Neoadjuvant nivolumab or nivolumab plus LAG-3 inhibitor relatlimab in resectable esophageal/gastroesophageal junction cancer: a phase Ib trial and ctDNA analyses.

Gastroesophageal cancer dynamics and drivers of clinical responses with immune checkpoint inhibitors (ICI) remain poorly understood. Potential synergistic activity of dual programmed cell death protein 1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) inhibition may help improve immunotherapy responses for these tumors. We report a phase Ib trial that evaluated neoadjuvant nivolumab (Arm A, n = 16) or nivolumab-relatlimab (Arm B, n = 16) in combination with chemoradiotherapy in 32 patients with resectable stage II/stage III gastroesophageal cancer together with an in-depth evaluation of pathological, molecular and functional immune responses. Primary endpoint was safety; the secondary endpoint was feasibility; exploratory endpoints included pathological complete (pCR) and major pathological response (MPR), recurrence-free survival (RFS) and overall survival (OS). The study met its primary safety endpoint in Arm A, although Arm B required modification to mitigate toxicity. pCR and MPR rates were 40% and 53.5% for Arm A and 21.4% and 57.1% for Arm B. Most common adverse events were fatigue, nausea, thrombocytopenia and dermatitis. Overall, 2-year RFS and OS rates were 72.5% and 82.6%, respectively. Higher baseline programmed cell death ligand 1 (PD-L1) and LAG-3 expression were associated with deeper pathological responses. Exploratory analyses of circulating tumor DNA (ctDNA) showed that patients with undetectable ctDNA post-ICI induction, preoperatively and postoperatively had a significantly longer RFS and OS; ctDNA clearance was reflective of neoantigen-specific T cell responses. Our findings provide insights into the safety profile of combined PD-1 and LAG-3 blockade in gastroesophageal cancer and highlight the potential of ctDNA analysis to dynamically assess systemic tumor burden during neoadjuvant ICI that may open a therapeutic window for future intervention. ClinicalTrials.gov registration: NCT03044613 .

Ablative radiation alone in stage I lung cancer produces an adaptive systemic immune response: insights from a prospective stud.

Stereotactic ablative body radiation (SABR) delivers high rates of local control in early-stage non-small cell lung cancer (NSCLC); however, systemic immune effects are poorly understood. Here, we evaluate the early pathologic and immunologic effects of SABR. Blood/core-needle tumor biopsies were collected from six patients with stage I NSCLC before and 5-7 days after SABR (48 Gy/4 or 50 Gy/5 fractions). Serial blood was collected up to 1-year post-SABR. We used immunohistochemistry to evaluate pathological changes, immune-cell populations (CD8, FoxP3), and PD-L1/PD-1 expression within the tumor. We evaluated T-cell receptor (TCR) profile changes in the tumor using TCR sequencing. We used the MANAFEST (Mutation-Associated Neoantigen Functional Expansion of Specific T-cells) assay to detect peripheral neoantigen-specific T-cell responses and dynamics. At a median follow-up of 40 months, 83% of patients (n=5) were alive without tumor progression. Early post-SABR biopsies showed viable tumor and similar distribution of immune-cell populations as compared with baseline samples. Core-needle samples proved insufficient to detect population-level TCR-repertoire changes. Functionally, neoantigen-specific T-cells were detected in the blood prior to SABR. A subset of these patients had a transient increase in the frequency of neoantigen-specific T-cells between 1 week and 3-6 months after SABR. SABR alone could induce a delayed, transient neoantigen-specific T-cell immunologic response in patients with stage I NSCLC.

DAART: a deep learning platform for deeply accelerated adaptive radiation therapy for lung cancer.

