Centre Oscar Lambret Research Articles

Therapeutic impact of 18F-FDG PET/CT for initial staging in patients with clinical stage I and IIA, HER2-positive, or triple-negative breast cancer.

While 18F-FDG PET/CT (FDG-PET/CT) is consensual for clinical stage ≥ IIB breast cancers (BC), its benefit for stage I or IIA HER2+ or triple-negative breast cancer (TNBC) patients lacks sufficient evidence. We reported a single-institution, retrospective study evaluating FDG-PET/CT impact on patient management and staging for stage I or IIA HER2+ or Triple-Negative BC. Patients who underwent FDG-PET/CT staging before any treatment between January 2015 and December 2020 at Oscar Lambret Center were included. patients with symptoms or conventional imaging suggestive of metastatic dissemination, or with prior malignancies. Initial stage was determined from mammography, breast ultrasound, breast MRI, and clinical examination. Staging and therapeutic impact based on FDG-PET/CT findings collected, including intra- (modification of dose/site/strategy in a type of management previously indicated) and inter-modality (modification of planned treatment strategy) changes. The cohort included 287 female patients with clinical stage I or IIA, HER2+ , or TNBC. Therapeutic impact observed for 18% of patients (n = 52), with 2% (n = 7) undergoing inter-modality change with omission of planned surgery. The impact on patient management was higher for stage IIA patients (20%, 47/237) than for stage I patients (10%, 5/50). Among stage IIA disease, changes in management were more important for T2N0 patients (22%, 44/205) than for T1N1 patients (9%, 3/32). While not statistically significant, trends suggest usefulness of FDG-PET/CT for T2N0 patients. Considering substantial therapeutic implications, our study suggests the usefulness of FDG-PET/CT for patients with stage IIA, HER2-positive, or Triple-Negative BC with tumor size > 2cm (T2N0).

Extreme hypofractionated stereotactic radiotherapy for localized prostate Cancer: Efficacy and late urinary toxicity according to transurethral resection of the prostate history

Background and purposeExtreme hypofractionated stereotactic body radiotherapy (SBRT) is a therapeutic alternative for localized low- or intermediate-risk prostate cancer. Despite the availability of several studies, the toxicity profile of SBRT has not been comprehensively described. This real-world evidence study assessed the efficacy and toxicities associated with this regimen, and potential prognosis factors for genitourinary toxicities. Materials and methodsThis retrospective study included 141 consecutive patients with localized prostatic adenocarcinoma treated with CyberKnife™ SBRT, as primary irradiation, at the Oscar Lambret Center between 2010 and 2020. The prescribed dose was 36.25 Gy in 5 fractions. Acute and late toxicities were graded according to the CTCAE (version 5.0). Biochemical recurrence-free survival (bRFS) and overall survival (OS) were estimated using the Kaplan–Meier method. The cumulative incidence of biochemical recurrence (cBR) was estimated using the Kalbfleisch–Prentice method. ResultsAmong the included patients, 13.5 % had a history of transurethral resection of the prostate (TURP). The median follow-up was 48 months. At 5 years, bRFS, cBR, and OS were 72 % (95 %CI: 61–81), 7 % (95 %CI: 3–14), and 82 % (95 %CI: 73–89), respectively. Twenty-nine patients experienced at least one late toxicity of grade ≥ 2; genitourinary (N = 29), including 3 cases of chronic hematuria, and/or gastrointestinal (N = 1). The cumulative incidence of late urinary toxicity of grade ≥ 2 was 20.6 % at 5 years (95 %CI: 13.9–28.1). Multivariate analysis revealed that a history of TURP was significantly associated with late urinary toxicity of grade ≥ 2, after adjusting for clinical target volume (Odds Ratio = 3.06; 95%CI: 1.05–8.86; P = 0.04). ConclusionExtreme hypofractionated SBRT is effective for localized prostate cancer with a low risk of late toxicity. A history of TURP is associated with a higher risk of late urinary toxicity. These findings may contribute to the optimal management of patients treated with this regimen, particularly those with a history of TURP.

Stereotactic reirradiation in the treatment of head and neck cancers: A retrospective study on the long-term experience of the Oscar Lambret Center

Background and purposeStereotactic radiotherapy potentially treats unresectable recurrences of previously irradiated head and neck (H&N) cancer. This study aimed to assess its efficacy and safety and evaluate prognostic factors. Materials and methodsWe conducted a large retrospective series that included 110 patients who had undergone 36-Gy, six-fraction stereotactic reirradiation (CyberKnife®) for recurrent/secondary H&N cancer between 2007 and 2020 at the Oscar Lambret Center. Patient characteristics and toxicities were assessed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method. ResultsMedian follow-up time was 106.3 months. The 2-year OS rate was 43.8 % (95 % confidence interval, 95 % CI, 34.3–52.9) and the median survival was 20.8 months (95 % CI, 16.5–26.3). The cumulative 2-year local-recurrence, regional-recurrence, and distant-metastasis rates were 52.2 % (95 % CI, 42.4–61.1 %), 12.8 % (95 % CI, 7.4–19.8 %), and 11 % (95 % CI, 6.0–17.6 %), respectively. 73 patients received concomitant cetuximab, and it was not significantly beneficial (HR = 1.34; 95 % CI, 0.80–2.26; p = 0.26). The cumulative incidences of grade ≥ 2 late toxicity was 42 % (CI95%: 33–51) at 24 months. Two grade 4 bleedings and no treatment-related deaths were reported. ConclusionIn a large retrospective series of SBRT reirradiation for recurrent or second primary H&N cancers, we observed a median OS of 20.8 months, with a cumulative incidence of grade ≥ 2 late toxicity of 42 % at 24 months. Such a treatment is feasible. However, local recurrence rates remain non-negligible, warranting further research. Radiosensitizer use is currently under study. Therefore, establishing a balance between therapeutic modifications and toxicity is essential.

