Individualised cumulative cisplatin dose for locoregionally advanced nasopharyngeal carcinoma patients based on induction chemotherapy response and tumour volume.

Background and objectives: To evaluate the prognostic value of an integrated model consisting of tumour response to induction chemotherapy (IC) and gross tumour volume (GTV) after IC in nasopharyngeal carcinoma (NPC) and elucidate optimal cumulative cisplatin dose (CCD) in concurrent chemoradiotherapy (CCRT) for different subgroups. Design and methods: This retrospective study enrolled 896 patients with NPC diagnosed from 2010 to 2017 receiving IC plus radiotherapy. The primary endpoint was disease-free survival (DFS). Cut-off points for GTV were combined with IC response to develop an integrated model. Propensity score matching (PSM) was used to adjust for potential confounders. Survival outcomes and acute toxicity were compared between the different CCD groups. Results: Unsatisfactory IC response and large GTV after IC were correlated with poor survival outcomes; the AUC increased to 0.668 when these factors were incorporated. The integrated model classified patients into three groups. After PSM, radiotherapy alone and CCRT demonstrated similar efficacy in the low-risk group (complete response (CR)/partial response (PR) and GTV <68 cm3 after IC). In the intermediate-risk group (CR/PR but GTV ⩾68 cm3), CCD of >200 mg/m2 and 101-200 mg/m2 increased the 5-year DFS rates (83.7% vs 81.1% vs 65.3%, p = 0.042). In the high-risk group (stable disease/progressive disease and any GTV), the use of different CCDs did not result in significantly different survival outcomes (p = 0.793). Additionally, high CCD was significantly associated with increased incidence of grade 1-4 acute toxicity. Conclusion: The integrated model incorporating IC response and GTV after IC demonstrates satisfactory value in risk stratification and the potential to guide individualised decision-making in CCD selection. Balancing toxicity and efficacy, RT alone seems to be the optimal treatment for patients in low-risk groups and 200 mg/m2 might be the optimal dose for intermediate-risk groups. Moreover, increasing CCD does not benefit patients in high-risk groups, and treatment options for these patients require further consideration.

Induction Chemotherapy for Sinonasal Tumors in Patients Presenting with Brain Invasion and/or Neurological Deficits.

Objective The aim of this study was to investigate the safety of induction chemotherapy (IC) for patients with sinonasal malignancies with brain invasion or a neurological deficit. Methods We conducted a retrospective analysis of patients who underwent IC for sinonasal malignancies with intracranial invasion or a neurological deficit at a single tertiary cancer center from 1992 to 2020. Results In total, 460 patients with sinonasal malignancies were included in the study. Of the patients reviewed, 341 underwent IC and within this group 40 had brain invasion (BI) and 31 had a neurological deficit (ND) at presentation. The most prevalent malignancy was sinonasal undifferentiated carcinoma (BI 40%, ND 41.9%), followed by esthesioneuroblastoma (BI 27.5%, ND 9.7%). All tumors were stage T4 with the majority lacking nodal metastases (BI N0: 72.5%, ND N0: 77.5%). All patients completed at least two cycles of IC. Partial or complete response to IC was seen in 80% of BI and 71% of ND patients. No patients had cessation of treatment due to neurologic decline and none required urgent surgery. Five patients (12.5%) with BI and 2 (6.5%) with ND had interruption of IC for reasons other than neurological decline. In patients with ND, IC led to improvement of 54.5% NDs. Conclusion In patients with sinonasal malignancies with BI or ND who underwent IC, no patients had cessation of treatment due to neurologic decline. In contrast, most patients had improvement of neurologic symptoms with IC. IC was safely administered without interruption due to neurological decline or symptom progression.

Guiding induction chemotherapy of locoregionally advanced nasopharyngeal carcinoma with ternary classification of predicted individual treatment effect.

