Utilization and Survival Impact of Hypofractionated Radiotherapy in Stage I Non-small Cell Lung Cancer.

OBJECTIVES: The optimal fractionation schedule in unresected stage I non-small cell lung cancer (NSCLC) unsuitable for stereotactic body radiation therapy is unclear. Given the lack of comparative data regarding nonstereotactic body radiation therapy schemas, we compared overall survival (OS) with hypofractionated radiotherapy (HFRT) versus conventionally fractionated radiotherapy (CFRT) and examined the OS impact of different HFRT doses. MATERIALS AND METHODS: This retrospective analysis included 2159 patients from the National Cancer Database diagnosed with stage I (cT1-2aN0M0) NSCLC between 2008 and 2016. Patients underwent CFRT (70≤BED10 [biologically effective dose] <100 Gy10 in ≥30 fractions), low-dose HFRT (LD-HFRT; 70≤BED10 [assuming α/ß=10] <100 Gy10 in 11 to 24 fractions), or high-dose HFRT (HD-HFRT; 100≤BED10 ≤120 Gy10 in 6 to 10 fractions). Patients who received surgery, chemotherapy, or immunotherapy were excluded. We compared CFRT versus all HFRT, and separately CFRT versus LD-HFRT and CFRT versus HD-HFRT. OS was evaluated with the Kaplan-Meier estimator, log-rank test, and Cox regression. RESULTS: A total of 63.2% of patients underwent CFRT, 23.5% LD-HFRT, and 13.3% HD-HFRT. OS was significantly longer with HFRT versus CFRT on univariable (28.2 mo [95% CI, 25.6-31.7] vs 26.4 mo [25.0-27.9]; log-rank=0.0025) but not multivariable analysis (MVA; hazard ratio [HR] 0.90; P=0.062). MVA yielded no significant difference in OS between CFRT and LD-HFRT (HR 0.96, P=0.53). OS was significantly longer with HD-HFRT versus CFRT on MVA (HR, 0.75; P=0.003). However, on sensitivity analysis using different multivariable modeling techniques, this did not retain statistical significance (HR, 0.83; P=0.12). CONCLUSIONS: For stage I NSCLC, HFRT does not show a robust OS benefit compared with CFRT but may be preferred given the convenience and lower costs.

Early-Stage Primary Lung Neuroendocrine Tumors Treated With Stereotactic Body Radiation Therapy: A Multi-Institution Experience.

PURPOSE: Current guidelines recommend surgery as standard of care for primary lung neuroendocrine tumor (LNET). Given that LNET is a rare clinical entity, there is a lack of literature regarding treatment of LNET with stereotactic body radiation therapy (SBRT). We hypothesized that SBRT could lead to effective locoregional tumor control and long-term outcomes. METHODS AND MATERIALS: We retrospectively reviewed 48 tumors in 46 patients from 11 institutions with a histologically confirmed diagnosis of LNET, treated with primary radiation therapy. Data were collected for patients treated nonoperatively with primary radiation therapy between 2006 and 2020. Patient records were reviewed for lesion characteristics and clinical risk factors. Kaplan-Meier analysis, log-rank tests, and Cox multivariate models were used to compare outcomes. RESULTS: Median age at treatment was 71 years and mean tumor size was 2 cm. Thirty-two lesions were typical carcinoid histology, 7 were atypical, and 9 were indeterminate. The most common SBRT fractionation schedule was 50 to 60 Gy in 5 daily fractions. Overall survival at 3, 6, and 9 years was 64%, 43%, and 26%, respectively. Progression-free survival at 3, 6, and 9 years was 88%, 78%, and 78%, respectively. Local control at 3, 6, and 9 years was 97%, 91%, and 91%, respectively. There was 1 regional recurrence in a paraesophageal lymph node. No grade 3 or higher toxicity was identified. CONCLUSIONS: This is the largest series evaluating outcomes in patients with LNET treated with SBRT. This treatment is well tolerated, provides excellent locoregional control, and should be offered as an alternative to surgical resection for patients with early-stage LNET, particularly those who may not be ideal surgical candidates.

Prediction of Distant Metastases After Stereotactic Body Radiation Therapy for Early Stage NSCLC: Development and External Validation of a Multi-Institutional Model.

