Adaptive radiotherapy (up to 74 Gy) or standard radiotherapy (66 Gy) for patients with stage III non-small-cell lung cancer, according to [18F]FDG-PET tumour residual uptake at 42 Gy (RTEP7-IFCT-1402): a multicentre, randomised, controlled phase 2 trial.

BACKGROUND: Thoracic radiation intensification is debated in patients with stage III non-small-cell lung cancer (NSCLC). We aimed to assess the activity and safety of a boost radiotherapy dose up to 74 Gy in a functional sub-volume given according to on-treatment [18F]fluorodeoxyglucose ([18F]FDG)-PET results. METHODS: In this multicentre, randomised, controlled non-comparative phase 2 trial, we recruited patients aged 18 years or older with inoperable stage III NSCLC without EGFR mutation or ALK rearrangement with an Eastern Cooperative Oncology Group performance status of 0-1, and who were affiliated with or a beneficiary of a social benefit system, with evaluable tumour or node lesions, preserved lung function, and who were amenable to curative-intent radiochemotherapy. Patients were randomly allocated using a central interactive web-response system in a non-masked method (1:1; minimisation method used [random factor of 0·8]; stratified by radiotherapy technique [intensity-modulated radiotherapy vs three-dimensional conformal radiotherapy] and by centre at which patients were treated) either to the experimental adaptive radiotherapy group A, in which only patients with positive residual metabolism on [18F]FDG-PET at 42 Gy received a boost radiotherapy (up to 74 Gy in 33 fractions), with all other patients receiving standard radiotherapy dosing (66 Gy in 33 fractions over 6·5 weeks), or to the standard radiotherapy group B (66 Gy in 33 fractions) over 6·5 weeks. All patients received two cycles of induction platinum-based chemotherapy cycles (paclitaxel 175 mg/m2 intravenously once every 3 weeks and carboplatin area under the curve [AUC]=6 once every 3 weeks, or cisplatin 80 mg/m2 intravenously once every 3 weeks and vinorelbine 30 mg/m2 intravenously on day 1 and 60 mg/m2 orally [or 30 mg/m2 intravenously] on day 8 once every 3 weeks). Then they concomitantly received radiochemotherapy with platinum-based chemotherapy (three cycles for 8 weeks, with once per week paclitaxel 40 mg/m2 intravenously and carboplatin AUC=2 or cisplatin 80 mg/m2 intravenously and vinorelbine 20 mg/m2 intravenously on day 1 and 40 mg/m2 orally (or 20 mg/m2 intravenously) on day 8 in 21-day cycles). The primary endpoint was the 15-month local control rate in the eligible patients who received at least one dose of concomitant radiochemotherapy. This RTEP7-IFCT-1402 trial is registered with ClinicalTrials.gov (NCT02473133), and is ongoing. FINDINGS: From Nov 12, 2015, to July 7, 2021, we randomly assigned 158 patients (47 [30%] women and 111 [70%] men) to either the boosted radiotherapy group A (81 [51%]) or to the standard radiotherapy group B (77 [49%)]. In group A, 80 (99%) patients received induction chemotherapy and 68 (84%) received radiochemotherapy, of whom 48 (71%) with residual uptake on [18F]FDG-PET after 42 Gy received a radiotherapy boost. In group B, all 77 patients received induction chemotherapy and 73 (95%) received radiochemotherapy. At the final analysis, the median follow-up for eligible patients who received radiochemotherapy (n=140) was 45·1 months (95% CI 39·3-48·3). The 15-month local control rate was 77·6% (95% CI 67·6-87·6%) in group A and 71·2% (95% CI 60·8-81·6%) in group B. Acute (within 90 days from radiochemotherapy initiation) grade 3-4 adverse events were observed in 20 (29%) of 68 patients in group A and 33 (45%) of 73 patients in group B, including serious adverse events in five (7%) patients in group A and ten (14%) patients in group B. The most common grade 3-4 adverse events were febrile neutropenia (seven [10%] of 68 in group A vs 16 [22%] of 73 in group B), and anaemia (five [7%] vs nine [12%]). In the acute phase, two deaths (3%) occurred in group B (one due to a septic shock related to chemotherapy, and the other due to haemotypsia not related to study treatment), and no deaths occurred in group A. After 90 days, one additional treatment-unrelated death occurred in group A and two deaths events occurred in group B (one radiation pneumonitis and one pneumonia unrelated to treatment). INTERPRETATION: A thoracic radiotherapy boost, based on interim [18F]FDG-PET, led to a meaningful local control rate with no difference in adverse events between the two groups in organs at risk, in contrast with previous attempts at thoracic radiation intensification, warranting a randomised phase 3 evaluation of such [18F]FDG-PET-guided radiotherapy dose adaptation in patients with stage III NSCLC. FUNDING: Programme Hospitalier de Recherche Clinique National 2014.

