Addition Of Induction Chemotherapy Research Articles

Outcomes of Induction Chemotherapy Followed by Chemoradiotherapy Versus Chemoradiotherapy Alone in Esophageal Squamous Cell Carcinoma Induction chemotherapy in Esophageal Squamous Cell Carcinoma.

There is still no definite conclusion regarding the effect of Induction Chemotherapy (IC) combined with concurrent Chemoradiotherapy (CRT). Thus this study was aimed to assess outcomes of IC followed By CRT versus CRT alone in Esophageal Squamous Cell Carcinoma (ESCC). This multicenter retrospective study performed on 105 patients who underwent CRT and 73 patients who underwent IC+CRT, between January 2016 and December 2018. The primary endpoints were OS (from the date of treatment to the date of death or 3- years follow-Up). The toxicities of CRT were graded according to the National Cancer Institute Common Toxicity Criteria (version 3.0). one-year (73.8% vs. 53.2%) and 2-year (53.4% vs. 38.5%) OS rate of the IC+CRT group was significantly higher than that of the CRT group (p < 0.05). No statistically significant differences were observed between the IC+CRT group and the CRT group (31.5% vs. 27.4%) in terms of the 3-year OS rate (p > 0.05). In multivariate logistic regression, age<60 (OR: 1.48; CI 95% 1.02-1.97), clinical staging II (OR: 1.36; CI 95% 1.11-1.88), and the addition of IC (OR: 1.66; CI 95% 1.07-2.19) were independent prognostic factors that affected survival positively. Our data demonstrated that a combination of IC and CRT might be a promising treatment strategy to further improve OS in ESCC patients.

Abstract 3272: PJA1 inhibits docetaxel-induced pyroptosis and results in chemoresistance in nasopharyngeal carcinoma

Abstract Background: Nasopharyngeal carcinoma (NPC) is highly prevalent in South China. More than 70% of patients are diagnosed with locoregionally advanced NPC (LA-NPC) at initial presentation, and the addition of induction chemotherapy (IC) to concurrent chemoradiotherapy is recommended for these patients. However, chemoresistance is a main reason for treatment failure in NPC patients, and the exact regulatory mechanism underlying chemoresistance in NPC remains to be elucidated. Methods: A gene expression dataset and STRING database were used to identify core module and gene that are related to the efficacy of docetaxel-cisplatin-5-fluorouracil (TPF) IC in NPC patients. In vitro and in vivo functional experiments were used to test the effects of PJA1 on docetaxel chemoresistance of NPC cells. The flow cytometric analysis, western blot, and lactate dehydrogenase (LDH) release assays were performed to determine the effects of PJA1 on GSDME-mediated cell pyroptosis. Co-immunoprecipitation, mass spectrometry, immunofluorescence staining, and ubiquitination assays were performed to explore the regulatory manners between PJA1 and PGAM5-DRP1 axis. Finally, multiplex immunofluorescence and immunohistochemical staining were used to evaluate the clinical significance of PJA1 -PGAM5-DRP1 axis in patients with NPC. Results: PJA1 was identified as a key E3 ligase of the top-ranked module ubiquitin-proteasome system dysregulation that involved in NPC chemoresistance, which was highly expressed in NPC patients with nonresponse to the TPF IC. PJA1 facilitated the docetaxel resistance of NPC cells through inhibiting the GSDME-mediated pyroptosis. Mechanistically, PJA1 promoted the degradation of the mitochondrial protein PGAM5 by increasing its K48-linked ubiquitination at K88, further increasing the phosphorylation of DRP1 at S637 and reducing the mitochondrial reactive oxygen species (ROS) production, in turn resulting in a suppressive of GSDME-mediated pyroptosis. PGAM5 knockdown fully restored the docetaxel sensitization effect of PJA1 knockdown. Moreover, RTA402, a pharmacological inhibitor of PJA1, enhanced the docetaxel sensitivity of NPC cells. Clinically, high PJA1 expression indicated resistance to TPF IC an inferior survival in NPC patients. Conclusions: Our study emphasizes the essential role of E3 ligase PJA1 in regulating chemoresistance in NPC and provides new therapeutic strategies for NPC patients based on targeting the ubiquitin-proteasome system. Citation Format: Na Liu, Ying-Qing Li, Sheng-Yan Huang. PJA1 inhibits docetaxel-induced pyroptosis and results in chemoresistance in nasopharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3272.

