Platinum-based Concurrent Chemoradiotherapy Research Articles

A new treatment approach of toripalimab in combination with concurrent platinum-based chemoradiotherapy for locally advanced cervical cancer: A phase II clinical trial.

This study investigated the efficacy and safety of toripalimab in combination with concurrent platinum-based chemoradiation in patients with untreated locally advanced cervical cancer. Eligible patients received toripalimab 240 mg once every 3 weeks in combination with concurrent platinum-based chemoradiotherapy, followed by the maintenance of toripalimab once every 6 weeks up to 1 year. The primary endpoint was objective response rate (ORR). Secondary endpoints included 2-year and 3-year progression-free survival (PFS) rates, 3-year overall survival (OS) rate, and safety. Biomarker analysis of PD-L1 expression and genomic mutational analysis by next-generation sequencing were conducted, as well as PD-L1 expression on tumor biopsies. A total of 82 patients were enrolled. The median follow-up was 21 months (range, 5.2-44.5 months). The ORR and disease control rate were both 87.8% among the 82 patients. Median PFS and OS were not reached. A trend toward longer PFS was observed in the populations with a PD-L1 combined positive score ≥10, low tumor mutation burden and loss of heterozygosity in human leukocyte antigen (HLA LOH) detected populations. A total of 37 patients experienced treatment-related adverse events, of which 17 (20.7%) patients experienced grade 3 or higher adverse events. Collectively, toripalimab plus concurrent platinum-based chemoradiotherapy showed promising antitumor efficacy with acceptable safety profiles in patients with untreated locally advanced cervical cancer.

Durvalumab after Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer.

Adjuvant therapy with durvalumab, with or without tremelimumab, may have efficacy in patients with limited-stage small-cell lung cancer who do not have disease progression after standard concurrent platinum-based chemoradiotherapy. In a phase 3, double-blind, randomized, placebo-controlled trial, we assigned patients to receive durvalumab at a dose of 1500 mg, durvalumab (1500 mg) plus tremelimumab at a dose of 75 mg (four doses only), or placebo every 4 weeks for up to 24 months. Randomization was stratified according to disease stage (I or II vs. III) and receipt of prophylactic cranial irradiation (yes vs. no). Results of the first planned interim analysis of the two primary end points of overall survival and progression-free survival (assessed on the basis of blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1) with durvalumab as compared with placebo (data cutoff date, January 15, 2024) are reported; results in the durvalumab-tremelimumab group remain blinded. A total of 264 patients were assigned to the durvalumab group, 200 to the durvalumab-tremelimumab group, and 266 to the placebo group. Durvalumab therapy led to significantly longer overall survival than placebo (median, 55.9 months [95% confidence interval {CI}, 37.3 to not reached] vs. 33.4 months [95% CI, 25.5 to 39.9]; hazard ratio for death, 0.73; 98.321% CI, 0.54 to 0.98; P = 0.01), as well as to significantly longer progression-free survival (median 16.6 months [95% CI, 10.2 to 28.2] vs. 9.2 months [95% CI, 7.4 to 12.9]; hazard ratio for progression or death, 0.76; 97.195% CI, 0.59 to 0.98; P = 0.02). The incidence of adverse events with a maximum grade of 3 or 4 was 24.4% among patients receiving durvalumab and 24.2% among patients receiving placebo; adverse events led to discontinuation in 16.4% and 10.6% of the patients, respectively, and led to death in 2.7% and 1.9%. Pneumonitis or radiation pneumonitis with a maximum grade of 3 or 4 occurred in 3.1% of the patients in the durvalumab group and in 2.6% of those in the placebo group. Adjuvant therapy with durvalumab led to significantly longer overall survival and progression-free survival than placebo among patients with limited-stage small-cell lung cancer. (Funded by AstraZeneca; ADRIATIC ClinicalTrials.gov number, NCT03703297.).

Small cell cancer of the esophagus, treatment outcomes of a rare histological type

Purpose: To demonstrate treatment outcomes in two patients with small cell esophageal cancer. Cases reports. Patient M. was assigned to receive polychemotherapy (PC H) composed of etoposide 100 mg/ m2 intravenously on days 1–3 + cisplatin 80 mg/m2 on day 1, every 21 days for 6 cycles and lanreotide 120 mg subcutaneously, every 28 days, followed by chemoradiotherapy (CRT). The patient received 1 cycle of PCT , which was well tolerated. Then, the patient received a cycle of 3D-conformal radiation therapy concurrently with 2 cycles of chemotherapy: etoposide 120 mg/m2 + cisplatin 80 mg/m2. Chemoradiotherapy was well tolerated. Dysphagia regression to grade I was observed. Currently, the patient continues to receive treatment (etoposide 100 mg/ m2 intravenously on days 1–3 + cisplatin 80 mg/m2 on day 1, every 21 days for 6 cycles and lanreotide 120 mg subcutaneously, every 28 days) and tolerates it well. Patient A. was assigned to receive PCT with etoposide 120 mg/m2 + cisplatin 80 mg/m2. After 4 cycles of PCT , the follow-up CT images revealed disease progression (enlarged retroperitoneal lymph nodes). The patient underwent external bean radiation therapy to the primary tumor. Radiotherapy was relatively well tolerated. The patient underwent the course of radiation therapy relatively satisfactorily. Due to the progression of the disease, symptomatic treatment was assigned. The patient died 9 months after diagnosis. Conclusion. Small cell carcinoma of the esophagus is a rare histological type with poor prognosis. Concurrent platinum-based chemoradiotherapy allows achievement of stable disease and disease control.

