Stereotactic ablative radiotherapy for unresectable inferior vena cava tumor thrombus in a patient with renal cell carcinoma: a case report.

PURPOSE: Treatment options for renal cell carcinoma (RCC) with inferior vena cava tumor thrombus (IVC-TT) are limited and carry substantial risks. Currently, there are no standard treatment options in the setting of recurrent or unresectable RCC with IVC-TT. METHODS: We report our experience of treating an IVC-TT RCC patient with stereotactic body radiation therapy (SBRT). RESULTS: This 62-year-old gentleman presented renal cell carcinoma with IVC-TT and liver metastases. Initial treatment consisted of radical nephrectomy and thrombectomy followed by continuous sunitinib. At 3 months, he developed an unresectable IVC-TT recurrence. A fiducial marker was implanted into the IVC-TT by catheterization. New biopsies were performed at the same time, demonstrating a recurrence of the RCC. SBRT consisted of 5 fractions of 7 Gy to the IVC-TT with excellent initial tolerance. He subsequently received anti-PD1 therapy (nivolumab). At 4 years follow-up, he is doing well with no IVC-TT recurrence and no late toxicity. CONCLUSION: SBRT appears to be a feasible and safe treatment for IVC-TT secondary to RCC in patients who are not candidates for surgery.

New photobiomodulation device for prevention and cure of radiotherapy-induced oral mucositis and dermatitis: results of the prospective Safe PBM study.

PURPOSE: The study aims to assess the feasibility, safety, and tolerability of CareMin650, a new photobiomodulation device, in patients treated by radiotherapy (RT) and to collect preliminary data on efficacy for prevention and treatment of oral mucositis (OM) and radiation dermatitis (RD). METHODS: Safe PBM is a French, multicentric, prospective, non-comparative study which include patients with head and neck cancer (H&NC, cohort A) or breast cancer (BC, cohort B) treated in prophylactic (cohorts A1 and B1) or curative setting (cohort A2 and B2). Prophylactic treatment was administered from D1 to end of RT, at a dose of 3 J/cm2. Curative treatment started when a grade 1 to grade 3 lesion had occurred and was pursued until end of RT. Primary endpoint was incidence of device-related adverse events (AEs). OM and RD lesions were graded according to CTCAE V3. RESULTS: Overall, 72 patients were included (22, 9, 23, and 18 in cohorts A1, A2, B1, and B2, respectively). No device-related AE was reported after 1312 CareMin650 sessions. In cohorts A1 and B1, median time to first OM or RD lesion was 20 days. One BC patient developed G3 RD after completion of RT and discontinuation of CareMin650. Four H&NC patients developed G3 OM. In cohorts A2 and B2, lesions improved or stabilized in 71% of patients. Rates of satisfaction were high among patients and users. CONCLUSION: CareMin650 is feasible, safe, and well tolerated for preventive or curative treatment of OM and RD in cancer patients treated with RT. Preliminary efficacy results are promising.

Actionability of HER2-amplified circulating tumor cells in HER2-negative metastatic breast cancer: the CirCe T-DM1 trial.

BACKGROUND: In this prospective phase 2 trial, we assessed the efficacy of trastuzumab-emtansine (T-DM1) in HER2-negative metastatic breast cancer (MBC) patients with HER2-positive CTC. METHODS: Main inclusion criteria for screening were as follows: women with HER2-negative MBC treated with ≥ 2 prior lines of chemotherapy and measurable disease. CTC with a HER2/CEP17 ratio of ≥ 2.2 by fluorescent in situ hybridization (CellSearch) were considered to be HER2-amplified (HER2amp). Patients with ≥ 1 HER2amp CTC were eligible for the treatment phase (T-DM1 monotherapy). The primary endpoint was the overall response rate. RESULTS: In 154 screened patients, ≥ 1 and ≥ 5 CTC/7.5 ml of blood were detected in N = 118 (78.7%) and N = 86 (57.3%) patients, respectively. ≥1 HER2amp CTC was found in 14 patients (9.1% of patients with ≥ 1 CTC/7.5 ml). Among 11 patients treated with T-DM1, one achieved a confirmed partial response. Four patients had a stable disease as best response. Median PFS was 4.8 months while median OS was 9.5 months. CONCLUSIONS: CTC with HER2 amplification can be detected in a limited subset of HER2-negative MBC patients. Treatment with T-DM1 achieved a partial response in only one patient. TRIAL REGISTRATION: NCT01975142, Registered 03 November 2013.

