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Background There is a paucity of prognostic factors for patients with stage I non-small cell lung cancer (NSCLC) undergoing operations. We investigated the prognostic role of preoperative complete blood count values in patients with stage I NSCLC patients undergoing operations. Methods A retrospective medical record review was performed of patients who underwent operations for stage I NSCLC between 2000 and 2015. Patients who died within 30 days of the operations were excluded. The primary end point was recurrence. Preoperative complete blood count values were analyzed, and a median value was used as the cutoff. Statistical analysis used χ2 and t tests along with univariate and multivariate analyses by Cox regression modeling. Results The study included 103 patients. A high lymphocyte count was significantly associated with recurrence (5-year recurrence-free survival [RFS] of 69.8% for high vs 95.7% for low, P = .003), as well as high platelet (5-year RFS of 72.0% for high vs 91.8% for low, P = .02). Independent prognostic factors on multivariate analysis were high lymphocyte (hazard ratio [HR], 7.27; P = .005) and platelet counts (HR, 7.49; P = .003) as well as tumor (HR, 5.40; P = .008) and treatment characteristics (HR, 4.59; P = .01). Among patients with pT1 lesions, high lymphocyte (HR, 8.41; P = .03) and high platelet counts (HR, 19.78; P = .004) remained independent prognostic factors. Neither NLR nor PLR were significantly associated with recurrence. Conclusions In patients with pathologic stage I NSCLC undergoing surgical resection, the preoperative blood count from peripheral blood may provide prognostic value. Of significance, in patients with pT1 N0 NSCLC, high lymphocyte count and high platelet count were associated with higher recurrence.

Objective Transoral incisionless fundoplication (TIF) is a completely endoscopic approach to treat gastroesophageal reflux disease (GERD). We previously reported our initial results demonstrating safety and early effectiveness. We now present an updated experience describing outcomes with longer follow-up. Methods For a three-year period, TIF procedures were performed on 80 patients. Preoperative workup routinely consisted of contrast esophagram and manometry. PH testing was reserved for patients with either atypical symptoms or typical symptoms unresponsive to protonpump inhibitors (PPIs). Heartburn severity was longitudinally assessed using the GERD health-related quality of life index. Safety analysis was performed on all 80 patients, and an effectiveness analysis was performed on patients with at least 6-month follow-up. Results Mean procedure time was 75 minutes. There were seven (8.75%) grade 2 complications and one (1.25%) grade 3 complication (aspiration pneumonia). The median length of stay was 1 day (mean, 1.4). Forty-one patients had a minimum of 6-month of follow-up (mean, 24 months; range, 6–68 months). The mean satisfaction scores at follow-up improved significantly from baseline ( P < 0.001). Sixty-three percent of patients had completely stopped or reduced their PPI dose. Results were not impacted by impaired motility; however, the presence of a small hiatal hernia or a Hill grade 2/4 valve was associated with reduced GERD health-related quality of life scores postoperatively. Conclusions At a mean follow-up of 24 months, TIF is effective. Although symptoms and satisfaction improved significantly, many patients continued to take PPIs. Future studies should focus on longer-term durability and comparisons with laparoscopic techniques.

Objective: To determine if induction chemotherapy with concurrent high-dose radiation followed by resection is associated with improved survival in patients with nonsuperior sulcus lung cancer with chest wall invasion. Methods: We performed a retrospective review of clinical T3 (chest wall invasion) N0/N1 patients with non-small cell lung cancer who underwent surgical resection between January 1, 1992, and January 31, 2017. Exclusion criteria included superior sulcus tumors and resection performed for palliation/recurrence. Patients undergoing induction chemoradiation followed by surgical resection were compared to those undergoing resection first or those receiving induction radiation followed by resection. Overall survival was calculated using the Kaplan-Meier method. Results: Thirty-four patients were included in the analysis, with 5-year overall survival (OS) of 30%. By clinical stage, 31 (91%) were IIB (T3N0) and 3 (9%) were IIIA (T3N1). Sixteen patients (47%) received induction chemoradiation before surgery. Of the remaining 18 patients, 5 (15%) received induction radiation followed by surgery, and 13 (38%) underwent surgery as the first treatment. Three patients belonging to the group not receiving induction chemoradiation died within 30 days after surgery and were excluded from survival analysis. In the remaining 31 patients, induction chemoradiation was associated with improved 5-year OS (53% for induction chemoradiation vs 7% for others; PConclusion: In patients with nonsuperior sulcus lung cancer with chest wall invasion, induction chemoradiation therapy followed by resection is associated with improved OS.

The purpose of this study was to establish the correlation and reliability among the pathologic tumor volume and gradient and fixed threshold segmentations of (18)F-FDG PET metabolic tumor volume of human solid tumors.There were 52 patients included in the study who had undergone baseline PET/CT with subsequent resection of head and neck, lung, and colorectal tumors. The pathologic volume was calculated from three dimensions of the gross tumor specimen as a reference standard. The primary tumor metabolic tumor volume was segmented using gradient and 30%, 40%, and 50% maximum standardized uptake value (SUVmax) threshold methods. Pearson correlation coefficient, intraclass correlation coefficient, and Bland-Altman analyses were performed to establish the correlation and reliability among the pathologic volume and segmented metabolic tumor volume.The mean pathologic volume; gradient-based metabolic tumor volume; and 30%, 40%, and 50% SUVmax threshold metabolic tumor volumes were 13.46, 13.75, 15.47, 10.63, and 7.57 mL, respectively. The intraclass correlation coefficients among the pathologic volume and the gradient-based and 30%, 40%, and 50% SUVmax threshold metabolic tumor volumes were 0.95, 0.85, 0.80, and 0.76, respectively. The Bland-Altman biases were -0.3, -2.0, 2.82, and 5.9 mL, respectively. Of the small tumors (10 mL), 23 of the 35 patients had PET segmented volume outside 50% of the pathologic volume, and among the large tumors (≥ 10 mL) three of the 17 patients had PET segmented volumes that were outside 50% of pathologic volume.FDG PET metabolic tumor volume estimated using gradient segmentation had superior correlation and reliability with the estimated ellipsoid pathologic volume of the tumors compared with threshold method segmentation.

Over the last 30 years neoadjuvant treatment of stage IIIA non-small cell lung cancer (NSCLC) followed by surgical resection for stage IIIB disease has significantly improved the overall results of treatment for patients with stage III NSCLC as well as for those with locally invasive tumors. Different chemotherapy regimens have been used, although in most studies some combination of drugs that include cisplatin is the standard. Radiation when given as part of the induction protocol appears to offer a higher rate of resection and complete resection, and higher doses of radiation are associated with better nodal downstaging. Resection in patients with persistent N2 disease and pneumonectomy following induction therapy remain controversial. Resection in patients with persistent N2 disease and pneumonectomy following induction therapy remain controversial.

