Unraveling the spectrum of inflammatory myofibroblastic tumors in the lung: A comprehensive case series highlighting endobronchial, pleural, and lung parenchymal tumors.

Objectives: Diverse cases of inflammatory myofibroblastic tumors (IMTs) in the lung (pleural, endobronchial, and parenchymal) are presented while discussing the (preoperative) diagnostic challenges and treatment modalities. Other objectives include emphasizing the significance of gene rearrangements and highlighting the multidisciplinary approach in addressing IMTs. Methods: Four cases of IMT in the lung are presented, including a young adolescent girl with an ETV6-neurotrophic tyrosine receptor kinase 3 (NTRK3) gene rearrangement, a 5-year-old boy with challenging preoperative diagnosis, and 2 middle-aged women with respectively pleural and endobronchial tumors with one peribronchial relapse. Results: The cases demonstrate the diverse clinical presentations and diagnostic complexities associated with IMT in the lung. Surgical resection remains the primary treatment modality, with complete resection leading to a cure in most patients. Unfortunately, aggressive relapse can occur, as in our last case of an endobronchial tumor. Frozen section may confirm the presence of malignant cells perioperatively and impact further treatment. The presence of gene rearrangements, such as ETV6-NTRK3, suggests potential therapeutic implications. Conclusions: Early detection and complete surgical removal of IMT are crucial for effective treatment. Identifying gene rearrangements such as ETV6-NTRK3 holds promise for targeted therapies. Diagnostic challenges, including the controversy of biopsies and preoperative evaluations, underscore the importance of a multidisciplinary approach. Anatomopathological recognition of IMT stays demanding. Close surveillance is necessary due to potential relapse, whereas frozen section perioperatively can help further treatment. This case series emphasizes the diagnostic challenges and therapeutic considerations for IMT in the lung.

Modification of the Abramson procedure for minimally invasive repair of pectus carinatum: introduction of a pectus carinatum compression system.

Pectus carinatum is characterized by a protruding sternum. This deformity can be surgically corrected through the minimally invasive Abramson technique. In this procedure, a presternal metal correctional bar, secured to rib-attached stabilizers, is implanted to redress the sternum to a neutral position. To anticipate the intended position of the sternum, manual compression is applied over the sternal deformity. We describe a modified version of the Abramson procedure, encompassing a table-mounted PectusAssist™ System which generates a constant mechanical compression over the protruding sternum. The PectusAssist™ System, most importantly, eliminates the necessity of manually applying repetitive pressure on the deformity, and therefore maintains a more stable sternal position. This will ensure accuracy of the template used to bend the bar into its desired configuration. The modification we propose also simplifies presternal tunnel creation as the two bilateral retromuscular tunnels, that need to be connected presternally, are potentially better aligned due to a more stable and reduced position of the sternum. The PectusAssist™ System makes the procedure less labor intensive and reduces variability without interfering with the safety of the procedure. Therefore, we advise standard use of the PectusAssist™ System during minimally invasive repair of pectus carinatum by the Abramson procedure.

Pectus Excavatum: Consensus and Controversies in Clinical Practice.

BACKGROUND: Pectus excavatum is the most common congenital anterior chest wall deformity. Currently, a wide variety of diagnostic protocols and criteria for corrective surgery are being used. Their use is predominantly based on local preferences and experience. To date, no guideline is available, introducing heterogeneity of care as observed in current daily practice. The aim of this study was to evaluate consensus and controversies regarding the diagnostic protocol, indications for surgical correction, and postoperative evaluation of pectus excavatum. METHODS: The study consisted of 3 consecutive survey rounds evaluating agreement on different statements regarding pectus excavatum care. Consensus was achieved if at least 70% of participants provided a concurring opinion. RESULTS: All 3 rounds were completed by 57 participants (18% response rate). Consensus was achieved on 18 of 62 statements (29%). Regarding the diagnostic protocol, participants agreed to routinely include conventional photography. In the presence of cardiac impairment, electrocardiography and echocardiography were indicated. Upon suspicion of pulmonary impairment, spirometry was recommended. In addition, consensus was reached on the indications for corrective surgery, including symptomatic pectus excavatum and progression. Participants moreover agreed that a plain chest radiograph must be acquired directly after surgery, whereas conventional photography and physical examination should both be part of routine postoperative follow-up. CONCLUSIONS: Through a multiround survey, international consensus was formed on multiple topics to aid standardization of pectus excavatum care.

Thoracic surgery in the Netherlands.

