Cancer-related hypercalcemia is a common finding typically seen in patients with advanced cancer and occurs in about 20 to 30 percent of cases. The most common cause of hypercalcemia in hospitalized ...patients is hypercalcemia due to malignancy.This clinical problem is seen in patients with both solid tumors and patients with hematologic malignancies. Hypercalcemia is associated with a poor prognosis in oncology patients. This pathologic condition can occur due to many different mechanisms but is usually caused by abnormal calcium use resulting from bone resorption, intestinal absorption, or renal excretion. Hypercalcemia may present with a wide range of symptoms ranging from gastrointestinal system symptoms to neurologic symptoms. Timely diagnosis and initiation of treatment by the physician significantly reduce the risk of complications. Treatment aims to decrease serum calcium by increasing calciuresis, decreasing bone resorption, and decreasing intestinal calcium absorption. The mainstays of treatment are IV hydration, bisphosphonates and calcitonin, denosumab, and in some patients, prednisone, and cinacalcet. Patients with underlying advanced kidney disease and refractory severe hypercalcemia should be evaluated for hemodialysis. Every physician dealing with oncology patients should know the fastest and most effective management of hypercalcemia. We aimed to contribute in this sense.
Albumin-bilirubin (ALBI) grade is an objective measure of liver function for patients with hepatocellular carcinoma (HCC). The tyrosine kinase inhibitor cabozantinib is approved for patients with ...advanced HCC who have received prior sorafenib based on the phase 3 CELESTIAL trial (NCT01908426). Cabozantinib improved overall survival (OS) and progression-free survival (PFS) versus placebo in patients with previously treated HCC.
Patients were randomised 2:1 to receive cabozantinib 60 mg or placebo orally every day. Clinical outcomes in patients with ALBI grade 1 or 2 at baseline were evaluated in CELESTIAL. ALBI scores were retrospectively calculated based on baseline serum albumin and total bilirubin, with an ALBI grade of 1 defined as ≤ -2.60 score and a grade of 2 as a score of > -2.60 to ≤ -1.39.
Cabozantinib improved OS and PFS versus placebo in both ALBI grade 1 (hazard ratio HR 95% CI: 0.63 0.46-0.86 and 0.42 0.32-0.56) and ALBI grade 2 (HR 95% CI: 0.84 0.66-1.06 and 0.46 0.37-0.58) subgroups. Adverse events were consistent with those in the overall population. Rates of grade 3/4 adverse events associated with hepatic decompensation were generally low and were more common among patients in the ALBI grade 2 subgroup.
These results provide initial support of cabozantinib in patients with advanced HCC irrespective of ALBI grade 1 or 2.
ClinicalTrials.gov number, NCT01908426.
Background
Trifluridine and tipiracil (FTD/TPI) demonstrated survival benefit vs placebo and manageable safety in previously treated patients with metastatic gastric/gastroesophageal junction cancer ...(mGC/GEJC) in the randomized, placebo-controlled, phase 3 TAGS study. This subgroup analysis of TAGS examined efficacy/safety outcomes by age.
Methods
In TAGS, patients with mGC/GEJC and ≥ 2 prior therapies were randomized (2:1) to receive FTD/TPI 35 mg/m
2
or placebo, plus best supportive care. A preplanned subgroup analysis was performed to evaluate efficacy and safety outcomes in patients aged < 65, ≥ 65, and ≥ 75 years.
Results
Among 507 randomized patients (
n
= 337 FTD/TPI;
n
= 170 placebo), 55%, 45%, and 14% were aged < 65, ≥ 65, and ≥ 75 years, respectively. Overall survival hazard ratios for FTD/TPI vs placebo were 0.67 (95% CI 0.51–0.89), 0.73 (95% CI 0.52–1.02), and 0.67 (95% CI 0.33–1.37) in patients aged < 65, ≥ 65, and ≥ 75 years, respectively. Regardless of age, patients receiving FTD/TPI experienced improved progression-free survival and stayed longer on treatment than those receiving placebo. Among FTD/TPI-treated patients, frequencies of any-cause grade ≥ 3 adverse events (AEs) were similar across age subgroups (80% each), although grade ≥ 3 neutropenia was more frequent in older patients 40% (≥ 65 and ≥ 75 years); 29% (< 65 years); AE-related discontinuation rates did not increase with age 14% (< 65 years), 12% (≥ 65 years), and 12% (≥ 75 years).