French-style genetics v. 2.0: The "e-CohortE" project.

In the digital age, a genetics cohort has become much more than a simple means of determining the cause of a disease. Two-sided markets, of which 23andMe, Ancestry DNA and MyHeritage are the best known, have showed this perfectly over the last few years: a cohort has become a means of producing massive amounts of data for medical, scientific and commercial exploitation, and for genetic use in particular. French law does not currently allow these foreign private companies to develop on French national territory and also forbids the creation of similar entities in France. However, at least in theory, this same law does not preclude the creation of new types of cohorts in France inspired by the success of two-sided markets but retaining features specific to the French healthcare management system. We propose an optimal solution for France, for genomic studies associated with multi-subject questionnaires, still purely theoretical for the moment: the development, with no need for any change in the law, of France's own version of "Genetics v.2.0": "e-CohortE."

Comparison between two different algorithms used for pretreatment QA via aSi portal images.

Several algorithms exist to perform quality assurance for volumetric-modulated arc therapy (VMAT) treatments based on electronic portal imaging devices (EPID). These algorithms are used to compare doses (convert into water, GLAaS) and fluences (in amorphous silicon (aSi), Varian portal dosimetry). The aim of this study is to compare the two methods using clinical data. In this study, Varian portal dosimetry (VPD) and Epiqa solutions were compared. We used a same set of patient images data treated with 6 MV and 20 MV photon energies and different locations. The response of the portal imaging device was also investigated with different field sizes, monitor units, dose rates, sag effect, and linac daily output. All images were acquired on an electronic portal imaging device (EPID) positioned at source detector distance (SDD) of 100 cm. A virtual water phantom was used for Epiqa to calculate the dose matrices at the maximum depth doses dmax. The 2D gamma evaluation index (GAI) was performed to quantitatively compare the results given by the two solutions. The response of the EPID gave a good agreement with Epiqa (deviation less than 1%) for MU greater than 20 for both 6 MV and 20 MV photon energies. For VPD, the upward sloping trend showed a good agreement for MU higher than 50. Dose rate evaluations for both methods gave a deviation of, respectively, 0.4 and 0.5 % for 6 MV and 20 MV. The gamma criteria of 3 mm for distance to agreement and 3 % for dose difference was, as mean ± 1SD, 99.81% ± 1.48% and 99.42% ± 0.97% for VPD and Epiqa, respectively, for 6 MV photon energy. The mean values of the gamma criteria for the collected data using 20 MV photon energy were, respectively, 98.33% ± 2.41% and 98.12% ± 1.99% for VPD and Epiqa. The output constancy deviation correction (a 10 × 10cm² reference field plan to obtain absorbed dose despite the linac monitor daily variations) showed a mean deviation of, respectively, 0.07% ± 0.57% and 0.16% ± 1.38% for 6 MV and 20 MV photon energies. For sag effect, a slight improvement was noticed for realignment of the integrated image and was 0.25%± 0.69% for 6 MV and 0.40% ± 0.57% for 20 MV. The clinical data were used for pretreatment QA with the two systems, both VPD and Epiqa software, showed acceptable and similar results for low and high energies. Furthermore, Epiqa shows better linearity response for low MU.

Loss of heterozygosity at 13q13 and 14q32 predicts BRCA2 inactivation in luminal breast carcinomas.

BRCA2 is the major high-penetrance predisposition gene for luminal (estrogen receptor [ER] positive) breast cancers. However, many BRCA2 mutant carriers lack family history of breast/ovarian cancers and do not benefit from genetic testing. Specific genomic features associated with BRCA2 inactivation in tumors could help identify patients for whom a genetic test for BRCA2 may be proposed. A series of ER-positive invasive ductal carcinomas (IDCs) including 30 carriers of BRCA2 mutations and 215 control cases was studied by single-nucleotide polymorphism (SNP) arrays. Cases and controls were stratified by grade and HER2 status. Independently, 7 BRCA2 and 51 control cases were used for validation. Absolute copy number and Loss of heterozygosity (LOH) profiles were obtained from SNP arrays by the genome alteration print (GAP) method. BRCA2 tumors were observed to display a discriminatively greater number of chromosomal breaks calculated after filtering out and smoothing <3 Mb variations. This argues for a BRCA2-associated genomic instability responsible for long-segment aberrations. Co-occurrence of two genomic features-LOH of 13q13 and 14q32-was found to predict BRCA2 status with 90% of sensitivity and 87% of specificity in discovery series of high-grade HER2-negative IDCs and 100% of sensitivity and 88% of specificity in an independent series of 58 IDCs. Estimated positive predictive value was 17.2% (confidence interval: 6.7-33.5) in the whole series. In conclusion, the simplified BRCA2 classifier based on the co-occurrence of LOH at 13q13 and 14q32 could provide an indication to test for BRCA2 mutation in patients with ER-positive IDC.

