Surgical treatment of T3 and T4 non-small cell lung cancer

The primary goal of lung cancer therapy is complete eradication of the disease. Surgery remains the most curative modality for non-small cell lung cancer. The goal of surgical treatment is to perform a complete resection. Resectability is closely related to the stage of the disease. The thesis focuses on patients with T3 and T4 non-small cell lung cancer. T3 tumours comprise a heterogeneous group, including tumours with invasion of the chest wall, mediastinal structures, or diaphragm, Pancoast tumours, tumours with involvement of the main bronchus within 2 cm of the carina, and tumours associated with atelectasis or obstructive pneumonitis of the entire lung. The data presented in this thesis confirm that surgery is the treatment of choice for patients with a T3 tumour. The most important prognostic factor is to perform a complete resection, as an incomplete resection predicts poor survival. Regarding several subgroups of T3 tumours, survival was better for tumours located in the main bronchus, but the difference was not statistically significant. Another important factor regarding survival of resected T3 tumours is the presence of mediastinal lymph node metastases. Similar results have been published for Pancoast tumours, which can be staged as a T3 or T4 tumour, depending on invasion of adjacent structures. Recent results of combination of chemoradiotherapy and surgical resection suggest that this combined modality treatment offers the best survival results for these tumours. Characterisation of the primary tumour as T4 involves the presence of any of the following: invasion of the mediastinum, heart or great vessels, trachea, oesophagus, vertebral body, or the carina, the presence of a malignant pleural or pericardial effusion or satellite tumour nodule(s) within the same lobe as the primary tumour. The role of surgery for T4 tumours remains unclear due to high hospital mortality rates and few data about long-term survival. The largest experience and the best results for long-term survival are described in patients with T4 tumours invading the carina and trachea. Recently, multimodality treatment has become the recommended therapy for patients with locally advanced T4 tumours. It remains an important issue to demonstrate histopathological downstaging, as patients with persistent N2/N3 disease do not benefit from surgical resection. However, repeat mediastinoscopy does not seem a useful tool for restaging of the mediastinum after induction therapy, as adhesions and fibrosis cause incomplete procedures and false-negative results

Radical Treatment of Non-Small-Cell Lung Cancer Patients with Synchronous Oligometastases Long-Term Results of a Prospective Phase II Trial (Nct01282450)

BackgroundStage IV non–small-cell lung cancer (NSCLC) patients with oligometastases (< 5 metastatic lesions) may experience long-term survival when all macroscopic tumor sites are treated radically, but no prospective data on NSCLCs with synchronous oligometastases are available.MethodsA prospective single-arm phase II trial was conducted. The main inclusion criteria were pathologically proven NSCLC stage IV with less than five metastases at primary diagnosis, amendable for radical local treatment (surgery or radiotherapy). The study is listed in clinicaltrials.gov, number NCT01282450.ResultsForty patients were enrolled, 39 of whom were evaluable (18 men, 21 women); mean age was 62.1 ± 9.2 years (range, 44–81). Twenty-nine (74%) had local stage III; 17 (44%) brain, seven (18%) bone, and four (10%) adrenal gland metastases. Thirty-five (87%) had a single metastatic lesion. Thirty-seven (95%) of the patients received chemotherapy as part of their primary treatment. Median overall survival (OS) was 13.5 months (95% confidence interval 7.6–19.4); 1-, 2-, and 3-year OS was 56.4%, 23.3%, and 17.5%, respectively. Median progression-free survival (PFS) was 12.1 months (95% confidence interval 9.6–14.3); 1-year PFS was 51.3%, and both 2- and 3-year PFS was 13.6%. Only two patients (5%) had a local recurrence. No patient or tumor parameter, including volume and 18F-deoxyglucose uptake was significantly correlated with OS or PFS. The treatment was well tolerated.ConclusionIn this phase II study, long-term PFS was found in a subgroup of NSCLC patients with synchronous oligometastases when treated radically. Identification of this favorable subgroup before therapy is needed

Treatment with curative intent of stage III non-small cell lung cancer patients of 75years: A prospective population-based study

