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Purpose: Metastatic endocrine-resistant breast cancer (MBC) is a disease with poor prognosis and few treatment options. Low lymphocyte count is associated with limited overall survival. In a prospective cohort of lymphopenic patients with HER-2 negative MBC, we assessed the clinical and biological impact of pembrolizumab combined with metronomic cyclophosphamide. Experimental Design: This multicenter Phase II study evaluated the safety and clinical activity of pembrolizumab (intravenous (IV), 200mg, every 3 weeks) combined with metronomic cyclophosphamide (50mg/day, per os) in lymphopenic adult patients with HER2-negative MBC previously treated by at least one line of chemotherapy in this setting according to a Simon's minimax two-stage design. Blood and tumor samples were collected to assess the impact of the combined treatment on circulating immune cells and the tumor immune microenvironment through multiparametric flow cytometry and multiplex immunofluorescence analyses. Primary endpoint was the clinical benefit rate at 6 months of treatment (CBR-6M). Secondary endpoints were objective response rate (ORR), duration of response, progression free survival (PFS), and overall survival (OS). Results: Two out of the twenty treated patients presented clinical benefit (one Tumor Mutational Burden (TMB)-high patient with complete response (CR) and one patient with objective response (OR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1) associated with a strong increase of cytokine-producing and proliferating CD4+ T cells and higher CD8+ T cells to macrophage ratios in the tumor. This impact on CD4+ and CD8+ T cell polyfunctionality was still observed more than one year for the patient with CR. A decreased in their absolute number of CD4+ and CD8+ memory T cells was observed in other patients. Conclusion: Pembrolizumab combined with metronomic cyclophosphamide was well tolerated, and displayed limited anti-tumoral activity in lymphopenic MBC. Correlative translational data of our trial advocates for additional studies with other chemotherapy combinations. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cancer is often diagnosed at an advanced stage, complicated to manage, and highly lethal due to its aggressivity. Optimizing its diagnosis and care pathways is a key challenge. This multicentric French cohort included 538 patients with pancreatic adenocarcinoma in 76 French centers. Among the most important results, the delays of care did not statistically influence survival in this cohort; high access to a general practitioner was associated with better chances to be resectable and survival was correlated with volume of pancreatic surgeries in healthcare centers. Background and aims: Pancreatic cancer is highly lethal and often diagnosed at an advanced stage. This cohort study analyzes the impact of care pathways, delays, and socio-spatial determinants on pancreatic cancer patients' diagnosis, treatment, and prognosis. Method: Patients with pancreatic adenocarcinoma newly diagnosed at all stages between January and June 2016 in the AuRA French region were included. The influence on survival of delays of care, healthcare centers' expertise, and socio-spatial determinants was evaluated. Results: Here, 538 patients were included in 76 centers including 116 patients (21.8%) with resectable, 64 (12.0%) borderline-resectable, 147 (27.6%) locally-advanced tumors, and 205 (38.5%) with metastatic disease. A delay between first symptoms and CT scans did not statistically influence overall survival (OS). In resected patients, OS was significantly higher in centers with more than 20 surgeries (HR<5 surgeries/year = 2.236 and HR5-20 surgeries/year = 1.215 versus centers with > 20 surgeries/year p = 0.0081). Regarding socio-spatial determinants, patients living in municipalities with greater access to a general practitioner (HR = 1.673, p = 0.0153) or with a population density below 795.1 people/km2 (HR = 1.881, p = 0.0057) were significantly more often resectable. Conclusion: This cohort study supports the pivotal role of general practitioner in cancer care and the importance of the centralization of pancreatic surgery to optimize pancreatic cancer patients' care and outcomes. However, delays of care did not impact patient survival. [ABSTRACT FROM AUTHOR]

Clear cell endometrial carcinoma represents an uncommon and poorly understood entity. Data from molecular/genomic profiling highlighted the importance of various signatures in assessing the prognosis of endometrial cancer according to four classes of risk (POLE mutated, MMRd, NSMP, and p53 abnormal). Unfortunately, data specific to clear cell histological subtype endometrial cancer are lacking. More recently, data has emerged to suggest that most of the patients (more than 80%) with clear cell endometrial carcinoma are characterized by p53 abnormality or NSMP type. This classification has important therapeutic implications. Although it is an uncommon entity, clear cell endometrial cancer patients with POLE mutation seem characterized by a good prognosis. Chemotherapy is effective in patients with NSMP (especially in stage III and IV) and patients with p53 abnormal disease (all stages). While, preliminary data suggested that patients with MMRd are less likely to benefit from chemotherapy. The latter group appears to benefit much more from immune checkpoint inhibitors: recent data from clinical trials on pembrolizumab plus lenvatinib and nivolumab plus cabozantinib supported that immunotherapy plus tyrosine kinase inhibitors (TKI) would be the most appropriate treatment for recurrent non-endometrioid endometrial cancer (including clear cell carcinoma) after the failure of platinum-based chemotherapy. Moreover, ongoing clinical trials testing the anti-tumor activity of innovative products will clarify the better strategies for advanced/recurrent clear cell endometrial carcinoma. Further prospective evidence is urgently needed to better characterize clear cell endometrial carcinoma. • Clear cell endometrial cancer represents uncommon uterine tumor. • Multi-modal treatment should be considered in patient with clear cell endometrial cancer. • Immunotherapy might play a role in patients with MMRd clear cell endometrial cancer. • ATr , PIK3CA , DDR , and HER2 might be potential targets in clear cell endometrial cancer [ABSTRACT FROM AUTHOR]

Cervical cancer is one of the most common and lethal cancers among women worldwide. Treatment options are limited in patients with persistent, recurrent, or metastatic cervical cancer, with <20% of women living >5 years. Persistent human papillomavirus (HPV) infection has been implicated in almost all cases of cervical cancer. HPV infection not only causes normal cervical cells to transform into cancer cells, but also creates an immunosuppressive environment for cancer cells to evade the immune system. Recent clinical trials of drugs targeting the PD-(L)1 pathway have demonstrated improvement in overall survival in patients with cervical cancer, but only 20% to 30% of patients show overall survival benefit beyond 2 years, and resistance to these treatments remains common. Therefore, novel treatment strategies targeting HPV infection–associated factors are currently being evaluated in clinical trials. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β "trap") fused to a human immunoglobulin G1 monoclonal antibody that blocks PD-L1. Early clinical trials of bintrafusp alfa have shown promising results in patients with advanced cervical cancer. [ABSTRACT FROM AUTHOR]