Preliminary experience of whole-brain radiation therapy (WBRT) in breast cancer patients with brain metastases previously treated with bevacizumab-based chemotherapy.

We report our experience of bevacizumab-based chemotherapy (BBCT) followed by whole-brain radiation therapy (WBRT) for breast cancer (BC) patients (pts) with inoperable brain metastases (BM) or who refused surgery. This is a retrospective study of seven metastatic BC pts treated at the Institut Curie with at least one course of BBCT before WBRT, with a delay of ≤ 12 months between the two treatments. Toxicity was scored according to the common terminology criteria for adverse events (v4. 2010). Median age was 56 years (41-65). Median follow-up was 5.9 months (0.4-24.6). The median dose of bevacizumab was 10 mg/kg. Median number of cycles BBCT was six (5-17). Different chemotherapy regimens were used, the most common combination was paclitaxel-bevacizumab. WBRT was delivered in ten fractions, five fractions/week, for two weeks, to a total of 30 Gy. One pt underwent stereotactic radio surgery (SRS) after WBRT. No pt received BBCT during RT. Most common reported side-effects were nausea (n = 4), headache (n = 3), vomiting (n = 1), and vertigo (n = 3). All pts had mild or moderate grade ≤ 2 neurologic toxicity. There were no radiological signs of necrosis or cerebral ischemia. BBCT before WBRT was not associated with severe brain toxicity. Because of the limited number of pts, the different BBCT regimens, and important delays between treatments, these results must be confirmed prospectively.

Targeting poly(ADP-ribose) polymerase activity for cancer therapy.

Poly(ADP-ribosyl)ation is a ubiquitous protein modification found in mammalian cells that modulates many cellular responses, including DNA repair. The poly(ADP-ribose) polymerase (PARP) family catalyze the formation and addition onto proteins of negatively charged ADP-ribose polymers synthesized from NAD(+). The absence of PARP-1 and PARP-2, both of which are activated by DNA damage, results in hypersensitivity to ionizing radiation and alkylating agents. PARP inhibitors that compete with NAD(+) at the enzyme's activity site are effective chemo- and radiopotentiation agents and, in BRCA-deficient tumors, can be used as single-agent therapies acting through the principle of synthetic lethality. Through extensive drug-development programs, third-generation inhibitors have now entered clinical trials and are showing great promise. However, both PARP-1 and PARP-2 are not only involved in DNA repair but also in transcription regulation, chromatin modification, and cellular homeostasis. The impact on these processes of PARP inhibition on long-term therapeutic responses needs to be investigated.

Management of phyllodes breast tumors.

Phyllodes tumors are a rare distinctive fibroepithelial tumors of the breast and their management continues to be questioned. The aim of our study was to examine the treatment and outcome of 165 patients with phyllodes tumors and to review the options for surgical management. This is a retrospective study of 165 patients who presented to the Institut Curie between January 1994 and November 2008 for benign, borderline or malignant phyllodes tumors. The median follow-up was 12.65 months [range 0-149.8]. The median age at diagnosis was 44 years [range 17-79]. One hundred and sixty patients (97%) had breast-conserving treatment, of whom 3 patients (1.8%) had oncoplastic breast surgery. Younger women had a significantly higher chance of having a benign phyllodes tumor (p = 0.0001) or a tumor of small size (p < 0.0001). Histologic examination showed 114 benign (69%), 37 borderline (22%) and 14 malignant tumors (9%). The median tumor size was 30 mm [range 5-150]. The tumor margins were considered incomplete (< 10 mm) in 46 out of 165 cases (28%) with 52% revision surgery. Only the tumor grade was a significant risk factor for incomplete tumor margins (p = 0.005). Fifteen patients developed local recurrence (10%) and two, metastases. In univariate analysis, the histologic grade (p = 0.008), and tumor size (p = 0.02) were significative risk factors for local recurrence with an accentuated risk for "borderline" tumors and tumors of large size.).Similar results were obtained using multivariate analysis (p = 0.07). The mainstay of treatment for phyllodes tumors remains excision with a safe surgical margin, taking advantage breast conserving surgery where amenable. For borderline or malignant phyllodes tumors or in cases of local tumor recurrence, mastectomy, and immediate breast reconstruction may become the preferred option. Genetic analysis will potentially supplement classical histologic examination in order to improve our management of these tumors. The role of adjuvant treatments is unproven and must be considered on a case-by-case basis.

