NCCN Guidelines® Insights: Head and Neck Cancers, Version 1.2022.

The NCCN Guidelines for Head and Neck Cancers address tumors arising in the oral cavity (including mucosal lip), pharynx, larynx, and paranasal sinuses. Occult primary cancer, salivary gland cancer, and mucosal melanoma (MM) are also addressed. The specific site of disease, stage, and pathologic findings guide treatment (eg, the appropriate surgical procedure, radiation targets, dose and fractionation of radiation, indications for systemic therapy). The NCCN Head and Neck Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's most recent recommendations regarding management of HPV-positive oropharynx cancer and ongoing research in this area.

Head and Neck Cancers, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.

Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a multidisciplinary team of experts. This article describes supportive care recommendations in the NCCN Guidelines for Head and Neck Cancers, as well as the rationale supporting a new section on imaging recommendations for patients with H&N cancers. This article also describes updates to treatment recommendations for patients with very advanced H&N cancers and salivary gland tumors, specifically systemic therapy recommendations.

The radiation dose-response of non-retroperitoneal soft tissue sarcoma with positive margins: An NCDB analysis.

OBJECTIVES: Positive margins can increase the risk of local recurrence of soft tissue sarcomas (STS). Utilizing a national registry, we investigated patterns of care and overall survival (OS) of patients with margin-positive non-retroperitoneal STS who received preoperative radiation therapy, adjuvant radiation therapy, or both. METHODS: Adult patients with non-retroperitoneal STS who underwent resection and RT from 2004 to 2015 were included. Kaplan-Meier, log-rank analysis, and Cox regression analysis were performed. RESULTS: We identified 5726 patients. Most had a tumor size >5 cm (60%), grade 3 disease (67%), and microscopically positive margins (57%). Compared to ≤50.4 Gy, a dose of 66 to 69.99 Gy was associated with decreased risk of death on multivariate analysis (HR 0.69, 95%; CI, 0.50-0.94). Receipt of a boost was associated with decreased risk of death on univariate analysis (HR 0.54, 95%; CI, 0.29-0.99). In patients with grade 2 to 3 tumors without the gross disease, there was an OS benefit associated with a boost on multivariate analysis (HR 0.39, 95%; CI, 0.16-0.97). CONCLUSION: This analysis appears to show an OS benefit of dose escalation to 66 to 69 Gy for margin-positive non-retroperitoneal STS. A Postoperative boost is associated with higher OS in grade 2 to 3 STS without the gross disease.

NCCN Guidelines Insights: Head and Neck Cancers, Version 1.2018.

The NCCN Guidelines for Head and Neck (H&N) Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the H&N, and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding evaluation and treatment of nasopharyngeal carcinoma.

NCCN Guidelines Insights: Head and Neck Cancers, Version 2.2017.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the head and neck (H&N), and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding the increase in human papillomavirus-associated oropharyngeal cancer and the availability of immunotherapy agents for treatment of patients with recurrent or metastatic H&N cancer.

Early radiotherapy has an essential role for improving survival in patients with stage I-II nasal-type of NK/T cell lymphoma treated with L-asparaginase-containing chemotherapy--a single institution experience.

The purpose of this study was to investigate the role of early radiotherapy in patients with localized-stage nasal-type natural killer (NK)/T cell lymphoma treated with L-asparaginase-containing chemotherapy. Sixty-four patients with stage I-II nasal-type NK/T cell lymphoma were enrolled in this study. All patients received an L-asparaginase-containing regimen. Thirty-four patients received late radiotherapy (RT), which was defined as receiving 6 cycles of prior chemotherapy (CT) followed by RT, and 30 patients received early RT, which was defined as receiving no more than 3 cycles of CT followed by early RT. With a median follow-up of 35 months (range, 12-49 months), 19 patients (29.7 %) died from lymphoma-related causes, and 22 patients (34.4 %) developed local and/or distant relapse. The 3-year overall survival (OS) and progression-free survival (PFS) were 84.2 and 74.3 % for early RT and 57.6 and 55.9 % for late RT, respectively, and these differences were significant (OS, p = 0.027; PFS, p = 0.034). After 2 cycles of initial CT, 58 patients achieved treatment response (complete response and partial response). For the 58 patients, there were still significant differences for 3-year OS and PFS when early RT was compared with late RT (3-year OS 94.4 vs. 58 %, P = 0.005; 3-year PFS 82.9 vs. 56.3 %, P = 0.01). Early RT has an essential role in improving survival for localized-stage nasal-type NK/T cell lymphoma (TCL) patients even when used in combination with L-asparaginase-containing CT. Prospective, randomized studies should to be performed to confirm these results.

