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BACKGROUND: The optimal treatment for metastatic colorectal cancer (mCRC) after the second line is still controversial. Regorafenib has been the standard of care in this setting as it improved overall survival (OS) compared to placebo. In real-world practice chemotherapy rechallenge is also a preferred option even though supporting evidence is not enough. We aim to compare the efficacy of regorafenib and 5-fluorouracil-based (5-FU) rechallenge treatment in the third line setting of mCRC. METHODS: In this retrospective multi-institutional trial, mCRC patients from 21 oncology centers who progressed after 2 lines of chemotherapy were analyzed. Patients who were treated with regorafenib or rechallenge therapy in the third-line setting were eligible. Rechallenge chemotherapy was identified as the re-use of the 5-FU based regimen which was administered in one of the previous treatment lines. OS, disease control rate (DCR), progression free survival (PFS) and toxicity were analyzed. RESULTS: Three hundred ninety-four mCRC patients were included in the study. 128 (32.5%) were in the rechallenge, and 266 (67.5%) were in the regorafenib group. Median PFS was 5.82 months in rechallenge and 4 months in regorafenib arms (hazard ratio:1.45,95% CI, p = 0.167). DCR was higher in the rechallenge group than regorafenib (77% vs 49.5%, respectively, p = < 0.001). Median OS after the third-line treatment was 11.99 (95% CI, 9.49-14.49) and 8.08 months (95% CI, 6.88-9.29) for rechallenge and regorafenib groups, respectively (hazard ratio:1.51, 95% CI, p < 0.001). More adverse effects and discontinuation were seen with regorafenib treatment. CONCLUSION: Our study revealed that higher disease control and OS rates were achieved with rechallenge treatment compared to regorafenib, especially in patients who achieved disease control in one of the first two lines of therapy.
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Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Humanos , Fluoruracila/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Estudos Retrospectivos , Neoplasias do Colo/tratamento farmacológico , Compostos de Fenilureia/efeitos adversos , Neoplasias Retais/tratamento farmacológicoRESUMO
PURPOSE: This study aimed to evaluate clinical pharmacist's contribution to the pneumococcal vaccination rate by providing education to cancer patients in hospital settings. METHODS: This study was conducted in 2 tertiary-care hospitals' medical oncology outpatient clinics. Patients over 18 years of age and diagnosed with cancer for less than 2 years, in remission stage, and have not previously received the pneumococcal vaccine were included. Patients were randomized to intervention and control groups. The intervention group was provided vaccination education and recommended to receive the PCV13 vaccine. The control group received routine care. Patients' knowledge about pneumonia/pneumococcal vaccine, Vaccine Attitude Examination Scale (VAX) score, and vaccination rates were evaluated at baseline and 3 months after the education. RESULTS: A total of 235 patients (intervention: 117, control: 118) were included. The mean age ± SD was 57.86 ± 11.88 years in the control and 60.68 ± 11.18 years in the intervention groups. The numbers of correct answers about pneumonia/pneumococcal vaccine (p = 0.482) and VAX scores (p = 0.244) of the groups were similar at baseline. After the intervention, the median (IQR) number of correct answers in intervention group [10(3)] was higher than control group [8(4)] (p < 0.001). After the education, the total VAX score (mean ± SD) was less in intervention group (33.09 ± 7.018) than the control group (36.07 ± 6.548) (p = 0.007). Three months after the education, 20.2% of the patients in the intervention and 6.1% in the control groups were vaccinated with pneumococcal vaccine (p = 0.003). CONCLUSIONS: The pneumococcal vaccination rate in cancer patients has increased significantly by the education provided by a clinical pharmacist in hospital settings.
