Early Interventional Treatment of High Output Chyle Leak After Esophagectomy is Associated With Improved Survival.

OBJECTIVE: To investigate overall survival and length of stay (LOS) associated with differing management for high output (>1 L over 24 hours) leaks (HOCL) after cancer-related esophagectomy. BACKGROUND: Although infrequent, chyle leak after esophagectomy is an event that can lead to significant perioperative sequelae. Low-volume leaks appear to respond to nonoperative measures, whereas HOCLs often require invasive therapeutic interventions. METHODS: From a prospective single-institution database, we retrospectively reviewed patients treated from 2001 to 2021 who underwent esophagectomy for esophageal cancer. Within that cohort, we focused on a subgroup of patients who manifested a HOCL postoperatively. Clinicopathologic and operative characteristics were collected, including hospital LOS and survival data. RESULTS: A total of 53/2299 patients manifested a HOCL. These were mostly males (77%), with a mean age of 62 years. Of this group, 15 patients received nonoperative management, 15 patients received prompt (<72 hours from diagnosis) interventional management, and 23 received late interventional management. Patients in the late intervention group had longer LOSs compared with early intervention (slope = 9.849, 95% CI: 3.431-16.267). Late intervention (hazard ratio: 4.772, CI: 1.384-16.460) and nonoperative management (hazard ratio: 4.731, CI: 1.294-17.305) were associated with increased mortality compared with early intervention. Patients with early intervention for HOCL had an overall survival similar to patients without chyle leaks in survival analysis. CONCLUSIONS: Patients with HOCL should receive early intervention to possibly reverse the prognostic implications of this potentially detrimental complication.

Stereotactic ablative radiotherapy with or without immunotherapy for early-stage or isolated lung parenchymal recurrent node-negative non-small-cell lung cancer: an open-label, randomised, phase 2 trial.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small-cell lung cancer (NSCLC), but regional or distant relapses, or both, are common. Immunotherapy reduces recurrence and improves survival in people with stage III NSCLC after chemoradiotherapy, but its utility in stage I and II cases is unclear. We therefore conducted a randomised phase 2 trial of SABR alone compared with SABR with immunotherapy (I-SABR) for people with early-stage NSCLC. METHODS: We did an open-label, randomised, phase 2 trial comparing SABR to I-SABR, conducted at three different hospitals in TX, USA. People aged 18 years or older with histologically proven treatment-naive stage IA-IB (tumour size ≤4 cm, N0M0), stage IIA (tumour size ≤5 cm, N0M0), or stage IIB (tumour size >5 cm and ≤7 cm, N0M0) as per the American Joint Committee on Cancer version 8 staging system or isolated parenchymal recurrences (tumour size ≤7 cm) NSCLC (TanyNanyM0 before definitive surgery or chemoradiotherapy) were included in this trial. Participants were randomly assigned (1:1; using the Pocock & Simon method) to receive SABR with or without four cycles of nivolumab (480 mg, once every 4 weeks, with the first dose on the same day as, or within 36 h after, the first SABR fraction). This trial was unmasked. The primary endpoint was 4-year event-free survival (local, regional, or distant recurrence; second primary lung cancer; or death). Analyses were both intention to treat (ITT) and per protocol. This trial is registered with ClinicalTrials.gov (NCT03110978) and is closed to enrolment. FINDINGS: From June 30, 2017, to March 22, 2022, 156 participants were randomly assigned, and 141 participants received assigned therapy. At a median 33 months' follow-up, I-SABR significantly improved 4-year event-free survival from 53% (95% CI 42-67%) with SABR to 77% (66-91%; per-protocol population, hazard ratio [HR] 0·38; 95% CI 0·19-0·75; p=0·0056; ITT population, HR 0·42; 95% CI 0·22-0·80; p=0·0080). There were no grade 3 or higher adverse events associated with SABR. In the I-SABR group, ten participants (15%) had grade 3 immunologial adverse events related to nivolumab; none had grade 3 pneumonitis or grade 4 or higher toxicity. INTERPRETATION: Compared with SABR alone, I-SABR significantly improved event-free survival at 4 years in people with early-stage treatment-naive or lung parenchymal recurrent node-negative NSCLC, with tolerable toxicity. I-SABR could be a treatment option in these participants, but further confirmation from a number of currently accruing phase 3 trials is required. FUNDING: Bristol-Myers Squibb and MD Anderson Cancer Center Alliance, National Cancer Institute at the National Institutes of Health through Cancer Center Core Support Grant and Clinical and Translational Science Award to The University of Texas MD Anderson Cancer Center.

