Induction Chemotherapy Group Research Articles

Selection of induction chemotherapy cycles for stage N3 nasopharyngeal carcinoma based on pre-treatment plasma EBV DNA.

This study aimed to explore the selection of induction chemotherapy (IC) cycles for stage N3 nasopharyngeal carcinoma (NPC). We employed propensity score matching (PSM) to categorize patients into 3-cycle and 4-cycle IC groups (IC = 3 and IC = 4). The log-rank and chi-squared tests were used respectively to evaluate the differences in survival and acute toxicities. Survival outcomes including overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) were evaluated among the two groups. After PSM, each group comprised 99 patients. The IC = 4 group exhibited markedly improved survival outcomes compared with the IC = 3 group. Multivariate analysis revealed that pre-EBV DNA was an independent risk factor affecting PFS and DMFS. For high-risk patients with pre-EBV DNA ≥ 7800 copies/ml, the IC = 4 group demonstrated greater survival compared to the IC = 3 group. Among low-risk patients with pre-EBV DNA < 7800 copies/ml, both groups showed comparable survival outcomes. In terms of acute adverse reactions, the IC = 4 group experienced higher incidences, particularly with grade 2-4 alanine transaminase elevation and thrombocytopenia. For stage N3 NPC, pre-EBV DNA could be a powerful predictor for guiding the selection of IC cycles. The IC = 4 regimen is probably more beneficial to high-risk patients due to superior survival, while for low-risk patients, the IC = 3 regimen may be sufficient.

Long-Term Outcomes in Patients With Locally Advanced Rectal Cancer Following R1 Resection After Either Induction Chemotherapy and Chemoradiotherapy or Chemoradiotherapy Alone

IntroductionTotal neoadjuvant treatment (TNT) with induction chemotherapy (ICT) followed by chemoradiotherapy (CRT) has improved long-term outcomes for patients with locally advanced rectal cancer (LARC). However, long-term outcomes have not been investigated for patients with incomplete (R1) resection separately. This study investigates overall survival (OS), disease-free survival (DFS) and local and distant recurrence rates in patients with R1 resection after preoperative treatment with ICT and CRT or CRT. Patients and methodsFrom the NORD database 689 patients with LARC who received treatment between 2006 and 2017 were screened for inclusion. All patients with R1 resection were included. ICT consisted of at least 1 cycle of capecitabine and oxaliplatin (CAPOX) and was followed by radiotherapy concomitant with capecitabine. ResultsAmong 46 patients with R1 resection, 27 (59%) received both ICT and CRT, and 19 (41%) patients received CRT. The 5-year OS was 44% (95% CI, 26%-63%) (ICT + CRT) versus 37% (95% CI, 15%-59%) (CRT) (P = .25) and 5-year DFS was 44% (95% CI, 26%-63%) (ICT + CRT) versus 32% (95% CI, 11%-53%) (CRT) (P = .22). The local recurrence rates showed a small nonstatistical significant difference in local control in the ICT group: 15% compared to 26% in the CRT group (P = .22). Distant recurrence rates were similar: 41% (ICT + CRT) versus 47% (CRT) (P = .48). ConclusionThere was no significant difference in OS, DFS or local and distant recurrence rates between patients who received ICT + CRT versus patients who received CRT only.

Induction chemoimmunotherapy followed by radiotherapy in locally advanced head and neck squamous cell carcinoma: A real-world study.

131 Background: Patients with locally advanced head and neck squamous cell cancers (LAHNSCC) present poor prognosis despite multi-disciplinary comprehensive treatment, and novel treatment strategies are urgently needed. Recently, several phase II clinical trials reported encouraging pathological complete response rate of induction chemoimmunotherapy (IC+ICI) in LAHNSCC, suggesting potentially long-term survival benefits. Therefore, we conducted this real-world study to compare the efficacy of IC+ICI followed by radiotherapy (RT) versus induction chemotherapy (IC) followed by RT in LAHNSCC. Methods: We retrospectively included patients with LAHNSCC from Sun Yat-sen University Cancer center database treated with IC+ICI followed by RT or IC followed by RT between 1/2018-12/2021. Survival outcomes and adverse effects (AEs) were compared between the two groups. Results: A total of 262 patients were included: 128 (48.9%) in the IC+ICI group, and 134 (51.1%) in the IC group. Median age for the whole cohort was 60 (53–66) years, and the male-to-female ratio is 8.9:1. Most patients (84.4%) had stage IV disease. The median follow-up time was 26.7 (IQR 25.8-29.6) months. Marginally significant higher objective response rate (ORR) was observed in the IC+ICI group than that in the IC group (81.25% vs 72.39%, P=0.09). Patients in the IC+ICI group had significantly better results than those in the IC group in 2-year overall survival (OS; 88.9% vs. 71.5%, P&lt;0.001), disease-free survival (DFS; 77.5% vs. 58.3%, P=0.005), locoregional relapse-free survival (LRRFS; 78.4% vs. 59.7%, P=0.009) and distant metastasis-free survival (DMFS; 87.5% vs. 64.6%, P&lt;0.001). Multivariate analysis confirmed that combining immunotherapy in the induction stage was an independent prognostic factor for OS (HR 0.40, 95%CI 0.19-0.84), DFS (HR 0.45, 95%CI 0.28-0.72), LRRFS (HR 0.56, 95%CI 0.31-0.99), and DMFS (HR 0.37, 95%CI 0.19-0.73). The incidences of G3/4 AEs between the IC+ICI group and the IC group were comparable during the induction stage (6.25% vs 12.69%, P = 0.076) as well as the radiotherapy stage (14.06% vs 14.18%, P = 0.978). Conclusions: This study firstly reported that IC+ICI followed by RT was superior to IC followed by RT in long-term survival outcome in LAHNSCC.