Background Thermal ablation is increasingly used to treat pulmonary tumors in medically inoperable patients. Most procedures are performed with sedation in the radiology suite. Ideally, the ablation should encompass the entire tumor volume with a surrounding margin of necrosis; however, ablation may not be as effective in the normal aerated lung surrounding a denser tumor. Inducing atelectasis of the lung may potentially increase ablation volumes and increase local cancer control. This study examines the effect of single-lung ventilation on ablation size using a microwave system. Methods Twenty microwave ablation procedures were performed in the lungs of 10 swine. Bilateral thoracotomy using a clamshell approach was used. In one lung, ablation was performed with continuous ventilation. In the contralateral lung, single-lung ventilation was achieved by clamping the bronchus before ablation. The ablated lobes were resected and sent for pathologic analysis. Routine and supravital staining was performed. Results The ablation zone was clearly demarcated on gross examination, and in all cases 100% ablation occurred, without skip areas of viability. The ablation zones were elliptical with the long axis parallel to the axis of the ablation probes (active tip, 3.7 cm). Ablation diameters and volume were compared between the ventilated and nonventilated lungs. Ablation volume was superior in nonventilated lungs (10.74 cm 3 versus 7.35 cm 3 ; p = 0.039) primarily because of differences in the short axis of the ablation zone. Conclusions Microwave energy can effectively ablate normal pulmonary parenchyma without skip areas of viable tissue within the gross ablation field. The volume of necrosis is increased in nonventilated lungs, suggesting that ablation results can be improved in patients by using general anesthesia with single-lung ventilation. Future studies will be required to confirm this hypothesis.

Purpose We evaluated an electromagnetic (EM) navigation system (Veran Medical Technologies Inc, St. Louis, MO) to determine its potential to reduce the number of skin punctures and instrument adjustments during computed tomographic-guided percutaneous ablation and biopsy of lung nodules. Description Ten patients undergoing lung percutaneous ablation were prospectively enrolled. The mean age was 70 years. Positioning of the needle device was verified with computed tomographic fluoroscopy prior to the execution of any biopsy or ablation. Each EM navigation-guided procedure was defined as an EM-intervention. Evaluation Nineteen EM interventions were performed. When an EM-guided biopsy was performed, the intervention was done immediately prior to ablation. For all 19 EM interventions, only one skin-puncture was required. The mean number of instrument adjustments required was 1.2 (range, 0 to 2). The mean time for each EM intervention was 5.2 minutes (range, 1 to 20 minutes). Pneumothorax occurred in 5 patients (50%). Only the number of instrument adjustments was significantly related to the pneumothorax rate (p = 0.005). Conclusions The EM navigation is feasible and seems to be a useful aid for image-guided procedures. Early experience suggests a low number of skin-puncture and instrument adjustments using the EM navigation system. Instrument adjustments were a key factor in pneumothorax development.

There seems to be no role for adjuvant radiation in stage I NSCLC patients treated by lobectomy. Adjuvant brachytherapy in combination with sublobar resection is a promising approach that seems to decrease local recurrence rates similar to that reported following lobectomy. If the results of the current American College of Surgeons Oncology Group randomized trial are favorable, it may be possible in the future to define subgroups of patients with stage I NSCLC who are able to be treated with this approach in preference to lobectomy. Until further data are available, lobectomy should remain the standard of care. RFA is an alternative for the high-risk patient with NSCLC who is considered too high-risk even for sublobar resection. Although long-term results are not yet available, it does seem that local recurrence is a significant problem. In a similar fashion to the approach currently being investigated with sublobar resection, the addition of radiation may improve local control after RFA. In particular, adjuvant stereotactic radiation should be investigated as a potential method of decreasing local recurrence and preserving lung function in these high-risk patients.

BackgroundIncreasing data implicate histologic grade and radiographic appearance along with tumor size as key prognostic indicators for pulmonary adenocarcinoma. The impact of tumor location on prognosis has not been examined.MethodsThe records of 530 consecutive patients with pulmonary adenocarcinoma pathologically staged between June 1979 and July 2002 were reviewed. All patients had a preoperative computed tomographic scan of the chest and underwent surgical staging by mediastinoscopy, lymph node sampling, or lymph node dissection. Patients with bronchioalveolar cell carcinoma were excluded. Peripheral tumors were compared with central tumors with regard to stage and survival. A tumor was considered to be central if visualized within the inner third of the lung field or seen bronchoscopically. Patients with T1 cancers were further analyzed on the basis of tumor size. Survival was determined by the Kaplan-Meier analysis and comparisons were made by the log-rank method.ResultsCentral tumors were more advanced and demonstrated a significantly (P < .0001) poorer survival than peripheral tumors (median 18 vs 39 months). Sixty percent of patients with central tumors had stage III or stage IV disease compared with 25% of those with peripheral tumors. Central T1 tumors, however, demonstrated a 50% incidence of lymph node involvement. Although the incidence of lymph node metastases increased incrementally with the size of peripheral T1 tumors, it remained 50% for central T1 tumors irrespective of size.ConclusionTumor location for pulmonary adenocarcinoma should be considered when planning therapy. Central tumors have a high incidence of lymph node metastases (regardless of size) and a poorer prognosis.

Background Pneumonectomy after high-dose radiotherapy and concurrent chemotherapy has been associated with high operative mortality. Therefore, most induction protocols limit radiation to 5,000 cGy or less. Additionally, the safety of right pneumonectomy after induction therapy has been questioned. The feasibility of pneumonectomy after high-dose radiotherapy and concurrent chemotherapy is reviewed. Methods From 1990 to 2005, 30 patients with locally advanced nonsmall-cell lung cancer underwent pneumonectomy after 5,940 cGy of radiation and two cycles of etoposide and cisplatin. To minimize postpneumonectomy pulmonary edema, patients were treated with a protocol that included fluid restriction and 48 hours of mechanical ventilation. Morbidity, mortality, and survival were examined. Results There were 18 right and 12 left pneumonectomies. Death occurred in 4 patients (13.3%) but in only 1 (5.6%) after right pneumonectomy. Causes of death included aspiration, bronchopleural fistula, pneumonia, and massive pulmonary embolus. Major morbidity occurred in 5 (pnemonia in 2 and aspiration in 3). Median hospital stay was 9 days (range, 2 to 45), and intensive care unit stay was 2 days (range, 2 to 35). Median overall survival was 22 months with a 5-year survival of 33%. Patients surviving operation had a median survival of 33 months and a 5-year survival of 38%. Conclusions The mortality rate after pneumonectomy after high-dose radiation and concurrent chemotherapy is relatively high but results in significant survival. The mortality rate is not increased after right-sided operations. Pneumonectomy should continue to be offered to patients with advanced locoregional disease after induction high-dose radiotherapy and concurrent chemotherapy when a complete resection cannot be carried out with a lesser procedure.

Therapeutic pulmonary metastectomy is accepted therapy for pulmonary metastases. However, more than 50% of patients who undergo this treatment will experience recurrences, many within the same lobe. Minimally invasive approaches provide an option for therapy that minimizes morbidity and, in the case of RFA, preserves pulmonary function. The long-term results of RFA, even for non-small cell lung cancer, are not yet determined. Resection using a VATS or open approach should continue to remain the standard of care.

