Inoperable Early-stage Non-small Cell Research Articles

Prospective study investigating hypofractionated proton beam therapy in patients with inoperable early stage non-small cell lung cancer.

To report the results of hypofractionated proton beam therapy (PBT) for the treatment of early stage lung cancer in patients not suitable for surgical resection. Data from 27 adult patients, who were diagnosed with inoperable cT1-3N0 non-small cell lung cancer (NSCLC) between March 2018 and August 2020, were analyzed. PBT was prescribed as 64 Cobalt Grey equivalents delivered in 8 fractions (Sumitomo, Japan). The primary endpoint was local control; secondary endpoints included overall survival, quality of life, and grade ≥3 toxicity. The median follow-up was 28.9 months (range, 1.1-62.1 months). During follow-up, 13 (48.1%) patients experienced disease progression, including local progression in 7. Two-year local control rates were 73.5%, 85.7% for T1, and 61.4% for T2-3. The worse local control rate was observed in those with large clinical target volumes (≥ 47.5 cc) and heavy smoking history (≥30 pack-years). The two-year overall survival rate was 76.5%. Grade 3 radiation-related toxicities were observed in 2 (7.4%) patients. In the European Organization for Research and Treatment of Cancer Quality of Life Core 30 results, the global score did not change significantly from baseline. However, dyspnea score increased from 19.8 before PBT to 33.3 at 4 months' post-PBT (p=0.047) and was maintained until 13 months (p=0.028). Hypofractionated PBT was a safe treatment option for inoperable early stage NSCLC and appeared to be appropriate for small tumor volumes. However, local control for larger tumors requires further improvement.

EP07.02-07 Prospective Study of Hypofractionated Proton Therapy for Inoperable Early Stage Non-small Cell Lung Cancer

EP07.02-07 Prospective Study of Hypofractionated Proton Therapy for Inoperable Early Stage Non-small Cell Lung Cancer

Lobar Gross Endobronchial Disease Predicts for Overall Survival and Grade 5 Pulmonary Toxicity in Medically Inoperable Early Stage Non-Small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy.

PurposeStereotactic body radiation therapy (SBRT) is considered standard of care for medically inoperable early stage non-small cell lung cancer (ES-NSCLC). Central tumor location is a known risk factor for severe SBRT related toxicity. Bronchoscopy allows for visualization of the central airways prior to treatment. Five fraction SBRT approaches have been advocated to mitigate treatment induced toxicity. In this report, we examine the mature clinical outcomes of a diverse cohort of ES-NSCLC patients with both peripheral and central tumors treated with a conservative 5 fraction SBRT approach and evaluate the role of lobar gross endobronchial disease (LGED) in predicting overall survival and treatment-related death.MethodsMedically inoperable biopsy-proven, lymph node-negative ES-NSCLC patients were treated with SBRT. Bronchoscopy was completed prior to treatment in all centrally located cases. The Kaplan-Meier method was used to estimate overall survival (OS), local control (LC), regional control (RC), distant metastasis free survival (DMFS) and disease-free survival (DFS). Overall survival was stratified based on clinical stage, histology, tumor location and LGED. Toxicities were scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0.ResultsFrom December 2010 to December 2015, 50 consecutive patients were treated uniformly with a 50 Gy in 5 fraction SBRT approach (tumor BED10 ≥ 100 Gy) and followed for a minimum of 5 years or until death. At a median follow up of 42 months for all patients, 3-year OS was 50%. Three-year OS did not statistically differ between stage I and stage II disease (51% vs. 47%; p=0.86), adenocarcinoma and squamous cell carcinoma (50% vs. 45%; p=0.68), or peripheral and central tumors (56% vs. 45%; p=0.46). Five central tumors were found to have LGED, and 3-year OS for this cohort was quite poor at 20%. Cox regression analysis identified LGED as a predictor of OS while controlling for age, stage and location (OR:4.536, p-value=0.038). Despite the relatively low dose delivered, treatment likely contributed to the death of 4 patients with central tumors. Lobar gross endobronchial disease was an independent predictor for grade 5 pulmonary toxicity (n=4, p=0.007). Specifically, 3 of the 5 patients with LGED developed fatal radiation-induced bronchial stricture. Three-year LC, RC, DMFS and DFS results for the group were similar to contemporary studies at 90%, 90%, 82% and 65%.ConclusionsCentral location of ES-NSCLC is a well-established predictor for severe SBRT-related toxicity. Here we identify LGED as a significant predictor of poor overall survival and grade 5 pulmonary toxicity. The relatively high rates of severe treatment-related toxicity seen in patients with central ES-NSCLC may be due in part to LGED. Underlying LGED may cause irreparable damage to the lobar airway, unmitigated by SBRT treatment thus increasing the risk of severe treatment-related toxicity. These findings should be verified in larger data sets. Future prospective central ES-NSCLC clinical trials should require staging bronchoscopy to identify LGED and further assess its clinical significance.