In the absence of randomised head-to-head trials, we conducted a population-adjusted indirect treatment comparison (PA-ITC) of phase III trial data to evaluate the relative efficacy and safety of maintenance olaparib and bevacizumab alone and in combination in patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation (BRCAm). An unanchored PA-ITC was performed on investigator-assessed progression-free survival (PFS) data. Individual patient data from SOLO1 (olaparib versus placebo) and from BRCA-mutated patients in PAOLA-1/ENGOT-ov25 (olaparib plus bevacizumab versus placebo plus bevacizumab) were pooled. Each arm of PAOLA-1 was weighted so that key baseline patient characteristics were similar to the SOLO1 cohort. Analyses were performed in patients with complete baseline data. Weighted Cox regression analysis was used to estimate the comparative efficacy of different maintenance therapy strategies, supplemented by weighted Kaplan–Meier analyses. Data from SOLO1 patients (olaparib, n = 254; placebo, n = 126) were compared with data from BRCA-mutated PAOLA-1 patients (olaparib plus bevacizumab, n = 151; placebo plus bevacizumab, n = 71). Adding bevacizumab to olaparib was associated with a numerical improvement in PFS compared with olaparib alone (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.45–1.09). Statistically significant improvements in PFS were seen with olaparib alone versus placebo plus bevacizumab (HR 0.48; 95% CI 0.30–0.75), olaparib plus bevacizumab versus placebo (0.23; 0.14–0.34), and placebo plus bevacizumab versus placebo (0.65; 0.43–0.95). Results of this hypothesis-generating PA-ITC analysis support the use of maintenance olaparib alone or with bevacizumab in patients with newly diagnosed, advanced ovarian cancer and a BRCAm. [Display omitted] • We compared olaparib maintenance strategies in newly diagnosed BRCA-mutated OC. • Our population-adjusted indirect treatment comparison used SOLO1 and PAOLA-1 data. • Results support the use of maintenance olaparib alone or with bevacizumab. [ABSTRACT FROM AUTHOR]

Quantitative lymphocyte alterations are frequent in patients with cancer, and strongly impact prognosis and survival. The development of cancers in immunosuppressed patients has demonstrated the contribution of different T cell populations, including CD4+ cells, in the control of cancer occurrence. Whereas absolute numbers of neutrophils, platelets and red blood cells are routinely monitored in clinic following treatments, because of possible short-term complications, absolute lymphocyte counts (ALC), their subpopulations or diversity (phenotype, TCR) are rarely analyzed and never used to choose therapy or as prognostic criteria. The recent identification of immune checkpoint inhibitors (ICPi) as powerful therapeutic agents has revitalized immunotherapy of cancer in a broader group of diseases than anticipated. The status of the immune system is now recognized as an important biomarker for response to these novel treatments. Blood ALC values, along with tumor infiltration by CD8+T cells, and ICPi and ICPi-ligand expression, are likely to be a potential marker of sensitivity to anti-ICPi therapy. In this article, we review the current knowledge on the incidence and significance of lymphopenia in cancer patients, and discuss therapeutic strategies to restore lymphocyte numbers. [ABSTRACT FROM AUTHOR]

Selinexor is an oral inhibitor of the nuclear export protein called Exportin 1 (XPO1) with demonstrated antitumor activity in hematological and solid tumors. Selinexor, blocking XPO1, induces nuclear localization of tumor suppressor proteins (including p53, p73, BRCA1, and pRB), leading to the selective induction of apoptosis, and inhibition of DNA damage repair proteins. XPO1 overexpression is common in endometrial cancers. Phase I and II trials reported the antitumor activity of selinexor in patients with endometrial carcinoma. The preliminary results of the phase III Selinexor in ENDOmetrial Cancer (SIENDO/ENGOT-EN5/GOG-3055) trial supported the use of selinexor as maintenance therapy in advanced endometrial cancer patients achieving at least partial response after a minimum of 12 weeks of first-line platinum-based chemotherapy. Selinexor maintenance resulted in a (nonsignificant) 30% reduction in the risk of disease progression or death. Looking at the endometrial cancer molecular subgroup characterized by TP53 wild type, the antitumor activity of selinexor seemed more pronounced, resulting in approximately a 60% reduction in the risk of disease progression or death. The SIENDO and the XPORT-EC trials will clarify the benefits and risks of adding selinexor as a first-line chemotherapy maintenance treatment in all-comer and TP53 wild-type endometrial cancers. Preclinical data highlights the potential for selinexor to be synthetically lethal with PARP inhibitors and may also plan a role in overcoming acquired resistance to those therapies. Therefore, new possible combinations with PARP inhibitors and should be evaluated. Furthermore, the combination of selinexor plus immune checkpoint inhibitors deserves further investigation in clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: The prostate cancer impacts on the future life of survivors. The complexity of sexual health problems in prostate cancer survivors is underestimated or often reduced to the erectile dysfunction. Especially, factors influencing sexual desire of patients have to be more explored. This study aims to describe the therapeutic management of patients with prostate cancer and assess their sexual desire 2 years after diagnosis.Methods: This study is part of the National VICAN survey (Vie après le CANcer) implemented in France in 2012. This analysis was performed on a population of 414 men who had prostate cancer. The questionnaire dealt with several topics including socioeconomic status, treatments received, and sexual desire.Results: Prostatectomy (42.8%), radiotherapy + hormonotherapy (17.6%), and radiotherapy alone (12.8%) were the main treatments used. 41.3% of men stated that their sexual desire was all gone since disease. The "satisfying" perceived financial situation was significantly associated to a sexual desire loss (p = 0.008). Radiotherapy + hormonotherapy treatment only is significantly associated with a loss of sexual desire (P = 0.003).Conclusions: Two years after diagnosis, the sexual desire of prostate cancer survivors is deteriorated with the cancer experience. However, clinical characteristics do not seem to be decisive unlike a "satisfying" financial situation. Research about the impact of socio economics characteristics on sexual health should probably be engaged. Programs have to be developed in France to have personalized sexual support progressed for survivors and take spouses into consideration in this context. [ABSTRACT FROM AUTHOR]

