Portal-hypertension features are associated with ascites occurrence and survival in patients with hepatocellular carcinoma treated by external radiotherapy.

BACKGROUND AND AIMS: We studied the impact of Portal hypertension (PHT) on ascites occurrence and on radiotherapy outcome in cirrhotic patients with hepatocellular carcinoma (HCC). METHOD: All cirrhotic patients that received radiotherapy for HCC between 2012 and 2022 were included. Portal hypertension-Score was built using univariate analysis with the presence of esophageal varices (EV), platelet count, history of acute variceal bleeding (AVB) and spleen size. Time-to-events data were estimated using Kaplan-Meier method with log-rank and Cox-models. RESULTS: 60 patients were included (female 27%, age 67 years-old, Child-Pugh A 82%, alcoholic/non-alcoholic steatohepatitis/hepatitis C virus 55/40/32%). 38% and 15% presented history of ascites and AVB respectively, 25% had large EV, 53.5% presented PHT score ≥ 5. 92% were BCLC-0/A, median tumor size was 30 mm. At 6 months, ascites incidence was 19% and precluded access to further HCC treatment for all patients with HCC recurrence. All PHT parameters included in the score and PHT score ≥ 5 (hazard ratio (HR) = 14.07, p = 0.01) were associated with ascites occurrence. Transplantation free survival and recurrence free survival at 1 year were 56% and 47% respectively. Albi grade 3 (HR = 3.01; p = 0.04) was independently associated with Transplantation free survival. CONCLUSION: Radiotherapy should be cautiously performed in patients with PHT score ≥ 5 because of ascites occurrence risk precluding access to further HCC treatments.

Circulating microvesicles correlate with radiation proctitis complication after radiotherapy.

In a large retrospective study, we assessed the putative use of circulating microvesicles (MVs), as innovative biomarkers of radiation toxicity in a cohort of 208 patients with prostate adenocarcinoma overexposed to radiation. The level of platelet (P)-, monocyte (M)- and endothelial (E)-derived MVs were assessed by flow cytometry. Rectal bleeding toxicity scores were collected at the time of blood sampling and during the routine follow-up and were tested for association with MVs using a multivariate logistic regression. MVs dosimetric correlation was investigated using dose volume histograms information available for a subset of 36 patients. The number of PMVs was significantly increased in patients with highest toxicity grades compared to lower grades. Risk prediction analysis revealed that increased numbers of PMVs, and an increased amount of MMVs relative to EMVs, were associated with worst rectal bleeding grade compared to the time of blood sampling. Moreover, a significant correlation was found between PMV and MMV numbers, with the range of doses up to the median exposure (40 Gy) of bladder/rectum and anterior rectal wall, respectively. MVs could be considered as new biomarkers to improve the identification of patients with high toxicity grade and may be instrumental for the prognosis of radiation therapy complications.

The Safety and Efficacy of Salvage Stereotactic Radiation Therapy in Patients with Intraprostatic Tumor Recurrence After Previous External Radiation Therapy: Phase 1 Results from the GETUG-AFU 31 Study.

BACKGROUND: There is no consensus on the best local salvage treatment for prostate cancer recurrence after primary external beam radiotherapy. Prospective data on stereotactic body radiation therapy (SBRT) are very scarce. OBJECTIVE: To determine the optimal dose regimen for salvage SBRT. DESIGN, SETTING, AND PARTICIPANTS: The present report concerns the phase 1 part of the GETUG-AFU 31 multicenter open-label study. The main inclusion criteria were histologically proven biochemical recurrence, clinical stage T1-T2 upon relapse, multiparametric magnetic resonance imaging data, prostate-specific antigen (PSA) level ≤10 ng/ml prior to salvage SBRT, PSA doubling time >10 mo, and an International Prostate Symptom Score of ≤12. INTERVENTION: Five or six fractions of 6 Gy were delivered using focal SBRT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Dose-limiting toxicity (DLT) was defined as grade ≥3 gastrointestinal or genitourinary tract toxicity, or any grade 4 toxicity (according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03) occurring in the first 18 wk following treatment initiation. A time-to-event continual reassessment method was used to select the dose regimen. RESULTS AND LIMITATIONS: Twenty-one patients were treated (median [interquartile range] age: 76.8 yr [72.2-80.8]), including 12 at 6 × 6 dose level. No DLT was observed. The acute grade 2 genitourinary tract toxicity rate was 19%. With a median follow-up of 12.3 mo, the estimated cumulative incidence of late grade 2 genitourinary toxicity was 41.2% (95% confidence interval: 18.1-63.1%). No grade >2 genitourinary toxicity and no grade ≥2 gastrointestinal toxicity were reported. All treated patients were alive and relapse free at the last follow-up. CONCLUSIONS: A 6 × 6 Gy dose regimen was selected for our phase 2 study of salvage SBRT. With a short follow-up period, the level of toxicity appears to be acceptable. PATIENT SUMMARY: There is no consensus on the best local treatment for patients with local relapse after radiotherapy for prostate cancer. Prospective data are very scarce. Our early phase trial allowed us to recommend six fractions of 6 Gy using high-precision radiotherapy for further studies.