ADRIATIC: Durvalumab (D) as consolidation treatment (tx) for patients (pts) with limited-stage small-cell lung cancer (LS-SCLC).

LBA5 Background: The standard of care (SoC) for pts with LS-SCLC is concurrent platinum-based chemoradiotherapy (cCRT) ± prophylactic cranial irradiation (PCI). ADRIATIC (NCT03703297), a phase 3, randomized, double-blind, placebo (PBO)-controlled, multicenter, global study, assessed D ± tremelimumab (T) as consolidation tx for pts with LS-SCLC who had not progressed after cCRT. Here we report results for D vs PBO from the first planned interim analysis (IA). Methods: Eligible pts had stage I–III LS-SCLC (stage I/II inoperable) and WHO performance status 0/1, and had not progressed after cCRT. PCI was permitted before randomization. Pts were randomized 1–42 days after cCRT to D 1500 mg + PBO, D 1500 mg + T 75 mg, or PBO + PBO every 4 weeks (Q4W) for 4 cycles, followed by D (D±T arms) or PBO Q4W until investigator-determined progression or intolerable toxicity, or for a maximum of 24 months (mo). The first 600 pts were randomized in a 1:1:1 ratio; subsequent pts were randomly assigned 1:1 to D or PBO. Randomization was stratified by stage (I/II vs III) and receipt of PCI (yes vs no). The dual primary endpoints were OS and PFS (blinded independent central review per RECIST v1.1) for D vs PBO. OS and PFS for D+T vs PBO were alpha-controlled secondary endpoints. Results: 730 pts were randomized, including 264 to D and 266 to PBO. Baseline characteristics and prior tx were well balanced between arms. Radiation schedule in the D vs PBO arms was once daily in 73.9% vs 70.3% of pts and twice daily in 26.1% vs 29.7%; 53.8% of pts in each arm received PCI. At this IA (data cutoff 15Jan2024), median (range) duration of follow-up for OS and PFS in censored pts was 37.2 (0.1–60.9) and 27.6 (0.0–55.8) mo, respectively. OS was significantly improved with D vs PBO (HR 0.73 [95% CI 0.57–0.93]; p=0.0104; median OS 55.9 [95% CI 37.3 – not estimable] vs 33.4 [25.5–39.9] mo; 24-mo OS rate 68.0% vs 58.5%; 36-mo OS rate 56.5% vs 47.6%). PFS was also significantly improved with D vs PBO (HR 0.76 [95% CI 0.61–0.95]; p=0.0161; median PFS 16.6 [95% CI 10.2–28.2] vs 9.2 [7.4–12.9] mo; 18-mo PFS rate 48.8% vs 36.1%; 24-mo PFS rate 46.2% vs 34.2%). Tx benefit was generally consistent across predefined pt subgroups for both OS and PFS. With D vs PBO, maximum grade 3/4 all-cause adverse events (AEs) occurred in 24.3% vs 24.2% of pts; AEs led to tx discontinuation in 16.3% vs 10.6% of pts and to death in 2.7% vs 1.9%. Any-grade pneumonitis/radiation pneumonitis was reported in 38.0% vs 30.2% of pts with D vs PBO (maximum grade 3/4 in 3.0% vs 2.6%). The D+T arm remains blinded until the next planned analysis. Conclusions: D as consolidation tx after cCRT demonstrated a statistically significant and clinically meaningful improvement in OS and PFS compared with PBO in pts with LS-SCLC. D was well tolerated and AEs were consistent with the known safety profile, with no new signals observed. These data support consolidation D as a new SoC for pts with LS-SCLC who have not progressed after cCRT. Clinical trial information: NCT03703297 .

Efficacy of nimotuzumab added to concurrent chemoradiotherapy after induction chemotherapy for patients with locally advanced nasopharyngeal carcinoma.

6024 Background: To investigate the efficacy and toxicities associated with adding nimotuzumab to concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal carcinoma (LANPC) patients who received induction chemotherapy (IC). Methods: Patients with stage III-IVA nasopharyngeal carcinoma who received IC (TPF/TP/GP) and platinum-based CCRT between January 2017 and October 2021 were retrospectively included. We performed propensity score matching (PSM) to balance and control confounding factors, and the matching variables included gender, age, T stage, N stage, and Epstein-Barr virus (EBV) status. Patients were divided into two treatment groups: CCRT+nimotuzumab (200mg iv, weekly for 7 courses) and CCRT alone. Primary endpoints were overall survival (OS) and disease-free survival (DFS), the secondary endpoints were locoregional recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS). Results: We screened 242 patients in the analysis. After PSM, 121 (50.0%) and 121 (50.0%) had CCRT+nimotuzumab and CCRT alone, respectively. The 3-year OS was 95.4% and 88.0% in those with and without nimotuzumab treatment (P=0.041), and the 3-year DFS of the CCRT+nimotuzumab group was significantly better than that in the CCRT alone group (90.3% vs. 77.5%, P=0.003). Similar LRFS was found between those with and without nimotuzumab treatment (96.5% vs. 93.7%, P=0.297). The 3-year DMFS for CCRT+nimotuzumab versus CCRT alone was 92.9% versus 82.5% (P=0.008). No significant differences in major toxicities were found between the two treatment arms including hematologic toxicities, hepatoxicity, nephrotoxicity, gastrointestinal reactions, and mucositis (P>0.05). Conclusions: The addition of nimotuzumab to CCRT after IC in LANPC has shown promising results in treatment outcomes and acceptable toxicities.