Several studies have demonstrated an increased local recurrence rate with sublobar resection (SR) when compared with lobar resection for the treatment of non-small-cell lung cancer (NSCLC). Therefore, lobectomy has remained the gold standard therapy for NSCLC with lesser resection reserved as a compromise operation for high-risk patients. The increased identification of small NSCLC tumors by CT scan is leading many surgeons to question the appropriateness of lobectomy for these tumors. There has been increasing interest by many surgeons to use SR as intentional therapy for patients with small peripheral NSCLC. This article reviews the recent literature and evidence supporting intentional SR for NSCLC. Although lobectomy should continue to be regarded as the procedure of choice for NSCLC, we believe that a subset of patients with favorable characteristics may be appropriately treated with intentional SR as long as good assessment of nodal involvement is made. Future investigation is required to better define when SR is appropriate.

Purpose A major concern with sublobar resection (SR) for non–small-cell lung cancer (NSCLC) is high local recurrence (LR). Adjuvant brachytherapy may reduce LR This multicenter randomized trial compares SR to SR with brachytherapy (SRB). Patients and Methods High-risk operable patients with NSCLC ≤ 3 cm were randomly assigned to SR or SRB. The primary end point was time to LR, where LR included recurrence at the staple line (local progression), in the primary tumor lobe away from the staple line, and in ipsilateral hilar nodes. The trial was designed to have a 90% power to detect a hazard ratio (HR) of 0.315 in favor of SRB, using a one-sided type I error rate of 0.05 with a sample size of 100 eligible patients in each arm. Results Two hundred twenty-four patients were randomly assigned; 222 patients were evaluable for intent-to-treat analysis. Median age was 71 years (range, 49 to 87 years). No differences were found in baseline characteristics. Median follow-up time was 4.38 years (range, 0.04 to 5.59 years). There was no difference in time to LR (HR, 1.01; 95% CI, 0.51 to 1.98; log-rank P = .98) or in the types of LR. Local progression occurred in only 17 (7.7%) of 222 patients. In patients with potentially compromised margins (margin < 1 cm, margin-to-tumor ratio < 1, positive staple line cytology, wedge resection, nodule size > 2.0 cm), SRB did not reduce LR, although trends favored the SRB arm. This was most marked in 14 patients with positive staple line cytology (HR, 0.22; P = .24). Three-year overall survival rates were similar for patients in the SR (71%) and SRB (71%) arms (P = .97). Conclusion Brachytherapy did not reduce LR after SR. This finding may have been related to closer attention to parenchymal margins by surgeons participating in this study.

BACKGROUND. The current study was conducted to review the authors' experience in treating consecutive patients with American Joint Committee on Cancer (1997 revision) Stage III nonsmall cell lung carcinoma with aggressive preoperative chemoradiation followed by surgical resection. METHODS. The records of all patients who received preoperative chemoradiation were evaluated. Patients received 2 cycles of concurrent cisplatin and etoposide with 5940 centigrays of radiation therapy. They then were reevaluated to determine whether they were surgical candidates. If so, resection of the primary tumor with mediastinal lymph node dissection was performed 4-6 weeks after the completion of preoperative treatment. After adequate healing, an additional four cycles of cisplatin/etoposide or carboplatin/paclitaxel was given. RESULTS. Forty-two patients received preoperative chemoradiation, 33 of whom underwent surgical resection (79%), including 9 patients who underwent pneumonectomies. Complete pathologic responses were observed in 27% of these patients. Postoperative complications were noted in 21% of the patients and included persistent air leak, supraventricular arrhythmia, and empyema. There were no reported treatment-related deaths. The median follow-up was 26 months. The overall 5-year survival rate for all patients was 36.5% and was 45.3% for patients who underwent resection. A trend toward increased 5-year survival was observed in patients who had a complete pathologic response (57.1%). Univariate analysis revealed the N stage classification to be significant for predicting a complete response. Patterns of failure revealed the brain to be the most common site of first recurrence (50%) and the only site of recurrence in 36% of patients. There was only one case of local failure. CONCLUSIONS. Preoperative chemoradiation using high radiation doses is feasible with acceptable toxicity. The results of the current study suggest an increased complete pathologic response rate and increased overall survival rate compared with reports in the published literature.

Background and Objectives: This cross-sectional study of postoperative non-small cell lung cancer (NSCLC) patients examined possible effects of vitamin intake and folate status on disease-free survival. Methods Supplemental vitamin usage, dietary vitamin intake (Willett Food Frequency Questionnaire), red blood cell (RBC) folate, and serum folate concentrations were assessed in patients with a history of NSCLC. Exclusion criteria included factors that alter folate status or that are associated with altered nutritional habits: (1) evidence of cancer on history, physical, or chest radiograph; (2) tobacco, alcohol ingestion (>2 drinks/day), or cancer treatment within 3 months; (3) use of folate antagonists; and (4) age

Patients who undergo induction therapy for N2 NSCLC should have histologically documented N2 disease and should be restaged following induction therapy to determine the post-induction status of the mediastinal lymph nodes. Patients who have demonstrable disease need to be stratified to determine if the nodal disease is single station, non-bulky, and macroscopic versus microscopic to determine their potential for cure. Invasive restaging has limited sensitivity and negative predictive indices. Patients with limited single station disease and patients with negative restaging are likely to benefit from surgery. Patients requiring a pneumonectomy should not be offered resection.

The ability to successfully exercise has been used to assess the cardiopulmonary risk of thoracotomy for lung cancer. Because of musculoskeletal, neurologic, peripheral vascular, or behavioral problems, not all patients presenting for pulmonary resection are capable of exercising. Using a multifactorial cardiopulmonary risk index (CPRI) consisting of a cardiac risk index (CRI) and a pulmonary risk index, we studied 74 patients (60 capable of exercising and 14 incapable of exercising) who underwent thoracotomy for lung cancer resection. The groups were similar in reference to history of pulmonary disease, preoperative pulmonary function, and pulmonary risk index score. The no-exercise patients were more likely to have a history of cardiac disease (64 vs 28%; p0.01) and had a higher CRI score (2.0 +/- 0.2 vs 1.4 +/- 0.1; p0.05). Cardiopulmonary postoperative complications (POCs) and mortality were more likely among those in the no-exercise group vs those in the exercise group (POCs, 79 vs 35%, p0.01; mortality, 21 vs 2%, p0.05). Among the eight no-exercise patients with a CPRI of 4 or more, all eight suffered a POC (100%) and three died (38%). Using multiple logistic regression analysis, both the CPRI score and the inability to exercise were independently associated with increased risk for POCs. We conclude that patients unable to perform even minimal preoperative exercise are at substantially increased risk for morbidity and mortality after lung resection. This results both from greater identifiable preoperative cardiopulmonary risk factors (as assessed by the CPRI) and from an independent effect related to the inability to exercise.

