected. Among these, metastases from breast carcinoma were analyzed according to year of irradiation. An analysis of breast cancer incidence and prevalence with respect to inhabitants in this macro-area was conducted using literature and census data.From January 2004 to December 2011, irradiation was delivered in 4419 bone metastasis patients. Among these, 1617 had a primary breast cancer with a median treatment per year of 206.5 (range, 164-251); 211 patients were treated in 2004 and 206 in 2011. In 2004, there were 1,048,957 female residents in the three provinces and 1,065,422 in 2011. The reported breast cancer incidence and prevalence in Sicily was respectively 100.79/100,000 and 908.54/100,000 in 2004 and 108.41/100,000 and 1091.29/100,000 in 2010.There has been an increase in both incidence and prevalence of breast cancer in Sicily. Nevertheless, it seems that there was no increment in skeletal-related events requiring irradiation in such patients in eastern Sicily radiation departments.

Long-term survival after organ transplantation is increasing. As a result, many physicians may encounter various solid organ cancers during follow up. We review papers who address their attention on those malignancies and their treatment. Aim of this work is to discuss the role of radiotherapy especially when helped by new technologies in the management of brain, skin, head and neck, lung, breast, prostate and anal cancer. In our institution we are used to treat such patients by Helical Tomotherapy in order to avoid graft and to limit high risk toxicity. As example, we include a scalp and pelvic irradiation in which high dose conformality is linked to best organ sparing.

Urinary incontinence consist in voluntary urine leakage. Female affected in the world are about 200 thousand. Urinary incontinence affect severely women quality of life. There are different kinds of urinary incontinence that can be treated in different ways. We can use pelvic floor rehabilitation, drug therapy, invasive and non-invasive surgical treatment. Different treatments are used for different incontinence types. Periurethral injection is the most common procedure between non-invasive surgery. The most recent bulking agents occasionally determine severe adverse reaction or complication. Frequently we can have just pain during injection and a temporary urine retention. During the latest years we used a lot of bulking agents: bovine collagen, autologous fat, carbon particles, macroplastique, calcium hydroxylapatite, ethylene vinyl alcohol copolymer, dextranomer. Urethral injection have success in 40-90%. We can assert that macroplastique is the most efficacy and safe on the basis of literature data and of our experience data. This surgical procedure, in fact, has good percentage of success in accurately selected patients. In our experience Macroplastique can also be used in oncological patients, in elderly women, in patients with important comorbidity and with high surgical risk with good objective and subjective results.

Aims and Background The aim of surveys on clinical practice is to stimulate discussion and optimize practice. In this paper the current Italian radiotherapy practice after breast-conserving surgery for early breast cancer is described and adherence to national and international guidelines is assessed. Furthermore, results are compared with an earlier survey in northern Italy and international reports. Study Design A multiple-choice questionnaire sent to all 138 Italian radiation oncology centers. Results 48% of centers responded. Most performed breast-conserving surgery when tumor size was ≤3 cm. All centers routinely performed axillary dissection; 45 carried out sentinel node biopsy followed by axillary dissection when the sentinel node was positive. Most centers re-excised when resection margins were positive. The median interval between surgery and radiotherapy, when chemotherapy was not administered, was 60 days. Adjuvant chemotherapy was preferably administered before radiotherapy. Regional lymph nodes were never irradiated in 10 centers; in all others irradiation depended on the number of positive lymph nodes and/or involvement of axillary fat and/or tumor location in medial quadrants. All centers used standard fractionation; hypofractionated schemes were available in 6. Most centers used 4–6 MV photons. In 59 centers the boost dose of 10 Gy could be increased if margins were not negative. All centers ensured patient setup reproducibility. Treatment planning was computerized in 59 centers. The irradiation dose was prescribed at the ICRU point in 56 centers and portal films were made in 54 centers. Intraoperative radiotherapy was used in 4 centers: for partial breast irradiation in 1 and for boost administration in 3 centers. Conclusions Although the quality of radiotherapy delivery has improved in Italy in recent years, approaches that do not conform to international standards persist.

The aim of this study was to evaluate the role of radiation therapy alone, employing standard fractionation, in stage III-IV hypopharyngeal carcinoma.Fourteen (38.9%) stage III and 22 (61.1%) stage IV patients with hypopharyngeal carcinoma were submitted, with curative intent, to exclusive radiotherapy to the primary tumor and regional draining lymph nodes, level II, III, IV, V and VI. Total dose ranged from 68 to 72 Gy.The 5-year overall survival (OS) and disease-specific survival (DSS) rates were 15.6% and 28.1%, respectively. Five-year OS in stage III and IV patients was, respectively, 33% and 5% (p=0.028) and DSS was, respectively, 50% and 16% (p=0.029). Five-year OS and DSS rate in N0 versus N+ patients were respectively 37.5% and 75% versus 8.3% and 12.5% (p=0.07 and p=0.05).Overall survival at 5 years for III-IV hypopharyngeal tumor treated with radiotherapy alone is poor. It is possible that the addition of the best radiation fractionation to the best concurrent chemotherapy may improve the results, with acceptable toxicity.

A randomized trial was conducted to determine (a) the role of radiotherapy and chemotherapy on local control and (b) to determine the timing of radiotherapy for early-stage breast cancer.Five hundred and ninety patients were treated with both conservative surgery and radiotherapy (group A). The average time interval between surgery and radiation was 90 days for 452 patients and over 90 days for 138 patients. One hundred and ninety-four patients underwent adjuvant therapy based on CMF regimens (group B).Among 396 patients of group A, 8.1% had local failure; we observed 7.2% local recurrences in 363 patients who received therapy before 90 days and 18.2% in patients who received therapy after 90 days. Among patients of group B, 7.7% had local failure; for patients who underwent radiotherapy before 90 days, the local recurrence rate was 6.6%, compared with 12.3% for patients who underwent therapy more than 90 days after surgery.In patients who are eligible to receive chemotherapy, it is possible to administer radiotherapy after systemic treatment, while in patients who have to be treated with radiotherapy more then 90 days after breast surgery, chemotherapy can reduce the local failure rate.

