The International Association for the Study of Lung Cancer Staging Project for Lung Cancer: Proposals for the Revision of the M Descriptors in the Forthcoming Ninth Edition of the TNM Classification for Lung Cancer.

INTRODUCTION: This study analyzed all metastatic categories of the current TNM classification of NSCLC to propose modifications of the M component in the next edition (ninth) of the classification. METHODS: A database of 124,581 patients diagnosed between 2011 and 2019 was established; of these, 14,937 with NSCLC in stages IVA to IVB were available for this analysis. Overall survival was calculated using the Kaplan-Meier method, and prognosis was assessed using multivariable-adjusted Cox proportional hazards regression. RESULTS: The eighth edition M categories revealed good discrimination in the ninth edition data set. Assessments revealed that an increasing number of metastatic lesions were associated with decreasing prognosis; because this seems to be a continuum and adjustment for confounders was not possible, no specific lesion number was deemed appropriate for stage classification. Among tumors involving multiple metastases, decreasing prognosis was found with an increasing number of organ systems involved. Multiple assessments, including after adjustment for potential confounders, revealed that M1c patients who had metastases to a single extrathoracic organ system were prognostically distinct from M1c patients who had involvement of multiple extrathoracic organ systems. CONCLUSIONS: These data validate the eighth edition M1a and M1b categories, which are recommended to be maintained. We propose the M1c category be divided into M1c1 (involvement of a single extrathoracic organ system) and M1c2 (involvement of multiple extrathoracic organ systems).

Gastric Extent of Tumor Predicts Peritoneal Metastasis in Siewert II Adenocarcinoma.

BACKGROUND: Whereas current guidelines recommend staging laparoscopy for most patients with potentially resectable gastric cancer, such a recommendation for patients with adenocarcinoma of the gastroesophageal junction (AEG) is lacking. This study sought to identify baseline clinicopathologic characteristics associated with peritoneal metastasis (PM) among patients with Siewert II AEG. METHODS: Trimodality therapy-eligible patients with Siewert II AEG (2000-2015, single institution) were retrospectively identified. A composite PM outcome was defined as follows: (1) PM at staging laparoscopy; (2) PM diagnosed during neoadjuvant chemoradiation; or (3) PM ≤6 months postoperatively. Logistic regression was used to identify features associated with PM; bootstrapped analysis (Youden J) identified the distal tumor extension that best discriminated the composite outcome. RESULTS: Of 188 patients, a composite PM outcome was observed in 26 of 188 (13.8%); 12 of 26 had positive staging laparoscopy, 10 of 26 experienced PM during chemoradiation, and 4 of 26 had PM ≤6 months postoperatively. Tumor extension below the GEJ was greater in patients with PM (median, 4.0 cm [interquartile range, 3.0-5.0] vs 3.0 cm [interquartile range, 2.0-3.0]; P < .001). All patients with PM had cT3 to cT4 tumors. Among patients with cT3 to cT4 tumors (n = 168 of 188; 89.4%), distal tumor extent (odds ratio, 1.67/cm; 95% CI, 1.23-2.28; P = .001) was independently associated with increased odds of PM. Gastric tumor extension ≥4 cm remained independently associated with PM (OR, 5.14; 95% CI, 2.11-12.53; P < .001) after adjustment for signet ring cell status. CONCLUSIONS: Distal tumor extent beyond the GEJ is independently associated with increased odds of PM in patients with Siewert II AEG. Patients with extensive gastric involvement should therefore be considered for staging laparoscopy before trimodality therapy.

SABR for Sarcoma Lung Metastases: Indications for Treatment and Guidance for Patient Selection.

