IntroductionSexual wellbeing is an important yet often overlooked aspect of quality of life for many Adolescent and Young Adult patients with sarcoma. Given the significant impact of this issue and the dearth of previous research, this study aims to explore the sexual wellbeing and psychosexual needs of this group.Materials and methodsA descriptive, phenomenological, qualitative study was conducted. Open-ended, face-to-face interviews were used to achieve data saturation, following Giorgi’s approach. The Lincoln and Guba criteria and the COREQ guidelines were used to enhance methodological rigor and reporting quality. For descriptive purposes, information was collected on sociodemographic, clinical, quality of life and patient distress issues. Given the complexity of obtaining informed consent from parents or legal guardians of minors, the study included participants between the ages of 18 and 39 at the time of data collection.ResultsTwenty interviews with patients aged 18–39 years were collected. One overall domain, five themes, and 21 related sub-themes emerged from the thematic analysis. They were mainly related to the impact of the cancer diagnosis on patients’ priorities, scars and their symbolism and relationships with healthcare professionals and partners to promote sexual wellbeing. Patients reported relatively low levels of symptoms and high levels of functioning. The main symptom was insomnia, whereas fatigue and pain were less severe. Slight impairments were observed in the subject’s emotional functioning. 70% of patients had clinically significant Distress (≥4).DiscussionCancer significantly impacts the emotional relationships and sexual health of patients. A lack of information and taboos surrounding sexuality in oncology are significant barriers to patients’ psychological and physical wellbeing. Psychologists and nurses, in particular, should implement strategies to encourage open discussion about sexuality within this patient group.

BackgroundWith the rapid progress of molecular medicine, new target therapies for solid tumors have become available, leading to the creation of molecular tumor boards (MTBs) designated to evaluate potential individualized treatment options. Unlike other solid or liquid tumors, there is no standard and customized tool to analyze sarcoma. We analyzed the organization of MTB in referral centers for sarcomas treatment in Italy.Materials and methodsA 30-question survey was designed in 2021 by the Regina Elena National Cancer Institute and distributed among Italian referral centers for pediatric and adult sarcomas. This survey was developed as part of Alliance Against Cancer (Alleanza Contro il Cancro, ACC) project to provide a descriptive analysis of the availability and organization of MTBs as well as the propensity to offer genomic profiling to sarcoma patients.ResultsA total of 6 out of 10 centers contacted answered the survey, and all stating centers declared to have an MTB. The composition of MTB was variable, with a dedicated oncologist in 83% of centers, although all cases discussed required the presence of the oncologist. 83% of centers met the ACC criteria for eligibility at MTB discussion. In 83% of cases both the primary and the metastases were analyzed, while in 17% only the metastasis were analyzed. The type of analysis available were target panel sequencing and whole exome sequencing (WES) in 100% of centers, whole genome sequencing (WGS) in 83%, RNA sequencing in 53%. Bioinformatics analysis software used were Illumina pipeline in 50% of centers; Ion Reporter (Thermo Fisher Scientific), QIAGEN CLC Genomics Variant Reporter and Archer Analysis in 33%, 17% and 33% of centers respectively. The knowledge base software for variant interpretation in precision oncology were Oncomine Reporter and Sophia, both in 17%. Other specific tools (e.g., CibersortX, GATK suite, and DEseq2) were used in 33% of centers. The time required for the analysis was ≤ 10 days in 33% of centers and > 10 days in 67%. In 83% of centers results are stored locally, and a database with clinical data and follow-up was recorded.ConclusionMTBs were present in most sarcoma referral centers that answered the survey, albeit with different organizational arrangements. Although this survey should be regarded merely as a descriptive analysis of the early stages of MTB use in sarcomas, and is not representative of the national landscape as a whole, it highlights the clinical need to develop expertise in using MTB for rare cancers and to standardize the process and may serve as a basis for future larger-scale, prospective efforts aimed at harmonizing MTB practices across Italian sarcoma centers.

