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- Predictive Factors for PCR and Relapse Following Neoadjuvant Dual HER2-Blockade in HER2+ Breast Cancer: an International Cohort Study.Publication . Luz, Paulo; Lopes-Brás, Raquel; Pinho, Inês Soares; Patel, Vanessa; Esperança-Martins, Miguel; Gonçalves, Lisa; Gonçalves, Joana; Freitas, Rita; Simão, Diana; Galnares, Maria Roldán; Criado, Silvia Artacho; Nobre, Amanda; Medina, Elias A Gracia; Vega, Isabel M Saffie; Sousa, Rita Teixeira; Costa, Luís; Gregório, João; Costa, João G; Fernandes, Ana SPurpose: Neoadjuvant systemic therapy with dual HER2-blockade, trastuzumab and pertuzumab, combined with chemotherapy has become a standard approach in patients with HER2-positive (HER2+) breast cancer (BC). However, the variability in treatment outcomes, such as pathological complete response (pCR) or relapse rates, underscores the need to identify predictive factors to optimize therapeutic strategies. This study aims to explore the relationship between clinicopathological factors and both pCR and disease-free survival (DFS) in an international cohort of patients with HER2+ BC, contributing to defining personalized treatment strategies. Methods: An international, multicenter, retrospective cohort study was conducted, including 517 patients with HER2+ BC who received neoadjuvant therapy comprising trastuzumab, pertuzumab, and chemotherapy. Data were collected between January 2016 and December 2023. The relationship between clinicopathological factors and treatment outcomes was analyzed using univariate tests, logistic regression for pCR, and Cox proportional hazards regression for DFS. Kaplan-Meier survival curves with log-rank tests and hazard ratios were used to compare DFS across subgroups. Results: Multivariable analysis revealed that hormonal receptor (HR) expression and nodal status significantly predicted the achievement of pCR in this cohort. Factors such as age, HR status, tumor grade, Ki-67 index, nodal status, and pathological response were associated with relapse risk. Conclusion: Our real-world data demonstrates that a comprehensive approach considering pCR, age, HR status, and nodal involvement is essential for personalized treatment strategies. These factors should be taken into account when deciding whether to escalate or de-escalate treatment, contributing to improved HER2+ BC patient outcomes.
- Real-Life Experience of HER2 (Human Epidermal Growth Factor Receptor 2)-Positive Advanced Breast Cancer Patients Treated With T-DXd (Trastuzumab Deruxtecan): A Multicentric Portuguese Study.Publication . Bizarro, Rita; Pazos, Isabel; Teixeira, Alexandra; Pereira, Margarida; Gonçalves, Joana; Abreu, Catarina; Ferreira, Rita; Oliveira, Sónia; Duarte Mendes, Ana; Eiriz, Inês; Santiago, Mariana; Teixeira, Carina; Leitão, Maria; Guedes, Helena; Bento, Sandra; Inácio, Mariana; Alpoim, Tiago; Correia, Jorge; Branco, Francisco; Passos-Coelho, José; Casa-Nova, Mafalda; Teixeira, José AlbertoBackground: Substantial improvements in survival have been observed in HER2 (human epidermal growth factor receptor 2)-positive (HER2+) inoperable or metastatic breast cancer (advanced breast cancer [ABC]) in recent years, driven by the introduction and widespread use of multiple novel agents. The DESTINY-Breast02 trial compared the efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients with HER2+ ABC formerly treated with trastuzumab emtansine (T-DM1), demonstrating significant improvements in both overall survival (OS) and progression-free survival (PFS). Methods: We conducted a national, multicentric, retrospective study to describe real-world treatment patterns, PFS, OS, safety, and key toxicities associated with T-DXd use in Portugal, following the DESTINY-Breast02 inclusion criteria. Results: A total of 100 women with HER2+ ABC from 17 centers were included, all of whom had received at least two prior treatments for advanced disease and were treated with T-DXd between July 2021 and May 2023. The mean age was 53.9 years n(standard deviation: 9.9). Thirty-six patients presented with synchronous metastatic disease. The most common metastatic site was bone, in 61 (61%) patients; 72 (72%) had visceral metastases, and 21 patients (21%) had brain metastases. The median follow-up was 10 months, with a median of 11 T-DXd cycles administered. Prior treatments included pertuzumab in 71 (71%) patients and T-DM1 in 84 (84%). T-DXd was administered as third-line therapy in 52 (52%) patients, as fourth-line therapy in 15 (15%), and as fifth-line therapy and beyond in 23 (23%) patients. The overall response rate (ORR) was 44%, and the clinical benefit rate (CBR) was 80%. The most frequent toxicities of any grade were nausea in 49 patients (49%), neutropenia in 37 (37%), and alopecia in 34 (34%). Serious adverse events (grade ≥ 3) occurred in 16 (16%) patients, with treatment discontinuation or delays due to adverse events observed in 46 cases (46%). Median OS was not reached, with a 12-month OS rate of 74%. The median PFS was 13 months (95% CI: 10-16 months), and the 12-month PFS rate was 54%. Conclusions: This real-world analysis revealed that the efficacy, safety, and tolerability of T-DXd in the Portuguese population are consistent with the outcomes observed in the DESTINY-Breast02 clinical trial.
