Early Interventional Treatment of High Output Chyle Leak following Esophagectomy is Associated with Improved Survival.

OBJECTIVES: Our objective was to investigate overall survival (OS) and length of stay (LOS) associated with differing management for high output (>1 liter over 24 h) leaks (HOCL) following cancer related esophagectomy. SUMMARY BACKGROUND: Although infrequent, chyle leak following esophagectomy is an event that can lead to significant perioperative sequelae. Low volume leaks appear to respond to non-operative measures, while HOCL often require invasive therapeutic interventions. METHODS: From a prospective single-institution database, we retrospectively reviewed patients treated from 2001-2021 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 length of stay 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 non-operative management, 15 patients received prompt (<72 h from diagnosis) interventional management, and 23 received late interventional management. Patients in the late intervention group had longer length of stay compared to early intervention (Slope=9.849, 95% Confidence Interval [CI] 3.431 to 16.267). Late intervention (Hazard Ratio (HR) 4.772, CI: 1.384 to 16.460) and non-operative management (HR 4.731, CI: 1.294 to 17.305) were associated with increased mortality compared to 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 in order to possibly reverse the prognostic implications of this potentially detrimental complication.

Enhancing NSCLC recurrence prediction with PET/CT habitat imaging, ctDNA, and integrative radiogenomics-blood insights.

While we recognize the prognostic importance of clinicopathological measures and circulating tumor DNA (ctDNA), the independent contribution of quantitative image markers to prognosis in non-small cell lung cancer (NSCLC) remains underexplored. In our multi-institutional study of 394 NSCLC patients, we utilize pre-treatment computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to establish a habitat imaging framework for assessing regional heterogeneity within individual tumors. This framework identifies three PET/CT subtypes, which maintain prognostic value after adjusting for clinicopathologic risk factors including tumor volume. Additionally, these subtypes complement ctDNA in predicting disease recurrence. Radiogenomics analysis unveil the molecular underpinnings of these imaging subtypes, highlighting downregulation in interferon alpha and gamma pathways in the high-risk subtype. In summary, our study demonstrates that these habitat imaging subtypes effectively stratify NSCLC patients based on their risk levels for disease recurrence after initial curative surgery or radiotherapy, providing valuable insights for personalized treatment approaches.

Synthetic PET from CT improves diagnosis and prognosis for lung cancer: Proof of concept.

[18F]Fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) are indispensable components in modern medicine. Although PET can provide additional diagnostic value, it is costly and not universally accessible, particularly in low-income countries. To bridge this gap, we have developed a conditional generative adversarial network pipeline that can produce FDG-PET from diagnostic CT scans based on multi-center multi-modal lung cancer datasets (n = 1,478). Synthetic PET images are validated across imaging, biological, and clinical aspects. Radiologists confirm comparable imaging quality and tumor contrast between synthetic and actual PET scans. Radiogenomics analysis further proves that the dysregulated cancer hallmark pathways of synthetic PET are consistent with actual PET. We also demonstrate the clinical values of synthetic PET in improving lung cancer diagnosis, staging, risk prediction, and prognosis. Taken together, this proof-of-concept study testifies to the feasibility of applying deep learning to obtain high-fidelity PET translated from CT.

Personal history of cancer as a risk factor for second primary lung cancer: Implications for lung cancer screening.

BACKGROUND: Personal history of cancer is an independent risk factor for lung cancer but is omitted from existing lung cancer screening eligibility criteria. In this study, we assess the lung cancer risk among cancer survivors and discuss potential implications for screening. METHODS: This was a retrospective, secondary analysis of data from the Surveillance, Epidemiology and End Results (SEER) registry and the MD Anderson Cancer Center (MDACC). We estimated the standardized incidence ratios (SIRs) for lung cancer by site of first primary cancer using data from SEER. We assessed the lung cancer risk among head and neck cancer survivors from MDACC using cumulative incidence and compared the risk ratios (RR) by individuals' screening eligibility status. RESULTS: Other than first primary lung cancer (SIR: 5.10, 95% CI: 5.01-5.18), cancer survivors in SEER with personal history of head and neck cancer (SIR: 3.71, 95% CI: 3.63-3.80) had the highest risk of developing second primary lung cancer, followed by bladder (SIR: 1.86, 95% CI: 1.81-1.90) and esophageal cancers (SIR: 1.78, 95% CI: 1.61-1.96). Head and neck cancer survivors had higher risk to develop lung cancer compared to the National Lung Screening Trial's subjects, (781 vs. 572 per 100,000 person-years, respectively). Head and neck cancer survivors ineligible for lung cancer screening seen at MDACC had significantly higher lung cancer risk than head and neck cancer survivors from SEER (RR: 1.9, p < 0.001). CONCLUSION: Personal history of cancer, primarily head and neck cancer, is an independent risk factor for lung cancer and may be considered as an eligibility criterion in future lung cancer screening recommendations.