BACKGROUND AND PURPOSE: Induction chemotherapy (IC) before concurrent chemoradiotherapy does not universally improve long-term overall survival (OS) in locoregionally advanced nasopharyngeal carcinoma (LANPC). Conventional risk stratification often yields suboptimal IC decisions. Our study introduces a ternary classification of predicted individual treatment effect (PITE) to guide personalized IC decisions. MATERIALS AND METHODS: A two-center retrospective analysis of 1,213 patients with LANPC was conducted to develop and validate prognostic models integrating magnetic resonance imaging and clinical data to estimate individual 5-year OS probabilities for IC and non-IC treatments. Differences in these probabilities defined PITE, facilitating patient stratification into three IC recommendation categories. Model effectiveness was validated using Kaplan-Meier estimators, decision curve-like analysis, and evaluations of variable importance and distribution. RESULTS: The models exhibited strong predictive performance in both treatments across training and cross-validation sets, enabling accurate PITE calculations and patient classification. Compared with non-IC treatment, IC markedly improved OS in the IC-preferred group (HR = 0.62, p = 0.02), had no effect in the IC-neutral group (HR = 1.00, p = 0.70), and worsened OS in the IC-opposed group (HR = 2.00, p = 0.03). The ternary PITE classification effectively identified 41.7 % of high-risk patients not benefiting from IC, and yielded a 2.68 % higher mean 5-year OS probability over risk-based decisions. Significantly increasing distributions of key prognostic indicators, such as metastatic lymph node number and plasma Epstein-Barr virus DNA level from IC-opposed to IC-preferred groups, further validated the clinical relevance of PITE classification. CONCLUSION: The ternary PITE classification offers an accurate and clinically advantageous approach to guide personalized IC decision-making in patients with LANPC.

Myeloid Sarcoma: Novel Advances Regarding Molecular Pathogenesis, Presentation and Therapeutic Options.

Myeloid sarcoma (MS), an extramedullary form of acute myeloid leukemia (AML) is a rare tumor mass of myeloid blasts. It can disseminate to any one or multiple anatomical sites, with (synchronous MS) or without (isolated MS) bone marrow (BM) involvement. The aim of this review is to describe the most recent advances in MS regarding diagnosis, molecular background, various clinical manifestations from several organs, and treatment approaches. Due to the lack of prospective, randomized clinical trials, therapeutic decisions are a challenge for the clinician. In the era of novel targeted AML treatments, a critical analysis of how to decide the best option for individual patients, also covering the possible central nervous system (CNS) prophylaxis is provided. For the majority of the patients, AML induction chemotherapy, followed by hematopoietic stem cell transplantation (HSCT) is generally recommended. This paper discusses the role of radiotherapy, the treatment of refractory and relapsed disease, along with the therapeutic approach of difficult-to-treat patients, due to specific problems related to different anatomical sites of MS.

Sarcopenia as a predictive factor for febrile neutropenia during induction chemotherapy in head and neck squamous cell cancer.

OBJECTIVE: Febrile neutropenia (FN) is the most serious toxicity in patients with head and neck squamous cell carcinoma (HNSCC) treated with induction chemotherapy (IC). Although it is well-known that sarcopenia is a risk factor for severe toxicity of (chemo)radiotherapy, the data on the association between sarcopenia and FN during IC in HNSCC patients is rare. This study determined the impact of sarcopenia on FN during IC. METHODS: IC-treated patients with HNSCC were enrolled in this study. Skeletal muscle mass (SMM) at the C3 vertebral body was used to define sarcopenia from computed tomography (CT) scans. To determine the predictive effect of low SMM on FN, logistic regression analysis was performed. RESULTS: In this study, 71 patients were included, of whom 28 had low SMM and 14 experienced FN. In multivariate analysis, low SMM and high CRP were the independent predictive factors for FN. The combination index of sarcopenia and CRP showed a greater odds ratio than sarcopenia alone suggesting a more significant predicting indicator. CONCLUSIONS: Sarcopenia defined by CT imaging is associated with FN in patients with HNSCC treated with IC. The combination of sarcopenia and high CRP is a more significant risk factor, and it helps determine patients at risk of FN during IC.

Induction Chemotherapy for Locoregionally Advanced Sinonasal Squamous Cell Carcinoma.

