Salvage surgery for local recurrences after stereotactic ablative radiotherapy of colorectal pulmonary metastases.

INTRODUCTION: Local control following stereotactic ablative radiotherapy (SABR) for patients with colorectal pulmonary metastases is reportedly lower than for metastases from other tumors. Such recurrences may still be amenable to salvage therapy. We describe our experience with salvage surgery in 17 patients. METHODS: Patients who underwent salvage metastasectomy for a local recurrence following SABR for colorectal pulmonary metastases were identified from the surgical institutional databases of three Dutch major referral hospitals. Kaplan-Meier survival analysis was performed to determine survival. RESULTS: Seventeen patients underwent 20 salvage resections for local recurrence of colorectal pulmonary metastases. All patients had a progressive lesion on consecutive CT scans, with local uptake on 18 fluorodeoxyglucose-positron emission tomography computed tomography (FDG-PET CT), and were discussed in a thoracic oncology tumor board. Median time to local recurrence following SABR was 20 months (interquartile range [IQR]: 13-29). Fourteen procedures were performed minimally invasively. Extensive adhesions were observed during three procedures. A Clavien-Dindo grade III-IV complication occurred after four resections (20%). The 90-day mortality was 0%. The estimated median overall survival and progression-free survival following salvage resection were 71 months (confidence intervals [CI]: 50-92) and 39 months (CI: 19-58), respectively. Salvage resections were significantly more extensive, compared to the potential resection assessed on pre-SABR imaging. CONCLUSIONS: Our experience with 20 salvage pulmonary metastasectomy procedures for local recurrences following SABR in colorectal cancer patients demonstrates that salvage resection is a feasible option with acceptable morbidity and good oncological outcome in a highly selected cohort.

Spontaneous haemoperitoneum in pregnancy: Nationwide surveillance and Delphi audit system.

OBJECTIVE: To evaluate the incidence, diagnostic management strategies and clinical outcomes of women with spontaneous haemoperitoneum in pregnancy (SHiP) and reassess the definition of SHiP. DESIGN: A population-based cohort study using the Netherlands Obstetric Surveillance System (NethOSS). SETTING: Nationwide, the Netherlands. POPULATION: All pregnant women between April 2016 and April 2018. METHODS: This is a case study of SHiP using the monthly registry reports of NethOSS. Complete anonymised case files were obtained. A newly introduced online Delphi audit system (DAS) was used to evaluate each case, to make recommendations on improving the management of SHiP and to propose a new definition of SHiP. MAIN OUTCOME MEASURES: Incidence and outcomes, lessons learned about clinical management and the critical appraisal of the current definition of SHiP. RESULTS: In total, 24 cases were reported. After a Delphi procedure, 14 cases were classified as SHiP. The nationwide incidence was 4.9 per 100 000 births. Endometriosis and conceiving after artificial reproductive techniques were identified as risk factors. No maternal and three perinatal deaths occurred. Based on the DAS, adequate imaging of free intra-abdominal fluid, and identifying and treating women with signs of hypovolemic shock could improve the early detection and management of SHiP. A revised definition of SHiP was proposed, excluding the need for surgical or radiological intervention. CONCLUSIONS: SHiP is a rare and easily misdiagnosed condition that is associated with high perinatal mortality. To improve care, better awareness among healthcare workers is needed. The DAS is a sufficient tool to audit maternal morbidity and mortality.

Recurrent Disease After Esophageal Cancer Surgery: A Substudy of The Dutch Nationwide Ivory Study.

OBJECTIVE: This study investigated the patterns, predictors, and survival of recurrent disease following esophageal cancer surgery. BACKGROUND: Survival of recurrent esophageal cancer is usually poor, with limited prospects of remission. METHODS: This nationwide cohort study included patients with distal esophageal and gastroesophageal junction adenocarcinoma and squamous cell carcinoma after curatively intended esophagectomy in 2007 to 2016 (follow-up until January 2020). Patients with distant metastases detected during surgery were excluded. Univariable and multivariable logistic regression were used to identify predictors of recurrent disease. Multivariable Cox regression was used to determine the association of recurrence site and treatment intent with postrecurrence survival. RESULTS: Among 4626 patients, 45.1% developed recurrent disease a median of 11 months postoperative, of whom most had solely distant metastases (59.8%). Disease recurrences were most frequently hepatic (26.2%) or pulmonary (25.1%). Factors significantly associated with disease recurrence included young age (≤65 y), male sex, adenocarcinoma, open surgery, transthoracic esophagectomy, nonradical resection, higher T-stage, and tumor positive lymph nodes. Overall, median postrecurrence survival was 4 months [95% confidence interval (95% CI): 3.6-4.4]. After curatively intended recurrence treatment, median survival was 20 months (95% CI: 16.4-23.7). Survival was more favorable after locoregional compared with distant recurrence (hazard ratio: 0.74, 95% CI: 0.65-0.84). CONCLUSIONS: This study provides important prognostic information assisting in the surveillance and counseling of patients after curatively intended esophageal cancer surgery. Nearly half the patients developed recurrent disease, with limited prospects of survival. The risk of recurrence was higher in patients with a higher tumor stage, nonradical resection and positive lymph node harvest.

