Long-term clinical outcomes of preoperative brachytherapy in early-stage cervical cancer.

OBJECTIVE: The treatment of early-stage cervical cancer (CC) is primarily based on surgery. Adjuvant (chemo)radiotherapy can be necessary in presence of risk factors for relapse (tumor size, deep stromal invasion, lymphovascular space invasion (LVSI), positive margins, parametrial or lymph node involvement), increasing the risk of treatment toxicity. Preoperative brachytherapy can reduce tumor extension before surgery, potentially limiting the need for adjuvant radiotherapy. This study reports long-term clinical outcomes on efficacy and toxicity of preoperative pulse-dose-rate (PDR) brachytherapy in early-stage CC. METHODS: All patients treated at Institut Curie between 2007 and 2022 for early-stage CC by preoperative brachytherapy were included. A PDR technique was used. Patients underwent hysterectomy associated with nodal staging following brachytherapy. RESULTS: 73 patients were included. The median time from brachytherapy to surgery was 45 days [range: 25-78 days]. With a median follow-up of 51 months [range: 4-185], we reported 3 local (4 %), 1 locoregional (1 %) and 8 metastatic (11 %) relapses. At 10 years, OS was 84.1 % [95 % CI: 70.0-100], DFS 84.3 % [95 % CI:74.6-95.3] and LRFS 92.8 % [95 % CI:84.8-100]. Persistence of a tumor residue, observed in 32 patients (44 %), was a significant risk factor for metastatic relapse (p = 0.02) and was associated with the largest tumor size before brachytherapy (p = 0.04). Five patients (7 %) experienced grade 3 toxicity. One patient (1 %) developed grade 4 toxicity. Ten patients (14 %) received adjuvant radiotherapy, increasing the risk of lymphedema (HR 1.31, 95 % CI [1.11-1.54]; p = 0.002). CONCLUSIONS: PDR preoperative brachytherapy for early-stage cervical cancer provides high long-term tumor control rates with low toxicity.

Management of second ipsilateral breast tumor event: An advocacy for a randomized trial.

For a second ipsilateral breast tumor event, salvage mastectomy is the standard of care while second conservative treatment is a possible option. However, level 1 proofs are missing, leading to perform salvage mastectomy for patients who could receive second conservative treatment and consequently avoid psychological/quality of life salvage mastectomy deleterious impacts. A phase 3 randomized trial comparing salvage mastectomy to second conservative treatment is needed. Here we discuss what would be to us the optimal design of such trial to confirm the non-inferiority between the two salvage options, with a focus on methodological aspects in terms of patient characteristics and statistical issues.

Five simultaneous artificial intelligence data challenges on ultrasound, CT, and MRI.

PURPOSE: The goal of this data challenge was to create a structured dynamic with the following objectives: (1) teach radiologists the new rules of General Data Protection Regulation (GDPR), while building a large multicentric prospective database of ultrasound, computed tomography (CT) and MRI patient images; (2) build a network including radiologists, researchers, start-ups, large companies, and students from engineering schools, and; (3) provide all French stakeholders working together during 5 data challenges with a secured framework, offering a realistic picture of the benefits and concerns in October 2018. MATERIALS AND METHODS: Relevant clinical questions were chosen by the Société Francaise de Radiologie. The challenge was designed to respect all French ethical and data protection constraints. Multidisciplinary teams with at least one radiologist, one engineering student, and a company and/or research lab were gathered using different networks, and clinical databases were created accordingly. RESULTS: Five challenges were launched: detection of meniscal tears on MRI, segmentation of renal cortex on CT, detection and characterization of liver lesions on ultrasound, detection of breast lesions on MRI, and characterization of thyroid cartilage lesions on CT. A total of 5,170 images within 4 months were provided for the challenge by 46 radiology services. Twenty-six multidisciplinary teams with 181 contestants worked for one month on the challenges. Three challenges, meniscal tears, renal cortex, and liver lesions, resulted in an accuracy>90%. The fourth challenge (breast) reached 82% and the lastone (thyroid) 70%. CONCLUSION: Theses five challenges were able to gather a large community of radiologists, engineers, researchers, and companies in a very short period of time. The accurate results of three of the five modalities suggest that artificial intelligence is a promising tool in these radiology modalities.

[Placental site trophoblastic tumor: When do we suspect it and which treatment shall we decide?] / Tumeur du site d'implantation trophoblastique : quand la suspecter et quel traitement décider ?