Induction chemotherapy plus re-irradiation versus re-irradiation alone in locally recurrent nasopharyngeal carcinoma: A model-based analysis

ObjectiveTo investigate the role of additional induction chemotherapy (IC) prior to re-irradiation in locally recurrent nasopharyngeal carcinoma (lrNPC). MethodsA total of 480 patients from three cancer treatment centers who received re-irradiation between 2012 and 2020 were retrospectively analyzed. Overall survival (OS) was determined using the Kaplan-Meier method and compared with log-rank method. Inverse probability of treatment weighting (IPTW) was performed to match the patients in pairwise treatment groups. Multivariate analysis using the Cox proportional hazards regression method identified predictors of OS. The risk stratification model was defined by the risk score calculated with the sum of coefficients. ResultsIn the entire cohort, the addition of IC was associated with similar OS compared with radiotherapy alone (P = 0.58) or with concomitant chemoradiation (P = 0.76). A risk stratification model was constructed and validated based on significant prognostic factors (coefficient) including male (0.6), age ≥ 60 years (0.9), volume of recurrence gross tumor volume ≥ 16 cc (0.7), and lactate dehydrogenase (LDH)-ratio ≥ 0.5 (0.4). In the intermediate-risk group (sum of coefficient: 0.9–––1.6), patients with IC plus re-irradiation had a significantly better OS than those who received re-irradiation (P = 0.03). After adjustments for several potentially confounding variables with IPTW, survival benefit of IC was also observed (P = 0.031). However, no significant difference in OS for the additional IC prior to re-irradiation was demonstrated in the low- (sum of coefficient: <0.9) and high-risk group (sum of coefficient: > 1.6). ConclusionAdditional IC prior to re-irradiation was associated with improved OS in the intermediate-risk group of lrNPC, whereas there was no difference for the low-risk and high-risk group. Prospective validation is required to validate these findings.

Induction chemotherapy plus definitive chemoradiotherapy versus chemoradiotherapy alone in esophageal squamous cell carcinoma: Long-term results and exploratory analyses of a randomized controlled trial.

4061 Background: The previous results of our trial demonstrated that the addition of induction chemotherapy (IC) prior to definitive chemoradiotherapy (CRT) failed to significantly improve response rate or 3-year survival in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Here, we report the long-term results and exploratory analyses to further evaluate the therapeutic value of IC in ESCC. Methods: This was a single-institution, open-label, randomized, phase II trial. Patients with previously untreated, unresectable, stage II–IVA ESCC were randomly assigned in a 1:1 ratio to receive induction docetaxel (75 mg/m2 on day 1) and cisplatin (75 mg/m2 on day 1) every 3 weeks for two cycles, followed by concurrent CRT, or CRT alone. The primary endpoint was overall response rate at 3 months after CRT. Second endpoints were overall survival (OS) and progression-free survival (PFS). The relationship between tumor response to IC and long-term survival was analyzed as an exploratory, post-hoc analysis. Moreover, baseline tumor biopsies were evaluated by RNA-seq to identify patients who are more likely to benefit from IC. Results: Between May 2015 and September 2017, 110 eligible patients were randomly assigned to the IC+CRT group (n=55) or the CRT group (n=55). The overall response rate was 74.5% in the IC+CRT group versus 61.8% in the CRT group (P=0.15). At a median follow-up of 74.9 months, the 5-year OS rate was 31.8% in the IC+CRT group and 29.1% in the CRT group (P=0.68; HR, 0.91; 95% CI, 0.58–1.43). Similarly, no significant differences were identified in 5-year PFS between groups (30.5% vs. 25.5%, P=0.51; HR, 0.86; 95% CI, 0.56 to 1.34). Patients who responded to IC had significantly better survival than nonresponders. Six key genes were identified based on RNA-seq and gene expression comparison between responders and nonresponders after IC. Risk-score model was constructed by these key genes and then validated. Conclusions: Addition of induction docetaxel plus cisplatin before definitive CRT still failed to provide an obvious survival benefit in ESCC based on long-term follow-up. However, this strategy did result in a significantly improved survival in IC responders. Our results also revealed potential molecular biomarkers to predict who may benefit from IC. Clinical trial information: NCT02403531 .

Risk stratification and beneficiary selection among elderly nasopharyngeal carcinoma patients from concurrent chemoradiotherapy combined with induction chemotherapy.

