Induction and maintenance of sequential intravesical gemcitabine/docetaxel for intermediate and high-risk non-muscle invasive bladder cancer with different dosage protocols.

INTRODUCTION: The combination of sequential intravesical gemcitabine and docetaxel (Gem/Doce) chemotherapy has been considered a feasible option for BCG (Bacillus Calmette-Guérin) treatment in non-muscle invasive bladder cancer (NMIBC), gaining popularity during BCG shortage period. We seek to determine the efficacy of the treatment by comparing Gem/Doce induction alone vs induction with maintenance, and to evaluate the treatment outcomes of two different dosage protocols. METHODS: A bi-center retrospective analysis of consecutive patients treated with Gem/Doce for NMIBC between 2018 and 2023 was performed. Baseline characteristics, risk group stratification (AUA 2020 guidelines), pathological, and surveillance reports were collected. Kaplan-Meier survival analysis was performed to detect Recurrence-free survival (RFS). RESULTS: Overall, 83 patients (68 males, 15 females) with a median age of 73 (IQR 66-79), and a median follow-up time of 18 months (IQR 9-25), were included. Forty-one had an intermediate-risk disease (49%) and 42 had a high-risk disease (51%). Thirty-seven patients (45%) had a recurrence; 19 (23%) had a high-grade recurrence. RFS of Gem/Doce induction-only vs induction + maintenance was at 6 months 88% vs 100%, at 12 months 71% vs 97%, at 18 months 57% vs 91%, and at 24 months 31% vs 87%, respectively (log-rank, p < 0.0001). Patients who received 2 g Gemcitabine with Docetaxel had better RFS for all-grade recurrences (log-rank, p = 0.017). However, no difference was found for high-grade recurrences. CONCLUSION: Gem/Doce induction with maintenance resulted in significantly better RFS than induction-only. Combining 2 g gemcitabine with docetaxel resulted in better RFS for all-grade but not for high-grade recurrences. Further prospective trials are necessary to validate our results.

The efficacy and safety of adding PD-1 blockade to induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) for locoregionally advanced nasopharyngeal carcinoma: an observational, propensity score-matched analysis.

BACKGROUND: Despite the success of PD-1 blockade in recurrent/metastatic nasopharyngeal carcinoma (NPC), its effect for locoregionally advanced NPC (LANPC) remains unclear. This study aimed to evaluate the benefit of adding PD-1 blockade to the current standard treatment (gemcitabine and cisplatin IC  plus cisplatin CCRT ) for LANPC patients. METHODS: From January 2020 to November 2022, 347 patients with non-metastatic high-risk LANPC (stage III-IVA, excluding T3-4N0) were included. Of the 347 patients, 268 patients were treated with standard treatment (IC-CCRT), and 79 received PD-1 blockade plus IC-CCRT (PD-1 group). For the PD-1 group, PD-1 blockade was given intravenously once every 3 weeks for up to 9 cycles (3 induction and 6 adjuvant). The primary endpoint was disease-free survival (DFS) (i.e. freedom from local/regional/distant failure or death). The propensity score matching (PSM) with the ratio of 1:2 was performed to control confounding factors. RESULTS: After PSM analysis, 150 patients receiving standard treatment and 75 patients receiving additional PD-1 blockade remained in the current analysis. After three cycles of IC, the PD-1 group had significantly higher rates of complete response (defined as disappearance of all target lesions; 24% vs. 9%; P = 0.006) and complete biological response (defined as undetectable cell-free Epstein-Barr virus DNA, cfEBV DNA; 79% vs. 65%; P = 0.046) than that in the standard group. And the incidence of grade 3-4 toxicity during IC was 47% in the PD-1 group and 41% in the standard group, with no significant difference (P = 0.396). During follow-up period, additional PD-1 blockade to standard treatment improved 3-year DFS from 84 to 95%, with marginal statistical significance (HR, 0.28; 95%CI, 0.06-1.19; P = 0.064). CONCLUSION: Additiaonl PD-1 blockade to gemcitabine and cisplatin IC and adjuvant treatment results in significant improvement in tumor regression, cfEBV DNA clearance, superior DFS, and comparable toxicity profiles in high-risk LANPC patients.

Induction Chemotherapy Followed by Radiotherapy vs Chemoradiotherapy in Nasopharyngeal Carcinoma: A Randomized Clinical Trial.

