Conflict of Interest Disclosure in Oncology: Preliminary Insights From the Global ONCOTRUST-1 Cross-Sectional Study.

PURPOSE: Conflicts of interest (COIs) between oncologists and industry might considerably influence how the presentation of the research results is delivered, ultimately affecting clinical decisions and policy-making. Although there are many regulations on reporting COI in high-income countries (HICs), little is known about their reporting in low- and middle-income countries (LMICs). Oncology Transparency Under Scrutiny and Tracking (ONCOTRUST-1) is a pilot global survey to explore the knowledge and perceptions of oncologists regarding COI. MATERIALS AND METHODS: We designed an online 27-question-based survey in the English language to explore the perceptions and knowledge of oncologists regarding COI, with an emphasis on LMICs. Descriptive statistics and the Consensus-Based Checklist for Reporting of Survey Studies guidelines were used to report the findings. RESULTS: ONCOTRUST-1 surveyed 200 oncologists, 70.9% of them practicing in LMICs. Median age of the respondents was 36 (range, 26-84) years; 47.5% of them were women. Of the respondents, 40.5% reported weekly visits by pharmaceutical representatives to their institutions. Regarding oncologists' perceptions of COI that require disclosure, direct financial benefits, such as honoraria, ranked highest (58.5%), followed by gifts from pharmaceutical representatives (50%) and travel grants for attending conferences (44.5%). By contrast, personal or institutional research funding, sample drugs, consulting or advisory board, expert testimony, and food and beverage funded by pharmaceutical industry were less frequently considered as COI. Moreover, only 24% of surveyed oncologists could correctly categorize all situations representing a COI. CONCLUSION: These findings underscore the importance of clear guidelines, education, and transparency in reporting COI in oncology. This hypothesis-generating pilot survey provided the rationale for ONCOTRUST-2 study, which will compare perceptions of COI among oncologists in LMICs and HICs.

Everolimus plus endocrine therapy beyond CDK4/6 inhibitors progression for HR+ /HER2- advanced breast cancer: a real-world evidence cohort.

PURPOSE: Everolimus in combination with endocrine therapy (ET) was formerly approved as 2nd-line therapy in HR(+)/HER2(-) advanced breast cancer (aBC) patients (pts) progressing during or after a non-steroidal aromatase inhibitor (NSAI). Since this approval, the treatment landscape of aBC has changed dramatically, particularly with the arrival of CDK 4-6 inhibitors. Endocrine monotherapy after progression to CDK4/6 inhibitors has shown a limited progression-free survival (PFS), below 3 months. Evidence of the efficacy of everolimus plus ET after CDK4/6 inhibitors is scarce. METHODS: A retrospective observational study of patients with aBC treated with everolimus and ET beyond CDK4/6-i progression compiled from February 2015 to December 2022 in 4 Spanish hospitals was performed. Clinical and demographic data were collected from medical records. The main objective was to estimate the median progression-free survival (mPFS). Everolimus adverse events (AE) were registered. Quantitative variables were summarized with medians; qualitative variables with proportions and the Kaplan-Meier method were used for survival estimates. RESULTS: One hundred sixty-one patients received everolimus plus ET (exemestane: 96, fulvestrant: 54, tamoxifen: 10, unknown: 1) after progressing on a CDK4/6 inhibitor. The median follow-up time was 15 months (interquartile range: 1-56 months). The median age at diagnosis was 49 years (range: 35-90 years). The estimated mPFS was 6.0 months (95%CI 5.3-7.8 months). PFS was longer in patients with previous CDK4/6 inhibitor therapy lasting for > 18 months (8.7 months, 95%CI 6.6-11.3 months), in patients w/o visceral metastases (8.0 months, 95%CI 5.8-10.5 months), and chemotherapy-naïve in the metastatic setting (7.2 months, 95%CI 5.9-8.4 months). CONCLUSION: This retrospective analysis cohort of everolimus plus ET in mBC patients previously treated with a CDK4/6 inhibitor suggests a longer estimated mPFS when compared with the mPFS with ET monotherapy obtained from current randomized clinical data. Everolimus plus ET may be considered as a valid control arm in novel clinical trial designs.

