The Comparison of FLOT and DCF Regimens as Perioperative Treatment for Gastric Cancer.

INTRODUCTION: Locoregional gastric cancer is a still serious problem and perioperative treatments may improve success of management. Different regimens were examined. The present study purposed to compare efficacy of FLOT and DCF regimens. METHODS: Retrospective multicenter study assesed the patients with locoregional gastric cancer. There are 240 patients (137 DCF, 103 FLOT). Survival rates were compared. RESULTS: Demographic features were similar between two groups, but time period was different. FLOT group had 7.8% pathological complete response, while DCF group did not have. Disease-free survival was longer in FLOT than DCF group (median not reached-13.94 months respectively). Median overall survival was similar (30.9 vs 37.8 months) but median follow-up affected the analysis. Survival for 36 months was 63% for FLOT and 40% for DCF group (p=0.015). CONCLUSION: FLOT regimen was superior on DCF regimen for response and survival rates. DCF is historical approach. Long term follow up period needed for FLOT treatment.

Efficacy and safety of bevacizumab in patients with low-grade serous ovarian cancer.

Aim: To investigate the efficacy and safety of bevacizumab in patients with recurrent low-grade serous ovarian carcinoma. Materials & methods: The data of patients who received at least two cycles of bevacizumab in combination with chemotherapy were retrospectively recorded. Results: The median age of 51 patients was 56 (range: 33-75) years. The complete response rate was 10.4% and the partial response rate was 43.7%. The objective response rate was 54.1%. Median progression-free survival was 15.9 months (95% CI: 9.1-22.6) and median overall survival was 42.5 months (95% CI: 37.2-47.8). Conclusion: Bevacizumab with chemotherapy is an effective option for treating recurrent ovarian low-grade serous carcinoma.

Gemcitabine-associated digital necrosis in metastatic breast cancer.

INTRODUCTION: Gemcitabine is a nucleoside analog antimetabolite used in various malignancies, including metastatic breast cancer. Objective response rates in its use as a single agent in the treatment of metastatic breast cancer are not to be underestimated. Cutaneous, hematological, pulmonary, and vascular side effects are well-known side effects. Venous thromboembolism may occur with antineoplastics, such as platinum compounds. Arterial thromboembolism is rare in cancer, almost rare with chemotherapy. Here, we present a metastatic breast cancer patient who had digital necrosis due to arterial occlusion with gemcitabine monotherapy. CASE REPORT: A 54-year-old metastatic breast cancer female patient had digital ischemia and necrosis in the left hand's fifth finger after the second course of single-agent gemcitabine as the fourth line setting. Gemcitabine was discontinued, and medical treatment was started. Thrombus was detected in the left subclavian artery digital angiography. Balloon angioplasty and stenting were applied. However, digital amputation had to be performed since tissue necrosis had not regressed despite radiological interventions and medical treatment. MANAGEMENT AND OUTCOME: Gemcitabine was discontinued. Low molecular weight heparin and acetylsalicylic acid were started. The distal phalanx was amputated due to necrosis during follow-up. Gemcitabine was permanently stopped. DISCUSSION: Gemcitabine-related vascular events, including arterial thrombosis, may also occur in cancer patients, especially those with higher tumor burden. Therefore, predisposing factors for hypercoagulability and vascular occlusion should be questioned in more detail even before starting antineoplastics which are known to have a lower risk for thrombosis, such as gemcitabine monotherapy.

Real-Life Analysis of Efficacy and Safety of Everolimus Plus Exemestane in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-2-Negative Metastatic Breast Cancer Patients: A Turkish Oncology Group (TOG) Study.

