Stereotactic Body Reirradiation in Gynaecological Cancer: Outcomes and Toxicities from a Single Institution Experience.

AIMS: To report toxicity profile, outcomes and quality of life (QoL) data in patients with recurrent gynaecological cancer who underwent stereotactic body radiotherapy (SBRT) retreatment. MATERIALS AND METHODS: Data from patients' folders were retrospectively extracted, focusing on the primary neoplasm, previous systemic therapies and previous radiotherapy. Concerning SBRT, the total dose (five daily fractions) was delivered with a linear accelerator using intensity-modulated radiotherapy techniques. Acute and late toxicities were assessed by the CTCAE 4.03 scale. QoL was evaluated according to the Cancer Linear Analogue Scale [CLAS1 (fatigue), CLAS2 (energy level), CLAS3 (daily activities)]. RESULTS: Between December 2005 and August 2021, 23 patients (median age 71 years, range 48-80) with 27 lesions were treated. Most patients had endometrial (34.8%), ovarian (26.1%) and cervical cancer (26.1%) as the primary tumour. The most common SBRT schedules in five fractions were 30 Gy (33.3%), 35 Gy (29.6%) and 40 Gy (29.6%). The median follow-up was 32 months (range 3-128). There were no patients reporting acute or late toxicities higher than grade 2, except for a bone fracture. One- and 2-year local control was 77.9% and 70.8%, respectively. One- and 2-year overall survival was 82.6% and 75.1%, respectively. The overall response rate was 96.0%. Regarding QoL, no statistically significant difference was identified between the baseline and follow-up values: the median CLAS1, CLAS2 and CLAS3 scores for each category were 6 (range 4-10) at baseline and 6 (range 3-10) 1 month after SBRT. CONCLUSIONS: This preliminary experience suggests that SBRT retreatment for recurrent gynaecological cancer is a highly feasible and safe treatment with limited side-effects and no short-term QoL impairment.

MRI-derived radiomics to guide post-operative management of glioblastoma: Implication for personalized radiation treatment volume delineation.

Background: The glioblastoma's bad prognosis is primarily due to intra-tumor heterogeneity, demonstrated from several studies that collected molecular biology, cytogenetic data and more recently radiomic features for a better prognostic stratification. The GLIFA project (GLIoblastoma Feature Analysis) is a multicentric project planned to investigate the role of radiomic analysis in GB management, to verify if radiomic features in the tissue around the resection cavity may guide the radiation target volume delineation. Materials and methods: We retrospectively analyze from three centers radiomic features extracted from 90 patients with total or near total resection, who completed the standard adjuvant treatment and for whom we had post-operative images available for features extraction. The Manual segmentation was performed on post gadolinium T1w MRI sequence by 2 radiation oncologists and reviewed by a neuroradiologist, both with at least 10 years of experience. The Regions of interest (ROI) considered for the analysis were: the surgical cavity ± post-surgical residual mass (CTV_cavity); the CTV a margin of 1.5 cm added to CTV_cavity and the volume resulting from subtracting the CTV_cavity from the CTV was defined as CTV_Ring. Radiomic analysis and modeling were conducted in RStudio. Z-score normalization was applied to each radiomic feature. A radiomic model was generated using features extracted from the Ring to perform a binary classification and predict the PFS at 6 months. A 3-fold cross-validation repeated five times was implemented for internal validation of the model. Results: Two-hundred and seventy ROIs were contoured. The proposed radiomic model was given by the best fitting logistic regression model, and included the following 3 features: F_cm_merged.contrast, F_cm_merged.info.corr.2, F_rlm_merged.rlnu. A good agreement between model predicted probabilities and observed outcome probabilities was obtained (p-value of 0.49 by Hosmer and Lemeshow statistical test). The ROC curve of the model reported an AUC of 0.78 (95% CI: 0.68-0.88). Conclusion: This is the first hypothesis-generating study which applies a radiomic analysis focusing on healthy tissue ring around the surgical cavity on post-operative MRI. This study provides a preliminary model for a decision support tool for a customization of the radiation target volume in GB patients in order to achieve a margin reduction strategy.

