Impact of opioid analgesics on survival in cancer patients receiving immune checkpoint inhibitors.

PURPOSE: This study aimed to assess the effects of concurrent opioid analgesic (OA) use with immune checkpoint inhibitors (ICIs) on progression-free survival (PFS) and overall survival (OS). METHODS: In this observational retrospective study, we included advanced cancer patients who received ICIs at Hacettepe University Hospital's Department of Medical Oncology between June 2018 and January 2023. RESULTS: Our study included 375 recurrent or metastatic cancer patients treated with ICIs in the first, second line, or beyond. There were no significant differences between the OA-treated and OA-untreated groups regarding median age, age group, gender, primary tumor location, ICI type, or the presence of baseline liver and lung metastases. However, the OA-treated group exhibited a significantly higher proportion of patients who had received three or more prior treatments before initiating ICIs (p = 0.015). OA-Untreatment was significantly correlated with prolonged mPFS (6.83 vs. 4.30 months, HR 0.59, 95% CI 0.44-0.79, p < 0.001) and mOS (17.05 vs. 7.68 months, HR 0.60, 95% CI 0.45-0.80, p < 0.001). CONCLUSIONS: Our study demonstrates an association between the concurrent use of OAs and reduced OS and PFS in patients treated with ICIs. While OA treatment serves as a surrogate marker for higher disease burden, it may also suggest a potential biological relationship between opioids and immunotherapy efficacy.

Immunogenicity of two doses of inactive COVID-19 vaccine and third booster dose mRNA vaccine in patients with cancer receiving active systemic therapy.

We aimed to evaluate the seroconversion rates after two doses of inactive COVID-19 vaccine (CoronaVac) and the benefit of a third dose mRNA vaccine booster in patients with cancer receiving active treatment. Patients with solid tumors receiving active treatment (n = 101) and patients with no-cancer (n = 48) as the control group were included in the study. All the patients and controls had received two doses of CoronaVac and a third booster dose of the mRNA vaccine (Bnt162b2). Anti-SARS-CoV-2 Spike Receptor Binding Domain IgG antibody levels after the second and third dose were measured with quantitative ELISA. The median age of the patients was 66 (IQR 60-71). 79% of the patients were receiving chemotherapy, and 21% were receiving immunotherapy at the time of vaccination. Antibody levels measured after two doses of CoronaVac were significantly lower in patients with cancer than in the control group (median 0 µg/ml [IQR 0-1.17 µg/ml] vs median 0.91 µg/ml [IQR 0-2.24 µg/ml], respectively, P = .002). Seropositivity rates were 46.5% in patients with cancer and 72.9% in the control group (P = .002). Antibody measurement was performed in 26 patients after the third dose. Seroconversion rate increased from 46.5% to 88.5% (P < .001), and the antibody titers significantly increased with the third-dose booster (median 0 µg/ml [IQR 0-1.17 µg/ml] after two doses vs 12.6 µg/ml [IQR 1.8-69.1 µg/ml] after third booster dose, P < .001). Immunogenicity of CoronaVac is low in patients with cancer receiving active treatment, and administering a third dose of an mRNA vaccine is effective in terms of improving seroconversion rates.

Prognostic factors of overall and prostate-specific antigen-progression-free survival in metastatic castration-resistant prostate cancer patients treated with 177 Lu-PSMA-617. A single-center prospective observational study.

