Dose-volume metric-based prediction of radiotherapy-induced lymphocyte loss in patients with non-small-cell lung cancer treated with modern radiotherapy techniques.

Background and Purpose: Radiation-induced lymphopenia (RIL) is a common side effect of radiotherapy (RT) that may negatively impact survival. We aimed to identify RIL predictors in patients with non-small-cell lung cancer (NSCLC) treated intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). Materials and Methods: We retrospectively analysed data of 306 patients who underwent radical RT for NSCLC. Absolute lymphocyte count (ALC) loss was evaluated for each patient by fitting an exponential decay curve to data from first 45 days since treatment start, and percentage ALC loss relative to baseline was calculated based on area under the decay curve and baseline ALC. We compared IMRT and VMAT treatment plans and used linear regression to predict ALC loss. Results: ALC decreased during RT in the whole patient group, while neutrophil counts remained stable and decreased only in those treated with concurrent chemoradiotherapy (CRT). Percentage ALC loss ranged between 11 and 78 % and was more strongly than lymphocyte nadir correlated with dose-volume metrics for relevant normal structures. We found evidence for the association of high radiation dose to the lungs, heart and body with percentage ALC loss, with lung volume exposed to 20-30 Gy being most important predictors in patients treated with IMRT. A multivariable model based on CRT use, baseline ALC and first principal component (PC1) of the dose-volume predictors showed good predictive performance (bias-corrected R2 of 0.40). Conclusion: Percentage lymphocyte loss is a robust measure of RIL that is predicted by baseline ALC, CRT use and dose-volume parameters to the lungs, heart and body.

Trimodality Treatment of Superior Sulcus Non-Small Cell Lung Cancer: An Institutional Series of 47 Consecutive Patients.

OBJECTIVES: Treatment of superior sulcus tumors (SST) using concurrent chemoradiation followed by surgery is a current standard. However, due to the rarity of this entity, clinical experience in its treatment remains scarce. Here, we present the results of a large consecutive series of patients treated with concurrent chemoradiation followed by surgery at a single academic institution. MATERIALS AND METHODS: The study group included 48 patients with pathologically confirmed SST. The treatment schedule consisted of preoperative 6-MV photon-beam radiotherapy (45-66 Gy delivered in 25-33 fractions over 5-6.5 weeks) and concurrent two cycles of platinum-based chemotherapy. Five weeks after completion of chemoradiation, pulmonary and chest wall resection was performed. RESULTS: From 2006 to 2018, 47 of 48 consecutive patients meeting protocol criteria underwent two cycles of cisplatin-based chemotherapy and concurrent radiotherapy (45-66 Gy) followed by pulmonary resection. One patient did not undergo surgery due to brain metastases that occurred during induction therapy. The median follow-up was 64.7 months. Chemoradiation was well tolerated, with no toxicity-related deaths. Twenty-one patients (44%) developed grade 3-4 side effects, of which the most common was neutropenia (17 patients; 35.4%). Seventeen patients (36.2%) had postoperative complications, and 90-day mortality was 2.1%. Three- and five-year overall survival (OS) were 43.6% and 33.5%, respectively, and three- and five-year recurrence-free survival were 42.1% and 32.4%, respectively. Thirteen (27.7%) and 22 (46.8%) patients had a complete and major pathological response, respectively. Five-year OS in patients with complete tumor regression was 52.7% (95% CI 29.4-94.5). Predictive factors of long-term survival included age below 70 years, complete resection, pathological stage, and response to induction treatment. CONCLUSIONS: Chemoradiation followed by surgery is a relatively safe method with satisfactory outcomes.

Contralateral esophageal sparing technique in definitive radiotherapy for non-small cell lung cancer: dosimetric parameters and normal tissue complication probability modeling.