Background There is emerging evidence to suggest the role of induction chemotherapy (IC) in definitive management of locoregionally advanced sinonasal squamous cell carcinoma (SNSCC). We evaluated the influence of IC on survival and predictors of its use in SNSCC patients. Methods The 2004 to 2017 National Cancer Database was queried for patients with locoregionally advanced SNSCC (T4/M0). Treatments were stratified into seven groups: definitive chemoradiation (CRT), IC with definitive CRT (IC + CRT), IC + CRT with salvage surgery (IC + CRT + Sx), definitive surgery (Sx), IC with definitive surgery (IC + Sx), definitive surgery with adjuvant radiation or CRT (Sx + ATx), or IC + Sx + ATx. Cox proportional-hazards regression assessed overall survival (OS) and logistic regression identified predictors of IC. Results Of 3,162 patients, 1,088 (34.4%) were female with a mean age of 63.4 ± 13.4 years. The 2- and 5-year OS rates were 58.6 and 42.0%, respectively. Compared with CRT, Sx + ATx (hazard ratio [HR]: 0.663; p < 0.001), IC + Sx (HR: 0.606; p = 0.005), or IC + Sx + ATx (HR: 0.468; p = 0.001) exhibited reduced mortality. Among patients who were treated with definitive surgery, those receiving IC had additional OS benefit (all p s < 0.05). Older age (odds ratio [OR]: 0.607; p < 0.001), female sex (OR: 0.759; p = 0.028), Black race (OR: 1.650; p < 0.001, T4b stage (OR: 1.674; p < 0.001), and higher N stage (OR: 1.395; p < 0.001) were predictors of IC. Conclusion IC prior to definitive surgery with or without adjuvant therapy exhibited the highest OS for locoregionally advanced SNSCC. Age, sex, race, and T/N staging were predictors of IC. Multimodal treatment regimens involving surgery as the primary modality may, therefore, provide the greatest therapeutic response.

Posthepatectomy Liver Failure in Patients with Splenomegaly Induced by Induction Chemotherapy for Colorectal Liver Metastases.

PURPOSE: With advances in chemotherapy, conversion surgery is often performed for initially unresectable colorectal cancer liver metastasis (CLM). However, unexpected posthepatectomy liver failure (PHLF) is sometimes associated with chemotherapy-associated liver injuries following long-term chemotherapy. We aimed to identify predictive factors for PHLF after conversion surgery for initially unresectable CLM. METHODS: We retrospectively identified 774 consecutive patients who underwent initial liver resections for histologically confirmed CLMs between 2010 and 2019 at our institute. We enrolled 107 patients with initially unresectable CLMs. Clinicopathological characteristics were evaluated to determine their association with PHLF. Logistic regression analysis was performed to analyze the predictors of PHLF. RESULTS: Among the 107 patients, PHLF occurred in 15 cases (14%). Multivariate analysis revealed that splenomegaly during preoperative chemotherapy (> 135%) was an independent risk factor for PHLF (P = 0.002; odds ratio 14.30; 95% confidence interval 2.69-76.08). In the analysis limited to the splenomegaly group, lower platelet counts, increased blood loss and operative times, and large liver resection areas (> 100 cm2) were significant risk factors for PHLF (P = 0.018, 0.043, 0.020, and 0.024, respectively). Among them, a liver resection area > 100 cm2 can be calculated preoperatively and correlate with a complex hepatectomy. CONCLUSION: These findings could help predict PHLF after conversion surgery and induction chemotherapy for initially unresectable CLMs. Careful decisions, including detailed procedures and timing of hepatectomy, should be made before conversion hepatectomy in patients who develop splenomegaly after induction chemotherapy and require complex hepatectomies with a large liver resection area.

Gemcitabine/Cisplatin versus docetaxel, cisplatin and 5-fluorouracil as induction chemotherapy in locally advanced nasopharyngeal carcinoma.

Induction chemotherapy followed by concomitant chemoradiation is the standard therapy for patients with locoregionally advanced NPC. There is a limitation of clinical studies that compare different induction regimens. The purpose of this work is to analyze the efficacy of two distinct chemotherapy regimens, docetaxel, cisplatin, and 5-fluorouracil (TPF) and gemcitabine/cisplatin (GP), in treating patients with loco-regionally advanced nasopharyngeal carcinoma (NPC). We analyzed 81 patients initially presented with stage III-IVA NPC from January 2019 to June 2023. Participants were randomized in 1:1 ratio to obtain GP regimen or TPF regimen followed by concurrent CRT. The overall response rate was 97.5% after induction chemotherapy in both groups (In GP arm, 78% of patients achieved complete remission compared to 70% of patients treated with TPF regimen). The satisfactory tumor response to induction chemotherapy was linked with significant enhanced progression free survival [CI (3.37-13.92), HR=2.16, P=0.001] and overall survival [CI (3.717-9.443), HR=1.873, P=0.001]. The GP regimen was both efficacious and well-tolerated. Leucopenia and neutropenia (Grade 3-4) were significantly lower in GP group contrasted to in TPF group. There was no significant difference in the 3-year DFS and OS between GP and TPF protocols.

