Population-based survival rates after curative surgical and non-surgical treatment of stage III NSCLC since 2017.

OBJECTIVES: In stage III non-small cell lung cancer (NSCLC), curative treatment approaches used to include neoadjuvant therapy followed by surgery, and definitive chemoradiotherapy followed by consolidation durvalumab (CRT-ICI). Surgical strategies included either neoadjuvant chemotherapy (CTx-surg) or chemoradiotherapy (CRT-surg). We studied the outcomes of these three radical intent strategies in the Netherlands Cancer Registry (NCR) for patients diagnosed from 2017 to 2021. MATERIALS AND METHODS: Patients with clinical stage III NSCLC (TNM edition 8) were identified in the NCR after excluding patients with known driver mutations, ECOG performance status >=2, N3-disease and those undergoing sequential chemoradiotherapy or single modality/palliative treatments. Overall survival (OS) was calculated from date of surgery or start of durvalumab. RESULTS: Treatments delivered were CRT-ICI (n = 1016 patients), CRT-surg (n = 166) and CTx-surg (n = 111). The surgical series comprised 224 lobectomies, 21 bilobectomies and 32 pneumonectomies, with a 90-day postoperative mortality rate of 3.3 %. Use of CRT-surg decreased steeply after 2018, when durvalumab became fully reimbursed, and use of CRT-ICI increased. Three-year OS was better following CRT-surg (78.7 %) compared to CTx-surg (66.7 %) or CRT-ICI (63.2 %). After controlling for age, ECOG performance status and histology, the hazard ratios for CRT-surg and CTx-surg were 0.66 (95 % CI 0.47-0.91) and 0.82 (95 % CI 0.58-1.17), respectively, compared to CRT-ICI. CONCLUSION: Population survivals after curative strategies for clinical stage III NSCLC in The Netherlands exceed those reported historically for both surgical and non-surgical approaches. Use of surgery decreased from 2018 following the formal reimbursement of durvalumab. While variations in case-mix hamper comparison between curative treatment strategies, there is a clear need for randomized studies in subgroups with potentially resectable disease.

Compact portable higher harmonic generation microscopy for the real time assessment of unprocessed thyroid tissue.

During thyroid surgery fast and reliable intra-operative pathological feedback has the potential to avoid a two-stage procedure and significantly reduce health care costs in patients undergoing a diagnostic hemithyroidectomy (HT). We explored higher harmonic generation (HHG) microscopy, which combines second harmonic generation (SHG), third harmonic generation (THG), and multiphoton excited autofluorescence (MPEF) for this purpose. With a compact, portable HHG microscope, images of freshly excised healthy tissue, benign nodules (follicular adenoma) and malignant tissue (papillary carcinoma, follicular carcinoma and spindle cell carcinoma) were recorded. The images were generated on unprocessed tissue within minutes and show relevant morphological thyroid structures in good accordance with the histology images. The thyroid follicle architecture, cells, cell nuclei (THG), collagen organization (SHG) and the distribution of thyroglobulin and/or thyroid hormones T3 or T4 (MPEF) could be visualized. We conclude that SHG/THG/MPEF imaging is a promising tool for clinical intraoperative assessment of thyroid tissue.

Feasibility of salvage resection following locoregional failure after chemoradiotherapy and consolidation durvalumab for unresectable stage III non-small cell lung cancer.