Radiotherapy for gastric mucosa-associated lymphoid tissue lymphoma.

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a rare disease which is often associated with Helicobacter pylori (H. pylori) infection. First-line treatment of stage IE and IIE localized gastric MALT lymphoma is based on the eradication of H. pylori. The presence of H. pylori resistance factors such as translocation t (11;18), peri-gastric lymph node involvement and the degree of tumor infiltration of the gastric wall; or lack of response to antibiotic therapy are two main indications to treat with definitive radiotherapy (RT). RT is an effective treatment in localized gastric MALT lymphoma. A moderate dose of 30 Gy allows a high cure rate while being well tolerated. After treatment, regular gastric endoscopic follow-up is necessary to detect a potential occurrence of gastric adenocarcinoma.

Is There a Benefit of Oxaliplatin in Combination with Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer? An Updated Meta-Analysis.

BACKGROUND: Neoadjuvant fluoropyrimidine (5FU or capecitabine)-based chemoradiotherapy (CRT) has been considered the standard of care for locally advanced rectal cancer (LARC). Whether addition of oxaliplatin (OXP) will further improve clinical outcomes is still unclear. METHODS: To identify clinical trials combining oxaliplatin in preoperative CRT or perioperative chemotherapy for LARC published until March 2021, we searched PubMed and the Cochrane Library. We also searched for relevant ASCO conference abstracts. The primary endpoint was disease-free survival (DFS). Data were extracted from every study to perform a meta-analysis using Review Manager (version 5.3). RESULTS: A total of seven randomized clinical trials (ACCORD-12, CARO-AIO-04, FOWARC, JIAO, NSABP, PETACC-6, and STAR-01) with 5782 stage II or III rectal cancer patients were analyzed, including 2727 patients with OXP + 5FU regimen and 3055 patients with 5FU alone. Compared with the 5FU alone group, the OXP + 5FU regimen improved DFS (HR = 0.90, 95% CI: 0.81-0.99, p = 0.03) and pathologic complete response (pCR) (OR = 1.21, 95% CI: 1.07-1.37, p = 0.002). Patients treated with the OXP + 5FU regimen had significantly less metastatic progression (OR = 0.79; 95% CI, 0.67 to 0.94; p = 0.007). Considering adverse events (AEs), there was more grade 3-4 diarrhea with OXP + 5FU (OR = 2.41, 95% CI: 1.74-3.32, p < 0.00001). However, there were no significant differences grade 3-4 hematologic AEs (OR = 1.16, 95% CI: 0.87-1.57, p = 0.31). CONCLUSIONS: Our meta-analysis with long-term results from the randomized studies showed a benefit of the addition of OXP + 5FU regiment in terms of DFS, metastatic progression, and pCR rate that did not translate to improved OS.

Clinical practice guidelines for BRCA1 and BRCA2 genetic testing.

BRCA1 and BRCA2 gene pathogenic variants account for most hereditary breast cancer and are increasingly used to determine eligibility for PARP inhibitor (PARPi) therapy of BRCA-related cancer. Because issues of BRCA testing in clinical practice now overlap with both preventive and therapeutic management, updated and comprehensive practice guidelines for BRCA genotyping are needed. The integrative recommendations for BRCA testing presented here aim to (1) identify individuals who may benefit from genetic counselling and risk-reducing strategies; (2) update germline and tumour-testing indications for PARPi-approved therapies; (3) provide testing recommendations for personalised management of early and metastatic breast cancer; and (4) address the issues of rapid process and tumour analysis. An international group of experts, including geneticists, medical and surgical oncologists, pathologists, ethicists and patient representatives, was commissioned by the French Society of Predictive and Personalised Medicine (SFMPP). The group followed a methodology based on specific formal guidelines development, including (1) evaluating the likelihood of BRCAm from a combined systematic review of the literature, risk assessment models and expert quotations, and (2) therapeutic values of BRCAm status for PARPi therapy in BRCA-related cancer and for management of early and advanced breast cancer. These international guidelines may help clinicians comprehensively update and standardise BRCA testing practices.