Impact of pembrolizumab treatment duration on overall survival and prognostic factors in advanced non-small cell lung cancer: a nationwide retrospective cohort study.

Background: The efficacy of front-line pembrolizumab has been established in studies that limit treatment duration to 2 years, but decision to stop pembrolizumab after 2 years is often at physician's discretion. ATHENA is a retrospective cohort study using a comprehensive administrative database aimed firstly at exploring the optimal duration of pembrolizumab and secondly real-life prognosis factors in patients with advanced non-small cell lung cancer (NSCLC). Methods: Using the French National Health Insurance database (SNDS), we identified patients with incident lung cancer in France from 2015 to 2022. Treatments and patients' characteristics were extracted or inferred from hospital, outpatient care, pharmacy delivery reports. The duration's hazard ratio (HR) was estimated with Cox model weighted by inverse of propensity score to account for confounding. Prognostics factors in first line population were identified with Cox model selected by a LASSO procedure. Findings: 391,106 patients with lung cancer were identified, of whom 43,359 received up-front pembrolizumab for an advanced disease. There were 67% (29,040/43,359) of male and the median age at diagnosis was 65 years old. After a median follow-up time of 25.9 months (min-max, [0-97.6]), the median overall survival (OS) after pembrolizumab initiation in first line was 15.7 [CI 95, 15.3-16.0] months. In multivariable analysis, several covariables were independently associated with worse OS, including male sex with chemo-immunotherapy, age, hospital category, high deprivation index, inpatient hospitalization for first pembrolizumab, and history of diabetes, diuretic, beta blocker, painkiller prescription. At landmark time of 29 months after pembrolizumab initiation, continuation beyond 2 years was not associated with better OS than a fixed 2-year treatment, HR = 0.97 [0.75-1.26] p = 0.95. Interpretation: This study supports the notion that stopping pembrolizumab after 2 years could be safe for patients with advanced NSCLC. However, because observational studies are prone to confounding and selection bias, causality cannot be affirmed. Funding: This study did not receive any specific grant.

Vena cava leiomyosarcoma surgery results in a retrospective cohort of 41 patients from two centers.

BACKGROUND: Leiomyosarcoma of the vena cava (LMS-VC) is a rare entity with poor oncological outcomes and a lack of histological staging prognostic factors. METHODS: Outcomes of consecutive patients operated on LMS-VC between March 2003 and May 2022, in two specialized sarcoma centers were reported. RESULT: Forty-one patients were identified. Median size of LMS-VC was 9 cm with 68% of complete obstruction. After surgery, severe complication rate was 30%. No postoperative mortality was reported. Microscopic complete excision was obtained for 71% of patients, R1 for 27% and one patient presented an R2 resection. Grade 3 was found in 24%. After a median follow-up of 70 months, 3 years disease-free survival (DFS) and 5 years DFS were 34% and 17%, and 3 years overall survival (OS) and 5 years OS were 74% and 50%. Distant metastasis concerned 54% of recurrences, local 7% and local and distant 5%. Multivariate analysis showed that FNCLCC grade (p < 0.001) and perioperative chemotherapy (p = 0.026) were significant factors for DFS. In multivariate analysis, FNCLCC grade was a significant factor for OS (p = 0.004). DISCUSSION: Perioperative chemotherapy may have a role to play in lowering the risk of recurrence for LMS-VC, particularly in high-grade tumor.

