Diagnostic impact of F-FDG PET/CT imaging on the detection of immune-related adverse events in patients treated with immunotherapy

Introduction: Immunotherapy is an effective treatment method for cancer cells with humoral and cellular immune mechanisms of action but triggers an inflammatory response and disrupts standard protective immune tolerance. Early detection of immune-related adverse events (irAEs) on PET/CT is crucial for patient management and subsequent therapy decisions. In this study, we aimed to evaluate the impact of 18F-FDG PET/CT on detecting of irAEs in patients receiving immunotherapy.Patients and methodsForty-six patients with advanced RCC (n: 32), malign melanoma (n: 9), lung cancer (n: 4), and laryngeal carcinoma (n: 1), who underwent 18F-FDG PET/CT imaging for response assessment after immunotherapy, were enrolled in the study. Newly detected findings associated with irAEs on posttreatment PET/CT images were compared with the pretreatment PET/CT, both qualitatively and semi-quantitatively.ResultsTwenty-eight (61%) patients developed irAEs as observed on PET/CT. Enteritis/colitis was the most frequent irAE visualized on PET/CT with 13 patients (28.2%), followed by gastritis (17.3%), thyroiditis (13%), and myositis/arthritis (13%). Hepatitis (6.5%), pneumonitis (6.5%), sarcoid-like reaction (4.3%), and hypophysitis (4.3%) were observed to a lesser extent. The median time between the appearance of irAEs on PET/CT and the initiation of immunotherapy was 4.3 months. There were no significant differences in age, sex, and treatment response status of patients with and without irAEs.Conclusion18F-FDG PET/CT plays a fundamental role in cancer immunotherapy with the potential to show significant irAEs both in the diagnosis and in follow-up of irAEs. IrAEs were present on PET/CT images of more than half of the patients who received immunotherapy in our study. (AU)

Diagnostic impact of 18F-FDG PET/CT imaging on the detection of immune-related adverse events in patients treated with immunotherapy.

INTRODUCTION: Immunotherapy is an effective treatment method for cancer cells with humoral and cellular immune mechanisms of action but triggers an inflammatory response and disrupts standard protective immune tolerance. Early detection of immune-related adverse events (irAEs) on PET/CT is crucial for patient management and subsequent therapy decisions. In this study, we aimed to evaluate the impact of 18F-FDG PET/CT on detecting of irAEs in patients receiving immunotherapy. PATIENTS AND METHODS: Forty-six patients with advanced RCC (n: 32), malign melanoma (n: 9), lung cancer (n: 4), and laryngeal carcinoma (n: 1), who underwent 18F-FDG PET/CT imaging for response assessment after immunotherapy, were enrolled in the study. Newly detected findings associated with irAEs on posttreatment PET/CT images were compared with the pretreatment PET/CT, both qualitatively and semi-quantitatively. RESULTS: Twenty-eight (61%) patients developed irAEs as observed on PET/CT. Enteritis/colitis was the most frequent irAE visualized on PET/CT with 13 patients (28.2%), followed by gastritis (17.3%), thyroiditis (13%), and myositis/arthritis (13%). Hepatitis (6.5%), pneumonitis (6.5%), sarcoid-like reaction (4.3%), and hypophysitis (4.3%) were observed to a lesser extent. The median time between the appearance of irAEs on PET/CT and the initiation of immunotherapy was 4.3 months. There were no significant differences in age, sex, and treatment response status of patients with and without irAEs. CONCLUSION: 18F-FDG PET/CT plays a fundamental role in cancer immunotherapy with the potential to show significant irAEs both in the diagnosis and in follow-up of irAEs. IrAEs were present on PET/CT images of more than half of the patients who received immunotherapy in our study.

Role of 18F-FDG PET/CT in the assessment of therapy response and clinical outcome in metastatic renal cell carcinoma treated with tyrosine kinase inhibitors or immunotherapy.

