Operable Early-stage Lung Cancer Research Articles

Proton and carbon ion radiotherapy for operable early-stage lung cancer; a prospective nationwide registry

Background and purposeTo investigate the toxicity and survival outcomes of proton and carbon ion radiotherapy for patients with operable early-stage lung cancer who are eligible for lobectomy. Materials and methodsThis multicenter nationwide prospective cohort study included patients with operable early-stage lung cancer. Proton and carbon ion radiotherapy was performed according to the schedule stipulated in the unified treatment policy. Progression-free survival (PFS), overall survival (OS) and treatment-related toxicities were evaluated. ResultsA total of 274 patients were enrolled and included in efficacy and safety analyses. The most common tumor type was adenocarcinoma (44 %), while 105 cases (38 %) were not histologically confirmed or diagnosed clinically. Overall, 250 (91 %) of the 274 patients had tumors that were peripherally situated, while 138 (50 %) and 136 (50 %) patients were treated by proton and carbon ion radiotherapy, respectively. The median follow-up time for all censored patients was 42.8 months (IQR 36.7–49.0). Grade 3 or severe treatment-related toxicity was observed in 4 cases (1.5 %). Three-year PFS was 80.5 % (95 % CI: 75.7 %–85.5 %) and OS was 92.5 % (95 % CI: 89.3 %–95.8 %). Pathological confirmation and clinical stage were factors significantly associated with PFS, while tumor location and particle-ion type were not. Meanwhile, clinical stage was significantly associated with OS, but pathological confirmation, tumor location, and particle-ion type were not. ConclusionsParticle therapy for operable early-stage lung cancer resulted in excellent 3-year OS and PFS in each subset. In this disease context, proton and carbon ion beam therapies are feasible alternatives to curative surgery.

Proton and Carbon Ion Radiotherapy for Operable Early-Stage Lung Cancer: 3-Year Results of a Prospective Nationwide Registry

The purpose of this analysis was to report subset analysis as to progression-free survival (PFS) and overall survival (OS) of particle-beam radiation therapy for operable early-stage lung cancer. Patients of early-stage lung cancer (T1-T2aN0) who were eligible for radical surgery but did not wish to undergo surgery were treated by proton-ion (PT) or carbon-ion (CT) radiation therapy and enrolled in Japanese prospective registry. In this analysis, PFS and OS by clinical stage, tumor location, pathological confirmation and particle-ion type were evaluated. A total of 274 patients were enrolled and included in efficacy and safety analyses. Most tumors were adenocarcinoma (44%), and 105 (38%) were not histologically confirmed and diagnosed clinically. 250 (91%) of 274 patients had tumors that were peripherally situated. 138 (50%) and 136 (50%) patients were treated by PT and CT, respectively. The median follow-up time for all censored patients was 42.8 months (IQR 36.7 - 49.0). No grade 3 or severe treatment-related toxicity was observed. 3-year PFS was 81% (95% CI;76-86) and OS was 93% (95% CI;89-96), respectively. As to particle-ion type, 3-year PFS were 79.0% and 81.9% in PT and CT (p = 0.19), and 3-year OS were 93.9% and 91.1% in PT and CT (P = 0.72), respectively. For PFS, pathological confirmation, clinical stage was significant factors but there were no significant differences by tumor location or particle-ion type; for OS, clinical stage was significant factor but there was no significant difference on pathological confirmation, tumor location or particle-ion type (Table1). Table 1. 3-year PFS and OS CONCLUSION: Particle therapy for operable early-stage lung cancer resulted in excellent 3-year OS and PFS on each subset.

Prognosis Analysis of Early-stage Non-small Cell Lung Cancer Patients Treated with Stereotactic Body Radiotherapy

With the aging of the population and the increased importance of lung cancer screening, the number of early-stage lung cancer patients has been on the rise in recent years, which can be classified into operable early-stage lung cancer and inoperable early-stage lung cancer. The most common pathological type is non-small cell lung cancer (NSCLC). Stereotactic body radiation therapy (SBRT) is the optimal treatment for inoperable early-stage NSCLC. The aim of this study was to investigate the prognosis of early-stage NSCLC patients treated with SBRT and its influencing factors in order to reduce the side effects of radiotherapy and improve the survival and quality of life. Clinical data and follow-up outcomes of early-stage NSCLC patients treated with SBRT in our hospital from August 2010 to August 2020 were collected. Kaplan-Meier method was used to assess the prognosis, and the Cox proportional risk model was used for multivariate prognostic analysis. A total of 165 patients were included with a median follow-up time of 43.2 (range: 4.8-132.1) mon. The local control (LC) rates at 1-yr, 2-yr and 5-yr were 98.1%, 94.8% and 86.5% respectively. Karnofsky performance status (KPS) score greater than 80 was an independent prognostic factor for LC (P=0.02). The overall survival (OS) rates at 1-yr, 2-yr and 5-yr were 97.6%, 93.0% and 68.9% respectively. A biological equivalent dose when α/β=10 (BED10) greater than 132 Gy was an independent prognostic factor for OS (P=0.04). Progression-free survival (PFS) rates at 1-yr, 2-yr and 5-yr were 93.3%, 79.5% and 55.3% respectively. The distance metastasis free survival (DMFS) rates at 1-yr, 2-yr and 5-yr were 94.5%, 83.2% and 58.4% respectively. BED10 greater than 150 Gy was an independent prognostic factor for DMFS (P=0.02). The regional control (RC) rates at 1-yr, 2-yr and 5-yr were 98.8%, 95.4% and 87.9% respectively. SBRT is effective in treating early-stage NSCLC. KPS greater than 80 is an independent prognostic factor for LC; BED10 greater than 132 Gy is an independent prognostic factor for OS; BED10 greater than 150 Gy is an independent prognostic factor for DMFS.

