RESUMO
BACKGROUND AND PURPOSE: Metaplastic breast carcinoma (BC-Mp) is an uncommon subtype that poses unique challenges. The limited information on patient prognosis and therapeutic strategies motivated our research initiative. We aimed to assess disease-free survival (DFS), overall survival (OS), and influential factors in patients with nonmetastatic BC-Mp. MATERIALS AND METHODS: In this multicenter retrospective cohort study, clinicopathological data for nonmetastatic BC-Mp patients treated at four oncology units in Poland (2012-2022) were gathered. RESULTS: Among 115 women (median age 61, range: 28-91), the median tumor size was 40 mm (range 20-130); 30% of patients exhibited positive local lymph nodes. The majority of patients presented with stage II (46%) and triple-negative breast cancer (TNBC) (84%). Radiotherapy was administered to 61% of patients. Surgical procedures included breast-conserving surgery in 31% of patients and mastectomy in 68%. Eighty-three per cent of patients received chemotherapy. The median estimated DFS and OS were 59 and 68 months, respectively. Multivariable analysis revealed that tumor size influenced DFS and OS (Hazard ratios [HR] = 1.02, 95%CI 0.01-0.03 for both endpoints) and taxanes application improved DFS (HR = 0.47, 95%CI 0.24-0.93), but other factors did not. For patients receiving neoadjuvant systemic therapy (N = 51), taxanes improved DFS and OS according to univariable analysis. INTERPRETATION: Our findings highlight poor DFS and OS regardless of receiving optimal treatment, emphasizing the need for tailored therapeutic strategies for BC-Mp patients. Taxanes appear promising in a neoadjuvant setting, particularly within the current standard of care for the TNBC subtype.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Idoso , Prognóstico , Neoplasias da Mama/terapia , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Idoso de 80 Anos ou mais , Resultado do Tratamento , Intervalo Livre de Doença , Metaplasia/patologia , Metaplasia/terapia , Mastectomia , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapia , Neoplasias de Mama Triplo Negativas/mortalidadeRESUMO
Immune checkpoint inhibitors have significantly improved the prognosis of melanoma patients. However, these therapies may trigger unexpected immune-related adverse events (irAEs), which are challenging in making the proper diagnosis and providing treatment. Hematological toxicities are possible irAEs, but were poorly evaluated in clinical trials and treatment recommendations of this specific complications are limited. We present a stage IV melanoma patient who developed an extremely rare toxicity - hemophagocytic lymphohistiocytosis (HLH) after the 4th course of combined immunotherapy with nivolumab and ipilimumab. The patient was steroid resistant and only the treatment with various immunosuppressive agents provided control of the disease and finally melanoma regression. In this report, we evaluated the methods of HLH treatment and described our modification of available protocols. Immediate immunosuppression can be life-saving and due to rarity of this condition as well as lack of specific recommendations, every report is valuable for clinicians, especially when treatment was effective.
Assuntos
Linfo-Histiocitose Hemofagocítica , Melanoma , Humanos , Imunoterapia , Ipilimumab/efeitos adversos , Linfo-Histiocitose Hemofagocítica/induzido quimicamente , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/terapia , Melanoma/tratamento farmacológico , Nivolumabe/efeitos adversosRESUMO
Primary cardiac sarcomas are extremely uncommon. We report two patients with primary cardiac atrial sarcomas: a case report of a 34-year old woman with intimal sarcoma of the left atrium and a case report of a 30-year old man with synovial sarcoma of the right atrium. Clinicopathological and differential diagnosis with a discussion regarding the role of molecular studies is presented.