PURPOSE: The lungs are the most common site of metastasis for patients with soft tissue sarcoma. SABR is commonly employed to treat lung metastases among select patients with sarcoma with limited disease burden. We sought to evaluate outcomes and patterns of failure among patients with sarcoma treated with SABR for their lung metastases. METHODS AND MATERIALS: We performed a retrospective review of patients treated at a tertiary cancer center between 2006 and 2020. Patient disease status at the time of SABR was categorized as either oligorecurrent or oligoprogressive. The Kaplan-Meier method was used to estimate disease outcomes. Uni- and multivariable analyses were conducted using the Cox proportional hazards model. RESULTS: We identified 70 patients with soft tissue sarcoma treated with SABR to 98 metastatic lung lesions. Local recurrence-free survival after SABR treatment was 83% at 2 years. On univariable analysis, receipt of comprehensive SABR to all sites of pulmonary metastatic disease at the time of treatment was associated with improved progression-free survival (PFS; hazard ratio [HR], 0.51 [0.29-0.88]; P = .02). On multivariable analysis, only having systemic disease controlled at the time of SABR predicted improved PFS (median PFS, 14 vs 4 months; HR, 0.37 [0.20-0.69]; P = .002) and overall survival (median overall survival, 51 vs 14 months; HR, 0.17 [0.08-0.35]; P < .0001). CONCLUSIONS: SABR provides durable long-term local control for sarcoma lung metastases. The most important predictor for improved outcomes was systemic disease control. Careful consideration of these factors should help guide decisions in a multidisciplinary setting to appropriately select the optimal candidates for SABR.

Considerations for Imaging of Malignant Pleural Mesothelioma: A Consensus Statement from the International Mesothelioma Interest Group.

Malignant pleural mesothelioma (MPM) is an aggressive primary malignancy of the pleura that presents unique radiologic challenges with regard to accurate and reproducible assessment of disease extent at staging and follow-up imaging. By optimizing and harmonizing technical approaches to imaging MPM, the best quality imaging can be achieved for individual patient care, clinical trials, and imaging research. This consensus statement represents agreement on harmonized, standard practices for routine multimodality imaging of MPM, including radiography, computed tomography, 18F-2-deoxy-D-glucose positron emission tomography, and magnetic resonance imaging, by an international panel of experts in the field of pleural imaging assembled by the International Mesothelioma Interest Group. In addition, modality-specific technical considerations and future directions are discussed. A bulleted summary of all technical recommendations is provided.

Liver Injury in Patients With Distal Esophageal Carcinoma After Precision Radiation Therapy: Systematic Review of FDG-PET/CT Patterns.

OBJECTIVE: To determine the incidence and various patterns of radiation-induced liver injury (RILI) and its temporal evolution on fluorodeoxiglucose-positron emission tomography/computed tomography (FDG-PET/CT) after neoadjuvant chemoradiation using precision radiation in patients with esophageal carcinoma. MATERIAL AND METHODS: We evaluated 639 patients with locally advanced esophageal carcinoma who had serial FDG-PET/CTs after neoadjuvant chemoradiation. Two readers reviewed the imaging studies in consensus and recorded the cases where new foci of increased FDG uptake were identified within the radiated liver parenchyma. RILI was confirmed by follow-up imaging or percutaneous biopsy. RESULTS: FDG-avid RILI developed in 39/639 (6%) of patients. The caudate and left hepatic lobe were involved in all cases. There were various patterns of increased FDG uptake: 38% of patients had a single focus of increased FDG uptake and 62% had 2 regions of increased FDG uptake, which were focal nodular or diffuse or a combination of focal nodular and diffuse FDG uptake. On CT, 72% of patients had a poorly-marginated region of low attenuation and 28% had a well-defined region of low attenuation with sharp, well-defined linear borders in the location of the radiation, as confirmed by the treatment plan. CONCLUSION: The caudate and left hepatic lobes were involved in all cases of RILI. The various imaging patterns of RILI on FDG-PET/CT include 1 or 2 regions of increased FDG uptake with a nodular, diffuse, or combined appearance. Awareness of this potential complication of radiation therapy and knowledge of the imaging manifestations of RILI is important to avoid misinterpretation as a metastasis.

Clinical Significance of [18F] Fluoro-2-Deoxy-d-Glucose/Computed Tomographic Avid Hilar Lymph Nodes in Esophageal Carcinoma Patients.