PURPOSE: This study evaluated the efficacy and safety of everolimus (EVE) plus exemestane (EXE) in hormone-receptor positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) metastatic breast cancer (MBC) patients in real-life settings. METHODS: Overall, 204 HR+, HER2- MBC patients treated with EVE + EXE after progressing following prior endocrine treatment were included. Overall survival (OS) and progression-free survival (PFS) and safety data were analyzed. RESULTS: The objective response rate, median PFS, and median OS were 33.4%, 8.9 months, and 23.4 months, respectively. Multivariate analysis revealed that negative progesterone receptor status was a significant determinant of poor treatment response (p = 0.035) and PFS (p = 0.024). The presence of bone-only metastasis was associated with better treatment response (p = 0.002), PFS (p < 0.001), and OS (p = 0.001). CONCLUSION: We confirmed the favorable efficacy and safety profile of EVE + EXE for HR+, HER - MBC patients.

Prognostic factors of perioperative FLOT regimen in operable gastric and gastroesophageal junction tumors: real-life data (Turkish Oncology Group).

BACKGROUND: Perioperative FLOT regimen is a standard of care in locally advanced operable gastric and GEJ adenocarcinoma. We aimed to determine the efficacy, prognostic factors of perioperative FLOT chemotherapy in real-life gastric and GEJ tumors. METHODS: The data of patients who were treated with perioperative FLOT chemotherapy were retrospectively analyzed from 34 different oncology centers in Turkey. Baseline clinical and demographic characteristics, pretreatment laboratory values, histological and molecular characteristics were recorded. RESULTS: A total of 441 patients were included in the study. The median of age our study population was 60 years. The majority of patients with radiological staging were cT3-4N(+) (89.9%, n = 338). After median 13.5 months (IQR: 8.5-20.5) follow-up, the median overall survival was NR (95% CI, NR to NR), and median disease free survival was 22.9 (95% CI, 18.6 to 27.3) months. The estimated overall survival at 24 months was 62%. Complete pathological response (pCR) and near pCR was achieved in 23.8% of all patients. Patients with lower NLR or PLR have significantly longer median OS (p = 0.007 and p = 0.033, respectively), and patients with lower NLR have significantly longer median DFS (p = 0.039), but PLR level did not affect DFS (p = 0.062). The OS and DFS of patients with better ECOG performance scores and those who could receive FLOT as adjuvant chemotherapy instead of other regimens were found to be better. NLR was found to be independent prognostic factor for OS in the multivariant analysis. At least one adverse event reported in 57.6% of the patients and grade 3-4 toxicity was seen in 23.6% patients. DISCUSSION: Real-life perioperative FLOT regimen in operable gastric and GEJ tumors showed similar oncologic outcomes compared to clinical trials. Better performance status, receiving adjuvant chemotherapy as same regimen, low grade and low NLR and PLR improved outcomes in real-life. However, in multivariate analysis, only NLR affected OS.

The Effect of Primary Surgery in Patients with De Novo Stage IV Breast Cancer with Bone Metastasis Only (Protocol BOMET MF 14-01): A Multi-Center, Prospective Registry Study.

BACKGROUND: More evidence shows that primary surgery for de novo metastatic breast cancer (BC) prolongs overall survival (OS) in selected cases. The aim of this study was to evaluate the role of locoregional treatment (LRT) in BC patients with de novo stage IV bone only metastasis (BOM). METHODS: The prospective, multicenter registry study BOMET MF14-01 was initiated in May 2014. Patients with de novo stage IV BOM BC were divided into two groups: those receiving systemic treatment (ST group) and those receiving LRT (LRT group). Patients who received LRT were further divided into two groups: ST after LRT (LRT + ST group) and ST before LRT (ST + LRT group). RESULTS: We included 505 patients in this study; 240 (47.5%) patients in the ST group and 265 (52.5%) in the LRT group. One hundred and thirteen patients (26.3%) died in the 34-month median follow-up, 85 (35.4%) in the ST group and 28 (10.5%) in LRT group. Local progression was observed in 39 (16.2%) of the patients in the ST group and 18 (6.7%) in the LRT group (p = 0.001). Hazard of death was 60% lower in the LRT group compared with the ST group (HR 0.40, 95% CI 0.30-0.54, p < 0.0001). CONCLUSION: In this prospectively maintained registry study, we found that LRT prolonged survival and decreased locoregional recurrence in the median 3-year follow-up. Timing of primary breast surgery either at diagnosis or after ST provided a survival benefit similar to ST alone in de novo stage IV BOM BC patients.