Importance: Induction chemotherapy plus concurrent chemoradiotherapy is recommended for locoregionally advanced nasopharyngeal carcinoma but is associated with higher rates of acute toxic effects and low compliance. Evidence on de-escalating treatment intensity after induction chemotherapy is limited. Objective: To assess if radiotherapy was noninferior to chemoradiotherapy after induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma. Design, Setting, and Participants: From April 2015 to March 2018, a multicenter, open-label, randomized, noninferiority, phase 3 trial was conducted at 5 Chinese hospitals. A total of 383 patients aged 18 to 70 years with an untreated histologically confirmed nonkeratinizing tumor, Karnofsky performance status score not worse than 70, proper organ function, and stage III to IVB nasopharyngeal cancer were enrolled. Data were analyzed from April 2023 to June 2023. Interventions: Patients were assigned randomly. Both groups received 3 cycles of induction chemotherapy consisting of intravenous administration (on day 1) of cisplatin at 60 mg/m2 and docetaxel at 60 mg/m2 and continuous intravenous infusion (from day 1 to day 5) of daily fluorouracil (600 mg/m2), repeated every 21 days. Subsequently, the patients received radiotherapy alone (induction chemotherapy in combination with radiotherapy [IC-RT] group) or concomitant cisplatin (30 mg/m2/week) with radiotherapy for 6 to 7 weeks (induction chemotherapy combined with chemoradiotherapy [IC-CCRT] group). Main Outcomes and Measures: The primary end point was 3-year progression-free survival (time from the initiation of therapy until the first indication of disease progression or death), with a noninferiority margin of 10%. The secondary end points included overall survival, locoregional failure-free survival, distant metastasis-free survival, response rate, and toxic effects. Results: A total of 383 patients (median [range] age, 48 [19-70] years; 100 women [26%]). Median follow-up time was 76 months (IQR, 70-89 months). The 3-year progression-free survival was 76.2% and 76.8% in the IC-RT (n = 193) and IC-CCRT groups (n = 190), respectively, in the intention-to-treat population, showing a difference of 0.6% (95% CI, -7.9% to 9.1%; P = .01 for noninferiority). Identical outcomes were reported in the per-protocol population. The incidence of grade 3 to 4 short-term toxic effects in the IC-RT group was less than the IC-CCRT group. No differences were observed in late toxic effects. Conclusions and Relevance: The results of this randomized clinical trial suggest that after induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma, radiotherapy alone was noninferior to chemoradiotherapy in terms of 3-year progression-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT02434614.

Phase 3 RCT comparing docetaxel-platinum with docetaxel-platinum-5FU as neoadjuvant chemotherapy in borderline resectable oral cancer.

BACKGROUND: Neoadjuvant chemotherapy (NACT) with TPF (docetaxel, cisplatin, and 5FU) is one of the treatment options in very locally advanced oral cancer with a survival advantage over PF (cisplatin and 5FU). TP (docetaxel and cisplatin) has shown promising results with a lower rate of adverse events but has never been compared to TPF. METHODS: In this phase 3 randomized superiority study, adult patients with borderline resectable locally advanced oral cancers were randomized in a 1:1 fashion to either TP or TPF. After the administration of 2 cycles, patients were evaluated in a multidisciplinary clinic and further treatment was planned. The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS) and adverse events. RESULTS: 495 patients were randomized in this study, 248 patients in TP arm and 247 in TPF arm. The 5-year OS was 18.5% (95% CI 13.8-23.7) and 23.9% (95% CI 18.1-30.1) in TP and TPF arms, respectively (Hazard ratio 0.778; 95% CI 0.637-0.952; P = 0.015). Following NACT, 43.8% were deemed resectable, but 34.5% underwent surgery. The 5-year OS was 50.7% (95% CI 41.5-59.1) and 5% (95%CI 2.9-8.1), respectively, in the surgically resected versus unresected cohort post NACT (P < 0.0001). Grade 3 or above adverse events were seen in 97 (39.1%) and 179 (72.5%) patients in the TP and TPF arms, respectively (P < 0.0001). CONCLUSION: NACT with TPF has a survival benefit over TP in borderline resectable oral cancers, with an increase in toxicity which is manageable. Patients who undergo surgery achieve a relatively good, sustained survival.