Do resected colorectal cancer patients need early chest imaging? Impact of clinicopathologic characteristics on time to development of pulmonary metastases.

BACKGROUND AND OBJECTIVES: For patients with colorectal cancer (CRC), the lung is the most common extra-abdominal site of distant metastasis. However, practices for chest imaging after colorectal resection vary widely. We aimed to identify characteristics that may indicate a need for early follow-up imaging. METHODS: We retrospectively reviewed charts of patients who underwent CRC resection, collecting clinicopathologic details and oncologic outcomes. Patients were grouped by timing of pulmonary metastases (PM) development. Analyses were performed to investigate odds ratio (OR) of PM diagnosis within 3 months of CRC resection. RESULTS: Of 1600 patients with resected CRC, 233 (14.6%) developed PM, at a median of 15.4 months following CRC resection. Univariable analyses revealed age, receipt of systemic therapy, lymph node ratio (LNR), lymphovascular and perineural invasion, and KRAS mutation as risk factors for PM. Furthermore, multivariable regression showed neoadjuvant therapy (OR: 2.99, p < 0.001), adjuvant therapy (OR: 6.28, p < 0.001), LNR (OR: 28.91, p < 0.001), and KRAS alteration (OR: 5.19, p < 0.001) to predict PM within 3 months post-resection. CONCLUSIONS: We identified clinicopathologic characteristics that predict development of PM within 3 months after primary CRC resection. Early surveillance in such patients should be emphasized to ensure timely identification and treatment of PM.

Octreotide's role in the management of post-esophagectomy chylothorax.

The use of octreotide in managing intrathoracic chyle leak following esophagectomy has gained popularity in the adult population. While the benefits of octreotide have been confirmed in the pediatric population, there remains limited evidence to support its use in the adults post-esophagectomy. Thus, we performed a single-institution cohort study to characterize its efficacy. The study was performed using a prospective, single-center database, from which clinicopathologic characteristics were extracted of patients who had post-esophagectomy chyle leaks. Kaplan-Meier and multivariable Cox regression analyses were performed to investigate the effect of octreotide use on chest tube duration (CTD), hospital length of stay (LOS), and overall survival (OS). In our cohort, 74 patients met inclusion criteria, among whom 27 (36.5%) received octreotide. Kaplan-Meier revealed no significant effect of octreotide on CTD (P = 0.890), LOS (P = 0.740), or OS (P = 0.570). Multivariable Cox regression analyses further corroborated that octreotide had no effect on CTD (HR = 0.62, 95% confidence interval [CI]: 0.32-1.20, P = 0.155), LOS (HR = 0.64, CI: 0.34-1.21, P = 0.168), or OS (1.08, CI: 0.53-2.19, P = 0.833). Octreotide use in adult patients with chyle leak following esophagectomy lacks evidence of association with meaningful clinical outcomes. Level 1 evidence is needed prior to further consideration in this population.

Financial Toxicity in Patients With Resected Lung Cancer.

OBJECTIVES: To describe financial toxicity (FT) in patients with resected lung cancer and identify risk factors in this population. BACKGROUND: FT describes the financial burden associated with cancer care and its impact on the quality of survivorship. Few prior studies have examined FT in patients with lung cancer. METHODS: Patients who underwent lung cancer resection at our institution between January 1, 2016 and December 31, 2021, were surveyed to gather demographic information and evaluate FT using a validated questionnaire. A multivariable model was built to identify risk factors for FT. RESULTS: Of the total, 1477 patients were contacted, of whom 463 responded (31.3%). Most patients were stage I (n = 349, 75.4%) and lobectomy was performed often (n = 290, 62.8%). There were 196 patients (42.3%) who experienced FT. Upon multivariable analyses, divorced marital status [odds ratio (OR) = 3.658, 95% CI: 1.180-11.337], household income <$40,000 (OR = 2.544, 95% CI: 1.003-6.455), credit score below 739 (OR = 2.744, 95% CI: 1.326-5.679), clinical stage >I (OR = 2.053, 95% CI: 1.088-3.877), and change in work hours or work cessation (all P < 0.05) were associated with FT. Coping mechanisms, such as decreased spending on food or clothing and increased use of savings or borrowing money, were more likely to be reported by patients experiencing FT than those who did not ( P < 0.001). CONCLUSIONS: Patients undergoing lung cancer resection often experienced significant financial stress with several identifiable risk factors. FT should be considered early in the care of these patients to alleviate detrimental coping mechanisms and enhance their quality of survivorship.