Stereotactic Body Radiotherapy for Centrally Located Inoperable Early-Stage NSCLC: EORTC 22113-08113 LungTech Phase II Trial Results.

INTRODUCTION: The international phase II single-arm LungTech trial 22113-08113 of the European Organization for Research and Treatment of Cancer assessed the safety and efficacy of stereotactic body radiotherapy (SBRT) in patients with centrally located early-stage NSCLC. METHODS: Patients with inoperable non-metastatic central NSCLC (T1-T3 N0 M0, ≤7cm) were included. After prospective central imaging review and radiation therapy quality assurance for any eligible patient, SBRT (8 × 7.5 Gy) was delivered. The primary endpoint was freedom from local progression probability three years after the start of SBRT. RESULTS: The trial was closed early due to poor accrual related to repeated safety-related pauses in recruitment. Between August 2015 and December 2017, 39 patients from six European countries were included and 31 were treated per protocol and analyzed. Patients were mainly male (58%) with a median age of 75 years. Baseline comorbidities were mainly respiratory (68%) and cardiac (48%). Median tumor size was 2.6 cm (range 1.2-5.5) and most cancers were T1 (51.6%) or T2a (38.7%) N0 M0 and of squamous cell origin (48.4%). Six patients (19.4%) had an ultracentral tumor location. The median follow-up was 3.6 years. The rates of 3-year freedom from local progression and overall survival were 81.5% (90% confidence interval [CI]: 62.7%-91.4%) and 61.1% (90% CI: 44.1%-74.4%), respectively. Cumulative incidence rates of local, regional, and distant progression at three years were 6.7% (90% CI: 1.6%-17.1%), 3.3% (90% CI: 0.4%-12.4%), and 29.8% (90% CI: 16.8%-44.1%), respectively. SBRT-related acute adverse events and late adverse events ≥ G3 were reported in 6.5% (n = 2, including one G5 pneumonitis in a patient with prior interstitial lung disease) and 19.4% (n = 6, including one lethal hemoptysis after a lung biopsy in a patient receiving anticoagulants), respectively. CONCLUSIONS: The LungTech trial suggests that SBRT with 8 × 7.5Gy for central lung tumors in inoperable patients is associated with acceptable local control rates. However, late severe adverse events may occur after completion of treatment. This SBRT regimen is a viable treatment option after a thorough risk-benefit discussion with patients. To minimize potentially fatal toxicity, careful management of dose constraints, and post-SBRT interventions is crucial.

Recommendations for Post-Operative RadioTherapy After Complete Resection of Thymoma-a French DELPHI Consensus Initiative.

INTRODUCTION: Thymomas are rare intrathoracic malignancies that can relapse after surgery. Whether or not Post-Operative RadioTherapy (PORT) should be delivered after surgery remains a major issue. RADIORYTHMIC is an ongoing, multicenter, randomized phase 3 trial addressing this question in patients with completely R0 resected Masaoka-Koga stage IIb/III thymoma. Experts in the field met to develop recommendations for PORT. METHODS: A scientific committee from the RYTHMIC network identified key issues regarding the modalities of PORT in completely resected thymoma. A DELPHI method was used to question 24 national experts, with 115 questions regarding the following: (1) imaging techniques, (2) clinical target volume (CTV) and margins, (3) dose constraints to organs at risk, (4) dose and fractionation, and (5) follow-up and records. Consensus was defined when opinions reached more than or equal to 80% agreement. RESULTS: We established the following recommendations: preoperative contrast-enhanced computed tomography (CT) scan is recommended (94% agreement); optimization of radiation delivery includes either a four-dimensional CT-based planning (82% agreement), a breath-holding inspiration breath-hold-based planning, or daily control CT imaging (81% agreement); imaging fusion based on cardiovascular structures of preoperative and planning CT scan is recommended (82% agreement); right coronary and left anterior descending coronary arteries should be delineated as cardiac substructures (88% agreement); rotational RCMI/volumetric modulated arc therapy is recommended (88% agreement); total dose is 50 Gy (81% agreement) with 1.8 to 2 Gy per fraction (94% agreement); cardiac evaluation and follow-up for patients with history of cardiovascular disease are recommended (88% agreement) with electrocardiogram and evaluation of left ventricular ejection fraction at 5 years and 10 years. CONCLUSION: This is the first consensus for PORT in thymoma. Implementation will help to harmonize practices.