INTRODUCTION: In patients with unresectable stage III non-small cell lung cancer, high-dose chemoradiotherapy (CRT) followed by consolidation durvalumab improves the 5-year overall survival compared to CRT alone. The feasibility and safety of salvage surgery for such patients who subsequently develop locoregional failure (LRF) is unclear. We evaluated our institutional experience with radical-intent salvage surgery in this patient population. MATERIALS AND METHODS: Details of patients undergoing salvage surgery for locoregional failure after CRT and durvalumab were identified from an institutional surgical database. Each patient's case underwent multidisciplinary discussion at initial disease presentation, and again at time of progression. RESULTS: Ten patients underwent salvage surgery for LRF after prior concurrent (n = 9) or sequential (n = 1) platinum-based high-dose chemo-radiotherapy followed by durvalumab. Consolidation durvalumab was completed in 4 patients, and discontinued in 6, due to either toxicity or disease progression. Median time between end of radiotherapy to detection of LRF was 19 months (range 6-75). Seven patients underwent a lobectomy, 1 a bilobectomy and 2 patients a pneumonectomy. Postoperative morbidity (Clavien-Dindo grade III-V) and 90-day mortality were 10% and 0%, respectively. Median follow-up after surgery was 7 months (range 1-25) during which 2 patients died (both 9 months post-operatively), one due to distant progression, and one of sepsis/bleeding. Eight patients are alive at 1-23 months post-surgery, with 6 showing no evidence of disease. CONCLUSIONS: Our results suggest that salvage pulmonary resection can be performed safely in selected patients with LRF following chemoradiotherapy and durvalumab. This radical-intent treatment option merits consideration by multidisciplinary lung tumor boards.

Long-Term Outcomes After Chemoradiotherapy and Surgery for Superior Sulcus Tumors.

Introduction: Superior sulcus tumors (SSTs) are uncommon, and their anatomical location can make treatment challenging. We analyzed late outcomes of patients with SST treated with concurrent chemoradiotherapy followed by surgical resection (trimodality) in a single tertiary institution. Methods: Patients with non-small cell SSTs, who underwent trimodality therapy between 2002 and 2017, were selected from a prospective institutional surgical database. Patients were uniformly staged with 18F-fluorodeoxyglucose-positron emission tomography, computed tomography scan of the chest and upper abdomen, and brain imaging. Patients undergoing resection of the lung plus chest wall were grouped as limited SST and those needing extensive resections (e.g., including the vertebral body) as extended SST. Kaplan-Meier survival analysis was performed to determine difference in survival. Multivariate Cox regression was used to identify prognostic factors. Results: A total of 123 patients were identified with a median follow-up of 4.9 years (interquartile range: 1.6-8.9 y). The 90-day postoperative mortality and morbidity (Clavien-Dindo grades III-V) were 6.5% and 21.1%, respectively. Patients with a radical resection (R0: 92.7%) had better survival (p = 0.002), as did those who had major pathologic response (73%) (p = 0.001). Ten-year overall survival (OS) and disease-free survival were 48.1% and 42.6%, respectively. There were no differences in 90-day mortality (p = 0.31) and OS (p = 0.79) between extended SST and limited SST patients. Conclusions: In patients with SST, trimodality resulted in a 10-year estimated OS and disease-free survival of 48.1% and 42.6%, respectively, which were improved after radical resection (R0) and major pathologic response. Survival for limited and extended resections was comparable, and distant relapse was the main pattern of failure. Better systemic treatments are therefore needed.

Thyroid Lobectomy for Low-Risk 1-4 CM Papillary Thyroid Cancer is not Associated with Increased Recurrence Rates in the Dutch Population with a Restricted Diagnostic Work-Up.

INTRODUCTION: The 2015 American Thyroid Association guidelines recommend to de-escalate treatment such as Thyroid lobectomy instead of total thyroidectomy for 1-4 cm papillary thyroid cancer (PTC). Dutch guidelines endorse restricted work-up for thyroid incidentalomas recommending only fine needle aspiration in case of a 'palpable thyroid nodule'. This diagnostic work-up algorithm may result in the identification of less indolent PTCs and may lead to a patient population with relatively more aggressive PTCs. This study aims to retrospectively analyze recurrence rates of low-risk 1-4 cm PTC in the Netherlands. METHODS: From the national cancer registry, patients with low-risk 1-4 cm PTC between 2005 and 2015 were included for analysis. Disease free survival (DFS) and overall survival were compared between patients who underwent TT ± RAI and TL without RAI. Post-hoc propensity score analysis was performed correcting for age, sex, T-stage, and N-stage. RESULTS: In total 901 patients were included, of which 711 (78.9%) were females, with a median follow-up of 7.7 years. TT was performed in 893 (94.8%) patients. Recurrence occurred in 23 (2.6%) patients. Multivariable analysis showed no significant correlation between extent of surgery and DFS (p = 0.978), or overall survival (p = 0.590). After propensity score matching, multivariable analysis showed no significant difference on extent of surgery and recurrence. CONCLUSION: Low-risk PTC patients with 1-4 cm tumor who underwent TL showed similar recurrence rates as those who underwent TT ± adjuvant RAI, which suggests that TL can be sufficient in treating low-risk 1-4 cm PTC, possibly reducing morbidity of these patients in the Netherlands.