High-Risk Features of Esophageal Adenocarcinoma Following Neoadjuvant Chemoradiation: Patients for Whom Surgery Should Not Be Delayed.

OBJECTIVE: Clinical predictors of pathological complete response have not reliably identified patients for whom an organ-sparing approach following neoadjuvant chemoradiation be undertaken for esophageal cancer patients. We sought to identify high-risk predictors of residual carcinoma that may preclude patients from a selective surgical approach. BACKGROUND: Patients treated with neoadjuvant chemoradiation followed by esophagectomy for esophageal adenocarcinoma were identified. PATIENTS AND METHODS: Correlation between clinical and pathologic complete responses were examined. Regression models and recursive partitioning were utilized to identify features associated with residual carcinoma. External validation of these high-risk factors was performed on a data set from an independent institution. RESULTS: A total of 326 patients were identified, in whom clinical complete response was noted in 104/326 (32%). Pathologic complete response was noted in only 33/104 (32%) of these clinical complete responders. Multivariable analysis identified that the presence of stricture ( P =0.011), positive biopsy ( P =0.010), and signet ring cell histology ( P =0.019) were associated with residual cancer. Recursive partitioning corroborated a 94% probability of residual disease, or greater, for each of these features. The positive predictive value was >90% for these characteristics. A SUV max >5.4 at the esophageal primary in the absence of esophagitis was also a high-risk factor for residual carcinoma. External validation confirmed these high-risk factors to be implicated in the finding of residual carcinoma. CONCLUSIONS: Clinical parameters of response are poor predictors of complete pathologic response leading to challenges in selecting candidates for active surveillance. However, we characterize several high-risk features for residual carcinoma which indicate that esophagectomy should not be delayed.

The Role of Surgery in the Treatment of Melanoma Pulmonary Metastases in the Modern Era.

INTRODUCTION: The lung represents a frequent site of spread for metastatic melanoma, which has historically been managed with surgical resection achieving promising outcomes. We hypothesized that the role of surgery in the management of melanoma pulmonary metastases (MPM) is evolving among the development of less invasive diagnostic and novel systemic therapeutic strategies. MATERIALS AND METHODS: A single-center thoracic surgery database was reviewed and patients who underwent surgical resection of MPM between 1998 and 2019 were identified. Demographic, clinicopathologic, and surgical data were collected and analyzed, as were the annual volumes and indications for surgical resection. A Cochran-Armitage test was used to assess the trend in surgical indication. RESULTS: Three hundred and seventy seven surgical procedures for MPM were performed during the years of study in the care of 347 patients. Patients were predominantly male, with a mean age of 59.3 y. The mean number of annual resections was 17 and while this number initially increased from six in 1998 to a peak of 39 cases in 2008, a decline was subsequently observed. Diagnostic resection decreased from 22% in 1998-1999 to 5% at the peak of procedures in 2008-2009 and to 0 in 2018-2019 (P = 0.02). Curative resection increased from 44% in 1998-1999 to 73% in 2008-2009 (P < 0.001) and remained the dominant reason for surgery in later years. CONCLUSIONS: Surgical indications in the management of MPM have transformed in conjunction with systemic modalities, and the volume of resections has decreased in the modern era. Despite innovations in systemic management and shifting goals of operative interventions, surgeons continue to play a vital role in caring for these patients with an advanced disease.

Single Chest Drain Practice Reduces Discharge Opioid Prescriptions in Thoracic Surgery.

