Seroconversion and Abundance of IgG Antibodies against S1-RBD of SARS-CoV-2 and Neutralizing Activity in the Chilean Population.

COVID-19 is a pandemic caused by SARS-CoV-2. In Chile, half a million people have been infected and more than 16,000 have died from COVID-19. As part of the clinical trial NCT04384588, we quantified IgG against S1-RBD of SARS-CoV-2 (anti-RBD) in recovered people in Santiago and evaluated their suitability as COVID-19 convalescent plasma donors. ELISA and a luminescent SARS-CoV-2 pseudotype were used for IgG and neutralizing antibody quantification. 72.9% of the convalescent population (468 of 639) showed seroconversion (5-55 µg/mL anti-RBD IgG) and were suitable candidates for plasma donation. Analysis by gender, age, and days after symptom offset did not show significant differences. Neutralizing activity correlated with an increased concentration of anti-RBD IgG (p < 0.0001) and showed a high variability between donors. We confirmed that the majority of the Chilean patients have developed anti-SARS-CoV-2 antibodies. The quantification of anti-RBD IgG in convalescent plasma donors is necessary to increase the detection of neutralizing antibodies.

The use of radiotherapy for early breast cancer in woman at different ages.

Age is an important feature at the time of early breast cancer diagnosis. Radiotherapy is a mandatory component of treatment for breast-conserving strategies in early disease stages. Breast radiotherapy has rapidly evolved in the last 20 years. A tendency to less treatment volume (partial-breast irradiation) and less treatment time (hypofractionation) is consolidated in modern radiation oncology practice. Age and risk for local recurrence guide the decision-making process to electro-optimal treatment. Radiotherapy technological versatility offers multiple options for individualized (risk-age adapted) recommendations.

Clinical and technical characteristics of intraoperative radiotherapy. Analysis of the ISIORT-Europe database.

BACKGROUND: A joint analysis of clinical data from centres within the European section of the International Society of Intraoperative Radiation Therapy (ISIORT-Europe) was undertaken in order to define the range of intraoperative radiotherapy (IORT) techniques and indications encompassed by its member institutions. MATERIALS AND METHODS: In 2007, the ISIORT-Europe centres were invited to record demographic, clinical and technical data relating to their IORT procedures in a joint online database. Retrospective data entry was possible. RESULTS: The survey encompassed 21 centres and data from 3754 IORT procedures performed between 1992 and 2011. The average annual number of patients treated per institution was 42, with three centres treating more than 100 patients per year. The most frequent tumour was breast cancer with 2395 cases (63.8 %), followed by rectal cancer (598 cases, 15.9 %), sarcoma (221 cases, 5.9 %), prostate cancer (108 cases, 2.9 %) and pancreatic cancer (80 cases, 2.1 %). Clinical details and IORT technical data from these five tumour types are reported. CONCLUSION: This is the first report on a large cohort of patients treated with IORT in Europe. It gives a picture of patient selection methods and treatment modalities, with emphasis on the main tumour types that are typically treated by this technique and may benefit from it.

Stereotactic ablative radiotherapy delivered by image-guided helical tomotherapy for extracranial oligometastases.

PURPOSE: To investigate the outcomes and risk factors of patients treated with stereotactic ablative radiotherapy (SABR) delivered by image-guided helical tomotherapy (HT) for extracranial oligometastases. METHODS: From August 2006 through July 2011, 42 consecutive patients (median age 69 years [range 16-87]) with oligometastases (≤3) received HT to all known cancer sites (lung, n = 28; liver, n = 12; adrenal, n = 2). Prognostic factors were assessed by Cox's proportional hazards regression analysis. RESULTS: A total of 60 lesions were treated with hypofractionated HT (median dose 39 Gy [range 36-72.5]; median dose per fraction 12 Gy [range 5-20]). Complete or partial response was observed in 40 (54 %) patients. With a median follow-up period of 15 months, 1- and 2-year overall survival (OS) was 84 and 63 %, respectively; and 1- and 2-year local control (LC) was 92 and 86 %, respectively. Four patients had pneumonitis Grade ≥2 and two patients had lower gastrointestinal toxicity Grade ≥2. Only the lack of complete/partial response was associated with higher risk of mortality on univariate (HR = 3.8, P = 0.04) and multivariate (HR = 6.6, P = 0.01) analyses. CONCLUSIONS: SABR delivered by image-guided HT is well tolerated and offers adequate LC with low acute morbidity in patients with extracranial oligometastatic disease. We found that the response to HT was the only predictor for OS.

