Stereotactic ablative radiotherapy before resection to avoid delay for early-stage lung cancer or oligometastases during the COVID-19 pandemic: Pathologic outcomes from the SABR-BRIDGE protocol.

BACKGROUND: During coronavirus disease 2019 (COVID-19)-related operating room closures, some multidisciplinary thoracic oncology teams adopted a paradigm of stereotactic ablative radiotherapy (SABR) as a bridge to surgery, an approach called SABR-BRIDGE. This study presents the preliminary surgical and pathological results. METHODS: Eligible participants from four institutions (three in Canada and one in the United States) had early-stage presumed or biopsy-proven lung malignancy that would normally be surgically resected. SABR was delivered using standard institutional guidelines, with surgery >3 months following SABR with standardized pathologic assessment. Pathological complete response (pCR) was defined as absence of viable cancer. Major pathologic response (MPR) was defined as ≤10% viable tissue. RESULTS: Seventy-two patients underwent SABR. Most common SABR regimens were 34 Gy/1 (29%, n = 21), 48 Gy/3-4 (26%, n = 19), and 50/55 Gy/5 (22%, n = 16). SABR was well-tolerated, with one grade 5 toxicity (death 10 days after SABR with COVID-19) and five grade 2-3 toxicities. Following SABR, 26 patients underwent resection thus far (13 pending surgery). Median time-to-surgery was 4.5 months post-SABR (range, 2-17.5 months). Surgery was reported as being more difficult because of SABR in 38% (n = 10) of cases. Thirteen patients (50%) had pCR and 19 (73%) had MPR. Rates of pCR trended higher in patients operated on at earlier time points (75% if within 3 months, 50% if 3-6 months, and 33% if ≥6 months; p = .069). In the exploratory best-case scenario analysis, pCR rate does not exceed 82%. CONCLUSIONS: The SABR-BRIDGE approach allowed for delivery of treatment during a period of operating room closure and was well-tolerated. Even in the best-case scenario, pCR rate does not exceed 82%.

Circulating tumor cells detected in follow-up predict survival outcomes in tri-modality management of advanced non-metastatic esophageal cancer: a secondary analysis of the QUINTETT randomized trial.

BACKGROUND: Our aim was to establish if presence of circulating tumor cells (CTCs) predicted worse outcome in patients with non-metastatic esophageal cancer undergoing tri-modality therapy. METHODS: We prospectively collected CTC data from patients with operable non-metastatic esophageal cancer from April 2009 to November 2016 enrolled in our QUINTETT esophageal cancer randomized trial (NCT00907543). Patients were randomized to receive either neoadjuvant cisplatin and 5-fluorouracil (5-FU) plus radiotherapy followed by surgical resection (Neoadjuvant) or adjuvant cisplatin, 5-FU, and epirubicin chemotherapy with concurrent extended volume radiotherapy following surgical resection (Adjuvant). CTCs were identified with the CellSearch® system before the initiation of any treatment (surgery or chemoradiotherapy) as well as at 6-, 12-, and 24-months post-treatment. The threshold for CTC positivity was one and the findings were correlated with patient prognosis. RESULTS: CTC data were available for 74 of 96 patients and identified in 27 patients (36.5%) at a median follow-up of 13.1months (interquartile range:6.8-24.1 months). Detection of CTCs at any follow-up visit was significantly predictive of worse disease-free survival (DFS;hazard ratio [HR]: 2.44; 95% confidence interval [CI]: 1.41-4.24; p=0.002), regional control (HR: 6.18; 95% CI: 1.18-32.35; p=0.031), distant control (HR: 2.93; 95% CI: 1.52-5.65;p=0.001) and overall survival (OS;HR: 2.02; 95% CI: 1.16-3.51; p=0.013). After adjusting for receiving neoadjuvant vs. adjuvant chemoradiotherapy, the presence of CTCs at any follow-up visit remained significantly predictive of worse OS ([HR]:2.02;95% [Cl]:1.16-3.51; p=0.013) and DFS (HR: 2.49;95% Cl: 1.43-4.33; p=0.001). Similarly, any observed increase in CTCs was significantly predictive of worse OS (HR: 3.14; 95% CI: 1.56-6.34; p=0.001) and DFS (HR: 3.34; 95% CI: 1.67-6.69; p<0.001). CONCLUSION: The presence of CTCs in patients during follow-up after tri-modality therapy was associated with significantly poorer DFS and OS regardless of timing of chemoradiotherapy.

Surgery crisis simulation during the COVID-19 pandemic.