Purpose: The study aimed to implement a novel, deeply accelerated adaptive radiation therapy (DAART) approach for lung cancer radiotherapy (RT). Lung cancer is the most common cause of cancer-related death, and RT is the preferred medically inoperable treatment for early stage non-small cell lung cancer (NSCLC). In the current lengthy workflow, it takes a median of four weeks from diagnosis to RT treatment, which can result in complete restaging and loss of local control with delay. We implemented the DAART approach, featuring a novel deepPERFECT system, to address unwanted delays between diagnosis and treatment initiation. Materials and methods: We developed a deepPERFECT to adapt the initial diagnostic imaging to the treatment setup to allow initial RT planning and verification. We used data from 15 patients with NSCLC treated with RT to train the model and test its performance. We conducted a virtual clinical trial to evaluate the treatment quality of the proposed DAART for lung cancer radiotherapy. Results: We found that deepPERFECT predicts planning CT with a mean high-intensity fidelity of 83 and 14 HU for the body and lungs, respectively. The shape of the body and lungs on the synthesized CT was highly conformal, with a dice similarity coefficient (DSC) of 0.91, 0.97, and Hausdorff distance (HD) of 7.9 mm, and 4.9 mm, respectively, compared with the planning CT scan. The tumor showed less conformality, which warrants acquisition of treatment Day1 CT and online adaptive RT. An initial plan was designed on synthesized CT and then adapted to treatment Day1 CT using the adapt to position (ATP) and adapt to shape (ATS) method. Non-inferior plan quality was achieved by the ATP scenario, while all ATS-adapted plans showed good plan quality. Conclusion: DAART reduces the common online ART (ART) treatment course by at least two weeks, resulting in a 50% shorter time to treatment to lower the chance of restaging and loss of local control.

Safety and clinical efficacy of immune checkpoint inhibition and stereotactic body radiotherapy in patients with spine metastasis.

OBJECTIVE: Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has revolutionized the treatment of patients with many tumor histologies. Simultaneously, stereotactic body radiotherapy (SBRT) provides excellent local control (LC) and plays an important role in the management of spine metastasis. Promising preclinical work suggests the potential therapeutic benefit of combining SBRT with ICI therapy, but the safety profile of combined therapy is unclear. This study aimed to evaluate the toxicity profile associated with ICI in patients receiving SBRT and, secondarily, whether ICI administration sequence with respect to SBRT affects LC or overall survival (OS) outcomes. METHODS: The authors retrospectively reviewed patients with spine metastasis treated with SBRT at an academic center. Patients who received ICI at any point during their disease course were compared to those with the same primary tumor types who did not receive ICI by using Cox proportional hazards analyses. Primary outcomes were long-term sequelae, including radiation-induced spinal cord myelopathy, esophageal stricture, and bowel obstruction. Secondarily, models were created to evaluate OS and LC in the cohort. RESULTS: Two hundred forty patients who received SBRT to 299 spine metastases were included in this study. The most common primary tumor types were non-small cell lung cancer (n = 59 [24.6%]) and renal cell carcinoma (n = 55 [22.9%]). One hundred eight patients received at least 1 dose of ICI, with the most common regimen being single-agent anti-PD-1 (n = 80 [74.1%]), followed by combination CTLA-4/PD-1 inhibitors (n = 19 [17.6%]). Three patients experienced long-term radiation-induced sequelae: 2 had esophageal stricture and 1 had bowel obstruction. No patients developed radiation-induced myelopathy. There was no association between receipt of ICI and development of any of these adverse events (p > 0.9). Similarly, ICI was not significantly associated with either LC (p = 0.3) or OS (p = 0.6). In the entire cohort, patients who received ICI prior to beginning SBRT had worse median survival, but ICI sequence with respect to SBRT was not significantly prognostic of either LC (p > 0.3) or OS (p > 0.07); instead, baseline performance status was most predictive of OS (HR 1.38, 95% CI 1.07-1.78, p = 0.012). CONCLUSIONS: Treatment regimens that combine ICIs before, concurrent with, and after SBRT for spine metastases are safe, with minimal risk for increased rates of long-term toxicity.

Improving Quality Metrics in Radiation Oncology: Implementation of Pretreatment Peer Review for Stereotactic Body Radiation Therapy in Patients with Thoracic Cancer.