Efficacy and safety of bevacizumab in neoadjuvant and concurrent chemoradiotherapy for refractory cervical cancer patients.

A platinum-based concurrent chemoradiotherapy (CCRT) is the standard treatment for refractory cervical cancer (CC). However, the recurrence of disease and the occurrence of metastasis remain prevalent. We observed the long-term efficacy and safety of bevacizumab combined with neoadjuvant chemotherapy (NACT) and CCRT in refractory CC. A total of 62 patients with refractory CC were enrolled in this study from January 2016 to December 2019. The NACT regimen included bevacizumab (7.5 mg/kg), docetaxel (75 mg/m2), and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. The CCRT regimen included bevacizumab (7.5 mg/kg) and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. A dose of 45-50 Gy was prescribed for external beam radiotherapy (EBRT), while 30-35 Gy in 4-5 fractions was prescribed for brachytherapy (BT). Among the patients, 21 patients (33.9%) were at stages IIB-IIIB, 8 patients (12.9%) were at stage IIIC1, 19 patients (30.6%) were at stage IIIC2, and 14 patients (22.6%) were at stage IVB. Pelvic, para-aortic, supraclavicular, and inguinal lymph node metastases were discovered in 41 patients (66.1%). The median follow-up was 49.8 months (12.3-82.7 months). The median tumor volumes pre-treatment, after NACT, and before BT were 84.64 ± 53.15 cm3, 1.64 ± 13.15 cm3, and 0 ± 1.5 cm3, respectively. Complete clinical response (cCR) rates after NACT and EBRT were 35.5% and 66.1%, respectively. Four years after the diagnosis, the overall survival (OS) rate was 78.6%, the local region-free survival (LRFS) rate was 91.3%, the disease-free survival (DFS) rate was 70.6%, and the distant metastasis-free survival (DMFS) rate was 81.4%. A total of 29 patients (46.8%) experienced grade 3/4 hematological toxicity, 3 patients (4.8%) experienced grade 3 gastrointestinal toxicities, and none experienced grade 5 adverse events. Bevacizumab combined with NACT and CCRT significantly improved cCR and OS in refractory CC with acceptable toxicity.

Body composition radiomic features as a predictor of survival in patients with non-small cellular lung carcinoma: A multicenter retrospective study

ObjectivesThis study combined two novel approaches in oncology patient outcome predictions—body composition and radiomic features analysis. The aim of this study was to validate whether automatically extracted muscle and adipose tissue radiomic features could be used as a predictor of survival in patients with non-small cell lung cancer. MethodsThe study included 178 patients with non-small cell lung cancer receiving concurrent platinum-based chemoradiotherapy. Abdominal imaging was conducted as a part of whole-body positron emission tomography/computed tomography performed before therapy. Methods used included automated assessment of the volume of interest using densely connected convolutional network classification model - DenseNet121, automated muscle and adipose tissue segmentation using U-net architecture implemented in nnUnet framework, and radiomic features extraction. Acquired body composition radiomic features and clinical data were used for overall and 1-y survival prediction using machine learning classification algorithms. ResultsThe volume of interest detection model achieved the following metric scores: 0.98 accuracy, 0.89 precision, 0.96 recall, and 0.92 F1 score. Automated segmentation achieved a median dice coefficient >0.99 in all segmented regions. We extracted 330 body composition radiomic features for every patient. For overall survival prediction using clinical and radiomic data, the best-performing feature selection and prediction method achieved areas under the curve–receiver operating characteristic (AUC-ROC) of 0.73 (P < 0.05); for 1-y survival prediction AUC-ROC was 0.74 (P < 0.05). ConclusionAutomatically extracted muscle and adipose tissue radiomic features could be used as a predictor of survival in patients with non-small cell lung cancer.