Project for interventional Oncology LArge-database in liveR Hepatocellular carcinoma - Preliminary CT-based radiomic analysis (POLAR Liver 1.1).

OBJECTIVE: The objective of this study is to find a contrast-enhanced CT-radiomic signature to predict clinical incomplete response in patients affected by hepatocellular carcinoma who underwent locoregional treatments. PATIENTS AND METHODS: 190 patients affected by hepatocellular carcinoma treated using focal therapies (radiofrequency or microwave ablation) from September 2018 to October 2020 were retrospectively enrolled. Treatment response was evaluated on a per-target-nodule basis on the 6-months follow-up contrast-enhanced CT or MR imaging using the mRECIST criteria. Radiomics analysis was performed using an in-house developed open-source R library. Wilcoxon-Mann-Whitney test was applied for univariate analysis; features with a p-value lower than 0.05 were selected. Pearson correlation was applied to discard highly correlated features (cut-off=0.9). The remaining features were included in a logistic regression model and receiver operating characteristic curves; sensitivity, specificity, positive and negative predictive value were also computed. The model was validated performing 2000 bootstrap resampling. RESULTS: 56 treated lesions from 42 patients were selected. Treatment responses were: complete response for 26 lesions (46.4%), 18 partial responses (32.1%), 10 stable diseases (17.9%), 2 progression diseases (3.6%). Area-Under-Curve value was 0.667 (95% CI: 0.527-0.806); accuracy, sensitivity, specificity, positive and negative predictive values were respectively 0.66, 0.85, 0.50, 0.59 and 0.79. CONCLUSIONS: This contrast-enhanced CT-based model can be helpful to early identify poor responder's hepatocellular carcinoma patients and personalize treatments.

Developing and validating ultrasound-based radiomics models for predicting high-risk endometrial cancer.

OBJECTIVES: The primary aim of this study was to develop and validate radiomics models, applied to ultrasound images, capable of differentiating from other cancers high-risk endometrial cancer, as defined jointly by the European Society for Medical Oncology, European Society of Gynaecological Oncology and European Society for Radiotherapy & Oncology (ESMO-ESGO-ESTRO) in 2016. The secondary aim was to develop and validate radiomics models for differentiating low-risk endometrial cancer from other endometrial cancers. METHODS: This was a multicenter, retrospective, observational study. From two participating centers, we identified consecutive patients with histologically confirmed diagnosis of endometrial cancer who had undergone preoperative ultrasound examination by an experienced examiner between 2016 and 2019. Patients recruited in Center 1 (Rome) were included as the training set and patients enrolled in Center 2 (Milan) formed the external validation set. Radiomics analysis (extraction of a high number of quantitative features from medical images) was applied to the ultrasound images. Clinical (including preoperative biopsy), ultrasound and radiomics features that were statistically significantly different in the high-risk group vs the other groups and in the low-risk group vs the other groups on univariate analysis in the training set were considered for multivariate analysis and for developing ultrasound-based machine-learning risk-prediction models. For discriminating between the high-risk group and the other groups, a random forest model from the radiomics features (radiomics model), a binary logistic regression model from clinical and ultrasound features (clinical-ultrasound model) and another binary logistic regression model from clinical, ultrasound and previously selected radiomics features (mixed model) were created. Similar models were created for discriminating between the low-risk group and the other groups. The models developed in the training set were tested in the validation set. The performance of the models in discriminating between the high-risk group and the other groups, and between the low-risk group and the other risk groups for both validation and training sets was compared. RESULTS: The training set comprised 396 patients and the validation set 102 patients. In the validation set, for predicting high-risk endometrial cancer, the radiomics model had an area under the receiver-operating-characteristics curve (AUC) of 0.80, sensitivity of 58.7% and specificity of 85.7% (using the optimal risk cut-off of 0.41); the clinical-ultrasound model had an AUC of 0.90, sensitivity of 80.4% and specificity of 83.9% (using the optimal cut-off of 0.32); and the mixed model had an AUC of 0.88, sensitivity of 67.3% and specificity of 91.0% (using the optimal cut-off of 0.42). For the prediction of low-risk endometrial cancer, the radiomics model had an AUC of 0.71, sensitivity of 65.0% and specificity of 64.5% (using the optimal cut-off of 0.38); the clinical-ultrasound model had an AUC of 0.85, sensitivity of 70.0% and specificity of 80.6% (using the optimal cut-off of 0.46); and the mixed model had an AUC of 0.85, sensitivity of 87.5% and specificity of 72.5% (using the optimal cut-off of 0.36). CONCLUSIONS: Radiomics seems to have some ability to discriminate between low-risk endometrial cancer and other endometrial cancers and better ability to discriminate between high-risk endometrial cancer and other endometrial cancers. However, the addition of radiomics features to the clinical-ultrasound models did not result in any notable increase in performance. Other efficacy studies and further effectiveness studies are needed to validate the performance of the models. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