SummaryCOVID-19 puts health care providers at risk for infection with SARS-CoV-2. Personal protective equipment (PPE) can reduce viral transmission if used properly. We used simulation of an intraoperative crisis involving an infectious outbreak to assess PPE adherence and confidence in PPE use. Simulation of an intraoperative crisis with a patient with COVID-19 revealed gaps in PPE adherence; however, simulation training successfully increased confidence in PPE use and received positive feedback.

The Potential Dangers of Recruitment Maneuvers During One Lung Ventilation Surgery.

BACKGROUND: Existing evidence regarding lung-protective ventilation (LPV) during one-lung ventilation (OLV) focuses on surrogate outcomes. Our objective was to assess whether an LPV protocol during OLV surgery is associated with reduced respiratory complications. MATERIALS AND METHODS: This was a matched control retrospective cohort study of patients undergoing pulmonary resection at a tertiary Canadian hospital. The experimental group (n = 50) was derived from primary data of two crossover RCTs, which utilized protocolized LPV strategies with varying levels of positive end-expiratory pressure and recruitment maneuvers. The control group was drawn from a prospectively maintained database; these patients received conventional nonprotocolized ventilation (2000-2010). Each experimental group patient was matched 1:1 with a control group patient with respect to clinically relevant variables (age, sex, diagnosis, smoking status, cardiovascular disease status, comorbidity, BMI, preoperative forced expiratory volume in 1 s, surgery type). Major respiratory complications were defined as composite of acute respiratory distress syndrome, need for new positive-pressure ventilation, and atelectasis requiring bronchoscopy. Paired and unpaired statistical tests were used. RESULTS: Patients appeared well matched. Major respiratory complications occurred in 8% (n = 4) and 2% (n = 1) of patients in experimental and control groups, respectively (P = 0.50). There was a trend toward increased mortality (4 versus 0, P = 0.06) with protocolized LPV. The patients who died had respiratory complications; one had acute respiratory distress syndrome and two had profound hypoxemia. CONCLUSIONS: There was a nonsignificant trend toward increased mortality with LPV during OLV. Although limited by a small sample size, our findings identify a potential danger to excessive recruitment maneuvers. Larger studies, with clinically important outcomes are needed to better define the risk/benefit trade-offs for LPV during OLV.

RBC transfusion is associated with increased risk of respiratory failure after pneumonectomy.

BACKGROUND AND OBJECTIVES: Pneumonectomy is associated with high risk of respiratory complications. Our objective was to determine if transfusions are associated with increased rate of ARDS and respiratory failure in adults undergoing elective pneumonectomy. METHODS: Retrospective cohort study of consecutive pneumonectomies undertaken at a tertiary hospital (2003-2013). Multivariable logistic regression was performed to adjust for confounding factors. RESULTS: ARDS and respiratory failure occurred in 12.4% (n = 20) and 19.2% (n = 31) of 161 pneumonectomy patients, respectively, and were more likely to occur in transfused patients (P = 0.03, P < 0.001). pRBCs, FFP and platelets were transfused in 27% (n = 43), 6% (n = 9), and 2% (n = 3), respectively. On multivariable analyses utilizing blood products as continuous and binary variables, pRBC use was the only independent predictor of ARDS with odds ratio (OR) = 1.23 (95%CI:1.08-1.39, P = 0.002) and OR = 2.45 (95%CI:1.10-5.49, P = 0.03), respectively. On multivariable analyses utilizing blood products as continuous and binary variables, pRBCs were the only independent predictor of respiratory failure with OR = 1.37 (95%CI:1.16-1.60, P < 0.001) and OR = 3.17 (95%CI:1.25-8.02, P = 0.02), respectively. CONCLUSIONS: Peri-operative pRBC use appears to be an independent risk factor for ARDS and respiratory failure after pneumonectomy. There is a significant dose-response relationship. Platelets and FFP did not appear to increase ARDS risk but this may be due to low utilization.

Is it safe to wait? The effect of surgical wait time on survival in patients with non-small cell lung cancer.