Assuntos
Neoplasias Cardíacas , Sarcoma Sinovial , Sarcoma , Adulto , Diagnóstico Diferencial , Feminino , Átrios do Coração/patologia , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/patologia , Humanos , Masculino , Sarcoma Sinovial/genéticaRESUMO
The introduction of immunotherapy into the treatment of cancer patients has revolutionised the oncological approach and significantly improved patient survival. The key drugs are immune checkpoint inhibitors (CPIs), whose mechanism of action is to elicit immune response against cancer cell antigens. Three types of CPIs are currently used and approved: an anti-CTLA-4 antibody, ipilimumab; anti-PD-1 antibodies, nivolumab and pembrolizumab; and anti-PD-L1 antibodies: atezolizumab, avelumab and durvalumab. CPIs have been widely used in metastatic and adjuvant melanoma settings, metastatic lung cancer, Hodgkin's lymphoma, renal cancer, bladder cancer, head and neck tumours, and Merkel cell carcinoma. However, side effects of CPIs differ from toxicities of other oncological drugs. According to literature data, in 10-30% of patients CPIs are responsible for immune-related adverse events (irAE) associated with excessive activation of the immune system. Systemic irAEs include enterocolitis, pneumonitis, hepatitis, nephritis, hypophysitis, and autoimmune thyroid disease. However, the most common irAEs of checkpoint inhibitors are dermatologic toxicities ranging from pruritus and mild dermatoses to severe reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis. Each irAE can become serious if not early diagnosed and appropriately treated. In the article we present different types of skin irAEs related to CPIs together with the recommended therapies.
RESUMO
INTRODUCTION: The use of immunotherapy in older patients remains challenging due to very few data on the efficacy and safety of treatment in this group. AIM: To analyse the efficacy and safety of immunotherapy with checkpoint inhibitors in older patients (≥ 70 years) with metastatic melanoma. MATERIAL AND METHODS: In the Maria Sklodowska-Curie Institute - Oncology Centre, between 2011 and 2017, 318 non-resectable or metastatic melanoma patients were treated with immune checkpoint inhibitors: anti-CTLA-4 or/and anti-PD-1. Eighty-two patients were ≥ 70 years (median age: 76 years; range: 70-90 years). Among this group 10% of patients had brain metastases, 24% of patients had BRAF mutant melanoma, and co-morbidities were present in 86% of patients (mainly hypertension, cardiovascular diseases and/or diabetes). RESULTS: Median PFS and OS were similar in patients < 70 years and ≥ 70 years. In the group of patients ≥ 70 years old, the 2-year OS rate (from the start of immunotherapy) was 27%, and in patients aged < 70 it was 28% (p = NS). Two-year progression-free survival was 13.7% in the group of patients ≥ 70 years old and in patients aged < 70 it was 13% (p = NS). Patients ≥ 70 years of age were significantly less likely to have a BRAF mutation (p = 0.020). The presence of co-morbidities was not associated with an increased risk of immunotherapy (p = 0.790). CONCLUSIONS: The survival and toxicity profile in the older patients treated with immune checkpoint inhibitors are similar to younger patients. Therefore, the age as a clinical factor should not exclude this population from the most effective therapy used nowadays in melanoma treatment.
RESUMO
Cancer growth is determined by the proportion of proliferating to dying cells; thus, the aim of the study was to analyze how proliferation rate and apoptosis level affect disease-free survival (DFS) of breast cancer (BC) patients treated with anthracycline-based chemotherapy. For 172 BC, proliferation rate was investigated by Ki-67 labeling index (Ki-67 LI)-assessed immunohistochemically. Apoptosis level was analyzed by apoptotic index (AI) estimated by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. To stratify patients into subgroups with higher and lower DFS and to achieve optimal categorization, optimal cutoff points were searching by minimal P value method. The best separation of DFS curves (P = 0.001) was observed for three categories of AI: (i) AI >1.8 % (DFS = 100 %), (ii) AI ≤0.3 % (DFS = 84.6 %), and (iii) 1.8 % <= AI >0.3 % (DFS = 64.0 %). The highest DFS (86.1 %) was shown for the subgroup with low-proliferating BC (Ki-67 LI ≤18.0 %), intermediate (73.9 %) for patients characterized by Ki-67 LI in the range 18.0-37.0 % and the lowest (60.0 %) for women with fast-proliferating tumors (Ki-67 LI >37.0 %) (P = 0.022). Summarized, minimal P value method allows for optimal separation of survival curves. Apoptosis level and proliferation rate have some prognostic potential for early stage breast cancer patients treated with anthracyclines in adjuvant setting, however, as suggested by multivariate analysis, not as independent prognostic factors.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Adulto , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Antígenos de Neoplasias/análise , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Diferenciação Celular , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Marcação In Situ das Extremidades Cortadas , Antígeno Ki-67/análise , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