INTRODUCTION: Chest drains are placed following pulmonary resection to promote lung re-expansion. The superiority of two chest drains at preventing postoperative complications has not been established, and practice remains largely dictated by surgeon preference. We sought to compare patient outcomes based on number of chest drains used. METHODS: This is a retrospective analysis including patients undergoing lobectomies and segmentectomies between March 2016 and April 2020. Patients were categorized based on number of chest drains placed and were matched 1:1 using the nearest neighbor (greedy) technique. Our primary outcome was opioid prescriptions at discharge (in morphine equivalent daily dose [MEDD]). Associations were tested using multilevel mixed-effects regression to account for variability between surgeons. RESULTS: A total of 1,094 patients met inclusion criteria. Single chest drain was used in 922 patients, whereas 172 had two chest tubes. After matching, there were 111 patients in each group. In multilevel mixed-effects logistic regression, patients treated with a single chest drain received fewer opioid prescriptions (ß: -194 MEDD, 95% confidence interval [CI]: -302 to -86 MEDD, p < 0.01), were more likely to be opioid-free at hospital discharge (odds ratio [OR] = 2.11, 95% CI: 1.08-4.12, p = 0.03), and had lower readmission rates within 30 days (OR = 0.33, 95% CI: 0.13-0.84, p = 0.02). Single chest drain practice did not affect the risk of pulmonary complications and there was no statistically significant difference in length of hospital stay (3 days [interquartile range: 2-5] vs. 4 days [3-6], p = 0.08). CONCLUSION: Single chest drain practice in lobectomies and segmentectomies was associated with less opioid prescription requirement without any increase in complications.

Intraoperative Dexmedetomidine and Ketamine Infusions in an Enhanced Recovery After Thoracic Surgery Program: A Propensity Score Matched Analysis.

OBJECTIVES: To assess the impact of intraoperative dexmedetomidine and ketamine on postoperative pain and opioid consumption within an ERAS program in thoracic pulmonary oncologic surgery. DESIGN: Retrospective, propensity-score matched analysis SETTING: Enhanced Recovery After Surgery (ERAS) program. PARTICIPANTS: Patients undergoing thoracic pulmonary oncologic surgery between March 2016 and April 2020. INTERVENTIONS: Continuous infusion of dexmedetomidine and ketamine. MEASUREMENTS & MAIN RESULTS: The authors initially analyzed data of 1,630 patients undergoing thoracic pulmonary oncologic surgery within their ERAS program. In total, 117 matched pairs were included in this analysis. Patients in the intraoperative dexmedetomidine + ketamine group were more likely to be opioid-free (76.6% vs 60.9%, P<0.01). Raw analysis showed lower pain scores at PACU admission (2.8±2.0 vs 3.4±2.0, P=0.03) and less opioid consumption at PACU admission (5 MED [0-10] vs 7.5 MED [0-15], P=0.03) in the dexmedetomidine + ketamine group; however, these differences were not present after adjusting for multiplicity. There were no significant differences in the length of PACU stay (1.9 hours [1.5-2.8] vs 2.0 hours [1.4-2.9], P=0.48) or hospital stay (three days [two-five] vs three days [two-five], P=0.08). Both groups had similar rates of pulmonary complications (5.9% vs 9.4%, P=0.326), ileus (0.9% vs 0.9%, P=1.00), and 30-day readmission (2.6% vs 4.3%, P=0.722). CONCLUSIONS: There were no differences in postoperative pain scores and opioid consumption throughout their hospital stay between patients receiving concomitant dexmedetomidine and ketamine infusions versus patients who did not receive these infusions during thoracic surgery.

Prolonged neutrophilia is associated with worse outcomes after Esophagectomy.

Neutrophilia is a potential biomarker for postoperative complications and oncologic outcomes. There is a paucity of data regarding neutrophilia in patients with esophageal adenocarcinoma. Our Institutional Database was queried for esophageal adenocarcinoma patients who underwent esophagectomy from 2006 to 2019. Complete blood counts (CBC), demographic characteristics, perioperative and oncologic outcomes were evaluated. Two groups were created based on the presence of prolonged neutrophilia (PN, >7,000 absolute neutrophils 90 days after surgery). Univariate, multivariable, and survival analysis were performed (P-value < 0.05). We identified 686 patients with complete CBC data: 565 in the no prolonged neutrophilia (NPN) and 121 in the PN groups (17.6%). The mean age was 54 versus 48 years in the NPN and PN groups (P = 0.01). There was no difference in height, weight, gender, race, tumor size, histology, pTNM, PS, ASA, salvage procedure, neoadjuvant treatment and comorbidities. On multivariable analysis, the PN group had increased transfusions (19.8% vs. 11.9%; P = 0.02), aspiration (13.2% vs. 2.5%; P = 0.002), pulmonary embolus (3.3% vs. 0.4%; P = 0.02), cardiac arrest (5% vs. 0.4%; P = 0.02) and hematologic complications (23.1% vs. 12.6%; P = 0.01). After controlling for any postoperative complication, PN had increased distant recurrence (24% vs. 12.7%; hazard ration [HR]: 2.3, 95% confidence interval [CI] 1.42-3.9; P = 0.001) and decreased OS (33.8% vs. 49.7%, HR: 1.83, 95% CI: 1.19-2.81; P = 0.006); median follow up 77 months (46-109). PN was predictive of distant recurrence and decreased overall survival. Further work investigating these neutrophil populations represents a potential area for biomarker research, immunomodulation, and may guide postoperative surveillance strategies.

