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- Real-World Experience in Treatment of Patients with Non-Small-Cell Lung Cancer with BRAF or cMET Exon 14 Skipping MutationsPublication . Janzic, Urska; Shalata, Walid; Szymczak, Katarzyna; Dziadziuszko, Rafał; Jakopovic, Marko; Mountzios, Giannis; Płużański, Adam; A, Araujo; Charpidou, Andriani; Agbarya, AbedBRAF and cMET exon 14 skipping are rare mutations of NSCLC. The treatment sequence in these cases for the first and second line is not clear. An international registry was created for patients with advanced NSCLC harboring BRAF or cMET exon 14 skipping mutations, diagnosed from January 2017 to June 2022. Clinicopathological and molecular data and treatment patterns were recorded. Data on 58 patients, from eight centers across five countries, were included in the final analysis. We found that 40 patients had the cMET exon 14 skipping mutation and 18 had the BRAF V600E mutation. In total, 53 and 28 patients received first- and second-line treatments, respectively, among which 52.8% received targeted therapy (TT) in the first line and 53.5% in the second line. The overall response rate (ORR) and disease control rate (DCR) for first-line treatment with TT vs. other treatment such as immune checkpoint inhibitors ± chemotherapy (IO ± CT) were 55.6% vs. 21.7% (p = 0.0084) and 66.7% vs. 39.1% (p = 0.04), respectively. The type of treatment in first-line TT vs. other affected time to treatment discontinuation (TTD) was 11.6 m vs. 4.6 m (p= 0.006). The overall survival for the whole group was 15.4 m and was not statistically affected by the type of treatment (19.2 m vs. 13.5 m; p = 0.83).
- Evaluation of Current Antiemetic Therapy Response in Patients Undergoing MEC or HEC Regimens in PortugalPublication . A, Araujo; Tavares, Nuno; Faria, Ana Luísa; Gomes, Rosa; Mendonça, Joana Carvalho; Parente, Bárbara; Capela, Andreia; Barata, Fernando; Macedo, AnaChemotherapy-induced nausea and vomiting (CINV) negatively impact cancer patients' quality of life and treatment outcomes. This study evaluated the achievement of complete response to CINV prophylaxis during the first five days after chemotherapy in adult outpatient cancer clinics with solid malignant tumours receiving Moderate or Highly Emetogenic Chemotherapy (MEC or HEC) in Portugal. During the study, patients completed three evaluations, and nausea severity and CINV impact on patients' daily life was assessed. A complete response (no emetic episodes, no use of rescue antiemetic medication, and no more than mild nausea) was observed in 72% of the cycles (N = 161) throughout the five days after chemotherapy. Amongst the patient population, 25% classified their CINV episodes as severe. Though more than half of the patients achieved a complete response, suggesting that a therapeutic effort is being made to minimise this side effect, the overall scenario is barely optimistic. Significantly, new CINV-control measures in MEC/HEC patients should be adopted, specifically avoiding the single use of dexamethasone and 5-HT3 and raising awareness of using NK1-RAs. Thus, it is critical to improve CINV prophylactic treatment and implement practical international antiemetic guidelines in Portuguese clinical practice, envisaging the improvement of supportive care for cancer patients.
- A Challenge Called Ogilvie´s SyndromePublication . Soares Miranda, Luisa; Silva Gonçalves, Carla; Silva, Ezequiel; Ferreira, Álvaro; Araújo Correia, João; Cruz, Ana RitaOgilvie´s syndrome is a colonic dilation without any existing mechanical obstruction. The risk factors that cause it are not completely understood, but if untreated, the distension can result in rupture or ischaemic bowel perforation. Additionally, the existing guidelines do not agree with each other about the next steps if conservative treatment fails. We report the case of a 71-year-old woman in whom Ogilvie´s syndrome was particularly difficult to manage, and with it, we try to add clinical data to a field with scarce evidence.