The best treatment of Nasopharyngeal Carcinoma (NPC) is still an open question. The purpose of this retrospective study was to determine risk factors that affect locoregional control and treatment outcome of NPC patients after radiotherapy, with or without chemotherapy.Between January 1976 and December 1996, 66 consecutive patients (stage I = 0; stage II = 13; stage III = 32; stage IV = 21) were given definitive radiotherapy at a single Institution. Concurrent or adjuvant chemotherapy was also given to 14 of them (21%). Multivariate analysis was performed to evaluate age, T stage, N stage, radiotherapy dose, histology, chemotherapy bone of skull erosions or cranial nerve palsies and base of skull involvement as prognostic factors of locoregional control and overall survival.By the end of January 2000, after a median follow-up of 66 months and a minimal follow-up of 36 months, the event-free overall survival rate of 5 years was 48% and the overall survival 54%. Risk factor analysis revealed that radiotherapy dose, age and stage were the most important factors for overall survival of these patients. The 5 year overall survival was 89% for stage II and 49% for stage III-IV (p = 0.004), 62% for dose higher than 60 Gy and 20% for dose below 60 Gy (p = 0.007), 62% for age below 65 years and 36% for age higher than 65 years (p = 0.027). The concurrent or adjuvant chemotherapy did not have prognostic significance.We confirm the need to determine the risk factors in patients with NPC. The choice of treatment, whether radiotherapy alone, at dose60 Gy, or radiotherapy plus chemotherapy, should be made after identification of patients with high risk disease, suitable for the combined modality.

We have analysed our experience with medically inoperable IIIA and IIIB elderly patients (agedor = 70 years), treated with radiotherapy alone, to better define the potential benefit of this approach.From 1992 to 1995, 41 patients with NSCLC (Non Small Cell Lunc Cancer), stage III, agedor = 70 years were irradiated with curative intent.Median follow-up was 20 months (range 9-53). The 2 year OS (Overall Survival) and DFS (Disease Free Survival) were respectively 27% and 14.6% for all patients. Patients presenting weight loss10% experienced 14% OS at 24 months compared to 58% for those without weight loss (p = 0.0027). A 64% OS at 24 months was seen in patients with tumor size less than 4 cm compared to 7% of patients with tumor size4 cm (p = 0.0009).Radiotherapy is a good management for locally advanced NSCLC in the elderly patients assuring good quality of life, high rates of relief of symptoms and OS and DFS similar to those obtained with chemotherapy and chemotherapy plus radiotherapy.

Radiation therapy holds a fundamental role in oncological emergencies such as superior vena cava syndrome, spinal cord compression and endocranial hypertension. The purpose of our study was, by comparing schedules of treatment, to confirm the efficacy of hypofractionated radiation therapy.From January 1994 to December 1998, 43 patients with superior vena cava syndrome, 37 patients with metastatic spinal cord compression and 108 patients with endocranial hypertension secondary to metastasis were treated at our institution. In the group of patients with superior vena cava syndrome, radiotherapy schedules were: 4 Gy x 5 to a total dose of 20 Gy (23 patients) and 3 Gy x 10 to a total dose of 30 Gy (20 patients). In the group of patients with spinal cord compression, radiation schedules were: 3 Gy x 10 to a total dose of 30 Gy (15 patients); 4 Gy x 5 to a total dose of 20 Gy (12 patients); a single fraction of 8 Gy in 10 cases, repeated after 1 week in 7 responder cases to a total dose of 16 Gy. 5 out of 37 patients were underwent to laminectomy plus stabilization of the spine and post-operative radiotherapy. In the group of patients with endocranial hypertension, radiotherapy schedules were: 6 Gy x 2 to a total dose of 12 Gy (53 patients), repeated after 4 weeks in 34 responder patients and 3 Gy x 10 to a total dose of 30 Gy (55 patients).The patients with superior vena cava syndrome, revaluated after 4 weeks at the end of treatment, obtained a partial remission of symptomatology in 73.9% with 20 Gy and in 75% with 30 Gy. The patients with spinal cord compression obtained symptomatic relief in 73.3% with 30 Gy, in 66.6% with 20 Gy and in 70% of cases treated with 8 Gy. The patients with endocranial hypertension obtained symptomatic relief in 64.1% with 12 Gy and in 63.3% with 30 Gy.Histology, pretreatment and performance status were important prognostic factors for the response to therapy. Our results demonstrated no significant difference among different schedules of radiotherapy and confirmed the importance of radiotherapy for oncological emergencies: it improves the quality of life and, in responding patients, is associated with a longer survival time.

Patients affected by Hodgkin's disease (HD) in pathologic stage IA-IIA have a strong possibility of remission and long-term survival when treated with radiotherapy to extended fields. However, 20-30% of cases relapse in the five years following treatment and consequently need further therapy. This study examines the occurrence of relapse and other complications in patients with pathologic stage IIA Hodgkin's disease and mediastinal involvement treated in different ways: radiotherapy alone vs radiotherapy plus one cycle of adriamycin, bleomycin, vinblastine and dacarbazine (ABVD).Our series consisted of 73 HD patients with mediastinal involvement treated by the Department of Radiation Oncology and the Hematology Department of "La Sapienza" University of Rome from 1983 to 1989. The patients were randomized into two groups according to their initial treatment. The first group contained 37 patients treated, initially, with supradiaphragmatic radiotherapy and para-aortic irradiation (STNI); the second group was made up of 36 patients treated, initially, with supradiaphragmatic radiotherapy and para-aortic irradiation (STNI) combined with one course of adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). For 28 (38%) of the patients, the follow-up period was longer than 10 years. The average follow-up period was 114 months (range 22-174 months). Overall survival and relapse-free survival were assessed using the Kaplan and Meier method, while differences were tested by the log-rank test.We recorded twelve cases of relapse after initial treatment. The period of time which elapsed between the end of treatment and the evidence of relapse ranged from 6 to 51 months, with an average of 22 months. Ten relapses occurred in the STNI group and two in the ABVD/STNI group. No statistically significant differences emerged between the two groups in the overall survival analysis but did in the relapse-free survival analysis (p0.01). In the group treated with ABVD and STNI one patient developed acute non-lymphocytic leukemia and another patient treated at the age of 44 developed primary breast cancer. X-ray-related asymptomatic pulmonary fibrosis was observed in 12 patients: 10 cases in the STNI and ABVD group and 2 cases in the group treated with RT alone. The other sequelae of combined CT/RT treatment in our study were thyroid dysfunction (2 cases, hypothyroidism), whereas the sequela of RT treatment was cardiac disease (2 cases).We conclude that one cycle of ABVD and radiotherapy in early-stage HD patients with mediastinal involvement may reduce the risk of relapse. Moreover, the combination of low-toxicity CT and RT, administered preferably to limited fields, in patients who have not undergone laparotomy could be a valid alternative to current treatment for early-stage HD. However, additional data and a longer follow-up are mandatory in order to evaluate late toxicity and the potential risk of treatment.

