Single-photon emission computed tomography-defined active bone marrow-sparing volumetric-modulated arc therapy reduces the incidence of acute hematologic toxicity in locally advanced cervical cancer patients who receive chemoradiotherapy: A single-center prospective randomized controlled trial.

BACKGROUND: This study aims to test the efficacy of single-photon emission computed tomography (SPECT)-defined active bone marrow-sparing (ABMS) volumetric-modulated arc therapy (VMAT) in reducing grade 3+ acute hematologic toxicity (HT) in locally advanced cervical cancer patients treated with chemoradiotherapy. METHODS: This was a prospective, single-center, open label, randomized clinical trial that enrolled locally advanced cervical cancer patients. Participants were randomized to the 99m Tc sulfur colloid SPECT-defined ABMS VMAT (ABMS group) or control group, who received weekly cisplatin concurrently with VMAT followed by high-dose-rate intracavitary brachytherapy. The ABMS group additionally received SPECT-defined ABM dose constraints. The primary end point was the incidence of grade 3+ acute HT. RESULTS: A total of 192 Federation of Gynaecology and Obstetrics stage IB-IIIB patients were randomly treated (96 each in the ABMS control groups). The median follow-up was 24.0 months. The incidence of grade 3+ acute HT in the ABMS group was significantly lower than that in the control group (32.3% vs. 53.1%, p < .01). The number of patients completing five cycles of cisplatin was 88.5% in the ABMS group and 75% in the control group, and the difference was significant (p = .02). There were no differences in planning target value coverage, organs at risk dosimetric parameters, 2-year progression-free survival, or 2-year overall survival between the two groups. Patients in the control group had nonsignificantly worse 2-year distant metastasis than patients in the ABMS group (17.8% vs. 11.1%, p = .19). CONCLUSIONS: ABMS VMAT significantly reduced grade 3+ acute HT and improved chemotherapy delivery compared with the control treatment. We found weak evidence of the effect of ABMS VMAT on distant metastasis.

Apatinib-induced Grade 3 hand-foot syndrome in advanced lung adenocarcinoma successful treated with thalidomide: A case report.

Hand-foot syndrome (HFS) is a specific cutaneous toxicity caused by a variety of antitumor drugs. The most common drugs include capecitabine, pegylated liposomal doxorubicin and fluorouracil (PLD), tyrosine kinase inhibitor. It is a dose-limiting cutaneous toxicity of these drugs. We reported an advanced lung adenocarcinoma female patient, who developed a Grade 3 HFS after a third-line treatment with apatinib of 250 mg for 10 days, the patient developed intolerable pain with pruritus. Large erythema on the skin of the hand, with local ulceratio, exudation, and desquamation of cutaneous lesions. After treatment with 100 mg of thalidomide every night for 1 week, the patient's HFS was significantly relieved, and the duration of the remission was about 2 months, which not only significantly improved the patient's quality of life, but also maintained the antitumor strength.

Phase 2 dose-ranging study to evaluate the efficacy and safety of liposomal irinotecan (LY01610) as a second-line treatment for patients with relapsed small cell lung cancer.