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.

Efficacy and safety of autologous tumor-infiltrating lymphocytes in recurrent or refractory ovarian cancer, colorectal cancer, and pancreatic ductal adenocarcinoma.

BACKGROUND: Tumor-infiltrating lymphocyte (TIL) therapy has shown efficacy in metastatic melanoma, non-small cell lung cancer, and other solid tumors. Our preclinical work demonstrated more robust CD8 predominant TIL production when agonistic anti-4-1BB and CD3 antibodies were used in early ex vivo TIL culture. METHODS: Patients with treatment-refractory metastatic colorectal (CRC), pancreatic (PDAC) and ovarian (OVCA) cancers were eligible. Lymphodepleting chemotherapy was followed by infusion of ex vivo expanded TIL, manufactured at MD Anderson Cancer Center with IL-2 and agonistic stimulation of CD3 and 4-1BB (urelumab). Patients received up to six doses of high-dose IL-2 after TIL infusion. Primary endpoint was evaluation of objective response rate at 12 weeks using Response Evaluation Criteria in Solid Tumors version 1.1 with secondary endpoints including disease control rate (DCR), duration of response, progression-free survival (PFS), overall survival (OS), and safety. RESULTS: 17 patients underwent TIL harvest and 16 were treated on protocol (NCT03610490), including 8 CRC, 5 PDAC, and 3 OVCA patients. Median age was 57.5 (range 33-70) and 50% were females. Median number of lines of prior therapy was 2 (range 1-8). No responses were observed at 12 weeks. Ten subjects achieved at least one stable disease (SD) assessment for a DCR of 62.5% (95% CI 35.4% to 84.8%). Best response included prolonged SD in a patient with PDAC lasting 17 months. Median PFS and OS across cohorts were 2.53 months (95% CI 1.54 to 4.11) and 18.86 months (95% CI 4.86 to NR), respectively. Grade 3 or higher toxicities attributable to therapy were seen in 14 subjects (87.5%; 95% CI 61.7% to 98.4%). Infusion product analysis showed the presence of effector memory cells with high expression of CD39 irrespective of tumor type and low expression of checkpoint markers. CONCLUSIONS: TIL manufactured with assistance of 4-1BB and CD3 agonism is feasible and treatment is associated with no new safety signals. While no responses were observed, a significant portion of patients achieved SD suggesting early/partial immunological effect. Further research is required to identify factors associated with resistance and functionally enhance T cells for a more effective therapy.

Gastric Extent of Tumor Predicts Peritoneal Metastasis in Siewert II Adenocarcinoma.

BACKGROUND: Whereas current guidelines recommend staging laparoscopy for most patients with potentially resectable gastric cancer, such a recommendation for patients with adenocarcinoma of the gastroesophageal junction (AEG) is lacking. This study sought to identify baseline clinicopathologic characteristics associated with peritoneal metastasis (PM) among patients with Siewert II AEG. METHODS: Trimodality therapy-eligible patients with Siewert II AEG (2000-2015, single institution) were retrospectively identified. A composite PM outcome was defined as follows: (1) PM at staging laparoscopy; (2) PM diagnosed during neoadjuvant chemoradiation; or (3) PM ≤6 months postoperatively. Logistic regression was used to identify features associated with PM; bootstrapped analysis (Youden J) identified the distal tumor extension that best discriminated the composite outcome. RESULTS: Of 188 patients, a composite PM outcome was observed in 26 of 188 (13.8%); 12 of 26 had positive staging laparoscopy, 10 of 26 experienced PM during chemoradiation, and 4 of 26 had PM ≤6 months postoperatively. Tumor extension below the GEJ was greater in patients with PM (median, 4.0 cm [interquartile range, 3.0-5.0] vs 3.0 cm [interquartile range, 2.0-3.0]; P < .001). All patients with PM had cT3 to cT4 tumors. Among patients with cT3 to cT4 tumors (n = 168 of 188; 89.4%), distal tumor extent (odds ratio, 1.67/cm; 95% CI, 1.23-2.28; P = .001) was independently associated with increased odds of PM. Gastric tumor extension ≥4 cm remained independently associated with PM (OR, 5.14; 95% CI, 2.11-12.53; P < .001) after adjustment for signet ring cell status. CONCLUSIONS: Distal tumor extent beyond the GEJ is independently associated with increased odds of PM in patients with Siewert II AEG. Patients with extensive gastric involvement should therefore be considered for staging laparoscopy before trimodality therapy.

Surgical outcomes after chemotherapy plus nivolumab and chemotherapy plus nivolumab and ipilimumab in patients with non-small cell lung cancer.