INTRODUCTION: Distant metastases (DMs) are the primary driver of mortality for patients with early stage NSCLC receiving stereotactic body radiation therapy (SBRT), yet patient-level risk is difficult to predict. We developed and validated a model to predict individualized risk of DM in this population. METHODS: We used a multi-institutional database of 1280 patients with cT1-3N0M0 NSCLC treated with SBRT from 2006 to 2015 for model development and internal validation. A Fine and Gray (FG) regression model was built to predict 1-year DM risk and compared with a random survival forests model. The higher performing model was evaluated on an external data set of 130 patients from a separate institution. Discriminatory performance was evaluated using the time-dependent area under the curve (AUC). Calibration was assessed graphically and with Brier scores. RESULTS: The FG model yielded an AUC of 0.71 (95% confidence interval [CI]: 0.57-0.86) compared with the AUC of random survival forest at 0.69 (95% CI: 0.63-0.85) in the internal test set and was selected for further testing. On external validation, the FG model yielded an AUC of 0.70 (95% CI: 0.57-0.83) with good calibration (Brier score: 0.08). The model identified a high-risk patient subgroup with greater 1-year DM rates in the internal test (20.0% [3 of 15] versus 2.9% [7 of 241], p = 0.001) and external validation (21.4% [3 of 15] versus 7.8% [9 of 116], p = 0.095). A model nomogram and online application was made available. CONCLUSIONS: We developed and externally validated a practical model that predicts DM risk in patients with NSCLC receiving SBRT which may help select patients for systemic therapy.

Hazardous Attitudes: Physician Decision Making in Radiation Oncology.

Purpose: The Federal Aviation Administration quantifies hazardous attitudes (HAs) among pilots using a scale. HAs have been linked to aviation risk. We assessed the influence of HAs and other factors in treatment decision making in radiation oncology (RO). Methods and Materials: An anonymous survey was sent to 809 radiation oncologists in US cities housing the top 25 cancer centers. The survey included an HA scale adapted for RO and presented 9 cases assessing risk-tolerant radiation therapy prescribing habits and compliance with the American Society for Radiation Oncology's Choosing Wisely recommendations. Demographic and treatment decision data were dichotomized to identify factors associated with prescribing habits using univariable and multivariable (MVA) logistic regression analyses. Results: A total of 139 responses (17.1%) were received, and 103 were eligible for analysis. Among respondents, 40% were female, ages were evenly distributed, and 83% were in academics. Median scores for all attitudes (macho, anti-authority, worry, resignation, and impulsivity) were below the aviation thresholds for hazard and data from surgical specialties. On MVA, responders >50 years old with >5 years' experience were 4.45 times more likely to recommend risk-tolerant radiation (P = .016). Macho attitude was negatively associated with Choosing Wisely compliant treatments (odds ratio [OR], 0.12; P = .001). Physicians who reported having previously retreated the supraclavicular fossa without complication were more likely to recommend retreatment in medically unfit patients if they felt the complication was avoided owing to careful planning (OR, 5.2; P = .008). Conclusions: To our knowledge, this represents the first study analyzing physician attitudes in RO and their effect on self-reported treatment decisions. This work suggests that attitude may be among the factors that influence risk-tolerant prescribing practices and compliance with Choosing Wisely recommendations.

A guide for managing patients with stage I NSCLC: deciding between lobectomy, segmentectomy, wedge, SBRT and ablation-part 1: a guide to decision-making.

Background: Clinical decision-making for patients with stage I lung cancer is complex. It involves multiple options (lobectomy, segmentectomy, wedge, Stereotactic Body Radiotherapy, thermal ablation), weighing multiple outcomes (e.g., short-, intermediate-, long-term) and multiple aspects of each (e.g., magnitude of a difference, the degree of confidence in the evidence, and the applicability to the patient and setting at hand). A structure is needed to summarize the relevant evidence for an individual patient and to identify which outcomes have the greatest impact on the decision-making. Methods: Based on a systematic review from 2000-2021, evidence regarding relevant outcomes was assembled, with attention to aspects of applicability, uncertainty and effect modifiers. A framework was developed to present this information a format that enhances decision-making at the point of care for individual patients. Results: While patients often cross over several boundaries, the evidence fits into categories of healthy patients, compromised patients, and favorable tumors. In healthy patients with typical (i.e., solid spiculated) lung cancers, the impact on long-term outcomes is the major driver of treatment selection. This is only slightly ameliorated in older patients. In compromised patients increasing frailty accentuates short-term differences and diminishes long-term differences especially when considering non-surgical vs. surgical approaches; nuances of patient selection (technical treatment feasibility, anticipated risk of acute toxicity, delayed toxicity, and long-term outcomes) as well as patient values are increasingly influential. Favorable (less-aggressive) tumors generally have good long-term outcomes regardless of the treatment approach. Discussion: A framework is provided that organizes the evidence and identifies the major drivers of decision-making for an individual patient. This facilitates blending available evidence and clinical judgment in a flexible, nuanced manner that enhances individualized clinical care.