Head and Neck Cancers, Version 1.2015.

These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Head and Neck (H&N) Cancers. These Insights describe the different types of particle therapy that may be used to treat H&N cancers, in contrast to traditional radiation therapy (RT) with photons (x-ray). Research is ongoing regarding the different types of particle therapy, including protons and carbon ions, with the goals of reducing the long-term side effects from RT and improving the therapeutic index. For the 2015 update, the NCCN H&N Cancers Panel agreed to delete recommendations for neutron therapy for salivary gland cancers, because of its limited availability, which has decreased over the past 2 decades; the small number of patients in the United States who currently receive this treatment; and concerns that the toxicity of neutron therapy may offset potential disease control advantages.

Head and neck cancers, Version 2.2014. Clinical practice guidelines in oncology.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers focuses on glottic laryngeal cancer, which is the most common type of laryngeal cancer and has an excellent cure rate. The lymphatic drainage of the glottis is sparse, and early stage primaries rarely spread to regional nodes. Because hoarseness is an early symptom, most glottic laryngeal cancer is early stage at diagnosis. Updates to these guidelines for 2014 include revisions to "Principles of Radiation Therapy" for each site and "Principles of Surgery," and the addition of a new section on "Principles of Dental Evaluation and Management."

Patterns of failure and predictors of outcome in cutaneous malignant melanoma of the scalp.

BACKGROUND: Patients with melanoma of the scalp may have higher failure (recurrence) rates than melanoma of other body sites. OBJECTIVE: We sought to characterize survival and patterns of failure for patients with scalp melanoma. METHODS: Between 1998 and 2010, 250 nonmetastatic patients underwent wide local excision of a primary scalp melanoma. Kaplan-Meier analyses were performed to evaluate overall survival, scalp control, regional neck control, distant metastases-free survival, and disease-free survival. RESULTS: Five-year overall survival was 86%, 57%, and 45% for stages I, II, and III, respectively, and 5-year scalp control rates were 92%, 75%, and 63%, respectively. Five-year distant metastases-free survival for these stages were 92%, 65%, and 45%, respectively. Of the 74 patients who recurred, the site of first recurrence included distant disease in 47%, although 31% recurred in the scalp alone. LIMITATIONS: This is a retrospective review. CONCLUSION: Distant metastases-free survival and overall survival for stage II and III patients with scalp melanoma are poor, and stage III patients experience relatively high rates of scalp failure suggesting that these patients may benefit from additional adjuvant systemic and local therapy. Further research is needed to characterize the environmental, microenvironmental, and genetic causes of the increased aggressiveness of scalp melanoma and to identify more effective treatment and surveillance methods.

Head and neck cancers, version 2.2013. Featured updates to the NCCN guidelines.

These NCCN Guidelines Insights focus on nutrition and supportive care for patients with head and neck cancers. This topic was a recent addition to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers. The NCCN Guidelines Insights focus on major updates to the NCCN Guidelines and discuss the new updates in greater detail. The complete version of the NCCN Guidelines for Head and Neck Cancers is available on the NCCN Web site (NCCN.org).

Survival outcomes for patients with T3N0M0 squamous cell carcinoma of the glottis treated with definitive radiation alone versus chemoradiation.

BACKGROUND: Given the poor lymphatics of the glottis, we evaluated omission of chemotherapy in patients treated definitely for T3N0M0 squamous cell carcinoma (SCC) of the glottis. METHODS: We performed survival analysis of patients with T3N0M0 SCC of the glottis identified in the National Cancer Database treated with radiation alone versus chemoradiation. RESULTS: A total of 3785 patients were identified. Patients age ≥70 and those with comorbidities were less likely to receive chemotherapy (odds ratio [OR] 0.30, 95% CI [0.25-0.37] and 0.48 [0.31-0.76], respectively). Five-year OS was lower in patients treated with radiation versus chemoradiation (33.8% [30.3%-37.2%] vs. 58.0% [55.8%-60.0%]). In patients <70 with no comorbidities this difference persisted (51.0% [44.5%-57.0%] versus 66.7% [64.0%-69.3%]). CONCLUSION: Overall survival was higher in patients treated with chemoradiation compared to radiation alone, even when controlling for age and comorbidities. Radiotherapy with chemotherapy omission is not appropriate in patients with T3N0M0 SCC of the glottis.