Stereotactic ablative radiotherapy for operable stage I non-small-cell lung cancer (revised STARS): long-term results of a single-arm, prospective trial with prespecified comparison to surgery.

BACKGROUND: A previous pooled analysis of the STARS and ROSEL trials showed higher survival after stereotactic ablative radiotherapy (SABR) than with surgery for operable early-stage non-small-cell lung cancer (NSCLC), but that analysis had notable limitations. This study reports long-term results of the revised STARS trial, in which the SABR group was re-accrued with a larger sample size, along with a protocol-specified propensity-matched comparison with a prospectively registered, contemporary institutional cohort of patients who underwent video-assisted thoracoscopic surgical lobectomy with mediastinal lymph node dissection (VATS L-MLND). METHODS: This single-arm prospective trial was done at the University of Texas MD Anderson Cancer Center (Houston, TX, USA) and enrolled patients aged 18 years or older with a Zubrod performance status of 0-2, newly diagnosed and histologically confirmed NSCLC with N0M0 disease (squamous cell, adenocarcinoma, large cell, or NSCLC not otherwise specified), and a tumour diameter of 3 cm or less. This trial did not include patients from the previous pooled analysis. SABR dosing was 54 Gy in three fractions (for peripheral lesions) or 50 Gy in four fractions (for central tumours; simultaneous integrated boost to gross tumour totalling 60 Gy). The primary endpoint was the 3-year overall survival. For the propensity-matching analysis, we used a surgical cohort from the MD Anderson Department of Thoracic and Cardiovascular Surgery's prospectively registered, institutional review board-approved database of all patients with clinical stage I NSCLC who underwent VATS L-MLND during the period of enrolment in this trial. Non-inferiority could be claimed if the 3-year overall survival rate after SABR was lower than that after VATS L-MLND by 12% or less and the upper bound of the 95% CI of the hazard ratio (HR) was less than 1·965. Propensity matching consisted of determining a propensity score using a multivariable logistic regression model including several covariates (age, tumour size, histology, performance status, and the interaction of age and sex); based on the propensity scores, one patient in the SABR group was randomly matched with one patient in the VATS L-MLND group using a 5:1 digit greedy match algorithm. This study is registered with ClinicalTrials.gov, NCT02357992. FINDINGS: Between Sept 1, 2015, and Jan 31, 2017, 80 patients were enrolled and included in efficacy and safety analyses. Median follow-up time was 5·1 years (IQR 3·9-5·8). Overall survival was 91% (95% CI 85-98) at 3 years and 87% (79-95) at 5 years. SABR was tolerated well, with no grade 4-5 toxicity and one (1%) case each of grade 3 dyspnoea, grade 2 pneumonitis, and grade 2 lung fibrosis. No serious adverse events were recorded. Overall survival in the propensity-matched VATS L-MLND cohort was 91% (95% CI 85-98) at 3 years and 84% (76-93) at 5 years. Non-inferiority was claimed since the 3-year overall survival after SABR was not lower than that observed in the VATS L-MLND group. There was no significant difference in overall survival between the two patient cohorts (hazard ratio 0·86 [95% CI 0·45-1·65], p=0·65) from a multivariable analysis. INTERPRETATION: Long-term survival after SABR is non-inferior to VATS L-MLND for operable stage IA NSCLC. SABR remains promising for such cases but multidisciplinary management is strongly recommended. FUNDING: Varian Medical Systems and US National Cancer Institute (National Institutes of Health).

Matched Pairs Comparison of an Enhanced Recovery Pathway Versus Conventional Management on Opioid Exposure and Pain Control in Patients Undergoing Lung Surgery.