A guide for managing patients with stage I NSCLC: deciding between lobectomy, segmentectomy, wedge, SBRT and ablation-part 2: systematic review of evidence regarding resection extent in generally healthy patients.

Background: Clinical decision-making for patients with stage I lung cancer is complex. It involves multiple options (lobectomy, segmentectomy, wedge, stereotactic body radiotherapy, thermal ablation), weighing multiple outcomes (e.g., short-, intermediate-, long-term) and multiple aspects of each (e.g., magnitude of a difference, the degree of confidence in the evidence, and the applicability to the patient and setting at hand). A structure is needed to summarize the relevant evidence for an individual patient and to identify which outcomes have the greatest impact on the decision-making. Methods: A PubMed systematic review from 2000-2021 of outcomes after lobectomy, segmentectomy and wedge resection in generally healthy patients is the focus of this paper. Evidence was abstracted from randomized trials and non-randomized comparisons with at least some adjustment for confounders. The analysis involved careful assessment, including characteristics of patients, settings, residual confounding etc. to expose degrees of uncertainty and applicability to individual patients. Evidence is summarized that provides an at-a-glance overall impression as well as the ability to delve into layers of details of the patients, settings and treatments involved. Results: In healthy patients there is no short-term benefit to sublobar resection vs. lobectomy in randomized and non-randomized comparisons. A detriment in long-term outcomes is demonstrated by adjusted non-randomized comparisons, more marked for wedge than segmentectomy. Quality-of-life data is confounded by the use of video-assisted approaches; evidence suggests the approach has more impact than the resection extent. Differences in pulmonary function tests by resection extent are not clinically meaningful in healthy patients, especially for multi-segmentectomy vs. lobectomy. The margin distance is associated with the risk of recurrence. Conclusions: A systematic, comprehensive summary of evidence regarding resection extent in healthy patients with attention to aspects of applicability, uncertainty and effect modifiers provides a foundation on which to build a framework for individualized clinical decision-making.

A guide for managing patients with stage I NSCLC: deciding between lobectomy, segmentectomy, wedge, SBRT and ablation-part 3: systematic review of evidence regarding surgery in compromised patients or specific tumors.

Background: Clinical decision-making for patients with stage I lung cancer is complex. It involves multiple options [lobectomy, segmentectomy, wedge, stereotactic body radiotherapy (SBRT), thermal ablation], weighing multiple outcomes (e.g., short-, intermediate-, long-term) and multiple aspects of each (e.g., magnitude of a difference, the degree of confidence in the evidence, and the applicability to the patient and setting at hand). A structure is needed to summarize the relevant evidence for an individual patient and to identify which outcomes have the greatest impact on the decision-making. Methods: A PubMed systematic review from 2000-2021 of outcomes after lobectomy, segmentectomy and wedge resection in older patients, patients with limited pulmonary reserve and favorable tumors is the focus of this paper. Evidence was abstracted from randomized trials and non-randomized comparisons (NRCs) with adjustment for confounders. The analysis involved careful assessment, including characteristics of patients, settings, residual confounding etc. to expose degrees of uncertainty and applicability to individual patients. Evidence is summarized that provides an at-a-glance overall impression as well as the ability to delve into layers of details of the patients, settings and treatments involved. Results: In older patients, perioperative mortality is minimally altered by resection extent and only slightly affected by increasing age; sublobar resection may slightly decrease morbidity. Long-term outcomes are worse after lesser resection; the difference is slightly attenuated with increasing age. Reported short-term outcomes are quite acceptable in (selected) patients with severely limited pulmonary reserve, not clearly altered by resection extent but substantially improved by a minimally invasive approach. Quality-of-life (QOL) and impact on pulmonary function hasn't been well studied, but there appears to be little difference by resection extent in older or compromised patients. Patient selection is paramount but not well defined. Ground-glass and screen-detected tumors exhibit favorable long-term outcomes regardless of resection extent; however solid tumors <1 cm are not a reliably favorable group. Conclusions: A systematic, comprehensive summary of evidence regarding resection extent in compromised patients and favorable tumors with attention to aspects of applicability, uncertainty and effect modifiers provides a foundation for a framework for individualized decision-making.

