Rethinking surgical revisions: impact of the MonarchE trial on axillary dissection in hormone-positive HER2-negative early breast cancer patients potentially eligible for abemaciclib.

INTRODUCTION: The MonarchE trial explored the use of abemaciclib, a CDK4/6 inhibitor, as an adjuvant treatment in high-risk early-stage luminal-like breast cancer. The study's inclusion criteria, especially the N2 status, may require revisiting surgical interventions, including invasive axillary lymph node dissection (ALND)-a procedure that current guidelines generally do not recommend. METHODS: We conducted a single-centre, retrospective, observational cohort study on non-metastatic breast cancer patients managed from 2002 to 2011, at the Institut Curie. Data collection involved clinical and histological characteristics plus treatment follow-up. RESULTS: Out of 8715 treated patients, 721 met the inclusion criteria. Overall, 12% (87) were classified as N2 ( ≥ 4 positive lymph nodes), thus eligible for abemaciclib per "node criterion." Tumour size, positive sentinel lymph nodes, and lobular histology showed a significant correlation with N2 status. Approximately 1000 ALNDs would be required to identify 120 N2 cases and prevent four recurrences. CONCLUSION: The MonarchE trial may significantly affect surgical practices due to the need for invasive procedures to identify high-risk patients for adjuvant abemaciclib treatment. The prospect of unnecessary morbidity demands less invasive N2 status determination methods. Surgical decisions must consider patient health and potential treatment benefits.

Sex-related differences in oncological surgery and postoperative outcomes: comprehensive, nationwide study in France.

BACKGROUND: The main objective of this study was to undertake an exhaustive investigation of sex-related differences in cancer surgery. METHODS: This observational study used data from the French national health insurance system database covering 98.8% of the population. Patients diagnosed with non-sex-specific solid invasive cancers between January 2018 and December 2019 were included. The main outcomes were likelihood of undergoing cancer surgery, type of oncological surgery performed, and associated 30-, 60-, and 90-day postoperative reoperation and mortality rates, by sex. RESULTS: For the 367 887 patients included, women were 44% more likely than men to undergo cancer surgery (OR 1.44, 95% c.i. 1.31 to 1.59; P < 0.001). However, the likelihood of surgery decreased with advancing age (OR 0.98, 0.98 to 0.98; P < 0.001), and with increasing number of co-morbid conditions (OR 0.95, 0.95 to 0.96; P < 0.001), especially in women. Men had higher 90-day reoperation (21.2 versus 18.8%; P < 0.001) and mortality (1.2 versus 0.9%; P < 0.001) rates than women, overall, and for most cancer types, with the exception of bladder cancer, for which the 90-day mortality rate was higher among women (1.8 versus 1.4%; P < 0.001). After adjustment for age, number of co-morbid conditions, and surgical procedure, 90-day mortality remained higher in men (OR 1.16, 1.07 to 1.26; P < 0.001), and men were 21% more likely than women to undergo reoperation within 90 days (OR 1.21, 1.18 to 1.23; P < 0.001). CONCLUSION: Women were much more likely than men to undergo cancer surgery than men, but the likelihood of surgery decreased with advancing age and with increasing number of co-morbid conditions, especially in women. These findings highlight a need for both increased awareness and strategies to ensure gender equality in access to oncological surgical treatment and improved outcomes.

Akt-Activated Endothelium Increases Cancer Cell Proliferation and Resistance to Treatment in Ovarian Cancer Cell Organoids.