This study aims to evaluate the risk stratification among elderly Nasopharyngeal carcinoma (NPC) patients (≥60 years old) and select the beneficiaries from concurrent chemotherapy (CCRT) combined with induction chemotherapy (IC). A total of 909 elderly non-metastatic NPC patients treated with cisplatin-based CCRT or IC + CCRT between January 2007 and December 2016 were included. Prognostic nomograms were generated according to clinical characteristics and serum biomarkers. The survival outcomes of patients treated with CCRT versus IC + CCRT were compared in three well-matched risk groups (high, medium, and low risk) after PSM analysis. Benefit of IC in people older or younger than 70 years and effect of different IC regimens and cycles on prognosis were analyzed. Nomograms of overall survival (OS) (C-index: 0.64, 95% CI, 0.61-0.89) and disease special survival (DSS) (C-index: 0.65, 95% CI, 0.62-0.71) showed good prognostic accuracy. The nomogram for DSS included variables of age, gender, ACE, EBV DNA, N stage, and T stage. OS included variables of age, smoking history, ACE, ALB, EBV DNA, N stage, and T stage. The corresponding 5-year OS rates of high, medium and low risk groups were 87.4%, 82.2%, and 60.9%, respectively (p < 0.001), while the 5-year DSS rates were 92.2%, 84.3%, and 69.0%, respectively (p < 0.001). In the high risk group, IC + CCRT led to significantly higher 5-year OS and DSS rate compared with CCRT (5-year OS rate, 73.5% versus 51.8%, p=0.006; 5-year DSS rate, 81.4% versus 61.3%, p=0.002). While in the medium and low risk groups, OS and DSS were not significantly different (OS: p=0.259, 0.186; DSS: p=0.29, 0.094). Subgroup analysis showed in the high risk group, only people younger than 70 years old could benefit from IC. TPF and IC cycles of three could lead to the best survival results. Compared with CCRT, OS, and DSS among high risk elderly patients were significantly improved by the addition of IC in patients younger than 70 years old. TPF and three IC cycles were recommended.

A Nomogram to Identify the Optimal Candidates for Induction Chemotherapy in Advanced N-Stage Nasopharyngeal Carcinoma.

PurposeWe aimed to select optimal candidates benefiting from the addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in advanced N-stage nasopharyngeal carcinoma (NPC).Patients and MethodsA total of 624 NPC patients with N2-3 stage received CCRT with or without IC were retrospectively reviewed. We constructed a nomogram for predicting overall survival (OS) based on the result of the multivariate analysis in the training cohort (n = 468) and then tested it on the validation cohort (n = 156). Harrell’s concordance indices (C-index) and time-independent receiver operating characteristic (tdROC) analysis were applied to evaluate the discriminatory ability of the nomogram and compare it with TNM staging. IC plus CCRT was compared with CCRT in the whole cohort and two risk groups based on the nomogram with balanced baseline characteristics. In addition, acute toxicities were compared between different treatment groups.ResultsThe nomogram showed good prognostic accuracy with a C-index of 0.716 (95% CI 0.669–0.763) in the validation cohort. The 5-year OS of low and high-risk groups stratified by the nomogram were significantly different. IC+CCRT was significantly associated with superior OS as compared with CCRT (75.4 vs 52.6%, p = 0.009) in the high-risk group. However, no significant difference between IC plus CCRT and CCRT was observed (p = 0.843) in the low-risk group. IC plus CCRT was associated with more grade 1–4 acute toxicities.ConclusionOur study can help clinicians select NPC patients with advanced N stage who benefit from IC.

Survival impact of additional induction chemotherapy in nasopharyngeal carcinoma with chronic hepatitis B infection: a retrospective, bi-center study.

BackgroundPatients with nasopharyngeal carcinoma (NPC) who have hepatitis B virus (HBV) infection tend to be treated with induction chemotherapy (IC) due to a higher metastasis rate. However, additional IC may lead to immunosuppression and can negatively affect the prognosis. We evaluated whether receiving IC improved the prognosis of patients with NPC co-infected with HBV, on the basis of concurrent chemoradiotherapy (CCRT).MethodsThis large-scale retrospective cohort study included data of patients with pathologically confirmed NPC that were collected from two hospitals between January 2010 and March 2014. Patients were followed-up every 3 months during the first 2 years and once every 6 months thereafter. Univariate analysis identified confounding factors associated with prognosis. Stage-based subgroup analyses and 1:1 random-matched pair analyses were performed to compare the survival differences between patients treated with IC + CCRT and those treated with CCRT alone.ResultsAmong the 1,076 enrolled patients, 16.6% were hepatitis B surface antigen (HBsAg)-positive. Among HBsAg-positive patients with stage II/III/IV NPC, distant metastasis-free survival (DMFS) (79.3% vs. 89.9%; P=0.045) and progression-free survival (PFS) (70.6% vs. 83.7%; P=0.025) were lower in patients who received IC + CCRT than in those who received CCRT alone. After adjusting for confounding factors, IC + CCRT was validated as a negative prognosticator for DMFS and PFS, while matched-pair analysis with HBsAg-negative patients showed a better overall survival (OS) for IC + CCRT (88.4% vs. 82.6%; P=0.04).ConclusionsCompared with CCRT alone, IC + CCRT negatively affects DMFS and PFS in patients with NPC with chronic HBV infection. We advocate withholding IC but administering stronger initial treatment in NPC patients complicated with HBV infection.

