GR 03.05 Any Roles of Systemic Therapy (Chemotherapy, Targeted Therapy, Immunotherapy) for Early Stage NSCLC with Limited Pulmonary Reserve?

Abstract

The standard treatment of early stage non-small cell lung cancer (NSCLC) is lobectomy with systematic mediastinal lymph node evaluation. Unfortunately, up to 25% of patients with stage I NSCLC are not lobectomy candidates because of severe medical comorbidity including limited pulmonary reserve. During the past decade, stereotactic ablative radiotherapy (SABR) has resulted in local control in excess of 90% of tumors with medically inoperable and operable clinical stage I NSCLC. The local treatment including surgery and SABR is the stand of care for these patients. No definite evidence-based medicine data about the systemic therapy had been reported in this subgroup patients. A systemic therapy approach to the treatment of patients with medically inoperable, early stage NSCLC is not warranted. The management suggestions were unanimously agreed upon based on available literature. Systemic Therapy combined with local treatment could be a good option for these patients. 1. Chemotherapy+ local treatment: It seems that it is not recommended to add chemotherapy to local treatment for those medically inoperable, early stage NSCLC. It is reported that no evidence of an improvement in event-free survival was seen with the addition of weekly gemcitabine at this dose for patients with early stage NSCLC unfit for surgery, although the power of the study was low. 2. Targeted Therapy+ local treatment: No clear data about the targeted therapy for those medically inoperable, early stage NSCLC patients. For those driven gene positive patients, targeted therapy combined with local treatment seems to be a good choice. Some people worried about the combined therapy may increase the potential for pulmonary toxicity in patients with baseline pulmonary dysfunction, however, there is no cases of interstitial lung disease in early stage NSCLC as adjuvant therapy in 2017 ASCO (CTONG 1104). Further studies should be developed for these patients. 3. Immunotherapy + local treatment: The integration of radiation with immunotherapy is a conceptually promising strategy, as radiation has potent immune-modulatory effects and may contribute not only to local control but also augment systemic antitumor immune response. The advent of novel immunotherapy agents affords patients and clinicians therapeutic modalities to improve patient longevity and avenues to study innovative combinations of therapies. Preclinical data and case reports suggest the potential for robust clinical responses in metastatic NSCLC patients using this strategy, but prospective clinical trials evaluating the integration of radiation and immunotherapy are limited. The use of immunotherapy in non-metastatic settings is also intriguing but understudied. Summary: The assessment of treatment options for limited pulmonary reserve patients that requires uniform reporting of comorbidities and outcomes in clinical studies, which often is lacking. Systemic Therapy combined with local treatment could be a good option for these patients. Trials involving systemic therapy for patients with medically inoperable NSCLC should be developed.