- Burden of Disease and Cost of Illness of Triple-Negative Breast Cancer in Portugal.Publication . Silva, Joana; Sousa, Gabriela; Costa, Luís; Brito, Margarida; Oliveira, Sónia; Rodrigues, Bernardo; Ferreira, João; Borges, Margarida; Miguel, LuísBackground: Triple-negative breast cancer accounts for 15% of all breast cancer cases, and it has a lower survival rate and higher incidence of early recurrence, particularly during the first 10 years after diagnosis. Objective: This study aimed to estimate the cost and burden of triple-negative breast cancer among the female population in 2019 in Portugal from a societal perspective. Methods: The prevalence of triple-negative breast cancer was calculated using a cumulative incidence model on the basis of national epidemiological data. The burden of disease was expressed as disability-adjusted life years, including the years lost due to disability and years of life lost. Healthcare resource utilization was quantified with input from an expert panel, and costs were estimated on the basis of diagnosis-related groups. Indirect costs were established following the human capital approach and supported by inputs from an expert panel. Results: Considering a prevalence of 7052 cases of triple-negative breast cancer in 2019, the expert panel confirmed that approximately 24%, 29%, 28% and 19% of the patients were in stages I, II, III and IV, respectively. The burden of this disease in Portugal was estimated at 22,566 disability-adjusted life years per year, 94% of which resulted from premature deaths. The total annual cost was equal to €50,351,934, with direct and indirect costs representing 56% and 44%, respectively. The average cost per patient with triple-negative breast cancer was €7140. Direct costs accounted for €28 million and were associated mainly with triple-negative breast cancer locoregional stage treatment and follow-up (65%). Indirect costs represented €22 million and were largely linked to withdrawal from the job market (94%). Conclusion: Triple-negative breast cancer is an impactful disease with high humanistic and economic costs at the national level. The high mortality and low survival rates of this subtype mean that most disability-adjusted life years are due to years of life lost rather than years lost due to disability. Its prevalence is greater among women aged 45-49 years, suggesting a considerable burden regarding labour absenteeism and withdrawal from the job market.
- Body Composition Analysis in Metastatic Non-Small-Cell Lung Cancer: Depicting Sarcopenia in Portuguese Tertiary Care.Publication . Leão Mendes, José; Ferreira, Rita Quaresma; Mata, Inês; Vasco Barreira, João; Rodrigues, Ysel Chiara; Silva Dias, David; Capelas, Manuel Luís; Mäkitie, Antti; Guerreiro, Inês; Pimenta, Nuno M; Ravasco, PaulaSarcopenia is an emergent prognostic biomarker in clinical oncology. Albeit increasingly defined through skeletal muscle index (SMI) thresholding, the literature cut-offs fail to discern heterogeneous baseline muscularity across populations. This study assesses the prognostic impact of using cohort-specific SMI thresholds in a Portuguese metastatic non-small-cell lung cancer (mNSCLC) cohort. : Retrospective study including mNSCLC patients treated between January 2017 and December 2022. ImageJ v1.54 g was used to assess cross-sectional CT imaging at the third lumbar vertebra (L3) and calculate L3SMI. Sarcopenia was defined both according to Prado et al. and L3SMI thresholds derived from receiver operating characteristic analysis. Overall survival (OS) was the primary endpoint. Secondary endpoints included first-line (1L) progression-free survival (PFS) and sarcopenia subgroup analysis regarding body mass index impact on OS. : The initial cohort included 197 patients. Mean age was 65 years (±11.31). Most tumors were adenocarcinomas ( = 165) and presented with metastasis ( = 154). SMI was evaluable in 184 patients: cohort-specific thresholds (<49.96 cm/m for men; <34.02 cm/m for women) yielded 46.74% sarcopenic patients ( = 86) versus 66.30% ( = 122) per the literature definition. Cohort-specific thresholds predicted both OS (12.75 versus 21.13 months, hazard ratio [HR] 1.654, = 0.002) and PFS (7.92 versus 9.56 months, HR 1.503, = 0.01). Among sarcopenic patients, overweight (HR 0.417, = 0.01) and obesity (HR 2.723, = 0.039) had contrasting impacts on OS. : Amid reclassification of nearly one-fifth of the cohort, cohort-specific thresholds improved sarcopenia prognostication in mNSCLC. Homogeneity regarding both cancer treatment setting and ethnicity could be key to defining sarcopenia based on SMI.
- Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms of the Rectum: A Case Report.Publication . Verdasca, Filipa Ribeiro; Ferreira, Rita; Montenegro, Alexandra; Mendes, José Leão; Furtado, Ivánia; Escaleira, Rui; Fernandes, Válter; Seladas, Marta; Cristovão, Miguel; Luz, Ricardo; Guerreiro, InêsIntroduction: Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) represent roughly 1-2% of all colorectal malignancies. Given the rareness and heterogeneity of these mixed tumors, recognition and accurate diagnosis remain a challenge. In the absence of established guidelines, they are treated according to the standard of care for pure neuroendocrine carcinomas or adenocarcinomas from similar sites of origin. Case presentation: We herein report a case of a rectal MiNEN in a 55-year-old male. He underwent colonoscopy for rectal bleeding and mucus emission, which revealed a vegetating lesion located approximately 8 cm from the anal verge, corresponding to a moderately differentiated low-grade adenocarcinoma of the rectum. Computed tomography scan and magnetic resonance imaging uncovered the presence of lung, lymph node, and subcutaneous implant metastases. The biopsy of the cutaneous implant showed neuroendocrine carcinoma Ki-67 90%. The patient underwent systemic chemotherapy. Conclusion: High-grade MiNEN tumors are the most commonly encountered in clinical practice and have an aggressive biological behavior. Little is known about the genetic drivers of this neoplasm and its pathogenesis remains controversial. Clinical and pathological awareness of this rare entity is a key step to design future targeted therapies and improve treatment options. The aim of this case report is to further our understanding regarding the clinical presentation, radiological features, pathology, management, and prognosis of MiNEN.
- Symptom Clusters in Patients With Advanced Cancer: a Prospective Longitudinal Cohort Study to Examine Their Stability and Prognostic SignificancePublication . Simão, D; Barata, P; Alves, M; Papoila, AL; Oliveira, S; Lawlor, PThis study's purpose was to assess symptom cluster (SC) stability during disease progression and determine their strength of association with survival in patients with advanced cancer . Consecutively eligible patients with advanced cancer not receiving cancer-specific treatment and referred to a Tertiary Palliative Care Clinic were enrolled in a prospective cohort study. At first consultation (D0) and in subsequent consultations at day 15 (D15) and day 30 (D30), patients rated 9 symptoms through the Edmonton Symptom Assessment System scale (0-10) and 10 others using a Likert scale (1-5). Principal components factor analysis with varimax rotation was used to determine SCs at each consultation. Of 318 patients with advanced cancer, 301 met eligibility criteria with a median age of 69 years (range 37-94). Three SCs were identified: neuro-psycho-metabolic (NPM), gastrointestinal, and sleep impairment, with some variations in their constitution over time. Exploratory factor analysis accounted for 40% of variance of observed variables in all SCs. Shorter median survival was observed continuously for NPM cluster (D0 23 vs. 58 days, P < .001; D15 41 vs. 104 days, P=.004; D30 46 vs. 114 days, P = .002), although the presence of 2 or more SCs on D0 and D15 also had prognostic significance (D0: 21 vs. 45 days, P = .005; D30: 50 vs. 96 days, P = .040). In a multivariable model, NPM cluster (D0 hazard ratio estimate: HR 1.64; 95%CI, 1.17-2.31; P = .005; D15 HR: 2.51; 95%CI, 1.25-5.05; P = .009; D30 HR: 3.9; 95%CI, 1.54-9.86; P = .004) and hospitalization (D0 HR: 2.27; 95%CI, 1.47-3.51; P < .001; D15 HR: 2.43; 95%CI, 1.18-5.01; P = .016; D30 HR: 3.41; 95%CI, 1.35-8.62; P = .009) were independently and significantly associated with worse survival. Three clinically relevant SCs were identified, and their constitution had small variations, maintaining a stable set of nuclear symptoms through disease progression. Presence of the NPM cluster and hospitalization maintained their prognostic value over time.