Safety and Pharmacokinetics of Quizartinib Combination Therapy With Standard Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia: Results from Two Phase 1 Trials in Japan and China.

Quizartinib is a potent, oral, second-generation, selective type II FMS-like receptor tyrosine kinase 3 (FLT3) inhibitor. It has shown improved overall survival in a randomized, multinational, Phase 3 (QuANTUM-First) study in patients with FLT3-internal tandem duplication (ITD)-positive newly diagnosed acute myeloid leukemia. We conducted 2 Phase 1b studies in Japan and China to evaluate the safety, pharmacokinetics, and efficacy of quizartinib in combination with standard induction and consolidation chemotherapy in patients with newly diagnosed acute myeloid leukemia. Quizartinib was started at a dose level of 20 mg/day and then escalated to 40 mg/day, the dose used in the Phase 3 study. Seven patients were enrolled according to the 3 + 3 dose-escalation method in each study, including 3 patients who were FLT3-ITD positive. No dose-limiting toxicities were observed at dose levels up to 40 mg/day in both studies. Grade 3 or higher, quizartinib-related, treatment-emergent adverse events included febrile neutropenia, hematologic toxicities, and infections. QT prolongation on electrocardiogram was observed in 5 patients. The pharmacokinetics of quizartinib and its metabolite AC886 were similar between the studies and consistent with previous findings in the United States. We confirmed the tolerability of Japanese and Chinese patients to the dose of quizartinib and chemotherapy regimens used in the QuANTUM-First study.

Induction chemotherapy followed by response evaluation and esophagectomy for advanced esophageal cancer.

INTRODUCTION: Patients with limited metastatic/advanced esophageal cancer not amenable for neoadjuvant therapy plus surgery have a poor prognosis and often receive palliative care. Alternatively, induction chemotherapy with response evaluation can be considered and in some patients surgery with curative intent may become feasible. The aim of this study was to evaluate the outcomes of patients treated with induction chemotherapy and to identify patient and/or tumor characteristics associated with survival. MATERIAL AND METHODS: Patients with esophageal or junctional cancer who underwent induction chemotherapy between 2005 and 2021 were identified from an institutional database of a tertiary referral center. Response to therapy was assessed by (18F-FDG PET)/CT. Response to therapy and treatment options, including surgery or palliation, were discussed in the multidisciplinary tumor board. Overall survival (OS) was calculated using the Kaplan Meier method. Uni- and multivariable analyses were performed to identify prognostic factors for survival. RESULTS: 238 patients were identified. The majority had esophageal adenocarcinoma (68.9 %) and were treated with a taxane/platinum-based chemotherapy (79.4 %). Response evaluation was performed in 233 patients and 154 of 238 patients (64.7 %) underwent surgical exploration. Resection was performed in 127 patients (53.4 %) resulting in a median and 5-year OS of 26.3 months (95 % CI 18.8-33.8) and 29.6 %, respectively. Presence of T4b (HR = 2.01, 95 % CI 1.02-3.92) and poorly differentiated tumor (HR = 1.45, 95 % CI 1.02-2.10) was associated with worse survival (p = 0.04). CONCLUSION: In carefully selected patients with advanced disease not amenable for standard curative treatment, induction chemotherapy followed by esophagectomy may result in a 5-year overall survival of approximately 30 %.

Machine Learning-assisted immunophenotyping of peripheral blood identifies innate immune cells as best predictor of response to induction chemo-immunotherapy in head and neck squamous cell carcinoma - knowledge obtained from the CheckRad-CD8 trial.

PURPOSE: Individual prediction of treatment response is crucial for personalized treatment in multimodal approaches against head-and-neck squamous cell carcinoma (HNSCC). So far, no reliable predictive parameters for treatment schemes containing immunotherapy have been identified. This study aims to predict treatment response to induction chemo-immunotherapy based on the peripheral blood immune status in patients with locally advanced HNSCC. METHODS: The peripheral blood immune phenotype was assessed in whole blood samples in patients treated in the phase II CheckRad-CD8 trial as part of the pre-planned translational research program. Blood samples were analyzed by multicolor flow cytometry before (T1) and after (T2) induction chemo-immunotherapy with cisplatin/docetaxel/durvalumab/tremelimumab. Machine Learning techniques were used to predict pathological complete response (pCR) after induction therapy. RESULTS: The tested classifier methods (LDA, SVM, LR, RF, DT, and XGBoost) allowed a distinct prediction of pCR. Highest accuracy was achieved with a low number of features represented as principal components. Immune parameters obtained from the absolute difference (lT2-T1l) allowed the best prediction of pCR. In general, less than 30 parameters and at most 10 principal components were needed for highly accurate predictions. Across several datasets, cells of the innate immune system such as polymorphonuclear cells, monocytes, and plasmacytoid dendritic cells are most prominent. CONCLUSIONS: Our analyses imply that alterations of the innate immune cell distribution in the peripheral blood following induction chemo-immuno-therapy is highly predictive for pCR in HNSCC.