Patients with early-stage lung cancer and limited pulmonary reserve may not be appropriate candidates for lobectomy. In these situations, sublobar resection (wedge or segmentectomy) is generally performed. Many physicians believe that segmentectomy is superior because it allows for an improved parenchymal margin and nodal sampling.We performed an analysis using operative and pathology reports collected as part of planned data collection for American College of Surgeons Surgical Oncology Group (ACOSG) Z4032. This was a prospective trial in which patients with clinical stage I lung cancer and limited pulmonary function were randomized to sublobar resection with or without brachytherapy. The operative approach (video-assisted thoracic surgery [VATS] vs thoracotomy), extent of resection, and degree of lymph node evaluation were at the discretion of the individual surgeon. The primary aim of this analysis was to compare the parenchymal margin achieved between segmentectomy and wedge resection. Secondary aims included the extent of nodal staging and whether the operative approach (VATS vs open) had an effect on margin status and nodal evaluation.Among 210 patients, 135 (64%) underwent a VATS approach and 75 (36%) a thoracotomy. A segmentectomy was performed in 57 patients (27%) and a wedge resection in 153 patients (73%). There were no significant differences in the degree of nodal upstaging, stations sampled, or parenchymal margin obtained between VATS and thoracotomy. However, significant differences were observed between patients who underwent a segmentectomy and those who underwent a wedge resection with regard to parenchymal margin (1.5 cm vs 0.8 cm, p = 0.0001), nodal upstaging (9% vs 1%, p = 0.006), and nodal stations sampled (3 vs 1, p0.0001) . Notably, 41% of patients treated by wedge resection had no nodes sampled at the time of operation compared with 2% of those who underwent segmentectomy (p0.0001).In ACOSG Z4032, wedge resection, regardless of the approach, was associated with a smaller parenchymal margin and a lower yield of lymph nodes and rate of nodal upstaging when compared with segmentectomy.

Objective Electromagnetic (EM) navigation is increasingly used to assist with bronchoscopic interventions such as biopsy or fiducial placement. Electromagnetic navigation can also be a useful adjunct to computed tomography (CT)–guided thermal ablation and biopsy of lung tumors. This study compares procedures carried out using an EM navigation system (Veran Medical Technologies Inc, St Louis, MO) with procedures using CT fluoroscopy only. Methods Over a 23-month period, 17 patients scheduled for thermal ablation were prospectively enrolled in this study. The mean age was 72 years (range, 60–84 years). Seven patients were women. Patients were randomized to EM navigation (n = 7) or CT fluoroscopy alone (n = 10). In some cases, additional ablation or biopsies were performed with or without EM navigation depending on the randomization arm. All procedures were performed under general anesthesia either by a thoracic surgeon or a radiologist. Results A total of 23 procedures were performed in 17 patients: 20 were ablation procedures and 3 were biopsies. Fourteen were performed for non–small cell lung cancer, and 9 for pulmonary metastases from other organs. Despite randomization, patients receiving EM navigation had a trend for smaller tumors (mean diameter, 1.45 vs 2.90 cm; P = 0.06). For thermal ablation procedures, the time to complete intervention was significantly less when EM navigation was used (mean, 7.6 vs 19 minutes; P = 0.022). Although not statistically significant, there were fewer skin punctures (mean, 1 vs 1.25; P = 0.082), fewer adjustments (mean, 5.6 vs 11.8; P = 0.203), less CT fluoroscopy time (mean, 21.3 vs 34.3 seconds; P = 0.345), and fewer CT scans (mean, 7 vs 15; P = 0.204) whenever EM navigation was used. Conclusions Electromagnetic navigation reduces the time to successfully place an ablation probe in a target tumor. Further study is required to determine whether EM navigation may also reduce the number of adjustments, skin punctures, and CT scans as well as decrease CT fluoroscopy time.

Background Patients with nonpalpable rib lesions (NPRL) requiring biopsy present a challenging problem for the thoracic surgeon. Ideally, a small incision directly over the NPRL should be performed to minimize morbidity, particularly if the lesion is benign. The Navigator probe is routinely used after lymphoscintigraphy by surgical oncologists to isolate sentinel lymph nodes requiring removal, but can also be used to guide resection of nonpalpable focal rib lesions demonstrating increased technetium-99m hydroxymethylene diphosphonate (Tc-99m HDP) uptake. This report describes our initial experience with this technique. Methods Over a 5-month period, 3 patients with focal NPRL underwent rib resection. All patients had solitary lesions demonstrated on recently performed Tc-99m HDP bone scanning. Prior cancers were reported in 2 patients, and pain in 2 patients. Before surgery, all patients underwent intravenous injection of 20 to 25 mCi Tc-99m HDP at least 2 hours before the Navigator probe-guided procedure. Results The Navigator probe identified all 3 lesions, allowing a single 4 cm or smaller incision in all cases. Histology included metastatic breast cancer (1), pathologic fracture secondary to metastatic palatal cancer (1), and eosinophilic granuloma (1). No patient required further resection. Conclusions Intraoperative localization of NPRL that are positive on Tc-99m HDP bone scanning using the Navigator probe is feasible and was 100% successful in our initial experience. This technique allows a minimally invasive approach, which is beneficial for those patients who do not require further resection.

ObjectiveTransoral incisionless fundoplication (TIF) is a promising approach for gastroesophageal reflux disease (GERD) that may decrease morbidity compared with conventional antireflux procedures. We report our initial experience with this minimally invasive approach.MethodsOver a 24-month period, 46 patients (mean age, 49 years; 50% female) underwent 48 TIF procedures. All procedures were performed under general anesthesia. Two surgeons participated in all cases; one served as the endoscopist, and the other performed the partial fundoplication. Heartburn severity was measured using the GERD health-related quality of life (GERD-HRQL) instrument (best score = 0, worst score = 45), which includes an additional question assessing overall satisfaction.ResultsPreoperatively, 33 (72%) of 46 patients had small (

Recent studies have used preoperative cardiopulmonary exercise testing to improve risk assessment of pulmonary resection for lung cancer. These studies have demonstrated inconsistent correlation between peak oxygen uptake ( V ˙ O 2 ) and postoperative complications but have not systematically examined other methods of risk stratification. We analyzed the findings in 42 patients who had cardiopulmonary exercise testing prior to lung cancer resection. Preoperative clinical data combining pulmonary factors (obesity, productive cough, wheezing, tobacco use, ratio of the forced expiratory volume in 1 s over the forced vital capacity [FEV1/FVC] 45 mm Hg), and an established cardiac risk index were used to generate a cardiopulmonary risk index (CPRI). When analyzed using the risk index, the incidence of postoperative complications increased with higher CPRI scores. Those with a CPRI of 4 or greater were 22 times more likely to develop a complication, compared to a CPRI of less than 4 (p

Small peripheral pulmonary nodules ranging in size from 1 mm to 20 mm were excised in 58 patients. Computed tomography was used to mark the skin overlying the nodules to minimize the surgical exposure needed for operative identification. The nodules were 1 cm or less in maximum diameter in 76% of the patients. Twenty-six patients had single nodules and 32 patients had multiple nodules. The preoperative diagnosis was inaccurate in 67% of the patients. In 61% of the patients in whom malignancy was suspected, no tumor was demonstrated. Conversely, of the 20 patients in whom a malignant nodule was excised, the preoperative diagnosis was correct in only 50%. Thirty-one patients required no further treatment apart from their biopsy and 27 required additional intervention. Small peripheral pulmonary nodules require biopsy for diagnosis. When percutaneous needle aspiration biopsy is unsuccessful, or technically difficult, a computed tomography-guided thoracotomy is an effective and minimally invasive surgical alternative.