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is characterized by heterogeneity among patients as well as therapy responses due to diverse genetic, epigenetic differences, and resistance mechanisms. At this stage of the disease, therapy modalities should be individualized in light of the patients' clinical state, symptoms, and genetic characteristics. In this prospective study, we aimed to evaluate the outcome of patients with mCRPC treated with 177 Lutetium labeled PSMA-617 therapy (PSMA-RLT), as well as baseline and therapy-related parameters associated with survival. METHODS: This prospective study included 52 patients who received two to six cycles of PSMA-RLT. Primary endpoints were overall survival (OS) and prostate-specific antigen (PSA)-progression-free survival (PFS). 18 F-Fluorodeoxyglucose (FDG) and 68 Ga-PSMA (PSMA) Positron Emission Tomography/Computer Tomography (PET/CT) scans were performed for a comprehensive assessment of tumor burden and heterogeneity. Biochemical, imaging, clinical, and therapy-related parameters were analyzed with the Kaplan-Meier, log-rank, and Cox regression analyses to predict OS and PFS. RESULTS: Median OS and PSA-PFS were 17.7 (95% confidence interval [CI]: 15.2-20.2) and 6.6 months (95% CI: 4.5-8.8), respectively. Primary resistance to PSMA-RLT (hazard ratio [HR]: 12.57, 95% CI: 2.4-65.2, p: 0.003), <30% PSA response rate after first cycle of PSMA-RLT (HR: 1.016, 95% CI: 1.006-1.03, p: 0.003), FDG > PSMA disease (HR: 4.9, 95% CI: 1.19-20.62, p: 0.03), PSA doubling time (PSA DT) of ≤2.4 months (HR: 15.7, 95% CI: 3.7-66.4, p: <0.0001), and low hemoglobin levels (HR: 0.59, 95% CI: 0.41-0.83, p: 0.003) were correlated with poor OS in the multivariate analysis. Bone scintigraphy > PSMA disease (HR: 5.6; 95% CI: 1.8-17, p: 0.002) and high C-reactive protein (HR: 1.4, 95% CI: 1.1-1.7, p: 0.001) were significant predictive biomarkers for PFS in the multivariate analysis. CONCLUSION: PSA response rate and pattern to PSMA-RLT are the most important predictors of survival in patients receiving PSMA-RLT. Being a strong predictive biomarker, combined FDG and PSMA PET can be helpful for the decision of PSMA-RLT eligibility.

The incidence and risk factors for acute kidney injury in patients treated with immune checkpoint inhibitors.

Recent observational studies reported acute kidney injury (AKI) events in over 10% of the patients treated with immune checkpoint inhibitors (ICIs). However, these studies included patients treated in high-resource settings and earlier lines. Therefore, we aimed to assess the AKI rates and predisposing factors in ICI-treated patients from a limited resource setting. We evaluated 252 patients with advanced cancer for this retrospective cohort study. AKI events were defined by Kidney Disease Improving Global Outcomes criteria. The median age was 59 years. The melanoma (18.3%), non-small cell lung cancer (14.7%) and renal cell carcinoma (22.6%) patients comprised over half of the cohort. During the follow-up, 45 patients (17.9%) had at least one AKI episode. In multivariable analyses, patients with chronic kidney disease (CKD) [odds ratio (OR), 3.385; 95% confidence interval (CI), 1.510-7.588; P = 0.003], hypoalbuminemia (OR, 2.848; 95% CI, 1.225-6.621; P = 0.015) or renin-angiotensin-aldosterone system (RAAS) inhibitor use (OR, 2.236; 95% CI, 1.017-4.919; P = 0.045) had increased AKI risk. There was a trend towards increased AKI risk in patients with diabetes (OR, 2.042; 95% CI, 0.923-4.518; P = 0.78) and regular proton pump inhibitors use (OR, 2.024; 95% CI, 0.947-4.327; P = 0.069). In this study, we observed AKI development under ICIs in almost one in five patients with cancer. The increased AKI rates in CKD, hypoalbuminemia or RAAS inhibitor use pointed out a need for better onco-nephrology collaboration and efforts to improve the nutritional status of ICI-treated patients.

Response to first-line chemotherapy regimen is associated with efficacy of immune checkpoint blockade therapies in patients with metastatic urothelial carcinoma.

BACKGROUND: Atezolizumab (ATZ) has demonstrated antitumor activity in previous studies in patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of ATZ was modest. Therefore, finding biologic or clinical biomarkers that could help to select patients who respond to the immune checkpoint blockade remains important. PATIENTS AND METHODS: In this study, we present the retrospective analysis of 105 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of patients were obtained from patient files and hospital records. The association between response to first-line chemotherapy and ATZ was using Fisher's exact test. Median follow-up was calculated using the reverse Kaplan-Meier method. OS was estimated by using the Kaplan-Meier method. RESULTS: The median follow-up time was 23.5 months. Forty (74.1%) of patients who experienced clinical benefit after firs-line chemotherapy also had clinical benefit after atezolizumab, while only 14 (25.9%) of patients with initial PD after first-line chemotherapy subsequently experienced clinical benefit with ATZ (p = 0.001). The median OS on ATZ of 14.8 and 3.4 months for patients with clinical benefit and progressive disease in response to first-line chemotherapy, respectively (p = 0.001). Three of the adverse prognostic factors according to the Bellmunt criteria were independent factors of short survival: liver metastases {Hazard ratio [HR] = 1.9; p = 0.04}, ECOG PS ≥ 1 (HR = 2.7; p = 0.001), and Hemoglobin level below 10 mg/dl (HR = 2.8; p < 0.001). In addition, patients with clinical benefit from first-line chemotherapy (HR = 0.39; p < 0.001) maintained a significant association with OS in multivariate analysis. CONCLUSIONS: Our study demonstrated that clinical benefit from first-line chemotherapy was independent prognostic factors on OS in patients' use of ATZ as second-line treatment in metastatic bladder cancer. Furthermore, these findings are important for stratification factors for future immunotherapy study design in patients with bladder cancer who have progressed after first-line chemotherapy.