A guide for managing patients with stage I NSCLC: deciding between lobectomy, segmentectomy, wedge, SBRT and ablation-part 4: systematic review of evidence involving SBRT and ablation.

Background: Clinical decision-making for patients with stage I lung cancer is complex. It involves multiple options [lobectomy, segmentectomy, wedge, stereotactic body radiotherapy (SBRT), thermal ablation], weighing multiple outcomes (e.g., short-, intermediate-, long-term) and multiple aspects of each (e.g., magnitude of a difference, the degree of confidence in the evidence, and the applicability to the patient and setting at hand). A structure is needed to summarize the relevant evidence for an individual patient and to identify which outcomes have the greatest impact on the decision-making. Methods: A PubMed systematic review from 2000-2021 of outcomes after SBRT or thermal ablation vs. resection is the focus of this paper. Evidence was abstracted from randomized trials and non-randomized comparisons with at least some adjustment for confounders. The analysis involved careful assessment, including characteristics of patients, settings, residual confounding etc. to expose degrees of uncertainty and applicability to individual patients. Evidence is summarized that provides an at-a-glance overall impression as well as the ability to delve into layers of details of the patients, settings and treatments involved. Results: Short-term outcomes are meaningfully better after SBRT than resection. SBRT doesn't affect quality-of-life (QOL), on average pulmonary function is not altered, but a minority of patients may experience gradual late toxicity. Adjusted non-randomized comparisons demonstrate a clinically relevant detriment in long-term outcomes after SBRT vs. surgery. The short-term benefits of SBRT over surgery are accentuated with increasing age and compromised patients, but the long-term detriment remains. Ablation is associated with a higher rate of complications than SBRT, but there is little intermediate-term impact on quality-of-life or pulmonary function tests. Adjusted comparisons show a meaningful detriment in long-term outcomes after ablation vs. surgery; there is less difference between ablation and SBRT. Conclusions: A systematic, comprehensive summary of evidence regarding Stereotactic Body Radiotherapy or thermal ablation vs. resection with attention to aspects of applicability, uncertainty and effect modifiers provides a foundation for a framework for individualized decision-making.

Hypofractionated vs. standard radiotherapy for locally advanced limited-stage small cell lung cancer.

Background: Hypofractionated radiotherapy in locally advanced limited-stage small cell lung cancer is preferred in many Western countries but not used regularly in the United States. We examined practice patterns and overall survival with definitive hypofractionated radiotherapy and chemotherapy vs. standard radiotherapy in this setting. Methods: We included patients in the National Cancer Database with unresected primary stage II-III small cell lung cancer in 2008-2016 who underwent chemotherapy within six months of either hypofractionated radiotherapy (40-45 Gy/15 fractions) or standard radiotherapy (45 Gy/30 fractions or 60-70 Gy/30-35 fractions) in this retrospective cohort study. Patient characteristics were assessed with univariable and multivariable logistic regression. Kaplan-Meier estimator, log-rank test, and multivariable Cox regression were used to evaluate overall survival. Propensity score matching (PSM) was performed as a sensitivity analysis. Early concurrent chemotherapy consisted of radiotherapy and chemotherapy initiated within 30 days of each other. Results: Seven thousand and one hundred forty-three patients were included: 97.9% received standard radiotherapy and 2.1% hypofractionated radiotherapy. Multivariable analysis on the whole cohort yielded comparable overall survival (HR for hypofractionated radiotherapy 1.09, CI: 0.90-1.32, P=0.37). On PSM (N=292), median overall survival was similar between standard radiotherapy [22.9 months (95% CI: 18.2-30.4 months)] vs. hypofractionated radiotherapy [21.2 months (CI: 16.3-24.7 months); P=0.13]. Overall survival was shorter with hypofractionated radiotherapy in the early concurrent chemotherapy subset (15.8 vs. 22.1 months, P=0.007) and longer with hypofractionated radiotherapy in the non-early concurrent chemotherapy subset (29.5 vs. 18.5 months, P=0.027). Conclusions: Overall survival with hypofractionated radiotherapy appears similar to standard radiotherapy in locally advanced limited-stage small cell lung cancer. Chemotherapy timing may modify the effect of fractionation on overall survival, though larger numbers must confirm. Hypofractionated radiotherapy may be considered in those unable to receive early concurrent chemotherapy.

