Efficacy and safety of anlotinib plus XELOX regimen as first-line therapy for mCRC: a single-arm, multicenter, phase II study (ALTER-C-001).

Background: Anlotinib showed encouraging anti-tumor activity in metastatic colorectal cancer (mCRC). This study was designed to assess the efficacy and safety of anlotinib plus XELOX as first-line therapy in mCRC patients. Materials and Methods: Eligible patients aged ≥18 with mCRC were enrolled in this multicenter, single-arm, phase II, exploratory study. Patients received at least 6 cycles of anlotinib, oxaliplatin, and capecitabine as initial therapy. Subsequently, patients received anlotinib monotherapy as maintenance therapy until tumor progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Results: Thirty-one patients were included between December 2019 and March 2022. The median follow-up was 17.5 (95% CI, 3.0-17.5) months. The median PFS was 8.3 (95% CI, 6.3-10.0) months, with 6- and 12-month PFS rates of 82.3% (95% CI, 59.2%-93.0%) and 18.9% (95% CI, 4.8%-40.1%), respectively. Fifteen (48.4%) achieved partial response for an ORR of 48.4% (95% CI, 30.2%-66.9%). The disease control rate was 71.0% (95% CI, 52.0%-85.8%) due to 7 (22.6%) stable diseases. The median duration of response was 6.0 (95% CI, 3.6-8.0) months and 1 patient had the longest ongoing response of 17.3 months. Of 24 patients with evaluable imaging, 23 (74.2%) obtained tumor shrinkage. The median PFS (11.0 vs. 6.9 months) and ORR (66.7% vs. 60.0%) for patients with RAS/BRAF wild-type were numerically better than those with mutation. Three patients are still ongoing treatment. The grade 3 or more treatment-emergent adverse events (TEAEs) were mainly hypertension (12.9%) and decreased neutrophil count (12.9%). Four (12.9%) had serious TEAEs, primarily including abdominal pain and incomplete intestinal obstruction. Conclusion: Anlotinib plus XELOX as first-line therapy in patients with mCRC showed anti-tumor activity and safety profile, which is worth further investigation. Clinical Trial Registration: chictr.org.cn, identifier ChiCTR1900028417.

Reducing Target Volumes of Intensity Modulated Radiation Therapy After Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: Long-Term Results of a Prospective, Multicenter, Randomized Trial.

PURPOSE: The objective of this study was to estimate the long-term survival, late toxicity profile, and quality of life of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with combined induction chemotherapy (IC) and concurrent chemoradiotherapy from a clinical trial focused on reducing the target volume of intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS: This prospective, randomized clinical trial was conducted across 6 Chinese hospitals and included 212 patients with stage III-IVB NPC who were randomly allocated to a pre-IC or post-IC group. Eligible patients were treated with 2 cycles of IC + CCRT. All patients underwent radical IMRT. Gross tumor volumes of the nasopharynx were delineated according to pre-IC and post-IC tumor extent in the pre-IC and post-IC groups, respectively. RESULTS: After a median follow-up of 98.4 months, 32 of 97 (32.9%) and 33 of 115 (28.7%) patients experienced treatment failure or died in the pre-IC and post-IC groups, respectively. None of the patients developed grade 4 late toxicity. Late radiation-induced toxicity predominantly manifested as grade 1 to 2 subcutaneous fibrosis, hearing loss, tinnitus, and xerostomia, whereas grade 3 late toxicity included xerostomia and hearing loss. The 5-year estimated overall, progression-free, locoregional recurrence-free, and distant metastasis-free survival rates in the pre-IC and post-IC groups were 78.2% versus 83.3%, 72.0% versus 78.1%, 90.2% versus 93.5%, and 78.1% versus 82.1%, respectively. The pre-IC group had a significantly higher incidence of xerostomia and hearing damage than the post-IC group. In terms of quality of life, compared with the pre-IC group, the post-IC group showed significant improvement in cognitive function (P = .045) and symptoms including dry mouth (P = .004), sticky saliva (P = .047), and feeling ill (P = .041). CONCLUSIONS: After long-term follow-up, we confirmed that reducing the target volumes of IMRT after IC in locoregionally advanced NPC showed no inferiority in terms of the risk of locoregional relapse and potentially improved quality of life and alleviated late toxicity.

Effect of 3-Dimensional Interstitial High-Dose-Rate Brachytherapy With Regional Metastatic Lymph Node Intensity-Modulated Radiation Therapy in Locally Advanced Peripheral Non-Small Cell Lung Cancer: 5-Year Follow-up of a Phase 2 Clinical Trial.