Comparison of immunochemotherapy and chemotherapy alone in conversion therapy for locally advanced unresectable esophageal squamous cell carcinoma.

The clinical value of preoperative immunochemotherapy and simple chemotherapy induction regimen in the conversion therapy of locally advanced unresectable esophageal squamous cell carcinoma (ESCC) is still unclear. Retrospective analysis was conducted on patients with unresectable cT4b stage ESCC who underwent conversion surgery in our hospital from January 2020 to December 2022. According to the preoperative induction treatment plan, they were divided into induction immunochemotherapy group (iICT group) and induction chemotherapy group (iCT group). The conversion surgery rate, R0 resection rate, radiological and pathological tumor responses, safety, and short-term survival outcomes were analyzed. The results showed that a total of 199 patients with cT4b locally advanced unresectable ESCC who underwent preoperative induction therapy were included in this study. Among them, there were 64 cases (32.2%) in the iICT group, 135 cases (67.8%) in the iCT group. There was a statistically significant difference in objective response rate (73.5% vs 48.9%) and conversion surgery rate (81.3% vs 66.7%), between the iICT and iCT groups (P=0.001 and P=0.019). Among the two groups of patients who underwent surgery, there were statistically significant differences in R0 resection rate (94.2% vs 82.2%) and pathological complete remission rate (23.1% vs 6.7%) between the iICT and iCT groups (P=0.043 and P=0.004). And there was no statistically significant difference in the incidence of grade 3 and above between two groups (P=0.928). The 2-year EFS of the iICT group and iCT group were 76.4% and 42.4%, respectively, with statistically significant differences (P=0.006). Compared with simple chemotherapy, the combination of PD-1 inhibitors and chemotherapy can achieve better conversion surgery rate, tumor response and event-free survival in the conversion therapy of locally advanced unresectable ESCC.

Incorporation of PD-1 blockade into induction chemotherapy improved tumor response in patients with locoregionally advanced nasopharyngeal carcinoma in a retrospective patient cohort

ObjectiveTo investigate the short-term efficacy and safety of induction chemotherapy (IC) combined with anti-PD-1 immunotherapy in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). MethodsA total of 217 patients diagnosed with LA-NPC at the First Affiliated Hospital of Nanchang University, including 67 who received IC combined with anti-PD-1 and 150 who received IC, were retrospectively enrolled. Efficacy was evaluated at the end of the IC cycles and one month after radiotherapy based on RECIST v1.1 criteria. Acute toxicities were graded based on the CTCAE v5.0 criteria. Quantitative variables were compared by unpaired t-tests, and categorical variables were evaluated by Fisher Freeman-Halton test or Pearson Chi-square test. ResultsAt the end of all induction therapy cycles, the objective response rate (ORR) of the IC + anti-PD-1 group was 88.1 % (59/67) as opposed to 70.0 % (105/150) in the IC group. Subgroup analysis showed that patients in both stage Ⅲ and ⅣA achieved a significant improvement in ORR with the inclusion of anti-PD-1 therapy. Patients with T3-4 or N2-3 category appeared to benefit more from anti-PD-1 compared to patients with T1-2 or N0-1 category. However, neither ORR nor the complete response (CR) rate was significantly different between the two treatment groups one month after the end of radiotherapy. In addition, the frequency of Grade 3–4 adverse events were also similar in both groups. ConclusionsIC combined with anti-PD-1 immunotherapy significantly improved the ORR of LA-NPC patients after induction therapy compared to IC alone.

Induction immunotherapy plus chemotherapy followed by definitive chemoradiation therapy in locally advanced esophageal squamous cell carcinoma: a propensity-score matched study

BackgroundFor patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC), concurrent chemoradiotherapy (CCRT) is the current standard treatment; however, the prognosis remains poor. Immunotherapy combined with chemotherapy has demonstrated improved survival outcomes in advanced ESCC. Nevertheless, there is a lack of reports on the role of induction immunotherapy plus chemotherapy prior to CCRT for unresectable locally advanced ESCC. Therefore, this study aimed to evaluate the efficacy and safety of induction immunotherapy plus chemotherapy followed by definitive chemoradiotherapy in patients with unresectable locally advanced ESCC.MethodsThis study retrospectively collected clinical data of patients diagnosed with locally advanced ESCC who were treated with radical CCRT between 2017 and 2021 at our institution. The patients were divided into two groups: an induction immunotherapy plus chemotherapy group (induction IC group) or a CCRT group. To assess progression-free survival (PFS) and overall survival (OS), we employed the Kaplan–Meier method after conducting propensity score matching (PSM).ResultsA total of 132 patients with unresectable locally advanced ESCC were included in this study, with 61 (45.26%) patients in the induction IC group and 71 (54.74%) patients in the CCRT group. With a median follow-up of 37.0 months, median PFS and OS were 25.2 and 39.2 months, respectively. The patients in the induction IC group exhibited a significant improvement in PFS and OS in comparison with those in the CCRT group (median PFS: not reached [NR] versus 15.9 months, hazard ratio [HR] 0.526 [95%CI 0.325–0.851], P = 0.0077; median OS: NR versus 25.2 months, HR 0.412 [95%CI 0.236–0.719], P = 0.0012). After PSM (50 pairs), both PFS and OS remained superior in the induction IC group compared to the CCRT group (HR 0.490 [95%CI 0.280–0.858], P = 0.011; HR 0.454 [95%CI 0.246–0.837], P = 0.0093), with 2-year PFS rates of 67.6 and 42.0%, and the 2-year OS rates of 74.6 and 52.0%, respectively. Multivariate analysis revealed that lower tumor stage, concurrent chemotherapy using double agents, and induction immunotherapy plus chemotherapy before CCRT were associated with better prognosis.ConclusionsOur results showed for the first time that induction immunotherapy plus chemotherapy followed by CCRT for unresectable locally advanced ESCC provided a survival benefit with manageable safety profile. More prospective clinical studies should be warranted.