The burden of polypharmacy and drug-drug interactions in older cancer patients treated with immunotherapy.

INTRODUCTION: Polypharmacy is a common problem in older cancer patients, although the data about polypharmacy and potentially inappropriate prescription practices is limited in patients treated with immune checkpoint inhibitors (ICIs). Therefore, we aimed to evaluate the polypharmacy frequency and drug-drug interactions in older cancer patients (≥65 years) treated with ICIs. METHODS: A total of 70 geriatric patients with advanced cancer were included. The polypharmacy was defined as regular use of 5 or more drugs. The START/STOPP Criteria Version 2 was used for the potentially inappropriate medications (PIM) and potential prescription omissions (PPO). The Medscape Drug Interaction Checker was used for potential drug-drug interactions. RESULTS: The patients had a median of 6 regular drugs, and polypharmacy was present in 77.1%. The polypharmacy risk was significantly increased in patients over 75 years of age (p = 0.028) and with opioid use (p = 0.048). The 50% of patients had category D or X interactions. Patients with higher Charlson Comorbidity Index had significantly increased risk for drug interactions (CCI ≤10 vs. >10, p = 0.017). The PIMs were present in 44.3% and the PPOs in 68.6% of the patients. While the overall survival and immune related adverse events were similar according to polypharmacy, in patients using seven or more drugs, the acute kidney injury risk was increased (HR: 4.667, p = 0.038). CONCLUSION: In this study, we observed a high rate of polypharmacy and inappropriate prescription practices in ICI-treated patients. These issues pointed out the need for improved general medical care and attention for better comedication management in ICI-treated patients.

Clinical features and outcomes of COVID-19 in patients with solid tumors: Turkish National Registry Data.

We present demographic, clinical, laboratory characteristics and outcomes of the patients with solid malignancies and novel coronavirus disease (COVID-19) collected from the National COVID-19 Registry of Turkey. A total of 1523 patients with a current or past diagnosis of solid tumors and diagnosed with COVID-19 (confirmed with PCR) between 11 March and 20 May 2020 were included. The primary outcome was 30-day mortality. Median age was 61 (range: 18-94), and 752 (49%) were male. The most common types of cancers were breast (19.8%), prostate (10.9%) and colorectal cancer (10.8%). 65% of the patients had at least one comorbidity. At least one COVID-19-directed therapy was given in 73% of the patients.. Hospitalization rate of the patients was 56.6% and intensive care unit admission rate was 11.4%. Seventy-seven (5.1%) patients died within 30 days of diagnosis. The first multivariate model which included only the demographic and clinical characteristics showed older age, male gender and presence of diabetes and receipt of cytotoxic therapy to be associated with increased 30-day mortality, while breast and prostate cancer diagnoses were associated with lower 30-day mortality. In the second set, we further included laboratory parameters. The presence of leukocytosis (OR 6.7, 95% CI 3.3-13.7, P < .001), lymphocytopenia (OR 3,1, 95% CI 1,6-6,1, P = .001) and thrombocytopenia (OR 3,4 95% CI 1,5-8,1, P = .005) were found to be associated with increased 30-day mortality. Relatively lower mortality compared to Western countries and China mainly results from differences in baseline risk factors but may also implicate the importance of intensive supportive care.

Prospective observational study on Pazopanib in patients treated for advanced or metastatic renal cell carcinoma in countries in Asia Pacific, North Africa, and Middle East regions: PARACHUTE study.

