Daniela Musio

Texture analysis as imaging biomarker of tumoral response to neoadjuvant chemoradiotherapy in rectal cancer patients studied with 3-T magnetic resonance.

ObjectiveThe aim of this study was to determine whether texture features of rectal cancer on T2-weighted (T2w) magnetic resonance images can predict tumoral response in patients treated with neoadjuvant chemoradiotherapy (CRT). Materials and MethodsWe prospectively enrolled 15 consecutive patients (6 women, 63.2 ± 13.4 years) with rectal cancer, who underwent pretreatment and midtreatment 3-T magnetic resonance imaging. Treatment protocol consisted of neoadjuvant CRT with oxaliplatin and 5-fluorouracile. Texture analysis using a filtration-histogram technique was performed using a commercial research software algorithm (TexRAD Ltd, Somerset, England, United Kingdom) on unenhanced axial T2w images by manually delineating a region of interest around the tumor outline for the largest cross-sectional area. The technique selectively filters and extracts textures at different anatomic scales followed by quantification of the histogram using kurtosis, entropy, skewness, and mean value of positive pixels. After CRT, all patients underwent complete surgical resection and the surgical specimen served as the gold standard. ResultsSix patients showed pathological complete response (pCR), and 4 patients, partial response (PR). Five patients were classified as nonresponders (NRs). Pretreatment medium texture-scale quantified as kurtosis was significantly lower in the pCR subgroup in comparison with the PR + NR subgroup (P = 0.01). Midtreatment kurtosis without filtration was significantly higher in pCR in comparison with PR + NR (P = 0.045). The change in kurtosis between midtreatment and pretreatment images was significantly lower in the PR + NR subgroup compared with the pCR subgroup (P = 0.038). Pretreatment area under the receiver operating characteristic curves, to discriminate between pCR and PR + NR, was significantly higher for kurtosis (0.907, P < 0.001) compared with all other parameters. The optimal cutoff value for pretreatment kurtosis was 0.19 or less. Using this value, the sensitivity and specificity for pCR prediction were 100% and 77.8%, respectively. ConclusionTexture parameters derived from T2w images of rectal cancer have the potential to act as imaging biomarkers of tumoral response to neoadjuvant CRT.

Risk-reducing salpingo-oophorectomy: a meta-analysis on impact on ovarian cancer risk and all cause mortality in BRCA 1 and BRCA 2 mutation carriers.

BackgroundWomen with BRCA1 and BRCA2 mutation carriers are at substantially elevated risk of developing ovarian cancer. The aim of the meta-analysis is to clarify the role of risk-reducing salpingo-oophorectomy (RRSO) to reduce ovarian cancer risk and mortality in women with BRCA 1 and BRCA 2 mutation carriers.MethodsPubmed, Medline and Scopus were searched to select English-language articles. Two investigators independently extracted characteristics and results of selected studies. Articles were included only if prospective and if absolute numbers of ovarian cancer and death events were available or derivable from the test. Pooled hazard ratio (HR) with 95% confidence interval (CI) was calculated using fixed effects model.ResultsMeta-analysis of 3 prospective studies demonstrated a significant risk reduction of ovarian cancer with RRSO in BRCA 1 and BRCA 2 mutation carriers, as well as benefit in all-causes mortality incidence.ConclusionsIt may be justified to recommend RRSO to reduce ovarian cancer risk and all-causes mortality in women with a mutation in BRCA 1 and BRCA 2.

Immunotherapy of Ovarian Cancer: The Role of Checkpoint Inhibitors

Ovarian cancer is the most important cause of gynecological cancer-related mortality, with the majority of women presenting with advanced disease. Although surgery and chemotherapy can improve survival rates, it is necessary to integrate alternative strategies to improve the outcomes. Advances in understanding the role of immune system in the pathogenesis of cancer have led to the rapid evolvement of immunotherapy, which might establish a sustained immune system response against recurring cancer cells. Recently, it has emerged that powerful immunologic effector cells may be blocked by inhibitory regulatory pathways controlled by specific molecules often called “immune checkpoints,” which turn off the immune system. Similarly, cancer cells are able to use these checkpoints to avoid immune control and rejection. Inhibition of these inhibitory pathways represents a potent strategy in the fight against cancer and is currently under investigation with encouraging results in some cancers, such as melanoma. In ovarian cancer researches are still in an early phase, but with promising results. In this review we will explore the rationale of immunotherapy in ovarian cancer with a special focus on these emerging molecules.

Diffusion-Weighted Magnetic Resonance Application in Response Prediction before, during, and after Neoadjuvant Radiochemotherapy in Primary Rectal Cancer Carcinoma

Introduction. Our interest was to monitor treatment response using ADC value to predict response of rectal tumour to preoperative radiochemotherapy. Materials and Methods. Twenty-two patients were treated with long course of radiochemotherapy, followed by surgery. Patients were examined by diffusion-weighted imaging MRI at three-time points (prior, during, and after radiochemotherapy) and were classified as responders and nonresponders. Results. A statistical significant correlation was found between preradiochemotherapy ADC values and during treatment ADC values, in responders (F = 21.50, P value <0.05). An increase in ADC value during treatment was predictive of at least a partial response. Discussion. Response of tumour to neoadjuvant therapy cannot be easily evaluated, and such capability might be of great importance in clinical practice, because the number of irradiated and operated patients may be superior to the number of who will really benefit from this multimodal treatment. A reliable prediction of the final clinical TN stage would allow radiotherapist to adapt multidisciplinary approach to a less invasive management, sparing surgical procedure in responder patients or even allowing an early surgery in nonresponders, which would significantly reduce radiochemotherapy related toxicity. Conclusion. Early evaluation of response during neoadjuvant radiochemotherapy treatment shows great promise to predict tumour response.

