Early-stage Peripheral Lung Cancer Research Articles

Non-invasive diagnosis of pulmonary nodules by circulating tumor DNA methylation: A prospective multicenter study

BackgroundWith the popularization of computed tomography, more and more pulmonary nodules (PNs) are being detected. Risk stratification of PNs is essential for detecting early-stage lung cancer while minimizing the overdiagnosis of benign nodules. This study aimed to develop a circulating tumor DNA (ctDNA) methylation-based, non-invasive model for the risk stratification of PNs. MethodsA blood-based assay (“LUNG-TRAC”) was designed to include novel lung cancer ctDNA methylation markers identified from in-house reduced representative bisulfite sequencing data and known markers from the literature. A stratification model was trained based on 183 ctDNA samples derived from patients with benign or malignant PNs and validated in 62 patients. LUNG-TRAC was further single-blindly tested in a single- and multi-center cohort. ResultsThe LUNG-TRAC model achieved an area under the curve (AUC) of 0.810 (sensitivity = 74.4 % and specificity = 73.7 %) in the validation set. Two test sets were used to evaluate the performance of LUNG-TRAC, with an AUC of 0.815 in the single-center test (N = 61; sensitivity = 67.5 % and specificity = 76.2 %) and 0.761 in the multi-center test (N = 95; sensitivity = 50.7 % and specificity = 80.8 %). The clinical utility of LUNG-TRAC was further assessed by comparing it to two established risk stratification models: the Mayo Clinic and Veteran Administration models. It outperformed both in the validation and the single-center test sets. ConclusionThe LUNG-TRAC model demonstrated accuracy and consistency in stratifying PNs for the risk of malignancy, suggesting its utility as a non-invasive diagnostic aid for early-stage peripheral lung cancer. Clinical trial registrationwww.clinicaltrials.gov (NCT03989219).

Bronchoscopic treatment of early-stage peripheral lung cancer.

This review article focuses on bronchoscopic treatment of early-stage peripheral lung cancer. Bronchoscopic treatment modalities have garnered considerable attention for early-stage lung cancer. Studies using photodynamic therapy, thermal vapor ablation, laser ablation, cryoablation, and intra-tumoral injection have recently been published. However, the evidence supporting these approaches largely derives from single-arm studies with small sample sizes. Based on the IDEAL-D framework, no technology has progressed passed the idea phase (1). The main weakness of these technologies to date is lack of evidence suggesting they can achieve local control. Presently, no bronchoscopic intervention for lung cancer has sufficient data to warrant its use as part of the standard of care. Despite notable progress, current technologies remain suboptimal, and there is insufficient evidence to support their use outside of a research setting.

Segmentectomy for patients with early-stage pure-solid non-small cell lung cancer.

For decades, lobectomy has been the recommended surgical procedure for non-small cell lung cancer (NSCLC), including for small-sized lesions. However, two recent pivotal clinical trials conducted by the Japanese Clinical Oncology Group/West Japan Oncology Group (JCOG0802/WJOG4607L) and the Cancer and Leukemia Group B (CALGB140503), which compared the survival outcomes between lobectomy and sublobar resection (the JCOG0802/WJOG4607L included only segmentectomy, not wedge resection), demonstrated the efficacy of sublobar resection in patients with early-stage peripheral lung cancer measuring ≤ 2 cm. The JCOG0802/WJOG4607L demonstrated the superiority of segmentectomy over lobectomy with respect to overall survival, implying the survival benefit conferred by preservation of the lung parenchyma. Subsequently, the JCOG1211 also demonstrated the efficacy of segmentectomy, even for NSCLC, measuring up to 3 cm with the predominant ground-glass opacity phenotype. Segmentectomy has become the standard of care for early-stage NSCLC and its indications are expected to be further expanded to include solid lung cancers > 2 cm. However, local control is still a major concern for segmentectomy for higher-grade malignant tumors. Thus, the indications of segmentectomy, especially for patients with radiologically pure-solid NSCLC, remain controversial due to the aggressive nature of the malignancy. In this study, we reviewed previous studies and discussed the efficacy of segmentectomy for patients with such tumors.