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Neoplasias , Farmacêuticos , Humanos , Adolescente , Adulto , Projetos de Pesquisa , Vacinação , Vacinas PneumocócicasRESUMO
Background and Objective: This study evaluated the relationship between microsatellite status (MSI) and pan-immune-inflammation score (PIV) in tumor response to neoadjuvant chemotherapy (NAC) in patients with clinical stage III gastric cancer (cStage III GC). Materials and Methods: Microsatellite instability (MSI) status was evaluated based on pathology preparations. Pan-immune-inflammation score (PIV) was obtained from pre-treatment blood tests. The relationship of both parameters with pathological complete response (pCR) was evaluated. Results: A total of 104 patients were included in this study. All the patients were stage III GC patients receiving perioperative treatment. There were 13 patients in total who achieved a pCR response. While CNS was detected in 11 of the patients who achieved a pCR, the MSI status of the other two patients was unknown. No pCR was observed in any patient with MSI-H. According to the cut-off value for PIV, 25 (24%) patients were in the PIV-low (≤53.9) group, while 79 (76%) were in the PIV-high (>53.9) group. Based on univariate analysis, a higher PIV was associated with worse outcomes for pathological response, disease recurrence, and survival (p < 0.05). Conclusions: In patients with clinically stage III GC, the presence of MSI-H may predict no benefit from perioperative treatment. Conversely, a pre-treatment PIV score using specific cut-off values may provide a positive prediction of pathological response and survival.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirurgia , Repetições de Microssatélites/genética , Instabilidade de Microssatélites , Inflamação , Terapia NeoadjuvanteRESUMO
In our study, we aimed to evaluate the pathological response rates and side effect profile of adding pertuzumab to the treatment of HER2+ locally advanced, inflammatory, or early-stage breast cancer. This study was conducted by the Turkish Oncology Group (TOG) with data collected from 32 centers. Our study was multicentric, and a total of 364 patients were included. The median age of the patients was 49 years (18-85 years). Two hundred fifteen (60%) of the cases were hormone receptor/HER2+ positive(ER+ or PR+, or both), and 149 (40%) of them were HER2-rich (ER and PR negative). The number of complete responses was 124 (54%) in the docetaxel+trastuzumab+pertuzumab arm and 102 (45%) in the paclitaxel+trastuzumab+pertuzumab arm, and there was no difference between the groups in terms of complete response. In 226 (62%) patients with complete response, a significant correlation was found with DCIS, tumor focality, removed lymph node, and ER status P < 0.05. Anemia, nausea, vomiting, myalgia, alopecia, and mucosal inflammation were significantly higher in the docetaxel arm, P < 0.05. In our study, no statistical difference was found between the before-after echocardiography values. DCIS positivity in biopsy before neoadjuvant chemotherapy, tumor focality; the number of lymph nodes removed and ER status were found to be associated with pCR. In conclusion, we think that studies evaluating pCR-related clinicopathological variables and radiological imaging features will play a critical role in the development of nonsurgical treatment approaches.
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Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/etiologia , Docetaxel/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Receptor ErbB-2/metabolismo , Trastuzumab/efeitos adversosRESUMO
Aims: In this multicenter study, the authors aimed to determine the real-life efficacy and safety of first-line alectinib. Materials & methods: This retrospective trial included advanced-stage, ALK-positive non-small-cell lung cancer patients who were treated with first-line alectinib in terms of ALK-tyrosine kinase inhibitors, regardless of previous chemotherapy. The co-primary end points were progression-free survival both for all patients and for the treatment-naive population. The secondary end points were overall response rate, overall survival, rate of CNS progression and safety. Results & conclusion: A total of 274 patients (n = 177 for treatment-naive patients) were enrolled in the study. The median progression-free survival was 26 and 28.8 months for all patients and the treatment-naive group, respectively. The overall response rate, CNS progression rate and 1-year overall survival ratio were 77.9, 12.4 and 77%. Alectinib is a highly effective therapy with a favorable safety profile.