- Ewing Sarcoma Developed at the Site of Previous Mast Cell ProliferationPublication . Ranchor, Ridhi; Magalhães, Manuel; Rosendo, Eugénia; Coelho, André; Cardoso, PedroKIT gene mutations in Ewing sarcomas are rare; however, they are much more frequent in other neoplasms, namely mastocytosis. We describe a case of an adult male with a one-year duration of recurrent episodes of pain, swelling, and redness on the proximal phalanx of the third finger of his right hand. A core biopsy suggested a possible mastocytosis. After four years of recurrent episodes and worsening symptoms, an incisional biopsy revealed an Ewing sarcoma with a KIT gene mutation (M541L, on exon 10). KIT gene mutations with gain-of-function were identified in 2.6% of Ewing sarcomas. In this case, the detection of a KIT mutation in an Ewing sarcoma developed at the site of previous mast cell proliferation raises the hypothesis of a possible sarcomatous evolution of the original lesion. To the best of our knowledge, similar cases are not described in the current literature. This is also the first report describing the KIT M541L mutation (exon 10) in Ewing sarcoma
- Adjuvant Hyperthermic Intravesical Chemotherapy in Intermediate- and High-Risk Non-muscle Invasive Bladder CancerPublication . Magalhães, Joana C; Sousa, Maria João; Basto, Raquel; Fraga, Teresa; Gomes, Inês; Fernandes, Catarina; Mariano, Mónica; Paulo, Judy; Madeira, Pedro; Sousa, GabrielaIntroduction: Non-muscle invasive bladder cancer (NMIBC) is a frequently diagnosed neoplasm, which is typically managed with transurethral resection of bladder tumor (TURBT) eventually followed by intravesical therapies. Bacillus Calmette-Guérin (BCG) is used as first-line adjuvant treatment in high- (HR) and intermediate-risk (IR) NMIBC, although, in the latter, mitomycin C (MMC) may also be used. Multiple limitations to the use of BCG encouraged the search for therapeutic alternatives. In this context, hyperthermic intravesical chemotherapy with MMC (HIVEC-MMC) emerged as a promising therapy in the adjuvant setting for NMIBC. The aim of our study was to evaluate the tolerability, compliance, and survival outcomes of HIVEC-MMC in patients with IR- and HR-NMIBC. Material and methods: This was a single-center retrospective analysis of IR- and HR- NMIBC patients who received HIVEC-MMC after TURBT between August 2018 and August 2022. Levels of risk stratification were defined using the European Association of Urology (EAU) criteria. The protocol consisted of four weekly HIVEC-MMC instillations (induction) followed by six monthly instillations (maintenance). The primary outcomes were to evaluate the tolerability and compliance with the HIVEC-MMC protocol and secondary outcomes were disease-free survival (DFS) and overall survival (OS). For the purpose of statistical analysis, methods of descriptive statistics, survival analysis (Kaplan-Meier estimation), and multivariate analysis (Cox regression, and binary logistic regression) were used. Results: Fifty-seven patients were enrolled with a median age of 67.9 (34.4-83.5) years old. In this cohort, 40 patients (70.2%) had primary tumors. At the time of referral for HIVEC-MMC, the majority of the patients had IR-NMIBC (n= 33, 57.9%). A total of 41 patients (71.9%) completed the HIVEC-MMC protocol. Disease recurrence and adverse events (AEs) were the most common reasons to stop the protocol. After a median follow-up of 31 months (95% CI, 5.0-54.0), 32 patients (61.4%) were disease-free, 22 (38.6%) experienced recurrent disease and six patients (10.5%) died, although only one death was directly attributable to bladder cancer. The median DFS was 42 months (95% CI, 28.0-56.0). Completion of the HIVEC-MMC maintenance phase protocol stood as a predictive factor for DFS (44 months, 95% CI 29.1-58.9 vs. 14 months, 95% CI 0.0-29.6, p < 0.001; HR 4.48, 95% CI 1.65-12.15). The median OS was not reached; the 24- and 48-month OS were 92.6% and 82.7%, respectively. EAU risk group, ECOG-PS, and completion of HIVEC protocol were found to be significant predictive factors of OS but lost their significance on multivariate analysis. However, if we exclude those who experienced recurrence during the maintenance phase protocol, treatment completion had a significant positive impact on OS (HR: 42.8, 95% CI 1.75-1045.072, p= 0.021). Conclusions: Our study suggests that HIVEC is a secure and well-tolerated treatment with promising efficacy data, making this therapeutic approach a feasible option in IR- and HR-NMIBC patients, mainly in those who cannot tolerate or have contraindications to BCG therapy, but also as an alternative during BCG shortages.
