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: Pulmonary rehabilitation has shown significant benefit for patients with chronic obstructive pulmonary disease (COPD). The effect on non-COPD pulmonary patients is less well established.

Objectives: To determine whether pulmonary rehabilitation is also beneficial for non-COPD pulmonary patients.

Methods: Clinical and demographic data on non-COPD pulmonary patients who participated in our institutional pulmonary rehabilitation program between January 2009 and December 2016 were collected. Participants engaged in a 60-minute, twice-weekly, ambulatory hospital-based program lasting 12 to 24 sessions. Sessions included both endurance and muscle training as well as healthy lifestyle educational activities. The six-minute walk test (6MWT) and the St. George's Respiratory Questionnaire (SGRQ) were conducted before and after the rehabilitation program.

Result: We recruited 214 non-COPD patients, of whom 153 completed at least 12 sessions. Of these, 59 presented with interstitial lung disease (ILD), 18 with non-ILD restrictive lung defects, 25 with asthma, 30 with lung cancer, and 21 with other conditions (e.g., pulmonary hypertension, bronchiectasis) The groups demonstrated significant improvement in 6MWT and in SGRQ scores. Non-COPD patients gained a 61.9 meter (19%) improvement in the 6MWT (P < 0.0001) and 8.3 point reduction in their SGRQ score (P < 0.0001).

Conclusions: Pulmonary rehabilitation is effective in non-COPD pulmonary patients. As such, it should be an integral part of the treatment armament provided to the vast majority of those suffering from chronic respiratory disease.

Background: Neoadjuvant chemo-radiation therapy (CRT) dosages in locally advanced non-small cell lung cancer (NSCLC) were traditionally limited to 45 Gray (Gy).

Objectives: To retrospectively analyze outcomes of patients treated with 60 Gy CRT followed by surgery.

Methods: A retrospective chart review identified patients selected for CRT to 60 Gy followed by surgery between August 2012 and April 2016. Selection for surgery was based on the extent of disease, cardiopulmonary function, and response to treatment. Pathological response after neoadjuvant CRT was scored using the modified tumor regression grading. Local control (LC), disease free survival (DFS), and overall survival (OS) were estimated by the Kaplan–Meier method.

Results: Our cohort included 52 patients: 75% (39/52) were stage IIIA. A radiation dose of 60 Gy (range 50–62Gy) was delivered in 82.7%. Surgeries performed included: lobectomy, chest-wall resection, and pneumonectomy in 67.3%, 13.4%, and 19.2%, respectively. At median follow-up of 22.4 months, the 3 year OS was 74% (95% confidence interval [CI] 52–87%), LC was 84% (95%CI 65–93), and DFS 35% (95%CI 14–59). Grade 4–5 postoperative complications were observed in 17.3% of cases and included chest wall necrosis (5.7%), bronco-pleural fistula (7.7%), and death (3.8%). A major pathologic regression with < 10% residual tumor occurred in 68.7% of patients (36/52) and showed a trend to improved OS (P = 0.1). Pneumonectomy cases had statistically worse OS (P = 0.01).

Conclusions: Major pathologic regression was observed 68.7% with 60 Gy neoadjuvant CRT with a trend to improved survival. Pneumonectomy correlated with worse survival.

Taxanes are often used in the treatment of many types of cancers. Side effects of docetaxel are not as well documented as paclitaxel, but both can cause pulmonary injury. We present a dramatic case of a patient being treated for prostatic adenocarcinoma with docetaxel who presented with interstitial pneumonitis and responded dramatically to the early treatment with corticosteroids. This case is important as it reveals the side effects of docetaxel administration without administration of other chemotherapeutic agents, and it illustrates the importance of early diagnosis and treatment of docetaxel-induced interstitial pneumonitis. Further research into the mechanism of the side effects of docetaxel is warranted.

Background: Stereotactic ablative radiation therapy (SABR) is the application of a very high radiation dose to a small treatment volume. It is the new standard of care in medically inoperable early-stage lung cancer. 

Objectives: To report the outcomes of SABR in stage I lung cancer at Sheba Medical Center since its introduction in 2009.

