Israel Medical Association Journal

Background: The main acquired resistance mechanism to first- and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR mutant non-small cell lung cancer (NSCLC) is the propagation of T790M clones, which can be detected in circulating tumor DNA (ctDNA).

Objectives: To analyze osimertinib outcomes according to T790M testing method.

Methods: The study comprised 33 consecutive patients with advanced EGFR mutant NSCLC who were diagnosed with a T790M mutation after progression on first- or second-generation EGFR TKIs and treated with osimertinib. The patients were divided into groups A (diagnosed by tumor testing) and B (by ctDNA testing). Osimertinib outcomes were compared between the groups.

Results: Objective response rate with osimertinib comprised 54% and 62% in groups A and B, respectively (P = 0.58). Median progression-free survival (PFS) with osimertinib was 8.9 months (95% confidence interval [95%CI] 1.8–17.5) and 9.1 months (95%Cl 5.3–12.6) in groups A and B, respectively (log-rank test 0.12, P = 0.73). Median overall survival (OS) was 13.8 months (95%CI 4.9–25.5) and 13.8 months (95%Cl 7.7–27.7) in groups A and B, respectively (log-rank test 0.09, P = 0.75). T790M testing technique did not affect PFS (hazard ratio [HR] 1.16, 95%CI 0.50–2.69, P = 0.73) or OS (HR = 1.16, 95%CI 0.45–3.01, P = 0.76). The proportion of patients diagnosed by ctDNA grew from 56% in 2015 to 67% in 2016–2017.

Conclusions: Our study provides a ctDNA validation for the purpose of T790M testing in EGFR mutant NSCLC.

Background: Ga-prostate-specific membrane antigen positron emission tomography/computerized tomography (Ga-PSMA PET/CT) is part of the initial workup of patients with intermediate and high-risk prostate cancer provided by the Israeli national health services.

Objectives: To assess the incidence of metastatic spread in consecutive patients with newly diagnosed cancer, and the potential added value of Ga-PSMA PET/CT to the staging imaging algorithm.

Methods: Patients with newly diagnosed intermediate- and high-risk prostate cancer were referred for initial staging by Ga-PSMA PET/CT between May 2016 and April 2017. Blood prostate-specific antigen (PSA) levels, clinical history, imaging reports and histopathological reports (including Gleason scores) were obtained. Maximal standardized uptake values (SUVmax) were determined for the primary lesions detected within the prostate.

Results: The study included 137 consecutive patients with intermediate- and high-risk disease who underwent Ga-PSMA PET/CT staging. Of these, 75 had Ga-PSMA uptake in both prostate lobes, 57 had unilateral uptake, and 5 patients had no uptake. SUVmax in the primary tumor correlated significantly with PSA levels. Thirty-five patients had increased uptake compatible with metastatic disease involving lymph nodes, bone, and viscera. Twenty-seven patients had available bone scintigraphy results: 18 (69%) of their 26 bone metastases detected by Ga-PSMA PET/CT were missed on bone scintigraphy.

Conclusions: Ga-PSMA PET/CT shows promise as a sole whole-body imaging modality for assessing the presence of soft tissue and bone metastases in the setting of prostate cancer.

Background: Brain-derived neurotrophic factor (BDNF) is a neuronal growth factor that is important for the development, maintenance, and repair of the peripheral nervous system. The BDNF gene commonly carries a single nucleotide polymorphism (Val66Met-SNP), which affects the cellular distribution and activity-dependent secretion of BDNF in neuronal cells.

Objectives: To check the association between BDNF Val66Met-SNP as a predisposition that enhances the development of chemotherapy-induced peripheral neuropathy in an Israeli cohort of patients with breast cancer who were treated with paclitaxel.

Methods: Peripheral neuropathy symptoms were assessed and graded at baseline, before beginning treatment, and during the treatment protocol in 35 patients, using the reduced version of the Total Neuropathy Score (TNSr). Allelic discrimination of BDNF polymorphism was determined in the patients' peripheral blood by established polymerase chain reaction and Sanger sequencing.

