Radiation therapy of the primary tumour and oligometastatic sites in patients with breast cancer with synchronous metastases: A literature review.

De novo metastatic breast cancer represents 5 to 8% of all breast cancers (2500 new cases per year in France). Systemic treatment is the cornerstone of treatment, whereas radiation therapy usually has a palliative intent. Advances in systemic and local treatments (surgery and radiation therapy) have substantially improved overall survival. In the recent breast cancer statistics in the United States, the 5-year relative survival for patients diagnosed during 2012-2018 was 29% for stage IV (Breast Cancer Statistics). Thus, an increasing proportion of metastatic breast cancers present a prolonged complete response to systemic therapy, which raises the question of the impact of local treatment on patient survival. Radiation therapy has shown its value for early breast cancer, but its place in the local management of the primary tumour or oligometastatic sites for de novo metastatic breast cancer remains under debate. This article is a literature review assessing the role of radiation therapy directed to the primary tumour and oligometastatic sites of breast cancer in patients with synchronous metastases, in order to highlight clinicians in their therapeutic decision.

Radiation therapy in the thoracic region: Radio-induced cardiovascular disease, cardiac delineation and sparing, cardiac dose constraints, and cardiac implantable electronic devices.

Radiation therapy in the thoracic region may deliver incidental ionizing radiation to the surrounding healthy structures, including the heart. Radio-induced heart toxicity has long been a concern in breast cancer and Hodgkin's lymphoma and was deemed a long-term event. However, recent data highlight the need to limit the dose to the heart in less favorable thoracic cancers too, such as lung and esophageal cancers in which incidental irradiation led to increased mortality. This article will summarize available cardiac dose constraints in various clinical settings and the types of radio-induced cardiovascular diseases encountered as well as delineation of cardiac subheadings and management of cardiac devices. Although still not completely deciphered, heart dose constraints remain intensively investigated and the mean dose to the heart is no longer the only dosimetric parameter to consider since the left anterior descending artery as well as the left ventricle should also be part of dosimetry constraints.

Aqua polo: Preliminary feasibility and efficacy study of a programme of adapted, supervised water polo to reduce fatigue and improve women's psychological and social recovery after breast cancer treatment: A mixed-methods design.

Physical activity has been shown to have many benefits, including reducing cancer-related fatigue (CRF) and improving psychological and physical recovery from breast cancer. Some authors have shown the benefits of aquatic practice, while others have detailed the benefits of group and supervised practice. We hypothesize that an innovative sports coaching proposal could allow a significant adherence of patients and contribute to their health improvement. The main objective is to study the feasibility of an adapted water polo programme (aqua polo) for women after breast cancer. Secondarily we will analyse the effect of such a practice on patients' recovery and study the relationship between coaches and participants. The use of mixed methods will allow us to question the underlying processes precisely. This is a prospective, non-randomized, monocentric study with a sample of 24 breast cancer patients after treatment. The intervention is a 20 week programme (1 session per week) of aqua polo in a swim club facility, supervised by professional water-polo coaches. The variables measured are patient participation, quality of life (QLQ BR23), CRF (R-PFS) and post-traumatic growth (PTG-I) as well as different variables to observe physical capacity (strength with dynamometer, step-test and arm amplitude). The quality of the coach-patient relationship will be evaluated (CART-Q) to explore its dynamics. Participatory observations and interviews will be carried out to report on the interactions between the coach and the participants during the sessions. Registration number and name of trial registry: No. EudraCT or ID-RCB: 2019-A03003-54 and NCT: NCT04235946.

[What do we need to deliver "online" adapted radiotherapy treatment plans?] / Que faut-il pour faire de la radiothérapie adaptative « online ¼ ?

During the joint SFRO/SFPM session of the 2019 congress, a state of the art of adaptive radiotherapy announced a strong impact in our clinical practice, in particular with the availability of treatment devices coupled to an MRI system. Three years later, it seems relevant to take stock of adaptive radiotherapy in practice, and especially the "online" strategy because it is indeed more and more accessible with recent hardware and software developments, such as coupled accelerators to a three-dimensional imaging device and algorithms based on artificial intelligence. However, the deployment of this promising strategy is complex because it contracts the usual time scale and upsets the usual organizations. So what do we need to deliver adapted treatment plans with an "online" strategy?