Patterns of Care in Stereotactic Body Radiation Therapy Fractionation Schedules in Non-Small Cell Lung Cancer in the United States From 2004-2016

Stereotactic Body Radiation Therapy (SBRT) is considered standard of care for inoperable early stage non-small cell lung cancer (NSCLC) and is commonly delivered in 1-5 fractions. Single fraction SBRT is supported by randomized data demonstrating equivalent safety compared to fractionated approaches. The purpose of this study is to measure trends in the utilization of SBRT fractionation in NSCLC patients in the National Cancer Database (NCDB) from 2004-2016.The NCDB was queried for patients with cT1-T3N0M0 NSCLC who were treated with a known SBRT dosing schema during the study period (including 30-34 Gy/1 fraction, 54-60 Gy/3 fractions, 48-50 Gy/4 fractions, and 50-60 Gy/5 fractions). Adjusted logistic regression was used to assess the association of treatment year with the annual percentage of patients who received SBRT using 1, 3, 4, and 5 fractions. Average annual percentage changes (AAPC) were computed and compared to determine if a significant change (defined a priori as P < 0.01) occurred in the use of different fractionation schemes over time. Multivariable analysis was used to evaluate factors associated with receipt of single fraction SBRT.The analytic cohort consisted of 39,536 patients. Use of 3 fraction SBRT decreased from 72.6% in 2004 to 20.3% in 2016 (AAPC -10.6% per year, 95% CI: [-12.1%, -9.1%], P < 0.001). During this interval, a corresponding increase in the use of 5 fraction SBRT also occurred, from 6.5% in 2004 to 53.7% in 2016 (AAPC +18.3% per year, 95% CI: [+13.3%, +23.4%], P < 0.001). No significant change was observed in single fraction and 4 fraction SBRT utilization; < 1% of patients per year received single fraction SBRT in all but three years of the study with a 1.1% percent utilization rate in 2016. On logistic regression, cT2 patients were less likely to receive single fraction SBRT (Odds Ratio 0.592, 95% CI: 0.414-0.846) while academic facility (Odds Ratio 5.821, 95% CI: 4.331-7.823) and Charlson Deyo Score > 2 (Odds Ratio 1.447, 95% CI: 1.038-2.017) were significantly associated with receipt of single fraction SBRT. Age, insurance, distance to treatment facility, and treatment year were not significantly associated with single fraction SBRT.Single fraction SBRT use remained scarce in the United States during 2004-2016, with no clear indication of increased utilization after 2014 when RTOG0915 was first reported. With prospective evidence that long-term toxicity, local control, and survival are similar to 3-4 fraction regimens, the application of single fraction SBRT in the clinic may warrant further interest in light of the recent COVID-19 pandemic and the implementation of the alternative payment model.

Stereotactic Ablative Radiation Therapy for Large (≥5 cm) Non-small Cell Lung Carcinoma

AimsStereotactic ablative radiation therapy (SABR) is a standard of care for medically inoperable early stage non-small cell lung carcinoma. Tumours greater than 5 cm have been excluded from randomised trials using SABR and, hence, it is not used as a standard for larger lung tumours. However, improvements in radiation therapy techniques and the success of SABR in treatment of early stage disease may allow safe delivery of ablative doses to larger tumours. We analysed our experience with tumours ≥5 cm to determine the efficacy and toxicity profile of SABR in this setting. Materials and methodsWe evaluated survival, control rates, patterns of failure and toxicity in patients with a tumour diameter larger than 5 cm that had no nodal or distant metastases treated with SABR technology. Patients had been treated in two centres since 2009 and were retrospectively analysed. All patients had positron emission tomography staging, were discussed at a tumour board and were documented to have no nodal or distant metastatic disease. Treatment outcomes were analysed using Kaplan–Meier estimates and compared using the Log-rank test. Cox regression was used to investigate the association between the survival outcomes and predictor variables. ResultsIn total, 86 patients were identified. Six patients had no follow-up imaging. Therefore, 80 patients were available for analysis. All patients were reclassified according to the updated AJCC eighth edition. The median follow-up was 19.6 months. No patients received neoadjuvant or concurrent systemic therapy. One patient received adjuvant systemic therapy. The median age at treatment was 77 years (range 58–91). Eighty-four per cent were stage T3N0M0 and 16% were staged T4N0M0. The median tumour diameter was 5.8 cm (range 5.0–9.3 cm). The median gross tumour volume, measured on a single phase of the respiratory cycle, was 45.7 cm3 (range 12.1–203.3 cm3). The median overall survival was 20.9 months (95% confidence interval 12.6–29.1 months). One-, 2- and 3-year overall survival was 71%, 48% and 32%, respectively. The median local failure-free survival was 19.5 months (95% confidence interval 14.4–24.6). The median disease-free survival was 15.1 months (95% confidence interval 9.9–20.4 months). Local control at 1, 2 and 3 years was 85% (95% confidence interval 76–94%), 71% (95% confidence interval 58–84%) and 57% (95% confidence interval 40–74%), respectively. Forty-four patients (55%) had any treatment failure (local, mediastinal, intrapulmonary or distant metastases). Out-of-field intrapulmonary disease progression was the most common mode of failure, occurring in 21 patients (26%). Local failure occurred in 19 patients (24%) – alone or in combination with other progression. Distant metastases occurred in 20 patients (25%). Neither histological subtype, tumour size nor gross tumour volume had a statistically significant effect on local failure-free survival. Two patients experienced grade 3 late dyspnoea. There were no other reported grade 3 or higher acute or late toxicities. ConclusionSABR for larger lung tumours ≥5 cm results in high local control and acceptable survival in patients with medically inoperable large non-small cell lung carcinoma treated with radiation alone. Such patients should be considered for SABR owing to fewer treatment fractions and acceptable toxicity. Local control analysis reveals a sustained pattern of local failure emphasising the need for long-term follow-up. Improvements in technical strategies are required to further improve local control.