AbstractBackgroundThere is little data on the survival of elderly patients with stage III non-small cell lung cancer (NSCLC).MethodsPatients with stage III NSCLC in the Netherlands Cancer Registry/Limburg from January 1, 2002 to December 31, 2008 were included.FindingsOne thousand and two patients with stage III were diagnosed, of which 237 were 75years or older. From 228 patients, co-morbidity scores were available. Only 33/237 patients (14.5%) had no co-morbidities, 195 (85.5%) had one or more important co-morbidities, 60 (26.3%) two or more co-morbidities, 18 (7.9%) three or more co-morbidities and 2 patients (0.9%) suffered from four co-morbidities. Forty-eight percent were treated with curative intent. No significant difference in Charlson co-morbidity, age or gender was found between patients receiving curative or palliative intent treatment. Treatment with curative intent was associated with increased overall survival (OS) compared to palliative treatment: median OS 14.2 months (9.6–18.7) versus 5.2months (4.3–6.0), 2-year OS 35.5% versus 12.1%, for curative versus palliative treatment.Patients who received only radiotherapy with curative intent had a median OS of 11.1months (95% confidence interval [95% CI] 6.4–15.8) and a 5-year OS of 20.3%; for sequential chemotherapy and radiotherapy, the median OS was 18.0months (95% CI 12.2–23.7), with a 5-year OS of 14.9%. Only four patients received concurrent chemo-radiation.InterpretationIn this prospective series treating elderly patients with stage III NSCLC with curative intent was associated with significant 5-year survival rates

Invasive aspergillosis mimicking metastatic lung cancer

In a patient with a medical history of cancer, the most probable diagnosis of an (18)FDG-avid pulmonary mass combined with intracranial abnormalities on brain imaging is metastasized cancer. However, sometimes a differential diagnosis with an infectious cause such as aspergillosis can be very challenging as both cancer and infection are sometimes difficult to distinguish. Pulmonary aspergillosis can present as an infectious pseudotumour with clinical and imaging characteristics mimicking lung cancer. Even in the presence of cerebral lesions, radiological appearance of abscesses can look like brain metastasis. These similarities can cause significant diagnostic difficulties with a subsequent therapeutic delay and a potential adverse outcome. Awareness of this infectious disease that can mimic lung cancer, even in an immunocompetent patient, is important. We report a case of a 65-year-old woman with pulmonary aspergillosis disseminated to the brain mimicking metastatic lung cancer

Investigation of the added value of CT-based radiomics in predicting the development of brain metastases in patients with radically treated stage III NSCLC

Introduction: Despite radical intent therapy for patients with stage III non-small-cell lung cancer (NSCLC), cumulative incidence of brain metastases (BM) reaches 30%. Current risk stratification methods fail to accurately identify these patients. As radiomics features have been shown to have predictive value, this study aims to develop a model combining clinical risk factors with radiomics features for BM development in patients with radically treated stage III NSCLC. Methods: Retrospective analysis of two prospective multicentre studies. Inclusion criteria: adequately staged [18F-fluorodeoxyglucose positron emission tomography-computed tomography (18-FDG-PET-CT), contrast-enhanced chest CT, contrast-enhanced brain magnetic resonance imaging/CT] and radically treated stage III NSCLC, exclusion criteria: second primary within 2 years of NSCLC diagnosis and prior prophylactic cranial irradiation. Primary endpoint was BM development any time during follow-up (FU). CT-based radiomics features (N = 530) were extracted from the primary lung tumour on 18-FDG-PET-CT images, and a list of clinical features (N = 8) was collected. Univariate feature selection based on the area under the curve (AUC) of the receiver operating characteristic was performed to identify relevant features. Generalized linear models were trained using the selected features, and multivariate predictive performance was assessed through the AUC. Results: In total, 219 patients were eligible for analysis. Median FU was 59.4 months for the training cohort and 67.3 months for the validation cohort; 21 (15%) and 17 (22%) patients developed BM in the training and validation cohort, respectively. Two relevant clinical features (age and adenocarcinoma histology) and four relevant radiomics features were identified as predictive. The clinical model yielded the highest AUC value of 0.71 (95% CI: 0.58–0.84), better than radiomics or a combination of clinical parameters and radiomics (both an AUC of 0.62, 95% CIs of 0.47–076 and 0.48–0.76, respectively). Conclusion: CT-based radiomics features of primary NSCLC in the current setup could not improve on a model based on clinical predictors (age and adenocarcinoma histology) of BM development in radically treated stage III NSCLC patients