Postoperative radiotherapy results in 192 epithelial thymic tumours patients with 10 years of follow-up.

PURPOSE: To assess the prognostic factors and patterns of failure of patients consecutively treated with surgery and postoperative radiation therapy (PORT) for thymic epithelial tumours (TET). PATIENTS AND METHODS: Data from 192 TET patients who were operated and received PORT at a single centre from 1990 to 2019 was retrospectively analysed. RESULTS: Most patients had thymoma (77 %, B247%), were classified Masaoka-Koga stage III (35 %) or IV (32 %) and had a R0 (75 %) resection. Radiotherapy was delivered at a median dose of 50.4 Gy (range, 42-66 Gy; ≥ 60 Gy in 17 %), 63 (33 %) patients were treated by intensity-modulated radiation therapy and elective nodal radiotherapy was used for 37 %. At a median follow-up of 10.9 years, the 10-year overall survival (OS) and progression-free survival (PFS) rates were 62 % (95 % CI: 54-70 %) and 47 % (95 % CI: 39-55 %), respectively. Locoregional recurrence (LRR) occurred in 72/192 (38 %) patients, distributed as 6 local, 45 regional and 21 both local and regional. LRR were mainly located to the pleura: 66/72 (92 %) and 16/72 (22 %; 16/192 in total, 8 %) were in-field. Distant relapse (DR) were observed in 30 patients (16 %), resulting in 10-year locoregional (LRC) and distant control rates of 58 % (95 % CI: 50-66 %) and 82 % (95 % CI: 77-88 %), respectively. In the multivariate analysis, Masaoka-Koga stage (HR [hazard ratio]: 1.9; p = 0.001), thymic carcinomas/neuroendocrine tumours (TC) (HR: 1.6; p = 0.045) and ECOG PS > 1 (HR: 1.9; p = 0.02) correlated with poorer OS. Higher Masaoka-Koga stage (HR: 2.6; p < 0.001) associated with a decreased LRC but not R1 status (HR: 1.2; p = 0.5) or WHO histology classification. TC (HR: 3.4; p < 0.001) and a younger age (HR: 2.5; p = 0.02) correlated with DR. CONCLUSION: Approximately one-third of the TET in our study experienced a LRR, mainly to the pleura, and 8% in total were in-field. The place of radiotherapy should be better defined in higher risk thymoma patients within prospective randomized studies.

Meta-Analysis on the Combination of Chemotherapy With Programmed Death-Ligand 1 and Programmed Cell Death Protein 1 Blockade as First-Line Treatment for Unresectable Pleural Mesothelioma.