Technical challenges of linac-based stereotactic ablative body radiotherapy: short review for non-radiation oncologists.

Stereotactic ablative radiotherapy (SABR) is a radiation technique delivering high doses of radiation in a small number of treatments, to extracranial targets. It is standard of care in patients with inoperable early stage non-small cell lung cancer, and it is increasingly used in patients with oligometastatic disease. The main advantage of SABR is a steep dose gradient, allowing delivery of high biologically effective doses to the target, while minimizing irradiation exposure of the neighboring normal tissues. This results in high rates of local control of the treated target and minimal toxicity risks, and minimal impact on the quality of life of the patients. However, it requires high precision, accuracy and reproducibility during the entire process, from simulation to treatment planning and treatment delivery. This article will focus on general principles of SABR treatment planning and delivery, with emphasis on the strategies to reduce errors related to immobilization, respiratory management and treatment verification.

A meta-analysis comparing stereotactic body radiotherapy vs conventional radiotherapy in inoperable stage I non-small cell lung cancer.

Stereotactic body radiotherapy (SBRT) superseded conventional radiotherapy (CRT) for the treatment of patients with inoperable early stage non-small cell lung cancer (NSCLC) over a decade ago. However, the direct comparisons of the outcomes of SBRT and CRT remain controversial. This meta-analysis was performed to compare the survival and safety of SBRT and CRT in patients with inoperable stage I NSCLC. We systematically searched the Cochrane Library, Embase, PubMed, Web of Science, Ovid MEDLINE, ScienceDirect, Scopus and Google Scholar for relevant articles. Overall survival (OS), progression-free survival (PFS), lung cancer-specific survival (LCSS), local control rate (LCR) and adverse effects (AEs) were the primary outcomes. We identified 11,110 articles, 17 of which were eventually included in this study; these 17 articles had 17,973 patients (SBRT: 7395; CRT: 10,578). Compared to CRT for the treatment of inoperable stage I NSCLC, SBRT had superior survival in terms of OS (hazard ratio [HR]: 0.66, 95% confidence interval [CI]: 0.62-0.70, P < .00001), LCSS (HR: 0.42 [0.35-0.50], P < .00001), and PFS (HR: 0.34 [0.25-0.48], P < .00001). The 4-year OS rate (OSR); 4-year LCSS rate (LCSSR); 3-year local control rate (LCR); 5-year PFS rate (PFSR) with SBRT were all higher than those with CRT. With regard to all-grade AEs, the SBRT group had a significantly lower rate of dyspnea, esophagitis and radiation pneumonitis; no significant difference was found in grade 3-5 AEs (risk ratio [RR]: 0.68 [0.30-1.53], P = .35). With better survival and a lower rate of dyspnea, esophagitis and radiation pneumonitis than CRT, SBRT appears to be more suitable for patients with inoperable stage I NSCLC.

An Externally Validated Nomogram to Predict Distant Metastases after Stereotactic Body Radiation Therapy in Early Stage Non-Small Cell Lung Cancer Patients