The role of radiotherapy in Kimura's disease: a multicenter systematic review of literature.

OBJECTIVE: From a clinical point of view, Kimura's disease is typically characterized by a subcutaneous mass occurring predominantly in the head and neck region. It occurs predominantly in young men of Asian descent, with a peak incidence in the second and third decades of life. However, KD has been also reported in other ethnic groups and in children. The most frequently used local treatments are surgical excision, radiotherapy, and surgical excision followed by radiotherapy. The aim of this multicenter systematic review is to highlight the available literature evidence about the outcome of RT in this setting. MATERIALS AND METHODS: A systematic review of any relevant literature in the principal medical databases, such as PubMed, Scopus and Cochrane library, was conducted. The inclusion criteria were original articles specifically reporting about KD and RT, including both prospective and retrospective studies. RESULTS: We were able to identify 11 studies, published from 1989 to 2021, eligible for inclusion in this review. Overall, data on 124 patients were recorded and are presented in this systematic review. The median recurrence rate, considering all patients, was 11% (ranging from 0% to 41.2%). In seven out of 11 studies, the relapse rate was less than 20%. Moreover, the relapse rate was 0% in four studies. CONCLUSIONS: The results of this multicenter systematic literature review show that evidence on RT of KD is limited and derives only from retrospective studies. In this setting RT seems to be well-tolerated and able to produce very high response rates in unresected lesions and reasonable results in terms of local control both as an exclusive and adjuvant treatment.

Radiotherapy for benign disorders: current use in clinical practice.

OBJECTIVE: The aim of this paper is to provide an update about the current clinical indications of RT in this poorly explored field outside the traditional oncological setting. MATERIALS AND METHODS: We performed a literature search on the main databases, including PubMed, Scopus and Cochrane from their inception until 31st December 2020. An additional manual check of scientific meeting proceedings and books was conducted in order to identify all the potentially useful sources. Only essays published in English have been considered for the purposes of this analysis. The searched items included: "Radiotherapy or Radiation Therapy" and "Benign disorder or Benign disease". RESULTS: We provided a list of current clinical indications for benign disorders based on the latest international surveys available, including major sites: eye, bone, head and neck, skin, brain, heart and peripheral vascular system. CONCLUSIONS: Radiotherapy for benign diseases is still a feasible therapeutic strategy, which may allow to treat several invalidating conditions, especially after medical therapies have failed thus avoiding potentially invalidating major surgical procedures. A careful evaluation in selecting the indication is essential and all the choices should be thoroughly discussed with the patients.

The role of brachytherapy (interventional radiotherapy) for primary and/or recurrent vulvar cancer: a Gemelli Vul.Can multidisciplinary team systematic review.