IMRT in the treatment of locally advanced or inoperable NSCLC in the pre-durvalumab era: clinical outcomes and pattern of relapses, experience from the Oscar Lambret Center.

Intensity-modulated conformal radiotherapy (IMRT) has become the technique of choice for the treatment of locally advanced or inoperable non-small cell lung cancer (NSCLC). Nevertheless, this technique presents dosimetric uncertainties, particularly in treating moving targets such as pulmonary neoplasms. Moreover, it theoretically increases the risk of isolated nodal failure (INF) due to reduced incidental irradiation. The objective of this study was to evaluate the efficacy and safety of IMRT in patients with inoperable NSCLC and to describe the pattern of relapses. Patients with locally advanced NSCLC treated with radiotherapy and chemotherapy between 2015 and 2018 at the Oscar Lambret Center were retrospectively included in the study. Overall and progression-free survival were estimated using the Kaplan-Meier method. The cumulative incidence of the different components of relapse was estimated using the Kalbfleisch and Prentice method. Prognostic factors for relapse/death were investigated using the Cox model. A comparison with literature data was performed using a one-sample log-rank test. Seventy patients were included, and 65 patients (93%) had stage III disease. All the patients received chemotherapy, most frequently with cisplatin and navelbine. The dose received was 66 Gy administered in 33 fractions. The median follow-up and survival were 49.1 and 39.1 months, respectively. A total of 35 deaths and 43 relapses, including 29 with metastatic components, were reported. The overall survival rates at 1 and 2 years were 80.2% (95% confidence interval 68.3%-88.0%) and 67.2% (95% confidence interval 54.2%-77.3%), respectively. Locoregional relapse was observed in 14 patients, including two INF, one of which was located in the lymph node area adjacent to the clinical target volume. Median relapse-free survival was 15.2 months. No variable was statistically associated with the risk of relapse/death in multivariate analysis. Seven patients (10%) experienced grade 3 or higher toxicity. The use of IMRT for locally advanced or inoperable NSCLC led to favorable long-term clinical outcomes. The rate of locoregional relapse, particularly isolated lymph node failure, was low and comparable with that of the three-dimensional radiotherapy series, as was the rate of early and late toxicities.

Apport de l’IRM corps entier au bilan initial du liposarcome myxoïde

IntroductionMyxoid liposarcoma is a soft tissue sarcoma associated with multifocal metastases at diagnosis. These metastases are asymptomatic and occult on CT and FDG-PET and can alter the therapeutic management and prognosis. In this context, we evaluated the contribution of whole-body MRI to the initial workup of patients with myxoid liposarcoma. MethodThis retrospective study was conducted between January 2015 and December 2020 at the Oscar Lambret Center. We enrolled 22 patients who were diagnosed with myxoid liposarcoma and underwent whole-body MRI at diagnosis. The number of metastases at diagnosis, their location, and the visibility of these lesions on CT were evaluated. Associations between clinical features, presence of metastasis, and their impact on management were assessed. ResultsSixteen patients (72.7%) had non-metastatic disease at the initial diagnosis, and 15 of these patients were managed using local treatment. Six patients (27.3%) had metastases at multiple locations and received chemotherapy. The main locations were the bones (n=5) and lungs (n=3). In five patients with metastases, whole-body MRI demonstrated additional lesions that were not visible on CT (bone and soft tissue lesions). Only the presence of a round cell contingent (P=0.009) was found as a criterion associated with the presence of metastases. ConclusionThe patients’ young age, absence of reliable prognostic factors at diagnosis, asymptomatic nature of the lesions, and the benefits of early and targeted therapeutic management encourage the use of whole-body MRI as part of the initial work-up as it seems to provide a better initial staging compared with conventional imaging.

Abstract P6-02-16: Breast cancer prognosis of germline BRCA1/BRCA2 mutation carriers of young women: a retrospective hospital-based cohort

Abstract Background Studies evaluating prognostic impact of germline BRCA1/2 mutations (gBRCAm) on breast cancer patients reported controversial results. The primary aim of this study was to investigate outcomes of young gBRCAm patients with very early onset of breast cancer (< 30 years) compared with noncarriers. Methods In this retrospective study, 149 patients 30 years aged or younger at early breast cancer diagnosis between 2005 and 2019 were included in Oscar Lambret Center. Outcomes were overall survival (OS) and disease-free survival (DFS), defined as time from first diagnosis to first recurrence, second cancer or death from any cause, at 2 years, 5 years, and 10 years. Key patient data, kaplan-meier plots and outcomes were described by BRCA mutation status. Hazard ratios (HR) were calculated using Cox proportional-hazards models. Results Twenty-eight (18.8%) patients were gBRCAm carriers. The median follow-up was 6.5 years (IQR 0.25-16.5). Twenty-three deaths, 41 recurrences and 2 second cancers were reported. OS was 89.3% [70.4–96.4] in gBRCAm patients vs 99.1% [95% CI 93.9–99.9] in non-carriers patients at 2 years; 85.0% [64.7–94.1] vs 92.3% [85.1–96.1] at 5 years and 75.3% [52.5–88.3] vs 80.2% [66.6–88.7] at 10 years. There was no difference in OS between groups in multivariable analysis (HR=1.63 [0.55–4.77], p=0.37). Similar results were noted when comparing disease-free survival (HR=1.42 [0.64–3.11], p=0.38). Conclusions In this cohort of 149 patients with very early onset breast cancer, outcomes of gBRCAm mutation carriers did not differ from non-carriers when adjusted for others prognostic factors. Citation Format: Florent HEGO, Maël BARTHOULOT, Charles PIERARD, Audrey Mailliez. Breast cancer prognosis of germline BRCA1/BRCA2 mutation carriers of young women: a retrospective hospital-based cohort [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-02-16.