The autoperfused working heart-lung preparation has been proposed as a method for long-term heart-lung preservation. We investigated the effects of acellular oxygen-carrying perfusates (study 1) and the effect of donor pretreatment with indomethacin (study 2) on the working ex vivo heart-lung block. In study 1 perfusion with stroma-fee hemoglobin resulted in significantly reduced survival (118 +/- 46 minutes) compared with autologous blood (561 +/- 125 minutes, p less than 0.05) or perfluorocarbon (438 +/- 114 minutes, p less than 0.05). Decrease in survival with stroma-free hemoglobin perfusate is associated with a marked decrease in left ventricular performance and a significant increase in pulmonary vascular resistance. Perfusion with autologous blood is associated with a significant increase in pulmonary vascular resistance after 240 minutes of explantation, which is significantly delayed by perfusion with perfluorocarbon. Perfusion for 6 hours with blood pretreated with indomethacin (study 2) resulted in a decrease in the concentration of prostacyclin and thromboxane A2 metabolites but an increase in the prostaglandin/thromboxane A2 metabolite ratio. This is associated with abrogation of the increase in pulmonary vascular resistance (12,787 +/- 1682 dynes/sec/cm-5, T = 0; 13,134 +/- 2654 dynes/sec/cm-5, T = 360 minutes) observed in preparations perfused with autologous blood (13,194 +/- 1942 dynes/sec/cm-5, T = 0; 24,768 +/- 3325 dynes/sec/cm-5, T = 360 minutes, p less than 0.05). We conclude that alteration of the cellular and humoral components of autologous blood may prove advantageous for increasing the utility of the autoperfused working heart-lung preparation as a preservation technique.

Background . The cancer cachexia syndrome occurs in patients with non-small cell lung cancer (NSCLC) and includes elevated resting energy expenditure (REE). This increase in REE leads to weight loss, which in turn confers a poor prognosis. This study was undertaken to determine whether the cancer cachexia syndrome occurs in patients with nonmetastatic NSCLC. Methods . In this case-control study, 18 patients with nonmetastatic NSCLC (stages IA to IIIB) were matched to healthy controls on age (± 5 years), gender, and body mass index (± 3 kg/m 2 ). Only 4 cancer patients had experienced > 5% weight loss. Cancer patients and controls were compared on the basis of: (1) unadjusted REE, as measured by indirect calorimetry; (2) REE adjusted for lean body mass, as measured by dual x-ray absorptiometry; (3) REE adjusted for body cell mass, as measured by potassium-40 measurement; and (4) REE adjusted for total body water, as measured by tritiated water dilution. Results . We observed no significant difference in unadjusted REE or in REE adjusted for total body water. However, with separate adjustments for lean body mass and body cell mass, cancer patients manifested an increase in REE: mean difference ± standard error of the mean: 140 ± 35 kcal/day ( p = 0.001) and 173 ± 65 kcal/day ( p = 0.032), respectively. Further adjustment for weight loss yielded similarly significant results. Conclusions . These results suggest that the cancer cachexia syndrome occurs in patients with nonmetastatic NSCLC and raise the question of whether clinical trials that target cancer cachexia should be initiated before weight loss.

Background and Objectives This case control study explored the purported inverse relationship between folate status and lung cancer development. Methods Folate status of 46 postoperative non-small cell lung cancer (NSCLC) patients was compared to that of 44 non-cancer patients. Cancer patients had completed treatment > 3 months prior and had no evidence of cancer. Ineligibility criteria for all patients included (1) > 2 alcoholic drinks/day (2) ongoing tobacco use, or (3) folate supplementation > 400 μg/day. Results No differences were found between groups in serum and RBC folate after adjustment for age and use of folate-interfering medications: geometric means (GM) × /geometric standard error (GSE): 7.9 ng/ml × /1.1 vs. 7.8 ng/ml × /1.1, respectively (P = 0.91) for serum folate; 264 ng/ml × /1.1 vs. 263 ng/ml × /1.1, respectively (P = 0.97) for RBC folate. Age- and creatinine-adjusted homocysteine was no different between groups: GM × /GSE: 9.4 μmol/L × /1.0 vs. 8.6 μmol/L × /1.0, respectively (P = 0.17). No difference were seen in folate intake. Frequencies of the homozygous genotype for the MTHFR polymorphism, an enzyme important in folate metabolism and associated with a reduced risk of other cancers, were no different. Conclusions This case control study does not support the hypothesis that low folate is an independent risk factor for NSCLC. J. Surg. Oncol. 2001;77:247–252. © 2001 Wiley-Liss, Inc.

We studied pulmonary function tests, maximal voluntary ventilation, arterial blood gases, and respiratory muscle strength and recruitment pattern in a 37-yr-old symptomatic man before and after surgical plication for a left unilateral diaphragmatic paralysis. After plication, FVC, FEV1, TLC and FRC increased, whereas residual volume remained unchanged. Arterial PO2 improved from 70 to 87 mm Hg. Diaphragmatic strength, as expressed by the maximal transdiaphragmatic pressure increased from 30 to 75 cm H2O, and maximal voluntary ventilation increased from 74 to 123 L/min. Ventilatory muscle recruitment also changed: there was a shift from a positive to a negative delta Pg/delta Ppl slope during tidal breathing. This indicates more effective diaphragmatic recruitment after the procedure. We conclude that surgical plication may be of benefit to patients with symptomatic unilateral diaphragmatic paralysis. The improvement is due to improved respiratory muscle function.

Increased resting energy expenditure (REE) is thought to confer a poor prognosis in patients with non-small cell lung cancer (NSCLC). However, no study has validated this hypothesis to date. This study's objective was to examine the prognostic significance of REE in NSCLC.Seventeen patients with NSCLC (stages IA-IIIB) underwent measurement of REE with indirect calorimetry before the initiation of cancer treatment. Similar measurements were performed in 17 control subjects, each of whom was matched to a cancer patient by age ( +/-5 years), sex and body mass index ( +/-3 kg/m2). Patients were classified as hypermetabolic or hypometabolic based on a direct comparison of measured REE between cancer patients and their matched controls. After cancer treatment, these 17 patients were followed for evidence of metastatic disease for up to 32 months.Six patients developed metastatic disease. The eight hypometabolic cancer patients had a significantly shorter mean disease-free survival compared to the nine hypermetabolic cancer patients: 19 months (95% confidence interval (CI) 12, 26) versus 29 months (95% CI 24, 34), respectively (P0.05 by log-rank test). In contrast, Cox regression showed no relationship between disease-free survival and differences in REE between cancer patients and their matched controls (P = 0.20).These results suggest that hypermetabolism may predict a longer disease-free survival in NSCLC patients. This finding differs from the prevailing hypothesis that hypometabolic patients with NSCLC survive longer, and deserves further investigation.