BACKGROUND:Primary breast sarcomas (PBS) and malignant phyllodes tumors (MPT) represent less than 1 % of breast malignancies. Current evidence relies on heterogeneous retrospective series, resulting in controversial therapeutic approaches. This study aimed to analyze long-term outcomes in a large multicentric cohort treated with consistent strategies. MATERIALS AND METHODS:We conducted a multicentric retrospective study involving 113 patients treated for PBS (n = 42), MPT (n = 47), and mixed cases (MC, n = 24) at 11 European breast units between 2000 and 2020. Primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS), local recurrence rate (LRR), and positive margin, re-excision, and axillary involvement rates. Survival analyses were performed using the Kaplan-Meier method and log-rank test. RESULTS:With a median follow-up of 95 months, the 10-year OS, DFS, and LRR for the entire cohort were 75.2 %, 61.9 %, and 18.4 %, respectively. Mixed cases exhibited the poorest outcomes (10-year OS: 57.6 %, DFS: 46.1 %), followed by PBS (OS: 67.5 %, DFS: 46.5 %). MPT demonstrated better survival rates (OS: 89.2 %, DFS: 82.9 %). Significant survival factors included histological subtype, surgical margins, and age. Notably, adjuvant chemotherapy was linked to worse outcomes (HR 5.11, 95 % CI 2.16-12.09, p < 0.001 for OS), likely indicating selection bias for high-risk patients. CONCLUSIONS:This study represents the largest European series with a homogeneous treatment approach and long-term follow-up. MC emerge as a distinct high-risk entity, with outcomes akin to angiosarcomas. While surgery remains the cornerstone of treatment, our data challenge the current paradigm regarding adjuvant chemotherapy, highlighting the need for new strategies, particularly for high-risk subtypes.

Giant cell tumor of bone (GCTB) is a benign but locally aggressive neoplasm that can rarely undergo malignant transformation, with a poor prognosis. The most frequent histotypes of the sarcomatous transformation of GCTB are osteosarcoma, fibrosarcoma, and undifferentiated pleomorphic sarcoma, and the treatment approach mirrors that of high-grade sarcomas. This case report describes the malignant transformation of a maxillary GCTB treated with standard systemic treatments for bone tumors and local treatment, resulting in a progression of disease until the patient’s death. Nevertheless, a marked radiological and clinical response was achieved with local carbon ion therapy. This case highlights the diagnostic and therapeutic challenges of malignant transformation of GCTB, emphasizing the importance of a multidisciplinary approach at specialized centers and the potential role of local therapies in selected cases.

Ifosfamide (IFO) is a nitrogen derivative used at different doses, alone or in combination, in the treatment of various types of solid and hematologic cancers. It is a pro-drug activated by cytochrome P450 enzymatic system into ifosforamide mustard, the alkylating component that carries out the cytotoxic effect of the IFO. The most common toxicities of IFO are gastrointestinal, cutaneous, hematological, urological, and neurological. The neurotoxicity may occur in up to 30% of patients and can manifest with a wide spectrum of clinical presentations (lethargy, somnolence, confusion, hallucinations, irritability, excitement, disorientation, weakness, seizures, movement disorders, coma) and a variety of EEG abnormalities, and is known as IFO-induced encephalopathy (IIE). There is no definitive explanation of the mechanism underlying this phenomenon, even though metabolism of IFO, which leads to the formation of neurotoxic components, is probably at the basis of neurotoxicity according to many hypotheses. Consequently, the different factors involved in IFO metabolism (i.e., genetic polymorphism of CYP2B6, GSTM1, GSTP1, and GSTT1; concomitant administration of drugs that affect the cytochrome P450 enzyme system; drug formulation) could be responsible of IIE. IIE is usually reversible by interrupting the IFO infusion and starting intravenous hydration but in some cases further interventions are needed. The most used pharmacological treatment is methylene blue, whose efficacy both as a curative and a prophylactic treatment has been the object of many studies, with mixed results. Other interventions that showed efficacy are thiamine (tested also as a prophylactic drug), dexmedetomidine, and hemodialysis. Other pharmaceuticals have been tested in a preclinical setting showing some activity: trifluoperazine, morin, caffeic acid phenethyl ester (CAPE), and alpha lipoic acid (ALA). The aim of this review is to gather the current knowledge about the mechanisms underlying the IIE and the current therapeutic approach and the future perspectives.