Background: This was a multicenter, single-arm dose-ranging phase 2 study aimed to assess the efficacy and safety of LY01610, a liposomal irinotecan, at various doses for patients with relapsed small cell lung cancer (SCLC). Methods: This study (NCT04381910) enrolled patients with relapsed SCLC at 10 hospitals across China, who have failed with previous platinum-based treatments. LY01610 was administered at doses of 60 mg/m2, 80 mg/m2, and 100 mg/m2. Primary endpoints were investigator-assessed objective response rate (ORR) and investigator-assessed duration of response (DoR). Secondary endpoints included investigator-assessed disease control rate (DCR), investigator-assessed progression-free survival (PFS), overall survival (OS), and safety. Findings: From September 3, 2020 to March 3, 2022, a total of 66 patients were enrolled, with 6, 30, and 30 allocated to the 60 mg/m2, 80 mg/m2, and 100 mg/m2 dose groups, respectively, with 68% (45/66) having a chemotherapy-free interval <90 days. In all 66 patients, the ORR was 32% (21/66, 95% confidence interval [CI], 21-44), with a median DoR of 5.2 months (95% CI, 3.0-8.3). Median PFS and OS were 4.0 (95% CI, 2.9-5.5) and 9.7 (95% CI, 7.2-12.3) months, respectively. The ORR of 60 mg/m2, 80 mg/m2, and 100 mg/m2 dose group were 33% (2/6), 33% (10/30), and 30% (9/30), respectively. The median DoR of 60 mg/m2, 80 mg/m2, and 100 mg/m2 dose group were 4.2 (95% CI, 2.8-not reached), 6.9 (95% CI, 2.5-9.9), and 4.0 (95% CI, 2.7-6.8) months, respectively. The incidence of ≥ grade 3 treatment-related adverse events (TRAEs) in the 60 mg/m2, 80 mg/m2, and 100 mg/m2 dose group were 33% (2/6), 47% (14/30), and 50% (15/30), respectively. The most common ≥ grade 3 TRAEs of all 66 patients were neutropenia (27%), leukopenia (24%) and anemia (15%). Interpretation: LY01610 exhibited promising clinical efficacy and manageable safety profiles in patients with relapsed SCLC, the 80 mg/m2 dose group had the best benefit-risk ratio. Funding: This study was supported by Luye Pharma Group Ltd.

Complete remission of reactive cutaneous capillary endothelial proliferation caused by the programmed cell death-1 inhibitor camrelizumab achieved through thalidomide monotherapy: A case report.

Reactive cutaneous capillary endothelial proliferation (RCCEP) is a common adverse effect of the anti-programmed cell death-1 (PD-1) monoclonal antibody camrelizumab and usually occurs on the skin. This condition causes bleeding nodules of varying severity depending on disease grade; these affect a person's appearance and quality of life. The exact mechanism remains elusive and its occurrence in visceral organs has not been previously reported, to the best of our knowledge. Furthermore, there is currently a lack of standard, uniform treatments. The present study reported on a patient who experienced RCCEP during treatment with camrelizumab and benefited greatly from thalidomide, which caused no serious adverse events. An elderly Chinese female initially diagnosed with stage II endometrial cancer had previously undergone surgery, radiotherapy and intravenous chemotherapy but developed multiple metastases in the peritoneum and vaginal remnant. The patient was subsequently prescribed camrelizumab after systemic treatment failed. Soon after commencing treatment with this PD-1 inhibitor, the patient developed RCCEP, whereupon oral low-dose thalidomide monotherapy (100 mg nightly) was prescribed. At two weeks after commencing thalidomide, the RCCEP symptoms were alleviated. Based on this patient's successful treatment, it is suggested that low-dose thalidomide may be an alternative intervention for patients with camrelizumab-induced RCCEP.

Continuous Low-Dose Apatinib Combined With WBRT Significantly Reduces Peritumoral Edema and Enhances the Efficacy of Symptomatic Multiple Brain Metastases in NSCLC.

