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עמוד בית
Tue, 16.04.24

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October 2017
Sarit Appel MD, Jeffry Goldstein MD, Marina Perelman MD, Tatiana Rabin MD, Damien Urban MBBS MD, Amir Onn MD, Tiberiu R. Shulimzon MD, Ilana Weiss MA, Sivan Lieberman MD, Edith M. Marom MD, Nir Golan MD, David Simansky MD, Alon Ben-Nun MD PhD, Yaacov Richard Lawrence MBBS MRCP, Jair Bar MD PhD and Zvi Symon MD PhD

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.

January 2017
Sarit Appel MD, Yaacov R. Lawrence MRCP, Jeffery Goldstein MD, Raphael M. Pfeffer MD, Ilana Weiss MA, Tatiana Rabin MD, Shira Felder MD, Maoz Ben-Ayun PhD, Lev Tzvang MSc, Dror Alezra PhD, David Simansky MD, Alon Ben-Nun MD PhD, Jair Bar MD PhD and Zvi Symon MD

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.

 

March 2006
H. Schayek, M. Krupsky, P. Yaron, A. Yellin, D.A. Simansky and E. Friedman

Background: The contribution of the abnormal DNA mismatch repair system to non-small cell lung cancer tumorigenesis is controversial and has not been reported in Jewish Israeli patients. Similarly, the involvement of 3p deletions in NSCLC[1] in the same population has not been assessed.

Objectives: To assess the contribution of the DNA-MMR[2] system to NSCLC pathogenesis by analyzing microsatellite instability, and evaluate loss of heterozygosity at 3p rates in Israeli NSCLC patients.

Methods: Paired DNA from tumorous and non-tumorous tissue was extracted, and genotyping for MSI[3] determination was carried out using the five Bethesda markers and for determining LOH[4] two 3p markers were used. Genotyping was performed using polymerase chain reaction amplification and size separation on an ABI semiautomatic DNA sequencer, and the allelic patterns of tumorous and non-tumorous tissue were compared.

Results: Forty-four NSCLCs from 35 smokers and 9 non-smokers were analyzed, with 26 of the 44 (59%) at stage I disease. Using five microsatellite markers (D17S250, D5S346, D2S123, BAT-25, BAT-26) (known as Bethesda markers) for MSI determination, 6 of the 44 tumors (13.6%) exhibited MSI in at least one marker. Similarly, genotyping for LOH at chromosome 3p was performed using two markers (D3S4103, D3S1234) located at 3p14.2 l. With D3S4103, 33 of the 44 patients successfully analyzed were homozygous and therefore non-informative with respect to LOH. Using D3S1234, 33 of 36 patients (91.7%) were heterozygous, and 23 of these individuals' tumors (69.7%) displayed LOH. Unexpectedly, 4 of 33 tumors (12.1%) genotyped by D3S4103, and 16 of 36 tumors (44.5%) genotyped by D3S1234 showed a pattern of MSI, even though only one of these tumors showed a similar pattern when genotyped with the five consensus markers. Overall, 23 of 44 tumors (52.3%) demonstrated MSI on at least one marker, and 5 of these 23 tumors (21.7%) had MSI on two or more markers.

Conclusions: MSI using 3p markers and not the Bethesda markers occurs at a high rate and in early stages in Jewish NSCLC patients.






[1] NSCLC = non-small cell lung cancer

[2] DNA-MMR = DNA mismatch repair

[3] MSI = microsatellite instability

[4] LOH = loss of heterozygosity


November 2005
A. Yellin, S.T. Zwas, J. Rozenman, D.A. Simansky and E. Goshen
Background: Somatostatin receptor scintigraphy has been used widely for the evaluation of neuroendocrine tumors in the gastrointestinal tract. Its use for detecting and staging thoracic carcinoids is only sporadically reported.
Objectives: To evaluate the possible roles of SRS[1] in the management of proven or suspected pulmonary carcinoids. 

Methods: We conducted a retrospective study of all patients undergoing SRS for known or suspected pulmonary carcinoids in a tertiary referral center during a 10 year period. During this period 89 patients underwent resection of pulmonary carcinoids and SRS was used for detection, staging or localization purposes in 8 of them (9%). Scans were labeled true positive, true negative, false positive, or false negative in comparison with histologic or follow-up results. 

Results: SRS was true positive in 6/6 lung locations; true positive in 2/8, true negative in 4/8 and false positive in 2/8 lymph node locations; and true positive in 1/8, true negative in 6/8 and false negative in 1/8 distant locations. The sensitivity, specificity, positive and negative predictive values and accuracy were 90%, 83%, 83%, 91% and 87% respectively. The scans were strongly positive in the tumors and involved lymph nodes. SRS correctly localized an occult secreting pulmonary carcinoid. Granulomatous and reactive lymph nodes showed increased uptake. SRS was accurate in ruling out distant metastases. 

Conclusions: SRS is effective for visualizing and localizing pulmonary carcinoids. It assists in the staging of these tumors by detecting lymph node involvement and confirming or ruling out distant metastases. Inflamatory areas in the lung or lymph nodes may be falsely positive.


[1] SRS = somatostatin receptor scintigraphy

 
September 2005
I. Greenberg-Wolff, E. Konen, I. Ben Dov, D. Simansky, M. Perelman and J. Rozenman
Background: Cryptogenic organizing pneumonia is increasingly being recognized as a major cause of diffuse infiltrative lung disease. The differential diagnosis of non-infectious diseases that resemble pneumonia should include this entity. Understanding the radiologic features of this entity will help in defining the correct diagnosis, although lung biopsy is needed to provide histopathologic confirmation. Treatment with steroids achieves an excellent response.

Objectives: To present a variety of radiologic findings on high resolution computerized tomography in eight sequential patients with COP[1], together with clinical and pathologic correlation.

Methods: Sequential HRCT[2] examinations of eight patients (four males) aged 53–80 years (mean 65.5 years) with pathologically proven COP were retrospectively analyzed by a consensus of two experienced chest radiologists for the existence and distribution of airspace consolidation, ground-glass opacities, nodular thickening along bronchovascular bundles, small (<1 cm) and large (>1 cm) nodules. The distribution of radiologic findings was classified as unilateral or bilateral, located in the upper, lower or middle lobe, and central or peripheral. Also recorded was the presence or absence of mediastinal lymphadenopathy and pleural effusion. Correlation with clinical symptoms was analyzed.

Results: All eight patients had bilateral airspace consolidations: in two cases consolidations were limited to central fields, in four they were peripheral, and in the remaining two cases they were both central and peripheral. Small nodules were noted in six cases and large nodules in three. Ground-glass opacities were found in four cases. All patients had enlarged lymph nodes (1–1.5 cm) in the mediastinum. Radiologic abnormalities resolved or improved after steroid treatment in all patients.

Conclusions: HRCT findings of bilateral multiple heterogenic lung infiltrates and nodules associated with mild mediastinal lymphadenopathy in a patient with non-specific clinical symptoms are suggestive of COP; in such cases, lung biopsy is indicated. Radiologic resolution of abnormalities correlates well with clinical improvement under adequate steroid treatment.

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[1] COP = cryptogenic organizing pneumonia

[2] HRCT = high resolution computerized tomography

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