Recurrent Lung Tumors Research Articles

Comparison of 68Ga-FAPI and 18F-FDG PET/CT in the Evaluation of Advanced Lung Cancer.

Background Gallium 68 (68Ga)-labeled fibroblast-activation protein inhibitor (FAPI) has recently been introduced as a promising tumor imaging agent. Purpose To compare 68Ga-FAPI PET/CT with fluorine 18 (18F)-labeled fluorodeoxyglucose (FDG) PET/CT in evaluating lung cancer. Materials and Methods In this prospective study conducted from September 2020 to February 2021, images from participants with lung cancer who underwent both 68Ga-FAPI and 18F-FDG PET/CT examinations were analyzed. The tracer uptakes, quantified by maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR), were compared for paired positive lesions between both modalities using the paired t test or Wilcoxon signed-rank test. Results Thirty-four participants (median age, 64 years [interquartile range: 46-80 years]; 20 men) were evaluated. From visual evaluation, 68Ga-FAPI PET/CT and 18F-FDG PET/CT showed similar performance in the delineation of primary tumors and detection of suspected metastases in the lungs, liver, and adrenal glands. The metabolic tumor volume in primary and recurrent lung tumors showed no difference between modalities (mean: 11.6 vs 10.8, respectively; P = .68). However, compared with 18F-FDG PET/CT, 68Ga-FAPI PET/CT depicted more suspected metastases in lymph nodes (356 vs 320), brain (23 vs 10), bone (109 vs 91), and pleura (66 vs 35). From semiquantitative evaluation, the SUVmax and TBR of primary or recurrent tumors, positive lymph nodes, bone lesions, and pleural lesions at 68Ga-FAPI PET/CT were all higher than those at 18F-FDG PET/CT (all P < .01). Although SUVmax of 68Ga-FAPI and 18F-FDG in brain metastases were not different (mean SUVmax: 9.0 vs 7.4, P = .32), TBR was higher with 68Ga-FAPI than with 18F-FDG (mean: 314.4 vs 1.0, P = .02). Conclusion Gallium 68-labeled fibroblast-activation protein inhibitor PET/CT may outperform fluorine 18-labeled fluorodeoxyglucose PET/CT in staging lung cancer, particularly in the detection of metastasis to the brain, lymph nodes, bone, and pleura. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Jacobson and Van den Abbeele in this issue.

Classical versus non-classical EGFR mutations: Erlotinib response and impact of renal insufficiency.

Erlotinib is an effective treatment option for EGFR-mutant non-small cell lung cancer. It is important to predict patients who will respond better to erlotinib. We designed this study to investigate the effect of renal insufficiency (RI) on erlotinib treatment outcomes. All patients receiving erlotinib were stratified into 3 groups. Group 1 consisted of non-RI subjects with classical epidermal growth factor receptor (EGFR) mutations, Group 2 consisted of those with RI (Estimated glomerular filtration rate <60 mL/min) and classical EGFR mutations, and Group 3 consisted of those with non-classical EGFR mutations. 82 patients were included in the study. Median progression-free survival (PFS) in patients with classical mutation was approximately 6 months shorter in those with RI, although not statistically significant. Median overall survival (OS) in Group 1, 2 and 3 was 34.1 months, 35.2 months, and 15 months, respectively and although not statistically significant, median OS was 20 months shorter in Group 3. Univariate and multivariate cox-regression analysis revealed shorter PFS and OS in males and those with ECOG ≥2 while PFS and OS were longer in those with recurrent lung tumors and generating rash during erlotinib treatment. There was no difference between RI and non-RI patients in terms of adverse events except for fatigue and appetite loss. This research showed OS in patients with and without RI was comparable. Although not statistically significant, PFS in patients with classical mutation was approximately 6 months shorter in those with RI patients.

