Quality of Large Language Model Responses to Radiation Oncology Patient Care Questions.

Importance: Artificial intelligence (AI) large language models (LLMs) demonstrate potential in simulating human-like dialogue. Their efficacy in accurate patient-clinician communication within radiation oncology has yet to be explored. Objective: To determine an LLM's quality of responses to radiation oncology patient care questions using both domain-specific expertise and domain-agnostic metrics. Design, Setting, and Participants: This cross-sectional study retrieved questions and answers from websites (accessed February 1 to March 20, 2023) affiliated with the National Cancer Institute and the Radiological Society of North America. These questions were used as queries for an AI LLM, ChatGPT version 3.5 (accessed February 20 to April 20, 2023), to prompt LLM-generated responses. Three radiation oncologists and 3 radiation physicists ranked the LLM-generated responses for relative factual correctness, relative completeness, and relative conciseness compared with online expert answers. Statistical analysis was performed from July to October 2023. Main Outcomes and Measures: The LLM's responses were ranked by experts using domain-specific metrics such as relative correctness, conciseness, completeness, and potential harm compared with online expert answers on a 5-point Likert scale. Domain-agnostic metrics encompassing cosine similarity scores, readability scores, word count, lexicon, and syllable counts were computed as independent quality checks for LLM-generated responses. Results: Of the 115 radiation oncology questions retrieved from 4 professional society websites, the LLM performed the same or better in 108 responses (94%) for relative correctness, 89 responses (77%) for completeness, and 105 responses (91%) for conciseness compared with expert answers. Only 2 LLM responses were ranked as having potential harm. The mean (SD) readability consensus score for expert answers was 10.63 (3.17) vs 13.64 (2.22) for LLM answers (P < .001), indicating 10th grade and college reading levels, respectively. The mean (SD) number of syllables was 327.35 (277.15) for expert vs 376.21 (107.89) for LLM answers (P = .07), the mean (SD) word count was 226.33 (191.92) for expert vs 246.26 (69.36) for LLM answers (P = .27), and the mean (SD) lexicon score was 200.15 (171.28) for expert vs 219.10 (61.59) for LLM answers (P = .24). Conclusions and Relevance: In this cross-sectional study, the LLM generated accurate, comprehensive, and concise responses with minimal risk of harm, using language similar to human experts but at a higher reading level. These findings suggest the LLM's potential, with some retraining, as a valuable resource for patient queries in radiation oncology and other medical fields.

GlioPredictor: a deep learning model for identification of high-risk adult IDH-mutant glioma towards adjuvant treatment planning.

Identification of isocitrate dehydrogenase (IDH)-mutant glioma patients at high risk of early progression is critical for radiotherapy treatment planning. Currently tools to stratify risk of early progression are lacking. We sought to identify a combination of molecular markers that could be used to identify patients who may have a greater need for adjuvant radiation therapy machine learning technology. 507 WHO Grade 2 and 3 glioma cases from The Cancer Genome Atlas, and 1309 cases from AACR GENIE v13.0 datasets were studied for genetic disparities between IDH1-wildtype and IDH1-mutant cohorts, and between different age groups. Genetic features such as mutations and copy number variations (CNVs) correlated with IDH1 mutation status were selected as potential inputs to train artificial neural networks (ANNs) to predict IDH1 mutation status. Grade 2 and 3 glioma cases from the Memorial Sloan Kettering dataset (n = 404) and Grade 3 glioma cases with subtotal resection (STR) from Northwestern University (NU) (n = 21) were used to further evaluate the best performing ANN model as independent datasets. IDH1 mutation is associated with decreased CNVs of EGFR (21% vs. 3%), CDKN2A (20% vs. 6%), PTEN (14% vs. 1.7%), and increased percentage of mutations for TP53 (15% vs. 63%), and ATRX (10% vs. 54%), which were all statistically significant (p < 0.001). Age > 40 was unable to identify high-risk IDH1-mutant with early progression. A glioma early progression risk prediction (GlioPredictor) score generated from the best performing ANN model (6/6/6/6/2/1) with 6 inputs, including CNVs of EGFR, PTEN and CDKN2A, mutation status of TP53 and ATRX, patient's age can predict IDH1 mutation status with over 90% accuracy. The GlioPredictor score identified a subgroup of high-risk IDH1-mutant in TCGA and NU datasets with early disease progression (p = 0.0019, 0.0238, respectively). The GlioPredictor that integrates age at diagnosis, CNVs of EGFR, CDKN2A, PTEN and mutation status of TP53, and ATRX can identify a small cohort of IDH-mutant with high risk of early progression. The current version of GlioPredictor mainly incorporated clinically often tested genetic biomarkers. Considering complexity of clinical and genetic features that correlate with glioma progression, future derivatives of GlioPredictor incorporating more inputs can be a potential supplement for adjuvant radiotherapy patient selection of IDH-mutant glioma patients.