INTRODUCTION: Dual immune checkpoint blockers regimen represents a standard first-line therapy in unresectable pleural mesothelioma (PM). Novel combination strategies, including immune checkpoint blockers and antiangiogenic drugs, are currently under investigation in this setting. We aimed to assess the efficacy of the chemoimmunotherapy combination by reference to literature evidence. METHODS: A systematic review and meta-analysis of trials with first-line platinum-based chemotherapy associated with programmed death-ligand 1 and programmed cell death protein 1 agent in unresectable PM. We estimated the weighted summary proportion of disease response, along with the landmark probability of survival outcomes. RESULTS: A total of 349 patients with unresectable PM from four trials (DREAM, PrE0505, JME-001, and IND.227) were included, 79% (n = 274) with epithelioid and 21% (n = 75) with nonepithelioid histologic type. In aggregate, the objective response rate was 59.2% (95% confidence interval [CI]: 50.3%-67.9%) and disease control rate was 92.2% (95% CI: 89.2%-94.8%). Comparing epithelioid versus nonepithelioid tumors, the objective response rate was 64.5% versus 46.4%, (p < 0.001) and the disease control rate was 92.3% versus 80.0%, (p = 0.043), with an OR of 2.56 (95% CI: 1.51-4.32) for disease response and of 3.37 (95% CI: 0.99-11.47) for disease control. The aggregated estimated probability of progression-free survival was 63% (95% CI: 53%-71%) at 6 months and 25% (95% CI: 21%-31%) at 12 months, whereas the 6-, 12- and 24-month overall survival rates were 88% (95% CI: 81%-93%), 71% (95% CI: 61%-79%) and 39% (95% CI: 34%-45%), respectively. CONCLUSIONS: According to our analysis, first-line chemoimmunotherapy holds promise as a new treatment approach for PM, exhibiting encouraging survival outcomes and an enhanced response rate, including for the epithelioid subtype. Ongoing studies are necessary to establish its precise placement within the treatment algorithm.

Desmoid-type fibromatosis: Current therapeutic strategies and future perspectives.

Desmoid tumors (DT) are rare, slow-growing, locally invasive soft tissue tumors that often pose significant therapeutic challenges. Traditional management strategies including active surveillance, surgery, radiotherapy, and systemic therapy which are associated with varying recurrence rates and high morbidity. Given the challenging nature of DT and the modest outcomes associated with current treatment strategies, there has been a growing interest in the field of γ-secretase inhibitors as a result of its action on the Wnt/ß-catenin signaling pathway. In this review article, we will shed the light on the pathogenesis and molecular biology of DT, discuss its symptoms and diagnosis, and provide a comprehensive review of the traditional therapeutic approaches. We will also delve into the mechanisms of action of γ-secretase inhibitors, its efficacy, and the existing preclinical and clinical data available to date on the use of these agents, as well as the potential challenges and future prospects in the treatment landscape of these tumors.

A CT-based radiomics classification model for the prediction of histological type and tumour grade in retroperitoneal sarcoma (RADSARC-R): a retrospective multicohort analysis.

BACKGROUND: Retroperitoneal sarcomas are tumours with a poor prognosis. Upfront characterisation of the tumour is difficult, and under-grading is common. Radiomics has the potential to non-invasively characterise the so-called radiological phenotype of tumours. We aimed to develop and independently validate a CT-based radiomics classification model for the prediction of histological type and grade in retroperitoneal leiomyosarcoma and liposarcoma. METHODS: A retrospective discovery cohort was collated at our centre (Royal Marsden Hospital, London, UK) and an independent validation cohort comprising patients recruited in the phase 3 STRASS study of neoadjuvant radiotherapy in retroperitoneal sarcoma. Patients aged older than 18 years with confirmed primary leiomyosarcoma or liposarcoma proceeding to surgical resection with available contrast-enhanced CT scans were included. Using the discovery dataset, a CT-based radiomics workflow was developed, including manual delineation, sub-segmentation, feature extraction, and predictive model building. Separate probabilistic classifiers for the prediction of histological type and low versus intermediate or high grade tumour types were built and tested. Independent validation was then performed. The primary objective of the study was to develop radiomic classification models for the prediction of retroperitoneal leiomyosarcoma and liposarcoma type and histological grade. FINDINGS: 170 patients recruited between Oct 30, 2016, and Dec 23, 2020, were eligible in the discovery cohort and 89 patients recruited between Jan 18, 2012, and April 10, 2017, were eligible in the validation cohort. In the discovery cohort, the median age was 63 years (range 27-89), with 83 (49%) female and 87 (51%) male patients. In the validation cohort, median age was 59 years (range 33-77), with 46 (52%) female and 43 (48%) male patients. The highest performing model for the prediction of histological type had an area under the receiver operator curve (AUROC) of 0·928 on validation, based on a feature set of radiomics and approximate radiomic volume fraction. The highest performing model for the prediction of histological grade had an AUROC of 0·882 on validation, based on a radiomics feature set. INTERPRETATION: Our validated radiomics model can predict the histological type and grade of retroperitoneal sarcomas with excellent performance. This could have important implications for improving diagnosis and risk stratification in retroperitoneal sarcomas. FUNDING: Wellcome Trust, European Organisation for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group, the National Institutes for Health, and the National Institute for Health and Care Research Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research.