Surgical treatment of T3 and T4 non-small cell lung cancer

The primary goal of lung cancer therapy is complete eradication of the disease. Surgery remains the most curative modality for non-small cell lung cancer. The goal of surgical treatment is to perform a complete resection. Resectability is closely related to the stage of the disease. The thesis focuses on patients with T3 and T4 non-small cell lung cancer. T3 tumours comprise a heterogeneous group, including tumours with invasion of the chest wall, mediastinal structures, or diaphragm, Pancoast tumours, tumours with involvement of the main bronchus within 2 cm of the carina, and tumours associated with atelectasis or obstructive pneumonitis of the entire lung. The data presented in this thesis confirm that surgery is the treatment of choice for patients with a T3 tumour. The most important prognostic factor is to perform a complete resection, as an incomplete resection predicts poor survival. Regarding several subgroups of T3 tumours, survival was better for tumours located in the main bronchus, but the difference was not statistically significant. Another important factor regarding survival of resected T3 tumours is the presence of mediastinal lymph node metastases. Similar results have been published for Pancoast tumours, which can be staged as a T3 or T4 tumour, depending on invasion of adjacent structures. Recent results of combination of chemoradiotherapy and surgical resection suggest that this combined modality treatment offers the best survival results for these tumours. Characterisation of the primary tumour as T4 involves the presence of any of the following: invasion of the mediastinum, heart or great vessels, trachea, oesophagus, vertebral body, or the carina, the presence of a malignant pleural or pericardial effusion or satellite tumour nodule(s) within the same lobe as the primary tumour. The role of surgery for T4 tumours remains unclear due to high hospital mortality rates and few data about long-term survival. The largest experience and the best results for long-term survival are described in patients with T4 tumours invading the carina and trachea. Recently, multimodality treatment has become the recommended therapy for patients with locally advanced T4 tumours. It remains an important issue to demonstrate histopathological downstaging, as patients with persistent N2/N3 disease do not benefit from surgical resection. However, repeat mediastinoscopy does not seem a useful tool for restaging of the mediastinum after induction therapy, as adhesions and fibrosis cause incomplete procedures and false-negative results

Long-term survival of stage T4N0-1 and single station IIIA-N2 NSCLC patients treated with definitive chemo-radiotherapy using individualised isotoxic accelerated radiotherapy (INDAR)

Non-small cell lung cancer (NSCLC) stage T4N0-1 or single nodal station IIIA-N2 are two stage III sub-groups for which the outcome of non-surgical therapy is not well known. We investigated the results of individualised isotoxic accelerated radiotherapy (INDAR) and chemotherapy in this setting.Analysis of NSCLC patients included in 2 prospective trials (NCT00573040 and NCT00572325) stage T4N0-1 or IIIA-N2 with 1 pathologic nodal station, treated with chemo-radiotherapy (CRT) using INDAR with concurrent or sequential platinum-based chemotherapy. Overall survival (OS) was updated and calculated from date of diagnosis (Kaplan-Meier). Toxicity was scored following CTCAEv3.0. To allow comparison with other articles the subgroups were also analysed separately for toxicity, progression free and overall survival.83 patients (42 T4N0-1 and 41 IIIA-N2) were identified: the median radiotherapy dose was 65Gy. Thirty-seven percent of patients received sequential CRT and 63% received concurrent CRT. At a median follow-up of 48 months the median OS for T4N0-1 patients was 34 months with 55% 2-year survival and 25% 5-year survival. For stage IIIA-N2 at a median follow-up of 50 months the median OS was 26 months with 2- and 5-year survival rates of 53% and 24%, respectively.Chemo-radiation using INDAR yields promising survival results in patients with single-station stage IIIA-N2 or T4N0-1 NSCLC