SBRT vs. Y90: HCC Treatment Outcomes and Costs.

OBJECTIVES: Stereotactic Body Radiotherapy (SBRT) and Yttrium-90 (Y90) are among the ablative therapies used as treatment options for localized hepatocellular carcinoma (HCC). To date, direct comparisons of the 2 modalities' outcomes and costs are lacking. This study aimed to analyze demographic, treatment, and cost information for patients with HCC treated with SBRT and Y90. METHODS: Patients with HCC treated with SBRT or Y90 radioembolization between January 2018 and January 2020 at one institution were retrospectively reviewed. Demographic and treatment data were compared utilizing χ 2 tests. Kaplan-Meier curves and log-rank tests were applied to compare overall survival and progression-free survival in different treatment groups. Cox proportional hazard models were applied to analyze the unadjusted and adjusted survival differences. Ten SBRT and 10 Y90 patients were randomly selected for Medicare cost analysis. RESULTS: Sixty-three patients received Y90, and 21 received SBRT. On univariable and multivariable analysis, there was no significant difference in overall survival or progression-free survival between the Y90 and SBRT cohorts. SBRT patients had higher American Joint Committee on Cancer staging ( P =0.039), greater tumor size (4.07 vs. 2.96 cm, P =0.013), and greater rates of prior liver-directed therapy (71.4% SBRT vs. 12.7% Y90, P <0.001). The average cost for SBRT was $15,148, and Y90 was $41,360. CONCLUSIONS: SBRT and Y90 are effective therapies in the treatment of HCC, specifically having similar overall survival and progression-free survival. Y90 was found to have a significantly higher cost than SBRT. This study demonstrates the need for prospective studies to assess these modalities in treating HCC.

Integrating POLE/POLD1 mutated for immunotherapy treatment planning of advanced stage non-small cell lung cancer.

BACKGROUND: In this study, we evaluated the potential of DNA polymerase epsilon (POLE) and DNA polymerase delta 1 (POLD1) as prognostic biomarkers for immune checkpoint inhibitor (ICI) treatment in patients with advanced stage non-small cell lung cancer (NSCLC). METHODS: Disease stage, PD-L1 positivity, histological subtypes, POLE/POLD1 mutation status, tumor mutation burden (TMB), and response to ICIs in NSCLC cases were derived from AACR GENIE dataset (n = 24 120), TCGA-Pan Lung Cancer dataset (n = 1144), AACR GENIE BPC NSCLC v2.0-public (n = 2004), and Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets dataset (n = 350). The smoking history from TCGA and AACR GENIE datasets was grouped into current, former or never-smokers. RESULTS: POLE and POLD1 genetic alterations were identified in 5% and 2.6% of NSCLC patients, respectively. Current smokers had 9% and 4% of POLE/POLD1 mutations, respectively, versus 1.7% for both POLE and POLD1 mutations prevalence in never-smokers. POLE/POLD1 mutations were associated with elevated mutation counts than those with wild-type (median mutation counts 16 vs. 7, p < 0.0001), more advanced disease stages (stage I disease 15.19% vs. 29.42%), more prevalent squamous histology subtype (21.69% vs. 9.05%, p = 0.0427), and a higher percentage of PD-L1 positivity (66.67% vs. 43.87%, p < 0.001). Treatment with ICIs improved survival in patients with both POLE/POLD1 mutated and those with TMB > 18 (p < 0.001). CONCLUSION: Current smokers have a five-fold increased risk of having POLE mutations than never-smokers. POLE/POLD1 mutation status and TMB > 18 can be a composite biomarker for selecting NSCLC patients with survival benefits to ICI treatment.

Local Therapies for Hepatocellular Carcinoma and Role of MRI-Guided Adaptive Radiation Therapy.