Patient Satisfaction with Fentanyl Pectin Nasal Spray in Breakthrough Cancer Pain Management During Radiotherapy for Head and Neck Cancer.

OBJECTIVE: The severity of breakthrough cancer pain (BTcP) impacts patients' quality of life, increases the risk of anxiety and depression, lowers functional capacities, and may lead to poor compliance with cancer treatments. The aim of the current study was to assess, in a real-life setting, patient satisfaction with a fentanyl-pectin-nasal-spray (FPNS) for BTcP management in head and neck (H&N) cancer patients treated by radiotherapy. MATERIALS AND METHODS: This non-interventional, prospective study was conducted in 92 adult H&N-cancer patients undergoing radiotherapy and who started FPNS treatment for BTcP. Throughout the radiotherapy period, the patients completed self-diaries to assess their BTcP episodes, FPNS use, satisfaction on FPNS efficiency (primary outcome), tolerability and ease of use. RESULTS: Prior to FPNS treatment, 86% of the patients were experiencing ≤4 BTcP episodes/day. During the radiotherapy period, the BTcP episodes were treated with a median dose of 100µg of FPNS. Patients were "satisfied/very-satisfied" with the efficiency (73% of assessments), ease of use (87% of assessments) and tolerability (87% of assessments) of FPNS. In total, 27% of patients reported at least one adverse event related to FPNS and 4% of patients discontinued treatment due to adverse events. None of the adverse events were serious. Patient quality of life was maintained throughout the radiotherapy period. CONCLUSION: This study showed, in a real-life setting, that a clear majority of H&N cancer patients treated with FPNS for BTcP throughout radiotherapy expressed satisfaction with this analgesic treatment.

Tumor aromatase expression as a prognostic factor for local control in young breast cancer patients after breast-conserving treatment.

INTRODUCTION: We sought to determine whether the levels of expression of 17 candidate genes were associated with locoregional control after breast-conserving treatments of early-stage breast cancers in young, premenopausal women. METHODS: Gene expression was measured by using RT-PCR in the breast tumors of a series of 53 young (younger than 40 years), premenopausal patients. All treatments consisted of primary breast-conserving surgery followed by whole-breast radiotherapy (+/- regional lymph nodes) with or without systemic treatments (chemotherapy +/- hormone therapy). The median follow-up was 10 years. RESULTS: The 10-year locoregional control rate was 70% (95% CI, 57% to 87%). In univariate analysis, no clinical/pathologic prognostic factors were found to be significantly associated with decreased locoregional control. Expression of three genes was found to be significantly associated with an increased locoregional recurrence rate: low estrogen-receptor beta, low aromatase, and high GATA3. Two others were associated with only a trend (P < 0.10): low HER1 and SKP2. In multivariate analysis, only the absence of aromatase was significantly associated with an increased locoregional recurrence rate (P = 0.003; relative risk = 0.49; 95% CI 0.29 to 0.82). CONCLUSIONS: Recent data give credit to the fact that breast cancer in young women is a distinct biologic entity driven by special oncogenic pathways. Our results highlight the role of estrogen-signaling pathways (mainly CYP19/aromatase, GATA3, and ER-beta) in the risk of locoregional recurrence of breast cancer in young women. Confirmation in larger prospective studies is needed.

Urokinase-type plasminogen activator and plasminogen-activator-inhibitor type 1 predict metastases in good prognosis breast cancer patients.

UNLABELLED: This retrospective analysis was designed to confirm the predictive role of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type I (PAI-1) in the outcome of early stage, node-negative breast cancer patients. PATIENTS AND METHODS: Node-negative patients having not received adjuvant chemotherapy, and for whom frozen samples were available, were selected. RESULTS: Among the 169 patients included, 56.8% presented with uPA >3 ng/mg of proteins and/or PAI-1 >14 ng/mg of proteins. The median follow-up was 73 months. Significant correlations were found between uPA and disease-free survival (p [univariate]=0.003; p [multivariate]=0.01), and between uPA, PAI-1, and uPA plus PAI-1 and distant relapses (p=0.002). No significant correlation was found between uPA/PAI-1 and the risk of locoregional recurrence. CONCLUSION: This study demonstrated that uPA and PAI-1 are useful predictors of distant metastases in a subset of early stage, node-negative breast cancer patients.