The aim of this study was to measure contemporaneously HCV-RNA load, HIV-RNA load and CD4+ lymphocyte count in HCV/HIV coinfected patients with coagulopathy and to examine the relationship between these parameters and the liver failure.A cross-sectional study was performed on 54 patients with severe coagulopathy: 39 HCV/HIV coinfected and 15 HCV+/HIV- comparable for age and HCV exposure time. HCV-RNA and HIV-RNA load, CD4+ lymphocyte count, biochemical and ultrasonographic parameters were evaluated at the time of entry to the study.Mean HCV-RNA load was significantly higher in coinfected patients (643,872 717,687 copies/mL) than in HCV+/HIV- (mean 161,573 276,896 copies/mL) (p = 0.01). The 39 HCV/HIV coinfected patients had a mean HIV-RNA load of 205,913 456,311 copies/mL (range 4,000-2,500,000) and a mean CD4+ lymphocyte count of 206.5171/microL (range 5-693). Five of the 39 (12.8%) coinfected patients had liver failure. In these five patients the mean HCV-RNA load (770,200 996,426 copies/mL) was high but not significantly different from that in the 34 HCV+/HIV+ patients (623,496 682,239 copies/mL) without liver failure (p = 1.0). Coinfected patients with liver failure had a significantly higher HIV-RNA load (mean 764, 599 978,542 copies/mL) and lower CD4+ lymphocyte count (mean 52.655. 6/microL) than those observed in coinfected patients without liver failure (p = 0.007 and p = 0.03, respectively). A significant inverse correlation was found between CD4+ lymphocyte count and HIV-RNA load (r = -0.37, p = 0.01).HCV-RNA load is significantly higher in HIV+ than in HIV- patients with coagulopathy. Liver failure was found only in the HCV/HIV coinfected patients with severe immunodepression, expressed either by low CD4+ lymphocyte count or by high HIV-RNA load.

To analyze the results of standard versus alternative myeloablative conditioning regimens in allogeneic hematopoietic stem cell transplantation for high-risk acute leukemia.From October 1986 to February 2000, 104 consecutive patients (male: n = 63; median age: 21, range 1.3-44.2 years) with high-risk acute leukemia underwent a non-T-cell depleted graft from an HLA-identical sibling following a standard or alternative myeloablative conditioning regimen. Sixty patients were affected by acute lymphoblastic leukemia (ALL) and 44 by acute myeloid leukemia (AML); the phase at transplant was= 2nd complete remission (CR) in 76, untreated 1st relapse with20% blasts in 11, refractory leukemia or overt resistant relapse in 17. Pre-transplant regimens consisting of either 12 Gy fractionated total body irradiation (TBI) or 16 mg/kg busulphan (BU) combined with cyclophosphamide (CY) were defined standard (n = 38), whereas all other myeloablative regimens (TBI plus 60 mg/kg etoposide and three-drug combinations) were considered alternative (n = 66).No significant differences in terms of baseline characteristics, incidence and severity of either acute or chronic graft-versus-host disease (GVHD) were observed between the two groups, but a significantly higher proportion of patients prepared with an alternative regimen were not evaluable for chronic GVHD (36% vs 16%) (p = 0.026). Sixty-six patients died, 38 of relapse, 26 of transplant-related mortality (TRM) and 2 of other causes. Thirty-eight patients are still alive with a follow-up ranging from 0.7 to 13.8 years (median, 7.1 years); only 1 of 39 patients who relapsed after transplant is alive in CR at 5.7 years from relapse. At the median follow-up, the actuarial probabilities of overall survival, relapse and TRM for patients conditioned with standard and alternative regimens are respectively 52% vs 25% (95% CI, 36-68% vs 13-37%; p = 0.0163), 34% vs 58% (95% CI, 18-51% vs 43-73%; p = 0.0377) and 25% vs 32% (95% CI, 9-40% vs 19-44%; p = ns). After adjustment for diagnosis, age, period, leukemia phase, duration of 1st CR, GVHD prophylaxis and donor-recipient sex combination, the multivariate analysis showed that alternative regimens are associated with a significantly worse survival (hazard ratio 2.31; p = 0.0071) and relapse rate (hazard ratio 2.75; p = 0.0187).From this retrospective analysis we can conclude that the alternative myeloablative conditioning regimens we used did not improve the outcome of patients transplanted for high-risk acute leukemia.

Vulvodynia is a women's health problem that may affect as many as 15% of women who seek gynecological care, and yet little attention is given to this condition and it is frequently dismissed as psychosomatic. Thus, vulvodynia still remains a major health problem in Western countries, leading to significant morbidity and a reduced quality of life for many women. This condition carries large costs incurred as a result of both medical treatment and lost productivity. Vulvodynia is becoming a universal priority in the prevention, care, education, and research areas of pain and its consequences and it remains one of the poorly understood complex chronic pain syndromes, representing a multifactorial clinical syndrome of unexplained vulvar pain and sexual dysfunction.

Ovarian cancer is burdened by the highest mortality rate among gynecological cancers. Gold standard is represented by the association of platinum-taxane -based chemotherapy and radical surgery. Despite several adjustments occurred in cytotoxic drug in last decades, most patients continue to relapse, and no significant enhancement has been reached in the overall survival. The development of drug resistance and the recurrence of disease have prompted the investigations of other targets that can be used in the treatment of ovarian cancers. Among such targets, polyadenosine diphosphate-ribose polymerase (PARP) represents a novel way to target specific patways involved in tumor growth. PARP accelerates the reaction of the polyADP-ribosylation of proteins implicated in DNA repair. PARP inhibitors have shown activity in cancers with BRCA mutations, with other deficient DNA repair genes or signaling pathways that modulate DNA repair, or in association with DNA damaging agents not involved in DNA repair dysfunction. A number of inhibitors for PARP has been developed, and such drugs are under investigation in clinical trials to identify their impact in the treatment of ovarian cancers. This review aims to summarize the recent researches and clinical progress on PARP inhibitors as novel target agents in ovarian cancer.

To evaluate efficacy of short-course radiotherapy in elderly and/or poor performance status patients with high grade glioma.Twenty-one patients with high grade astrocytoma were selected in our Institute to receive hypofractionated radiotherapy. We considered two radiotherapy treatment arms: in arm I there were 22 patients treated with 60 Gy in 30 fractions at 5 fractions per week; in arm 2 there were 21 patients who received hypofractionated radiotherapy course of 30 Gy in 10 fractions at 5 fractions per week.In arm1 the median survival time was 8.2 months and the 1 year overall survival was 36%; in arm 2 the estimated median survival was 6.2 months and the 1 year overall survival was 23%. Treatment was without acute toxicity.In our experience, hypofractionated radiotherapy seems to be a reasonable treatment option for poor prognosis patients with high grade astrocytoma. It is well tolerated and can reduce the overall treatment time without negative effects on survival compared with conventional fractionation.

