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IMPORTANCE: Triple-negative breast cancer (TNBC) cells are sensitive to poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors used as radiosensitizers. Whether combining PARP inhibitors with radiotherapy in patients with TNBC would enhance the biological effectiveness of the irradiation and improve locoregional control is unclear. OBJECTIVE: To assess the safety and tolerability of PARP inhibition with olaparib used concurrently with radiotherapy in patients with TNBC with residual disease after neoadjuvant chemotherapy. DESIGN, SETTING, AND PARTICIPANTS: This phase 1 prospective dose-escalation trial (Olaparib and Radiation Therapy for TNBC [RadioPARP] trial) using a time-to-event continual reassessment method was performed from September 2017 to November 2019, with follow-up until November 2021. Participants had an incomplete pathologic response after neoadjuvant chemotherapy or unresectable TNBC despite previous neoadjuvant chemotherapy, an Eastern Cooperative Oncology Group Performance Status score of 0 or 1, and adequate organ functions. INTERVENTIONS: Olaparib was administered orally in the form of tablets and given at increasing doses (50 mg, 100 mg, 150 mg, or 200 mg twice daily). Olaparib therapy was started 1 week before radiotherapy and was continued concomitantly with radiotherapy. After breast-conserving surgery, a total dose of 50.4 Gy was delivered to the whole breast, with a 63-Gy simultaneously integrated boost to the tumor bed for patients younger than 60 years. After radical mastectomy or for unresectable tumors despite neoadjuvant chemotherapy, a total dose of 50.0 Gy was delivered to the chest wall (after mastectomy) or to the whole breast (for unresectable tumors). Regional lymph node stations could be treated with a total dose of 50.0 Gy to 50.4 Gy in cases of node-positive disease. MAIN OUTCOMES AND MEASURES: Main outcomes were the safety and tolerability of PARP inhibition with radiotherapy for early-stage, high-risk TNBC. Secondary outcomes included overall survival (OS) and event-free survival (EFS). RESULTS: Among the 24 patients included in the trial (100% female; median age, 46 years [range, 25-74 years]), no dose-limiting toxic effects were observed, and olaparib was escalated to 200 mg twice daily without reaching the maximum tolerated dose. No late treatment-related grade 3 or greater toxic effect was observed, and the maximum observed treatment-related toxic effects at the 2-year follow-up were grade 2 breast pain, fibrosis, and deformity in 1 patient (4.2%). Three-year OS and EFS were 83% (95% CI, 70%-100%) and 65% (95% CI, 48%-88%), respectively. Homologous recombination status was not associated with OS or EFS. CONCLUSIONS AND RELEVANCE: The findings of this phase 1 dose-escalation trial suggest that PARP inhibition with olaparib concurrently with radiotherapy for early-stage, high-risk TNBC is well tolerated and should continue to be evaluated in further clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03109080

Abstract: Women from hereditary breast cancer families with BRCA1/2 germline mutation are at increased risk for contralateral breast cancer (BC) and for ovarian cancer (OC). It is less clear whether [...]