Pathologic Complete Response and Clinical Outcomes in Patients With Localized Soft Tissue Sarcoma Treated With Neoadjuvant Chemoradiotherapy or Radiotherapy: The NRG/RTOG 9514 and 0630 Nonrandomized Clinical Trials.

Importance: Pathologic complete response (pCR) may be associated with prognosis in patients with soft tissue sarcoma (STS). Objective: We sought to determine the prognostic significance of pCR on survival outcomes in STS for patients receiving neoadjuvant chemoradiotherapy (CT-RT) (Radiation Therapy Oncology Group [RTOG] 9514) or preoperative image-guided radiotherapy alone (RT, RTOG 0630) and provide a long-term update of RTOG 0630. Design, Setting, and Participants: RTOG has completed 2 multi-institutional, nonrandomized phase 2 clinical trials for patients with localized STS. One hundred forty-three eligible patients from RTOG 0630 (n = 79) and RTOG 9514 (n = 64) were included in this ancillary analysis of pCR and 79 patients from RTOG 0630 were evaluated for long-term outcomes. Intervention: Patients in trial 9514 received CT interdigitated with RT, whereas those in trial 0630 received preoperative RT alone. Main Outcomes and Measures: Overall and disease-free survival (OS and DFS) rates were estimated by the Kaplan-Meier method. Hazard ratios (HRs) and P values were estimated by multivariable Cox model stratified by study, where possible; otherwise, P values were calculated by stratified log-rank test. Analysis took place between December 14, 2016, to April 13, 2017. Results: Overall there were 42 (53.2%) men; 68 (86.1%) were white; with a mean (SD) age of 59.6 (14.5) years. For RTOG 0630, at median follow-up of 6.0 years, there was 1 new in-field recurrence and 1 new distant failure since the initial report. From both studies, 123 patients were evaluable for pCR: 14 of 51 (27.5%) in trial 9514 and 14 of 72 (19.4%) in trial 0630 had pCR. Five-year OS was 100% for patients with pCR vs 76.5% (95% CI, 62.3%-90.8%) and 56.4% (95% CI, 43.3%-69.5%) for patients with less than pCR in trials 9514 and 0630, respectively. Overall, pCR was associated with improved OS (P = .01) and DFS (HR, 4.91; 95% CI, 1.51-15.93; P = .008) relative to less than pCR. Five-year local failure rate was 0% in patients with pCR vs 11.7% (95% CI, 3.6%-25.1%) and 9.1% (95% CI, 3.3%-18.5%) for patients with less than pCR in 9514 and 0630, respectively. Histologic types other than leiomyosarcoma, liposarcoma, and myxofibrosarcoma were associated with worse OS (HR, 2.24; 95% CI, 1.12-4.45). Conclusions and Relevance: This ancillary analysis of 2 nonrandomized clinical trials found that pCR was associated with improved survival in patients with STS and should be considered as a prognostic factor of clinical outcomes for future studies. Trial Registration: ClinicalTrials.gov Identifiers: RTOG 0630 (NCT00589121); RTOG 9514 (NCT00002791).

Stereotactic Radiosurgery vs Conventional Radiotherapy for Localized Vertebral Metastases of the Spine: Phase 3 Results of NRG Oncology/RTOG 0631 Randomized Clinical Trial.