Detection of non-metastatic non-small-cell lung cancer in urine by methylation-specific PCR analysis: A feasibility study.

BACKGROUND: Lung cancer has the highest cancer-related mortality worldwide and earlier detection could improve outcomes. Urine circulating tumor DNA (ctDNA) represents a true non-invasive means for ambulant sample collection. In this prospective study, the potential of urine for perioperative detection of non-metastatic non-small cell lung cancer (NSCLC) using ctDNA methylation analysis is evaluated. METHODS: Preoperative urine samples of 46 surgical NSCLC patients and 50 sex and age-matched controls were analyzed for DNA methylation of NSCLC-associated methylation markers CDO1, SOX17, and TAC1, using quantitative methylation-specific PCR (qMSP). The accuracy for NSCLC detection was determined by univariable and multivariable logistic regression analysis, followed by leave-one-out cross-validation. Fourteen additional urine samples were collected postoperatively to evaluate whether DNA methylation levels alter after surgery with curative intent. RESULTS: Methylation levels of CDO1 and SOX17 were significantly elevated in patients compared to controls (P =.016 and P <.001, respectively). This marker combination yielded an area under the receiver operating curve (AUC) value of 0.71 upon leave-one-out cross-validation for non-metastatic NSCLC detection in urine. Stage I patients tended to have higher methylation levels of SOX17 as compared to stage III patients. Similar methylation levels were found across the different histological subtypes of NSCLC. In some patients with preoperative elevated methylation levels, reduced methylation levels were found in post-operative urine samples. CONCLUSIONS: Urine CDO1 and SOX17 showed increased methylation levels in NSCLC patients as compared to sex- and age-matched controls. This demonstrates that urine ctDNA methylation analysis may provide an interesting non-invasive means to detect non-metastatic NSCLC. Further studies are needed to validate the clinical usefulness of this approach and to assess the potential of post-operative monitoring.

The role of surgery in the treatment of oligoprogression after systemic treatment for advanced non-small cell lung cancer.

OBJECTIVES: Patients with advanced stage non-small cell lung cancer (NSCLC) are generally considered incurable. The mainstay of treatment for these patients is systemic therapy. The addition of local treatment, including surgery, remains controversial. Oligoprogression is defined as advanced stage NSCLC with limited progression of disease after a period of prolonged disease stabilisation or after a partial or complete response on systemic therapy. In this retrospective study we evaluated outcome and survival of patients who underwent a resection for oligoprogression after systemic therapy for advanced stage NSCLC. MATERIALS AND METHODS: Patients with oligoprogression after systemic treatment for advanced NSCLC who were operated in the Antoni van Leeuwenhoek Hospital were included. Patient and treatment characteristics were collected in relation to progression free survival (PFS) and overall survival (OS). RESULTS: Between January 2015 and December 2019, 28 patients underwent surgery for an oligoprogressive lesion (primary tumor lung (n = 12), other metastatic site (n = 16)). Median age at time of resection was 60 years (39-86) and 57% were female. Postoperative complications were observed in 2 patients (7%). Progression of disease after resection of the oligoprogressive site was observed in 17 patients (61%). Median PFS was 7 months since date of resection (95% CI 6.0-25.0) and median OS was not reached. Seven patients (25%) died during follow-up. Age was predictive for OS and clinical T4 stage was predictive for PFS. M1 disease at initial presentation was predictive for better PFS compared to patients who were diagnosed with M0 disease initially. Patients who underwent resection because of oligoprogression of the primary lung tumour had a better PFS, when compared to oligoprogression of another metastastic site. CONCLUSION: Surgical resection of an oligoprogressive lesion in patients with advanced NSCLC treated with systemic treatment is feasible and might be considered in order to achieve long term survival.