Electronic malignant bowel obstruction symptom monitoring smartphone application for patients with gynecologic cancers.

OBJECTIVES: Implementation of an interprofessional program at Princess Margaret Cancer Centre, including nurse-led proactive calls to support patients with gynecologic cancers with malignant bowel obstruction, demonstrated improved outcomes compared with historical controls. The aim of the study was to convert the proactive calls into an electronic monitoring program to assess it's feasibility and scalability in patients with gynecologic cancers with or at risk of malignant bowel obstruction. METHODS: 'My Bowels on Track' smartphone application included weekly/biweekly electronic patient-reported outcomes (PROs), educational materials, and a secure messaging system. Based on PRO answers, an alerting system flagged patients with symptoms or uncompleted PROs. Nurses tracked and called patients on receiving clinical or compliance alerts. The primary objective was to assess adherence (≥70% PRO completion per patient considered an adherent patient) in the first 2 months on the program. A secondary objective was to assess the positive predictive value (PPV) of the alerts to trigger recommendations. RESULTS: Forty patients were enrolled between August 2021 and September 2022. Median age was 64.5 years (range 29-79 years). Primary diagnosis was ovarian (75%), endometrial (17.5%), or cervical (7.5%) cancer, and 92.5% of patients were receiving systemic therapy. Median duration on the program was 55 days (range 8-121 days). The 2-month adherence was 65% (95% CI 50% to 80%) and the overall adherence was 60% (95% CI 43% to 75%). Sixty-five symptom-related alerts (75% severe, 25% moderate) were reported in 60% (24/40) of patients. There were 59 recommendations triggered by the alerts. The PPV of the alerts to trigger actions was 72% (95% CI 58% to 82%). CONCLUSIONS: This pilot electronic malignant bowel obstruction monitoring program with real-time PRO assessment was feasible, and 65% of participants were adherent during the first 2 months on the program. The PRO response-based alerting system flagged concerning symptoms in 60% of participants, with a PPV of 72% to trigger nurse-led actions and/or management recommendations. TRIAL REGISTRATION NUMBER: NCT03260647.

HER2-low and Overexpression in Mucinous Ovarian Cancer: Analysis of ASCO/CAP and ToGA Immunohistochemical Scoring.

Mucinous ovarian carcinoma is an uncommon malignancy characterized by resistance to chemotherapy and poor survival in the metastatic setting. HER2 amplification is a frequent late event in carcinogenesis, yet the incidence of HER2-low in mucinous ovarian carcinoma is unknown. Further, the optimal method for determining overexpression in these tumors is not established. We sought to assess the ASCO/CAP and ToGA trial scoring methods for HER2 IHC with correlation to FISH, p53, and mismatch repair protein status and to determine the incidence of HER2-low in mucinous ovarian carcinoma. A total of 29 tumors from 23 patients were included. Immunohistochemistry for HER2, p53, MLH1, PMS2, MSH2, and MSH6 was performed. Scoring was performed according to the ASCO/CAP and ToGA trial criteria. HER2 FISH was performed and scored according to the ASCO/CAP criteria. The proportion of HER2-low, defined as 1+ or 2+ staining with negative FISH, was determined. Using ASCO/CAP, 26% demonstrated 3+ while 35% demonstrated 2+ staining. Using ToGA, 30% demonstrated 3+ while 57% demonstrated 2+ staining. By FISH, 26% were positive for HER2 amplification. Both systems captured all FISH-positive cases; the use of ASCO/CAP resulted in fewer equivocal and false-positive cases. Among HER2-negative cases, 88% were HER2-low. Aberrant p53 expression was detected in 55% of cases; mismatch repair deficiency was not identified in any cases. ASCO/CAP guidelines are accurate and resource-effective in determining HER2 overexpression in mucinous ovarian carcinoma. HER2-low is common in these tumors; further studies to determine the role of HER2-targeted therapy including antibody-drug conjugates are indicated.