Multicenter randomized phase III study of high-dose therapy with autologous stem cell transplantation versus observation for patients with newly diagnosed peripheral T-cell lymphoma who achieved complete metabolic response after induction therapy (JCOG2210, TRANSFER study).

Patients with peripheral T-cell lymphoma demonstrated a poor prognosis after obtaining a complete response with induction treatment compared to those with B-cell lymphoma. Once it relapsed, curative treatment is frequently limited to invasive treatments with significant treatment-related mortality, including allogeneic stem cell transplantation. The limitations of these treatment choices indicate the necessity for developing optimal consolidation therapies to prevent relapse. This multicenter randomized phase III trial aims to confirm the superiority of the high-dose therapy with autologous stem cell transplantation over observation alone in terms of progression-free survival for patients with newly diagnosed peripheral T-cell lymphoma who achieved complete metabolic response after induction therapy. A total of 140 patients from 52 hospitals will be enrolled in Japan over 5.5 years. This trial is registered in the Japan Registry of Clinical Trials as jRCTs031240169 (https://jrct.niph.go.jp/latest-detail/jRCTs031240169).

p16 status or response to induction chemotherapy, which predicts survival outcomes in Chinese oropharyngeal cancer treated with definitive radiotherapy?

PURPOSE: To identify whether p16 status or response to induction chemotherapy (IC) predicts the radiotherapy (RT) response and survival outcomes in Chinese oropharyngeal squamous cell carcinoma (OPSCC). METHODS: A total of 211 patients, including 128 p16-positive and 83 p16-negative were analyzed. All patients underwent IC followed by definitive RT or concurrent chemoradiotherapy (CCRT). Propensity score matching (PSM) was used to eliminate the baseline variations. RESULTS: Age, sex, smoking history, alcohol history, and primary site were unbalanced between different p16 status subgroups. Before PSM, the objective response rates to IC between p16-positive and p16-negative groups were 80.5 % and 85.5 % (p = 0.344). After RT, the complete response (CR) rates were 73.4 % and 66.3 %, respectively (p = 0.264). IC-sensitive (IC-s) subgroups had a higher percentage of RT-CR rate than the IC-resistant (IC-r) subgroups in both p16-positive and p16-negative patients. IC-s showed significant improvement in cancer-specific survival (CSS) (92.9 % vs. 53.6 %, p < 0.0001), progression-free survival (PFS) (p < 0.0001), locoregional relapse-free survival (LRFS) (p < 0.0001) and distant metastasis-free survival (DMFS) (p = 0.025). After PSM, the CR rates among different p16 groups remained comparable following RT (71.2 % vs. 65.8 %, p = 0.476). Before or after PSM, CSS, PFS, LRFS, and DMFS were similar between different p16 status either in IC-s or IC-r subgroups (p > 0.05). IC-r was independently associated with shorter PFS (HR = 2.661, p = 0.002) and LRFS (HR = 2.876, p = 0.002; HR = 2.78, p = 0.018). CONCLUSIONS: Response to IC is an important predictor of prognosis in Chinese OPSCC treated with definitive RT. Poor response to IC is associated with unsatisfactory outcomes either in p16-positive or p16-negative OPSCC.

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.

Induction chemotherapy with cemiplimab in a patient with coexistent vulvar cancer and autoimmune disease: A case report.

There is limited data regarding the use of immunotherapy for patients with vulvar squamous cell carcinoma and coexisting autoimmune disease. Cemiplimab is a PD-1 inhibitor approved for use in patients with locally advanced and metastatic cutaneous squamous cell carcinoma. However, little is known about its efficacy in the setting of vulvar cancer. We present a case of advanced vulvar squamous cell carcinoma treated with induction chemotherapy and immunotherapy with cemiplimab followed by definitive chemoradiation in the setting of multiple autoimmune diseases. She achieved a complete clinical response and experienced no worsening of her autoimmune conditions despite cessation of her immunosuppressants and initiating an immune checkpoint inhibitor. We review existing data on neoadjuvant treatment of vulvar cancer and the use of cemiplimab in genital and inguinal squamous cell carcinomas. Ongoing exploration of cemiplimab's efficacy in vulvar cancer and safety in immunosuppressed patients is critical.