[Accelerated partial breast irradiation for early breast cancer]. / Irradiation partielle accélérée du cancer du sein : aspect théorique.

Hypofractionated and accelerated partial breast irradiation are more and more widely used for early breast cancer. Here, this short communication would expose the role of hypofractionated radiotherapy in adjuvant breast radiotherapy, rational, techniques and indications of accelerated partial breast irradiation.

[Conformal accelerated partial breast irradiation: state of the art]. / Irradiation partielle accélérée conformationnelle du sein : état des lieux.

Breast conserving treatment (breast conserving surgery followed by whole breast irradiation) has commonly been used in early breast cancer since many years. New radiation modalities have been recently developed in early breast cancers, particularly accelerated partial breast irradiation. Three-dimensional conformal accelerated partial breast irradiation is the most commonly used modality of radiotherapy. Other techniques are currently being developed, such as intensity-modulated radiotherapy, arctherapy, and tomotherapy. The present article reviews the indications, treatment modalities and side effects of accelerated partial breast irradiation.

[Breast reconstruction: state of the arts]. / Reconstruction mammaire et irradiation adjuvante des cancers du sein.

Radical mastectomy is still required in many cases, such as inflammatory breast cancer, multicentric breast cancer, large tumour volume and small breast size. In this setting, immediate breast reconstruction is more and more offered for breast cancer patients. But such plastic surgery is still debated, owing to risks of implant complications when postoperative radiotherapy of chest wall is mandatory in locoregional breast cancer management. Here, the review is focused on different type of immediate breast reconstruction and on risk of implants complications with or without postoperative radiotherapy.

[Debate about breast cancer: "Cons: Intraoperative radiotherapy"]. / Débats autour du cancer du sein : « contre ¼ la radiothérapie peropératoire.

Early breast cancer incidence increases owing to mammography screening. Hypofractionated radiotherapy is more and more proposed in women with low local relapse risk breast cancer, especially accelerated partial breast irradiation. Various irradiation modalities have been reported: brachytherapy, intraoperative irradiation, 3D-conformal accelerated partial breast irradiation. We describe limitations of intraoperative irradiation and the advantages of alternative techniques.

[Intensity modulation in breast radiotherapy: development of an innovative field-in-field technique at Institut Gustave-Roussy]. / Modulation d'intensité en radiothérapie mammaire : développement d'une méthode innovante de champ dans le champ à l'institut Gustave-Roussy.

PURPOSE: To assess the potential dosimetric gain of presegmentation modulated radiotherapy (OAPS, DosiSoft™) of breast, compared to routine 3D conformal radiotherapy. PATIENTS AND METHODS: Twenty patients treated with conservative surgery for breast cancer (9 right and 11 left sided) with various breast volume (median 537 cm(3); range [100-1049 cm(3)]) have been selected. For each patient, we have delineated a breast volume and a compensation volume (target volumes), as well as organs at risk (lungs and heart). Two treatment plans have been generated: one using the routine 3D conformal technique and the other with the presegmentation algorithm of DosiSoft™ (OAPS). The dose distribution were analyzed using the conformity index for target volumes, mean dose and V30 Gy for the heart, and mean dose, V20 Gy and V30 Gy for lungs. RESULTS: Over the 20 patients, the conformity index increased from 0.897 with routine technique to 0.978 with OAPS (P<0,0001). For heart and lung, OAPS decreased irradiation (mean cardiac dose 1,3 vs 1,6 Gy [P<0,0001] and pulmonary V20 Gy 6,6 vs 7,1 [P<0,0001]). CONCLUSION: OAPS (DosiSoft™) is an original method of segmentation of breast. It is automatic, fast and easy, and is able to increase the conformity index, while sparing organ at risk.

Radiotherapy for invasive breast cancer: guidelines for clinical practice from the French expert review board of Nice/Saint-Paul de Vence.