Impact of the COVID-19 pandemic on surgical care in the Netherlands.

BACKGROUND: The COVID-19 pandemic caused disruption of regular healthcare leading to reduced hospital attendances, repurposing of surgical facilities, and cancellation of cancer screening programmes. This study aimed to determine the impact of COVID-19 on surgical care in the Netherlands. METHODS: A nationwide study was conducted in collaboration with the Dutch Institute for Clinical Auditing. Eight surgical audits were expanded with items regarding alterations in scheduling and treatment plans. Data on procedures performed in 2020 were compared with those from a historical cohort (2018-2019). Endpoints included total numbers of procedures performed and altered treatment plans. Secondary endpoints included complication, readmission, and mortality rates. RESULTS: Some 12 154 procedures were performed in participating hospitals in 2020, representing a decrease of 13.6 per cent compared with 2018-2019. The largest reduction (29.2 per cent) was for non-cancer procedures during the first COVID-19 wave. Surgical treatment was postponed for 9.6 per cent of patients. Alterations in surgical treatment plans were observed in 1.7 per cent. Time from diagnosis to surgery decreased (to 28 days in 2020, from 34 days in 2019 and 36 days in 2018; P < 0.001). For cancer-related procedures, duration of hospital stay decreased (5 versus 6 days; P < 0.001). Audit-specific complications, readmission, and mortality rates were unchanged, but ICU admissions decreased (16.5 versus 16.8 per cent; P < 0.001). CONCLUSION: The reduction in the number of surgical operations was greatest for those without cancer. Where surgery was undertaken, it appeared to be delivered safely, with similar complication and mortality rates, fewer admissions to ICU, and a shorter hospital stay.

COVID-19 has had a significant impact on healthcare worldwide. Hospital visits were reduced, operating facilities were used for COVID-19 care, and cancer screening programmes were cancelled. This study describes the impact of the COVID-19 pandemic on Dutch surgical healthcare in 2020. Patterns of care in terms of changed or delayed treatment are described for patients who had surgery in 2020, compared with those who had surgery in 2018­2019. The study found that mainly non-cancer surgical treatments were cancelled during months with high COVID-19 rates. Outcomes for patients undergoing surgery were similar but with fewer ICU admissions and shorter hospital stay. These data provide no insight into the burden endured by patients who had postponed or cancelled operations.

Short-term outcome for high-risk patients after esophagectomy.

Transthoracic esophagectomy (TTE) for esophageal cancer facilitates mediastinal dissection; however, it has a significant impact on cardiopulmonary status. High-risk patients may therefore be better candidates for transhiatal esophagectomy (THE) in order to prevent serious complications. This study addressed short-term outcome following TTE and THE in patients that are considered to have a higher risk of surgery-related morbidity. This population-based study included patients who underwent a curative esophagectomy between 2011 and 2018, registered in the Dutch Upper GI Cancer Audit. The Charlson comorbidity index was used to assign patients to a low-risk (score ≤ 1) and high-risk group (score ≥ 2). Propensity score matching was applied to produce comparable groups between high-risk patients receiving TTE and THE. Primary endpoint was mortality (in-hospital/30-day mortality), secondary endpoints included morbidity and oncological outcomes. Additionally, a matched subgroup analysis was performed, including only cervical reconstructions. Of 5,438 patients, 945 and 431 high-risk patients underwent TTE and THE, respectively. After propensity score matching, mortality (6.3 vs 3.3%, P = 0.050), overall morbidity, Clavien-Dindo ≥ 3 complications, pulmonary complications, cardiac complications and re-interventions were significantly more observed after TTE compared to THE. A significantly higher mortality after TTE with a cervical reconstruction was found compared to THE (7.0 vs. 2.2%, P = 0.020). Patients with a high Charlson comorbidity index predispose for a complicated postoperative course after esophagectomy, this was more outspoken after TTE compared to THE. In daily practice, these outcomes should be balanced with the lower lymph node yield, but comparable positive node count and radicality after THE.