BACKGROUND: The assumption that increased [18F] fluoro-2-deoxy-d-glucose (FDG) uptake in hilar nodes on positron emission tomography/computed tomography (PET/CT) imaging is indicative of distant metastasis can result in palliative rather than curative care in patients with esophageal cancer. This study aimed to determine the significance of increased FDG uptake in hilar nodes in patients with potentially curable, locally advanced disease at initial staging. METHODS: We included patients with biopsy specimen-proven esophageal carcinoma who had pretreatment FDG-PET/CT at initial staging and follow-up imaging >1 year. We excluded patients with distant hematogeneous metastases. Hilar nodes were considered concerning for metastatic disease when the maximum standardized uptake value was >2.5 or FDG uptake was visually greater than the mediastinal background. RESULTS: We reviewed FDG-PET CT scans from 806 patients treated for esophageal cancer from 2010 to 2018 and identified 42 patients with FDG-avid hilar adenopathy. Thirteen patients underwent histologic assessment, and 29 were monitored with imaging. None of the 42 patients had distant metastatic disease on the initial workup, and all were treated curatively. In follow-up, 2 of 42 patients eventually manifested hilar nodal metastases after treatment; 1 who had a biopsy specimen-negative hilar node at initial staging and another who did not have a biopsy of the hilar node. CONCLUSIONS: Increased FDG uptake in hilar nodes in patients with localized esophageal cancer was not indicative of nonregional nodal metastasis. Patients in these situations should be approached with curative intent. The need for biopsy of FDG-avid hilar nodes in this cohort should be carefully considered due to the low diagnostic utility.

Pitfalls and Pearls in Esophageal Carcinoma.

The management of patients with esophageal carcinoma (EC) requires accurate clinical staging and post-therapeutic evaluation. Currently, esophagogastroduodenoscopy/endoscopic ultrasound (EGD/EUS), endoscopic ultrasound-fine needle aspiration (EUS-FNA), computed tomography (CT), 18F- fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) and magnetic resonance (MR) imaging are used for the initial clinical staging, evaluation of therapeutic response and follow-up in patients with EC. However, there are limitations and pitfalls that are commonly encountered when imaging these patients that can limit accurate assessment. Knowledge of the limitations and pitfalls associated with the use of these different imaging modalities is essential in avoiding misinterpretation and guaranteeing the appropriate management for patient with EC.

High-dose irradiation in combination with non-ablative low-dose radiation to treat metastatic disease after progression on immunotherapy: Results of a phase II trial.

AIM: To report early findings from a phase II trial of high-dose radiotherapy (HD-RT) with or without low-dose RT (LD-RT) for metastatic cancer. METHODS: Eligible patients had metastatic disease that progressed on immunotherapy within 6 months. Patients were given either HD-RT (20-70 Gy total; 3-12.5 Gy/f), or HD-RT + LD-RT (0.5-2 Gy/f up to 1-10 Gy total) to separate lesions, with continued immunotherapy. Radiographic response was assessed per RECIST 1.1 and Immune-Related Response Criteria (irRC). Primary endpoints: (1) 4-month disease control (DCR, complete/partial response [CR/PR] or stable disease [SD]) or an overall response (ORR, CR/PR) at any point in ≥10% of patients, per RECIST 1.1; (2) dose-limiting toxicity within 3 months not exceeding 30%. Secondary endpoint was lesion-specific response. RESULTS: Seventy-four patients (NSCLC, n = 38; melanoma n = 21) were analyzed (39 HD-RT and 35 HD-RT + LD-RT). The median follow-up time was 13.6 months. The primary endpoint was met for 72 evaluable patients, with a 4-month DCR of 42% (47% [16/34] vs. 37% [14/38] in HD-RT + LD-RT vs. HD-RT, P = 0.38), and 19% ORR at any time (26% [9/34] vs. 13% [5/38] in HD-RT + LD-RT vs. HD-RT, P = 0.27). Three patients had toxicity ≥grade 3. LD-RT lesion response (53%) was improved compared to nonirradiated lesions in HD-RT + LD-RT (23%, P = 0.002) and HD-RT (11%, P < 0.001). T- and NK cell infiltration was enhanced in lesions treated with LD-RT. CONCLUSIONS: HD-RT plus LD-RT safely improved lesion-specific response in patients with immune resistant solid tumors by promoting infiltration of effector immune cells into the tumor microenvironment.

Addition of Metformin to Concurrent Chemoradiation in Patients With Locally Advanced Non-Small Cell Lung Cancer: The NRG-LU001 Phase 2 Randomized Clinical Trial.