High grade adverse event reporting and enrolment in gynecologic oncology clinical trials.

OBJECTIVE: The primary objective is to assess factors associated with treatment related high grade (CTCAE grade ≥ 3) adverse event (AE) reporting among participants in gynecologic oncology clinical trials. METHODS: All AEs recorded in the Princess Margaret Clinical Trial adverse event database between 01/2016 and 12/2018 were evaluated. Gynecologic oncology clinical trials assessing systemic therapy were included. Inferential statistics on risk factors of related grade ≥ 3 adverse event reporting and GEE logistic models with Odds Ratios (OR) were performed. Multivariable analysis adjusting for age, clinical trial phase, sponsor, and therapy type. RESULTS: The gynecology cancer clinical trials accrued 317 unique patients (359 nested on trials) in 42 systemic therapy trials. In the period, 17,175 related AEs were reported in the gynecological cancer trials, 7.4% were grade ≥ 3. On multivariable analysis, no odds differences of grade ≥ 3 related AEs were detected according to study phase. Patients in immunotherapy clinical trials had lower odds of related grade ≥ 3 AEs than patients on targeted or other therapy (adjusted OR [aOR] 0.43; 95% CI 0.24-0.75). There was greater odds of related grade ≥ 3 AEs in clinical trials assessing combination vs single therapeutics (aOR 2.26, 95% CI 1.34-3.80). Patients aged ≥65 (aOR 1.77; 95% CI 1.08-2.89) had greater odds of related grade ≥ 3 AEs than patients aged 50 to 65 years. When compared to other disease sites, the odds of having a grade  ≥ 3 related AE reported in gynecology clinical trials was no different. CONCLUSIONS: In this cohort, factors influencing the odds of related grade ≥ 3 AE reporting in gynecologic trials included type of therapy and age. The study phase did not correlate with odds of high-grade AE reporting.

New horizons for platinum-resistant ovarian cancer: insights from the 2023 American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) Annual Meetings.

Platinum-resistant ovarian cancer is difficult to treat and has a poor prognosis. Patients with platinum-resistant ovarian cancer have limited treatment options and often have a limited benefit from existing chemotherapeutic agents. There is a lack of contemporary effective anticancer drugs and reliable predictive biomarkers for this aggressive cancer. Recent cutting-edge research presented at the 2023 American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) Annual Meetings has provided insights into several potential therapeutic targets, such as DNA damage repair proteins, cell-cycle regulators, and immune-modulating agents. In addition, antibody-drug conjugates have provided new practice-changing results in platinum-resistant ovarian cancer. Here, we review the results of research presented at this annual event, with a focus on clinical trials investigating novel treatment approaches for platinum-resistant ovarian cancer, in addition to predictive and prognostic biomarkers for optimal patient selection, and other topics, such as real-world evidence.

Heterogeneity and treatment landscape of ovarian carcinoma.

Ovarian carcinoma is characterized by heterogeneity at the molecular, cellular and anatomical levels, both spatially and temporally. This heterogeneity affects response to surgery and/or systemic therapy, and also facilitates inherent and acquired drug resistance. As a consequence, this tumour type is often aggressive and frequently lethal. Ovarian carcinoma is not a single disease entity and comprises various subtypes, each with distinct complex molecular landscapes that change during progression and therapy. The interactions of cancer and stromal cells within the tumour microenvironment further affects disease evolution and response to therapy. In past decades, researchers have characterized the cellular, molecular, microenvironmental and immunological heterogeneity of ovarian carcinoma. Traditional treatment approaches have considered ovarian carcinoma as a single entity. This landscape is slowly changing with the increasing appreciation of heterogeneity and the recognition that delivering ineffective therapies can delay the development of effective personalized approaches as well as potentially change the molecular and cellular characteristics of the tumour, which might lead to additional resistance to subsequent therapy. In this Review we discuss the heterogeneity of ovarian carcinoma, outline the current treatment landscape for this malignancy and highlight potentially effective therapeutic strategies in development.