Ovarian cancer (OC) is a heterogeneous disease characterized by its late diagnosis (FIGO stages III and IV) and the importance of abdominal metastases often observed at diagnosis. Detached ovarian cancer cells (OCCs) float in ascites and form multicellular spheroids. Here, we developed endothelial cell (EC)-based 3D spheroids to better represent in vivo conditions. When co-cultured in 3D conditions, ECs and OCCs formed organized tumor angiospheres with a core of ECs surrounded by proliferating OCCs. We established that Akt and Notch3/Jagged1 pathways played a role in angiosphere formation and peritoneum invasion. In patients' ascites we found angiosphere-like structures and demonstrated in patients' specimens that tumoral EC displayed Akt activation, which supports the importance of Akt activation in ECs in OC. Additionally, we demonstrated the importance of FGF2, Pentraxin 3 (PTX3), PD-ECGF and TIMP-1 in angiosphere organization. Finally, we confirmed the role of Notch3/Jagged1 in OCC-EC crosstalk relating to OCC proliferation and during peritoneal invasion. Our results support the use of multicellular spheroids to better model tumoral and stromal interaction. Such models could help decipher the complex pathways playing critical roles in metastasis spread and predict tumor response to chemotherapy or anti-angiogenic treatment.

Impact of Sociodemographic Characteristics on the Quality of Care in the Surgical Management of Endometrial Cancer: An Analysis of a National Database in the United States.

INTRODUCTION: Quality of care is an emerging concern, notably in oncology. The aim of the present study was to identify the sociodemographic factors influencing the quality of care in the USA concerning the surgical management of endometrial cancer (EC) through the Surveillance Epidemiology and End Results (SEER) database using already published Belgian quality indicators (QI). METHODS: Using the SEER database 1988-2013, we identified 151,752 patients treated for EC. Six QI were extracted from a Belgian study on quality of care in EC because of their applicability to the SEER. These QI evaluated only the surgical management. We examined the association between sociodemographic characteristics and quality of care with a logistic regression model. We compared our results with those defined as theoretical target by the Belgian initiative and considered a QI to be accurately met if >80% of the population met the indicator, moderately met between 50 and 80%, and poorly met under 50%. RESULTS: Concerning the 6 surgical QIs, one was accurately met, 3 were moderately met, and 2 were poorly met. For example, 73% of the patients with a high-risk EC underwent a pelvic lymphadenectomy. Age over 75 years old, black ethnicity, lower-income group, without partner, and uninsured had a negative impact on adherence to QIs. CONCLUSION: Demographic discrepancies persist in the surgical management of EC, impacting evidence-based care.

Breast Cancer and Mediastinal Hodgkin's Lymphomas: Multidisciplinary Discussion.

Treatment for Hodgkin's lymphoma (HL) has evolved, with modern treatments combining less toxic chemotherapy and radiation, leading to improved long-term disease-free survival. However, there is a higher chance of second cancer, especially breast cancer, following effective HL treatment. The impact of reduced radiation doses and volumes, as well as the use of advanced irradiation techniques, on the risk of second malignancy is not clear. According to medical organizations, the history of chest irradiation is a relative contraindication to breast preservation therapy for women with initial breast cancer, leading to a paradigm of mastectomy. This article proposes a discussion between radiation oncologists and surgeons to review major trials and recent developments on the prevalence of breast cancer following HL therapy, the risk of contralateral cancer, the feasibility of breast conserving surgery (BCS), as well as breast reconstruction modalities.

Sentinel Lymph Node Biopsy in Uterine Cancer: Time for a Modern Approach.

Since the validation of the sentinel node technique (SLN) for vulvar cancer 20 years ago, this technique has been introduced in the management of operable cervical cancer and endometrial cancer. For cervical cancer a "one fits all" attitude has mainly been presented. However, this approach, consisting of a frozen section during the operation, can be discussed in some stages. We present and discuss the main option for each stage, as well as some secondary possibilities. For endometrial cancer, SLN is now the technique of choice for the nodal staging of low- and intermediate-risk groups. Some discussion exists for the high-risk group. We also discuss the impacts of using preoperatively the molecular classification of endometrial cancer. Patients with POLE or TP53 mutations could have different nodal staging. The story of SLN in uterine cancers is not finished. We propose a comprehensive algorithm of SLN in early cervical and endometrial cancers. However, several ongoing trials will give us important data in the coming years. They could substantially change these propositions.

Effects of gender and socio-environmental factors on health-care access in oncology: a comprehensive, nationwide study in France.