Comprising 1.6% of primary bone malignancies, parosteal osteosarcomas are rare. Rib parosteal osteosarcomas are even rarer, with only 2 cases in the literature. We report a third such case, with a 32-month disease-free survival. Issues relevant to the management of rib parosteal osteosarcomas are discussed.

7524 Background: A multicenter study (Z4032) compared sublobar resection (SR) to sublobar resection with brachytherapy (SRB) for stage I NSCLC. Local recurrence (LR) and overall survival (OS) rates at 3-years (3-yr) were similar between arms (see abstract 113613). This analysis combines arms, and evaluates the effect of factors previously reported to impact oncological outcomes after SR. Methods: 213 patients (pts) were evaluable for analysis. LR was defined as recurrence at the staple line (local progression), same lobe away from the staple line, or within hilar nodes. Factors assessed for impact on 3-yr outcomes were: resection type (wedge/segmentectomy), margin size (2cm) and staple line cytology (+/-). Results: LR occurred in 27/213 (12.6%) pts and included local progression in 12/213 (5.6%). OS rate at 3-yr was 152/213 (71.4%). Trends favored the use of segmentectomy, margin:tumor ratio≥1, tumor size ≤2cm and negative staple line cytology; no factor reached statistical significance at 3-yr. The only factor significantly (p=0.02) associated with decreased 3-yr LR was margin size ≥1cm (8.3%) compared to margin

The objective of this study was to assess the prevalence of pathologically proven intrapulmonary lymph nodes and to evaluate their appearance on CT.Over a 15-year period (1980-1994), 184 patients underwent minithoracotomies for evaluation of CT-detected peripheral pulmonary abnormalities. Of these 184 patients, 96 had well-circumscribed peripheral pulmonary nodules. The size, position, and radiographic features of all pathologically proven intrapulmonary lymph nodes were independently assessed by two experienced radiologists.The nodules in 17 (18%) of the 96 patients with well-circumscribed peripheral pulmonary nodules were pathologically proven to be intrapulmonary lymph nodes. Two of the 17 patients had two nodules; the remaining patients had solitary nodules. The maximum diameter of the nodules varied from 7 to 12 mm. All the nodes were located within 20 mm of a visceral pleural surface. Twelve of the nodules were located in the lower lobes, and the remaining nodules were located in the right middle lobe.Although intrapulmonary lymph nodes are not a well-known entity, our results indicate that they are discovered in a significant number of patients who undergo minithoracotomies for the evaluation of CT-detected pulmonary nodules. Although these lymph nodes do not possess any specific CT appearance, they should be considered in the differential diagnosis of single (or multiple) parenchymal nodules, particularly those found in the lower lobes.

A 38-year-old woman came for treatment with massive hemoptysis. A hilar density was observed on a chest radiograph. Transthoracic echocardiography demonstrated an intravascular pulmonary arterial mass that was studied in further detail with multiplane and panoramic transesophageal echocardiography. Surgical resection proved the mass to be a sarcoma arising from the main pulmonary artery. This case report demonstrates the utility of multiplane and panoramic transesophageal echocardiography in the study of intravascular tumors of the thorax.

4029 Background: Cetuximab is an IgG1, chimerized, monoclonal antibody that binds specifically to the epidermal growth factor receptor. Cetuximab improves survival when combined with radiation for patients with locally advanced head and neck cancer. We evaluated the safety and efficacy of the addition of cetuximab to concurrent chemoradiation for patients with esophageal and gastric cancer. Methods: Patients with adenocarcinoma or squamous cell cancer of the esophagus or stomach without distant organ metastases were eligible. Patients with locally advanced disease from mediastinal, celiac, portal and gastric lymphadenopathy were eligible. Surgical resection was not required. Clinical complete response was defined as no tumor on postreatment endoscopic biopsy. Patients received cetuximab, 400mg/m2 week #1 then 250 mg/m2/week for 5 weeks, paclitaxel, 50 mg/m2/week, and carboplatin, AUC =2 weekly for 6 weeks, with concurrent 50.4 Gy radiation. Results: Thirty-seven patients have been entered. The median age was 61 (range of 30–87). Thirty-four have esophageal cancer and 3 have gastric cancer. Of the patients with esophageal cancer, twenty-five have adenocarcinoma and nine have squamous cell cancer. Thus far, 30 patients have completed treatment and are evaluable for toxicity. There have been no grade 4 non-hematologic toxicities and 1 pt had grade 4 neutropenia (3%). Six patients (20%) had grade 3 esophagitis. Other grade 3 toxicities included dehydration (n=5), rash (n=9), and paclitaxel/cetuximab hypersensitivity reactions (n=2). Eighteen of 27 patients (67%) have had clinical complete response. Seven pts out of 16 (43%) who have gone to surgery have had a pathologic CR. Conclusions: Cetuximab can be safely administered with chemoradiation for patients with esophageal cancer. Consistent with the data in head and neck cancer, cetuximab increases cutaneous toxicity but does not increase mucositis/esophagitis when combined with chemoradiation. Further evaluation is ongoing. [Table: see text]

Computed tomographic scans of the chest were utilized to stage mediastinal disease in 148 instances of bronchogenic carcinoma considered for resection in 146 patients. Nodes ≥ 1.5 cm in diameter were interpreted as abnormal. All nodes positive by computed tomography were evaluated by mediastinoscopy, anterior mediastinotomy, or thoracotomy. All patients with negative computed tomographic findings underwent thoracotomy without prior surgical staging. Patients undergoing thoracotomy were divided into two groups. In Group I (first 51 instances) routine mediastinal exploration was not carried out; in Group II (last 97 instances) the mediastinum was explored in every patient and nodes were submitted for histopathological study. The computed tomographic and pathological findings on the mediastinal lymph nodes were compared. The sensitivity, specificity, and accuracy of computed tomography in Group I were 88%, 94%, and 92%, respectively, in Group II 75%, 89%, and 86%, and in the combined group, 80%, 91 %, and 88 %. The positive predictive index in Group I, Group II, and in the combined group was 88%, 69 %, and 77 %, respectively. It was lower for central than peripheral lesions (74 % versus 88 %) and was lowest for lesions in the right upper and left lower lobes. The negative predictive index was greater than 90% for all groups and all tumor sites except the left upper lobe, where it was 89%. Ten patients had false-positive scans, three with old mediastinitis and seven with postobstructive pneumonia; nine of the 10 had central lesions, and seven of these lesions were located in the right upper lobe. Eight patients had false-negative scans; six had para-aortic, subaortic, or postsubcarinal nodes. These nodes would not have been accessible to mediastinoscopy. In only one patient with false-negative nodes would routine mediastinoscopy have prevented thoracotomy and resection. Computed tomographic staging of mediastinal disease is indicated for all patients with lung cancer in whom operation is contemplated. Computed tomography directs the most appropriate staging procedure for patients with positive findings and obviates invasive staging for patients with negative findings.