Risk factors and clinical impact of thrombosis during induction chemotherapy for pediatric acute lymphoblastic leukemia: A report from CYP-C.

Thromboembolism (TE) is associated with reduced survival in pediatric acute lymphoblastic leukemia (ALL). It has been hypothesized that TE might signal leukemic aggressiveness. The objective was to determine risk factors for TE during ALL induction (TEind ) therapy and whether TEind is associated with treatment refractoriness. This retrospective cohort study using the population-based Cancer in Young People Canada (CYP-C) registry included children <15 years of age diagnosed with ALL (2000-2019) and treated at one of 12 Canadian pediatric centers outside of Ontario. Univariate and multivariable logistic regression models were used to determine risk factors for TEind and whether TEind predicted induction failure and ALL treatment intensification. The impact of TEind on overall and event-free survival was estimated using Cox proportional hazard regression models. The study included 2589 children, of which 45 (1.7%) developed a TEind . Age (<1 year and ≥10 years vs. 1-<10 years), T-cell phenotype, high-risk ALL, and central nervous system involvement were all associated with TEind in univariate analysis. Age and T-cell phenotype remained independent predictors of TEind in multivariable analysis. Induction failure occurred in 53 patients (2.1%). TEind was not associated with induction failure (OR: not estimable) or treatment intensification (adjusted OR [95% CI]: 0.66 [0.26-1.69]). TEind was independently associated with overall survival (adjusted HR [95% CI]: 2.54 [1.20-5.03]) but not event-free survival (adjusted HR [95% CI] 1.86 [0.98-3.51]). In this population-based study of children treated with contemporary chemotherapy protocols, TEind was associated with age and T-cell phenotype and mortality but did not predict induction failure.

Maintenance of clinical remission with biologics and small molecules in inflammatory bowel disease according to trial design: Meta-analysis.

BACKGROUND AND AIMS: Design of randomised controlled trials (RCTs) examining maintenance of clinical remission in inflammatory bowel disease (IBD) varies, with some trials re-randomising patients who have responded to active drug during induction to either active drug or placebo and others treating patients through with active drug or placebo from baseline. Whether this influences therapeutic gain of drug over placebo is unknown. METHODS: We searched the literature to January 2023 for maintenance of remission trials of biologics or small molecules versus placebo in IBD. We extracted maintenance of remission rates according to trial design; either trials re-randomising patients or trials treating patients through. We pooled data in a meta-analysis for all patients, and according to type of IBD. We calculated the number needed to treat (NNT), with a 95% confidence interval (CI), to assess therapeutic gain of active drug over placebo according to trial design. RESULTS: We identified 37 maintenance of remission trials (12,075 patients). Rates of maintenance of clinical remission were higher (41.9% with active drug, versus 20.3% with placebo), and NNT lowest (5; 95% CI 4-6), in trials re-randomising patients compared with those treating through (maintenance of remission rate 30.9% with active drug versus 14.6% with placebo, NNT = 7; 95% CI 5-9). Results were similar when trials were analysed according to IBD type but were more marked in ulcerative colitis RCTs (maintenance of remission rates in re-randomised trials 39.4% with active drug versus 17.8% with placebo, NNT = 5; 95% CI 3-7; treat-through trials 27.3% with active drug versus 11.9% with placebo, NNT = 7; 95% CI 5-11.5). CONCLUSION: Trials re-randomising patients had generally higher maintenance of remission rates, lower NNTs, and greater therapeutic gains over placebo.

Neoadjuvant chemotherapy for organ preservation in sinonasal squamous cell carcinoma.

