Pneumonectomy after chemoradiation

Abstract

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. The current treatment protocol for ALL involves an intense chemotherapy regimen yielding cure rates of nearly 80%. However, new therapies need to be designed not only to increase the survival rate but also to combat the risk of severe therapy associated toxicities including secondary malignancies, growth problems, organ damage, and infertility. The c‐Myb proto‐oncogene is highly expressed in immature hematopoietic cells. In this study, we demonstrate that loss of c‐Myb itself decreased the viability of these leukemic cells. Additionally, the inhibition of c‐Myb caused a decrease in cell proliferation, significantly increased the number of cells in G0/G1 phase of the cell cycle, increased the sensitivity of pre‐B‐ALL cells to cytotoxic agents in vitro, and significantly delayed disease onset in a mouse model of leukemia. Furthermore, we demonstrate that Bcl‐2 is a target of c‐Myb in pre‐B‐ALL cells. Our results identify c‐Myb as a potential therapeutic target in pre‐B‐ALL and suggest that suppression of c‐Myb levels or activity, in combination with currently used therapies and/or dose reduction, may lead to a decrease in toxicity and an increase in patient survival rates. Because c‐Myb is aberrantly expressed in several other malignancies, targeting c‐Myb will have broad clinical applications. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc.

Trimodally treatment for stage IIIa NSCLC patients increases survival while not effecting surgical mortality or complexity

“…Nonetheless, when exploring the long term benefits of the NA therapy the survival rate, was found to be 30% eight years post-OP, significantly higher than the adjuvant group that was 0% at 5.5 years post-op [10]. The long-term outcomes of the pneumonectomy + adjuvant treatment group observed in our cohort are in concordance with the historically poor outcomes of single-modality therapy in stage IIIa NSCLC patients [10–12].…”

Proteasome Inhibitors Block DNA Repair and Radiosensitize Non-Small Cell Lung Cancer

“…Right pneumonectomy following neoadjuvant therapy has been associated with significantly increased mortality risk, regardless of addition of novel systemic agents. For example, there has been a reported 18% treatment-related mortality rate after right pneumonectomy, compared to a 4% rate after left pneumonectomy, after neoadjuvant radiotherapy to a median dose of 54 Gy with concurrent chemotherapy [46].…”

High-Dose Radiotherapy as Neoadjuvant Treatment in Non-Small-Cell Lung Cancer

“…The main reason was the morbidity and mortality rates of pneumonectomy (26% mortality), especially right pneumonectomy. Since the publication of INT 0139 a number of studies have shown that in experienced hands the mortality rate of pneumonectomy is unchanged following chemoradiation [18, 19]. Moreover, a number of trials have been published showing a lack of clear survival benefit for chemoradiation over induction chemotherapy followed by surgery [20-22].…”

“…Since the publication of the results of the intergroup trial multiple investigators have shown that in experienced hands pneumonectomy following chemoradiation is indeed safe even with increased doses of preoperative radiation therapy [3, 4]. The question that can then be asked is: would increased-intensity preoperative chemoradiation lead to improved nodal downstaging and thereby improved long-term survival?…”