Efficacy and Safety of Trastuzumab Emtansine in Her2 Positive Metastatic Breast Cancer: Real-World Experience.

AIM: The aim of this study is to evaluate the efficacy and toxicity of trastuzumab emtansine (T-DM1) in cases with metastatic breast cancer (mBC) in different lines of treatment. METHOD: Retrospective analysis of T-DM1 results of human epidermal growth factor receptor 2 (Her2) positive 414 cases with mBC from 31 centers in Turkey. FINDINGS: Except 2, all of the cases were female with a median age of 47. T-DM1 had been used as second-line therapy in 37.7% of the cases and the median number of T-DM1 cycles was 9. Progression-free survival (PFS) and overall survival (OS) times were different according to the line of treatment. The median OS was found as 43, 41, 46, 23 and 17 months for 1st, 2nd, 3rd, 4th and 5th line, respectively (p = 0.032) while the median PFS was found as 37, 12, 8, 8 and 8 months, respectively (p = 0.0001). Treatment was well tolerated by the patients. The most common grade 3-4 adverse effects were thrombocytopenia (2.7%) and increased serum gamma-glutamyl transferase (2%). DISCUSSION: The best of our knowledge this is the largest real-life experience about the safety and efficacy of T-DM1 use in cases with mBC after progression of Her2 targeted treatment. This study suggests and supports that T-DM1 is more effective in earlier lines of treatment and is a reliable option for mBC.

Immunogenicity and safety of the CoronaVac vaccine in patients with cancer receiving active systemic therapy.

Aim: To evaluate the immunogenicity and safety of the CoronaVac vaccine in patients with cancer receiving active systemic therapy. Methods: This multicenter, prospective, observational study was conducted with 47 patients receiving active systemic therapy for cancer. CoronaVac was administered as two doses (3 µg/day) on days 0 and 28. Antibody level higher than 1 IU/ml was defined as 'immunogenicity.' Results: The immunogenicity rate was 63.8% (30/47) in the entire patient group, 59.5% (25/42) in those receiving at least one cytotoxic drug and 100% (five of five) in those receiving monoclonal antibody or immunotherapy alone. Age was an independent predictive factor for immunogenicity (odds ratio: 0.830; p = 0.043). Conclusion: More than half of cancer patients receiving active systemic therapy developed immunogenicity.

"Swords and Shields" against COVID-19 for patients with cancer at "clean" and "pandemic" hospitals: are we ready for the second wave?

PURPOSE: COVID-19 will continue to disrupt the diagnosis-treatment process of cancer patients. Dr. Abdurrahman Yurtaslan Ankara Oncology Hospital has been considered as a 'non-pandemic' center ('clean') in Ankara, the capital city of Turkey. The other state hospitals that also take care of cancer patients in Ankara were defined as 'pandemic' centers. This study aimed to evaluate hospital admission changes and the precautionary measures in clean and pandemic centers during the pandemic. The effect of these measures and changes on COVID-19 spreading among cancer patients was also evaluated. METHODS: The patients admitted to the medical oncology follow-up, new diagnosis, or chemotherapy (CT) outpatient clinics during the first quarter of pandemic period (March 15-June 1, 2020) of each center were determined and compared with the admissions of the same frame of previous year (March 15-June 1, 2019). COVID-19 PCR test results in clean and pandemic centers were compared with each other. Telemedicine was preffered in the clean hospital to keep on follow-up of the cancer patients as 'noninfected'. RESULTS: In the clean hospital, COVID-19-infected patients that needed to be hospitalized were referred to pandemic hospitals. COVID-19 test positivity rate was eight-fold higher for outpatient clinic admissions in pandemic hospitals (p < 0.001). The number of patients admitted new diagnosis outpatient clinics in both clean and pandemic hospitals decreased significantly during the pandemic compared with the previous year. CONCLUSION: We consider that local strategic modifications and defining 'clean' hospital model during infectious pandemic may contribute to protect and treat cancer patients during pandemic.

