Parallel to the ever-growing elderly population, cancer incidence increases with age, due to the fact that population ageing and the consequent increase of life expectancy give more time for cellular dysfunctions including senescence to appear, indirectly favoring carcinogenesis. Geriatric assessment has been increasingly recognized as a prognostic tool to detect frailty in elderly cancer patients. In particular, the G8 score is a simple and reproducible instrument to identify elderly patients who should undergo full geriatric evaluation. The aim of this study was to evaluate the impact of frailty assessment by the G8 screening tool on the outcome of cancer patients. Patients > 65 years, with a confirmed cancer diagnosis, referred to our cancer center, received a G8 assessment at the time of first access. Patients were classified as frail if G8 score ≤14. The prognostic role of G8 score was assessed by univariable and multivariable analysis including age, type of tumor, stage and treatment. The primary endpoint was overall survival (OS). This retrospective analysis was performed on patients referred to Maggiore Hospital in Novara, IT, between 01/2017 and 02/2022. Overall, 411 patients were screened by G8; median age was 76 years (range 64-92) and 298 (72.5%) had a G8 score ≤14. Most represented diagnosis included lung, breast, skin, and colon cancer and 52.5% of patients had metastatic disease; 65.0% of them received an active cancer therapy. Median overall survival (OS) was 26 months; 23 months in patients with a G8 score ≤14 vs 30 months in non-frail patients (HR 2.43; 95% CI 1.53- 3.85 p value<0.0001). By multivariable analysis G8 score and male sex were significantly associated with a worse outcome: HR 2.32; CI 95% 1.46-3.68 for G8 ≤14 and HR 2.24; CI 95% 1.59-3.15 for male sex. In patients with metastatic disease, median OS was 13 months in frail patients vs 29 months in non-frail patients (HR 2.09; 95% CI 1.15-3.82 p=0.016). Our analysis indicates that elderly cancer patients with a G8 score ≤14 have a significantly increased risk of death as compared to elderly fit patients, underlying the strong prognostic role of a simple screening tool such as G8.

ConclusionThese findings support IMRT as a safe technique for the treatment of endometrial cancer with no difference in efficacy and an apparently lower incidence of acute GI toxicities.Results of long-term prospective trials are needed to confirm these results.

Purpose or ObjectiveTo evaluate apoptotic pathways in prostate cancer treated with intraoperative radiotherapy (IORT), studying the effects on cancer cells, prostatic intraepithelial neoplasia (PIN) and healthy cells.We evaluated correlations between p53, Bcl-2 and ki-67, pathological staging and local control Material and MethodsWe selected 20 patients.Proteins involved in the apoptotic cascade (Bax, Caspases -3 and -9) were studied before and after 12 Gy in neoplastic tissues, high grade PIN areas and in healthy prostate cells.Immunofluorescent detection of antigens (anti-Bax, anticaspases-3 and -9), were performed on bioptic sample and on surgical specimens 5-mm slices.Before and after IORT, also Bcl-2, p53, and ki-67 with immunoistochimical analysis were detected.A count of positive spots for immunofluorescence (Bax+, Caspases-3 and -9+/all nuclei) was performed on tumour cells, PIN and healthy tissue areas.Bax and caspases immunofluorescent positivity was compared in different areas and in neoplastic areas before and after single shot high dose Results Before IORT, mean Bcl-2 in neoplastic cells is 2.23% (range: 1-23), mean ki-67 in neoplastic area is 4.5% (range: 1-17) and mean p53 is 22.5% (1-36).After IORT mean Bcl-2 in neoplastic cells is 8.85% (range: 1-28), mean ki-67 in neoplastic area is 7.8% (range: 1-18) and mean p53 is 24.9% (1-94).A significant increase in Bax expression was detected in tumour and PIN areas comparing treated and untreated samples (p<0.05).After 12 Gy-single dose, healthy areas expressed significantly lower level of Bax positive with respect to neoplastic cells (p<0.0001), while in PIN areas, Bax positive cells were significantly more present than in neoplastic areas (p=0.0001).Results about Caspases 3 and 9 were conflicting and we did not find significant differences in expression between neoplastic and healthy tissue cells after IORT.With multivariate analysis, we find that cancer cells with ki-67 ≥ 8% show a trend toward greater expression of Bax (p=0.0641).We do not find correlations between ki-67 and caspases activation.We also found an increasing in Bcl-2 expression after IORT in neoplastic areas (p=0.0041); with multivariate analysis, we found that neoplastic cells with higher Bcl-2 expression after IORT had a worsen local control with higher incidence in biochemical failure.Bioptic specimens with p53 higher than 18% and ki-67 higher than 8% had worst postoperative staging with higher incidence in extracapsular invasion (p<0.05) and nodal positivity (p<0.05)Conclusion After 12 Gy, Bax is overexpressed in tumour and PIN cells.PIN areas seem to be more radiosensitive than