INTRODUCTION: Hepatic visceral crisis (VC), characterized by a rapid total bilirubin increase with disease progression, poses a life-threatening risk in advanced breast cancer (ABC). International consensus guidelines define VC and touch on impending VC (IVC). Limited data exist on systemic treatments for hepatic VC/IVC. This study explores the safety and efficacy of cisplatin monotherapy in patients with Human Epidermal Growth Factor Receptor 2- negative breast cancer (BC) and hepatic IVC/VC. METHODS: In this retrospective single-center cohort study data of patients treated with cisplatin monotherapy (60-80 mg/m2, every 3-4 weeks) between 2016 and 2023 at a reference Cancer Centre in Southern Poland were analyzed. RESULTS: 33 female patients (24/33 hormonal-positive) with the mean age 53.84 years were included. Participants progressed on median 2 prior palliative systemic treatment lines. In 10/23 patients hepatic VC and in 23/33 IVC (rapid, symptomatic liver progression; extensive liver involvement; alanine or aspartate aminotransferase > 2 × normal limit; significant increases in lactate dehydrogenase, alkaline phosphatase, or gamma-glutamyl transferase) were identified. Median progression-free survival was 1.87 months and median overall survival 2.67 months. 33% of the patients presented stable disease or partial response. Eight patients experienced adverse events grade ≥ 3: in five the dose of cisplatin was reduced; two stopped the treatment. CONCLUSION: Due to the hepatotoxicity of BC-active drugs, specific recommendations for systemic treatment are scarce. Our study explored cisplatin's potential use, finding it to be a viable option in patients with performance status 0 or 1 experiencing hepatic IVC/VC, irrespective of liver function parameters and other factors.
RESUMO
Background: Primary neuroendocrine neoplasms of the breast (Br-NENs) are rare. The classification has been updated in recent years making interpretation of the data published challenging. It is unclear whether neuroendocrine differentiation is associated with poorer prognosis and what treatment approaches should be applied. Methods: The database for breast cancer patients treated between 2009 and 2022 at the Maria Sklodowska-Curie National Research Institute of Oncology Branch Krakow was explored to search for Br-NENs. Patients' medical and pathological data were collected and analyzed. Results: We included 22 females with Br-NEN without metastases at the time of diagnosis. The median age was 64 years (range: 28-88), Of the cases, 18 were hormone receptor positive, all were HER-2 negative, the median Ki67 was 27% (10-100%). The median tumor size at the time of diagnosis was 29.5mm (7-75mm), 9 patients were N-positive. DCIS was present in 5 cases. Only one case was negative for chromogranin and synaptophysin staining, but data were missing for 4 cases. Nine patients received adjuvant chemotherapy, mainly based on anthracyclines and taxanes, while 16 received adjuvant hormonal therapy and 15 received postoperative radiotherapy. Radical surgery was performed in all patients, but two underwent suboptimal tumorectomy. One patient had local recurrence, three experienced metastatic disease, all involving the lungs, but these patients are still alive. The median follow-up was 96 months (8-153). Two patients died, with a follow up time of no recurrence >4 years. Our results were compared to twelve case series collecting clinical data on Br-NENs, with median patient number of 10.5 (range: 3-142). Conclusion: Br-NENs represent a heterogenous group of diseases, lacking data from prospective studies or clinical trials. There are no established treatment standards tailored for Br-NENs. Our patients' cohort exhibited a favorable prognosis, potentially attributed to lower tumor stage and Ki67 index compared to other reported case series. We suggest that radical surgery and postoperative radiotherapy be administered akin to standard treatment for breast cancer of no special type. ESMO also advocates for this approach in systemic treatment, although we recommend considering platinum-based chemotherapy for patients with poorly differentiated Br-NENs exhibiting high Ki67.