BACKGROUND: Symptomatic multiple brain metastases with peritumoral brain edema (PTBE) occur in non-small cell lung cancer patients (NSCLC) who are without driver mutations or are resistant to epidermal growth factor tyrosine kinase (EGFR-TKI) are often associated with an unfavorable prognosis. Whole brain radiation therapy (WBRT) which comes with many complications and unsatisfactory effects, is the only option for the treatment. Previous studies have shown that bevacizumab can reduce the volume of PTBE and improve efficiency of radiotherapy. This study evaluated the effects and safety of apatinib combined with WBRT in NSCLC patients with symptomatic multiple brain metastases and PTBE. METHODS: We performed a retrospective review of 34 patients with symptomatic multiple brain metastases from NSCLC (number >4, and at least 1 measurable brain metastasis lesion with cerebral edema). Intracranial objective response rate (IORR), peritumoral edema and intracranial tumor volumetric measurement, Karnofsky performance status (KPS) and adverse events (AEs) were evaluated. Median intracranial progression-free survival (mIPFS) and median overall survival (mOS) were also analyzed. RESULTS: Thirteen cases received apatinib (125 mg or 250 mg, QD, oral) combined with WBRT and 21 cases received chemotherapy combined with WBRT were inclued. Apatinib combination group can better reduce the volume of intracranial tumors and PTBE and total steroid dosage used. It was associated with a better IORR (84.6% vs 47.6%, P = 0.067), longer mIPFS (6.97 vs 4.77months; P = 0.014). There was no significant difference in mOS(7.70 vs 6.67 months; P = 0.14) between the 2 groups. The most common adverse events of apatinib combination WBRT included grade 1/2 nausea (4/13), fatigue (3/13), hypertension (2/13) and white blood cell decrease (2/13). No grade 3/4 AEs were observed. CONCLUSION: Apatinib plus WBRT is well tolerated and may be a potential choice for relapsed or drug-resistant advanced NSCLC patients with symptomatic multiple brain metastases and PTBE.

Significant response of low-dose apatinib monotherapy in brain metastases of triple-negative breast cancer: A case report.

RATIONALE: The potential efficacy of apatinib in patients with advanced triple-negative breast cancer (TNBC) has been observed in a previous phase II clinical study. However, there is no study to evaluate its efficacy and safety in TNBC patients with brain metastasis (BM). Here we report one case that apatinib exhibited excellent antitumor effects in a breast cancer patient with brain metastasis, with no serious treatment-associated with adverse event. PATIENT CONCERNS: In this case report, one Chinese woman who was diagnosed with stage IV TNBC with multiple bone, lung, and brain metastases was unable to tolerate chemotherapy and refused whole-brain radiation therapy (WBRT) due to her poor physical condition. She had previously undergone radical mastectomy and intravenous chemotherapy. DIAGNOSES: Triple-negative breast cancer. INTERVENTIONS: The patient underwent left radical mastectomy with ipsilateral axillary lymph node dissection, and the following adjuvant chemotherapy, but developed multiple bone, lung, and brain metastases. Due to her poor physical condition, chemotherapy was not eligible for her. And she refused WBRT and chose to take low-dose apatinib (250 mg, oral, daily) monotherapy. OUTCOMES: After 2 months of treatment, the symptom of headache and vomiting relieved and all the brain metastases (BMs) lesions disappeared. LESSONS: Low-dose apatinib monotherapy may be an alternative treatment for patients with poor physical condition. Preclinical and clinical studies should be conducted to further evaluate the mechanism and efficacy of apatinib in the treatment of BM from TNBC, as well as to explore the optimal dose of the drug.

The volume of 99m Tc sulfur colloid SPET-defined active bone marrow can predict grade 3 or higher acute hematologic toxicity in locally advanced cervical cancer patients who receive chemoradiotherapy.