BACKGROUND: Clinical effectiveness and safety data of pazopanib in patients with advanced or mRCC in real-world setting from Asia Pacific, North Africa, and Middle East countries are lacking. METHODS: PARACHUTE is a phase IV, prospective, non-interventional, observational study. Primary endpoint was the proportion of patients remaining progression free at 12 months. Secondary endpoints were ORR, PFS, safety and tolerability, and relative dose intensity (RDI). RESULTS: Overall, 190 patients with a median age of 61 years (range: 22.0-96.0) were included. Most patients were Asian (70%), clear-cell type RCC was the most common (81%), with a favourable (9%), intermediate (47%), poor (10%), and unknown (34%) MSKCC risk score. At the end of the observational period, 78 patients completed the observational period and 112 discontinued the study; 60% of patients had the starting dose at 800 mg. Median RDI was 82%, with 52% of patients receiving < 85%. Of the 145 evaluable patients, 56 (39%) remained progression free at 12 months, and the median PFS was 10 months (95% CI: 8.48-11.83). 19% of patients (21/109) were long-term responders (on pazopanib for ≥18 months). The best response per RECIST 1.1 was CR/PR in 24%, stable disease in 44%, and PD in 31%. Most frequent (> 10%) TEAEs related to pazopanib included diarrhoea (30%), palmar-plantar erythrodysesthesia syndrome (15%), and hypertension (14%). CONCLUSIONS: Results of the PARACHUTE study support the use of pazopanib in patients with advanced or mRCC who are naive to VEGF-TKI therapy. The safety profile is consistent with that previously reported by pivotal and real-world evidence studies.

The Predictive Value of Red Blood Cell Distribution Width for Survival Outcomes of Metastatic Renal Cell Carcinoma Patients Treated with Targeted Therapy.

BACKGROUND: We aimed to investigate the prognostic value of red cell distribution width (RDW) in metastatic renal cell carcinoma (mRCC) patients treated with targeted therapy, including sunitinib and pazopanib. METHODS: A total of 104 mRCC patients were included. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS), and the long-rank test was used for comparison. Univariate and multivariate Cox proportional hazards models were used to determine the association between RDW and PFS and OS. RESULTS: The PFS and OS of all cohorts were 11.8 mo and 25.9 mo, respectively. Receiver operating characteristic analysis revealed that RDW level ≥15.4 was the optimal cutoff value for OS prediction with 73.53% sensitivity and 61.11% specificity (area under curve: 0.64, P = 0.012). RDW level ≥15.4 was found as an independent prognostic parameter for OS when adjusted for the number of covariates, including the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) scoring system (hazard ratio: 1.125, 95% confidence interval: 1.024-2.235, P = 0.014). CONCLUSIONS: Our study revealed that high RDW level, a routinely and easily assessed marker, was significantly associated with worse survival outcomes in mRCC patients treated with targeted therapy.

Evaluation of emergency departments visits in patients treated with immune checkpoint inhibitors.

BACKGROUND: The emergency department (ED) is a crucial encounter point in cancer care. Yet, data on the causes of ED visits are limited in patients treated with immune checkpoint inhibitors (ICI). Therefore, we evaluated ED visits in patients treated with ICIs in attempt to determine the predisposing factors. METHODS: We performed a retrospective chart review on adult cancer patients treated with ICIs for any type of cancer in the Hacettepe University Cancer Center. The data on ED visits after the first dose of ICIs to 6 months after the last cycle of ICIs were collected. RESULTS: A total of 221 patients were included in the study. The mean age was 58.46 ± 13.87 years, and 65.6% of patients were males. Melanoma was the most common diagnosis (27.6%), followed by kidney and lung cancers. Eighty-three of these patients (37.6%) had at least one emergency department (ED) visit. Most of the ED visits were related to symptoms attributable to the disease burden itself, while immune-related adverse events comprised less than 10% of these visits. While baseline Eastern Cooperative Oncology Group performance status, age, polypharmacy, concomitant chemotherapy, eosinophilia, and lactate dehydrogenase levels did not significantly increase the risk, patients with regular opioid use and baseline neutrophilia (> 8000/mm3) had a statistically significant increased risk of visiting the ED (p = 0.001 and 0.19, respectively). These two factors remained significant in the multivariate analyses. CONCLUSION: In this study, almost 40% of ICI-treated patients had ED visits. Collaboration with other specialties like emergency medicine is vital for improving the care of patients receiving immunotherapy.

Poorer baseline performance status is associated with increased thromboembolism risk in metastatic cancer patients treated with immunotherapy.