IMPORTANCE: Non-small cell lung cancer (NSCLC) has relatively poor outcomes. Metformin has significant data supporting its use as an antineoplastic agent. OBJECTIVE: To compare chemoradiation alone vs chemoradiation and metformin in stage III NSCLC. DESIGN, SETTING, AND PARTICIPANTS: The NRG-LU001 randomized clinical trial was an open-label, phase 2 study conducted from August 24, 2014, to December 15, 2016. Patients without diabetes who were diagnosed with unresectable stage III NSCLC were stratified by performance status, histology, and stage. The setting was international and multi-institutional. This study examined prespecified endpoints, and data were analyzed on an intent-to-treat basis. Data were analyzed from February 25, 2019, to March 6, 2020. INTERVENTIONS: Chemoradiation and consolidation chemotherapy with or without metformin. MAIN OUTCOMES AND MEASURES: The primary outcome was 1-year progression-free survival (PFS), designed to detect 15% improvement in 1-year PFS from 50% to 65% (hazard ratio [HR], 0.622). Secondary end points included overall survival, time to local-regional recurrence, time to distant metastasis, and toxicity per Common Terminology Criteria for Adverse Events, version 4.03. RESULTS: A total of 170 patients were enrolled, with 167 eligible patients analyzed after exclusions (median age, 64 years [interquartile range, 58-72 years]; 97 men [58.1%]; 137 White patients [82.0%]), with 81 in the control group and 86 in the metformin group. Median follow-up was 27.7 months (range, 0.03-47.21 months) among living patients. One-year PFS rates were 60.4% (95% CI, 48.5%-70.4%) in the control group and 51.3% (95% CI, 39.8%-61.7%) in the metformin group (HR, 1.15; 95% CI, 0.77-1.73; P = .24). Clinical stage was the only factor significantly associated with PFS on multivariable analysis (HR, 1.79; 95% CI, 1.19-2.69; P = .005). One-year overall survival was 80.2% (95% CI, 69.3%-87.6%) in the control group and 80.8% (95% CI, 70.2%-87.9%) in the metformin group. There were no significant differences in local-regional recurrence or distant metastasis at 1 or 2 years. No significant difference in adverse events was observed between treatment groups. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the addition of metformin to concurrent chemoradiation was well tolerated but did not improve survival among patients with unresectable stage III NSCLC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02186847.

Outcomes and toxicities following stereotactic ablative radiotherapy for pulmonary metastases in patients with primary head and neck cancer.

BACKGROUND: Metastatic head and neck cancers (HNCs) predominantly affect the lungs and have a two-year overall survival (OS) of 15% to 50%, if amenable for pulmonary metastasectomy. METHODS: Retrospective review of the two-year local control (LC), local-regional control (LRC) within the same lobe, OS, and toxicity rates in consecutive patients with metastatic pulmonary HNC who underwent stereotactic ablative radiotherapy (SABR) January 2007 to May 2018. RESULTS: Evaluated 82 patients with 107 lung lesions, most commonly squamous cell carcinoma (SCC; 64%). Median follow-up was 20 months (range: 9.0-97.6). Systemic therapy administered in 34%. LC, LRC, and OS rates were 94%, 90%, and 62%. Patients with oligometastatic disease had a higher OS than polymetastatic disease, 72% vs 44% (HR = 0.30, 95% CI: 0.14-0.64; P = .008). OS in oligometastatic non-SCC and SCC were 100% and 66% (P = .03). There were no grade ≥3 toxicities. CONCLUSIONS: Metastatic pulmonary HNCs after SABR have a two-year OS rate comparable to pulmonary metastasectomy.

Implementing Decision Coaching for Lung Cancer Screening in the Low-Dose Computed Tomography Setting.