Ipilimumab plus nivolumab and chemoradiotherapy followed by surgery in patients with resectable and borderline resectable T3-4N0-1 non-small cell lung cancer: the INCREASE trial.

BACKGROUND: The likelihood of a tumor recurrence in patients with T3-4N0-1 non-small cell lung cancer following multimodality treatment remains substantial, mainly due distant metastases. As pathological complete responses (pCR) in resected specimens are seen in only a minority (28-38%) of patients following chemoradiotherapy, we designed the INCREASE trial (EudraCT-Number: 2019-003454-83; Netherlands Trial Register number: NL8435) to assess if pCR rates could be further improved by adding short course immunotherapy to induction chemoradiotherapy. Translational studies will correlate changes in loco-regional and systemic immune status with patterns of recurrence. METHODS/DESIGN: This single-arm, prospective phase II trial will enroll 29 patients with either resectable, or borderline resectable, T3-4N0-1 NSCLC. The protocol was approved by the institutional ethics committee. Study enrollment commenced in February 2020. On day 1 of guideline-recommended concurrent chemoradiotherapy (CRT), ipilimumab (IPI, 1 mg/kg IV) and nivolumab (NIVO, 360 mg flat dose IV) will be administered, followed by nivolumab (360 mg flat dose IV) after 3 weeks. Radiotherapy consists of once-daily doses of 2 Gy to a total of 50 Gy, and chemotherapy will consist of a platinum-doublet. An anatomical pulmonary resection is planned 6 weeks after the last day of radiotherapy. The primary study objective is to establish the safety of adding IPI/NIVO to pre-operative CRT, and its impact on pathological tumor response. Secondary objectives are to assess the impact of adding IPI/NIVO to CRT on disease free and overall survival. Exploratory objectives are to characterize tumor inflammation and the immune contexture in the tumor and tumor-draining lymph nodes (TDLN), and to explore the effects of IPI/NIVO and CRT and surgery on distribution and phenotype of peripheral blood immune subsets. DISCUSSION: The INCREASE trial will evaluate the safety and local efficacy of a combination of 4 modalities in patients with resectable, T3-4N0-1 NSCLC. Translational research will investigate the mechanisms of action and drug related adverse events. TRIAL REGISTRATION: Netherlands Trial Registration (NTR): NL8435 , Registered 03 March 2020.

Definitive Chemoradiotherapy Versus Trimodality Therapy for Resectable Oesophageal Carcinoma: Meta-analyses and Systematic Review of Literature.

BACKGROUND: Standard therapy for loco-regionally advanced, resectable oesophageal carcinoma is trimodality therapy (TMT) consisting of neoadjuvant chemoradiotherapy and oesophagectomy. Evidence of survival advantage of TMT over organ-preserving definitive chemoradiotherapy (dCRT) is inconclusive. The aim of this study is to compare survival between TMT and dCRT. METHODS: A systematic review and meta-analyses were conducted. Randomised controlled trials and observational studies on resectable, curatively treated, oesophageal carcinoma patients above 18 years were included. Three online databases were searched for studies comparing TMT with dCRT. Primary outcomes were 1-, 2-, 3- and 5-year overall survival rates. Risk of bias was assessed using the Cochrane risk of bias tools for RCTs and cohort studies. Quality of evidence was evaluated according to Grading of Recommendation Assessment, Development and Evaluation. RESULTS: Thirty-two studies described in 35 articles were included in this systematic review, and 33 were included in the meta-analyses. Two-, three- and five-year overall survival was significantly lower in dCRT compared to TMT, with relative risks (RRs) of 0.69 (95% CI 0.57-0.83), 0.76 (95% CI 0.63-0.92) and 0.57 (95% CI 0.47-0.71), respectively. When only analysing studies with equal patient groups at baseline, no significant differences for 2-, 3- and 5-year overall survival were found with RRs of 0.83 (95% CI 0.62-1.10), 0.81 (95% CI 0.57-1.14) and 0.63 (95% CI 0.36-1.12). CONCLUSION: These meta-analyses do not show clear survival advantage for TMT over dCRT. Only a non-significant trend towards better survival was seen, assuming comparable patient groups at baseline. Non-operative management of oesophageal carcinoma patients might be part of a personalised and tailored treatment approach in future. However, to date hard evidence proving its non-inferiority compared to operative management is lacking.

