Prognostic factors in Kaposi sarcoma, single centre experience.

BACKGROUND: Kaposi sarcoma (KS) is a multicentric vascular and lymphatic neoplasm caused by human herpesvirus 8 (HHV-8). It generally concerns the elderly and immunosuppressed population. Four major clinical types of KS have been described. The most common subtype is Classical KS (CKS). OBJECTIVES: Our retrospective study aimed to better define prognostic subgroups among patients with CKS, which is the most common in our country. METHOD: Between 2014 and 2020, 43 patients with CKS were treated with local excision, radiotherapy and chemotherapy. Reviewed information included demographics, clinical features, laboratory findings, treatment responses and overall survival. RESULTS: During the follow-up, eight patients (18.6%) died of CKS. The complete response rate was 46.5%, partial response and stable disease 51.2%, and progressive disease 2.3% of all patients. Gender, haemoglobin level at diagnosis, and disseminated involvement were prognostic factors affecting survival in all patients. CONCLUSION: We confirmed that male gender, low haemoglobin levels, and disseminated involvement are associated with poor prognosis in CKS patients. It is the only Turkish study in which prognostic analysis was performed for this rare cancer.

PROPSEA, safety evaluation of palbociclib and ribociclib in older patients with breast cancer: A prospective real-world TOG study.

INTRODUCTION: In this study, the toxicities and management of palbociclib and ribociclib in older patients (≥65 years) with metastatic breast cancer patients were investigated. MATERIALS AND METHODS: Among older patients receiving palbociclib and ribociclib, Geriatric 8 (G8) and Groningen Frailty Index were used to evaluate frailty status. Dose modifications, drug withdrawal and other serious adverse events (SAEs) were recorded and analyzed according to baseline patient characteristics. RESULTS: A total of 160 patients from 28 centers in Turkey were included (palbociclib = 76, ribociclib = 84). Forty-three patients were ≥ 75 years of age. The most common cause of first dose modification was neutropenia for both drugs (97% palbociclib, 69% ribociclib). Liver function tests elevation (10%) and renal function impairment (6%) were also causes for ribociclib dose modification. Drug withdrawal rate was 3.9% for palbociclib and 6% for ribociclib. SAEs were seen in 11.8% of those taking palbociclib and 15.5% of those on riboclib. An ECOG performance status of ≥2 and being older than 75 years were associated with dose reductions. Severe neutropenia was more common in patients with non-bone-only metastatic disease, those receiving treatment third-line therapy or higher, coexistance of non-neutropenic hematological side effects (for ribociclib). Neutropenia was less common among patients with obesity. DISCUSSION: Our results show that it can be reasonable to start palbociclib and ribociclib at reduced dose in patients aged ≥75 years and/or with an ECOG performance status ≥2.

Effect of antibiotic treatment on immune checkpoint inhibitors efficacy in patients with advanced non-small cell lung cancer.

BACKGROUND: Gut microbiotaplays a crucial role in immune response. Recent data have shown that antibiotic (ATB) usage influences efficacy of immune check point inhibitors (ICIs) via altering microbiota of the gut. METHODS: We retrospectively analyzed patients with advanced non-small cell lung cancer (NSCLC) treated with ICIs as monotherapy or combination with chemotherapy (ChT) at the one academic center. Those receiving ATB for the first 12 weeks of the initiation of ICIs were compared with those who did not. The primary objective of this study was to assess the impact of ATB use on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) during ICIs therapy. RESULTS: 90 patients were included in our analysis. Of these 90 patients, 27 (30%) received ATB in the first 12 weeks of the treatment. In patients who received ATB in the first 12 weeks of ICIs administration, PFS was significantly shorter (4.9 vs. 24.8 months, HR 2.52, 95% CI (1.52-4.18), p < 0.001). OS was also significantly shorter (5.4 vs. 37.8 months, HR 2.55, 95% CI (1.48-4.40), p = 0.001). We also examined the impact of ATB on ORR. Exposure to ATB for the first weeks consistently worsened the response rate; the ORR was 25.9% in the ATB group and 55.6% in the no ATB group (p = 0.01). CONCLUSION: Our findings demonstrated that the use of antibiotics around ICIs initiation was associated with decreased OS, PFS, and ORR in patients with NSCLC. This suggests that microbiota diversity may be one of the factors predicting the efficacy of ICIs.