Successful pregnancy in women with metastatic cancer is rare in the published literature. We report here on four women with sarcoma who started and conducted their first pregnancies while in metastatic disease. All four pregnancies were first pregnancies, and all four women are long‐term survivors from 20 to 248 months after pregnancy. One patient had three pregnancies. All four women stopped systemic cancer treatment during their pregnancies, and two had RECIST progression during treatment interruption. Three patients still have unresectable metastatic disease, whereas one is in complete remission. In selected metastatic sarcomas with indolent courses, successful pregnancies are possible with no or minor impact on cancer progression and with prolonged life duration after pregnancy. As metastatic cancer becomes more often a chronic disease, this possibility opens important practical and ethical questions on how to best to advise women of childbearing age with metastatic cancers who are long‐term survivors. This case series reports four women with sarcoma who successfully conceived and managed their first pregnancies while in metastatic disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Given the importance of genomic instability signatures in the management of ovarian cancer and the difficulties in defining the role of immunotherapy, our objective was to describe the tumor immune microenvironment in the light of genomic instability signatures. Intratumoral CD3+ T lymphocytes confirmed its prognostic value. HLA-E appears to be a robust prognostic biomarker and preferentially overexpressed in homologous recombination deficiency (HRD) ovarian cancers. Our data provide a rationale for future immunotherapy strategies targeting the inhibitory CD94/NKG2A receptor of HLA-E in HRD tumors. Background: Following disappointing results with PD-1/PD-L1 inhibitors in ovarian cancer, it is essential to explore other immune targets. The aim of this study is to describe the tumor immune microenvironment (TME) according to genomic instability in high grade serous ovarian carcinoma (HGSOC) patients receiving primary debulking surgery followed by carboplatin-paclitaxel chemotherapy +/− nintedanib. Methods: 103 HGSOC patients' tumor samples from phase III AGO-OVAR-12 were analyzed. A comprehensive analysis of the TME was performed by immunohistochemistry on tissue microarray. Comparative genomic hybridization was carried out to evaluate genomic instability signatures through homologous recombination deficiency (HRD) score, genomic index, and somatic copy number alterations. The relationship between genomic instability and TME was explored. Results: Patients with high intratumoral CD3+ T lymphocytes had longer progression-free survival (32 vs. 19.6 months, p = 0.009) and overall survival (OS) (median not reached). High HLA-E expression on tumor cells was associated with a longer OS (median OS not reached vs. 52.9 months, p = 0.002). HRD profile was associated with high HLA-E expression on tumor cells and an improved OS. In the multivariate analysis, residual tumor, intratumoral CD3, and HLA-E on tumor cells were more predictive than other parameters. Conclusions: Our results suggest HLA-E/CD94-NKG2A/2C is a potential immune target particularly in the HRD positive ovarian carcinoma subgroup. [ABSTRACT FROM AUTHOR]

Background: We aimed to validate prognostic scores for survival in patients undergoing chemotherapy for advanced or metastatic cancer after first-line treatment. Methods: We previously described two models with good prognostic value based on a combination of Performance Status (PS) and either lactate dehydrogenase (LDH) level or lymphocyte count. These factors were evaluated for their ability to predict overall survival (OS) in a prospective cohort of 299 patients. Clinical and blood parameters were prospectively recorded. Candidate prognostic factors for OS with 0.05 significance level in univariate analysis were included in a multivariate Cox model. Results: Median age was 59 years (range: 26-85). Primary tumor sites were breast (45%), lung (15%), ovaries (11%) and others (29%). The number of metastatic sites was 1 (29%), 2 (48%), >2 (23%). Median follow-up and median OS were 12 and 6 months, respectively. Multiple regression analysis confirmed that PS >1, lymphocyte count ≤700/μL and LDH >600 UI/L were independent predictors of short OS, as well as interleukin 6 (IL-6) level, serum albumin concentration and platelet count. Conclusions: Prognostic scores using PS plus LDH level or PS plus lymphocyte count were validated for predicting survival in metastatic cancer patients in relapse beyond first-line treatment. A score combining PS, LDH, lymphocyte and platelet count, serum albumin and IL-6 level was superior in determining patients' prognosis. [ABSTRACT FROM AUTHOR]

Background: Little is known about prognosis of metastatic patients after receiving a first-line treatment and failure. Our group already showed in pre-treated patients enrolled in phase I clinical trials that a performance status (PS) > 2 and an LDH > 600 UI/L were independent prognostic factors. In this prospective study, which included 45 patients, we identified clinical and biological variables as outcome predictors in metastatic Non-Small Cell lung cancer after first line chemotherapy were identified. Findings: Forty-five patients that were previously treated for metastatic disease from 12/2000 to 11/2005 in the comprehensive cancer centre (Centre Léon Bérard). Clinical assessment and blood parameters were recorded and considered. Patient prognostic factors for overall survival (OS) with a 0.05-significance level in univariate analysis were entered in a multivariate Cox model for further analysis. Patients' median age was 58.5 years (range: 37 - 76). Sixty two percent of the patients were PS = 0 or 1. After inclusion, nine patients received second-line (22.5%), and two received third-line chemotherapy (5%). Univariate analysis showed that the factors associated with reduced OS were: PS > 2, weight loss >10%, more than one line of chemotherapy treatment and abnormal blood parameters (hemoglobin (Hb), platelet and neutrophils counts). Multiple regression analysis confirmed that PS > 2 and abnormal hemoglobin were independent predictors for low overall survival. According to the presence of none (33%), 1 (37%) and 2 (30%) prognostic factors, median OS were 12, 5 and 2 months respectively. Conclusion: From this prospective study, both PS and anemia were found as independent determinants of survival, we found that both PS and anemia were independent determinants of survival. The combination of poor PS and anemia is an effective strategy to predict survival in the case of patients with metastatic NSCLC receiving further treatment after the first line. [ABSTRACT FROM AUTHOR]

Background: We have investigated predictors of 90-day-mortality in a large cohort of non-specific cancer of unknown primary patients. Methods: Predictors have been identified by univariate and then logistic regression analysis in a single-center cohort comprising 429 patients (development cohort). We identified four predictors that produced a predictive score that has been applied to an independent multi-institutional cohort of 409 patients (validation cohort). The score was the sum of predictors for each patient (0 to 4). Results: The 90-day-mortality-rate was 33 and 26% in both cohorts. Multivariate analysis has identified 4 predictors for 90- day-mortality: performance status>1 (OR = 3.03, p = 0.001), at least one co-morbidity requiring treatment (OR = 2.68, p = 0.004), LDH>1.5xthe upper limit of normal (OR = 2.88, p = 0.007) and low albumin or protein levels (OR = 3.05, p = 0.007). In the development cohort, 90-day-mortality-rates were 12.5%, 32% and 64% when the score was [0-1], 2 and [3-4], respectively. In the validation cohort, risks were 13%, 25% and 62% according to the same score values. Conclusions: We have validated a score that is easily calculated at the beside that estimates the 90-days mortality rate in non-specific CUP patients. This could be helpful to identify patients who would be better served with palliative care rather than aggressive chemotherapy. [ABSTRACT FROM AUTHOR]