OBJECTIVE To investigate factors predicting the risk of developing 90-day postoperative complications and lymphatic-specific morbidity in patients undergoing surgical staging for high-risk endometrial cancer. METHODS This is a multi-institutional retrospective cohort study. Patients affected by apparent early-stage high-risk endometrial cancer (endometrioid FIGO grade 3 with deep myometrial invasion and non-endometrioid endometrial cancer) undergoing surgical staging between 2007 and 2019. Complications were graded according to the Clavien-Dindo classification system. Martin criteria were applied to improve quality of complications reporting. RESULTS Charts of 279 patients were evaluated. Lymphadenectomy, sentinel node mapping (SNM), and SNM followed by back-up lymphadenectomy were performed in 83 (29.7%), 50 (17.9%), and 146 (52.4%) patients, respectively. The former group of patients included 13 patients who had lymphadenectomy after the failure of the SNM technique. Thirteen (4.6%) patients developed severe postoperative events (grade 3 or worse). At multivariate analysis, body mass index (OR: 1.08 (95%CI: 1.01, 1.17)) and open abdominal surgery (OR: 2.27 (95%CI: 1.02, 5.32)) were the two independent factors predictive of surgery-related morbidity. Seven severe lymphatic complications occurred. The adoption of laparoscopic approach (p��

Constitutional BRCA1/BRCA2 pathogenic or likely pathogenic variants (PVs) are associated with an increased risk for developing breast and ovarian cancers. Current evidence indicates that BRCA1/2 PVs are also associated with pancreatic cancer, and that BRCA2 PVs are associated with prostate cancer risk. The identification of carriers of constitutional PVs in the BRCA1/2 genes allows the implementation of individual and family prevention pathways, through validated screening programs and risk-reducing strategies. According to the relevant and increasing therapeutic predictive implications, the inclusion of BRCA testing in the routine management of patients with breast, ovarian, pancreatic and prostate cancers represent a key requirement to optimize medical or surgical therapeutic and prevention decision-making, and access to specific anticancer therapies. Therefore, accurate patient selection, the use of standardized and harmonized procedures, and adherence to homogeneous testing criteria, are essential elements to implement BRCA testing in clinical practice. This consensus position paper has been developed and approved by a multidisciplinary Expert Panel of 64 professionals on behalf of the AIOM-AIRO-AISP-ANISC-AURO-Fondazione AIOM-SIAPEC/IAP-SIBioC-SICO-SIF-SIGE-SIGU-SIU-SIURO-UROP Italian Scientific Societies, and a patient association (aBRCAdaBRA Onlus). The working group included medical, surgical and radiation oncologists, medical and molecular geneticists, clinical molecular biologists, surgical and molecular pathologists, organ specialists such as gynecologists, gastroenterologists and urologists, and pharmacologists. The manuscript is based on the expert consensus and reports the best available evidence, according to the current eligibility criteria for BRCA testing and counseling, it also harmonizes with current Italian National Guidelines and Clinical Recommendations.

Objective Coronavirus disease 2019 (COVID-19) outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer (EC) is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms. Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of EC patients. Methods This is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of EC patients before (period 1: March 1, 2019 to February 29, 2020) and during (period 2: April 1, 2020 to March 31, 2021) the COVID-19 outbreak. Results Medical records of 5,164 EC patients have been retrieved: 2,718 and 2,446 women treated in period 1 and period 2, respectively. Surgery was the mainstay of treatment in both periods (p=0.356). Nodal assessment was omitted in 689 (27.3%) and 484 (21.2%) patients treated in period 1 and 2, respectively (p, Synopsis The prevalence of patients with early-stage endometrial cancer (EC) has been lower during coronavirus disease 2019 (COVID-19) pandemic than before its onset. Further evidence is needed to assess the impact of COVID-19 pandemic on survival outcomes of EC patients.

OBJECTIVE Sentinel node mapping (SLN) has replaced lymphadenectomy for staging surgery in apparent early-stage low and intermediate risk endometrial cancer (EC). Only limited data about the adoption of SNM in high risk EC is still available. Here, we evaluate the outcomes of high-risk EC undergoing SNM (with or without back-up lymphadenectomy). METHODS This is a multi-institutional international retrospective study, evaluating data of high-risk (FIGO grade 3 endometrioid EC with myometrial invasion >50% and non-endometrioid histology) EC patients undergoing SNM followed by back-up lymphadenectomy and SNM alone. RESULTS Chart of consecutive 196 patients were evaluated. The study population included 83 and 113 patients with endometrioid and non-endometrioid EC, respectively. SNM alone and SNM followed by back-up lymphadenectomy were performed in 50 and 146 patients, respectively. Among patients having SNM alone, 14 (28%) were diagnosed with nodal disease. In the group of patients undergoing SNM plus back-up lymphadenectomy 34 (23.2%) were diagnosed with nodal disease via SNM. Back-up lymphadenectomy identified 2 (1%) additional patients with nodal disease (in the para-aortic area). Back-up lymphadenectomy allowed to remove adjunctive positive nodes in 16 (11%) patients. After the adoption of propensity-matched algorithm, we observed that patients undergoing SNM plus back-up lymphadenectomy experienced similar disease-free survival (p��=��0.416, log-rank test) and overall survival (p��=��0.940, log-rank test) than patients undergoing SLN alone. CONCLUSIONS Although the small sample size, and the retrospective study design this study highlighted that type of nodal assessment did not impact survival outcomes in high-risk EC. Theoretically, back-up lymphadenectomy would be useful in improving the removal of positive nodes, but its therapeutic value remains controversial. Further prospective evidence is needed.

Objective: To evaluate the outcomes of high-risk (HR) HPV-positive and -negative women affected by high-grade cervical dysplasia. Methods: This is a retrospective multi-institutional study. Medical records of consecutive patients with high-grade cervical dysplasia undergoing conization between 2010 and 2014 were retrieved. All patients included had at least 5 years of follow-up. A propensity-score matching was adopted in order to reduce the presence of confounding factors between groups. Kaplan-Meir and Cox hazard models were used to estimate 5-year outcomes. Results: Overall, data of 2966 women, affected by high-grade cervical dysplasia were reviewed. The study population included 1478 (85%) and 260 (15%) women affected by HR-HPV-positive and HR-HPV-negative high-grade cervical dysplasia. The prevalence of CIN2 and CIN3 among the HR-HPV-positive and -negative cohort was similar (p = 0.315). Patients with HR-HPV-positive high-grade cervical dysplasia were at higher risk of 5-year recurrence (after primary conization) that HR-HPV-negative patients (p < 0.001, log-rank test). Via multivariate analysis, HR-HPV-negative women were at low risk of recurrence (HR: 1.69 (95%CI: 1.05, 4.80); p = 0.018, Cox Hazard model). A propensity-score matched comparison was carried out in order to reduce biases that are related to the retrospective study design. In comparison to HR-HPV-negative patients, thosewith HR-HPV-positive CIN3 was associate with a 8-fold increase in the risk of recurrence (p < 0.001, log-rank test). Conclusions: HR-HPV-negative high-grade cervical dysplasia is not uncommon, accounting for 15% of our study population. Those patients experience more favorable outcomes than patients with documented HR-HPV infection(s). Further prospective studies are needed to corroborate our data.