The advancements in cancer treatment, particularly in the last two decades, have been promising. Non-small-cell lung cancer (NSCLC) is one of the most important diseases experiencing these promising developments. ALK positivity, which is caused by the rearrangement of different gene fragments between two chromosomes, affects about 5% of NSCLC patients. This provides a target for next-generation therapies. One of these targeted therapy drugs is alectinib. The authors examined the outcomes of 271 patients with body-disseminated NSCLC who received alectinib as initial targeted therapy. These patients were not chosen to participate in a clinical phase study. They were treated with an approved drug; the study also included 97 patients who had previously received chemotherapy. The median duration of survival without disease worsening was 26 months for all patients receiving alectinib treatment. This value was 28.8 months in 177 patients who had not received any treatment before alectinib. Regardless of disease status, 77% of all patients were found to be alive at the end of the first year. Alectinib treatment resulted in a significant improvement of the disease in approximately four out of five patients. The treatment's side effects were generally tolerable or manageable. Only four patients were reported to have discontinued their medication due to treatment-related side effects. These real-world findings are compatible with previous clinical research. Alectinib is an important first-line treatment option for patients with advanced, ALK-positive NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Quinase do Linfoma Anaplásico/genética , Carbazóis , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Crizotinibe/uso terapêutico , Humanos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Piperidinas , Inibidores de Proteínas Quinases/efeitos adversos , Receptores Proteína Tirosina Quinases , Estudos RetrospectivosRESUMO
Background/aim: Cervical spondylotic myelopathy (CSM) develops as a result of compression of the spinal cord in the cervical region. Early diagnosis and surgical treatment can limit the progression of symptoms. Various surgical approaches and strategies have been described in the literature. This study aims to evaluate the clinical and radiological results of open-door laminoplasty for the treatment of CSM. Materials and methods: In this study, we retrospectively analyzed the patients who underwent expansive open-door laminoplasty secured with titanium miniplates. Thirty-four patients with CSM who were followed up postoperatively for more than 12 months were included in the study. The modified Japanese Orthopaedic Association (mJOA) score was used to assess the degree of myelopathy. We evaluated cervical sagittal alignment with C2C7 Cobb angle, the ambulatory status with the Nurick grade, and measured postoperative neck pain with the visual analogue scale (VAS). Results: Themeanm JOA score was 11 (range 615) preoperatively, and 13.5 (range 916) postoperatively with an average 55% recovery rate (range 075) (p < 0.001). ThemeanNurick grade was 2 (range 13) preoperatively and 1 (range 03) postoperatively (p < 0.001). The median cervical lordotic angle increased from 7.5 ° preoperatively to 12.5 ° postoperatively (p = 0.044). K-line (+) patients> mean mJOA scores significantly increased from 10.8 ± 1.7 to 13.3 ± 1.7 postoperatively (p < 0.001). The mean preoperative VAS reduced from 2.66 ± 1.4 to 1.59 ± 1.4 postoperatively (p < 0.001). Conclusion: Open-door laminoplasty technique is an effective surgical procedure that can be used safely to treat cervical spondylotic myelopathy. Our findings suggest that it can limit the progression of symptoms and alter the poor prognosis in CSM.
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Laminoplastia/efeitos adversos , Doenças da Medula Espinal/cirurgia , Espondilose/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Doenças da Medula Espinal/diagnóstico por imagem , Espondilose/diagnóstico por imagem , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of this study was to evaluate depression and sleep quality in Turkish women receiving neoadjuvant or adjuvant chemotherapy for breast cancer and investigate their relationship. METHODS: This cross-sectional, descriptive, and analytical study included 183 patients who received chemotherapy for non-metastatic breast cancer. Data were collected using the Beck Depression Inventory-II, the Pittsburgh Sleep Quality Index, and a disease-related/sociodemographic information form. RESULTS: The mean age of the participants was 50.2 years, and 50.3% were in menopause. The mean Beck Depression Inventory-II score was 19.64±10.4. Mild depression was detected in 25.7% (n=47) of the women, and moderate or severe depression in 55.2% (n=101). The mean global score of sleep quality was found to be 8.28±2.62, and the majority of the participants (79.7%, n=146) had poor sleep quality. There was a positive correlation (p<0.001, r=0.43) between depression and sleep quality scores. While a negative correlation was found between depression scores and age (p<0.001, r=0.26), the surgical procedure performed did not significantly affect depression scores (p=0.705). Additionally, depression scores were positively correlated with sleep duration (p<0.001, r=0.42) and sleep latency (p=0.01, r=0.48). CONCLUSION: Very high rates of depression and poor sleep quality were detected among Turkish women receiving neoadjuvant or adjuvant chemotherapy for breast cancer. The entire healthcare team involved in the treatment process should take this relationship into consideration and use the necessary preventive and therapeutic methods.