PURPOSE: The uptake of shared decision making (SDM) for lung cancer screening (LCS) as required by the Centers for Medicare & Medicaid Services (CMS) is suboptimal. Alternative models for delivering SDM are needed, such as decision coaching in the low-dose computed tomography (LDCT) setting. METHODS AND MATERIALS: The Replicating Effective Programs framework guided our implementation of decision coaching, which included a patient-facilitated component before screening followed by in-person coaching that addressed the required elements for the SDM visit from CMS. We surveyed two LCS patient cohorts (pre-implementation and implementation of decision coaching) about their knowledge of LCS and perception of the SDM process. We conducted time-motion studies to assess the feasibility of implementing decision coaching and audio recorded clinical encounters from the implementation cohort to assess fidelity of the SDM conversation to the CMS requirements. RESULTS: Compared with the pre-implementation cohort (n = 51), the implementation cohort (n = 30) had greater knowledge of LCS (P < .01) and reported a better SDM process (P = .01). Coaching took 7.6 ± 4.1 minutes and did not increase visit time (P = .72). Coaches addressed an average of 6.4 of 7 SDM elements required by CMS. CONCLUSION: Decision coaching in the LDCT setting provides an opportunity for patients to confirm their screening decision by ensuring that patients are truly informed about the potential harms and benefits of LCS. The decision coaching had excellent fidelity in addressing the required SDM elements from CMS and is feasible.

Stereotactic ablative radiation therapy for pulmonary metastases: Improving overall survival and identifying subgroups at high risk of local failure.

BACKGROUND & PURPOSE: Stereotactic ablative radiation therapy (SABR) is an emerging treatment option for patients with pulmonary metastases; identifying patients who would benefit from SABR can improve outcomes. MATERIALS & METHODS: We retrospectively analyzed local failure (LF), distant failure (DF), overall survival (OS), and toxicity in 317 patients with 406 pulmonary metastases treated with SABR in January 2006-September 2017 at a tertiary cancer center. RESULTS: Median follow-up time was 23 months. Primary adrenal, colorectal, sarcoma, or pancreatic ("less responsive") tumors led to high rates of LF. LF rates for patients with less responsive vs. responsive tumors were 4.6% vs. 1.6% at 12 months and 12.8% vs. 3.9% at 24 months (hazard ratio [HR] 0.29, 95% confidence interval [CI] 0.11-0.73; Log-Rank P = 0.0087). A nomogram for 24-month local control was created using Cox multivariate factors (surgical history, planning target volume, primary disease site, lung lobe location). Treating patients with ≤3 pulmonary metastases vs. >3 pulmonary metastases was associated with improved 24-month (74.2% vs. 59.3%) and 48-month (47.7% vs. 35.1%) OS (HR 0.66, 95% CI 0.47-0.95; Log-Rank P = 0.043), and reduced 12-month (22.5% vs. 50.8%) and 24-month (31.8% vs. 61.4%) intrathoracic DF (HR 0.53, 95% CI 0.38-0.74; Log-Rank P < 0.0001). The most common toxicity was asymptomatic pneumonitis (14.8%). Six patients had grade 3 events (5 pneumonitis, 1 brachial plexus). CONCLUSIONS: SABR for pulmonary metastases was effective and well tolerated. Irradiating limited intrathoracic sites of disease led to improved OS and intrathoracic DM. Higher SABR doses or surgery could be considered for less radio-responsive primary tumors.

IASLC Multidisciplinary Recommendations for Pathologic Assessment of Lung Cancer Resection Specimens After Neoadjuvant Therapy.

Currently, there is no established guidance on how to process and evaluate resected lung cancer specimens after neoadjuvant therapy in the setting of clinical trials and clinical practice. There is also a lack of precise definitions on the degree of pathologic response, including major pathologic response or complete pathologic response. For other cancers such as osteosarcoma and colorectal, breast, and esophageal carcinomas, there have been multiple studies investigating pathologic assessment of the effects of neoadjuvant therapy, including some detailed recommendations on how to handle these specimens. A comprehensive mapping approach to gross and histologic processing of osteosarcomas after induction therapy has been used for over 40 years. The purpose of this article is to outline detailed recommendations on how to process lung cancer resection specimens and to define pathologic response, including major pathologic response or complete pathologic response after neoadjuvant therapy. A standardized approach is recommended to assess the percentages of (1) viable tumor, (2) necrosis, and (3) stroma (including inflammation and fibrosis) with a total adding up to 100%. This is recommended for all systemic therapies, including chemotherapy, chemoradiation, molecular-targeted therapy, immunotherapy, or any future novel therapies yet to be discovered, whether administered alone or in combination. Specific issues may differ for certain therapies such as immunotherapy, but the grossing process should be similar, and the histologic evaluation should contain these basic elements. Standard pathologic response assessment should allow for comparisons between different therapies and correlations with disease-free survival and overall survival in ongoing and future trials. The International Association for the Study of Lung Cancer has an effort to collect such data from existing and future clinical trials. These recommendations are intended as guidance for clinical trials, although it is hoped they can be viewed as suggestion for good clinical practice outside of clinical trials, to improve consistency of pathologic assessment of treatment response.