Research Progress in the Effect of Consolidation Tumor Ratio on the Diagnosis and Treatment of Early-stage Peripheral Lung Cancer

Consolidation tumor ratio (CTR) is a hot issue in lung cancer imaging studies in recent years. It is defined as the proportion of the maximum consolidation diameter divided by the maximum tumor diameter in the lung window scanned by high resolution computed tomography (HRCT). Many studies have also confirmed that it can be used as an indicator to identify whether a lung tumor is benign or malignant at the early stage, the main basis on which to decide whether sublobectomy can be performed, and is an independent factor for the recurrence and prognosis of early-stage lung cancer. Especially after tumor size and CTR results of JCOG0804 and JCOG0802 trials in Japan were published, a breakthrough in the treatment method upends the conventional surgical approach, which benefits patients with early-stage lung cancer. But insufficient research data on CTR leads to the fact that an evaluation system to measure CTR is yet to be built. This paper discusses the research progress in CTR prediction of benign or malignancy of pulmonary nodules, how to choose a surgical approach, lymph node dissection, spread through air spaces (STAS) and other hot issues. It also investigates the possible indicators to predict efficacy based on CTR, summarizes and analyzes the development trend of surgical methods to treat early-stage peripheral lung cancer and challenges, to provide new ideas for clinical application. .

Liquid Biopsy — A Novel Diagnostic Tool for Management of Early-Stage Peripheral Lung Cancer

Abstract Lung cancer is the leading cause of cancer-related mortality worldwide. Early diagnosis of lung cancer is hampered by the absence of specific symptoms and the lack of a widely recognised cost-effective screening programme. Acquisition of a tumour tissue sample for morphological and molecular genetic examination is of paramount importance for cancer diagnosis. We describe diagnostic challenges for early-stage lung cancer and their possible current solutions. Liquid biopsy is a relatively new technology that was developed for evaluation of tumour-related circulating genetic material. Recent achievements in data processing provide more opportunities for wider implementation of Next Generation Sequencing (NGS) in clinical practice. This article summarises available data on the current and future role of liquid biopsy in the management of lung cancer. We also present an ongoing Latvian lung cancer study that focuses on integration of liquid biopsy with comprehensive clinical data utilising advantages of information technologies.

Ten-Year Experience in Implementing Single-Fraction Lung SBRT for Medically Inoperable Early Stage Lung Cancer

PURPOSE To review ten years of employing single-fraction lung SBRT (SF-SBRT) for medically inoperable peripheral early stage lung cancer. METHODS An IRB-approved prospective lung SBRT data registry was surveyed until the end of December 2019 for all patients receiving SF-SBRT with minimum 6-month follow up. Doses employed were either 34 Gy or 30 Gy. Outcomes of interest included rates of local failure (LF) and overall survival (OS), as well as treatment-related toxicity graded per CTCAE version 3.0. RESULTS 229 patients met study criteria. Patient characteristics included: female (55%); median age 74.6 years (range 47-94); median KPS 80 (range 50-100). Tumor characteristics included: median diameter 1.6 cm (range 0.7-4.1); median PET SUVmax 6.1 (range 0.8-24.3); 63.6% of patients biopsied. SF-SBRT dose was 34 Gy in 72.1% cases and 30 Gy in 27.9%, with patient and tumor characteristics balanced between cohorts. Overall median follow up times for 30 Gy and 34 Gy were 36.7 and 17.2 months, respectively (p <0.0001). At analysis, 55.9% patients were alive. Two (0.9%) patients developed grade 3 toxicities and none grade 4/5 toxicities. Grades 1-2 pneumonitis and chest wall toxicity were seen in 7% and 12.7% patients, respectively. Median overall survival was 44.1 months. Rates (in %) of 2-year local, nodal and distant failure were 7.3, 9.4 and 12.2, respectively. There were no significant differences in outcomes by dose. CONCLUSIONS This is the largest institutional series to date reporting on SF-SBRT outcomes for medically inoperable peripheral early stage lung cancer and the first to report on a decade's experience in implementing this schedule. Outcomes from this analysis are comparable to published results from two randomized trials and validate the utilization of this schedule in routine practice. In the absence of phase III trials, this study should encourage increased utilization of SF-SBRT for inoperable tumors.

