Treatment outcome of patients with synchronous oligometastatic non-small cell lung cancer in the immunotherapy era: Analysis of a real-life intention-to-treat population.

The standard first-line treatment for non-oncogene driven metastatic non-small cell lung cancer (NSCLC) is an immune checkpoint inhibitor (ICI) based strategy. Although guidelines increasingly advise adding local radical treatment (LRT) to patients with synchronous oligometastatic (sOMD) NSCLC responding to systemic therapy, this recommendation is based on the studies without ICI. Furthermore, the majority of published oligometastatic studies were not on an intention-to-treat basis, resulting in selection bias. Moreover, staging Positron Emission Tomography-Computed Tomography (PET-CT) and brain imaging were often not mandatory and definitions of oligometastatic were heterogeneous. Therefore, this study focused on a single centre retrospective series, including all adequately staged patients with sOMD NSCLC according to the European Organisation for Research and Treatment of Cancer definition (maximum of 5 metastases in 3 organs) that were treated with induction (chemo)-ICI and compared outcomes to those treated with chemotherapy only, with and without LRT. The primary end-points were median progression-free survival (PFS) and overall survival (OS) for patients treated with induction (chemo)-ICI versus chemotherapy. Out of 68 included patients, 38 (56%) eventually received LRT. With a median follow-up of 26.7 months, the median PFS was 19.0 months for (chemo)-ICI (n = 18) versus 6.8 for chemotherapy-only (n = 50) (HR 0.5, p = 0.03), the median OS was 19.3 versus 15.7 months, respectively (HR 0.8, p = 0.4). In patients having received LRT, median PFS was 19.0 months for (chemo)-ICI versus 8.3 for chemotherapy-only (HR 0.6, p = 0.2). In conclusion, an ICI-based systemic treatment is feasible and may result in superior survival outcomes. This should be investigated in prospective trials. Strategies to improve response rates to systemic treatment are also needed.

Associations between pretreatment physical performance tests and treatment complications in patients with non-small cell lung cancer: A systematic review.

This systematic review evaluated which outcome variables and cut-off values of pretreatment exercise tests are associated with treatment complications in patients with stage I-III non-small cell lung cancer (NSCLC). PRISMA and Cochrane guidelines were followed. A total of 38 studies with adult patients undergoing treatment for stage I-III NSCLC who completed pretreatment exercise tests, and of whom treatment-related complications were recorded were included. A lower oxygen uptake at peak exercise amongst several other variables on the cardiopulmonary exercise test and a lower performance on field tests, such as the incremental shuttle walk test, stair-climb test, and 6-minute walk test, were associated with a higher risk for postoperative complications and/or postoperative mortality. Cut-off values were reported in a limited number of studies and were inconsistent. Due to the variety in outcomes, further research is needed to evaluate which outcomes and cut-off values of physical exercise tests are most clinically relevant.

Early Loss of Fat Mass During Chemoradiotherapy Predicts Overall Survival in Locally Advanced Squamous Cell Carcinoma of the Lung, but Not in Locally Advanced Squamous Cell Carcinoma of the Head and Neck.

Background: Cancer cachexia is highly prevalent in advanced non-small cell lung cancer (NSCLC) and locally advanced head and neck squamous cell carcinoma (LAHNSCC), and compromises treatment tolerance and overall survival (OS). NSCLC and LAHNSCC patients share similar risk factors, and receive comparable anti-cancer treatment regimens. The aim of this study was to determine the predictive value of body composition assessed by bioelectrical impedance analysis (BIA) and handgrip strength (HGS) (baseline and early changes during therapy) on OS in NSCLC and LAHNSCC patients treated with platinum-based chemoradiotherapy (CRT) or cetuximab-based bioradiotherapy (BRT). To elucidate potential underlying determinants of early changes in body composition and HGS, specific (fat and fat free) mass loss patterns of squamous NSCLC (sNSCLC) were compared to human papilloma virus negative (HPV-) LAHNSCC patients treated with CRT. Methods: Between 2013 and 2016, BIA and HGS were performed at baseline and after 3 weeks of CRT/BRT in LAHNSCC and NSCLC patients treated with curative intent. Results: Two hundred thirty-three patients were included for baseline measurements. Fat free mass index (FFMI) and HGS<10th percentile of reference values at baseline were both prognostic for poor OS in NSCLC and LAHNSCC [HR 1.64 [95%CI 1.13-2.39], p = 0.01 and HR 2.30 [95%CI 1.33-3.97], p = 0.003, respectively], independent of Charlson Comorbidity Index, cancer site, and gross tumor volume. Early fat mass (FM) loss during CRT was predictive for poor OS in sNSCLC (n = 64) [HR 3.80 [95%CI 1.79-8.06] p ≤ 0.001] but not in HPV- LAHNSCC (n = 61). In patients with significant weight loss (>2%) in the first 3 weeks of CRT (sNSCLC n = 24, HPV- LAHNSCC n = 23), the FM change was -1.4 ± 14.5% and -8.7 ± 9.0% in sNSCLC and HPV- LAHNSCC patients, respectively (p < 0.05). Fat fee mass change was -5.6 ± 6.3% and -4.0 ± 4.3% for sNSCLC and HPV- LAHNSCC, respectively (p = 0.31). Conclusion: FFMI and HGS<10th percentile at baseline are independent prognostic factors for poor OS in NSCLC and LAHNSCC patients treated with CRT/BRT. The specific composition of mass loss during first 3 weeks of CRT significantly differs between sNSCLC and HPV- LAHNSCC patients. Early FM loss was prognostic in sNSCLC only.