Radio-induced cardiotoxicity: From physiopathology and risk factors to adaptation of radiotherapy treatment planning and recommended cardiac follow-up.

Cancer and cardiovascular disease (CVD) are the leading cause of mortality worldwide, and breast cancer (BC) the most common malignancy affecting women worldwide. Radiotherapy is an important component of BC treatment and participates in CVD occurrence. It seems, therefore, crucial to gather both radiation oncology and cardiology medical fields to improve the follow-up quality of our BC patients. This review aims at updating our knowledge regarding cardiotoxicities risk factors, and consequently, doses constraints in case of 3D-conformal and IMRT treatment planning. Then we will develop how to reduce cardiac exposure and what kind of cardiac follow-up we could recommend to our breast cancer patients.

Role of radiation therapy in brain metastases management.

The challenge of the management of brain metastases has not finished yet. Although new diagnosis-specific prognostic assessment classifications and guidelines for patients with brain metastases help to guide treatment more appropriately, and even if the development of modern technologies in imaging and radiation treatment, as well as improved new systemic therapies, allow to reduce cognitive side effects and make retreatment or multiple and combined treatment possible, several questions remain unanswered. However, tailoring the treatment to the patient and his expectations is still essential; in other words, patients with a poor prognosis should not be over-treated, and those with a favorable prognosis may not be subtracted to the best treatment option. Some ongoing trials with appropriate endpoints could better inform our choices. Finally, a case-by-case inter-disciplinary discussion remains essential.

A 1-year survey of catheter-related infections in a pediatric university hospital: A prospective study.

BACKGROUND: Central venous catheters (CVCs) provide a great comfort for hospitalized children. However, CVCs increase the risk of severe infection. As there are few data regarding pediatric epidemiology of catheter-related infections (CRIs), the main objective of this study was to measure the incidence rate of CRIs in our pediatric university hospital. We also sought to characterize the CRIs and to identify risk factors. MATERIALS AND METHODS: We conducted an epidemiological prospective monocentric study including all CVCs, except Port-a-Caths and arterial catheters, inserted in children from birth to 18 years of age between April 2015 and March 2016 in the pediatric University Hospital of Nantes. Our main focus was the incidence rate of CRIs, defined according to French guidelines, while distinguishing between bloodstream infections (CRBIs) and non-bloodstream infections (CRIWBs). The incidence rate was also described for each pediatric ward. We analyzed the association between infection and potential risk factors using univariate and multivariate analysis by Cox regression. RESULTS: We included 793 CVCs with 60 CRBIs and four CRIWBs. The incidence rate was 4.6/1000 catheter-days, with the highest incidence rate occurring in the neonatal intensive care unit (13.7/1000 catheter-days). Coagulase-negative staphylococci were responsible for 77.5% of the CRIs. Factors independently associated with a higher risk of infection in neonates were invasive ventilation and low gestational age. CONCLUSIONS: The incidence of CRIs in children hospitalized in our institution appears to be higher than the typical rate of CRIs reported in the literature. This was particularly true for neonates. These results should lead us to reinforce preventive measures and antibiotic stewardship but they also raise the difficulty of diagnosing with certainty CRIs in neonates.

Pelvic exenterations for gynecologic cancers: A retrospective analysis of a 30-year experience in a cancer center.