Modeling the COVID Pandemic: Do Delays in Surgery Justify Using Stereotactic Radiation to Treat Low-Risk Early Stage Non–Small Cell Lung Cancer?

IntroductionIt was suggested that stereotactic radiation (SBRT) is an “alternative if no surgical capacity is available” for non–small cell lung cancer (NSCLC) care during the COVID-19 pandemic. The purpose of this study was to compare the oncologic outcomes of delayed surgical resection and early SBRT among operable patients with early stage lung cancer. MethodsThe National Cancer Database was queried for patients with cT1aN0M0 NSCLC who underwent surgery or SBRT (2010-2016) with no comorbidity. Patients with any comorbidities or age >80 were excluded. The outcome of interest was overall survival. Delays in surgical care were modeled using different times from diagnosis to surgery. A 1:1 propensity match was performed and survival was analyzed using multivariable Cox regression. ResultsOf 6720 healthy cT1aN0M0 NSCLC patients, 6008 (89.4%) received surgery and 712 (10.6%) received SBRT. Among surgery patients, time to surgery >30 d was associated with inferior survival (HR > 1.4, P ≤ 0.013) compared with patients receiving surgery ≤14 d. Relative to SBRT, surgery demonstrated superior survival at all time points evaluated: 0-30 d, 31-60 d, 61-90 d, and >90 d (all P < 0.001). Among a propensity-matched cohort of 256 pairs of patients, delayed surgery (>90 d) remained association with better overall survival relative to early SBRT (5-year survival 76.9% versus 32.3%, HR = 0.266, P < 0.001). ConclusionsAlthough longer time to surgery is associated with inferior survival among surgery patients, delayed surgery is superior to early SBRT. Surgical resection should remain the standard of care to treat operable early stage lung cancer despite delays imposed by the COVID-19 pandemic.

Stereotactic ablative radiation therapy for operable early-stage lung cancer—considerations and controversies

Stereotactic ablative radiation therapy (SABR) is the current standard of care for patients with stage I non-small cell lung cancer (NSCLC) who are not fit for surgery or who refuse an operation. The available evidence suggests that SABR is effective in obtaining durable local control in operable patients as well, but whether it can currently be recommended as an alternative to surgery in this population is contentious because of the absence of high quality long-term prospective randomized survival data. Retrospective comparisons of SABR with surgery are available, but have been subject to bias from the confounding effect of operability. Previous attempts to prospectively compare SABR with surgery in a randomized fashion have been unsuccessful due to poor accrual. From these efforts, the randomized data from two of these prematurely closed trials were combined to explore the potential outcome if they had completed accrual, though the analyses were largely dismissed by the academic community. In this review, we give a critical overview of the available data in this context, and address key areas of controversy which include the questioned importance of pathologic staging of the mediastinum, the appropriate thresholds for empiric treatment of suspicious lung nodules without biopsy confirmation, and the challenges of post-treatment surveillance of the irradiated lung. We also address design considerations aimed at maximising enrolment into ongoing prospective phase III trials of SABR versus surgery.

Postoperative Imaging and Complications in Resection of Lung Cancer

Surgical resection offers the best hope of cure for patients with operable early-stage lung cancer. Wedge resection, segmentectomy, lobectomy, or pneumonectomy may be performed depending on the size and location of the tumor. Radiologists must be familiar with the types of surgical resection utilized in the treatment of lung carcinoma and with their normal and abnormal postsurgical appearance on imaging studies. Prompt identification of postoperative complications on imaging is essential to appropriate patient management and helps to determine when additional intervention is warranted.

Triaging early-stage lung cancer patients into non-surgical pathways: who, when, and what?

More lung cancer patients are being diagnosed at an earlier stage due to improved diagnostic imaging techniques, a trend that is expected to accelerate with the dissemination of lung cancer screening. Surgical resection has always been considered the standard treatment for patients with early-stage non-small cell lung cancer (NSCLC). However, non-surgical treatment options for patients with early-stage NSCLC have evolved significantly over the past decade with many new and exciting alternative treatments now available. These alternative treatments include radiofrequency ablation (RFA), microwave ablation (MWA), percutaneous cryoablation therapy (PCT), photodynamic therapy (PDT) and external beam radiation therapy (EBRT), including stereotactic body radiation therapy (SBRT) and accelerated hypofractionated radiation therapy. We describe the established alternatives to surgical resection, their advantages and disadvantages, potential complications and efficacy. We then describe the optimal treatment approach for patients with early-stage NSCLC based on tumor operability, size and location. Finally, we discuss future directions and whether any alternative therapies will challenge surgical resection as the treatment of choice for patients with operable early-stage lung cancer.