Assuntos
Neoplasias da Mama , Tumores Neuroendócrinos , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Adulto , Idoso , Tumores Neuroendócrinos/terapia , Tumores Neuroendócrinos/patologia , Idoso de 80 Anos ou mais , Prognóstico , Estudos Retrospectivos , SeguimentosRESUMO
Metaplastic breast cancer (BC-Mp), which includes a range of epithelial and mixed epithelial-mesenchymal tumours, are rare malignancies with an unfavourable prognosis. The limited literature on BC-Mp focuses mainly on retrospective data for radically treated patients. Notably absent are studies dedicated to the palliative treatment of BC-Mp with distant metastases. The present retrospective study investigated treatment modalities and prognosis in a multi-centre cohort of 31 female participants diagnosed with distant metastatic BC-Mp, including 7 patients with de novo metastatic disease. The median age of the patients was 61 years (range, 33-87 years), with 38.7% presenting local lymph node involvement. Lungs were the most common site for the metastatic disease (61.3%). Median Ki-67 index was 50% (range, 35-70%), and 80.7% of cases were classified as grade 3. Human epidermal growth factor receptor 2 (HER2)+ and estrogen receptor+ were detected in 12.9 and 6.5% of cases, respectively. A total of 62.4% of patients received first-line palliative systemic treatment. The 1- and 2-year overall survival (OS) were 38.5 and 19.2%, respectively. Receiving ≥1 line of palliative treatment was significantly associated with improved OS (P<0.001). Factors such as age, Ki-67 index, HER2 or hormonal status, presence of specific epithelial or mesenchymal components, location of metastases or chemotherapy regimen type did not influence OS. The present study provided insights into the clinicopathological profile, systemic treatment experience, prognostic factors and OS data of BC-Mp with distant metastases, emphasizing the imperative for clinical trials in this population.
RESUMO
AIM OF THE STUDY: The study examined the response rate, response duration and toxicity of vinorelbine and fluorouracil or vinorelbine alone in pretreated metastatic breast cancer. MATERIAL AND METHODS: Between June 2001 and September 2009, a group of 103 patients with locally advanced or metastatic breast cancer, who had progressed after anthracycline/taxane chemotherapy, was treated with a vinorelbine-based regimen. The treatment consisted of vinorelbine 25 mg/m(2) and 5-fluorouracil (5-FU) 500 mg/m(2) administered intravenously on days 1 and 8 of each cycle (53 patients) or vinorelbine alone at a dose of 30 mg/m(2) on day 1 and 8 of the cycle, every 3 weeks (50 patients). Patients received chemotherapy as a second or further line of therapy. Treatment was continued until disease progression or unacceptable toxicity. The median age of patients treated with vinorelbine with 5FU was 54 years (range 38-76), and 55.5 years (range 38-73) in the group receiving vinorelbine monotherapy. A total of 417 cycles of chemotherapy were administered - 177 cycles of vinorelbine with 5-FU and 137 cycles of vinorelbine monotherapy. Patients were treated for a median of 4 cycles (range: 1 to 11 cycles). The evaluation of treatment effect was possible in 93 patients (10 patients received only one treatment cycle). RESULTS: The overall response rate (ORR) was 17% (7), including 2 (4%) complete responses (CR) and 5 (10.5%) partial responses (PR). Stable disease (SD) was observed in 50% of patients receiving vinorelbine with 5-FU (24 patients). In a group receiving vinorelbine alone the ORR was 20% (9), including 9 PR (20%) and 16 SD (35.5%). The median time to progression (TTP) for the entire group was 18 weeks (95% CI), 22 weeks among patients treated with vinorelbine with 5-FU and 16 weeks for a second group. The most common hematologic adverse events were neutropenia (20% of cycles) and thrombocytopenia (4%), with grade 3/4 incidence of 8% and 1.5% [according to National Cancer Institute Common Toxicity Criteria (NCI CTC)]. Nausea and vomiting were the most frequent non-hematologic forms of toxicity, occurring in 13% of cycles. The doses of cytotoxics were reduced in 26 (25%) cases. There were no treatment-related deaths. CONCLUSIONS: Vinorelbine alone or in combination with 5-FU is an effective and safe treatment for pretreated advanced/ metastatic breast cancer patients. The combination of vinorelbine with 5-FU appears to be a more efficacious regimen than vinorelbine alone.