Clinical Outcomes and Safety Profile in the Treatment of Synchronous Nonmetastatic Lung Tumors With Stereotactic Body Radiation Therapy.

PURPOSE: Stereotactic body radiation therapy (SBRT) has increasingly been used to treat early-stage primary lung cancers, but its effectiveness and safety in patients with multiple synchronous primary lung tumors is not as well established. Our aim was to evaluate clinical outcomes, patterns of recurrence, and toxicities for these patients. METHODS AND MATERIALS: We queried an institutional database of patients treated with SBRT for primary lung tumors from 2007 to 2019. Patients with known metastatic disease were excluded. Recurrences were described as new primaries (NP) if they occurred as an isolated pulmonary mass outside the previous planning target volume. RESULTS: We analyzed 126 lesions from 60 consecutive patients who received SBRT synchronously to ≥2 lesions for nonmetastatic lung cancers. Median total dose per lesion was 50 Gy (range, 30-60 Gy) delivered over 3 to 5 fractions. All but 4 lesions were treated to a biologically effective dose ≥100 Gy. The median follow-up time was 47.3 months (interquartile range, 34.1-65.6). Median overall survival was 46.2 months. Two and 5-year overall survival for all patients was 70% and 48%, respectively. Median progression-free survival was 26 months (interquartile range, 7.6-32.6), and at the time of data collection 25 patients (42%) had experienced any disease progression. Median time to progression was 36 months: 9 (15%) patients experienced local failure, with 1- and 2-year local failure rates of 8% and 13%, respectively. Four patients (7%) experienced regional failure, at 3, 10, 30, and 50 months. Eleven patients (18%) experienced distant failure, with 2-year distant failure rate of 13%. Thirteen patients (21%) developed NPs, with 2-year NP rate of 15.1%. Fourteen patients (23%) experienced Common Terminology Criteria for Adverse Events grade ≥2 toxicity, and 2 patients (3%) experienced Common Terminology Criteria for Adverse Events grade ≥3 toxicity (pneumonitis and hemoptysis). CONCLUSIONS: Synchronous SBRT to biologically effective dose ≥100 Gy appears safe and effective for selected patients with synchronous primary lung tumors.

Brachytherapy and non-cancer mortality in patients with oral cavity and oropharynx SCCs.

BACKGROUND: Oral cavity and oropharyngeal squamous cell cancers (OC-OPSCC) display high cancer-specific mortality and increased non-cancer mortality. We examined cause of death in patients treated for OC-OPSCC with brachytherapy, chemotherapy, external beam radiation, surgery, or combination of modalities. We hypothesized that brachytherapy does not increase non-cancer mortality comparably with external beam radiation. METHODS: A database was constructed from institutional tumor registry and electronic medical record data from all patients with first OC-OPSCC diagnosis at our institution between 2000 and 2010, excluding patients with a second primary cancer at diagnosis. The primary outcome was association between treatment modality and non-cancer mortality. RESULTS: Of 693 eligible patients, 460 were deceased; 84 from primary malignancy and 96 from a non-primary cancer cause, including 24 with a second primary cancer. 193 patients received brachytherapy. Cox proportional hazards regression was performed on treatment regimen, stratified by AJCC stage, race, and sex. Age, smoking history, and alcohol had HRs for death of 1.05 (p < 0.005), 1.37 (p = 0.106), and 2.24 (p < 0.005), respectively, while brachytherapy had a 0.53 HR (p < 0.005) for death. Non-smoking OPC patients had an 88% 5-year OS, suggesting these were largely HPV-driven cancers. In smoking OPC patients, 5-year OS was 61%. Non-cancer mortality HR of 0.36 for brachytherapy-treated patients. CONCLUSION: We report non-cancer mortality from a cohort of curatively treated OC-OPSCC and show a significant correlation between brachytherapy and non-cancer survival, independent of remission status. The impact of brachytherapy in OPC was strongest in smokers.

Post-operative radiation therapy for non-small cell lung cancer: A comparison of radiation therapy techniques.