Background: The purpose of this study was to assess the benefit of the contralateral esophageal sparing technique (CEST) in definitive radiotherapy of non-small cell lung cancer (NSCLC). Materials and methods: We retrospectively reviewed radiation plans for 13 patients who underwent definitive chemoradiation for locally advanced NSCLC. Alternative plans were prepared with the use of CEST, with an additional margin of 5 mm from planning treatment volume (PTV). Normal tissue complication probability (NTCP) analyses for the esophagus and tumor control probability (TCP) for the PTV were performed for original and CEST plans using the equivalent uniform dose (EUD)-based mathematical model. Results: In all cases, the CEST plan allowed for the reduction of esophageal dose, with a mean of 3.8 Gy (range, 0.7 to 8.7 Gy). The mean reductions of V40 and V60 to the esophagus were 6.4 Gy (range, 2.1 to 17.2 Gy) and 1.9 Gy (range, 3.4 to 10.0 Gy), respectively. There was no substantial decrease in the maximal dose to the esophagus. Reduction of NTCP was achieved for all patients (range, 5-73%), and TCP was not affected (-1.8 to +6.7%). Conclusions: The application of CEST in definitive radiotherapy of locally advanced NSCLC allows for reducing selected dosimetric parameters to the esophagus without compromising TCP.

Concurrent chemoradiotherapy for stage III non-small-cell lung cancer: recent progress and future perspectives (a narrative review).

Concurrent chemoradiotherapy (CHRT) remains the therapeutic standard for locally advanced inoperable non-small-cell lung cancer (NSCLC). The median overall survival (OS) with this approach is in the range of 20-30 months, with five-year survival of approximately 30%. These outcomes have recently been further improved by supplementing CHRT with maintenance durvalumab, a monoclonal anti-PD-L1 agent. The progress in treatment outcomes of locally advanced NSCLC before the era of immunotherapy has been achieved mainly by virtue of developments in diagnostics and radiotherapy techniques. Routine implementation of endoscopic and endobronchial ultrasonography for mediastinal lymph nodes assessment, positron emission tomography/computed tomography and magnetic resonance imaging of the brain allows for more accurate staging of NSCLC and for optimizing treatment strategy. Thorough staging and respiratory motion control allows for higher conformity of radiotherapy and reduction of radiotherapy related toxicity. Dose escalation with prolonged overall treatment time does not improve treatment outcomes of CHRT. In consequence, 60 Gy in 2 Gy fractions or equivalent biological dose remains the standard dose for definitive CHRT in locally advanced NSCLC. However, owing to increased toxicity of CHRT, this option may not be applicable in a proportion of elderly or frail patients. This article summarizes recent developments in curative CHRT for inoperable stage III NSCLC, and presents perspectives for further improvements of this strategy.

Treatment patterns and real-world evidence for stage III non-small cell lung cancer in Central and Eastern Europe.

Background The aim of this project was to collect real-world evidence and describe treatment patterns for stage III non-small cell lung cancer in Central and Eastern Europe. Based on real-world evidence, an expert opinion was developed, and the unmet needs and quality indicators were identified. Patients and methods A systematic literature search and a multidisciplinary expert panel of 10 physicians from 7 countries used a modified Delphi process to identify quality indicators and unmet needs in patients with stage III non-small cell lung cancer. The profound questionnaire was used to characterize treatment patterns used for stage III non-small cell lung cancer, and a systematic review identified patterns in Central and Eastern Europe. The first questionnaire was completed by a group of medical oncologists, radiation oncologists and pneumologists. The panel of experts attended an in-person meeting to review the results of the questionnaire and to process a second round Delphi. An additional survey was then compiled and completed by the panel. Results A complete consensus was reached by the panel of experts on a set of evidence-based clinical recommendations. The experience-based questionnaire generated a highly variable map of treatment patterns within the region. A list of unmet needs and barriers to quality care were developed with near-unanimous consent of the panel of experts. Conclusions The current landscape of diagnostic and therapeutic approaches in Central and Eastern European countries is highly variable. We identified several significant barriers, mainly related to the availability of diagnostic and imaging methods and low rates of chemoradiotherapy with curative intention as initial treatment for unresectable stage III NSCLC.

Castleman's disease mimicking lymph node metastases in a young woman with laryngeal cancer.

Laryngeal cancer occurs rarely in adolescents and young people. Castleman's disease is a rare lymphoproliferative disorder of uncertain etiopathogenesis and heterogeneous clinicopathological forms. Involved lymph nodes and extranodal lesions in the course of Castleman's disease may mimic malignant involvement. We report a case of an 18-year-old woman with T2N0M0 laryngeal glottis cancer treated with definitive radiotherapy. During the irradiation, the patient underwent an excision of incidentally discovered left-sided enlarged cervical lymph nodes located outside the irradiated area. Coincidental hyaline vascular type of Castleman's disease was diagnosed. During six-year follow-up she has been free of cancer relapse and Castleman's disease symptoms.