The prognostic impact of tumor-infiltrating lymphocytes (TILs) within invasive lobular carcinoma (ILC) remains to be better characterized. In estrogen receptor (ER)-negative invasive ductal carcinomas of no special type (IDC-NST), TILs are associated with good prognosis. The aim of this study was to examine TILs in ILC, with particular focus on prognostic and clinicopathologic features. A cohort comprising 459 consecutive ILCs diagnosed in a single institution from 2005 to 2008 met the eligibility criteria for this study. The percentage of tumor area occupied by TILs was quantified by two breast pathologists and categorized into three groups: no TILs, =5%, >5%. Clinicopathologic features were tested by Fisher’s exact tests or Chi2tests. Overall survival (OS) and invasive disease-free survival (iDFS) were estimated by Kaplan–Meier and Cox proportional hazard statistics. There were 239 TIL-negative cases, 185 cases with =5% TILs, and 35 cases with >5% TILs. TILs were associated with younger age, larger tumors, lymph node involvement, poor Nottingham prognostic index, HER2 amplification, multinucleation, and prominent nucleoli (p?5% TILs, respectively, vs. absence of TILs). Prominent nucleoli was the only nuclear feature associated with poor OS (p?=?0.05) and iDFS (p?=?0.05) in univariate Cox survival analysis. TILs represent a promising new morphologic biomarker associated with poor outcome of ILC, in contrast with that observed in ER-negative IDC-NST.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon histologic variant, and the optimal treatment of stage I-II NLPHL is undefined. We conducted a multicenter retrospective study including patients ≥16 years of age with stage I-II NLPHL diagnosed from 1995 through 2018 who underwent all forms of management, including radiotherapy (RT), combined modality therapy (CMT; RT+chemotherapy [CT]), CT, observation after excision, rituximab and RT, and single-agent rituximab. End points were progression-free survival (PFS), freedom from transformation, and overall survival (OS) without statistical comparison between management groups. We identified 559 patients with median age of 39 years: 72.3% were men, and 54.9% had stage I disease. Median follow-up was 5.5 years (interquartile range, 3.1-10.1). Five-year PFS and OS in the entire cohort were 87.1% and 98.3%, respectively. Primary management was RT alone (n = 257; 46.0%), CMT (n = 184; 32.9%), CT alone (n = 47; 8.4%), observation (n = 37; 6.6%), rituximab and RT (n = 19; 3.4%), and rituximab alone (n = 15; 2.7%). The 5-year PFS rates were 91.1% after RT, 90.5% after CMT, 77.8% after CT, 73.5% after observation, 80.8% after rituximab and RT, and 38.5% after rituximab alone. In the RT cohort, but not the CMT cohort, variant immunoarchitectural pattern and number of sites >2 were associated with worse PFS (P < .05). Overall, 21 patients (3.8%) developed large-cell transformation, with a significantly higher transformation rate in those with variant immunoarchitectural pattern (P = .049) and number of involved sites >2 (P = .0006). OS for patients with stage I-II NLPHL was excellent after all treatments.

Les carcinomes canalaires in situdu sein avec micro-invasion sont rares et de bon pronostic, assimilés dans la classification TNM 2017 aux carcinomes infiltrants de stade précoce. Cette étude évaluait les décisions de traitement des praticiens et leurs justifications en comparaison à la littérature.

Radiotherapy (RT) can be curative in patients with localized follicular lymphoma (FL), with historical series showing a 10-year disease-free survival of 40 to 50%. As 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography with computerized tomography (PET-CT) upstages 10 to 60% of patients compared to CT, we sought to evaluate outcomes in patients staged by PET-CT, to determine if more accurate staging leads to better patient selection and results. We conducted a multicenter retrospective study under the direction of the International Lymphoma Radiation Oncology Group (ILROG). Inclusion criteria were: RT alone for untreated stage I to II FL (grade 1-3A) with dose equivalent ≥24 Gy, staged by PET-CT, age ≥18 years, and follow-up ≥3 months. End points were freedom from progression (FFP), local control, and overall survival (OS). A total of 512 patients treated between 2000 and 2017 at 16 centers were eligible for analysis; median age was 58 years (range, 20-90); 410 patients (80.1%) had stage I disease; median RT dose was 30 Gy (24-52); and median follow-up was 52 months (3.2-174.6). Five-year FFP and OS were 68.9% and 96%. For stage I, FFP was 74.1% vs 49.1% for stage II (P < .0001). Eight patients relapsed in-field (1.6%). Four had marginal recurrences (0.8%) resulting in local control rate of 97.6%. On multivariable analysis, stage II (hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.44-3.10) and BCL2 expression (HR, 1.62; 95% CI, 1.07-2.47) were significantly associated with less favorable FFP. Outcome after RT in PET-CT staged patients appears to be better than in earlier series, particularly in stage I disease, suggesting that the curative potential of RT for truly localized FL has been underestimated.

Background: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon peripheral T-cell lymphoma most frequently arising around a textured surface breast implant. It has been shown that capsule infiltration (T2, T3 and T4 of the TNM staging system) was an adverse prognostic factor. In this context, chemotherapy (with or without brentuximab vedotin [BV]) may be proposed, considering other factors such as metastatic disease or incomplete resection. Furthermore, the need for adjuvant chemotherapy in patients with stage IIA (T4N0M0) and complete en-bloc excision without residual disease is debated.