Purpose: Traditional peer reviews occur weekly, and can take place up to 1 week after the start of treatment. The American Society for Radiation Oncology peer-review white paper identified stereotactic body radiation therapy (SBRT) as a high priority for contour/plan review before the start of treatment, considering both the rapid-dose falloff and short treatment course. Yet, peer-review goals for SBRT must also balance physician time demands and the desire to avoid routine treatment delays that would occur in the setting of a 100% pretreatment (pre-Tx) review compliance requirement or prolonging the standard treatment planning timeline. Herein, we report on our pilot experience of a pre-Tx peer review of thoracic SBRT cases. Methods and Materials: From March 2020 to August 2021, patients undergoing thoracic SBRT were identified for pre-Tx review, and placed on a quality checklist. We implemented twice-weekly meetings for detailed pre-Tx review of organ-at-risk/target contours and dose constraints in the treatment planning system for SBRT cases. Our quality metric goal was to peer review ≥90% of SBRT cases before exceeding 25% of the dose delivered. We used a statistical process control chart with sigma limits (ie, standard deviations [SDs]) to access compliance rates with pre-Tx review implementation. Results: We identified 252 patients treated with SBRT to 294 lung nodules. When comparing pre-Tx review completion from initial rollout to full implementation, our rates improved from 19% to 79% (ie, from 1 sigma limit [SDs]) below to >2 sigma limits (SDs) above. Additionally, early completion of any form of contour/plan review (defined as any pre-Tx or standard review completed before exceeding 25% of the dose delivered) increased from 67% to 85% (March 2020-November 2020) to 76% to 94% (December 2020-August 2021). Conclusions: We successfully implemented a sustainable workflow for detailed pre-Tx contour/plan review for thoracic SBRT cases in the context of twice-weekly disease site-specific peer-review meetings. We reached our quality improvement objective to peer review ≥90% of SBRT cases before exceeding 25% of the dose delivered. This process was feasible to conduct in an integrated network of sites across our system.

A digital physician peer to automatically detect erroneous prescriptions in radiotherapy.

Appropriate dosing of radiation is crucial to patient safety in radiotherapy. Current quality assurance depends heavily on a physician peer-review process, which includes a review of the treatment plan's dose and fractionation. Potentially, physicians may not identify errors during this manual peer review due to time constraints and caseload. A novel prescription anomaly detection algorithm is designed that utilizes historical data from the past to predict anomalous cases. Such a tool can serve as an electronic peer who will assist the peer-review process providing extra safety to the patients. In our primary model, we create two dissimilarity metrics, R and F. R defining how far a new patient's prescription is from historical prescriptions. F represents how far away a patient's feature set is from that of the group with an identical or similar prescription. We flag prescription if either metric is greater than specific optimized cut-off values. We use thoracic cancer patients (n = 2504) as an example and extracted seven features. Our testing set f1 score is between 73%-94% for different treatment technique groups. We also independently validate our results by conducting a mock peer review with three thoracic specialists. Our model has a lower type II error rate compared to the manual peer-review by physicians.

Definitive Chemoradiation and Durvalumab Consolidation for Locally Advanced, Unresectable KRAS-mutated Non-Small Cell Lung Cancer.

BACKGROUND: Consolidation durvalumab immunotherapy following definitive chemoradiation (CRT) for unresectable stage III non-small cell lung cancer (NSCLC) improves overall survival. As therapeutic options for patients with KRAS-driven disease evolve, more understanding regarding genomic determinants of response and patterns of progression for durvalumab consolidation is needed to optimize outcomes. METHODS: We conducted a single-institutional retrospective analysis of real-world patients with locally advanced, unresectable NSCLC who completed CRT and received durvalumab consolidation. Kaplan-Meier analyses compared progression-free survival (PFS) and overall survival (OS) from start of durvalumab consolidation between patients with KRAS-mutated and non-mutated tumors. Fisher's exact test was used to compare rates of intrathoracic or extrathoracic progression. RESULTS: Of 74 response-evaluable patients, 39 had clinical genomic profiling performed. 18 patients had tumors with KRAS mutations, 7 patients had tumors with non-KRAS actionable alterations (EGFR, ALK, ERBB2, BRAF, MET, RET, or ROS1), and 14 patients had tumors without actionable alterations. Median PFS for the overall cohort was 16.1 months. PFS for patients with KRAS-mutated NSCLC was 12.6 months versus 12.7 months for patients with non-actionable tumors (P= 0.77, log-rank). Fisher's exact test revealed a statistically significantly higher rate of extrathoracic progression versus intrathoracic-only progression for patients with KRAS-driven disease compared to patients with non-actionable tumors (P= 0.015). CONCLUSION: Patients with KRAS-mutated NSCLC derived similar benefit from durvalumab as patients with non-actionable tumors. A higher rate of extrathoracic progression was also observed among the patients with KRAS-mutated NSCLC compared to patients with non-actionable tumors. This highlights the potential unmet needs for novel systemic therapies and surveillance methods for KRAS-mutated stage III NSCLC.

