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Journal and News Scan

Source: Journal of the National Cancer Institute
Submitted by: Marcelo Jimenez
August 26, 2015
Author(s): Andrew J. Gentles, Scott V. Bratman, Luke J. Lee, Jeremy P. Harris, Weiguo Feng, Ramesh V. Nair, David B. Shultz, Viswam S. Nair, Chuong D. Hoang, Robert B. West, Sylvia K. Plevritis, Ash A. Alizadeh and Maximilian Diehn
Investigators from Stanford developed a nine-gene expression predictor for survival outcome in early-stage nonsquamous NSCLC. They developed and validated a quantitative real-time polymerase chain reaction assay easily applicable to routinely obtained paraffin-embedded tumor specimens. Because the molecular prognostic index provides independent prognostic information when compared with standard clinical and pathologic covariates (age, sex, and stage), the authors decided to combine both in order to create a more robust risk index. These findings will be useful for assessing recurrence risk for patients with nonsquamous NSCLC and could guide indications for adjuvant treatment in order to improve outcomes for high-risk patients.
Source: JAMA Surgery
Submitted by: Mark Ferguson
August 22, 2015
Author(s): Franz Yanagawa; Martin Perez; Ted Bell; Rod Grim; Jennifer Martin; Vanita Ahuja
Outcomes of robotic vs nonrobotic cardiac surgery were evaluated using 1:2 propensity score matching of patients in the Nationwide Inpatient Sample.  Operations included valves/septae (10%), coronary arteries (47%), and other.  Mean costs were 7.5% higher for robotic cases.  Robotic procedures had shorter length of stay (5 vs 6 days), lower mortality (1.0% vs 1.9%), and fewer complications (27% vs 30%).
Source: JAMA Surgery
Submitted by: Mark Ferguson
August 22, 2015
Author(s): Wayne S. Lee; Vincent E. Chong; Gregory P. Victorino
Among patients with blunt trauma, the authors studied the implications of pneumomediastinum identified on CT.  The incidence was 2.2%.  Pneumomediastinum was associated with a 4-fold increase in mortality, a 2-fold increase in length of stay, and a 3-fold increase in ICU stay.  Air in the posterior mediastinum, air in all mediastinal compartments, and pneumomediastinum associated with a hemothorax were each associated with an increased risk of mortality.
Source: Journal of Thoracic Diseases
Submitted by: Mark Ferguson
August 22, 2015
Author(s): Travis, William D.; Brambilla, Elisabeth; Nicholson, Andrew G.; Yatabe, Yasushi; Austin, John H. M.; Beasley, Mary Beth; Chirieac, Lucian. R.; Dacic, Sanja; Duhig, Edwina; Flieder, Douglas B.; Geisinger, Kim; Hirsch, Fred R.; Ishikawa, Yuichi; Kerr, Keith M.; Noguchi, Masayuki; Pelosi, Giuseppe; Powell, Charles A.; Tsao, Ming Sound; Wistuba, Ignacio; On Behalf of the WHO Panel
This comprehensive review outlines changes in the WHO classification of lung tumors, chagnes that will affect our clinical practice in the near future.