OBJECTIVES: Post-operative radiation therapy (PORT) in locally advanced non-small cell lung cancer (LA-NSCLC) has historically been associated with toxicity. Conformal techniques like intensity modulated radiation therapy (IMRT) have the potential to reduce acute and long-term toxicity from radiation therapy. Among patients receiving PORT for LA-NSCLC, we identified factors associated with receipt of IMRT and evaluated the association between IMRT and toxicity. METHODS: We queried the Surveillance, Epidemiology, and End Results (SEER)-Medicare database between January 1, 2006 to December 31, 2014 to identify patients diagnosed with Stage II or III NSCLC and who received upfront surgery and subsequent PORT. Baseline differences between patients receiving 3-dimentional conformal radiation therapy (3D-CRT) and IMRT were assessed using the chi-squared test for proportions and the t-test for means. Multivariable logistic regression was used to identify predictors of receipt of IMRT and pulmonary, esophageal, and cardiac toxicity. Propensity-score matching was employed to reduce the effect of known confounders. RESULTS: A total of 620 patients met the inclusion criteria, among whom 441 (71.2%) received 3D-CRT and 179 (28.8%) received IMRT. The mean age of the cohort was 73.9 years and 54.7% were male. The proportion of patients receiving IMRT increased from 6.2% in 2006 to 41.4% in 2014 (P < 0.001). IMRT was not associated with decreased pulmonary (OR 0.89; 95% CI, 0.62-1.29), esophageal (OR 1.09; 95% CI, 0.0.75-1.58), or cardiac toxicity (OR 1.02; 95% CI, 0.69-1.51). These findings held on propensity-score matching. Clinical risk factors including comorbidity and prior treatment history were associated with treatment toxicity. CONCLUSION: In a cohort of elderly patients, the use of IMRT in the setting of PORT for LA-NSCLC was not associated with a difference in toxicity compared to 3D-CRT. This finding suggests that outcomes from PORT may be independent of radiotherapy treatment technique.

Optimal Radiation Dose for Stage III Lung Cancer-Should "Definitive" Radiation Doses Be Used in the Preoperative Setting?

INTRODUCTION: There are currently two recommended radiation strategies for clinical stage III NSCLC: a lower "preoperative" (45-54 Gy) and a higher "definitive/nonsurgical" (60-70 Gy) dose. We sought to determine if definitive radiation doses should be used in the preoperative setting given that many clinical stage III patients planned for surgery are ultimately managed with chemoradiation alone. METHODS: Using the National Cancer Database data from 2006 to 2016, we performed a comparative effectiveness analysis of stage III N2 patients who received chemoradiotherapy. Patients were stratified into subgroups across 2 parameters: (1) radiation dose: lower (45-54 Gy) and higher (60-70 Gy); and (2) the use of surgery (i.e., surgical and nonsurgical treatment approaches). Long-term survival and perioperative outcomes were evaluated using multivariable Cox proportional hazards and logistic regression models. RESULTS: A cohort of 961 patients received radiation before surgery including 321 who received a higher dose and 640 who received a lower dose. A higher preoperative dose revealed similar long-term mortality risk (hazard ratio = 0.99, 95% confidence interval: 0.82-1.21, p = 0.951) compared with a lower dose. There was no significant association between radiation dose and 90-day mortality (p = 0.982), 30-day readmission (p = 0.931), or prolonged length of stay (p = 0.052) in the surgical cohort. A total of 17,904 clinical-stage IIIA-N2 patients were treated nonsurgically, including 15,945 receiving higher and 1959 treated with a lower dose. A higher dose was associated with a reduction in long-term mortality risk (hazard ratio = 0.64, 95% confidence interval: 0.60-0.67, p < 0.001) compared with a lower dose. CONCLUSIONS: For clinical stage III NSCLC, the administration of 60 to 70 Gy of radiation seems to be more effective than the lower dose for nonsurgical patients without compromising surgical safety for those that undergo resection. This evidence supports the implementation of 60 to 70 Gy as a single-dose strategy for both preoperative and definitive chemoradiotherapy.

Rates of invasive disease and outcomes in NSCLC patients with biopsy suggestive of carcinoma in situ.