Abstract 5128: Identification and characterization of nasopharyngeal carcinoma prognostic subtypes based on a circRNA classifier: Implications of stratified treatment

Abstract Accurate risk stratification for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) is crucial for treatment decisions and prognosis. Here, we introduce a circRNA-based classifier that could improve the prognostic stratification of LA-NPC patients. The circRNAs are identified by microarray profiling, followed by qRT-PCR validation and selection using a machine learning method in the training cohort (n = 170). Based on the proposed classifier, two prognostic-distinctive NPC subtypes are identified, namely the high-risk subtype (subtype H) and low-risk subtype (subtype L), which have significantly different disease-free survival (HR 2.99, 95% CI 1.58-5.67, P &amp;lt; 0.001). Validation in the internal cohort (n = 170) and external cohort (n = 150) yield similar results and the circRNA-based classifier is an independent risk factor of posttreatment relapse. Meanwhile, multiple interdependent features of different subtypes are observed, including relatively higher immune cell infiltration and immune-related pathways activation in subtype L; and predominant stromal, immunosuppressive and tumor-promoting components with moderate immune activation in subtype H. With a less aggressive and more immune-active tumor microenvironment, patients of subtype L could benefit from the addition of induction chemotherapy. In contrast, patients of subtype H, who are vulnerable to chemoresistance, display a strong tendency to benefit from additional immunotherapy. Overall, we define two NPC prognostic subtypes based on a circRNA classifier across multiple cohorts, which exhibit distinct biological ecosystems and suggest opportunities for the personalization of therapeutic regimens. Citation Format: Yelin Liang, Yuheng Zhao, Qian Li, Wei Jiang, Jun Ma, Na Liu, Yingqin Li. Identification and characterization of nasopharyngeal carcinoma prognostic subtypes based on a circRNA classifier: Implications of stratified treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5128.

État des lieux et perspectives thérapeutiques pour les carcinomes nasopharyngés localement évolués

Nasopharyngeal carcinoma diagnosis is often made at a locally advanced stage (75 to 90% of cases) due to its deep localization. Concomitant radio-chemotherapy is the cornerstone of the treatment of locally advanced forms. The advent of intensity-modulated radiotherapy has improved oncological outcomes and reduced toxicity and is currently the gold standard for irradiation technique. For the locally advanced stage, the addition of induction chemotherapy has become the new standard care according to the latest international recommendations to reduce tumor volumes and act early on micro-metastases. Despite these therapeutic advances, the local and especially distant failure rate remains high. This article reviews current treatment strategies and discuss new approaches and perspectives of locoregional and systemic treatment to reduce treatment failures.

Differential benefit of induction chemotherapy according to body mass index in nasopharyngeal carcinoma – Pooled analysis of two randomized trials

ObjectiveInduction chemotherapy followed by concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). However, survival benefits from additional induction chemotherapy varied significantly among patients. This study aimed to determine the predictive value of body mass index (BMI) in induction chemotherapy in NPC. Materials and methodsThis post-hoc analysis included patients from two multicenter, randomized, phase 3 trials (NCT01245959 and NCT01872962), in which patients were randomized to receive induction chemotherapy plus concurrent chemoradiotherapy or concurrent chemoradiotherapy alone. ResultsAmong 960 patients participated, 957 were included in this analysis. 82 (8.6%) patients had baseline BMI < 18.5 kg/m2 (underweight) and 875 (91.4%) had BMI ≥ 18.5 kg/m2 (normal /overweight). Higher proportion of normal/overweight patients completed ≥2 cycles of induction chemotherapy than underweight patients (96.5% vs. 88.4%, p = 0.042). A strong trend for interaction was observed between BMI and induction chemotherapy regarding failure-free survival (FFS) and overall survival (OS, both pinteraction < 0.001). Normal/overweight patients benefited from induction chemotherapy regarding FFS (83.8% vs. 72.9%, p < 0.001) or OS (93.1% vs. 86.9%, p < 0.001), while underweight patients did not (p = 0.24 and p = 0.65, respectively). These results were confirmed in multivariate analysis and multiple sensitivity analyses. ConclusionUsing pooled data from two landmark phase III trials, we found that underweight patients might not benefit from additional induction chemotherapy in locoregionally advanced NPC. If confirmed in prospective studies, this could help guide individual treatment in the clinic.