Source: The Lancet Oncology
Submitted by: Lisa Brown
August 20, 2015
Author(s): Joe Y Chang, Suresh Senan, Marinus A Paul, Reza J Mehran, Alexander V Louie, Peter Balter, Harry J M Groen, Stephen E McRae, Joachim Widder, Lei Feng, Ben E E M van den Borne, Mark F Munsell, Coen Hurkmans, Donald A Berry, Erik van Werkoven, John J Kresl, Anne-Marie Dingemans, Omar Dawood, Cornelius J A Haasbeek, Larry S Carpenter, Katrien De Jaeger, Ritsuko Komaki, Ben J Slotman, Egbert F Smit, Jack A Roth
Thus far, only 3 randomized controlled trials (RCTs) have compared stereotactive ablative radiotherapy (SABR) versus surgery in patients with early stage NSCLC (STARS trial, ROSEL trial, and ACOSOG Z4099 trial). Unfortunately all 3 were unable to meet the accrual goals and were closed early. The current study is a pooled analysis of patients in the STARS trial and ROSEL trial (n=31 in SABR group and n=27 in surgery group). All patients had clinical stage I NSCLC (<4 cm) and were surgical candidates for lobectomy with a performance status of 0 to 2. Of note, patients in the STARS trial required histologic confirmation of NSCLC prior to randomization, but patients in the ROSEL trial did not. Overall 1 and 3-year survival was 100% and 95% in the SABR group and 88% and 79% in the surgery group. There was no significant difference in local, regional, or distant metastases or recurrence-free survival between the two groups. In terms of complications, in the SABR group, 3 (10%) patients had treatment related grade 3 adverse events. In the surgery group, one patient died of complications and 12 (44%) had postoperative grade 3-4 adverse events. The authors concluded that SABR is better tolerated and may lead to improved survival over surgery in patients with stage I NSCLC.  
Source: The Lancet Oncology
Submitted by: Lisa Brown
August 20, 2015
Author(s): Tom Treasure, Robert C Rintoul, Fergus Macbeth
This is an invited commentary on the article by Chang and colleagues (Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials). The authors congratulate Chang and colleagues for merging the data from the two trials in attempt to answer the controversial question of which therapy is most efficacious and agree that the results show that SABR is not inferior to surgery and that SABR may even be more effective than lobectomy. They point out that comparing SABR versus lobectomy may be complicated by the fact that a mediastinal lymph node dissection (MLND) is done at the time of lobectomy, thereby upstaging some of the surgical patients rendering a true comparison subject to bias. In addition, they point out that MLND is widely accepted without evidence of improvement in outcomes. They conclude by stating that clinicians have an obligation to seek evidence to support current practice and patients have a duty to participate in trials.
Source: The Journal of Thoracic and Cardiovascular Surgery
Submitted by: Lisa Brown
August 20, 2015
Author(s): Bryan F. Meyers, Varun Puri, Stephen R. Broderick, Pamela Samson, Kathleen Keogan, Traves Crabtree
This expert opinion editorial is published in JTCVS in response to the article by Chang and colleagues. Meyers and colleagues begin by emphasizing that a large randomized controlled trial (RCT) would be the best way to answer the question of whether SABR or lobectomy is superior treatment for patients with early stage NSCLC. This editorial highlights the limitations of analyzing and publishing data from failed trials and demonstrates how this contributes little to the ongoing debate. First, neither the STARS trial nor the ROSEL trial achieved 4% of the target sample size which leads to inaccurate results especially since the outcome of interest, death, occurred in an exceedingly small number of patients. Second, this cohort of patients differs significantly from the full cohort, had accrual been successful; early planned analyses in RCTs (when accrual is low) are conservative to prevent false positive results (Type I error). Third, the mortality rate in the surgical arm is 2-4 times the expected mortality for patients with stage I NSCLC undergoing resection. Fourth, the low accrual limits the external validity of these data. Fifth, the fact that there was one treatment-related death in the surgical arm, none in the SABR arm, and no difference with regard to recurrence does not seem to add up to the original article's claim that there is a statistically significant difference in survival favoring SABR. Sixth, the degree of surgical risk for these patients was unclear and it is difficult to account for variation in surgical treatment at different centers. Seventh, in Figure 2, A (overall survival) the hazard ratio is 0.14 in favor of SABR with a confidence interval that includes 1.0 (insignificant), but the p-value listed is 0.037 (significant). Lastly, the authors point out that equipoise existed prior to these RCTs and is still very much present as this controversy continues.