Tumors of trophoblast implantation site TTSI are rare gestational tumors. This case highlights the diagnostic difficulties and treatment of tumors of trophoblastic implantation site early. Patient of 28 years with no medical history, G1P1 who gave birth 11 months ago presented bleeding with an HCG level of 73IU that led to the diagnosis of early miscarriage. Treatment of miscarriage by hysteroscopy and curettage is complicated leading to the realization of an abdominopelvic CT and pelvic ultrasound that show an atypical uterine vascularity and an intracavitary heterogeneous mass. The pelvic MRI performed evokes a TTSI stage I. A hysterectomy with bilateral salpingectomy and ovarian conservation is achieved. Despite the standard treatment with surgery the HCG levels do not normalize before seven months after surgery. This indicates an adjuvant chemotherapy, the patient refuses. The presented case illustrates the diagnostic difficulties of the disease. He noted the importance of the second reading network proposed by the specialized center in Lyon. It also raises the question of adjuvant chemotherapy in some cases of early stage TTSI. The challenge is to define cases requiring adjuvant therapy. Predictors of chemotherapy in early stages could be tumor size, degree of infiltration of the myometrium and mutation p53. Amenorrhea, bleeding associated with uterine atypical vascularization, and atypical development of HCG<1000IU and/or unusual complications of treatment of miscarriage should evoke a tumor site trophoblastic implantation. Hysterectomy is the first treatment in early stages. Tumor size, degree of infiltration of the myometrium and mutation p53 are predictors to assess in multicentre studies to define the indications of postoperative chemotherapy.

Clinico-pathology and prognosis of endometrial cancer in patients previously treated for breast cancer, with or without tamoxifen: a comparative study in 363 patients.

OBJECTIVE: To compare the clinic-pathologic variables and the prognosis of endometrial cancer in patients with and without previous breast cancer, with and without Tamoxifen. METHODS: We analyzed patients treated for an endometrial carcinoma from 1994 to 2004: patients without breast cancer (group 1), patients with a previous breast cancer without tamoxifen (group 2) and patients treated for breast cancer with tamoxifen (group 3). Survival rates were calculated according to Kaplan-Meier method and compared using a Log rank test, multivariate analysis was performed with a Cox regression model. RESULTS: 363 patients were analyzed. 80 patients had a previous history of breast cancer (43 received tamoxifen). Although it was not statistically significant, more carcinosarcomas were observed in patients in group 3 than patients in groups 1 and 2 (11.7% versus 4.2% and 5.4% respectively, p = 0.17).) Median follow-up was 87 months [2-185]. 5-year overall survival rate was respectively in groups 1, 2 and 3: 82%, 73.2%, and 61% (p = 0.0006). 5-year local relapse-free survival rate was respectively: 95.9%, 93.1% and 82.5% (p = 0.02). In multivariate analysis, factors affecting overall survival rate were: age ≥65 ans (HR 3.62, p < 0.0001), FIGO stage (HR 3.33 p < 0.0001 for locally advanced stage versus early stage, HR 8.87 p = 0.03 for distant extension versus early stage), and group 3 (HR 2.83 p < 0.001 versus group 1). CONCLUSION: Patients with endometrial cancer previously treated for breast cancer show a worse prognostic, particularly if they reveived tamoxifen.

Histological grade concordance between diagnostic core biopsy and corresponding surgical specimen in HR-positive/HER2-negative breast carcinoma.

BACKGROUND: The identification and validation of suitable predictive and prognostic factors are a challenge to improve the treatment scheme selection. Discordances in histological grade can be established between core biopsy and surgical specimens. This is important in HR-positive/HER2-negative subgroup where histological grade identifies patients at high risk and is a strong determinant for treatment scheme. METHODS: A total of 350 consecutive invasive breast carcinoma biopsies were assessed and compared with surgical specimens in Institut Curie, Paris, France. Clinical, radiological and pathological data were recorded. RESULTS: Histological grade concordance rate in the HR+/HER2- group was 75%. A grade underestimation was mainly due to mitotic index misgrading (23%). Large tumours (P<0.05), premenopausal patients (P=0.005) and non-ultrasound-guided biopsies (P=0.04) were risk factors for misgrading. The highest discordance was found in tumours that required chemotherapy (39%, P<0.05), and it was related to an underestimation of histological grade on core biopsies (94%). CONCLUSIONS: Histological grade in HR+/HER2- group is important to identify patients with poor prognosis and start a systemic therapy. Histological grade discordance was correlated with an underestimation of mitotic index and factors probably associated with intratumor heterogeneity (premenopausal status, tumour size and the type of core biopsy performed). But such discordance did not appear to modify the therapeutic decision, because systemic treatment decision-making also integrates other variables. Determining histological grade in core biopsy can be especially important in HR-positive/HER2-negative subgroup where it identifies patients at high risk and is a strong determinant of the treatment scheme.