S842ESTRO 37Therefore, a systematic review on acute and late toxicity after postoperative HFRT was performed.Even outcome data in terms of local control (LC), overall survival (OS), and biochemical relapse-free survival (bRFS) were analyzed. Material and MethodsA systematic search based on PRISMA methodology was performed using PubMed.Only studies published in English reporting clinical results (toxicity and outcome) after adjuvant or salvage HFRT were included. ResultsA total of 1205 patients from 17 eligible studies were included.These retrospective (7) or prospective (10) studies had heterogeneous characteristics in terms of dose, fractionation, target definition, and combination with hormonal therapy.Median follow-up ranged between 11.5 and 111 months (median: 30.0 months).No case of grade ≥ 3 acute gastrointestinal (GI) toxicity was recorded.Grade ≥ 3 acute genitourinary (GU) toxicity ranged between 0.0% and 3.0% (median: 0%).Crude and actuarial rates of grade ≥ 2 late GI toxicity were 0.0% -8.7% (median: 3.8%) and 1.1% at 5-year, respectively.Crude and actuarial rates of grade ≥ 2 late GU toxicity were 0.0% -66.0%(median: 12.0%) and 7.3% at 5 years.LC was reported in only three studies: 93.7% as crude rate, and 69.0% and 94.9% at 5 years.Crude and actuarial rates of OS were 96.4% and 100% (median: 98.5%) and 91.0% at 10 years and 100% at 5 years.Actuarial rates of bRFS ranged between 83.7% and 92.0% at 1 year, 72.9 % and 83.0% at 2 years, and 74.0% and 94.0% (median: 84.0%), 67.0% and 75.0%, 86.5% at 3, 4 and 5 years, respectively. ConclusionAcute toxicity does not seem to be increased in patients with PCa receiving HFRT after radical prostatectomy (RP).Results in terms of late GU toxicity are conflicting and therefore further prospective studies are needed to clarify this issue before including postoperative HFRT in clinical practice.

Purpose or Objective: To evaluate the rate of complications and the aesthetic outcome in previously irradiated patients who underwent mastectomy and subsequent prosthetic reconstruction in 2 times.

Aims: The contribution of mitochondrial DNA (mtDNA) variations to clinical radiosensitivity is largely unknown. In the present study, we evaluated the association between mtDNA haplogroups and the risk of radiation-induced subcutaneous fibrosis after postoperative radiotherapy in breast cancer patients.Materials and methods: Subcutaneous fibrosis was scored according to the Late Effects of Normal Tissue-Subjective Objective Management Analytical (LENT-SOMA) scale in 286 Italian breast cancer patients who received radiotherapy after breast-conserving surgery. Eight mtDNA single nucleotide polymorphisms that define the nine major haplogroups in the European population were determined by polymerase chain reaction restriction fragment length polymorphism analysis on genomic DNA extracted from peripheral blood.Results: In a Kaplan-Meier analysis evaluated by the Log-rank test, carriers of haplogroup H were found to be at lower risk of grade >= 2 subcutaneous fibrosis (P = 0.018) compared with all other haplotypes combined. In the multivariate Cox regression analysis adjusted for clinical factors (body mass index, breast diameter, adjuvant treatment, dose per fraction, radiation type and acute skin toxicity), haplogroup H emerged as a protective factor for moderate to severe radiation-induced fibrosis at a nominal significance level (hazard ratio: 0.50, 95% confidence interval 0.27-0.92, P = 0.027), which did not survive correction for multiple testing.Conclusions: Our results suggest a protective effect of the mitochondrial haplogroup H in the development of radiation-induced fibrosis in breast cancer patients. However, the loss of statistical significance after correction for multiple comparisons and the lack of an independent validation cohort make our findings preliminary, requiring further confirmation in large-scale prospective studies. (C) 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Modern multidisciplinary cancer treatments aim at obtaining minimal influence on patients’ quality of life (QoL). The purpose of this study was to assess QoL and correlate it with dose–volume parameters of organ at risks (OARs) in patients who received adjuvant radiotherapy for endometrial and cervical cancers.

Conclusions: CT guided high dose brachytherapy can be successfully implemented in a cancer centre achieving good levels of local control and overall survival.Node positivity on original MRI is predictive for recurrence.A complete response on week 5 MRI predicts for excellent long term pelvic control.