Results: We found Val/Val in 20 patients (57.14%), Val/Met in 15 patients (42.86%), and Met/Met in none of the patients (0%). Baseline TNSr scores were higher in Met-BDNF patients compared to Val-BDNF patients. The maximal TNSr scores that developed during the follow-up in Met-BDNF patients were higher than in Val-BDNF patients. However, exclusion of patients with pre-existing peripheral neuropathy from the analysis resulted in equivalent maximal TNSr scores in Met-BDNF and Val-BDNF patients.

Conclusions: These observations suggest that BDNF Val66met-SNP has no detectable effect on the peripheral neuropathy that is induced by paclitaxel. The significance of BDNF Val66Met-SNP in pre-existing peripheral neuropathy-related conditions, such as diabetes, should be further investigated.

Background: Unlike the elective treatment of metastatic colorectal cancer (MCRC), sufficient data and consensual guidelines on acute care are lacking.

Objectives: To analyze a cohort of MCRC patients who required urgent surgery due to acute abdomen and to identify risk factors contributing to the patient's perioperative mortality and morbidity.

Methods: A retrospective analysis was conducted of patients diagnosed with stage IV colorectal cancer who required urgent laparotomy at the Rabin Medical Center. Comparative analysis was performed using Pearson’s chi-square and Student`s t-test.

Results: Between 2010 and 2015, 113 patients underwent urgent laparotomy due to colorectal cancer complications, of which 62 patients were found to have a metastatic, stage IV, disease. Large bowel obstruction was the most common indication for urgent laparotomy. In-hospital mortality was 30% (n=19), and overall 30 day mortality was 43%. Fifteen patients (24%) required more than one surgery. The average length of hospital stay was 21 days. Age and lactate levels at presentation were the only prognostic factor found for mortality (P < 0.05).

Conclusions: MCRC laparotomy patients incur a significant burden of care and have a relatively high incidence of early mortality. Our data suggest high, verging on unacceptable, mortality and complication rates in this subgroup of patients. This finding is further accentuated in the subgroup of older patients presenting with lactatemia. These data should be considered by surgeons when discussing treatment options with patients and families.

Background: Adjuvant radiotherapy for breast cancer reduces local recurrence and improves survival. In patients with left sided breast cancer, anterior heart position or medial tumor location may cause inadequate breast coverage due to heart shielding. Respiration gating using the Real-time Position Management (RPM) system enables pushing the heart away from the tangential fields during inspiration, thus optimizing the treatment plan.

Objectives: To compare breathing inspiration gating (IG) techniques with free breathing (FB), focusing on breast coverage.

Methods: The study comprised 49 consecutive patients with left sided breast cancer who underwent lumpectomy and adjuvant radiation. RPM was chosen due to insufficient breast coverage caused by an anterior heart position or medial lumpectomy cavity. FB and IG computed tomography simulations were generated for each patient. Breast (PTVbreast) and lumpectomy cavity (CTVlump) were defined as the target areas. Optimized treatment plans were created for each scan. A dosimetric comparison was made for breast coverage and heart and lungs doses.

Results: PTVbreast V95% and mean dose (Dmean) were higher with IG vs. FB (82.36% vs. 78.88%, P = 0.002; 95.73% vs. 93.63%, P < 0.001, respectively). CTVlump V95% and Dmean were higher with IG (98.87% vs. 88.92%, P = 0.001; 99.14% vs. 96.73%, P = 0.003, respectively). The cardiac dose was lower with IG. The IG left lung Dmean was higher. No statistical difference was found for left lung V20.

Conclusions: In patients with suboptimal treatment plans due to anterior heart position or medial lumpectomy cavity, RPM IG enabled better breast/tumor bed coverage and reduced cardiac doses.