Can Dosimetry Affect Overall Survival in Patients with Medically Inoperable Peripheral Early Stage Lung Cancer Treated with Stereotactic Ablative Radiotherapy (SABR)? An Analysis of 1300 Patients

SABR is an established treatment option for early stage medically inoperable peripheral lung cancer. Recent studies have shown that tight conformity of radiotherapy plans i.e., reducing the radiation dose outside the target volume might worsen loco-regional control and can predict more distant metastases. The aim of the study is to report overall survival and dosimetry of early stage peripheral lung cancer patients treated with SABR and to try to explore if any dosimetric parameters can predict overall survival. Patients treated with SABR in a single institute in UK between May 2009 and August 2018 were included. Electronic medical records were reviewed for baseline characteristics, treatment details and outcomes. Dosimetric data was extracted from software. For the planning target volume (PTV), plan conformity was assessed using three indices, i.e., R100-volume receiving the 100% dose /volume (PTV), R50- volume receiving the 50% dose/volume (PTV), and maximum dose to >2 cm of PTV(D2cm). Patients were treated according to the UK SABR consortium guidelines. Kaplan Meier survival analysis was done for univariate analysis and Cox regression model was used for multivariate analysis, using IBM software. 1300 patients received SABR treatment for 1357 tumors. Median age of the patients were 75 years (range 38-97 years). Median follow up was 26 months. Median overall survival was 37 months with 1,2,3,4 and 5 years survival rates of 84.4%, 65%, 50.7%, 39.5% and 30.8%, respectively. Median PTV volume was 30 cc ((range 5.5-213.4 cc, Inter quartile range (IQR)-29.6). Median values of R100, R50 and D2cm were 1.1(range 0.68-3.19, IQR-0.08), 5.6(range 2.2-16.2, IQR- 2.08), 32.7Gy (range 9.3-56.3Gy, IQR-5.9Gy). Median value of mean lung dose, V20 and V12.5 were 3.9Gy (range 0.6-11.5Gy, IQR-2Gy), 5 %( range 0.2-19.3%, IQR-3.4%) and 9.3% (range 1.4-30.8%, IQR-5.4%). On univariate analysis, only R100 of ≤ 1.10 was found to be significantly associated with improved survival (median survival 40 months vs 33 months, hazard ratio 0.85, 95% confidence interval 0.73-0.98) which was also confirmed in multivariate cox regression analysis. Although treatments with R50 of ≤ 6 have shown to have better survival (38 months vs 35 months) but that was not significant in univariate or multivariate analysis. A more conformal plan with high dose matching to the PTV with R100 of < 1.10 is associated with improved survival in medically inoperable early stage lung cancer patients treated with SABR, which emphasizes the importance of plan conformity. However, this data needs to be interpreted cautiously taking into account other possible confounding variables, particularly higher dose to heart +/- lung with less conformal SABR plans.

ENB Guided MWA for Early-stage Peripheral Lung Cancer

ENB Guided MWA for Early-stage Peripheral Lung Cancer

Evaluation of Novel Imaging Devices for Nanoparticle-Mediated Fluorescence-Guided Lung Tumor Therapy

Nonsurgical and minimally invasive approaches for early-stage peripheral lung cancer are needed to avoid the known morbidity of surgical resection, particularly in high-risk patients. We previously demonstrated the utility of multifunctional porphyrin-phospholipid nanoparticles (porphysomes) for fluorescence imaging and phototherapy after preferential accumulation into tumors. The objective of this study was to demonstrate the feasibility ofporphysome-mediated imaging and photothermal therapy using a newly developed fiberscope and thoracoscope. To prepare this technology for clinical translation, we developed a porphysome-specific fiberscope (scanning fiber endoscope and porphysome-specific thoracoscope), both capable of detecting porphysome fluorescence, for image-guided transbronchial and transpleural photothermal therapy to treat endobronchial/peribronchial and subpleural tumors, respectively. These were tested in three animal models: human lung cancer xenografts (A549) in mice, orthotopic VX2 lung tumors in rabbits, and exvivo pig lung into which A549 tumor tissue was transplanted. The scanning fiber endoscope, with a 1.2-mm diameter, is small enough to pass through the working channel of a conventional bronchoscope and could visualize porphysome-laden tumors located inside or close to the peripheral bronchial wall. The porphysome-specific thoracoscope system had high sensitivity for porphysome fluorescence and enabled image-guided thoracoscopic resection of porphysome-accumulating tumors close to the pleura. Porphysomes also enhanced the efficacy of scanning fiber endoscope-guided transbronchial photothermal therapy and porphysome-specific thoracoscope-guided transpleural photothermal therapy, resulting in selective and efficient tumor tissue ablation in the rabbit and pig models. These results support the potential for clinical translation of this novel platform to affect nonsurgical and minimally invasive treatment options for early-stage peripheral lung cancer.