Digging into phenotype change in mismatch repair deficient endometrial carcinoma and treatment with immune checkpoint inhibition, a case report.

•False negative cases for mismatch repair determination by immunohistochemistry may occur.•The mismatch repair phenotype in endometrial carcinoma impacts on therapeutic decision making.•Retesting for mismatch repair at relapse of endometrial carcinoma should be considered.

Side effects screening and early intervention to impact in quality of life of patients with gynecological cancers (HALIS study).

BACKGROUND: Advances in the treatment of gynecological cancers have led to increased survival in patients with gynecological cancers. Nevertheless, patients may still experience prevalent long term consequences, including lower limb lymphedema, depression, anxiety, sexual dysfunction, malnutrition, and sarcopenia, that negatively impact their quality of life. PRIMARY OBJECTIVE: To assess the impact on self-perceived quality of life of systematic screening and early treatment of lower limb lymphedema, anxiety and depression, sexual dysfunction, and sarcopenia and malnutrition compared with standard practice. STUDY HYPOTHESIS: Systematic screening with validated questionnaires leading to early diagnosis and treatment of side effects will have a positive impact on quality of life. TRIAL DESIGN: This prospective clinical trial will randomize candidates for surgery to either standard of care or systematic screening every 2 months for 2 years. Quality of life data will be collected every 4 months. After randomization, patients in the control group will follow standard usual care. Their screening scales will not be considered. In the experimental group, positive screenings will generate an alert to the physician, and patients will be referred to the corresponding specific area (rehabilitation unit, psycho-oncology unit, sexual health unit, or nutrition unit). MAJOR INCLUSION AND XCLUSION CRITERIA: Patients aged ≥18 years with ovarian, cervical, or endometrial cancer who are candidates for surgery will be included. PRIMARY ENDPOINT: Self-reported quality of life questionnaire score. SAMPLE SIZE: 168 patients will be randomized to detect a difference of 6 points in the questionnaires. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Study completion is estimated for January 2026 and the results will be presented in May 2026. TRIAL REGISTRATION NUMBER: NCT05918770.

Analysis of the association of HER-2 low carcinomas and PAM50 assay in hormone receptor positive early-stage breast cancer.

BACKGROUND: HER2-low has emerged as a new predictive biomarker in metastatic breast cancer. However, its prognostic value in early-stage carcinomas needs to be revisited. We aimed to evaluate the association of HER2-low carcinomas with PAM50 risk groups combined with clinicopathological variables in early breast cancer. METHODS: We conducted a retrospective analysis of 332 patients with early-stage breast cancer that underwent PAM50 signature analysis between 2015 and 2021at Hospital Universitario 12 de Octubre (Madrid, Spain). Clinical and pathological variables were collected from medical records. After adjusting for potential confounders, we estimated Odds Ratio (OR) and 95% confidence interval for high-risk PAM50 subgroup, comparing HER2-low versus HER2-zero carcinomas by multivariable logistic regression. P values below 0.05 were deemed statistically significant. RESULTS: 192 (57%) patients were classified as HER2-low carcinomas. Median follow-up was 34 months. Adjusted OR for high-risk PAM50 when comparing HER2-low versus HER2-zero carcinomas was 1.31 (95% CI: 0.75-2.30, p = 0.33). The multivariable model detected significant associations for Ki-67% (≥20% vs. <20%: OR = 4.03, 95% CI: 2.15-7.56, p < 0.001), T staging category (T2/T3 vs. T1: OR = 3.44, 95% CI: 1.96-6.04, p < 0.001), progesterone receptor (PR ≥ 20% vs. <20%: OR = 0.44, 95% CI: 0.23-0.83, p = 0.01), nodal staging category (N+ vs. N0: OR = 3.8, 95% CI: 1.89-7.62, p < 0.001) and histological grade (grade 2 vs. 1: OR = 2.41, 95% CI: 1.01-5.73, p = 0.04; grade 3 vs 1: OR = 5.40, 95%CI: 1.98-14.60, p = 0.001). CONCLUSIONS: In this early-stage breast cancer cohort, HER2-low was not associated with a high-risk PAM50 compared to HER2-zero carcinomas. Ki-67 ≥ 20%, T2/T3, histological grade 2/3, N+ and PR<20% were significantly associated to a high-risk PAM50.