A nationwide population-based cohort study of surgical care for patients with superior sulcus tumors: Results from the Dutch Lung Cancer Audit for Surgery (DLCA-S).

OBJECTIVES: Data on national patterns of care for patients with superior sulcus tumors (SST) is currently lacking. We investigated the distribution of surgical care and outcome for patients with SST in the Netherlands. MATERIAL AND METHODS: Data was retrieved from the Dutch Lung Cancer Audit for Surgery (DLCA-S) for all patients undergoing resection for clinical stage IIB-IV SST from 2012 to 2019. Because DLCA-S is not linked to survival data, survival for a separate cohort (2015-2017) was obtained from the Netherlands Cancer Registry (NCR). RESULTS: In the study period, 181 patients had SST surgery, representing 1.03% (181/17488) of all lung cancer pulmonary resections. For 2015-2017, the SST resection rate was 14.4% (79/549), and patients with stage IIB/III SST treated with trimodality had a 3-year overall survival of 67.4%. 63.5% of patients were male, and median age was 60 years. Almost 3/4 of tumors were right sided. Surgery was performed in 20 hospitals, with average number of annual resections ranging from ≤ 1 (n = 17) to 9 (n = 1). 39.8% of resections were performed in 1 center and 63.5% in the 3 most active centers. 12.7% of resections were extended (e.g. vertebral resection). 85.1% of resections were complete (R0). Morbidity and 30-day mortality were 51.4% and 3.3% respectively. Despite treating patients with a higher ECOG performance score and more extended resections, the highest volume center had rates of morbidity/mortality, and length of hospital stay that were comparable to those of the medium volume (n = 2) and low-volume centers (n = 1). CONCLUSION: In the Netherlands, surgery for SST accounts for about 1% of all lung cancer pulmonary resections, the number of SST resections/hospital/year varies widely, with most centers performing an average of ≤ 1/year. Morbidity and mortality are acceptable and survival compares favourably with the literature. Although further centralisation is possible, it is unknown whether this will improve outcomes.

Neoadjuvant immune checkpoint inhibitors in resectable non-small-cell lung cancer: a systematic review.

BACKGROUND: The neoadjuvant use of immune checkpoint inhibitors (ICIs) in resectable non-small-cell lung cancer (NSCLC) is currently an area of active ongoing research. The place of neoadjuvant ICIs in the treatment guidelines needs to be determined. We carried out a systematic review of published data on neoadjuvant ICIs in resectable NSCLC to study its efficacy and safety. PATIENTS AND METHODS: A literature search was carried out using the MEDLINE (PubMed) and Embase databases to retrieve articles and conference abstracts of clinical trials measuring the efficacy [major pathological response (MPR) and pathological complete response (pCR)] and safety (failure to undergo resection, surgical delay, treatment-related adverse events (trAEs) grade ≥3) of neoadjuvant immunotherapy in resectable NSCLC until July 2021. RESULTS: Nineteen studies with a total of 1066 patients were included in this systematic review. Neoadjuvant immunotherapy was associated with improved pathological response rates, especially in combination with chemotherapy. Using mono ICI, dual therapy-ICI, chemoradiation-ICI, radiotherapy-ICI, and chemo-ICI, the MPR rates were 0%-45%, 50%, 73%, 53%, and 27%-86%, respectively. Regarding pCR, the rates were 7%-16%, 33%-38%, 27%, 27%, and 9%-63%, respectively. Safety endpoints using monotherapy-ICI, dual therapy-ICI, chemoradiation-ICI, radiotherapy-ICI, and chemo-ICI showed a failure to undergo resection in 0%-17%, 19%-33%, 8%, 13%, and 0%-46%, respectively. The trAEs grade ≥3 rates were 0%-20%, 10%-33%, 7%, 23%, and 0%-67%, respectively. CONCLUSION: In patients with resectable NSCLC stage, neoadjuvant immunotherapy can improve pathological response rates with acceptable toxicity. Further research is needed to identify patients who may benefit most from this approach, and adequately powered trials to establish clinically meaningful benefits are awaited.

Morbidity and extent of surgical resection of carcinoid tumors after endobronchial treatment.