Alectinib continuation during COVID 19 'antiviral' treatment: Risk or benefit?

INTRODUCTION: Serious Acute Respiratory Syndrome Coronavirus 2 (SARSCoV2) has led to COVID 19 pandemic a year ago and it has not been globally taken under control yet. COVID 19 tends to have poorer prognosis in cancer patients. Additionally, we have no well-established guidelines for management of these patients during pandemic, in terms of treatment of 'cancer' and treatment of 'COVID 19'. Tyrosine kinase inhibitors (TKIs) are given without any break in cancer patients to have better survival outcomes in daily routine. However, there is no well-established data to continue or delay ALK inhibitors in lung cancer patients infected with SARS-CoV2. Concomittant use of ALK inhibitors and COVID 19 antiviral treatment is a dilemma because of the lack of data in this area. CASE REPORT: A 47-year old female metastatic ALK positive nonsquamous cell lung cancer patient on alectinib, a second generation ALK inhibitor was diagnosed with symptomatic COVID 19. She was given favipiravir for COVID 19 while continuing alectinib.Management and outcome: The patient continued alectinib during COVID 19 antiviral treatment without any break. She tolerated 'concomittant' alectinib & favipiravir. She had partial remission after three months of alectinib without any dose adjustment despite active COVID 19 medication. DISCUSSION: To best of our knowledge, this is the first case who continued alectinib without dose adjustment during antiviral COVID-19 medication without clinically worsening. There is limited data about 'concomittant' use of TKIs and antiviral COVID 19 medication in the literature. There are some case reports, but they generally tended to delay or suspend TKIs during COVID 19 antiviral medication. Our case differs from them in terms of continuation of alectinib without any break or additional side effects during favipiravir for symptomatic COVID 19. We consider that our case might contribute to the literature in terms of management of cancer patients on targeted therapy during COVID 19 antiviral treatment. However, clinical trials are needed in this area.

Does primary tumor resection contribute to overall survival in unresectable synchronous metastatic colorectal cancer?

BACKGROUND: Primary tumor resection (PTR) in metastatic colorectal cancer (mCRC) has not been suggested by guidelines, since new systemic chemotherapy options have improved overall survival. However, the effect of PTR is still controversial in mCRC. In this study, we aimed to evaluate the effect of PTR on survival in unresectable mCRC. MATERIALS AND METHODS: Two hundred and fifty-two patients with unresectable mCRC were screened retrospectively between January 2007 and December 2017 and a total of 147 patients who met inclusion criteria were included. The patients with emergency or elective PTR and the patients without surgery were compared for baseline features and overall survival. RESULTS: The median follow-up time was 15.6 months (range; 1.2-78.9) in whole patients. There were 91 patients in nonsurgical (NS) group and 56 patients in PTR group. The median overall survival was significantly longer in PTR group compared NS group (21.8 vs. 17.0 months, P = 0.01), but it was not associated to better overall survival in multivariate Cox analysis (hazard ratio: 0.65, 95% confidence interval: 0.41-1.02, P = 0.06). There was no significant difference in overall survival between emergency and elective surgery subgroups (22.9 vs. 16.1 months, respectively, P = 0.9). CONCLUSION: PTR did not offer an overall survival benefit in this study. Although it is debated, we think that it is better to start treatment with chemotherapy and biological agent combinations in patients with asymptomatic mCRC. Thus, the patients can be protected from the morbidity and mortality of the surgery.

Endpoints in oncology clinical trials.

In oncology clinical trials, many different endpoints can be used as primary or secondary endpoints. Advances in cancer treatment have provided longer survival outcomes, particularly in certain types of cancer. Overall survival is accepted as the gold standard endpoint for demonstrating clinical benefit; however, it is associated with some disadvantages such as requirement of long-term follow-up, requirement of higher number of patients, and high cost. Thus, the question "what is the most appropriate endpoint in clinical trials?" comes to mind. The present review discusses the endpoints in oncology clinical trials.