Video-assisted thoracic surgery for lung cancer: republication of a systematic review and a proposal by the guidelines committee of the Japanese Association for Chest Surgery 2014.

Patients with early-stage non-small cell lung cancer (NSCLC) are candidates for surgical intervention with curative intent. For these early-stage lung cancer surgeries, video-assisted thoracic surgery (VATS) is considered. The purpose of this article is to propose a recommendation for this according to the evidence and provide information for patients with operable early-stage lung cancer from the Japanese Association for Chest Surgery. The clinical question here is whether VATS lobectomy is recommended for patients with clinical stage I NSCLC. The Japanese Association for Chest Surgery guidelines committee reviewed and summarized the available literature and assessed the quality of the evidence. The available literature on VATS was examined using references from MEDLINE. The recommendations were provided according to the Medical Information Network Distribution Service in Japan (Minds). VATS lobectomy may be considered and applied to patients with clinical stage I NSCLC; however, well-established evidence is lacking. VATS showed better or at least equivalent outcomes regarding intra- or postoperative complications compared with thoracotomy, with less invasiveness. Additionally, long-term survival by VATS lobectomy was suggested to be at least equivalent, although there is a lack of evidence. VATS lobectomy by an experienced surgeon is associated with minimal invasiveness and an outcome equivalent to that of open lobectomy in stage I NSCLC. (Recommendation grade: Level C1).

SBRT in operable early stage lung cancer patients.

Since decades the gold standard for treatment of early stage non-small cell lung cancer (NSCLC) is surgical lobectomy plus mediastinal lymph node dissection. Patients in worse health status are treated with sublobar resection or radiation treatment. With development of stereotactic-body-radiotherapy (SBRT), outcome of patients treated with radiation was substantially improved. Comparison of SBRT and surgical techniques is difficult due to the lack of randomized trials. However, all available evidence in form of case control studies of population based studies show equivalence between sublobar resection and SBRT indicating that SBRT-when performed by a trained and experienced team-should be offered to all high-risk surgical patients. For patients not willing to take the risk of lobectomy and therefore refusing surgery, SBRT is an excellent treatment option.

RTOG 0618: Stereotactic body radiation therapy (SBRT) to treat operable early-stage lung cancer patients.

7523 Background: The Radiation Therapy Oncology Group (RTOG) protocol 0618 was a phase II trial utilizing SBRT to treat early stage non-small cell lung cancer in operable patients (pts). Methods: All pts were deemed operable by a thoracic surgeon utilizing specific criteria. Pts with biopsy proven peripheral T1-T3, N0, M0 tumors were eligible. The prescription dose was 18 Gy X 3 fractions delivered in 1½-2 weeks. The primary endpoint was 2-year primary tumor control (PTC, avoidance of in-field (INF) and marginal failure (MF)) with overall and progression free survival (OS, PFS), adverse events (AE), local (LF), regional (RF), and distant failure (DF) as secondary endpoints. Early surgical salvage was directed as part of protocol design in the event of LF after SBRT. Results: The study opened December 2007 and closed May 2010 after accruing a total of 33 pts. Of 26 evaluable pts, 23 had T1, and 3 had T2 tumors. Median age was 72 years. Median FEV1, DLCO at enrollment were 72%, 68% predicted, respectively. 4 pts (16%) had SBRT related grade 3 AEs while 0 had grade 4-5 AEs. Median follow-up was 25 months. 2 pts have been scored with INF (11.7 and 12.4 months post SBRT) and 1 with MF (32.5 months post SBRT) giving an estimated 2-year primary tumor failure rate of 7.7% (95% CI: 0.0%, 18.1%). 2-year estimates of LF (primary tumor plus involved lobe failure), RF, and DF are 19.2% (95% CI: 3.7%, 34.7%), 11.7% (95% CI: 0.0%, 24.5%), and 15.4% (95% CI: 1.2%, 29.6%), respectively. Only one patient was eligible for attempted surgical salvage and underwent lobectomy 1.2 years post SBRT complicated by a grade 4 cardiac arrhythmia. 2-year estimates of PFS and OS are 65.4% (95% CI: 44.0%, 80.3%) and 84.4% (95% CI: 63.7%, 93.9%), respectively. Conclusions: SBRT given appears to be associated with a high rate of PTC, moderate treatment related morbidity, and infrequent need for surgical salvage in operable early stage lung cancer pts with peripheral lesions. These results support ongoing enrollment into the ACOSOG Z4099-RTOG 1021 trial comparing SBRT to sublobar resection in high risk operable pts. The project was supported by RTOG grant U10 CA21661, CCOP grant U10 CA37422, and ATC U24 CA81647 from the National Cancer Institute. Clinical trial information: NCT00551369.