The Heterogeneous Impact of Prediagnostic Folate Intake for Fluorouracil-Containing Induction Chemotherapy for Head and Neck Cancer.

Fluorouracil (FU) exerts its antitumor activity by inhibiting folate-mediated one-carbon metabolism. Evidence that folate may play a role in the carcinogenic process via folate-mediated one-carbon metabolism has given rise to the hypothesis that pre-diagnostic folate intake may induce heterogeneous chemosensitivity to FU-containing induction chemotherapy (IC) in head and neck cancer. To assess this hypothesis, we conducted a cohort study to investigate whether the association between prediagnostic dietary folate intake and cancer survival differed between treatment regimens with and without FU-containing IC in 504 cases of locally advanced (stage III/IV) HNSCC, using an epidemiologic database combined with clinical data. In total, 240 patients were treated with FU-containing IC followed by definitive treatment, and 264 patients were treated with definitive treatment alone. Definitive treatment is defined as (1) the surgical excision of a tumor with clear margins, with or without neck lymph node dissection; or (2) radiotherapy with or without chemotherapy. In the overall cohort of the FU-containing IC group, a higher folate intake was significantly associated with better overall survival (adjusted hazard ratios (HRs) for the highest compared to the lowest folate tertiles (HRT3-T1) = 0.42, 95%CI, 0.25-0.76, Ptrend = 0.003). Conversely, no apparent association between prediagnostic folate intake and survival was observed with definitive treatment alone (HRT3-T1: 0.83, 95%CI, 0.49-1.42, Ptrend = 0.491)). A consideration of the cumulative dose of FU-containing IC showed that the survival impact of prediagnostic folate intake differed statistically significantly by treatment regimen (Pinteraction = 0.012). In conclusion, an association between prediagnostic folate intake and HNSCC survival significantly differed by FU-containing IC. This finding indicates that in the carcinogenic process, folate status causes HNSCC to be heterogenous in terms of one-carbon metabolism.

Prospective Efficacy of Two Cycles Toripalimab Plus Induction Chemotherapy in T4 or N3 Locoregionally Advanced Nasopharyngeal Carcinoma: A Retrospective and Mechanistic Study

Gemcitabine-cisplatin (GP) as the most commonly used induction chemotherapy is the standard first-line systemic treatment for advanced nasopharyngeal carcinoma. However, the toxicity of three cycles induction chemotherapy following on chemoradiotherapy remains a pertinent issue. Additional monoclonal antibody against human programmed death-1 (PD-1) has shown promising efficacy in recurrent or metastatic nasopharyngeal carcinoma. In this study, we compared three cycles of gemcitabine and cisplatin as classical induction chemotherapy with two cycles of induction chemotherapy plus toripalimab, and then both groups treated with the similar concurrent chemoradiotherapy. Patients with locoregionally advanced nasopharyngeal carcinoma staging T4 or N3 were randomly assigned in a 1:1 ratio to receive gemcitabine (at a dose of 1 g per square meter of body-surface area on days 1 and 8) plus cisplatin (80 mg per square meter on day 1-3), administered every 3 weeks for three cycles, or GP combined with toripalimab (at a dose of 240mg) for two cycles. The primary end point was recurrence-free survival (i.e., freedom from disease recurrence [distant metastasis or locoregional recurrence] or death from any cause) in the intention-to-treat population. Secondary end points included overall survival, treatment adherence, and safety. A total of 60 patients were included in the trial (30 patients in the toripalimab combined induction chemotherapy group and another 30 in the standard-therapy group). Among 60 patients evaluable for response assessment after induction therapy, all patients had overall response in combined group, including 10 patients (30%) with complete response (CR) in the primary tumor site. 21 patients (70%) were evaluated as partial response (PR) in the standard induction chemotherapy, and another 9 patients were assessed as SDa. At a median follow-up of 27.6 months, the 6-months, 1-, 2-year recurrence-free survival was 100% vs 86.7%, 100% vs 80%, 93% vs 70% in the toripalimab combined induction chemotherapy group and standard-therapy group (stratified hazard ratio for recurrence or death, 0.62; 95% confidence interval [CI], 0.38 to 0.87; P = 0.001). Overall survival at 2 years was 93.3% and 100%, respectively (stratified hazard ratio for death, 0.53; 95% CI, 0.29 to 0.79). The incidence of acute adverse events of grade 3 or 4 was 76.8% in the standard-induction chemotherapy group and 56% in the standard-therapy group, with a higher incidence of neutropenia, thrombocytopenia, anemia, nausea, and vomiting in the induction chemotherapy group. The incidence of grade 3 or 4 late toxic effects was 10.2% in the induction chemotherapy group and 10.4% in the combined-therapy group. Two cycles of toripalimab combined with induction chemotherapy of and CCRT shows excellent distant metastatic control with acceptable safety, which is a new promising and effective systemic therapy regimen for high-risk of metastatic NPC patients.

