Patients' Preferences for Adjuvant Osimertinib in Non-Small-Cell Lung Cancer After Complete Surgical Resection: What Makes It Worth It to Patients?

BACKGROUND: The ADAURA trial confirmed adjuvant Osimertinib's efficacy in EGFR-mutated Non-small-cell lung cancer (NSCLC), yet the limited mature overall survival (OS) data at approval poses a challenge. This study explores patient preferences in the absence of complete OS information, hypothesizing that disease-free survival (DFS) benefit alone may influence adjuvant Osimertinib pursuit. METHODS: At Roswell Park Comprehensive Cancer Center (Jan-Dec 2021), patients assessed for adjuvant therapy received a survey probing OS and DFS preferences. Scenarios were (a) minimum OS justifying Osimertinib, (b) minimum DFS improvement justifying 3-years of adjuvant Osimertinib, (c) minimum 5-year DFS percent change, and (d) minimum OS justifying copay changes. Results were analyzed. RESULTS: Of 524 NSCLC patients, 51 participated. Scenario 1 saw 56% requiring a 12-month OS benefit for Osimertinib justification. In scenario 2, 72% deemed a 12-month DFS benefit sufficient. Scenario 3 revealed 31% opting out despite a 10% OS increase. Scenario 4 showed varied willingness to pay, with 33% unwilling to any shoulder copayment even with a 10-year OS benefit. CONCLUSION: This study explores patient preferences without complete OS data, revealing diverse thresholds. Factors include employment, education, and willingness to pay. Findings underscore shared decision-making importance. Limitations include sample size, potential biases, and regional focus; larger cohorts are needed for validation.

Safety of sequential immune checkpoint inhibitors after prior immune therapy.

BACKGROUND: The use of immune checkpoint inhibitors (ICI) has transformed cancer treatment. Subsequent ICI use has become increasingly common following disease progression. We aim to evaluate the safety and tolerability of the sequential ICI treatment modality. METHODS: Retrospective review of confirmed carcinoma from January 2014 to December 2018. Patients were categorized into "initial ICI arm" and "sequential ICI arm" defined as patients receiving single, dual or chemo-immunotherapy ICI following an initial ICI regimen. Primary outcome was the development of a new or recurrent immune related adverse event (irAE) during sequential therapy. Secondary outcomes were the number of cycles prior to the development of irAE and grade of irAE. RESULTS: A total of 483 patients received ICI during the timeframe. Of those, 22 patients received sequential ICI. The diagnoses included ten lung cancer, seven melanoma, four renal cell carcinoma and one bladder cancer. 16 patients received single agent ICI following the initial ICI, three patients received dual ICI following the initial ICI, one patient received chemotherapy-immunotherapy following initial ICI, and two patients received chemo-immunotherapy after dual ICI. Four patients developed new irAE and one patient developed the same irAE on sequential treatment. A higher proportion of patients experienced grade 3 irAE in the sequential arm compared to the initial ICI arm (p = 0.03). No statistical difference was found between the development of irAE and the number of cycles prior to development of irAE in either treatment groups (p = 0.5). CONCLUSION: Our data shows overall safety of sequencing ICI when close monitoring was employed.

Participation of Black Americans in Cancer Clinical Trials: Current Challenges and Proposed Solutions.

Low participation of Black Americans in cancer clinical trials is a well-established predicament. Many factors resulted in this current dilemma with racism being the fundamental unit. Here, we discuss some current challenges and proposed solutions to help in increasing the enrollment of Black Americans in cancer clinical trials. We suggest implementing the least acceptable race-specific percentage as a new bar that registrational clinical trials need to pass before cancer drugs approval. Clinical trials will continue to draw the future of cancer therapeutics in which we believe that a prompt improvement of Black Americans participation is warranted.

Transplant-associated Thrombotic Microangiopathy Treated with Eculizumab and Romiplostim.

Transplant-associated thrombotic microangiopathy (TA-TMA) can occur after solid organ transplantation. It results in thrombocytopenia, haemolytic anaemia and microvascular occlusion. TA-TMA is not fully understood and treatment has not been clearly established. However, there is increasing evidence to suggest an immune-complement mediated component to its development. Eculizumab is a monoclonal antibody that inhibits the cleavage of C5 into pro-inflammatory, prothrombotic terminal complement elements and has been utilized in the treatment of atypical haemolytic uremic syndrome. We report a case of TA-TMA successfully treated with eculizumab and romiplostim. This case adds to the evidence that TA-TMA is triggered by complement dysregulation and suggests possible interventions for refractory cases. LEARNING POINTS: Transplant-associated thrombotic microangiopathy (TA-TMA) may occur in solid organ transplant patients.Eculizumab may be used for the treatment of TA-TMA.

KRAS and NRAS mutational gene profile of metastatic colorectal cancer patients in Jordan.

