Background
Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies of patients with metastatic platinum-resistant urothelial carcinoma. However, the response ...rate of Atezolizumab was modest. In the current study, we evaluated the pretreatment prognostic factors for overall survival in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy in the Expanded-Access Program of Atezolizumab.
Patients and methods
In this study, we present a retrospective analysis of 113 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of the patients was obtained from patient files and hospital records. Eligible patients included metastatic urothelial carcinoma patients treated with at least one course of ATZ. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (
p
< 0.1), and then included a final model of
p
< 0.05.
Results
The median follow-up duration was 23.5 months. Of the patients, 98 (86.7%) were male and 13.3% were female. The median age was 65 years of age (37–86). In univariate analysis, primary tumor location in the upper tract, increasing absolute neutrophil count (ANC), increasing absolute lymphocyte count, neutrophil-to-lymphocyte ratio (NLR) > 3, liver metastases, baseline creatinine clearance less (GFR) than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 ≥), and hemoglobin levels below 10 mg/dl were all the significantly associated with OS. Three of the five adverse prognostic factors according to the Bellmunt criteria were independent of short survival: liver metastases HR 3.105; 95% CI 1.673–5.761;
p
< (0.001), ECOG PS (1 ≥) HR 2.184; 95% CI 1.120–4.256;
p
= 0.022, and Hemoglobin level below 10 mg/dl HR 2.680; 95% CI 1.558–4.608;
p
< (0.001). In addition, NLR > 3 hazard ratio HR 2.092; 95% CI 1.031–4.243;
p
= 0.041 and GFR less than 60 ml/min HR 1.829; 95% CI 1.1–3.041;
p
= 0.02, maintained a significant association with OS in multivariate analysis.
Conclusions
This model confirms the Bellmunt model with the addition of NLR > 3 and GFR less than 60 ml/min and can be associated with clinical trials that use immunotherapy in patients with bladder cancer.
Cancer was a common noncommunicable disease in Syria before the present conflict and is now a major disease burden among 3.6 million Syrian refugees in Turkey. Data to inform health care practice are ...needed.
To explore sociodemographic characteristics, clinical characteristics, and treatment outcomes of Syrian patients with cancer residing in the southern border provinces of Turkey hosting more than 50% of refugees.
This was a retrospective hospital-based cross-sectional study. The study sample consisted of all adult and children Syrian refugees diagnosed and/or treated for cancer between January 1, 2011, and December 31, 2020, in hematology-oncology departments of 8 university hospitals in the Southern province of Turkey. Data were analyzed from May 1, 2022, to September 30, 2022.
Demographic characteristics (date of birth, sex, and residence), date of first cancer-related symptom, date and place of diagnosis, disease status at first presentation, treatment modalities, date and status at last hospital visit, and date of death. The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision and International Classification of Childhood Cancers, Third Edition, were used for the classification of cancer. The Surveillance, Epidemiology, and End Results system was applied for staging. The diagnostic interval was defined as the number of days from first symptoms until the diagnosis. Treatment abandonment was documented if the patient did not attend the clinic within 4 weeks of a prescribed appointment throughout the treatment.
A total of 1114 Syrian adult and 421 Syrian children with cancer were included. The median age at diagnosis was 48.2 (IQR, 34.2-59.4) years for adults and 5.7 (IQR, 3.1-10.7) years for children. The median diagnostic interval was 66 (IQR, 26.5-114.3) days for adults and 28 (IQR, 14.0-69.0) days for children. Breast cancer (154 13.8%), leukemia and multiple myeloma (147 13.2%), and lymphoma (141 12.7%) were common among adults, and leukemias (180 42.8%), lymphomas (66 15.7%), and central nervous system neoplasms (40 9.5%) were common among children. The median follow-up time was 37.5 (IQR, 32.6-42.3) months for adults and 25.4 (IQR, 20.9-29.9) months for children. The 5-year survival rate was 17.5% in adults and 29.7% in children.
Despite universal health coverage and investment in the health care system, low survival rates were reported in this study for both adults and children with cancer. These findings suggest that cancer care in refugees requires novel planning within national cancer control programs with global cooperation.
Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies in patients with locally advanced or metastatic platinum-resistant urothelial carcinoma.
To compare ...the real-life experience and data of clinical trials on ATZ treatment in metastatic urothelial carcinoma.
Patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy from an expanded access program were retrospectively studied. Data of patients were obtained from their files and hospital records. Safety was evaluated for patients treated with at least one cycle of ATZ.
The primary endpoint was objective response rate (ORR). The secondary endpoints are overall survival (OS), progression-free survival (PFS), duration of response, and safety profile of patients. Kaplan-Meier methods were used to calculate median follow-up and estimate PFS and OS.