OBJECTIVE: This study aimed to determine the role and prognostic significance of 18F-FDG PET/CT on treatment response and survival outcomes in metastatic renal cell carcinoma patients treated with immunotherapy or tyrosine kinase inhibitors (TKIs). PATIENTS AND METHODS: Forty patients scheduled for a standard treatment protocol with TKIs (n = 17; group-1) or PD-1 inhibitors (nivolumab, n = 23; group-2) were evaluated by 18F-FDG PET/CT. Peak standardized uptake value corrected for lean body mass (SULpeak) and maximum standardized uptake value (SUVmax) were calculated, and their relationship to treatment response was evaluated. RESULTS: Complete response (CR) in three patients, partial response (PR) in two patients and stable disease (SD) in eight patients were observed in group-1, and the results were as follows for group-2: PR in seven and SD in five patients. At a mean of 17.5-month observation period (range, 7-47), 35.2% of patients progressed, and 23.5% achieved a CR, and no recurrence was observed on PET/CT scans during follow-up. Among all patients enrolled in the study, the 5-year OS in patients with progressive disease (PD) was significantly shorter than patients with clinical benefit (CB = CR and PR and SD) (P = 0.016). Significant differences in both ΔSULpeak and ΔSUVmax were found between PD versus CB (P = 0.001 and P < 0.001, respectively). CONCLUSION: 18F-FDG-PET/CT can accurately assess therapy response and predict patient outcome in metastatic RCC. 18F-FDG PET/CT may facilitate patient management by evaluating the biological and immunological responses to treatment in patients treated with TKIs or ICIs.

Comparison of iodine-125 plaque brachytherapy and gamma knife stereotactic radiosurgery treatment outcomes for uveal melanoma patients.

PURPOSE: To compare the efficacies of iodine-125 brachytherapy (IBT) and gamma knife stereotactic radiosurgery (GKRS) in the treatment of posterior uveal melanoma. METHODS: The demographic data and tumor characteristics at diagnosis of 201 patients treated with IBT and 52 patients treated with GKRS were recorded. The two treatments were then compared in terms of complications, local control, eye retention, metastasis, and overall survival rate. RESULTS: The median follow-up time was 56 months for the GKRS group and 45 months for the IBT group (p = 0.167). There were no significant differences in demographic data or tumor characteristics between the groups at diagnosis. Radiation retinopathy, radiation optic neuropathy, and neovascular glaucoma occurred at similar rates in both groups. However, radiation maculopathy and cataracts occurred more frequently in the GKRS group. The number of cases that have developed vision loss (worsening of best-corrected visual acuity on three or more lines on the Snellen chart) was significantly higher in the GKRS group (60%) compared to the IBT group (44%) (p = 0.048). Local control, metastasis, and 5-year overall survival rates were statistically similar in both groups. CONCLUSIONS: GKRS can be preferred as an eye-sparing treatment option for posterior uveal melanoma in cases where brachytherapy cannot be used.

The Relationship Between Symptom Severity and Caregiver Burden in Cancer Patients Under Palliative Care: A Cross-Sectional Study.

BACKGROUND: Hospitalization is a stressful experience both for primary caregivers (PCs) and cancer patients alike. Although there is significant evidence that PCs of cancer patients can experience significant caregiver burden (CB), less is known about the relationships between PCs and patient symptom severity that influence CB. Methods: In this cross-sectional study, measures of the symptom severity were obtained from cancer patients. The PCs were assessed for CB. Associations between patients' symptoms and demographic characteristics and CB were investigated using multivariate analyses. Results: A total of 98 participants (patient-caregiver dyads) filled the questionnaires. According to the Zarit Burden Interview results, 65.3% of PCs had a high CB. Pain, tiredness, nausea, depression, drowsiness, well-being, and dyspnea had significantly higher mean values in those with high CB (p < .05). Financial difficulties, first-degree relationships with the patient, higher anxiety levels, and more pronounced tiredness appear to be the variables most predictive with high CB. Conclusion: In conclusion, the present study showed CB of PCs among a group of hospitalized incurable cancer patients. PCs of more symptomatic cancer patients had a higher CB, according to our findings. This emphasized the significance of palliative care. Appropriate guidance should be provided for the psychostress caused by the CB.

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.

Use of volumetric CT scanning to predict tumor staging and survival in pancreatic cancer patients that are to be administered curative resection.