The Renal Insufficiency and Anticancer Medications (IRMA) study reported the high prevalence of renal insufficiency in cancer patients. In this special report, we focused on patients with lung cancer, emphasizing some specific findings in this population of patients. Data on patients with lung cancer who were in the IRMA study were analyzed. Renal function was calculated using Cockcroft–Gault and abbreviated Modification of Diet in Renal Disease (aMDRD) formulas to estimate the prevalence of renal insufficiency (RI) according to the KDOQI-KDIGO definition. Anticancer drugs were studied with regard to their potential renal toxicity and need for dosage adjustment. Of the 445 IRMA lung cancer patients, 14.4% had a serum creatinine (SCR) level ≥110 μmol/L. However, when they were assessed using the formulas, 62.1 and 55.9% had abnormal renal function. Of the 644 anticancer drug prescriptions, 67.5% required dose adjustments for RI or were drugs with no available data, and 78.3% of the patients received at least one such drug. Furthermore, 71.6% received potentially nephrotoxic drugs. Seventy percent of the patients had anemia but prevalence was not significantly associated with the existence of associated renal insufficiency. In the 445 IRMA patients with lung cancer, the prevalence of RI was high in spite of a normal SCR in most cases. Some anticancer drugs such as platinum salts may be nephrotoxic and need dosage adjustment. However, other important drugs such as gemcitabine do not require dose reduction and do not present with a high potential for nephrotoxicity. Lung cancer patients often present with anemia, which was not associated with the presence of RI. [ABSTRACT FROM AUTHOR]

Simple Summary: With an increasing incidence, late diagnosis, and high mortality rate, pancreatic adenocarcinoma remains, in 2021, a real challenge for health institutions and professionals worldwide. Despite significant therapeutic progress, the five-year survival after diagnosis remains poor. Furthermore, disparities in the access to care (often participating in late diagnosis) have been described in demographic, clinical, and/or socioeconomic factors. We decided to assess in our region, over 1 year (2016), the real-life pancreatic cancer's management by the analysis of French hospital discharge summaries database system. We pointed out, in a large patient population (n = 1872), the inverse correlation between the level of expertise of the health facility in which the patient had his first hospital stay and the likelihood of undergoing any specific treatment for PDAC. A deeper analysis of the medical pathway for pancreatic adenocarcinomas patients is ongoing in order to suggest adapted public health measures. Pancreatic ductal adenocarcinoma (PDAC) remains a major public health challenge, and faces disparities and delays in the diagnosis and access to care. Our purposes were to describe the medical path of PDAC patients in the real-life setting and evaluate the overall survival at 1 year. We used the national hospital discharge summaries database system to analyze the management of patients with newly diagnosed PDAC over the year 2016 in Auvergne-Rhône-Alpes region (AuRA) (France). A total of 1872 patients met inclusion criteria corresponding to an incidence of 22.6 per 100,000 person-year. Within the follow-up period, 353 (18.9%) were operated with a curative intent, 743 (39.7%) underwent chemo- and/or radiotherapy, and 776 (41.4%) did not receive any of these treatments. Less than half of patients were operated in a high-volume center, defined by more than 20 PDAC resections performed annually, mainly university hospitals. The 1-year survival rate was 47% in the overall population. This study highlights that a significant number of patients with PDAC are still operated in low-volume centers or do not receive any specific oncological treatment. A detailed analysis of the medical pathways is necessary in order to identify the medical and territorial determinants and their impact on the patient's outcome. [ABSTRACT FROM AUTHOR]

Reports that between 1993 and 1994, physicians in the French comprehensive cancer center, Leon Berard, developed and implemented a Clinical Practice Guidelines (CPG) projects. Results of a study designed to assess the impact of CPGs on management of breast and colon cancer; Design; Setting; Results; Conclusions.

Simple Summary: In about half of the cases, endometrial stromal sarcomas lack the canonical oncogenic fusions JAZF1-SUZ12 or YWHAE-NUTM2, which are mutually exclusive. The aim of this study was to explore by RNA sequencing a retrospective series of uterine sarcomas diagnosed as endometrial stromal sarcomas but negative for JAZF1 and/or YWHAE rearrangement in FISH, in order to provide a better description of their molecular landscape, improve the classification of endometrial stromal sarcomas and provide guidance for disease management. A series of 42 patient tumors diagnosed as endometrial stromal sarcoma (ESS) based on the morphology but negative for JAZF1 and/or YWHAE rearrangement in FISH was analyzed by RNA-sequencing. A chromosomal rearrangement was identified in 31 (74%) of the cases and a missense mutation in known oncogenes/tumor suppressor genes in 11 (26%). Cluster analyses on the expression profiles from this series together with a control cohort composed of five samples of low grade ESS harboring a JAZF1-SUZ12 fusion, one high grade ESS harboring a BCOR-ITD, two uterine tumors resembling ovarian sex cord tumors, two samples each of uterine leiomyoma and leiomyosarcomas and a series of BCOR-rearranged family of tumor (n = 8) indicated that tumors could be gather in three distinct subgroups: one mainly composed of BCOR-rearranged samples that contained seven ESS samples, one mainly composed of JAZF1-fused ESS (n = 15) and the last composed of various molecular subtypes (n = 19). These three subgroups display different gene signatures, different in silico cell cycle scores and very different clinical presentations, natural history and survival (log-rank test, p = 0.004). While YWHAE-NUTM2 fusion genes may be present in both high and low grade ESS, the high-grade presents with additional BCOR or BCORL1 gene mutations. RNAseq brings clinically relevant molecular classification, enabling the reclassification of diseases and the guidance of therapeutic strategy. [ABSTRACT FROM AUTHOR]