INTRODUCTION: Carcinoma in situ is a rare non-invasive histology of non-small cell lung cancer (NSCLC) with excellent survival outcomes with resection. However, management of lung biopsy suggestive of in situ disease remains unclear. To inform decision-making in this scenario, we determined the rate of invasive disease presence upon resection of lesions with an initial biopsy suggestive of purely in situ disease. METHODS: The study included 960 patients diagnosed with NSCLC from 2003 to 2017 in the National Cancer Database whose workup included a lung biopsy suggestive of in situ disease. Among the cohort who proceeded to resection, we identified the rate of invasive disease discovered on surgical pathology along with significant demographic and clinical contributors to invasion risk. Survival outcomes were measured for the observed cohort that did not receive local therapy after biopsy. RESULTS: Invasive disease was identified at resection in 49.3 % of patients. Lesion size was associated with risk of invasive disease: 35.7 % for ≤1 cm, 45.2 % for 1-2 cm, 55.7 % for 2-3 cm, and 87.5 % for 3-5 cm (p < 0.001). Of patients with squamous histology, 61.5 % had invasive disease versus 46.5 % with adenocarcinoma histology (p = 0.026). On multivariable logistic regression, invasive disease remained associated with tumor size (OR 1.9 per cm, 95 % CI 1.5-2.4, p < 0.001), and squamous histology (OR 1.8, 95 % CI 1.1-3.2, p = 0.028). Overall survival at 3 years was 51.5 % in the observed cohort. CONCLUSION: Nearly half of patients with biopsy suggestive of in situ disease had invasive disease at resection. Tumor size and histology are strong predictors of invasive disease and may be used for risk stratification. However, the findings support the practice of definitive therapy whenever feasible.

A Dose-finding Study Followed by a Phase II Randomized, Placebo-controlled Trial of Chemoradiotherapy With or Without Veliparib in Stage III Non-small-cell Lung Cancer: SWOG 1206 (8811).

BACKGROUND: We conducted a 2-part study to evaluate the incorporation of veliparib, a PARP inhibitor, into chemoradiotherapy (CRT) for stage III non-small-cell lung cancer. PATIENTS AND METHODS: In the phase I part, patients were treated successively at 3 dose levels of veliparib (40, 80, and 120 mg) twice daily during CRT. In the phase II part, patients were randomized to receive veliparib or placebo during thoracic radiotherapy with concurrent weekly carboplatin and paclitaxel, followed by 2 cycles of consolidation carboplatin and paclitaxel with veliparib or placebo. The study was prematurely discontinued owing to the emergence of adjuvant immunotherapy as standard of care. RESULTS: Of 21 patients enrolled in phase I, 2 patients developed dose-limiting toxicities (DLTs): 1 grade 3 esophagitis with dysphagia (at 40 mg) and 1 grade 3 esophagitis with dehydration (at 80 mg). No DLTs were seen at veliparib dose of 120 mg twice daily, which was selected for the phase II part that enrolled 31 eligible patients. Progression-free survival (PFS) was not different between the 2 arms (P = .20). For the veliparib and placebo arms, response rates were 56% and 69%, PFS at 1 year 47% and 46%, and overall survival at 1 year 89% and 54%, respectively. CONCLUSION: Veliparib with CRT was feasible and well tolerated. Efficacy could not accurately be determined because of early study closure. Nonetheless, there is enthusiasm for the evaluation of PARP inhibitors in lung cancer as predictive biomarkers are being developed and combinations with immunotherapy are attractive.

Radiation Therapy for Small-Cell Lung Cancer: ASCO Guideline Endorsement of an ASTRO Guideline.

PURPOSE: The American Society for Radiation Oncology (ASTRO) produced an evidence-based guideline on radiation therapy (RT) for small-cell lung cancer (SCLC). Because of the relevance of this topic to ASCO membership, ASCO reviewed the guideline, applying a set of procedures and policies used to critically examine guidelines developed by other organizations. METHODS: The ASTRO guideline on RT for SCLC was reviewed for developmental rigor by methodologists. Then, an ASCO Expert Panel reviewed the content and the recommendations. RESULTS: The ASCO Expert Panel determined that the recommendations from ASTRO guideline on RT for SCLC, published in June 2020, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorsed ASTRO guideline on RT for SCLC with a few discussion points. RECOMMENDATIONS: Recommendations addressed thoracic radiotherapy for limited-stage SCLC, role of stereotactic body radiotherapy in stage I or II node-negative SCLC, prophylactic cranial radiotherapy, and thoracic consolidation for extensive-stage SCLC.Additional information is available at www.asco.org/thoracic-cancer-guidelines.

A Blinded, Prospective Study of Error Detection During Physician Chart Rounds in Radiation Oncology.

