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.

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.

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.

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).

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.

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.

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.

Focal 18 F-FDG uptake predicts progression of pre-invasive squamous bronchial lesions to invasive cancers.

INTRODUCTION: Pre-invasive squamous lesions of the central airways can progress into invasive lung cancers. Identifying these high-risk patients could enable detection of invasive lung cancers at an early stage. In this study, we investigated the value of 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET) scans in predicting progression in patients with pre-invasive squamous endobronchial lesions. METHODS: In this retrospective study, patients with pre-invasive endobronchial lesions, who underwent an 18 F-FDG PET scan at the VU University Medical Center Amsterdam, between January 2000 and December 2016, were included. Autofluorescence bronchoscopy (AFB) was used for tissue sampling and was repeated every 3 months. The minimum and median follow-up was 3 and 46.5 months. Study endpoints were the occurrence of biopsy proven invasive carcinoma, time-to-progression and overall survival (OS). RESULTS: A total number of 40 of 225 patients met the inclusion criteria of which 17 (42.5%) patients had a positive baseline 18 F-FDG PET scan. A total of 13 of 17 (76.5%) developed invasive lung carcinoma during follow-up, with a median time to progression of 5.0 months (range, 3.0-25.0). In 23 (57.5%) patients with a negative 18 F-FDG PET scan at baseline, 6 (26%) developed lung cancer, with a median time to progression of 34.0 months (range, 14.0-42.0 months, p < 0.002). With a median OS of 56.0 months (range, 9.0-60.0 months) versus 49.0 months (range, 6.0-60.0 months) (p = 0.876) for the 18 F-FDG PET positive and negative groups, respectively. CONCLUSIONS: Patients with pre-invasive endobronchial squamous lesions and a positive baseline 18 F-FDG PET scan were at high-risk for developing lung carcinoma, highlighting that this patient group requires early radical treatment.

Incomplete patient information exchange and unnecessary repeat diagnostics during oncological referrals in the Netherlands: exploring the role of information exchange.

Data management in transmural care is complex. Without digital innovations like Health Information Exchange (HIE), patient information is often dispersed and inaccessible across health information systems between hospitals. The extent of information loss and consequences remain unclear. We aimed to quantify patient information availability of referred oncological patients and to assess its impact on unnecessary repeat diagnostics by observing all oncological multidisciplinary team meetings (MDTs) in a tertiary hospital. During 84 multidisciplinary team meetings, 165 patients were included. Complete patient information was provided in 17.6% (29/165, CI = 12.3-24.4) of patients. Diagnostic imaging was shared completely in 52.5% (74/141, CI = 43.9-60.9), imaging reports in 77.5% (100/129, CI = 69.2-84.2), laboratory results in 55.2% (91/165, CI = 47.2-62.8), ancillary test reports in 58.0% (29/50, CI = 43.3-71.5), and pathology reports in 60.0% (57/95, CI = 49.4-69.8). A total of 266 tests were performed additionally, with the main motivation not previously performed followed by inconclusive or insufficient quality of previous tests. Diagnostics were repeated unnecessarily in 15.8% (26/165, CI = 10.7-22.4) of patients. In conclusion, patient information was provided incompletely in majority of referrals discussed in oncological multidisciplinary team meetings and led to unnecessary repeat diagnostics in a small number of patients. Additional research is needed to determine the benefit of Health Information Exchange to improve data transfer in oncological care.

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.

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.

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.

Salvage Surgery for Patients With Local Recurrence or Persistent Disease After Treatment With Chemoradiotherapy for SCLC.

INTRODUCTION: The role of salvage surgery for patients with locoregional (LR) recurrence or persistent SCLC after radical chemoradiotherapy (CRT) for limited-stage disease is not well established. We evaluated our experience. METHODS: We conducted a retrospective study of consecutive patients who underwent salvage pulmonary resection for LR-recurrent or persistent SCLC between 2008 and 2020 at the Amsterdam University Medical Center. RESULTS: A total of 10 patients were identified. Median age at initial diagnosis of limited-stage SCLC was 58.5 years (48-71 y). All patients had radical-intent concurrent CRT. Of the 10 patients, 9 were diagnosed with LR-recurrent or persistent disease with a median of 18 months (3-78 y) after CRT. All patients underwent an anatomical radical resection and mediastinal lymph node dissection. No 90-day mortality was recorded. In addition, one patient developed a LR recurrence 7 months after resection. Distant progression was found in three patients at 6, 32, and 61 months after surgery, all of whom subsequently died of progressive SCLC. Median follow-up was 22.5 months (2-86 mos). Disease-free survival was 34 months; overall survival was not reached. CONCLUSIONS: For highly selected patients with LR-recurrent or persistent SCLC after CRT, salvage surgery is feasible and can result in clinically meaningful survival. Such patients should be presented to the multidisciplinary tumor board.

Variation in incidence, prevention and treatment of persistent air leak after lung cancer surgery.