OBJECTIVE: The aim of our systematic review was to assess the role of interventional radiotherapy (IRT, brachytherapy) in the management of primary and/or recurrent vulvar carcinoma. EVIDENCE ACQUISITION: A systematic research using PubMed, Scopus and Cochrane library was performed. ClinicalTrials.gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. Only full-text English-language articles related to IRT for treatment of primary or recurrent VC were identified and reviewed. Conference paper, survey, letter, editorial, book chapter and review were excluded. Time restriction (1990-2018) as concerns the years of the publication was considered. EVIDENCE SYNTHESIS: Primary disease: the median 5-year LC was 43.5% (range 19-68%); the median 5-year DFS was 44.5% (range 44-81%); the median 5-year OS was 50.5% (range 27-85%). Recurrent disease: the median 5-year DFS was 64% (range 56-72%) and the median 5-year OS was 45% (range 33%-57%). Acute ≥ grade 2 toxicity was reported in three patients (1.6%). The severe late toxicity rates (grade 3-4) ranged from 0% to 14.3% (median 7.7%). CONCLUSION: IRT as part of primary treatment for primary and/or recurrent vulvar cancer is associated with promising clinical outcomes.

Preoperative chemoradiotherapy affects postoperative outcomes and functional results in patients treated with transanal endoscopic microsurgery for rectal neoplasms.

BACKGROUND: The aim of this study was to quantify the incidence of short-term postoperative complications and functional disorders at 1 year from transanal endoscopic microsurgery (TEM) for rectal neoplasms, to compare patients treated with TEM alone and with TEM after preoperative chemoradiotherapy (CRT) and to analyse factors influencing postoperative morbidity and functional outcomes. METHODS: A retrospective study was conducted on all patients treated with TEM for rectal neoplasms at our institution in January 2000-December 2017. Data from a prospectively maintained database were retrospectively analysed. Patients were divided into two groups: adenoma or early rectal cancer (no CRT group) and locally advanced extraperitoneal rectal cancer with major or complete clinical response after preoperative CRT (CRT group). Short-term postoperative mortality and morbidity and the functional results at 1 year were recorded. The two groups were compared, and a statistical analysis of factors influencing postoperative morbidity and functional outcomes was performed. Functional outcome was also evaluated with the low anterior resection syndrome (LARS) score (0-20 no LARS, 21-29 minor LARS and 30-42 major LARS). RESULTS: One hundred and thirteen patients (71 males, 42 females, median age 64 years [range 41-80 years]) were included in the study (46 in the CRT group). The overall postoperative complication rate was 23.0%, lower in the noCRT group (p < 0.001), but only 2.7% were grade ≥ 3. The most frequent complication was suture dehiscence (17.6%), which occurred less frequently in the noCRT group (p < 0.001). At 1 year from TEM, the most frequent symptoms was urgency (11.9%, without significant differences between the CRT group and the noCRT group); the noCRT group experienced a lower rate of soiling than the CRT group (0% vs. 7.7%; p: 0.027). The incidence of LARS was evaluated in 47 patients from May 2012 on and was 21.3% occurring less frequently in the noCRT group (10% vs. 41.2%; p: 0.012). Only 6.4% of the patients evaluated experienced major LARS. In multivariate analysis, preoperative CRT significantly worsened postoperative morbidity and functional outcomes. CONCLUSIONS: TEM is a safe procedure associated with only low risk of severe postoperative complications and major LARS. Preoperative CRT seems to increase the rate of postoperative morbidity after TEM and led to worse functional outcomes at 1 year after surgery.

The role of interventional radiotherapy (brachytherapy) in stage I esophageal cancer: an AIRO (Italian Association of Radiotherapy and Clinical Oncology) systematic review.