An Oncology Urgent Care Clinic for the Management of Immune-Related Adverse Events: A Descriptive Analysis.

Introduction: With the increasing use of immune checkpoint inhibitors (ICI) for cancer, there is a growing burden on the healthcare system to provide care for the toxicities associated with these agents. Herein, we aim to identify and describe the distribution of encounters seen in an urgent care setting for immune-related adverse events (irAEs) and the clinical outcomes from irAE management. Methods: Patient demographics, disease characteristics, and treatment data were collected retrospectively from encounters at an oncology Urgent Care Clinic (UCC) from a single tertiary center for upper aerodigestive malignancies from 1 July 2018 to 30 June 2019. Data were summarized using descriptive statistics with odds ratios for associations between patient features and hospitalization after UCC evaluation. Results: We identified 494 encounters from 289 individual patients over the study period. A history of ICI therapy was noted in 34% (n = 170/494) of encounters and 29 encounters (29/170, 17%) were confirmed and treated as irAEs. For those treated for irAEs, the majority (n = 19/29; 66%) were discharged home. Having an irAE was associated with an increased risk of hospitalization compared to non-irAEs (OR 5.66; 95% CI 2.15−14.89; p < 0.001). Conclusion: In this single institution experience, the majority of UCC encounters for confirmed irAEs were safely managed within the UCC. In ICI-treated patients, having an irAE was associated with an increased risk of hospitalization versus non-irAEs.

Evaluating Proton Dose and Associated Range Uncertainty Using Daily Cone-Beam CT.

Purpose: This study aimed to quantitatively evaluate the range uncertainties that arise from daily cone-beam CT (CBCT) images for proton dose calculation compared to CT using a measurement-based technique. Methods: For head and thorax phantoms, wedge-shaped intensity-modulated proton therapy (IMPT) treatment plans were created such that the gradient of the wedge intersected and was measured with a 2D ion chamber array. The measured 2D dose distributions were compared with 2D dose planes extracted from the dose distributions using the IMPT plan calculated on CT and CBCT. Treatment plans of a thymoma cancer patient treated with breath-hold (BH) IMPT were recalculated on 28 CBCTs and 9 CTs, and the resulting dose distributions were compared. Results: The range uncertainties for the head phantom were determined to be 1.2% with CBCT, compared to 0.5% for CT, whereas the range uncertainties for the thorax phantom were 2.1% with CBCT, compared to 0.8% for CT. The doses calculated on CBCT and CT were similar with similar anatomy changes. For the thymoma patient, the primary source of anatomy change was the BH uncertainty, which could be up to 8 mm in the superior-inferior (SI) direction. Conclusion: We developed a measurement-based range uncertainty evaluation method with high sensitivity and used it to validate the accuracy of CBCT-based range and dose calculation. Our study demonstrated that the CBCT-based dose calculation could be used for daily dose validation in selected proton patients.

Pretreatment Lung Function and Checkpoint Inhibitor Pneumonitis in NSCLC.

INTRODUCTION: Checkpoint inhibitor pneumonitis (CIP) is a serious toxicity of anti-programmed death-(ligand) 1 immunotherapy. Whether pretreatment differences in pulmonary function exist in patients who develop CIP is unknown. We analyzed the pulmonary function tests (PFTs) of patients with NSCLC treated with immune checkpoint inhibitors (ICIs) to evaluate whether pretreatment lung function was associated with CIP development. METHODS: Patients were included if they completed greater than or equal to 1 PFT within 2 years preceding ICI initiation. CIP status (CIP+: developed CIP, CIP-: did not develop CIP) was determined clinically. Generalized estimating equation-based linear regression was used to evaluate the effects of time and CIP on lung function. Primary outcomes included the following: percent-predicted forced expiratory volume in 1 second (FEV1pp), percent-predicted forced vital capacity (FVCpp), and FEV1/FVC. RESULTS: A total of 43 patients (34 CIP-, 9 CIP+) with 79 PFTs (59 CIP-, 20 CIP+) were included. CIP+ patients had a 21.7% lower pretreatment FEV1pp compared with the CIP- group (95% confidence interval: -38.6 to -4.7). No statistically significant differences in FVCpp or FEV1/FVC were observed. The prevalence of obstructive lung disease was similar in both groups at 67% and 62% for the CIP+ and CIP- cohorts, as was the prevalence of current/former smoking at 100% and 93%, respectively. CONCLUSIONS: Pretherapy differences in lung function were evident between patients who did and did not develop CIP, though the prevalence of obstructive lung disease was similar. Prospective studies are needed to validate these findings, inform potential risk factors for CIP, and investigate the effects of ICI treatment and CIP on pulmonary function in patients with NSCLC.