PURPOSE: Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in cancer patients. However, the association of VTE with immunotherapy remains poorly defined. We therefore evaluated the frequency of VTE in patients receiving immunotherapy and tried to determine predisposing factors. METHODS: A total of 133 adult metastatic cancer patients treated with immunotherapy for any cancer between were included. Baseline demographics, ECOG performance status, type of tumors, and baseline blood count parameters were recorded. Possible predisposing factors were evaluated with univariate and multivariate analyses. RESULTS: The median age was 60 (interquartile range (IQR) 48-66) years, and the median follow-up was 10.1 (IQR 5.8-18.5) months. Renal cell carcinoma (26.3%) and melanoma (24.1%) were most common diagnoses. Fifteen patients (11.3%) had an episode of VTE. Most of the VTEs were diagnosed as pulmonary emboli (10/15; 67%). Eighty percent (12/15) of these VTE cases were detected incidentally. Patients with a baseline ECOG performance status of 1 or more (29.3% of patients) had a significantly increased risk of venous thrombosis (ECOG ≥1 vs. 0, HR: 3.023, 95% CI: 1.011-9.039, p=0.048). Other factors, including patient age, tumor type, body mass index, baseline thrombocyte, neutrophil, and lactate dehydrogenase levels were not significantly associated with VTE risk. CONCLUSIONS: In this study, we observed VTE development in more than 10% of immunotherapy-treated patients and increased VTE risk in patients with poorer ECOG status. With the asymptomatic nature of VTEs in most cases, a high index of suspicion level for VTE is required in patients treated with immunotherapy.

Prognostic factors in patients with metastatic urothelial carcinoma who have treated with Atezolizumab.

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.

The platelet to lymphocyte ratio predicts overall survival better than the neutrophil to lymphocyte ratio in metastatic renal cell carcinoma

Background/aim: The prognostic values of systemic inflammatory markers, neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) on overall survival (OS) of metastatic renal cell carcinoma patients (mRCC) treated with tyrosine kinase inhibitors (TKI) remain unclear. Thus, the present study aimed to investigate the prognostic impact of these markers on OS of mRCC patients. Materials and methods: A total of 150 patients receiving TKIs were retrospectively analyzed. Progression-free survival and OS times were analyzed with the Kaplan­Meier method, and the log­rank test was used for comparison. Univariable and multivariable Cox regression models evaluated the impact of NLR and PLR on OS of the patients. The receiver operating characteristic curve analysis determined that the optimal cut-off values of NL, and PLR in predicting OS were 2 and 204, respectively. Results: Patient with PLR > 204 had significantly lower median OS time than those with PLR ≤ 204 (14.6 months vs. 31.6 months, P < 0.001). While the univariate analyses showed that both NLR and PLR associated with OS (NLR: P = 0.002; PLR: P < 0.001), PLR, not NLR, was an independent determinant for OS in the multivariate analyses (Hazard Ratio: 2.535, 95% CI: 1.564-4.108, P < 0.001). Additionally, the presence of brain metastases and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic scoring system were identified as independent prognostic factors for OS (brain metastases: P = 0.040; IMDC: P < 0.001). Conclusion: The PLR is a readily and inexpensively obtained marker, which may predict OS in patients with mRCC treated with TKIs.

Drug-related problems with targeted/immunotherapies at an oncology outpatient clinic.

BACKGROUND: Some studies in the literature describe drug-related problems in patients with cancer, although few studies focused on patients receiving targeted chemotherapy and/or immunotherapy. To identify the incidence of drug-related problems in patients receiving targeted chemotherapy and/or immunotherapy, and demonstrate the impact of a clinical pharmacist in an outpatient oncology care setting. METHODS: Prospective study was conducted in a hospital outpatient oncology clinic between October 2015 and March 2016. Patients greater than 18 years old receiving cetuximab, nivolumab, ipilimumab, or pembrolizumab were included in the study and monitored over a three-month period by a clinical pharmacist. Drug-related problems were analyzed using the Pharmaceutical Care Network Europe classification system. The main outcome measures were the frequency and causes of drug-related problems and the degree of resolution achieved through the involvement of a clinical pharmacist. RESULTS: A total of 54 patients (mean age: 57 ± 12 years) were included. There were 105 drug-related problems and 159 associated causes. Among the planned interventions (n = 149), 92 interventions were at the patient-level with 88 (96%) being accepted by the doctors. This resulted in 68 (65%) drug-related problems being completely resolved and 9 (8.6%) being partially resolved. The most common drug-related problem identified was "adverse drug event" (n = 38, 36%). Of the 105 drug-related problems, 63 (60%) related to targeted chemotherapy and/or immunotherapy with 34 (54%) classified as an "adverse drug event." CONCLUSION: Adverse drug events were the most common drug-related problems in patients with cancer. The involvement of a clinical pharmacist improved the identification of drug-related problems and helped optimize treatment outcomes in patients receiving targeted chemotherapy/immunotherapy.