Importance: Spine metastasis can be treated with high-dose radiation therapy with advanced delivery technology for long-term tumor and pain control. Objective: To assess whether patient-reported pain relief was improved with stereotactic radiosurgery (SRS) as compared with conventional external beam radiotherapy (cEBRT) for patients with 1 to 3 sites of vertebral metastases. Design, Setting, and Participants: In this randomized clinical trial, patients with 1 to 3 vertebral metastases were randomized 2:1 to the SRS or cEBRT groups. This NRG 0631 phase 3 study was performed as multi-institutional enrollment within NRG Oncology. Eligibility criteria included the following: (1) solitary vertebral metastasis, (2) 2 contiguous vertebral levels involved, or (3) maximum of 3 separate sites. Each site may involve up to 2 contiguous vertebral bodies. A total of 353 patients enrolled in the trial, and 339 patients were analyzed. This analysis includes data extracted on March 9, 2020. Interventions: Patients randomized to the SRS group were treated with a single dose of 16 or 18 Gy (to convert to rad, multiply by 100) given to the involved vertebral level(s) only, not including any additional spine levels. Patients assigned to cEBRT were treated with 8 Gy given to the involved vertebra plus 1 additional vertebra above and below. Main Outcomes and Measures: The primary end point was patient-reported pain response defined as at least a 3-point improvement on the Numerical Rating Pain Scale (NRPS) without worsening in pain at the secondary site(s) or the use of pain medication. Secondary end points included treatment-related toxic effects, quality of life, and long-term effects on vertebral bone and spinal cord. Results: A total of 339 patients (mean [SD] age of SRS group vs cEBRT group, respectively, 61.9 [13.1] years vs 63.7 [11.9] years; 114 [54.5%] male in SRS group vs 70 [53.8%] male in cEBRT group) were analyzed. The baseline mean (SD) pain score at the index vertebra was 6.06 (2.61) in the SRS group and 5.88 (2.41) in the cEBRT group. The primary end point of pain response at 3 months favored cEBRT (41.3% for SRS vs 60.5% for cEBRT; difference, -19 percentage points; 95% CI, -32.9 to -5.5; 1-sided P = .99; 2-sided P = .01). Zubrod score (a measure of performance status ranging from 0 to 4, with 0 being fully functional and asymptomatic, and 4 being bedridden) was the significant factor influencing pain response. There were no differences in the proportion of acute or late adverse effects. Vertebral compression fracture at 24 months was 19.5% with SRS and 21.6% with cEBRT (P = .59). There were no spinal cord complications reported at 24 months. Conclusions and Relevance: In this randomized clinical trial, superiority of SRS for the primary end point of patient-reported pain response at 3 months was not found, and there were no spinal cord complications at 2 years after SRS. This finding may inform further investigation of using spine radiosurgery in the setting of oligometastases, where durability of cancer control is essential. Trial Registration: ClinicalTrials.gov Identifier: NCT00922974.

Comparing adjuvant radiation to adjuvant chemoradiation in postsurgical p16+ oropharyngeal carcinoma patients with extranodal extension or positive margins.

BACKGROUND: Adjuvant guidelines in surgically resected p16+ oropharyngeal carcinoma (OPC) with positive surgical margins (PSM) or extranodal extension (ENE) are based on randomized controlled trials predating p16 status. It remains unclear if adjuvant chemotherapy is necessary in p16+ patients with these features. METHODS: The National Cancer Database was used to identify cases of nonmetastatic p16+ OPC diagnosed from 2010 to 2017. Patients treated with surgical resection followed by adjuvant radiation (aRT) or adjuvant chemoradiation (aCRT) were eligible for analysis. RESULTS: A total of 14 071 patients were eligible for analysis. Overall survival (OS) was not statistically different between aRT and aCRT in patients with PSM (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.56-1.28), ENE (HR 0.93, 95% CI 0.69-1.27) or both (HR 0.73, 95% CI 0.41-1.31). CONCLUSIONS: In patients with p16+ OPC with ENE, PSM, or both, adding chemotherapy to aRT was not associated with improved OS.

Evaluation of the dosimetric impact of changes in shoulder position on target coverage for spine SBRT to metastases in the lower cervical spine region.

For patients treated with SBRT for spinal metastases in the cervical area, a thermoplastic mask is the usual immobilization technique. This project investigates the impact of shoulder position variability on target coverage for such cases. Eight HN patients treated in a suite equipped with a CT-on-rails system (CTOR) were randomly chosen. Of these, three were treated with shoulder depressors. For each patient, their planning CT was used to contour spine targets at the C5, C6 and C7 levels for which two VMAT plans were developed to deliver 18 Gy to each target per the RTOG 0631 protocol. One plan used full arcs while the other used avoidance sectors around the lateral positions. For each patient, IGRT CTOR images were used to recalculate doses that would have been delivered from these plans. Target coverage and dose to the spinal cord were compared for four scenarios: full and partial arcs, with or without depressors. A Dunn test showed significant differences between groups with and without shoulder depressors, but not between those with full versus partial arcs. For most of the investigated cases, the coverage ended up being higher than planned due to the shoulder position being inferior at treatment compared to simulation. In some cases, this led to higher spinal cord doses than allowed per protocol. The results of this study confirm that, when treating lower cervical spine lesions with SBRT, special care should be taken to ensure that the shoulders are positioned as they were during planning CT acquisition.