INTRODUCTION: The objective of this study was to report a 30-year experience of PE for gynecologic malignancies in a cancer center. MATERIALS AND METHODS: A retrospective study was conducted at Institut Paoli-Calmette including patients who underwent PE for gynecologic malignancies. Four periods were evaluated: P1 before 1992, P2 between 1993 and 1999, P3 between 2000 and 2006 and P4 after 2006. The study evaluated the number of PE performed during each period, the type of PE, its level, indication, location of the primary tumor, patient age, previous radiotherapy ≥45 Gy, the rate of "curative" PE and exenteration-related reconstructive techniques. 90-day post-operative mortality and morbidity using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) v 4.03 were reported. RESULTS: 277 PE were performed. The number of PE performed for recurrences rose during the study period (p = 0.042), PE performed for central tumors increased during P3 (64.4%) and P4 (67.4%) (p < 0.0001) and administration of radiotherapy ≥45 Gy was more frequent (p < 0.0001). The rate of "curative" PE increased (p < 0.0001). In multivariate analysis, "curative" PE were correlated with PE type, central locations and study period. Pelvic filling was progressively more frequently performed (p = 0.002). 90-day complication rate was 56.3%. In multivariate analysis there was a significant difference in distribution of CTCAE grade 3-4-5 morbidity depending on the period. Overall survival (OS) improved during the 2 last periods (p = 0.008). CONCLUSION: A better selection of eligible patients for PE, namely through improvement in imaging techniques, has enabled to raise the rate of curative PE.

Combined irradiation and targeted therapy or immune checkpoint blockade in brain metastases: toxicities and efficacy.

BACKGROUND: Targeted therapies (TT) and immune checkpoint inhibitors (ICI) are currently modifying the landscape of metastatic cancer management and are increasingly used over the course of many cancers treatment. They allow long-term survival with controlled extra-cerebral disease, contributing to the increasing incidence of brain metastases (BMs). Radiation therapy remains the cornerstone of BMs treatment (either whole brain irradiation or stereotactic radiosurgery), and investigating the safety profile of radiation therapy combined with TT or ICI is of high interest. Discontinuing an efficient systemic therapy, when BMs irradiation is considered, might allow systemic disease progression and, on the other hand, the mechanisms of action of these two therapeutic modalities might lead to unexpected toxicities and/or greater efficacy, when combined. PATIENTS AND METHODS: We carried out a systematic literature review focusing on the safety profile and the efficacy of BMs radiation therapy combined with targeted agents or ICI, emphasizing on the role (if any) of the sequence of combination scheme (drug given before, during, and/or after radiation therapy). RESULTS: Whereas no relevant toxicity has been noticed with most of these drugs, the concomitant use of some other drugs with brain irradiation requires caution. CONCLUSION: Most of available studies appear to advocate for TT or ICI combination with radiation therapy, without altering the clinical safety profiles, allowing the maintenance of systemic treatments when stereotactic radiation therapy is considered. Cognitive functions, health-related quality of life and radiation necrosis risk remain to be assessed. The results of prospective studies are awaited in order to complete and validate the above discussed retrospective data.

Survival after breast cancer local recurrence according to therapeutic strategies.

AIMS: To compare survival outcomes after mastectomy (Mt) and lumpectomy plus interstitial brachytherapy (LpIB) in the treatment of breast cancer local recurrence (LR) occurring after conservative surgery. METHODS: Medical records of patients treated for an isolated LR from January 1, 1981 to December 31, 2009 were reviewed. To overcome the bias due to the fact that treatment choice (Mt or LpIB) was based on prognostic factors with LpIB proposed preferentially to women with good prognosis, Mt and LpIB populations were matched and compared with regard to overall survival (OS) and metastasis free survival (MFS). RESULTS: Among 348 patients analyzed, 66.7% underwent Mt, 17.8% LpIB and 15.5% Lp alone. After a median follow-up of 73.3 months, 65 patients had died (42/232 Mt, 8/62 LpIB, 15/54 Lp). Before matching, OS and MFS at 5 years were significantly better in the LpIB compared to the Mt group, due to significantly more frequent poor prognostic factors in the latter (p = 0,07 and p = 0,09 respectively, log-rank significance limit of 10%). After matching, the benefits of LpIB disappeared since MFS and OS rates were not significantly different in both groups (p = 0.68 and 0.88 respectively). After LpIB, the second LR rate was 17% at 5 years and 30% at 10 years. CONCLUSION: A second conservative breast cancer treatment associating lumpectomy and interstitial brachytherapy is possible for selected patients with LR, without decrease in neither OS nor MFS compared to mastectomy.

Pathological complete response in invasive breast cancer treated by skin sparing mastectomy and immediate reconstruction following neoadjuvant chemotherapy and radiation therapy: Comparison between immunohistochemical subtypes.