Hepatocellular carcinoma (HCC) is the most common liver tumor, with a continually rising incidence. The curative treatment for HCC is surgical resection or liver transplantation; however, only a small portion of patients are eligible due to local tumor burden or underlying liver dysfunction. Most HCC patients receive nonsurgical liver-directed therapies (LDTs), including thermal ablation, transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and external beam radiation therapy (EBRT). Stereotactic ablative body radiation (SABR) is a specific type of EBRT that can precisely deliver a high dose of radiation to ablate tumor cells using a small number of treatments (or fractions, typically 5 or less). With onboard MRI imaging, MRI-guided SABR can improve therapeutic dose while minimizing normal tissue exposure. In the current review, we discuss different LDTs and compare them with EBRT, specifically SABR. The emerging MRI-guided adaptive radiation therapy has been reviewed, highlighting its advantages and potential role in HCC management.

Pilot Study Demonstrating the Value of Interdisciplinary Education on the Integration of Radiation Therapy in Lung Cancer Management.

This study aimed to understand baseline knowledge of basic principles of radiation therapy for lung cancer among medical oncology, thoracic surgery, and pulmonology trainees and practicing physicians and also assess whether a didactic lecture will improve objective knowledge and perceived comfort level in making appropriate referrals to radiation oncology (RO). Radiation oncologists at 8 academic institutions offered a presentation covering indications, logistics, efficacy, and toxicity of thoracic radiation. Participants completed a survey to assess their prior exposures to RO and perceived value of the lecture, and objective knowledge gained based on pre/post-lecture questions. Among 121 attendees, 76 completed the pre-test, and 25 the post-test (response rates 62.8% and 20.7%, respectively). Fifty-seven (75.0%) had never previously experienced a RO didactic about lung cancer, 62 (81.6%) had never seen a linear accelerator, and 65 (85.5%) had never rotated in a RO department. The mean pre-test score was 53.5% (SD 17.6%), with a trend (p = 0.066) towards thoracic surgeons (61.5%) performing better than medical oncologists (55.5%) or pulmonologists (48.3%). Level of training (p = 0.130), and prior RO exposures (p = 0.240), did not significantly impact pre-test scores. The mean post-test score of 75.1% (SD 3.6%) was significantly higher than mean pre-test score (p < 0.001). After the lecture, 25 participants (100%) felt more knowledgeable about RO, and 24 (96%) felt more comfortable making appropriate referrals to RO. A didactic lecture about RO for trainees and physicians who treat lung cancer at 8 academic institutions was feasible, filled a gap in exposure, and improved knowledge.

Outcomes following stereotactic radiosurgery for foramen magnum meningiomas: a single-center experience and systematic review of the literature.

OBJECTIVE: Foramen magnum meningiomas (FMMs) pose a unique challenge given their intimate anatomical relationship with the craniovertebral junction. While resection has been studied extensively, much less has been reported about the use of stereotactic radiosurgery (SRS) for FMMs. This study includes what is to the authors' knowledge the first systematic review in the literature that summarizes patient and treatment characteristics and synthesizes outcomes following SRS for FMMs. METHODS: A retrospective chart review was conducted at a single major academic institution, and a systematic review was performed according to PRISMA guidelines. The initial search on the PubMed and Scopus databases yielded 530 results. Key data extracted from both databases included Karnofsky Performance Status (KPS) score and neurological deficits at presentation, tumor location, treatment indication, target volume, single versus multiple fractions, marginal and maximum doses, isodose line, clinical and radiographic follow-up times, and primary (clinical stability and local control at last follow-up) and secondary (mortality, adverse radiation events, time to regression, progression-free survival) outcomes. RESULTS: The study patients included 9 patients from the authors' institution and 165 patients across 4 studies who received SRS for FMMs. The weighted median age at treatment was 60.2 years, and 73.9% of patients were female. Common presenting symptoms included headache (33.9%), dizziness/ataxia (29.7%), cranial nerve deficit(s) (27.9%), numbness (22.4%), weakness (15.2%), and hydrocephalus (4.2%). Lateral/ventrolateral (64.2%) was the most common tumor location. SRS was utilized as the primary therapy in 63.6% of patients and as salvage (21.8%) or adjuvant (14.5%) therapy for the rest of the patients. Most patients (91.5%) were treated with a single fraction. A tumor with a weighted median target volume of 2.9 cm3 was treated with a weighted median marginal dose, maximum dose, and isodose line of 12.9 Gy, 22.8 Gy, and 58%, respectively. Clinical stability and local control at last follow-up were achieved in 98.8% and 97.0% of patients, respectively. Only one possible adverse radiation event occurred, and no mortality directly related to the tumor or SRS was reported. CONCLUSIONS: In this retrospective analysis and systematic review, the authors demonstrate SRS to be an effective and safe treatment option for carefully selected patients with FMMs.

