This is a case of resectable clinical Stage IIIA ALK-positive adenocarcinoma treated with upfront surgery followed by adjuvant treatment. The patient was diagnosed with clinical Stage IIIA adenocarcinoma originating in the left lower lobe with station 11L lymph node positive on EBUS-TBNA. The patient was discussed at Tumour Board Rounds and deemed a good candidate for neoadjuvant chemotherapy + immunotherapy as per the Checkmate 816 protocol. However, molecular testing revealed the tumour to be ALK+, therefore, the patient underwent upfront resection (VATS left lower lobectomy with mediastinal lymph node dissection) followed by adjuvant treatment. Surgical pathology poorly differentiated solid predominant adenocarcinoma, pT4N2.
This case was chosen as a representative of the management of a patient with pleural mesothelioma combined with adenocarcinoma in situ of the lung.
Key areas addressed:
Recognizing the diagnosis and treatment process of lung AIS and pleural mesothelioma according to NCCN.
Comprehend the surgical indications for lung adenocarcinoma and pleural mesothelioma.
Choosing appropriate systemic therapies for pleural mesothelioma based on histologic subtype and genomic profiling.
Genetic mutations in family members of patients with germline BAP1 mutation should be monitored for the possibility of developing BAP1 cancer syndrome.
Our case focuses on the management of a patient with metastatic combined histology lung cancer, specifically featuring both adenocarcinoma and small cell lung cancer (SCLC). The primary objective is to provide insights into the nuanced diagnosis and treatment approaches required for managing lung cancer with combined histology.
Key Areas Addressed:
Diagnosis of Combined Histology Lung Cancer: The case highlights the challenges of accurately diagnosing de novo combined histology lung cancer, which includes both adenocarcinoma and small cell lung cancer (SCLC) components, using biopsies and molecular profiling.
Management of Combined Histology Lung Cancer: Emphasizes the need for a tailored treatment approach combining chemotherapy and targeted therapy, with adjustments based on disease progression and response.
Importance of Biomarker Testing: Highlights the crucial role of biomarker and molecular testing, including liquid biopsy when tissue is insufficient, to guide personalized treatment. Somatic mutations like EGFR p.L858R influence therapy choices and effectiveness.
Multidisciplinary and Palliative Care: Underlines the importance of a multidisciplinary approach and palliative care integration for advanced-stage lung cancer patients, focusing on symptom management, goals of care discussions, and improving quality of life through supportive care services.
This case focuses on the management of patients with extensive stage small cell lung cancer. Key areas addressed include:
Recognizing and effectively treating paraneoplastic syndromes.
Recognizing the potential benefit and long-term survival from the implementation of currently approved immune checkpoint inhibitors (ICIs) in the frontline setting of patients with extensive-stage SCLC.
Identifying and managing immune-related adverse events (irAEs) in patients undergoing ICI treatment.
Considerations for immunotherapy treatment duration in responders to ICIs.
This case focuses on:
1. Recognizing the management of solitary, symptomatic brain metastasis in NSCLC.
2. The role of NGS in the initial management of metastatic Stage IV NSCLC.
3. Recognizing the role of the patient’s perspective and values in guiding treatment considerations.
This case focuses on the management of locally advanced NSCLC. He presents clinically well, with few symptoms, and a good performance status (ECOG 1), with a diagnosis of stage IIIA lung adenocarcinoma (AJCC 8th edition). Several key points that are important include:
Molecular testing
Invasive mediastinal staging
Multidisciplinary discussion
Need for adaptation
Ongoing multidisciplinary review
Consideration of new data
The ADAURA study demonstrated significant benefits in progression-free survival and overall survival with three years of adjuvant osimertinib treatment.
Highlights from this case include:
1. This patient has had stable disease with maintenance chemotherapy for more than three years
2. Would you have referred the patient for radiotherapy or switched his systemic treatment upfront?
3. For Rad Oncs: What dose and technique would you have ordered to treat this oligoprogressive site of disease?
This case focuses on the treatment of locally advanced thymic epithelial tumors with emphasis on the appropriate sequencing of treatment options as backed up by international clinical practice guidelines tailored to the patient’s clinical presentation. The audience should have increased vigilance on presenting symptoms or have a high index of suspension to address emergent concerns.
The management of a rare and difficult tumour, a large cell neuroendocrine tumour of the lung with metastatic disease to the brain. The patient had a poor response to upfront chemotherapy with carboplatin and etoposide. With a high tumour mutation burden, access to immunotherapy with ipilimumab and nivolumab was granted. The patient had initial intracranial progression and was treated with SRS to the new cranial lesions.
The management of symptomatic brain metastases in lung cancer. Urgent neurosurgical intervention followed by cavity radiation and systemic therapy is generally recommended. On progression, small new cranial lesions were managed with SRS.
The management of multiple immune-related endocrinopathies, dermatitis and hepatitis experienced by the patient. Prompt steroid use and delay of immune checkpoint inhibitors should occur.
This case demonstrates a complete response to immunotherapy in patients with metastatic neuroendocrine tumour, typically a malignancy with a poor prognosis.
This case focuses on the management of progressive disease during durvalumab consolidation in unresectable, locally advanced NSCLC treated with curative intent.
Keypoints are:
Durvalumab is recommended after curative chemoradiation in unresectable, locally advanced NSCLC.
Suspected progression during durvalumab consolidation should be reviewed by a multidisciplinary team for further work-up and management.
Recommended evaluations include FDG-PET and brain MRI, with histological confirmation if needed.
Oligometastatic disease may be treated with locoregional therapy, while systemic treatment is recommended for metastatic disease.