Systemic Therapy in Advanced Pleomorphic Liposarcoma: a Comprehensive Review.

OPINION STATEMENT: The therapeutic approach of pleomorphic liposarcoma (PLPS), a rare high-grade subgroup of soft tissue sarcoma, is commonly extrapolated from the management of other LPS subtypes. Only published retrospective data on PLPS currently serve as a guide for oncologists without clear recommendations or specific guidelines. In the advanced setting, specific systemic therapy such as eribulin and trabectedin showed promising activity in comparison to conventional therapy (doxorubicin- and gemcitabine-based protocols), which currently remains the current standard of care at initial stages of the disease. The better understanding of soft tissue sarcoma (STS) pathophysiology and disease course has led to the development of adapted clinical trial designs for rare STS histotypes with specific treatment approach.

Local control strategies for management of NSCLC with oligoprogressive disease.

Progresses of systemic treatments in advanced non-small cell lung cancer (NSCLC), such as immune checkpoint blockers (ICB) and targeted therapies, led to the increased incidence of oligoprogressive disease (OPD). The OPD is a subtype of oligometastatic disease (OMD) defined as a progression of a limited number of lesions during systemic treatment exposure. The hypothesis was formulated that local radical treatments (LRT) could eradicate progressive lesions resulting from resistant clones, ultimately leading to systemic treatment sensitivity restoration. Recently published international consensuses and guidelines aim to obtain a uniform definition of OMD NSCLC, to standardize the inclusion of these patients in future clinical trials, as well as their management in daily practice. Although there is no specific definition of OPD, LRT strategies in OPD are supported after reporting promising results. Both retrospective and preliminary prospective randomized data of LRT for patients with OPD NSCLC are encouraging. More clinical and translational data are needed for selecting best scenarios where LRT should be delivered. In this review, we analyze the current available literature on LRT for patients with OPD in advanced NSCLC and discuss about future trial design and challenges.

Stereotactic body radiotherapy for extra-cranial oligoprogressive or oligorecurrent small-cell lung cancer.

Introduction: The role of local ablative treatments, including stereotactic body radiotherapy (SBRT), is an area of active research in oligometastatic patients. Small cell lung cancer (SCLC) has a poor prognosis, with common diffuse metastatic evolution. We evaluated the outcomes after SBRT in uncommon oligoprogressive/oligorecurrent SCLC presentation. Methods: Data of SCLC patients who received SBRT for oligoprogressive/oligorecurrent metastatic disease at four centers were retrospectively analyzed. Patients with synchronous oligometastatic disease, SBRT for primary lung tumor and brain radiosurgery were not included. Relapse and survival rates were defined as the time between the date of SBRT and the first event. Results: Twenty patients (60% with initially limited-disease [LD]) presenting 24 lesions were identified. Oligoprogression and oligorecurrence were observed in 6/20 (30%) and 14/20 (70%) patients, respectively. SBRT was delivered to one (n = 16) to two (n = 4) lesions (median size, 26 mm), mainly to lung [n = 17/24] metastases. At a median follow-up of 2.9 years, no local relapse was observed and 15/20 patients experienced a distant relapse (DR). The median DR and OS were 4.5 months (95 %CI: 2.9-13.7 months) and 17.2 months (95 %CI: 7.5-65.2 months), respectively. The 3-year distant control and OS rates were 25% (95 %CI: 6-44%) and 37% (95 %CI: 15-59%), respectively. Initial LD (vs extensive-disease) was the only prognosis factor associated with a lower risk of post-SBRT DR (HR: 0.3; 95% CI: 0-0.88; p = 0.03). There was no severe observed SBRT-related toxicities. Conclusion: Prognosis was poor, with DR occurring in most patients. However, local control was excellent and long term response after SBRT may rarely occur in patients with oligoprogressive/oligorecurrent SCLC. Local ablative treatments should be discussed in a multidisciplinary setting on well-selected cases.