Methods: We conducted a retrospective chart review of patients with stage I lung cancer treated during the period 2009–2015. Survival status was retrieved from the electronic medical records and confirmed with the national registry. Local failure was defined as increased FDG uptake on PETCT scan within a 2 cm radius of the treated region. Toxicity was estimated from medical records and graded according to common toxicity criteria for adverse events (CTCAE) version 4.03. Overall survival and local control were estimated by the Kaplan-Meier method.

Results: During the study period 114 patients were treated for 122 stage I lung cancer lesions. Median follow-up time was 27 months (range 8.2–69.5 months), median age was 76 years. Eighty-two percent of the tumors were stage IA (size ≤ 3 cm). Median survival was 46 months; estimated 3 year overall survival was 59% (95%CI 47–69%) and local control was 88% (95%CI 78–94%). Toxicity included chest wall pain in 8.4% of patients, rib fracture in 0.9%, grade 1–2 pneumonitis in 12%, grade 3 in 12% and grade 5 (death) in 0.9%.

Conclusions: SABR has been successfully implemented at Sheba Medical Center for the treatment of stage I lung cancer in inoperable patients. It is associated with excellent local control, minor toxicity and an acceptable overall survival.

 

Background: Studies in lung transplantation demonstrate that the ancestry and gender dissimilarities of donor–recipients lead to a decrease in survival of the recipient. 

Objectives: To evaluate the survival of lung transplant recipients in Israel based on whether the donors and recipients are of Jewish or Arab ancestry as well as survival based on gender match or mismatch.

Methods: We performed a retrospective observational cohort study of 345 lung transplant recipients at the Rabin Medical Center, Petah Tikva, Israel between January 1997 and January 2013. We compared the survival of lung transplant recipients in two ancestry categories: ancestry matched (Jewish donors to Jewish recipients or Arab donors to Arab recipients) and ancestry mismatched (Jewish donors to Arab recipients and vice versa). We also compared the survival among the four gender donor and recipient combinations (male to male, female to female, male to female, and female to male). 

Results: Survival analysis revealed no significant differences between the two ancestry groups (P = 0.51) and among the four gender combinations (P = 0.58). On Cox multivariate analysis, younger donor age was the only significant parameter for longer survival (hazards ratio 1.025, 95% confidence interval 1.012–1.037).

Conclusions: Gender and ancestry mismatches in these two Israeli populations do not appear to alter the clinical outcomes following lung transplantation.

 

Lung involvement is a well-recognized extra-articular manifestation of ankylosing spondylitis (AS). Anecdotal reports suggest that the use of anti-TNF drugs may be related to lung disease and pulmonary fibrosis. To examine the association between anti-TNF drugs and the development of lung disease in patients with AS or  psoriatic arthritis (PsA) we conducted a systematic review. Of the 670 papers identified by means of key word and hand search, only one full-text paper was considered potentially relevant but had to be discarded as it did not meet the eligibility criteria. Although no conclusion was reached, this is the first systematic review to examine this problem which is becoming increasingly important as these drugs are widely prescribed in patients with spondyloarthritis.

Background: The efficacy of video-assisted thoracoscopic surgery lobectomy in patients with previous coronary artery bypass grafting (CABG) surgery is controversial.

Objectives: To investigate whether skeletonized left internal mammary artery (LIMA) mobilization contributes to the development of severe adhesions, which will affect what type of lung surgery (open or closed procedure) will be required in the future.

Methods: Eight patients (mean age 73.9 years) with previous CABG surgery using a LIMA to left anterior descending (LAD) graft underwent left-sided lobectomy for operable non-small cell lung carcinoma. 

Results: The lobectomy by thoracotomy rate was 62.5% (5 patients), generally in patients with tumors in the left upper lobe or in patients post-neoadjuvant chemotherapy, while the video-assisted thoracic surgery lobectomy rate was 37.5% (3 patients). Mean hospital stay was 8.3 days. There was no mortality or major morbidity, apart from six minor complications in four patients (50%) (air leak, atrial fibrillation, atelectasis, pneumonia). 

Conclusions: Patients with operable non-small cell lung carcinoma following CABG surgery who need left upper lobe resection do not benefit from the video-assisted thoracoscopic surgery technique due to significant adhesions between the LIMA to LAD graft and the lung. The method of preserving a small portion of the lung on the LIMA to LAD graft may help during left upper lobe resections. Adhesions in the left pleural space after LIMA mobilization appear to generally minimally affect left lower lobe video-assisted thoracoscopic surgery.