Do metastatic volumes measured in breast cancer patients with bone metastases correlate with the numbers of skeletal and extraskeletal events?

OBJECTIVES: The study aimed to investigate the relationship between metastatic volume measurement, skeletal-related events, and survival in women diagnosed with breast cancer and bone metastases. PATIENTS AND METHODS: This retrospective study was conducted with 82 female breast cancer patients (mean age: 53±14.3 years; range, 23 to 87 years) diagnosed, treated, and followed up between January 2005 and December 2019. The collected data included information on metastasis sites and the presence of skeletal-related events. Metastatic volume was measured in two ways: the number of metastases (high to low) and their localization (the first, second, and third groups). The first group consisted of vertebrae, ribs, sternum, and calvarial bones; the second group included scapula, clavicle, proximal humerus, and proximal femur regions; the third group consisted of femur and humerus diaphyseal and distal regions, as well as metastasis regions in other long bones. RESULTS: Sixty-three (76.8%) patients were diagnosed with ductal carcinoma. Half of the patients had bone metastases at the time of initial diagnosis, while 62 (75.6%) experienced skeletal-related events, with at least three events occurring in 30 (36.6%) patients. Bone pain was the most common skeletal-related event. No correlation was found between metastatic volume measurement based on the localization of bone metastases and the number of bones and the occurrence of skeletal-related events (p>0.05 for each). Patients' survival time spanned from one to 231 months (median: 56.8 months) from their first diagnosis. Patients with high metastatic volume, those in the third group, those whose pelvis and lung were involved, and elderly patients had a shorter survival time (p<0.05 for each). CONCLUSION: The study indicates that measuring metastatic volume may be a critical factor in evaluating the survival of breast cancer patients with bone metastases. Future prospective and randomized controlled studies can explore the potential of this measurement to create practical clinical tools.

[Clinical features of the ALK-mutant non-small cell lung cancer patients who received first-line alectinib treatment]. / Birinci basamak alektinib tedavisi alan ALK mutasyonu pozitif akciger kanseri hastalarinin klinik özelliklerinin degerlendirilmesi.

INTRODUCTION: Lung cancer is the most common cancer type and the leading cause of cancer-related mortality worldwide. The positivity rate of the anaplastic lymphoma kinase (ALK) mutation in non-small cell lung cancer (NSCLC) patients has been reported as 3-7%. This study aimed to investigate the pathological, clinical and demographic characteristics of ALK-mutant NSCLC patients who received first-line alectinib as a tyrosine kinase inhibitor in two different centers. MATERIALS AND METHODS: The study was performed at the Medical Oncology Departments of Ankara City Hospital and Atatürk Chest Diseases and Thoracic Surgery Training and Research Hospital. Patients diagnosed with ALK-mutant NSCLC and received alectinib treatment as a first-line tyrosine kinase inhibitor were enrolled to study and retrospectively analyzed. RESULT: A total of 38 patients (15 males, 23 females) were included in the study. Median age was 56.5. 55.3% of the patients were non-smokers. All of the patients had adenocarcinoma histology. Thirty-four patients (89.5%) were metastatic. Brain metastasis was detected in 44.7% of the patients. Thirty-three patients (86.8%) were using alectinib in first-line treatment. The remaining five patients were seen to have received at least one course of chemotherapy before. The objective response rate was 78.9% with alectinib treatment. The percentage of the patients who experienced at least one side effect was 34.2% and serious side effects were 7.9%. After median 9.5 months follow-up, median progression-free survival (PFS) was not achieved. 24-month PFS was 67% and 24-month overall survival was 84%. CONCLUSIONS: Our results were compatible with previous studies in terms of the clinical, pathological and demographic features of the patients with ALK mutation. We observed that the majority of patients were non-smokers, relatively young, and female patients. The objective response rate and survival results were similar with phase 3 studies.

A historical turning point for the treatment of advanced renal cell carcinoma: inhibition of immune checkpoint.

