K. Eric Sommers

Clinical Efficacy and Predictive Molecular Markers of Neoadjuvant Gemcitabine and Pemetrexed in Resectable Non-Small-Cell Lung Cancer

Background: A trial of neoadjuvant gemcitabine and pemetrexed (GP) chemotherapy in patients with resectable non-small cell lung cancer was conducted. The goal was to achieve a disease response rate of 50% and to determine if the expression levels of genes associated with GP metabolism are predictive of response. Methods: Patients had staging with a computed tomography scan, whole body F-18 fluorodeoxyglucose positron emission tomography, and mediastinoscopy. Four biweekly cycles of GP were given. Patients were restaged, and those with resectable stage IB-III disease had thoracotomy. Fresh frozen tumor specimens were collected before and after chemotherapy and the mRNA levels of 14 target genes determined by real-time reverse transcription polymerase chain reaction. Results: Fifty-two patients started therapy. The radiographic disease response rate was 35% (95% confidence interval 21.7-49.6%), and the progression rate was 6%. Forty-six patients had a thoracotomy. The complete tumor resection rate was 77% (40/52). There were no perioperative deaths or deaths related to chemotherapy. Tumor response to chemotherapy was inversely correlated with the level of expression of RRM1 (p < 0.001; regulatory subunit of ribonucleotide reductase) and TS (p = 0.006; thymidylate synthase); i.e., the reduction in tumor size was greater in those with low levels of expression. Conclusions: Neoadjuvant GP is well tolerated and produces an objective response rate of 35%. Tumoral RRM1 and TS mRNA levels are predictive of disease response and should be considered as parameters for treatment selection in future trials with this regimen.

Relationship between Tumor Size and Survival among Patients with Resection of Multiple Synchronous Lung Cancers

Background: Multiple synchronous non-small cell lung cancers (NSCLCs) without extrathoracic metastasis are relatively uncommon. Some patients are treated as metastatic disease by chemotherapy alone; others are treated as multiple primary cancers by surgery. For those undergoing surgery, limited information exists on the relationship between tumor size and survival. Methods: We retrospectively reviewed medical records of patients with resection of at least two synchronous NSCLC located in ≥2 lobes during 1997–2008. Those with only satellite nodules in single lobe were excluded. Cox proportional hazard model was used to examine the prognostic significance of tumor size in the context of other clinical parameters including tumor stage, nodal stage, age, gender, laterality, histology, and pneumonectomy. Results: There were 116 patients: 57 patients had cancers distributed in one lung and 59 in both lung. Overall, 186 thoracotomies were performed, with a 90-day mortality rate of 2.6%. The median overall survival was 65.1 months (95% confidence interval [CI]: 49.2–83.7). The median size of the largest tumor and the median sum of tumor sizes were 3.0 and 4.5 cm, respectively. Both were a significant predictor of survival: hazard ratios per centimeter increase where 1.17 (95% CI: 1.06–1.30, p = 0.003) and 1.15 (95% CI: 1.05–1.26, p = 0.003), respectively. Multivariable regression analysis identified tumor size and lung function as independent survival predictors. Conclusion: Among patients with resected multiple synchronous NSCLC, tumor size is an independent predictor of survival. The size of the largest tumor performs slightly better than the sum of tumor sizes in the survival prediction; however, both are much better than the American Joint Committee on Cancer stage for this purpose.

Increased age is an independent risk factor for radiographic aspiration and laryngeal penetration after thoracotomy for pulmonary resection

OBJECTIVES Aspiration is an increasingly recognized complication after thoracotomy for pulmonary resection, but mechanisms of postoperative aspiration are poorly characterized. This study sought to evaluate risk factors to better define postthoracotomy aspiration. METHODS Three hundred twenty-one consecutive patients underwent clinical bedside swallowing evaluations after thoracotomy for pulmonary resection on postoperative day 1. Results of videofluoroscopic swallowing studies were independently reviewed by 2 speech pathologists and were assigned aspiration-penetration scores of either 1 (normal) or greater than 1 (abnormal) based on the worst swallow. Operative, demographic, and outcomes data were abstracted for each patient, and multivariate regression analysis was performed. RESULTS Seventy-three (22.7%) patients failed bedside evaluation and proceeded to undergo videofluoroscopic swallowing studies. Forty-four (60.3%) patients had an abnormal videofluoroscopic swallowing study result with a mean aspiration-penetration score of 3.9 +/- 0.3. Multivariate analysis showed that older age (68.8 vs 56.2 years, P = .002), prior premature spillage (P = .0006), and vallecular residuals after the swallow (P < .0002) were all associated with aspiration. Interestingly, certain variables were not independently associated with aspiration, including presence of gastroesophageal reflux disease, operative approach or degree of resection, mediastinal lymphadenectomy, preoperative thoracic radiation, same hospitalization reoperation, and pathology. CONCLUSIONS Postoperative risk of aspiration after thoracotomy for pulmonary resection is characterized by repeatable episodes of oropharyngeal discoordination on videofluoroscopic swallowing studies. We recommend routine videofluoroscopic swallowing studies for all patients older than 67 years before the initiation of oral intake to diminish the incidence of postoperative aspiration.

Induction chemoradiotherapy versus chemotherapy alone for superior sulcus lung cancer

OBJECTIVES Although treatment of superior sulcus tumors with induction chemoradiotherapy (CRT) followed by surgery employed in the Intergroup INT-0160 trial is widely adopted as a standard of care, there may be significant associated morbidity and mortality. We describe our experience using standard and alternative induction regimens to assess survival rates and treatment toxicity in these patients. MATERIALS AND METHODS Electronic medical records of all patients who underwent multimodality treatment including resection of lung cancer invading the superior pulmonary sulcus between 1994 and 2016 were retrospectively reviewed. Multivariable Cox Proportional Hazards model was constructed. RESULTS Of 102 consecutive patients, 53 (52%) underwent induction CRT, 34 (33%) underwent induction chemotherapy only (Ch) followed by adjuvant radiotherapy, and 15 (15%) underwent no induction therapy followed by adjuvant therapy. There were 2 postoperative deaths (1.9%). To date, 42 patients are alive with a median follow-up 72.5 months. Overall 5-year survival rate was 45.4%. Survival was significantly influenced by age, FEV1, positive resection margins, surgical complications, but not the induction regimen. CRT resulted in higher complete pathological response rate than Ch: 38% vs. 3% (p < 0.001). CRT was associated with higher post-operative re-intubation rate: 13% vs. 0% (p = 0.03). CONCLUSIONS Our single-institutional experience indicated that while induction CRT produced greater complete pathological response than Ch, it also increased the risk of post-operative complications. With careful patient selection, induction Ch followed by adjuvant radiotherapy may provide comparable survival outcomes to induction CRT. Since induction Ch is associated with lower risk of complications, it may be a particularly desirable choice for patients with impaired performance status.