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Neoplasias da Mama , Depressão , Qualidade do Sono , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Transversais , Turquia/epidemiologia , Adulto , Depressão/epidemiologia , Quimioterapia Adjuvante/efeitos adversos , Transtornos do Sono-Vigília/epidemiologia , Idoso , Escalas de Graduação Psiquiátrica , Inquéritos e Questionários , Fatores Socioeconômicos , Índice de Gravidade de Doença , Terapia Neoadjuvante/efeitos adversosRESUMO
The only phase 3 study on the effectiveness of CDK 4-6 inhibitors in first-line treatment in premenopausal patients with hormone receptor (HR) positive, HER2 negative metastatic breast cancer is the MONALEESA-7 study, and data on the effectiveness of palbociclib is limited. Data are also limited regarding the effectiveness of CDK 4-6 inhibitors in patients whose dose was reduced due to neutropenia, the most common side effect of CDK 4-6 inhibitors. In our study, we aimed to evaluate the effectiveness of palbociclib and ribociclib in first-line treatment in patients with premenopausal metastatic breast cancer and the effect of dose reduction due to neutropenia on progression-free survival. Our study is a multicenter, retrospective study, and factors affecting progression-free survival (PFS) were examined in patients diagnosed with metastatic premenopausal breast cancer from 29 different centers and receiving combination therapy containing palbociclib or ribociclib in the metastatic stage. 319 patients were included in the study. The mPFS for patients treated with palbociclib was 26.83 months, and for those receiving ribociclib, the mPFS was 29.86 months (p = 0.924). mPFS was 32.00 months in patients who received a reduced dose, and mPFS was 25.96 months in patients who could take the initial dose, and there was no statistical difference (p = 0.238). Liver metastasis, using a fulvestrant together with a CDK 4-6 inhibitor, ECOG PS 1 was found to be a negative prognostic factor. No new adverse events were observed. In our study, we found PFS over 27 months in patients diagnosed with premenopausal breast cancer with CDK 4-6 inhibitors used in first-line treatment, similar to post-menopausal patients. We did not detect any difference between the effectiveness of the two CDK 4-6 inhibitors, and we showed that there was no decrease in the effectiveness of the CDK 4-6 inhibitor in patients whose dose was reduced due to neutropenia.
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The prognosis of patients with advanced HCC can vary widely depending on factors such as the stage of the cancer, the patient's overall health, and treatment regimens. This study aimed to investigate survival outcomes and associated factors in patients with hepatocellular carcinoma (HCC). In this retrospective study, data from 23 medical oncology clinics were analyzed. Progression-free survival (PFS) and overall survival (OS) values were estimated using the Kaplan-Meier method. Prognostic factors associated with survival which were identified in univariate analysis were subsequently evaluated in a multivariate Cox-regression survival analysis was conducted using the backward stepwise (Conditional LR) method to determine the independent predictors of PFS and OS. Of 280 patients, 131 received chemotherapy and 142 received sorafenib, 6 received atezolizumab plus bevacizumab and 1 received nivolumab for first-line setting. The median follow-up time was 30.4 (95%CI 27.1-33.6) months. For-first line, median PFS was 3.1 (95%CI2.7-3.5) months, and it was significantly longer in patients who received sorafenib or atezolizumab-bevacizumab or nivolumab (PFS 5.8 (95%CI 4.2-7.5) than in those received chemotherapy (PFS 2.1 (95%CI 1.9-2.3) in the first-line setting (p < 0.001). Multivariate analysis revealed that male gender (HR: 2.75, 95% CI: 1.53-4.94, p = 0.01), poor ECOG performance score (HR: 1.88, 95% CI: 1.10-3.21, p = 0.02), higher baseline AFP level (HR: 2.38, 95% CI: 1.54-3.67, p < 0.001) and upfront sorafenib treatment (HR,0.38; 95% CI: 0.23-0.62, p < 0.001) were significantly associated with shorter PFS. The median OS was 13.2 (95%CI 11.1-15.2) months. It was significantly longer in patients who received sorafenib or atezolizumab-bevacizumab or nivolumab in the first-line setting followed by TKIs (sorafenib or regorafenib, OS 18.6 (95%CI 13.8-23.5)) compared to those who received chemotherapy (OS 10.3 (95%CI 6.6-14.1)) in the first-line setting. The multivariate analysis revealed that upfront chemotherapy treatment approach, male gender (HR: 1.77, 95% CI: 1.07-2.94, p = 0.02), poor ECOG performance score (HR: 1.96, 95% CI: 1.24-3.09, p = 0.004) and Child-Pugh score, presence of extrahepatic disease (HR: 1.54, 95% CI: 1.09-2.18, p = 0.01), and higher baseline AFP value (HR: 1.50, 95% CI: 1.03-2.19, p = 0.03) were significantly associated with poor prognosis. Additionally, regarding of treatment sequence, upfront sorafenib followed by regorafenib showed a significantly lower risk of mortality (HR: 0.40, 95% CI: 0.25-0.66, p < 0.001). Sorafenib followed by regorafenib treatment was associated with a significantly lower risk of mortality rather than upfront sorafenib followed by BSC group or upfront chemotherapy followed by TKIs. These findings underscore the importance of the optimal treatment sequences to improve survival in patients with advanced HCC.