RESUMO
Patients with hormone-receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer constitute about 70% of the breast cancer population. About 35% of these patients develop distant metastases and their treatment will be palliative. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors were shown to significantly improve the outcomes of these patients. In combination with endocrine therapy, they have become the standard first-line treatment for HR-positive, HER2-negative breast cancer. In Poland, treatment with CDK4/6 inhibitors is reimbursed only for patients participating in the drug program of the Ministry of Health. However, fulfilling the eligibility criteria for the program may be challenging both for patients and for clinicians. This may lead to a delay in treatment with CDK4/6 inhibitors or a decision to use older and less effective drugs that are more widely available. The aim of this review was to compare the efficacy of first-line therapies in patients with HR-positive, HER2-negative metastatic breast cancer depending on the use of CDK4/6 inhibitors. We compared the efficacy of previous standard therapies with that of ribociclib, a CDK4/6 inhibitor, based on the median progression-free survival (PFS) as an outcome. Median PFS is not affected by the efficacy of subsequent treatment lines and is easy to interpret both for clinicians and for patients. The first-line treatment with chemotherapy or endocrine therapy (without CDK4/6 inhibitors) prolongs median PFS by several months and even to over a dozen months. The first-line treatment with endocrine therapy plus CDK4/6 inhibitors provides an opportunity to achieve a median PFS of more than 25 months and to prolong it by about 9 to 14 months.
RESUMO
BACKGROUND: On 24th of February 2022, Ukrainian cancer patients had to face a new war. Here we describe an experience of the Maria Sklodowska-Curie National Research Institute of Oncology Branch Krakow in providing cancer care for Ukrainian refugees during the initial 6 weeks of war. We present patients' characteristic, point out the main challenges and share initiatives undertaken. MATERIALS AND METHODS: For this cross-sectional analysis, we have gathered demographic and clinical data together with date of crossing the Polish-Ukrainian border for 112 Ukrainian refugees with cancer who had their first-time oncology consultation between 24th February and 8th April 2022. We have also implemented national guidelines and created local procedures, interventions and policies to manage this situation. RESULTS: The peak of patient inflow was the third week of War and refugees accounted for 13% of all first-time patients within that period of time. The majority of refugees were women (86%), treated radically (57%) with breast cancer (43%). Most of the patients required systemic treatment (67%). Amongst the main challenges at the time were differences in the reimbursement system, communication issues, lack of patients' documentation or tissue samples, prolonged diagnostic or treatment interruptions, increased risk of COVID-19 infections, chemotherapy side effects, and lack of procedures. Legal, procedural and organizational steps implemented at the local and national level were described. CONCLUSIONS: The Russian invasion on Ukraine forced an unexpectedly high number of Ukrainian cancer patients to seek help abroad, leading to the straining of the health care system in Poland.
Assuntos
COVID-19 , Neoplasias , Refugiados , Feminino , Humanos , Masculino , Estudos Transversais , Neoplasias/terapia , PolôniaRESUMO
Metaplastic breast cancer (BC-Mp) presents diagnostic and therapeutic complexities, with scant literature available. Correct assessment of tumor size by ultrasound (US) and full-field digital mammography (FFDM) is crucial for treatment planning. METHODS: A retrospective cohort study was conducted on databases encompassing records of BC patients (2012-2022) at the National Research Institutes of Oncology (Warsaw, Gliwice and Krakow Branches). Inclusion criteria comprised confirmed diagnosis in postsurgical pathology reports with tumor size details (pT) and availability of tumor size from preoperative US and/or FFDM. Patients subjected to neoadjuvant systemic treatment were excluded. Demographics and clinicopathological data were gathered. RESULTS: Forty-five females were included. A total of 86.7% were triple-negative. The median age was 66 years (range: 33-89). The median pT was 41.63 mm (6-130), and eight patients were N-positive. Median tumor size assessed by US and FFDM was 31.81 mm (9-100) and 34.14 mm (0-120), respectively. Neither technique demonstrated superiority (p > 0.05), but they both underestimated the tumor size (p = 0.002 for US and p = 0.018 for FFDM). Smaller tumors (pT1-2) were statistically more accurately assessed by any technique (p < 0.001). Only pT correlated with overall survival. CONCLUSION: The risk of underestimation in tumor size assessment with US and FFDM has to be taken into consideration while planning surgical procedures for BC-Mp.