Among adult lymphoma survivors, radiation treatment techniques that increase the excess radiation dose to organs at risk (OARs) put patients at risk for increased side effects, especially late toxicities. Minimizing radiation to OARs in adults patients with Hodgkin and non-Hodgkin lymphomas involving the mediastinum is the deciding factor for the choice of treatment modality. Proton therapy may help to reduce the radiation dose to the OARs and reduce toxicities, especially the risks for cardiac morbidity and second cancers. Because proton therapy may have some disadvantages, identifying the patients and the circumstances that may benefit the most from proton therapy is important. We present modern guidelines to identify adult lymphoma patients who may derive the greatest benefit from proton therapy, along with an analysis of the advantages and disadvantages of proton treatment.

IMPORTANCE: The use of a radiotherapy (RT) boost to the tumor bed after whole-breast RT (WBRT) for ductal carcinoma in situ (DCIS) is largely extrapolated from invasive cancer data, but robust evidence specific to DCIS is lacking. OBJECTIVE: To compare ipsilateral breast tumor recurrence (IBTR) in women with DCIS treated with vs without the RT boost after breast-conserving surgery and WBRT. DESIGN, SETTING, AND PARTICIPANTS: This retrospective analysis pooled deidentified patient-level data from 10 academic institutions in the United States, Canada, and France from January 1, 1980, through December 31, 2010. All patients had newly diagnosed pure DCIS (no microinvasion), underwent breast-conserving surgery, and received WBRT with or without the boost with a minimum of 5 years of follow-up required for inclusion in the analysis. Given the limited events after WBRT, an a priori power analysis was conducted to estimate the DCIS sample size needed to detect the anticipated benefit of the boost. Data were uniformly recoded at the host institution and underwent primary and secondary reviews before analysis. Sample size calculations (ratio of patients who received the boost dose to those who did not, 2:1; α = .05; power = 80%) estimated that 2982 cases were needed to detect a difference of at least 3%. The final analysis included 4131 patients (2661 in the boost group and 1470 in the no-boost group) with a median follow-up of 9 years and media boost dose of 14 Gy. Data were collected from July 2011 through February 2014 and analyzed from March 2014 through August 2015. INTERVENTIONS: Radiotherapy boost vs no boost. MAIN OUTCOMES AND MEASURES: Ipsilateral breast tumor recurrence. RESULTS: The analysis included 4131 patients (median [SD] age, 56.1 [10.9] years; range, 24-88 years). Patients with positive margins, unknown estrogen receptor status, and comedo necrosis were more likely to have received an RT boost. For the entire cohort, the boost was significantly associated with lower IBTR (hazard ratio [HR], 0.73; 95% CI, 0.57-0.94; P = .01) and with IBTR-free survival (boost vs no-boost groups) of 97.1% (95% CI, 0.96-0.98) vs 96.3% (95% CI, 0.95-0.97) at 5 years, 94.1% (95% CI, 0.93-0.95) vs 92.5% (95% CI, 0.91-0.94) at 10 years, and 91.6% (95% CI, 0.90-0.93) vs 88.0% (95% CI, 0.85-0.91) at 15 years. On multivariable analysis accounting for confounding factors, the boost remained significantly associated with reduced IBTR (HR compared with no boost, 0.68; 95% CI, 0.50-0.91; P = .01) independent of age and tamoxifen citrate use. CONCLUSIONS AND RELEVANCE: This patient-level analysis suggests that the RT boost confers a statistically significant benefit in decreasing IBTR across all DCIS age groups, similar to that seen in patients with invasive breast cancer. These findings suggest that a DCIS RT boost to the tumor bed could be considered to provide an added incremental benefit in decreasing IBTR after a shared discussion between the patient and her radiation oncologist.

La mise en place d’un contrôle de qualité interne est indispensable à la fiabilité des résultats du statut HER2 dans les cancers du sein.