The Short-Term Efficacy and Safety of Induction Chemotherapy Combined with PD-1 Inhibitor or Anti-EGFR in Locoregionally Advanced Nasopharyngeal Carcinoma

This study aimed to investigate the short-term efficacy and safety of induction chemotherapy (IC) combined with PD-1 inhibitor or anti-EGFR in the treatment of locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We retrospectively reviewed the clinical data of 206 patients with LA-NPC, including IC combined with anti-PD1 (57 patients), IC combined with anti-EGFR (28 patients), and IC alone (121 patients). The short-term efficacy was assessed at the end of IC and one month after overall treatment. According to the RECIST v1.1, the short-term efficacy of cervical lymph nodes and primary nasopharynx foci was divided into complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD). The overall response (ORR) was defined as the sum of CR and PR. Acute toxicities were graded according to the CTCAE v5.0. One-way analysis of variance (ANOVA) was used to compare differences in the numerical variables among groups. Fisher Freeman-Halton test or Pearson Chi-square test was used to compare classified variables. The ORR rates of primary nasopharynx foci in IC, anti-EGFR, and anti-PD1 group were 68.60%, 67.9%, and 94.7%, respectively, and the corresponding rates of ORR in cervical lymph nodes were 78.5%, 71.4%, and 93.0%, respectively. There was a statistical difference in the ORR between the three groups. Further analysis showed that after IC or overall treatment, the CR rate of primary nasopharynx foci in the anti-PD1 group was significantly higher than the other two groups. The most common adverse effects were hematotoxicity, gastrointestinal toxicity, and transaminase elevation. However, there were no statistical differences in the frequency of any common adverse effects between the three groups. The addition of anti-PD1 based on IC significantly improved the short-term efficacy of LA-NPC and toxicities were tolerable.

Induction chemotherapy plus radiotherapy alone versus cisplatin-based concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: An open-label, non-inferiority, randomized phase 3 trial.

6001 Background: Cisplatin-based concurrent chemoradiotherapy (CCRT) has long been regarded as standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) due to its favorable local control. However, concurrent platinum is associated with intolerable toxicities and ineffective in preventing distant metastasis. Since IMRT enhances the local control and induction chemotherapy (IC) decreases the risk of distant failure, it is worth exploring whether IC plus IMRT alone regimen could replace CCRT for patients with LA-NPC. Methods: This open-label, phase 3, non-inferiority clinical trial was conducted from June 12, 2015 to April 30, 2019. Patients with stage T1-4N2-3 or T3-4N0-1 M0 NPC were randomly assigned (1:1) to receive gemcitabine (1000 mg/m²) and cisplatin (80 mg/m²) IC for 2 cycles followed by IMRT alone or IMRT plus concomitant weekly cisplatin (40 mg/m²) up to 7 cycles. 2-year failure-free survival was set as primary endpoint and non-inferiority margin of 10% was established. Efficacy analysis and safety analysis were dividedly performed in the intention-to-treat and safety population. Results: A total of 249 patients were enrolled, including 124 patients in IC group and 125 patients in CCRT group. Median follow-up time was 60 months (IQR, 48-71). 2-year failure-free survival was 90.2% in IC group versus 86.3% in CCRT group, with an HR of 0.818 (95% CI, 0.479-1.397) and absolute difference of 3.9% (1-sided 95%CI, -4.2 to 11.9). No significant differences were observed between groups in overall survival, locoregional relapse, or distant metastasis. Compared with CCRT group, fewer grade ≥3 AEs occurred in IC group (47.5% vs 61.5%, p = 0.015), including leucopenia, anemia, mucositis, nausea and dysphagia. The IC group had significantly better QoL during and short periods after IMRT, including domains of global health status, physical functioning, fatigue, nausea and vomiting, pain, and appetite loss. Conclusions: For LA-NPC, gemcitabine and cisplatin induction chemotherapy plus IMRT alone was not inferior in 2-year failure-free survival to concurrent chemoradiotherapy. Clinical trial information: NCT02460887 .

Responses in patients with AML and treated with entospletinib monotherapy.

