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 (AU)

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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 (AU)

Hypofractionated helical tomotherapy using 2.5-2.6 Gy daily fractions for localized prostate cancer

BACKGROUND: The purpose of this study is to evaluate the tolerability of hypofractionated helical tomotherapy (HT) in the treatment of localized prostate cancer. MATERIALS AND METHODS: We evaluated 48 patients with primary adenocarcinoma of the prostate (cT1-T3N0M0) who were treated with hypofractionated HT from August 2008 through July 2011. Hypofractionated regimens included: 68.04 Gy at 2.52 Gy/fraction, 70 Gy at 2.5 Gy/fraction, and 70.2 Gy at 2.6 Gy/fraction. Genitourinary (GU) and gastrointestinal (GI) toxicity was scored using the Radiation Therapy Oncology Group scoring system. RESULTS: Thirty-two patients were treated with 68.04 Gy, 5 patients with 70 Gy, and 11 with 70.2 Gy. The median age at diagnosis was 69 years (range 49-87) and the median follow-up 11 months (range 7-40). Grade 2 acute GI toxicity occurred in 9 patients (19 %). No grade 3 or higher acute GI toxicity was observed. Grade 2 and 3 acute GU toxicities occurred in 19 and 6 % of patients, respectively. The incidence of late grade 2 GI and GU toxicity was 4 and 2 %, respectively. No grade 3 or higher late toxicities were observed. Multivariate analysis showed that patients treated at 2.6 Gy/fraction or those who received a total radiation dose ≥70 Gy had higher rates of grade ≥2 acute GU toxicity (P = 0.004 and P = 0.048, respectively). CONCLUSION: Hypofractionated HT in the treatment of localized prostate cancer is well tolerated with no grade 3 or higher early or late GI and GU toxicities. Further research is needed to assess definitive late toxicity and tumor control (AU)

Intra-operative electron beam radiotherapy for newly dignosed and recurrent malignant gliomas: feasibility and lon-term outcomes

INTRODUCTION: Intra-operative electron beam radiotherapy (IOERT) is an alternative to dose escalation for the treatment of central nervous system tumors. The objective of this study was to describe the feasibility and long-term outcomes of IOERT in the treatment of primary and recurrent gliomas. MATERIALS AND METHODS: From January 1992 through December 2002, all patients treated with IOERT at the Hospital San Francisco de Asis, Madrid/Spain were retrospectively reviewed. The selection criteria included patients with superficial tumors, KPS >70 % and lesions <6 cm. Irradiation was administered in one section. The prescribed dose considered the amount of post-resection residual tumor, previous radiotherapy and the tolerance level of brain structures exposed to IOERT. RESULTS: There were 17 patients (53 %) with newly diagnosed malignant brain gliomas and 15 patients with recurrent tumors. The delivered dose varied from 8 to 20 Gy (median 12.5 Gy) for primary and from 8 to 16 Gy (median 10 Gy) for recurrent tumors. The median overall survival for the entire cohort was 13 months (14 and 10.4 months for the primary and recurrent, respectively). Three patients presented with radionecrosis, one patient with osteomyelitis at the craniotomy bone flap, one with intracerebral hemorrhage, and another patient experienced a pulmonary embolism. CONCLUSIONS: IOERT is a feasible technique and can be viewed as a tool in the treatment of newly diagnosed or recurrent brain gliomas (AU)

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.

Overview of preoperative radiochemotherapy in breast cancer: past or future?

Radiochemotherapy is a standard approach in human solid tumours, with localised stage and radical treatment intention. In the early-intermediate stages of breast cancer model, neoadjuvant radiochemotherapy is an alternative to induction chemotherapy alone and might further impact the surgical technical treatment characteristics (a downsizing effect). In the era of targeted therapy and personalised treatment for breast cancer patients with initial localised disease, radiochemotherapy needs to be explored as a component of optimised local treatment to potentially improve relevant local results, such as breast conservation, breast cosmesis and individualised breast cancer radiochemotherapy response prediction. An overview of available literature data regarding neoadjuvant treatment including radiotherapy component is analysed and discussed (AU)

[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.

Helical tomotherapy in patients with breast cancer and complex treatment volumes

PURPOSE: To describe early clinical results of tomotherapy treatment in patients with breast cancer and complex treatment volumes. METHODS AND MATERIALS: Ten patients were treated with tomotherapy between January 2009 and March 2010. Treatment planning objectives were to cover at least 95% of the planning target volume with the 95% isodose; to have a minimum dose of 90% and a maximum dose of 105%. All treatments included daily CT/megavoltage image guidance. Acute toxicity was recorded weekly. RESULTS: Six patients were treated because constraints were not accomplished for heart, lung or contralateral breast in a previous three-dimensional conformal plan; two for preexisting cardiac or pulmonary disease, and two more for bilateral breast irradiation. Treatment volumes included the whole breast in the majority of patients, as well as the supraclavicular and the internal mammary chain nodes when indicated. Most patients were older than 50 years, and had an early breast cancer, with positive oestrogen receptors, negative HER2 expression and a poorly differentiated, infiltrating ductal carcinoma. The majority of patients had received neoadjuvant chemotherapy associated to breast-conserving surgery and adjuvant hormonotherapy. Median homogeneity index was 1.09; median coverage index was 0.81. Median V20Gy and V10Gy for ipsilateral lung was 20% and 37.1% respectively. Median V25 and V35 for heart was 15% and 4% respectively. Median dose for contralateral breast was 7 Gy. Skin acute toxicity was grade 1 in 41.7% and grade 2 in 58.3%. CONCLUSION: Tomotherapy is a technique capable of delivering a well tolerated treatment with high homogeneity and coverage indexes and high capabilities for sparing the organs at risk in patients with anatomically complex breast cancer, bilateral breast cancer, indication for internal mammary chain node irradiation, cardiac toxicity derived from chemotherapy, or preexisting cardiac or pulmonary disease. Further studies are required to evaluate local control and late toxicity (AU)

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.