Improved Alignment of PET and CT Images in Whole-Body PET/CT in Cases of Respiratory Motion During CT.

Respiratory motion during the CT and PET parts of a PET/CT scan leads to imperfect alignment of anatomic features seen by the 2 modalities. In this work, we concentrate on the effects of motion during CT. We propose a novel approach for improving the alignment. Methods: Respiratory waveform data were gathered during the CT and PET parts of 28 PET/CT scans of cancer patients with 40 lesions up to 3 cm in size in the lung or upper abdomen. PET list-mode data were reconstructed by 3 reconstruction methods: PET/static (the standard method with no motion correction); PET/ex (a method that calculates a range of expiratory amplitudes from the lowest one to the highest one); and PET/matched (a novel method that uses both waveforms). The 3 methods were compared. The distance between tumor positions in PET and CT were characterized in visual interpretation by physicians as well as quantitatively. Tumor SUVs (SUVmax and SUVpeak) were determined relative to SUV based on the static method. Image noise was evaluated in the liver and compared with PET/static. Results: In visual interpretation, the rate of good alignment was 13 of 21, 13 of 23, and 18 of 21 for the PET/static, PET/ex, and PET/matched methods, respectively, and the mean PET/CT distances were 3.5, 5.1, and 2.8 mm. In visual comparison with PET/ex, the rate of good alignment was increased in 1 of 10 and 7 of 10 cases for PET/static and PET/matched, respectively. SUVmax was on average 21% higher than PET/static when either PET/ex or PET/matched was used. SUVpeak was 12% higher. Image noise in the liver was 15% higher than PET/static for the PET/ex method, and 40% higher for PET/matched; that is, noise was much lower than in gated PET. Conclusion: Acquiring respiratory waveforms both in PET (as in the current state of the art) and in CT (an unusual key step in this approach) has the potential to improve the alignment of PET and CT images. A proposed method for using this information was tested. Improved alignment was demonstrated.

Characterization of continuous bed motion effects on patient breathing and respiratory motion correction in PET/CT imaging.

Continuous bed motion (CBM) was recently introduced as an alternative to step-and-shoot (SS) mode for PET/CT data acquisition. In CBM, the patient is continuously advanced into the scanner at a preset speed, whereas in SS, the patient is imaged in overlapping bed positions. Previous investigations have shown that patients preferred CBM over SS for PET data acquisition. In this study, we investigated the effect of CBM versus SS on patient breathing and respiratory motion correction. One hundred patients referred for PET/CT were scanned using a Siemens mCT scanner. Patient respiratory waveforms were recorded using an Anzai system and analyzed using four methods: Methods 1 and 2 measured the coefficient of variation (COV) of the respiratory cycle duration (RCD) and amplitude (RCA). Method 3 measured the respiratory frequency signal prominence (RSP) and method 4 measured the width of the HDChest optimal gate (OG) window when using a 35% duty cycle. Waveform analysis was performed over the abdominothoracic region which exhibited the greatest respiratory motion and the results were compared between CBM and SS. Respiratory motion correction was assessed by comparing the ratios of SUVmax, SUVpeak, and CNR of focal FDG uptake, as well as Radiologists' visual assessment of corresponding image quality of motion corrected and uncorrected images for both acquisition modes. The respiratory waveforms analysis showed that the RCD and RCA COV were 3.7% and 33.3% lower for CBM compared to SS, respectively, while the RSP and OG were 30.5% and 2.0% higher, respectively. Image analysis on the other hand showed that SUVmax, SUVpeak, and CNR were 8.5%, 4.5%, and 3.4% higher for SS compared to CBM, respectively, while the Radiologists' visual comparison showed similar image quality between acquisition modes. However, none of the results showed statistically significant differences between SS and CBM, suggesting that motion correction is not impacted by acquisition mode.