OBJECTIVE: Chemotherapy plus nivolumab is the standard of care neoadjuvant treatment for patients with resectable stage IB to IIIA non-small cell lung cancer. The influence of dual checkpoint blockade with chemotherapy on surgical outcomes remains unknown. We aimed to determine operative complexity and perioperative outcomes associated with neoadjuvant chemotherapy and nivolumab with or without ipilimumab. METHODS: A total of 44 patients with stage IB (≥4 cm) to IIIA non-small cell lung cancer were treated on sequential platform arms of the NEOSTAR trial. A total of 22 patients were treated with nivolumab + chemotherapy, and 22 patients were treated with ipilimumab + nivolumab + chemotherapy. The safety of surgical resection after neoadjuvant therapy was estimated using 30-day complication rates. Operative reports and surgeons' narratives were evaluated to determine procedural complexity and operative conduct. RESULTS: All 22 of 22 patients (100%) treated with nivolumab + chemotherapy underwent surgical resection: 20 R0 (90.9%), 17 (77.3%) lobectomies, 1 wedge resection, 2 segmentectomies, and 2 pneumonectomies. The majority, 21 of 22 (95%), were performed by thoracotomy. A total of 13 of 22 (59.1%) were rated as challenging resections. A total of 4 of 22 patients (18.2%) experienced grade 3 or greater Clavien-Dindo complication. A total of 20 of 22 patients (90.9%) treated with ipilimumab + nivolumab + chemotherapy underwent surgical resection: 19 R0 (95%), 18 (90%) lobectomies, 1 pneumonectomy, and 1 segmentectomy. A total of 16 of 20 (80%) resections were performed via thoracotomy, 3 of 20 (15%) via robotics, and 1 of 20 (5%) via thoracoscopy. A total of 9 of 20 (45%) resections were considered challenging. A total of 4 of 20 patients (20%) experienced grade 3 or greater Clavien-Dindo complication. CONCLUSIONS: Surgical resections are feasible and safe, with high rates of R0 after neoadjuvant chemotherapy and nivolumab with or without ipilimumab. Overall, approximately half of cases (22/42, 52.3%) were considered to be more challenging than a standard lobectomy.

Lung Cancer Screening in Head and Neck Cancer Patients: An Untapped Opportunity.

BACKGROUND: Despite evidence demonstrating that lung cancer screening (LCS) decreases mortality, widespread implementation is lagging. Efforts to identify and recruit patients for LCS are in need. Candidacy for LCS is based on identifiable risk factors, many of which overlap with those of head and neck malignancies. Thus, we aimed to evaluate the prevalence of candidacy for LCS in the head and neck cancer patient population. METHODS: We performed a review of anonymous surveys collected from patients who presented to a head and neck cancer clinic. Variables collected from these surveys included age, biologic sex, smoking history, and head and neck cancer history. Patients' candidacy for screening was determined, and descriptive analyses were performed. RESULTS: A total of 321 patient surveys were reviewed. Mean age was 63.7 years, and 195 (60.7%) were men. In this sample, 19 (5.91%) were current smokers, and 112 (34.9%) were former smokers, having quit an average of 19.4 years prior to completing the survey. Average pack-years was 29.3. Of the 321 patients surveyed, 60 (18.7%) would qualify for LCS using current guidelines. However, among those 60 patients who qualified for LCS, only 15 (25%) patients had been offered screening and only 14 (23.3%) had been screened. CONCLUSIONS: We have importantly demonstrated both a substantial prevalence of candidacy for LCS in the head and neck cancer population as well as disappointingly low levels of screening utilization in this group of patients. We have identified this setting as a key patient population that ought to be targeted for information about and access to LCS.

Perspectives, risk factors, and coping mechanisms in patients with self-reported financial burden following lung cancer surgery.

