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Background: Autologous hematopoietic stem cell transplantation (ASCT) has emerged as a cornerstone in multiple myeloma (MM) management, offering the prospect of prolonged disease control. However, the induction chemotherapy drugs required prior to ASCT carry cardiovascular toxicity (CVT), potentially leading to a range of cardiovascular complications. Methods and Results: This retrospective observational study, conducted at Guangdong Provincial People's Hospital from January 2020 to December 2023, analyzed 47 of the initial 173 patients who met the criteria. The cohort, comprising 22 males (46.81%) and 25 females (53.19%), had a mean age of 55.68 ± 11.38 years. They underwent various induction chemotherapy regimens, receiving a median of 5 (4–6) cycles of the course over an average duration of 7.10 ± 2.46 months. Before ASCT treatment following induction chemotherapy, echocardiographic findings indicated reductions in left ventricular end‐systolic dimension, right atrial diameter, E‐wave velocity, E/e' ratio, and the E/A ratio. The latter altered from a pretreatment value greater than 1 to posttreatment less than 1, marking diastolic dysfunction emergence or aggravation in 51.06% of patients. The electrocardiographic data indicate a reduced heart rate and prolonged P‐wave duration and P‐R duration, with an increase in arrhythmia incidence to 19.15% following induction chemotherapy. Conclusion: Induction chemotherapy, administered prior to ASCT in patients with MM, can lead to the emergence or aggravation of cardiac diastolic dysfunction and increase the incidence of arrhythmic events. Therefore, it is crucial to emphasize the importance of balancing the benefits and risks of induction chemotherapy to maximize its efficacy while minimizing CVT. [ABSTRACT FROM AUTHOR]

Simple Summary: Oropharyngeal squamous cell carcinoma (OPSCC) and its treatments often result in dysphagia, necessitating prolonged use of a nasogastric (NG) tube. NG tube removal rates in patients with OPSCC were compared between two strategies (induction chemotherapy followed by surgery versus induction chemotherapy followed by chemoradiation therapy). The outcomes related to swallowing function and NG tube dependence were shared with clinical physicians for guidance. Objectives: This retrospective observational study investigated to determine whether surgery or chemoradiation therapy after induction chemotherapy leads to better swallow function for oropharyngeal cancer patients. Methods: We documented the treatment paths and results of 267 patients with oropharyngeal squamous cell cancer (OPSCC). By quantifying nasogastric (NG) tube usage, surgery after induction chemotherapy (IC–surgery), and chemoradiation therapy after induction chemotherapy (IC-CRT) could be compared to determine the effectiveness of each. Cancer stages were also recorded concerning treatment options. The differences in NG tube usage IC–surgery and IC-CRT groups were compared. The NG tube dependence rates were also presented. Results: The prognosis and tube dependence differed significantly between the two groups. The IC–surgery had a better prognosis compared to IC-CRT for oropharyngeal cancer. The findings indicated that NG tube dependence was greater in advanced tumor stage 4 compared to stages 1–3, and NG tube dependence rates were higher for patients who underwent chemoradiation therapy after induction chemotherapy. Swallowing function was better in the IC–surgery group compared to the IC-CRT group. Conclusions: Higher NG tube retention rates and NG dependence are found in OPSCC patients who choose CRT as their treatment and also in the advanced-stage group. [ABSTRACT FROM AUTHOR]

This study aims to investigate the clinical characteristics of infections following induction chemotherapy for acute myeloid leukemia (AML) in children and identify risk factors associated with severe infections. Newly diagnosed children with AML treated at the Hematology Oncology Center of Beijing Children's Hospital affiliated to Capital Medical University (referred to as the "Beijing ward") and Baoding Hospital of Beijing Children's Hospital (referred to as the "Baoding ward") between November 2019 and August 2022 were enrolled. The diagnosis and treatment of the patients were carried out in accordance with the CCLG-AML 2019 protocol. Their essential information and infection-related indicators were collected. The various indicators between the two centers were compared. The incidence of infection in children with AML was 100%, with a severe infection rate of 15.3% and an infection-related mortality rate of 2.4%. Respiratory infections accounted for 39.7% of all infections events, and unspecified site infection for 32.2%. Bacterial infections were predominant at 51.2%. The bed unit area (BUA) varied significantly with 4.1 m2 in the Beijing ward and 10 m2 in the Baoding ward. Significant differences were observed in gastrointestinal infections (P < 0.001) and severe infections (P = 0.014) between the two wards. Several factors were identified as risk factors for severe infections, including BUA difference (OR = 4.353, 95% CI: 1.078–17.578), time of entering neutropenia phase after chemotherapy (OR = 6.369, 95% CI: 1.713–23.675) and bloodstream infection (OR = 7.466, 95% CI: 1.889–29.507). Respiratory tract infections and infections of unspecified site are most common during induction phase for pediatric AML. Bacteria, especially G− bacteria, are the leading pathogens. Risk factors for severe infections include a small BUA, entering neutropenia phase ≤ 5.5 days after chemotherapy, and bloodstream infection. Recognizing these risk factors can aid in the early identification and intervention of severe infections. [ABSTRACT FROM AUTHOR]