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Background: Breast cancer (BC) is one of the most common cancers worldwide. In recent years, numerous non-chemotherapy agents have been developed for BC treatment, including targeted agents, new hormonal therapies, and immunotherapies. However, despite the widespread use of these agents, chemotherapies are still an important cornerstone in BC treatment. Similarly, serious de-escalation studies in radiotherapy use have been conducted in recent years. These two treatment modalities, which we frequently use in the treatment of BC due to their effectiveness, may also have serious side effects. Case Presentation: In this article, I will present a case of multiple myeloma (MM) and myxofibrosarcoma (MFS) that occurred many years later in a patient who completed adjuvant chemotherapy and radiotherapy for BC. MM has developed due to previous chemotherapy and MFS has developed due to previous radiotherapy. Conclusion: We usually treat our cancer patients with chemotherapy or radiotherapy to prolong their lives. In addition to the benefits we provide, may negatively affect the lifetime and quality of life by causing the development of metachronous secondary cancers in some patients. In this case report, I will present the "ironic" side of oncology science and treatment.
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Antineoplásicos , Neoplasias da Mama , Segunda Neoplasia Primária , Humanos , Adulto , Feminino , Qualidade de Vida , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Terapia Combinada , Quimioterapia Adjuvante , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/terapiaRESUMO
Cranial metastasis (CM) is a serious problem in breast cancer patients. In patients with CM, quality of life is adversely affected and the survival of patients is reduced. It is also very difficult to manage breast cancer patients with cranial metastases whose life expectancy is generally 1 year or less. There is no case report in the literature of CM with more than 5 years of progression-free survival (PFS) with oncological treatment. I presented a rare case about the widespread CM developed with tamoxifen treatment in an advanced breast cancer patient who completed chemotherapy and radiotherapy after primary surgery. Systemic treatment was started as a combination of capecitabine and lapatinib after whole-brain radiotherapy was applied to the patient with extensive CM. At the end of about 3 years, there is complete response of cranial metastases, and PFS is over 5 years. The treatment was well tolerated, and she is still being followed up in the 74th month of this treatment without recurrence. There are no case reports of HER-2-positive breast cancer patients with such widespread cranial metastases in complete remission at 34 months of systemic therapy and 74 months of PFS. Our article is unique in this respect. It should be kept in mind that it is not appropriate to change the treatment plan of patients with only one case report. Although the options have increased with the use of new generation antihuman epidermal growth factor receptor 2 treatments, lapatinib can be a very effective treatment tool in selected patients.
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Neoplasias da Mama , Qualidade de Vida , Humanos , Feminino , Lapatinib , Capecitabina , Quinazolinas/efeitos adversos , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologiaRESUMO
OBJECTIVE: Hepatocellular cancer (HCC) is an aggressive tumor with an increasing incidence in recent years. Life expectancy is limited, especially due to limited effective treatments and tumor biology. In this study, we aimed to examine the effect of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), prognostic nutritional index (PNI) parameters of treatment efficacy of patients using sorafenib in primary systemic therapy, progression-free survival (PFS), and overall survival (OS). MATERIALS AND METHODS: In this study, we retrospectively analyzed 78 patients who used sorafenib as a first-line systemic treatment. NLR, PLR, and PNI values were calculated with the existing formulas. Cut-off values for these markers were determined by performing ROC curve analysis. These values were determined respectively as 2.88, 111.05, and 38.25. Patients were divided into two groups according to this threshold value. OS and PFS values were calculated using a Cox proportional risk model. The effects of markers on OS and PFS were examined based on the cut-off value. RESULTS: The mean PFS was 7.1 (range 1-46) months, and the mean OS was 14.1 (range 1.5-94) months. The pre-treatment decreased NLR (< 2.88) value was prognostic for higher PFS and OS rates. These values were determined respectively as 9.23 ± 1.79 and 3.45 ± 0.32 months for PFS and 21.17 ± 4.53 and 5.32 ± 0.53 months for OS. Pre-treatment decreased PLR (< 111.05) was found to be a positively significant prognostic value for both survival. These values were determined respectively as 7.37 ± 1.43 months and 3.16 ± 0.47 months for PFS and 21.12 ± 5.52 months and 6.16 ± 0.87 months for OS. And also, low PNI (< 38.25) value was prognostic for lower PFS and rates. These values were determined respectively as 7.47 ± 0.59 months and 3.25 ± 0.21 months for PFS and 16.36 ± 4.37 months and 5.15 ± 