Comparison of pigmentary side effects of taxanes and anthracyclines: an onychoscopic evaluation.

BACKGROUND: Taxanes and anthracyclines are considered as fundamental drugs for the treatment of a broad range of cancers. They have several side effects, which may limit their usage. Drug-induced nail pigmentation (DHNP) has been reported as one of the most striking dermatological side effect of both taxanes and doxorubicin. OBJECTIVE: This study aimed to evaluate and compare pigmentary side effects of taxanes and doxorubicin with the help of onychoscopy. METHODS: Forty-one consecutive patients (30 women, 11 men) with a diagnosis of cancer (16 gastric cancer, 25 breast cancer) were prospectively enrolled in a period of six months. Patients were categorized according to the chemotherapy regimens they had been administered: docetaxel received group [docetaxel (60 mg/m2, day 1), cisplatin (60 mg/m2, day 1) and fluorouracil (500 mg/m2, days 1-5) every 3 weeks], paclitaxel received group [paclitaxel (80-175 mg/m2) every 21 days with or without trastuzumab/zoledronic acid] and doxorubicin received group [doxorubicin 50-60 mg/m2 and cyclophosphamide 600-750 mg/m2 every 21 days]. All the patients were asked whether they had diabetes mellitus (DM) and peripheral neuropathy. At the 16 weeks of chemotherapy, for each patient, all fingernails and toenails were evaluated in clinical and dermoscopic examinations for nail pigmentation. Dermoscopic examination was performed using a videodermatoscope. Descriptive statistics were computed for means, standard deviations, and frequencies. Chi-square test or Fisher's exact tests were used for the statistical analysis, with a significance threshold of p < 0.05. RESULTS: 34.1% of the patients (14/41) demonstrated clinical signs of nail pigmentation. Nail pigmentation was observed in 4 of 13 patients (30.8%), who had received doxorubicin; 10 of 28 patients (35.7%), who had received taxanes (docetaxel and paclitaxel). There was no statistically significant relationship between the nail pigmentation and the type of the chemotherapeutic regimen administered (Fisher's exact test, p = 1.000). In addition, no statistically significant results were observed between nail pigmentation and DM (Fisher's exact test, p = 0.393), and nail pigmentation and peripheral neuropathy (Fisher's exact test, p = 1.000). CONCLUSIONS: DHNP may cause considerable distress to patients. Dermoscopy is a noninvasive imaging method that increases diagnostic accuracy of both pigmented and nonpigmented lesions. Typical dermoscopic features of DHNP consist of a homogeneous brownish-gray coloration of the background with thin, longitudinal, gray lines, which allow the examiner to clearly make the correct diagnosis. Further studies are needed to assess both clinical and dermoscopical findings of DHNP.

Effectiveness of low-dose oral etoposide treatment in patients with recurrent and platinum-resistant epithelial ovarian cancer.

The aim of this study was to evaluate the efficacy and toxicity profile of oral etoposide (50 mg/day, days 1-14, every 3 weeks) in recurrent platinum-resistant epithelial ovarian cancer (EOC). 52 recurrent platinum-resistant EOC patients followed up in four centres between April 2000 and December 2013 were analysed retrospectively. There was response in a total of 21 patients [partial response (PR) and stable disease (SD)], 12 of them used etoposide in second and third, and 9 of them used it in fourth- to fifth-lines of treatment. The overall response rate was 19.2% and clinical benefit rate was 40.4% [PR (19.2%), SD (21.2%)]. Median overall survival (OS) and progression-free survival (PFS) was 9.95 months (95%CI, 0.2-19.7 months) and 3.2 months (95%CI 2.6-3.8 months), respectively. Grade III-IV haematologic and non-haematologic adverse events were observed in 7 (13.4%) patients. We consider that oral etoposide (50 mg/day, days 1-14, every 3 weeks) is an effective treatment with a manageable adverse effect profile in recurrent platinum-resistant EOC patients. Impact statement What is already known on this subject: Oral etoposide is an effective option for recurrent EOC patients at a dose of 50-100 mg/m2/day (1-21 days, every 28 days) regimen. However, it has a high toxicity rate. What the results of this study add: Oral etoposide at a dose of 50 mg/kg (1-14 days, every 21 days) is an effective treatment with a manageable toxicity profile in platinum- resistant ovarian cancer patients when it is used as ≤4th-line palliative setting. What the implications are of these findings for clinical practice and/or further research: We need trials evaluating the effect of low-dose oral etoposide combination with bevacizumab or other chemotherapy agents (irinotecan and gemcitabine) in platinum-resistant EOC patients.