Major and minor salivary gland cancers: A multicenter retrospective study.

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.

Relationship between pathological response and molecular subtypes in locally advanced breast cancer patients receiving neoadjuvant chemotherapy.

Majority of patients with breast cancer were diagnosed with locally advanced stages of the disease (54%). This study aimed to explain the pathological response received to neoadjuvant chemotherapy (NACT) according to the molecular classification of breast cancer in patients with locally advanced tumors. One hundred and one patients with locally advanced breast cancer treated with neoadjuvant chemotherapy were analyzed. Patients were classified into five molecular subtypes based on the profile of the estrogen receptor, progesterone receptor, HER2, and Ki-67. We determined associations between complete pathological response (no invasive tumor after neoadjuvant chemotherapy) and molecular subgroups. Most patients had luminal A tumors (n: 28, 27.7%). The overall rate of complete pathological response (pCR) was 34.7% (n:35). Tumors that presented with the highest rate of pCR were pure HER2-positive, at 60% (n:6; OR, 3.2; 95% CI, 0.8-12.2). According to logistic regression analysis, the factors affecting pCR were HER2 positivity and clinically positive axilla before NACT. Luminal A tumors had a significantly lower pCR rate. (7.1%,p: 0.001). Despite the low pCR rate, Luminal A tumor had the best survival rate in the subgroups (p < 0.001). However, there was no difference between EFS and OS according to pCR in any molecular subgroups. Pathological complete response is directly related to the subtypes of breast cancer. A high complete pathological response rate is observed in the pure HER2-positive group. However, EFS and OS were not statistically significant in patients with and without pCR.

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.

A rare case of cardiac toxicity in a patient with imatinib treatment: Case report.

Imatinib, a tyrosine kinase inhibitor, primarily used to treat chronic myeloid leukemia, has shown a survival benefit in gastrointestinal stromal tumors (GISTs). The most common toxicities of imatinib include fluid retention, diarrhea, nausea, fatigue, muscle cramps, abdominal pain, and rash. Imatinib-related cardiotoxicity is a rare condition, and its clinical severity varies between asymptomatic mild ventricular dysfunction and severe congestive heart failure (CHF). We report the case of a 64-year-old woman with a history of GIST who presented to our clinic with rapidly progressive dyspnea. After 8 weeks of imatinib treatment, the patient developed CHF. Echocardiography showed decreased ejection fraction. Imatinib was stopped and diuretic therapy was started. Two weeks later, she died. Cardiac shock was her cause of death.

A single center's experience of the extrapulmonary neuroendocrine carcinomas.

Objective: Extrapulmonary neuroendocrine carcinoma (EP-NEC) is a rare tumor type, and a standard therapy for EP-NEC has not yet been established. The purpose of this research was to explore the overall survival (OS) and therapeutic effects of platinum-etoposide combination therapy in EP-NEC. Methods: This retrospective study was conducted based on the medical records from January 2010 to March 2020. Eligible patients had been pathologically diagnosed with EP-NEC. Results: Forty-seven patients were included in the study. About 72.3% (n=34) of the patients were diagnosed with metastatic disease at the first diagnosis. The most common primary tumor site was the stomach. The median progression-free survival (PFS) of the patient group, who received the combination of platinum/etoposide, was 5.83 months (95% CI 4.46-7.20), whereas the median OS of the patients, who were found to have metastatic disease at the first diagnosis, was 13.6 months (95% CI 9.01-18.18). There was no difference in PFS and OS between patients with and without liver metastasis. Conclusion: The outcome of advanced EP-NECs with platinum/etoposide chemotherapy remains poor. Obviously, there is a need for new, more effective treatment options.