Trimodality therapy for esophageal cancer: The role of surgical and radiation treatment parameters in the development of anastomotic complications.

BACKGROUND: Here, we investigated the relationship between clinical parameters, including the site of surgical anastomosis and radiation dose to the anastomotic region, and anastomotic complications in esophageal cancer patients treated with trimodality therapy. METHODS: Between 2007 and 2016, esophageal cancer patients treated with trimodality therapy at a tertiary academic cancer center were identified. Patient, treatment, and outcome parameters were collected. Radiation dose to the gastric regions were extracted. Anastomotic complication was defined as leak and/or stricture. We used Fisher's exact and Wilcoxon rank-sum tests to compare the association between clinical parameters and anastomotic complications. RESULTS: Of 89 patients identified, the median age was 63 years, 82% (n = 73) were male, and 82% had distal (n = 47) or gastroesophageal junction (n = 26) tumors. Median follow-up was 25.8 months. Esophagectomies were performed with cervical (65%, n = 58) or thoracic anastomoses (35%, n = 31). Anastomotic complications developed in 60% (n = 53). Cervical anastomosis was associated with anastomotic complications (83%, n = 44/53, p < 0.01). Radiation to any gastric substructure was not associated with anastomotic complications (p > 0.05). In the subset of patients with distal/gastroesophageal junction tumors undergoing esophagectomy with cervical anastomosis where radiation was delivered to the future neoesophagus, 80% (n = 35/44) developed anastomotic complications. In this high-risk subgroup, radiation was not associated with anastomotic complications (p > 0.05). CONCLUSIONS: Our analysis did not demonstrate an association between radiation dose to gastric substructures and anastomotic complications. However, it showed an association between esophagectomy with cervical anastomosis and anastomotic complications. Patients with distal/gastroesophageal junction tumors who undergo esophagectomy with cervical anastomosis have higher rates of anastomotic complications unrelated to radiation to gastric substructures.

Improving Early Identification of Significant Weight Loss Using Clinical Decision Support System in Lung Cancer Radiation Therapy.

PURPOSE: Early identification of patients who may be at high risk of significant weight loss (SWL) is important for timely clinical intervention in lung cancer radiotherapy (RT). A clinical decision support system (CDSS) for SWL prediction was implemented within the routine clinical workflow and assessed on a prospective cohort of patients. MATERIALS AND METHODS: CDSS incorporated a machine learning prediction model on the basis of radiomics and dosiomics image features and was connected to a web-based dashboard for streamlined patient enrollment, feature extraction, SWL prediction, and physicians' evaluation processes. Patients with lung cancer (N = 37) treated with definitive RT without prior RT were prospectively enrolled in the study. Radiomics and dosiomics features were extracted from CT and 3D dose volume, and SWL probability (≥ 0.5 considered as SWL) was predicted. Two physicians predicted whether the patient would have SWL before and after reviewing the CDSS prediction. The physician's prediction performance without and with CDSS and prediction changes before and after using CDSS were compared. RESULTS: CDSS showed significantly better prediction accuracy than physicians (0.73 v 0.54) with higher specificity (0.81 v 0.50) but with lower sensitivity (0.55 v 0.64). Physicians changed their original prediction after reviewing CDSS prediction for four cases (three correctly and one incorrectly), for all of which CDSS prediction was correct. Physicians' prediction was improved with CDSS in accuracy (0.54-0.59), sensitivity (0.64-0.73), specificity (0.50-0.54), positive predictive value (0.35-0.40), and negative predictive value (0.76-0.82). CONCLUSION: Machine learning-based CDSS showed the potential to improve SWL prediction in lung cancer RT. More investigation on a larger patient cohort is needed to properly interpret CDSS prediction performance and its benefit in clinical decision making.