Evaluating the Efficacy of Different Treatment Intensities in Nasopharyngeal Carcinoma Patients: A Nationwide Cancer Registry-Based Study.

OBJECTIVE: The aim of this study was to evaluate the efficacy of different treatment intensities (TIs) in patients with nasopharyngeal carcinoma (NPC). METHODS: The study assessed newly diagnosed, non-metastatic NPC patients from the Taiwan Cancer Registry between 2010 and 2017. TIs were divided into four groups: TI1 [radiotherapy (RT) alone or induction chemotherapy (IC) followed by RT); TI2 (concurrent chemoradiotherapy (CRT) alone); TI3 (IC followed by CRT or CRT followed by adjuvant chemotherapy (AC)]; and TI4 (IC followed by CRT followed by AC). The primary outcome was cancer-specific survival (CSS). RESULTS: The study included 9863 patients. For stage I-II NPC patients, there was no significant difference in CSS among the different TI groups. For stage III patients, those receiving TI3 had better CSS (hazard ratio [HR] 0.69) compared with those receiving TI1. No significant differences in CSS were noted among those receiving TI2, TI3, and TI4. For stage IVA-B patients, those receiving TI2 (HR 0.70), TI3 (HR 0.49), and TI4 (HR 0.43) had better CSS compared with those receiving TI1. Compared with stage IVA-B patients receiving TI2, those receiving TI3 (HR 0.70) and TI4 (HR 0.61) had significantly better CSS. No differences in CSS were noted between those receiving TI3 and TI4. CONCLUSIONS: For stage I-II NPC patients, RT alone is appropriate. For stage III and IVA-B patients, IC + CRT or CRT + AC may be needed to achieve optimal outcomes. No advantage of IC + CRT + AC over IC + CRT or CRT + AC was observed.

New induction chemotherapy using intra-arterial infusion for tongue squamous cell carcinoma to avoid reconstructive surgery: A 6 case reports.

Most tongue squamous cell carcinoma (TSCC) classified as T3 require reconstructive surgery, which inevitably causes problems with oral functions. We propose new induction chemotherapy using intra-arterial infusion for TSCC classified as T3 to avoid reconstructive surgery. This chemotherapy regimen consists of intra-arterial infusion of docetaxel and cisplatin and systemic administration of 5-fluorouracil. As a result of this treatment, the therapeutic effect was a complete response in five patients and a partial response in one patient, and the overall response rate was 100%. All six patients underwent partial resection because their tumors shrank with this induction chemotherapy. In addition, adverse events of grade 3 or more did not occur in all six patients. The median follow-up duration for all patients was 34 months, and they are alive. This intra-arterial chemotherapy regimen was shown to be highly efficacious and safe.

Pathologic response evaluation of localized or locally advanced esophageal carcinoma to induction chemotherapy followed by preoperative concurrent chemotherapy and hypofractionated radiotherapy: a clinical trial.