e19010 Background: AML is a disease defined by the acquisition of genetic lesions in normal hematopoietic stem cells and progenitors resulting in poorly differentiated and highly proliferative leukemic blasts. Spleen tyrosine kinase (SYK) is a nonreceptor tyrosine kinase that maintains de-differentiation and leukemogenesis. MLL rearrangements (MLL-r) occur in up to 10% of adult AML and are associated with upregulated expression of the transcription factors HOXA9 and MEIS1 and worse clinical outcomes. Entospletinib (ENTO), an oral, selective inhibitor of SYK, has been studied in clinical trials for unselected AML patients as well as MLL-r patients. ENTO plus standard induction chemotherapy in front line had a 76% (13/17) composite complete response (CR) in AML patients with high HOXA9 and MEIS1. We have 3 patients that achieved CRs with ENTO monotherapy; one patient achieved CR to 14 days of ENTO monotherapy prior to initiation of chemotherapy; 2 patients with relapsed/refractory AML with MLL-r treated with ENTO monotherapy achieved CRs. Methods: This was part of an international multicenter phase Ib/II study (NCT02343939) which evaluated the efficacy, safety, and tolerability of ENTO in subjects with AML. During dose escalation, ENTO was administered in combination with induction chemotherapy (Group A) or with a hypomethylating agent (Group B). ENTO was administered as monotherapy for R/R AML in Group C. This report includes one patient from group A (newly diagnosed AML, MLL-r, 14-day monotherapy lead-in with ENTO) and two patients from group C monotherapy (relapsed/refractory AML, MLL-r). Results: Three patients receiving ENTO monotherapy had CRs. 18-year-old male from group A, that was MLL-r, NPM1-mutant (-). Patient treated at 400 mg PO, BID, achieved a cytogenetic CR with incomplete count recovery after cycle 0 (before chemotherapy); the patient continued study with induction chemotherapy and ultimately received ASCT in CR. Two additional patients in group C (with multiple therapies), both at 400 mg bid: (i) 37-year-old male, MLL-r, NPM1(-), was on study for 28 days, achieved CR; (ii) 28-year-old female, MLL-r, NPM1(-) on study for 60 days, achieved CR, both proceeded to SCT. Conclusions: Based on the results from these three patients, the clinical activity of SYK inhibition should be explored further in AML. We are testing Lanraplenib, a next-generation SYK inhibitor with enhanced selectivity, and more favorable pharmacologic properties in combination in genetically defined subsets of AML (NCT05028751). Clinical trial information: NCT02343939 .

Total Neoadjuvant Therapy in Rectal Cancer: Multi-center Comparison of Induction Chemotherapy and Long-Course Chemoradiation Versus Short-Course Radiation and Consolidative Chemotherapy

BackgroundTotal neoadjuvant therapy for locally advanced rectal cancer may include induction chemotherapy and chemoradiation or short-course radiotherapy and consolidative chemotherapy. MethodsPatients with clinical stage 2 or 3 rectal cancer who received induction chemotherapy followed by long-course chemoradiation at the University of Colorado (2016–2020) or short-course radiotherapy followed by consolidative chemotherapy at Washington University (2017–2020) were assessed. ResultsEighty-four patients received induction chemotherapy and chemoradiation and 83 received short-course radiotherapy and consolidative chemotherapy. Among patients with complete re-staging evaluation, clinical complete response rates were similar, 49% (18/37) and 53% (44/83), respectively (p = 0.659). In the induction chemotherapy and chemoradiation group, 80% (n = 67) underwent surgery and 28% (n = 19) achieved a pathologic complete response. In the short-course radiotherapy and consolidative chemotherapy group, 44 (53%) patients underwent surgery and 11% (n = 5) had a pathologic complete response. Overall, a complete response was observed in 43% (n = 36) of patients who received induction chemotherapy and chemoradiation compared to 53% (n = 44) who received short-course radiotherapy and consolidative chemotherapy (p = 0.189). Perioperative outcomes were similar in patients who received induction chemotherapy and chemoradiation compared to short-course radiotherapy and consolidative chemotherapy: intraoperative complications (2% vs 7%), complete mesorectal specimen (85% vs 84%), anastomotic leak (9% vs 7%), organ/space infection (9% vs 5%), readmission (19% vs 21%), and reoperation (8% vs 9%), respectively (all p > 0.05). ConclusionsIn patients with clinical stage 2 or 3 rectal cancer, total neoadjuvant therapy with either induction chemotherapy and chemoradiation or short-course radiotherapy followed by consolidative chemotherapy were associated with similar perioperative morbidity and complete response rates.

Preliminary Results of a Prospective Phase II Study of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer

<h3>Purpose/Objective(s)</h3> To analyze the safety and efficacy of total neoadjuvant therapy (TNT) followed by TME surgery for patients with locally advanced rectal cancer. <h3>Materials/Methods</h3> This study was designed as a prospective, multicenter, randomized phase II clinical study, which included patients aged 18-75 years with stage II / III rectal adenocarcinoma (including at least one of high-risk factors: mesorectal fascia involvement, T4, N2, positive lateral lymph node or extramural vessel invasion). According to the ratio of 1:1:1, eligible patients were randomly assigned into three groups: Chemoradiotherapy (CRT) → Surgery (S) → Adjuvant chemotherapy (Standard group), CRT → Neoadjuvant chemotherapy (NACT) → S (Consolidation chemotherapy group); or NACT → CRT → S (Induction chemotherapy group). CRT included pelvic radiotherapy with 50 Gy in 25 fractions and simultaneous oral capecitabine. NACT was adopted with XELOX scheme. The primary end point of this study was to explore the proportions of downstage, which included yp0-II or complete clinical response (cCR), for rectal cancer on two TNT strategies. <h3>Results</h3> From August 15, 2020 to February 15, 2022, a total of 224 patients were enrolled in this study (Standard group: Consolidation chemotherapy group: Induction chemotherapy group=69:78:75). Among them, 110 patients who completed preoperative treatment were included in safety analysis, and the median distance from the tumor to the anus was 5cm (range: 0-15cm), of which 81 cases (73.6%) and 29 (26.4%) were T3 and T4, 25 cases (22.7%) and 85 (77.3%) were N1 and N2, respectively; In addition, 83 patients (75.5%) were found to be mesorectal fascia involvement (MRF+). The probability of ≥ G3 acute toxicity in Standard group, Consolidation chemotherapy group and Induction chemotherapy group were 8.2% (5 / 61), 13.3% (4 / 30) and 31.6% (6 / 19), respectively, with myelosuppression being of most common. There was no toxicity-related death in all patients. In terms of tolerance, the completion rates of neoadjuvant therapy (Including treatment delay and dose reduction) in Standard group, Consolidation chemotherapy group and Induction chemotherapy group were 100% (61 / 61), 90% (27/ 30) and 100% (19 / 19), with the full dose completion rates of 100% (61/61), 73.3% (22/30) and 63.2% (12/19), respectively. 68 patients who completed the surgery or chose Wait / Watch strategy were included in efficacy analysis. The proportion of patients in the Standard group, Consolidation chemotherapy group and Induction chemotherapy group who reached stage 0-II after neoadjuvant treatment were 77.1% (27 / 35), 84.2% (16 / 19) and 57.1% (8 / 14), respectively, with CR rates (pCR + sustained cCR) of 22.9% (8 / 35), 42.1% (8 / 19) and 28.6% (4 / 14), respectively. <h3>Conclusion</h3> The acute toxicities of two TNT groups were acceptable and well tolerated. And the tumor downstage rate of Consolidation chemotherapy group was encouraging. <i>ClinicalTrials.gov</i> No.: NCT04543695