PUB057 Re-Irradiation of Non-Small Cell Lung Cell Cancer Recurrences with Stereotactic Body Radiotherapy

Decision of salvage therapy for lung cancer recurrences is a major problem because of poor results with re-treatments having greater risk of side-effects. Stereotactic body radiotherapy (SBRT) is a promising technique in re-irradiation of lung cancer recurrences. In this study, we intent to present our results, including the toxicity and outcome of our patients treated with SBRT after radiotherapy failure. 403 patients were treated with SBRT for lung cancer at our department between June 2010 and August 2015. Among these, we identified 16 patients who were re-irradiated using SBRT. PET-CT was used in staging in all patients. All patients had recurrent disease only within the previous radiotherapy treatment volume. The median previous EBRT dose was 66 Gy (range, 46 - 66 Gy). Tumor responses were evaluated with PET-CT 3 months after SBRT and with computerized tomography (CT) every 3 months interval. Outcomes analyzed were > grade 3 radiation pneumonitis, overall survival (OS), local control (LC), progression free survival (PFS) and distant metastasis. The median follow-up time was 30 months from salvage SBRT. The locations of recurrent tumors were central in 12 and peripheral in 4 patients. The median largest tumor size was 4.35 cm (range; 1.4 and 6.6 cm) and planning target volume was median 47.3 cm3 (range; 5.4 and 153.4 cm3). The median SBRT dose was 38 Gy (range; 30 – 60Gy). Total biological equivalent dose (BED) was 63 Gy10 (range, 48 - 115 Gy10) and SBRT was applied after a median time of 12 months (range; 3-36 months) from prior radiation. Complete response was in 13, partial response was in 2, stable or progressive disease was observed in 1 patient. The 1 year, 2 year and 3 year LC rate was 93.8%, 85.2% and 85.2% respectively. The 1 year, 2 year and 3 year OS rate was 87.5% - 67.3% and 40.4% respectively. One and 3-year PFS rates were 49.2% and 28.1% respectively. At the last follow-up 5 patients were alive with no evidence of disease and one patient was alive with systemic metastases. The rate of symptomatic > grade 3 pneumonitis was 12.5 % and one patient developed fatal pneumonitis. Symptomatic > grade 3 chest wall pain or esophagitis was not observed. Salvage therapy with re-irradiation with SBRT technique for in-field recurrent lung tumors appears to be a effective and well-tolerated option for cautiously selected patients even centrally located. Our results suggest that, lower BED doses could still provide excellent LC for recurrent lung tumors in the previous RT field with an acceptable complication rate.

Stereotactic Body Radiation Therapy for Central Lung Tumors: Outcomes and Toxicity: Treatment Toxicity

Stereotactic body radiation therapy (SBRT) is increasingly employed for the treatment of primary, recurrent, and oligometastatic lung tumors. The outcomes and toxicities of SBRT for central lung tumors are not well defined. We investigated our institutional experience using SBRT for central lung tumors. Our institutional SBRT database prospectively collects demographic and treatment-related data from all patients treated at our center. We retrospectively analyzed all patients with central lung tumors treated with SBRT between April 2008 and May 2013. The most common radiation dose was 50 Gy in 5 fractions delivered over consecutive days using coplanar plans. Dose constraints for organs at risk followed the recommendations of the American Association of Physicists in Medicine Task Group 101 report. Local control (LC) and overall survival (OS) were calculated using Kaplan-Meier estimates. Toxicity was graded using the Radiation Therapy Oncology Group Common Terminology Criteria. Tumor response was scored using Response Evaluation Criteria in Solid Tumors, version1.1. Predictors for toxicity, LC, and OS were analyzed using Cox proportional hazard regression models. A total of 142 central lung tumors from 132 patients were identified and included for analysis. Median age was 71 years (range, 24-91 years) and median follow up was 31.0 months (range, 2.5-62.5 months). There were 55 primary, 33 recurrent, and 54 metastatic tumors. Median tumor size was 2.1 cm (range, 0.5-5.5 cm). Overall, there were 13 local failures resulting in 3-year LC rates of 94.2%, 91.7%, and 58.3%, in primary, recurrent, and metastatic lung tumors, respectively. There were 19 patients (14.4%) with grade 3 or higher pneumonitis including 1 grade 4 and 1 grade 5 toxicity. There were no grade 3 or higher acute toxicities. Rates of complete response, partial response, stable disease, and progressive disease were 34% (n=48), 45% (n=64), 20% (n=29), and 1% (n=1), respectively. The median survival for primary, recurrent, and metastatic lung tumors was 46.1, 43.6, and 16.5 months, respectively. Toxicity, LC, and OS were not associated with tumor size, radiation dose, or previous local therapy on univariate or multivariate analysis. SBRT for central lung tumors offers high rates of local control and acceptable toxicity rates comparable to published data for peripheral tumors. Patients with primary or recurrent lung tumors had comparable LC and OS which were better than patients with metastatic lung tumors. Appropriate patient selection and dose fractionation remains critical while outcomes from prospective trials mature.

