Pneumonitis in Irradiated Lungs After Nivolumab: A Brief Communication and Review of the Literature

Nivolumab is a feasible therapy option in patients with advanced non-small cell lung cancer (NSCLC) who progress on first-line treatment. However, there is limited information about an overlapping toxicity of PD-1 inhibitors when administered following thoracic radiotherapy (TRT). Three of 25 patients with advanced NSCLC were treated with palliative or curative intent. Nivolumab was initiated as second or third-line therapy after TRT for recurrent or progressive disease. All 3 patients developed grade 3 pneumonitis at some point during nivolumab therapy. Herein, we describe 3 cases of pneumonitis in patients with NSCLC started on nivolumab following TRT. Imaging analysis was strongly consistent with heterogenous lung parenchyma changes in the irradiated lung volume receiving a total dose of 15-20Gy. Pulmonary toxicity was manageable;however, interruption of immunotherapy was necessary

Moderate hypofractionated image-guided thoracic radiotherapy for locally advanced node-positive non-small cell lung cancer patients with very limited lung function: a case report

Patients with locally advanced lung cancer and very limited pulmonary function (forced expiratory volume in 1 second [FEV1] <= 1 L) have dismal prognosis and undergo palliative treatment or best supportive care. We describe two cases of locally advanced node-positive non-small cell lung cancer (NSCLC) patients with very limited lung function treated with induction chemotherapy and moderate hypofractionated image-guided radiotherapy (Hypo-IGRT). Hypo-IGRT was delivered to a total dose of 45 Gy to the primary tumor and involved lymph nodes. Planning was based on positron emission tomography-computed tomography (PET/CT) and four-dimensional computed tomography (4D-CT). Internal target volume (ITV) was defined as the overlap of gross tumor volume delineated on 10 phases of 4D-CT. ITV to planning target volume margin was 5 mm in all directions. Both patients showed good clinical and radiological response. No relevant toxicity was documented. Hypo-IGRT is feasible treatment option in locally advanced node-positive NSCLC patients with very limited lung function (FEV1 <= 1 L)

Hypofractionated radiotherapy for prostate cancer

In the last few years, hypofractionated external beam radiotherapy has gained increasing popularity for prostate cancer treatment, since sufficient evidence exists that prostate cancer has a low alpha/beta ratio, lower than the one of the surrounding organs at risk and thus there is a potential therapeutic benefit of using larger fractionated single doses. Apart from the therapeutic rationale there are advantages such as saving treatment time and medical resources and thereby improving patient's convenience. While older trials showed unsatisfactory results in both standard and hypofractionated arm due to insufficient radiation doses and non-standard contouring of target volumes, contemporary randomized studies have reported on encouraging results of tumor control mostly without an increase of relevant side effects, especially late toxicity. Aim of this review is to give a detailed analysis of relevant, recently published clinical trials with special focus on rationale for hypofractionation and different therapy settings

Dose-volumetric parameters and prediction of severe acute esophagitis in patients with locally-advanced non small-cell lung cancer treated with neoadjuvant concurrent hyperfractionated-accelerated chemoradiotherapy

Background: To identify dose-volume parameters predictive for severity of acute esophagitis (CTC &gt; grade 2) in locally-advanced non small-cell lung cancer (LA-NSCLC) patients treated with neoadjuvant concurrent hyperfractionated-accelerated chemoradiotherapy (HA-CRT) a retrospective analysis was performed. 88 patients were treated with HA-CRT followed by radical surgery. Predictive power of absolute oesophageal length, absolute and relative oesophageal volume included in the 95\%-isodose, patient-and tumor-related factors for severity of acute esophagitis was assessed. Findings: A total of 82 patients (93\%) developed radiation-induced acute esophagitis. Grade 1 was documented in 1 (1\%), grade 2 in 55 (67\%), grade 3 in 23 (28\%) and grade 4 in 3 (4\%) patients, respectively. Absolute oesophageal volume included in the 95\%-isodose (42.8 Gy) achieved 13.5 cm(3) (range: 3 - 29 cm(3)). Of the tested variables in univariate analysis, absolute oesophageal volume included in the 95\%-Isodose was found to be the only significant variable (p = 0.03) predicting severe acute esophagitis (CTC &gt; grade 2). For this volume a gradation scale of the likelihood of severity was built. Conclusion: Increase of absolute oesophageal volume included in the 95\%-isodose correlates with severity of acute esophagitis in LA-NSCLC patients treated with neo-adjuvant concurrent HA-CRT