IMPORTANCE: Prognostic factors of ipsilateral breast tumor recurrence (IBTR) may change over time following breast-conserving therapy. OBJECTIVE: The EORTC “boost no boost” trial showed that young age and high-grade invasive carcinoma were the most important risk factors for IBTR. This study reanalyses pathological prognostic factors related to IBTR using long-term follow-up. DESIGN, SETTING, AND PARTICIPANTS: Participants included 5569 early-stage breast cancer patients, treated with breast-conserving surgery (BCS) and whole-breast irradiation (WBI), who were randomized between no boost and a 16-Gy boost in the EORTC phase III “boost no boost” trial (1989-1996). A total of 1616 patients with a microscopically complete resection (according to local pathologists), included in the central pathology review, have been analyzed in this study. Median follow-up was 18.2 years. INTERVENTIONS: No further treatment or 16-Gy boost, after BCS and 50-Gy WBI. MAIN OUTCOMES AND MEASURES: Time to ipsilateral breast tumor recurrence (IBTR) as first event. RESULTS: The 20-year cumulative incidence of IBTR in 1616 patients (160 events observed) was 15% (95% CI, 12%-17%). Young age (P &lt; .001) and presence of ductal carcinoma in situ (DCIS) (HR, 2.15; 95% CI, 1.36-3.38; P = .001) were associated with an increased risk of IBTR in multivariable analysis. The cumulative incidence of IBTR at 20 years was 34% (95% CI, 25%-41%), 14% (95% CI, 10%-18%), and 11% (95% CI, 8%-15%), in patients 40 years or younger, 41 to 50 years and 50 years or older, respectively (P &lt; .001). This incidence was 18% (95% CI, 14%-22%) and 9% (95% CI, 6%-12%) for tumors with and without DCIS (P &lt; .001). High-grade tumors relapsed more frequently early during follow-up but the relative effect of age and presence of DCIS seemed stable over time. The boost reduced the 20-year IBTR incidence from 31% (95% CI, 22%-39%) to 15% (95% CI, 8%-21%) (HR, 0.37; 95% CI, 0.22-0.62; P &lt; .001) in high-risk patients (≤50 years with DCIS present). CONCLUSIONS AND RELEVANCE: The association of high-grade invasive tumor with IBTR diminished during follow-up, while the effect of DCIS adjacent to invasive tumor seemed to remain stable. Therefore, patients with high-grade invasive tumors should be monitored closely, especially in the first 5 years, while additional DCIS is an indication for longer follow-up, emphasizing the importance of long-term trial follow-up to estimate absolute effects accurately. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02295033

Background: Ophthalmic lymphomas, a subgroup of extra-nodal lymphomas, have seen an increase in incidence in recent decades. Of these, the NK/T-cell lymphoma (NKTL) subtype is particularly aggressive. Though prevalent mostly in Asian patients, data on ophthalmic NKTL is still limited, especially in the western population. This study aimed to provide an additional analysis of primary ophthalmic NKTL using the Surveillance, Epidemiology, and End Results (SEER) database.

Aims and background Current advances in radiotherapy for breast cancer require knowledge of the anatomy of irradiated areas to minimize geographic miss and spare organs at risk. This study aimed at defining a contouring approach for supraclavicular (SC) and infraclavicular (IC) nodes after mastectomy or conservative surgery in patients with breast cancer.Methods and Study Design In 15 patients, SC and IC nodes were contoured on computed tomography slices according to Madu et al and Dijkema et al. After analyzing relapse sites, as reported by Reed et al, our approach was defined. The 3 methods were compared in all patients, quantifying differences in contours by percentage overlap (PO).Results In our approach, SC node delineation is similar to Madu et al in the ventral and medial landmarks, but includes the lateral SC nodes described by Dijkema et al. The lateral landmarks are the scalenus anterior and medius muscle lateral border and the clavicle. Dorsal boundaries are the scalenus anterior and medius muscle ventral and lateral surfaces and the subclavian artery ventral border. In IC node delineation, major differences emerged in cranial and dorsal limits which, in our approach, are the pectoralis minor muscle upper edge and the subclavian axillary artery ventral side. Our mean and median volumes and POs were between the other 2 methods.Conclusions This study contributes to standardizing draining node contouring, so as to reduce variability and minimize geographic miss.

SUMMARY Helical tomotherapy (HT) is a technique of rotational intensity-modulated radiation therapy allowing dose escalation and normal tissue sparing for various types of cancer. Dosimetric studies of HT in breast cancers showed an improvement in dose homogeneity, conformity and a decrease in high doses of organs at risk compared with standard techniques. On the other hand, HT increases low dose of organs at risk, which in rare cases can increases the risk of secondary cancer. The benefits of HT seem to be greater in complex target volumes in which dose coverage is difficult with standard techniques (funnel chest, tumor in the inner quadrant, obese patients). Indications for breast HT should be personalized and selected according to the expected benefit for every patient.