Mesenchymal stem cells limit vascular and epithelial damage and restore the impermeability of the urothelium in chronic radiation cystitis.

BACKGROUND: Cellular therapy seems to be an innovative therapeutic alternative for which mesenchymal stem cells (MSCs) have been shown to be effective for interstitial and hemorrhagic cystitis. However, the action of MSCs on chronic radiation cystitis (CRC) remains to be demonstrated. The aim of this study was to set up a rat model of CRC and to evaluate the efficacy of MSCs and their mode of action. METHODS: CRC was induced by single-dose localized irradiation of the whole bladder using two beams guided by tomography in female Sprague-Dawley rat. A dose range of 20-80 Gy with follow-up 3-12 months after irradiation was used to characterize the dose effect and the kinetics of radiation cystitis in rats. For the treatment, the dose of 40 Gy was retained, and in order to potentiate the effect of the MSCs, MSCs were isolated from adipose tissue. After expansion, they were injected intravenously during the pre-chronic phase. Three injections of 5 million MSCs were administered every fortnight. Follow-up was performed for 12 months after irradiation. RESULTS: We observed that the intensity and frequency of hematuria are proportional to the irradiation dose, with a threshold at 40 Gy and the appearance of bleeding from 100 days post-irradiation. The MSCs reduced vascular damage as well as damage to the bladder epithelium. CONCLUSIONS: These results are in favor of MSCs acting to limit progression of the chronic phase of radiation cystitis. MSC treatment may afford real hope for all patients suffering from chronic radiation cystitis resistant to conventional treatments.

Long-Term Outcomes in Head and Neck Paragangliomas Managed with Intensity-Modulated Radiotherapy.

OBJECTIVES: Head & Neck Paragangliomas have been historically relying on surgery mostly, with worsened quality of life and major sequelae. Conventional external radiation therapy seems to offer an equivalent control rate with a low toxicity profile. The aim of this study was to assess the safety and efficiency of intensity-modulated radiation therapy in Head & Neck paragangliomas. METHODS: This is a retrospective monocentric study conducted in a referral center, including all patients treated with IMRT, whether as an exclusive or post-operative treatment for a tympanic and jugular, carotid, or vagal paraganglioma. Data collection was performed through the manuscript and computerized medical files, including consultation, operative, imaging, pathological analyses, delineation, and treatment planning reports. Success was defined as the complete or partial regression or stabilization without progression, or relapse in accordance with the RECIST criteria. Acute toxicities and long-term sequelae were assessed. RESULTS: Our cohort included 39 patients included between 2011 and 2021: 18 patients treated for a TJ PG (45.9%), 11 patients for a carotid PG (28.4%), and 9 for a vagal PG (23.1%). Twenty-nine patients had IMRT as an exclusive treatment (74.4%), whereas 10 patients had a post-operative complementary treatment (25.6%). Median follow-up in our cohort was 2318 days (average = 2200 days, 237-5690, sd = 1281.9). Among 39 patients, 37 were successfully controlled with IMRT (94.8%), and the toxicity profile was low without any major toxicity. CONCLUSION: IMRT seems an ideal treatment, whether exclusive or post-operative for Head & Neck paragangliomas. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:607-614, 2023.