MEDIASTinal staging of non-small cell lung cancer by endobronchial and endoscopic ultrasonography with or without additional surgical mediastinoscopy (MEDIASTrial): study protocol of a multicenter randomised controlled trial.

BACKGROUND: In case of suspicious lymph nodes on computed tomography (CT) or fluorodeoxyglucose positron emission tomography (FDG-PET), advanced tumour size or central tumour location in patients with suspected non-small cell lung cancer (NSCLC), Dutch and European guidelines recommend mediastinal staging by endosonography (endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS)) with sampling of mediastinal lymph nodes. If biopsy results from endosonography turn out negative, additional surgical staging of the mediastinum by mediastinoscopy is advised to prevent unnecessary lung resection due to false negative endosonography findings. We hypothesize that omitting mediastinoscopy after negative endosonography in mediastinal staging of NSCLC does not result in an unacceptable percentage of unforeseen N2 disease at surgical resection. In addition, omitting mediastinoscopy comprises no extra waiting time until definite surgery, omits one extra general anaesthesia and hospital admission, and may be associated with lower morbidity and comparable survival. Therefore, this strategy may reduce health care costs and increase quality of life. The aim of this study is to compare the cost-effectiveness and cost-utility of mediastinal staging strategies including and excluding mediastinoscopy. METHODS/DESIGN: This study is a multicenter parallel randomized non-inferiority trial comparing two diagnostic strategies (with or without mediastinoscopy) for mediastinal staging in 360 patients with suspected resectable NSCLC. Patients are eligible for inclusion when they underwent systematic endosonography to evaluate mediastinal lymph nodes including tissue sampling with negative endosonography results. Patients will not be eligible for inclusion when PET/CT demonstrates 'bulky N2-N3' disease or the combination of a highly suspicious as well as irresectable mediastinal lymph node. Primary outcome measure for non-inferiority is the proportion of patients with unforeseen N2 disease at surgery. Secondary outcome measures are hospitalization, morbidity, overall 2-year survival, quality of life, cost-effectiveness and cost-utility. Patients will be followed up 2 years after start of treatment. DISCUSSION: Results of the MEDIASTrial will have immediate impact on national and international guidelines, which are accessible to public, possibly reducing mediastinoscopy as a commonly performed invasive procedure for NSCLC staging and diminishing variation in clinical practice. TRIAL REGISTRATION: The trial is registered at the Netherlands Trial Register on July 6th, 2017 ( NTR 6528 ).

Recurrent Falls Due to Hypoglycemia: Case of an IGF-2-producing Fibrous Tumor of the Pleura.

This case report delineates the clinical presentation of a 77-year-old male who experienced falls and sustained a humerus fracture attributed to hypoglycemia. Despite the absence of insulin use and normal laboratory results for cortisol, TSH, blood count, and liver and kidney function, a fasting test revealed diminished C-peptide and insulin levels, ruling out insulinoma, exogenous insulin use, or ß-cell hyperplasia. Subsequent laboratory investigations demonstrated lowered IGF-1 and elevated IGF-2 levels, indicative of an IGF-2-producing tumor as the etiology of the hypoglycemia. A positron emission tomography computed tomography scan identified a right-sided thoracic cavity tumor, prompting an open resection. Postoperatively, hypoglycemic episodes abated within 2 days, and pathology confirmed a 14.9-cm solitary fibrous tumor. Nonislet cell tumor hypoglycemia (NICTH), also known as Doege Potter syndrome, arises from aberrant production of IGF-2 or its precursors. Elevated IGF-2 levels induce hypoglycemia through heightened glucose uptake on binding to insulin receptors. The literature supports the efficacy of both surgical intervention and corticosteroids in managing NICTH. This case underscores the importance of considering NICTH as a rare etiology in unexplained hypoglycemia cases, advocating for the utility of fasting tests in diagnosis, and suggesting surgical resection as a viable treatment option when radical excision is feasible.

Chest wall resections for sulcus superior tumors.