BackgroundDue to their rarity and complexity sarcomas require specialized multidisciplinary team management. COVID-19 pandemic brought to a rapid implementation of telemedicine and activation of digital tools. This study evaluates the perception of virtual disease multidisciplinary team among healthcare professionals of an European rare cancer referral center.MethodsAn online survey was administered to the participants of Regina Elena National Cancer Institute’s Sarcoma disease multidisciplinary team meetings held between 2020 and 2022. It was composed of 40 questions comparing face-to-face and virtual meetings. Data from the Institutional disease multidisciplinary team from 2019 to 2022 were also analyzed retrospectively to compare the pre-covid, covid, and post-covid phases.ResultsTwenty-two healthcare professionals answered the survey. In their opinion, decision-making process was not affected by virtual modality (86.0%). Regarding virtual meetings 90.0% were highly/moderately satisfied with depth of discussion, 95.0%–100% were able to interact adequately and access all relevant data. The most important improvements of virtual disease multidisciplinary team were better quality of clinical approach/research (22.7%–31.8%), technological innovations (50.0%), and logistical setting (95.5%). 90.0% to 100% thought that virtual disease multidisciplinary team could be approved thereafter. We observed an increase in participation rate from 58.0, to 62.0%, to 64.0% (p = 0.0159) and a rise in the new cases discussed at meetings compared to the re-discussed ones from 30.1% to 37.9% to 42.3% (p < 0.0001) in the pre-covid, covid, and post-covid phases, respectively.ConclusionVirtual disease multidisciplinary team enhances participation and discussion quality without compromising patient care.

Background: Trabectedin is an antineoplastic drug approved for patients (pts) with advanced soft tissue sarcomas (STS). Interestingly, the radiological evaluation of response during trabectedin therapy is peculiar. Methods: The aim of this single-center retrospective study is to analyze the concordance of response assessment according to RECIST compared with Choi criteria in patients with STS treated with trabectedin between 2009 and 2020 at Regina Elena National Cancer Institute in Rome. Results: We present the preliminary data collected in the last 2 months (mos) on 37 pts who received the diagnosis between 2015 and 2020, with a median age of 52.5 years (range 32-78). The median number of trabectedin cycles administered was four (range 2-50) for a median follow up of 5.83 months (range 1-60). Histological subtypes of STS were five (13.5%) leiomyosarcoma, 14 (37.8%) liposarcoma, nine (24.3%) undifferentiated pleomorphic sarcoma, three (8.1%) synovial sarcoma, and six (16.2%) other rare histological subtypes. Eight pts (21.6%) received trabectedin in the first line setting, 21 (56.8%) in the second line, and seven (18.9%) received it in subsequent lines. One pt received trabectedin as neoadjuvant therapy in a clinical trial (ISG-STS 1001). Median progression-free survival was 3.6 months (CI95% 2.7-4.6); median overall survival was 34.3 months (CI95% 0-75.4). The radiological responses were evaluated with both RECIST and Choi criteria; responses matched in 33 pts (89.2%) but not in four (10.8%). The best responses obtained according to RECIST criteria were two (5.4%) partial response (PR), 13 (35.1%) stable disease (SD), and 22 (59.5%) progressive disease (PD). Instead, two (5.4%), 13 (35.1%), and 22 (59.5%) pts obtained PR, SD, and PD respectively, according to Choi criteria. Cohen's kappa coefficient of concordance was 0.792 (p-value <0.002). A specialized radiologist performed all imaging examinations using a dedicated workstation in the same center. Conclusion: In this first analysis, the concordance between RECIST and Choi assessments demonstrates no statistically significant difference. Responses did not match for four pts. We are expanding the analysis to all pts included in the original cohort to confirm or deny these initial results.

BackgroundRheumatological toxicity associated with immunotherapy, particularly Sjögren’s syndrome (SjS), has been observed with variable incidence in patients treated with immune checkpoint inhibitors (ICIs). Although SjS is a well-known autoimmune disease, its occurrence as an immune-related adverse event (irAE) during cancer treatment is less well understood. Current literature documents a range of incidence rates and clinical manifestations of SjS in patients undergoing ICI therapy, highlighting the need for early diagnosis and multidisciplinary management.Case presentationA 40-year-old woman underwent mammography, which revealed a 43 mm mass in the left breast. Core biopsy confirmed grade 3 infiltrating triple negative ductal carcinoma with high MIB-1. She received neoadjuvant chemotherapy, followed by surgery and radiotherapy. A CT scan in September 2022 showed lung nodules and lymph node involvement. A lung biopsy confirmed breast cancer metastasis. She started treatment with atezolizumab and nab-paclitaxel with evidence of a partial response. Nab-paclitaxel was discontinued due to side effects and atezolizumab was continued as maintenance therapy. After four cycles, the patient developed symptoms consistent with Sjögren’s syndrome (SjS), which were confirmed by diagnostic tests. Treatment with prednisone, pilocarpine and hydroxychloroquine was initiated alongside ongoing immunotherapy. The patient continues to receive atezolizumab with stable disease and good quality of life.ConclusionThis case highlights the importance of recognizing SjS as a potential irAE in patients treated with ICIs, particularly those with TNBC. Multidisciplinary collaboration is essential for the prompt diagnosis and effective management of SjS to maintain both cancer control and patient quality of life. Given the recent emergence of these events and the lack of specific guidelines, our case report may provide valuable insights into the management of a little-known adverse event and pave the way for further real-world data collection on the management of these rare but significant toxicities that impact on patient quality of life. Further research is needed to optimize treatment protocols and outcomes for patients experiencing rheumatological irAEs during cancer immunotherapy.