Radiotherapy and extent of surgical resection in retroperitoneal soft-tissue sarcoma: multi-institutional analysis of 261 patients.

BACKGROUND AND OBJECTIVE: To examine the impact of adjuvant radiotherapy (RT) and surgical technique on survival in retroperitoneal soft-tissue sarcoma. METHODS: A retrospective analysis was conducted using the National Oncology Database, a proprietary database of aggregated tumor registries owned by IMPAC(R) Medical Systems (Sunnyvale, CA). Patients who received definitive surgery with negative or microscopic-positive margins were included. Multivariate analysis was performed using the Cox proportional hazards model. Survival curves were estimated by the Kaplan-Meier method and were compared for statistical significance (P < 0.05) using the log-rank test. RESULTS: Two hundred sixty-one patients met inclusion criteria. The median follow-up was 59 months (range 0.2-186 months). The 5-year cause-specific survival (CSS) and local failure-free survival (LFFS) were 73% and 66%, respectively. Grade, margin status, and histology were independent predictors for CSS (P < 0.05). Adjuvant RT was associated with a significant improvement in LFFS over surgery alone (hazard ratio = 0.42, 95% confidence interval 0.21-0.86, P < 0.05). Patients receiving simple excision and RT had a 5-year LFFS of 88%, significantly higher than wide resection with or without RT (log-rank, P < 0.05). CONCLUSION: Adjuvant RT is associated with a lower risk of local relapse compared to surgery alone. The impact of surgical technique on adjuvant RT efficacy warrants further study.

Evaluation of fluence-smoothing feature for three IMRT planning systems.

Commercially available intensity-modulated radiation therapy (IMRT) inverse treatment planning systems (ITPS) typically include a smoothing function which allows the user to vary the complexity of delivered beam fluence patterns. This study evaluated the behavior of three ITPSs when varying smoothing parameters. We evaluated four cases treated with IMRT in our clinic: sinonasal carcinoma (SNC), glioblastoma multiforme (GBM), base of tongue carcinoma (BOT), and prostate carcinoma (PST). Varian Eclipse v6.5, BrainLAB BrainScan v5.31, and Nomos Corvus v6.2 ITPSs were studied for the SNC, GBM, and PST sites. Only Eclipse and Corvus were studied for BOT due to field size constraints of the BrainLAB MM3 collimator. For each ITPS, plans were first optimized using vendor- recommended default "smoothing" values. Treatment plans were then reoptimized, exploring various smoothing values. Key metrics recorded included a delivery complexity (DC) metric and the Ian Paddick Conformality Index (IPCI). Results varied widely by vendor with regard to the impact of smoothing on complexity and conformality. Plans run on the Corvus ITPS showed the logically anticipated increase in DC as smoothing was decreased, along with associated improved organ-at-risk (OAR) sparing. Both Eclipse and BrainScan experienced an expected trend for increased DC as smoothing was decreased. However, this increase did not typically result in appreciably improved OAR sparing. For Eclipse and Corvus, and to a much lesser extent BrainScan, increases in smoothing decreased DC but eventually caused unacceptable losses in plan quality. Depending on the ITPS, potential benefits from optimizing fluence smoothing levels can be significant, allowing for increases in either efficiency or conformality. Because of variability in smoothing function behavior by ITPS, it is important that users familiarize themselves with the effects of varying smoothing parameters for their respective ITPS. Based on experience gained here, we provide recommended workflows for each ITPS to best exploit the fluence-smoothing features of the system.

Evaluation of dose distribution differences from five algorithms implemented in three commercial treatment planning systems for lung SBRT.