Extensive pure ductal carcinoma in situ of the breast: identification of predictors of associated infiltrating carcinoma and lymph node metastasis before immediate reconstructive surgery.

AIM: To identify predictors for infiltrating carcinoma and lymph node involvement, before immediate breast reconstructive surgery, in patients with an initial diagnosis of extensive pure ductal carcinoma in situ of the breast (DCIS). PATIENTS AND METHODS: Between January 2000 and December 2009, 241 patients with pure extensive DCIS in preoperative biopsy had underwent mastectomy. Axillary staging (sentinel node and/or axillary dissection) was performed in 92% (n = 221) of patients. Patients with micro-invasive lesions at initial diagnosis, recurrence or contralateral breast cancer were excluded. RESULTS: Respectively 14% and 21% of patients had a final diagnosis of micro-invasive carcinoma (MIC) and invasive ductal carcinoma (IDC). Univariate analysis showed that the following variables at diagnosis were significantly correlated with the presence of either MIC or IDC in the mastectomy specimen: palpable tumor (p = 0.002), high grade DCIS (p = 0.002) and detection of an opacity by mammography (p = 0.019). Axillary lymph node (ALN) involvement was reported in 9% of patients. Univariate analysis suggested that a body mass index higher than 25 (p = 0.007), a palpable tumor (p = 0.012) and the detection of an opacity by mammography (p = 0.044) were associated with an increased rate of ALN involvement. CONCLUSION: Skin-sparing mastectomy and immediate breast reconstruction (IBRS) has become increasingly popular, especially for patients with extended DCIS of the breast. This study confirmed that extended DCIS is associated with a substantial risk of finding MIC or IDC on the surgical specimen but also ALN involvement. Adjuvant systemic treatment and/or radiotherapy could be indicated for some of these patients after the surgery. Patients should be informed of the rate of 1) complications associated to IBRS that will potentially delay the introduction of systemic or local therapy 2) complications associated to radiotherapy after IBRS.

Comparison of two experimental methods for the mechanical characterization of thin or thick films from the study of micromachined circular diaphragms.

The purpose of this study was to compare two experimental methods and evaluate the effectiveness of a set of analytical models in order to measure the initial stress and the Young's modulus value of thin and thick film materials. Two types of experiments were performed on micromachined circular diaphragms: bulge testing and vibrometry. The range of validity and accuracy of the analytical models with respect to the vibration of the diaphragms was discussed from the finite element simulations. It was shown that the a/t ratio should be considered carefully to determine the value of the Young's modulus by vibrometry with an acceptable error. A relative error of approximately ±10% on E was obtained for a/t ≤ 750. For 750 ≤ a/t ≤ 1000, the value of the dimensionless parameter k must also be considered. It has been shown that the residual stress value can be obtained with an accuracy of 10% or less, given that k > 12. As an illustration, experimental methods and models were applied to the characterization of a thick electroplated gold film and a sputter-deposited Inconel thin film. Circular structures were defined by vertical sidewalls etched on the back of a Si wafer using the deep reactive ion etching technique. In addition to analytical models, parametric finite element simulations and a design optimization technique were used to determine the material's mechanical properties. The static deflections of the diaphragms were measured as a function of the applied pressure. The resonant frequencies and mode shapes of the vibrating structures were observed under vacuum by white-light interferometric microscopy. For gold, it was found that E = (53 ± 20) GPa and σ(0) = (180 ± 10) MPa. For Inconel, it was found that E = (157 ± 14) GPa and σ(0) = (172 ± 5) MPa.

Vacuum-assisted biopsies under MR guidance: results of 72 procedures.