The purpose of this article, part of the Thoracic Surgery Worldwide series, is to provide a descriptive review of how thoracic surgery is organized in the Netherlands. General information is provided on the Dutch healthcare system, as well as on how Dutch thoracic surgeons are organized and trained. Additionally, this study provides information on our national quality surveillance system, an overview of the most common thoracic surgeries performed in our country, and details of academic research conducted by Dutch medical specialists. Furthermore, we discuss current challenges and future perspectives. In the Netherlands general thoracic surgical procedures are performed by approximately 110 general thoracic surgeons and 25 of the 135 cardiothoracic surgeons. Dutch thoracic surgeons provide minimally invasive lung surgery, chest wall surgery, thymic and mediastinal surgery, and surgical diagnosis and treatment of pleural disorders. Some recently published data on hospital mortality and postoperative adverse events of thoracic surgeries are reported. Furthermore, the structure of the thoracic surgical education and training program is discussed, highlighting the particular structure of two educational programs for thoracic surgery via a general thoracic and cardiothoracic surgery program. To assure high-quality surgical care, the Netherlands has a well-structured national quality surveillance system, involving frequent site visits and mandatory participation in the national lung cancer surgery registry for all hospitals. In terms of academic research, the Netherlands ranked 14th worldwide on number of clinical trials conducted across all medical disciplines in 2021. Furthermore, several thoracic-related (inter-)national multicenter randomized trials which are currently performed and initiated by Dutch hospital research groups are mentioned. Finally, future challenges and advances of Dutch thoracic surgery are addressed, including the implementation of lung cancer screening, imbalanced labor market, and centralization of care.

Translation, cultural adaptation and linguistic validation of the pectus excavatum evaluation questionnaire.

Background: Pectus excavatum often imposes significant burden on the patients' quality of life. However, despite the known biopsychosocial effects, the deformity remains underappreciated. Patient reported outcome measures can be used to measure and appreciate results from a patient's perspective. The pectus excavatum evaluation questionnaire (PEEQ) is the most employed disease specific instrument to measure patient-reported outcome measures (PROMs). A translation and linguistic validation of this questionnaire is presented for its use in the Dutch pediatric pectus excavatum population. By providing an insight in our translation process, we want to encourage other researchers to perform translations to other languages to make the questionnaire available to clinicians and researchers worldwide. Methods: The 22-item PEEQ was translated and adapted according to the leading guidelines for the translation of patient reported outcome measures. Conceptual equivalence and cultural adaptation were emphasized. Results: One forward translation was produced through reconciliation of two forward translations. Back translation resulted in 15 identical items, as well as 6 literal, and 1 conceptual discrepancy. The latter was expected as during the forward translation a more culturally appropriate translation was chosen. Ten patients were involved during the cognitive debriefing process, following which one item was revised and the final Dutch version was established. Conclusions: We provide a culturally appropriate and linguistically validated Dutch version of the PEEQ.

Low-Dose Nivolumab with or without Ipilimumab as Adjuvant Therapy Following the Resection of Melanoma Metastases: A Sequential Dual Cohort Phase II Clinical Trial.

BACKGROUND: Optimal dosing and duration of adjuvant treatment with PD-1 and CTLA-4 immune checkpoint inhibitors have not been established. Prior to their regulatory approval we investigated a low-dose regimen of nivolumab with or without ipilimumab in a sequential dual-cohort phase II clinical trial. METHODS: Following the complete resection of melanoma metastases, patients were treated with a single fixed dose of ipilimumab (50 mg) plus 4 bi-weekly fixed doses of nivolumab (10 mg) (cohort-1), or nivolumab for 1 year (10 mg fixed dose, Q2w x9, followed by Q8w x4) (cohort-2). Twelve-months relapse-free survival (RFS) served as the primary endpoint. RESULTS: After a median follow-up of 235 weeks for cohort-1 (34 patients), and 190 weeks for cohort-2 (21 patients), the 12-months RFS-rate was, respectively, 55.9% (95% CI, 39-72), and 85.7% (95% CI, 70-100). Treatment-related adverse events occurred in 27 (79%), and 18 (86%) patients, with 3 (9%), and 1 (5%) grade 3 adverse events in cohort-1 and -2, respectively. Immunohistochemical quantification of intra- and peritumoral CD3+ T cells and CD20+ B cells, but not PD-1/PD-L1 staining, correlated significantly with RFS. CONCLUSIONS: One year of adjuvant low-dose nivolumab could be an effective and economically advantageous alternative for standard dosing, at the condition of further confirmation in a larger patient cohort. A shorter low-dose nivolumab plus ipilimumab regimen seems inferior and less tolerable.

The role of local therapy in the treatment of solitary melanoma progression on immune checkpoint inhibition: A multicentre retrospective analysis.