- HER2 Status in RAS and BRAF Wild-Type Metastatic Colorectal Cancer: A Portuguese StudyPublication . Fraga, Teresa; Sousa, Maria João; Magalhães, Joana; Basto, Raquel; Paulo, Judy; Bonito, Nuno; Magalhães, José Paulo; Figueiredo, Paulo; Sousa, Gabriela MIntroduction: Colorectal cancer (CRC) is the second-most deadly cancer worldwide. However, there remains a scarcity of precision treatments available for this type of cancer. Amplification or overexpression of human epidermal growth factor receptor 2 (HER2+) is a well-established therapeutic target in gastric and breast cancer. HER2 is positive in approximately 5% of CRC cases and has been implicated in resistance to therapy with anti-epidermal growth factor receptor antibodies. The aim of this study was to evaluate HER2 status in RAS and BRAF wild-type metastatic CRC (mCRC) and its correlation with survival outcomes. Materials and methods: A single-center retrospective analysis of RAS and BRAF wild-type mCRC patients undergoing systemic treatment was conducted from July 2014 to September 2020. Tissue HER2 status was determined by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH) and/or chromogenic in situ hybridization (CISH). HER2+ was defined as IHC3 (+) or IHC2 (+) through FISH or CISH (+). Results: Fifty-nine patients were included. The median age of all the included patients was 64 years (33-82). Four patients had HER2+ tumors (7%). Four patients had HER2+ tumors (7%). The majority of HER2+ mCRC cases were males (n=3) and left-sided CRC (n=3). All patients received FOLFIRI plus cetuximab as first-line treatment. At the median follow-up of 24.0 months, patients with HER2-negative mCRC presented with a median overall survival (mOS) of 39.4 months (95% confidence interval (CI) 32.7-46.0) and the four patients with HER2+ mCRC had a mOS of 20.4 months (95% CI; 9.5-31.3; p=0.07). In HER2-negative patients, the median PFS (mPFS) was 11.3 months (95% CI; 9.2-13.4) vsHER2-positive patients with a mPFS of 10.9 months (95% CI; 1.3-20.4; p=0.47). Conclusions: To our knowledge, this is the first study reporting HER2+ in mCRC patients in a Portuguese population and the HER2+ rate was consistent with previous studies. Our study suggests that HER2+ may potentially be a marker that is able to predict poor prognosis in RAS and BRAF wild-type mCRC.
- T790M-EGFR mutation frequency in advanced NSCLC patients on progression from a previous TKI therapy: results from a Portuguese studyPublication . Teixeira, Encarnação; A, Araujo; Hespanhol, Venceslau; Parente, Bárbara; Barata, Fernando
- Limitations and perceived delays for diagnosis and staging of lung cancer in Portugal: A nationwide survey analysisPublication . Barata, Fernando; Fidalgo, Paula; Figueiredo, Sara; Tonin, Fernanda S.; Duarte-Ramos, FilipaBackground: We aimed to identify the perception of physicians on the limitations and delays for diagnosing, staging and treatment of lung cancer in Portugal. Methods: Portuguese physicians were invited to participate an electronic survey (Feb-Apr-2020). Descriptive statistical analyses were performed, with categorical variables reported as absolute and relative frequencies, and continuous variables with non-normal distribution as median and interquartile range (IQR). The association between categorical variables was assessed through Pearson's chi-square test. Mann-Whitney test was used to compare categorical and continuous variables (Stata v.15.0). Results: Sixty-one physicians participated in the study (45 pulmonologists, 16 oncologists), with n = 26 exclusively assisting lung cancer patients. Most experts work in public hospitals (90.16%) in Lisbon (36.07%). During the last semester of 2019, responders performed a median of 85 (IQR 55-140) diagnoses of lung cancer. Factors preventing faster referral to the specialty included poor articulation between services (60.0%) and patients low economic/cultural level (44.26%). Obtaining National Drugs Authority authorization was one of the main reasons (75.41%) for delaying the begin of treatment. The cumulative lag-time from patients' admission until treatment ranged from 42-61 days. Experts believe that the time to diagnosis could be optimized in around 11.05 days [IQR 9.61-12.50]. Most physicians (88.52%) started treatment before biomarkers results motivated by performance status deterioration (65.57%) or high tumor burden (52.46%). Clinicians exclusively assisting lung cancer cases reported fewer delays for obtaining authorization for biomarkers analysis (p = 0.023). Higher waiting times for surgery (p = 0.001), radiotherapy (p = 0.004), immunotherapy (p = 0.003) were reported by professionals from public hospitals. Conclusions: Physicians believe that is possible to reduce delays in all stages of lung cancer diagnosis with further efforts from multidisciplinary teams and hospital administration.