Stereotactic prostate focal reirradiation therapy for local recurrence: preliminary results of Hartmann Oncology Radiotherapy Group.

OBJECTIVE: Our objective was to report our experience and to evaluate the feasibility and toxicity of focal salvage stereotactic body radiation therapy (SBRT) in patients with post-radiation local recurrence of prostate cancer. METHODS: We retrospectively reviewed medical records of patients treated with Cyberknife ® between October 2014 and April 2017 at our institution for a focal reirradiation delivered to the prostate/prostatic bed for local recurrence after radical or adjuvant radiotherapy. All patients underwent prostate biopsies at recurrence at the time of fiducial markers placement, had choline PET/CT and pelvic MRI. The treatment consisted in 36 Gy in six fractions delivered every other day. Post reirradiation toxicities were assessed according to the CTCAE v4 (Common Terminology Criteria for Adverse Events). RESULTS: 42 patients were treated with followed with a median follow-up of 21 months (range 3 - 31). 34 patients had biopsy proven recurrence. The initial treatment was radical prostatectomy and radiation therapy for 9 patients and radiation therapy alone for 33 patients. 23 patients from the group of prostate reirradiation had placement of rectal spacers. No Grade 4 or 5 toxicity were observed. 27 acute urinary events were recorded: 18 patients experienced Grade 1, 9 patients experienced Grade 2 toxicity and 1 patient experienced Grade 3 urinary toxicity, namely cystitis and/or dysuria. No Grade 2 or more digestive toxicity was observed. Rectal doses were significantly lower with rectal spacers. CONCLUSION: Salvage focal Cyberknife ® seems feasible and show promising results. ADVANCES IN KNOWLEDGE: SBRT for local prostate cancer recurrence after initial radiotherapy is well tolerated with short follow-up.

A Wake-Up Call for Routine Morbidity and Mortality Review Meeting Procedures as Part of a Quality Governance Programs in Radiation Therapy Departments: Results of the PROUST Survey.

PURPOSE: Morbidity and mortality review (MMR) meetings in radiation therapy (RT) departments aim to monitor radiation-induced toxicities and identify potential factors that may be correlated with their development and severity, particularly treatment planning errors. The aims of the Prospective Registration of Morbidity and Mortality, Individual Radiosensitivity and Radiation Technique (PROUST) survey were to make an inventory of existing MMR procedures and to describe their procedures. METHODS AND MATERIALS: The link to the web-based questionnaire of the PROUST survey was sent to 351 radiation oncologists working at 172 centers. The questionnaire included items related to organization, frequency, membership, governance, reasons for nonimplementation of MMR, and interest in its creation. RESULTS: As of July 2017, 108 responses had been received from the 172 centers, of which 107 responses were completed for analysis. All centers declared that they had initiated a quality assurance program in their department, including implementation of feedback committees dedicated to the registration, analysis, and correction of precursor events. Less than half of the centers (47%) had implemented MMR procedures. However, there was significant confusion regarding feedback committees in a majority of the centers. MMRs were organized every 6 and 12 months in 21% and 15%, respectively, of the centers. In 60% of the centers, toxicity grade ≥3 was the main reason for the MMR initiation. In routine practice, contouring and dosimetry files were reviewed by 66% and 83%, respectively, of centers practicing MMR. However, only 40% of the centers enrolled data in a registry dedicated to surveillance. Finally, 78% of centers expressed interest in initiating a consensual procedure. CONCLUSIONS: MMRs are not systematically implemented in RT departments worldwide. In France and in Europe, few departments with quality assurance programs have implemented MMRs. This survey showed that a large majority of centers are interested in implementing an MMR with a formalized procedure. Our project could help increase the interest of the RT community worldwide in this topic.

Safety and efficacy of fiducial marker implantation for robotic stereotactic body radiation therapy with fiducial tracking.