Development and validation of radiologic scores for guiding individualized induction chemotherapy in T3N1M0 nasopharyngeal carcinoma

ObjectivesWe aimed to develop and validate radiologic scores from [18F]FDG PET/CT and MRI to guide individualized induction chemotherapy (IC) for patients with T3N1M0 nasopharyngeal carcinoma (NPC).MethodsA total of 542 T3N1M0 patients who underwent pretreatment [18F]FDG PET/CT and MRI were enrolled in the training cohort. A total of 174 patients underwent biopsy of one or more cervical lymph nodes. Failure-free survival (FFS) was the primary endpoint. The radiologic score, which was calculated according to the number of risk factors from the multivariate model, was used for risk stratification. The survival difference of patients undergoing concurrent chemoradiotherapy (CCRT) with or without IC was then compared in risk-stratified subgroups. Another cohort from our prospective clinical trial (N = 353, NCT03003182) was applied for validation.ResultsThe sensitivity of [18F]FDG PET/CT was better than that of MRI (97.7% vs. 87.1%, p < 0.001) for diagnosing histologically proven metastatic cervical lymph nodes. Radiologic lymph node characteristics were independent risk factors for FFS (all p < 0.05). High-risk patients (n = 329) stratified by radiologic score benefited from IC (5-year FFS: IC + CCRT 83.5% vs. CCRT 70.5%; p = 0.0044), while low-risk patients (n = 213) did not. These results were verified again in the validation cohort.ConclusionsT3N1M0 patients were accurately staged by both [18F]FDG PET/CT and MRI. The radiologic score can correctly identify high-risk patients who can gain additional survival benefit from IC and it can be used to guide individualized treatment of T3N1M0 NPC.Key Points• [18F]FDG PET/CT was more accurate than MRI in diagnosing histologically proven cervical lymph nodes.• Radiologic lymph node characteristics were reliable independent risk factors for FFS in T3N1M0 nasopharyngeal carcinoma patients.• High-risk patients identified by the radiologic score based on [18F]FDG PET/CT and MRI could benefit from the addition of induction chemotherapy.

A Clinical Scoring Model to Predict the Effect of Induction Chemotherapy With Definitive Concurrent Chemoradiotherapy on Esophageal Squamous Cell Carcinoma Prognosis.

PurposeThe aim of the study was to compare the clinical outcomes of induction chemotherapy (IC) followed by definitive concurrent chemoradiotherapy (dCCRT) versus chemoradiotherapy alone in patients with esophageal squamous cell carcinoma (ESCC) on the basis of a clinical scoring model.MethodsA retrospective review of 599 patients with ESCC treated with dCCRT at our institution from 2010 to 2019 was conducted. The patients were divided into two groups based on whether they received IC. A clinical scoring model was performed using the significant variables obtained from the multivariate analysis. The PFS and OS rates were estimated using the Kaplan–Meier method.ResultsDuring the study period, 182 patients receiving IC followed by dCCRT and 417 dCCRT alone were identified. No significant differences in the PFS and OS rates were observed between the IC group (P=0.532) and the non-IC group (P=0.078). A clinical scoring model was constructed based on independent prognostic factors with scores ranging from 0 to 10.4. The patients were divided into high- and low-risk groups by using the median score as the cutoff value. The PFS rate of patients receiving IC was higher than that of patients treated without IC (P=0.034), while there was no improvement in the OS rate (P=0.794) in the high-risk group. No significant differences in the PFS (P=0.207) or OS (P=0.997) rate were found between the two treatment groups in the low-risk group.ConclusionsThe addition of IC followed by dCCRT for patients with ESCC might be associated with better PFS rates based on a clinical scoring model but has no impact on OS rates. Further prospective studies are warranted for the validation of this model.

Acute myeloid leukemia: negative prognostic impact of early blast persistence can be in part overcome by a later remission prior to post-induction therapy.