Identifying Mechanisms of Resistance by Circulating Tumor DNA in EVOLVE, a Phase II Trial of Cediranib Plus Olaparib for Ovarian Cancer at Time of PARP Inhibitor Progression.

PURPOSE: To evaluate the use of blood cell-free DNA (cfDNA) to identify emerging mechanisms of resistance to PARP inhibitors (PARPi) in high-grade serous ovarian cancer (HGSOC). EXPERIMENTAL DESIGN: We used targeted sequencing (TS) to analyze 78 longitudinal cfDNA samples collected from 30 patients with HGSOC enrolled in a phase II clinical trial evaluating cediranib (VEGF inhibitor) plus olaparib (PARPi) after progression on PARPi alone. cfDNA was collected at baseline, before treatment cycle 2, and at end of treatment. These were compared with whole-exome sequencing (WES) of baseline tumor tissues. RESULTS: At baseline (time of initial PARPi progression), cfDNA tumor fractions were 0.2% to 67% (median, 3.25%), and patients with high ctDNA levels (>15%) had a higher tumor burden (sum of target lesions; P = 0.043). Across all timepoints, cfDNA detected 74.4% of mutations known from prior tumor WES, including three of five expected BRCA1/2 reversion mutations. In addition, cfDNA identified 10 novel mutations not detected by WES, including seven TP53 mutations annotated as pathogenic by ClinVar. cfDNA fragmentation analysis attributed five of these novel TP53 mutations to clonal hematopoiesis of indeterminate potential (CHIP). At baseline, samples with significant differences in mutant fragment size distribution had shorter time to progression (P = 0.001). CONCLUSIONS: Longitudinal testing of cfDNA by TS provides a noninvasive tool for detection of tumor-derived mutations and mechanisms of PARPi resistance that may aid in directing patients to appropriate therapeutic strategies. With cfDNA fragmentation analyses, CHIP was identified in several patients and warrants further investigation.

Safety of fertility sparing management in invasive mucinous ovarian carcinoma.

BACKGROUND: The aim of the study was to evaluate the safety of fertility-sparing surgery in invasive mucinous ovarian carcinomas (MOC). METHODS: Retrospective review was performed of MOCs diagnosed between 1999 and 2019 at two tertiary cancer centers. Pathology was reviewed to rule out metastasis from gastrointestinal tract. The demographics and survival outcomes were compared between women who underwent fertility-sparing surgery and those who underwent radical surgery (at least hysterectomy, bilateral salpingo-oophorectomy +/- staging). Cox proportional hazard models were constructed to evaluate the effect of fertility sparing surgery on survival. RESULTS: Of 134 with stage I disease, 42 (31%) underwent fertility-sparing surgery with unilateral salpingo-oophorectomy. Compared to women who underwent radical surgery, these women were younger with low grade, early-stage disease. Two patients (5%) in the fertility-sparing cohort experienced a recurrence and 1 of these 2 patients died due to disease progression. There was no difference in either OS or RFS between those that underwent fertility-sparing surgery and radical surgery. In a multivariable analysis adjusting for age and use of adjuvant chemotherapy, fertility-sparing surgery was not significantly associated with OS (HR 0.18; 95% CI 0.01-2.78) or RFS (HR 0.19; 95% CI 0.03-1.45). There were 4 patients (9%) with documented full-term delivery with median interval to conception of 11 months. CONCLUSIONS: Fertility-sparing surgery in stage I MOC is not associated with worse outcomes compared to radical surgery and is reasonable to offer to those with early stage disease who wish to retain fertility.