OBJECTIVE: We evaluated self-reported financial burden (FB) after lung cancer surgery and sought to assess patient perspectives, risk factors, and coping mechanisms within this population. METHODS: Patients with lung cancer resected at our institution between January 1, 2016, and December 31, 2021, were surveyed. Descriptive and multivariable analyses were performed to evaluate the association between clinical and financial characteristics with patient-reported major ("significant" or "catastrophic") FB. RESULTS: Of 1477 patients contacted, 31.3% (n = 463) completed the survey. Major FB was reported by 62 (13.4%) patients. multivariable analyses demonstrated increasing age (odds ratio [OR], 0.92; 95% CI, 0.88-0.96), credit score >740 (OR, 0.29; 95% CI, 0.14-0.60), and employer-based insurance (OR, 0.24; 95% CI, 0.07-0.80) were protective factors. In contrast, an out of pocket cost greater than expected (OR, 3.63; 95% CI, 1.67-7.88), decrease in work hours (OR, 4.42; 95% CI, 1.59-12.25), or cessation of work (OR, 5.13; 95% CI, 2.06-12.78), chronic obstructive pulmonary disease diagnosis (OR, 5.39, 95% CI, 1.87-15.50), and hospital readmission (OR, 4.87; 95% CI, 1.11-21.42) were risk factors for FB. To pay for care, some patients reported "often" or "always" decreasing food (n = 102 [23.4%]) or leisure spending (n = 179 [40.7%]). Additionally, use of savings (n = 246 [62.9%]), borrowing funds (n = 72 [16.6%]), and skipping clinic visits (n = 36 [8.3%]) at least once were also reported. Coping mechanisms occurred more often in patients with major FB compared with those without (P < .001). CONCLUSIONS: Patients with resected lung cancer may experience major FB related to treatment with several identifiable risk factors. Targeted interventions are needed to limit the adoption of detrimental coping mechanisms and potentially affect survivorship.

Lung surveillance following colorectal cancer pulmonary metastasectomy: Utilization of clinicopathologic risk factors to guide strategy.

BACKGROUND: Appropriately selected patients clearly benefit from resection of colorectal cancer (CRC) pulmonary metastases (PMs). However, there remains equipoise surrounding optimal chest surveillance strategies following pulmonary metastasectomy. We aimed to identify risk factors that may inform chest surveillance in this population. METHODS: Patients who underwent CRC pulmonary metastasectomy were identified from a single institution's prospectively maintained surgical database. Clinicopathologic and genomic characteristics were collected. Patients were stratified by diagnosis of subsequent PM within 6 months of the index lung resection. Multivariate modeling was used to evaluate risk factors. RESULTS: A total of 197 patients met the study's inclusion criteria, of whom 52.3% (n = 103) developed subsequent PM, at a median of 9.51 months following the index metastasectomy. Patients with KRAS alterations (odds ratio [OR], 3.073; 95% confidence interval [CI], 1.363-6.926; P = .007), TP53 alterations (OR, 3.109; 95% CI, 1.318-7.341; P = .010) were found to be at risk of PM diagnosis within 6 months of the index metastasectomy, while those with an APC alteration (OR, .218; 95% CI, 0.080-0.598; P = .003) were protected. Moreover, patients who received systemic therapy within 3 months of the initial PM diagnosis also were more likely to develop early lung recurrence (OR, 2.105; 95% CI, 0.971-4.563; P = .059). CONCLUSIONS: Patients with KRAS alterations, TP53 alterations, and no APC alterations developed early recurrence in the lung following pulmonary metastasectomy, as did those who received chemotherapy after their initial PM diagnosis. As such, these groups benefit from early lung imaging after metastasectomy, as chest surveillance protocols should be based on patient-centered clinicopathologic and genomic risk factors.

Impact of travel distance on receipt of indicated adjuvant therapy in resected non-small cell lung cancer.

OBJECTIVE: We have previously demonstrated the negative impact of travel distance on adherence to surveillance imaging guidelines for resected non-small cell lung cancer (NSCLC). The influence of patient residential location on adherence to recommended postoperative treatment plans remains unclear. We sought to characterize the impact of travel distance on receipt of indicated adjuvant therapy in resected NSCLC. METHODS: We performed a single-institution, retrospective review of patients with stage II-III NSCLC who underwent upfront pulmonary resection, 2012-2016. Clinicopathologic and operative/perioperative details of treatment were collected. Travel distance was measured from patients' homes to the operative hospital. Our primary outcome was receipt of adjuvant systemic or radiotherapy. Travel distance was stratified as <100 or >100 miles. Multivariable logistic regression was performed. RESULTS: In total, 391 patients met inclusion criteria, with mean age of 65.9 years and fairly even sex distribution (182 women, 49.2%). Most patients were Non-Hispanic White (n = 309, 83.5%), and most frequent clinical stage was II (n = 254, 64.9%). Indicated adjuvant therapy was received by 266 (71.9%), and median distance traveled was 209 miles (interquartile range, 50.7-617). Multivariate analysis revealed that longer travel distance was inversely associated with receipt of indicated adjuvant therapy (odds ratio, 0.13; 95% confidence interval, 0.06-0.26; P < .001). In addition, Black patients were less likely to receive appropriate treatment (odds ratio, 0.05; 95% confidence interval, 0.02-0.15; P < .001). CONCLUSIONS: Travel distance >100 miles negatively impacts the likelihood of receiving indicated adjuvant therapy in NSCLC. Indications for systemic therapy in earlier staged disease are rapidly expanding, and these findings bear heightened relevance as we aim to provide equitable access to all patients.

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.