PURPOSE: We aimed to reveal the 5-year clinical outcomes of 3-dimensional (3D) interstitial high-dose-rate (HDR) brachytherapy with regional metastatic lymph node intensity modulated radiation therapy (IMRT) for locally advanced peripheral non-small cell lung cancer (NSCLC), which has been shown to have low toxicity and improved 2-year survival rates in patients with this disease. METHODS AND MATERIALS: In this phase 2, single-arm, open-label clinical trial, 83 patients with locally advanced peripheral NSCLC were enrolled (median follow-up [range], 53.7 [4.3-120.4] months). All eligible patients received 3D interstitial HDR brachytherapy with regional metastatic lymph node IMRT. The primary endpoint was overall survival (OS). Secondary endpoints were local recurrence-free survival, regional recurrence-free survival, progression-free survival, distant metastasis-free survival, toxicities, and quality of life. RESULTS: The final analysis included 75 patients (19 [25.3%] females, 56 [74.7%] males; median [range] age, 64 [44-80] years; stage IIIA, 34 [45.3%]; stage IIIB, 41 [54.7%]). At the latest follow-up, 32 (42.7%) patients had survived. The median OS was 38.0 months (5-year OS, 44.5%; 95% confidence interval [CI], 33.8%-58.6%). Local recurrence-free survival, recurrence-free survival, and distant metastasis-free survival at 5 years were 79.2% (95% CI, 68.5%-91.5%), 73.6% (95% CI, 61.5%-88.1%), and 50.3% (95% CI, 38.3%-66.1%), respectively. The dominant failure pattern was distant disease, corresponding to 40% (30 of 75) of patients and 65.2% (30 of 46) of all failures. Two (2.7%) patients developed grade 1 acute pneumonitis. Grade 2 and 3 acute esophagitis occurred in 11 (14.7%) and 4 (5.3%) patients, respectively. No late radiation-related grade ≥2 late adverse events were observed. CONCLUSIONS: 3D interstitial HDR brachytherapy with regional metastatic lymph node IMRT for locally advanced peripheral NSCLC shows significant OS and has a low toxicity rate. Additional evaluation in a phase 3 trial is recommended to substantiate these findings.

5-Fluorouracil combined with cisplatin via arterial induction for advanced T-stage nasopharyngeal carcinoma: A 10-year outcome of a phase I/II study.

Background and Purpose: Currently, there is no optimal dose recommendation for a 120-h continuous infusion of 5-fluorouracil via arterial cannulation for advanced T-stage nasopharyngeal carcinoma (NPC). Thus, the aim of this study was to determine the maximum tolerated dose (MDT), along with the efficacy, late adverse events, and 10-year survival outcome of 5-fluorouracil administered continuously for 120 h combined with cisplatin via the superficial temporal artery in patients with advanced T-stage NPC. Materials and Methods: Fifty-one patients with histologically confirmed advanced T-stage NPC were eligible for inclusion in this clinical trial. The patients received induction chemotherapy consisting of cisplatin (20 mg/m2/d for 1-5 d) and 5-fluorouracil, administered continuously for 120 h at different dose gradients via a superficial temporal artery. To identify the MTD of 5-fluorouracil infused arterially, we employed a 3 + 3 design during study phase I. The initial dose administered was 200 mg/m2/d, which then was gradually escalated by 50 mg/m2/d until the MTD was reached. Following two cycles of induction chemotherapy, current radical chemoradiotherapy commenced. We assessed the efficacy, survival, toxicity, and quality of life of patients following treatment. Results: The overall response (complete response + partial response) rates following induction chemotherapy in the primary mass and lymph nodes were 100% and 100%, respectively. All 51 (100%) patients achieved T-category down-staging after intra-arterial chemotherapy. The MTD was 450 mg/m2/d for 120 h. No late neurological toxicities, such as brain stem injury, temporal lobe necrosis, and spinal cord injury, were observed. The 5- and 10-year overall survival (OS) rates were 78.0% and 71.7%, respectively, with a median OS of 131 months. Conclusion: Continuous infusion of 5-fluorouracil combined with cisplatin via the superficial temporal artery showed promising survival benefits and few toxicities in patients with advanced T-stage NPC.

Preliminary report of a single-channel applicator in high dose rate afterloading brachytherapy for cervical cancer.

The aim of this study was to evaluate whether a patented single-channel applicator, which was modified from the traditional tandem applicator and wrapped with an oval-shield alloy around the source channel, has the same clinical efficacy and safety as the standard Fletcher-type applicator in high dose rate (HDR) brachytherapy for carcinoma of the cervix. Between December 2011 and February 2017, 299 patients with pathologically confirmed International Federation of Gynecology and Obstetrics (2009) stage Ib2-IVa cervical cancer were recruited to the trial and finished the allocated intervention. Of the first 151 patients, 71 were allocated to the Fletcher group and 80 to the single-channel group, satisfying the criteria for a preliminary analysis. All but 3 patients were treated with concurrent cisplatin chemotherapy and external beam radiotherapy followed by HDR brachytherapy. The 2-year overall survival, progression-free survival, and locoregional failure-free survival was 80.3%, 77.5%, and 78.9%, respectively, for the Fletcher group, and 86.3%, 82.5%, and 83.8%, respectively, for the single-channel group. The seriousness of acute treatment-related toxicities was similar in the 2 groups. The cumulative rate of late rectal complications of grade 3-4 in the Fletcher group and the single-channel group was 2.8% and 2.5%, respectively. The cumulative rate of grade 3 bladder complications was 2.8% for the Fletcher group and 1.3% for the single-channel group. The preliminary results of our study show that the patented single-channel intracavitary applicator might be able to provide protection for the rectum and bladder and seems to have the same clinical efficacy as the standard Fletcher-type 3-channel applicator in HDR brachytherapy for carcinoma of the cervix. This trial was registered with the Chinese Clinical Trial Registry (registration no. ChiCTR-TRC-12002321).