Outcomes and endpoints of relevance in gynecologic cancer clinical trials.

Drug development is paramount to improve outcomes in patients with gynecologic cancers. A randomized clinical trial should measure whether a clinically relevant improvement is detected with the new intervention compared with the standard of care, using reproductible and appropriate endpoints. Clinically meaningful improvements in overall survival and/or quality of life (QoL) are the gold standards to measure benefit of new therapeutic strategies. Alternative endpoints, such as progression-free survival, provide an earlier measure of the effect of the new therapeutic drug, and are not confounded by the effect of subsequent lines of therapy. Yet, its surrogacy with improved overall survival or QoL is unclear in gynecologic malignancies. Of relevance to studies assessing maintenance strategies are other time-to-event endpoints, such as progression-free survival two and time to second subsequent treatment, which provide valuable information on the disease control in the longer term. Translational and biomarker studies are increasingly being incorporated into gynecologic oncology clinical trials, as they may allow understanding of the biology of the disease, resistance mechanisms, and enable a better selection of patients who might benefit from the new therapeutic strategy. Globally, the endpoint selection of a clinical trial will differ according to the type of study, population, disease setting, and type of therapeutic strategy. This review provides an overview of primary and secondary endpoint selection of relevance for gynecologic oncology clinical trials.

Clinical outcome and biomarker assessments of a multi-centre phase II trial assessing niraparib with or without dostarlimab in recurrent endometrial carcinoma.

This multi-centre, non-randomized, open-label, phase II trial (NCT03016338), assessed niraparib monotherapy (cohort 1, C1), or niraparib and dostarlimab (cohort 2, C2) in patients with recurrent serous or endometrioid endometrial carcinoma. The primary endpoint was clinical benefit rate (CBR), with ≥5/22 overall considered of interest. Secondary outcomes were safety, objective response rate (ORR), duration of response, progression free survival and overall survival. Translational research was an exploratory outcome. Potential biomarkers were evaluated in archival tissue by immunohistochemistry and next generation sequencing panel. In C1, 25 patients were enrolled, and CBR was 20% (95% CI: 9-39) with median clinical benefit duration of 5.3 months. The ORR was 4% (95% CI: 0-20). In C2, 22 patients were enrolled, and the CBR was 31.8% (95% CI: 16-53) with median clinical benefit duration of 6.8 months. The ORR was 14% (95% CI: 3-35). No new safety signals were detected. No significant association was detected between clinical benefit and IHC markers (PTEN, p53, MMR, PD-L1), or molecular profiling (PTEN, TP53, homologous recombination repair genes). In conclusion, niraparib monotherapy did not meet the efficacy threshold. Niraparib in combination with dostarlimab showed modest activity.

Impact of lymphadenectomy and intra-operative tumor rupture on survival in early-stage mucinous ovarian cancers.

OBJECTIVE: Mucinous ovarian carcinoma is a rare subtype of epithelial ovarian cancer with scarce literature guiding its management. We aimed to investigate the optimal surgical management of clinical stage I mucinous ovarian carcinoma by examining the prognostic significance of lymphadenectomy and intra-operative rupture on patient survival. METHODS: We conducted a retrospective cohort study of all pathology-reviewed invasive mucinous ovarian carcinomas diagnosed between 1999 and 2019 at two tertiary care cancer centers. Baseline demographics, surgical management details, and outcomes were collected. Five-year overall survival, recurrence-free survival, and the association of lymphadenectomy and intra-operative rupture on survival were examined. RESULTS: Of 170 women with mucinous ovarian carcinoma, 149 (88%) had clinical stage I disease. Forty-eight (32%; n=149) patients had a pelvic and/or para-aortic lymphadenectomy, but only 1 patient with grade 2 disease was upstaged due to positive pelvic lymph nodes. Intra-operative tumor rupture was documented in 52 cases (35%). On multivariable analysis, after adjusting for age, final stage, and use of adjuvant chemotherapy, there was no significant association between intra-operative rupture with overall survival (HR 2.2 (0.6-8.0); p=0.3) or recurrence-free survival (HR 1.3 (0.5-3.3); p=0.6), or lymphadenectomy with overall survival (HR 0.9 (0.3-2.8); p=0.9) or recurrence-free survival (HR 1.2 (0.5-3.0); p=0.7). Advanced stage was the only factor that was significantly associated with survival. CONCLUSIONS: In clinical stage I mucinous ovarian carcinoma, systematic lymphadenectomy has low utility, as very few patients are upstaged and recurrence typically occurs in the peritoneum. Furthermore, intra-operative rupture does not appear to independently confer a worse survival, and therefore these women may not benefit from adjuvant treatment based on rupture alone.