BackgroundThe COVID-19 outbreak had a negative psychological impact on cancer patients. In this study, we analyzed emotional distress and quality of life in patients diagnosed with sarcoma during the first year of the pandemic compared to the previous year. MethodsWe retrospectively enrolled patients with soft tissue, bone sarcoma, and aggressive benign musculoskeletal diseases diagnosed during the pandemic (COVID group) or the year before (control group) at the IRCCS Regina Elena National Cancer Institute in Rome. Patients who had undergone a psychological assessment with the EORTC QLQ-C30 and the Distress Thermometer at diagnosis were included in the final analysis. We analyzed whether there is a difference in the various domains of quality of life between the two groups and whether there are changes over time in each group. ResultsWe enrolled 114 patients (72 control group; 42 COVID group), affected by soft tissue (64%), bone sarcoma (29%), and aggressive benign musculoskeletal diseases (7%). We did not observe significant differences in the health-related quality of life domains in the control and COVID groups, except for the financial domain (p = 0.039), with 9.7% vs. 23.8% of patients with a score > 0 in the control and COVID groups, respectively. We observed emotional distress at diagnosis in 48.6% of patients in the control group vs. 69.0% in the COVID group (p = 0.034). In the control group, we observed an improvement in physical function (p = 0.043) and in QoL (p = 0.022), while in the COVID group, we observed a deterioration in role function (p = 0.044) during follow-up. In the COVID group, 22.2% of patients were concerned about COVID-19, 61.1% by tumor, 91.1% stated that the pandemic worsened their subjective perception of cancer, and 19.4% perceived that their quality of care had worsened. ConclusionWe observed a higher level of distress among patients diagnosed during the pandemic compared to the year before, probably due to the increased concern for both infection and cancer, the worsened perception of health status, and the perception of a poorer quality of health care.

BACKGROUND:Despite the lack of evidence-based on prospective randomized studies, surgery has become the cornerstone of the treatment in patients with pulmonary oligometastatic sarcomas. Our study aimed to construct a composite prognostic score for metachronous oligometastatic sarcoma patients. METHODS:A retrospective analysis was performed on data patients who underwent radical surgery for metachronous metastases in six research institutes from January 2010 to December 2018. The log-hazard ratio (HR) obtained from the Cox model was used to derive weighting factors for a continuous prognostic index designed to identify differential outcome risks. RESULTS:A total of 251 patients were enrolled in the study. In the multivariate analysis, a longer disease-free interval (DFI) and a lower neutrophil-to-lymphocytes ratio (NLR) were predictive of a better overall survival (OS) and disease-free survival (DFS). A prognostic score was developed based on DFI and NLR data, identifying 2 risk class groups for DFS (3-years DFS 20.2% for the high-risk group [HRG]and 46.4% for the low-risk group [LRG] [<0.0001]) and 3 risk groups for OS (3 years OS 53.9% for the HRG vs. 76.9% for the intermediate-risk group and 100% of the LRG (p < 0.0001)). CONCLUSION:The proposed prognostic score effectively predicts outcomes for patients with lung metachronous oligo-metastases from the surgically treated sarcoma.