Interim Results of a Prospective, Randomized, Multicenter, Phase 3 Study of the Efficacy of Increasing the Cycles of Induction Chemotherapy in Locally Advanced Nasopharyngeal Carcinoma

<h3>Purpose/Objective(s)</h3> To assess whether increasing the cycles of induction chemotherapy (IC) improve the survival in locally advanced nasopharyngeal carcinoma (NPC). <h3>Materials/Methods</h3> Patients with previously untreated, histopathologically confirmed, stage II-IVA NPC, aged 18-70 years without severe comorbidities who achieved PR (partial response) or CR (complete response) after two cycles of IC were recruited into this prospective clinical trial. Eligible patients were randomly assigned (1:1) to group A (concurrent chemoradiotherapy) or group B (two additional cycles of IC followed by concurrent chemoradiotherapy). Induction chemotherapy consisted of intravenous docetaxel (60 mg/m² on day 1), intravenous cisplatin (60 mg/m²on day 1), and fluorouracil (600 mg/m² per day continuous infusion on day 1 to day 5) every 3 weeks (TPF). In this trial, intensity-modulated radiotherapy was mandatory for both groups. And cisplatin 40 mg/m² given intravenously weekly or 100 mg/m² every 3 weeks during concurrent chemoradiotherapy. The primary endpoint was overall survival calculated from randomization to death from any cause. This study was registered in the China Clinical Trial Center (ChiCTR-TRC-1800017109). <h3>Results</h3> From July 16, 2018, to September 6, 2021, 437 patients were screened. After the exclusion of 66 patients for ineligibility, 371 patients (median age, 46 years [IQR, 23-69 years]) were randomly assigned to the group A (n=186) or group B (n=185). At the last follow-up on January 21, 2022, the median follow-up time was 25.3 (IQR 3.5-41.3) months. All enrolled patients were included in the interim analysis. The demographic and clinical characteristics of the two groups at baseline were well balanced (p£¾.05). All patients finished scheduled treatment. The 2-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 98.4% vs 97.8%, 94.1 % vs 95.1%,98.4% vs97.8%, 95.7% vs 97.3%, respectively(p£¾.05). All patients received four cycles IC (group B) had higher incidences of leukopenia (P = .029), vomiting (P = .004), weigh loss(P=0.062) and thrombocytopenia (P = .043) than those treated with two cycles (group A). However, there was no difference in the incidence of late radiation toxicities between two groups. For advanced N (N3 and N2 who underwent lymph node biopsy) stage patients, we conducted a stratified analysis. The 2-year OS, DMFS of these patients in group A and group B were 96.6% and 98.7% (p=.687),94.4% and 97.3% (p=.275), group B has a trend of better survival. <h3>Conclusion</h3> In conclusion, the interim results demonstrate that increasing the cycles of IC with TPF to a mainstay of chemoradiotherapy with cisplatin did not improve the OS for locally advanced nasopharyngeal carcinoma, but it has the potential to reduce distant metastases for advanced N stage patients. These findings warrant validation with continuation of this trial and longer follow-up periods.

Timing of additional neoadjuvant chemotherapy in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy and total mesorectal excision

BackgroundIn locally advanced rectal cancer (LARC), the optimal sequence of neoadjuvant chemotherapy in relation to neoadjuvant chemoradiotherapy and before total mesorectal excision is unknown.MethodsA total of 426 LARC patients, treated with neoadjuvant chemoradiotherapy followed by total mesorectal excision, between January 2010 and December 2018, were studied retrospectively. Patients were divided into induction and consolidation chemotherapy groups. Overall, disease-free, locoregional relapse-free, and distant metastasis-free survival rates for the 2 groups were compared. Multivariate analysis hazard ratios (HR) with 95% confidence intervals (CI) to identify survival predictors.ResultsMedian follow-up was 37 (range, 7–162) months. The 3-year overall, disease-free, locoregional relapse-free, and distant metastasis-free survival rates were 93.8%, 71.6%, 93.5%, and 74.4%, respectively. For those receiving either induction or consolidation chemotherapy, 3-year disease-free survival rates were 82.5% and 67.7%, respectively (P = 0.021), distant metastasis-free rates were 85.4% and 70.8%, respectively (P = 0.024), and both overall and locoregional relapse-free survival rates did not differ significantly. Absence of neural invasion was an independent predictor of disease-free (HR = 0.49, 95% CI 0.25–0.97, P = 0.04) and distant metastasis-free (HR = 0.49, 95% CI 0.25–0.98, P = 0.04) survival. Both ypTN stage III (vs.0-II) and consolidation (vs. induction) chemotherapy were independent predictors of disease relapse (HR = 1.95, 95% CI 1.47–2.58, P < 0.001; HR = 1.68, 95% CI 1.01–2.79, P = 0.046; respectively) and distant metastasis (HR = 2.04, 95% CI 1.51–2.76, P < 0.001; HR = 1.75, 95% CI 1.03–2.99, P = 0.04; respectively).ConclusionsLARC patients receiving neoadjuvant chemoradiotherapy and total mesorectal excision had better disease-free and distant metastasis-free survival, with induction rather than consolidation neoadjuvant chemotherapy.