OBJECTIVE: To investigate the clinical accuracy of magnetic resonance imaging-guided breast vacuum-assisted biopsy (MR-VAB). METHODS: Of 97 scheduled MR-VAB for single MRI lesions (negative second-look sonography) categorised as BI-RADS 4 or 5, 4 were cancelled (undetected lesion = 2, technical problems = 2). Twenty-one patients lost to follow-up were excluded. RESULTS: Twenty-three patients (median age 51 years) were at high risk (BRCA1 = 11, BRCA2 = 7, familial risk = 5), 23 had a suspected local recurrence of breast cancer. Seventy-two imaged lesions (focus = 1, mass enhancement = 32, non-mass-like enhancement = 39) were targeted with a 10-gauge VAB probe using MRI guidance, with a median of 18 specimens per lesion (median procedural time 72 min, range 50-131 min) followed by clip placement. In the case of benignity, MRI follow-up was performed (19 patients, median 389 days, range 33-1,592) or mammography (3 patients, median 420 days, range 372-1,354). According to histopathology results, 29 lesions were benign, 10 were high-risk (papillary = 2, radial scar = 1, atypical epithelial hyperplasia = 7) and 33 malignant (ductal carcinoma in situ = 8, invasive cancers = 25). Three false negative results and 3 complications occurred (1 malaise, 1 skin defect, 1 infection). CONCLUSION: MRI-guided VAB represents an accurate tool for the histological diagnosis of lesions visible only at MRI.

Preoperative staging of liver metastases from uveal melanoma by magnetic resonance imaging (MRI) and fluorodeoxyglucose-positron emission tomography (FDG-PET).

BACKGROUND: Microscopically complete (R0) resection of metastases from uveal melanoma prolongs median overall survival compared to incomplete surgery. The aim of this study was to compare the sensitivity of dynamic-enhanced magnetic resonance imaging (MRI) with fluorodeoxyglucose-positron emission tomography (FDG-PET) in the preoperative diagnosis of liver metastases from uveal melanoma. PATIENTS AND METHODS: Fifteen consecutive patients (mean age: 56 years) underwent FDG-PET and liver MRI. Extrahepatic metastatic disease was excluded by whole body computed tomography and bone scintigraphy. MRI and FDG-PET were performed with a mean of 19 days (range: 1-30) before surgery. Imaging findings were compared with surgical (including intraoperative ultrasonography) and histological findings on a lesion by lesion analysis. RESULTS: R0 resection was performed in 12 patients. A total of 28 lesions were resected with 27 histologically proven metastases. Nine lesions were smaller than 5mm, 7 measured 5-10mm and 11 were larger than 10mm. Sensitivity and positive predictive value were 67% and 95% for MRI compared to 41% and 100% for FDG-PET. The difference between the two modalities was statistically significant (p=0.01; McNemar test). In remaining 3 patients, diffuse miliary disease (>10 capsular lesions) was discovered intraoperatively, and was suspected on preoperative MRI in 2 cases. Only one extrahepatic lesion identified by FDG-PET was falsely positive. CONCLUSIONS: In this preliminary study, MRI was superior to FDG-PET for staging of liver metastases from uveal melanoma. Although miliary disease was suggested by MRI in some cases, preoperative confirmation remains imperfect.

[MR breast screening in patients with genetic mutation]. / Dépistage du cancer du sein par IRM chez les femmes porteuses d'une mutation génétique.

PURPOSE: To compare screening breast MRI with conventional screening techniques in high-risk patients with genetic mutation. MATERIALS AND METHODS: Prospective study of 85 patients (mean age of 43 years) with genetic mutation and screening > or = 2 years (mean of 2.7 years, 231 screening examinations). BI-RADS lesions 3-5 were biopsied; isolated BI-RADS 3 lesions on MRI were followed. Results from both techniques were compared. The number of short interval follow-up examinations and biopsy results were reviewed. RESULTS: Eight cancers were diagnosed (3 in situ, 5 invasive carcinomas including an interval cancer, mean size of 14 mm). The sensitivity values for mammography, US and MRI were 12.5%, 50% and 95%, and specificity values were 98.7%, 97.3% and 94.8% respectively. Nineteen short interval follow-up MRI examinations were performed (19%): 14% of patients at initial screening and 5% and 6% at the the second and third screenings. Thirty-two biopsies were performed in 17 patients, including 18 after MRI (PPV of cytology: 30%, and biopsy: 58%). CONCLUSION: Our results confirm the value of MRI for screening of high-risk patients with genetic mutation.