RESUMO
AIM OF THE STUDY: The incidence of melanoma is increasing rapidly worldwide. Metastatic melanoma is still an incurable disease, although an era of new drugs is approaching. Current methods to predict outcomes in patients with advanced, metastatic melanoma are limited. A retrospective analysis of a contemporary large group of advanced melanomas was performed to determine clinical prognostic factors that accurately predict survival in patients with metastatic melanoma before the era of new targeted/immunological therapy. MATERIAL AND METHODS: The retrospective analysis of 427 patients with metastatic melanoma treated between 1995 and 2005 at two reference oncological centres. RESULTS: The median overall survival time (OS) was 7.1 months (95% CI: 6.7-7.9) and the 1-year, 2-year and 5-year survival rates were 32.3%; 12.5%; 3.9%, respectively. The median progression-free survival time (PFS) after the first line of treatment was 3.5 months (95% CI: 3.1-3.8). There were 19.1% objective responses (CR - 6.1%, PR - 13.0%) and SD - 45.5% after the first line of therapy. The most common adverse events were anaemia, neutropenia, thrombocytopenia, nausea and vomiting. IN MULTIVARIATE ANALYSES: PS (performance status) 0-1, normal serum levels of lactate dehydrogenase (LDH) and aspartate transaminase (AspAT), older age in women, palliative surgical treatment and palliative radiotherapy, type of the first line of therapy (DTIC), and metastatic melanoma of unknown primary site were independent positive predictors for survival. CONCLUSIONS: The survival rate of patients with metastatic melanoma has not changed significantly over the last years. We identified a set of independent positive predictors for OS treated with systemic therapy. DTIC still may be useful in treatment of patients in a good general condition and with normal serum levels of LDH. Because the results of treatment of metastatic melanoma are still not satisfactory, the majority of patients should be treated within prospective, randomized clinical trials.
RESUMO
Nivolumab and ipilimumab combination became the first-line standard in advanced melanoma. We assessed its efficacy in a real-life study in Poland. In a one-year follow-up, we evaluated the medical records of 50 melanoma patients treated with that modality in five oncology centers. We recorded therapy outcomes and adverse events (AEs) after 3 and 12 months of therapy. At the first checkpoint, the disease control rate (DCR) was recorded in 58% (n = 29) of patients, but the same number of patients (n = 29, 58%) stopped immunotherapy due to disease progression (PD, n = 14, 48.3%), toxicity (n = 11, 37.9%) or death (n = 4, 13.8%). Among patients with DCR after the induction phase, 8 (27.6%) terminated due to toxicity, and 21 (72.4%) continued. However, at the 12-month checkpoint, only 14 patients (27% of all) were still receiving immunotherapy. In 7 (33.3%) it was discontinued due to PD (n = 2), toxicity (n = 2, 28.6% each), or death (n = 3, 42.9%). AEs occurred in 66.7% (n = 34) of patients; severe (grade 3 or 4) in half of them. Interestingly, those with AEs had an 80% lower risk of death (hazard ratio [HR] 0.2, 95% confidence interval [CI] 0.07−0.57, p = 0.001) and PD (HR 0.2, 95%CI 0.09−0.47, p < 0.0001). In the entire group of patients, after a 12-month follow-up, the median overall survival was not reached (NR, range: 6.8 months-NR) and progression-free survival was 6.3 (range: 3-NR) months. Our results demonstrate that combined immunotherapy is less effective in real-life than in pivotal trials. However, early responders will likely continue the therapy after a one-year follow-up. AEs occurrence might be a predictor of clinical effectiveness.