Background: Gender-based disparities in health-care are common and can affect access to care. We aimed to investigate the impact of gender and socio-environmental indicators on health-care access in oncology in France. Methods: Using the national health insurance system database in France, we identified patients (aged ≥18 years) who were diagnosed with solid invasive cancers between the 1st of January 2018 and the 31st of December 2019. We ensured that only incident cases were identified by excluding patients with an existing cancer diagnosis in 2016 and 2017; skin cancers other than melanoma were also excluded. We extracted 71 socio-environmental variables related to patients' living environment and divided these into eight categories: inaccessibility to public transport, economic deprivation, unemployment, gender-related wage disparities, social isolation, educational barriers, familial hardship, and insecurity. We employed a mixed linear regression model to assess the influence of age, comorbidities, and all eight socio-environmental indices on health-care access, while evaluating the interaction with gender. Health-care access was measured using absolute and relative cancer care expertise indexes. Findings: In total, 594,372 patients were included: 290,658 (49%) women and 303,714 (51%) men. With the exception of unemployment, all socio-environmental indices, age, and comorbidities were inversely correlated with health-care access. However, notable interactions with gender were observed, with a stronger association between socio-environmental factors and health-care access in women than in men. In particular, inaccessibility to public transport (coefficient for absolute cancer care expertise index = -1.10 [-1.22, -0.99], p < 0.0001), familial hardship (-0.64 [-0.72, -0.55], p < 0.0001), social isolation (-0.38 [-0.46, -0.30], p < 0.0001), insecurity (-0.29 [-0.37, -0.21], p < 0.0001), and economic deprivation (-0.13 [-0.19, -0.07], p < 0.0001) had a strong negative impact on health-care access in women. Interpretation: Access to cancer care is determined by a complex interplay of gender and various socio-environmental factors. While gender is a significant component, it operates within the context of multiple socio-environmental influences. Future work should focus on developing targeted interventions to address these multifaceted barriers and promote equitable health-care access for both genders. Funding: None.

Impact of the Area of Residence of Ovarian Cancer Patients on Overall Survival.

Survival disparities persist in ovarian cancer and may be linked to the environments in which patients live. The main objective of this study was to analyze the global impact of the area of residence of ovarian cancer patients on overall survival. The data were obtained from the Surveillance, Epidemiology and End Results (SEER) database. We included all the patients with epithelial ovarian cancers diagnosed between 2010 and 2016. The areas of residence were analyzed by the hierarchical clustering of the principal components to group similar counties. A multivariable Cox proportional hazards model was then fitted to evaluate the independent effect of each predictor on overall survival. We included a total of 16,806 patients. The clustering algorithm assigned the 607 counties to four clusters, with cluster 1 being the most disadvantaged and cluster 4 having the highest socioeconomic status and best access to care. The area of residence cluster remained a statistically significant independent predictor of overall survival in the multivariable analysis. The patients living in cluster 1 had a risk of death more than 25% higher than that of the patients living in cluster 4. This study highlights the importance of considering the sociodemographic factors within the patient's area of residence when developing a care plan and follow-up.

Impact of Extent of Lymphadenectomy on Survival in Patients With Endometrial Cancer: A Matched Cohort Study.

BACKGROUND/AIM: This study aimed to determine whether a pelvic and para-aortic lymphadenectomy (PPAL) improves survival compared with a pelvic lymphadenectomy (PL) in patients with endometrial cancer. PATIENTS AND METHODS: Data from all women operated for endometrial cancer between 1998 and 2013 were extracted from the Surveillance, Epidemiology and End Results database. Women treated with PL were matched with those treated with PPAL according to age and risk of recurrence. The primary endpoint was disease-specific survival (DSS). RESULTS: A total of 1015 patients who underwent PL were matched with 1015 patients who underwent PPAL. The 3-year DSS probabilities for patients at intermediate- and high-risk (IHR) of recurrence were similar in the PPAL group and the PL group. Multivariate analysis of prognostic factors indicated that in patients with an IHR of recurrence, PPAL did not reduce the risk of death compared with PL. CONCLUSION: For patients with an IHR of recurrence, the extent of lymphadenectomy does not impact DSS.