Automated biological target volume delineation for radiotherapy treatment planning using FDG-PET/CT

Background: This study compared manually delineated gross tumour volume (GTV) and automatically generated biological tumour volume (BTV) based on fluoro-deoxy-glucose (FDG) positron emission tomography (PET)/CT to assess the robustness of predefined PET algorithms for radiotherapy (RT) planning in routine clinical practice. Methods: RT-planning data from 20 consecutive patients (lung-(40\%), oesophageal-(25\%), gynaecological-(25\%) and colorectal (10\%) cancer) who had undergone FDG-PET/CT planning between 08/2010 and 09/2011 were retrospectively analysed, five of them underwent neoadjuvant chemotherapy before radiotherapy. In addition to manual GTV contouring, automated segmentation algorithms were applied-among these 38\%, 42\%, 47\% and 50\% SUVmax as well as the PERCIST total lesion glycolysis (TLG) algorithm. Different ratios were calculated to assess the overlap of GTV and BTV including the conformity index and the ratio GTV included within the BTV. Results: Median age of the patients was 66 years and median tumour SUVmax 9.2. Median size of the GTVs defined by the radiation oncologist was 43.7 ml. Median conformity indices were between 30.0-37.8\%. The highest amount of BTV within GTV was seen with the 38\% SUVmax algorithm (49.0\%), the lowest with 50\% SUVmax (36.0\%). Best agreement was obtained for oesophageal cancer patients with a conformity index of 56.4\% and BTV within GTV ratio of 71.1\%. Conclusions: At present there is only low concordance between manually derived GTVs and automatically segmented FDG-PET/CT based BTVs indicating the need for further research in order to achieve higher volumetric conformity and therefore to get access to the full potential of FDG-PET/CT for optimization of radiotherapy planning

Automated biological target volume delineation for radiotherapy treatment planning using FDG-PET/CT

Background: This study compared manually delineated gross tumour volume (GTV) and automatically generated biological tumour volume (BTV) based on fluoro-deoxy-glucose (FDG) positron emission tomography (PET)/CT to assess the robustness of predefined PET algorithms for radiotherapy (RT) planning in routine clinical practice. Methods: RT-planning data from 20 consecutive patients (lung-(40\%), oesophageal-(25\%), gynaecological-(25\%) and colorectal (10\%) cancer) who had undergone FDG-PET/CT planning between 08/2010 and 09/2011 were retrospectively analysed, five of them underwent neoadjuvant chemotherapy before radiotherapy. In addition to manual GTV contouring, automated segmentation algorithms were applied-among these 38\%, 42\%, 47\% and 50\% SUVmax as well as the PERCIST total lesion glycolysis (TLG) algorithm. Different ratios were calculated to assess the overlap of GTV and BTV including the conformity index and the ratio GTV included within the BTV. Results: Median age of the patients was 66 years and median tumour SUVmax 9.2. Median size of the GTVs defined by the radiation oncologist was 43.7 ml. Median conformity indices were between 30.0-37.8\%. The highest amount of BTV within GTV was seen with the 38\% SUVmax algorithm (49.0\%), the lowest with 50\% SUVmax (36.0\%). Best agreement was obtained for oesophageal cancer patients with a conformity index of 56.4\% and BTV within GTV ratio of 71.1\%. Conclusions: At present there is only low concordance between manually derived GTVs and automatically segmented FDG-PET/CT based BTVs indicating the need for further research in order to achieve higher volumetric conformity and therefore to get access to the full potential of FDG-PET/CT for optimization of radiotherapy planning