Chemoradiotherapy followed by surgical resection (trimodality therapy) is a guideline recommended treatment for sulcus superior tumors (SST). By definition, SSTs invade the chest wall and therefore require en-bloc chest wall resection with the upper lung lobe or segments. The addition of a chest wall resection, potentially results in higher morbidity and mortality rates when compared to standard anatomical pulmonary resection. This, together with their anatomical location in the thoracic outlet, and varying grades of fibrosis and adhesions resulting from induction chemoradiotherapy in the operation field, make surgery challenging. Depending on the exact location of the tumor and extent to which it invades the surrounding structures, the preferred surgical approach may vary, e.g., anterior, posterolateral, hemi-clamshell, or combined approach; all with their own potential advantages and morbidities. Careful patient selection, adequate staging and discussion in a multidisciplinary tumor board in a center experienced in complex thoracic oncology leads to the best long-term survival outcomes with the least morbidity and mortality. Enhanced recovery guidelines are now available for thoracic surgery, promoting faster recovery and helping to minimize complications and morbidity, including infections and thoracotomy pain. Although minimally invasive surgery can enhance recovery and reduce chest wall morbidity, and is in widespread use in thoracic oncology, its use for SST has been limited. However, this is an evolving area and hybrid surgical approaches (including use of the robot) are being reported. Chest wall reconstruction is rarely necessary, but if so, the prosthetic materials are preferably radiolucent/non-scattering, rigid enough while still being somewhat flexible, and inert, providing structural support, allowing chest wall movement, and closing defects, while inciting a limited inflammatory response. New techniques such as 3D image reconstructions/volume rendering, 3D-printing, and virtual reality modules may help pre-operative planning and informed patient consent.

Population-based study on surgical care for primary spontaneous pneumothorax.

OBJECTIVES: The optimal surgical strategy for primary spontaneous pneumothorax remains a matter of debate and variation in surgical practice is expected. This variation may influence clinical outcomes, such as postoperative complications and length of stay. This national population-based registry study provides an overview and extent of variability of current surgical practice and outcomes in the Netherlands. METHODS: To identify national patterns of care and between-hospital variability in the treatment of primary spontaneous pneumothorax, patients who underwent surgical pleurodesis and/or bullectomy between 2014 and 2021, were identified from the Dutch Lung Cancer Audit-Surgery database. The type of surgical intervention, postoperative complications, length of stay and ipsilateral recurrences were recorded. RESULTS AND CONCLUSIONS: Out of 4338 patients, 1851 patients were identified to have primary spontaneous pneumothorax. The median age was 25 years (interquartile range 20-31) and 82% was male. The most performed surgical procedure was bullectomy with pleurodesis (83%). The overall complication rate was 12% (Clavien-Dindo grade ≥III 6%), with the highest recorded incidence for persistent air leak >5 days (5%). Median postoperative length of stay was 4 days (interquartile range 3-6) and 0.7% underwent a repeat pleurodesis for ipsilateral recurrence. Complication rate and length of stay differed considerably between hospitals. There were no differences between the surgical procedures. In the Netherlands, surgical patients with primary spontaneous pneumothorax are preferably treated with bullectomy plus pleurodesis. Postoperative complications and length of stay vary widely and are considerable in this young patient group. This may be reduced by optimization of surgical care.

The Impact of the COVID-19 Pandemic on Time to Treatment in Surgical Oncology: A National Registry Study in The Netherlands.

To avoid delay in oncological treatment, a 6-weeks norm for time to treatment has been agreed on in The Netherlands. However, the impact of the COVID-19 pandemic on health systems resulted in reduced capacity for regular surgical care. In this study, we investigated the impact of the COVID-19 pandemic on time to treatment in surgical oncology in The Netherlands. METHODS: A population-based analysis of data derived from five surgical audits, including patients who underwent surgery for lung cancer, colorectal cancer, upper gastro-intestinal, and hepato-pancreato-biliary (HPB) malignancies, was performed. The COVID-19 cohort of 2020 was compared to the historic cohorts of 2018 and 2019. Primary endpoints were time to treatment initiation and the proportion of patients whose treatment started within 6 weeks. The secondary objective was to evaluate the differences in characteristics and tumour stage distribution between patients treated before and during the COVID-19 pandemic. RESULTS: A total of 14,567 surgical cancer patients were included in this study, of these 3292 treatments were started during the COVID-19 pandemic. The median time to treatment decreased during the pandemic (26 vs. 27 days, p < 0.001) and the proportion of patients whose treatment started within 6 weeks increased (76% vs. 73%, p < 0.001). In a multivariate logistic regression analysis, adjusting for patient characteristics, no significant difference in post-operative outcomes between patients who started treatment before or after 6 weeks was found. Overall, the number of procedures performed per week decreased by 8.1% during the pandemic. This reduction was most profound for patients with stage I lung carcinoma and colorectal carcinoma. There were fewer patients with pulmonary comorbidities in the pandemic cohort (11% vs. 13%, p = 0.003). CONCLUSIONS: Despite pressure on the capacity of the healthcare system during the COVID-19 pandemic, a larger proportion of surgical oncological patients started treatment within six weeks, possibly due to prioritisation of cancer care and reductions in elective procedures. However, during the pandemic, a decrease in the number of surgical oncological procedures performed in The Netherlands was observed, especially for patients with stage I disease.