PURPOSE: In this study, we aimed to evaluate the role of induction chemotherapy (IC) in the treatment of locoregionally advanced sinonasal squamous cell carcinoma (SNSCC). METHODS: 130 patients who accepted IC between 2010 and 2022 were retrospectively reviewed. After IC, all the patients underwent chemoradiotherapy (CRT)/ radiotherapy (RT) or CRT/RT followed by surgery. We investigated the objective response to IC, the optimal treatment strategy, organ preservation, and long-term survival. RESULTS:  Eighty-seven patients (66.9%) achieved a partial response after IC. 86% (27/43) of the patients who did not respond to the IC still presented a sensitive response to radiotherapy (χ2 = 9.26, p = 0.005). Patients who respond to IC could benefit from CRT/RT followed by surgery over other treatment modalities. The 3-year overall survival (OS), progression-free survival (PFS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) rates of 61.2%, 51.3%, 52.1%, 58.1% for the IC response group were significantly superior to those of 37.3% (HR = 0.58, 95% CI 0.34-1.01, p = 0.030), 33.5% (HR = 0.49, 95% CI 0.30-0.82, p = 0.002), 35.9% (HR = 0.54, 95% CI 0.32-0.91, p = 0.009), 36.1% (HR = 0.60, 95% CI 0.35-1.03, p = 0.040) for the IC non-response group. Patients who responded to IC had a high rate of organ preservation compared with patients who did not respond to IC (90.8% vs. 74.4%, χ2 = 6.19, p = 0.013). CONCLUSIONS: The results demonstrated a response rate to IC in patients with advanced SNSCC; furthermore, the response to IC indicated better survival. Patients who responded to IC had a high rate of organ preservation.

Efficacy and safety of upadacitinib for 16-week extended induction and 52-week maintenance therapy in patients with moderately to severely active ulcerative colitis.

BACKGROUND: Upadacitinib is an oral, selective Janus kinase inhibitor. AIM: To assess the efficacy and safety of upadacitinib in patients with moderate-to-severe ulcerative colitis following 16-week extended induction therapy, and 52-week maintenance therapy in patients achieving clinical response after 16-week extended induction therapy METHODS: Patients without clinical response to 8 weeks' upadacitinib 45 mg once daily induction therapy in two induction trials were eligible for an additional 8 weeks of therapy. Patients achieving clinical response at Week 16 were subsequently re-randomised (1:1) to upadacitinib 15 or 30 mg once daily for 52-week maintenance therapy. Efficacy was assessed at induction Week 16 (integrated) and maintenance Week 52; safety was assessed throughout. RESULTS: Overall, 127/663 (19.2%) patients did not achieve clinical response to upadacitinib 45 mg at Week 8 and received an additional 8 weeks of therapy; 75/127 (59.1%) subsequently achieved clinical response at Week 16 and entered the maintenance trial. At Week 52, 26.5% of patients receiving upadacitinib 15 mg, and 43.6% receiving 30 mg, achieved clinical remission; efficacy was observed across all other endpoints with both doses. Herpes zoster rates increased with longer duration (16 weeks) of exposure to upadacitinib 45 mg during induction compared with the same population during the first 8 weeks. No other new safety signals were observed, and results are otherwise consistent with the known safety profile of upadacitinib. CONCLUSIONS: Patients without clinical response after 8 weeks' upadacitinib 45 mg induction therapy, may benefit from an additional 8 weeks of therapy. CLINICAL TRIAL REGISTRATION: NCT02819635; NCT03653026.

Understanding differential technologies for detection of MRD and how to incorporate into clinical practice.

Patient- and leukemia-specific factors assessed at diagnosis classify patients with acute myeloid leukemia (AML) in risk categories that are prognostic for outcome. The induction phase with intensive chemotherapy in fit patients aims to reach a complete remission (CR) of less than 5% blasts in bone marrow by morphology. To deepen and sustain the response, induction is followed by consolidation treatment. This postremission treatment of patients with AML is graduated in intensity based on this favorable, intermediate, or adverse risk group classification as defined in the European Leukemia Network (ELN) 2022 recommendations. The increment of evidence that measurable residual disease (MRD) after induction can be superimposed on risk group at diagnosis is instrumental in tailoring further treatment accordingly. Several techniques are applied to detect MRD such as multiparameter flow cytometry (MFC), quantitative (digital) polymerase chain reaction (PCR), and next-generation sequencing. The clinical implementation of MRD and the technique used differ among institutes, leading to the accumulation of a wide range of data, and therefore harmonization is warranted. Currently, evidence for MRD guidance is limited to the time point after induction using MFC or quantitative PCR for NPM1 and core binding factor abnormalities in intermediate-risk patients. The role of MRD in targeted or nonintensive therapies needs to be clarified, although some data show improved survival in patients achieving CR-MRD negativity. Potential application of MRD for selection of conditioning before stem cell transplantation, monitoring after consolidation, and use as an intermediate end point in clinical trials need further evaluation.