Conclusions
The results of this subgroup analysis show the efficacy and tolerability of FTD/TPI treatment regardless of age in patients with mGC/GEJC who had received 2 or more prior treatments.
Background
The aim of this study is to investigate of the relationship between GSTM1 gene variations and serum trace elements, plasma malondialdehyde levels in patient with colorectal cancer.
...Mateials and Methods.
Genotype distributions of GSTM1 gene variations were determined using real-time polymerase chain reaction method. Serum trace element levels were determined using atomic absorption spectrophotometer method and plasma MDA levels were measurement by spectrophotometric method.
Results
Serum Cu levels, plasma MDA levels and Cu/Zn ratio were determined significantly higher in the group of CRC patient carrying the GA heterozygous genotype of the GSTM1 (rs 112,778,559) gene variation compared to healthy controls (p < 0.05). Serum Cu, Zn levels, plasma MDA levels and Cu/Zn ratio were determined significantly higher in patients carrying GG homozygous genotype of the GSTM1 (rs 112778559) gene variation compared to healthy controls carrying same genotype (p < 0.05). Serum Cu, Zn levels, plasma MDA levels and Cu/Zn ratio were determined significantly higher in the group of CRC patient carrying the GG homozygous genotype of the GSTM1 (rs 12068997) gene variation compared to healthy controls (p < 0.05). On the other hand, serum Se levels were detected significantly lower in CRC patients carrying GA heterozygous and GG homozygous genotypes for GSTM1 (rs 112,778,559) and (rs 12,068,997) gene variations compared to healthy controls (p < 0.05).
Conclusion
In our study, the evaluation of serum Cu, Zn and Se trace element levels and plasma MDA levels according to GSTM1 gene variations genotype distributions were enabled to obtain important biomarkers in terms of CRC development and progression.
Background Indoleamine 2,3-dioxygenase 1 (IDO1) levels correlate with poor outcomes in urothelial carcinoma (UC). IDO1 and programmed death-ligand 1 (PD-L1) are often co-expressed. Epacadostat is a ...potent and highly selective inhibitor of IDO1. In a subgroup analysis of patients with advanced UC participating in a phase I/II study, epacadostat-pembrolizumab treatment produced an objective response rate (ORR) of 35%. Methods ECHO-303/KEYNOTE-698 was a double-blinded, randomized phase III study of adults with metastatic or unresectable locally advanced UC with recurrence or progression following first-line platinum-based chemotherapy. Participants were randomized to epacadostat 100 mg twice daily (BID) plus pembrolizumab or placebo plus pembrolizumab until completion of 35 pembrolizumab infusions, disease progression, or unacceptable toxicity. The primary endpoint was investigator-assessed ORR per Response Evaluation Criteria in Solid Tumors version 1.1. Results Target enrollment was 648 patients; enrollment was halted early based on efficacy results from the phase III ECHO-301/KEYNOTE-252 study in metastatic melanoma. Forty-two patients were randomized to each treatment arm. Median duration of follow-up was 62 days in each arm. The investigator-assessed ORR (unconfirmed) was 26.2% (95% CI 16.35-48.11) for epacadostat plus pembrolizumab and 11.9% (95% CI 4.67-29.50) for placebo plus pembrolizumab. Two complete responses were reported, both in the placebo-plus-pembrolizumab arm. Circulating kynurenine levels increased from C1D1 to C2D1 in the placebo-plus-pembrolizumab arm and numerically decreased in the epacadostat-plus-pembrolizumab arm. The safety profile of epacadostat plus pembrolizumab was similar to that of pembrolizumab monotherapy, although a numerically greater proportion of patients in the combination vs. control arm experienced treatment-related grade greater than or equal to 3 adverse events (16.7% vs. 7.3%). One patient in each arm died due to cardiovascular events, which were not deemed drug-related. No new safety concerns were identified for either agent. Conclusions Epacadostat plus pembrolizumab demonstrated anti-tumor activity and was generally tolerable as second-line treatment of patients with unresectable locally advanced or recurrent/progressive metastatic UC. Epacadostat 100 mg BID, when administered with pembrolizumab, did not normalize circulating kynurenine in most patients. Further study of combined IDO1/PD-L1 inhibition in this patient population, particularly with epacadostat doses that result in durable normalization of circulating kynurenine, may be warranted. Trial registration ClinicalTrials.gov, NCT03374488. Registered 12/15/2017. Keywords: IDO1, Epacadostat, PD-L1, Pembrolizumab, Urothelial carcinoma, Immune checkpoint inhibition, Randomized controlled study
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. We aimed to evaluate the clinicopathological features of the patients in Thrace and ...improve our management.
