4 Options in Treating Mesothelioma

Introduction

Malignant mesothelioma is an infrequent yet formidable neoplasm, primarily associated with chronic inhalational or ingestive exposure to asbestos fibres. These silicate minerals, once widely utilised in industrial and construction settings, exhibit latency periods ranging from decades to over half a century, thereby complicating early detection and epidemiological assessments.

The pathogenesis of mesothelioma centres on chronic inflammation and subsequent oncogenic mutation within mesothelial cells lining the pleural, peritoneal, pericardial, or tunica vaginalis regions. Pleural mesothelioma, the most prevalent subtype, comprises over 80% of reported cases.

Clinical presentation is notoriously nonspecific, often mimicking benign respiratory or gastrointestinal ailments, which significantly impairs timely diagnosis and effective staging. Nevertheless, substantial advancements in multimodal oncology have diversified the treatment paradigm, improving patient stratification and outcomes.

This comprehensive review explores 10 primary modalities in mesothelioma treatment, presenting a critical synthesis of contemporary methodologies and investigational strategies. Each section reflects clinical consensus, augmented by empirical evidence and translational potential.

1. Surgical Resection in Mesothelioma Management

Surgical excision remains foundational in the management of early-stage mesothelioma, primarily employed with curative or cytoreductive intent. Surgical suitability is determined through a multidisciplinary evaluation encompassing disease staging, histological subtype, and the patient’s overall performance status.

Principal Surgical Techniques

• Pleurectomy/Decortication (P/D): Involves en bloc resection of the parietal and visceral pleura while preserving the ipsilateral lung. Preferable for patients with epithelioid histology who may not tolerate pneumonectomy.
• Extrapleural Pneumonectomy (EPP): A radical approach involving resection of the lung, pleura, pericardium, and diaphragm. Indicated for patients with localized disease and sufficient cardiopulmonary reserve.
• Cytoreductive Surgery with HIPEC (Hyperthermic Intraperitoneal Chemotherapy): Predominantly utilised for peritoneal mesothelioma, this procedure combines extensive tumour debulking with intraoperative chemotherapeutic lavage to enhance locoregional cytotoxicity.

Benefits and Constraints

• Reduces tumour burden and alleviates compressive symptoms.
• Associated with significant perioperative morbidity; thus, patient selection is critical.

Image Alt Text: Thoracic oncology team conducting extrapleural pneumonectomy under general anaesthesia

2. Chemotherapeutic Strategies

Systemic chemotherapy is integral in managing unresectable mesothelioma and is frequently utilised adjunctively with surgery or radiotherapy. The therapeutic response is influenced by tumour histology and individual tolerability.

First- and Second-Line Agents

• Pemetrexed and Cisplatin: Considered the first-line regimen based on landmark trials demonstrating improved survival.
• Carboplatin: Used in lieu of cisplatin for patients with renal impairment or intolerance.
• Gemcitabine and Vinorelbine: Administered as second-line or salvage therapy in refractory disease.

Delivery Modalities

• Intravenous Infusion (IV): Standard route of administration.
• HIPEC: Applied following surgical cytoreduction to increase peritoneal penetration.

Efficacy and Toxicology

• Effective for tumour reduction in neoadjuvant settings and eradication of microscopic disease in adjuvant protocols.
• Toxicities include myelosuppression, nephrotoxicity, and gastrointestinal disturbances, necessitating vigilant monitoring.

Internal Link: Chemotherapy Mechanisms and Evidence in Oncology Practice

Image Alt Text: Chemotherapy protocol initiated in clinical oncology infusion suite

3. Radiotherapeutic Interventions

Radiotherapy plays a crucial role in both curative and palliative mesothelioma treatment strategies. Technological advancements in radiation delivery have improved targeting while minimizing collateral tissue damage.

Radiotherapeutic Techniques

• External Beam Radiation Therapy (EBRT): Delivers conformal radiation using image-guided techniques to minimize toxicity.
• Intraoperative Radiation Therapy (IORT): Administered during surgery to target high-risk areas.

Clinical Indications

• Employed postoperatively to reduce local recurrence.
• Palliates symptoms such as chest pain and obstructive syndromes.

Adverse Events

• Side effects may include oesophagitis, radiation pneumonitis, and dermal reactions, all of which require preemptive management.

External Link: Cancer Research UK – Evidence-Based Guidelines on Radiotherapy

Image Alt Text: Precision-guided radiotherapy administered to thoracic mesothelioma patient

4. Immunotherapy

Immunotherapy has emerged as a transformative modality in mesothelioma care, capitalising on immune checkpoint inhibitors to reactivate host antitumour responses.

Immunotherapeutic Agents

• Nivolumab (Opdivo): Inhibits PD-1 to sustain T-cell activation.
• Ipilimumab (Yervoy): Targets CTLA-4 to augment T-cell priming.

Indications and Outcomes

• Approved for advanced and refractory mesothelioma across several healthcare systems.
• Clinical trials, including CheckMate 743, have demonstrated improved survival in non-epithelioid subtypes.

Immune-Related Toxicities

• Includes endocrinopathies, colitis, and dermatological manifestations; these may require immunosuppressive therapy.