The efficacy of induction chemotherapy or adjuvant chemotherapy added to concurrent chemoradiotherapy in T3-4N0-1M0 nasopharyngeal carcinoma: a propensity score-matched analysis.

This research aimed to assess the effectiveness of combining induction chemotherapy (IC) or adjuvant chemotherapy (AC) with concurrent chemoradiotherapy (CCRT) in patients with T3-4N0-1M0 nasopharyngeal carcinoma (NPC). Before propensity score matching(PSM),we retrospectively collected 457 patients with T3-4N0-1M0 NPC treated with CCRT with or without IC/AC. PSM method selected 285 patients from two cohort(148 in CCRT±IC/AC group,137 in CCRT group). The 3-year overall survival(OS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) were estimated. The median follow-up was 41.03 months(range 2.13-94.67 months). No significant differences in 3 year-OS,LRFS and DMFS between CCRT±IC/AC group and CCRT group.Univariate analysis have shown that induction chemotherapy was significantly associated with 3 year LRFS(hazard ratio[HR] 0.214, 95%confidence interval[CI] 0.053-0.861,P = .030).Overall stage(HR 0.260, CI 0.078-0.870, P = .029) and T classification (HR 0.260, CI 0.078-0.870, P = .029)were significantly associated with OS.Multivariate analysis demonstrated no independent factors were related to 3-year OS,LRFS and DMFS. Subgroup analyses revealed that no significant survival differences in the two groups in patients with T3N1.In terms of T4N1 disease, patients received CCRT±IC/AC had lower 3-year DMFS than those treated with CCRT(90.4% vs 98.7%, P = .015). Adding IC or AC to CCRT did not significantly improve the prognosis of T3-4N0-1M0 NPC patients. Patients with T4N1M0 treated with CCRT had better DMFS than those received CCRT±IC/AC.However,more investigations should be confirmed the results.

A prospective phase II randomized study of docetaxel combined with lobaplatin versus TPF regimen induction chemotherapy followed by concurrent chemoradiotherapy for locally advanced head and neck squamous cell carcinoma.

PURPOSE: To compare the toxicity and clinical efficacy of TL (docetaxel + lobaplatin) induction chemotherapy combined with lobaplatin concurrent chemoradiotherapy and TPF (docetaxel + cisplatin + 5-fluorouracil) induction chemotherapy combined with cisplatin concurrent chemoradiotherapy in the treatment of locally advanced head and neck squamous cell carcinoma. METHODS AND PATIENTS: In total, 128 patients with locally advanced head and neck cancer were prospectively enrolled between August 2016 and April 2021. They were randomly divided into trial group and control group, all using chronological dosage mode. The trial group used TL regimen induction chemotherapy combined with lobaplatin concurrent chemoradiotherapy; the control group used TPF regimen induction chemotherapy and cisplatin concurrent chemotherapy. The endpoints were adverse events and survival rates at 1, 3 and 5 years. RESULTS: Median follow-up was 42 months (20-71 months). (1) Adverse events: During induction chemotherapy, compared with TPF group, grade 3-4 leukocytes and neutrophils, diarrhea, 1-2 hyperbilirubinemia, nausea / vomiting, oral mucositis, fatigue, anorexia, hyponatremia were significantly lower in TL group (p<0. 05): 6% vs. 35%, 14% vs. 53%, 0% vs. 6%, 15% vs. 40%, 9% vs. 56%, 0% vs. 10%, 3% vs. 13%, 2% vs. 23%, 15% vs. 74%. During chemoradiotherapy, the incidence of hyponatremia, hypokalaemia and grade 1-2 nausea was significantly lower in the TL group (p<0. 05), with 24% vs. 69%, 20% vs. 65% and 24% vs. 44%, respectively. However, more grade 3-4 thrombocytopenia were observed in the TL group (15% vs. 3%, p<0. 05). (2) There was no significant difference in the recent objective response rate (ORR) between patients with TL group and TPF group (p=0.961). (3) There was no statistical difference in 1, 3 and 5 years OS between TL group and TPF group, respectively, (71.0% vs. 67.5%, p=0.573), (56.6% vs. 56.9%, p=0.814), (52.5% vs. 52.9%, p=0.841); 1, 3 and 5 years PFS are: (63.4% vs. 64.0%, p=0.883), (51.1% vs. 54.0%, p=0.705) and (47.3% vs. 45.9%, p=0.887), None of them were significantly different. Multivariate analysis of COX regression showed that T stage (p=0.01) and surgery (p=0.046) were independent factors affecting PFS and OS, respectively. OS subgroup analysis shows that people receiving the TL regimen in postoperative and nodal stage N1 and N2 patients tended to survive longer than those receiving the TPF regimen. CONCLUSION: Patients with postoperative, N1 or N2 stage locally advanced head and neck squamous cell carcinoma (HNSCC) may have more significant clinical benefits when treated with TL regimen. TL regimen has advantages in reducing toxic side effects and can be used as one of the first-line treatment options. TRIAL REGISTRATION: ClinicalTrials.gov (No. NCT03117257).