Adjuvant Radiation Therapy Improves Local Control in the Treatment of Adnexal Carcinoma

Adnexal carcinoma (AC) is a rare subset of cutaneous malignancies derived from skin adnexa. There are limited data on the role of adjuvant radiation therapy (RT). This study investigates outcomes associated with adjuvant RT at our high-volume referral center. Using an institutional pathology database we identified 45 patients with locoregionally-confined AC treated between 2001-2020 with curative intent surgery and RT at initial diagnosis or at the time of locoregionally-confined recurrence. Clinicopathologic variables were described and time to relapse events were assessed by the Kaplan-Meier method. Median age was 64 yrs (IQR 57-71). Primary tumors were in the head and neck (H&N, n = 36, 80%), trunk/extremities (n = 8, 18%) or unknown (n = 1). The most common histologic subtypes were: sebaceous-14 (31%), microcystic adnexal carcinoma-9 (20%), eccrine-6 (13%), and trichilemmal-5 (11%). Twenty-two (50% of known primaries) had PNI. All patients had primary tumor excision. Six had clinically evident lymphadenopathy (13%), all of whom had lymph node dissection (LND). Five patients without evidence of nodal disease (13%) had sentinel lymph node biopsy (SLNB) with one having SLN+ disease. Thirty patients (67%) received adjuvant locoregional RT at initial diagnosis with the following targets: 21 (30%) primary only, 4 (13%) nodal only, and 5 (17%) both. Of those receiving nodal RT, 7 (78%) had LN+ LND with 2 of those receiving concurrent platinum-based chemoradiation. Sixteen were treated at recurrence with the following targets: 4 (25%) primary only (1 having had prior adjuvant nodal RT), 4 (25%) nodal only, and 8 (50%) both. Across the full cohort, median RT dose was 60 Gy in 30 fractions. Median follow-up from initial surgical resection was 60 months (IQR 30-160). 5-year LC, NC, DFS and DSS were 71%, 86%, 66%, and 91% respectively. The only evaluated factor associated with better outcome was adjuvant primary site RT (5-yr LC 83% vs. 56%, p = 0.01 and 5-yr DFS 83% vs. 46%, p = 0.0003). All 15 patients with local recurrence (LR) had salvage surgery with median subsequent follow-up of 75 months (IQR 2-94). Overall, 5 patients receiving adjuvant primary site RT at any time (initial or salvage) developed subsequent local recurrence (13%). Of the 8 patients who developed nodal recurrence (NR) during follow-up, 1 received adjuvant nodal RT at initial diagnosis. Six of 7 who did not receive prior RT then received adjuvant nodal RT after LND and only 1 developed subsequent NR. AC is a rare skin cancer with a primarily locoregional recurrence pattern. In our experience, adjuvant RT was associated with improved LC which, depending on the tumor location, may help prevent morbid or cosmetically-impactful salvage surgery. Patients with AC would benefit from radiation oncology referral to discuss adjuvant treatment.

Clinical Significance of Arginine Signaling in Patients with Cervical Cancer Receiving Cisplatin Chemoradiation Therapy

Many human malignancies do not produce sustainable amounts of arginine (Arg) because the rate-limiting enzyme, arginosuccinate synthetase 1 (ASS1), in the biosynthesis of Arg has been silenced. We investigated the clinical significance of ASS1 expression on cisplatin chemoradiation therapy for cervical cancer. A total of 118 consecutive patients with FIGO stages IB to IVA cervical cancer who had received platinum-based concurrent chemoradiotherapy were identified and their clinical courses were reviewed. Immunohistochemical studies were performed on their formalin-fixed, paraffin-embedded tissues. The prognostic value of ASS1 was investigated by performing univariate and multivariate analyses on factors affecting patient survival. Median follow-up for all patients was 5.5 years (range: 1 to 23.5 years). Overexpression of ASS1 was an independent prognostic factor. The 5-year disease-free survival for patients with ASS1-positive tumors was 72.3%, compared with 51.6% for patients with ASS1-negative tumors (P = 0.02). Univariate Cox proportional hazards models showed positive ASS1 immunostaining (hazard ratio [HR]: 0.50, 95% CI: 0.28-0.90), FIGO stage (HR: 0.33, 95% CI: 0.18-0.59) and brachytherapy (HR: 0.22, 95% CI: 0.10-0.48) were significant prognostic factors affecting disease-free survival. In multivariate analyses, positive ASS1 remained an independent significant prognostic factor for DFS (HR = 0.45, 95% CI: 0.25-0.83). Overexpression of ASS1 is an independent prognostic factor for cervical cancer patients receiving cisplatin concurrent chemoradiotherapy.

Efficacy of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine for the prevention of mucositis induced by platinum-based chemoradiation in head and neck cancer: A phase II study

The current standard treatment modality for advanced head and neck squamous cell carcinoma (HNSCC), namely platinum-based (PB) concurrent chemoradiotherapy (CRT), is associated with frequent severe mucositis which is responsible for the multiple acute and late adverse events. So far, effective preventive methods for this CRT-induced mucositis are not identified. In the current study, we examined the prophylactic effects of beta-hydroxy-beta-methylbutyrate (HMB), arginine (Arg), and glutamine (Gln) (HMB/Arg/Gln) mixture. Patients with HNSCC who were subject to PBCRT were randomly assigned to HMB/Arg/Gln intervention (Group I) and non-intervention (Group NI) cohort. The incidences of ≧ grade 3 mucositis (primary endpoint), ≧ grade 2 mucositis, and opioid usage and the degree of body weight loss (secondary endpoints) were compared between Group I and Group NI. A total of 75 patients were enrolled to this study and 38 patients were assigned to Group I, while 37 patients were to Group NI. After excluding patients who failed to complete CRT (3 in Group I and 2 in Group NI) or withdrew consents (11 in Group I and 1 in Group NI), 24 patients in Group I and 34 patients in Group NI were evaluated. HMB/Arg/Gln failed to reduce the incidences of ≧ grade 2 mucositis, but significantly (p=0.0003) inhibited grade 3 mucositis in the late phase CRT, reducing the incidence from 64.6% (Group NI) to 25% (Group I) at 70Gy. The degree of body weight loss was significantly (p=0.0038) lower in Group I (5.6%) compared to Group NI (8.9%), preventing the progression of PBCRT-induced cachexia. HMB/Arg/Gln administration demonstrated inhibitory effects on the progression of grade 3 mucositis and cancer cachexia in HNSCC patients treated with PBCRT. A larger scale phase III study is encouraged. This study is registered to the UMIN Clinical Trial Registry: UMIN000050011.