Objective: Esophageal cancer is a therapeutic challenge in most healthcare systems. Most patients present with locally advanced disease at diagnosis. Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced esophageal carcinoma. Since achieving a complete pathological response in postoperative specimens following neoadjuvant therapy is associated with improved patient survival, this study was designed to evaluate the pathologic response of localized or locally advanced esophageal carcinoma to induction chemotherapy followed by preoperative concurrent chemotherapy and hypofractionated radiotherapy (HFR). Methods: This single-arm clinical trial (IRCT20210623051676N1) evaluated patients with squamous cell carcinoma or adenocarcinoma of the esophagus, stage cT2-T4a N0 M0 or cT1-T4a N+ M0. Patients received 3-5 cycles of weekly induction chemotherapy with the paclitaxel (50 mg/m2) and carboplatin (AUC=2) regimen, followed by weekly concurrent CRT with the same chemotherapy regimen. The radiation dose was 40 Gy, delivered over 16 fractions, 5 days per week (2.5 Gray/fraction). Patients underwent surgery 4-6 weeks after completion of CRT. The surgical specimens were evaluated for pathological response. A p-value of < 0.05 was considered significant in all analyses. Results: Out of 54 patients enrolled in this study, 45 completed the neoadjuvant protocol. Of these 45 patients, 32 underwent surgery and were finally analyzed. The mean age of the patients was 59.9 ± 8.6 years (range, 37-75 years). The location of the tumor was in the mid-thoracic esophagus in most patients (21, 65.6%) and the most common histological type was SCC (29, 90.6%). The median number of induction and concurrent chemotherapy cycles was 5 (4.8 ± 1.3 course, range, 1-10) and 3 (2.6 ± 0.8 course, range, 0-4), respectively. Among 45 patients who completed the neoadjuvant protocol, the most common toxicities were grade 3 neutropenia (15.6%), acute renal failure (4.4%), and odynophagia (37.8%). Nearly two-thirds of the patients experienced complete or near-complete responses (71.9%, 23 patients). Partial response was reported in 6 patients (18.8%) and poor response in 3 patients (9.4%). Conclusion: Preoperative induction chemotherapy followed by HFR with concurrent chemotherapy has low toxicity and side effects, good tolerance, and significant efficacy in the treatment of patients with esophageal cancer. Clinical trial registration: https://irct.behdasht.gov.ir/trial/59930, identifier NCT05745545.

Evaluation of pembrolizumab plus cisplatin and fluorouracil in radical treatment for patients with T4b esophageal squamous cell carcinoma.

BACKGROUND: Pembrolizumab plus cisplatin and 5-fluorouracil administered as first-line therapy for advanced esophageal cancer patients has shown a better objective response and survival than conventional chemotherapy with less severe hematological adverse events. The safety and efficacy of this regimen were evaluated in patients with T4b esophageal squamous cell carcinoma (ESCC). METHODS: Eight consecutive patients with T4b ESCC received this regimen according to KEYNOTE-590 as induction, and they were evaluated after 1-3 courses. The programmed death-ligand 1 (PD-L1) combined positive score (CPS) was also evaluated before chemotherapy. Efficacy for the primary lesion was evaluated by our original formula for the tumor reduction rate. RESULTS: The numbers of patients with partial response (PR), stable disease, and progressive disease (PD) were 5, 1, and 2, respectively. The tumor reduction rate ranged from 69 to 87% in PR patients, and all PR patients had relief from T4b. Two patients underwent conversion surgery with R0 resection. PD-L1 CPS was over 90 in 2 PR patients, but under 10 in 2 other PR patients. PD-L1 CPS was under 10 in PD patients. One patient had hyperprogression, resulting in an esophago-pulmonary fistula. Greater than grade 3 adverse events were bleeding gastric ulcer in one patient (12.5%), neutropenia without G-CSF in 3 patients (37.5%), and hypopotassemia in 1 patient (12.5%). No patient had febrile neutropenia. CONCLUSIONS: Marked tumor reduction was confirmed in 62.5% of patients with pembrolizumab plus cisplatin and 5-fluorouracil with less adverse events. This regimen could be administered as induction chemotherapy for patients with T4b ESCC.

Adding venetoclax or hypomethylating agents to induction chemotherapy as first-line treatment for adults with acute myeloid leukemia: a retrospective case-cohort study.

Background: The response rate of traditional first-line induction chemotherapy (IC) for newly diagnosed acute myeloid leukemia needs to be improved, but it is not clear whether adding venetoclax or hypomethylating agents (HMAs) to IC will improve the response rate. Objective: To determine whether venetoclax or HMAs could increase the response rate of IC in patients with newly diagnosed acute myeloid leukemia (AML). Design: A retrospective, propensity score matching analysis. Methods: Newly diagnosed AML patients at Tongji Hospital between 2021 and 2023 were included in this study. By matching cases and controls based on age, gender, baseline bone marrow blast cell proportion, type of AML, and the National Comprehensive Cancer Network (NCCN) risk stratification group, we compared the response rate (CR, CR/CRi, ORR, and MRD negative) and hematological adverse events in newly diagnosed AML treated with IC plus venetoclax or HMAs versus IC alone after one cycle of IC. Results: The addition of venetoclax could improve CR/CRi of IC (83.8% for IC plus venetoclax vs 66.1% for IC alone, p = 0.029). The addition of venetoclax to IA regimen did not improve CR/CRi of IA regimen (76.9% for IA plus venetoclax vs 76.2% for IA alone, p = 0.986). The addition of HMAs could not only improves CR/CRi of IC (85.3%% for IC plus HMAs vs 65.4% for IC alone, p = 0.002) but also improves CR/CRi of IA regimen (91.3% for IA plus HMAs vs 70.0% for IA alone, p = 0.034). The addition of HMAs could improve CR/CRi of patients with adverse mutations (FLT3, IDH1/2, K/NRAS) after IC. The addition of venetoclax and HMAs both extended the duration of agranulocytosis and thrombocytopenia. Conclusion: Adding HMAs might improve CR/CRi of IC including IA. Adding venetoclax might not improve CR/CRi of IA. A well-designed prospective randomized controlled study is now warranted.