Prediction of early mortality following stereotactic body radiotherapy for peripheral early-stage lung cancer

Background/Purpose: To investigate prognostic factors for death within 6 months of stereotactic body radiotherapy (SBRT) for patients with peripheral early-stage non-small cell lung cancer (NSCLC).Materials and Methods: This analysis included 586 NSCLC patients with peripheral tumors treated with SBRT. Potential patient and tumor prognostic factors, including the Charlson Comorbidity Index (CCI) and Cumulative Illness Rating Scale (CIRS), were analyzed by logistic regression analysis for association with early mortality (death <6 months after SBRT). Additionally, CCI and CIRS were compared with respect to their predictive ability for early mortality by comparing multivariate models with each comorbidity index, and assessing their respective discriminatory abilities (C-index).Results: A total of 36 patients (6.1%) died within 6 months of the start of SBRT. With a median follow-up of 25 months, 3-year overall survival was 54%. CIRS and tumor diameter were significant predictors of early mortality on multivariate analysis (p = .001). Patients with a CIRS score of 8 or higher and a tumor diameter over 3 cm had a 6-month survival of 70% versus 97% for those lacking these two features (p < .001). CCI was not predictive for early mortality on univariate nor multivariate analysis; the model containing CCI had a C-index of 0.65 versus 0.70 for the model containing CIRS.Conclusion: CIRS and tumor diameter predict for early-mortality in peripheral early-stage NSCLC treated with SBRT. CIRS may be a more useful comorbidity index than CCI in this population when assessing short-term life expectancy.

P3.16-05 A Nanotechnology-Enabled Strategy for Image-Guided Transbronchial and Transpleural Photothermal Therapy of Peripheral Lung Cancer

Surgical resection has been established as standard of care for early-stage peripheral non-small cell lung cancer (NSCLC). However, the development of non-surgical treatment and minimally invasive therapeutics is urgently needed due to the known morbidity of surgery, particularly in high-risk patients. We have previously demonstrated the potential of porphysome nanoparticle-enabled fluorescence-guided photothermal therapy (PTT) of peripheral lung cancer in preclinical animal models. In an effort to prepare this technology for clinical application, we developed a porphysome-specific fiberscope (scanning fiber endoscope [SFE]) and porphysome-specific thoracoscope (P-PINPOINT), both capable of operating in fluorescence mode, for image-guided transbronchial and transpleural PTT to treat endo-/peribronchial and subpleural tumors respectively. In our study, we used three animal models: an in vivo human lung cancer xenograft (A549) in mice, another in vivo orthotopic VX2 tumor in rabbits, and an ex vivo pig lung into which A549 tumor tissue was transplanted. Forty-eight hours after intravenous injection of the porphysomes, the animals were used for imaging evaluation by SFE and P-PINPOINT, followed by photothermal ablation. The SFE, whose 1.2mm diameter is small enough to pass through the working channel of a conventional bronchoscope, could visualize porphysome-laden tumors located inside or close to the peripheral bronchial wall. The P-PINPOINT system had high sensitivity for porphysome fluorescence and enabled image-guided thoracoscopic resection of porphysome-accumulated tumors close to pleural. Porphysomes also enhanced the efficacy of SFE-guided transbronchial PTT and P-PINPOINT-guided transpleural PTT, resulting in selective and efficient tumor tissue ablation in the rabbit and pig models. These promising results suggest potential in the clinical translation of this novel platform to impact non-surgical and minimally invasive treatment options for early-stage peripheral lung cancer. This could offer new strategies for the treatment of non-small cell lung cancer.