Posterior thoracic para-aortic lymph node (TPAN) metastasis is a distant metastasis of esophageal cancer. Several case reports have shown that radical esophagectomy and lymphadenectomy for posterior TPAN improve the prognosis of patients with cStage IVB esophageal cancer and solitary posterior TPAN metastasis; however, the true value of this procedure is unclear. The primary objective of this study was to evaluate the short- and long-term outcomes of lymphadenectomy for posterior TPAN after induction chemotherapy in esophageal cancer. This study enrolled 15 patients who underwent radical esophagectomy for cStage IVB esophageal cancer with solitary posterior TPAN metastasis after induction chemotherapy between January 2013 and October 2022 at our hospital. The short- and long-term of radical esophagectomy and lymphadenectomy for posterior TPAN were retrospectively evaluated. All patients who underwent radical esophagectomy and lymphadenectomy for posterior TPAN achieved a pR0 in this study. The median operative time and intraoperative blood loss were 385 minutes and 164 ml, respectively. Four patients (26.7%) had postoperative complications of Clavien-Dindo grade II or more. The median postoperative hospital stay was 15 days. The 5-year overall survival and recurrence-free survival rates were 55.6% (95% confidence interval: 23.1–79.0) and 55.0% (95% confidence interval: 25.3–77.2), respectively. We showed that lymphadenectomy for posterior TPAN metastasis was associated with an improved prognosis of some patients with advanced esophageal cancer. This technique may serve as a viable treatment option for patients who respond well to induction chemotherapy. [ABSTRACT FROM AUTHOR]

Definitive chemoradiotherapy (DCRT) is administered as standard treatment for patients with cT4 and/or M1Lym esophageal squamous cell carcinoma (ESCC); however, its long-term result is inadequate. Although several studies have reported that conversion surgery can improve the survival of these patients, none have identified significantly better long-term survival than that achieved by DCRT. Thus, enhancing DCRT seems important to improve the survival of these patients. A strategy of shrinking tumor volume before DCRT and providing consolidation chemotherapy for systemic control is expected to improve the survival of these patients. Pembrolizumab plus cisplatin and fluorouracil has demonstrated good local control and significant improvement in the survival of patients with advanced esophageal cancer. Based on these results, the following strategy is proposed: This protocol should be applied as induction for these patients; then, DCRT should be provided depending on the initial response; and finally, adjuvant chemotherapy with an immune checkpoint inhibitor should be given to all responders. [ABSTRACT FROM AUTHOR]

The influence of human immunodeficiency virus (HIV) infection on clinical outcomes in patients receiving (chemo)radiation therapy (RT) for squamous cell carcinoma of the anus (SCCA) is debated. The objective of this study was to compare efficacy and safety according to HIV status in patients with SCCA treated with C/RT. Between January 2015 and April 2020, 488 patients with a known HIV status (17.6% HIV+) were treated with radiation therapy for SCCA and included in the FFCD-ANABASE multicentric prospective cohort. Clinical outcomes including overall survival (OS), locoregional recurrence-free survival, colostomy-free survival, response rate at 4 to 6 months, cancer-specific survival, relapse-free survival, and severe acute and late toxicity were compared between HIV+ and HIV− patients. The median follow-up was 35.8 months. HIV+ patients were younger (P <.01) and predominantly male (P <.01). Intensity modulated radiation therapy was performed in 80.7% of patients, and 80.9% received concurrent chemotherapy. A higher proportion of HIV+ patients received induction chemotherapy compared with HIV- patients. No statistically significant difference in overall treatment time or severe acute and late toxicities was found between HIV+ and HIV- patients. In univariate analyses, OS (HR = 2.1 [CI 95% 1.2;3.5], P =.007), locoregional recurrence-free survival (HR = 1.7 [1.1;2.7], P =.02), and colostomy-free survival (HR = 1.7 [1.1;2.6], P =.01) were significantly shorter in HIV+ patients than in HIV- patients. Response rate, cancer-specific survival, and relapse-free survival were not significantly different. The recurrence site was significantly different according to HIV status. In the multivariate analysis, prognostic factors for OS were a World Health Organization performance status of ≥1 for the whole population, as well as HIV+ status for the subgroup of women. HIV+ patients treated with chemo-RT for SCCA have poorer clinical outcomes, especially women. No difference was found in toxicity according to HIV status with intensity modulated radiation therapy technique. [ABSTRACT FROM AUTHOR]