Stereotactic body radiation therapy (SBRT) is the standard of care for medically inoperable early stage non-small cell lung cancer (NSCLC) patients and has shown excellent local control rates. However, the development of distant metastases (DM) is the most common form of failure. While there have been multiple international efforts to incorporate systemic therapy to SBRT, there is little guidance on determining which patients are at high risk of DM and would most benefit from systemic therapy. As such, we developed a nomogram to predict risk of DM in early stage NSCLC patient after SBRT. We conducted a retrospective cohort study utilizing a multi-institutional community practice database to identify consecutive patients with biopsy proven T1-3N0M0 NSCLC treated with definitive SBRT from 2006-2015. Univariate cause-specific Cox proportional hazards models were used to identify variables associated with DM, which were incorporated into a multivariate model if they had P<0.1 or if there was clinical rationale for their inclusion. The final model was internally validated with bootstrapping with 100 replications. A nomogram was generated from the model and discriminatory performance was evaluated with C-index. A separate academic institutional database was used to externally validate the model. Of 1,328 patients in the initial database, 821 met the study criteria for analysis. Patients were excluded if they did not have biopsy proven NSCLC, received chemotherapy, had synchronous primaries, and did not receive a BED10 of at least 100 Gy. The median time to the development of DM was 18 months, and the median follow-up time was 19 months. The raw rate of DM at 2 years was 9.6% (79/821). On multivariate analysis, higher PET SUV (<3 vs ≥3: HR: 2.52, P=0.022), larger tumor size (HR: 1.39, P=0.030), and adenocarcinoma as opposed to squamous cell carcinoma (HR: 1.62, P=0.036) were correlated with a higher rate of distant metastases. The final nomogram included PET SUV, size, age, performance status, histology, T-stage, gender, and prior lung cancer. All variables in the final model had a univariate P < 0.1 except for prior lung cancer, which was included based on clinical significance. On internal validation, the model had a C-index of 0.67 for DM. The model was validated on an institutional database of 185 patients with biopsy proven T1-3N0 NSCLC who did not receive chemotherapy, did not have synchronous primaries, and received a BED10 of at least 100 Gy and achieved an externally validated C-index of 0.63. We developed a nomogram from a large, heterogeneous patient population that uses clinical information to predict the risk of distant metastases in early stage NSCLC patients after SBRT, and externally validated the model on an independent dataset. The nomogram may be helpful in guiding clinical decision making regarding adjuvant systemic therapy and clinical trial development. Further research is ongoing to increase the predictive performance of the model.

PD-L1 Tumor Proportion Score is Associated with Distant Failure after Stereotactic Ablative Radiotherapy in Early Stage Non-Small Cell Lung Cancer

Stereotactic ablative radiotherapy (SABR) is standard treatment for patients with medically inoperable early stage non-small cell lung cancer (NSCLC). Ten to 30% of patients experienced disease progression or distant metastases afterwards. Molecular profiles such as status of oncogenic driver mutations and tumor PD-L1 have been associated with prognosis for surgically resected early stage disease. We aimed to analyze the outcomes and prognostic potentials of major driver gene mutations and tumor PD-L1 expression for early stage NSCLC treated by SABR. We retrospectively collected and reviewed early stage NSCLC patients received SABR at a single medical center between 2008 and 2018. Epidermal growth factor receptor (EGFR) mutation status was determined by either polymerase chain reaction-based genotyping or mass spectrometry-based assay. Status of tumor expressions of PD-L1, and ALK were assessed by immunohistochemistry stain. Survival was estimated by the Kaplan-Meier method and Log-rank test was performed for evaluation of prognostic factors. In total, 75 patients were enrolled for analysis with a median age of 82-year-old (range, 30-94) at SABR delivery. The median biological equivalent dose delivered was 105.6 Gy10 (range 91.7-180). Men (n=50) and ever smokers (n=46) comprised the majority of the study cohort. Adenocarcinoma and squamous cell carcinoma accounted for 61% and 31% of histology subtypes, respectively. EGFR mutation status were identified in 36 patients, and 41.7% harbored mutant EGFR. All patients with available ALK expression data were negative. PD-L1 expression data, recorded as tumor proportion score (TPS), was available in 34 patients. With a median follow-up time of 18.5 months for all patients, the 3-year overall survival (OS) rate, local control (LC) rate, and distant metastases (DM) rate were 71.7%, 85.8%, and 43.7%, respectively. Patients with adenocarcinoma histology showed a significant favorable OS compared to those with squamous cell carcinoma (3-year OS rate 81.6% versus 54.7%, p=0.002). All tested driver mutations and PD-L1 TPS classification had no significant impact on LC or OS. Noteworthy, PD-L1 TPS ≥ 50% was associated with a significant worse distant control (median DM-free survival of TPS ≥ 50% 7.1 months versus TPS < 50% not reached, p=0.02). SABR achieved excellent local control, with the majority of failures being distant in medically inoperable early stage NSCLC. While EGFR mutation status had no impact on clinical outcomes in our study cohort, PD-L1 TPS ≥ 50% seemed to significantly increase the risk of distant failure. Further study with a larger cohort is warranted to validate our findings and adjuvant immunotherapy might be evaluated for patients with high-risk feature for distant metastases.