Braindrive : qui peut conduire parmi les patients pris en charge pour une radiothérapie cérébrale ?

PurposeBrain tumors can be associated with various neurological symptoms impairing driving ability. We sought to assess patients’ knowledge on the French driving legislation. Materials and methodsThis is a prospective descriptive epidemiological study carried out at the Oscar Lambret center in Lille, among driving license holders treated by radiotherapy for one or more primary cerebral tumor or brain metastasis. The survey was carried out by hetero-administered questioners. The primary endpoint was the frequency of patients informed on the French driving legislation at the initial radiotherapy consultation, given with a 95% confidence interval by the Clopper-Pearson exact binomial method. ResultsFrom the 1st February to March 31st, 2022, 33 patients with brain tumors were evaluated. Three of them were excluded because they did not have a driving license. Among the 30 patients analyzed, 12 patients (40% IC95 [22.7; 59.4]) had been informed of the existence of a possible contraindication to drive before the radiotherapy consultation. Among the 30 patients, 21 (70%) had a contraindication to drive. Of the eight patients (26.6%) who drove, four (13.3%) should not. ConclusionMost patients have a contraindication to drive, but only 40% of the patients questioned stated that they had been informed of the existence of a possible contraindication before the radiotherapy consultation.

Total parietal peritonectomy for 61 patients: a retrospective study

Objective: To evaluate the morbidity of total parietal peritonectomy (TPP) during cytoreduction surgery, and its impact on the site of recurrence of different peritoneal surface malignancies (PSM). Methods: We led a retrospective study in a French tertiary cancer institution (Centre Oscar Lambret - Lille) experienced in treating PSM over a 6-year period from 2012 to 2018. All patients underwent a total parietal peritonectomy during a debulking surgery for PSM including ovarian cancer, appendiceal pseudomyxoma peritonei or peritoneal mesothelioma. Results: Among the 61 patients included in this study, 49 patients(80.3%) had an ovarian cancer. The rate of complete tumor resection reached 86.9% with almost 69% of surgeries being highly complex. 73.8% were transfused during the surgical procedure. The median length of hospital stay was 10 days including 7 days in Intensive Care Unit. Overall, 19 patients (31.1%) had an early postoperative complication, including 3 with a grade IIIB complication of Clavien Dindo classification. With a median follow-up of 30 months, the estimated disease-free survival in the ovarian cancer subgroup who had an initial peritonectomy (n = 42) was 84.7% at 1 year and 12.0% at 3 year. The main site of first and second recurrence was peritoneal (42% and 14%). Conclusion: TPP is a safe surgical procedure to treat peritoneal surface malignancies and their recurrences with a low rate of grade IIIB morbidity and no treatment-related death and allow optimal surgery. In this study there is no atypical recurrence site, such as abdominal muscle involvement.

Stereotactic body radiotherapy for intramedullary metastases: a retrospective series at the Oscar Lambret center and a systematic review

BackgroundIntramedullary metastasis (IMM) is a rare disease with poor prognosis. The incidence of IMMs has increased, which has been linked to improved systemic treatment in many cancers. Surgery and/or radiotherapy are the most commonly used treatments; only small-sample retrospective studies and case reports on stereotactic body radiotherapy (SBRT) have reported acceptable results in terms of local control and clinical improvement, with no reported toxicity. Thus, we performed this monocentric retrospective study on five cases treated with SBRT for IMMs, which we supplemented with a systematic review of the literature.MethodsWe included all patients treated for IMM with SBRT. The target tumor volume, progression-free survival, prescription patterns in SBRT, survival without neurological deficit, neurological functional improvement after treatment, and overall survival were determined. Results: Five patients treated with a median dose of 30 Gy in a median number of fractions of 5 (prescribed at a median isodose of 86%) included. The median follow-up duration was 23 months. Two patients showed clinical improvement. Three patients remained stable. Radiologically, 25% of patients had complete response and 50% had stable disease. No significant treatment-related toxicity was observed. Conclusion: SBRT appears to be a safe, effective, and rapid treatment option for palliative patients.