PURPOSE: While new strategies for the treatment of invasive breast cancer (BC) are emerging, radiotherapy (RT) modalities are still under debate. The French expert review board of Nice-Saint-Paul de Vence was asked firstly to conduct a qualitative evidence-based systematic review and then to establish clinical practice guidelines for the use of post operative RT in invasive BC. METHODS AND MATERIALS: A search to identify eligible studies was undertaken using the Medline® database. All phase III randomized trials and systematic reviews evaluating the role and modalities of RT in invasive BC were included, together with some noncontrolled studies if no randomized trials were identified. The quality and clinical relevance of the studies were evaluated to determine the level of evidence. RESULTS: The maximum delay between surgery and RT should ≤8 weeks when chemotherapy (CT) is not indicated. This should not exceed 24 weeks when adjuvant CT is administered. Whole breast RT delivering 50 Gy in 25 fractions followed by a boost of 10-16 Gy remains the standard of care after conservative surgery (CS). In the elderly population, for certain cases presenting comorbidities associated with a limited life expectancy, RT indication (even hypofractioned) and boost delivery may be unnecessary in the light of an unfavourable risk/benefit ratio. RT technique and indications should not vary in case of neoadjuvant CT followed by CS. After total mastectomy, RT should be indicated in N+ and in N- patients with high risk of local recurrence. The experts recommend to initiate tamoxifen at the end of RT, while aromatase inhibitors could be administered either concomitantly or sequentially with RT. There is no consistent data to delay (or suspend) trastuzumab administration during RT. As for all patients, in case of concurrent RT-trastuzumab administration, reduction of cardiac tissues exposure is highly recommended. After breast reconstruction, RT should be delivered as after standard CS without boost. CONCLUSION: Due to significant variations in practice in the treatment of patients with BC, our group aimed to provide guidelines for clinical practice. The systematic review of the literature formed the basis of our evidence-based recommendations; however expert agreements were necessary on those subjects that are still under debate. Our group will update these guidelines every 4 years, taking in consideration new advances in technology, new drugs administration, biologic tools and innovative therapeutic options.

[Early breast cancer without axillary lymph node involvement]. / Cancer du sein sans atteinte ganglionnaire axillaire.

Breast cancer is the most common cancer in women. In France, breast cancer incidence was 88.9 per 100,000 women in 2000. Early detection of breast tumours by screening mammography allows a breast conserving treatment, i.e., breast irradiation preceded by a lumpectomy and a sentinel node biopsy. The standard irradiation of early breast cancers consists in delivering 50 Gy to the whole breast in 2 Gy fractions over a five-week period followed by an additional dose targeting the tumour bed of 16 Gy in eight fractions. The 3D-conformal treatment planning optimizes dose distribution to the whole breast and to the tumour bed and lessens the normal tissue irradiation (heart and ipsilateral lung). The aim of this article is to describe epidemiologic, radio anatomic and prognostic features of early stage breast cancer and to propose guidelines for 3D-conformal treatment planning in early breast cancers. This review is illustrated by a case report.

[Breast cancer with axillary lymph node involvement]. / Cancer du sein avec atteinte ganglionnaire axillaire.

Breast cancer is the most frequent cancer of women in western countries. There are one million new cases per year in the world which represents 22% of all female cancers, and more than 370,000 deaths due to breast cancer per year (14% of cancer mortality). More than half of breast cancers are associated with axillary nodal involvement. Post-operative radiation therapy (XRT) is a crucial part of locoregional treatment in axillary nodal involvement breast cancer owing to a 15-years risk reduction of locoregional recurrence of 70% and to a 5.4% risk reduction of specific mortality. In 3D-conformal irradiation in such breast cancers, target volumes are chest wall when mastectomy was performed or breast and boost of tumor bed in case of breast conservative surgery, and supra-clavicular and/or axillary and/or internal mammary node areas. The main organs at risk are ipsilateral lung, heart and brachial plexus. The aim of this article is to describe epidemiologic, radio anatomic and prognostic features of axillary nodal involvement breast cancer and to propose guidelines for 3D-conformal treatment planning in locally advanced breast cancers. This review is illustrated by a case report.

[Accelerated partial breast irradiation: bifractionated 40Gy in one week. A French pilot phase II study]. / Étude pilote française de phase II d'irradiation partielle accélérée du sein conformationnelle tridimensionnelle bi-fractionnée hebdomadaire de 40Gy.