BACKGROUND: This study evaluates the achievability of CT volumetry of pancreatic cancer and its correlation with pTNM stage and survival. METHODS: Tumor volume was measured from contrast enhanced CT images of 58 patients who undergo curative resection for pancreatic cancer using the Segment Editor module implemented in 3D-Slicer-a free open source software platform. Receiver operating characteristic (ROC) analysis was used to evaluate correlation between Tvol and pTNM staging. RESULTS: The preoperative images of 58 pancreatic adenocarcinoma patients were included. The mean Tvol of pancreatic cancer is an increasing trend with T stage (The mean T1vol = 1.75 cm3 , the mean T2vol = 11.43 cm3 , the mean T3vol = 14.98 cm3 , the mean T4vol = 19.6 cm3 ). There were statistical differences between volumes (p = .000). On ROC analysis, the area under the ROC curve (Az) of Tvol to differentiate T1 stage from ≥T2 stage was 0.966 (p = .000). At a cut-off value of 3.050 cm3 , sensitivity of 92.3%, and specificity of 83.3% were achieved. Az value of Tvol to differentiate ≤T2 from ≥T3 stage was 0.750 (p = .010). At a cut-off value of 10.250 cm3 , sensitivity of 72.7% and specificity of 66% were achieved. In addition Az value of Tvol to differentiate ≤T3 from ≥T4 stage was 0.652 and was not significant (p = .380). At a cut-off value of 11.2 cm3 , sensitivity of 66.7% and specificity of 63.6% were achieved. CONCLUSION: CT volumetry in pancreatic cancer is feasible with excellent reproducibility. It is one of the prognostic factors affecting survival in operated patients with pancreatic cancer.

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.

The Relationship between Ocular Vascular Changes and the Levels of Malondialdehyde and Vascular Endothelial Growth Factor in Patients with Inflammatory Bowel Disease.

Background: We evaluated ocular hemodynamic changes, malondialdehyde(MDA) and vascular endothelial growth factor (VEGF) levels in patients with IBD.Methods: We used ocular color Doppler ultrasonography to analyze 56 eyes with Crohn's disease (CD), 62 eyes with ulcerative colitis (UC), 68 eyes of healthy volunteers. We measured peak systolic velocity (PSV),end-diastolic velocity (EDV),and the resistivity index (RI) of ophthalmic artery (OA) and central retinal artery (CRA). MDA and VEGF levels were measured in the plasma samples.Results: MDA levels were significantly higher in both UC and CD patients, whereas VEGF levels were only higher in the CD group (p = .003,p < .001,p = .01).The PSV and EDV of the OA were significantly lower in CD patients (p = .017,p = .001). The EDV of the CRA was significantly lower in CD patients than UC patients and controls (p = .014,p < .001).Conclusions: CD patients exhibited decreased blood flow in both the OA and CRA. Ocular vascular flow was only affected in CD patients. We found that ocular ischemia may occur in CD patients even in the absence of any clinical finding.

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.

Mean platelet volume and platelet distribution width correlates with prognosis of early colon cancer.

PURPOSE: Several platelet indices have been linked to prognosis of various cancers, including metastatic colorectal cancer. The aim of this study was to investigate the prognostic effect of mean platelet volume (MPV) and platelet distribution width (PDW) in early colon cancer (CC) patients. METHODS: This retrospective study included early CC patients who were followed up and treated between 2005 and 2017. Relapse free survival (RFS) and overall survival (OS) were determined with respect to several demographic and clinical characteristics of patients, including MPV and PDW. The cut-off value was determined as >8.5 fL for MPV (sensitivity: 67.1%, specificity 54.5%) and ≤16% for PDW (sensitivity: 66.7%, specificity: 60.0%). RESULTS: The study included 394 patients, 53.3% of which were male. Stage I, II, and III patients constituted 8.9%, 46.4%, and 44.7% of the study population, respectively. Among all patients, RFS and OS were significantly longer in patients with MPV≤8.5 fL and PDW>16 fL (p<0.001 and p=0.011 for MPV, respectively; and p<0.001 and p=0.026 for PDW, respectively). In patients with stage III disease, those with MPV≤8.5 fL had significantly longer RFS and OS compared to those with MPV >8.5 fL (p<0.001 and p=0.001, respectively). On the other hand, those with PDW>16% had significantly longer RFS than that in those with PDW ≤16 fL among stage III patients (p<0.001). In multivariate analysis, stage, perineural invasion, lymphovascular invasion, adjuvant treatment, CEA, CA19-9, PDW, and MPV were found the most significant factors affecting RFS. CONCLUSION: Our study suggests that elevated MPV and decreased PDW appear to be unfavorable prognostic factors in early CC, especially in patients with stage III disease. Considering the wide availability and accessibility of these indices, it is reasonable to designate further larger prospective studies to clarify and verify their potential roles in early CC.