Abstract PS1-58: The role of resection of the primary tumour in patients with de novo oligometastatic breast cancer (OMBC)

Abstract Purpose: The role of resection of the primary tumour in management of patients with OMBC is controversial. Loco-regional treatment (LRT) with curative intent could be discussed considered for OMBC patients, who experience good response to systemic therapy. We retrospectively studied the impact of resection of the primary tumour on overall survival (OS) for de novo OMBC treated at Oscar Lambret Center in Lille.Patients and methods: Between 2005 and 2017, all consecutive patients were selected. De novo OMBC was defined by 1 to 5 metastases in 1 or 2 organs, diagnosed within three months after primary tumor. Clinical data, tumor characteristics, metastatic sites, locoregional treatment, systemic first line treatment were recorded retrospectively. We set up 2 groups according to therapeutic strategy. Group 1 patients were managed with a prior planned curative intent surgery and systemic treatments and group 2 included patients with systemic therapy alone, without plan of surgery.Results: 116 patients were included in our analysis; 78 patients in group 1 and 38 patients in group 2. Median age was 54,9 years (25,2-86,2) with no difference between both groups (p=0,08). TNM stage, cancer histologies were comparable in both groups, excluding that there were more HER2+ tumour in Group 2 (p=0.003). 81 patients underwent LRT, 69 patients in group 1 and 12 patients in group 2. 59% of them had radical mastectomy and 89% had axillary surgery. For 29% of them, surgery was performed before knowledge of metastatic disease. The other main indications of breast surgery included stable disease (50%), local progression (9%), palliation (5%), single metastasis (5%) and complete metastatic response after chemotherapy (2%). 59 of 81 patients had adjuvant radiotherapy. Regarding systemic first line treatment, patients in group 1 received more chemotherapy (63% vs 86%, p=0.01), anti-HER2 treatment was appropriate except for 6 patients because of heart disease and 69% of patients had hormone therapy with no difference in both groups. Regarding metastases at diagnosis, the mean number of metastases was 2,1 (SD=1,2), 103 patients (89%) had one metastatic site, and 13 patients (11%) had two metastatic sites, with no difference between both groups. Secondary bone involvement was most prevalent site (69%). There was no difference between both groups in metastasis distribution. Median OS was 70,2 months in our cohort. LRT did not improve OS (HR 1,23; 95% CI [0,75-2,00] p=0,41), even after adjustment on age and HER2 status. Median progression free survival (PFS) was 30,2 months in our cohort. LRT did not improve PFS in comparison with systemic treatment alone (HR 1,38; 95% CI [0,91- 2,11] p=0,13).Conclusion: We found that LRT did not improve outcome (PFS or OS) in OMBC patients. This is in line with recently issued large randomized phase III trial. LRT is not a standard of care in OMBC, nevertheless, further clinical studies are needed to better identify the subgroup of OMBC patients that could benefit from LRT, at least in term of quality of life. Citation Format: Charlotte Debuquoy, Claudia Regis, Jennifer Wallet, David Pasquier, Nicolas Penel, Marie-Cecile Le Deley, Marie-Pierre Chauvet, Emilie Kaczmarek. The role of resection of the primary tumour in patients with de novo oligometastatic breast cancer (OMBC) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-58.

Abstract PS18-36: Proteomic profiling of specific tumor clones using spatially resolved mass spectrometry technologies for precision oncology

Abstract Background Breast cancer (BC) remains a leading cause of cancer-related death among women worldwide. The complexity of this disease, especially its heterogeneity, have prevented its eradication and driven resistance to treatments. To reach precision oncology to eradicate BC, therapy needs to be specific to each tumor clone. Yielding enough molecular information from tumor clones to identify new drug targets represents a technical challenge due to sample size limitation or loss of spatial resolution. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry combined with microproteomics enables a spatially-resolved unlabeled tumor imaging of its protein distribution, thus revealing proteomic clones. Our aims were to analyze the clonal proteome of luminal breast cancers, and explore its potential to expand new drug target discovery and drug repurposing. Methods A retrospective study at the Comprehensive Cancer Centre Oscar Lambret (Lille, France) was conducted to analyze 76 FFPE luminal HER2 negative tumors: 52 primary tumors from patients with early BC and 24 BC metastases. Patients gave their informed consent and the study was approved by the local institutional review board. MALDI mass spectrometry imaging and spatially-resolved on-tissue shotgun microproteomics were performed on FFPE slides of tumor tissue to determine the proteomic profile of selected clones using nanoLC-MS & MS/MS. Protein identification was performed using MaxQuant software against the Uniprot database. Functional annotation and characterization of the identified proteins were performed using Panther software. Candidate druggable targets were searched using DrugCentral druggable genome database, and their druggability level was assessed using the classification by the Illuminating the Druggable Genome Knowledge Management Center. The clonal proteome dataset was compared to publically available TCGA, BC360, and CDx datasets. Results The clonal proteome analysis identified a total of 2868 different proteins; 780 proteins were found in more than 50% of the patients. Panther analysis showed that 22% of the proteins were classified as enzymes, 15% were related to DNA processes, 6% were structural proteins, and less than 2% were related to immunity. Panther identified 139 pathways in the clonal proteome dataset. The clonal proteome analysis yielded the highest number of pathways compared to TCGA, BC360, and CDx datasets. 41 pathways (mainly metabolic pathways) were exclusive to the clonal proteome dataset. 1495 proteins of this dataset had an entry and were druggable in DrugCentral database, with 52% of them with known mechanisms of action and drug interaction. The main target classes were enzymes (60%), kinases (23%) and transporters (7%), whereas kinases were dominant in TCGA, BC360, and CDx datasets (46% to 77%). To explore the clonal proteome potential for repurposing anticancer drugs in luminal breast cancers, protein targets matching approved antineoplastic agents were searched using DrugCentral database. 97 approved anticancer drugs were identified, mostly chemotherapy (33%) or protein kinase inhibitors (28%), of whom only 17 were approved for breast cancer treatment. Compared to publically available TCGA, BC360, and CDx datasets, the clonal proteome analysis yielded the highest number of drug target candidate. Conclusion Mass spectrometry-based analysis of BC proteomic clones provides the technological means to access large functional molecular information at a clonal level to develop clone specific strategies for drug target discovery and drug repurposing in BC. Citation Format: Nawale Hajjaji, Soulaimane Aboulouard, Delphine Bertin, Yves Marie Robin, Isabelle Fournier, Michel Salzet. Proteomic profiling of specific tumor clones using spatially resolved mass spectrometry technologies for precision oncology [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS18-36.