- Reviewing Treatment Options for Advanced Renal Cell Carcinoma: Is There Still a Place for Tyrosine Kinase Inhibitor (TKI) Monotherapy?Publication . Fontes-Sousa, M; Magalhães, H; Oliveira, A; Carneiro, F; Palma dos Reis, F; Silvestre Madeira, P; Meireles, SRenal cell carcinoma (RCC) comprises a highly heterogeneous group of kidney tumours built upon distinct genetic- and epigenetic-driven mechanisms and molecular pathways. Therefore, responsiveness to treatment is considerably variable across patients, adding an extra layer of complexity to the already challenging therapeutic decision process. The last decade brought an unprecedented shift in the medical approach to advanced or metastatic RCC; in fact, immunotherapy-based combinations have significantly transformed the therapeutic arsenal and clinical outcomes of these patients. These strategies were quickly adopted by international guidelines committees as the new standards of care. However, this enhanced efficacy comes at the expense of tolerability, with a predictable negative impact on patients' quality of life. Moreover, subgroup and post hoc analyses of the major clinical trials have shown that not all patients benefit equally from these innovative approaches. In this context, a group of experts on kidney cancer met and discussed the state of the art in the field, with a special emphasis on the appropriateness of using monotherapy with an anti-angiogenesis tyrosine kinase inhibitor (TKI) to treat specific subgroups of patients with RCC. This article reviews the main topics that were considered to be pertinent for that discussion and establishes the profile of patients for whom TKI monotherapy remains a sensible frontline option by avoiding overtreatment and an unnecessary exposure to treatment-related toxicity.
- Personalized Medicine: Paradigm Shift in ALK Positive Non-Small Cell Lung Cancer: a Case ReportPublication . Barreira, JV; Leão Mendes, J; Parmanande, ABackground: Since the identification of multiple therapeutic targets, as is the case of anaplastic lymphoma kinase (ALK) translocation, the paradigm of treating patients with non-small cell lung cancer (NSCLC) has improved. In order to guarantee the possibility of longer survival outcomes with a better quality of life we must invest in the determination, in suitable time, of the consensual biomarkers and in the availability of the best treatments to our patients. Case presentation: We present a case of a caucasian male in his fifth decade of life, non-smoker, who highlights the complex journey of ALK-positive patients. This particular case, demonstrates the efficacy and tolerability of the new ALK target therapies, allowing our patients to maintain their routines without compromising the effectiveness of the therapy. Conclusion: Focusing on the reality of ALK positive patients and the impact that this therapy has on the daily lives of our patients, we can contribute to the awareness of this specific pathology.
- Hyperleukocytosis in Solid Tumors: a Rare Paraneoplastic Syndrome Associated with Poor PrognosisPublication . Ferrão, J; Sardinha, M; Dutra, EHematological paraneoplastic syndromes are fairly uncommon. While mild leukocytosis in solid tumors is well reported, white blood cell (WBC) count over 50,000 u/L, described as paraneoplastic leukemoid reaction (PLR), is not. Indeed, when found, it is usually associated with a higher burden of disease, tumor activity and worse clinical outcomes. We report the case of a challenging and burdensome diagnosis of a presumptive hematological paraneoplastic syndrome in a patient with a locally advanced lung cancer admitted in the Internal Medicine ward. After the end of chemotherapy, clinical and laboratory benefit was observed; however, the aggressive course of the disease became clear, with progression and downhill course that was unresponsive to treatment.
- Myocardial Work Brings New Insights into Left Ventricular Remodelling in Cardio-Oncology PatientsPublication . Vaz Ferreira, V; Mano, T; Cardoso, I; Coutinho Cruz, M; Branco, LM; Almeida-Morais, L; Timóteo, AT; Galrinho, A; Castelo, A; Garcia Brás, P; Simão, D; Sardinha, M; Gonçalves, A; Cruz Ferreira, RSerial transthoracic echocardiographic (TTE) assessment of 2D left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) are the gold standard screening methods for cancer therapeutics-related cardiac dysfunction (CTRCD). Non-invasive left ventricular (LV) pressure-strain loop (PSL) provides a novel method of quantifying myocardial work (MW) with potential advantages to evaluate the impact of cardiotoxic treatments on heart function. We prospectively assessed breast cancer female patients undergoing cancer therapy through serial monitoring by 2D and 3D TTE. Patients were evaluated at T0, T1 and T2 (before, 4-6 and 12-14 months after starting therapy, respectively). Through PSL analysis, MW indices were calculated. A total of 122 patients, with a mean age of 54.7 years, who received treatment with anthracyclines (77.0%) and anti-HER2 (75.4%) were included. During a mean follow-up of 14.9 ± 9.3 months, LVEF and GLS were significantly diminished, and 29.5% developed CTRCD. All MW indices were significantly reduced at T1 compared with baseline and tended to return to baseline values at T2. Global work index and global work efficiency showed a more pronounced variation in patients with CTRCD. The presence of more than one cardiovascular risk factor, obesity and baseline left atrium volume were predictors of changes in MW parameters. In conclusion, breast cancer treatment was associated with LV systolic dysfunction as assessed by MW, with its peak at 4-6 months and a partial recovery afterwards. Assessment of myocardial deformation parameters allows a more detailed characterization of cardiac remodelling and could enhance patient screening and selection for cardioprotective therapeutics.
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