Health-related quality of life after prophylactic cranial irradiation for stage III non-small cell lung cancer patients: Results from the NVALT-11/DLCRG-02 phase III study.

BACKGROUND AND PURPOSE: The NVALT-11/DLCRG-02 phase III trial (clinicaltrials.gov identifier: NCT01282437) showed that, after standard curative intent treatment, prophylactic cranial irradiation (PCI) decreased the incidence of symptomatic brain metastases (BM) in stage III non-small cell lung cancer (NSCLC) patients compared to observation. In this study we assessed the impact of PCI on health-related quality of life (HRQoL). In addition, an exploratory analysis was performed to assess the impact of neurocognitive symptoms and symptomatic BM on HRQoL. MATERIALS AND METHODS: Stage III NSCLC patients were randomized between PCI and observation. HRQoL was measured using the EuroQol 5D (EQ-5D-3L), EORTC QLQ-C30 and QLQ-BN20 instruments at completion of standard curative intent treatment and 4 weeks, 3, 6, 12, 24 and 36 months thereafter. Generalized linear mixed effects (GLM) models were used to assess the impact of PCI compared to observation over time on three HRQoL metrics: the EORTC QLQ-C30 global health status and the EQ-5D-3L utility and visual analogue scale (EQ VAS) scores. RESULTS: In total, 86 and 88 patients were included in the PCI and observation arm, with a median follow-up of 48.5 months (95% CI 39-54 months). Baseline mean HRQoL scores were comparable between the PCI and observation arm for the three HRQoL metrics. In the GLM models, none of the HRQoL metrics were clinically relevant or statistically significantly different between the PCI and the observation arm (p-values ranged between 0.641 and 0.914). CONCLUSION: No statistically significant nor a clinically relevant impact of PCI on HRQoL was observed.

Variation in causes of death in patients with non-small cell lung cancer according to stage and time since diagnosis.

BACKGROUND: Many patients with non-small cell lung cancer (NSCLC) die within the first few years of diagnosis, and considerable excess mortality remains even after 5 years. We investigated the death rate and the distribution of causes of death for NSCLC patients by age and stage at diagnosis during long-term follow-up. PATIENTS AND METHODS: All 72 021 patients aged 45-89 years diagnosed with stage I-III NSCLC between 1989 and 2008 in the Netherlands and who died up till 2011 were derived from the Netherlands Cancer Registry and linked with the database of Statistics Netherlands for underlying causes of death. Mortality ratios and proportional distribution of causes of death were calculated during 5 time periods after diagnosis of NSCLC (up to 15 years). RESULTS: Median follow-up was 9.6 years (range: 0-23 years). Lung cancer was the predominant cause of death in the first 6 years after diagnosis (being 80%-85% and ∼90% up to 3 years for localized and locally advanced disease, respectively, and ∼60%-75% and ∼75%-85% during years 4-6 for both stage groups, respectively). Thereafter, lung cancer as cause of death proportionally decreased with time since diagnosis, but remained over 30%. Hence, cardiovascular diseases and chronic obstructive pulmonary diseases (COPD) became more important causes of death, especially for patients aged >60 years at diagnosis (up to 34% for cardiovascular diseases and up to 19% for COPD). CONCLUSIONS: With time, the relative contribution of cardiovascular and COPD causes of death increased, although the absolute contribution of lung cancer remained high in non-metastatic NSCLC. Therefore, managing morbidity of these diseases remains relevant.

Complete metabolic remission of an irresectable mediastinal solitary fibrous tumour with concurrent chemoradiation.

Solitary fibrous tumour is a rare mesenchymal tumour of uncertain origin that occurs most frequently in the pleura, although it has also been described in extraserosal sites. The biological behaviour of the tumour is unpredictable. The case history is described of a patient diagnosed with a large symptomatic irresectable mediastinal solitary fibrous tumour who achieved a clinical, radiological and metabolic response after concurrent chemotherapy and radiotherapy.