Brief Report: Durvalumab After Chemoradiotherapy in Unresectable Stage III EGFR-Mutant NSCLC: A Post Hoc Subgroup Analysis From PACIFIC

IntroductionConsolidation durvalumab (the “PACIFIC regimen”) is standard of care for patients with unresectable stage III NSCLC who have not progressed after chemoradiotherapy, on the basis of data from the phase 3 placebo-controlled PACIFIC study (NCT02125461). Nevertheless, the benefit of immunotherapy in patients with stage III EGFR-mutant (EGFRm) NSCLC is not well characterized. Here, we report a post hoc exploratory efficacy and safety analysis from a subgroup of patients with EGFRm NSCLC from the PACIFIC. MethodsPatients with stage III unresectable NSCLC and no progression after more than or equal to two cycles of platinum-based concurrent chemoradiotherapy were randomized (2:1) to receive durvalumab (10 mg/kg intravenously every 2 weeks [wk], for up to 1 y) or placebo; stratified by age, sex, and smoking history. Enrollment was not restricted by oncogenic driver gene mutation status or programmed death-ligand 1 expression. Patients with NSCLC with an EGFR mutation, determined by local testing only, were included in this subgroup analysis. The primary end points were progression-free survival (PFS; assessed by blinded independent central review) and overall survival (OS). Secondary end points included objective response rate and safety. Statistical analyses for the subgroup of patients with EGFRm NSCLC were post hoc and considered exploratory. ResultsOf 713 patients randomized, 35 had locally confirmed EGFRm NSCLC (durvalumab, n = 24; placebo, n = 11). At data cutoff (January 11, 2021), median duration of follow-up for survival was 42.7 months (range: 3.7–74.3 mo) for all randomized patients in the subgroup. Median PFS was 11.2 months (95% confidence interval [CI]: 7.3–20.7) with durvalumab versus 10.9 months (95% CI: 1.9–not evaluable [NE]) with placebo; hazard ratio = 0.91 (95% CI: 0.39–2.13). Median OS was 46.8 months (95% CI: 29.9–NE) with durvalumab versus 43.0 months (95% CI: 14.9–NE) with placebo; hazard ratio = 1.02 (95% CI: 0.39–2.63). The safety profile of durvalumab was generally consistent with the overall population and known profile for durvalumab. ConclusionsPFS and OS outcomes with durvalumab were similar to placebo for patients with EGFRm tumors, with wide CIs. These data should be interpreted with caution owing to small patient numbers and lack of a prospective study that evaluates clinical outcomes by tumor biomarker status. Further research to determine the optimal treatment for unresectable stage III EGFRm NSCLC is warranted.

Integrated strategies for chemotherapy cycles in nasopharyngeal carcinoma patients: Real-world data from two epidemic centers guiding decision-making.

Two cycles of induction chemotherapy (IC) followed by 2 cycles of platinum-based concurrent chemoradiotherapy (CCRT) (2IC+2CCRT) for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) is widely adopted but not evidence-confirmed. This study aimed to determine the clinical value of 2IC+2CCRT regarding efficacy, toxicity and cost-effectiveness. This real-world study from two epidemic centers used propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analyses. The enrolled patients were divided into three groups based on treatment modality: Group A (2IC+2CCRT), Group B (3IC+2CCRT or 2IC+3CCRT) and Group C (3IC+3CCRT). Long-term survival, acute toxicities and cost-effectiveness were compared among the groups. We developed a prognostic model dividing the population into high- and low-risk cohorts, and survivals including overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) were compared among the three groups according to certain risk stratifications. Of 4,042 patients, 1,175 were enrolled, with 660, 419, and 96 included in Groups A, B and C, respectively. Five-year survivals were similar among the three groups after PSM and confirmed by IPTW. Grade 3-4 neutropenia and leukocytopenia were significantly higher in Groups C and B than in Group A (52.1% vs. 41.5% vs. 25.2%; 41.7% vs. 32.7% vs. 25.0%) as were grade 3-4 nausea/vomiting and oral mucositis (29.2% vs. 15.0% vs. 6.1%; 32.3% vs. 25.3% vs. 18.0%). Cost-effective analysis suggested that 2IC+2CCRT was the least expensive, while the health benefits were similar to those of the other groups. Further exploration showed that 2IC+2CCRT tended to be associated with a shorter PFS in high-risk patients, while 3IC+3CCRT potentially contributed to poor PFS in low-risk individuals, mainly reflected by LRRFS. In LA-NPC patients, 2IC+2CCRT was the optimal choice regarding efficacy, toxicity and cost-effectiveness; however, 2IC+2CCRT and 3IC+3CCRT probably shortened LRRFS in high- and low-risk populations, respectively.