A Meta-analysis of Total Neoadjuvant Therapies Combining Chemoradiotherapy with Induction or Consolidated Chemotherapy for Locally Advanced Rectal Cancer.

Total neoadjuvant therapy (TNT) combining chemoradiotherapy (CRT) with chemotherapy (CT) was a novel pre-surgical approach to cancer treatment. This meta-analysis aimed to compare the clinical outcomes between neoadjuvant CRT (nCRT) with induction CT and nCRT with consolidated CT in locally advanced rectal cancer (LARC) patients. In July 2022, a literature search was conducted using the following public databases: PubMed, MEDLINE, Embase, the Cochrane Library, and Web of Science, retrieved all relevant articles comparing nCRT-combining induction CT with nCRT-combining-consolidated CT treatments for LARC patients. Four eligible studies were identified, including a total of 995 LARC patients: 473 in the nCRT with consolidated CT group and 522 in the nCRT with induction CT group. The organ preservation (OP) rate of the nCRT with consolidated CT group was higher than that of the nCRT with induction CT group (RR [relative risk]: 1.53; 95% CI (confidence interval): 1.09-2.14). The pathological complete response (PCR, RR: 1.22; 95% CI 0.37-2.17), the 3-year disease-free survival (DFS, RR 1.02; 95% CI 0.71-1.46), the local recurrence (LR, RR 0.98; 95% CI 0.52-1.85), rates of R0 resection (RR 0.74; 95% CI 0.55-1.10), compliance (RR 0.52; 95% CI 0.12-2.26), and grade 3--4 toxicities (RR 0.78; 95% CI 0.57-1.06) were all similar between the two groups. In this meta-analysis of TNT regimens for rectal cancer, consolidative CT following nCRT was associated with similar PCR, 3-year DFS, LR, R0 resection, compliance, and grade 3-4 toxicities compared to induction CT prior to nCRT but a higher rate of organ preservation.

A Study of Peripheral Blood Parameters to Predict Response to Induction Chemotherapy and Overall Survival in Advanced Laryngeal Squamous Cell Carcinoma.

Purpose: the purpose of this study was to screen peripheral blood parameters and construct models predicting the prognosis and induction chemotherapy (IC) response in locally advanced laryngeal squamous cell carcinoma (LSCC) patients. Methods: A total of 128 stage III/IVa LSCC patients (who required a total laryngectomy) were enrolled in a retrospective study from January 2013 to September 2020 at Beijing Tongren Hospital of Capital Medical University. Among them, 62 patients received IC (IC group), and 66 patients immediately underwent a total laryngectomy (TL) after diagnosis (surgery group). Demographic information and peripheral blood parameters were collected for further analysis. The overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS) were compared between the two groups. The prognosis and survival were also compared between patients with laryngeal function preservation (LFP) and those with TL. Results: The Receiver Operating Characteristic (ROC) curve for IC response in the IC group showed that the AUC of the blood model based on the four peripheral blood parameters of fibrinogen (FIB), platelet (PLT), high-density lipoprotein cholesterol (HDL), and albumin (ALB) was significantly higher than the TNM stage model’s AUC (0.7932 vs. 0.6568). We constructed a nomogram blood model to predict IC response (C-Index = 0.793). Regarding the OS of all patients, an ROC analysis for overall survival, the Kaplan–Meier (K-M) method with a log-rank test, and multivariate analysis indicated age, clinical stage, FIB, and hemoglobin (HGB) were independent prognostic factors for the OS of LSCC patients. The blood–clinical logistic model (AUC = 0.7979) was constructed based on the four prognosis factors, which were superior to the blood (AUC = 0.6867) or clinical models (AUC = 0.7145) alone to predict OS. We constructed a nomogram model based on age, clinical stage, FIB, and HGB to predict OS for LSCC patients (C-Index = 0.792). Besides this, there were no significant differences in OS, PFS, and DSS between IC and surgery groups or LFP and TL groups. Conclusion: Peripheral blood parameters help predict IC response and overall survival. Furthermore, induction chemotherapy significantly improves laryngeal function preservation without lowering the survival prognosis.

Induction chemotherapy regimen of docetaxel plus cisplatin versus docetaxel, cisplatin plus fluorouracil followed by concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: Preliminary results of an open-label, noninferiority, multicentre, randomised, controlled phase 3 trial.