Initial outcome and toxicity of stereotactic ablative body radiotherapy (SABR) for early stage lung cancer in a single UK centre

Purpose: SABR is standard practice for peripheral early stage lung cancer patients' who are medically inoperable. SABR was implemented from July 2014 at our centre. As part of quality reassurance, we analysed the survival outcomes and early toxicity of data in our patients.

An Integrated Nanotechnology-Enabled Transbronchial Image-Guided Intervention Strategy for Peripheral Lung Cancer.

Early detection and efficient treatment modality of early-stage peripheral lung cancer is essential. Current nonsurgical treatments for peripheral lung cancer show critical limitations associated with various complications, requiring alternative minimally invasive therapeutics. Porphysome nanoparticle-enabled fluorescence-guided transbronchial photothermal therapy (PTT) of peripheral lung cancer was developed and demonstrated in preclinical animal models. Systemically administered porphysomes accumulated in lung tumors with significantly enhanced disease-to-normal tissue contrast, as confirmed in three subtypes of orthotopic human lung cancer xenografts (A549, H460, and H520) in mice and in an orthotopic VX2 tumor in rabbits. An in-house prototype fluorescence bronchoscope demonstrated the capability of porphysomes for in vivo imaging of lung tumors in the mucosal/submucosal layers, providing real-time fluorescence guidance for transbronchial PTT. Porphysomes also enhanced the efficacy of transbronchial PTT significantly and resulted in selective and efficient tumor tissue ablation in the rabbit model. A clinically used cylindrical diffuser fiber successfully achieved tumor-specific thermal ablation, showing promising evidence for the clinical translation of this novel platform to impact upon nonsurgical treatment of early-stage peripheral lung cancer. Cancer Res; 76(19); 5870-80. ©2016 AACR.

A dosimetric and treatment efficiency evaluation of stereotactic body radiation therapy for peripheral lung cancer using flattening filter free beams.

To investigate potential dosimetric benefits and treatment efficiency of dynamic conformal arc therapy (DCA), intensity modulated radiation therapy (IMRT), and double partial arcs Rapidarc (RA) techniques in the treatment of early-stage peripheral lung cancer using stereotactic body radiotherapy (SBRT) with flattening filter free (FFF) beams. Twenty early-stage peripheral lung cancer patients were selected. For each patient, DCA, IMRT and RA plans were created to meet Radiation Therapy Oncology Group (RTOG) 0915 objectives with 48 Gy covering 95% of the planning target volume (PTV) in 4 fractions. PTV coverage, organs at risk (OARs) doses, planning time, monitor units (MU) and treatment time were evaluated. RA was significantly better than DCA for PTV coverage. RA provided a lower V32Gy to chest wall and less V20Gy to lung over those of DCA and IMRT. For other OARs, there is no significant difference among all three techniques. DCA plans showed significantly less planning time, shorter treatment time and lower MU number than those of RA and IMRT. RA provides a superior dosimetric benefit to DCA and IMRT in the treatment of early-stage lung cancer using SBRT with FFF beams. Considering the MU number, planning time and treatment efficiency, DCA technique is an effective treatment strategy.

Lung stereotactic ablative radiotherapy (SABR): dosimetric considerations for chest wall toxicity.

To investigate chest wall pain in patients with peripheral early stage lung cancer treated with stereotactic ablative radiotherapy (SABR), and to identify factors predictive of Common Terminology Criteria of Adverse Events Grade 2 + chest wall pain. Patients who received 55 Gy in five fractions were included. A chest wall structure was retrospectively defined on planning scans, and chest wall dosimetry and tumour-related factors recorded. Logistic regression was performed to identify factors predictive of ≥Grade 2 chest wall pain. 182 patients and 187 tumours were included. There were 20 (10.9%) episodes of ≥Grade 2 chest wall pain. Multivariate logistic regression demonstrated that the maximum dose received by 1 cm(3) of chest wall (Dmax1 cm(3)) and tumour size were significant predictors of ≥Grade 2 chest wall pain [Dmax1 cm(3) odds ratio : 1.104, 95% confidence interval : 1.012-1.204, p = 0.025; tumour size (mm) odds ratio : 1.080, 95% confidence interval : 1.026-1.136, p = 0.003]. This model was an adequate fit to the data (Hosmer and Lemeshow test non-significant) and a fair discriminator for chest wall pain (area under receiver-operating characteristic curve: 0.74). Using the multivariate logistic regression model, parameters for Dmax1 cm(3) are provided, which predict <10% and <20% risks of ≥Grade 2 chest wall pain for different tumour sizes. Grade 2+ chest wall pain is an uncommon side effect of lung SABR. Larger tumour size and increasing Dmax1 cm(3) are significant predictors of ≥Grade 2 chest wall pain. When planning lung SABR, it is prudent to try to avoid hot volumes in the chest wall, particularly for larger tumours. This article demonstrates that Grade 2 or greater chest wall pain following lung SABR is more common when the tumour is larger in size and the Dmax1 cm(3) of the chest wall is higher. When planning lung SABR, the risk of chest wall pain may be reduced if maximum doses are minimized, particularly for larger tumours.