OBJECTIVE: This review aimed at examining efficacy of interventional radiotherapy (brachytherapy-IRT) alone or combined with external beam radiotherapy (EBRT) in stage I esophageal cancer as exclusive treatment. MATERIALS AND METHODS: A systematic research using PubMed, Scopus, and Cochrane library was performed. ClinicalTrials.gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. We analyzed only clinical study as full-text publication, reporting on patients with stage I esophageal cancer treated with IRT alone or in combination with other treatments (e.g., EBRT). Conference paper, survey, letter, editorial, book chapter, and review were excluded. Patients who underwent previous surgery were excluded. Time restriction (1990-2018) was applied for years of the publication. RESULTS: Twelve studies have been selected. The number of evaluated patients was 514; the median age was 69 years. In the IRT group, the median: local control (LC) was 77% (range 63%-100%), disease-free survival (DFS) was 68.4% (range 49%-86.3%), the overall survival (OS) was 60% (range 31%-84%), the cancer specific survival (CSS) was 80% (range 55-100%), and grade 3-4 toxicity range was 0%-26%. CONCLUSIONS: IRT alone or combined to EBRT is an effective and safe treatment option for patients with stage I esophageal cancer. Definitive radiation therapy could be an alternative to surgery in patients with superficial cancer.

Radiation therapy technologists' involvement and opinion in research: A national survey in Italy.

INTRODUCTION: This survey describes Italian RTTs' involvement and opinions in research activities related to radiation oncology. Primary aim was to assess the degree of involvement of the national RTTs community in research and to describe how RTTs can integrate their skills collaborating with other professionals. MATERIALS AND METHODS: A ten-items multiple-choice questionnaire, with 2-8 possible responses, was developed by a steering committee and generated on a survey platform. Links were sent via email to Italian RTTs.The questions were divided in 3 domains: demographic data; scientific research and activity; opinions about RTTs role in scientific research. The survey started on October 1, 2018 and ended on January 31, 2019. RESULTS: One hundred thirty-five out of 509 (26.5%) RTTs responded to the questionnaire at its expiring date; 97.73% think to be valid contributors in radiation oncology research, expressing clear interest in "data collection" tasks (52.71%); 38.64% feel unsupported by other professionals in the research team and 59.85% of the respondents are not members in any scientific society. CONCLUSIONS: The role of Italian RTTs in research is heterogeneous. Mainly RTTs in the age range from 30 to 40 years responded to the survey showing their interest in scientific research. This might be related to different informatics and educational skills as well as to personal attitudes. RTTs particular skills, like data management and technical hypothesis generation abilities, are of benefit to realize research projects. Therefore, engaging RTTs in research activities is strongly suggested.

DW-MRI predictive factors for radiation-induced vaginal stenosis in patients with cervical cancer.

AIM: To find diffusion-weighted (DW) magnetic resonance imaging (MRI) parameters predictive for radiation-induced vaginal stenosis (VS) in locally advanced cervical cancer (LACC) treated with neoadjuvant chemoradiation therapy (CRT). MATERIALS AND METHODS: Retrospective analysis of 43 patients with LACC who underwent 1.5 T DW-MRI before (baseline), after 2 weeks (early), and at the end of CRT (final). At MRI, vaginal length, thickness, width, and cervical tumour volume (TV) were measured. Vaginal signal intensity at DW-MRI was analysed at final MRI. CRT-induced VS was graded using Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Correlations between DW-MRI and clinical data were made using Wilcoxon's test, Mann-Whitney test, Fisher's exact test, or chi-squared test as appropriate. Receiver operating characteristic (ROC) curves were generated for variables to evaluate diagnostic ability to predict CRT-induced VS using a logistic regression model. RESULTS: Asymptomatic vaginal toxicity (CTCAE Grade 1) was observed in 14 patients and symptomatic CRT-induced VS (CTCAE Grade ≥2) was detected in 29 patients. Baseline TV was higher in Grade 1 than in Grade ≥2 (p=0.013). Median vaginal length, thickness, and width decreased between baseline and final MRI in all patients (p<0.0001) without significant variances between CTCAE grades. Significant differences were observed in DW-MRI patterns (p<0.0001). In Grade ≥2, DWI showed signal loss of vaginal mucosa in 17 patients (63%) and diffuse restricted diffusion of vaginal wall in eight patients (30%). AUC was 0.938 (coefficient=4.72; p<0.001) for DWI and 0.712 (coefficient=-2.623×10 -5; p=0.004) for TV. CONCLUSIONS: This is the first study using DW-MRI for predicting CRT-induced VS. DWI is useful tool in patients with LACC after CRT for early prevention and management strategies for VS.