In acute myeloid leukemia, there is an ongoing debate on the prognostic value of the early bone marrow assessment in patients receiving intensive therapy. In this retrospective study, we analyzed the prognostic impact of the early response in 1,008 patients with newly diagnosed acute myeloid leukemia, who were treated at our institution with intensive chemotherapy followed by consolidation chemotherapy and/or allogeneic hematopoietic stem cell transplantation (HSCT). We found that early blast persistence has an independent negative prognostic impact on overall survival, event-free survival and relapse-free survival. This negative prognostic impact may only be overcome in patients showing at least a partial remission at the early bone marrow assessment and who subsequently achieve blast clearance by additional induction chemotherapy prior to consolidation therapy with allogeneic HSCT. In accordance, we propose that the time slope of remission is an additional leukemia-related dynamic parameter that reflects chemosensitivity and thus may inform post-induction therapy decision-making. In addition to patient-related factors, European LeukemiaNet risk group, measurable residual disease monitoring and donor availability, this may particularly apply to European LeukemiaNet intermediate-risk patients, for whom a decision between consolidation chemotherapy and allogeneic HSCT remains challenging in many cases.

Impact of pretreatment second look 18FDG-PET/CT on stage and treatment changes in head and neck cancer

BackgroundPatients diagnosed with locoregionally advanced head and neck squamous cell carcinoma (LAHNSCC) regularly undergo staging with 18F-FDG PET/CT in our center. In cases of delays in radiotherapy (RT) planning CT more than 4 weeks after initial PET/CT or clinically suspected progress, PET/CT is repeated for restaging and as an RT planning reference. Our aim was to determine the impact of second-look PET/CT on stage migration, treatment change and RT planning. MethodsConsequent treatment changes were categorized as minor and major. Minor changes were defined as PET/CT-based modifications of RT plans, e.g., the addition of anatomical compartments, changes in high- and low-risk dose levels or both. Major changes included changes from curative to palliative treatment intent and alterations of interdisciplinary treatment plans, such as the addition of induction chemotherapy, switch to primary surgery, no treatment and/or the necessity of additional diagnostic work-up resulting in the postponement or cancellation of treatment. ResultsThirty-two newly diagnosed LAHNSCC patients who were treated between 2014 and 2018 underwent second-look PET/CT (median interval 42.5 days). Second-look PET/CT led to locoregional and distant upstaging in 3/32 and 1/32 patients, respectively. In 1/32 patients (3%), second-look PET/CT led to a palliative approach with systemic treatment. New lymph node metastases were discovered in 16 patients, 6 of whom also showed significant progression of the primary tumor, resulting in minor changes in 16 of the remaining 31 patients (52%) who were treated curatively. ConclusionIf RT treatment planning of LAHNSCC was delayed by more than 4 weeks after initial PET/CT staging or when progression was clinically suspected, a second look at 18FDG-PET/CT was performed. This led to changes in treatment planning in more than half of the cases, which is expected to directly influence oncologic outcomes.

Functional Larynx Preservation in Patients With Locally Advanced Squamous Cell Carcinoma of the Larynx and Hypopharynx Treated With Induction Chemotherapy vs. Concurrent Chemoradiation Alone.

ObjectivesChemoradiation therapy (CRT) has been established as a standard treatment for locally advanced hypopharynx/larynx squamous cell carcinoma (SCC) but the role of induction chemotherapy (IC) remains unclear. The primary outcome of this study is to determine whether functional larynx-preservation survival (FLPS) is improved with the addition of IC in these patients. Secondary outcomes were overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and laryngectomy rates.MethodsRecords for patients with AJCC 8th edition clinical stage III-IVB laryngeal and hypopharyngeal SCC treated with CRT +/- IC from 2005-2019 were reviewed. FLPS was defined as time until death, progression, laryngectomy, or non-functional larynx. Kaplan-Meier curves were generated for FLPS, OS, PFS, and DMFS. Outcomes were compared using the stratified log-rank test. Laryngectomy rates were compared using Fisher’s exact test.ResultsWe included 52 patients with laryngeal and 38 with hypopharyngeal SCC (n=90); 19 patients with laryngeal SCC and 19 with hypopharyngeal SCC received IC (median three cycles). There were no differences in the three-year FLPS (61% vs 67.8%; p=0.88), OS (73.9% vs 86.2%; p=0.42), PFS (53.6% vs 62.6%; p=0.44), or DMFS (65.2% vs 71.5%, p= 0.85) between patients who did and did not receive IC all patients. Laryngectomy rates did not differ with and without IC (18.4 % vs 7.7%; p=0.19).ConclusionIn this study of advanced laryngeal and hypopharyngeal SCC, IC did not improve three-year FLPS, OS, PFS, or laryngectomy rates compared to CRT alone. A large prospective series would provide a more robust understanding of the role of IC in this group of patients.