RESUMO
Trastuzumab-induced cardiotoxicity (TIC) can lead to early treatment discontinuation. The aim of this study was to evaluate: N-terminal brain natriuretic peptide (NT-proBNP), creatine kinase-MB (CK-MB), myoglobin, and selected biochemical and clinical factors as predictors of TIC. One hundred and thirty patients with HER2-positive BC receiving adjuvant trastuzumab therapy (TT) were enrolled. Measurement of cardiac markers and biochemical tests as well as echocardiography were performed prior to TT initiation and every three months thereafter. Cardiotoxicity leading to treatment interruption occurred in 24 patients (18.5%). While cardiotoxicity caused early treatment discontinuation in 14 patients (10.8%), the TIC resolved in 10 (7.7%) and TT was resumed. The most common complication was a decrease in left ventricular ejection fraction of more than 10% from baseline or below 50% (7.7%). In patients with TIC, there was no increase in the levels of NT-proBNP, myoglobin, and CK-MB. BMI, hypertension, ischemic heart disease, diabetes, age, cancer stage, type of surgery, use of radiotherapy, chemotherapy, and hormone therapy were shown to not have an effect on TIC occurrence. NT-proBNP, myoglobin, and CK-MB are not predictors of TIC. There is an ongoing need to identify biomarkers for TIC.
RESUMO
INTRODUCTION: Recently, the prognosis of patients with HER2positive breast cancer (BC) has improved significantly owing to the use of combined treatment modalities. However, systemic treatment is as-sociated with increased risk of cardiotoxicity. OBJECTIVES: We aimed to assess subclinical cardiac alterations during the final stage of adjuvant com-bined therapy, that is, trastuzumab therapy (TT), as potential predictors of late cardiac complications in patients with HER2positive BC. PATIENTS AND METHODS: We enrolled 251 patients with HER2positive BC treated with a radical local therapy, adjuvant chemotherapy (anthracyclines or anthracyclines + taxanes), and immunotherapy (trastuzumab). Patients underwent 6 echocardiographic examinations: at baseline, during TT, and after TT, with assessment of left ventricular ejection fraction (LVEF), degree of valvular regurgitation, and cardiac chamber diameters. RESULTS: Valvular fibrosis (28.4% of patients) was associated with older age, hypertension at baseline, and a higher degree of regurgitation during TT. Reduced LVEF, greater regurgitation, and larger cardiac chamber diameters were noted during TT. The patients who received higher anthracycline doses showed a greater degree of aortic insufficiency and a larger right ventricular diameter. Reduced LVEF during TT was associated with radiotherapy or chemotherapy and the degree of valvular regurgitation. Significantly larger diameters were observed in older patients and in those with comorbidities at baseline, high body mass index, and regurgitation. CONCLUSIONS: Asymptomatic subclinical cardiac alterations during TT may predict late cardiac complica-tions; however, longer followup is necessary to confirm this hypothesis. Patients with HER2positive BC should be closely monitored for possible cardiac alterations during and after therapy to ensure optimal care and guide therapeutic decisionmaking.
Assuntos
Neoplasias da Mama , Idoso , Antraciclinas/efeitos adversos , Neoplasias da Mama/complicações , Feminino , Humanos , Receptor ErbB-2/uso terapêutico , Volume Sistólico , Trastuzumab/efeitos adversos , Função Ventricular EsquerdaRESUMO
BACKGROUND: Some studies suggest that Human Papilloma Virus (HPV) infection is important factor in carcinogenesis of breast tumors. This study' objective was to analyze HPV prevalence in breast cancers of patients from south-central Poland. MATERIALS AND METHODS: The study was performed based on archival paraffin embebbed and formalin fixed blocks in the group of 383 patients with breast cancer. HPV prevalence and its genotype were assessed, respectively by: nested PCR (with two groups of primers: PGMY09/PGMY11 and GP5+/GP6+), quantitative PCR (qPCR). Tumors were classified as HPV positive in case of at least one positive result in nested PCR and positive results in genotyping procedure. For all HPV positive tissues P16 immunostaining was applied in order to confirm active viral infection. RESULTS: In the group of 383 breast cancers, HPV positivity was found in 17 samples (4.4%) in nested PCR. All these samples were subjected to HPV genotyping. This analysis revealed presence of HPV type 16 into two tumors (0.5%). In these two cancers, P16 overexpression was reported. CONCLUSION: In breast tumors of patients from south-central Poland in Poland, HPV positivity is demonstrated in very low percentage of cases.