Objective 'The Endometrial Cancer Conservative Treatment (E.C.Co.). A multicentre archive' is a worldwide project endorsed by the Gynecologic Cancer Inter-Group, aimed at registering conservatively treated endometrial cancer (EC) patients. This paper reports the oncological and reproductive outcomes of intramucous, G2, endometrioid EC patients from this archive. Methods Twenty-three patients (Stage IA, G2, endometrioid EC) were enrolled between January 2004 and March 2019. Primary and secondary endpoints were, respectively, complete regression (CR) and recurrence rates, and pregnancy and live birth rates. Results A median follow-up of 35 months (9-148) was achieved. Hysteroscopic resection (HR) plus progestin was adopted in 74% (17/23) of cases. Seventeen patients showed CR (median time to CR, 6 months; 3-13). Among the 6 non-responders, one showed persistence and 5 progressed, all submitted to definitive surgery, with an unfavorauble outcome in one. The recurrence rate was 41.1%. Ten (58.8%) complete responders attempted to conceive, of whom 3 achieved at least one pregnancy with a live-birth. Two out of the 11 candidate patients underwent definitive surgery, while the remaining 9 have so far refused. To date, 22 patients show no evidence of disease, and one is still alive with disease. Conclusions Fertility-sparing treatment seems to be feasible even in G2 EC, although caution should be kept considering the potential pathological undergrading or non-endometrioid histology misdiagnosis. The low rate of attempt to conceive and of compliance to definitive surgery underline the need for a 'global' counselling extended to the follow-up period.

Objective: Conization aims to remove pre-neoplastic lesions of the uterine cervix. Several techniques for conization have been compared, but evidence regarding the most effective therapeutic option is scant. Here, we aimed to compare the recurrence rate following laser conization and loop electrosurgical excision procedure (LEEP) in patients with high-grade cervical dysplasia (HSIL/CIN2+). Methods: This is a retrospective multi-institutional study. Medical records of consecutive patients with HSIL/CIN2+ undergoing conization between 2010 and 2014 were retrieved. A propensity-score matching (PSM) was applied in order to reduce allocation bias. The risk of developing recurrence was estimated using Kaplan-Meir and Cox hazard models. Results: Overall, 2966 patients had conization over the study period, including 567 (20%) and 2399 (80%) patients having laser conization and LEEP, respectively. Looking at predictors of recurrence, diagnosis of CIN3 (HR:3.80 (95%CI:2.01,7.21); p < 0.001) and HPV persistence (HR:1.81 (95%CI:1.11,2.96); p < 0.001) correlated with an increased risk of recurrence. After applying a PSM we selected 500 patients undergoing laser conization and 1000 undergoing LEEP. Patients undergoing LEEP were at higher risk of having positive surgical margins in comparison to patients undergoing laser conization (11.2% vs. 4.2%). The risk of having persistence of HPV was similar between the two groups (15.0% vs. 11.6%;p = 0.256). Five-year recurrence rate was 8.1% and 4% after LEEP and laser conization, respectively (p = 0.023). HPV persistence was the only factor associated with [5-]year recurrence after both laser conization (p = 0.003) and LEEP (p = 0.001). Conclusions: HPV persistence is the only factor associated with an increased risk of recurrence after either laser conization or LEEP. Owing to the lack of data regarding obstetrical outcomes, we are not able to assess the best therapeutic option for women with cervical dysplasia.

Surgery is the mainstay of treatment in the management of early-stage cervical cancer. Until the publication of the Laparoscopic Approach to Cervical Cancer (LACC) trial, minimally invasive radical hysterectomy was the recommended approach to treat patients with early-stage disease. The results of the LACC trial questioned the adoption of minimally invasive surgery in cervical cancer. In comparison with the open approach, minimally invasive surgery correlated with worse disease-free and cancer-specific survival. Similarly, other retrospective studies highlighted this correlation, thus corroborating the results of the LACC trials. In the present review, we evaluated current evidence and further prospective of the adoption of minimally invasive radical hysterectomy in cervical cancer. Moreover, we sought to assess some unsolved issues regarding the role of minimally invasive surgery in early-stage cervical cancer patients.

Clear cell endometrial carcinoma represents an uncommon and poorly understood entity. Data from molecular/genomic profiling highlighted the importance of various signatures in assessing the prognosis of endometrial cancer according to four classes of risk (POLE mutated, MMRd, NSMP, and p53 abnormal). Unfortunately, data specific to clear cell histological subtype endometrial cancer are lacking. More recently, data has emerged to suggest that most of the patients (more than 80%) with clear cell endometrial carcinoma are characterized by p53 abnormality or NSMP type. This classification has important therapeutic implications. Although it is an uncommon entity, clear cell endometrial cancer patients with POLE mutation seem characterized by a good prognosis. Chemotherapy is effective in patients with NSMP (especially in stage III and IV) and patients with p53 abnormal disease (all stages). While, preliminary data suggested that patients with MMRd are less likely to benefit from chemotherapy. The latter group appears to benefit much more from immune checkpoint inhibitors: recent data from clinical trials on pembrolizumab plus lenvatinib and nivolumab plus cabozantinib supported that immunotherapy plus tyrosine kinase inhibitors (TKI) would be the most appropriate treatment for recurrent non-endometrioid endometrial cancer (including clear cell carcinoma) after the failure of platinum-based chemotherapy. Moreover, ongoing clinical trials testing the anti-tumor activity of innovative products will clarify the better strategies for advanced/recurrent clear cell endometrial carcinoma. Further prospective evidence is urgently needed to better characterize clear cell endometrial carcinoma.