Induction Chemotherapy Followed by Radiation Therapy Versus Surgery Followed by Concurrent Chemo-Radiation Therapy in Locally Advanced Squamous Cell Carcinoma of the Oral Cavity.

IntroductionSquamous cell carcinoma of the oral cavity is one of the top 10 malignancies reported globally. Pakistan has a high incidence of oral cancers due to the prevailing poor lifestyle habits/addictions of Pakistanis, and most patients with squamous cell carcinoma present with stage III or IV locally advanced disease. Recommended guidelines indicate surgery as the mainstay of treatment followed by radiotherapy (RT). The addition of induction chemotherapy before surgery or radiation therapy might improve outcomes with increased locoregional control rates.MethodsThis was a retrospective cohort study comparing the outcomes between surgery followed by concurrent chemoradiotherapy (CCRT) and induction chemotherapy followed by RT. This study primarily aimed to evaluate progression-free survival (PFS) and determine the toxicity of chemotherapy.ResultsWe found out that the mean PFS among patients undergoing surgery and CCRT and those receiving induction chemotherapy followed by RT were 6.40 (± 2.38) months and 7.6 (± 4.76) months, respectively.ConclusionInduction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil followed by RT shows satisfactory results with acceptable toxicity. However, the results are not statistically significant but support the already published data on this treatment aspect of oral cavity cancers.

Impact Of Adding Induction Chemotherapy To Chemoradiotherapy In The Management Of Locally Advanced Squamous Cell Cancers Of The Head And Neck Presenting With Radiographic Extranodal Extension

In patients with locally advanced squamous cell cancers of the head and neck (LAHNC), the presence of radiographic extranodal extension (rENE) is known to predict for worse local control (LC), distant control (DC), and overall survival (OS). We investigated whether the addition of induction chemotherapy (IC-CRT) to standard chemoradiation (CRT) improved outcomes among this population. From our IRB approved database, we conducted a single-institution retrospective study of patients with LAHNC who were determined to have rENE by an expert head and neck radiologist and underwent definitive therapy with either IC-CRT or CRT. Kaplan-Meier analyses were performed to evaluate impact of treatment regimen (IC-CRT vs CRT) on locoregional control (LRC), distant control (DC), and OS. Survival was calculated from time of pathologic diagnosis. Cox regression multivariate analyses evaluated for independent predictors of survival. Toxicity was evaluated using CTCAE v4.0 and acute toxicity was defined as occurring within 3 months of starting treatment. The association between IC and acute toxicity was evaluated using Chi-Square analysis. Of 141 LAHNC patients who were identified with rENE, 68 received IC-CRT and 73 received CRT. Radiation dose was generally 70Gy and 68% of IC was TPF regimen, of whom 98% completed 2-3 cycles. Median follow up was 4.8 years, and among survivors was 7.1 years. At time of analysis, 52 patients (37%) had died. AJCC 8th edition stage was not significantly different between treatment groups (p = 0.14). Comparing IC-CRT vs. CRT, patients achieved similar 5-year LRC (79.8% vs 68.5%, p = 0.33), DC (73.1% vs 71.9%, p = 0.64), and OS (64.6% vs 59.0%, p = 0.62). Among patients with p16 negative disease (n = 52; 29 IC-CRT vs. 23 CRT, similar stages p = 0.27), use of IC-CRT vs. CRT yielded improved 5-year LRC (78.3% vs 38.4%, p = 0.02), while DC (65.1% vs 63.6%, p = 0.15) and OS (54.8% vs 38.3%, p = 0.23) was similar. MVA showed a trend toward improved LRC for p16 negative cancer with use of IC-CRT (HR 0.33, 95% CI: 0.14-1.10, p = 0.07). Acute grade 3-5 toxicity was significantly more prevalent with IC-CRT than CRT (71% vs 51%, p = 0.01), driven by higher hematologic toxicity (56% vs 33%, p = 0.006). In these long-term results of a retrospective series of patients with LAHNC and rENE, patients who received IC-CRT demonstrated similar LRC, DC, and OS vs. standard CRT. For patients with p16-negative disease, IC-CRT yielded significantly improved LRC. Nevertheless, IC-CRT was associated with worse toxicity, and additional studies are needed to examine ideal treatment strategies among this poorly performing population.