Cancer patients are thought to have an increased risk of developing severe Coronavirus Disease 2019 (COVID-19) infection and of dying from the disease. In this work, predictive factors for COVID-19 severity and mortality in cancer patients were investigated. In this large nationwide retro-prospective cohort study, we collected data on patients with solid tumours and COVID-19 diagnosed between March 1 and 11th June 2020. The primary end-point was all-cause mortality and COVID-19 severity, defined as admission to an intensive care unit (ICU) and/or mechanical ventilation and/or death, was one of the secondary end-points. From April 4 to 11th June 2020, 1289 patients were analysed. The most frequent cancers were digestive and thoracic. Altogether, 424 (33%) patients had a severe form of COVID-19 and 370 (29%) patients died. In multivariate analysis, independent factors associated with death were male sex (odds ratio 1.73, 95%CI: 1.18–2.52), The Eastern Cooperative Oncology Group Performance Scale (ECOG PS) ≥ 2 (OR 3.23, 95%CI: 2.27–4.61), updated Charlson comorbidity index (OR 1.08, 95%CI: 1.01–1.16) and admission to ICU (OR 3.62, 95%CI 2.14–6.11). The same factors, age along with corticosteroids before COVID-19 diagnosis, and thoracic primary tumour site were independently associated with COVID-19 severity. None of the anticancer treatments administered within the previous 3 months had any effect on mortality or COVID-19 severity, except for cytotoxic chemotherapy in the subgroup of patients with detectable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcriptase polymerase chain reaction (RT-PCR), which was associated with a slight increase of the risk of death (OR 1.53; 95%CI: 1.00–2.34; p = 0.05). A total of 431 (39%) patients had their systemic anticancer treatment (such as chemotherapy, targeted or immune therapy) interrupted or stopped following diagnosis of COVID-19. Mortality and COVID-19 severity in cancer patients are high and are associated with general characteristics of patients. We found no deleterious effects of recent anticancer treatments, except for cytotoxic chemotherapy in the RT-PCR-confirmed subgroup of patients. In almost 40% of patients, the systemic anticancer therapy was interrupted or stopped after COVID-19 diagnosis. • A total of 1289 patients with solid tumours and COVID-19 were analysed. • Mortality and COVID-19 severity were mainly driven by patients′ general characteristics. • Overall, we found no deleterious effects of recent anticancer treatments on mortality. • Systemic anticancer treatment was interrupted or stopped in 39% of patients. [ABSTRACT FROM AUTHOR]

Abstract Background Carboplatin and pegylated liposomal doxorubicin combination is a standard regimen in platinum-sensitive recurrent ovarian cancer patients. The pegylated liposomal doxorubicin shortage from 2011 to 2013 urged assessment of the efficacy and tolerance of non-pegylated liposomal doxorubicin in combination with carboplatin. Methods MYCA was a multicenter 2-step phase Ib-II single arm trial meant to assess the safety and efficacy of carboplatin AUC 5 mg/min.mL combined with non-pegylated liposomal (dose escalation from 40 to 50 mg/m2 during phase Ib step; and 50 mg/m2 during phase II step), every 4 weeks in patients with platinum-sensitive relapse. The primary objective was disease control rate (DCR) at 12 months. Results From 2012 to 2014, 87 patients were enrolled. They were treated as second (78%) or third line (22%) treatment. Total of 67 patients (78%) completed 6 cycles. G-CSF support was prescribed to 58% patients. The DCR at 12 months was 30.0% (95% CI, 20.3–39.7); the median PFS was 10.0 months (95% CI, 8.6–11.0). The median overall survival was 28.1 months (95% CI, 22.3–32.5); and the objective response rate was 58% (95% CI, 47–68). Grade 3–4 neutropenia, anemia and thrombocytopenia were observed in 17%, 13% and 1%, respectively; febrile neutropenia in 6%. One patient who did not receive GCSF support died from febrile neutropenia. Conclusion Non-pegylated liposomal doxorubicin-carboplatin combination exhibits an acceptable safety profile, with GCSF prophylaxis. Acknowledging the lack of direct comparison, efficacy in terms of 12 month DCR was comparable with standard treatments. Highlights • Carboplatin + non-pegylated liposomal doxorubicin (NPLD) is effective in platinum-sensitive recurrent ovarian cancers. • The disease control rate at 12 months was 30%. • This combination is well tolerated but should be prescribed with G-CSF support. • NPLD could be an alternative to pegylated liposomal doxorubicin in association with carboplatin. [ABSTRACT FROM AUTHOR]

PARP inhibitors (PARPi) have revolutionized the management of high-grade epithelial ovarian cancer (HGOC) treatment. However, a significant number of patients relapse or progress under PARPi, leading to the introduction of a new line of systemic therapy such as chemotherapy. In patients with a limited number of metastatic sites at progression, −referred to as an oligometastatic progression- a potential indication for local therapy followed by re-introduction or continuation of PARPi treatment rather than initiating a new line of chemotherapy could be proposed. However, the impact of such strategies on progression free survival (PFS) in these patients remains unknown. This international multicenter retrospective study evaluated the efficacy of PARPi continuation or re-introduction in patients with HGOC after local treatment for oligometastatic progression. The main objective was to assess PFS under PARPi after local therapy (PFS post-LT). Secondary objectives included safety and overall survival (OS). 74 patients were identified in 20 centers between April 2020 and November 2021. 65% of patients were BRCA mutated and 92% had received ≥2 lines of prior systemic chemotherapy before the initial introduction of PARPi. Main progression sites were lymph nodes (42%), peritoneum (27%), liver (16%), other visceral (16%) and abdominal wall (4%). Local therapies included radiotherapy (45%), surgery (43%), both (7%), percutaneous thermal ablation (4%) or chemoembolization (1%). Median PFS post-LT was 11.5 months [95% CI 7.4; 17.2]. After a median follow up of 14.8 months, 6 patients (8.1%) discontinued PARPi due to toxicity. The 1-year overall survival rate was 90.7% [95% CI 79.1; 96.0]. With close to one year without progression or introduction of a new line of systemic therapy, this study reports the feasibility and potential benefit of this original strategy in patients with oligometastatic progression under PARPi. • Oligoprogression on PARP inhibitors is a potential indication for local therapy followed by reintroduction or continuation of PARP inhibitors. • This is a multicenter international retrospective cohort-type study. • The sites of progression were mainly lymph nodes and the local treatment mainly radiotherapy. • After a median follow-up of 14.8 months, median progression-free survival after local treatment was 11.5 months. • Patients with a single target lesion seem to benefit the most from this strategy. [ABSTRACT FROM AUTHOR]