Background: Renal cell carcinoma (RCC) is the most common type of renal malignancy with 87% frequency. As a global health problem, kidney cancer is responsible for 2.2% of new cancer cases. One of the highly effective mechanisms that renal cancer cells avoid in the immune system is PD-1 and PD-L1 interaction.Scope: Literature search is made from PubMed, Medline, and ASCO and ESMO Annual Meeting abstracts using the following search keywords: "nivolumab," "pembrolizumab," "atezolizumab," "avelumab," "durvalumab," and "renal cell cancer." The last search was on November 1, 2019.Findings: The combination of nivolumab and ipilimumab have better survival results than sunitinib for intermediate and poor risk patients but not for favorable risk groups. In 2019, two combination regimens with pembrolizumab plus axitinib and avelumab plus axitinib demonstrated efficacy over sunitinib for every risk group. The overall survival data of these trials are still immature.Conclusions: Advanced RCC has high morbidity and mortality with an increasing prevalence. Following tyrosine kinase inhibitors, checkpoint inhibitors have a great influence on treatment of advanced RCC, especially the combination of these two strategies. In 2019 these combined strategies demonstrated 5% complete remission with up to 60% objective response rate. While not immediately, but perhaps in the near future, advanced RCC will become a manageable chronic disease, even if a cure is not possible.

Expanding treatment options for resectable gastric cancer: Is it a countdown for radiotherapy?

Chemoradiotherapy (CRT) and chemotherapy in the perioperative or postoperative settings are the different neoadjuvant/adjuvant treatment approaches for resectable gastric cancer. After the results of the ARTIST trial, CRT lost its importance on a large scale in the adjuvant setting. Also, according to the results of the CRITICS trial, CRT does not seem beneficial in the perioperative treatment setting. The beneficial effect of neoadjuvant/adjuvant radiotherapy as a therapeutic option became more questionable as the evidence grows, but still needs further studies to identify its effects on a subgroup of patients who have R1 or

Charlson Comorbidity Index, inappropriate medication use and cognitive impairment : Bermuda Triangle.

BACKGROUND: The aim is to evaluate the association between the Charlson Comorbidity Index (CCI), polypharmacy, inappropriate medication use and cognitive impairment in long-term care facility patients. METHODS: A cross-sectional study including 105 long-term care facility residents was performed. The Charlson Comorbidity Index (CCI) was used. Inappropriate drug use (IDU) was defined according to the STOPP (Screening Tool of Older People's Prescriptions) criteria. Univariate analysis to identify variables associated with patient outcome related with cognitive impairment was investigated with χ2, Pearson correlation, Fisher exact, and Mann-Whitney U test where appropriate. For the multivariate analysis, the possible factors identified with univariate analysis were further entered into logistic regression analysis. RESULTS: A significant difference was found between gender, CCI and cognitive impairment (p = 0.038, p = 0.01). While every one point increment in the CCI increases the risk of cognitive impairment 3.1 fold (95% CI = 1.8-5.4, p < 0.001), hypertension increases the risk 12 fold (95% CI = 2.5-67.8, p = 0.002). While the correlation between Mini-Mental Status Examination (MMSE) score and polypharmacy is significant (p = 0.015), the correlation between MMSE and IDU was insignificant (p = 0.739). The association of urogenital system drugs and dementia was significant (p = 0.044). CONCLUSIONS: Comorbidities, especially hypertension and old age, are risk factors for cognitive impairment. Polypharmacy correlates with MMSE and is considered a risk factor for cognitive impairment. Inappropriate medication use is high among long-term care facility residents. More studies on large cohorts are needed regarding optimal drug prescription and detection of specific drugs that may have an impact on cognitive performance.

A current and comprehensive review of cyclin-dependent kinase inhibitors for the treatment of metastatic breast cancer.

BACKGROUND: Resistance to endocrine treatment generally occurs over time, especially in the metastatic stage. In this paper, we aimed to review the mechanisms of cyclin-dependent kinase (CDK) 4/6 inhibition and clinical usage of new agents in the light of recent literature updates. SCOPE: A literature search was carried out using PubMed, Medline and ASCO and ESMO annual-meeting abstracts by using the following search keywords; "palbociclib", "abemaciclib", "ribociclib", "cyclin-dependent kinase inhibitors" and "CDK 4/6" in metastatic breast cancer (MBC). The last search was on 10 June 2017. FINDINGS: CDKs and cyclins are two molecules that have a key role in cell cycle progression. Today, there are three highly selective CDK4/6 inhibitors in clinical development - palbociclib, ribociclib and abemaciclib. Palbociclib and ribociclib were recently approved by the US FDA in combination with letrozole for the treatment of MBC in a first-line setting, as well as palbociclib in combination with fulvestrant for hormone-receptor (HR)-positive MBC that had progressed while on previous endocrine therapy according to the PALOMA-1, MONALEESA-2 and PALOMA-3 trials, respectively. In the recently published randomized phase III MONARCH 2 trial, abemaciclib plus letrozole had longer progression-free survival and higher objective response rates with less serious adverse events in advanced HR-positive breast cancer previously treated with hormonal treatment. CONCLUSION: CDK4/6 inhibition is a new and promising target for patients with hormone-receptor-positive MBC. Both palbociclib and ribociclib showed significant additive benefit for patients receiving first-line treatment for HR-positive, epidermal growth factor receptor-2-negative advanced breast cancer. Palbociclib and abemaciclib also had significant activity in combination with fulvestrant for patients with MBC that progressed on previous endocrine therapy.