Surveillance After Treatment of Non-Small-Cell Lung Cancer: A Call for Multidisciplinary Standardization.

OBJECTIVE: Though interest in expansion of the use of less-invasive therapies among operable non-small-cell lung cancer (NSCLC) patients is growing, it is not clear that post-treatment surveillance has been comparable between treatment modalities. We sought to characterize institutional surveillance patterns after NSCLC therapy with stereotactic body radiation therapy (SBRT) and lobectomy. METHODS: NSCLC patients treated with lobectomy or SBRT (2005 to 2016) at a single institution were identified. Natural language processing searched data fields within axial surveillance imaging reports for findings suggestive of recurrence. Duration and patterns of institutional surveillance were compared between the 2 groups. RESULTS: Three thousand forty-two patients (73.5% lobectomy, 26.5% SBRT) met inclusion criteria. Patients had a longer median duration of surveillance after lobectomy (28.0 months vs SBRT 12.3 months, P < 0.001) and were more likely to undergo histopathological evaluation of clinically suspected relapse (206/274 [75.2%] vs SBRT 54/113 [47.8%], P < 0.001). Patients with clinical suspicion of recurrence had longer durations of institutional surveillance than those who did not among both cohorts (lobectomy 44.4 months vs 25.9, P < 0.001; SBRT 27.9 vs 10.3, P < 0.001). Landmark analyses at 1 and 3 years after therapy identified associations between receipt of lobectomy and ongoing surveillance at each time point (1 year odds ratio [OR] 2.10, P < 0.001; 3 years OR 1.71, P < 0.001) among all patients and those with documented stage I disease. CONCLUSIONS: We identified potential heterogeneity in institutional surveillance patterns after treatment of NSCLC with 2 therapeutic modalities. As less-invasive treatment options for operable patients expand, it will be critical to implement rigorous surveillance paradigms across all modalities.

Results of a Phase 1/2 Trial of Chemoradiotherapy With Simultaneous Integrated Boost of Radiotherapy Dose in Unresectable Locally Advanced Esophageal Cancer.

Importance: Effective treatment options for locally advanced esophageal cancer are limited, and rates of local recurrence after standard chemoradiotherapy remain high. Objective: To evaluate toxic effects, local control, and overall survival rates after chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose to the gross tumor and nodal disease for patients with unresectable locally advanced esophageal cancer. Design, Setting, and Participants: A phase 1/2, single-arm trial was conducted in 46 patients from April 28, 2010, to April 9, 2015 (median follow-up, 52 months [range, 2-86 months]), at a tertiary academic cancer center. Outcomes of the study patients were compared with those of 97 similar patients treated at the same institution from January 10, 2010, to December 5, 2014, as part of the interim analysis. Statistical analysis was performed from December 15, 2018, to February 12, 2019. Interventions: Chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose (50.4 Gy to subclinical areas at risk and 63.0 Gy to the gross tumor and involved nodes, all given in 28 fractions) with concurrent docetaxel and capecitabine or fluorouracil. Main Outcomes and Measures: Toxic effects, local (in-field) control, and overall survival rates. Results: All 46 patients (11 women and 35 men; median age, 65.5 years [range, 37.3-84.4 years]) received per-protocol therapy, as intensity-modulated photon therapy (39 [85%]) or intensity-modulated proton therapy (7 [15%]); 11 patients (24%) ultimately underwent resection. No patients experienced grade 4 or 5 toxic effects; the 10 acute grade 3 toxic events were esophagitis (4), dysphagia (3), and anorexia (3) and the 3 late grade 3 toxic events were all esophageal strictures. The actuarial local recurrence rates were 22% (95% CI, 11%-35%) at 6 months, 30% (95% CI, 18%-44%) at 1 year, and 33% (95% CI, 20%-46%) at 2 years. Overall, 15 patients (33%) experienced local failure, at a median interval of 5 months (range, 1-24 months). The median overall survival time was 21.5 months (range, 2.3-86.4 months). Exploratory comparison with a 97-patient contemporaneous institutional cohort receiving standard-dose (non-simultaneous integrated boost) chemoradiotherapy showed superior local control (hazard ratio, 0.49; 95% CI, 0.26-0.92; P = .03) and overall survival (hazard ratio, 0.66; 95% CI, 0.47-0.94; P = .02) in the group that received chemoradiotherapy with a simultaneous integrated boost. Conclusions and Relevance: These findings suggest that chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose for locally advanced esophageal cancer is well tolerated, with encouraging local control, and thus warrants further study. Trial Registration: ClinicalTrials.gov identifier: NCT01102088.