Data of 115 enrolled patients were analyzed. Most of the patients (92.3%, n = 106) had received chemotherapy regimen only once prior to ATZ. The median follow-up duration was 23.5 mo. The complete response rate, partial response rate, and ORR were 8.7% (n = 10), 20.0% (n = 23), and 28.7% (n = 33), respectively. The median duration of response was 20.4 mo (95% confidence interval CI, 6.47–28.8). Of the 33 patients who responded to treatment, 60% (n = 20) had an ongoing response at the time of the analysis. PFS and OS with ATZ were 3.8 mo (95% CI, 2.25–5.49) and 9.8 mo (95% CI, 6.7–12.9), respectively. All-cause and any-grade adverse events were observed in 113 (98%) patients. Of the patients, 64% experienced a treatment-related adverse event of any grade and 24 (21.2%) had a grade 3–4 treatment-related adverse event. Limitations of the study included its retrospective design, and determination of treatment response based on clinical notes and local radiographic studies.
In these real-life data, ATZ was effective and well tolerated in patients with metastatic urothelial carcinoma who have progressed with platinum-based first-line chemotherapy. ATZ is an effective and tolerable treatment for patients with locally advanced or metastatic platinum-resistant urothelial carcinoma in our study, similar to previously reported trials.
Atezolizumab is effective and well-tolerated in patients with metastatic urothelial cancer who progressed with first-line chemotherapy, consistent with the outcomes of the previous clinical trials in this setting.
Atezolizumab is an effective and tolerable treatment option for patients with urothelial cancer after progression by the chemotherapy. Clinical activity and safety of atezolizumab treatment in real-life patients were consistent with the outcomes of the previous clinical trials in this setting
This study aimed to investigate the frequency in which familial Mediterranean fever (FMF) coexists with other diseases and determine whether Mediterranean fever
gene mutations are involved in such ...coexistence.
In total, 142 consecutive patients with FMF investigated for
mutation were enrolled in this study Female: 87; Male: 55, mean age 32±12 years (11-62). All the patients were questioned for the presence of concurrent disorders, and the medical records of these patients were revised retrospectively. A previous diagnosis of inflammatory disorder other than FMF was considered true if it met the relevant criteria.
mutations were divided into 2 groups, namely M694V and its subgroup (homozygous or heterozygous) (Group I) and others (Group II). Compound heterozygosity for M694V mutation was included in Group II to form a homogeneous group for Group I. Group I and Group II were compared according to phenotypical features. The presence of
mutation was investigated in exons 2, 3, 5, and 10 by the multiplex-PCR reverse hybridization method.
Concomitant disorders were found in 17 of 73 patients with FMF (23%) in Group I and 5 of 56 patients (8.9%) in Group II (p=0.04). Concomitant disorders in Group I were as follows: 7 cases of amyloidosis, 2 cases of Behcet's disease (BD), 4 cases of ankylosing spondylitis (AS), 1 case of antiphospholipid syndrome, 1 case of Henoch-Schonlein purpura (HSP), 1 case of combination of psoriatic arthritis, HSP, and membranoproliferative glomerulonephritis, and 1 case of AS and amyloidosis. In Group II, the following disorders were found: 1 case of amyloidosis, 1 case of BD, 1 case of AS, 1 case of ulcerative colitis, and 1 case of vitiligo.
The presence of M694V mutation may predispose patients with FMF to developing other inflammatory disorders.
The aim of this study is to determine the incidence of isoniazid (INH)-related hepatotoxicity in patients with rheumatologic diseases receiving tumor necrosis factor-α (TNF-α) antagonists along with ...a disease-modifying antirheumatic drug (DMARD).
We have retrospectively evaluated 87 patients receiving anti-TNFα agents who were followed up between June 2005 and February 2010 at our rheumatology department. Sixty-one of 87 patients have received INH prophylaxis for 9 months for latent tuberculosis infection.
A total of 61 (70.1%) of 87 patients used INH prophylaxis (Group I), while the remaining 26 (29.9%) (Group II) had not; 53 patients had used any DMARD in Group I, while 21 patients had used in Group II. No significant differences were found among Group I and II with respect to clinical features. When two groups were compared, in Group I, elevations of liver enzymes were detected in five patients (8.1%) who had normal baseline values. Among these patients, hepatotoxicity developed in two patients. Hepatotoxicity developed one patient in Group II (p=0.85).
INH chemoprophylaxis was well tolerated in patients using anti-TNF-α agent and a DMARD. It seems not to be a strong risk factor for hepatotoxicity. However, comorbidities and other drugs used may be additional factors in the elevation of transaminases.
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