GISTs are rare soft tissue neoplasms harboring, in most cases, activating mutations in KIT and PDGFRA genes. The aim of this study is to describe the molecular characteristics of GIST samples from Regina Elena National Cancer Institute. We collected sequencing data from 153 samples from GIST patients between January 2017 and March 2023. Next generation sequencing was performed on samples derived from surgical excision or biopsy of the primary or metastatic lesions. The Ion AmpliSeq Cancer Hotspot panel V2 and the Oncomine Focus Assay (Thermofisher Scientific) were used. The analysis was performed with R-4.2.2 and oncokb-annotator. The top 5 mutated genes were KIT (69% of the cases), TP53 (63%), PDGFRA (20%), KDR (20%), and PIK3CA (17%); the median number of variants per sample was 3. The most affected exons in KIT were 11 (51%), 9 (13.9%), 10 (13.3%); exon 17 harbored 3.3% of the variants; exon 13 1.3%. The most affected exons in PDGFRA were 18 (36.6%) and 10 (34.1%); the mutations in exons 14 and 12 accounted, respectively, for 7.3% and 4.9% of the cases. We annotated the variants according to OncoKB Therapeutic Levels of Evidence V2: 74 out of 631 total variants (11.7%) were annotated as oncogenic, 86 (13.6%) as likely oncogenic, 14 (2.2%) as likely neutral and 457 (72.4%) as inconclusive or unknown. Among the 160 oncogenic or likely oncogenic variants, 103 (64.4%) had a therapeutic level 1, 18 (11.3%) level 2, 9 (5.6%) level R1, 5 (3.1%) level R2. As for the KIT gene, 90 of the 151 variants (59.6%) were annotated as oncogenic or likely oncogenic, all of them had a therapeutic level 1, 5 (3.3%) had level R2. Regarding the PDGFRA gene, 14 out of 41 variants (34.1%) were annotated as oncogenic or likely oncogenic, all but one had a therapeutic level 1, 14 level 2, 9 level R1. The remaining oncogenic or likely oncogenic variants affected the following genes: KDR (19.4%), TP53 (8.8%), CTNNB1, JAK2, FBXW7, GNAS, NF1, PIK3CA, RB1, RET; 2 of them had a therapeutic level 3B, 1 level 4. Most of the recorded variants were in KIT and PDGFRA genes. More than half of them are oncogenic and targetable. Notably, we found other oncogenic variants that can have a role in the development of the disease and in the onset of resistance to the treatment.

Although patient narratives have been increasingly introduced in various fields of medicine, a standard method in clinical practice is still lacking. The objectives of this pilot study were to evaluate the feasibility and usefulness of a digital narrative diary integrated into the care pathway of patients with bone sarcoma and limb soft tissue sarcoma both from the patients’ and the healthcare professionals’ (HCPs) perspectives. A digital platform, DNMLAB, was designed to obtain guided narratives from patients during their pathway of care in compliance with confidentiality and data protection laws. The diary was used for patients, often young, facing a rare and impactful disease that is difficult to manage and with few opportunities to share experiences. The multidisciplinary team shared the narratives and integrated them into the patient’s treatment pathway. Narrative prompts were adequate for the care pathway. Patients correctly considered the diary as a shared area to think about their condition, and HCPs considered it “a shared area growing at each meeting with the patient”. The main advantages reported by patients were increased awareness, the opportunity to express their opinion on cures and important personal needs and the perception of better taking charge (score ≥ 4.6). The main advantages of HCP were improved communication, therapeutic alliance, and deeper knowledge of patients. This study confirmed the authors’ previous experiences, showing that a digital narrative process is feasible and useful for oncology clinical practice according to patients and HCPs.

The aim of molecular tumor board (MTB) is to identify potential therapeutic strategies, based on genetic analysis, for patients (pts) not responding to standard therapies. All tumor types are eligible for MTB discussion and sarcomas are one of common target due to low number of standard and innovative treatments. Here we analyze the role of MTB in a sarcoma referral center. We presented data from MTB including pts affected by soft tissue (STS) and bone sarcoma (BS) followed at Regina Elena National Cancer Institute in Rome and discussed from Dec 2019 to May 2022. We discussed 19 pts affected by STS (14 pts) and BS (5 pts). FoundationOne was performed in 74%, Archer FusionPlex Sarcoma Panel in 37%, DNA Focus Assay in 26%, Whole exome sequencing in 26%, Oncomine Comprehensive Assay Plus in 16%, Promega MSI PCR Testing Kit in 16% and immunohistochemistry for PD-L1 in 16% of pts. Techniques were chosen depending on the type of kit available, the cost, the alterations searched and the time to obtain results. Druggable targets were found in 11 pts: mTOR mutation (m), HGF amplification (amp), ATM splice site m, MET amp, KRAS m, CDK4 amp, MYC amp, PTCH1 m, PIK3CA m, MDM4 amp and PD-L1 overexpression. Three patients (16%) received precision therapy: Imatinib and everolimus for mTOR m in cordoma, Cabozantinib for HGF amp in osteosarcoma and Pembrolizumab in angiosarcoma with PD-L 1 >10%. Eight pts continued standard therapy due to maintenance of response (5 pts) or to absence of literature supporting target treatment (3 pts). Molecular analysis allowed reformulation of diagnosis for one patient due to the presence of EWSR1-CREB3L2 fusion, typical of low-grade fibromyxoid sarcoma, that led to a histology-based treatment choice. Four patients were addressed to best supportive care (21%) while 2 pts (10,5 %) died. MTB could be an effective tool for decision-making in sarcoma, but the lack of literature data and drug access hinder treatment choice. Enrollment in clinical trials could lead to overcome the problem. Moreover, the timing for requesting molecular analyses, at diagnosis or at the end of standard therapies, needs to be defined, considering both the tumor heterogeneity and the delay in obtaining results and starting treatment.