Safety of bevacizumab and olaparib as frontline maintenance therapy in advanced ovarian cancer: expert review for clinical practice.

Olaparib, a poly(ADP-ribose) polymerase inhibitor, in combination with the antiangiogenic agent bevacizumab, is approved as maintenance therapy for patients with newly diagnosed stage III or IV epithelial ovarian cancer who have homologous recombination deficient tumors with a deleterious or suspected deleterious BRCA mutation and/or genomic instability based on the long-lasting survival benefit observed in the PAOLA-1 trial. Despite treatment with olaparib and bevacizumab showing an acceptable safety profile, the rate of discontinuations due to adverse events was relatively high, and toxicity related to this regimen may restrict its clinical use. Proper management of olaparib/bevacizumab-related adverse events is important for the improvement of quality of life and maximization of the efficacy of maintenance therapy. Here, we summarize the safety results of the PAOLA-1 study, focusing on treatment discontinuation reasons and adverse event profiles. We sought to shed light on toxicity monitoring and prevention, providing concise recommendations for the clinical management of the most relevant side effects.

Accuracy and Limitations of Sentinel Lymph Node Biopsy after Neoadjuvant Chemotherapy in Breast Cancer Patients with Positive Nodes.

Background: Axillary surgical management in patients with node-positive breast cancer at the time of diagnosis converted to negative nodes through neoadjuvant chemotherapy (NAC) remains unclear. Removal of more than two sentinel nodes (SLNs) in these patients may decrease the false negative rate (FNR) of sentinel lymph node biopsies (SLNBs). We aim to analyse the detection rate (DR) and the FNR of SLNB assessment according to the number of SLNs removed. Methods: A retrospective study was performed from October 2012 to December 2018. Patients with invasive breast cancer who had a clinically node-positive disease at diagnosis and with a complete axillary response after neoadjuvant chemotherapy were selected. Patients included underwent SLNB and axillary lymph node dissection (ALND) after NAC. The SLN was considered positive if any residual disease was detected. Descriptive statistics were used to describe the clinicopathologic features and the results of SLNB and ALND. The DR of SLNB was defined as the number of patients with successful identification of SLN. Presence of residual disease in ALND and negative SLN was considered false negative. Results: A total of 368 patients with invasive breast cancer who underwent surgery after complete NAC were studied. Of them, 85 patients met the eligibility criteria and were enrolled in the study. The mean age at diagnosis was 50.8 years. Systematic lymphadenectomy was performed in all patients, with an average of 10 lymph nodes removed. The DR of SLNB was 92.9%, and the FNR was 19.1. The median number of SLNs removed was 3, and at least, three SLNs were obtained in 42 patients (53.2%). When at least three sentinel nodes were removed, the FNR decreased to 8.7%. Conclusions: In this cohort, the SLN assessment was associated with an adequate DR and a high FNR. Removing three or more SLNs decreased the FNR from 19.1% to 8.7%. Complementary approaches may be considered for axillary lymph node staging after neoadjuvant chemotherapy. The study was approved by our institution's ethics committee (Instituto de Investigacion Sanitaria Hospital 12 de Octubre (imas12), Universidad Complutense de Madrid, Madrid, Spain) (https://clinicaltrials.gov/ct2/show/NCEI:20/0048).