Efficacy of induction chemotherapy in lymph node-positive stage III nasopharyngeal carcinoma and identification of beneficiaries based on clinical features: A propensity score matching analysis.

PURPOSE: To investigate the role of induction chemotherapy (IC) in lymph node-positive (LN-positive) stage III nasopharyngeal carcinoma (NPC) receiving concurrent chemoradiotherapy (CCRT). METHODS: In total, 627 patients with newly diagnosed LN-positive stage III NPC receiving CCRT or IC plus CCRT were included. The primary endpoint was progression-free survival (PFS). Propensity-score matching (PSM) was conducted to balance the intergroup covariates. Kaplan-Meier method with log-rank test was employed to compare survival curves. Subgroup analyses were conducted based on baseline characteristics. RESULTS: After 1:1 PSM, 414 patients were identified (207 patients per group). Compared with CCRT, IC plus CCRT provided better survival (5-year PFS 88.4% vs. 78.6%, P = 0.01; overall survival [OS] 94.8% vs. 85.3%, P = 0.003; and distant metastasis-free survival [DMFS] 93.1% vs. 85.6%, P = 0.03). The IC beneficial effects on PFS were mainly present in patients with grade 2-3 ENE, elevated serum lactate dehydrogenase (LDH > 170U/L), and N2 disease. Patients with grade 2 CNN had comparable PFS benefits to those with grade 0-1 CNN. For patients with grade 0-1 ENE combined with LDH ≤ 170U/L, survival between the two groups was similar with 5-year PFS 93.6% vs. 90.4% (P = 0.50), OS 94.2% vs. 93.0% (P = 0.72), and DMFS 98.6% vs. 97.7% (P = 0.98). CONCLUSION: Adding IC before CCRT improved survival in LN-positive stage III NPC patients. Additional IC did not provide better survival for patients with grade 0-1 ENE combined with LDH ≤ 170U/L and could be avoided in this population. CNN may not be a good risk factor for tailoring a personalized treatment plan.

Clinical observational study on the efficacy of induction chemotherapy sequential concurrent radiotherapy combined with targeted therapy in patients with locally advanced EGFR-positive nasopharyngeal carcinoma: prediction model construction and efficacy testing.