Lenvatinib and pembrolizumab (LEN+PEMBRO) demonstrated clinically meaningful and statistically significant improvements in efficacy versus treatment of physician's choice (TPC) in patients with advanced endometrial cancer (aEC) in the phase 3 Study 309/KEYNOTE-775. Health-related quality-of-life (HRQoL) is reported. Patients were randomly assigned to receive LEN+PEMBRO (n = 411; LEN 20 mg/day; PEMBRO 200 mg Q3W) or TPC (n = 416; doxorubicin 60 mg/m2 Q3W or paclitaxel 80 mg/m2 [weekly, 3 weeks on/1 week off]). Impact of treatment on HRQoL assessed by the global health status/quality of life (GHS/QoL) score of the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) was a secondary objective; other scales of the Quality-of-Life Questionnaire (QLQ-C30), EORTC QLQ-Endometrial, 24 questions (EORTC QLQ-EN24), and EuroQoL 5 dimensions, 5 levels (EQ-5D-5L) were exploratory objectives. HRQoL was assessed on day 1 of each cycle. Completion/compliance, change from baseline, time to first and definitive deterioration were assessed. No multiplicity adjustments were applied for HRQoL endpoints. The latest timepoint at which the predefined rates of completion (≥60%) and compliance (≥80%) were met was week 12. HRQoL at week 12 between treatment groups was generally similar. Time to first deterioration symptom scales favoured LEN+PEMBRO for QLQ-C30 dyspnoea, and QLQ-EN24 for poor body image, tingling/numbness, and hair loss; and TPC was favoured for QLQ-C30 pain, appetite loss, and diarrhoea, and QLQ-EN24 muscular pain. While the QLQ-C30 physical functional scale favoured TPC, other functional scales were generally similar between arms. Time to definitive deterioration favoured LEN+PEMBRO on most scales. HRQoL data from Study 309/KEYNOTE-775, with previously published efficacy and safety results, indicate that LEN+PEMBRO has an overall favourable benefit/risk profile versus TPC for the treatment of patients with aEC. NCT03517449. • HRQoL was assessed in patients with endometrial cancer in Study 309/KEYNOTE-775. • Week 12 declines from baseline in most scales were similar between treatment arms. • Some differences existed (e.g. diarrhoea favoured TPC, dyspnoea favoured LEN+PEMBRO). • Coupled with efficacy and safety data, the PRO data support use of LEN+PEMBRO in EC. [ABSTRACT FROM AUTHOR]

The phase III PAOLA-1/ENGOT-ov25 study (NCT02477644) showed that addition of olaparib to bevacizumab maintenance improved progression-free survival (PFS) in patients with newly diagnosed advanced ovarian cancer. We evaluated maintenance olaparib plus bevacizumab in older patients in PAOLA-1. Baseline clinical and molecular data, and PFS, were compared between older (aged ≥65 years) and younger patients (<65 years). Factors associated with olaparib efficacy, and safety in age subgroups, were also assessed. Of 806 randomised patients, 292 (36.2%) were ≥65 years. A lower proportion of older versus younger patients had an Eastern Cooperative Oncology Group performance status of 0 (61.0% versus 76.2%) and upfront surgery (42.0% versus 55.7%). Older patients were less likely to have a BRCA1/2 mutation (17.1% versus 36.7%) or homologous recombination deficiency-positive status (34.1% versus 55.7%). After median follow-up of 22.1 months, median PFS was 21.6 months with olaparib versus 16.6 months with placebo in the older population (hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.41–0.75), comparable with the younger population (median 22.9 versus 16.9 months; HR 0.61, 95% CI 0.49–0.77). PFS benefits were observed in patients with a BRCA mutation or homologous recombination deficiency-positive tumours. Incidence of olaparib-related grade ≥3 adverse events in older patients was comparable with that of younger patients (36.8% versus 31.7%) although hypertension and anaemia were more common in older patients. No treatment-related deaths occurred in older patients receiving olaparib. Older patients enrolled in PAOLA-1 achieved similar PFS benefits compared with younger patients, with a similar safety profile. • Older patients in PAOLA-1 had unfavourable baseline clinical and molecular features. • Benefits of olaparib plus bevacizumab were similar in older and younger patients. • Improved progression-free survival was limited to those with HRD-positive tumours. • Safety and tolerability profiles were similar in older and younger patients. [ABSTRACT FROM AUTHOR]

We report a phase II trial (OSAD93) testing CDDP with ifosfamide (IFO), without doxorubicin in neoadjuvant phase, in adult osteosarcoma with a 25 years follow-up. This is a multicentric phase II study of neoadjuvant chemotherapy with IFO and CDDP in localized high-grade osteosarcoma of patients. Patients received 4 pre-operative courses of IFO 9 g/m2 and CDDP 100 mg/m2 on day 4 (SHOC regimen), followed by local treatment. Doxorubicin was added post-operatively (HOCA regimen) in patients with > 10 % residual tumor cells. A Good Histological Response (GHR), ie ≤ 10 % residual tumor cells in > 30 % of patients, was the primary objective. Disease-free survival (DFS), overall survival (OS) and toxicity were secondary objectives. From Jan 1994 to Jun 1998, 60 patients were included. Median age was 27 (range: 16–63). Primary tumor sites were limbs (76 %), trunk, head or neck (24 %). After neoadjuvant SHOC, grade 3–4 and febrile neutropenia, thrombopenia, and re-hospitalization occurred in 58 %, 17 %, 17 % and 22 % of SHOC courses and in 76 %, 28 %, 47 %, 47 % of HOCA courses, respectively. GHR was obtained in 16/60 (27.5 %) patients. With a median follow-up of 322 months, the DFS and OS were 51.8 % and 64.4 % at 5 years. At 10 years, DFS and OS were 49.9 % and 64.4 %. At 25 years, DFS and OS were 47.8 % and 55.9 %. No long-term cardiac toxicity was observed. Three patients developed a second malignancy (one fatal) after 300 months. Though the primary endpoint of OSAD93 was not met, this pre-operative doxorubicin-free regimen led to excellent long-term survival with limited toxicity in localized osteosarcoma. OSAD93 used a 2 drugs neoadjuvant chemotherapy regimen in adult osteosarcoma. The primary endpoint (good histological response in >30 % of patients) was not met The long term (>25y) OS & DFS are high in this adult osteosarcoma series. Limited long-term toxicity and no cardiac toxicity was observed in cured patients. This protocol provides excellent long-term results, deserving further investigations. [ABSTRACT FROM AUTHOR]