Midazolam sedation in palliative medicine: retrospective study in a French center for cancer control

BackgroundFrench legislation about sedation in palliative medicine evolved in 2016 with the introduction of a right to deep and continuous sedation, maintained until death. The objective was to describe midazolam sedation at the COL (Centre Oscar Lambret [Oscar Lambret Center], French regional center for cancer control), in order to establish a current overview before the final legislative changes.MethodsDescriptive, retrospective and single-center study, concerning major patients in palliative care hospitalized from 01/01/2014 to 12/31/2015, who had been sedated by midazolam. The proven sedations (explicitly named) and the probable sedations were distinguished.ResultsA total of 54 sedations were identified (48 proven, 6 probable). Refractory symptoms accounted for 48.1% of indications, complications with immediate risk of death 46.3%, existential suffering 5.6%. Titration was performed in 44.4% of cases. Sedation was continuous until death for 98.1% of the cases. Probable sedation had a higher failure rate than proven sedation. Significant differences existed for the palliative care unit compared to other units regarding information to the patient, their consent, anticipation, mention by correspondence and carrying out titrations. When patients had already been treated with midazolam, the induction doses, initial maintenance doses, and doses at the time of death were significantly higher. For those receiving opioids, the maintenance dose at the time of death was higher. No comparison found a difference in overall survival.ConclusionsAfter a sufficient follow-up has enabled teams to familiarize with this new legislation, reflection on sedation should be conducted to adapt to final recommendations.

Symptomatic acute hypotension associated with high-dose dacarbazine

We observed several cases of hypotension associated with high-dose dacarbazine. We conducted a retrospective observational analysis of all patients treated with high-dose dacarbazine from January 2018 to August 2019 in Oscar Lambret Center, Lille, France. In our study, a total of 23 patients in outpatient care were analyzed, they underwent 57 treatment cycles. We observed 8 episodes of hypotension in 7 of the 23 consecutive treated patients (30.4%). We discuss herein several hypotheses explaining dacarbazine-induced hypotension. Dacarbazine high dose and administration methods seem to be the main causes of hypotension adverse events. Administration methods include administration duration, which should be above 2 hours, concomitant hydration with 500 ml 0.9% sodium chloride, and UV-resistant pump tube downstream the administration tree.

Abstract P5-16-04: Evaluation of autologous fat grafting local morbidity (fat necrosis and biopsy rates) in breast reconstruction after breast cancer: A retrospective study on 257 patients in Oscar Lambret Center

Abstract Background.Autologous fat grafting (AFG) is a widely used procedure in breast reconstruction after breast cancer. Indications are in constant increase but there is a lack of dataabout global morbidity, especially fat necrosis and management of local complications. The purpose of this study was to evaluate the complications rate in term of abnormal clinical examination or imaging and the proportion of additional explorations. Methods. We retrospectively reviewed the computerized files of consecutive patients who underwent AFG for breast reconstruction after breast cancer or for preventive surgery and aesthetic sequelae after lumpectomy in the Oscar Lambret center between January 2013 and December 2016. Fat grafts were harvested with a fat trap then processed and injected according the Coleman technique. We collected demographics, operative details, local complications, incidence of palpable masses and/or suspicious breast imaging findings leading to additional explorations (breast imaging or biopsy), and locoregional cancer recurrence. Descriptive statistics were generated. Results. Over a 4-year period, 257 women underwent autologous fat grafting for breast reconstruction and aesthetic sequelae after lumpectomy. Their mean age was 50 years [range 28-75], the mean BMI was 25 [range 18-44], 26% (n=66) were smoking and 74% (n=190) underwent radiotherapy. A total of 303 breasts were operated by 270 mastectomies (89%) or33 lumpectomies (11%). The reconstruction was delayed in 63% (n=171) and the main techniques used were breast implant (44%, n=119) and autologous latissimus dorsi (31%, n=84). The mean number of fat grafting procedures was 1,9 per patient [range 1-7] with a mean volume of 181 mL [range 30-535]. The mean time interval between cancer diagnosis and first fat graft session was 56 months [range 3-285], and the follow-up ranged from 0 to 51 months (mean=16). The prevalence of donor site complications was 6% (n=16) and infections was 2% (n=5). Sixty six (25,6%) patients had a clinically palpable lesion and 54 (21%) underwent additional imagings, mostly by ultrasounds (53 patients, 98%) except the usual follow-up. Twenty one biopsies (8%) were performed and showed 16 benign results (76,2%) and 5 malignant results (23,8%) leading to 6,2% of fat necrosis and 1,9% of locoregional recurrence after AFG in our study.Tobacco (p=0.45), BMI (p=0.95), radiotherapy (p=0.56) and amount of fat grafted ( p=0.09) didn't appear to be risk factors for fat necrosis. Conclusions. A good knowledge of local complications by surgeons and radiologists enables to avoid systematic and repeated further imaging explorations. Multicentric, prospective studies with long term follow up and evaluation of patients reported outcomes are needed to evaluate anxiety generated by biopsies and costs generated by repeated imagings. Key words: autologous fat grafting, breast cancer, local morbidity, fat necrosis. Citation Format: Hannebicque K, Renaudeau C, Giard S, Regis C, Boulanger L, Bogart E, Le Deley M-C, Ceugnart L, Chauvet M-P. Evaluation of autologous fat grafting local morbidity (fat necrosis and biopsy rates) in breast reconstruction after breast cancer: A retrospective study on 257 patients in Oscar Lambret Center [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-16-04.