PURPOSE: The purpose of this study was to assess the feasibility, efficacy and toxicity of fiducial marker implantation and tracking in CyberKnife® stereotactic radiation therapy (SBRT) applied to extracranial locations. MATERIALS AND METHOD: This is a retrospective, single-centre, observational study to collect the data of all patients treated by stereotactic radiation therapy with fiducial marker tracking at extracranial locations, conducted between June 2014 and November 2017. Information regarding the implantation procedure, the types of toxicity related to marker implantation and the number of markers implanted/tracked during treatment were collected. Complication rates were evaluated using the CTCAE v4 [Common Terminology Criteria for Adverse Events] scale. The technical success rate was based on the ability to optimally track the tumor throughout all treatment fractions. RESULTS: Out of 2505 patients treated by stereotactic radiation therapy, 25% received treatment with fiducial marker tracking. The total number of implantation procedures was 616 and 1543 fiducial markers were implanted. The implantation-related complication rate was 3%, with 16 Grade 1 events and 4 Grade 2 events. The number of treated patients and the number of implanted markers has gradually increased since the technique was first implemented. The median treatment time was 27 min (range 10-76). 1295 fiducials were effectively tracked throughout all treatment fractions, corresponding to a technical success rate of 84%. The difference between the number of fiducials implanted and those tracked during treatment decreased significantly as the site's experience increased. CONCLUSION: Fiducial marker implantation and tracking is feasible, well-tolerated, and technically effective technique in SBRT for extracranial tumors.

How to boost the breast tumor bed? A multidisciplinary approach in eight steps.

PURPOSE: To describe a new procedure for breast radiotherapy that will improve tumor bed localization and radiotherapy treatment using a multidisciplinary approach. PATIENTS AND METHODS: This pilot study was conducted by departments of radiation oncology, surgery, and radiology. A new procedure has been implemented, summarized as eight steps: from pre-surgery contrast CT to surgery, tumor bed planning target volume (PTV) determination, and finally breast and tumor bed irradiation. RESULTS: Twenty patients presenting with T1N0M0 tumors were enrolled in the study. All patients underwent lumpectomy with the placement of surgical clips in the tumor bed region. During surgery, 1 to 5 clips were placed in the lumpectomy cavity before the plastic procedure. All patients underwent pre- and postoperative CT scans in the treatment position. The two sets of images were registered with a match-point registration. All volumes were contoured and the results evaluated. The PTV included the clips region, the gross tumor volume, and the surgical scar, with an overall margin of 5-10 mm in all directions, corresponding to localization and setup uncertainties. For each patient the boost PTV was discussed and compared with our standard forward-planned PTV. CONCLUSIONS: We demonstrate the feasibility of a tumor bed localization and treatment procedure that seems adaptable to routine practice. Our study shows the advantages of a multidisciplinary approach for tumor bed localization and treatment. The use of more than 1 clip associated with pre- to postoperative CT image registration allows better definition of the PTV boost volume.

Postmastectomy electron beam chest wall irradiation in women with breast cancer: a clinical step toward conformal electron therapy.

PURPOSE: Electron beam radiotherapy of the chest wall with or without lymph node irradiation has been used at the Institut Curie for >20 years. The purpose of this report was to show the latest improvements of our technique developed to avoid hot spots and improve the homogeneity. METHODS AND MATERIALS: The study was split into two parts. A new electron irradiation technique was designed and compared with the standard one (dosimetric study). The dose distributions were calculated using our treatment planning software ISIS (Technologie Diffusion). The dose calculation was performed using the same calculation parameters for the new and standard techniques. Next, the early skin toxicity of our new technique was evaluated prospectively in the first 25 patients using Radiation Therapy Oncology Group criteria (clinical study). RESULTS: The maximal dose found on the five slices was 53.4 +/- 1.1 Gy for the new technique and 59.1 +/- 2.3 Gy for the standard technique. The hot spots of the standard technique plans were situated at the overlap between the internal mammary chain and chest wall fields. The use of one unique field that included both chest wall and internal mammary chain volumes solved the problem of junction. To date, 25 patients have been treated with the new technique. Of these patients, 12% developed Grade 0, 48% Grade 1, 32% Grade 2, and 8% Grade 3 toxicity. CONCLUSIONS: This report describes an improvement in the standard postmastectomy electron beam technique of the chest wall. This new technique provides improved target homogeneity and conformality compared with the standard technique. This treatment was well tolerated, with a low rate of early toxicity events.