Breast cancer survivors suffer from persistent postmastectomy pain syndrome and posttraumatic stress disorder (ORTHUS study): a study of the palliative care working committee of the Turkish Oncology Group (TOG).

PURPOSE: Persistent postmastectomy pain syndrome (PMPS) is one of the most important disturbing symptoms. Posttraumatic stress disorder (PTSD) is an anxiety disorder which is characterized by reactions to reminders of the trauma that has been experienced. The purpose of this study is to evaluate the predictors of PMPS and PTSD in Turkish breast cancer survivors and the correlation between PMPS and PTSD. METHOD: The study is designed as a multicenter survey study. Breast cancer patients in remission were evaluated. Patients were evaluated with structured questionnaires to assess the PMPS and clinical parameters associated with it. The Turkish version of the posttraumatic stress disorder checklist-civilian version (PCL-C) was used. RESULTS: Between February 2015 and October 2015, 614 breast cancer survivors in outpatient clinics were evaluated. The incidence of PMPS documented is 45.1 %. In the multivariate analysis low income, presence of PTSD and <46 months after surgery were associated with increased risk of PMPS. PTSD was documented in 75 %, and the mean PCL-C score was 32.4 ± 11.1. PMPS and being married at the time of the evaluation were linked with PTSD. CONCLUSIONS: It is the first data about the association between PMPS and PTSD. The clinicians should be aware of PMPS and PTSD in breast cancer survivors.

Evaluation of the effects of red blood cell distribution width on survival in lung cancer patients.

AIM OF THE STUDY: Data are available indicating that red blood cell distribution width (RDW) is higher in cancer patients compared to healthy individuals or benign events. In our study, we aimed to investigate the influence of different RDW levels on survival in lung cancer patients. MATERIAL AND METHODS: Clinical and laboratory data from 146 patients with lung cancer and 40 healthy subjects were retrospectively studied. RDW was recorded before the application of any treatment. Patients were categorised according to four different RDW cut-off values (median RDW, RDW determined by ROC curve analysis, the upper limit at the automatic blood count device, and RDW cut of value which used in previous studies). Kaplan-Meier survival analysis was used to examine the effect of RDW on survival for each cut-off level. RESULTS: The median age of patients was 56.5 years (range: 26-83 years). The difference in median RDW between patients and the control group was statistically significant (14.0 and 13.8, respectively, p = 0.04). There was no difference with regard to overall survival when patients with RDW ≥ 14.0 were compared to those with RDW < 14.0 (p = 0.70); however, overall survival was 3.0 months shorter in low values of its own group in each of the following cut-off values: ≥ 14.2 (p = 0.34), ≥ 14.5 (p = 0.25), ≥ 15 (p = 0.59), although no results were statistically significant. DISCUSSION: We consider that the difference between low and high RDW values according to certain cut-off values may reflect the statistics of larger studies although there is a statistically negative correlation between RDW level and survival.

Prognostic factors in non-metastatic HER2 'low' and HER2 'negative' breast cancer: single institute experience.

