In-house Implementation of Tumor Mutational Burden Testing to Predict Durable Clinical Benefit in Non-small Cell Lung Cancer and Melanoma Patients.

Tumor mutational burden (TMB) has emerged as an important potential biomarker for prediction of response to immune-checkpoint inhibitors (ICIs), notably in non-small cell lung cancer (NSCLC). However, its in-house assessment in routine clinical practice is currently challenging and validation is urgently needed. We have analyzed sixty NSCLC and thirty-six melanoma patients with ICI treatment, using the FoundationOne test (FO) in addition to in-house testing using the Oncomine TML (OTML) panel and evaluated the durable clinical benefit (DCB), defined by >6 months without progressive disease. Comparison of TMB values obtained by both tests demonstrated a high correlation in NSCLC (R2 = 0.73) and melanoma (R2 = 0.94). The association of TMB with DCB was comparable between OTML (area-under the curve (AUC) = 0.67) and FO (AUC = 0.71) in NSCLC. Median TMB was higher in the DCB cohort and progression-free survival (PFS) was prolonged in patients with high TMB (OTML HR = 0.35; FO HR = 0.45). In contrast, we detected no differences in PFS and median TMB in our melanoma cohort. Combining TMB with PD-L1 and CD8-expression by immunohistochemistry improved the predictive value. We conclude that in our cohort both approaches are equally able to assess TMB and to predict DCB in NSCLC.

Magnetic resonance hysterosalpingography in diagnostic work-up of female infertility - comparison with conventional hysterosalpingography: a randomised study.

OBJECTIVE: To compare diagnostic accuracy of MR-hysterosalpingography (MR-HSG) and conventional hysterosalpingography (X-HSG) in the evaluation of female infertility. METHODS: Forty women received prospectively both X-HSG, the gold standard technique, and MR-HSG on the same day but the order in which they were conducted was randomised. A 1.5 Tesla MRI was performed with classical sequences for pelvic analysis and an additional 3D T1-weighted sequence with intra-uterine injection of gadolinium. Two radiologists independently interpreted X-HSG and MR-HSG according to randomisation, blinded to the other results. They both then performed a second interpretation of MR-HSG blinded to the first reading with a minimum time delay of 1 week. Diagnostic performance of MR-HSG for analysis of tubal and intracavity abnormalities was evaluated by calculating sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV). RESULTS: Twenty-six patients were included. Diagnostic performance of MR-HSG was: Se: 91.7% (95% CI 61.5-99.8); Sp: 92.9% (95% CI 66.1-99.8) ; PPV: 91.7% (95% CI 61.5-99.8); NPV: 92.9% (95% CI 66.1-99.8). Pain analysis showed a significant statistical difference between the two procedures: average VAS for X-HSG was 4.43 (95% CI 3.50-5.36) versus 3.46 (95% CI 2.62-4.31) for MR-HSG, p=0,01. Intra- and inter-rater agreements for detection of tubal or intracavity abnormalities were 0.92 (95% CI 0.78-1.00) and 0.76 (95% CI 0.52-1.00). CONCLUSION: MR-HSG is a well-tolerated technique demonstrating high accuracy in investigating tubal patency and intra-uterine abnormalities for diagnostic work-up of female infertility. KEY POINTS: • MR-hysterosalpingography is an innovative technique. • Hysterosalpingography can be used to investigate tubal patency and intracavity abnormalities. • Hysterosalpingography is a potential 'one-stop-shop' imaging technique for a single comprehensive examination of female infertility.

The value of pelvic MRI in the diagnosis of posterior cul-de-sac obliteration in cases of deep pelvic endometriosis.

OBJECTIVE: The objective of our study was to define relevant MRI signs allowing preoperative diagnosis of posterior cul-de-sac obliteration in patients with deep pelvic endometriosis. MATERIALS AND METHODS: This retrospective study included patients who underwent pelvic MRI completed by a laparoscopic examination. Three radiologists performed the MRI review blinded and recorded the following signs: sign 1, retroflexed uterus; sign 2, retrouterine mass; sign 3, displacement of intraperitoneal fluid; sign 4, elevation of the fornix; and sign 5, adherence of bowel loops. Laparoscopic results provided the criterion standard for diagnosis of posterior cul-de-sac obliteration. The performance of MRI was evaluated by calculating the average sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI results of the two more experienced radiologists for each sign and for combinations of signs. Interobserver agreement for each sign and impression for posterior cul-de-sac obliteration were calculated for all radiologists. RESULTS: Sixty-three patients were included in the study. Posterior cul-de-sac obliteration was diagnosed in 43 patients at laparoscopy. The mean sensitivity, specificity, and accuracy of each sign and impression of posterior cul-de-sac obliteration were, respectively, as follows: sign 1, 24.4%, 77.5%, 41.3%; sign 2, 97.1%, 83.7%, 92.8%; sign 3, 95.0%, 88.7%, 93.1%; sign 4, 30.2%, 97.5%, 51.6%; sign 5, 83.7%, 91.2%, 86.1%; and impression of posterior cul-de-sac obliteration, 91.9%, 91.2%, 91.7%. Interobserver concordance varied from 0.26 to 0.81 with best results obtained with the combination of signs 2, 3, and 5. Best concordances for junior radiologist evaluations were obtained with assessment of sign 3. CONCLUSION: MRI allows posterior cul-de-sac obliteration diagnosis. Pelvic fluid displacement may be the sign with greatest utility when considering both diagnostic accuracy and interobserver agreement.