Treatment outcomes after reduction of the target volume of intensity-modulated radiotherapy following induction chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: A prospective, multi-center, randomized clinical trial.

PURPOSE: To investigate whether reducing the target volume of intensity-modulated radiotherapy (IMRT) after induction chemotherapy (IC) improves the quality of life (QOL) in locoregionally advanced nasopharyngeal carcinoma (NPC) without decreasing the local control and survival rate. PATIENTS AND METHODS: A total number of 212 NPC patients staged as III-IVb were randomly assigned to group A (n=97) or group B (n=115) in this prospective clinical trial. All patients received IC followed by cisplatin concurrent with IMRT. IMRT was planned using the images of pre-IC in group A and post-IC in group B. RESULTS: The dose received by normal tissues in group B was lower than that of group A (P<0.05). The recovery of the dry mouth symptoms in group B was significantly improved than group B. The quality of life (QOL) scores in group B were higher than group A. With a median follow-up of 35months, the 1-year estimated overall survival (OS), progression-free survival (PFS), locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS) in group A versus group B were 97.9% vs 97.3%, 90.7% vs 92,2%, 99.0% vs 98.2%, 91.8% vs 94.8%. The 2-year OS, PFS, LRFFS, DMFS in group A versus group B were 93.7% vs 92.9%, 83.4% vs 84.3%, 96.8% vs 95.5%, 86.5% vs 89.5%. The 3-year OS, PFS, LRFFS, DMFS in group A versus group B were 82.3% vs 87%, 74.7% vs 83.4%, 91.8 vs 93.9%, 81.3% vs 88.6%, respectively. CONCLUSION: Reducing the IMRT target volume after IC did not reduce the local control and survival rate in locoregionally advanced NPC but the doses received by normal tissues were decreased, and the QOL scores were improved.

Lymph node tuberculosis mimicking malignancy on 18F-FDG PET/CT in two patients: A case report.

18F-fluorodeoxyglucose positron emission/computed tomography (18F-FDG PET/CT) imaging, an established procedure for evaluation of malignancy, reports an increased 18F-FDG uptake in acute or chronic inflammatory condition. Lymph node tuberculosis (LNTB) is the most common form of extrapulmonary tuberculosis. However, the absence of clinical symptoms and bacteriological basis makes it difficult to diagnose. In the current case report, two patients with LNTB mimicking malignant lymphoma are presented by 18F-FDG PET/CT. The objective of the present report is to emphasize that LNTB should be considered as a noteworthy differential diagnosis in patients with enlarged lymph nodes, particularly in tuberculosis-endemic countries, and that lymph node biopsy serves a vital role in diagnosing LNTB.

Computed Tomography-Guided Interstitial High-Dose-Rate Brachytherapy in Combination With Regional Positive Lymph Node Intensity-Modulated Radiation Therapy in Locally Advanced Peripheral Non-Small Cell Lung Cancer: A Phase 1 Clinical Trial.

PURPOSE: To assess the technical safety, adverse events, and efficacy of computed tomography (CT)-guided interstitial high-dose-rate (HDR) brachytherapy in combination with regional positive lymph node intensity modulated radiation therapy in patients with locally advanced peripheral non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Twenty-six patients with histologically confirmed NSCLC were enrolled in a prospective, officially approved phase 1 trial. Primary tumors were treated with HDR brachytherapy. A single 30-Gy dose was delivered to the 90% isodose line of the gross lung tumor volume. A total dose of at least 70 Gy was administered to the 95% isodose line of the planning target volume of malignant lymph nodes using 6-MV X-rays. The patients received concurrent or sequential chemotherapy. We assessed treatment efficacy, adverse events, and radiation toxicity. RESULTS: The median follow-up time was 28 months (range, 7-44 months). There were 3 cases of mild pneumothorax but no cases of hemothorax, dyspnea, or pyothorax after the procedure. Grade 3 or 4 acute hematologic toxicity was observed in 5 patients. During follow-up, mild fibrosis around the puncture point was observed on the CT scans of 2 patients, but both patients were asymptomatic. The overall response rates (complete and partial) for the primary mass and positive lymph nodes were 100% and 92.3%, respectively. The 1-year and 2-year overall survival (OS) rates were 90.9% and 67%, respectively, with a median OS of 22.5 months. CONCLUSION: Our findings suggest that HDR brachytherapy is safe and feasible for peripheral locally advanced NSCLC, justifying a phase 2 clinical trial.