Bevacizumab-induced isolated oculomotor nerve palsy in glioblastoma multiforme.

INTRODUCTION: Bevacizumab, a monoclonal antibody against the vascular endothelial growth factor receptor, is the standard treatment of recurrent glioblastoma multiforme. In addition to common systemic side effects of bevacizumab, there are rare cases of cranial nerve palsy. CASE REPORT: We report a case of transient oculomotor nerve palsy after systemic administration of bevacizumab. Twenty-four hours after the systemic infusion of bevacizumab, transient oculomotor nerve palsy developed in a 49-year-old male patient. In the cranial MRI, there was no malignancy-related progression. MANAGEMENT AND OUTCOME: Bevacizumab treatment was discontinued. Methylprednisolone was started considering that bevacizumab increased the inflammatory response. Oculomotor nerve palsy resolved in 14 days. DISCUSSION: There are many side effects of bevacizumab whose mechanisms of action have not been fully explained. Cranial nerve involvement is rarely reported. Our case is the first reported case of bevacizumab-induced oculomotor nerve palsy.

The demographic characteristics, prognosis, and relationship with cancer subtypes of hospitalized COVID-19 patients with malignancy: A single-center experience.

Undoubtedly, cancer patients have suffered the most from the COVID-19 pandemic process. However, cancer is a heterogeneous disease, and each patient has responded differently to COVID-19. We aimed to describe the clinical characteristics and outcomes of patients with cancer and COVID-19. We retrospectively reviewed 45 cancer patients hospitalized in the Cerrahpasa Medical Faculty COVID-19 department from March 23 to October 23, 2020. We analyzed the demographic characteristics, symptoms, laboratory findings, treatment, prognosis, and cancer subtypes of patients and mortality who were hospitalized for COVID-19. Between March 23 and October 23, 2020, 45 hospitalized cancer patients who had laboratory-confirmed COVID-19 infection were included, with a median age of 60 years (range: 23-92). Patients were divided into two groups a survivor and a non-survivor. Symptoms, demographic information, comorbidities, treatments for COVID-19, and laboratory findings of the two groups were evaluated separately. Two parameters were found, which showed a significant difference between non-survivors and survivors displaying a disadvantage for COPD and low platelet count (p = 0.044-0.038). The mortality rate of all patients was 66%. The presence of comorbidities such as COPD and low platelet count in cancer patients with COVID-19 infection may draw the attention of physicians.

Immune-related adverse events associated with immune checkpoint inhibitors in patients with cancer.

INTRODUCTION: With the widespread use of immune checkpoint inhibitors (ICIs), we are facing challenges in the management of immune-related adverse events (irAEs). We aimed to characterize the spectrum of toxicity, management, and outcomes for irAEs. METHODS: Patients who were treated with at least one ICI in clinical trials, expanded access programs, or routine clinical practice were included. Clinical and laboratory parameters were collected retrospectively to determine the incidence of irAEs, methods of management, and treatment outcomes. RESULTS: A total of 255 patients were screened retrospectively. Of these, 71 (27.8%) patients developed irAEs. More than 2 different types of irAEs were detected in 16 (6.2%) out of 255 patients. A total of 3177 doses were given to 255 patients. In 93 (2.9%) of the 3177 doses, 1 episode of irAEs was experienced. A total of 22 out of 93 (23.7%) episodes were reported as grade 1, 49 (52.7%) as grade 2, 19 (20.4%) as grade 3, and 3 (3.2%) as grade 4. The most frequently seen irAEs were pneumonitis, hepatitis, and hypothyroidism. With regard to treatment, 39 out of 93 episodes (42%) of any grade irAEs occurred after anti-programmed cell death-1 therapy, 47 (50.5%) occurred following administration of anti-programmed death-ligand 1, and 7 (7.5%) occurred after combination treatments. CONCLUSION: With the increased use of immunotherapeutic agents, increased awareness and early recognition are required for effective management of irAEs. Our experience as a single institution might be of use for health care providers in oncology.