CT-guided percutaneous catheter drainage of acute infectious necrotizing pancreatitis: assessment of effectiveness and safety.

OBJECTIVE: The purpose of this study is to assess retrospectively the effectiveness and safety of CT-guided percutaneous drainage and to determine the factors influencing clinical success and mortality in patients with infectious necrotizing pancreatitis. MATERIALS AND METHODS: From April 1997 to December 2005, 48 consecutive patients (33 men and 15 women; median age, 58.5 years) with proven infectious necrotizing pancreatitis underwent percutaneous catheter drainage via CT guidance. Evaluated factors included clinical, biologic, and radiologic scores; drainage and catheter characteristics; and complications. Clinical success was defined as control of sepsis without requirement for surgery. Univariate analysis was performed to determine factors that could have affected the clinical success and the mortality rates. RESULTS: Clinical success was achieved in 31 of 48 patients (64.6%) and was significantly associated with Ranson score (p = 0.01) and with the delay between admission and the beginning of the drainage (p = 0.005), with a calculated threshold delay of 18 days (p = 0.001). The global mortality rate (14/48 [29%]) was also influenced by the Ranson score (p = 01) and the delay of drainage (p = 0.04) with the same threshold delay (p = 0.01). Only two major nonlethal procedure-related complications were observed. CONCLUSION: Percutaneous catheter drainage is a safe and effective technique to treat acute infectious necrotizing pancreatitis.

MRI characteristics of the uterine junctional zone: from normal to the diagnosis of adenomyosis.

OBJECTIVE: MRI was the first imaging technique to permit the visualization of the uterine junctional zone and remains the imaging method of choice to evaluate it and its associated pathology. CONCLUSION: Adenomyosis can be diagnosed using MRI with a diagnostic accuracy of 85%. The most important MR finding in making the diagnosis is thickness of the junctional zone exceeding 12 mm. The principal limitation of MRI is the absence of a definable junctional zone on imaging, which occurs in 20% of premenopausal women.

MR features of the levator ani muscle in the immediate postpartum following cesarean delivery.

INTRODUCTION AND HYPOTHESIS: We wanted to show that at the time of cesarean delivery, the active process of labor itself was sufficient to create early alterations of the pelvic floor musculature as detectable via magnetic resonance imaging (MRI). METHODS: Thirty primipara patients underwent pelvic MRI between the second and third day after cesarean delivery. Ten patients had a cesarean without labor while 20 patients underwent urgent cesarean delivery after the onset of labor. RESULTS: Patients undergoing active labor during cesarean had 2.7 times more abnormalities than the patients with cesareans without labor. The abnormalities the most frequently found were a hypersignal in the puborectalis (p = .004), a hypersignal in the iliococcygeus (p = .064) and a defect in the orientation of this same muscular bundle (p = .049). CONCLUSION: This preliminary study suggests that active labor during the time of a cesarean induces early lesions of the pelvic muscular floor.

Outcome of osteoporotic pelvic fractures: an underestimated severity. Survey of 60 cases.

The aim is to describe the characteristics of osteoporotic pelvic fractures and their outcome. We recorded clinical and biological characteristics of 60 osteoporotic pelvic fractures hospitalized in our Department of Rheumatology and assessed their outcome in 51 cases, using a questionnaire administrated by phone call. In our population, pelvic fractures mainly affected elderly women (81.6% of women, mean age 79 years), presenting, in more than 50% of the cases, a past medical history of osteoporosis, previous fracture and cardiovascular disease. The fractures were triggered by a fall in 89% of the cases and mainly located at the pubic rami (65%). There was a high rate of vitamin D deficiency (80.6%) associated with a secondary hyperparathyroidism (51.6%). Before the pelvic fracture, all patients lived at their personal home and 84.1% were autonomous. During hospitalization, 52.5% of the patients experienced an adverse event, mostly related to urinary tract infection and bedsore. At time to discharge, only 31% directly returned to their own home. At the final assessment (mean delay from the fracture: 29 months), 11 patients were dead (mean delay: 190 days). Among living patients, 74.5% lived at home, 60% required assistance for at least one daily life activity and 18.6% experienced a new fracture. Only 63.2% were still treated for osteoporosis. Osteoporotic pelvic fractures requiring initial hospitalization share most characteristics of hip fracture: elderly people, women predominance, vitamin D insufficiency, fall triggering the fracture, and also the severity assessed by a high morbidity and mortality and loss of autonomy.

Can low-dose computed tomographic scan of the spine replace conventional radiography? An evaluation based on imaging myelomas, bone metastases, and fractures from osteoporosis.

We evaluated and compared the radiological images of the spine of 111 patients affected by myeloma, bone metastases, and fractures secondary to osteoporosis demonstrated in low-dose computed tomographic (CT) scans and those demonstrated in conventional radiographic studies. From the analysis of the data obtained, it appears that the duration of the CT procedure is definitely shorter and that its diagnostic sensitivity is superior to that of conventional radiography. We should mention that the dose of radiation delivered by CT scanning does not constitute an unfavorable element in patients, usually elderly, for whom CT scanning was indicated.