947P - Circulating tumor cells as prognostic marker in ovarian carcinoma: Results from the ANTHALYA study

Background: Circulating tumor cells (CTC) are detected in 12–30% of advanced stage/relapsing ovarian carcinoma (OC). We evaluated the prognostic value of CTC counts among patients (pts) from the ANTHALYA trial, an open-label randomized phase II study evaluating addition of bevacizumab (Beva) to neoadjuvant carboplatin-paclitaxel (CP) in first line for pts with unresectable FIGO stage IIIc/IV ovarian, tubal or peritoneal adenocarcinoma. Methods: We obtained CTC counts at baseline and before interval debulking surgery (IDS). A CTC threshold of ≥ 1 CTC/7.5 mL blood was considered as CTC+. We assessed the prognostic impact of CTCs on objective response rate (ORR), interval debulking surgery (IDS) rate, complete resection rate and progression-free survival (PFS), and explored their potential predictive impact on ORR and PFS according to bevacizumab therapy. Results: In 88 pts with an available CTC count at baseline, CTC+ pts (n = 29) had a 75.9% ORR (at IDS), vs 59.3% for pts with 0 CTC (n = 59): OR = 2.2 [0.8-5.8] (OR-adj=1.8 [0.8-5.8]). Respectively, 58.6% vs 66.1% were amenable to IDS and 55.2% vs 54.2% achieved a complete resection. Median PFS was 21 m [15.0-25.4] in CTC+ pts and 25.8 m [18.5-27.2] in pts with 0 CTC (HR = 1.5 [0.8-2.8] and HR-adj=1.7 [0.9-3.2]). CTC counts at IDS were available in 70 pts. At IDS, a complete resection was achieved in 66.7% of CTC+ pts (n = 6), and in 68.8% of pts with 0 CTC (n = 64). Exploration of the potential predictive impact of CTC is described in the table.Table947PPrognostic approach0 CTC at baseline (n = 59)CTC+ at baseline (n = 29)ORR at IDS59.3%75.9%Median PFS [95% CI]25.8 m [18.5-27.2]21.0 m [15.0-25.4]Predictive approachBeva (n = 36)CP (n = 23)Beva (n = 17)CP (n = 12)ORR at IDS61.1%56.5%82.4%66.7%Median PFS [95% CI]25.8 [20.9-NE]20.3 [13.8-27.2]21.0 [15.0-30.6]20.6 [8.0-25.4]Progression rate at M3636.1%56.5%52.9%83.3% Open table in a new tab Conclusions: Baseline CTC counts in OC patients receiving neoadjuvant chemotherapy +/- bevacizumab carry dual prognostic information: CTC count at IDS do not add any information, CTC+ seems to be associated with a higher ORR, while 0 CTC count seems to be a prognostic factor with better PFS, in the whole population and among patients treated with bevacizumab. Clinical trial identification: 2012-01144-22 Legal entity responsible for the study: ROCHE Funding: Roche Disclosure: T. de La Motte Rouge: Consultancy work: AstraZeneca, Roche, MSD, Eisai, Sanofi Travel grants/meeting support: Roche, Novartis, Pfizer Corporate-sponsored research: Novartis. P. Cottu: Novartis, Roche, AstraZeneca, Nanostring, Pfizer. P. Pautier: Membership on an advisory board or board of directors: Roche: Travel grants/meeting support: Roche, Astra Zeneca, Pharmamar Corporate-sponsored research; Pharmamar, Novartis. A. Floquet: Membership on an advisory board or board of directors: Roche, AstraZeneca; Travel grants/meeting support: Roche, AstraZeneca. F. Selle: Consultancy work: Roche: Travel grants/meeting support: Roche, AstraZeneca, Pharmamar. M. Fabbro: Travel grants/meeting support: Roche. E. Kalbacher: Travel grants/meeting support: Roche, Pharmamar, GSK, Leo Pharma, AstraZeneca. P. Follana: Consultancy work: AstraZeneca, Novartis Travel grants/meeting support: Roche, AstraZeneca, Amgen. A.F. Lesoin: Employment: Centre Oscar Lambret, Lille. J. Medioni: Membership on an advisory board or board of directors: AstraZeneca, Pierre Fabre Consultancy work: Clovis Oncology; Travel grants/meeting support: Roche, Sanofi Aventis. J. Dupin: Employment: Roche. R-M. Ferri: Employment: Roche SAS. C. Dubot: Corporate-sponsored research: Roche. R. Rouzier: Membership on an advisory board or board of directors: Roche; Consultancy work: Roche; Travel grants/meeting support: Roche; Corporate-sponsored research: Roche. F. Joly Lobbedez: Consultancy work: AstraZeneca, Janssen, Tesaro, Roche, Sanofi, Novartis, Bristol-Myers Squib Travel grants/meeting support: Roche, Janssen, AstraZeneca, Tesaro Corporate-sponsored research: Astellas, Janssen. All other authors have declared no conflicts of interest.