Molecular Mechanisms and Key Processes in Interstitial, Hemorrhagic and Radiation Cystitis.

Cystitis is a bladder disease with a high rate of prevalence in the world population. This report focuses on Interstitial Cystitis (IC), Hemorrhagic Cystitis (HC) and Chronic Radiation Cystitis. These pathologies have different etiologies, but they share common symptoms, for instance, pain, bleeding, and a contracted bladder. Overall, treatments are quite similar for abacterial cystitis, and include bladder epithelium protective or anti-inflammatory agents, alleviating pain and reducing bleeding. This review summarizes the mechanisms that the pathologies have in common, for instance, bladder dysfunction and inflammation. Conversely, some mechanisms have been described as present in only one pathology, such as neural regulation. Based on these specificities, we propose identifying a mechanism that could be common to all the above-mentioned pathologies.

Possible Primary Thyroid Nuclear Protein in Testis Carcinomas with NSD3::NUTM1 Translocation Revealed by RNA Sequencing: A Report of Two Cases.

Background: Nuclear protein in testis (NUT) carcinomas (NC) are a rare, highly aggressive, subset of squamous cell carcinomas, characterized by a translocation involving the NUTM1 gene. Thyroid location of NUT carcinomas has rarely been described. Methods: We report here two cases of thyroid NC with NSD3::NUTM1 translocation. Results: The first case presented as a very aggressive undifferentiated thyroid carcinoma in a 38-year-old man who died 21 months after the diagnosis. The second case was diagnosed after multiple lymphadenopathy recurrences mainly in the neck in a 37-year-old woman 7 years after total thyroidectomy for papillary thyroid carcinoma with a classic and a solid/trabecular component. Conclusions: Our case reports highlight the challenges in diagnosing these exceptional carcinomas. The therapeutic impact of the administration of pharmacological compounds with epigenetic action, in line with the physiopathology of these carcinomas, is also discussed.

Highly hypofractionated schedules for localized prostate cancer: Recommendations of the GETUG radiation oncology group.

Stereotactic body radiotherapy (SBRT) has become treatment option for localized prostate cancer but the evidence base remains incomplete. Several clinical studies, both prospective and retrospective, have been published. However, treatment techniques, target volumes and dose constraints lack consistency between studies. Based on the current available literature, the French Genito-Urinary Group (GETUG) suggests that.

Circulating tumor DNA: a help to guide therapeutic strategy in patients with borderline and locally advanced pancreatic adenocarcinoma?

BACKGROUND: prognostic biomarkers could be useful to better select patients with borderline resectable (BR) or locally advanced (LA) pancreatic adenocarcinoma (PA) for chemoradiotherapy (CRT) and/or secondary resection. AIMS: The main objective of this work was to study characteristics, received treatments and prognostic of patients with BR or LA PA according to their baseline circulating tumor DNA status and, for secondary objective, neutrophil-to-lymphocyte Ratio (NLR). METHODS: ctDNA status at baseline was determined using Next Generation Sequencing in a consecutive monocentric cohort of patients with a BR or LA PA. RESULTS: 69 patients were included, 31 with BR PA and 38 with LA PA. 14 (20.3%) patients had baseline positive ctDNA. Five (7.8%) patients had NLR> 5. Patients with positive ctDNA had 3.7 months shorter progression free survival (p = 0.006). Patients with positive ctDNA had earlier progression after the beginning of CRT (4.4 vs 7.1 months; p = 0.068) and shorter relapse free survival after secondary resection (9.2 vs 22.9 months; p = 0.016). CONCLUSIONS: positive ctDNA at baseline was associated with a worse prognosis in patients with BR or LA PA. These data are exploratory and must be confirmed in further prospective trials.

Understanding Molecular Mechanisms and Identifying Key Processes in Chronic Radiation Cystitis.

Chronic radiation cystitis (CRC) is a consequence of pelvic radiotherapy and affects 5-10% of patients. The pathology of CRC is without curative treatment and is characterized by incontinence, pelvic pain and hematuria, which severely degrades patients' quality of life. Current management strategies rely primarily on symptomatic measures and have certain limitations. Thanks to a better understanding of the pathophysiology of radiation cystitis, studies targeting key manifestations such as inflammation, neovascularization and cell atrophy have emerged and are promising avenues for future treatment. However, the mechanisms of CRC are still better described in animal models than in human models. Preclinical studies conducted to elucidate the pathophysiology of CRC use distinct models and are most often limited to specific processes, such as fibrosis, vascular damage and inflammation. This review presents a synthesis of experimental studies aimed at improving our understanding of the molecular mechanisms at play and identifying key processes in CRC.