La surexpression du récepteur Human Epidermal Growth Factor Receptor2 (HER2) est observée dans 15 % des cancers du sein et associée à un pronostic défavorable en termes de survie globale. Le trastuzumab est une thérapie ciblée anti-HER2, entraînant une inhibition spécifique des mécanismes moléculaires déclenchés par ce récepteur. En situation adjuvante, le trastuzumab et la radiothérapie ont chacun montré leur efficacité oncologique dans la prise en charge des tumeurs mammaires présentant ce profil moléculaire. Cependant, ces deux traitements exposent à un risque accru de toxicités, en particulier sur le plan cardiovasculaire. D’autre part, l’effet radiosensibilisant du trastuzumab a été montré in vitroet in vivo. De ce fait, le rapport bénéfice/risque d’un traitement concomitant reste à définir.

Alors que le panel thérapeutique dans le cancer du sein s’élargit et que le pronostic de la maladie s’améliore, la toxicité cardiaque des traitements reste une problématique de premier plan. Cette toxicité revêt plusieurs présentations cliniques et s’explique par des mécanismes moléculaires complexes et variés. Les traitements systémiques (anthracyclines, inhibiteurs de la voie de signalisation HER2, hormonothérapie, antiangiogéniques) et la radiothérapie ont leur toxicité cardiaque propre. Cependant, les toxicités liées à ces traitements peuvent se potentialiser et l’existence de facteurs de risque cardiovasculaire préexistants joue un rôle important. L’évaluation du risque cardiaque évolue vers l’intégration des différents traitements dans une approche multifactorielle. Plusieurs pistes existent afin de minimiser l’incidence de ces complications. Elles passent par des innovations pharmacologiques et technologiques, par une meilleure sélection des patients et par une implication croissante des praticiens dans ce domaine, gage d’une prise en charge précoce adaptée.

The lack of pathologic breast cancer response to neoadjuvant chemotherapy (NCT), a negative prognostic factor, has prompted the addition of chemotherapy to adjuvant radiotherapy. This study aims to investigate prospectively the toxicities of adjuvant concurrent chemoradiotherapy versus radiotherapy alone.

Les avancées diagnostiques et thérapeutiques de ces dernières décennies ont modifié la prise en charge des métastases cérébrales qui est à l’heure actuelle adaptée au type tumoral du site initial et aux facteurs pronostiques isolés dans les analyses multivariées. Cet article a pour objectif de faire le point sur l’état actuel des connaissances concernant les facteurs reconnus pronostiques dans le cas de métastases cérébrales de cancer du sein, ainsi que les classifications pronostiques proposées dans ce contexte. Une prise en charge adaptée à chaque classe pronostique sera discutée à la lumière des résultats des essais principaux randomisés incluant des patientes porteuses de métastases cérébrales secondaires à un cancer du sein.

SUMMARY Whole-breast irradiation in combination with breast-conserving surgery is a recognized standard alternative to mastectomy for the local treatment of early breast cancer. This article will review the evidence on the relationship of local control in the treated breast and survival, the indications of a boost dose to the tumor bed and the need for breast irradiation in ductal carcinoma in situ. Novel, shorter fractionation schemes allow the constraints of daily treatment courses over several weeks to be reduced, and recent technical improvements in treatment delivery will improve the results of treatment – in terms of local control and reduction of toxicity, and long-term sequelae. Research should focus on identifying molecular markers of radiation sensitivity and designing specific, targeted modulators of the radiation response in breast cancer.

La place de l’irradiation axillaire dans la prise en charge du cancer du sein reste très discutée. Alors que la valeur pronostique péjorative d’une atteinte ganglionnaire axillaire a été largement démontrée, le bénéfice d’un traitement axillaire reste plus incertain. Les grands essais cliniques, ayant montré le bénéfice de la radiothérapie postopératoire des tumeurs localement évoluées, ont comporté une irradiation ganglionnaire large, incluant la région axillaire. Cependant, l’étendue variable du curage dans ces études rend l’interprétation du bénéfice de la radiothérapie axillaire difficile. Bien que l’irradiation axillaire postopératoire des patientes, présentant une atteinte ganglionnaire étendue ou un curage insuffisant, demeure consensuelle, le pronostic de ces patientes reste bien souvent lié à l’évolution métastatique de la maladie et une telle stratégie majore la toxicité et les séquelles fonctionnelles potentielles. Des évaluations complémentaires devraient permettre de mieux définir les indications et le bénéfice réel de l’irradiation axillaire.