OBJECTIVES: Persistent air leak (PAL; >5 days after surgery) is the most common complication after pulmonary resection and associated with prolonged hospital stay and increased morbidity. Literature is contradictory about the prevention and treatment of PAL. Variation is therefore hypothesized. The aim of this study is to understand the variation in the incidence, preventive management and treatment of PAL. METHODS: Data from the Dutch Lung Cancer Audit for Surgery were combined with results of an online survey among Dutch thoracic surgeons. The national incidence of PAL and case-mix corrected between-hospital variation were calculated in patients who underwent an oncological (bi)lobectomy or segmentectomy between January 2012 and December 2018. By multivariable logistic regression, factors associated with PAL were assessed. A survey was designed to assess variation in (preventive) management and analysed using descriptive statistics. Hospital-level associations between management strategies and PAL were assessed by univariable linear regression. RESULTS: Of 12 382 included patients, 9.0% had PAL, with a between-hospital range of 2.6-19.3%. Factors associated with PAL were male sex, poor lung function, low body mass index, high American Society of Anesthesiologists (ASA) score, pulmonary comorbidity, upper lobe resection, (bi)lobectomy (vs segmentectomy), right-sided tumour and robotic-assisted thoracic surgery. Perioperative (preventive) management of PAL differed widely between hospitals. When using water seal compared to suction drainage, the average incidence of PAL decreased 2.9%. CONCLUSIONS: In the Netherlands, incidence and perioperative (preventive) management of PAL vary widely. Using water seal instead of suction drainage and increasing awareness are potential measures to reduce this variation.

Completeness of lymph node dissection in patients undergoing minimally invasive- or open surgery for non-small cell lung cancer: A nationwide study.

OBJECTIVE: In patients with NSCLC, lymph node metastases are an important prognostic factor. Despite an accurate pre-operative work up, for optimal staging an intrapulmonary- and mediastinal lymph node dissection (LND) as part of the operation is mandatory. The aim of this study is to assess the completeness of LND in patients undergoing an intended curative resection for NSCLC in the Netherlands and to compare performance between open surgery and minimally invasive surgery (MIS). MATERIALS AND METHODS: The intraoperative LND was evaluated in 7460 patients who had undergone a lobectomy for clinically staged N0-1 NSCLC (2013-2018). The LND was considered complete, when three mediastinal (N2) lymph node stations, including station 7, were sampled or dissected, in addition to the lymph nodes from station 10 and 11. A comparison was made between open surgery and MIS. RESULTS: Of 5154 patients, who had MIS, a sufficient intrapulmonary LND was performed in 47.9% and a sufficient mediastinal LND in 58.6%. A complete LND was performed in 31.6%. For 2306 patients who had an open resection, these numbers were 45.0%, 59.0%, and 30.6%, respectively. The overall between-hospital variation in a complete LND ranged between 0 and 72.5%. CONCLUSION: In the Netherlands, a complete LND of both intrapulmonary- and mediastinal lymph nodes is performed only in a minority of patients with clinically staged N0-1 NSCLC, with substantial between-hospital variation. No differences were seen between open surgery and MIS. Because of poor performance, completeness of lymph node dissection will be recorded as a mandatory performance indicator in our national audit, to improve the quality of resection.

The Association of Textbook Outcome and Long-Term Survival After Esophagectomy for Esophageal Cancer.

BACKGROUND: Esophagectomy is the key component of curative esophageal cancer treatment. Textbook outcome is a composite measure describing an optimal perioperative course, including variables related to radical resection, including at least 15 lymph nodes, and an uncomplicated postoperative course without hospital readmission. This study assessed clinicopathologic predictors of textbook outcome and the association of textbook outcome with survival in 2 tertiary referral centers. METHODS: All patients with esophageal cancer who underwent esophagectomy with gastric tube reconstruction and curative intent between 2007 and 2016 were included. Patients with carcinoma in situ and patients undergoing a salvage or nonelective procedure were excluded. The primary end point was the association of textbook outcome of esophageal cancer surgery with long-term survival. Secondary end points were clinicopathologic predictors of textbook outcome. RESULTS: In total, 1065 patients were included, of whom 327 achieved textbook outcome (30.7%). Squamous cell carcinoma (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.39 to 0.80), hybrid approach (OR, 0.30; 95% CI, 0.10 to 0.89), and American Society of Anesthesiologists (ASA) class II or higher predicted worse textbook rates (ASA class II: OR, 0.33, 95% CI, 0.22 to 0.49; ASA class III or IV: OR, 0.68; 95% CI, 0.48 to 0.96), whereas neoadjuvant therapy predicted a better textbook rate (OR, 1.58; 95% CI, 1.08 to 2.31). Superior overall (hazard ratio, 0.77; 95% CI, 0.64 to 0.93) and disease-free survival (hazard ratio, 0.80; 95% CI, 0.67 to 0.96) were observed in the textbook outcome group. CONCLUSIONS: Achieved textbook outcome was associated with better overall and disease-free survival, thus illustrating the association of improved short-term outcomes and long-term survival and the importance of pursuing textbook outcome.

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.