OBJECTIVES: This study assessed whether endobronchial therapy (EBT) for bronchial carcinoid, if not curative, reduces the extent of the surgical resection and whether EBT is associated with increased surgical morbidity. MATERIAL AND METHODS: Analysis was performed in a cohort of patients with bronchial carcinoid who have undergone surgical resection. A group that underwent EBT before the surgery (S + EBT) was compared with a group where no EBT was performed (S-EBT). Postoperative complications were also compared between both groups. RESULTS: A total of 254 patients treated for a bronchial carcinoid tumor between 2003 and 2019 were screened for inclusion. A total of 65 surgically treated patients were included, of whom 41 (63%) underwent EBT prior to surgery. In 5 out of 41 patients (12%) from the S + EBT group, less parenchyma was resected versus 2 out of 24 (8%) from the S-EBT group (OR 1.528, 95% CI 0.273-8.562, p = 1.000). Two patients from the S + EBT group (5%) underwent lobectomy instead of sleeve lobectomy versus 0 from the S-EBT group (OR 1.051, 95% CI 0.981-1.127, p = 0.527). Comparing complications between the S + EBT and S-EBT group did not result in increased postoperative surgical morbidity (15% S + EBT, 24% S-EBT). CONCLUSION: EBT, if not curative, does not reduce the extent of the subsequent surgical resection. Therefore, if curative EBT is not anticipated, patients should directly be referred for surgery. If curative EBT seems feasible, it should be attempted not only because surgical resection can be prevented, but also because failure of EBT is not associated with excess surgical morbidity.

Hemithyroidectomy versus total thyroidectomy for well differentiated T1-2 N0 thyroid cancer: systematic review and meta-analysis.

BACKGROUND: Evidence for limiting the extent of surgery in patients with low-risk thyroid cancer is lacking. METHODS: A systematic search was performed according to the PRISMA and MOOSE guidelines to assess the effect of total thyroidectomy (TT) with or without radioactive iodine (RAI) treatment versus hemithyroidectomy (HT) on recurrence and overall mortality in patients with differentiated (papillary or follicular) T1-2 N0 thyroid cancer. PubMed, Embase and Cochrane databases were searched, and two authors independently assessed the articles. RESULTS: A total of ten eligible articles were identified. All were observational cohort series, representing a total of 23 134 patients, of which 17 699 were available for meta-analysis. Six studies included patients who had TT followed by RAI treatment. The pooled recurrence rate after TT ± RAI and HT was 2·3 and 2·8 per cent respectively (odds ratio (OR) 1·12, 95 per cent c.i. 0·82 to 1·53; P = 0·48). The pooled 20-year overall survival rate after TT ± RAI was 96·8 per cent, compared with 97·4 per cent for HT (OR 1·30, 0·71 to 2·37; P = 0·40). Overall, higher complication rates were found in the TT ± RAI group. CONCLUSION: Recurrence rates after HT for treatment of well differentiated T1-2 N0 thyroid cancer were similar to those after TT ± RAI, with a lower incidence of treatment-related complications.

ANTECEDENTES: No hay evidencia para limitar la extensión de la cirugía en pacientes con cáncer de tiroides de bajo riesgo. MÉTODOS: Se realizó una búsqueda sistemática siguiendo las recomendaciones PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) y MOOSE (Meta-analysis of Observational Studies in Epidemiology) para evaluar el efecto de la tiroidectomía total (TT) +/− yodo radioactivo (radioactive iodine treatment, RAI) versus hemitiroidectomía (HT) en la recidiva y en la mortalidad global en el cáncer de tiroides diferenciado (papilar/folicular) T1-T2N0. Se realizaron búsquedas en las bases de datos PubMed, Embase y Cochrane, y dos autores evaluaron los artículos de forma independiente. RESULTADOS: Se identificaron un total de 10 artículos de interés. Todos ellos eran estudios de cohortes observacionales, con un total de 23.134 pacientes, de los cuales 17.699 se incluyeron en el metaanálisis. En seis estudios, los pacientes fueron tratados mediante TT seguida de RAI. Las tasas agrupadas de recidiva tras TT +/− RAI y HT fueron 2,3% and 2,8%, respectivamente (razón de oportunidades, odds ratio, OR = 1,12, i.c. del 95% 0,82-1,54, P = 0.48). La supervivencia global a 20 años de TT +/− RAI fue del 96,8% en comparación con el 97,4% para la HT (OR = 1,30, i.c. del 95% 0,71-2,37, P = 0,40). Globalmente, se observaron más complicaciones en el grupo de TT +/− RAI. CONCLUSIÓN: Esta revisión sistemática con metaanálisis demuestra tasas de recidiva similares tras una HT para el tratamiento del cáncer de tiroides T1-2N0 bien diferenciado en comparación con TT +/− RAI, con una menor incidencia de complicaciones relacionadas con el tratamiento.