Long-term treatment with panitumumab monotherapy for recurrent colorectal cancer

With the development of new chemotherapy agents and methods, metastatic colorectal cancer patients can now achieve a survival time of >30 months. Higher line therapies have had a significant influence on the survival of these patients. However, it remains uncertain as to which therapy is the most effective and best tolerated. Herein, we describe the case of a patient with metastatic KRAS wild-type colorectal cancer who received panitumumab monotherapy as a third-line therapy after failure of 5-fluorouracil, irinotecan, oxaliplatin and bevacizumab. This patient had both lymph node and lung recurrence. The patient achieved a partial response time of 15 months. The lymph node and recurrent lung tumor had shrunk by 74 and 100 %, respectively, and the treatment was well tolerated with limited cutaneous toxicity. Panitumumab monotherapy may be an effective and well-tolerated treatment of KRAS wild-type metastatic colorectal cancer patients who have undergone many prior therapies. The present case showed a response to panitumumab monotherapy extending over a period of >1 year.

Stereotactic Body Radiation Therapy for Central Lung Tumors: Outcomes and Toxicity

Stereotactic body radiation therapy (SBRT) is increasingly employed for the treatment of primary, recurrent, and oligometastatic lung tumors. The outcomes and toxicities of SBRT for central lung tumors are not well defined. We investigated our institutional experience using SBRT for central lung tumors. Our institutional SBRT database prospectively collects demographic and treatment-related data from all patients treated at our center. We retrospectively analyzed all patients with central lung tumors treated with SBRT between April 2008 and May 2013. The most common radiation dose was 50 Gy in five fractions delivered over consecutive days using coplanar plans. Dose constraints for organs at risk followed the recommendations of the American Association of Physicists in Medicine Task Group 101 report. Local control (LC) and overall survival (OS) were calculated using Kaplan-Meier estimates. Toxicity was graded using the Radiation Therapy Oncology Group Common Toxicity Criteria. Tumor response was scored using Response Evaluation Criteria in Solid Tumors v1.1. Predictors for toxicity, LC, and OS were analyzed using Cox proportional hazard regression models. A total of 142 central lung tumors from 132 patients were identified and included for analysis. Median age was 71 years (range, 24-91) and median follow up was 31.0 months (range, 2.5-62.5). There were 55 primary, 33 recurrent, and 54 metastatic tumors. Median tumor size was 2.1 cm (range, 0.5-5.5). Overall, there were 13 local failures resulting in 3-year LC rates of 94.2%, 91.7%, and 58.3%, in primary, recurrent, and metastatic lung tumors, respectively. There were 19 patients (14.4%) with grade 3 or higher pneumonitis including one grade 4 and one grade 5 toxicity. There were no grade 3 or higher acute toxicities. Rates of complete response, partial response, stable disease, and progressive disease were 34% (n = 48), 45% (n = 64), 20% (n = 29), and 1% (n = 1), respectively. The median survival for primary, recurrent, and metastatic lung tumors was 46.1, 43.6, and 16.5 months, respectively. Toxicity, LC, and OS were not associated with tumor size, radiation dose, or previous local therapy on univariate or multivariate analysis. SBRT for central lung tumors offers high rates of local control and acceptable toxicity rates comparable to published data for peripheral tumors. Patients with primary or recurrent lung tumors had comparable LC and OS which were better than patients with metastatic lung tumors. Appropriate patient selection and dose fractionation remains critical while outcomes from prospective trials mature.

Abstract 1947: Tumor-derived circulatory exosomal miRNAs as biomarkers of recurrent lung tumors.