SummaryBackgroundInduction chemotherapy regimens of docetaxel and cisplatin plus fluorouracil (TPF) are currently clinically used for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) but have well-known side effects, such as myelosuppression and diarrhea. A docetaxel plus cisplatin (TP) regimen was developed to decrease the toxic effects induced by fluorouracil. In this trial, we assessed whether the TP induction chemotherapy regimen was noninferior to the TPF regimen.MethodsWe performed an open-label, noninferiority, phase 3, multicentre, randomised, controlled trial at six centres in China. Eligible patients with NPC (stage III-IVA (excluding T3-4N0), Karnofsky's Performance Scoring ≥70) were randomly assigned (1:1) to receive either TP (docetaxel (75 mg per square meter, d1, intravenous infusion) and cisplatin (75 mg per square meter of body-surface area, d1, intravenous infusion)) or TPF (docetaxel (60 mg per square meter, d1, intravenous infusion) plus cisplatin (60 mg per square meter, d1, intravenous infusion) and 5-fluorouracil (600 mg per square meter, d1-d5, intravenous 120-hour infusion)) administered every 3 weeks for 3 cycles followed by concurrent chemoradiotherapy. The primary endpoint was failure-free survival at 2 years. Secondary endpoints included overall survival, safety, and treatment compliance. The trial was stopped early because of strong evidence for noninferiority (margin was -10%) of TP in failure-free survival. Efficacy analyses were performed in both the intention-to-treat and per-protocol trial populations and we included the patients who started treatment in each group for the safety analysis. The study was registered with chictr.org.cn, ChiCTR1800016337.FindingsBetween June 1, 2018 and October 31, 2021, we randomly assigned 361 patients to the TP (n = 181) or TPF (n = 180) induction chemotherapy group. The 2-year failure-free survival was 91·3% (95% CI 86·2-96·4) in the TP group and 82·4% (84·8-88·9) in the TPF group (P = 0·029). Patients in the TPF group had a higher frequency of grade 1 or 2 neutropenia (53 (30·0%) vs. 28 (15·7%); P = 0·0010), grade 1 or 2 diarrhea (20 (11·3%) vs. 9 (5·1%); P = 0·032), and grade 3 or 4 neutropenia (43 (24·3%) vs. 25 (14·0%); P = 0·014) in the induction chemotherapy period. There was no treatment-related death.InterpretationThe preliminary results revealed that TP induction chemotherapy regimen was found to be clearly non-inferior compared to the TPF regimen in failure-free survival, with a lower frequency of neutropenia, anaemia and diarrhoea. The more convenient and beneficial survival regimen of the TP regimen should be recommended in patients with LA-NPC.FundingThis study was supported by grants from the Natural Science Foundation of Guangdong Province, China [grant number 2021A1515011182], Natural Science Foundation of Guangdong Province, China [grant number 2022A1515012272], National Natural Science Foundation of China [grant number 82072029] and National Natural Science Foundation of China [grant number 81903037].

Induction chemotherapy of modified docetaxel, cisplatin, 5-fluorouracil for laryngeal preservation in locally advanced hypopharyngeal squamous cell carcinoma.

Previous studies have investigated the value of induction chemotherapy (IC) in organ preservation strategies for head and neck cancers. This study evaluated the effectiveness of sequential IC with radiotherapy as a laryngeal preservation strategy for locally advanced hypopharyngeal carcinoma (LAHSCC). One hundred and forty-two consecutive patients with LAHSCC were retrospectively analyzed who received three IC regimens from 2015 to 2019. In the TP (docetaxel plus cisplatin), TPF (TP plus 5-fluorouracil), and TPX (TP plus capecitabine) IC groups, there were 51, 29, and 62 patients, respectively. The primary tumor objective response rates were 51%, 55.2%, and 71%, and the 3-year survival rates with preserved larynx were 36.6%, 31.8%, and 51.2%, respectively (p= 0.03). There was no difference in overall survival and the adverse events were tolerable. The TPX regimen displayed good efficacy and safety, indicating its potential as a therapeutic IC regimen for LAHSCC.

Long-term clinical outcomes and prognostic factors of upfront surgery as a first-line therapy in biopsy-proven clinical N2 non-small cell lung cancer.

BackgroundMultimodality therapy offers the best opportunity to improve pathological N2 non-small cell lung cancer (NSCLC) prognosis. This paper aimed to evaluate the long-term clinical outcomes and the prognostic factors of upfront surgery as first-line therapy in biopsy-proven clinical N2.MethodsRetrospective review of biopsy-proven cN2 NSCLC patients operated between 2007 and 2017. Upfront surgery was considered if the primary tumour was deemed completely resectable, with mediastinal nodal involvement confined to a single station and no preoperative evidence of extranodal tumour invasion.ResultsTwo hundred eighty-five patients who underwent radical resections were included. One hundred fifty-nine patients (55.8%) received induction chemotherapy. At follow-up completion, 127 (44.6%) patients had died. For the induction chemotherapy group, the median overall survival (OS) was 49 months [95% confidence interval (CI): 38–70 months], and the 5-year OS was 44.4%. The median and 5-year OS for the up front surgery group was 66 months (95% CI: 40–119 months) and 66.3%, respectively. There were no statistically significant differences between treatment approaches (p = 0.48). One hundred thirty-four patients (47.0%) developed recurrence. The recurrence-free survival (RFS) at 5 years was 17% (95% CI: 11–25%) for induction chemotherapy and 22% (95% CI: 9–32%) for upfront surgery; there were no statistically significant differences between groups (p = 0.93). No significant differences were observed based on the clinical N status (OS, p = 0.36; RFS, p = 0.65).ConclusionsUpfront surgery as first-line therapy for biopsy-proven cN2 NSCLC showed favourable clinical outcomes, similar to those obtained after induction chemotherapy followed by surgery. Therefore, it should be considered one of the multimodality treatment options in resectable N2 NSCLC.