Identifying optimal candidates for induction chemotherapy among stage II-IVa nasopharyngeal carcinoma based on pretreatment Epstein-Barr virus DNA and nodal maximal standard uptake values of [18 F]-fluorodeoxyglucose positron emission tomography.

ObjectiveThis study aimed to select optimal candidates benefiting from the addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in stage II–IVa nasopharyngeal carcinoma (NPC) based on Epstein–Barr virus (EBV) DNA and nodal maximal standardized uptake values (SUVmax‐N) of [18F]‐fluorodeoxyglucose positron emission tomography.Patients and materialsA total of 679 patients diagnosed with stage II–IVa (except N0) NPC were retrospectively included in this study. Overall survival was the primary endpoint. Survival differences between different groups were compared using the log‐rank test. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using a multivariable Cox proportional hazards model.ResultsBoth high levels of EBV DNA (>1500 copies/mL) and SUVmax‐N (>12.3) indicated worse survival conditions. All patients were divided into low‐ and high‐risk groups based on these two biomarkers. The risk group was an independent prognostic factor in OS, progression‐free survival (PFS), and distant metastasis‐free survival (DMFS) (all p‐values<0.05). The addition of IC to CCRT was associated with survival improvement in OS, PFS, and DMFS in high‐risk patients, while no survival difference was found between CCRT and IC+CCRT in low‐risk patients.ConclusionsOur study can help clinicians select stage II–IVa NPC patients who benefit from IC, which is important in guiding individual treatment.

Induction chemotherapy followed by neoadjuvant chemoradiotherapy and surgery for patients with locally advanced rectal cancer: a systematic review and meta-analysis.

Controversy persists about whether additional induction chemotherapy (ICT) before neoadjuvant chemoradiation (NCRT) yields improved oncological outcomes. We performed a systematic review and meta-analysis to compare ICT+ NCRT+ surgery(S) with NCRT+ S in patients with locally advanced rectal cancer (LARC). We searched the PubMed, EMBASE, Cochrane Library, and China Biology Medicine (CBM) databases. The data were analyzed with Stata version 12.0 software. We identified 9 relevant trials that enrolled 1538 patients. We detected no significant difference in the 5-year overall survival (OS) (OR 1.50, 95% CI 0.48-4.64), disease-free survival (DFS) (OR 1.03, 95% CI 0.73-1.46), local recurrence (LR) (OR 0.80, 95% CI 0.45-1.43), and distant metastasis (DM) rates (OR 1.03, 95% CI 0.55-1.93) between patients who did and did not receive ICT. The addition of ICT before NCRT had a similar pathological complete response rate compared to NCRT (OR 1.26, 95% CI 0.90-1.77). Our findings suggest that between the ICT + NCRT+S and NCRT+S groups, ICT improved the incidence of grade 3 to 4 toxicity effects (OR 4.81, 95% CI 2.38-9.37), but between the ICT + NCRT+S and NCRT+S+ adjuvant chemotherapy (ACT) groups, ICT might reduce toxicity (OR 0.19, 95% CI 0.08-0.50). ICT had no significant impact on surgical complications (OR 0.97, 95% CI 0.63-1.51). The addition of ICT before NCRT seemingly shows no survival benefit on patients with LARC, and might increase the toxicity.

Blood product administration during high risk neuroblastoma therapy

The increasing intensity of high-risk neuroblastoma (HR NB) treatment over the last decades has resulted in improved survival at the expense of prolonging therapy and exposure to additional potentially toxic agents. Anemia and thrombocytopenia requiring transfusion are common during therapy for HR NB. Risks of cumulative red blood cell and platelet transfusions are incompletely defined in pediatric oncology patients, however, risks of transfusional iron overload are well described in other populations. This study aimed to determine the number of packed red blood cell (pRBC) and platelet transfusions throughout treatment for HR NB and how these numbers have changed with modern therapy. We performed a retrospective review of 92 patients with HR NB from June 2002 until September 2017. Patients received a median of 20 pRBC and 32 platelet transfusions. Our results demonstrated large numbers of transfusions with significantly increased blood product exposures among patients who received intensified therapy, either with additional induction chemotherapy, tandem autologous stem cell transplants, or dinutuximab plus cytokines with isotretinoin. Similar volumes of pRBC transfusions have been associated with iron overload in other populations and warrant further discussion of guidelines for long-term follow up of HR NB patients.