[Treatment of patients with stage III non-small cell lung cancer: concurrent high-dose chemotherapy and radiotherapy]. / Behandeling van patiënten met niet-kleincellig longcarcinoom stadium III: gelijktijdig hooggedoseerde chemotherapie en radiotherapie.

The treatment of patients with locally advanced non-small cell lung cancer (stage III) has changed significantly in the past few years. Patients with a non-resectable stage IIIA/B tumour are given combined treatment consisting ofchemotherapy and radiotherapy. These can be administered sequentially or concurrently. It has been shown recently that concurrent chemoradiotherapy gives a survival advantage in comparison with sequential chemoradiotherapy. Cisplatin and etoposide are usually the drugs of choice for chemotherapy in patients with stage III cancer. A biologically effective dose of radiotherapy equivalent to 60-66 Gy, over a maximum of 6.5 weeks, should be given. Surgery is possible for a selected group of patients, provided a complete objective mediastinal response has been achieved after chemoradiotherapy and a complete resection appears to be technically feasible. It is recommended to apply this treatment in a research setting. High-dose concurrent chemoradiotherapy is advised as the standard treatment for stage III non-small cell lung cancer in patients in good physical condition.

[Protons and ions in the treatment of cancer; a systematic review of the literature]. / Protonen en ionen in de behandeling van kanker; systematisch literatuuroverzicht.

OBJECTIVE: To provide an overview of the present role of proton and ion therapy, also referred to as 'charged particle therapy', in the treatment of cancer. DESIGN: Systematic literature study. METHOD: Systematic electronic searches were carried out in 12 databases according to the Cochrane Collaboration criteria, without restriction as to year of publication or study design. Manual searches of bibliographies and journals were also performed. The inclusion criteria were: at least 20 patients and a follow-up of at least 2 years. In addition, experts on the subject were consulted by correspondence for their opinion. RESULTS: The search identified 36 relevant articles on proton therapy and 15 on ion therapy. Based on prospective and retrospective studies, proton irradiation emerged as the treatment of choice for ocular tumours, chordomas and skull-base tumours. For prostate cancer, the results were comparable with the best results of photon therapy. Ion therapy was still in an experimental phase. CONCLUSION: According to the current literature, proton therapy is looked upon as the preferred treatment modality for certain rare tumours, such as ocular tumours, chordoma, and skull-base tumours. However, charged particle therapy as a whole, and especially ion therapy, is not supported as the treatment of choice for cancer by published evidence. Nevertheless, the potential theoretical benefit of this treatment is great.

Phased attenuation correction in respiration correlated computed tomography/positron emitted tomography.

The motion of lung tumors with respiration causes difficulties in the imaging with computed tomography (CT) and positronemitted tomography (PET). Since an accurate knowledge of the position of the tumor and the surrounding tissues is needed for radiation treatment planning, it is important to improve CT/PET image acquisition. The purpose of this study was to evaluate the potential to improve image acquisition using phased attenuation correction in respiration correlated CT/PET, where data of both modalities were binned retrospectively. Respiration correlated scans were made on a Siemens Biograph Sensation 16 CT/PET scanner which was modified to make a low pitch CT scan and list mode PET scan possible. A lollipop phantom was used in the experiments. The sphere with a diameter of 3.1 cm was filled with approximately 20 MBq 18F-FDG. Three longitudinal movement amplitudes were tested: 2.5, 3.9, and 4.8 cm. After collection of the raw CT data, list mode PET data, and the respiratory signal CT/PET images were binned to ten phases with the help of in-house-built software. Each PET phase was corrected for attenuation with CT data of the corresponding phase. For comparison, the attenuation correction was also performed with nonrespiration correlated (non-RC) CT data. The volume and the amplitude of the movement were calculated for every phaseof both the CT and PET data (with phased attenuation correction). Maximum and average activity concentrations were compared between the phased and nonphased attenuation corrected PET. With a standard non-RC CT/PET scan, the volume was underestimated by as much as 46% in CT and the PET volume was overestimated to 370%. The volumes found with RC-CT/PET scanning had average deviations of 1.9% (+/- 4.8%) and 1.5% (+/- 3.4%) from the actual volume, for the CT and PET volumes, respectively. Evaluation of the maximum activity concentration showed a clear displacement in the images with non-RC attenuation correction, and activity values were on average14% (+/- 12%) lower than with phased attenuation correction. The standard deviation of the maximum activity values found in the different phases was a factor of 10 smaller when phased attenuation correction was applied. In this phantom study, we have shown that a combination of respiration correlated CT/PET scanning with application of phased attenuation correction can improve the imaging of moving objects and can lead to improved volume estimation and a more precise localization and quantification of the activity.