Classical versus non-classical EGFR mutations: Erlotinib response and impact of renal insufficiency.

INTRODUCTION: Erlotinib is an effective treatment option for EGFR-mutant non-small cell lung cancer. It is important to predict patients who will respond better to erlotinib. We designed this study to investigate the effect of renal insufficiency (RI) on erlotinib treatment outcomes. METHODS: All patients receiving erlotinib were stratified into 3 groups. Group 1 consisted of non-RI subjects with classical epidermal growth factor receptor (EGFR) mutations, Group 2 consisted of those with RI (Estimated glomerular filtration rate <60 mL/min) and classical EGFR mutations, and Group 3 consisted of those with non-classical EGFR mutations. RESULTS: 82 patients were included in the study. Median progression-free survival (PFS) in patients with classical mutation was approximately 6 months shorter in those with RI, although not statistically significant. Median overall survival (OS) in Group 1, 2 and 3 was 34.1 months, 35.2 months, and 15 months, respectively and although not statistically significant, median OS was 20 months shorter in Group 3. Univariate and multivariate cox-regression analysis revealed shorter PFS and OS in males and those with ECOG ≥2 while PFS and OS were longer in those with recurrent lung tumors and generating rash during erlotinib treatment. There was no difference between RI and non-RI patients in terms of adverse events except for fatigue and appetite loss. CONCLUSIONS: This research showed OS in patients with and without RI was comparable. Although not statistically significant, PFS in patients with classical mutation was approximately 6 months shorter in those with RI patients.

Loss of skeletal muscle area and fat-free mass during dabrafenib/trametinib and vemurafenib/cobimetinib treatments in patients with BRAF-mutant metastatic malignant melanoma.

This study aimed to assess whether dabrafenib/trametinib and vemurafenib/cobimetinib treatments are associated with a change in skeletal muscle area (SMA) and total fat-free mass (FFM) assessed by computed tomography (CT), and to compare the efficacy and safety profile of these treatments in patients with metastatic melanoma. Thirty-one patients treated with B-Raf proto-oncogene, serine/threonine kinase/MAPK extracellular receptor kinase inhibitors were included between 2016 and 2019. Eighteen patients received dabrafenib/trametinib and remaining patients received vemurafenib/cobimetinib. CT scans were performed at baseline and at 4-6 months of follow-up to measure cross-sectional areas of SMA. FFM and skeletal muscle index (SMI) values were calculated. Of the patients, including 18 treated with dabrafenib/trametinib (58.1%) and 13 with vemurafenib/cobimetinib (41.9%); 58.1% were male, 41.9% were female and median age was 52 years. A significant decrease in SMA was observed after dabrafenib/trametinib and vemurafenib/cobimetinib treatments (P = 0.003 and P = 0.002, respectively). A significant decrease in FFM values was observed after dabrafenib/trametinib and vemurafenib/cobimetinib treatments (P = 0.003 and P = 0.002, respectively). Dose-limiting toxicity (DLT) was observed in 35.9% of the patients with sarcopenia. No significant difference was seen between the dabrafenib/trametinib and vemurafenib/cobimetinib groups in median progression-free survival (PFS) (11.9 vs. 7.3 months, respectively, P = 0.28) and in median overall survival (OS) (25.46 vs. 13.7 months, respectively, P = 0.41). Baseline sarcopenia was not significantly associated with PFS or OS (P = 0.172 and P = 0.326, respectively). We found a significant decrease in SMI values determined at 4-6 months compared to the values before treatment both in dabrafenib/trametinib and vemurafenib/cobimetinib groups. DLT was similar with both treatments. Baseline sarcopenia was not significantly associated with PFS or OS.