RESUMO
PURPOSE: Programmed death 1 (PD-1) pathway inhibitors have not been prospectively evaluated in patients with non-clear cell renal cell carcinoma (nccRCC). The phase II KEYNOTE-427 study (cohort B) was conducted to assess the efficacy and safety of single-agent pembrolizumab, a PD-1 inhibitor, in advanced nccRCC. METHODS: Patients with histologically confirmed, measurable (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) nccRCC and no prior systemic therapy received pembrolizumab 200 mg intravenously once every 3 weeks for ≤ 24 months. The primary end point was objective response rate (ORR) per RECIST v1.1. RESULTS: Among enrolled patients (N = 165), 71.5% had confirmed papillary, 12.7% had chromophobe, and 15.8% had unclassified RCC histology. Most patients (67.9%) had intermediate or poor International Metastatic RCC Database Consortium risk status and tumors with programmed death ligand 1 (PD-L1) combined positive score (CPS) ≥ 1 (61.8%). The median time from enrollment to database cutoff was 31.5 months (range, 22.7-38.8). In all patients, the ORR was 26.7%. The median duration of response was 29.0 months; 59.7% of responses lasted ≥ 12 months. The ORR by CPS ≥ 1 and CPS < 1 status was 35.3% and 12.1%, respectively. The ORR by histology was 28.8% for papillary, 9.5% for chromophobe, and 30.8% for unclassified. Overall, the median progression-free survival was 4.2 months (95% CI, 2.9 to 5.6); the 24-month rate was 18.6%. The median overall survival was 28.9 months (95% CI, 24.3 months to not reached); the 24-month rate was 58.4%. Overall, 69.7% of patients reported treatment-related adverse events, most commonly pruritus (20.0%) and hypothyroidism (14.5%). Two deaths were treatment related (pneumonitis and cardiac arrest). CONCLUSION: First-line pembrolizumab monotherapy showed promising antitumor activity in nccRCC. The safety profile was similar to that observed in other tumor types.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/patologia , Feminino , Seguimentos , Humanos , Agências Internacionais , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Adulto JovemRESUMO
Despite considerable progress made in the treatment of patients with advanced melanoma, the majority of the patients treated with BRAF and mitogen-activated protein inhibitors (BRAFi and MEKi) experience a disease progression due to acquired resistance. Currently, ongoing studies explore the possibility to overcome or reverse this process. Our multicenter retrospective analysis included 51 patients with metastatic BRAF-mutated melanoma who had previously progressed on BRAFi/MEKi than had progressed on immunotherapy (anti-progression disease-1 or anti-cytotoxic T-lymphocyte-associated protein 4) and next were rechallenged with BRAFi/MEKi. Median age at BRAFi/MEKi rechallenge was 56 (range: 31-82 y/o). Median overall survival from the start of the first BRAFi/MEKi therapy and from rechallenge BRAFi/MEKi treatment was 29.7 and 9.3 months, respectively, whereas median progression-free survival was 10.5 and 5.9 months, respectively. Six-month, annual, and 2-year overall survival rates on both treatments were: 98% and 55%, 92% and 29%, and 69% and 2%, respectively. A response rate to treatment was higher in the group receiving BRAFi/MEKi for the first time as compared with the group receiving BRAFi/MEKi rechallenge and was overall response rate 72% and 27%; disease control rate 92% and 63%. Time interval between the end of the first BRAFi/MEKi treatment and the beginning of BRAFi/MEKi rechallenge did not influence median overall survival or progression-free survival. A lower toxicity rate was noted with BRAFi/MEKi rechallenge. BRAFi/MEKi rechallenge treatment remains clinically important and is associated with the lower toxicity. BRAFi/MEKi rechallenge efficacy is higher in patients who are in good performance status, with normal lactate dehydrogenase, and without brain metastases.