Impact of health care organization on surgical lung cancer care.

OBJECTIVES: Organization and governance of national healthcare might play an important role in decision-making and outcomes in patients with lung cancer. Both Denmark and the Netherlands have a high level of healthcare but a different financial coverage, governance and level of centralization. By using both national databases we analyzed the consequences of these differences on patterns of care and outcomes with a focus on morbidity, mortality and clinical staging. MATERIALS AND METHODS: General numbers on both healthcare systems were requested. All patients who had surgery for lung cancer from 2013 to 2016 were included. Mortality, morbidity and clinical staging were analyzed for patients with NSCLC without metastases, only one operation and no neo-adjuvant therapy. RESULTS: In 2016 annual budget as share of gross national product was 10.4% for both countries. In Denmark 4 hospitals performed lung surgery in 2016, compared to 43 hospitals in the Netherlands. We included 4030 Danish and 8286 Dutch patients. In the subgroup 30-day mortality was 1.5% in Denmark compared to 1.9% in the Netherlands. The percentage of patients with a complicated course was 24.4% and 34.8% respectively (p < 0.05). Accuracy between cTNM and pTNM was 53.0% in Denmark and 52.9% in the Netherlands. CONCLUSION: Surgery for lung cancer is at a high level in both countries, reflected by low mortality-rates. Centralization has been implemented successfully in Denmark, which might explain the lower rate of patients with a complicated post-operative course, although different definitions preclude firm conclusions. In both countries correct clinical staging of lung cancer remains a challenge.

Endobronchial and surgical treatment of pulmonary carcinoid tumors: A systematic literature review.

The treatment of pulmonary carcinoid has changed over the last decades. Although surgical resection is still the gold standard, minimally invasive endobronchial procedures have emerged as a parenchyma sparing alternative for tumors located in the central airways. This review was performed to identify the optimal treatment strategy for pulmonary carcinoid, with a particular focus on the feasibility and outcome of parenchyma sparing techniques versus surgical resection. A systematic review of the literature was carried out using MEDLINE, Embase and the Cochrane databases, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. Two separate searches of publications in endobronchial and surgical treatment in patients with pulmonary carcinoid, were performed. Outcomes were overall survival, disease free survival, recurrence rate, complications, quality of life, and healthcare costs. Combining the two main searches for endobronchial therapy and surgical therapy yielded 3111 records. Finally, 43 studies concerning surgical treatment and 9 studies related to endobronchial treatment for pulmonary carcinoid were included. Assessment of included studies showed that lymph node involvement, histological grade, tumor location and tumor diameter were identified as poor prognostic factors and seem to be important for patients with pulmonary carcinoid. For patients with a more favorable prognosis, tumor location and tumor diameter are important factors that can help decide on the optimal treatment strategy. Centrally located small intraluminal pulmonary carcinoids, without signs of metastasis can be treated with minimally invasive alternatives such as endobronchial treatment or parenchyma sparing surgical resection. Patients with parenchyma sparing resections should be followed with long term follow up to exclude recurrence of disease. In a multidisciplinary setting, it should be determined whether individual patients are eligible for parenchyma sparing procedures or anatomical resection. Overall evidence is of low quality and future studies should focus on prospective trials in the treatment of pulmonary carcinoid.

Patterns of care and outcomes for stage IIIB non-small cell lung cancer in the TNM-7 era: Results from the Netherlands Cancer Registry.