BACKGROUND: The effect of surgical wait times on survival in patients with non-small cell lung cancer (NSCLC) remains largely unknown. Our objective was to determine the effect of surgical wait time on survival and incidence of upstaging in patients with stage I and II NSCLC. METHODS: All patients with clinical stage I and II NSCLC who underwent surgical resection in a single centre between January 2010 and December 2011 were reviewed. Analysis was stratified based on preoperative clinical stage. We assessed the effect of wait time on survival using a Cox proportional hazard model with wait time in months as a categorical variable. Incidence of upstaging at least 1 stage was assessed using logistic regression. RESULTS: We identified 222 patients: 180 were stage I and 42 were stage II. For stage I, wait times up to 4 months had no significant effect on survival or incidence of upstaging. For stage II, patients waiting between 2 and 3 months had significantly decreased survival (hazard ratio 3.6, p = 0.036) and increased incidence of upstaging (odds ratio 2.0, p = 0.020) than those waiting 0 to 1 month. For those waiting between 1 and 2 months, there was no significant difference in survival or upstaging. CONCLUSION: We did not identify an effect of wait time up to 4 months on survival or upstaging for patients with stage I NSCLC. For patients with stage II disease, wait times greater than 2 months adversely affected survival and upstaging.

CONTEXTE: En chirurgie, l'effet des temps d'attente sur la survie des patients atteints d'un cancer du poumon non à petites cellules (CPNPC) demeure pour une bonne part inconnu. Notre objectif était de déterminer l'effet des temps d'attente sur la survie et sur l'incidence de la restadification à un niveau plus élevé chez les patients atteints d'un CPNPC de stade I et II. MÉTHODES: Tous les patients présentant un CPNPC clinique de stade I et II ayant subi une résection chirurgicale dans un seul centre entre janvier 2010 et décembre 2011 ont été passés en revue. L'analyse a été stratifiée selon le stade clinique préopératoire. Nous avons évalué l'effet des temps d'attente sur la survie à l'aide d'un modèle de risques proportionnels de Cox, les temps d'attente en mois ayant servi de variable catégorielle. L'incidence de la restadification à la hausse d'au moins un stade a été évaluée par régression logistique. RÉSULTATS: Nous avons recensé 222 patients : 180 de stade I et 42 de stade II. Pour le stade I, les temps d'attente allant jusqu'à 4 mois n'ont eu aucun effet significatif sur la survie ou sur l'incidence de la restadification. Pour les stades II, les patients ayant attendu de 2 à trois 3 mois ont présenté une réduction significative de la survie (risque relatif 3,6, p = 0,036) et une incidence accrue de restadification (rapport des cotes 2,0, p = 0,02) comparativement à ceux qui avaient attendu 1 mois et moins. Chez les patients ayant attendu 1 ou 2 mois, on n'a noté aucune différence significative sur la survie ou la restadification. CONCLUSION: Nous n'avons observé aucun effet d'une attente allant jusqu'à 4 mois sur la survie ou la restadification chez les patients atteints d'un CPNPC de stade I. Pour les patients atteints d'une maladie de stade II, les temps d'attente de plus de 2 mois ont eu un impact négatif sur la survie et la restadification.

What is the predictive value of RECIST criteria following stereotactic lung radiation?

PURPOSE: Response EvaluationCriteriain Solid Tumors (RECIST) is commonly used to assess response to anti-cancer therapies. However, its application after lung stereotactic ablative radiotherapy (SABR) is complicated by radiation-induced lung changes. This study assesses the frequency of progressive disease (PD) by RECIST following lung SABR and correlates this with actual treatment outcomes as determined by longitudinal follow-up. METHODS AND MATERIALS: We reviewed patients treated with lung SABR for primary lung tumors or oligometastases between 2010 and 2015. Patients were treated with SABR doses of 54-60 Gy in 3-8 fractions. All follow-up scans were assessed and the treated lesion was serially measured over time, with the maximum diameter on axial CT slices used for RECIST calculations. Lesions demonstrating PD by RECIST criteria were identified and subsequently followed for long-term outcomes. The final 'gold-standard' assessment of response was based on size changes after PD and, as available, positron emission tomography scan and/or biopsy. RESULTS: Eighty-eight lesions met inclusion criteria. Seventy-five were lung primaries and thirteen were lung metastases. Median follow-up was 52 months (interquartile range: 33-68). Two-thirds (66 %, 58/88) of treated lesions met RECIST criteria for PD; however, local recurrence was only confirmed in 16 % (9/58) of cases. Most lesions that triggered PD by RECIST (47/58, 81 %) were ultimately found not to represent recurrence, while a minority (2/58, 3 %) had an uncertain response. The positive predictive value [PPV] of a RECIST defined PD event was 0.16. If PD was triggered within 12-months post-treatment, PPV was 0.08, compared to 0.21 for lesions triggering PD after 12-months. CONCLUSION: Using RECIST criteria, two-thirds of patients treated with lung SABR met criteria for PD. However, only a minority had recurrence, leading to a poor PPV of RECIST. This highlights the limitations of RECIST in this setting and provides context for physicians when interpreting post-lung SABR imaging.