Ultra High-risk Gestational Trophoblastic Neoplasia.

Ultra high-risk gestational trophoblastic neoplasia (GTN) refers to patients with World Health Organization prognostic risk scores of at least 13. The mortality risk for these patients averages 30%. Ultra high-risk GTN more frequently presents with higher tumor volume, liver and/or brain metastases, and very high human chorionic gonadotropin levels. The diagnostic evaluation must include a thorough evaluation for central nervous system disease. Prompt initiation of cisplatin - etoposide induction chemotherapy reduces the risks of early death. Collaborative services such as neurosurgery, radiation oncology, and interventional radiology may be required to manage hemorrhagic lesions.

Long-term results of induction chemotherapy for non-operable esophageal squamous cell carcinoma followed by concurrent chemoradiotherapy: a single-centre experience.

BACKGROUND: This study aimed to investigate the long-term clinical outcomes and toxicities of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) vs. CCRT alone in patients with non-operable esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Between 2008 and 2022, 271 ESCC patients who received definitive CCRT based on intensity modulated radiation therapy (IMRT)/volumetric modulated arc therapy (VMAT) were enrolled. Through a propensity score-matched (PSM) method, 71 patients receiving IC and CCRT were matched 1:1 to patients who received CCRT alone. The Kaplan-Meier method and Cox proportional hazards model were applied to analyze survival and prognosis. RESULTS: The IC + CCRT group had no improvement in 5-year overall survival (OS) rate, recurrence-free survival (RFS) rate, and distant metastasis-free survival (DMFS) rate (all p > 0.05) compared with the CCRT group. The 5-year OS rate (65.6% vs. 17.6% vs. 29.3%, p < 0.001), RFS rate (65.6% vs. 17.6% vs. 26.9%, p < 0.001), and DMFS rate (62.5% vs. 10.3% vs. 27.2%, p < 0.001) of the IC good responders were significantly higher than that of the IC poor responders and CCRT group. Multivariate analysis revealed that total radiotherapy time (≥ 49 days) and stage III/IV were independent predictive factors of OS, RFS, and DMFS. No significant differences were observed in the rates of grade 3-4 toxicities between both groups. CONCLUSIONS: Our results showed the addition of IC to CCRT was not superior to CCRT in unselected ESCC patients, while IC responders could benefit from this regime without an increase in toxicities.

Contemporary treatment and outcome of sinonasal undifferentiated carcinoma: A meta-analysis.

Induction chemotherapy (IC) recently gained importance for treatment of sinonasal undifferentiated carcinoma (SNUC). We analyzed our SNUC cases and performed a meta-analysis with focus on survival-rates stratified by treatment. SNUC cases at our institution were retrospectively evaluated. A systematic literature review was conducted to analyze treatment and outcome of SNUC. To calculate 5-year and 2-year overall survival (OS), individual patient data (IPD) were analyzed using Kaplan-Meier estimators and Cox proportional hazard regression to identify associations between types of therapy and survival. A random effects model for pooled estimates of 5-year survival was applied to studies without IPD data. Five-year OS of our SNUC cases (n = 9) was 44.4%. The IPD analysis (n = 192) showed a significantly better 5-year OS for patients who received induction chemotherapy (72.6% vs. 44.5%). The pooled 5-year OS of 13 studies identified in the literature search was 43.8%. IC should be considered in every patient diagnosed with SNUC.