Salvage robotic SBRT for local prostate cancer recurrence after radiotherapy: preliminary results of the Oscar Lambret Center

BackgroundCurrently, there is no standard option for local salvage treatment for local prostate cancer recurrence after radiotherapy. Our objective was to investigate the feasibility and efficiency of Robotic Stereotactic Body Radiation Therapy (SBRT) in this clinical setting.Methods/materialsWe retrospectively reviewed patients who were treated at our institution with SBRT for local prostate cancer recurrence after External Beam Radiation Therapy (EBRT) or brachytherapy.Multidisciplinary staff approved the treatment, and recurrence was biopsy-proven when feasible. A dose of 36 Gy was prescribed in six fractions. Treatment was delivered every other day.ResultsBetween August 2011 and February 2014, 23 patients were treated with SBRT for intra-prostate cancer recurrence with a median follow up of 22 months (6 to 40).Twenty patients had biopsy-proven recurrence.For 19 patients, EBRT was the initial treatment and in four patients, brachytherapy was the initial treatment; the median relapse-time from initial treatment was 65 months (28 to 150).At relapse, 10 patients had an extra-capsular extension.Fourteen patients were treated with androgen deprivation that could be stopped after a median of 1 month after SBRT (range 0–24).A PSA decrease occurred in 82.6% of the patients after SBRT.The 2-year disease-free survival and overall survival rates were 54 and 100%, respectively.Disease progression was observed for nine patients (39.1%) (five local, three metastatic and one nodal progression) after a median of 20 months (7–40 months).The median nadir PSA was 0.35 ng/ml and was achieved after a median of 8 months (1 to 30) after treatment.We observed no grade 4 or 5 toxicity. Two patients presented with grade 3 toxicities (two Cystitis and one neuralgia). Other toxicities included urinary toxicities (five grade 2 and nine grade 1) and rectal toxicities (two grade 2 and two grade 1).ConclusionSBRT for local prostate cancer recurrence seems feasible and well tolerated with a short follow up. Prospective evaluation is needed.

Intérêt d’une approche socioéducative dans l’accompagnement des adolescents et jeunes adultes atteints de cancer : l’exemple lillois

Within the second "Cancer plan" 2009-2013, the French national institute of cancer (INCa) recommended the implementation of programs dedicated to adolescents and youngs adults (AYA) with cancer. In this context and in parallel to the specific medical care developed for AYA, the Oscar-Lambret center created a psycho-social-educational team including among others a social worker (SW) and a special educational teacher (SET), offering multidisciplinary qualifications and views. The social approach, realized as a pair by SW-SET, takes into account every aspect of each AYA (family, academic, career/professional, personal, cultural aspects…). We expose the first 2years' experience of this special program for AYA through diagnosis to remission time. For this period, 164AYA were seen by the social professionals, with a total of 602consultations in the unit. The number of these consultations depended on the needs of AYA and their family. Nevertheless, only 10AYA required no further intervention (6.1%). The study highlights that the social interventions are most frequently about scolarity, work and disability recognition. These 2years of experience of the SW-SET team offered a way to reflect upon our values and our culture, and on the role of the social worker in a medical setting. Each AYA has a personal story, which affects significantly the way to overcome the challenges that come with the disease. Our findings underscore the need for AYA with cancer to have access to personalized supportive care, encouraging them in pursing their personal goals and rewarding themselves.

Abstract P2-09-15: Rapid BRCA analysis: Experience of a single institution

Abstract The interest of rapid BRCA analysis, even before the initial treatment could modify the surgical indications (ie total mastectomy and immediate reconstruction even in case where tumorectomy would be suitable). The aim of this study was to evaluate the indications and consequences of this rapid determination of BRCA status in our institution. Patients Rapid BRCA analysis was conducted in 129 patients (pts) treated for breast cancer and addressed to the genetician at Oscar Lambret Center between 2009 and 2014: in 98 pts to discuss breast and axilla surgical modalities, in 4 cases to discuss oophorectomy, in 3 cases to have access to PARP inhibitors. In the other 24 pts, the reasons were debatable: patient leaving abroad, patient requiring reproductive assisted technology..... Results 38 deleterious mutations (29,4%) were identified (31 BRCA1, 7 BRCA2) in 38 pts. Cancer treatment was on going for 107 pts, programmed for 12 pts and finished for 10. The median time between cancer diagnosis and genetic counseling was 81 days (5-5160), between blood sample collection and BRCAs analysis 37 days (13-132), between availability of the laboratory results and the information to the patient: 39 days (1-234); 7 pts (5.4%) never came to obtain the laboratory results. Treatment was modified after genetic counselling for 8 pts out of 119 (7%). Six of them had BRCA1 deleterious mutations. Three decided subsequent radical mastectomy and adjuvant radiation was cancelled, another had a radical mastectomy before radiation, another treated for bilateral breast cancer had a bilateral radical mastectomy before radiation and the last treated for unilateral breast cancer had a bilateral radical mastectomy before radiation. Out of these 8 pts, two did not have a deleterious mutation. One had a bilateral radical mastectomy before laboratory result and one with BRCA variant of unknown significance had a homolateral radical mastectomy. Conclusion discussion Our experience shows that rapid BRCA analysis is feasible. In this selected population the mutation rate is very high. However, first, it appears that indications for rapid BRCA analysis were variable and not always relevant. Second, genetic result impacts on treatment only in 7% of pts. Indications could be justified by the use of PARP inhibitors. Up to now, the indications of rapid genetic analysis are rare. Citation Format: Mailliez A, Herin H, Revillion F, Adenis C, Peyrat J-P, Bonneterre J. Rapid BRCA analysis: Experience of a single institution. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-09-15.