Dosimetric study between a single isocenter dynamic conformal arc therapy technique and Gamma Knife radiosurgery for multiple brain metastases treatment: impact of target volume geometrical characteristics.

PURPOSE: To compare linac-based mono-isocentric radiosurgery with Brainlab Elements Multiple Brain Mets (MBM) SRS and the Gamma Knife using a specific statistical method and to analyze the dosimetric impact of the target volume geometric characteristics. A dose fall-off analysis allowed to evaluate the Gradient Index relevancy for the dose spillage characterization. MATERIAL AND METHODS: Treatments were planned on twenty patients with three to nine brain metastases with MBM 2.0 and GammaPlan 11.0. Ninety-five metastases ranging from 0.02 to 9.61 cc were included. Paddick Index (PI), Gradient Index (GI), dose fall-off, volume of healthy brain receiving more than 12 Gy (V12Gy) and DVH were used for the plan comparison according to target volume, major axis diameter and Sphericity Index (SI). The multivariate regression approach allowed to analyze the impact of each geometric characteristic keeping all the others unchanged. A parallel study was led to evaluate the impact of the isodose line (IDL) prescription on the MBM plan quality. RESULTS: For mono-isocentric linac-based radiosurgery, the IDL around 70-75% was the best compromise found. For both techniques, the GI and the dose fall-off decreased with the target volume. In comparison, PI was slightly improved with MBM for targets < 1 cc or SI > 0.78. GI was improved with GP for targets < 2.5 cc. The V12Gy was higher with MBM for lesions > 0.4 cc or SI < 0.84 and exceeded 10 cc for targets > 5 cc against 6.5 cc with GP. The presence of OAR close to the PTV had no impact on the dose fall off values. The dose fall-off was higher for volumes < 3.8 cc with GP which had the sharpest dose fall-off in the infero-superior direction up to 30%/mm. The mean beam-on time was 94 min with GP against 13 min with MBM. CONCLUSIONS: The dose fall-off and the V12Gy were more relevant indicators than the GI for the low dose spillage assessment. Both evaluated techniques have comparable plan qualities with a slightly improved selectivity with MBM for smaller lesions but with a healthy tissues sparing slightly favorable to GP at the expense of a considerably longer irradiation time. However, a higher healthy tissue exposure must be considered for large volumes in MBM plans.

YpN0 rectal cancer patients with sterilized lymph nodes after neoadjuvant chemoradiotherapy are of greater risk of recurrence.

BACKGROUND: Indication for adjuvant chemotherapy in ypN0 rectal cancer patients after chemoradiotherapy (CRT) is debated. The clinical significance of the presence of sterilized lymph nodes (LNS) in ypN0 patients remains to be determined. AIMS: To assess the prognostic value of LNS in ypN0 rectal cancers after neoadjuvant CRT. METHODS: From 2006-2016, 235 patients underwent TME surgery for non-metastatic mid-low rectal cancer after CRT. A lymph node was considered sterilized if there were signs of treatment response (fibrosis, necrosis or mucus) without residual tumor cells. RESULTS: 180 patients (77%) were classified ypN0 and 55 (23%) ypN+. LNS was present in 20 patients (9%). In ypN0 patients, 5-year OS was similar between patients with and without LNS. In contrast, 5-year DFS was significantly lower in ypN0/LNS + patients (58% vs. 78%, p = 0.043) and was similar to those staged ypN+. In multivariate analysis, two factors were independent predictors of DFS: mesorectal grading (OR = 3.14; 95%CI: 1.10-8.34; p = 0.033) and the presence of LNS (OR = 3.93, 95% CI: 1.06-11.81, p = 0.042) CONCLUSION: The presence of LNS in ypN0 rectal cancer after neoadjuvant CRT is associated with an increased risk of recurrence and may be taken into account for the discussion of adjuvant chemotherapy.