OBJECTIVE: The aim of this study was to assess the effect of an enhanced recovery after surgery (ERAS) pathway on pain and opioid use following lung resection. SUMMARY BACKGROUND DATA: A major component ERAS pathways is opioid-sparing analgesia; however, the effect on postoperative pain and opioid use in patients undergoing lung resection is unknown. METHODS: Following implementation of an ERAS pathway for lung resection, 123 consecutive patients were identified. Patients were propensity-matched 1:1 with a group of consecutive patients (n = 907) undergoing lung resection before ERAS. Differences regarding in-hospital opioid consumption, discharge prescribing of opioids, and postoperative pain scores were examined. Morphine milligram equivalents were separately calculated including and excluding tramadol as an opioid medication. RESULTS: There were no significant differences between matched patients regarding age, sex, performance status, receipt of preoperative treatment, extent of lung resection, or operative approach. Epidural analgesia was used in 66% of controls and in none of the ERAS group (P < 0.001). The number of adjunct analgesics used postoperatively was greater in the ERAS group (median 3 vs 2, P < 0.001). There was a major reduction in morphine milligram equivalents in the ERAS group whether tramadol was included (median 14.2 vs 57.8, P < 0.001) or excluded (median 2.7 vs 57.8, P < 0.001) and regardless of surgical approach. Average daily pain scores were lower in the ERAS group (median 1.3 vs 1.8, P = 0.004); however, this difference was present only among patients undergoing thoracotomy. The proportion of patients who were prescribed discharge opioids varied whether tramadol was included (96% each group, P = 1.00) or excluded (39% vs 80%, P < 0.001) in the analysis. CONCLUSIONS: Implementation of an ERAS pathway was associated with effective post-operative analgesia, major reductions in in-hospital consumption of opioids, and reduced pain, compared to conventional management.

Simultaneous Sigmoid Colectomy, Bilobar Liver Resection and Lung Metastasectomy via a Transdiaphragmatic Approach for Stage IV Colonic Adenocarcinoma.

BACKGROUND: Current evidence supports the curative resection of colorectal cancer and synchronous liver and lung metastases in selected patients.1,2 This video shows simultaneous left colectomy, bilobar liver resection, and lung metastasectomy via a transdiaphragmatic approach for stage IV colorectal cancer.3 PATIENT: A 57-year-old man with a stage IV colonic adenocarcinoma was considered for simultaneous resection of primary, liver, and lung metastases without thoracic incision. The tumor mutational status was KRAS, NRAS, and BRAF wild-type, and the patient underwent preoperative chemotherapy. TECHNIQUE: After performing a midline laparotomy, atypical liver resection of segments 8/4a was performed under the guidance of intraoperative ultrasonography and intermittent Pringle maneuver using the two-surgeon's technique. A small capsular lesion in segment 3 also was intraoperatively detected and resected. Lung metastasectomy of the right lower lobe was performed via a transdiaphragmatic approach using an endoscopic stapler. Sigmoid colectomy with transanal circular-stapled anastomosis was performed. Duration of surgery and blood loss were 358 min and 400 ml, respectively. Histopathological examination showed metastatic colonic adenocarcinoma with negative surgical margins and final stage was T3N2aM1b. The patient was discharged on postoperative day 6 without complication. He was alive and free of disease at 90-day follow-up. CONCLUSIONS: Simultaneous colon, liver, and lung resection via a transdiaphragmatic approach is a feasible and safe surgical strategy in selected patients with peripheral lung metastases and favorable tumor biology.4 This surgical strategy avoids thoracic incision, multiple operations, and may reduce the healthcare costs and the recovery time to early implement postoperative therapy.

Simultaneous versus staged resections for bilateral pulmonary metastases.

BACKGROUND: For patients with bilateral pulmonary metastases, staged resections have historically been the preferred surgical intervention. During the spring of 2020, the COVID-19 pandemic made patient travel to the hospital challenging and necessitated reduction in operative volume so that resources could be conserved. We report our experience with synchronous bilateral metastasectomies for the treatment of disease in both lungs. METHODS: Patients with bilateral pulmonary metastases who underwent simultaneous bilateral resections were compared with a cohort of patients who underwent staged resections. We used nearest-neighbor propensity score (1:1) matching to adjust for confounders. Perioperative outcomes were compared between groups using paired statistical analysis techniques. RESULTS: Between 1998 and 2020, 36 patients underwent bilateral simultaneous metastasectomies. We matched 31 pairs of patients. The length of stay was significantly shorter in patients undergoing simultaneous resection (median 3 vs. 8 days, p < .001) and operative time was shorter (156 vs. 235.5 min, p < .001) when compared to the sum of both procedures in the staged group. The groups did not significantly differ with regard to postoperative complications. CONCLUSION: In a carefully selected patient population, simultaneous bilateral metastasectomy is a safe option. A single procedure confers benefits for both the patient as well as the hospital resource system.