Early stage cervical cancer: Brachytherapy followed by type a hysterectomy versus type B radical hysterectomy alone, a retrospective evaluation

BackgroundTwo options are possible for the management of early stage cervical cancer, without lymph node involvement: radical surgery or brachytherapy followed by surgery. The aim of this study was to compare overall survival (OS) and disease-free survival (DFS) of early stage cervical cancers managed by uterovaginale brachytherapy followed by extrafasciale hysterectomy (group 1) or by radical hysterectomy alone (group 2). The secondary objectives were to compare the morbidity of these two different approaches and to evaluate the parametrial involvement rate in patients managed by radical hysterectomy. Materials and methodsIt is a retrospective and collaborative study between the Paoli Calmettes Institute (Marseille) and the Oscar Lambret Center (Lille) from 2001 to 2013, in patients with tumors FIGO stages IA1, IA2, IB1 and IIA less than 2 cm of diameter, without pelvic lymph node involvement. ResultsOne hundred and fifty-one patients were included (74 in group 1 and 77 in group 2). The demographic characteristics of the two groups were comparable. OS and DFS were respectively 92.3% versus 100% (p = 0.046) and 92.3% and 98.7% (p = 0.18). Complication rates were 12.2% and 44.2%, respectively (p < 0.0001). In group 2, the parametrial invasion rate in this study was 1.30%. ConclusionIn our study, the two strategies are comparable in terms of DFS. Complications seem more frequent in the group 2, but more severe in the group 1. Finally, the low rate of parametrial invasion in group 2 confirms the interest of a less radical surgical treatment in these stages with good prognosis.

Determination of the KQclinfclin,Qmsr fmsr correction factors for detectors used with an 800 MU/min CyberKnife(®) system equipped with fixed collimators and a study of detector response to small photon beams using a Monte Carlo method.

In a previous work, output ratio (ORdet) measurements were performed for the 800 MU/min CyberKnife(®) at the Oscar Lambret Center (COL, France) using several commercially available detectors as well as using two passive dosimeters (EBT2 radiochromic film and micro-LiF TLD-700). The primary aim of the present work was to determine by Monte Carlo calculations the output factor in water (OFMC,w) and the [Formula: see text] correction factors. The secondary aim was to study the detector response in small beams using Monte Carlo simulation. The LINAC head of the CyberKnife(®) was modeled using the PENELOPE Monte Carlo code system. The primary electron beam was modeled using a monoenergetic source with a radial gaussian distribution. The model was adjusted by comparisons between calculated and measured lateral profiles and tissue-phantom ratios obtained with the largest field. In addition, the PTW 60016 and 60017 diodes, PTW 60003 diamond, and micro-LiF were modeled. Output ratios with modeled detectors (ORMC,det) and OFMC,w were calculated and compared to measurements, in order to validate the model for smallest fields and to calculate [Formula: see text] correction factors, respectively. For the study of the influence of detector characteristics on their response in small beams; first, the impact of the atomic composition and the mass density of silicon, LiF, and diamond materials were investigated; second, the material, the volume averaging, and the coating effects of detecting material on the detector responses were estimated. Finally, the influence of the size of silicon chip on diode response was investigated. Looking at measurement ratios (uncorrected output factors) compared to the OFMC,w, the PTW 60016, 60017 and Sun Nuclear EDGE diodes systematically over-responded (about +6% for the 5 mm field), whereas the PTW 31014 Pinpoint chamber systematically under-responded (about -12% for the 5 mm field). ORdet measured with the SFD diode and PTW 60003 diamond detectors were in good agreement with OFMC,w except for the 5 mm field size (about -7.5% for the diamond and +3% for the SFD). A good agreement with OFMC,w was obtained with the EBT2 film and micro-LiF dosimeters (deviation less than 1.4% for all fields investigated). [Formula: see text] correction factors for several detectors used in this work have been calculated. The impact of atomic composition on the dosimetric response of detectors was found to be insignificant, unlike the mass density and size of the detecting material. The results obtained with the passive dosimeters showed that they can be used for small beam OF measurements without correction factors. The study of detector response showed that ORdet is depending on the mass density, the volume averaging, and the coating effects of the detecting material. Each effect was quantified for the PTW 60016 and 60017 diodes, the micro-LiF, and the PTW 60003 diamond detectors. None of the active detectors used in this work can be recommended as a reference for small field dosimetry, but an improved diode detector with a smaller silicon chip coated with tissue-equivalent material is anticipated (by simulation) to be a reliable small field dosimetric detector in a nonequilibrium field.