Mismatch Repair System Deficiency Is Associated With Response to Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer.

PURPOSE: Defective mismatch repair system (dMMR) has been shown to have a favorable impact on outcome in patients with colorectal cancer treated with surgery or immunotherapy, with adjuvant chemotherapy being discouraged unless there is nodal involvement. Its impact on radiosensitivity is unknown in patients with colorectal cancer. METHODS AND MATERIALS: Patients treated for locally advanced rectal cancer between 2000 and 2016 were studied. Reported points included age, sex, clinical and radiologic tumor stages at diagnosis, modalities of neoadjuvant treatment, posttreatment pathologic staging, tumor regression score, and local, distant relapse-free, and overall survival. An inverse probability of treatment weighting propensity score analysis was performed to evaluate the association of mismatch repair proficiency with surgical and clinical outcomes. RESULTS: Among the 296 patients included, 23 (7.8%) had dMMR. Median follow-up was 43.0 months (interquartile range, 27.9-66.7). Patients with dMMR were significantly younger than the others. After inverse probability of treatment weighting propensity score matching, dMMR patients had higher pathologic downstaging rate (P < .0001), higher tumor regression grade (P = .024), and a longer recurrence-free survival (P < .0001). CONCLUSIONS: dMRR was associated with significant tumor downstaging after neoadjuvant chemoradiation and with increased recurrence-free survival. dMMR patients may have more radiosensitive tumors.

10-Year Locoregional Control with Postoperative External Beam Radiotherapy in Patients with Locally Advanced High-Risk Non-Anaplastic Thyroid Carcinoma De Novo or at Relapse, a Propensity Score Analysis.

(1) Background: To assess the role of postoperative external beam radiotherapy (pEBRT) on locoregional failure (LRF) for patients with locally advanced high-risk non-anaplastic thyroid carcinoma (naTC) at primary event or relapse. (2) Methods: Between 1995 and 2015, postoperative naTC patients with a theoretical indication for EBRT were included based on criteria that were common to American-British-French current guidelines, i.e., pT3-4, pN+, gross or microscopic residual disease. Inverse probability of treatment weighting (IPTW) after multiple imputation was used to reduce selection biases. (3) Results: Of 254 naTC patients, 216 patients underwent pEBRT (106 de novo, 110 at relapse, median dose 60 Gy) and 38 underwent surgery only. pEBRT patients had more gross residual disease, a major prognostic factor (p = 0.027) but less perineural invasion (p = 0.008) or lymphovascular emboli (p = 0.009). pEBRT patients more frequently underwent radioiodine therapy (p = 0.026). The 10-year cumulative incidence of LRF was 56% (95% CI, 32-74%) in operated patients, and 23% (95% CI, 17-30%) in pEBRT patients. After IPTW method, pEBRT reduced the risk of LRF (hazard ratio 0.30; 95% CI [0.18-0.49], p < 0.001), but had no impact on OS. In the pEBRT group, non-Intensity Modulated RadioTherapy (IMRT) plans and interruption of the radiotherapy were associated with poorer survival, while extended versus limited field strategy and dose were not. (4) Conclusions: In naTC patients who have pT3-4, pN+ disease or R1-2 resection, pEBRT improved LRF. Limited-field IMRT is preferred.

Stereotactic Radiation Therapy for Renal Cell Carcinoma Brain Metastases in the Tyrosine Kinase Inhibitors Era: Outcomes of 120 Patients.