Radiation Versus Immune Checkpoint Inhibitor Associated Pneumonitis: Distinct Radiologic Morphologies.

BACKGROUND: Patients with non-small cell lung cancer may develop pneumonitis after thoracic radiotherapy (RT) and immune checkpoint inhibitors (ICIs). We hypothesized that distinct morphologic features are associated with different pneumonitis etiologies. MATERIALS AND METHODS: We systematically compared computed tomography (CT) features of RT- versus ICI-pneumonitis. Clinical and imaging features were tested for association with pneumonitis severity. Lastly, we constructed an exploratory radiomics-based machine learning (ML) model to discern pneumonitis etiology. RESULTS: Between 2009 and 2019, 82 patients developed pneumonitis: 29 after thoracic RT, 23 after ICI, and 30 after RT + ICI. Fifty patients had grade 2 pneumonitis, 22 grade 3, and 7 grade 4. ICI-pneumonitis was more likely bilateral (65% vs. 28%; p = .01) and involved more lobes (66% vs. 45% involving at least three lobes) and was less likely to have sharp border (17% vs. 59%; p = .004) compared with RT-pneumonitis. Pneumonitis morphology after RT + ICI was heterogeneous, with 47% bilateral, 37% involving at least three lobes, and 40% sharp borders. Among all patients, risk factors for severe pneumonitis included poor performance status, smoking history, worse lung function, and bilateral and multifocal involvement on CT. An ML model based on seven radiomic features alone could distinguish ICI- from RT-pneumonitis with an area under the receiver-operating curve of 0.76 and identified the predominant etiology after RT + ICI concordant with multidisciplinary consensus. CONCLUSION: RT- and ICI-pneumonitis exhibit distinct spatial features on CT. Bilateral and multifocal lung involvement is associated with severe pneumonitis. Integrating these morphologic features in the clinical management of patients who develop pneumonitis after RT and ICIs may improve treatment decision-making. IMPLICATIONS FOR PRACTICE: Patients with non-small cell lung cancer often receive thoracic radiation and immune checkpoint inhibitors (ICIs), both of which can cause pneumonitis. This study identified similarities and differences in pneumonitis morphology on computed tomography (CT) scans among pneumonitis due to radiotherapy (RT) alone, ICI alone, and the combination of both. Patients who have bilateral CT changes involving at least three lobes are more likely to have ICI-pneumonitis, whereas those with unilateral CT changes with sharp borders are more likely to have radiation pneumonitis. After RT and/or ICI, severe pneumonitis is associated with bilateral and multifocal CT changes. These results can help guide clinicians in triaging patients who develop pneumonitis after radiation and during ICI treatment.

Bone density and fracture risk following SBRT for non-spine bone metastases.

PURPOSE/METHODS: This retrospective study evaluated local recurrence (LR) and fracture risk in non-spine bone metastases treated with SBRT. RESULTS: 181 lesions in 116 patients are reported. The median dose was 27 Gy (range 15-40) in 3 fractions (range 1-6). The cumulative incidence of LR was 2.8%, 7.2% and 12.5% at 6 mo, 1 yr and 2 yrs. Fractures occurred in 11 lesions (6%). Radioresistant histology and increasing PTV predicted for LR on univariate analysis, while rib location was associated with control. Increasing PTV remained a significant predictor for LR on multivariate analysis. Univariate predictors of fracture risk included female gender, lytic lesions and poorer KPS. Average CT-approximated L1 trabecular attenuation in patients with fracture was significantly lower than in patients without fracture (112.2 vs. 142.6 Hounsfield units). CONCLUSION: In the largest series to date, we report excellent local control for SBRT to non-spine bone metastases and a novel relationship between CT-based bone quality assessment and fracture risk.

Longitudinal Trends of Financial Toxicity in Patients With Lung Cancer: A Prospective Cohort Study.