Pre-Treatment Circulating Tumor Cell Levels Correlate with Regional and Distant Failure Rates Following Stereotactic Body Radiation Therapy for Early Stage Non-Small Cell Lung Cancer

Stereotactic body radiation therapy (SBRT) has become the standard of care for patients with medically inoperable early stage non-small cell lung cancer (NSCLC) due to good local control rates and minimal morbidity. However, of patients treated with SBRT, 10-15% patients fail regionally and 25% fail distantly. Our hypothesis underlying this prospective trial was that a high burden of circulating tumor cells (CTCs) prior to treatment is a useful prognostic marker for increased risk of recurrence following SBRT. 92 subjects with stage I NSCLC treated with SBRT were prospectively enrolled on an IRB-approved protocol. CTCs were enumerated by an assay utilizing a green fluorescent protein (GFP)-expressing adenoviral probe that detects the elevated telomerase activity in cancer cells. CTC “positivity” was defined as 1.3 GFP-positive cells per mL of peripheral blood samples. Pre-treatment samples were collected at the time of treatment consent for SBRT or at simulation. RT was delivered to a median dose of 50Gy (range, 40-60 Gy) in five fractions. Patient characteristics: female (58%), Caucasian (80%), and current (20%) or former (75%) smokers; median age was 71 years. Subjects had T1a (64%), T1b (23%), or T2a (13%) NSCLC with a median tumor size of 1.7 cm (range, 0.5-5.0 cm). Kaplan-Meier survival analysis and Cox multivariate regression analysis explored the relative effect of covariates on recurrence and survival outcomes, controlling for history of previous NSCLC, tumor size, and pre-treatment PET scan SUVmax. Receiver operating characteristic curves were generated for a series of baseline CTC values between 2 and 7 to identify if there were a threshold value prognostic of disease recurrence. With a median follow-up of 24 months (range, 2-62 months), the 2-year local, regional and distant control rates were 90.0%, 86.4%, and 86.5%, respectively. 38 of 92 subjects (40%) had a positive CTC test prior to treatment. Overall, a positive CTC test when compared to a negative test was not associated with local, nodal, or distant recurrence. A pre-SBRT cutoff of ≥5 CTCs/mL demonstrated the maximal area under the cure in predicting any event of recurrence (AUC=0.64, specificity=90.4%), therein defining favorable (n=78) and unfavorable (n=14) prognostic groups by baseline CTC. Increased risk of nodal and distant failure was observed in the unfavorable versus favorable cohorts, with 2-year freedom from nodal and distant failure of 83.9% and 75.7% versus 86.7% (HR 3.92, p=0.04) and 89.2%, (HR 4.29, p=0.03). Higher pre-treatment CTC counts appears to be predictive of increased risks of regional and distant recurrences following SBRT for early stage NSCLC, thus potentially identifying the subset of patients at highest risk of regional and distant recurrences who could benefit most from intensified or adjuvant systemic therapy.

Severe and Fatal Multilobar Nonclassic Radiation Pneumonitis following Stereotactic Body Radiation Therapy (SBRT) for Treatment of Inoperable Non-Small-Cell Lung Cancer: A Report of Two Cases and Possible Enhancement by Concurrent Amiodarone

Stereotactic body radiation therapy (SBRT) is considered the standard of care for treatment of inoperable early stage non-small cell carcinoma of the lung. SBRT delivers a very high dose of ionizing radiation to a relatively small region encompassing the tumor and spares a significant portion of the remaining lung from high doses. However, the conformal high dose comes at the expense of treating a larger volume of normal lung to lower doses. In general, this has been deemed to be acceptable with an overall lower risk of radiation pneumonitis. However, in the face of predisposing factors, the higher doses delivered by this technique may lead to an increase in radiation pneumonitis. We report on two patients being treated with SBRT in which severe radiation pneumonitis developed in spite of our radiation dosimetry being significantly below the acceptable limit for lung toxicity. Both patients developed a “fulminant” form of radiation pneumonitis with radiographic abnormalities well beyond the treated volume. In one patient, the disease proved fatal. Both patients were on amiodarone at the time SBRT was administered. Given the rarity of fulminant radiation pneumonitis, especially with the relatively small fields treated by SBRT, we suspect that amiodarone enhanced the pulmonary toxicity.

Survival after stereotactic radiotherapy in patients with early-stage non-small cell lung cancer