Imaging of GBM in the Age of Molecular Markers and MRI Guided Adaptive Radiation Therapy.

Glioblastoma (GBM) continues to be one of the most lethal malignancies and is almost always fatal. In this review article, the role of radiation therapy, systemic therapy, as well as the molecular basis of classifying GBM is described. Technological advances in the treatment of GBM are outlined as well as the diagnostic imaging characteristics of this tumor. In addition, factors that affect prognosis such as differentiating progression from treatment effect is discussed. The role of MRI guided radiation therapy and how this technology may provide a mechanism to improve the care of patients with this disease are described.

Evolution of Radiation Therapy in Pancreas Cancer Management toward MRI-Guided Adaptive Radiation Therapy.

Pancreas cancer has a poor prognosis despite aggressive treatment and is the fourth leading cause of cancer death in the United States. At diagnosis, most patients have either metastatic or locally advanced disease. In this article, we review the evolution of treatments in locally advanced pancreas cancer (LAPC) and discuss the various radiation therapy fractionation schemes. Furthermore, we examine the data supporting dose escalation and the delivery of ablative biologically effective doses in the setting of LAPC. Finally, we review the role of MRI-guided radiation therapy in escalating dose while sparing organs at risk in the era of stereotactic magnetic resonance-guided adaptive radiation therapy.

Impact of Race and Health Insurance Status on Response to Neoadjuvant Chemotherapy for Breast Cancer Patients.

We evaluated how race, insurance status, and other sociodemographic, tumor, and treatment variables influenced the response to neoadjuvant chemotherapy (NAC) in breast cancer. We performed an IRB-approved retrospective review of 298 breast cancer patients treated with NAC from 2006-2018 at our institution. Univariable and multivariable binary logistic regression analyses were performed to estimate the effects of race, insurance status, and other variables on outcomes. Outcomes of interest included pathologic complete response (pCR), partial response (pPR), and any response (pCR or pPR). Sixty-nine patients (23%) identified as African American. One hundred sixty-eight (57%) patients had private insurance, 71 (24%) had Medicare, 40 (14%) had Medicaid, and 17 (6%) had no insurance. Insurance status was a predictor for any clinical response to NAC in both univariable and multivariable analyses (p<0.01), where odds of pCR or pPR were lower for patients with Medicare compared to private insurance (OR 0.32, 95% CI: 0.15-0.70, p<0.01). Other variables significant for the response to NAC included body mass index, hormone receptor status, clinical group stage, and Ki-67. Race did not influence the response to NAC. Insurance provider, body mass index, hormone receptor status, clinical group stage, and Ki-67 may be useful predictors of treatment outcomes. Future studies that assess the impacts of insurance status and other identified factors on treatment response may help evaluate outcomes in at-risk populations with factors that preclude full benefit from NAC.

Failure mode and effects analysis of linac-based liver stereotactic body radiotherapy.

PURPOSE: Although stereotactic body radiation therapy (SBRT) is an attractive noninvasive approach for liver irradiation, it presents specific challenges associated with respiration-induced liver motion, daily tumor localization due to liver deformation, and poor visualization of target with respect to adjacent normal liver in computed tomography (CT). We aim to identify potential hazards and develop a set of mitigation strategies to improve the safety of our liver SBRT program, using failure mode and effect analysis (FMEA). MATERIALS AND METHODS: A multidisciplinary group consisting of two physicians, three physicists, two dosimetrists, and two therapists was formed. A process map covering ten major stages of the liver SBRT program from the initial diagnosis to posttreatment follow-up was generated. A total of 102 failure modes (FM), together with their causes and effects, were identified. The occurrence (O), severity (S), and lack of detectability (D) were independently scored using a scale from 1 (lowest risk) to 10 (largest risk). The ranking was done using the risk probability number (RPN) defined as the product of average O, S, and D numbers for each mode. Two fault tree analyses were performed. The failure modes with the highest RPN values as well as highest severity score were considered for investigation and a set of mitigation strategies was developed to address these. RESULTS: The median RPN (RPNmed ) values for all modes ranged from of 9 to 105 and the highest median S score (Smed ) was 8. Fourteen FMs were identified to be significant by both RPNmed and Smed (top ten RPNmed ranked and highest Smed FMs) and 12 of them were considered for risk mitigation efforts. The remaining two were omitted due to either sufficient checks already in place, or lack of practical mitigation strategies. Implemented measures consisted of five physics tasks, two physician tasks, and three workflow changes. CONCLUSIONS: The application of FMEA to our liver SBRT program led to the identification of potential FMs and allowed improvement measures to enhance the safety of our clinical practice.