In this retrospective study, 68 patients with a diagnosis of GIST referred to Trakya University Medical School Hospital between 1997 and 2015 were evaluated.
The most common symptom was abdominal pain (38.2%) and the location was small-intestine (42.6%). Large masses had higher metastasis and relapse rate. The mean tumor size with relapse was 11.8 ± 3.8 cm meanwhile it was 6.5 ± 3.0 cm in non-relapsed patients (p = 0.01). The mean size of the tumor was 13.5 ± 4.4 in the metastatic group although this data was 8.8 ± 4.7 cm in the non-metastatic group (p = 0.01). With necrotic tumors, mitotic rate and size were higher. The mean mitosis count was 21.0 ± 3.6 in necrotic tumors and 7.2 ± 9.9 in non-necrotic tumors (p = 0.005). The mean size was 10.8 ± 5.0 cm in necrotic tumors and 5.6 ± 3.0 cm in non-necrotic tumors (p = 0.009). According to AFIP criteria, most of the patients were in the high-risk group (57.4%). Overall survival (OS) was longer in non-smokers and non-drinkers. Median OS was 80.16 months in non-smoker group (95% CI, 27.83–132.49) and 24.64 months (95% CI, 15.49–33.78) in the smoker group (p = 0.001). The median OS was 80.09 months in the non-drinker group (95% CI, 13.99–146.20) and 24.64 months (95% CI, 13.18–36.10) in drinker group (p = 0.05). Median OS in stomach GIST was 41.39 months, in small-intestine were 80.09 months and in the colon were 35.68 months (p = 0.032). Patients underwent surgery had longer overall-survival. Median OS was 80.09 months in patients undergone surgery and 16.98 months in patients had not been operated (p = 0.001). Overall survival was longer in GIST with mitotic rate <5/50HPF than with >5/50HPF. Median OS was 80.16 months in patients who had less than 5 mitosis and 39.22 months in higher mitotic rate (95% CI, 31.58–46.87) (p = 0.034). Overall survival was shorter in GIST with Ki-67 > 5% than with 5%>. Median OS was 80.16 months (95% CI, 28.80–49.65) in <5% and 39.22 months (95% CI, 28.80–49.65) in 5%≤ Ki-67 (p = 0.004).
The most important factors about the survival and prognosis of GIST are location, size, mitotic rate, Ki-67, necrosis and surgery status. Using tobacco/alcohol may be related to survival. This study should be further investigated with extensive data.
Background: This study was designed to estimate economic burden of lung cancer in Turkey from payer perspective based on expert panel opinion on practice patterns in clinical practice. Methods: In ...this cost of illness study, direct medical cost was calculated based on cost items related to outpatient visits, laboratory and radiological tests, hospitalizations/interventions, drug treatment, adverse events and metastasis. Indirect cost was calculated based on lost productivity due to early retirement, morbidity and premature death resulting from the illness, the value of lost productivity due to time spent by family caregivers and cost of formal caregivers. Results: Cost analysis revealed the total per patient annual direct medical cost for small cell lung cancer to be €8772), for non-small-cell lung cancer to be €10,167. Total annual direct medical cost was €497.9 million, total annual indirect medical cost was €1.1 billion and total economic burden of lung cancer was €1.6 billion. Hospitalization/interventions (41%) and indirect costs (68.6%) were the major cost drivers for total direct costs and the overall economic burden of lung cancer, respectively. Conclusions: Our findings indicate per patient direct medical costs of small cell lung cancer and non-small-cell lung cancer to be substantial and comparable, indicating the substantial economic burden of lung cancer in terms of both direct and indirect costs. Our findings indicate that hospitalization/interventions cost item and indirect costs were the major cost drivers for total direct costs and the overall economic burden of lung cancer, respectively. Our findings emphasize the potential role of improved cancer prevention and early diagnosis strategies, by enabling cost savings related to drug treatment and metastasis management cost items, in sustainability of cancer treatments.