BACKGROUND: A constitutively active RAS protein in the absence of stimulation of the epidermal growth factor receptor (EGFR) is the result of mutations in KRAS and NRAS genes. Mutations in the KRAS exon 2 and outside exon 2 have been found to predict the resistance to anti-EGFR monoclonal therapy. A substantial proportion of metastatic colorectal cancer cases (mCRC) exhibit RAS mutations outside KRAS exon 2, particularly in KRAS exon 3 and 4 and NRAS exons 2 and 3. No data about RAS mutations outside KRAS exon 2 are available for Jordanian patients with mCRC. We aim to study the molecular spectrum, frequency, and distribution pattern of KRAS and NRAS mutations in Jordanian patients with mCRC. METHODS: A cohort of 190 Jordanian metastatic colorectal cancer patients were enrolled in the trial. We detected mutations in exon 2 of the KRAS and NRAS gene as well as mutations outside of exon 2 using the StripAssay technique. The KRAS StripAssay covered 29 mutations and 22 NRAS mutations. RESULTS: Mutations were observed in 92 (48.42%) cases, and KRAS exon 2 mutations accounted for 76 cases (83.69%). KRAS G12D was the most common mutation, occurring in 18 cases, followed by KRAS G12A in 16 cases, and G12T in 13 cases. Mutations outside of KRAS exon 2 represented 16.3% of the mutated cases. Among those, 6 cases (6.48%) carried mutations in NRAS exon 2 and 3, and 10 cases (10.87%) in KRAS exon 3 and 4. CONCLUSION: The frequency of NRAS and KRAS mutations outside of exon 2 appears to be higher in Jordanian patients in comparison with patients from western countries. KRAS mutations outside of exon 2 should be tested routinely to identify patients who should not be treated with anti-EGFR antibodies.

Contributing factors to iron deficiency anemia in women in Jordan: A single-center cross-sectional study.

OBJECTIVES: This study aimed to understand the impact of iron deficiency anemia in female users of a hematology service in a developing country. DESIGN: Retrospective cross-sectional study of adult and adolescent women with iron deficiency anemia who presented to a hospital department of hematology. SETTING: A tertiary university hospital inpatient and outpatient hematology service. PARTICIPANTS: All female patients who were ≥13 years of age with confirmed iron deficiency anemia and received hospital hematology services. RESULTS: A total of 208 patients were enrolled and analyzed in the registry. The mean age of the patients was 41.4 years (range, 14-82). A total of 195 patients had anemia that was moderate or severe according to the World Health Organization anemia classification with 13 patients having mild anemia. A total of 108 patients had comorbidities, which were primarily endocrine and cardiovascular. Iron deficiency anemia was associated with very heavy (n = 56, 30%) or heavy menses (n = 84, 45%) in 140 patients and was associated with poor (<200 g/week of red meat) (n = 101, 54%) or very poor (vegan, strict vegetarian) nutrition (n = 34, 18%) in 135 patients. A total of 101 patients had a previous pregnancy history with a mean of six previous pregnancies (range, 1-11 pregnancy episodes per patient). Blood film was performed on all patients; only four had a picture consistent with thalassemia minor. CONCLUSION: Iron deficiency anemia is caused by multiple factors. Heavy menses and low consumption of red meat were found to be associated with the severity of anemia. Our findings may be useful for healthcare planners and policy makers in increasing efforts to reduce the prevalence and severity of iron deficiency anemia among women in Jordan.

Prevalence of thrombophilic genetic factors among patients with retinitis pigmentosa.

PURPOSE: To determine the prevalence of thrombophilic factors in patients with retinitis pigmentosa (RP). METHODS: Fifty consecutive patients with RP and 50 controls matched by age and gender were tested for the presence of the following mutations: factor II (GA20210), factor V Leiden (GA1691), methylenetetrahydrofolate reductase (CT677), factor XIIIa (Val→Leu), ß-fibrinogen (GA455), tumor necrosis factor receptor (TNFRII) (M196R), plasminogen activator inhibitor-1 (PAI-1) (4 G/5 G), and plasminogen activator inhibitor-1 (PAI-1) (GA844). RESULTS: The following heterozygous mutations were found in patients/controls: factor V Leiden (12/14), factor XIIIa (20/30), methylenetetrahydrofolate reductase 677 TT (48/52), ß-fibrinogen GA455 (36/36), TNFRII (M196R) (40/42), PAI-1 4 G/5 G (40/48), and PAI-1 GA844 (50/52). The difference between patients with RP and the control group was not statistically significant for the prevalence of any of the studied factors (P > 0.05). CONCLUSION: In this study, thrombophilic mutations were not increased in patients with RP. Thrombophilic mutations do not seem to be risk factors for RP. Routine investigation of hereditary thrombophilia in these patients is not justified.