BackgroundThe COVID-19 pandemic led to a rapid reorganization of healthcare activities, leading to reduced access to clinics, interruption of screenings, and treatment schedule modifications in several cancer types. Few data are available on sarcomas. We analyzed COVID-19-related diagnostic delay in a sarcoma referral center in Italy.MethodsWe retrospectively enrolled in this study patients with histological diagnosis of soft tissue or bone sarcoma and aggressive benign musculoskeletal diseases obtained during the first year of the pandemic (Covid group) or the year before (Control group) and followed at the Regina Elena National Cancer Institute in Rome. The primary endpoint was the time from the first symptom to histological diagnosis.ResultsWe evaluated 372 patients, 185 of whom were eligible for primary endpoint analysis (92 patients in the Control group and 93 patients in the Covid group). The patients were affected by soft tissue sarcoma in most cases (63.0% and 66.7% in Covid and Control groups, respectively). We observed a diagnostic delay in the Covid group with a median time from the first symptom to the definitive histological diagnosis of 103.00 days (95% CI 92.77–113.23) vs. 90.00 days (95% CI 69.49–110.51) in the Control group (p = 0.024), but not a delay in treatment beginning (151 days, 95% CI 132.9–169.1 vs. 144 days, 95% CI 120.3–167.7, respectively, p = 0.208). No differences in stage at diagnosis were observed (12% vs. 16.5% of patients with metastatic disease at diagnosis in the Covid and Control groups, respectively, p = 0.380). Progression-free survival (p = 0.897) and overall survival (p = 0.725) were comparable in the subgroup of patients affected by soft tissue sarcoma.ConclusionsA delay in sarcoma diagnosis but not in starting treatment has been observed during the first year of the COVID-19 pandemic. Nevertheless, no difference in stage at diagnosis or in terms of survival has been observed.

Metastatic triple-negative breast cancer (mTNBC) is a poor prognostic disease with limited treatments and uncertain therapeutic algorithms. We performed a systematic review and multiple Bayesian network meta-analyses according to treatment line to establish an optimal therapeutic sequencing strategy for this lethal disease. We included 125 first-line trials (37,812 patients) and 33 s/further-lines trials (11,321 patients). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rates (ORR), overall survival (OS) and safety, for first and further lines, separately. We also estimated separate treatment rankings for the first and subsequent lines according to each endpoint, based on (surface under the cumulative ranking curve) SUCRA values. No first-line treatment was associated with superior PFS and OS than paclitaxel ± bevacizumab. Platinum-based polychemotherapies were generally superior in terms of ORR, at the cost of higher toxicity.. PARP-inhibitors in germline-BRCA1/2-mutant patients, and immunotherapy + chemotherapy in PD-L1-positive mTNBC, performed similar to paclitaxel ± bevacizumab. In PD-L1-positive mTNBC, pembrolizumab + chemotherapy was better than atezolizumab + nab-paclitaxel in terms of OS according to SUCRA values. In second/further-lines, sacituzumab govitecan outperformed all other treatments on all endpoints, followed by PARP-inhibitors in germline-BRCA1/2-mutant tumors. Trastuzumab deruxtecan in HER2-low mTNBC performed similarly and was the best advanced-line treatment in terms of PFS and OS after sacituzumab govitecan, according to SUCRA values. Moreover, comparisons with sacituzumab govitecan, talazoparib and olaparib were not statistically significant. The most effective alternatives or candidates for subsequent lines were represented by nab-paclitaxel (in ORR), capecitabine (in PFS) and eribulin (in PFS and OS).