Early stage lung cancer is increasingly being treated using stereotactic body radiation therapy (SBRT). Several advanced treatment planning algorithms are now available in various commercial treatment planning systems. This work compares the dose distributions calculated for the same treatment plan using, five algorithms, in three different treatment planning systems. All plans were normalized to ensure the prescription dose covers 95% of the planning target volume (PTV). Dose to the planning target volume (PTV) was compared using near-minimum dose (D98%), near-maximum dose (D2%) and dose homogeneity, while dose fall-off was compared using D2cm and R50. Dose to the lung was compared using V5Gy, V20Gy and mean lung dose. Statistical analysis shows that dose distributions calculated using Eclipse's Acuros XB and RayStation's Monte Carlo were significantly different from the other dose distributions for the PTV dose parameters investigated. For lung dosimetric parameters, this difference persisted for volumetric modulated arc therapy (VMAT) plans but not for conformal arc plans. While normal tissue complication probability (NTCP) differences were significant for some of the algorithms for VMAT delivery approaches, they were not significantly different for any algorithm for conformal arc plans. All parameters investigated here were within 5% between all algorithms. The results show that, while some small dosimetric differences can be expected around the PTV, the dose distribution to the rest of the treatment area, especially the lungs, should not be clinically-relevant when switching between one of the five algorithms investigated.

Radiation therapy and secondary malignancy in Li-Fraumeni syndrome: A hereditary cancer registry study.

BACKGROUND: Li-Fraumeni Syndrome (LFS) is a rare cancer-predisposing condition caused by germline mutations in TP53. Conventional wisdom and prior work has implied an increased risk of secondary malignancy in LFS patients treated with radiation therapy (RT); however, this risk is not well-characterized. Here we describe the risk of subsequent malignancy and cancer-related death in LFS patients after undergoing RT for a first or second primary cancer. METHODS: We reviewed a multi-institutional hereditary cancer registry of patients with germline TP53 mutations who were treated from 2004 to 2017. We assessed the rate of subsequent malignancy and death in the patients who received RT (RT group) as part of their cancer treatment compared to those who did not (non-RT group). RESULTS: Forty patients with LFS were identified and 14 received RT with curative intent as part of their cancer treatment. The median time to follow-up after RT was 4.5 years. Fifty percent (7/14) of patients in the curative-intent group developed a subsequent malignancy (median time 3.5 years) compared to 46% of patients in the non-RT group (median time 5.0 years). Four of seven subsequent malignancies occurred within a prior radiation field and all shared histology with the primary cancer suggesting recurrence rather than new malignancy. CONCLUSION: We found that four of14 patients treated with RT developed in-field malignancies. All had the same histology as the primary suggesting local recurrences rather than RT-induced malignancies. We recommend that RT should be considered as part of the treatment algorithm when clinically indicated and after multidisciplinary discussion.

Preliminary clinical experience with Calypso anchored beacons for tumor tracking in lung SBRT.

PURPOSE: To present our preliminary experience with the recently released Calypso lung beacons to track lung tumor location during stereotactic body radiation therapy (SBRT). MATERIALS/METHODS: Five recent lung SBRT patients had Calypso lung beacons implanted for tumor tracking during treatment. Beacons were placed by a pulmonologist using fluoroscopic navigation within 1 week prior to planning four-dimensional computed tomography (4DCT) acquisition. Patients were immobilized in a full-body double-vacuum bag. For the first three patients, a verification 4DCT was obtained prior to the first fraction with the patient in the treatment position to assess both beacon migration and motion of tumor and beacons relative to planning day. For each treatment fraction, Calypso was used to position the patient. A verification cone-beam CT (CBCT) confirmed the Calypso-defined target position was appropriate. Real-time Calypso tracking information was also acquired and compared to an action level that was used to determine if the tumor migrated outside of the planning target volume. RESULTS: For four patients, the implant procedure was well tolerated, with average CBCT-based shifts being within 0.2 mm of the shifts reported by Calypso at the time of imaging. The other patient had a small pneumothorax due to very peripheral tumor location and experienced beacon migration. However, the patient quickly recovered from the pneumothorax, and after deactivating that beacon, motion tracking was possible throughout his treatment. CONCLUSIONS: All patients were successfully treated with SBRT using the newly released Calypso lung beacons, with initial positioning confirmed by this clinic's current clinical standard of CBCT. The system allowed us to validate, with real-time confirmation, that the planned internal target volumes were appropriate to each day's extent of actual tumor motion. An efficient and effective workflow for utilizing the new lung beacons for SBRT treatments was developed.