Efficacy and safety of nimotuzumab combined with chemoradiotherapy in the treatment of locally advanced cervical cancer.

Platinum-based concurrent chemoradiotherapy (CCRT) is the primary treatment for locally advanced cervical cancer (LACC). Improving the efficacy of LACC treatment is the focus of clinical research, and nimotuzumab combined with CCRT is a new research direction. This retrospective study aimed to investigate the efficacy and safety of nimotuzumab combined with CCRT compared with CCRT alone for treating LACC. Data from LACC patients treated at The Affiliated Hospital of Qingdao University from March 2017 to December 2019 were collected, and patients were assigned to either a nimotuzumab plus chemoradiotherapy (N + CCRT) group or a CCRT group. Baseline data were also collected. Patients were followed up every 3 to 6 months by imaging examination or telephone. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoints were complete response rate (CRR), objective response rate (ORR), and incidence of adverse events (AEs). A total of 120 patients (65 in the N + CCRT group and 55 in the CCRT group) were enrolled, which baseline data were no statistical difference between the two groups (P>0.05). In the N + CCRT group, the 1-, 2-, and 3-year cumulative survival rates were 98.46%, 95.38%, and 90.50%, respectively, and the 1-, 2-, and 3-year cumulative PFS rates were 89.23%, 83.08%, and 79.73%, respectively. The CRR was 86.15% (56/65), and the ORR was 92.31% (60/65). In the CCRT group, the 1-, 2-, and 3-year cumulative survival rates were 94.55%, 87.27%, and 78.18%, respectively, and the 1-, 2-, and 3-year cumulative PFS rates were 81.82%, 69.09%, and 59.69%, respectively. The CRR was 70.91% (39/55), and the ORR was 87.27% (48/55). The CRR (86.15% vs. 70.91%, P=0.040) and 3-year cumulative PFS rates (79.73% vs. 59.69%, P=0.039) were significantly higher in the N + CCRT group than in the CCRT group. The incidences of various AEs were from 5.45% to 95.38%, without significant difference in AEs between the two groups (P>0.05). Nimotuzumab combined with CCRT enhanced the PFS and CRR of LACC patients and was well tolerated. The results can provide reference for clinical treatment of LACC.

The long-term survival of the doublet regimen of concurrent chemoradiation therapy for locoregionally advanced nasopharyngeal carcinoma: a retrospective study

ObjectiveThis study introduces innovative strategies, the doublet regimen of concurrent chemoradiotherapy, to ensure longer survival for locoregionally advanced nasopharyngeal carcinoma.MethodsWe retrospectively reviewed 104 locoregionally advanced nasopharyngeal carcinoma patients who underwent taxane combined platinum-based concurrent chemoradiotherapy in our center between January 2013 and December 2018. All statistical analyses were performed using the Kaplan–Meier method (SPSS 23.0). Different groups were compared with the Wilcoxon rank-sum test.ResultsUltimately, 104 patients were selected for this study, including 18 and 86 who received either concurrent chemoradiation therapy alone or concurrent chemoradiation therapy plus adjuvant chemotherapy, respectively. The median follow-up time for progression free survival was 53.0 months (IQR 48.5–57.5). The 3-years progression-free survival (PFS), overall survival (OS), local–regional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) rates of the doublet regimen of concurrent chemotherapy for locoregionally advanced nasopharyngeal carcinoma were 85.9%, 96.0%, 96.0% and 90.8%, respectively. Additionally, we analyzed the subgroups and found that the 3-years PFS, OS, LRRFS and DMFS rates for stage III versus stage IVa were 97.8% versus 75.5% (P = 0.000), 100% versus 92.5% (P = 0.004), 100% versus 92.4% (P = 0.015) and 97.8% versus 82.8% (P = 0.002), respectively. During concurrent chemotherapy, acute chemotherapy adverse events of grade 3 or 4 was only 18.3%. Leukopenia was the most common acute chemotherapy adverse event (in 10 patients [9.6%]), followed by neutropenia (in 8 patients [7.6%]).ConclusionThe doublet regimen of taxane plus platinum concurrent chemoradiotherapy resulted in improved long-term survival of locoregionally advanced nasopharyngeal carcinoma patients, especially for local control rate and warrants further prospective evaluation.