Pulmonary carcinosarcoma with an aggressive heterologous angiosarcoma component: A case report.

Pulmonary carcinosarcomas are rare biphasic lung tumors comprised of malignant epithelial and malignant mesenchymal components. The most common heterologous sarcomatous elements are osteosarcoma, rhabdomyosarcoma, and chondrosarcoma; a heterologous angiosarcoma component in a pulmonary carcinosarcoma is exceedingly rare. We report a case of a pulmonary carcinosarcoma containing adenocarcinoma, squamous cell carcinoma, undifferentiated malignant spindle cell, and heterologous angiosarcoma components. The patient, a 64-year-old woman, had initially presented to medical attention with hemoptysis. Although the tumor was thought to be confined to the lung at resection (pT3N0), she developed multiple metastatic foci within 3 weeks of lobectomy and required the evacuation of an intraparenchymal left occipital hematoma secondary to a hemorrhagic intra-axial focus of metastatic carcinosarcoma. She died 6 weeks after her primary lung resection from rapidly progressive metastatic disease. We hope the description and discussion provided herein will further the medical community's understanding of this rare malignancy.

SPECT/CT versus planar imaging to determine treatment strategy for non-small-cell lung cancer: a cost-effectiveness analysis.

Aim: SPECT/CT has been found to improve predicted postoperative forced expiratory volume in one second (ppoFEV1) assessments in patients with non-small-cell lung cancer (NSCLC). Methods: An economic simulation was developed comparing the cost-effectiveness of SPECT/CT versus planar scintigraphy for a US payer. Clinical outcomes and cost data were obtained through review of the published literature. Results: SPECT/CT increased the accuracy ppoFEV1 assessment, changing the therapeutic decision for 1.3% of nonsurgical patients to a surgical option, while 3.3% of surgical patients shifted to more aggressive procedures. SPECT/CT led to an expected cost of $4694 per life year gained, well below typical thresholds. Conclusion: SPECT/CT resulted in substantially improved health outcomes and was found to be highly cost-effective.

Lenvatinib in multimodal therapy for unresectable radioactive iodine-naïve differentiated thyroid cancer: A case report with literature review.

BACKGROUND: Patients with unresectable or metastatic differentiated thyroid carcinoma (DTC) are rare and require individualized therapy. This may require approaches not typically used in resectable disease. We report a patient treated with lenvatinib and external beam radiation therapy. CASE: An 87-year-old woman presented with cT4N1aM1 papillary thyroid carcinoma with tracheal invasion. She was not a candidate for surgery, radioactive-iodine, or radiation, so a trial of lenvatinib was offered. Her tumor showed clinical, biochemical, and radiological response after 5 months of lenvatinib, and she subsequently received external beam radiation. She enjoys good quality of life without evidence of cancer progression off therapy 21 months post-initiation of treatment. CONCLUSION: Lenvatinib may be effective in RAI-naïve advanced DTC patients as a component of individualized multimodal therapy when conventional options are not feasible.

The quality of life in neoadjuvant versus adjuvant therapy of esophageal cancer treatment trial (QUINTETT): Randomized parallel clinical superiority trial.

BACKGROUND: We compared the health-related quality of life (HRQOL) in patients undergoing trimodality therapy for resectable stage I-III esophageal cancer. METHODS: A total of 96 patients were randomized to standard neoadjuvant cisplatin and 5-fluorouracil chemotherapy plus radiotherapy (neoadjuvant) followed by surgical resection or adjuvant cisplatin, 5-fluorouracil, and epirubicin chemotherapy with concurrent extended volume radiotherapy (adjuvant) following surgical resection. RESULTS: There was no significant difference in the functional assessment of cancer therapy-esophageal (FACT-E) total scores between arms at 1 year (p = 0.759) with 36% versus 41% (neoadjuvant vs. adjuvant), respectively, showing an increase of ≥15 points compared to pre-treatment (p = 0.638). The HRQOL was significantly inferior at 2 months in the neoadjuvant arm for FACT-E, European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-OG25), and EuroQol 5-D-3 L in the dysphagia, reflux, pain, taste, and coughing domains (p < 0.05). Half of patients were able to complete the prescribed neoadjuvant arm chemotherapy without modification compared to only 14% in the adjuvant arm (p < 0.001). Chemotherapy related adverse events of grade ≥2 occurred significantly more frequently in the neoadjuvant arm (100% vs. 69%, p < 0.001). Surgery related adverse events of grade ≥2 were similar in both arms (72% vs. 86%, p = 0.107). There were no 30-day mortalities and 2% vs. 10% 90-day mortalities (p = 0.204). There were no significant differences in either overall survival (OS) (5-year: 35% vs. 32%, p = 0.409) or disease-free survival (DFS) (5-year: 31% vs. 30%, p = 0.710). CONCLUSION: Trimodality therapy is challenging for patients with resectable esophageal cancer regardless of whether it is given before or after surgery. Newer and less toxic protocols are needed.