Follicular lymphoma generating in a patient with non-small cell lung cancer following nivolumab discontinuation.

INTRODUCTION: Immune checkpoint inhibitors have demonstrated the benefit for many cancer types, melanoma, non-small cell lung cancer, urothelial cancer, renal cell cancer, etc. Especially in advanced non-small cell lung cancer, significant improvement in survival results has been shown. CASE REPORT: Here, we report a 66-year-old man with lung adenocarcinoma who received nivolumab for 80 cycles.Management and Outcome: Two months after discontinuing nivolumab, he developed follicular lymphoma. Pneumonitis was also accompanied, which was treated with metilprednisolon, but he died due to progressive respiratory failure. DISCUSSION: Our clinical knowledge with checkpoint inhibitors is increasing day by day, and to the best of our knowledge, this paper presents the first case in the English literature who developed follicular lymphoma after discontinuing nivolumab in non-small cell lung cancer patient.

Complete response after ceritinib treatment in non-small cell lung cancer in an elderly patient.

INTRODUCTION: Ceritinib is a selective second-generation ALK inhibitor that is highly sensitive to echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) molecule. CASE REPORT: In this paper, we report a 68-year-old female that was diagnosed with stage 4 ALK-positive non-small cell lung cancer (NSCLC).Management and outcome: She was treated with crizotinib first-line, cisplatin and gemcitabine as second-line. And for third-line, ceritinib was started. She had complete response over 3.5 years under ceritinib treatment. And she is still receiving ceritinib with no adverse event. DISCUSSION: Cases achieving complete response with ceritinib treatment are rare. In this paper, we aimed to emphasize the complete response in stage 4 NSCLC in an elderly patient.

The impact of tumor regression grade on long-term survival in locally advanced rectal cancer treated with preoperative chemoradiotherapy.

PURPOSE: The aim of this study is to investigate the prognostic effect of tumor regression grade (TRG) on long-term survival in locally advanced rectal cancer treated with preoperative chemoradiotherapy. METHODS: Medical records of 182 patients with locally advanced rectal cancer, who were treated with preoperative chemoradiotherapy followed by surgery between 2002 and 2016, were retrospectively reviewed. TRG was classified into five categories based on the pathological response as follows - TRG1: no viable cancer cell, TRG2: single cancer cell or small groups of cancer cells, TRG3: residual tumor outgrown by fibrosis, TRG4: residual tumor outgrowing fibrosis, TRG5: diffuse residual tumor without regression. TRG1, (TRG2+TRG3), and (TRG4+TRG5) were grouped as complete response, intermediate response, and no response, respectively. RESULTS: Of the 182 patients with locally advanced rectal cancer, 112 (61.5%) were male. The mean age was 54.4 (range, 25-87) years. The total number of patients in complete response, intermediate response, and no response group was 24 (13.2%), 105 (57.7%), and 53 (29.1%), respectively. The corresponding five-year relapse-free survival and overall survival rates were 79.8%-92.3%, 74.7%-79.4%, and 55.7%-55.8%, respectively (p < 0.05 for relapse-free survival, p < 0.05 for overall survival). According to ypTNM stage, there was no significant difference in relapse-free survival among TRG groups in ypStage I and II patients (p > 0.05). In ypStage III patients, relapse-free survival was 62 months in no response group vs. not reached in intermediate response group (p < 0.05). According to the ypTNM, there was no significant difference in overall survival among TRG groups in ypStage I, II, and III patients (p > 0.05). In the multivariate analysis, pathological complete response was found to be an independent variable for relapse-free survival and overall survival (hazard ratio (95% confidence interval), 0.34 (0.17-6.77), 0.39 (0.18-0.83), respectively). CONCLUSION: This study showed that patients with pathological complete response to preoperative chemoradiotherapy had longer relapse-free survival and overall survival rates than those with residual disease.