Le but de cette étude est de rapporter la tolérance et la réponse de l’association concomitante de radiothérapie à l’ensemble de l’encéphale et de trastuzumab pour des métastases encéphaliques de cancer du sein.

La radiothérapie encéphalique en totalité demeure le traitement de référence des patientes souffrant de métastases cérébrales d’un cancer du sein. Elle permet une amélioration symptomatologique et d’assurer un contrôle neurologique prolongé à la majorité des patientes. Cependant, ses résultats restent insuffisants, tant en termes d’efficacité que de toxicité tardive. La radiothérapie stéréotaxique permet d’assurer un très bon contrôle local au prix d’une toxicité le plus souvent modérée, mais doit être réservée à des patientes bien sélectionnées. Dans le but d’améliorer le rapport efficacité/toxicité, la biomodulation de la radiosensibilité tumorale a été l’objet d’évaluations récentes, dont les résultats préliminaires encourageants méritent d’être confirmés. En parallèle, les nouvelles technologies sont sujettes à un intérêt grandissant, permettant d’associer homogénéité dosimétrique, compléments de dose intégrés, et de limiter l’irradiation de certaines structures cérébrales impliquées dans la survenue d’une toxicité neurologique. Des évaluations complémentaires restent nécessaires, et l’inclusion de patientes dans les protocoles d’évaluation est largement encouragée.

Le cancer du sein est la deuxième cause de métastases cérébrales. L’incidence de ces métastases cérébrales est en augmentation, en partie grâce aux progrès thérapeutiques modifiant l’histoire naturelle des cancers du sein. Des facteurs prédictifs d’atteinte cérébrale ont été identifiés : la surexpression de HER2, l’absence d’expression des récepteurs hormonaux, la présence de métastases pulmonaires, le jeune âge et le statut triple négatif. Le pronostic à partir du diagnostic de métastases cérébrales demeure globalement sombre avec une survie médiane inférieure à un an sauf en cas de lésion unique ou en faible nombre pouvant bénéficier de traitements localisés tels que la chirurgie ou la radiochirurgie. Nous avons analysé les données des patientes suivies à l’Institut Curie (Paris, Saint-Cloud) pour des métastases cérébrales d’un cancer du sein au travers de deux études : une première s’intéressant aux patientes de moins de 65 ans porteusesd’un cancer du sein ne surexprimant pas HER2, et la seconde s’intéressant aux patientes de plus de 65 ans. La survie médiane à partir du diagnostic de métastases cérébrales est respectivement de 7,1 et 4 mois.

Brain metastases are a frequent complication in patients with advanced breast cancer. Whole-brain radiation therapy (WBRT) is the standard treatment for these patients, but it can cause neurocognitive damage, and results are suboptimal. Therapies that reduce toxic effects, improve local control, and prevent recurrences are needed. The authors of this Review outline the current strategies and novel developments in WBRT, and discuss new irradiation modalities that are improving outcomes in breast cancer patients with brain metastases.

Sarcomas are a rare complication of radiotherapy for breast carcinoma and patients have a poor prognosis. The incidence, histology, and management of patients with sarcomas were reviewed in the current study.The authors reviewed the records of 16,705 patients with breast carcinoma. Of these, 13,472 (81%) were treated with megavoltage radiotherapy and 3233 were treated without at the Institute Curie (Paris, France) between 1981 and 1997. Median doses of 50–55 grays (Gy) in 25–27 fractions were delivered to the whole breast over a period of 5–5.5 weeks (2 Gy/day, 5 weekly fractions) followed, when indicated, by a 16–26‐Gy boost to the tumor or tumor bed. Treatment of radiation‐induced sarcomas (RIS) consisted mostly of radical surgery and chemotherapy.Overall, 35 patients developed sarcomas. Of these, 27 fulfilled the Cahan criteria. The median follow‐up was 9.3 years (range, 1–22.4 years). The latency period ranged from 3 years to 20.3 years. Thirteen sarcomas were located in the breast, 5– in the chest wall, 3 in the sternum, 2 in the supraclavicle, 1 in the scapula, and 3 in the axilla. Histologic evaluation identified 13 angiosarcomas, 3 osteosarcomas, 5 undifferentiated sarcomas, 1 malignant fibrous histiocytoma, 2 leiomyosarcomas, 1 fibrosarcoma, 1 rhabdomyosarcoma, and 1 myosarcoma. The cumulative RIS incidence was 0.07% (± 0.02) at 5 years, 0.27% (± 0.05) at 10 years, and 0.48% (± 0.11) at 15 years. Standardized incidence ratios were 10.2 (95% confidence interval, 9.03–11.59) for irradiated patients and 1.3 (0.3–3.6) for nonirradiated patients. Of the 27 patients, 15 died of sarcoma within 1 month to 14.5 years (mean, 34.2 ± 0.7 months). The 5‐year actuarial survival rate after diagnosis of RIS was 36% (± 0.11).The current study confirmed the rarity of RIS. However, it showed that the risk increased with time. Therefore, careful, long‐term follow‐up of patients treated with radiotherapy is needed for early detection and efficacious treatment of these malignancies. Cancer 2005. © 2005 American Cancer Society.