Pembrolizumab- and/or pazopanib-induced remitting seronegative symmetrical synovitis with pitting edema in a patient with renal cell carcinoma.

INTRODUCTION: Immune checkpoint inhibitors and angiogenesis inhibitors are novel treatment options for renal cell carcinoma and widely used in clinical practice. They are related with adverse events that occur as a consequence of immune system activation and inhibition of angiogenesis. Herein, we report a rare case of inflammatory arthritis seen in a patient treated with an anti Programmed cell death-1 pembrolizumab and an anti-vascular endothelial growth factor pazopanib. CASE REPORT: A 60-year-old Caucasian male presented to our clinic with inflammatory arthritis with pitting edema. He had been started on pembrolizumab therapy for metastatic renal cell carcinoma after enrolling in the KEYNOTE-679 study. After six cycles of treatment with pembrolizumab, metastasis had been determined in the lung. Then, the patient's therapy was changed to pazopanib. While the patient was on pazopanib treatment, he noticed a gradual swelling of both hands. Rheumatoid factor, anti-nuclear antibody and anti-cyclic citrullinated peptide were negative. Joint ultrasonography revealed acute tenosynovitis and soft tissue swelling with pitting edema, and a diagnosis of remitting seronegative symmetrical synovitis with pitting edema was made. Management and outcome: He was started on 10 mg prednisolone daily. His symptoms dramatically responded to corticosteroid. He continued to take pazopanib. Then, the patient was discharged with 10 mg prednisolone daily. DISCUSSION: Pembrolizumab- and/or pazopanib-induced remitting seronegative symmetrical synovitis with pitting edema can be among the rare rheumatic immune-related adverse events that clinicians may encounter as the immune check point inhibitors and anti-VEGF use increases. Corticosteroid therapy can relieve symptoms and cessation of therapy may not be necessary.

Evaluation of cancer risk in patients with periodontal diseases

Background/aim: In this study, we aimed to assess the cancer risk among patients with periodontal disease. Materials and methods: Patients diagnosed with periodontal diseases at Hacettepe University between 2007 and 2012 were included and data on the diagnosis of any cancer after periodontal disease were collected from patient files. The age- and sex-standardized incidence rates (SIRs) were calculated using Turkish National Cancer Registry 2013 data. Results: A total of 5199 patients were included. Median follow-up was 7.2 years. Patients with periodontal diseases had 17% increased risk of cancer compared with the expected counts for the corresponding age and sex groups (SIR: 1.17; 95% CI: 1.04­1.3, P = 0.006). The increased cancer risk was statistically significant in women (SIR: 1.24; 95% CI: 1.05­1.45, P = 0.008) but not in men. Among women with periodontal disease, the risks of breast cancer (SIR: 2.19) and head and neck cancer (SIR: 4.71) were significantly increased. Among men, the risks of prostate cancer (SIR: 1.84), head and neck cancer (SIR: 3.55), and hematological cancers (SIR: 1.76) were significantly increased. Conclusion: This study showed that periodontal diseases were associated with increased risk of several cancers. Besides other well-known benefits for health, the provision of oral/dental health should be considered and employed as a cancer prevention measure.

Efficacy of Systemic Treatments in Patients With Metastatic Lung Invasive Mucinous Adenocarcinoma.