Abstract More people in the U.S. (157,300 per year) die of lung cancers than of prostate cancer, breast cancer and colon cancer combined. Eighty five percent of NSCLC patients die within 5 years. Even after resection of an early stage NSCLC, many patients die of relapse. Despite 2 decades of cisplatin-based chemotherapy for NSCLC, the survival benefit remains modest. Poor outcomes and relapse indicate need for new screening and early biomarkers for detection of recurrent lung tumors. In this study, first, we determined the frequency of lung tumor recurrence in female athymic nude mice (4-5 wk-old; n=25) using H1299 cells (1.5 x 106 cells). When tumors reached 300-400 mm3, the tumors were completely excised under anesthesia from 18/25 mice; the primary tumors in the remaining animals (n=7) were allowed to grow. We recorded the appearance of first tumor recurrence, 1 week after the surgery and the incidence rate of recurrent tumors was 60% (11/18). Average recurrent tumor volume at the end of the study was 431 ± 236 mm3. Second, we determined the circulating miRNA profiles by analyzing exosomal miRNAs in serum from control and H1299 lung tumor-bearing mice. Exosomes, nano-vesicles that carry load of miRNAs and mRNAs, were isolated from 1ml serum by pooling blood from five mice, using ExoQuick reagent (System Biosciences). Exosomes were visualized and their sizes measured by NanoSight (Wiltshire) and confirmed by transmission electron microscopy. Total RNA was isolated from exosomes with Trizol and was analyzed by qPCR using cancer-pathway finder miRNA array, containing 84 miRNAs (Qiagen). Our data showed i) the presence of circulatory exosomes with particle size 34-97 nm, ii) circulatory exosomal miRNAs iii) differences &amp;gt;2-fold in the up- and downregulated miRNAs in the H1299 primary tumors and recurrent tumors versus normal human bronchial epithelial cells, and serum exosomes from tumor-bearing versus control mice, iv) similarity of all 25 miRNAs expressed in the recurrent tumors with 25/34 miRNAs in primary tumors, suggesting that recurrent tumors originated from microscopic primary tumors, and v) similarity of 10 miRNAs expressed in serum exosomes with those expressed in primary tumors (e.g., miR-132 and let-7c), suggesting that serum exosomal miRNAs originated from the lung tumors and suggest their biomarker significance. Further, we performed immunoaffinity enrichment of tumor-specific exosomes with anti-EpCAM magnetic beads using serum from control and lung tumor-bearing mice. Western blot analysis revealed that the enriched exosomes were positive for the tumor marker EpCAM, and was significantly higher in exosomes from tumor-bearing vs. control nude mice. Thus, our initial observations suggest that the miRNAs carried by the tumor-derived exosomes can be a true representation of tumor-profile and a more stringent validation of miRNAs as circulatory biomarkers. (Supported by Agnes Brown Duggan Endowment and Helmsley Endowment). Citation Format: Radha Munagala, Farrukh Aqil, Douglas D. Taylor, Ramesh Gupta. Tumor-derived circulatory exosomal miRNAs as biomarkers of recurrent lung tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1947. doi:10.1158/1538-7445.AM2013-1947

Stereotactic Ablative Radiotherapy for Reirradiation of Locally Recurrent Lung Tumors

Patients with thoracic tumors that recur after irradiation currently have limited therapeutic options. Retreatment using stereotactic ablative radiotherapy (SABR) is appealing for these patients because of its high conformity but has not been studied extensively. Here we report our experience with SABR for lung tumors in previously irradiated regions. We conducted a retrospective study of patients with primary lung cancer or metastatic lung tumors treated with SABR. We identified 17 such tumors in 15 patients and compared their outcomes with those of a cohort of 135 previously unirradiated lung tumors treated with SABR during the same time period. Twelve-month local control (LC) for retreated tumors was 65.5%, compared with 92.1% for tumors receiving SABR as initial treatment. Twelve-month LC was significantly worse for reirradiated tumors in which the time interval between treatments was 16 months or less (46.7%), compared with those with longer intertreatment intervals (87.5%). SABR reirradiation did not lead to significant increases in treatment-related toxicity. SABR for locally recurrent lung tumors arising in previously irradiated fields seems to be feasible and safe for appropriately selected patients. LC of retreated lesions was significantly lower, likely owing to the lower doses used for retreatment. Shorter time to retreatment was associated with increased risk of local failure, suggesting that these tumors may be particularly radioresistant. Our findings suggest that dose escalation may improve LC while maintaining acceptable levels of toxicity for these patients.