Transbronchial cryobiopsy followed by as-needed surgical lung biopsy versus immediate surgical lung biopsy for diagnosing interstitial lung disease (the COLD study): a randomised controlled trial.

BACKGROUND: An adequate diagnosis for interstitial lung disease (ILD) is important for clinical decision making and prognosis. In most patients with ILD, an accurate diagnosis can be made by clinical and radiological data assessment, but in a considerable proportion of patients, a lung biopsy is required. Surgical lung biopsy (SLB) is the most common method to obtain tissue, but it is associated with high morbidity and even mortality. More recently, transbronchial cryobiopsy has been introduced, with fewer adverse events but a lower diagnostic yield than SLB. The aim of this study is to compare two diagnostic strategies: a step-up strategy (transbronchial cryobiopsy, followed by SLB if the cryobiopsy is insufficiently informative) versus immediate SLB. METHODS: The COLD study was a multicentre, randomised controlled trial in six hospitals across the Netherlands. We included patients with ILD with an indication for lung biopsy as assessed by a multidisciplinary team discussion. Patients were randomly assigned in a 1:1 ratio to the step-up or immediate SLB strategy, with follow-up for 12 weeks from the initial procedure. Patients, clinicians, and pathologists were not masked to the study treatment. The primary endpoint was unexpected chest tube drainage, defined as requiring any chest tube after transbronchial cryobiopsy, or prolonged (>24 h) chest tube drainage after SLB. Secondary endpoints were diagnostic yield, in-hospital stay, pain, and serious adverse events. A modified intention-to-treat analysis was performed. This trial is registered with the Dutch Trial Register, NL7634, and is now closed. FINDINGS: Between April 8, 2019, and Oct 24, 2021, 122 patients with ILD were assessed for study participation; and 55 patients were randomly assigned to the step-up strategy (n=28) or immediate SLB (n=27); three patients from the immediate SLB group were excluded. Unexpected chest tube drainage occurred in three of 28 patients (11%; 95% CI 4-27%) in the step-up group, and the number of patients for whom the chest tube could not be removed within 24 h was 11 of 24 patients (46%; 95% CI 2-65%) in the SLB group, with an absolute risk reduction of 35% (11-56%; p=0·0058). In the step-up strategy, the multidisciplinary team diagnostic yield after transbronchial cryobiopsy alone was 82% (64-92%), which increased to 89% (73-96%) when subsequent SLB was performed after inconclusive transbronchial cryobiopsy. In the immediate surgery strategy, the multidisciplinary team diagnostic yield was 88% (69-97%). Total in-hospital stay was 1 day (IQR 1-1) in the step-up group versus 5 days (IQR 4-6) in the SLB group. One (4%) serious adverse event occurred in step-up strategy versus 12 (50%) in the immediate SLB strategy. INTERPRETATION: In ILD diagnosis, if lung tissue assessment is required, a diagnostic strategy starting with transbronchial cryobiopsy, followed by SLB when transbronchial cryobiopsy is inconclusive, appears to result in a significant reduction of patient burden and in-hospital stay with a similar diagnostic yield versus immediate SLB. FUNDING: Netherlands Organisation for Health Research and Development (ZonMW) and Amsterdam University Medical Centers.

Single-arm trial of neoadjuvant ipilimumab plus nivolumab with chemoradiotherapy in patients with resectable and borderline resectable lung cancer: the INCREASE study.