Idiopathic Subglottic Stenosis: An Institutional Review of Outcomes With a Multimodality Surgical Approach.

OBJECTIVES: This article reports on a unique cohort of patients with idiopathic subglottic stenosis spilt fairly equally between endoscopic and open surgical approaches. Patients' sequence of operations and reinterventions over time are outlined, offering insight to improve surgical counseling and allow for informative, autonomous patient decision making. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care academic center. METHODS: Cases of consecutive adults with idiopathic subglottic stenosis managed surgically over a 12-year period (January 2006-December 2017) were retrospectively reviewed. Surgical workflow, complications, and outcomes, including reinterventions and tracheotomy dependence, are reported. RESULTS: Seventy-two patients (71 women; mean age, 50.4 years) with idiopathic subglottic stenosis requiring surgical airway intervention were identified. Six patients underwent tracheotomy prior to attempt at airway stenosis surgery. Initial surgical approach thereafter included endoscopic (73.5%, n = 53) and open (26.4%, n = 19) procedures. Thirty-one patients underwent cricotracheal resection; the reintervention rate was 22.5%. Sixty patients underwent 147 endoscopic procedures; the reintervention rate was 75.5%, and the mean time between dilations was 83 weeks (range, 5-402). Two (2.8%) patients remain tracheotomy dependent. Adverse events were significantly higher in the cricotracheal group, especially with respect to dysphonia and temporary gastrostomy tube placement (P < .01). CONCLUSIONS: Endoscopic and open surgical airway intervention can be employed successfully to avoid tracheotomy dependence and maintain airway patency; however, multiple procedures are usually required, regardless of surgical approach. Cricotracheal reintervention rates are lower than endoscopic dilation but with increased morbidity. Quality-of-life outcomes should be clearly discussed with patients before deciding on a surgical management strategy.

Predicting pathological complete response (pCR) after stereotactic ablative radiation therapy (SABR) of lung cancer using quantitative dynamic [18F]FDG PET and CT perfusion: a prospective exploratory clinical study.

BACKGROUND: Stereotactic ablative radiation therapy (SABR) is effective in treating inoperable stage I non-small cell lung cancer (NSCLC), but imaging assessment of response after SABR is difficult. This prospective study aimed to develop a predictive model for true pathologic complete response (pCR) to SABR using imaging-based biomarkers from dynamic [18F]FDG-PET and CT Perfusion (CTP). METHODS: Twenty-six patients with early-stage NSCLC treated with SABR followed by surgical resection were included, as a pre-specified secondary analysis of a larger study. Dynamic [18F]FDG-PET and CTP were performed pre-SABR and 8-week post. Dynamic [18F]FDG-PET provided maximum and mean standardized uptake value (SUV) and kinetic parameters estimated using a previously developed flow-modified two-tissue compartment model while CTP measured blood flow, blood volume and vessel permeability surface product. Recursive partitioning analysis (RPA) was used to establish a predictive model with the measured PET and CTP imaging biomarkers for predicting pCR. The model was compared to current RECIST (Response Evaluation Criteria in Solid Tumours version 1.1) and PERCIST (PET Response Criteria in Solid Tumours version 1.0) criteria. RESULTS: RPA identified three response groups based on tumour blood volume before SABR (BVpre-SABR) and change in SUVmax (ΔSUVmax), the thresholds being BVpre-SABR = 9.3 mL/100 g and ΔSUVmax = - 48.9%. The highest true pCR rate of 92% was observed in the group with BVpre-SABR < 9.3 mL/100 g and ΔSUVmax < - 48.9% after SABR while the worst was observed in the group with BVpre-SABR ≥ 9.3 mL/100 g (0%). RPA model achieved excellent pCR prediction (Concordance: 0.92; P = 0.03). RECIST and PERCIST showed poor pCR prediction (Concordance: 0.54 and 0.58, respectively). CONCLUSIONS: In this study, we developed a predictive model based on dynamic [18F]FDG-PET and CT Perfusion imaging that was significantly better than RECIST and PERCIST criteria to predict pCR of NSCLC to SABR. The model used BVpre-SABR and ΔSUVmax which correlates to tumour microvessel density and cell proliferation, respectively and warrants validation with larger sample size studies. TRIAL REGISTRATION: MISSILE-NSCLC, NCT02136355 (ClinicalTrials.gov). Registered May 8, 2014, https://clinicaltrials.gov/ct2/show/NCT02136355.