Pulmonary resection for tissue harvest in adoptive tumor-infiltrating lymphocyte therapy: Safety and feasibility.

BACKGROUND AND OBJECTIVES: Adoptive T-cell therapies (ACTs) using expansion of tumor-infiltrating lymphocyte (TIL) populations are of great interest for advanced malignancies, with promising response rates in trial settings. However, postoperative outcomes following pulmonary TIL harvest have not been widely documented, and surgeons may be hesitant to operate in the setting of widespread disease. METHODS: Patients who underwent pulmonary TIL harvest were identified, and postoperative outcomes were studied, including pulmonary, cardiovascular, infectious, and wound complications. RESULTS: 83 patients met inclusion criteria. Pulmonary TIL harvest was undertaken primarily via a thoracoscopy with a median operative blood loss and duration of 30 ml and 65 min, respectively. The median length of stay was 2 days. Postoperative events were rare, occurring in only five (6%) patients, including two discharged with a chest tube, one discharged with oxygen, one episode of urinary retention, and one blood transfusion. No reoperations occurred. The median time from TIL harvest to ACT infusion was 37 days. CONCLUSIONS: Pulmonary TIL harvest is safe and feasible, without major postoperative events in our cohort. All patients were able to receive intended ACT infusion without delays. Therefore, thoracic surgeons should actively participate in ongoing ACT trials and aggressively seek to enroll patients on these protocols.

Cancer Surgery Scheduling During and After the COVID-19 First Wave: The MD Anderson Cancer Center Experience.

OBJECTIVE: To summarize the multi-specialty strategy and initial guidelines of a Case Review Committee in triaging oncologic surgery procedures in a large Comprehensive Cancer Center and to outline current steps moving forward after the initial wave. SUMMARY OF BACKGROUND DATA: The impetus for strategic rescheduling of operations is multifactorial and includes our societal responsibility to minimize COVID-19 exposure risk and propagation among patients, the healthcare workforce, and our community at large. Strategic rescheduling is also driven by the need to preserve limited resources. As many states have already or are considering to re-open and relax stay-at-home orders, there remains a continued need for careful surgical scheduling because we must face the reality that we will need to co-exist with COVID-19 for months, if not years. METHODS: The quality officers, chairs, and leadership of the 9 surgical departments in our Division of Surgery provide specialty-specific approaches to appropriately triage patients. RESULTS: We present the strategic approach for surgical rescheduling during and immediately after the COVID-19 first wave for the 9 departments in the Division of Surgery at The University of Texas MD Anderson Cancer Center in Houston, Texas. CONCLUSIONS: Cancer surgeons should continue to use their oncologic knowledge to determine the window of opportunity for each surgical procedure, based on tumor biology, preoperative treatment sequencing, and response to systemic therapy, to safely guide patients through this cautious recovery phase.

Importance of resection for locoregional disease control in Masaoka stage IVA thymic neoplasms.

BACKGROUND AND OBJECTIVES: It is unclear if a specific strategy for simultaneous treatment of primary thymic neoplasms and pleural metastases confers benefit for Masaoka stage IVA disease. We reviewed our experience with thymic neoplasms with concurrent pleural metastases to identify factors influencing outcomes. METHODS: Records of patients who presented with stage IVA thymic neoplasms from 2000 to 2018 were assessed. Multivariate Cox proportional hazards analyses were completed to determine predictors of progression-free and overall survival. RESULTS: Forty-eight patients were identified, including 34 (71%) who underwent surgery. Median overall and progression-free survival were 123 and 21 months, respectively. The extent of resection varied, and was most commonly thymectomy plus partial pleurectomy (22, 65%). Median progression-free survival for patients who underwent surgical resection versus those who had not was 24 versus 12 months (P = .018). Following surgical resection, mediastinal recurrence was uncommon (2, 6%, vs 7, 50% nonoperatively). Five-year survival rates in these groups were suggestive of possible benefit to surgery (87% vs 68%). CONCLUSIONS: Thymic neoplasms with pleural dissemination represents a treatment challenge. As part of a multidisciplinary approach, surgery appears to be associated with more favorable long-term results, although selection bias may account for some of the survival differences observed.

Time trends and predictors of survival in surgically resected early-stage non-small cell lung cancer patients.