Endometrial carcinosarcoma is a rare and aggressive high-grade endometrial carcinoma with secondary sarcomatous trans-differentiation (conversion theory). The clinical presentation and diagnostic work-up roughly align with those of the more common endometrioid counterpart, although endometrial carcinosarcoma is more frequently diagnosed at an advanced stage. Endometrial carcinosarcoma is not a single entity but encompasses different histological subtypes, depending on the type of carcinomatous and sarcomatous elements. The majority of endometrial carcinosarcomas are characterized by p53 abnormalities. The proportion ofPOLEand microsatellite instablity-high (MSI-H) is directly related to the epithelial component, being approximately 25% and 3% in endometrioid and non-endometrioid components.The management of non-metastatic disease is based on a multimodal approach with optimal surgery followed by (concomitant or sequential) chemotherapy and radiotherapy, even for early stages. Palliative chemotherapy is recommended in the metastatic or recurrent setting, with carboplatin/paclitaxel doublet being the first-line regimen. Although the introduction of immunotherapy plus/minus a tyrosine kinase inhibitor shifted the paradigm of treatment of patients with recurrent endometrial cancer, patients with endometrial carcinosarcoma were excluded from most studies evaluating single-agent immunotherapy or the combination. However, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved the use of pembrolizumab and lenvatinib in endometrial cancer (all histotypes) after progression on chemotherapy and single-agent immunotherapy in MSI-H cancers. In the era of precision medicine, emerging knowledge on molecular endometrial carcinosarcoma is opening new promising therapeutic options for more personalized treatment. The present review outlines state-of-the-art knowledge and future directions for patients with endometrial carcinosarcoma.

Serous endometrial cancer represents a relative rare entity accounting for about 10% of all diagnosed endometrial cancer, but it is responsible for 40% of endometrial cancer-related deaths. Patients with serous endometrial cancer are often diagnosed at earlier disease stage, but remain at higher risk of recurrence and poorer prognosis when compared stage-for-stage with endometrioid subtype endometrial cancer. Serous endometrial cancers are characterized by marked nuclear atypia and abnormal p53 staining in immunohistochemistry. The mainstay of treatment for newly diagnosed serous endometrial cancer includes a multi-modal therapy with surgery, chemotherapy and/or radiotherapy. Unfortunately, despite these efforts, survival outcomes still remain poor. Recently, The Cancer Genome Atlas (TCGA) Research Network classified all endometrial cancer types into four categories, of which, serous endometrial cancer mostly is found within the "copy number high" group. This group is characterized by the increased cell cycle deregulation (e.g., CCNE1, MYC, PPP2R1A, PIKCA, ERBB2 and CDKN2A) and TP53 mutations (90%). To date, the combination of pembrolizumab and lenvatinib is an effective treatment modality in second-line therapy, with a response rate of 50% in advanced/recurrent serous endometrial cancer. Owing to the unfavorable outcomes of serous endometrial cancer, clinical trials are a priority. At present, ongoing studies are testing novel combinations of various targeted and immunotherapeutic agents in newly diagnosed and advanced/recurrent endometrial cancer - an important strategy for serous endometrial cancer, whereby tumors are usually p53+ and pMMR, making response to PD-1 inhibitor monotherapy unlikely. Here, the rare tumor working group (including members from the European Society of Gynecologic Oncology (ESGO), Gynecologic Cancer Intergroup (GCIG), and Japanese Gynecologic Oncology Group (JGOG)), performed a narrative review reporting on the current landscape of serous endometrial cancer and focusing on standard and emerging therapeutic options for patients affected by this difficult disease.

OBJECTIVE Sentinel lymph node mapping (SNM) has gained popularity in managing apparent early-stage endometrial cancer (EC). Here, we evaluated the long-term survival of three different approaches of nodal assessment. METHODS This is a multi-institutional retrospective study evaluating long-term outcomes of EC patients having nodal assessment between 01/01/2006 and 12/31/2016. In order to reduce possible confounding factors, we applied a propensity-matched algorithm. RESULTS Overall, 940 patients meeting inclusion criteria were included in the study, of which 174 (18.5%), 187 (19.9%), and 579 (61.6%) underwent SNM, SNM followed by backup lymphadenectomy (LND) and LND alone, respectively. Applying a propensity score matching algorithm (1:1:2) we selected 500 patients, including 125 SNM, 125 SNM/backup LND, and 250 LND. Baseline characteristics of the study population were similar between groups. The prevalence of nodal disease was 14%, 16%, and 12% in patients having SNM, SNM/backup LND and LND, respectively. Overall, 19 (7.6%) patients were diagnosed with low volume nodal disease. The survival analysis comparing the three techniques did not show statistical differences in terms of disease-free (p = 0.750) and overall survival (p = 0.899). Similarly, the type of nodal assessment did not impact survival outcomes after stratification based on uterine risk factors. CONCLUSION Our study highlighted that SNM provides similar long-term oncologic outcomes than LND.

Background. To evaluate the impact of the Laparoscopic Approach to Cervical Cancer (LACC) Trial on patterns of care and surgery-related morbidity in early-stage cervical cancer. Methods. This is a retrospective, a multi-institutional study evaluating 90-day surgery-related outcomes of patients undergoing treatment for early-stage cervical cancer before (period I: 01/01/2016-06/01/2018) and after (period II: 01/01/2019-06/01/2021) the publication of the results of the LACC trial. Results. Charts of 1295 patients were evaluated: 581 (44.9%) and 714 (55.1%) before and after the publication of the LACC trial, respectively. After the publication of the LACC trial, the number of patients treated with minimally invasive radical hysterectomy decreased from 64.9% to 30.4% (p < 0.001). Overall, 90-day complications occurred in 110 (18.9%) and 119 (16.6%) patients in the period I and period II, respectively (p = 0.795). Similarly, the number of severe (grade 3 or worse) complications did not differ between the two periods (38 (6.5%) vs. 37 (5.1%); p = 0.297). Overall and severe 90-day complications were consistent between periods even evaluating stage IA (p = 0.471), IB1 (p = 0.929), and IB2 (p = 0.074), separately. Conclusions. The present investigation highlighted that in referral centers the shift from minimally invasive to open radical hysterectomy does not influence 90-day surgery-related morbidity. (c) 2022 Elsevier Inc. All rights reserved.

Background/aim The aim of the study was to investigate boost volume definition, doses, and delivery techniques for rectal cancer dose intensification. Patients and methods An online survey was made on 25 items (characteristics, simulation, imaging, volumes, doses, planning and treatment). Results Thirty-eight radiation oncologists joined the study. Twenty-one delivered long-course radiotherapy with dose intensification. Boost volume was delineated on diagnostic magnetic resonance imaging (MRI) in 18 centres (85.7%), and computed tomography (CT) and/or positron emission tomography-CT in 9 (42.8%); 16 centres (76.2%) performed co-registration with CT-simulation. Boost dose was delivered on gross tumor volume in 10 centres (47.6%) and on clinical target volume in 11 (52.4%). The most common total dose was 54-55 Gy (71.4%), with moderate hypofractionation (85.7%). Intensity-modulated radiotherapy (IMRT) was used in all centres, with simultaneous integrated boost in 17 (80.8%) and image-guidance in 18 (85.7%). Conclusion A high quality of treatment using dose escalation can be inferred by widespread multidisciplinary discussion, MRI-based treatment volume delineation, and radiation delivery relying on IMRT with accurate image-guided radiation therapy protocols.