Introduction: Stereotactic radiotherapy (SBRT) is the treatment of choice for inoperable early stage non-small cell lung cancer (NSCLC). We report analyses of the influence of age on survival after SBRT.Methods and material: From 2005 to 2017, 544 previously un-irradiated patients with early stage NSCLC had SBRT. The data were analyzed in four age groups: A: –69 (176 pts), B: 70–74 (115 pts), C: 75–79 (131 pts) and D: 80 years or older (122 pts). Two SBRT dose regimes were used: 45 Gy/3F (N = 103) and 66 Gy/3F (N = 441).Results: All patients had a follow up (time to censoring, FU) of at least 16 months, the median FU being 48.0 months. The median age was 74.4 years. The overall survival (OS) was associated with age. The median OS was 50.7, 45.9, 45.4 and 33.0 months, and the 5-year OS was 45%, 32%, 33% and 18% in groups A, B, C and D, respectively. No difference was found between groups B and C, while OS in group A was significantly better than remaining groups, and the OS in group D significantly poorer. In multivariable analyses, OS was heavily influenced by age, Charlson’s comorbidity index (CCI) and performance status (PS). For lung cancer-specific survival (LCSS), only increasing tumor diameter and PS were associated with poor survival.Conclusions: The OS was influenced by age, but the study suggests that a cut point of 75 year is inappropriate in evaluating the effect of old age on survival. Poor PS was associated with poor OS. CCI influenced OS, but not LCSS, which was only affected by PS and tumor size.

Promising Clinical Outcome With Long Term Follow-Up After Body Gamma Knife Stereotactic Radiosurgery for Patients With Early Stage Non-small Cell Lung Cancer.

Introduction: Stereotactic ablative radiosurgery (SRS) or stereotactic ablative body radiotherapy (SABR) is the standard treatment for patients with inoperable early stage non-small cell lung cancer (NSCLC), the body gamma knife SRS (ɤ-SRS) is a special SABR technology developed in China. This study prospectively assessed the clinical outcome, toxicity and cost following body ɤ-SRS for early stage NSCLC.Methods: From 2007 to 2010, a total of 29 patients with early stage NSCLC were prospectively enrolled in this study. The prescription dose for Planning Target Volume (PTV), Clinical Target Volume (CTV), and Gross Target Volume (GTV) were 50, 60, and 70 gray (Gy) in 10 fractions. Isodose curves of 50, 60, and 70% covered at least 100% of PTV, 90% of CTV, and 80% of GTV, respectively. The body ɤ-SRS was delivered 5 days per week and completed in 2 weeks.Results: Median follow-up time was 62.0 (range 11.1-140.3) months. 1-, 3-, 5-year OS rates were 93.1%, 72.0%, 60.3%; PFS rates were 86.2, 64.2 and 48.8%; and LR, RR, and DM rates were 10.9%, 21.4%, 29.0%. The median cost of the body ɤ-SRS during treatment was 4,838 (range 4,615–4,923) dollars and the median cost through 5 years was 36,960 (range 9920-56,824) dollars.Conclusion: With existing clinical data, the body ɤ-SRS is an effective treatment option for patients with medically inoperable early stage NSCLC or patients who do not prefer operation, as they may benefit from the minimized toxicity. Due to excellent cost effectiveness, the availability of the body ɤ-SRS will expand, especially in developing nations, and underdeveloped countries.

Ct and Template-Guided Radioactive Seed Implantation for Inoperable Early Stage Non-Small Cell Lung Cancer

To investigate the efficacy and side effects of radioactive seed implantation in the treatment of non-surgical early stage non-small cell lung cancer on the guiding of Computer Tomography(CT) combined with template.

Hypo-fractionated stereotactic radiation therapy for lung malignancies by means of helical tomotherapy: report of feasibility by a single-center experience.

Several experiences in the literature report SBRT as an effective treatment option for medically inoperable early stage non-small cell lung cancer (NSCLC) and oligometastatic disease. The optimal fractionation schedules and total dose remain controversial. In this study, we evaluated the safety in terms of toxicity and efficacy of using of 8-10 fractions schedules with Helical Tomotherapy (HT) for primary and metastatic lung lesions. Between March 2014 and May 2016, a total of 39 patients (median age 72years, range 26-91) were treated with HT-SBRT for malignant lung lesions: 22 patients with early stage NSCLC, 17 with oligometastases. Patients received 8-10 fractions with lower daily dose for central and ultracentral lesions. Treatment-related toxicity was evaluated using CTCAE v 4.0 scale. Local control (LC), overall survival (OS) and toxicity rates were prospectively collected. Median duration of RT was 15days (range 10-26days) and no interruption occurred. With a median follow-up of 13months (range 3-29), we reported one G2 pneumonitis (2.6%) and one G2 chest pain (2.6%); no≥G2 esophagitis was registered. Actuarial local control rate was 95.5% both at 12 and 24months for early stage NSCLC and 92.9% both at 12 and 24months for metastatic patients. OS rate was 94.4 and 92.3% at 1year, and 94.4 and 83.9% at 2years in primary and metastatic group, respectively. The use of 8-10 fractions schedule HT-SBRT for lung malignancies results in high LC and OS rates with minimal toxicities reported.

Improvement of conformal arc plans by using deformable margin delineation method for stereotactic lung radiotherapy.