Adjuvant melatonin for the prevention of recurrence and mortality following lung cancer resection (AMPLCaRe): A randomized placebo controlled clinical trial.

BACKGROUND: Despite curative intent resection in patients with non-small cell lung cancer (NSCLC), recurrence leading to mortality remains too common. Melatonin has shown promise for the treatment of patients with lung cancer; however, its effect following cancer resection has not been studied. We evaluated if melatonin taken after complete resection reduces lung cancer recurrence and mortality, or impacts quality of life (QOL), symptomatology or immune function. METHODS: Participants received melatonin (20 mg) or placebo nightly for one year following surgical resection of primary NSCLC. The primary outcome was two-year disease-free survival (DFS). Secondary outcomes included five-year DFS, adverse events, QOL, fatigue, sleep, depression, anxiety, pain, and biomarkers assessing for immune function/inflammation. This study is registered at https://clinicaltrials.gov NCT00668707. FINDINGS: 709 patients across eight centres were randomized to melatonin (n = 356) versus placebo (n = 353). At two years, melatonin showed a relative risk of 1·01 (95% CI 0·83-1·22), p = 0·94 for DFS. At five years, melatonin showed a hazard ratio of 0·97 (95% CI 0·86-1·09), p = 0·84 for DFS. When stratified by cancer stage (I/II and III/IV), a hazard reduction of 25% (HR 0·75, 95% CI 0·61-0·92, p = 0·005) in five-year DFS was seen for participants in the treatment arm with advanced cancer (stage III/IV). No meaningful differences were seen in any other outcomes. INTERPRETATION: Adjuvant melatonin following resection of NSCLC does not affect DFS for patients with resected early stage NSCLC, yet may increase DFS in patients with late stage disease. Further study is needed to confirm this positive result. No beneficial effects were seen in QOL, symptoms, or immune function. FUNDING: This study was funded by the Lotte and John Hecht Memorial Foundation and the Gateway for Cancer Research Foundation.

Positron emission tomography in staging early lung cancer: a randomized trial.

BACKGROUND: Among patients with early-stage non-small cell lung cancer (NSCLC), preoperative imaging tests are important in defining surgical candidates. OBJECTIVE: To assess whether whole-body positron emission tomography and computed tomography (PET-CT) plus cranial imaging correctly upstages cancer in more patients with NSCLC than does conventional staging plus cranial imaging. DESIGN: Randomized clinical trial with recruitment from June 2004 to August 2007. The centralized, computer-generated, variable block size randomization scheme was stratified by treatment center and cancer stage. Participants, health care providers, and outcome assessors were not blinded to imaging modality assignment. SETTING: 8 hospitals and 5 PET-CT centers in academic institutions. PATIENTS: Eligible patients were older than 18 years; had histologic or cytologic proof of stage I, II, or IIIA NSCLC on the basis of chest radiography and thoracic CT; and had a tumor considered to be resectable. INTERVENTION: PET-CT or conventional staging (abdominal CT and bone scan). All patients also had cranial imaging using CT or magnetic resonance imaging. MEASUREMENTS: The primary outcome was correct upstaging, thereby avoiding stage-inappropriate surgery. Secondary outcomes were incorrect upstaging and incorrect understaging. RESULTS: 170 patients were assigned to PET-CT and 167 to conventional staging. Eight patients (3 who had PET-CT and 5 who had conventional staging) did not have planned surgery. Disease was correctly upstaged in 23 of 167 PET-CT recipients and 11 of 162 conventional staging recipients (13.8% vs. 6.8%; difference, 7.0 percentage points [95% CI, 0.3 to 13.7 percentage points]), thereby sparing these patients from surgery. Disease was incorrectly upstaged in 8 PET-CT recipients and 1 conventional staging recipient (4.8% vs. 0.6%; difference, 4.2 percentage points [CI, 0.5 to 8.6 percentage points]), and it was incorrectly understaged in 25 and 48 patients, respectively (14.9% vs. 29.6%; difference, 14.7 percentage points [CI, 5.7 to 23.4 percentage points]). At 3 years, 52 patients who had PET-CT and 57 patients who had conventional staging had died. LIMITATION: The relatively small sample and the fact that some patients did not have planned surgery limited the ability to determine precise differences in clinical outcomes that were attributable to testing strategies. CONCLUSION: Preoperative staging with PET-CT and cranial imaging identifies more patients with mediastinal and extrathoracic disease than conventional staging, thereby sparing more patients from stage-inappropriate surgery, but the strategy also incorrectly upstaged disease in more patients.