Stereotactic Ablative Radiotherapy (SABR) in Patients with Medically Inoperable Peripheral Early Stage Lung Cancer: Outcomes for the First UK SABR Cohort

AimsTo report outcomes for the first UK cohort treated for early stage peripheral lung cancer using stereotactic ablative radiotherapy (SABR). Materials and methodsPatients were included who received SABR between May 2009 and May 2012. Electronic medical records were reviewed for baseline characteristics, treatment details and outcomes. Patients were treated according to the UK SABR Consortium Guidelines. Univariate and multivariate Cox regression was used to determine factors that influenced overall survival and local control. ResultsIn total, 273 patients received SABR for 288 lesions in the time period examined. The median follow-up was 19.7 months. The median overall survival for all patients was 27.3 months, with 1, 2 and 3 year overall survival of 78.0, 54.9 and 38.6%, respectively. The 1, 2 and 3 year rates of local control were 98.2, 95.7 and 95.7%, respectively. All patients completed the planned course of treatment and rates of Common Toxicity Criteria grade 3+ toxicity were low. On multivariate analysis, patients with Medical Research Council (MRC) breathlessness scores of 3–5 had worse overall survival compared with patients with scores of 1–2 (hazard ratio: 2.10; 95% confidence interval: 1.25–3.59) and the presence of histological diagnosis conferred improved overall survival (hazard ratio: 0.54; 95% confidence interval: 0.31–0.93), probably reflecting that patients who are considered well enough to undergo biopsy are generally fitter overall. No factors were identified that significantly influenced local control. ConclusionsSABR is an effective and well-tolerated treatment option for patients with early stage peripheral lung cancer who are not suitable for surgery. No patient cohort was identified in whom SABR was considered inappropriate. This series adds to the existing positive data that support SABR for this patient group.

Target delineation variability and corresponding margins of peripheral early stage NSCLC treated with stereotactic body radiotherapy

PurposeTo quantify the target delineation variability in peripheral early stage lung cancer treated with SBRT and derive corresponding margins. Methods and materialsSixteen early stage NSCLC GTV’s were delineated by 11 radiation oncologists from 4 institutes. A median surface was computed and the delineation variation perpendicular to this surface was measured (local standard deviation=SD). The overall target delineation variability was quantified by the root-mean-square (rms) of the local SD. The required margin was determined by expanding all delineations to encompass the median surface, where after the underlying probability distribution was modeled by a number of uncorrelated ‘pimples-and-dimples’. ResultsThe overall target delineation variability was 2.1mm (rms). Institute I–III delineated significantly smaller volumes than institute IV, yielding target delineation variabilities of 1.2mm and 1.8mm respectively. The margin required to obtain 90% coverage of the delineated contours was 3.4mm and 5.9mm respectively. The factor α in M=αΣ required to calculate adequate margins was 2.8–3.2, which is larger than the 2.5 found for 3D rigid target displacement. ConclusionA relatively small target delineation uncertainty of 1.2mm–1.8mm (1SD) was observed for early stage NSCLC. A 3.4–5.9mm GTV-to-PTV margin was required to account for this uncertainty alone, ignoring other sources of geometric uncertainties.