Treatment Decisions for Resectable Non-Small-Cell Lung Cancer: Balancing Less With More?

For patients with non-small-cell lung cancer (NSCLC), the outcomes for patients with resectable disease are historically poor compared with other solid organ malignancies. In recent years, there have been significant advances in multidisciplinary care, which have resulted in improved outcomes. Innovations in surgical oncology include the use of limited resection and minimally invasive techniques. Recent data in radiation oncology have suggested refinements in pre- and postoperative radiation therapy, resulting in optimization of techniques in the curative setting. Finally, the success of immune checkpoint inhibitors and targeted therapies in the advanced setting has paved the way for inclusion in the adjuvant and neoadjuvant settings, resulting in recent regulatory approvals for four regimens (CheckMate-816, IMpower010, PEARLS, ADAURA). In this review, we will provide an overview of the seminal studies informing advancements in optimal surgical resection, radiation treatment, and systemic therapy for resectable NSCLC. We will summarize the key data on survival outcomes, biomarker analyses, and future directions for perioperative studies.

Outcomes of extended resection for locally advanced thymic malignancies.

BACKGROUND: Thymic malignancies are rare tumors about which data are limited. Our objective here was to evaluate the outcomes and risk factors for complications and death in patients who underwent extended surgery to remove thymic malignancies. METHODS: We retrospectively included patients who underwent extended resection of locally advanced, nonmetastatic thymic malignancies at our institution. Patients were deemed eligible for resection by a multidisciplinary team. During surgery, priority was given to achieving complete resection rather than to sparing organs. RESULTS: The 108 patients had a mean age of 53 ± 15 years (range, 9-83); among them, 91 had thymoma, 12 thymic carcinoma, and 5 neuroendocrine tumor. The Masaoka stage was III or higher in 86 patients; examination of operative specimens resulted in downstaging of 22 patients. Tumor-free resection margins were achieved in 98 patients. Overall 5- and 10-year survival rates were 80% and 68%, respectively. Myasthenia gravis, present in 36 patients, was the only independent significant risk factor for major postoperative complications. Age older than 70 years, thymic carcinoma or neuroendocrine tumor, pT3 or pT4 stage, and R1 or R2 resection margins independently predicted death. The number of resected structures was not associated with survival. Thymic carcinoma or neuroendocrine tumor was independently associated with shorter disease-free survival. CONCLUSION: In an expert center, extended resection targeting complete resection rather than organ preservation provided good outcomes in patients with locally advanced thymic malignancies. The risk/benefit ratio of surgery should be assessed with special care in patients who are elderly or have myasthenia gravis.

Reaching multidisciplinary consensus on the management of non-bulky/non-infiltrative stage IIIA N2 non-small cell lung cancer.

INTRODUCTION: The optimal management of patients with non-bulky/non-infiltrative stage IIIA N2 non-small cell lung cancer (NSCLC) remains controversial. In this modified Delphi study from France, we aimed to generate agreement through multidisciplinary decision-making on the clinical management of patients with non-bulky/non-infiltrative N2 NSCLC. METHODS: An expert panel of 30 physicians from different specialities completed two Delphi rounds of a 76-item questionnaire, pertaining to: pathological confirmation of N2 disease; initial treatment approach; treatment approach in case of disease progression/stability following neoadjuvant chemotherapy; treatment approach taking into account various patient and tumour characteristics. Each questionnaire item was scored using a 9-point Likert scale. Consensus in agreement was achieved if ≥ 80 % of responses to a questionnaire item were scored between 7 and 9 and if the median value of the score to the item was ≥ 7. RESULTS: Regarding the pathologic confirmation of N2 disease, agreement (up to 100 %) was reached on endobronchial ultrasound/endoscopic ultrasound as the preferred method of initial mediastinal staging for paratracheal lymph nodes. There was also panellist agreement (up to 93 %) on the adoption as first-line treatment of surgery and (neo)adjuvant chemotherapy in patients with single-station disease, and of concurrent chemoradiotherapy followed by adjuvant immunotherapy in those with multi-station N2 disease. Panellists further agreed on the use of a non-surgical strategy, i.e., concurrent chemoradiotherapy with adjuvant immunotherapy, in patients with single-station N2 disease in case of: involvement of ≥ 2 mediastinal lymph nodes; disease progression following neoadjuvant chemotherapy; compromised cardiopulmonary function if compatible with radiotherapy; anticipated right pneumonectomy. CONCLUSIONS: This Delphi study reinforces the importance of multidisciplinary discussions leading to the best individual approach to the clinical management of patients with non-bulky/non-infiltrative N2 NSCLC, a challenging heterogeneous population.