PurposeStereotactic body radiotherapy (SBRT) is an established treatment technique in the management of medically inoperable early stage non–small cell lung cancer (NSCLC). Different techniques such as volumetric modulated arc (VMAT) and three‐dimensional conformal arc (DCA) can be used in SBRT. Previously, it has been shown that VMAT is superior to DCA technique in terms of plan evaluation parameters. However, DCA technique has several advantages such as ease of use and considerable shortening of the treatment time. DCA technique usually results in worse conformity which is not possible to ameliorate by inverse optimization. In this study, we aimed to analyze whether a simple method – deformable margin delineation (DMD) – improves the quality of the DCA technique, reaching similar results to VMAT in terms of plan evaluation parameters.MethodsTwenty stage I–II (T1‐2, N0, M0) NSCLC patients were included in this retrospective dosimetric study. Noncoplanar VMAT and conventional DCA plans were generated using 6 MV and 10 MV with flattening filter free (FFF) photon energies. The DCA plan with 6FFF was calculated and 95% of the PTV was covered by the prescription isodose line. Hot dose regions (receiving dose over 100% of prescription dose) outside PTV and cold dose regions (receiving dose under 100% of prescription dose) inside PTV were identified. A new PTV (PTV‐DMD) was delineated by deforming PTV margin with respect to hot and cold spot regions obtained from conventional DCA plans. Dynamic multileaf collimators (MLC) were set to PTV‐DMD beam eye view (BEV) positions and the new DCA plans (DCA‐DMD) with 6FFF were generated. Three‐dimensional (3D) dose calculations were computed for PTV‐DMD volume. However, the prescription isodose was specified and normalized to cover 95% volume of original PTV. Several conformity indices and lung doses were compared for different treatment techniques.Results DCA‐DMD method significantly achieved a superior conformity index (CI), conformity number (CIP addick), gradient index (R50%), isodose at 2 cm (D2 cm) and external index (CΔ) with respect to VMAT and conventional DCA plans (P < 0.05 for all comparisons). CI ranged between 1.00–1.07 (Mean: 1.02); 1.00–1.18 (Mean: 1.06); 1.01–1.23 (Mean 1.08); 1.03–1.29 (Mean: 1.15); 1.04–1.29 (Mean: 1.18) for DCA‐DMD‐6FFF, VMAT‐6FFF, VMAT‐10FFF DCA‐6FFF and DCA‐10FFF respectively. DCA‐DMD‐6FFF technique resulted significantly better CI compared to others (P = 0.002; < 0.001; < 0.001; < 0.001). R50% ranged between 3.22–4.74 (Mean: 3.99); 3.24–5.92 (Mean: 4.15) for DCA‐DMD‐6FFF, VMAT‐6FFF, respectively. DCA‐DMD‐6FFF technique resulted lower intermediate dose spillage compared to VMAT‐6FFF, though the difference was statistically insignificant (P = 0.32). D2 cm ranged between 35.7% and 67.0% (Mean: 53.2%); 42.1%–79.2% (Mean: 57.8%) for DCA‐DMD‐6FFF, VMAT‐6FFF respectively. DCA‐DMD‐6FFF have significantly better and sharp falloff gradient 2 cm away from PTV compared to VMAT‐6FFF (P = 0.009). CΔ ranged between 0.052 and 0.140 (Mean: 0.085); 0,056–0,311 (Mean: 0.120) for DCA‐DMD, VMAT‐6FFF, respectively. DCA‐DMD‐6FFF have significantly improved CΔ (P = 0.002). VMAT‐ V20 Gy, V2.5 Gy and mean lung dose (MLD) indices are calculated to be 4.03%, 23.83%, 3.42 Gy and 4.19%, 27.88%,3.72 Gy, for DCA‐DMD‐6FFF and DCA techniques, respectively. DCA‐DMD‐6FFF achieved superior lung sparing compared to DCA technique. DCA‐DMD‐6FFF method reduced MUs 44% and 33% with respect to VMAT‐6FFF and 10FFF, respectively, without sacrificing dose conformity (P < 0.001; P < 0.001).ConclusionsOur results demonstrated that DCA plan evaluation parameters can be ameliorated by using the DMD method. This new method improves DCA plan quality and reaches similar results with VMAT in terms of dosimetric parameters. We believe that DCA‐DMD is a simple and effective technique for SBRT and can be preferred due to shorter treatment and planning time.

Stereotactic ablative radiotherapy in treatment of early-stage non-small cell lung cancer: Unsolved questions and frontiers ahead

Stereotactic ablative radiotherapy (SABR) has been recognized as a standard alternative treatment to surgery for inoperable early stage non-small cell lung cancer (NSCLC). Guaranteed local control rates over 90% makes oncologists wonder whether SABR is qualified enough to challenge surgery in operable patients. The role of SABR for centrally located lesions would be another question because of the increased risk of severe toxic effect. Plenty of studies suggest that optimization of dose regimen and appropriate case selection would be helpful. Additionally, the effect of adjuvant therapy following SABR in selected patients is worth looking forward, given that it significantly reduced risk of recurrence after complete resection. A consensus about salvage treatment after SABR also needs, given the current diversity of options. Finally, witnessing the emergence of proton therapy and immunotherapy, we believe that the future of SABR lay behind these novel forms of treatment.