Background:
Abemaciclib is the first and only cyclin-dependent kinases 4 and 6 inhibitor approved for adjuvant treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor ...2-negative (HER2−), node-positive, and high-risk early breast cancer (EBC), with indications varying by geography. Premenopausal patients with HR+, HER2− tumors may have different tumor biology and treatment response compared to postmenopausal patients.
Objectives:
We describe the efficacy and safety of abemaciclib plus endocrine therapy (ET) for the large subgroup of premenopausal patients with HR+, HER2− EBC in monarchE.
Design:
Randomized patients (1:1) received adjuvant ET with or without abemaciclib for 2 years plus at least 3 additional years of ET as clinically indicated.
Methods:
Patients were stratified by menopausal status (premenopausal versus postmenopausal) at diagnosis. Standard ET (tamoxifen or aromatase inhibitor) with or without gonadotropin-releasing hormone agonist was determined by physician’s choice. Invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) by menopausal status were assessed at data cutoff on 1 April 2021 (median follow-up of 27 months).
Results:
Among randomized patients, 2451 (43.5%) were premenopausal and 3181 (56.4%) were postmenopausal. The choice of ET for premenopausal patients varied considerably between countries. Treatment benefit was consistent across menopausal status, with a numerically greater effect size in premenopausal patients. For premenopausal patients, abemaciclib with ET resulted in a 42.2% and 40.3% reduction in the risk of developing IDFS and DRFS events, respectively. Absolute improvement at 3 years was 5.7% for IDFS and 4.4% for DRFS rates. Safety profile for premenopausal patients was consistent with the overall safety population.
Conclusion:
Abemaciclib with ET demonstrated clinically meaningful treatment benefit for IDFS and DRFS versus ET alone regardless of menopausal status and first ET, with a numerically greater benefit in the premenopausal compared to the postmenopausal population. Safety data in premenopausal patients are consistent with the overall safety profile of abemaciclib.
Introduction and aim
To investigate the effect of the prognostic nutritional index on treatment response and survival in patients with metastatic renal cell cancer.
Methods
We retrospectively ...analyzed the treatment modalities; the demographic, clinical and pathological features of 396 patients with RCC and prognostic nutritional index. Based on the median value, patients were grouped as having low and high prognostic nutritional index values. Kaplan-Meier method was used for survival analysis, and Cox-regression analysis was used for multivariate analysis.
Results
The median overall survival was 39 months (95% CI 26.1–51.8), 28 months (95% CI 17.9–38) and 7 months (95% CI 4.7–9.2) in patients with favorable, intermediate and poor International Metastatic Renal Cell Carcinoma Database Consortium risk group, respectively. The difference between the groups was statistically significant (p < 0001). Overall survival was 11 months (95% CI 7.5–14.5) in the low-prognostic nutritional index (prognostic nutritional index ≤38.5) group, and 41 months (95% CI 30.5–51.4) in the high prognostic nutritional index (prognostic nutritional index >38.5) group (p < 0.001). In Cox regression analysis, Eastern Cooperative Oncology Group performance score (HR: 2.5), time to systemic treatment (HR: 1.7) and prognostic nutritional index (HR: 1.8) were associated with overall survival.
Conclusion
In patients with renal cell cancer, prognostic nutritional index is closely related to survival and has prognostic significance.
The case of a patient who developed recurrent delayed immune-related pneumonitis (checkpoint inhibitor pneumonitis CIP) after immune checkpoint inhibitor (ICI) therapy for advanced osteosarcoma ...treatment is presented.
A 25-year-old female patient with metastatic osteosarcoma was treated with atezolizumab. Grade 2 pneumonitis developed three times in the first two years. Treatment was discontinued after recovery from the last episode of pneumonitis, which was complicated with secondary spontaneous pneumothorax. 2 years after discontinuation of immunotherapy, the patient again developed CIP. Pneumonitis symptoms were regressed with oral steroid therapy during follow-up and a stable disease response continued.
Immunotherapy can cause recurrent CIP at any time during the treatment period or after discontinuation of treatment.
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