PURPOSE: Since 2009, accelerated partial breast irradiation (APBI) in North America has been allowed to be used for selected group of patients outside a clinical trial according to the ASTRO consensus statement. In France, accelerated partial breast irradiation is still considered investigational, several clinical trials have been conducted using either intraoperative (Montpellier) or Mammosite(®) (Lille) or brachytherapy modality (PAC GERICO/FNCLCC). Here, we report the original dosimetric results of this technique. PATIENTS AND METHODS: Since October 2007, Institut Gustave-Roussy has initiated a phase II trial using 3D-conformal accelerated partial breast irradiation (40 Gy in 10 fractions BID in 1 week). Twenty-five patients with pT1N0 breast cancer were enrolled and were treated by two minitangent photons beams (6MV) and an "en face" electron beam (6-22 MeV). RESULTS: The mean clinical target volume and planning target volume were respectively 15.1cm(3) (range: 5.2-28.7 cm(3)) and 117 cm(3) (range: 52-185 cm(3)). The planning target volume coverage was adequate with at least a mean of 99% of the volume encompassed by the isodose 40 Gy. The mean dose to the planning target volume was 41.8 Gy (range: 41-42.4 Gy). Dose inhomogeneity did not exceed 5%. Mean doses to the ipsilateral lung and heart were 1.6 Gy (range: 1.0-2.3 Gy) and 1.2 Gy (range: 1.0-1.6 Gy), respectively. CONCLUSION: The 3D conformal accelerated partial breast irradiation using two minitangent and "en face" electron beams using a total dose of 40 Gy in 10 fractions BID over 5 days achieves appropriate planning target volume coverage and offers significant normal-tissue sparing (heart, lung). Longer follow-up is needed to evaluate the tissue tolerance to this radiation dose.

[Ductal carcinoma in situ of the breast (DCIS). Histopathological features and treatment modalities: analysis of 1,289 cases]. / Carcinomes canalaires in situ (CCIS). Caractéristiques histopathologiques et traitement : analyse de 1 289 cas.

From March 2003 to April 2004, were prospectively collected in France 1,289 ductal carcinoma in situ (DCIS) with data on diagnosis, patient and tumour characteristics, and treatments. Median age was 56 years (range, 30-84). DCIS was diagnosed by mammography in 87.6% of patients. Mastectomy (M), conservative surgery alone (CS) and conservative surgery with radiotherapy (CS + RT) were performed in 30.5, 7.8 and 61.7% of patients, respectively. Sentinel node biopsy (SNB) and axillary dissection (AD) were performed in 21.3 and 10.4% of patients, respectively. Hormone therapy was administered to 13.4% of the patients. Nuclear grade was low in 21% of patients, intermediate in 38.5% and high in 40.5%. Excision was considered complete in 92% (CS) and 88.3% (CS + RT) of patients. Treatment modalities varied widely according to region: mastectomy rate, 20-37%; adjuvant RT, 84-96%; hormone treatment, 6-34%. Our survey on current DCIS management in France has highlighted correlations between pathological features (tumour size, margin, grade) and treatment options, with several similar variations to those observed in recent UK and US studies.

Breast-conserving surgery with or without radiotherapy vs mastectomy for ductal carcinoma in situ: French Survey experience.

From March 2003 to April 2004, 77 physicians throughout France prospectively recruited 1289 ductal carcinoma in situ (DCIS) patients and collected data on diagnosis, patient and tumour characteristics, and treatments. Median age was 56 years (range, 30-84). Ductal carcinoma in situ was diagnosed by mammography in 87.6% of patients. Mastectomy, conservative surgery alone (CS) and CS with radiotherapy (CS+RT) were performed in 30.5, 7.8 and 61.7% of patients, respectively. Thus, 89% of patients treated by CS received adjuvant RT. Sentinel node biopsy (SNB) and axillary dissection (AD) were performed in 21.3 and 10.4% of patients, respectively. Hormone therapy was administered to 13.4% of the patients (80% tamoxifen). Median tumour size was 14.5 mm (6, 11 and 35 mm for CS, CS+RT and mastectomy, respectively, P<0.0001). Nuclear grade was high in 21% of patients, intermediate in 38.5% and low in 40.5%. Excision was considered complete in 92% (CS) and 88.3% (CS+RT) of patients. Oestrogen receptors were positive in 69.8% of assessed cases (31%). Treatment modalities varied widely according to region: mastectomy rate, 20-37%; adjuvant RT, 84-96%; hormone treatment, 6-34%. Our survey on current DCIS management in France has highlighted correlations between pathological features (tumour size, margin and grade) and treatment options, with several similar variations to those observed in recent UK and US studies.

[Accelerated partial breast irradiation in 2008: interrogations and perspectives]. / Irradiation partielle et accélérée du sein en 2008 : interrogations et perspectives.