Hybrid MRI guided radiotherapy in locally advanced cervical cancer: Case report of an innovative personalized therapeutic approach.

•The case report of a patient affected by locally advanced cervical MRgRT is described.•MRgRT appears to be feasible for cervical cancer and may improve treatment quality.•MRgRT insights are discussed focusing on adaptive response and toxicity monitoring.

Fertility preservation in chemo-radiotherapy for rectal cancer: A combined approach.

INTRODUCTION: Colorectal cancer is a very common form of cancer worldwide, affecting an increasing number of young women. Standard treatment for locally advanced rectal cancer (LARC) can pose a threat to fertility in these patients. CASE PRESENTATION: We present the case of a young woman affected by LARC who expressed a desire for child-bearing. The treatment she was proposed, according to guidelines, was neoadjuvant chemo-radiotherapy (CRT) followed by delayed surgery, carrying with it a high risk for amenorrhea. Counselling was performed before the initiation of treatment, with the aim of preserving fertility by the proposal of GnRH agonist administration, ovarian transposition and ovarian tissue cryopreservation, which the patient accepted. Treatment was then successfully completed. The patient presented regular menstrual period from before the surgery. DISCUSSION: Ovarian tissue is very sensitive to radiations. Transposition of the organ can prevent ovarian insufficiency by placing it outside the radiation field, while ovarian tissue cryopreservation and orthotopic transplantation offers the possibility to restore fertility in the case of organ failure. We performed both of the techniques. GnRH analogs administration allowed to diminish the risk of ovarian cytotoxicity. Radiation treatment plan was optimized in order to minimize the dose to organs at risk (ovary and vagina in particular); position of the uterus, which is quite radiosensitive too, was monitored with daily cone-beam CT (CBCT). CONCLUSION: The strategy proposed seemed safe and effective, resulting in radical treatment and persistence of regular menstrual period. Further studies are needed.

Prospective multimodal imaging assessment of locally advanced cervical cancer patients administered by chemoradiation followed by radical surgery-the "PRICE" study 2: role of conventional and DW-MRI.

OBJECTIVES: To assess the diagnostic performance of conventional and DW-MRI parameters in the detection of residual tumor in locally advanced cervical cancer (LACC) patients treated with neoadjuvant chemoradiotherapy (nCRT) and radical surgery METHODS: Between October 2010 and June 2014, 88 patients with histologically documented cervical cancer (FIGO stage IB2-IVA) were prospectively included in the study. Maximum tumor diameters (maxTD), tumor volume (TV), DWI signal intensity (SI), and ADCmean were evaluated at MRI after nCRT. Histology was the reference standard. Treatment response was classified as complete (CR) or partial (PR). Comparisons were made with Mann-Whitney, χ2, and Fisher's exact tests. ROC curves were generated for variables to evaluate diagnostic ability to predict PR and to determine the best cutoff value to predict PR. For each diagnostic test, sensitivity, specificity, and accuracy were calculated. RESULTS: TV and maxTD were significantly smaller in the CR than in the PR group (p < 0.001; p = 0.001) and showed, respectively, sensitivity of 68.8%, specificity of 72.5%, and accuracy of 70.5% and of 47.9, 87.5, and 65.9% in predicting PR. High DWI SI was more frequent in the PR (81.8%) than in the CR group (55.3%) (p < 0.009). ADCmean was higher in the CR (1.3 × 10-3 mm2/s, range 0.8-1.6 × 10-3 mm2/s) than in the PR group (1.1 × 10-3 mm2/s; range 0.7-1.8 × 10-3 mm2/s) (p < 0.018). High DWI SI showed sensitivity, specificity, and accuracy of 81.8, 44.7, and 64.6% in predicting PR. The ADCmean measurement increased sensitivity, specificity, and accuracy to 75.0, 76.2, and 75.4%. CONCLUSIONS: Conventional and DW-MRI is useful for predicting PR after nCRT in LACC. The ADCmean value ≤ 1.1 × 10-3 mm2/s was the best cutoff to predict PR. KEY POINTS: • Conventional and DW-MRI is useful for predicting PR after nCRT in LACC. • The combination of T2 sequences, DW-MRI, and the quantitative measurement of ADC mean showed the best results in predicting pathological PR. • The best cutoff for predicting pathological PR was ADCmeanvalue ≤ 1.1 × 10-3 mm2/s.

