The Lancet | Chinese Medical Team: A New Breakthrough in the Treatment of Limited-stage Small Cell Lung Cancer!

High-dose Accelerated Hyperfractionated Radiotherapy Helps Improve Treatment Efficacy

Lung Cancer

Small-cell lung cancer (SCLC) is a highly aggressive malignancy, accounting for 15% of all lung cancer cases. Among these, one-third are diagnosed with limited-stage SCLC (LS-SCLC), where the disease is confined to one side of the chest. For the past two decades, the standard treatment for LS-SCLC has been concurrent chemoradiotherapy, yet patients have seen little improvement in survival outcomes, with median survival ranging from 25-30 months.

A recent study led by a team of Chinese researchers has shed light on a new treatment strategy. Published in The Lancet Respiratory Medicine, this multicenter, open-label, randomized phase III trial demonstrated that a high-dose, accelerated, hyperfractionated thoracic radiotherapy (54 Gy/30 fractions) combined with chemotherapy significantly improves overall survival (OS) and progression-free survival (PFS) for LS-SCLC patients. Importantly, this breakthrough treatment does not increase toxicity compared to the standard 45 Gy/30 fractions regimen.

The trial, conducted between 2017 and 2021, enrolled 224 patients across 16 hospitals in China. The patients, aged 18-70, had histologically or cytologically confirmed LS-SCLC and had either not yet received treatment or had undergone 1-2 cycles of chemotherapy. After chemotherapy, they were randomly assigned to receive either the high-dose (54 Gy/30 fractions) or standard-dose (45 Gy/30 fractions) thoracic radiotherapy, delivered twice daily over three weeks. Both groups also underwent four cycles of chemotherapy and, if responsive, prophylactic cranial irradiation (PCI) to prevent metastasis.

The study’s results were groundbreaking. Patients in the high-dose group showed a remarkable improvement in OS, with a median survival of 60.7 months, compared to 39.5 months in the standard-dose group. Additionally, the high-dose group saw a 45% reduction in the risk of death. Two-year survival rates also favored the high-dose group, with 76% of patients alive at two years, compared to 54% in the standard-dose group.

Progression-free survival was similarly improved, with the high-dose group experiencing a median PFS of 30.5 months, significantly longer than the 16.7 months observed in the standard-dose group. This translates to a 30% reduction in the risk of disease progression or death.

Despite the higher radiotherapy dose, the incidence of adverse effects between the two groups was comparable. The most common severe side effects were neutropenia, thrombocytopenia, and anemia, which occurred at similar rates in both groups. The occurrence of acute radiation-induced toxicity, such as esophagitis and radiation pneumonitis, also showed no significant differences. Importantly, there were no cases of severe late-stage toxicity, such as grade 3 esophageal stenosis or pulmonary fibrosis.

This study demonstrates that high-dose, accelerated hyperfractionated thoracic radiotherapy can significantly improve the prognosis of LS-SCLC patients without increasing treatment toxicity. It provides a new first-line treatment option that offers hope for longer survival. These findings may shift the clinical landscape, offering a viable alternative to the current standard of care.

A groundbreaking study led by a Chinese medical team has demonstrated that high-dose accelerated hyperfractionated chest radiotherapy (54 Gy/30 fractions) combined with chemotherapy significantly improves the overall survival (OS) of patients with limited-stage small-cell lung cancer (LS-SCLC). The research was published in The Lancet Respiratory Medicine on August 12, 2024. Compared to the standard dose of 45 Gy/30 fractions, the 54 Gy regimen increased OS without raising treatment toxicity, marking a potential shift in LS-SCLC treatment strategy.

LS-SCLC, a highly aggressive form of lung cancer, affects around 15% of all lung cancer patients, with one-third of them diagnosed at a limited stage. Traditionally, concurrent chemoradiotherapy (CRT) has been the preferred treatment option for LS-SCLC, yet the median survival rate has remained stagnant at around 25-30 months over the past two decades. The new study, however, highlights the efficacy of using higher doses of radiation to improve outcomes.

This phase III clinical trial was conducted across 16 hospitals in China between June 2017 and April 2021, involving 224 LS-SCLC patients. The trial compared two groups: a high-dose radiotherapy group (54 Gy/30 fractions twice daily) and a standard-dose group (45 Gy/30 fractions twice daily). Patients were treated with four cycles of chemotherapy and monitored through regular follow-ups. The results were remarkable.

Overall Survival: The high-dose group had a significantly extended median OS of 60.7 months compared to 39.5 months in the standard-dose group, reducing the risk of death by 45%.

Progression-Free Survival (PFS): The median PFS was also improved in the high-dose group, standing at 30.5 months compared to 16.7 months in the standard-dose group, with a 30% reduction in the risk of disease progression or death.

Safety: Despite the higher radiation dose, there was no increase in severe treatment-related side effects, such as neutropenia, thrombocytopenia, or radiation-induced pneumonia. Both groups exhibited similar rates of acute and long-term radiation toxicity.

The study’s findings suggest that 54 Gy/30 fractions, delivered twice daily, may become a new standard of care for LS-SCLC patients. This approach significantly extends survival while maintaining a similar safety profile to the current standard dose. Moreover, with a two-year OS rate of 76% in the high-dose group, compared to 54% in the standard-dose group, the potential for long-term remission appears much greater.

While the current trial focused on radiotherapy and chemotherapy alone, future studies could explore combining this high-dose radiotherapy with immunotherapy. Recent breakthroughs, such as the ADRIATIC trial, have shown that immunotherapy following CRT can further improve survival outcomes for LS-SCLC patients. However, the safety of combining high-dose radiotherapy with immunotherapy needs further investigation due to potential risks like radiation-induced pneumonitis.

In conclusion, this study has paved the way for a new treatment option in LS-SCLC, offering hope for improved survival rates without additional toxicity. It marks a significant milestone in the battle against this aggressive form of lung cancer, providing a valuable alternative to the long-standing standard treatments.