Intravascular macrophages were found commonly in sections of calf lung capillaries. These cells were large with many pseudopodia of various sizes. The cell membrane was covered with an electron-opaque coat which remains between adjacent pseudopodial walls and results in structures suggesting “micropinocytosis vermiformis.” The cytoplasm of the macrophage was electron-lucent and contained endoplasmic reticulum, numerous mitochondria, free ribosomes, Golgi zones, dense bodies and vesicles of many sizes. These macrophages showed phagocytic activity. During erythrophagocytosis, a dense layer initially appeared at the red blood cell periphery. This layer moved toward the center together with the erythrocyte membrane as phagocytosis progressed. Simultaneously, the electron opacity of the red blood cell decreased until the cell was completely dispersed within the macrophage. This erythrophagocytosis occurred relatively seldom. The possibility that intravascular macrophages are the pre-cursors of alveolar macrophages is discussed.

To more clearly characterize the role of computed tomography in staging the mediastinal lymph nodes of patients with lung cancer, we analyzed computed tomographic and surgical findings in the chest in 345 consecutive patients with lung cancer who underwent operative staging. Patients were grouped according to the TNM staging system of the American Joint Commission, central or peripheral location of the primary tumor, lobar location of the tumor, and maximum tumor diameter as determined by computed tomography or gross pathology. One third of patients with abnormal findings on the computed tomographic scan did not have mediastinal lymph node metastases. Mediastinal metastases occurred frequently in patients with central cancers (38%). The predictive value of a negative scan in all patients was high (≥90%) except for patients with central T3 lesions (72%), left upper lobe lesions (83%), and central adenocarcinomas (75%). However, only the differences between central T3 and central T2 or T1 lesions, and between central adenocarcinomas and central squamous cell carcinomas, were unlikely to be due to chance alone (p

Scanning electron microscopy has been used to assess alveolar surface topography in a canine model of induced acute respiratory insufficiency (ARI). Mongrel dogs were infused with saline solution intermittently, continuously, or continuously with intermittent furosemide treatment. Ultrastructural and pathophysiological correlates of ARI were seen only in dogs that had fluid loading continuously at 100 ml. per kilogram of body weight per hour for 4 to 6 hours and that were not treated with furosemide. In acute pulmonary edema produced by continuous fluid overloading, the alveolar cell-air interface was altered. Irregular surface elevations, extravasated erythrocytes, and an apparent reduction in the diameter of the pores of Kohn were observed only in alveoli from dogs that died terminally after 4 to 6 hours of continuous fluid overloading. The morphological changes at the alveolar gas-exchange surface correlated with data indicating that respiratory function was being compromised by pulmonary edema. These observations and their relation to the genesis of ARI induced in the dog by continuous fluid overloading may provide a model for better understanding iatrogenic clinical respiratory failure.

ObjectiveRadiofrequency ablation for Barrett's esophagus in combination with an antireflux procedure has not been widely documented. We report our initial experience with radiofrequency ablation in association with antireflux procedure for Barrett's metaplasia and low-grade dysplasia.MethodsA total of 14 patients (10 male and 4 female patients) presented with Barrett's metaplasia (n=11) or low-grade dysplasia (n=3). Median age was 60 years (38–80 years). The severity of Barrett's esophagus was classified by length (in centimeters), appearance (circumferential/noncircumferential), and histology (1, normal; 2, Barrett's metaplasia; and 3, low-grade dysplasia). Radiofrequency ablation was performed with the HALO 360° or 90° systems (BARRX Medical, Sunnyvale, Calif).ResultsMedian follow-up was 17 months. The mean number of ablative procedures undertaken was 2.6 (range, 1–6). There was no mortality, but there were 2 perioperative complications after the antireflux procedure (pneumonia, 1; atrial fibrillation, 1). One patient had mild dysphagia requiring a single dilation 2 months after ablation. The mean length of Barrett's esophagus decreased from 6.2 to 1.2cm after treatment (P=.001). Barrett's grade decreased significantly (P=.003). Before therapy, circumferential Barrett's esophagus was present in 13 patients. At last endoscopy, only 1 patient had circumferential Barrett's esophagus present. The number of radiofrequency ablation treatments was significantly (P < .05) associated with success. All patients receiving 3 or more treatments had complete resolution of Barrett's metaplasia.ConclusionsRadiofrequency ablation performed either before or after an antireflux procedure is safe. This approach is effective for reducing or eliminating metaplasia and dysplasia. Long-term studies will be necessary to determine whether this approach can provide durable control of both reflux and Barrett's esophagus.

Objective Sublobar resection (SR) is commonly used for patients considered high risk for lobectomy. Nonoperative therapies are increasingly being reported for patients with similar risk because of perceived lower morbidity. We report 30- and 90-day adverse events (AEs) from American College of Surgeons Oncology Group Z4032, a multicenter phase III study for high-risk patients with stage I non–small cell lung cancer. Methods Data from 222 evaluable patients randomized to SR (n = 114) or SR with brachytherapy (n = 108) are reported. AEs were recorded using the Common Terminology Criteria for Adverse Events, Version 3.0, at 30 and 90 days after surgery. Risk factors (age, percent baseline carbon monoxide diffusion in the lung [DLCO%], percent forced expiratory volume in 1 second [FEV1%], upper lobe vs lower lobe resections, performance status, surgery approach, video-assisted thoracic surgery vs open and extent, and wedge vs segmentectomy) were analyzed using a multivariable logistic model for their impact on the incidence of grade 3 or higher (G3+) AEs. Respiratory AEs were also specifically analyzed. Results Median age, FEV1%, and DLCO% were similar in the 2 treatment groups. There was no difference in the location of resection (upper vs lower lobe) or the use of segmental or wedge resections. There were no differences between the groups with respect to "respiratory" G3+ AEs (30 days: 14.9% vs 19.4%, P = . 35; 0–90 days: 19.3% vs 25%, P = . 31) and "any" G3+ AEs (30 days: 25.4% vs 30.6%, P = . 37; 0–90 days: 29.8% vs 37%, P = . 25). Further analysis combined the 2 groups. Mortality occurred in 3 patients (1.4%) by 30 days and in 6 patients (2.7%) by 90 days. Four of the 6 deaths were thought to be due to surgery. When considered as continuous variables, FEV1% was associated with "any" G3+ AE at days 0 to 30 ( P = . 03; odds ratio [OR] = 0.98) and days 0 to 90 ( P = . 05; OR = 0.98), and DLCO% was associated with "respiratory" G3+ AE at days 0 to 30 ( P = . 03; OR = 0.97) and days 0 to 90 ( P = . 05; OR = 0.98). Segmental resection was associated with a higher incidence of any G3+ AE compared with wedge resection at days 0 to 30 (40.3% vs 22.7%; OR = 2.56; P 01) and days 0 to 90 (41.5% vs 29.7%; OR = 1.96; P = . 04). The median FEV1% was 50%, and the median DLCO% was 46%. By using these median values as potential cutpoints, only a DLCO% of less than 46% was significantly associated with an increased risk of "respiratory" and "any" G3+ AE for days 0 to 30 and 0 to 90. Conclusions In a multicenter setting, SR with brachytherapy was not associated with increased morbidity compared with SR alone. SR/SR with brachytherapy can be performed safely in high-risk patients with non–small cell lung cancer with low 30- and 90-day mortality and acceptable morbidity. Segmental resection was associated with increased "any" G3+ AE, and DLCO% less than 46% was associated with "any" G3+ AE and "respiratory" G3+ AE at both 30 and 90 days.