Management and prognosis in synchronous solitary resected brain metastasis from non-small-cell lung cancer.

BACKGROUND: Reports in the medical literature have described cases of extended survival of patients with non-small-cell lung cancer (NSCLC) with solitary metastatic disease who have received aggressive treatment both to the brain metastasis and to the local/regional disease. The objective of this research is to analyze prognostic factors that predict for outcome in this unique patient population. PATIENTS AND METHODS: A single-institution, retrospective chart review was performed on 35 patients with NSCLC and a synchronous solitary brain metastasis (SSBM) treated with craniotomy and whole-brain radiation therapy. Eight patients (22.9%) had chest surgery, 24 (68.6%) had chemotherapy, and 14 (40%) had thoracic radiation as part of their local management. Fourteen had stage I/II disease (42.9%), and 20 had stage III disease (57.1%). Mean age at diagnosis was 58.5 years. Eighteen patients (56.25%) had a brain metastasis < 3 cm, and 14 patients (43.75%) had a metastasis > 3 cm. RESULTS: Median survival was 7.8 months, and at last follow-up, 3 patients (8.6%) were alive and well, 6 patients (17.1%) were alive and with disease, 24 patients (68.6%) had died of disease, and 2 patients (5.7%) had died of other causes. Univariate analysis demonstrated that lung surgery (P = .0033), primary lung treatment > 8 weeks after brain surgery (P = .0128), and stage I/II disease (P = .0467) were predictive of overall survival. CONCLUSION: Survival remains poor for patients with NSCLC with an SSBM. However, patients with thoracic disease amenable to local resection should be considered for such therapy because a survival advantage could exist compared with patients with more locally advanced disease.

Case Report of a Rare Cystic Mediastinal Lymphangioma Mimicking Recurrent Pleural Effusion.

Mediastinal lymphangiomas are rare benign congenital malformations, but complications can occur, including infection, cystic hemorrhage, superior vena cava syndrome, airway compromise, and chylothorax. Radiologically, lymphangiomas are well-defined masses, with low attenuation ranging from simple to complex fluid and fat. They often encase adjacent mediastinal structures. We present a case of mediastinal lymphangioma in a young female, who presented with recurrent complex pleural effusions, initially thought to represent an empyema and/or necrotic mass. Despite surgical chest tube and interventional radiology drainage, fluid reaccumulated. Upon further review, the interventional and thoracic radiologist concurred that the complex collection was in fact predominantly extra pleural in location. The patient underwent partial resection after it was discovered intraoperatively that the extra pleural cystic mass was contiguous with and extended deeply into the mediastinum. Histopathology confirmed the diagnosis of lymphangioma.

Assessment of tumour response after stereotactic ablative radiation therapy for lung cancer: A prospective quantitative hybrid 18 F-fluorodeoxyglucose-positron emission tomography and CT perfusion study.

INTRODUCTION: Stereotactic ablative radiotherapy (SABR) is a guideline-recommended treatment for inoperable stage I non-small cell lung cancer (NSCLC), but imaging assessment of response after SABR is difficult. The goal of this study was to evaluate imaging-based biomarkers of tumour response using dynamic 18 F-FDG-PET and CT perfusion (CTP). METHODS: Thirty-one patients with early-stage NSCLC participated in this prospective correlative study. Each underwent dynamic 18 F-FDG-PET/CTP studies on a PET/CT scanner pre- and 8 weeks post-SABR. The dynamic 18 F-FDG-PET measured the tumour SUVmax , SUVmean and the following parameters: K1 , k2 , k3 , k4 and Ki , all using the Johnson-Wilson-Lee kinetic model. CTP quantitatively mapped BF, BV, MTT and PS in tumours and measured largest tumour diameter. Since free-breathing was allowed during CTP scanning, non-rigid image registration of CT images was applied to minimize misregistration before generating the CTP functional maps. Differences between pre- and post-SABR imaging-based parameters were compared. RESULTS: Tumour size changed only slightly after SABR (median 26 mm pre-SABR vs. 23 mm post-SABR; P = 0.01). However, dynamic 18 F-FDG-PET and CTP study showed substantial and significant changes in SUVmax , SUVmean , k3 , k4 and Ki . Significant decreases were evident in SUVmax (median 6.1 vs. 2.6; P < 0.001), SUVmean (median 2.5 vs. 1.5; P < 0.001), k3 (relative decrease of 52%; P = 0.002), Ki (relative decrease of 27%; P = 0.03), whereas there was an increase in k4 (+367%; P < 0.001). CONCLUSIONS: Hybrid 18 F-FDG-PET/CTP allowed the response of NSCLC to SABR to be assessed regarding metabolic and functional parameters. Future studies are needed, with correlation with long-term outcomes, to evaluate these findings as potential imaging biomarkers of response.