Advanced Imaging for the Early Diagnosis of Local Recurrence Prostate Cancer after Radical Prostatectomy

Currently the diagnosis of local recurrence of prostate cancer (PCa) after radical prostatectomy (RT) is based on the onset of biochemical failure which is defined by two consecutive values of prostate-specific antigen (PSA) higher than 0.2 ng/mL. The aim of this paper was to review the current roles of advanced imaging in the detection of locoregional recurrence. A nonsystematic literature search using the Medline and Cochrane Library databases was performed up to November 2013. Bibliographies of retrieved and review articles were also examined. Only those articles reporting complete data with clinical relevance for the present review were selected. This review article is divided into two major parts: the first one considers the role of PET/CT in the restaging of PCa after RP; the second part is intended to provide the impact of multiparametric-MRI (mp-MRI) in the depiction of locoregional recurrence. Published data indicate an emerging role for mp-MRI in the depiction of locoregional recurrence, while the performance of PET/CT still remains unclear. Moreover Mp-MRI, thanks to functional techniques, allows to distinguish between residual glandular healthy tissue, scar/fibrotic tissue, granulation tissue, and tumour recurrence and it may also be able to assess the aggressiveness of nodule recurrence.

c-Myc Sustains Transformed Phenotype and Promotes Radioresistance of Embryonal Rhabdomyosarcoma Cell Lines.

We have previously reported that the MEK/ERK pathway sustains in vitro and in vivo transformed phenotype and radioresistance of embryonal rhabdomyosarcoma (ERMS) cell lines. Furthermore, we found that aberrant MEK/ERK signaling activation promotes c-Myc oncoprotein accumulation. In this study, the role of c-Myc in sustaining the ERMS transformed and radioresistant phenotype is characterized. RD and TE671 cell lines conditionally expressing MadMyc chimera protein, c-Myc-dominant negative and shRNA directed to c-Myc were used. Targeting c-Myc counteracted in vitro ERMS adherence and in suspension, growth motility and the expression of pro-angiogenic factors. c-Myc depletion decreased MMP-9, MMP-2, u-PA gelatinolytic activity, neural cell adhesion molecule sialylation status, HIF-1α, VEGF and increased TSP-1 protein expression levels. Rapid but not sustained targeting c-Myc radiosensitized ERMS cells by radiation-induced apoptosis, DNA damage and impairing the expression of DNA repair proteins RAD51 and DNA-PKcs, thereby silencing affected ERMS radioresistance. c-Myc sustains ERMS transformed phenotype and radioresistance by protecting cancer cells from radiation-induced apoptosis and DNA damage, while promoting radiation-induced DNA repair. This data suggest that c-Myc targeting can be tested as a promising treatment in cancer therapy.

Squamous cell carcinoma of the rectum: The treatment paradigm

PURPOSE This study was planned to clarify the optimal treatment for squamous cell carcinoma of the rectum, an histological entity extremely rare. METHODS Ten patients with histologically proven squamous cell carcinoma of the rectum were treated with concomitant radiochemotherapy. Radiation therapy was delivered with a 3Dconformational multiple field technique to a dose ranging from 45 to 76.5 Gy, with 6-15 MV energy photons. Chemotherapy consisted of an antimetabolite drug in association with mitomycin C or oxaliplatin. Overall survival and disease free survival were considered in months from the end of the concomitant treatment. RESULTS All patients completed programmed radiochemotherapy treatment but two patients were excluded to the analysis. Six patients (75%) presented negative biopsy 6 months after the end of radiochemotherapy. Seven patients (87.5%) showed a tumour regression after initial treatment. Only 1 patient underwent salvage surgery. Considering a mean follow-up of 41.75 months, 7 patients are still disease free survivors. Only 1 patient developed local recurrence at 6 months and he died 14 months after abdomino-perineal resection. CONCLUSION Primary radio chemotherapy, with a curative intent, could be considered the treatment modality of choice for squamous carcinoma of the rectum.

Metabolic atrophy and 3-T 1H-magnetic resonance spectroscopy correlation after radiation therapy for prostate cancer

To correlate 3‐T magnetic resonance spectroscopic imaging (MRSI) with prostate‐specific antigen (PSA) levels in patients with prostate cancer treated with external beam radiation therapy to assess the potential advantages of MRSI.

Osteoradionecrosis and intensity modulated radiation therapy: An overview

Osteoradionecrosis (ORN) is an ongoing topic, especially about its definition, pathogenesis, staging system and management algorithm. But what about its real incidence in intensity modulated radiotherapy (IMRT) era? This paper discusses the mandible in radiation therapy planning as organ at risk and reviews the literature for evidence of radiation damage, discussing likely dose constraints and the use of IMRT to reduce radiation dose to this structure. PubMed search was performed.

Chemoradiation as definitive treatment for primary squamous cell cancer of the rectum

In this report, we present a case of advanced squamous cell cancer located in the rectum of a 78-year-old woman treated with chemoradiation with curative intent. The patient showed a complete clinical response to chemoradiation; multiple biopsies were performed at the site of the previous mass 5 mo after the end of treatment and histological examination showed no residual tumour in the specimens. Surgical intervention was avoided and the patient was free of disease 12 mo after the diagnosis of cancer. Primary chemoradiation should be considered as the treatment of choice for this rare malignancy.