Skeletal muscle includes satellite cells, which reside beneath the muscle fiber basal lamina and mainly represent committed myogenic precursor cells, and multipotent stem cells of unknown origin that are present in muscle connective tissue, express the stem cell markers Sca-1 and CD34, and can differentiate into different cell types. We tracked bone marrow (BM)-derived stem cells in both muscle connective tissue and satellite cell niches of irradiated mice transplanted with green fluorescent protein (GFP)-expressing BM cells. An increasing number of GFP+mononucleated cells, located both inside and outside of the muscle fiber basal lamina, were observed 1, 3, and 6 months after transplantation. Sublaminal cells expressed unambiguous satellite cell markers (M-cadherin, Pax7, NCAM) and fused into scattered GFP+muscle fibers. In muscle connective tissue there were GFP+cells located close to blood vessels that expressed the ScaI or CD34 stem-cell antigens. The rate of settlement of extra- and intralaminal compartments by BM-derived cells was compatible with the view that extralaminal cells constitute a reservoir of satellite cells. We conclude that both muscle satellite cells and stem cell marker-expressing cells located in muscle connective tissue can derive from BM in adulthood.

Our aim was to determine the long-term outcome and the possible role of neoadjuvant (preoperative) radiation therapy for breast cancers unsuitable for primary conservative surgery. From 1977 to 1992, 75 unifocal non-inflammatory and non-metastatic T2 and T3 breast cancers were treated in our department. All these patients underwent initial radiotherapy, followed by secondary limited surgery. A population of 74 patients, aged from 32 to 82 years (median 56 years), presenting 49 T2 and 26 T3 tumors, was studied. Seventy-two patients (96%) underwent secondary tumorectomy and three patients (4%) reduction mammaplasty. The secondary tumorectomy was followed by a postoperative boost. There were nine recurrences, treated by mastectomy in eight cases and by tumorectomy in one case. Twenty-five patients showed secondary dissemination. Forty-seven patients are still alive and free of disease. The cosmetic results were considered excellent or satisfactory in 71 cases. Under good conditions, preoperative radiotherapy (as well as preoperative chemotherapy) allows the possibility of conservative surgery for cancers of more than 3 cm. The choice between the two modalities depends on the patient's condition and on a precise analysis of all prognostic factors that would justify the need for systemic treatment. © 2001 Wiley-Liss, Inc.

Background:Breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is a rare form of T-cell lymphoma arising adjacent to a breast implant, recently recognized as a provisional entity in the 2017 revised World Health Organization (WHO) lymphoma classification. The pathogenesis of this entity remains elusive even if gene alterations in epigenetic modifiers and JAK-STAT signaling are frequent. ECHELON 2 trial (Horwitz S et al. The Lancet 2019) has set BV-CHP as a new standard of treatment for CD30-positive peripheral T-cell lymphoma, mainly in systemic ALCL patients (pts) but not in BIA-ALCL. Our objective is to describe a series of pts with BIA-ALCL included in the LYSA registry focusing on the use of BV CHP as front-line chemotherapy for patient requiring chemotherapy.

Background:BIA-ALCL is a rare subtype of T cell lymphomas associated with textured breast implants which has recently been recognized. The pathogenesis of this entity remains elusive even if mutations in the JAK/STAT pathway have been identified. Little is known about the causes, prognostic factors of this disease, and treatment outcome.