BACKGROUND: The purpose of the current study was to evaluate whether radiation dose-volume metrics to technetium-99m (99m Tc) sulfur colloid single-photon emission tomography (SPET)-defined active bone marrow (ABM) subregions can more accurately predict acute hematologic toxicity in locally advanced cervical cancer patients who receive chemoradiotherapy than conventional dosimetric parameters. METHODS AND MATERIALS: Thirty-nine patients with stage IB2-III cervical cancer who underwent 99m Tc sulfur colloid SPET imaging before treatment with cisplatin-based chemoradiation between January 2017 and March 2018 were analyzed. The total bone marrow (TBM) volume was defined as the external contours of all bones within the vertebral bodies from L4 to the coccyx, the pelvic bones, and the proximal femoral heads. The ABM volume was defined by SPET as the subregion of TBM with a nuclide uptake value greater than or equal to the mean total body nuclide uptake value. Student's t test was used to test for statistical significance between TBM and ABM dose-volume metrics. Receiver operating characteristic (ROC) curves were generated to compare the predictors of grade 3 or higher (grade 3+) hematologic toxicity. RESULTS: The mean ABM-V40 (23.22% ± 7.65%) and ABM-V30 (45.28% ± 9.20%) were significantly lower than the mean TBM-V40 (33.06% ± 6.72%) and TBM-V30 (53.08% ± 7.77%), respectively (t = 5.78, P = .001) (t = 4.13, P = .001). The ABM volume (<387.5 cm3 , AUC = 0.928, P = .001), ABM-V30 (>46.5%, AUC = 0.875, P = .001), and ABM-V40 (>23.5%, AUC = 0.858, P = .001) can predict the occurrence of grade 3+ hematologic toxicity. Among patients with an ABM volume < 387.5 cm3 , 16/19 (84.2%) had grade 3+ hematologic toxicity compared to 3/20 (15%) with an ABM volume > 387.5 cm3 . CONCLUSIONS: The ABM volume (<387.5 cm3 ) may be a better predictor of hematologic toxicity than conventional dose-volume metrics, but this finding needs to be further evaluated.

Continuous use of metformin can improve survival in type 2 diabetic patients with ovarian cancer: A retrospective study.

Evidence indicates that type 2 diabetes may stimulate the initiation and progression of several types of cancer. Metformin, a drug most commonly used to treat type 2 diabetes, may inhibit cancer cell growth and reduce the risk of cancer. However, evidence of the antitumor effects of metformin on ovarian cancer is still limited.In this study, we retrospectively examined the effects of metformin on ovarian cancer patients with diabetes at our institution.We identified 568 consecutive patients who were newly diagnosed with ovarian cancer and treated between January 2011 and March 2014. Patients with International Federation of Gynecology and Obstetrics (FIGO) stage I to IV epithelial ovarian, fallopian, or peritoneal cancer were included. Patients with type 1 diabetes, incomplete records (including medication records) and any other cancer before their ovarian cancer diagnosis, as well as those diagnosed with diabetes more than 6 months after their ovarian cancer diagnosis, were excluded. Out of 568 patients, 48 (8.5%) patients with type 2 diabetes continuously used metformin, 34 (5.9%) patients with type 2 diabetes did not take metformin, 22 (3.9%) patients with type 2 diabetes discontinued metformin, and 464 (81.7%) ovarian cancer patients were nondiabetic controls. Longer progression-free survival (PFS) and overall survival (OS) were observed in ovarian cancer patients with diabetes who were taking metformin than in diabetic patients not taking metformin, diabetic patients who discontinued metformin, and nondiabetic ovarian cancer patients (P = .001). After adjusting for possible confounders, metformin use was associated with a lower risk for disease relapse [hazard ratio (HR) = 0.34; 95% confidence interval (CI): 0.27-0.67; P < .01] and disease-related death (HR = 0.29; 95% CI: 0.13-0.58, P = .03) among ovarian cancer patients with diabetes.Metformin use may decrease the risk for disease recurrence and death in patients with ovarian cancer, but the drug treatment must be continuous.

Eyelash trichomegaly following treatment with erlotinib in a non-small cell lung cancer patient: A case report and literature review.

Inhibitors of epidermal growth factor receptor (EGFR), including tyrosine kinase inhibitors (TKIs), present significant clinical benefits in the treatment of non-small cell lung cancer (NSCLC), particularly in patients with an EGFR mutation. However, TKI treatment also results in unwanted cutaneous toxic side effects, such as a skin rash. Eyelash trichomegaly is rarely reported as a side effect; however, it causes cosmetic issues or eyeball irritation in patients, which may result in the early termination of TKI treatment. Therefore, although TKI-induced eyelash trichomegaly is rare, it should be considered carefully by lung cancer physicians. The present study reported a case of erlotinib-induced eyelash trichomegaly in a 65-year-old Chinese female patient suffering from NSCLC with an EGFR mutation. To the best of our knowledge, this is the first reported case of erlotinib-induced trichomegaly in a Chinese patient.