Influence of low-dose radiation on abscopal responses in patients receiving high-dose radiation and immunotherapy.

BACKGROUND: Preclinical evidence suggests that low-dose radiation may overcome the inhibitory effects of the tumor stroma and improve a tumor's response to immunotherapy, when combined with high-dose radiation to another tumor. The aim of this study was to evaluate tumor responses to this combination in a clinical setting. METHODS: A post-hoc analysis of 3 ongoing immunoradiation trials was performed. Twenty-six (of 155) patients received low-dose radiation (1-20 Gy total), either as scatter from high-dose radiation or from intentional treatment of a second isocenter with low-dose radiation, were evaluated for response. The low-dose lesions were compared to lesions that received no radiation (< 1 Gy total). Response rates, both defined as complete and partial responses as defined by RECIST criteria were used to compare lesion types. RESULTS: The 26 patients had a total of 83 lesions for comparison (38 receiving low-dose, 45 receiving no-dose). The average dose given to low-dose lesions was 7.3 Gy (1.1-19.4 Gy), and the average time to response was 56 days. Twenty-two out of 38 (58%) low-dose lesions met the PR/CR criteria for RECIST compared with 8 out of 45 (18%) no-dose lesions (P = 0.0001). The median change for longest diameter size for low-dose lesions was - 38.5% compared to 8% in no-dose lesions (P < 0.0001). Among the low-dose lesions that had at least one no-dose lesion within the same patient as a control (33 and 45 lesions respectively), 12 low-dose lesions (36%) responded without a corresponding response in their no-dose lesions; Conversely, two (4%) of the no-dose lesions responded without a corresponding response in their low-dose lesion (P = 0.0004). CONCLUSIONS: Low-dose radiation may increase systemic response rates of metastatic disease treated with high-dose radiation and immunotherapy.

Local failure after stereotactic body radiation therapy or wedge resection for colorectal pulmonary metastases.

OBJECTIVE: Several options are available for the local treatment of colorectal pulmonary metastases; however, the efficacy of each treatment has not been well characterized. We compared the risk of local recurrence after wedge resection or stereotactic body radiation therapy for pulmonary metastases of colorectal origin. METHODS: We retrospectively reviewed records of patients treated for pulmonary colorectal metastases with stereotactic body radiation therapy or wedge resection from 2006 to 2016 at a single institution. Local recurrence was defined as an enlarging nodule either adjacent to the staple line or within the radiation field on computed tomography. Matching weights using the propensity score with death as a competing event was used to estimate the risk of local recurrence for each metastatic nodule. RESULTS: A total of 381 patients underwent 762 wedge resections and 64 courses of stereotactic body radiation therapy for definitive treatment of 826 pulmonary nodules. The risk of local recurrence was increased with stereotactic body radiation therapy (hazard ratio, 3.28; 95% confidence interval, 1.53-7.04; P = .002) and larger tumor size (hazard ratio, 1.38 per additional centimeter; 95% confidence interval, 1.01-1.87; P = .042). After reweighting with matching weights, the marginal 2-year risk of local recurrence for each nodule was 14.1% (95% confidence interval, 9.8-18.5) after wedge resection and 29.4% (95% confidence interval, 13.8-45.0) after stereotactic body radiation therapy (P = .023). CONCLUSIONS: Pulmonary colorectal metastases treated with stereotactic body radiation therapy have a higher risk of local recurrence than those treated with wedge resection. Stereotactic body radiation therapy should be reserved for patients with comorbidities precluding surgical resection.