PURPOSE: Peer review during physician chart rounds is a major quality assurance and patient safety step in radiation oncology. However, the effectiveness of chart rounds in detecting problematic treatment plans is unknown. We performed a prospective blinded study of error detection at chart rounds to clarify the effectiveness of this quality assurance step. METHODS AND MATERIALS: Radiation Oncology Incident Learning System publications were queried for problematic plans approved for treatment that would be detectable at chart rounds. A resident physician, physicist, and dosimetrist collaboratively generated 20 treatment plans with simulated errors identical in nature to those reported to the Radiation Oncology Incident Learning System. These were inserted randomly into weekly chart rounds over 9 weeks, with a median of 2 problematic plans presented per chart rounds (range, 1-4). Data were collected on detection, attendance, length, and number of cases presented at chart rounds. Data were analyzed using descriptive statistics and univariable logistic regression with odds ratios. RESULTS: The median length of chart rounds over the study period was 60 minutes (range, 42-79); median number of cases presented per chart rounds was 45 (range, 38-50). The overall detection rate was 55% (11 of 20). Detection rates were higher for cases presented earlier in chart rounds: 75% versus 25% of problematic plans were detected within 30 minutes of start of chart rounds versus after 30 minutes (odds ratio, 0.11; 95% confidence interval, 0.01-0.88; P = .037). Detection rates showed a trend toward increase during the study period but this was not significant: 33% in weeks 1 to 5 and 73% during weeks 6 to 9 (5.3; 95% confidence interval, 0.78-36; P = .08). CONCLUSIONS: The detection of clinically significant problematic plans during chart rounds could be significantly improved. Problematic plans are more frequently detected earlier in chart rounds and inserting such plans into chart rounds may enhance detection; however, larger studies are needed to confirm these findings. A multi-institutional study is planned.

Multi-institutional retrospective review of stereotactic radiosurgery for brain metastasis in patients with small cell lung cancer without prior brain-directed radiotherapy.

Introduction: Patients with small cell lung cancer (SCLC) brain metastasis (BM) typically receive whole brain radiotherapy (WBRT) as data regarding upfront radiosurgery (SRS) in this setting are sparse. Methods: Patients receiving SRS for SCLC BM without prior brain radiation were identified at three U.S. institutions. Overall survival (OS), freedom from intracranial progression (FFIP), freedom from WBRT (FFWBRT), and freedom from neurologic death (FFND) were determined from time of SRS. Results: Thirty-three patients were included with a median of 2 BM (IQR 1-6). Median OS and FFIP were 6.7 and 5.8 months, respectively. Median FFIP for patients with ≤2 versus >2 BM was 7.1 versus 3.6 months, p=0.0303. Eight patients received salvage WBRT and the 6-month FFWBRT and FFND were 87.8%. and 90.1%, respectively. Conclusions: Most SCLC patients with BM who received upfront SRS avoided WBRT and neurologic death, suggesting that SRS may be an option in select patients.

Resident attitudes and benefits of mock oral board examinations in radiation oncology.

BACKGROUND: Presently, educational programming is not standardized across radiation oncology (RO) training programs. Specifically, there are limited materials through national organizations or structured practice exams for residents preparing for the American Board of Radiology (ABR) oral board examination. We present our 2019 experience implementing a formalized program of early mock oral board examinations (MOBE) for residents in post-graduate years (PGY) 3-5. METHODS: A mixed-methods survey regarding MOBE perception and self-reported comfort across five clinical domains were administered to PGY2-5 residents. MOBEs and a post-intervention survey were implemented for the PGY3-5. The pre and post-intervention score across clinical domains were compared using t-tests. Faculty and residents were asked for post-intervention comments. RESULTS: A total of 14 PGY2-5 residents completed the pre-intervention survey; 9 residents participated in the MOBE (5/14 residents were PGY2s) and post-intervention survey. This was the first mock oral radiation oncology examination experience for 65% of residents. 100% of residents felt the MOBE increased their clinical knowledge and comfort with clinical reasoning. Overall, there was a trend towards improved resident confidence giving planning dose parameters and (p = 0.08). There was also unanimous request for more MOBE experiences from residents and faculty, but time was identified as a significant barrier. CONCLUSIONS: Future directions for this MOBE program are inclusion of more disease sites, better emulation of the exam, the creation of a more rigorous consolidated format testing all sites at once, and consideration for grading of these sessions for future correlation with certifying oral board examination (OBE) performance.