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.

The PRICE study: The role of conventional and diffusion-weighted magnetic resonance imaging in assessment of locally advanced cervical cancer patients administered by chemoradiation followed by radical surgery.

OBJECTIVES: To analyse the role of DW-MRI in early prediction of pathologically-assessed residual disease in locally-advanced cervical cancer (LACC) treated with neoadjuvant chemoradiotherapy followed by radical surgery. METHODS: Between October 2010-June 2014, 108 women with histologically-proven cervical cancer were screened; 88 were included in this study. Tumour volume (TV) and ADCmean were measured before (baseline-MRI) and after 2 weeks of chemoradiotherapy (early-MRI). According to histopathology, treatment response was classified as complete (CR) or partial (PR). Comparisons were made with Mann-Whitney, Wilcoxon and χ2 tests. ROC curves were generated for statistically significant parameters on univariate analysis. RESULTS: CR and PR were documented in 40 and 48 patients. At baseline-MRI, TV did not differ between groups. At early-MRI, TV was higher in PR than in CR (p=0.001). ΔTV reduction after treatment was lower in PR than in CR (63.6% vs. 81.1%; p=0.001). At baseline-MRI and early-MRI, ADCmean did not differ between PR and CR. ROC curve showed best cut-off for predicting pathological PR was ΔTV reduction of 73% with sensitivity, specificity, accuracy, NPV, PPV of 73%, 72.5%, 72.7%, 76%, 69%. CONCLUSIONS: TV evaluated before and early after treatment could predict pathological response in LACC. ADCmean did not correlate with treatment outcome. KEY POINTS: • Early-MRI tumour volume assessment could predict pathological response to nCRT in LACC. • Best cut-off for predicting pathological PR was ΔTV reduction of 73 %. • Early-MRI ADC mean measurements did not correlate with treatment outcome.

PRospective Imaging of CErvical cancer and neoadjuvant treatment (PRICE) study: role of ultrasound to predict partial response in locally advanced cervical cancer patients undergoing chemoradiation and radical surgery.