Prospective evaluation of anxiety, depression and quality of life in medically inoperable early stage non-small cell lung cancer patients treated with stereotactic ablative radiotherapy.

The aim of this prospective study was to evaluate the level of anxiety, depression, and quality of life (QoL) in medically inoperable patients with early stage non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR). Prolonged survival is equally important as maintaining high QoL and good psychological functioning during the treatment of lung cancer. Nowadays available SABR has markedly changed clinical care and outcomes in the group of medically inoperable patients. To our knowledge, analysis of QoL and psychological state has not been performed in Polish patients with early NSCLC treated with SABR. Research group consisted of medically inoperable, early NSCLC (T1-2aN0M0) patients qualified to SABR. Patients were asked to complete Polish versions of the European Organization for Research and Treatment of Cancer Quality of Life - Core Questionnaire (EORTC QLQ-C30) with the Lung Cancer Questionnaire (LC13) and Hospital Anxiety and Depression Scale (HAD). These questionnaires were repeated 2 weeks and then 3 months after treatment completion. We enrolled 51 patients who met the inclusion criteria. SABR did not deteriorate QoL and psychological functioning. On the contrary, clinically meaningful improvement was observed in emotional functioning, level of insomnia, anxiety and depression. Significantly worse improvement was shown in patients with chronic obstructive pulmonary disease (COPD). Our results confirm that SABR is well tolerated and does not have a deleterious effect on QoL and psychological state. Results of our study indicate the importance of additional psychological care in the group of patients with COPD.

CT Guided Radiofrequency Ablation Followed Intratumoral Chemotherapy in the Treatment of Early Stage Non-small Cell Lung Cancer

背景与目的射频消融（radiofrequency ablation, RFA）已经成为无法手术的早期非小细胞肺癌（non-small cell lung cancer, NSCLC）的局部治疗方法之一。本研究观察计算机断层扫描（computed tomography, CT）引导下RFA与瘤内化疗（intratumoral chemotherapy, ITC）（RFA-ITC）的有效性和安全性。方法自2005年1月至2015年12月研究组前瞻性入组经病理学证实为早期NSCLC，因心肺功能较差或伴发其他疾病而无法耐受手术或拒绝手术的患者，接受RFA-ITC治疗。RFA采用导向器辅助CT引导穿刺准实时步进法，适形伞状电极、单点或多点消融，完成治疗计划并当CT显示肿瘤周围正常肺组织呈现磨玻璃样后结束消融治疗，经电极针将卡铂200 mg缓慢注射到肿瘤内。随访评估安全性和有效性。结果110例患者125次RFA-ITC治疗，技术成功率为100%。中位生存期为48.0个月，总生存率为55.4个月，无进展生存期为55.1个月；1年、2年、3年、5年总生存率分别为100%、90.7%、62.7%、21.9%。消融后有和无磨玻璃样改变的生存期分别是68.3个月、40.1个月，有统计学差异（P=0.001）。肿瘤的大小及有无N1分期的生存率无差异。无围手术期死亡发生，气胸、肺内出血、胸腔积液、发热、术中胸痛、皮下气肿、术中咳嗽等并发症轻微可耐受。结论CT引导RFA-ITC治疗不能手术的早期NSCLC，疗效好、并发症少，对患者损伤小，为不能手术治疗的早期NSCLC的治疗提供了一个良好方法。

Stereotactic body radiotherapy for early stage lung cancer: History and updated role.

Stereotactic Body Radiotherapy (SBRT) represents a consolidated treatment option for patients with medically inoperable early stage non-small cell lung cancer (NSCLC). The clinical evidence accumulated over the past decade supports its use as an alternative to surgery with comparable survival outcomes. Due to its limited toxicity, SBRT is also applicable to elderly patients with very poor baseline pulmonary function or other severe comorbidities. Recent comparative studies in operable patients raised the issue of the possible use of SBRT also for this subgroup, with quite promising results that still should be fully confirmed by prospective trials with long-term follow up. In early stage lung cancer, clinicians are now faced with a decision-making process that should take into account different factors. The need of pathological diagnosis and accurate nodal staging still represents a challenge, as well as the interpretation of radiological findings after SBRT, often confusing du to the difficulties in distinguishing between radiation-induced changes and local relapse. Aim of this review is to summarize and discuss the major studies on SBRT for early stage lung cancer, providing data on its efficacy and toxicity and discussing the still open issues on its role. Quality of life, pulmonary function and risk of secondary cancers are also discussed, as well as future perspectives and current research topics.