Factors Affecting the Length of Stay in the Intensive Care Unit: Our Clinical Experience.

BACKGROUND AND AIM: Long hospital days in intensive care unit (ICU) due to life-threatening diseases are increasing in the world. The primary goal in ICU is to decrease length of stay in order to improve the quality of medical care and reduce cost. The aim of our study is to identify and categorize the factors associated with prolonged stays in ICU. MATERIALS AND METHOD: We retrospectively analyzed 3925 patients. We obtained the patients' demographic, clinical, diagnostic, and physiologic variables; mortality; lengths of stay by examining the intensive care unit database records. RESULTS: The mean age of the study was 61.6 ± 18.9 years. The average length of stay in intensive care unit was 10.2 ± 25.2 days. The most common cause of hospitalization was because of multiple diseases (19.5%). The length of stay was positively correlated with urea, creatinine, and sodium. It was negatively correlated with uric acid and hematocrit levels. Length of stay was significantly higher in patients not operated on than in patients operated on (p < 0.001). CONCLUSION: Our study showed a significantly increased length of stay in patients with cardiovascular system diseases, multiple diseases, nervous system diseases, and cerebrovascular diseases. Moreover we showed that when urea, creatinine, and sodium values increase, in parallel the length of stay increases.

An effective treatment of atypical hemolytic uremic syndrome with plasma exchange and eculizumab: A case report.

Atypical hemolytic uremic syndrome is a rare thrombotic microangiopathy caused by chronic defective regulation of the complement activation. This activation results in systemic endothelial damage leading to renal failure. Eculizumab, an anti-C5 antibody, is effective in limiting complement activation in patients with aHUS and has recently came out as a therapeutic option for aHUS. Here we present a case showing that first-line eculizumab treatment successfully prevents the induction of the terminal complement cascade and blocked the progression of thrombotic microangiopathy in aHUS.

Patients treated with therapeutic plasma exchange: a single center experience.

INTRODUCTION: Therapeutic Plasma Exchange (TPE) is a therapeutic procedure that is used to remove high molecular weight substances from plasma. We analyzed data of patients who received TPE during the last 7 years, and focused on the efficiency of TPE in various disease groups. MATERIAL AND METHODS: We studied 110 patients treated with TPE by membrane plasma separation technique from 2007 to 2013. We examined the demographic data, underlying disease, biochemical parameters, volume and type of replacement fluid, complications, concomitant treatment, the need for hemodialysis and number of TPE sessions. RESULTS: One hundred ten patients, 58 male, 52 female were included. The mean age was 47.3 ± 17.6 years. A total of 734 TPE sessions were performed and the mean number of TPE sessions per patient was 6.6 ± 4.3. The underlying disease was renal transplantation in 26 patients, ANCA-associated vasculitis in 18, rapidly progressive glomerulonephritis in 17, hemolytic uremic syndrome in 11, thrombotic thrombocytopenic purpura in 9, autoimmunic hemolytic anemia in 6, focal segmental glomerulosclerosis in 6 and other diseases. Partial and complete remission was obtained in 65 (59.1%) and 24 patients (21.8%) respectively, while 14 (12.7%) patients had no response and 7 (6.4%) patients died. Complications were muscle cramps (6.4%), allergic reactions (4.5%), severe hypotension (3.6%), fever (1.8%), unconsciousness (0.9%), leukopenia (0.9%) and catheter related hematoma (0.9%). CONCLUSION: According to our 7 years of experience in TPE, we can say that therapeutic plasma exchange by membrane separation technique is a useful, easy, available and effective life-saving therapeutic treatment.