CONTEXT: Even if neoadjuvant chemotherapy (NACT) and oncoplastic techniques have increased the breast conserving surgery rate, mastectomy is still a standard for multifocal or extensive breast cancers (BC). In the prospect of increasing breast reconstruction, an alternative therapeutic protocol was developed combining NACT with neoadjuvant radiation therapy (NART), followed by mastectomy with immediate breast reconstruction (IBR). The oncological safety of this therapeutic plan still needs further exploration. We assessed pathological complete response (pCR) as a surrogate endpoint for disease free survival. METHODS: Between 2010 and 2016, 103 patients undergoing mastectomy after NACT and NART were recruited. After CT and RT were administrated, a completion mastectomy with IBR by latissimus dorsi flap was achieved 6 to 8 weeks later. pCR was defined by the absence of residual invasive disease in both nodes and breast. Histologic response was analyzed for each immunohistochemical subset. RESULTS: pCR was obtained for 53.4% of the patients. This pCR rate was higher in hormonal receptor negative (HER2 and triple negative) patients when compared to luminal tumours (69.7% vs 45.7%, p=0.023). DISCUSSION: The pCR rate found in this study is higher than those published in studies analyzing NACT (12.5%-27.1%). This can be explained by the combination of anthracycline and taxane, the use of trastuzumab when HER2 was overexpressed but also by RT associated to NACT. CONCLUSION: Inverting the sequence protocol for BC, requiring both CT and RT, allows more IBR without diminishing pCR and should therefore be considered as an acceptable therapeutic option.

Highly favorable outcome in BRCA-mutated metastatic breast cancer patients receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation.

Breast cancer carrying BRCA mutation may be highly sensitive to DNA-damaging agents. We hypothesized a better outcome for BRCA-mutated (BRCA(mut)) metastatic breast cancer (MBC) patients receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HDC AHSCT) versus unaffected BRCA (BRCA wild type; (BRCA(wt))) or patients without documented BRCA mutation (BRCA untested (BRCA(ut))). All female patients treated for MBC with AHSCT at Institut Paoli-Calmettes between 2003 and 2012 were included. BRCA(mut) and BRCA(wt) patients were identified from our institutional genetic database. Overall survival (OS) was the primary end point. A total of 235 patients were included. In all, 15 patients were BRCA(mut), 62 BRCA(wt) and 149 BRCA(ut). In multivariate analyses, the BRCA(mut) status was an independent prognostic factor for OS (hazard ratio (HR): 3.08, 95% confidence interval (CI): 1.10-8.64, P=0.0326) and PFS (HR: 2.52, 95% CI :1.29-4.91, P=0.0069). In this large series of MBC receiving HDC AHSCT, we report a highly favorable survival outcome in the subset of patients with documented germline BRCA mutations.

Immunohistochemical subtypes predict the clinical outcome in high-risk node-negative breast cancer patients treated with adjuvant FEC regimen: results of a single-center retrospective study.

BACKGROUND: Anthracycline-based adjuvant chemotherapy improves survival in patients with high-risk node-negative breast cancer (BC). In this setting, prognostic factors predicting for treatment failure might help selecting among the different available cytotoxic combinations. METHODS: Between 1998 and 2008, 757 consecutive patients with node-negative BC treated in our institution with adjuvant FEC (5FU, epirubicin, cyclophosphamide) chemotherapy were identified. Data collection included demographic, clinico-pathological characteristics and treatment information. Molecular subtypes were derived from estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status and Scarff-Bloom-Richardson (SBR) grade. Disease-free survival (DFS), distant disease-free survival (DDFS) and overall survival (OS) were estimated using the Kaplan-Meier Method, and prognostic factors were examined by multivariate Cox analysis. RESULTS: After a median follow-up of 70 months, the 5-year DFS, DDFS and OS were 90.6 % (95 % confidence interval (CI): 88.2-93.1), 92.8 % (95 % CI: 90.7-95) and 95.1 % (95 % CI, 93.3-96.9), respectively. In the multivariate analysis including classical clinico-pathological parameters, only grade 3 maintained a significant and independent adverse prognostic impact. In an alternative multivariate model where ER, PR and grade were replaced by molecular subtypes, only luminal B/HER2-negative and triple-negative subtypes were associated with reduced DFS and DDFS. CONCLUSIONS: Node-negative BC patients receiving adjuvant FEC regimen have a favorable outcome. Luminal B/HER2-negative and triple-negative subtypes identify patients with a higher risk of treatment failure, which might warrant more aggressive systemic treatment.