0.42 for OS. All three parameters were found to be statistically significant (p < 0.05) for both OS and PFS as independent prognostic markers. CONCLUSION: Today, as the standard first-line treatment of HCC has shifted to combinations with immunotherapy (IO), IO transportation is not possible in most countries of the world. However, there are also patients who achieve great survival with only sorafenib. The important point is to identify the biomarkers that predict which patient will benefit better from which treatment. With the markers in our study and a scoring system that can be obtained with these markers, it can be evaluated which patient will be given IO combination and which patient will be given only TKI treatment. We think that such a scoring system can be used to identify suitable patients, especially in countries where, for financial reasons, not every patient can access Immunotherapy. The advantage of these tests is that they are inexpensive, easily calculable and standardized. TRIAL REGISTRATION: Number and date of registration: 2021/2088, 01-06-2021, retrospectively registered.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Sorafenibe/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Prognóstico , Linfócitos , Neutrófilos , Estudos RetrospectivosRESUMO
AIM: To investigate the effects of cerebrolysin on inflammation, oxidative stress, apoptosis, and neurologic recovery in the setting of an experimental rabbit model of spinal cord ischemia/reperfusion injury (SCIRI). MATERIAL AND METHODS: Rabbits were randomly divided into five groups: control, ischemia, vehicle, methylprednisolone (30 mg/kg), and cerebrolysin (5 ml/kg) group. The rabbits in the control group underwent only laparotomy; the other groups underwent spinal cord ischemia and reperfusion injury for 20 minutes. Neurologic examination after 24 hours was based on the Modified Tarlov scale. Myeloperoxidase activities, catalase and malondialdehyde levels, and caspase-3 concentrations were determined in serum and tissue samples. Serum xanthine oxidase levels were studied and histopathological and ultrastructural changes were examined. RESULTS: After SCIRI, serum and tissue myeloperoxidase activities, malondialdehyde levels, caspase-3 concentrations, and serum xanthine oxidase activities were increased (p < 0.01?0.001). Catalase levels were significantly diminished (p < 0.001). Cerebrolysin treatment correlated with reduced myeloperoxidase and xanthine oxidase activities, malondialdehyde levels and caspase-3 concentrations; and with increased catalase levels (p < 0.001, for all). The cerebrolysin group showed improved histopathological, ultrastructural, and neurological outcomes. CONCLUSION: For the first time in the literature, the current study reports anti-inflammatory, antioxidant, antiapoptotic, and neuroprotective effects of cerebrolysin in a SCIRI rabbit model.
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Fármacos Neuroprotetores , Traumatismo por Reperfusão , Isquemia do Cordão Espinal , Animais , Coelhos , Catalase , Peroxidase/farmacologia , Caspase 3 , Xantina Oxidase/farmacologia , Medula Espinal , Isquemia do Cordão Espinal/patologia , Antioxidantes/farmacologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , MalondialdeídoRESUMO
Thrombocytopenia is a characteristic adverse event of trastuzumab emtansine (T-DM1), one of the essential treatment options for human epithelial growth factor receptor 2 (HER2)-positive breast cancer. The present study investigated the predictive value of thrombocytopenia for time-to-treatment discontinuation (TTD) in patients receiving T-DM1 for advanced-stage HER2-positive breast cancer. The present observational study enrolled 138 patients who received T-DM1 at six oncology centers from January 2016 to December 2021. Univariate and multivariate Cox regression analyses were performed to determine the factors affecting TTD. The median age of patients was 50 years (range, 26-83). The median number of T-DM1 cycles was 9 (range, 2-58), the overall response rate was 50.0% and the disease control rate was 69.6%. At a median follow-up time of 19.3 months, the median TTD was 9.5 months [95% confidence interval (CI), 7.3-11.7], and the median overall survival was 28.2 months (95% CI, 19.2-37.2). Thrombocytopenia during treatment was observed in 39% of all patients, and 66.7% of these patients experienced early thrombocytopenia (in the first four treatment cycles). Multivariate analysis revealed that the independent factors for TTD were hormone receptor status [hazard ratio (HR), 1.837; 95% CI, 1.249-2.701; P=0.002], Eastern Cooperative Oncology Group performance status score (HR, 3.269; 95% CI, 1.788-5.976; P<0.001) and thrombocytopenia during treatment (HR, 0.297; 95% CI, 0.198-0.446; P<0.001). Patients with early thrombocytopenia had a significantly longer TTD of 17.3 months (95% CI, 11.8-22.8) compared with 7.6 months (95% CI, 5.8-9.4) for patients without early thrombocytopenia (P<0.001). The results of the present study indicated that patients with early thrombocytopenia had improved survival outcomes compared with those without. Thus, maximum benefit from T-DM1 treatment may be achieved by confirming the predictive role of thrombocytopenia in T-DM1 treatment in prospective studies and large-scale cohorts.