BACKGROUND: The objective of the study was to evaluate the outcomes in terms of efficacy and safety of a large consecutive series of 362 patients with renal cell carcinoma (RCC) brain metastases treated using stereotactic radiosurgery (SRS) in the tyrosine kinase inhibitor (TKI) era. PATIENTS AND METHODS: From 2005 to 2015, 362 consecutive patients with brain metastases from RCC were treated using SRS in 1 fraction: 226 metastases (61 patients) using Gamma-Knife at a median of 18 Gy (50% isodose line); 136 metastases (63 patients) using linear accelerator at a median of 16 Gy (70% isodose line). The median patient age was 58 years. At the first SRS, 37 patients (31%) received a systemic treatment. Among systemic therapies, TKIs were the most common (65%). RESULTS: The local control rates were 94% and 92% at 12 and 36 months, respectively. In multivariate analysis, a minimal dose >17 Gy and concomitant TKI treatment were associated with higher rates of local control. The overall survival rates at 12 and 36 months were 52% and 29%, respectively. In multivariate analysis, factors associated with poor survival included age ≥65 years, lower score index for SRS, concomitant lung metastases, time between RCC diagnosis and first systemic metastasis ≤4 months, occurrence during treatment with a systemic therapy, no history of neurosurgery, and persistence or occurrence of neurological symptoms at 3 months after SRS. Seventeen patients had Grade III/IV adverse effects of whom 3 patients presented a symptomatic radionecrosis. CONCLUSION: SRS is highly effective in patients with brain metastases from RCC. Its association with TKIs does not suggest higher risk of neurologic toxicity.

How Does Chemoradiotherapy Following Induction FOLFIRINOX Improve the Results in Resected Borderline or Locally Advanced Pancreatic Adenocarcinoma? An AGEO-FRENCH Multicentric Cohort.

BACKGROUND: Patients with borderline (BR) or locally advanced (LA) pancreatic adenocarcinoma (PAC) are often treated with induction FOLFIRINOX (FLX). However, the role of additional preoperative chemoradiotherapy (CRT) is controversial. The aim of this study is to evaluate its impact in patients who underwent resection after induction FLX. PATIENTS AND METHODS: Retrospective analysis of prospective consecutive surgical BR or LA PAC patients after induction FLX in 23 French centers between November 2010 and December 2015, treated with or without preoperative additional CRT (FLX vs FLX + CRT groups). RESULTS: Two hundred three patients were included (106 BR, 97 LA PAC). Median number of FLX cycles was 6 (range 1-30); 50% (n = 102) of patients received additional CRT. Median duration between diagnosis and surgery was 5.4 and 8.7 months (P = 0.001) in the FLX and FLX + CRT group, respectively. The 90-day mortality, major complications, and pancreatic fistula rates were 4.4%, 17.7%, and 5.4%, respectively. After 45.1 months follow-up, overall survival (OS) and disease-free survival were 45.4 months and 16.2 months, respectively. Patients with additional CRT had higher R0 resection rate (89.2% vs 76.3%; P = 0.017), ypN0 rate (76.2% vs 48.5%; P < 0.001), and higher rate of pathologic major response (33.3% vs 12.9%; P = 0.001). In the FLX + CRT group, patients had lower rate of locoregional relapse (28.3% vs 50.7%; P = 0.004). Patients with additional CRT had longer OS than those receiving FLX alone (57.8 vs 35.5 months; P = 0.007). CONCLUSIONS: Pathological results and survival data argue for interest in additional CRT. Prospective studies on an intention-to-treat basis are needed to confirm these results.

Laparoscopic uterine fixation to spare fertility before pelvic radiation therapy.

OBJECTIVE: To describe a surgical technique for laparoscopic uterine fixation (LUF) to decrease uterine radiation therapy side effects in case of rectal or anal cancer. DESIGN: This video article uses a surgical case to demonstrate the detailed technique. Institutional Review Board approval was not required for this video presentation. SETTING: University hospital. PATIENT(S): A 26-year-old nulliparous female patient diagnosed with rectal adenocarcinoma and liver metastases. After the completion of right hepatectomy and neoadjuvant chemotherapy with the use of the FOLFOX regimen, pelvic radiation therapy was applied before tumor excision. INTERVENTION(S): The patient underwent laparoscopic ovarian transposition. During the same intervention, we fixed the uterus with three late resorbable sutures into the fascia of the anterior abdominal wall as cranial as possible to remove the uterus away from the radiation field. MAIN OUTCOME MEASURE(S): Value and feasibility of LUF. RESULT(S): LUF was feasible and effective. Estimated isodoses demonstrated that this intervention may decrease uterine consequences of pelvic radiotherapy. The patient did not report any specific pain or complication in the postoperative period. Three months after the completion of pelvic concurrent chemoradiation therapy, the patient had normal menstrual periods. Hormonal blood tests were satisfactory. Ultrasound showed persistent ovarian function. CONCLUSION(S): Considering its simplicity of realization, LUF should be discussed for reproductive-age patients before undergoing pelvic radiotherapy for anal or rectal cancer. A close collaboration is required between surgeons and radiation oncologists to optimize the treatment and to decrease side-effects of radiotherapy. Intensity-modulated radiation therapy may contribute to enhance a multimodal fertility-sparing strategy in global management of young patients.