Patients with cancer are at high risk of severe or lethal COVID-19. The impact of SARS-COV-2 vaccination on the risk of developing COVID-19 was investigated in an exhaustive series of patients from a comprehensive cancer center. This is a study of the exhaustive population of 2391 cancer patients who were prescribed SARS-COV-2 vaccination until 09/21. Patient characteristics, documented SARS-COV-2 infection with RT-PCR, and survival were collected. The primary endpoint was the rate of COVID-19 after vaccination. Secondary endpoints included risk factors to develop COVID-19 after vaccination, with a comparison with the cohort of vaccinated health care workers (HCW), and risk factors for death. From January to September 2021, among 2391 patients with cancer under active treatment in whom a SARS-COV-2 vaccine was prescribed, 659 (28%), 1498 (63%) and 139 (6%) received 1, 2, and 3 doses, respectively. Ninety five patients received a single dose of vaccine after a previous COVID-19. Two thousand two hundred eighty five health care workers (HCW) received one (N = 17, 0.7%), 2–3 (N = 2026, 88.7%) vaccine doses and one dose after COVID-19 (N = 242, 10.6%). With a median follow-up of 142 and 199 days for patients and HCW, respectively. Thirty nine (1.6%) patients and 35 (1.5%) HCW developed COVID-19 after vaccination. Six of 39 cancer patients and no HCW died because ofCOVID-19 within 50 days after diagnosis. Independent risk factors for COVID-19 in vaccinated patients were age, single dose of vaccine without previous COVID-19 and anti-CD20 treatment in the last three months. Independent risk factors for death included metastatic disease, gender, cancer type, but also documented COVID-19 before vaccination. Patients receiving two or more doses of COVID-19 vaccine have reduced risk of COVID-19. The risk of death of vaccinated cancer patients presenting COVID-19 remains high. COVID-19 before vaccination is associated with an increased overall risk of death. • Patients receiving two or more doses of COVID-19 vaccine have reduced risk of COVID-19. • Health workers having 2 or more doses of COVID-19 vaccine have reduced risk of COVID-19. • The risk of death of vaccinated cancer patients presenting COVID-19 remains high. • No severe forms of COVID-19 were observed in HCW. • COVID-19 before vaccination is associated with an increased overall risk of death. [ABSTRACT FROM AUTHOR]

Metastatic soft tissue sarcomas (STSs) management remains an unmet medical need. We assessed the activity and safety of regorafenib in patients with metastatic non-adipocytic STS who were previously treated with both chemotherapy and pazopanib. This double-blind, placebo-controlled, multicenter comparative randomized phase II trial included patients with histologically proven advanced and inoperable STS. Patients receiving placebo were offered optional cross-over for centrally confirmed disease progression. Primary end-point was centrally reviewed Response Evaluation Criteria in Solid Tumours–based progression-free survival (PFS), analysed on the intent-to-treat data set. In total, 24 events were required for 90% power, hazard ratio (HR) = 0.33 (median PFS, 3.6 versus 1.2 months), and 1-sided α = 0.1 (ClinicalTrials.gov , NCT01900743). From December 2015 to October 2017, 37 patients were randomized; 18 to regorafenib and 19 to placebo. Thirteen patients assigned to placebo switched to regorafenib after progression. Median follow-up was 27.2 months (95% confidence interval [CI]: 24.4–not reached). We observed a significant PFS benefit of regorafenib compared with placebo (adjusted HR = 0.33; 95% CI: 0.15–0.74; p = 0.0007 median PFS = 2.1 versus 1.1 months, respectively), and a large and nearly significant overall survival (OS) benefit despite the cross-over (adjusted HR = 0.49; 95% CI: 0.23–1.06; p = 0.007; median OS = 17.8 versus 8.2 months). Before cross-over, the most common grade III or higher adverse events were lymphopenia (5 versus 1, respectively), diarrhoea (4 versus 0), dyspnoea (3 versus 1), skin toxicity (3 versus 0), arterial hypertension (2 versus 0), and increased transaminases (2 versus 0). The present study demonstrated a meaningful clinical anti-tumour activity with regorafenib in heavily pre-treated patients with non-adipocytic STS. • This placebo-controlled double-blind randomized phase II trial shows that regorafenib is active in patients with advanced non-adipocytic soft tissue sarcoma. • The progression-free survival is significantly improved compared with placebo even after prior treatment with pazopanib. • Despite cross-over, we have observed overall survival improvement (8.2 versus 17.8 months). [ABSTRACT FROM AUTHOR]

In patients with advanced ovarian cancer, the modelled CA-125 ELIMination rate constant K (KELIM) is an early indicator of the tumour intrinsic chemosensitivity. We assessed the prognostic and surrogate values of KELIM with respect to those of surgery outcome (based on post-operative residual lesions) in the Gynaecologic Cancer Intergroup (GCIG) individual patient data meta-analysis MAOV (Meta-Analysis in OVarian cancer) built before the emergence of poly(ADP-ribose) polymerase (PARP) inhibitors. The dataset was split into learning and validation cohorts (ratio 1:2). The individual modelled KELIM values were estimated, standardised by the median value, then scored as unfavourable (<1.0) or favourable (≥1.0). Overall survival (OS) and progression-free survival (PFS) analyses were performed with a two-step meta-analytic approach and surrogacy through a two-level meta-analytic model. KELIM was assessed in 5884 patients from eight first-line trials (learning, 1962; validation, 3922). A favourable KELIM score was significantly associated with longer OS (validation set, median, 78.8 versus 28.4 months, hazard-ratios [HR] 0.46, 95% confidence interval [CI], 0.41–0.50, C-index 0.68), and longer PFS (validation set, median 30.5 versus 9.8 months, HR 0.49, 95% CI, 0.45–0.54, C-index 0.68), as were International Federation of Gynaecology and Obstetrics (FIGO) stage and debulking surgery outcome. Three prognostic groups were identified based on the surgery outcome and KELIM score, with large differences in OS (105.1, ∼45.0, and 22.1 months) and PFS (58.1, ∼15.0, and 8.0 months). Surrogacy for OS and for PFS was not established. KELIM is an independent prognostic biomarker for survival, complementary to surgery outcome, representing a new determinant of first-line treatment success. • Indicators of the tumour primary chemosensitivity in ovarian cancer are needed. • The KELIM score is a significant and independent prognostic factor for PFS and OS. • Combining KELIM and surgery outcome delineates three prognostic groups of patients. [ABSTRACT FROM AUTHOR]