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INTRODUCTION: Alectinib is an effective second-generation ALK tyrosine kinase inhibitor (TKI) used in the first-line treatment of patients with advanced ALK-positive NSCLC. Recent studies demonstrated that the percentage of ALK-positive tumor cells in patient groups receiving crizotinib might affect outcomes. This study aimed to investigate whether the percentage of ALK-positive cells had a predictive effect in patients with advanced NSCLC who received first-line Alectinib as ALK-TKI. MATERIALS AND METHODS: This retrospective study included patients with advanced-stage NSCLC who received alectinib as a first-line ALK-TKI and whose percentage of ALK-positive cells was determined by FISH at 27 different centers. Patients who received any ALK-TKI before alectinib were not included in the study. Patients were separated into two groups according to the median (40%) value of the percentage of ALK-positive cells (high-positive group ≥ 40% and low-positive group < 40%). The primary endpoint was PFS, and the secondary endpoints were OS, ORR, and PFS of the subgroups based on different threshold values for the percentage of ALK-positive cells. RESULTS: 211 patients were enrolled (48.3% female, 51.7% male) to study. 37% (n = 78) of the patients had received chemotherapy previously. After a median of 19.4 months of follow-up, the median PFS was not reached in the high-positive group (n = 113), but it was 10.8 months in the low-positive group (n = 98) (HR 0.39; 95% CI 0.25-0.60, p < 0.001). The median OS in the high-positive group was not reached, whereas it was 22.8 months in the low-positive group (HR 0.37; 95% CI 0.22-0.63, p < 0.001). ORR was significantly higher in the high-positive group (87.2 vs. 68.5%; p = 0.002). According to the cut-off values of < 20%, 20-39%, 40-59%, and ≥ 60%, the median PFS was 4.5, 17.1, and 26 months, respectively, and could not be reached in the ≥ 60% group. CONCLUSION: Our study demonstrated that the efficacy of alectinib varies significantly across patient subgroups with different percentages of ALK-positive cells. If these findings are prospectively validated, the percentage of ALK-positive cells may be used as a stratification factor in randomized trials comparing different ALK-TKIs.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Masculino , Feminino , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Quinase do Linfoma Anaplásico , Carbazóis/uso terapêutico , Carbazóis/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
Neoadjuvant chemotherapy (NACT) in gastroesophageal junction (GEJ) and gastric cancer (GC) was shown to improve survival in recent studies. We aimed to share our real-life experience of patients who received NACT to compare the efficacy and toxicity profile of different chemotherapy regimens in our country. This retrospective multicentre study included locally advanced GC and GEJ cancer patients who received NACT between 2007 and 2021. Relation between CT regimens and pathological evaluation were analysed. A total of 794 patients from 45 oncology centers in Turkey were included. Median age at the time of diagnosis was 60 (range: 18-86). Most frequent NACT regimens used were FLOT (65.4%), DCF (17.4%) and ECF (8.1%), respectively. In the total study group, pathological complete remission (pCR) rate was 7.2%, R0 resection rate 86.4%, and D2 dissection rate was 66.8%. Rate of pCR and near-CR (24%), and R0 resection (84%) were numerically higher in FLOT arm (p > 0.05). Patients who received FLOT had also higher chemotherapy-related toxicity rate compared to patients who received other regimens (p > 0.05). Median follow-up time was 16 months (range: 1-154 months). Estimated median overall survival (OS) was 58.4months (95% CI: 35.2-85.7) and disease-free survival (DFS) was 50.7 months (95% CI: 25.4-75.9). The highest 3-year estimated OS rate was also shown in FLOT arm (68%). We still do not know which NACT regimen is the best choice for daily practice. Clinicians should tailor treatment regimens according to patients' multifactorial status and comorbidities for to obtain best outcomes. Longer follow-up period needs to validate our results.