AIM: Comparison of prognosis and survival in human epidermal growth factor receptor 2 (HER2)-low and HER2-negative patients with early stage or locally advanced, hormone receptor-positive breast cancer. MATERIAL AND METHODS: In a retrospective single center study, the patients with early stage or locally advanced stage, hormone receptor (HR)-positive [estrogen receptor (ER) ≥ 1% and/or progesterone receptor (PR) ≥ 1%] and HER2 negative or HER2 low invasive breast cancer diagnosis were included. A total of 444 patients were included in the study. Patients were divided into two groups: HER2 negative and HER2 low. There were 235 (53%) patients in the HER2 negative group and 209 (47%) patients in the HER2 low group. RESULTS: The HER2 low group had significantly longer 5­year disease-free survival (DFS) than the HER2 negative group. The patients with lower Ki67 (< 20%) also had a longer 5­year DFS. CONCLUSION: Nonmetastatic HR+/HER2 low breast cancer patients had better DFS than HR+/HER2 negative ones. The Ki67 level and HER2 low status were independent prognostic factors. Randomized clinical trials are needed in early stage HER2 low breast cancer patients.

Treatment outcomes and prognostic factors in patients with driver mutant non-small cell lung cancer and de novo brain metastases.

Central nervous system (CNS) metastases can be seen at a rate of 30% in advanced stages for patients with non-small cell lung cancer (NSCLC). Growing evidence indicates the predictive roles of driver gene mutations in the development of brain metastases (BM) in recent years, meaning that oncogene-driven NSCLC have a high incidence of BM at diagnosis. Today, 3rd generation targeted drugs with high intracranial efficacy, which can cross the blood-brain barrier, have made a positive contribution to survival for these patients with an increased propensity to BM. It is important to update the clinical and pathological factors reflected in the survival with real-life data. A multi-center, retrospective database of 306 patients diagnosed with driver mutant NSCLC and initially presented with BM between between November 2008 and September 2022 were analyzed. The median progression-free survival (mPFS) was 12.25 months (95% CI, 10-14.5). While 254 of the patients received tyrosine kinase inhibitor (TKI), 51 patients received chemotherapy as first line treatment. The median intracranial PFS (iPFS) was 18.5 months (95% CI, 14.8-22.2). The median overall survival (OS) was 29 months (95% CI, 25.2-33.0). It was found that having 3 or less BM and absence of extracranial metastases were significantly associated with better mOS and iPFS. The relationship between the size of BM and survival was found to be non-significant. Among patients with advanced NSCLC with de novo BM carrying a driver mutation, long-term progression-free and overall survival can be achieved with the advent of targeted agents with high CNS efficacy with more conservative and localized radiotherapy modalities.

Efficacy of adjuvant CDK4/6 inhibitors in hormone receptor-positive breast cancer: a systematic review and meta-analysis.

BACKGROUND: The combination of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and standard endocrine therapy (ET) in the adjuvant treatment of hormone receptor (HR)-positive/HER2-negative breast cancer (BC) has yielded conflicting results. We performed a pooled analysis of the adjuvant efficacy of CDK4/6 inhibitors by including data from the NATALEE trial, the most recent trial on this topic. METHODS: We searched major databases and congress proceedings until 7 June 2023 to identify randomized controlled trials (RCT) comparing adjuvant CDK4/6 inhibitor plus ET combination versus ET in HR-positive/HER2-negative early-stage BC. RESULTS: Four RCTs involving a total of 17,749 patients were included. According to the pooled analysis of these four studies, significant improvement in invasive disease-free survival (iDFS) was observed with the addition of CDK4/6 inhibitors to standard ET (HzR: 0.81, 95% CI 0.67-0.97). IDFS benefit was irrespective from menopausal status, Ki-67 index, tumor grade, and previous chemotherapy. CDK4/6 inhibitors plus ET had a significant improvement in iDFS in stage 3 whereas there was a trend toward better iDFS in stage 2 (HzR for stage 3: 0.67, 95% CI 0.58-0.78; HzR for stage 2: 0.74, 95% CI 0.55-1.01). CONCLUSIONS: Addition of CDK4/6 inhibitors to standard ET in the adjuvant treatment of HR-positive/HER2-negative early-stage BC improves iDFS.