BACKGROUND: The improvement in the management of lung cancer have the potential to improve survival in patients undergoing resection for early-stage (stage I and II) non-small cell lung cancer (NSCLC), but few studies have evaluated time trends and identified predictors of overall survival (OS). METHODS: We identified surgically resected early-stage NSCLC between 1998 and 2016. The 3-year OS (1998-2014) and 5-year OS (1998-2012) rates were calculated for each year. Joinpoint regression was used to calculate annual percentage changes (APC) and to test time trends in OS. Multivariable Cox regression was used to identify predictors of OS. RESULTS: There was a significant upward trend in the 3-year (1998, 56%; 2014, 83%; APC = 1.8) and 5-year (1998, 47%; 2012, 76%; APC = 3.1) OS. Older age; male sex; history of diabetes, coronary artery disease, and chronic obstructive pulmonary disease; high ASA score; smoking pack-years; high-grade tumor; pneumonectomy; thoracotomy; neoadjuvant therapy; nodal disease; and positive tumor margin were predictors of poor OS. CONCLUSION: The upward time trend in OS suggests that improved staging, patient selection, and management have conferred a survival benefit in early-stage NSCLC patients. The prediction model of OS could be used to refine selection criteria for resection and improve survival outcomes.

High mutational concordance between primary colorectal tumors and associated pulmonary metastases.

BACKGROUND AND OBJECTIVES: Precision medicine has altered the management of colorectal cancer (CRC). However, the concordance of mutational findings between primary CRC tumors and associated pulmonary metastases (PM) is not well-described. This study aims to determine the concordance of genomic profiles between primary CRC and PM. METHODS: Patients treated for colorectal PM at a single institution from 2000 to 2017 were identified. Mutational concordance was defined as either both wild-type or both mutant alleles in lung and colorectal lesion; genes with opposing mutational profiles were reported as discordant. RESULTS: Thirty-eight patients met inclusion criteria, among whom KRAS, BRAF, NRAS, MET, RET, and PIK3CA were examined for concordance. High concordance was demonstrated among all evaluated genes, ranging from 86% (KRAS) to 100% concordance (NRAS, RET, and MET). De novo KRAS mutations were detected in the PM of 4 from 35 (11%) patients, 3 of whom had previously received anti-epidermal growth factor receptor (EGFR) therapy. Evaluation of Cohen's κ statistic demonstrated moderate to perfect correlation among evaluated genes. CONCLUSIONS: Because high intertumoral genomic homogeneity exists, it may be reasonable to use primary CRC mutational profiles to guide prognostication and targeted therapy for PM. However, the possibility of de novo KRAS-mutant PM should be considered, particularly among patients previously treated with anti-EGFR therapy.

Driver Mutations in Normal Airway Epithelium Elucidate Spatiotemporal Resolution of Lung Cancer.

Rationale: Uninvolved normal-appearing airway epithelium has been shown to exhibit specific mutations characteristic of nearby non-small cell lung cancers (NSCLCs). Yet, its somatic mutational landscape in patients with early-stage NSCLC is unknown.Objectives: To comprehensively survey the somatic mutational architecture of the normal airway epithelium in patients with early-stage NSCLC.Methods: Multiregion normal airways, comprising tumor-adjacent small airways, tumor-distant large airways, nasal epithelium and uninvolved normal lung (collectively airway field), matched NSCLCs, and blood cells (n = 498) from 48 patients were interrogated for somatic single-nucleotide variants by deep-targeted DNA sequencing and for chromosomal allelic imbalance events by genome-wide genotype array profiling. Spatiotemporal relationships between the airway field and NSCLCs were assessed by phylogenetic analysis.Measurements and Main Results: Genomic airway field carcinogenesis was observed in 25 cases (52%). The airway field epithelium exhibited a total of 269 somatic mutations in most patients (n = 36) including key drivers that were shared with the NSCLCs. Allele frequencies of these acquired variants were overall higher in NSCLCs. Integrative analysis of single-nucleotide variants and allelic imbalance events revealed driver genes with shared "two-hit" alterations in the airway field (e.g., TP53, KRAS, KEAP1, STK11, and CDKN2A) and those with single hits progressing to two in the NSCLCs (e.g., PIK3CA and NOTCH1).Conclusions: Tumor-adjacent and tumor-distant normal-appearing airway epithelia exhibit somatic driver alterations that undergo selection-driven clonal expansion in NSCLC. These events offer spatiotemporal insights into the development of NSCLC and, thus, potential targets for early treatment.