Durvalumab in Combination with Chemoradiotherapy (CRT) in Locally Advanced Cervical Cancer (LACC): Radiotherapy (RT) Delivery and Subgroup Analyses from CALLA

<h3>Purpose/Objective(s)</h3> Concurrent platinum-based CRT has been standard of care in LACC for 20+ years. Simultaneously, RT techniques/technology have advanced, providing opportunity for improved treatment outcomes. In LACC, global standardization is critical to enhance RT quality and brachytherapy (BT) utilization. CALLA was the first global, placebo-controlled, Phase 3 study evaluating durvalumab (D), in combination with and following CRT, in LACC . We examine RT technological approaches, quality assurance measures, and related RT-based findings from CALLA. <h3>Materials/Methods</h3> Newly diagnosed, untreated patients (pts) with high-risk LACC (FIGO 2009 IB2–IIB node positive, IIIA–IVA any node status) were randomized 1:1 to D (1500 mg IV) or placebo (P) Q4W (total ≤24 doses), in combination with and following CRT. CRT comprised concurrent weekly IV platinum agent with external beam radiotherapy (EBRT) and BT. Detailed EBRT/BT protocol guidelines were included to ensure regional alignment. Prior to site qualification, a feasibility questionnaire and credentialing process confirmed compliance. A global RT subcommittee reviewed RT quality/compliance and created a scoring system to identify plan variations and potential clinical significance. RT quality was evaluated for each pt, including detailed review of contouring, EBRT plan dose/metrics, BT utilization/quality, RT completion, and treatment plan dose/quality variations. <h3>Results</h3> A total of 770 women (105 sites,15 countries; 44% Hispanic, 39% Asian) were randomized. The primary endpoint of PFS was not met (hazard ratio [95% CI] for D+CRT vs P+CRT: 0.84 [0.65–1.08]; <i>P</i>=0.174). PFS at 12 and 24 months for D+CRT vs P+CRT were 76.0% vs 73.3% and 65.9% vs 62.1%, respectively. EBRT and BT were completed per protocol in 96.4% and 94.3% of pts for D+CRT and 98.4% and 95.3% for P+CRT. RT was delivered in ≤59 days in 72.2% and 72.5% for D+CRT and P+CRT, respectively. Intensity-modulated RT was used for 86.8% (D+CRT) and 88.1% (P+CRT) of pts. A majority of pts received volume-directed BT (59.7% D+CRT, 63.3% P+CRT), and 87.4% and 88.1% of BT was high-dose rate. In both arms, median RT dose delivered was 5400 cGy and median equivalent dose was 8387.0 cGy (median BT dose/fraction 700 cGy, 4 fractions) (RT doses omit Japan). Clinically significant unacceptable variations in RT delivery were low; <25% of unacceptable variations were clinically significant. PFS by RT subgroups were generally aligned with the ITT population. <h3>Conclusion</h3> CALLA integrated an exceptional quality assurance/control strategy to ensure global protocol compliance, showing high-quality RT delivery is achievable with high compliance. Although D+CRT did not significantly improve PFS vs P+CRT, CALLA illustrates the importance of strong multidisciplinary collaboration for optimal CRT delivery in high-risk LACC. Funding: AstraZeneca

Can laparoscopic nerve-sparing ultra-radical hysterectomy play a role in locally advanced cervical cancer? A single-center retrospective study.

The objective of this study is to investigate the outcomes of concurrent platinum-based chemoradiation therapy (CCRT), laparoscopic nerve-sparing ultra-radical hysterectomy (LNSURH), and open radical hysterectomy (ORH) on patients with locally advanced cervical carcinoma (LACC). A single-center retrospective study was conducted on LACC patients who received CCRT, ORH, or LNSURH from January 2011 to December 2019. Data on age, tumor size, overall survival (OS), disease-free survival (DFS), and early and late morbidities were collected. After 24 months of treatment, patients were asked a series of questions about their urinary, bowel, and sexual activities. Early morbidities were defined as those occurring during or within a month of treatment, whereas late morbidities and complications were defined as those occurring a month after treatment. The postoperative complications were classified with reference to the Clavien-Dindo classification (CD) system. The Kaplan-Meier curves revealed no significant differences in OS and DFS among the three groups (P = 0.106 for DFS and P = 0.190 for OS). The rates of early complications in the CCRT group were comparable with those in the operated groups (P = 0.46). However, late complications were significantly lower in the ORH and LNSURH groups relative to those in the CCRT group. The scores of urinary and bowel functions were restored to the pretreatment state, although the sexualfunction scores were not satisfactory. The treatments of CCRT, ORH, and LNSURH can be considered options for patients with LACC, as their OS and DFS showed no significant difference. In addition, LNSURH exhibited a lower incidence of late complications and high sexual function scores.

EP05.01-002 Real World Treatment Patterns and Outcomes among Unresectable Stage III Non-Small Cell Lung Cancer Patients Initiating Chemoradiotherapy

Concurrent platinum-based chemoradiation therapy (cCRT) with or without durvalumab consolidation for 12 months is the current standard of care for patients with unresectable stage III Non-Small Cell Lung Cancer (NSCLC). This study characterized the real-world treatment utilization patterns and associated outcomes after approval of durvalumab for this indication.