Calcifications and tungsten deposits after breast-conserving surgery and intraoperative radiotherapy for breast cancer.

AIM: To describe the presence of atypical calcifications on post-operative mammography after breast-conserving surgery (BCS) and intraoperative radiotherapy (IORT). MATERIALS AND METHODS: We retrospectively include all patients followed after BCS and IORT for breast cancer (n=271). All follow-up mammograms at 6 months after surgery were retrospectively evaluated by two board-certified radiologists. The radiologists had to notify the presence or the absence of atypical calcifications. RESULTS: Five patients had on follow-up mammography the presence of atypical calcifications. Two patients had a stereotactic breast biopsy. The pathologic examination showed the presence of small tungsten particles located in the breast parenchyma. CONCLUSION: The presence of atypical calcifications after BCS and IORT, presenting as multiple, scattered, round calcifications, should be rated as BIRADS 2 and do not require biopsy. They corresponded on tungsten deposits.

[Is there a rationale for regional node irradiation in pN1mi and pN0(i+) breast tumours?]. / Y a-t-il un rationnel pour irradier les aires ganglionnaires des tumeurs du sein de stades pN1mi et pN0(i+)?

The advent of sentinel lymph node technique has led to a shift in lymph node staging, due to the emergence of new entities, namely micrometastases and isolated tumour cells. In addition, the therapeutic role of axillary lymph node dissection is more and more questioned and radiotherapy has been shown to be equivalent to complementary axillary lymph node dissection in patients without clinical node involvement. This article looks at the literature in favour of performing axillary irradiation in patients with pN1mi stage breast cancer who have undergone a mastectomy without a complementary axillary lymph node dissection, and in favour of abstention of any further treatment of the axilla in patients with pN0(i+) or pN1mi tumours who have undergone breast conserving surgery and a sentinel lymph node procedure followed by systemic treatment. The impact of regional lymph nodes irradiation in case of axillary involvement 2mm or less is also discussed.

[Global brain metastases management strategy: a multidisciplinary-based approach]. / Stratégie globale de prise en charge des métastases cérébrales: une approche multidisciplinaire.

Brain metastases management has evolved over the last fifteen years and may use varying strategies, including more or less aggressive treatments, sometimes combined, leading to an improvement in patient's survival and quality of life. The therapeutic decision is subject to a multidisciplinary analysis, taking into account established prognostic factors including patient's general condition, extracerebral disease status and clinical and radiological presentation of lesions. In this article, we propose a management strategy based on the state of current knowledge and available therapeutic resources.

[Supportive care, cognition and quality of life in brain metastases]. / Soins de support, cognition, qualité de vie et métastases cérébrales.

Brain metastases impact on the survival of the patients, but on their quality of life as well. The objective of the management of these patients is then double. Currently, due to medical advances, survivals tend to improve, especially for some tumor subtypes. During the course of the disease, different neurological signs and symptoms can be observed according to the location, the number and the volume of the metastase(s). Patients and caregivers are especially worried about the loss of autonomy and cognitive impairments. A permanent dialogue, during the course of the disease, is mandatory, in order to adapt the management to the objectives determined by the patients and the medical team. These objectives may vary according to the objective response rates of the disease to anticancer therapies, according to the impact of the disease and its management in daily living. Anticancer therapies and supportive care must be appreciated according to their impact on the survival, on the preservation of the functional independence and the quality of life of the patient, on their abilities to preserve the neurological status and delay the apparition of new neurological signs and symptoms, and their adverse events. Supportive care, cognition and quality of life should be regularly evaluated and adapted according to the objectives of the management of brain metastases patients. Different approaches are described in this paper.