Source: The Lancet Oncology
Submitted by: Lisa Brown
August 20, 2015
Author(s): Christopher Cao, Thomas D'Amico, Todd Demmy, Joel Dunning, Dominique Gossot, Henrik Hansen, Jianxing He, Sanghoon Jheon, Rene H Peterson, Alan Sihoe, Scott Swanson, William Walker, Tristan D Yan, on behalf of the International VATS Interest Group
This is a letter in response to the article by Chang and colleagues. The authors point out that only 58 patients were enrolled from 38 centers over 66.3 months, and speculate that this might be due to patients' preference for surgery. Since the cohort was small, follow-up period brief, and analyses retrospective in nature without power calculations, at best these results may generate hypotheses. First, the conduct of the two randomised controlled trials (RCTs) was different and this was compounded by variation among the treatment centers within each trial. Second, a large proportion of patients in the surgical arm (3 of 27, 11%) did not undergo the intended treatment, lobectomy. Third, ROSEL trial patients did not require histologic confirmation of NSCLC prior to randomisation. Rather, patients with FDG avid lesions on preoperative PET scans were included; however, there were key differences in how PET scans were obtained at various centers. Fourth, only 5 of 27 patients in the surgical arm underwent VATS lobectomy, the majority underwent thoracotomy. The authors state that certain complications are less likely after VATS lobectomy compared with thoracotomy and that this approach is associated with similar and possibly better long-term survival than an open approach. They conclude by disagreeing that SABR is associated with better overal survival, concurring that SABR may be better tolerated than surgery, and express that further study of VATS lobectomy and subanatomic resection with lymph node assessement versus SABR and open thoracotomy are needed. 
Source: The Lancet Oncology
Submitted by: Lisa Brown
August 20, 2015
Author(s): Lei Zhang, Jingru Tian, Changli Wang
This is a letter in response to the article by Chang and colleagues. The authors focus on two key points: the difference in 3-year survival between the two treatment groups and the proposed use of endobronchial ultrasound (EBUS) in combination with SABR to decrease the likelihood of false-negative results from imaging for clinical staging of lymph nodes. First, the original article found a 3-year survival rate of 79% in the surgical arm and 95% in the SABR arm. They point out that this survival difference is driven by the small sample size of the STARS trial in which all 20 patients in the SABR arm survived and 5 of 16 patients in the surgical arm died. Furthermore,  although basic baseline characteristics were similar, differences in comorbidities between the two groups were not accounted for. Second, they disagree with using EBUS in the hopes of reducing the false-negative results associated with staging by PET/CT. A recent study demonstrated that the sensitivity of EBUS is 35% in patients with NSCLC who have negative CT and PET/CT. They conclude by disagreeing that surgery can be replaced by SABR and EBUS as staging would likely be inaccurate and for those who are understaged, adjuvant therapy would not be offered thereby worsening prognosis.
Source: The Lancet Oncology
Submitted by: Lisa Brown
August 20, 2015
Author(s): Masatsugu Hamaji, Shawn S Groth, David J Sugarbaker, Bryan M Burt
This is a letter in response to the article by Chang and colleagues. The authors warn to interpret the findings of the original article, that SABR is better tolerated and might lead to improved survival compared to surgery for good risk patients with clinical stage I NSCLC, with caution. They highlight two pitfalls of the original study. First, the comparison was between up to date SABR technology and outdated surgical techniques (primarily thoracotomy). They cite that thoracotomy should not be considered surgical standard of care for patients with early stage NSCLC as VATS is associated with lower morbidty and mortality without compromising outcomes from a cancer standpoint. According to large national databases, procedure-related mortality from SABR (0.7%) and VATS lobectomy (0.8%) are similar. Second, they highlight the methodological limitations of this study. Given the small sample size and short follow-up, they point out that the survival outcomes are inaccurate. The rate of locoregional recurrence was 16.1% in the SABR arm and 4.1% in the surgical arm, but it is unclear how this would affect cancer-specific survival as the study was not designed to properly answer that question. In addition, biopsy proof of NSCLC was not required in the ROSEL trial and therefore it is unknown how many patient in the SABR arm truly had NSCLC, whereas one patient in the surgical arm had benign disease.  They conclude that randomized controlled trials (RCTs) comparing best therapy in each arm are needed.

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