Computed tomography-guided re-radiofrequency ablation for unresectable lung tumor with local progression previously treated with the same procedure

The aim of this study was to evaluate the technical success, complications, and effectiveness of re-radiofrequency (re-RF) ablation for recurrent lung tumors previously treated with RF ablation. Reenlargement at the site of ablation seen on follow-up computed tomography (CT) is defined as local progression. CT-guided re-RF ablation was performed during 11 treatment sessions (mean tumor size 2.6 cm diameter) in 10 patients. The treated lesions consisted of five recurrences of primary lung cancer and six metastatic lung tumors from the esophagus (n = 2), bladder (n = 2), kidney (n = 1), and colon (n = 1). At 3 of the 11 treatment sessions there were no relapses; at 8 of the 11 sessions local progression was seen at a median of 7 months (range 3-17 months). The local progression rate was significantly higher for tumors > 2.5 cm (P < 0.05). Minor complications included pneumothorax not requiring drainage (n = 3), subcutaneous emphysema (n = 1), and self-limited hemoptysis (n = 2). Re-RF ablation for lung tumors was feasible without any major complications. Although our study comprised only a few cases with a short follow-up period, patients with re-RF ablation were at higher risk of local progression.

Reconstruction of Recurrent Laryngeal Nerve With Involvement by Metastatic Node in Esophageal Cancer

Recurrent laryngeal nerve paralysis represents one of the major complications in esophageal cancer surgery, and patients with esophageal cancer sometimes develop recurrent laryngeal nerve paralysis before treatment. We evaluated recurrent laryngeal nerve reconstruction in patients with lymph node metastasis infiltrating the recurrent laryngeal nerve. Five patients with preoperative recurrent laryngeal nerve paralysis as a result of involvement of metastasis were enrolled in the present study. Ansa cervicalis-recurrent laryngeal nerve anastomosis in the neck was performed in 4 patients and direct anastomosis of recurrent laryngeal nerve in the mediastinum in 1 patient. Six months after surgery, 3 patients who had undergone ansa cervicalis-recurrent laryngeal nerve anastomosis in the neck displayed good quality of life without hoarseness or aspiration. The patient who underwent direct anastomosis of the recurrent laryngeal nerve in the mediastinum experienced occasional aspiration and hoarseness. The remaining patient displayed poor condition because of recurrent lung tumor, and quality of life was decreased. If patients with recurrent laryngeal nerve paralysis before treatment can undergo potentially curative resection with lymph node dissection, including the metastatic lymph node infiltrating the recurrent laryngeal nerve, recurrent laryngeal nerve reconstruction should be performed to improve quality of life.

P-314 The highly selective COX-2 inhibitor demonstrates a significant growth inhibition of the recurrent lung tumor and its metastasis in C57/BL6 mice

P-314 The highly selective COX-2 inhibitor demonstrates a significant growth inhibition of the recurrent lung tumor and its metastasis in C57/BL6 mice

Analysis of treatment outcome for children with recurrent or metastatic hepatoblastoma.

For better total survival rate of children with hepatoblastoma, the therapeutic strategy for recurrent or metastatic hepatoblastoma should be improved. From 1991 to 1999, 134 cases of hepatoblastoma were treated by surgery and combination chemotherapy of cisplatin (CDDP) and THP-Adriamycin (THP-ADR) based on the JPLT-1 protocol. In 114 non-metastatic cases, 90 primary liver tumors were resected completely by partial hepatectomy, but 12 recurrences were observed in the liver (4 cases) and the lungs (8 cases). Distant metastases on the diagnosis were observed in 20 cases. The treatment outcome of these 12 recurrent and 20 metastatic tumors was analyzed. In four recurrent liver tumors, surgical resection was performed in all four cases, and all the patients were alive and well. In eight recurrent lung tumors, surgical resection was performed completely in six cases with unilateral lung disease, and five of the six patients were alive and well. In stage IV tumors, the survival rate of the patients having primary tumors within two hepatic sections was significantly higher than that of the patients having primary tumors over three hepatic sections. Active surgical intervention to lung metastases and a more intensive chemotherapy to facilitate complete resection of primary hepatic tumor could improve survival rate of children with refractory hepatoblastoma.