BACKGROUND: In non-small cell lung cancer (NSCLC), chemoradiotherapy (CRT) yields pathological complete response (pCR) rates of approximately 30%. We investigated using ipilimumab plus nivolumab (IPI-NIVO) with neoadjuvant CRT in resectable, and borderline resectable NSCLC. METHODS: This single-arm, phase-II trial enrolled operable T3-4N0-2 patients with NSCLC without oncogenic drivers. Primary study endpoints were safety, major pathological response (MPR) and pCR. Treatment encompassed platinum-doublet concurrent CRT, IPI 1 mg/kg intravenous and NIVO 360 mg intravenous on day-1, followed by chemotherapy plus NIVO 360 mg 3 weeks later. Thoracic radiotherapy was 50 or 60 Gy, in once-daily doses of 2 Gy. Resections were 6 weeks post-radiotherapy. RESULTS: In a total of 30 patients in the intention-to-treat (ITT) population, grades 3-4 treatment-related adverse events (TRAEs) occurred in 70%, one TRAE grade 5 late-onset pneumonitis on day 96 post-surgery (1/30, 3.3%) occurred, and one non-TRAE COVID-19 death (1/30, 3.3%). pCR and MPR were achieved in 50% (15/30) and 63% (19/30) of the ITT; and in 58% (15/26) and 73% (19/26) of the 26 patients who underwent surgery, respectively. Postoperative melanoma was seen in one non-pCR patient. The R0 rate was 100% (26/26), and no patient failed surgery due to TRAEs. In peripheral blood, proliferative CD8+ T cells were increased, while proliferative regulatory T cells (Tregs) were not. On-treatment, pCR-positives had higher CD8+CD39+ T cells and lower HLA-DR+ Tregs. CONCLUSIONS: Neoadjuvant IPI-NIVO-CRT in T3-4N0-2 NSCLC showed acceptable safety with pCR and MPR in 58% and 73% of operated patients, respectively. No patient failed surgery due to TRAEs. TRIAL REGISTRATION NUMBER: NCT04245514.

Minimally invasive technique for gastric GIST at challenging locations: single incision surgical gastroscopy.

Organ sparing resection of gastrointestinal stromal tumors (GISTs) located in the proximal stomach or esophagogastric junction can be challenging, resulting in proximal or total gastrectomy to facilitate a radical resection without tumor spill. We developed and evaluated a single incision surgical gastroscopy (SISG) procedure to provide a technically feasible alternative for the removal of gastric GISTs at these challenging locations. We developed an endoluminal resection of gastric GISTs through a small single abdominal incision and longitudinal ventral gastrotomy. Patients with a proximal tumor location, in whom a wedge resection was deemed challenging on pre-operative investigation were included in the current series. Safety, short-term oncological and surgical outcome were evaluated. We performed SISG in six consecutive patients with histopathological proven or suspected gastric GIST. In all patients, the procedure was performed successfully with no tumor rupture. The mean operative time was 61 min and there were no significant complications. Pathological examination showed a microscopically radical resection in all patients. Single incision surgical gastroscopy is a feasible technique with excellent short-term oncological and surgical outcomes. This technique serves as a good alternative for complicated resections for gastric GISTs at challenging locations.

Pulmonary metastasectomy and repeat metastasectomy for colorectal pulmonary metastases: outcomes from the Dutch Lung Cancer Audit for Surgery.

BACKGROUND: Surgical resection of recurrent pulmonary metastases in patients with colorectal cancer is an established treatment option; however, the evidence for repeat resection is limited. The aim of this study was to analyse long-term outcomes from the Dutch Lung Cancer Audit for Surgery. METHODS: Data from the mandatory Dutch Lung Cancer Audit for Surgery were used to analyse all patients after metastasectomy or repeat metastasectomy for colorectal pulmonary metastases from January 2012 to December 2019 in the Netherlands. Kaplan-Meier survival analysis was performed to determine the difference in survival. Multivariable Cox regression analyses were performed to identify predictors of survival. RESULTS: A total of 1237 patients met the inclusion criteria, of which 127 patients underwent repeat metastasectomy. Five-year overall survival was 53 per cent after pulmonary metastasectomy for colorectal pulmonary metastases and 52 per cent after repeat metastasectomy (P = 0.852). The median follow-up was 42 (range 0-285) months. More patients experienced postoperative complications after repeat metastasectomy compared with the first metastasectomy (18.1 per cent versus 11.6 per cent respectively; P = 0.033). Eastern Cooperative Oncology Group performance status greater than or equal to 1 (HR 1.33, 95 per cent c.i. 1.08 to 1.65; P = 0.008), multiple metastases (HR 1.30, 95 per cent c.i. 1.01 to 1.67; P = 0.038), and bilateral metastases (HR 1.50, 95 per cent c.i. 1.01 to 2.22; P = 0.045) were prognostic factors on multivariable analysis for pulmonary metastasectomy. Diffusing capacity of the lungs for carbon monoxide less than 80 per cent (HR 1.04, 95 per cent c.i. 1.01 to 1.06; P = 0.004) was the only prognostic factor on multivariable analysis for repeat metastasectomy. CONCLUSION: This study demonstrates that patients with colorectal pulmonary metastases have comparable median and 5-year overall survival rates after primary or recurrent pulmonary metastasectomy. However, repeat metastasectomy has a higher risk of postoperative complications.