OBJECTIVE: Chemoradiation-based neoadjuvant treatment followed by radical surgery is an alternative therapeutic strategy for locally advanced cervical cancer (LACC), but ultrasound variables used to predict partial response to neoadjuvant treatment are not well defined. Our goal was to analyze prospectively the potential role of transvaginal ultrasound in early prediction of partial pathological response, assessed in terms of residual disease at histology, in a large, single-institution series of LACC patients triaged to neoadjuvant treatment followed by radical surgery. METHODS: Between October 2010 and June 2014, we screened 108 women with histologically documented LACC Stage IB2-IVA, of whom 88 were included in the final analysis. Tumor volume, three-dimensional (3D) power Doppler indices and contrast parameters were obtained before (baseline examination) and after 2 weeks of treatment. The pathological response was defined as complete (absence of any residual tumor after treatment) or partial (microscopic and/or macroscopic residual tumor at pathological examination). Complete-response and partial-response groups were compared and receiver-operating characteristics (ROC) curves were generated for ultrasound variables that were statistically significant on univariate analysis to evaluate their diagnostic ability to predict partial pathological response. RESULTS: There was a complete pathological response to neoadjuvant therapy in 40 (45.5%) patients and a partial response in 48 (54.5%). At baseline examination, tumor volume did not differ between the two groups. However, after 2 weeks of neoadjuvant treatment, the tumor volume was significantly greater in patients with partial response than it was in those with complete response (P = 0.019). Among the 3D vascular indices, the vascularization index (VI) was significantly lower in the partial-response compared with the complete-response group, both before and after 2 weeks of treatment (P = 0.037 and P = 0.024, respectively). At baseline examination in the contrast analysis, women with partial response had lower tumor peak enhancement (PE) as well as lower tumor wash-in rate (WiR) and longer tumor rise time (RT) compared with complete responders (P = 0.006, P = 0.003, P = 0.038, respectively). There was no difference in terms of contrast parameters after 2 weeks of treatment. ROC-curve analysis of baseline parameters showed that the best cut-offs for predicting partial pathological response were 41.5% for VI (sensitivity, 63.6%; specificity, 66.7%); 16123.5 auxiliary units for tumor PE (sensitivity, 47.9%; specificity, 84.2%); 7.8 s for tumor RT (sensitivity, 68.8%; specificity, 57.9%); and 4902 for tumor WiR (sensitivity, 77.1%; specificity, 60.5%). ROC curves of parameters after 2 weeks of treatment showed that the best cut-off for predicting partial pathological response was 18.1 cm3 for tumor volume (sensitivity, 70.8%; specificity 60.0%) and 39.5% for VI (sensitivity; 62.5%; specificity, 73.5%). CONCLUSIONS: Ultrasound and contrast parameters differ between LACC patients with complete response and those with partial response before and after 2 weeks of neoadjuvant treatment. However, neither ultrasound parameters before treatment nor those after 2 weeks of treatment had cut-off values with acceptable sensitivity and specificity for predicting partial pathological response to neoadjuvant therapy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Transanal endoscopic microsurgery after neoadjuvant radiochemotherapy for locally advanced extraperitoneal rectal cancer.

PURPOSE: The aim of this study is to provide a prospective analysis of post-operative and oncological outcomes in patients affected by locally advanced rectal cancer (LARC), who obtained a major/complete clinical response after pre-operative radio-chemotherapy (RCT) and were treated with local excision (LE) by trans-anal endoscopic microsurgery (TEM) to confirm a pathological complete response (pCR) after to neo-adjuvant RCT. METHODS: All patients with LARC treated by pre-operative RCT and full-thickness LE by TEM (2000-2014) were included in the study. If the pathological analysis confirmed near complete or pCR, intensive follow up was proposed. If the pathological response was incomplete, a radical resection with TME was proposed. Post-operative (according to Clavien's classification), functional and long-term oncological outcome were analyzed. RESULTS: 36 patients were treated by TEM. The median post-operative hospital stay was 5 days. The post-operative morbidity was 41.6% (no grade ≥3). At pathological analysis, 23 specimens were ypT0 TRG1, and 4 were ypT1 TRG2. In 9 cases (ypT>1 and/or TRG>2), radical surgery with TME was proposed but 3 refused it. Median follow-up was 68 months. One local recurrence and 4 distant metastases occurred. The 5-yr actuarial local control, overall survival and disease-free survival were 96.0%, 92.0% and 82.8%. CONCLUSIONS: In case of major or complete clinical response of LARC after pre-operative RCT, LE by TEM can be used to confirm the pathological response. This avoids the necessity of radical surgery and, in our experience, this approach seems to guarantee oncological safety with the functional advantages of an organ-sparing procedure.