OBJECTIVE: To establish a nomogram for prediction of prognosis in EGFR-positive advanced nasopharyngeal carcinoma (NPC) patients who were treated with induction chemotherapy (IC) and concurrent chemoradiotherapy (CCRT). The clinical data of 124 NPC patients who received IC sequential CCRT combined with targeted therapy at the Department of Oncology of the Affiliated Hospital of North Sichuan Medical College between June 2017 and September 2022 were retrospectively reviewed. Logistic regression analysis was used to identify the prognostic factors for building the nomogram. RESULTS: Multifactorial regression analysis showed that the use of targeted drugs and T stage were independent factors of prognosis (p < 0.05) and the equation Y = 0.476 + 2.733X1 + - 0.758 × 2 (Y = efficacy, X1 = targeted drug therapy, X2 = T stage) was obtained. Then, a prognostic nomogram prediction model was constructed. The prediction model was validated internally for 1000 times using the Bootstrap resampling method with an accuracy of 79.29%. The calibration curve suggests that the predicted values fit well with the true values. The clinical decision curve (DCA) shows that the model has good clinical predictive value. CONCLUSION: The use of targeted therapy significantly improved the prognosis of patients with EGFR-positive advanced NPC. For advanced NPC patients with T1 and T2 stages, IC sequenced with CCRT is more effective, and the addition of targeted therapy can further improve patients' prognosis. For advanced NPC patients with T3 and T4 stages, IC sequenced with CCRT is ineffective, and the addition of targeted therapy can significantly improve patient prognosis.

Pretreatment dual-energy CT for predicting early response to induction chemotherapy and survival in nasopharyngeal carcinoma.

OBJECTIVES: To evaluate the predictive performance of pretreatment dual-energy CT (DECT) for early response to induction chemotherapy and survival in nasopharyngeal carcinoma (NPC). METHODS: In this retrospective study, 56 NPC patients who underwent pretreatment DECT scans with posttreatment follow-up were enrolled. The DECT-derived normalised iodine concentration (nIC), effective atomic number (Zeff), 40-180 keV (20 keV interval), and Mix-0.3 value of the tumour lesions were measured to predict the early response to induction chemotherapy and survival in nasopharyngeal carcinoma. The Mann‒Whitney U test, ROC analysis, Kaplan‒Meier method with log-rank test, and Cox proportional hazards model were performed to evaluate the predictive performance of DECT parameters, respectively. RESULTS: Among all DECT-derived parameters, ROC analysis showed the predictive performances of nIC and Zeff values for early objective response to induction chemotherapy (AUCs of 0.803 and 0.826), locoregional failure-free survival (AUCs of 0.786 and 0.767), progression-free survival (AUCs of 0.856 and 0.731) and overall survival (AUCs of 0.765 and 0.799) in NPC patients, respectively (all p < 0.05). Moreover, multivariate analysis showed that a high nIC value was an independent predictor of poor survival in NPC. In addition, survival analysis indicated that NPC patients with higher nIC values in primary tumours tend to have lower 5-year locoregional failure-free survival, progression-free survival and overall survival rates than those with lower nIC values. CONCLUSIONS: DECT-derived nIC and Zeff values can predict early response to induction chemotherapy and survival in NPC; in particular, a high nIC value is an independent predictive factor of poor survival in NPC. CLINICAL RELEVANCE STATEMENT: Preoperative dual-energy computed tomography may provide predictive value for early response and survival outcomes in patients with nasopharyngeal carcinoma, and facilitate their clinical management. KEY POINTS: • Pretreatment dual-energy computed tomography helps to predict early response to therapy and survival in NPC. • NIC and Zeff values derived from dual-energy computed tomography can predict early objective response to induction chemotherapy and survival in NPC. • A high nIC value is an independent predictive factor of poor survival in NPC.

Induction chemotherapy-based organ-preservation protocol improve the function preservation compared with immediate total laryngectomy for locally advanced hypopharyngeal cancer-Results of a matched-pair analysis.

BACKGROUND: We performed a paired analysis to compare the therapeutic effect between the induction chemotherapy-based organ-preservation approach and immediate total laryngectomy in hypopharyngeal squamous cell carcinoma patients requiring total laryngectomy. METHODS: 351 patients who were treated with organ-preservation approach were compared with 110 patients who were treated with total laryngectomy. The main measures and outcomes were progression-free survival (PFS), overall survival (OS), and larynx function preservation survival (LFPS). RESULTS: No statistical difference was observed for 3-, 5-, and 10-year PFS and OS in two groups. In the organ-preservation group, the 3-, 5-, and 10-year LFPS was 30.7%, 23.3%, and 16.6%, respectively. The LFPS of Stage III > Stage IV, N0 > N1 > N2 > N3, T2 > T3 > T4, CR > PR > SD > PD patients (all p values <0.05). CONCLUSIONS: Survival outcomes did not significantly differ between the two groups. The organ-preservation approach allowed more than 70% of the survivors to retain their larynx function.