Traditionally, BRCA genetic testing has been undertaken to identify patients and family members at future risk of developing cancer and patients have been referred for testing based on family history. However, the now recognised risk of ovarian cancer (OC) patients, even those with no known family history, harbouring a mutation in BRCA1/2 , together with the first poly adenosine diphosphate ribose polymerase inhibitor (PARPi; olaparib [Lynparza]) being licenced for the treatment of BRCA -mutated OC, has led to reconsideration of referral criteria for OC patients. Provided here is a review of the existing data and guidelines in the European Union, relating to recommendations, as well as considerations, for the referral of OC patients for BRCA genetic testing. Based on this review of newly updated guidance and up-to-date evidence, the following is recommended: all patients with invasive epithelial OC (excluding borderline or mucinous), including those with fallopian tube and peritoneal cancers, should be considered as candidates for referral for BRCA genetic testing, irrespective of age; genetic testing should ideally be offered at diagnosis, although patients can be referred at any stage; retrospective testing should be offered to patients in long-term follow-up because of the implications for family members and individual future breast cancer risk; and germline BRCA testing of a blood/saliva sample should initially be conducted and, if negative, tumour tissue should be tested (to identify non-germline [somatic] BRCA PARPi therapy candidates). [ABSTRACT FROM AUTHOR]

Background: The added value of tumoural genomic profiles to conventional clinico-biological factors to predict progression-free survival (PFS) and overall survival (OS) was prospectively investigated in patients with advanced gastrointestinal stromal tumours (GIST) treated in the BFR14 study. Methods: Of the 434 included patients, mutational analysis was performed in 322 patients. Survival analysis was performed in patients with validated mutational status. Results: Mutational status was validated in 228 patients. We identified 196 patients with tumours harbouring 200 KIT alterations (exon 11: 173 patients, exon 9: 22 patients, exon 17: 3 patients, exon 13: 2 patients; 4 patients had double KIT mutations), 6 patients with PDGFRA mutations and 26 patients with wild-type (WT) GIST genotype. On a median follow-up of 73 months, median PFS/OS were 12.3/54.9 months for WT GIST, 12.6/55 months for KIT exon 9, and 39.4 months/not reached (69.1% at 5 years) for KIT exon 11. Tumour size, female gender, KIT exon 11 mutations and CD34 positivity were independent prognostic factors for a higher PFS. A higher OS was predicted by performance status (PS) <2, low neutrophil and normal lymphocyte counts, KIT exon 11 mutations, non-advanced tumour and female gender. KIT exon 11 mutations at codons 557-558 showed better tumour response (p=0.028) but shorter PFS (p=0.0176). Conclusions: In GIST patients, presence of a KIT exon 11 mutation is an independent prognostic factor for PFS and OS, along with gender, PS, tumour size, lymphocyte and neutrophil counts. Subsets of exon 11 mutations are associated with significantly different response patterns and PFS. [ABSTRACT FROM AUTHOR]

Aims: BI 2536 is a selective and potent small-molecule inhibitor of polo-like kinase 1. We performed a multi-centre, multi-tumour phase II trial to investigate the efficacy, safety and pharmacokinetics of BI 2536 in five solid tumour types. Patients and methods: Patients with advanced head and neck, breast and ovarian cancer, soft tissue sarcoma and melanoma were selected according to protocol-defined general and tumour-specific criteria. They were ⩾18years old, had a good performance status, adequate bone marrow, renal and liver function, measurable progressive disease and had completed other relevant systemic treatments >4weeks ago. BI 2536 200–250mg was given intravenously on day 1 every 3 weeks until intolerance, progression or refusal. The study was based on a Simon two-stage design, with 12 patients entering in stage 1 and additional 25 patients to be entered in case of at least one response in the first stage. The rate of objective responses (RECIST criteria) was chosen as primary end-point. Results: Seventy six patients were included, 71 started treatment and received a median number of two cycles (four in ovarian cancer). Frequent grade 3–4 adverse events were neutropaenia (81.6%), thrombocytopaenia (19.7%), febrile neutropaenia (19.7%), anaemia (15.5%) and pain (9.9%). We did not observe confirmed objective responses. All cohorts were closed after the entry of 14–15 eligible non-responding patients. Pharmacokinetic analyses revealed multi-compartmental behaviour and a rapid distribution of BI 2536. Conclusions: BI 2536 showed limited antitumour activity according to the design of this trial in five different tumour types. Derivatives of BI 2536 with a more favourable pharmacological profile are currently explored further in prospective studies. [Copyright &y& Elsevier]

Abstract: The Renal Insufficiency and Anticancer Medications (IRMA) study is a French national, observational study which demonstrated the high prevalence of abnormal renal function in a population of 4684 solid tumor patients. Among them, 50–60% had decreased renal function, and 80% were treated with anticancer drugs that either necessitated dosage adjustment in case of renal insufficiency (RI) or were potentially nephrotoxic drugs. Since elderly patients are well-known to have reduced renal function, either due to physiological aging or their disease/medication history, a subgroup analysis of this particular population of patients was performed. In 1553 IRMA patients whose age was ≥65 years, the prevalence of RI was very high in spite of normal serum creatinine values in most cases. Anticancer drugs used may be nephrotoxic or need dosage adjustment in a high number of cases. [Copyright &y& Elsevier]

Purpose: To better identify prognostic factors for local control and survival, as well as the role of different therapeutic options, for phyllodes tumors, a rare fibroepithelial neoplasm of the breast. Methods and Materials: Data from 443 women treated between 1971 and 2003 were collected from the Rare Cancer Network. The median age was 40 years (range, 12–87 years). Tumors were benign in 284 cases (64%), borderline in 80 cases (18%), and malignant in 79 cases (18%). Surgery consisted of breast-conserving surgery (BCS) in 377 cases (85%) and total mastectomy (TM) in 66 cases (15%). Thirty-nine patients (9%) received adjuvant radiotherapy (RT). Results: After a median follow-up of 106 months, local recurrence (LR) and distant metastases rates were 19% and 3.4%, respectively. In the malignant and borderline group (n = 159), RT significantly decreased LR (p = 0.02), and TM had better results than BCS (p = 0.0019). Multivariate analysis revealed benign histology, negative margins, and no residual disease (no RD) after initial treatment and RT delivery as independent favorable prognostic factors for local control; benign histology and low number of mitosis for disease-free survival; and pathologic tumor size