Dose-volume relationship for laryngeal substructures and aspiration in patients with locally advanced head-and-neck cancer.

BACKGROUND: Literature has shown a significant relationship between radiation dose to the larynx and swallowing disorders. We prospectively studied the dose-volume relationship for larynx substructures and aspiration. METHODS: Forty nine patients with stage III/IV head-and-neck (H&N) squamous cell carcinoma were prospectively enrolled in this IRB-approved, federally funded study. All patients received IMRT-based chemoradiation therapy (CRT) and were scheduled for videofluorography (VFG) prior to CRT and at 3, 6, 9, 12, and 24 months post-CRT. Twelve laryngeal substructures were contoured in each patient: thyroid cartilage, cricoid cartilage, total epiglottis, suprahyoid epiglottis, infrahyoid epiglottis, total larynx, supraglottic larynx, subglottic larynx, glottic larynx, arytenoids, aryepiglottic (AE) folds, and glossoepiglottic fold. After exclusions, 29 patients were included in the final analysis. Incidence of aspiration at 1 year following CRT was correlated with dose-volume data to laryngeal substructures using logistic regression. RESULTS: The median age was 54 years with 79% being non-smokers. Tumor sites included oropharynx (22), unknown primary (6), and hypopharynx (1). One year following CRT, 10/29 (34%) showed aspiration on VFG. Dose to the AE folds showed the highest correlation with aspiration at 12 months and was significant on multivariate analysis (p = 0.025). A mean dose cutpoint of 6500 cGy or higher to the AE folds was associated with an increased risk of aspiration at 1 year [positive likelihood ratio (+LR) 2.81, positive predictive value (PPV) 60%, negative predictive value (NPV) 92.9%, relative risk (RR) 8.4]. CONCLUSIONS: In this analysis, mean dose to the AE folds was associated with an increased risk of aspiration at 1 year. However, these are hypothesis-generating data that require further research and validation in a larger patient subset.

Differences in United States Insurance Payer Policies and American Society for Radiation Oncology's (ASTRO) Model Policy on Stereotactic Body Radiation Therapy (SBRT).

PURPOSE: Insurance payers in the United States vary in the indications for which they consider stereotactic body radiation therapy (SBRT) "medically necessary." We compared changes in policies after the last update to the American Society for Radiation Oncology's (ASTRO) SBRT model policy. METHODS AND MATERIALS: We identified 77 payers with SBRT policies in 2015 from a policy aggregator, as well as 4 national benefits managers (NBMs). Of these, 65 payers and 3 NBMs had publicly available updates since 2015. For each of the indications in ASTRO's model policy, we calculated the proportion of payers that considered SBRT medically necessary. We used Fisher's exact test to compare these proportions between 2015 and now, between policies updated in the past 12 months and those updated less often, and between national and regional payers currently. RESULTS: Payers consider SBRT medically necessary most often for primary lung cancer (97%), reirradiation to the spine (91%), prostate cancer (68%), primary liver cancer (66%), and spinal metastases with radioresistant histologies (66%). Policies have become more aligned with ASTRO's model policy over time. National payers and NBMs cover indications in higher proportions than regional payers. CONCLUSIONS: Although there have been improvements over time, more work is needed to align payer policies with ASTRO's model SBRT policy, especially at the regional level.

Intraoperative Radiation "Boost" to the Surgical Resection Bed following Pancreaticoduodenectomy for a Borderline Resectable Pancreatic Carcinoma: A Case Report.

Neoadjuvant therapy including chemotherapy alone or concurrent chemotherapy with external bream radiation is a standard treatment strategy for borderline resectable pancreatic adenocarcinoma and is also used routinely for primary operable cancers at some institutions (1). The use of intraoperative radiation therapy (IORT) has been limited largely because of the logistical issues in delivery of radiation during surgery (2). This is the first reported case of a borderline resectable pancreas cancer patient who underwent neoadjuvant chemo-radiation therapy followed by resection with the use of IORT using the mobile IntraBeam device to boost the resection bed and improve local control by dose escalation.