Measuring the Integration of Stereotactic Ablative Radiotherapy Plus Surgery for Early-Stage Non-Small Cell Lung Cancer: A Phase 2 Clinical Trial.

IMPORTANCE: Stereotactic ablative radiotherapy (SABR) is a standard treatment option in patients with medically inoperable early-stage non-small cell lung cancer (NSCLC), yet the pathologic complete response (pCR) rate after SABR is unknown. Neoadjuvant SABR in patients with cancer who are fit for resection has been hypothesized to improve local control and induce antitumor immune activity, potentially leading to better outcomes. OBJECTIVES: To determine the pCR rate after SABR and to assess oncologic and toxicity outcomes after a combined approach of neoadjuvant SABR followed by surgery. DESIGN, SETTING, AND PARTICIPANTS: A phase 2, single-arm trial, with patient accrual from September 30, 2014, to August 15, 2017 (median follow-up, 19 months), was performed at a tertiary academic cancer center. Patients 18 years or older with T1T2N0M0 NSCLC and good performance status, with adequate pulmonary reserve to undergo surgical resection, were studied. INTERVENTIONS: Patients underwent neoadjuvant SABR using a risk-adapted fractionation scheme followed by surgery 10 weeks later. MAIN OUTCOMES AND MEASURES: The pCR rate as determined by hematoxylin-eosin staining. RESULTS: Forty patients (mean [SD] age, 68 [8] years; 23 [58%] female) were enrolled. Thirty-five patients underwent surgery and were evaluable for the primary end point. The pCR rate was 60% (95% CI, 44%-76%). The 30- and 90-day postoperative mortality rates were both 0%. Grade 3 or 4 toxic effects occurred in 7 patients (18%). In patients receiving surgery, 2-year overall survival was 77% (95% CI, 48%-91%), local control was 100% (95% CI, not defined), regional control was 53% (95% CI, 22%-76%), and distant control was 76% (95% CI, 45%-91%). Quality of life did not decline after treatment, with no significant changes in mean Functional Assessment of Cancer Therapy for Lung-Trial Outcome Index score during the first year of follow-up. CONCLUSIONS AND RELEVANCE: The pCR rate after SABR for early-stage NSCLC was 60%, lower than hypothesized. The combined approach had toxic effects comparable to series of surgery alone, and there was no perioperative mortality. Further studies are needed to evaluate this combined approach compared with surgical resection alone. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02136355.

Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer.

BACKGROUND: We undertook to determine whether adjuvant vinorelbine plus cisplatin prolongs overall survival among patients with completely resected early-stage non-small-cell lung cancer. METHODS: We randomly assigned patients with completely resected stage IB or stage II non-small-cell lung cancer to vinorelbine plus cisplatin or to observation. The primary end point was overall survival; principal secondary end points were recurrence-free survival and the toxicity and safety of the regimen. RESULTS: A total of 482 patients underwent randomization to vinorelbine plus cisplatin (242 patients) or observation (240); 45 percent of the patients had pathological stage IB disease and 55 percent had stage II, and all had an Eastern Cooperative Oncology Group performance status score of 0 or 1. In both groups, the median age was 61 years, 65 percent were men, and 53 percent had adenocarcinomas. Chemotherapy caused neutropenia in 88 percent of patients (including grade 3 febrile neutropenia in 7 percent) and death from toxic effects in two patients (0.8 percent). Nonhematologic toxic effects of chemotherapy were fatigue (81 percent of patients), nausea (80 percent), anorexia (55 percent), vomiting (48 percent), neuropathy (48 percent), and constipation (47 percent), but severe (grade 3 or greater) toxic effects were uncommon (<10 percent). Overall survival was significantly prolonged in the chemotherapy group as compared with the observation group (94 vs. 73 months; hazard ratio for death, 0.69; P=0.04), as was relapse-free survival (not reached vs. 46.7 months; hazard ratio for recurrence, 0.60; P<0.001). Five-year survival rates were 69 percent and 54 percent, respectively (P=0.03). CONCLUSIONS: Adjuvant vinorelbine plus cisplatin has an acceptable level of toxicity and prolongs disease-free and overall survival among patients with completely resected early-stage non-small-cell lung cancer.