Targeting the PD-1 pathway: a new hope for gastrointestinal cancers.

BACKGROUND: VEGF, HER2 and EGFR targeted agents are currently used in gastric, esophageal and colorectal cancers. However, treatment outcomes are still poor in most gastrointestinal (GI) cancers. Immune checkpoints are one of the most promising immunotherapy approaches. In this review article, we aim to discuss the efficacy and safety of anti-PD-1/PD-L1 therapies in GI cancers, including gastric, esophageal and colorectal cancer in published or reported recent studies. SCOPE: A literature search was made from PubMed and ASCO Annual Meeting abstracts by using the following search keywords: "nivolumab", "pembrolizumab", "avelumab", "GI cancers" "anti-PD1 therapy" and "anti-PD-L1 therapy". The last search was on 2 November 2016. The most important limitation of our review is that most of the data on anti-PD-1/PD-L1 therapies in GI cancers relies on phase 1 and 2 trials. FINDINGS: Currently, there are two anti-PD-1 (nivolumab and pembrolizumab) and one anti-PDL1 (atezolizumab) agents approved by FDA. After the treatment efficacy of immune checkpoint blockade was shown in melanoma, renal cell cancer and non-squamous lung cancer, trials which evaluate immune checkpoint blockade in GI cancers are ongoing. Early results of trials have been promising and encouraging for patients with advanced stage gastroesophageal cancer. According to early results of published trials, response to anti-PD1/PD-L1 agents appears to be associated with tumor PD-L1 levels. According to two recently published phase 2 trials, the clinical benefits of immune checkpoint blockade with both nivolumab and pembrolizumab were limited in patients with microsatellite instability (MSI) positive advanced colorectal cancer. However, several phase 2/3 trials are still ongoing. CONCLUSION: Both pembrolizumab and nivolumab show promising efficacy with acceptable safety data in published trials in GI cancers, especially in refractory MSI positive metastatic colorectal cancer.

Evaluation of prognostic factors and treatment in advanced small bowel adenocarcinoma: report of a multi-institutional experience of Anatolian Society of Medical Oncology (ASMO).

PURPOSE: Small bowel adenocarcinoma (SBA) is a rare tumor of the gastrointestinal system with poor prognosis. Since these are rarely encountered tumors, there are limited numbers of studies investigating systemic treatment in advanced SBA. The purpose of this study was to evaluate the prognostic factors and systemic treatments in patients with advance SBA. METHODS: Seventy-one patients from 18 Centers with advanced SBA were included in the study. Fifty-six patients received one of the four different chemotherapy regimens as first-line therapy and 15 patients were treated with best supportive care (BSC). RESULTS: Of the 71 patients, 42 (59%) were male and 29 (41%) female with a median age of 56 years. Median follow- up duration was 14.3 months. The median progression free survival (PFS) and overall survival (OS) were 7 and 13 months, respectively (N=71). In patients treated with FOLFOX (N=18), FOLFIRI (N=11), cisplatin-5-fluorouracil/ 5-FU (N=17) and gemcitabine alone (N=10), median PFS was 7, 8, 8 and 5 months, respectively, while median OS was 15, 16, 15 and 11 months, respectively. No significant differences between chemotherapy groups were noticed in terms of PFS and OS. Univariate analysis revealed that chemotherapy administration, de novo metastatic disease, ECOG PS 0 and 1, and overall response to therapy were significantly related to improved outcome. Only overall response to treatment was found to be significantly prognostic in multivariate analysis (p=0.001). CONCLUSIONS: In this study, overall response to chemotherapy emerged as the single significant prognostic factor for advanced SBAs. Platin and irinotecan based regimens achieved similar survival outcomes in advanced SBA patients.