BACKGROUND: Invasive mucinous adenocarcinoma (IMA) is a rare histological subtype of lung invasive adenocarcinoma with unique clinical, radiological, histopathological, and genomic characteristics. There have been limited studies on the effectiveness of systemic therapy for lung IMA, with conflicting results reported. METHODS: We retrospectively investigated the medical records of patients diagnosed with lung IMA. Patients who were ≥ 18 years of age and received at least 1 course of treatment for metastatic or locally advanced inoperable disease were included in the study. Archive records of 113 patients diagnosed with IMA were screened for the study. RESULTS: A total of 41 patients with lung IMA were included. The targetable mutation rate was 20.6% (in 6 of 29 patients). Most patients (83.1%) had received platinum-based chemotherapy as a first-line treatment. The objective response rate (ORR) was 25.7%, and median progression-free survival (PFS) and overall survival (OS) were 8.1 months (95% CI, 5.02-11.2) and 17.5 months (95% CI, 11.7-23.3 months), respectively, in the patients who received chemotherapy. The median PFS and ORR were 20.6 (95% CI, 18.9-66.5) and 66.6%, respectively, in epidermal growth factor receptor (EGFR) mutation-positive patients (n = 3) with relevant targeted therapy. Only 1 patient used oxaliplatin and capecitabine combination (XELOX) as chemotherapy in the second-line treatment and achieved a partial response (PR) at 7.2 months. CONCLUSION: Platinum-based chemotherapies moderately enhance IMA patients' survival rates. Anti-EGFR-targeted drugs are seen as potentially effective in patients with EGFR driver mutation positive. Large, prospective studies are needed to confirm our findings.

Adrenocortical Cancer in the Real World: A Comprehensive Analysis of Clinical Features and Management from the Turkish Oncology Group (TOG).

INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare yet highly malignant tumor associated with significant morbidity and mortality. This study aims to delineate the clinical features, survival patterns, and treatment modalities of ACC, providing insights into the disease's prognosis. MATERIALS AND METHODS: A retrospective analysis of 157 ACC patients was performed to assess treatment methodologies, demographic patterns, pathological and clinical attributes, and laboratory results. The data were extracted from the hospital's database. Survival analyses were conducted using the Kaplan-Meier method, with univariate and multivariate analyses being performed through the log-rank test and Cox regression analyses. RESULTS: The median age was 45, and 89.4% had symptoms at the time of diagnosis. The median tumor size was 12 cm. A total of 117 (79.6%) patients underwent surgery. A positive surgical border was detected in 26 (24.1%) patients. Adjuvant therapy was administered to 44.4% of patients. The median overall survival for the entire cohort was 44.3 months. Median OS was found to be 87.3 months (95% confidence interval [CI] 74.4-100.2) in stage 2, 25.8 (95% CI 6.5-45.1) months in stage 3, and 13.3 (95% CI 7.0-19.6) months in stage 4 disease. Cox regression analysis identified age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as significant factors associated with survival in patients with nonmetastatic disease. In metastatic disease, only patients who underwent surgery exhibited significantly improved overall survival in univariate analyses. CONCLUSION: ACC is an uncommon tumor with a generally poor prognosis. Understanding the defining prognostic factors in both localized and metastatic diseases is vital. This study underscores age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as key prognostic determinants for localized disease, offering critical insights into the complexities of ACC management and potential avenues for targeted therapeutic interventions.

A multicenter, retrospective archive study of radiological and clinical features of ALK-positive non-small cell lung cancer patients and crizotinib efficacy.

To evaluate radiological and clinical features in metastatic anaplastic lymphoma kinase+ non-small cell lung cancer patients and crizotinib efficacy in different lines. This national, non-interventional, multicenter, retrospective archive screening study evaluated demographic, clinical, and radiological imaging features, and treatment approaches in patients treated between 2013-2017. Totally 367 patients (54.8% males, median age at diagnosis 54 years) were included. Of them, 45.4% were smokers, and 8.7% had a family history of lung cancer. On radiological findings, 55.9% of the tumors were located peripherally, 7.7% of the patients had cavitary lesions, and 42.9% presented with pleural effusion. Pleural effusion was higher in nonsmokers than in smokers (37.3% vs. 25.3%, P = .018). About 47.4% of cases developed distant metastases during treatment, most frequently to the brain (26.2%). Chemotherapy was the first line treatment in 55.0%. Objective response rate was 61.9% (complete response: 7.6%; partial response: 54.2%). The highest complete and partial response rates were observed in patients who received crizotinib as the 2nd line treatment. The median progression-free survival was 14 months (standard error: 1.4, 95% confidence interval: 11.2-16.8 months). Crizotinib treatment lines yielded similar progression-free survival (P = .078). The most frequent treatment-related adverse event was fatigue (14.7%). Adrenal gland metastasis was significantly higher in males and smokers, and pleural involvement and effusion were significantly higher in nonsmokers-a novel finding that has not been reported previously. The radiological and histological characteristics were consistent with the literature data, but several differences in clinical characteristics might be related to population characteristics.