Objective Coronavirus disease 2019 (COVID-19) has caused rapid and drastic changes in cancer management. The Italian Society of Gynecology and Obstetrics (SIGO), and the Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) promoted a national survey aiming to evaluate the impact of COVID-19 on clinical activity of gynecologist oncologists and to assess the implementation of containment measures against COVID-19 diffusion. Methods The survey consisted of a self-administered, anonymous, online questionnaire. The survey was sent via email to all the members of the SIGO, and MITO groups on April 7, 2020, and was closed on April 20, 2020. Results Overall, 604 participants completed the questionnaire with a response-rate of 70%. The results of this survey suggest that gynecologic oncology units had set a proactive approach to COVID-19 outbreak. Triage methods were adopted in order to minimize in-hospital diffusion of COVID-19. Only 38% of gynecologic surgeons were concerned about COVID-19 outbreak. Although 73% of the participants stated that COVID-19 has not significantly modified their everyday practice, 21% declared a decrease of the use of laparoscopy in favor of open surgery (19%). However, less than 50% of surgeons adopted specific protection against COVID-19. Additionally, responders suggested to delay cancer treatment (10%-15%), and to perform less radical surgical procedures (20%-25%) during COVID-19 pandemic. Conclusions National guidelines should be implemented to further promote the safety of patients and health care providers. International cooperation is of paramount importance, as heavily affected nations can serve as an example to find out ways to safely preserve clinical activity during the COVID-19 outbreak.

Objective: To evaluate treatment outcomes and patterns of CT lung injury after hypofractionated image-guided radiotherapy delivered with helical tomotherapy (HHT) in a series of inoperable lung lesions. Methods: 68 patients who were medically inoperable (69 lesions) without evidence of viable extrathoracic disease were included. Dose prescription was driven by tumour location (hilar/pericentral vs peripheral) and/or target volume. 52% of the lesions received a biological equivalent dose (BED10) ≥100Gy. Assessment of tumour response was based on the Response Evaluation Criteria in Solid Tumours 1.1 criteria coupled with fluorine-18 fludeoxyglucose/positron emission tomography-CT. Toxicity monitoring was focused on treatment-related pulmonary adverse events according to the Common Terminology Criteria for Adverse Events v. 4.0. Acute and late events were classified as radiation pneumonitis (RP) and radiation fibrosis (RF), respectively. Survival curves were calculated using the Kaplan-Meier method. Univariate and multivariate analyses of survival were performed using the Cox proportional hazards model. Results: After a median follow-up of 12 months (range, 3-31 months), no instances of ≥Grade 4 RP was documented, and clinically severe (Grade 3) RP occurred in 5.8% of the patients. 2 (3%) patients developed a late severe (≥Grade 3) symptomatic RF. No specific pattern of CT lung injury was demonstrated, in both acute and late settings. Median overall survival (OS) and progression-free survival (PFS) for the entire population were 30.8 and 14.1 months, respectively. At multivariate analysis (MVA), BED10≥100Gy and KPS≥90 emerged as significant prognostic factors for OS (p=0.01 and p=0.001, respectively), and BED10≥100Gy for PFS (p=0.02). Conclusion: Our findings show that HHT adjusted for tumour location and/or target volume is an effective treatment with an acceptable toxicity profile in patients who are medically inoperable with lung tumours and is not associated with a specific pattern of lung injury. Therefore, it can represent a viable option when conventional stereotactic ablative radiotherapy facilities are not available. Advances in knowledge: The present study is among the largest series addressing the role of HHT for inoperable lung tumours. This technique is safe and effective and is not associated with a specific pattern of lung injury, at least at early and average time points

Objective: To evaluate toxicity and patterns of radiologic lung injury on CT images after hypofractionated imageguided stereotactic body radiotherapy (SBRT) delivered with helical tomotherapy (HT) in medically early stage inoperable non-small-cell lung cancer (NSCLC). Methods: 28 elderly patients (31 lesions) with compromised pulmonary reserve were deemed inoperable and enrolled to undergo SBRT. Patterns of lung injury based on CT appearance were assessed at baseline and during follow up. Acute (6 months or less) and late (more than 6 months) events were classified as radiation pneumonitis and radiation fibrosis (RF), respectively. Results: After a median follow-up of 12 months (range, 4-20 months), 31 and 25 lesions were examined for acute and late injuries, respectively. Among the former group, 25 (80.6%) patients showed no radiological changes. The CT appearance of RF revealed modified conventional, mass-like and scar-like patterns in three, four and three lesions, respectively. No evidence of late lung injury was demonstrated in 15 lesions. Five patients developed clinical pneumonitis (four patients, grade 2 and one patient, grade 3, respectively), and none of whom had CT findings at 3 months post-treatment. No instance of symptomatic RF was detected. The tumour response rate was 84% (complete response1partial response). Local control was 83% at 1 year. Conclusion: Our findings show that HT-SBRT can be considered an effective treatment with a mild toxicity profile in medically inoperable patients with early stage NSCLC. No specific pattern of lung injury was demonstrated. Advances in knowledge: Our study is among the few showing that HT-SBRT represents a safe and effective option in patients with early stage medically inoperable NSCLC, and that it is not associated with a specific pattern of lung injury.

Increasing attention is being devoted to the mechanisms by which cells receive signals and then translate these into decisions for growth, death, or migration. Recent findings have presented significant breakthroughs in developing a deeper understanding of the activation or repression of target genes and proteins in response to various stimuli and of how they are assembled during signal transduction in cancer cells. Detailed mechanistic insights have unveiled new maps of linear and integrated signal transduction cascades, but the multifaceted nature of the pathways remains unclear. Although new layers of information are being added regarding mechanisms underlying ovarian cancer and how polymorphisms in VDR gene influence its development, the findings of this research must be sequentially collected and re-interpreted. We divide this multi-component review into different segments: how vitamin D modulates molecular network in ovarian cancer cells, how ovarian cancer is controlled by tumor suppressors and oncogenic miRNAs and finally how vitamin D signaling regulates miRNA expression. Intra/inter-population variability is insufficiently studied and a better understanding of genetics of population will be helpful in getting a step closer to personalized medicine.

