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Summary: The combination of radiotherapy and concurrent chemotherapy followed by surgery (trimodality treatment) is currently regarded as optimal treatment for non-small cell lung cancer of the superior sulcus (SST) or Pancoast tumour. The possibility to administer intensive combined modality treatment is influenced by tumour stage, comorbidity and performance status of these patients, and therefore a strict patient selection is necessary. This study focuses on patient selection and its results. We retrospectively evaluated choices of treatment and outcome of all patients with SST treated in the Netherlands Cancer Institute from 1994 to 2004. After identification of patients with SST in registration databases, the following characteristics were analyzed: symptoms, comorbidity, tumour stage, treatment characteristics, toxicity, local control, disease-free and overall survival. Fifty-two patients, 37 men and 15 women, were identified. They were diagnosed with stage IIB (27%), stage IIIA (8%), stage IIIB (42%) and stage IV (23%). Twelve patients after induction (chemo)radiotherapy underwent surgical resection. In eight patients a pathologic complete response was found. The 2- and 5-year survival after induction treatment and surgery was 75 and 39%, respectively. Other patients did not receive surgical treatment because of stage IV disease (n =12), comorbidity (n =8), irresectability (extensive tumour growth and/or persisting N2–3 status; n =14) or insufficient response to induction treatment (n =6). Eleven patients were treated with concurrent chemoradiotherapy (5-year survival 20%) and 17 patients with (sequential) radiotherapy and/or chemotherapy (5-year survival 6%). Local recurrence rates were 0% after induction treatment and surgical resection, 32% after concurrent chemoradiotherapy and 72% after (sequential) radiotherapy and/or chemotherapy. In conclusion, only 30% of M0 patients with SST were eligible for combined modality treatment followed by surgery. In this subgroup, concurrent chemoradiotherapy followed by surgery was associated with excellent local control and acceptable survival. [Copyright &y& Elsevier]

Summary: Background: While developing and distributing clinical practice guidelines are important in optimising clinical healthcare, insight into actual care is necessary to achieve successful implementation. Developing quality indicators may be the first step to becoming aware of actual care. The Dutch national practice guideline Non-small cell lung cancer: staging and treatment is one of the first clinical, multidisciplinary guidelines for oncology in the Netherlands for which quality indicators were developed systematically. We describe indicator development based on this guideline as a practical experience. Methods: To develop a set of indicators for diagnosis and treatment of patients with non-small cell lung cancer, we systematically achieved consensus on the basis of a national, multidisciplinary, evidence-based guideline and the opinions of professionals and patients. After the researchers extracted the recommendations from the guideline, we carried out a so-called Rand-modified-Delphi procedure. This consisted of three rounds: a national panel of professionals and representatives of the national patient organization scored all recommendations, the professionals had a consensus meeting, and the final set of indicators was e-mailed for a last check. Subsequently, some clinimetric characteristics of this final set were assessed in a practice test. Results: Thirty-two of 83 recommendations were selected in the first round. After the consensus meeting, 8 recommendations met the final criteria and were incorporated into 15 indicators, which were tested in practice. The most successful indicators for quality improvement are indicators that are measurable, have potential for improvement, have a broad range between practices and are applicable to a large part of the population. Conclusions: For successful implementation of evidence-based guidelines, each new guideline should be developed and tested with a set of indicators based on the guideline. The procedure we describe can serve as an example for other new guidelines. [Copyright &y& Elsevier]

Enlarged mediastinal lymph nodes in patients with previous extrathoracic malignancy require pathological verification. However, surgical procedures lead to morbidity and (rarely) mortality. Endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is a minimally invasive, outpatient procedure. We prospectively assessed its usefulness in patients with mediastinal abnormalities and previous extrathoracic malignancy. All patients underwent EUS-FNA prior to planned surgical procedures. Specimens were categorised as positive, negative, or inconclusive. Surgical procedures were cancelled after positive EUS-FNA. Twenty patients underwent EUS-FNA, being positive in eleven and providing an alternative diagnosis in one patient (a total of 60%). In 8 patients, EUS-FNA was negative or inconclusive, while surgery was positive in five and negative in three. Sensitivity and specificity of EUS-FNA were 69 and 100%, respectively. EUS-FNA is useful in the assessment of mediastinal abnormalities in patients with previous extrathoracic malignancy. Surgical diagnostic procedures were precluded in 60% of such patients. [Copyright &y& Elsevier]