Intraoperative Radiotherapy With INTRABEAM: Technical and Dosimetric Considerations.

PURPOSE: We evaluate dose characteristics and clinical applications of treatment accessories used in intraoperative radiotherapy (IORT) and make site-specific recommendations for their optimal use. METHODS AND MATERIALS: Dose measurements were performed for a low energy (50 kV) X-ray INTRABEAM source. For spherical, flat, surface, and needle applicators, the following dosimetric parameters were measured: depth-dose (DD) profiles, surface dose (Ds), output factors (OF), and target dose homogeneity (DH). Optical density versus exposure calibration films were employed to obtain 2-dimensional dose distributions in planes parallel and perpendicular to beam direction. Film results were verified via repeat dose measurements with a parallel-plate ionization chamber in a custom water tank. The impact of applicator design on dose distributions was evaluated. RESULTS: Spherical applicators are commonly used for treating the inner-surface of breast lumpectomy cavity. Flat and surface applicators provide uniform planar dose for head and neck, abdomen, and pelvis targets. Needle applicators are designed for kypho-IORT of spinal metastasis. Typically, larger applicators produce a more homogeneous target dose region with lower surface dose, but require longer treatment times. For 4-cm diameter spherical, flat, and surface applicators, dose rates (DR) at their respective prescription points were found to be: 0.8, 0.3, and 2.2 Gy/min, respectively. The DR for a needle applicator was 7.04 Gy/min at 5 mm distance from the applicator surface. Overall, film results were in excellent agreement with ion-chamber data. CONCLUSION: IORT may be delivered with a variety of site-specific applicators. Appropriate applicator use is paramount for safe, effective, and efficient IORT delivery. Results of this study should help clinicians assure optimized target dose coverage and reduced normal tissue exposure.

Single-Fraction Radiotherapy for CD30(+) Lymphoproliferative Disorders.

OBJECTIVES: CD30(+) lymphoproliferative disorder is a rare variant of cutaneous T-cell lymphoma. Sustained complete response following first-line treatments is rare. This retrospective review evaluates the response of refractory or recurrent lesions to palliative radiation therapy. METHODS: The records of 6 patients with 12 lesions, treated with radiation therapy, were reviewed. All patients received previous first-line treatments. Patients with clinical and pathological evidence of symptomatic CD30(+) lymphoproliferative disorder, with no history of other cutaneous T-cell lymphoma variants, and with no prior radiation therapy to the index site were included. RESULTS: The median age of patients was 50.5 years (range, 15-83 years). Median size of the treated lesions was 2.5 cm (range, 2-7 cm). Four sites were treated with a single fraction of 750-800 cGy (n = 3) and 8 sites were treated with 4000-4500 cGy in 200-250 cGy fractions (n = 3). Radiation therapy was administered with electrons and bolus. Median follow-up was 113 months (range, 16-147 months). For all sites, there was 100% complete response with acute grade 1-2 dermatitis. CONCLUSIONS: For recurrent and symptomatic radiation-naïve CD30(+) lymphoproliferative disorder lesions, palliative radiation therapy shows excellent response. A single fraction of 750-800 cGy is as effective as a multifractionated course and more convenient.

Primary Treatment Options for High-Risk/Medically Inoperable Early Stage NSCLC Patients.

Lung cancer is among the most common cancers worldwide and is the leading cause of cancer death in both men and women. For patients with early stage (American Joint Committee on Cancer T1-2, N0) non-small-cell lung cancer, the current standard of care is lobectomy with systematic lymph node evaluation. Unfortunately, patients with lung cancer often have medical comorbities, which may preclude the option of surgical resection. In such cases, a number of minimally invasive to noninvasive treatment options have gained popularity in the treatment of these high-risk patients. These modalities provide significant advantages, including patient convenience, treatment in an outpatient setting, and acceptable toxicities, including reduced impact on lung function and a modest risk of postprocedure chest wall pain. We provide a comprehensive review of the literature, including reported outcomes, complications, and limitations of sublobar resection with or without intraoperative brachytherapy, radiofrequency ablation, microwave ablation, percutaneous cryoablation, photodynamic therapy, and stereotactic body radiotherapy.