The CyberKnife radiosurgery system for lung cancer

The CyberKnife is a frameless image-guided radiotherapy system involving a 6-MV linear accelerator mounted on a robotic arm. The imaging system consists of two diagnostic x-ray sources mounted to the ceiling paired with amorphous silicon detectors to acquire live digital radiographic images of the tumor or tumor surrogates including bony anatomy or implanted fiducial markers. The Synchrony system enables 4D real-time tracking of tumors that move with respiration. Owing to this complex system, moving tumors can be treated with an accuracy of 2 mm or less while patients breathe normally. Clinical results of inoperable patients with peripheral early-stage lung cancer are excellent. The toxicity is low and the treatment does not result in a loss in quality of life.

Application of Robotic Stereotactic Radiotherapy to Peripheral Stage I Non-small Cell Lung Cancer with Curative Intent

Aims To determine the effectiveness of robotic stereotactic radiotherapy with image guidance and real-time respiratory tracking against early stage peripheral lung cancer. Materials and methods We treated patients with stage I non-small cell lung cancer (NSCLC) with CyberKnife ® and analysed their clinical characteristics and outcomes. All patients had co-morbid conditions that precluded lobectomy. The clinical target volume (CTV) included the gross tumour volume (GTV) and a 6 mm margin in all directions to account for microscopic extension. The planning target volume (PTV) equalled CTV + 2 mm in all directions for uncertainty. Tumour motion was tracked using a combination of Synchrony ® and Xsight ® Spine tracking methods with the aid of a single gold marker implanted in the centre of the tumour, or using the newer Xsight ® Lung method without markers for selected tumours. A 60–67.5 Gy dose was prescribed to the 60–80% isodose line (median 65%) and given in three to five fractions. Patients were followed every 3 months for a median of 27.5 months (range 24–53 months). Results Of the 67 patients with NSCLC stage IA or IB treated between January 2004 and December 2008, we report the results of a cohort of 31 with peripheral stage I tumours of 0.6–71 cm 3 volume treated between January 2004 and December 2007 with total doses between 60 and 67.5 Gy in three to five fractions. The median D max was 88.2 Gy and the median V 95 of the PTV was 99.6% or 27.9 cm 3. No grade 3 or above toxicity was encountered. Four cases of radiation pneumonitis and one case of oesophagitis were observed. In those patients whose pre- and post-treatment results were available, no change in pulmonary function tests was observed. Actuarial local control was 93.2% for 1 year and 85.8% for up to 4.5 years. One-year overall survival was 93.6% and 83.5% for up to 4.5 years, as projected by Kaplan–Meier analyses. Conclusions In this small cohort of patients with stage I peripheral NSCLC, robotic stereotactic radiotherapy seems to be a safe and obviously superior alternative to conventionally fractionated radiotherapy, with results that may be approaching those obtained with lobectomy without the associated morbidity.

Tumor dimension and prognosis in surgically treated lung cancer: for intentional limited resection.

Tumors with a maximum dimension of 3 cm are categorized as T1, whereas those greater than 3 cm are T2 by TNM classification. Some physicians suggest that early-stage peripheral lung cancer should have a maximum tumor diameter of 2 cm and that limited surgery (segmentectomy without lymph node dissection) is acceptable for the patients. In this study, the relationship between the tumor dimension and prognosis was analyzed in 207 patients with surgically treated primary non-small-cell lung cancer (SCLC). The 5-year survival rate of those with tumors 3 cm or less and without lymph node (LN) metastases was 86%, which was significantly higher than that of those with tumors more than 3 cm and without hilar and mediastinal LN metastases (65%) (p < 0.05). However, 33% of the patients with tumors 3 cm or less had LN metastases, and the 5-year survival rate did not differ between those with tumors 3 cm or less (60%) and those with tumors more than 3 cm (54%). Twenty-eight percent of patients with tumors 2 cm or less had LN metastases, and the 5-year survival rate of the patients with tumors 2 cm or less was 62%. The 5-year survival rate of those with tumors 2 cm or less and without LN metastases was 88%. Forty-six patients with tumors 2 cm or less included 5 cases with an intrapulmonary metastasis in the same lobe (11%). In conclusion, a size of 3 cm is an appropriate boundary as the T factor. Because those with tumors 2 cm or less have a relatively high percentage of LN metastases, intraoperative frozen sections of LN should be considered for those undergoing limited surgery for primary non-SCLCs 2 cm or less. Intrapulmonary metastases also should be considered for those undergoing limited surgery even if the maximum dimension of the primary tumor is less than 2 cm.