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Adenocarcinoma , Neoplasias Gástricas , Humanos , Terapia Neoadjuvante , Turquia/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Junção Esofagogástrica/patologia , Adenocarcinoma/patologiaRESUMO
BACKGROUND: Most of the studies on salivary gland cancers are limited for various reasons such as being single-center, small number of patients, including only major or minor SGCs, or only including epidemiological data. METHODS: A total of 37 medical oncology clinics from different regions of Turkey participated in this retrospective-multicenter study. The analyzed data included clinical and demographical features, primary treatment, metastasis localizations, and treatments and includes certain pathologic features. RESULTS: The study included data from a total of 443 SGCs. 56.7% was in major salivary glands and 43.3% was in minor salivary glands. Distant metastasis in the major SGCs was statistically significantly more common than in the minor SGCs, locoregional recurrence was statistically significantly more common in the minor SGCs than in the major SGCs (p = 0.003). CONCLUSIONS: Epidemiological information, metastasis and recurrence patterns, treatment modalities, and survival analysis of the patients over 20 years of follow-up are presented.
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Recidiva Local de Neoplasia , Neoplasias das Glândulas Salivares , Humanos , Estudos Retrospectivos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Neoplasias das Glândulas Salivares/epidemiologia , Neoplasias das Glândulas Salivares/terapia , Glândulas Salivares Menores/patologiaRESUMO
BACKGROUND: The necessity of computed tomography (CT) has been questioned in pediatric mild traumatic brain injury (mTBI) because of concerns related to radiation exposure. Distinguishing patients with lower and higher risk of clinically important TBI (ciTBI) is paramount to the optimal management of these patients. OBJECTIVE: This study aimed to analyze the imaging predictors of ciTBI and develop an algorithm to identify patients at low and high risk for ciTBI to inform clinical decision making using a large single-center cohort of pediatric patients with mTBI. METHODS: We retrospectively identified pediatric patients with mTBI with repeat CT within 48 hours of injury using an institutional database. RESULTS: Among 3867 pediatric patients, 219 patients with mTBI with repeat CT were included. Thirty-eight had ciTBI (17%), 16 (7%) required intensive care unit admission, and 6 (3%) underwent surgery. Median time interval between initial and repeat CT was 7 hours (range, 4-10). Clinical worsening and radiologic progression were evident in 36 (16%) and 24 (11%) patients, respectively. Multivariate analysis showed that 5 pathologic findings (depressed skull fracture, pneumocephalus, epidural hematoma, subdural hematoma, and contusion) on initial CT and radiologic progression on repeat CT were independent predictors of ciTBI. A new scoring system based on these 5 factors on initial CT (IniCT [Initial CT scoring system] score) had excellent discrimination for ciTBI, need for intensive care unit admission, and neurosurgery (area under the curve >0.8). CONCLUSIONS: The IniCT scoring system can successfully differentiate low-risk and high-risk patients based on initial CT scan. Zero score can eliminate the need for a routine repeat CT, whereas scores ≥2 should prompt serial neurologic examinations and/or repeat CT depending on the clinical situation.
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Concussão Encefálica , Lesões Encefálicas Traumáticas , Concussão Encefálica/diagnóstico por imagem , Criança , Escala de Coma de Glasgow , Cabeça , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: Dexpanthenol (DXP) reportedly protects tissues against oxidative damage in various inflammation models. This study aimed to evaluate its effects on oxidative stress, inflammation, apoptosis, and neurological recovery in an experimental rabbit spinal cord ischemia/reperfusion injury (SCIRI) model. METHODS: Rabbits were randomized into 5 groups of 8 animals each: group 1 (control), group 2 (ischemia), group 3 (vehicle), group 4 (methylprednisolone, 30 mg/kg), and group 5 (DXP, 500 mg/kg). The control group underwent laparotomy only, whereas other groups were subjected to spinal cord ischemia by aortic occlusion (just caudal to the 2 renal arteries) for 20 min. After 24 h, a modified Tarlov scale was employed to record neurological examination results. Malondialdehyde and caspase-3 levels and catalase and myeloperoxidase activities were analyzed in tissue and serum samples. Xanthine oxidase activity was measured in the serum. Histopathological and ultrastructural evaluations were also performed in the spinal cord. RESULTS: After SCIRI, serum and tissue malondialdehyde and caspase-3 levels and myeloperoxidase and serum xanthine oxidase activities were increased (P < 0.05-0.001). However, serum and tissue catalase activity decreased significantly (P < 0.001). DXP treatment was associated with lower malondialdehyde and caspase-3 levels and reduced myeloperoxidase and xanthine oxidase activities but increased catalase activity (P < 0.05-0.001). Furthermore, DXP was associated with better histopathological, ultrastructural, and neurological outcome scores. CONCLUSIONS: This study was the first to evaluate antioxidant, anti-inflammatory, antiapoptotic, and neuroprotective effects of DXP on SCIRI. Further experimental and clinical investigations are warranted to confirm that DXP can be administered to treat SCIRI.