Colorectal Pulmonary Metastases: Pulmonary Metastasectomy or Stereotactic Radiotherapy?

BACKGROUND: Pulmonary metastasectomy and stereotactic ablative radiotherapy (SABR) are both guideline-recommended treatments for selected patients with oligometastatic colorectal pulmonary metastases. However, there is limited evidence comparing these local treatment modalities in similar patient groups. METHODS: We retrospectively reviewed records of consecutive patients treated for colorectal pulmonary metastases with surgical metastasectomy or SABR from 2012 to 2019 at two Dutch referral hospitals that had different approaches toward the local treatment of colorectal pulmonary metastases, one preferring surgery, the other preferring SABR. Two comparable patient groups were identified based on tumor and treatment characteristics. RESULTS: The metastasectomy group comprised 40 patients treated for 69 metastases, and the SABR group had 60 patients who were treated for 90 metastases. Median follow-up was 38 months (IQR: 26-67) in the surgery group and 46 months (IQR: 30-79) in the SABR group. Median OS was 58 months (CI: 20-94) in the metastasectomy group and 70 months (CI: 29-111) in the SABR group (p = 0.23). Five-year local recurrence-free survival (LRFS) was 44% after metastasectomy and 30% after SABR (p = 0.16). Median progression-free survival (PFS) was 15 months (CI: 3-26) in the metastasectomy group and 10 months (CI: 6-13) in the SABR group (p = 0.049). Local recurrence rate was 12.5/7.2% of patients/metastases respectively after metastasectomy and 38.3/31.1% after SABR (p < 0.001). Lower BED Gy10 was correlated with an increased likelihood of recurrence (p = 0.025). Clavien Dindo grade III-V complication rates were 2.5% after metastasectomy and 0% after SABR (p = 0.22). CONCLUSION: In this retrospective cohort study, pulmonary metastasectomy and SABR had comparable overall survival, local recurrence-free survival, and complication rates, despite patients in the SABR group having a significantly lower progression-free survival and local control rate. These data would support a randomized controlled trial comparing surgery and SABR in operable patients with radically resectable colorectal pulmonary metastases.

Superior Sulcus Tumors Invading the Spine: Multimodal Treatment Outcomes From the Preimmunotherapy Era.

Introduction: Curative-intent treatment of superior sulcus tumors (SSTs) of the lung invading the spine presents considerable challenges. We retrospectively studied outcomes in a single center, uniformly staged patient cohort treated with induction concurrent chemoradiotherapy followed by surgical resection (trimodality therapy). Methods: An institutional surgical database from the period between 2002 and 2021 was accessed to identify SSTs in which the resection included removal of at least part of the vertebral body. All patients were staged using fluorodeoxyglucose positron emission tomography (/computed tomography), computed tomography scan of the chest/upper abdomen, and brain imaging. Surgical morbidity was assessed using the Clavien-Dindo classification. Overall and disease-free survival were calculated using the Kaplan-Meier method. Results: A total of 18 patients were included: 8 complete and 10 partial vertebrectomies were performed, with six of the eight complete vertebrectomies involving two vertebral levels, resulting in Complete surgical resection (R0) in 94%. Nine patients had a 1-day procedure, and nine were staged over 2 days. The median follow-up was 30 months (interquartile range 11-57). The 90-day postoperative morbidity was 44% (grade III/IV), with no 90-day surgery-related mortality. There were 83% who had a major pathologic response, associated with improved survival (p = 0.044). The 5-year overall and disease-free survival were 55% and 40%, respectively. Disease progression occurred in 10 patients, comprising locoregional recurrences in two and distant metastases in eight patients. Conclusions: Multimodality treatment in selected patients with a superior sulcus tumor invading the spine is safe and results in good survival. Such patients should be referred to expert centers. Future research should focus on improving distant control (e.g. [neo]adjuvant immunotherapy).