Retrospective study of outcomes after extended resection for tracheobronchial adenoid cystic carcinoma.

OBJECTIVE: Tracheobronchial adenoid cystic carcinoma is a rare, slow-growing malignancy with a considerable propensity for local extension that may require complex airway resection to achieve tumor-free margins. The objective of this study was to assess whether our experience supports complex airway resection for tracheobronchial adenoid cystic carcinoma. METHODS: Consecutive patients who underwent curative resection for tracheobronchial adenoid cystic carcinoma at our institution between 1970 and 2019 were included retrospectively and classified as having had complex or standard resection. Complex surgery included total tracheal replacement, associated esophageal resection, pneumonectomy, total laryngectomy with tracheal resection, and carinal resection. Standard surgery included tracheal resection, bronchoplastic resection, lobectomy, and bilobectomy. We obtained data from medical records, referring physicians, patients, relatives, and public death records. RESULTS: Of 59 included patients, 38 had complex and 21 had standard surgery. All 4 (6.8%) patients who died postoperatively had undergone complex surgery. Postoperative morbidity was 32.2% overall and was significantly higher after complex surgery (P = .043). Overall 5- and 10-year survival rates were 81.5% and 60.2%, with no significant differences between groups (P = .31). By univariate analysis, T4 tumor and microscopically detectable tumor in the operative specimen margins and gross tumor in the operative specimen margins were associated with poorer survival (P < .05). In the subgroup with microscopically detectable tumor resection, survival was significantly better with adjuvant radiotherapy (P < .05). CONCLUSIONS: Complex resection for extended tracheobronchial adenoid cystic carcinoma may achieve local control and satisfying long-term survival. However, this demanding procedure is associated with high postoperative morbidity and mortality rates. Because adjuvant radiotherapy improved outcomes after resection resulting in microscopically detectable tumor in the operative specimen margins, expected outcomes after resection with no detectable tumor in the margins must be compared to those after resection resulting in microscopically detectable tumor in the margins plus radiotherapy, according to the operative risk.

Immune-related arthritis following pelvic radiation therapy in a patient with lung cancer receiving long-term immune checkpoint blocker treatment: Case report.

Radiotherapy can trigger immune-related out-of-field "abscopal" response. We report a patient with advanced NSCLC (non-small cell lung cancer) receiving long-term anti-PD1 (programmed cell death protein 1) who have developed out-of-field immune-related arthritis following pelvic irradiation.

Complete Remission After Immunotherapy-Induced Abdominal Tuberculosis in a Patient With Advanced NSCLC Treated With Pembrolizumab: A Case Report.

The use of immune checkpoint inhibitors (ICIs) has drastically transformed the therapeutic landscape in lung cancer. Special focus has been put on immune-related toxicity; however, infections can also seem during ICI treatment. Although rare, tuberculosis (TB) has been increasingly identified after ICIs, and it seems that the programmed cell death protein 1 and programmed death-ligand 1 pathway is directly involved in its pathophysiology. Here, we describe the case of a patient with advanced NSCLC who developed abdominal TB after 32 months of pembrolizumab and who remains in tumor remission 10 months after discontinuation of this drug. Routine screening for latent TB before ICI treatment is advised, with closer collaboration between infectious disease specialists and oncologists.