Cancer patients treated with chemotherapy are susceptible to bacterial infections. When an adult patient presents with febrile neutropenia, standard diagnostic care includes physical examination, laboratory diagnostics, chest X-ray (CXR) and sinus radiography. However, the yield of routine radiography in the diagnostic evaluation of ambulatory adult febrile neutropenic patients with normal findings at their physical examination is questionable. Two CXRs and one sinus X-ray were obtained in 109 and 106 febrile neutropenic episodes after chemotherapy in ambulatory adult patients who had no clinical signs suggesting pulmonary infection or sinusitis. We found that in only two of 109 (1.8%; 95% Confidence Interval (CI): 0.3–5.8%) febrile neutropenic episodes without clinical signs of new pulmonary disease, the CXR showed a consolidation suggesting pneumonia. In addition, in five of 88 (5.7%; 95% CI: 2.2–12.0%) febrile episodes in asymptomatic patients, sinus X-ray suggested sinusitis. In none of these seven episodes was a change of antibiotic therapy necessary. In the absence of clinical signs indicating pneumonia or sinusitis, the yield of CXR and sinus radiography in ambulatory adult cancer patients presenting with febrile neutropenia is minimal; CXR and sinus radiography should no longer be performed on a routine basis. [Copyright &y& Elsevier]

Immune related endonucleases have recently been described as potential therapeutic targets and predictors of response to treatment with immune checkpoint inhibitors (ICI). The aim is to evaluate the association between the expression of 5 biomarkers involved in the immune response (CD73, CD39, VISTA, Arl4d and Cytohesin-3) in parallel with the more common ICI-predictive markers, PD-L1 expression and Tumor Mutation Burden (TMB) with response to ICI therapy in an advanced non-small cell lung cancer (NSCLC) cohort. Patients with advanced NSCLC treated with ICI single agent were divided into responders and non-responders according to RECIST v1.1 and duration of response (DOR) criteria. Immunohistochemistry was performed on pretreatment tumor tissue samples for PD-L1, CD73, CD39, VISTA, Arl4d, and Cytohesin-3 expression. TMB was estimated with NEOplus v2 RUO (NEO New Oncology GmbH) hybrid capture next generation sequencing assay. Resistance mutations in STK11 / KEAP1 and positive predictive mutations in ARID1A / POLE were also evaluated. Included were 56 patients who were treated with ICI single agent. The median progression-free and overall survival for the whole cohort was 3.0 (95% CI, 2.4–3.6) and 15 (95% CI, 9.7–20.2) months, respectively. The distribution of CD73 in tumor cells and CD39, VISTA, Arl4d and Cytohesin-3 expression in immune cells were not different between responders and non-responders. Also, PD-L1 and TMB were not predictive for response. The frequency of STK11 , KEAP1 and ARID1A mutations was low and only observed in the non-responder group. Separate and combined expression of 5 biomarkers involved in the immune response (CD73, CD39, VISTA, Arl4d, and Cytohesin-3) was not associated with response in our cohort of advanced NSCLC patients receiving single agent ICI. To confirm our findings the analysis of independent larger cohorts is warranted. • IHC markers CD73, CD39, VISTA, Arl4d, Cytohesin-3 do not discriminate responders from non-responders in advanced NSCLC. • Combined IHC markers including PD-L1 and TMB does not differentiate responders from non-responders. • Arl4d and cytohesin-3 expression were correlated in immune cells in advanced NSCLC. [ABSTRACT FROM AUTHOR]