BACKGROUND: Cancer therapy is associated with severe financial burden. However, the magnitude and longitudinal patient relationship with financial toxicity (FT) in the initial course of therapy is unclear. METHODS: Patients with stage II-IV lung cancer were recruited in a prospective longitudinal study between July 2018 and March 2020. FT was measured via the validated COmprehensive Score for financial Toxicity (COST) at the time of cancer diagnosis and at 6-month follow-up (6MFU). 6MFU data were compared with corresponding baseline data. A lower COST score indicates increased financial hardship. RESULTS: At the time of analysis, 215 agreed to participate. Subsequently, 112 patients completed 6MFU. On average, slightly more FT was observed at diagnosis compared with 6MFU (median COSTbase 25 v COST6M 27; P < .001); however, individual patients experienced large changes in FT. At 6MFU, 27.7% of patients had made financial sacrifices to pay for treatment but only 4.5% refused medical care based on cost. Median reported out-of-pocket (OOP) costs for the initial 6 months of cancer treatment was $2,496 (range, $0-25,900). Risk factors for FT at diagnosis were unique from risk factors at 6MFU. Actual OOP expenses were not correlated with FT; however, inability to predict upcoming treatment expenses resulted in higher FT at 6MFU. DISCUSSION: FT is a pervasive challenge during the initiation of lung cancer treatment. Few patients are willing to sacrifice medical care regardless of the cost. Risk factors for FT evolve, resulting in unique interventional targets throughout therapy.

Patient-Reported Outcome Measures and Dosimetric Correlates for Early Detection of Acute Radiation Therapy-Related Esophagitis.

BACKGROUND: We investigate the time to and clinical factors associated with patient-reported difficulty swallowing in lung cancer patients treated with radiation therapy (RT). METHODS: Between October 2016 and October 2019, lung cancer patients treated with conventionally fractionated RT at a tertiary cancer center were identified. Weekly, patients reported difficulty swallowing (patient-reported outcome version of the Common Terminology Criteria for Adverse Events [PRO-CTCAE] v.1: 0-none, 1-mild, 2-moderate, 3-severe, 4-very severe). Physicians graded dysphagia (CTCAE v.4: 0-none, 1-symptoms without altered intake, 2-symptomatic; altered eating/swallowing, 3-severely altered eating/swallowing, 4-life-threatening consequences, 5-death). Tumor-related difficulty swallowing was not recorded at baseline; thus, patients reporting ≥moderate symptoms ≤7 days of RT start were excluded. We evaluated the time to new patient reports of ≥moderate difficulty swallowing and CTCAE grade 2+ dysphagia and development over time using the cumulative incidence method. Multivariable logistic regression evaluated associations between clinical factors, esophageal V60, and development of esophageal symptoms. RESULTS: Of the 200 patients identified: median age was 69 years, 52% were male, and 89% had stage III+ disease. Patients received a median of 63 Gy with chemotherapy (91.5%). At least moderate difficulty swallowing during RT was reported by 76 of 200 patients (38%); clinicians rated dysphagia as altering oral intake or worse for 26 of 200 (13%). Median time to first report of symptoms was 21 days (interquartile ratio [IQR], 18-34.5) for the 76 patients who reported ≥moderate symptoms and 33 days (IQR, 24-42) in the 26 patients whose provider reported grade 2+ dysphagia. The 30-day incidence of patient-reported ≥moderate swallowing difficulty and provider grade 2+ dysphagia was 26% (95% CI: 20%-32%) and 6% (95% CI: 3%-9%), respectively. Esophageal V60 >7 % was the clinical factor most associated with patient-reported ≥moderate esophageal symptoms (odds ratio 6.1, 95% CI: 3.0-12.3). CONCLUSIONS: Patients report at least moderate difficulty swallowing more often and earlier than providers report grade 2+ dysphagia. Esophageal V60 ≥7% was most associated with development of moderate severity or worse patient-reported swallowing difficulty.

Radiologic response of chemotherapy alone versus radiation and chemotherapy in the treatment of locally-advanced or advanced thymic epithelial tumors.