- Real-world data from the Portuguese Nivolumab Expanded Access Program (EAP) in previously treated Non Small Cell Lung Cancer (NSCLC)Publication . Figueiredo, A.; Almeida, M.A.; Almodovar, M.T.; Alves, P.; A, Araujo; Araújo, D.; Barata, F.; Barradas, L.; Barroso, A.; Brito, U.; Camacho, E.; Canário, D.; Cardoso, T.; Chaves, A.; Costa, L.; Cunha, J.; Duarte, J.; Estevinho, F.; Felizardo, M.; Fernandes, J.P.; Ferreira, L.; Ferreira, L.; Fidalgo, Paula; Freitas, C.; Garrido, P.; Gil, N.; Hasmucrai, D.; Jesus, E.; Lopes, J.A.; de Macedo, J.E.; Meleiro, A.; Neveda, R.; Nogueira, F.; Pantorotto, M.; Parente, B.; Pego, A.; Rocha, M.; Roque, J.; Santos, C.; Saraiva, J.; Silva, E.; Silva, S.; Simões, S.; Soares, M.; Teixeira, E.; Timóteo, T.; Hespanhol, V.Objective: The main aim of the study was to evaluate the efficacy and safety profile of Nivolumab, an immune-checkpoint-inhibitor antibody, in advanced, previously treated, Non-Small Cell Lung Cancer (NSCLC) patients, in a real world setting. Methods: We performed a retrospective, multicentre data analysis of patients who were included in the Portuguese Nivolumab Expanded Access Program (EAP). Eligibility criteria included histologically or citologically confirmed NSCLC, stage IIIB and IV, evaluable disease, sufficient organ function and at least one prior line of chemotherapy. The endpoints included Overall Response Rate (ORR), Disease Control Rate (DCR), Progression Free Survival (PFS) and Overall Survival (OS). Safety analysis was performed with the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, and immune-related Adverse Events (irAEs) were treated according to protocol treatment guidelines. Tumour response was assessed using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Data was analysed using SPSS, version 21.0 (IBM Statistics). Results: From June 2015 to December 2016, a total of 229 patients with advanced NSCLC were enrolled at 30 Portuguese centres. Clinical data were collected up to the end of July 2018. The baseline median age was 64 years (range 37-83) and the majority of patients were males (70.3%) and former/current smokers (69.4%). Patients with non-squamous histology predominated (88.1%), and 67.6% of the patients had received 2 or more prior lines of chemotherapy. Out of 229 patients, data was available for 219 patients (3 patients did not start treatment, while data was unavailable in 7 patients); of the 219 patients, 15.5% were not evaluated for radiological tumour assessment, 1.4% had complete response (CR), 21% partial response (PR), 31% stable disease (SD) and 31.1% progressive disease (PD). Thus, the ORR was 22.4% and DCR was 53.4% in this population. At the time of survival analysis the median PFS was 4.91 months (95% CI, 3.89-6.11) and median OS was 13.21 months (95% CI, 9.89-16.53). The safety profile was in line with clinical trial data. Conclusions: Efficacy and safety results observed in this retrospective analysis were consistent with observations reported in clinical trials and from other centres.
- Maxillary mesenchymal chondrosarcoma leading to a diagnosis of Li-Fraumeni syndromePublication . Ventura, Eduardo; Dionísio, Sílvia; Ferreira, Ângela; Saleiro, Rute; Marques, Hugo; Magalhães, Manuel; Monteiro, CarlosMesenchymal chondrosarcoma (MCS) is a rare histological variant of chondrosarcoma, with aggressive behaviour. Due to the unique nature of this disease, management strategies are not well established. Li-Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome with a wide tumour spectrum, associated with TP53 germline mutations. We report a case of MCS of the maxilla, treated with surgical excision and adjuvant chemotherapy, in a patient with a past medical history of choroid plexus papilloma and a family history of early age first-degree cervical uterine cancer, that led to the clinical suspicion of a cancer predisposition syndrome and the subsequent diagnosis of LFS. This is the first MCS described in a LFS case. It demonstrates that adjuvant chemotherapy should be considered, in conjunction with surgical excision, in MCS and that cancer predisposition syndromes should be suspected in patients with multiple neoplasms and a strong family history of cancer.