Anlotinib plus chemoradiotherapy in the treatment for FIGO stage IB3 and IIB-IVA cervical cancer: A prospective single-arm, single-center, exploratory phase II trial (299)

<b>Objectives:</b> Cervical carcinoma is the fourth leading cause of cancer-related death among women worldwide. Previous randomized clinical trials showed a 30% to 50% decrease in risk of death in locally advanced cervical cancer (LACC) with the addition of concurrent platinum-based chemoradiotherapy when compared with radiotherapy alone. Mechanisms to account for improved efficacy are thought to include direct cytotoxicity, radiosensitization of tumor cells, and control of subclinical metastases. Anlotinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that strongly inhibits VEGFR, PDGFR, FGFR, and c-kit. Anlotinib synergizes with radiation and cisplatin, as shown in preclinical and clinical studies. This phase II study aims to evaluate the efficacy and safety of adding anlotinib to concurrent chemoradiotherapy in FIGO stage IB3 and IIB-IVA cervical cancer. <b>Methods:</b> Inclusion criteria include treatment-naive histologically confirmed FIGO stage IB3 to IVA cervical cancer with at least one measurable lesion and ECOG performance score 0-2 within the age range of 18 to 75 years. Abundant organ functions are required, with no contraindication to anlotinib or chemoradiation present. Patients will be treated with oral anlotinib (12 mg qd, d1-14; 21 days per cycle; total 3 cycles) and X-ray external-beam radiotherapy (total 45Gy-50Gy in 25-28 fraction), followed by brachytherapy (6Gy/5 fractions or 7Gy/4 fractions) with concurrent cisplatin (40 mg/m2 weekly for 5-6 weeks). The primary endpoint is the progression-free survival (PFS) rate at three years. The secondary endpoints include overall response rate (ORR), disease control rate (DCR), overall survival (OS), and quality of Life (QOL). Safety will be evaluated in all patients who receive study drugs according to the treatment received (safety population) by recording clinical adverse events (AEs) using National Cancer Institute Common. The sample size calculation of 47 patients provides 80% power to detect a difference in survival at the two-sided 5% significance level using the log-rank test; considering a 10% reduction, a total of 53 samples are required. This study is currently open, and 23 patients have been enrolled. The estimated primary completion date is December 1, 2024, and the estimated study completion date is October 31, 2025.

Induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: A systematic review and meta-analysis.

BackgroundAdding induction chemotherapy to concurrent platinum-based chemoradiotherapy has significantly prolonged the survival time of patients with locoregionally advanced nasopharyngeal carcinoma. In this study, we intend to evaluate the survival outcomes, responses, and incidences of toxicities of induction chemotherapy and the differences between different strategies.MethodsA comprehensive search was conducted in PubMed, Embase, Web of Science, and Cochrane CENTRAL on August 10, 2021. Single-arm or multi-arm prospective clinical trials on induction chemotherapy without targeted therapies or immune checkpoint inhibitors were included. Primary outcomes included survival outcomes, objective response rate, and disease control rate, and the secondary outcome was the rates of grade 3 or higher treatment-related adverse events.ResultsThe 39 studies included in the systematic review and meta-analysis comprised 36 clinical trials and 5389 patients. The estimates for 3-year overall and fail-free survival rates were 87% and 77%. The estimates for 5-year rates of overall and fail-free survival were 81% and 73%. Gemcitabine plus platinum and docetaxel combined with 5-fluorouracil plus platinum strategies were associated with the highest rates of 3-year and 5-year overall survival. The objective response and disease control rates were 85% and 98% after the completion of induction chemotherapy. Neutropenia (27%) and nausea/vomiting (7%) were the most common grade 3 or higher treatment-related hematological and non-hematological adverse events during the induction phase.ConclusionsDifferent induction chemotherapeutic strategies appear to have varying effects and risks; a comprehensive summary of the survival outcomes, responses, and toxicities in clinical trials may provide a crucial guide for clinicians.

Toripalimab combined with concurrent platinum-based Chemoradiotherapy in patients with locally advanced cervical Cancer: an open-label, single-arm, phase II trial

BackgroundConcurrent chemoradiotherapy is currently the standard of care for patients with locally advanced cervical cancer. However, even with the application of modern radiotherapy techniques, a considerable number of patients still develop distant metastases. PD-L1 inhibitors show good efficacy in cervical cancer. This single-arm phase II study aims to explore the efficacy and tolerability of combining PD-L1 inhibitor with concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer.Methods/designThe primary endpoint of the study was the objective response rate assessed according to RECIST v1.1 criteria. The inclusion criteria were previously untreated patients aged 18–75 years with stage III-IVA (FIGO 2018 staging system) locally advanced cervical cancer. During concurrent chemoradiotherapy and consolidation chemotherapy, the enrolled patients will receive toripalimab (240 mg) every 3 weeks. After consolidation chemotherapy, the enrolled patients will be treated with toripalimab (240 mg) once every 6 weeks until the whole treatment cycle reaches 1 year. Intensity modulated radiotherapy was used for external beam radiation, and high-dose rate brachytherapy was delivered under image-guidance. Weekly DDP (40 mg/m2) was given concurrently with radiotherapy while 6 cycles of consolidated chemotherapy (paclitaxel plus DDP) were given after radiotherapy every three weeks. Secondary objectives included safety and tolerability, toxicity profile, progression-free survival, and overall survival.DiscussionPD-L1 inhibitor has shown good efficacy in recurrent/metastatic cervical cancer. However, there is still a lack of evidence about its combination with concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer. The purpose of this study is to explore the efficacy and tolerance of this combination therapy, so as to lay the foundation for the future phase III randomized study.Trial registrationclinicaltrials.govNCT05084677. Retrospectively registered on Octorber 07, 2021.