BackgroundMany authors have investigated the numerous connections between the nervous system and kidneys, and recent literature has indicated that these similar systems are interconnected. Recent scientific works have shown that there is similarity between the cerebral cortex 'viscera representation' and the 'motor omunculus'. We studied the connection between the brain and kidney in vivo using repetitive transcranial magnetic stimulation (rTMS). Proteinuria and albuminuria were used as markers of renal response in patients with diabetes (DP) and in a group of healthy subjects (HSs) who received rTMS for 5 consecutive days.MethodsThe study population consists of the following four groups: Group A (HS stimulated), Group B (HS sham), Group C (DP stimulated) and Group D (DP sham). All subjects in Groups A and C underwent rTMS delivered at a frequency corresponding to 90% of the threshold at rest for 5 consecutive days. All subjects in Groups B and D underwent rTMS delivered with the coil placed on the scalp without delivering electromagnetic stimuli, while another coil at a distance of ∼2 m emitted stimuli at a very low intensity. This strategy ensured that brain stimulation would not occur, so that the subjects felt the vibrations produced by the click of the TMS coil. The proteinuria and albuminuria of 24 h and creatinine clearance were measured at time 0 (T0), after the first session (T1), at the end of the treatment (T5) and 24 h after the last stimulation (Post 24 h).ResultsIn Group A, there was a statistically significant increase in albuminuria (5.65 ± 0.52 versus 12 ± 0.55 mg/24 h, P = 0.0001) and proteinuria (6.05 ± 0.48 versus 13.1 ± 0.60 mg/24 h, P = 0.0001) at the end of the treatment (T5) compared with the baseline values (T0). In Group C, the albuminuria was statistically higher at T5 than the baseline T0 (416.22 ± 181 versus 677.25 ± 280 mg/24 h, P = 0.04), as was proteinuria (561.37 ± 86 versus 865.125 ± 104 mg/24 h, P = 0.0001); in Group C, the increase in albuminuria (T0 versus post 24 h, P = 0.02) and proteinuria (T0 versus 24 h post, P = 0.0002) persisted at 24 h post. In Groups B and D, statistically significant changes were not found in proteinuria (Group B T0 versus T5, P = 0.61; Group D: T0 versus T5, P = 0.66) and albuminuria (Group B T0 versus T5, P = 0.15; Group D T0 versus T5, P = 0.44) measured at the same times.ConclusionsConsecutive rTMS is able to induce a statistically significant increase in albuminuria and proteinuria in HS and DP. A functional link between the brain and kidney is possible. For the first time, the results have indicated an increase of proteinuria in subjects undergoing transcranial stimulation. © 2013 © The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

OBJECTIVE: The purpose of this study was to explore in greater depth the outcomes of the Italian randomized trial investigating the role of pelvic lymphadenectomy in clinical early stage endometrial cancer. In the attempt to identify the patients with poorer prognosis, the impact of age and body mass index were also thoroughly investigated by cancer-specific survival (CSS) analyses. STUDY DESIGN: Survival outcomes of trial patients were analyzed in relation to age (≤65 years and >65 years) in the 2 arms (lymphadenectomy and no lymphadenectomy) and in the whole population of the trial. RESULTS: Univariate and multivariable analyses of CSS and overall survival (OS) of patients showed that age >65 years is a strong independent poor prognostic factor (5-y OS 92.1% and 78.4% in ≤65 years and >65 years patients, respectively, P < .0001; 5-y CSS 93.8% and 83.5% in ≤65 years and >65 years patients, respectively, P = .003). Among women ≤65 years, node negative patients had 94.4% 5-y OS and 96.3% 5-y CSS vs 74.3% 5-y OS and 74.3% 5-y CSS for node positive patients (P = .009 and P = .002, respectively), while among women >65 y, node negative patients had 75.7% 5-y OS and 83.6% 5-y CSS vs 74.1% 5-y OS and 83.3% 5-y CSS for node positive patients (P = .55 and P = .58, respectively). Univariate and multivariable survival analyses in the whole trial population showed that older age, and higher tumor grade and stage were significantly associated to a worse prognosis. CONCLUSION: Older women faced an intrinsic poorer survival whether or not they underwent lymphadenectomy, and, unexpectedly, irrespective of the presence of nodal metastasis. Only in older patients was obesity (body mass index >30) significantly associated with scarce prognosis.

Background Purpose of this study is to explore the trade-offs between radio-induced toxicities and second malignant neoplasm (SMN) induction risk of different emerging radiotherapy techniques for Hodgkin’s lymphoma (HL) through a comprehensive dosimetric analysis on a representative clinical model. Methods Three different planning target volume (PTVi) scenarios of a female patient with supradiaphragmatic HL were used as models for the purpose of this study. Five treatment radiation techniques were simulated: an anterior-posterior parallel-opposed (AP-PA), a forward intensity modulated (FIMRT), an inverse intensity modulated (IMRT), a Tomotherapy (TOMO), a proton (PRO) technique. A radiation dose of 30 Gy or CGE was prescribed. Dose-volume histograms of PTVs and organs-at-risk (OARs) were calculated and related to available dose-volume constraints. SMN risk for breasts, thyroid, and lungs was estimated through the Organ Equivalent Dose model considering cell repopulation and inhomogeneous organ doses. Results With similar level of PTVi coverage, IMRT, TOMO and PRO plans generally reduced the OARs’ dose and accordingly the related radio-induced toxicities. However, only TOMO and PRO plans were compliant with all constraints in all scenarios. For the IMRT and TOMO plans an increased risk of development of breast, and lung SMN compared with AP-PA and FIMRT techniques was estimated. Only PRO plans seemed to reduce the risk of predicted SMN compared with AP-PA technique. Conclusions Our model–based study supports the use of advanced RT techniques to successfully spare OARs and to reduce the risk of radio-induced toxicities in HL patients. However, the estimated increase of SMNs’ risk inherent to TOMO and IMRT techniques should be carefully considered in the evaluation of a risk-adapted therapeutic strategy.

Therapeutic exposure to ionising radiation can induce normal tissue side effects which consistently differ among individuals suggesting a possible genetic control. One approach to elucidate the underlying mechanisms is to analyse the relation between genetic traits, biomarkers of in vitro DNA damage and side toxicity in vivo. 43 breast cancer (BC) patients receiving radiotherapy after a breast-conserving surgery were recruited together with 34 age- and sex-matched healthy controls. Adverse tissue reactions were recorded as indicators of radiotherapy susceptibility. All blood samples from both patients (35) and controls (34) were irradiated in vitro and DNA primary damage and repair kinetic were measured through Comet assay. All study subjects were genotyped for XRCC1, OGG1 and XRCC3 gene polymorphisms. In our small groups we found a positive association between XRCC1 variant allele (399Gln) and the occurrence of breast cancer [p = 0.01; OR= 2.41, 95%CI (1.24–4.66)]. BC patients showed a higher degree of basal (p < 0.001) and X-ray induced DNA damage (p < 0.01) when compared to healthy controls. A reduced repair ability was found in BC patients showing high degrees of tissue side effects as classified by Radiation Morbidity Scoring Scheme. BC patients showed an impairment of their DNA repair capacity associated with the development of radiation sensitivity but not with polymorphisms in any of the considered genes.