Absence of correlation between radiation-induced CD8 T-lymphocyte apoptosis and sequelae in patients with prostate cancer accidentally overexposed to radiation.

PURPOSE: 454 patients with prostate adenocarcinoma were accidentally overexposed to radiation in Epinal hospital, France, between August 1999 and January 2007. We aimed toevaluate whether radiation-induced CD4 or CD8 T-lymphocyte apoptosis (RILA) correlates with the severity of radiation toxicity. METHODS: Between 2007 and 2013, all patients who received more than 108% of the prescribed radiation dose, after correction of the treatment plan, were convened, and blood was sampled at 6-months follow-up. Maximal Digestive toxicity (MDT) and maximal urinary toxicity (MUT) were graded using the Common Terminology Criteria for Adverse Events (NCI-CTCAE) v3.0 scale. RILA was assessed using flow cytometry. RESULTS: 245 patients were included in our study. After a median follow-up of 4.8 years, the MDT and MUT reached grade 3-4 in 37 patients and 56 patients, respectively. Patients with prostatectomy exhibited a statistically higher grade of MUT compared with those treated with definitive radiotherapy (p=0.03). The median RILA values were 11.8% and 15.3% for CD4 and CD8 T-lymphocytes, respectively. We found no significant correlation between CD4 or CD8 RILA and either MDT or MUT. CONCLUSION: RILA does not correlate with the inter-individual variation in MDT or MUT in the largest cohort of patients overexposed to radiation. The magnitude of the overdosage probably overrides biological predictors of toxicity, including individual radiosensitivity.

Dynamic contrast-enhanced imaging in localizing local recurrence of prostate cancer after radiotherapy: Limited added value for readers of varying level of experience.

BACKGROUND: The incremental value of dynamic contrast-enhanced (DCE) imaging in localizing radiorecurrent prostate cancer is uncertain. PURPOSE: To assess the added-value of DCE imaging to the combination T2 -weighted imaging (T2 W)+diffusion-weighted imaging (DWI) in detecting locally radiorecurrent prostate cancer (PCa), by radiologists with different levels of experience. STUDY TYPE: Analytic retrospective study. POPULATION: In all, 52 men with biological suspected PCa recurrence after radiotherapy were retrospectively included. FIELD STRENGTH/SEQUENCE: All men underwent prostatic MRI (1.5T or 3T), including T2 W, DWI, and DCE imagings, before biopsies. ASSESSMENT: Two junior (6 months' experience) and two senior readers (more than 3 years' experience) independently assigned a Likert score for each prostatic sextant on T2 W+DW+DCE imagings, then on T2 W+DW imagings, 4 weeks later. STATISTICAL TESTS: The reference standard was prostatic biopsies. For two levels of positivity of Likert score, 3/5 and 4/5, sensitivity, specificity, area under the receiver operating curve (AUC), and interreader agreement were compared. RESULTS: T2 W+DWI+DCE and T2 W+DWI imaging had similar AUC at lobe and sextant level (0.853-0.946 vs. 0.819-0.955, P from 0.071-0.534). Using a Likert score ≥4/5, T2 W+DWI+DCE significantly improved the sensitivity for junior readers at the patient, lobe, and sextant level (40-80% vs. 22-66%, P < 0.0001-0.041). Sensitivity was not significantly modified with DCE imaging for senior readers (54-95% vs. 50-91%, P from 0.074-1). Specificity was not modified for all readers (50-100% vs. 50%-100%, P from 0.134-1). DCE imaging improved interreader agreement for a Likert score ≥4/5 (kappa from 0.6-0.73 vs. 0.38-0.73). DATA CONCLUSION: The addition of DCE imaging did not significantly improve accuracy in recurrent PCa detection after radiotherapy, whatever the level of experience of the readers. However, the addition of DCE imaging slightly improved the sensitivity for less-experienced readers and increased their diagnostic confidence. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1012-1023.