Choosing the most appropriate treatment during durvalumab consolidation is challenging, as immune checkpoint inhibitors, alone or with platinum doublet chemotherapy, are the standard frontline approach in non-oncogene-addicted, advanced NSCLC.
Subsequent systemic treatment for metastatic disease should consider tumor biology (histology, molecular profile) and the patient’s clinical condition at progression.
Enrollment in a clinical trial should be considered.
This case focuses on the management of Checkpoint Inhibitor Pneumonitis (CIP) in patients with Non-Small Cell Lung Cancer (NSCLC) following neoadjuvant immunotherapy. The case aims to improve the learner’s ability to recognize, diagnose, and manage CIP, following evidence-based guidelines. Key areas addressed include:
Recognizing and Diagnosing CIP: Identifying symptoms and interpreting imaging findings to diagnose CIP in NSCLC patients after immunotherapy.
Performing Workup and Referrals: Conducting appropriate workup, including ordering high-resolution CT (HRCT) scans and lab tests.
Differentiating CIP from Other Pneumonitis Causes: Distinguishing CIP from other potential causes of pneumonitis in the clinical setting.
Monitoring and Evaluating Treatment Effectiveness: Assessing patient response to treatment through clinical improvement and imaging results.
This case focuses on the management of care for patients with advanced non-small cell lung cancer (NSCLC) with no molecular alterations and PD-L1 ≥50%. Key areas addressed:
Choosing between several first-line immunotherapy-based regimens currently approved in this setting.
Recognizing the need for validated biomarkers to prioritize the addition of chemotherapy to anti-PD-(L)1 immune checkpoint inhibitors (ICIs) in this setting.
Managing oligo-progression during ICI with a multidisciplinary approach after adequate diagnostic workup.
Choosing appropriate evidence-based strategies to treat oligo-progressive disease during first-line immunotherapy.
Local ablative therapy to the oligo-progressive sites on ICI therapy may extend the duration of benefit of the current systemic treatment.
Deciding the optimal duration of first-line ICI based on literature data.
This clinical case highlights the importance of recognizing histological transformation as a resistance mechanism to tyrosine kinase inhibitors (TKIs) in oncogene-addicted patients, especially those with ALK rearrangements. Along with liquid biopsy, re-biopsy at disease progression helps identify off-target mechanisms and detect histological changes. Transformation to small cell lung cancer (SCLC) is rare, and treatment strategies are not well defined, with these cancers often showing limited response to standard chemotherapy with platinum and etoposide. Some reports suggest sensitivity to third-generation ALK inhibitors, which have shown responses in certain cases, including ours. More data is needed to determine the best treatment strategy for these patients.
This case highlights the importance of a multidisciplinary approach to resectable lung cancer patients from the pulmonologist, pathologist, radiology, cardiothoracic (CT) surgery, and medical oncology. Furthermore, it highlights unique aspects of managing mixed histology NSCLC patients and treatment decisions to best manage the patient’s cancer, such as choosing a more histologic-agnostic systemic treatment plan. Lastly, it’s important to include biomarker testing for these patients, as targetable actionable mutations are still possible in these mixed histologies.
This case focuses on the management of advanced NSCLC in older patients with multiple comorbidities and relative contraindications to treatments. The main conclusion from this case is that with multidisciplinary decision-making and effective communication/collaboration between teams (thoracic oncology, hematology, geriatrics, palliative care, hepatology…), elderly patients with multiple comorbidities can benefit from innovative treatments such as immunotherapy and can have prolonged survival with a preserved quality of life. Key areas addressed:
Describing the recommended, evidence-based approaches to personalize immune checkpoint inhibitor (ICI) treatment for patients with advanced NSCLC and multiple comorbidities.
Diagnosing and managing immune-related adverse events ([irAEs]) in patients undergoing ICI treatment.
Managing pain and skeletal-related events in NSCLC patients.
This case focuses on the practical aspect of the presence of multiple complex health conditions in patients diagnosed with advanced NSCLC. We need to tailor our approach in managing these patients according to their health status so that we do no harm, like we avoided contrast Ct in this patient who already had CKD secondary to her existing medical condition. In addition to navigating the complexities in elderly with advanced NSCLC, we have to adapt our management approach according to local resources like we did a diffusion-weighted MRI of the body due to the unavailability of PET CT scan for metastatic workup and adopted low-dose immunotherapy to avoid financial toxicity.
Young adults with lung cancer often are found to be never or light smokers and subsequently also have biomarkers notable for actionable mutations such as EGFR, ALK, and ROS1. Early incorporation of palliative care in metastatic NSCLC patients can be helpful in controlling pain.
This case focuses on the management of care for patients with advanced non-small cell lung cancer (NSCLC) with no molecular alterations and PD-L1 ≥50%. Key areas addressed include:
Choosing between several first-line immunotherapy-based regimens currently approved in this setting.
Recognizing the need for validated biomarkers to prioritize the addition of chemotherapy to anti PD-(L)1 immune checkpoint inhibitors (ICIs) in this setting.
Managing oligo-progression during ICI with a multidisciplinary approach after adequate diagnostic workup.
Choosing appropriate evidence-based strategies to treat oligo-progressive disease during first-line immunotherapy.
Local ablative therapy to the oligo-progressive sites on ICI therapy may extend the duration of benefit of the current systemic treatment.
Deciding the optimal duration of first-line ICI based on literature data.
This case focuses on the management of patients with synchronous lung adenocarcinomas. Molecular testing is important to establish the relationship between the separate lung adenocarcinomas to determine if they represent metastatic disease or separate primaries.