From the beginning of 2000, accelerated and partial breast irradiation (APBI) progressively acquired maturity and used more and more sophisticated technologies. At this time, at least six international phase III trials are ongoing. The statistical design of these studies is elaborated in order to show equivalence between APBI and whole breast irradiation (WBI) in term of local control. What and when we have to wait from these randomized trials? The presented analysis discusses not only the advantages and different interrogations concerning APBI, but also the difficulties for radiation oncologists and patients to assume the long period until the publication of the ongoing phase III trial results. APBI will find its place beside WBI, as well as conservative treatment founded its place beside radical mastectomy 30 years ago. However, clinical investigation conditions appear now different and this is this difference we have to manage rigorously and precisely.

Concurrent trastuzumab with adjuvant radiotherapy in HER2-positive breast cancer patients: acute toxicity analyses from the French multicentric study.

BACKGROUND: Trastuzumab (T) combined with chemotherapy has been recently shown to improve outcome in HER2-positive breast cancer (BC). The aim of this study was to evaluate the toxic effects of concurrent radiation therapy (RT) and T administration in the adjuvant setting. PATIENTS AND METHODS: Data of 146 patients with stages II-III HER2-positive BC were recorded. Median age was 46 years. In all, 32 (23%) and 114 (77%) patients received a weekly and a 3-week T schedule, respectively. A median dose of 50 Gy was delivered after surgery. Internal mammary chain (IMC) was irradiated in 103 (71%) patients. RESULTS: Grade >2 dermatitis and esophagitis were noted in 51% and 12%, respectively. According to the Common Toxicity Criteria v3.0 scale and HERA (HERceptin Adjuvant) trial criteria, respectively, 10% and 6% of the patients had a grade >/=2 of left ventricular ejection fraction (LVEF) decrease after RT. Multivariate analyses revealed two independent prognostic factors: weekly T administration (for LVEF decrease) and menopausal status (for dermatitis). Higher level of T cumulative dose (>1600 mg) was only borderline of statistical significance for acute esophagitis toxicity. CONCLUSION: We showed that weekly concurrent T and RT are feasible in daily clinical practice with, however, a decrease of LVEF. Cardiac volume sparing and patient selections for IMC irradiation are highly recommended. Longer follow-up is warranted to evaluate late toxic effects.

[Progress in immediate breast reconstruction with skin sparing mastectomy]. / Reconstruction mammaire immédiate: les progrès apportés par la mastectomie avec conservation de l'etui cutané

Skin sparing mastectomy (SSM) and subcutaneous mastectomy (SCM) are recent techniques. They are always associated with immediate breast reconstruction (IBR). Their safety from an oncologic point of view and indications are of great concern. In early breast cancer, SSM and SCM are associated with the same risk of local recurrence as a modified radical mastectomy, when correctly indicated. This has been validated by numerous studies. In these non-randomised studies, overall survival cannot be evaluated. Such techniques can now be validated in the oncologic setting when correctly indicated and when decision-making is always concerted and multidisciplinary. Skin-sparing techniques are obviously associated with better cosmetic results than secondary reconstructions. Thus SSM with IBR are ideally indicated for ductal carcinoma in situ, pure infiltrating or mixed carcinomas requiring mastectomy without subsequent radiotherapy. The selection criterion of no postoperative radiotherapy allows the right candidates to be chosen for SSM. But often this criterion cannot be obtained preoperatively. In such cases, performing a two-step operation could be a good option. The interval between operations can be used by the patient to obtain more information and to make a mature decision regarding her choice of treatment. It seems essential to be able to offer every patient SSM with IBR which are validated standardised indications. Such is not the case everywhere in France today. The organisation of primary care through professional networks should provide us with an opportunity to fulfil these needs.

[Accelerated partial breast irradiation: a concept to individualize treatment in breast cancer]. / Irradiation partielle et accélérée du sein: un concept pour une individualisation thérapeutique dans le cancer du sein.

Whole breast irradiation delivering an equivalent dose of 50 Gy in 5 weeks, followed by a 10 to 16 Gy-boost to the tumor bed is the standard of care after breast-conserving surgery for early-breast cancer. Accelerated partial breast irradiation (APBI) is currently under investigations in large multi-institutional, prospective, randomized trials to objectively address the critical endpoints of treatment efficacy, toxicity and cosmesis. Patient's selection for this new approach is crucial to individualise treatments and define the subgroups of patients who will really benefit from APBI in terms of quality of life without decreasing long-term results of the disease control and cosmesis. In this review, we will discuss the patients' profiles selection for APBI regarding their general and tumor criteria. The differences between APBI techniques either performed intra or post operatively will be also discussed.