BACKGROUND: Here, we investigated radiological responses following chemotherapy alone as compared to both radiation/chemotherapy (chemoRT) in patients with thymic epithelial tumors (TETs) who did not receive upfront surgery. METHODS: TETs treated at a tertiary academic cancer center between January 2007 and July 2018 were identified. Patients received chemotherapy or chemoRT as initial therapy and pre- and post-treatment scans were available. Student's t-test, Wilcoxon rank-sum tests, and Cox proportional hazards method were used to compare clinical details and survival between groups. The primary outcome was change in tumor size, which was compared between groups using linear mixed-effects regression models, adjusting for baseline tumor size, age, and histology. RESULTS: A total of 24 of 114 patients with TETs identified met the inclusion criteria. The majority of patients had 67% thymoma (67%, n = 16) and AJCC8 III-IVA disease (58%, n = 14). Median age was 58.5 years (range: 33-76), median initial tumor volume was 187.1 cc (range: 28.7-653.6) and diameter was 8.5 cm (range: 4.5-14.3). Half of the patients received upfront chemotherapy (n = 12: 83% cisplatin/adriamycin/cyclophosphamide) or chemoRT (n = 12: 58% carboplatin/paclitaxel; median RT dose: 63 Gy [range: 60-70 Gy]). At a median imaging follow-up of 15 months (range: 0-86): ChemoRT was associated with increased average radiological response compared to chemotherapy alone (volume: -47.0 cc more, P < 0.001; diameter: -0.8 cm more, P = 0.03). In eight patients who received chemotherapy, 33% saw further tumor shrinkage (median volume: -42.3%, P = 0.03; diameter: -3.0%, P = 0.049) with additional radiation/chemoradiation. Median survival increased for patients ultimately receiving surgery versus those who did not (46 month, range: 16-127 vs. 14 month, range: 6-82; P < 0.01). CONCLUSIONS: ChemoRT produced a greater radiologic response compared to chemotherapy alone in patients with TETs not suitable for upfront resection. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: We found that chemoRT was associated with a greater radiologic response compared to patients who received chemotherapy alone. WHAT THIS STUDY ADDS: What this study adds: In patients with TET not amenable to upfront resection, chemoRT may be a feasible strategy for cytoreduction.

Consolidative Radiotherapy in Oligometastatic Lung Cancer: Patient Selection With a Prediction Nomogram.

BACKGROUND: Patients with stage IV oligometastatic (≤ 3 sites) non-small-cell lung cancer have a progression-free survival (PFS) and overall survival benefit when all sites of metastatic disease and the primary tumor are treated radically with consolidative radiotherapy (cRT). However, the optimal selection of patients most likely from cRT is yet to be defined. PATIENTS AND METHODS: Patients with metastatic non-small-cell lung cancer treated with definitive radiotherapy to all metastatic sites and primary tumor (2008-2019) were retrospectively identified. Univariable Cox proportional-hazards model was used to compare outcomes with demographic and clinical characteristics. A predictive nomogram model for selection of patients most likely to benefit from cRT was constructed. RESULTS: There were 91 patients identified with a total of 114 metastases treated. Median PFS from the start of cRT was 10.9 months (95% confidence interval [CI], 8.1-16.6), while the median survival time was 37.0 months (95% CI, 31.3-NR). On univariable modeling, patients with squamous histology (hazard ratio, 4.16; 95% CI, 1.99-8.71; P < .001) and those treated with non-stereotactic body radiotherapy hypofractionated therapy (hazard ratio, 5.43; 95% CI, 2.10-14.01; P < .001) had worse overall survival, while patients with targetable mutations (hazard ratio, 0.49; 95% CI, 0.25-0.98; P = .04) had a longer survival. Using a predictive nomogram model, patients with a solitary site of metastasis, targetable mutations, intracranial disease, and metachronous timing of oligometastases had a larger PFS benefit from cRT. CONCLUSION: cRT is associated with favorable outcomes in PFS and overall survival. These results may aid in patient counseling, selection for aggressive local therapy, and stratification in future prospective clinical trials.

Imaging in Therapy Response Assessment and Surveillance of Lung Cancer: Evidenced-based Review With Focus on the Utility of 18F-FDG PET/CT.

This review covers the state-of-the-art imaging in therapy assessment and surveillance of lung cancer with focus on the utility of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). We review different qualitative and quantitative response assessment criteria in lung cancer, common pitfalls and atypical patterns of response to immunotherapy, and imaging features of common immune-related adverse events. In addition, the currently recommended imaging workup in surveillance of asymptomatic patients with non-small-cell and small-cell lung cancer and future developments will be discussed.