INTRODUCTION: In patients with metastatic melanoma, progression of a single tumour lesion (solitary progression) after response to immune checkpoint inhibition (ICI) is increasingly treated with local therapy. We evaluated the role of local therapy for solitary progression in melanoma. PATIENTS AND METHODS: Patients with metastatic melanoma treated with ICI between 2010 and 2019 with solitary progression as first progressive event were included from 17 centres in 9 countries. Follow-up and survival are reported from ICI initiation. RESULTS: We identified 294 patients with solitary progression after stable disease in 15%, partial response in 55% and complete response in 30%. The median follow-up was 43 months; the median time to solitary progression was 13 months, and the median time to subsequent progression after treatment of solitary progression (TTSP) was 33 months. The estimated 3-year overall survival (OS) was 79%; median OS was not reached. Treatment consisted of systemic therapy (18%), local therapy (36%), both combined (42%) or active surveillance (4%). In 44% of patients treated for solitary progression, no subsequent progression occurred. For solitary progression during ICI (n = 143), the median TTSP was 29 months. Both TTSP and OS were similar for local therapy, ICI continuation and both combined. For solitary progression post ICI (n = 151), the median TTSP was 35 months. TTSP was higher for ICI recommencement plus local therapy than local therapy or ICI recommencement alone (p = 0.006), without OS differences. CONCLUSION: Almost half of patients with melanoma treated for solitary progression after initial response to ICI had no subsequent progression. This study suggests that local therapy can benefit patients and is associated with favourable long-term outcomes.

Whole-Body MRI for the Detection of Recurrence in Melanoma Patients at High Risk of Relapse.

Introduction: No standard protocol for surveillance for melanoma patients is established. Whole-body magnetic resonance imaging (whole-body MRI) is a safe and sensitive technique that avoids exposure to X-rays and contrast agents. This prospective study explores the use of whole-body MRI for the early detection of recurrences. Material and Methods: Patients with American Joint Committee on Cancer Staging Manual (seventh edition; AJCC-7) stages IIIb/c or -IV melanoma who were disease-free following resection of macrometastases (cohort A), or obtained a durable complete response (CR) or partial response (PR) following systemic therapy (cohort B), were included. All patients underwent whole-body MRI, including T1, Short Tau Inversion Recovery, and diffusion-weighted imaging, every 4 months the first 3 years of follow-up and every 6 months in the following 2 years. A total body skin examination was performed every 6 months. Results: From November 2014 to November 2019, 111 patients were included (four screen failures, cohort A: 68 patients; cohort B: 39 patients). The median follow-up was 32 months. Twenty-six patients were diagnosed with suspected lesions. Of these, 15 patients were diagnosed with a recurrence on MRI. Eleven suspected lesions were considered to be of non-neoplastic origin. In addition, nine patients detected a solitary subcutaneous metastasis during self-examination, and two patients presented in between MRIs with recurrences. The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were, respectively, 58%, 98%, 58%, 98%, and 98%. Sensitivity and specificity for the detection of distant metastases was respectively 88% and 98%. No patient experienced a clinically meaningful (>grade 1) adverse event. Conclusions: Whole-body MRI for the surveillance of melanoma patients is a safe and sensitive technique sparing patients' cumulative exposure to X-rays and contrast media.

Phase I clinical trial of decitabine (5-aza-2'-deoxycytidine) administered by hepatic arterial infusion in patients with unresectable liver-predominant metastases.

DNA demethylating agents may increase the immunogenicity of malignant tumours and increase the efficacy of subsequent treatment with immune check point inhibitors. We investigated the safety of administrating the demethylating agent decitabine by hepatic arterial infusionin patients with unresectable liver meta stases from solid tumours in a dose escalation phase I clinical trial. A total of nine eligible patients were enrolled and initiated study treatment at three different dose levels (two patients at 10, four at 15 and six at a dose level of 20mg decitabine/m2/day) (per protocol there was no intent to escalate the dose above the median tolerated intravenous dose level). Decitabine was administered as a 1-hour hepatic arterial infusion on five consecutive days every 4 weeks. Intrapatient dose escalation was applied in five patients. Grades 1 and 2 haematological toxicity was the most frequent treatment-related adverse event. None of the patients experienced treatment-limiting adverse events. Expression analysis of 30 cancer test is antigens (CTA) in pretreatment and post-treatment biopsies from patients indicated an increased expression of 21 CTAs after treatment. There were no objective tumour responses on study treatment or during post study exposure to immune checkpoint therapy in four patients with uveal melanoma liver metastases. We conclude that the investigate d hepatic arterial administration regimen for decitabine can be safely applied, and a dose level of 20 mg/m2/day on five consecutive days every 4 weeks can be considered for further investigation in combinatorial immunotherapy regimens. TRIAL REGISTRATION NUMBER: NCT02316028.