OBJECTIVES: There is limited data on the pattern of care for locally advanced, clinical (c) IIIB non-small cell lung cancer (NSCLC) in the TNM-7 staging era. The primary aim of this study was to investigate national patterns of care and outcomes in the Netherlands, with a secondary focus on the use of surgery. MATERIAL AND METHODS: Data from patients treated for TNM-7 cIIIB NSCLC between 2010 and 2014, was extracted from the Netherlands Cancer Registry (NCR). Survival data was obtained from the automated Civil Registry. RESULTS: 43.762 patients with NSCLC were recorded in the NCR during this 5-year period, with cIIIB accounting for 10% (n=4.401). Clinical N2 (37%) and N3 (63%) nodal involvement was pathologically confirmed in 50.8%. The use of endobronchial ultrasound (EBUS) increased with time from 9% to 29% (p<0.001), while the rate of pathological confirmation of N2 or N3 nodes increased from 44% to 54% (p<0.001). 48% of patients received chemoradiotherapy (CRT), 19% chemotherapy (CT), RT in 10% and surgery in 2.2%. 22% received best supportive care (BSC). The percentage of patients treated with CRT decreased from 65% for patients aged <60 years to 13% for patients aged 80 years or older. Overall survival for surgery was 28 months, followed by CRT (19mths), CT (9mths), RT (8mths) and BSC (3mths). CONCLUSION: In the Netherlands, CRT is the most frequent treatment for cIIIB NSCLC in the TNM-7 era. The use of surgery is limited. Accurate staging requires specific attention and the scarce use of radical treatment in elderly patients merits further evaluation.

[A woman with severe abdominal pain and endometriosis in the past]. / Een vrouw met hevige buikpijn en eerdere endometriose.

A 44-year-old woman came to the emergency department with severe pain in the right upper abdomen. Her medical history mentioned a low anterior resection 8 years ago because of severe endometriosis. The CT scan showed a ruptured right hemidiaphragm with herniation of the small intestine.

Good's syndrome: an uncommon cause of therapy-resistant diarrhoea.

Diarrhoea is a common symptom for which the aetiology will be straightforward in many cases. However, when a common aetiology is not found, the wide variety of other options can feel like finding a needle in a haystack. In this case report, we describe a patient who was referred to our centre with therapy-resistant, secretory diarrhoea, which was the presenting symptom of Good's syndrome, a rare form of adult-onset immunodeficiency associated with thymoma. The conclusions from this case report give direction for 'finding the needle' and contribute to a focused approach to patients who present with therapyresistant diarrhoea.

Salvage surgery for locoregional recurrence or persistent tumor after high dose chemoradiotherapy for locally advanced non-small cell lung cancer.

OBJECTIVES: Curative intent treatment options for locoregional recurrence or persistent tumor after radical chemoradiotherapy for locally-advanced non-small cell lung cancer (NSCLC) are limited. In selected patients, surgery can be technically feasible, although it is widely believed to be hazardous. As data regarding the outcome of this approach is sparse, we evaluated our institutional experience with salvage surgery. MATERIALS AND METHODS: Patients with a pulmonary resection for in-field locoregional recurrence or persistent tumor after high dose chemoradiotherapy (≥60 Gy) for the treatment of non-small cell lung cancer, were identified and retrospectively analyzed. RESULTS: A total of 15 patients treated between January 2007 and August 2015 were eligible for evaluation. In 13 patients (87%), the indication for surgery was a locoregional recurrence, while 2 patients had persistent tumor. The prior median radiotherapy dose was 66 Gy (range 60-70). All patients underwent an anatomical resection, with 8 patients having a pneumonectomy, and all pathological specimens revealed the presence of viable tumor. The in-hospital morbidity rate was 40% (6 patients), and the 90-day mortality rate was 6.7% (1 patient). Median follow-up was 12.1 months. The estimated median overall and event-free survivals were 46 months and 43.6 months, respectively. CONCLUSION: Salvage surgery for locoregional recurrence or persistent tumor after high dose chemoradiotherapy, resulted in acceptable morbidity, mortality and promising outcome. It should be considered as a treatment option for selected patients.