Le Bras: Amgen: Consultancy. Bachy:Roche: Research Funding; Celgene: Consultancy; Amgen: Honoraria; Takeda: Research Funding; Janssen: Honoraria; Gilead Sciences: Honoraria; Sandoz: Consultancy. Fornecker:Servier: Honoraria; Takeda: Honoraria. Traverse-Glehen:Takeda: Research Funding; Astra Zeneca: Other: Travel. Tilly:Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees. Xerri:Janssen: Other: Travel. Gaulard:Celgene: Research Funding; Roche: Honoraria; Takeda: Consultancy, Honoraria, Research Funding. Haioun:Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria; Sciences: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria.

Primary central nervous system lymphoma (PCNSL) is reported as having a dismal prognosis, due to the limited blood-brain barrier crossing capacity of lymphoma chemotherapies. Long-term remission and even cure could be achieved for a significant proportion of PCNSL patients using methotrexate-based chemotherapy regimens and intensive consolidation strategies. We report our single center experience of 27 consecutive patients with newly diagnosed PCNSL treated with Rituximab Methotrexate Temozolomide (RMT) regimen, and high-dose Etoposide Aracytine (EA) consolidation, with particular consideration for safety data.

No abstract.

Breast NHL represents less than 1% of all lymphomas and 2% of lymphomatous extranodal sites. We therefore reviewed all patients treated at the Institut Curie between 1986 and 2004 for a NHL having initial breast localization to define their initial characteristics, natural history and prognostic factors. Forty-six cases were selected for the study. Pathological review according to the WHO classification showed 2 patients with lymphocytic lymphoma, 3 cases of grade I follicular NHL, 1 case of MALT lymphoma, 1 case of grade III follicular NHL, 1 Burkitt’s lymphoma, and 38 diffuse large cell lymphomas [namely, 40 cases (87%) of high-grade NHL]. A complete analysis was performed on the 40 high-grade NHL patients. Initial characteristics were: median age 62 years (range: 22–86), B symptoms 17%, PS < 2 in 92%, stages III-IV 57%, nodal involvement 57% (47% axillary sites), 2 or more extra-nodal sites 32% (15% of bone marrow involvement and 2.5% of central nervous system (CNS) involvement), elevated LDH in 37%, and IPI score of 0–1/2/3/4–5 in 45%/12%/12% and 15%, respectively. Treatment consisted of chemotherapy in all cases (chlorambucil 3, anthracycline-based regimen with (30) or without (7) intrathecal prophylaxis), breast radiotherapy in 29 cases (72%), and rituximab in 4 patients. At the end of initial therapy, 36 patients (90%) achieved CR. With a median follow-up of 96 months (range: 14–188), nineteen patients (47%) relapsed. Relapses were localized in 8 cases and diffuse in 11 cases; breast localizations were observed in 10 cases (53%), one of which included contralateral involvement, axillary in 5 cases, and CNS site involvement in 3 cases. Among relapsed patients, 8 cases achieved second CR (47 %). Among the 10 patients with breast relapses, 8 received localized radiotherapy during first-line therapy. The 2- and 5-year disease-free survivals (DFS) were 65% (95% CI: 51 to 81%) and 54 % (95% CI: 40 to 72%), respectively; the 2- and 5-year overall survivals (OS) were 74% (95% CI: 62 to 89%) and 61% (95% CI: 47 to 78%), respectively. In univariate analysis, stage IV, 2 or more extranodal sites, elevated LDH level, high IPI score, and CNS involvement were prognostic for lower DFS; moreover, age greater than 60 years, PS > 1, ESR > 30, IPI score > 2, and 2 or more extranodal sites influence adversely OS. In multivariate analysis, the presence of 2 or more extranodal sites (p = 0.0008; RR 5.48; 95% CI: 2.01–14.9) was the only one factor that had a pejorative impact on DFS (Figure 1.A). PS > 1 (p = 0.02; RR 3.63; 95% CI: 1.18–11.07) and 2 or more extranodal sites (p = 0.05; RR 2.64; 95% CI: 1.0–6.96) were associated with poor OS (Figure 1.B). Finally, high-grade selected patients were compared to a historical series of 111 patients with aggressive lymphomas treated at the Institut Curie between 1982 and 1997 with an anthracycline-based regimen. Ann Arbor stage adjusted OS was significantly lower for patients with initial breast involvement (p < 0.0383). In conclusion, initial breast localization has a pejorative impact on the outcome of NHL patients, with an impressive adverse influence of additional extranodal sites on both DFS and OS. These results suggest a specific management of NHL with breast involvement in prospective clinical trials.