Introduction Homologous recombination repair (HRR) is a critical pathway for the repair of DNA damage caused by cisplatin or poly-ADP ribose polymerase (PARP) inhibitors. HRR may be impaired by multiple mechanisms in cancer, which complicates assessing the functional HRR status in cells. Here, we monitored the ability of non–small-cell lung cancer (NSCLC) cells to form subnuclear foci of DNA repair proteins as a surrogate of HRR proficiency. Methods We assessed clonogenic survival of 16 NSCLC cell lines in response to cisplatin, mitomycin C (MMC), and the PARP inhibitor olaparib. Thirteen tumor explants from patients with NSCLC were subjected to cisplatin ex vivo. Cells were assayed for foci of repair-associated proteins such as BRCA1, FANCD2, RAD51, and γ-H2AX. Results Four cell lines (25%) showed an impaired RAD51 foci-forming ability in response to cisplatin. Impaired foci formation correlated with cellular sensitivity to cisplatin, MMC and olaparib. Foci responses complemented or superseded genomic information suggesting alterations in the ATM/ATR and FA/BRCA pathways. Because baseline foci in untreated cells did not predict drug sensitivity, we adapted an ex vivo biomarker assay to monitor damage-induced RAD51 foci in NSCLC explants from patients. Ex vivo cisplatin treatment of explants identified two tumors (15%) exhibiting compromised RAD51 foci induction. Conclusions A fraction of NSCLC harbors HRR defects that may sensitize the affected tumors to DNA-damaging agents including PARP inhibitors. We propose that foci-based functional biomarker assays represent a powerful tool for prospective determination of treatment sensitivity, but will require ex vivo techniques for induction of DNA damage to unmask the underlying HRR defect.

Background Z4032 was a randomized study conducted by the American College of Surgeons Oncology Group comparing sublobar resection alone versus sublobar resection with brachytherapy for high-risk operable patients with non–small cell lung cancer (NSCLC). This evaluates early impact of adjuvant brachytherapy on pulmonary function tests, dyspnea, and perioperative (30-day) respiratory complications in this impaired patient population. Methods Eligible patients with stage I NSCLC tumors 3 cm or smaller were randomly allocated to undergo sublobar resection with (SRB group) or without (SR group) brachytherapy. Outcomes measured included the percentage predicted forced expiratory volume in 1 second (FEV1%), percentage predicted carbon monoxide diffusion capacity (DLCO%), and dyspnea score per the University of California San Diego Shortness of Breath Questionnaire. Pulmonary morbidity was assessed per the Common Terminology Criteria for Adverse Events version 3.0. Outcomes were measured at baseline and 3 months. A 10% change in pulmonary function test or 10-point change in dyspnea score was deemed clinically meaningful. Results Z4032 permanently closed to patient accrual in January 2010 at 224 patients. At 3-month follow-up, pulmonary function data are currently available for 148 (74 SR and 74 SRB) patients described in this report. There were no differences in baseline characteristics between arms. In the SR arm, 9 patients (12%) reported grade 3 respiratory adverse events, compared with 12 (16%) in the SRB arm ( P = .49). There was no significant change in percentage change in DLCO% or dyspnea score from baseline to 3 months within either arm. In the case of FEV1%, percentage change from baseline to 3 months was significant within the SR arm ( P = .03), with patients reporting improvement in FEV1% at month 3. Multivariable regression analysis (adjusted for baseline values) showed no significant impact of treatment arm, tumor location (upper vs other lobe), or surgical approach (video-assisted thoracoscopic surgery vs thoracotomy) on 3-month FEV1%, DLCO%, and dyspnea score. There was no significant difference in incidence of clinically meaningful (10% pulmonary function or 10-point dyspnea score change) change between arms. Twenty-two percent of patients with lower-lobe tumors and 9% with upper-lobe tumors demonstrated 10% decline in FEV1% (odds ratio, 2.79; 95 confidence interval, 1.07–7.25; P = .04). Conclusions Adjuvant intraoperative brachytherapy in conjunction with sublobar resection did not significantly worsen pulmonary function or dyspnea at 3 months in a high-risk population with NSCLC, nor was it associated with increased perioperative pulmonary adverse events. Lower-lobe resection was the only factor significantly associated with clinically meaningful decline in FEV1%.

Objective This study examined the impact of neoadjuvant chemotherapy and concurrent high-dose radiation therapy on survival in patients with node-negative T3 and T4 non–small cell lung cancer. Methods A total of 110 consecutive patients underwent surgical resection for invasive T3N0M0 (94 patients) and T4N0M0 (16 patients) non–small cell lung cancer between 1979 and 2008. Forty-seven patients received neoadjuvant chemotherapy and concurrent high-dose (5940 cGy) radiation therapy before resection (Chemo-RT group). Sixty-three patients underwent surgical resection without receiving induction chemoradiotherapy (Surg group), of whom 21 received neoadjuvant radiation, 19 received adjuvant radiation, 17 received surgery alone, 2 received adjuvant chemotherapy, 2 received adjuvant chemoradiotherapy, and 2 received brachytherapy. Survival of the Chemo-RT and Surg groups was compared using both crude and adjusted Cox proportional hazards models. Results The 5-year, 10-year, and median survivals were 61%, 50%, and 90 months, respectively, in the Chemo-RT group versus 22%, 14%, and 22 months, respectively, in the Surg group. Subjects in the Surg group had an increased risk of death (hazard ratio, 2.60; 95% confidence interval, 1.62–4.18; P = .0001) compared with the Chemo-RT group. After adjustment for potential confounding variables of age, sex, tumor size, tumor location, type of operation, and decade of care, subjects in the Surg group remained at increased risk of death (hazard ratio, 2.81; 95% confidence interval, 1.45–5.44, P = .002) compared with the Chemo-RT group. Conclusions Aggressive treatment of node-negative invasive T3 and T4 NSCLC with induction chemoradiotherapy may significantly prolong survival. This approach should be evaluated in a prospective multicenter national trial.