Backgrounds: AML patients with FLT3-ITD mutation experience a poor prognosis. Our study evaluated the clinical characteristics, remission, relapse, and clinical outcomes of these patients. We also assessed the effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and sorafenib in treating AML patients with FLT3-ITD mutation. Methods: Fifty-five newly diagnosed AML patients with FLT3-ITD mutation in our center were retrospectively enrolled between January 2018 and June 2023. Multiple fusion genes and gene mutations were identified for the diagnosis of AML. Survival curves were calculated by employing the Kaplan-Meier method, and the differences between them were evaluated by using the log-rank (Mantel-Cox) test. Results: Twenty-seven patients underwent allo-HSCT. The allo-HSCT group had a significantly extended followup period compared to the non-HSCT group (p < 0.001). Mutations in both NPM1 and FLT3-ITD were present in 18 out of the 55 patients (32.7%). Among them, eleven patients were given sorafenib plus chemotherapy induction therapy, and forty-four received mono-chemotherapy. The HSCT group had a higher overall survival (OS) rate than the non-HSCT group (p < 0.001), and a higher relapse-free survival (RFS) rate as well (p = 0.0017). No statistically significant difference in OS and RFS was observed when compared with sorafenib plus chemotherapy and mono-chemotherapy (p > 0.05). FLT3-ITD-positive patients with and without NPM1 mutation did not experience a significant difference in OS and RFS rates (p > 0.05). Conclusions: Allo-HSCT immediately following complete remission could improve outcomes for young adults diagnosed with FLT3-ITD-positive AML. However, we found no statistical difference in the overall response rate (ORR) and clinical outcome between sorafenib combined with chemotherapy and chemotherapy alone. [ABSTRACT FROM AUTHOR]

Background: Achieving first complete remission with induction chemotherapy (ICT) for acute myeloid leukemia (AML) correlates with patient's prognosis. This study aimed to determine the correlation between oxidative stress and the outcome of ICT in AML patients. Methods: A total of 195 AML patients underwent initial ICT at the Longyan First Affiliated Hospital of Fujian Medical University from 06-11-2018 to 12-30-2023. Three weeks after ICT, patients were divided into two groups, CR (complete remission) and PR (partial remission), by detecting blood parameters and bone marrow cells. Serum oxidative stress-related factors, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), and growth/differentiation factor-15 (GDF15) activities or levels were measured to assess the diagnostic value of these factors as a means of diagnosing the efficacy of ICT in patients. Factors affecting PR after initial ICT were analyzed. Results: Patients in the PR group had higher levels of oxidative stress three weeks after initial ICT. Compared with the CR group, patients in the PR group had elevated levels of MDA and GDF15 and reduced activities of SOD, GSH-Px, and T-AOC. Serum MDA levels (AUC 0.709; 95% CI. 0.618 - 0.781) and the combination of multiple indicators (AUC 0.791; 95% CI. 704 - 0.851) had diagnostic value for the efficacy of AML patients undergoing ICT. Serum MDA and GDF15 exceeding cutoff values were risk factors for PR in AML patients undergoing ICT, as were serum SOD and T-AOC below cutoff values. Preoperative malnutrition was associated with PR in patients. Conclusions: Serum oxidative stress-related factors in AML patients are helpful in detecting the efficacy of ICT. Oxidative stress in response to ICT is useful for characterizing the efficacy in AML patients after ICT. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background/Objectives: Frailty is a common condition among older adults and is associated with an increased risk of adverse health outcomes, including mortality, disability, dysmobility, falls, and hospitalization. In patients with atrial fibrillation (AF), these risks are further exacerbated. However, evidence linking AF and frailty, particularly in the South American context, is limited. This study aimed to assess frailty and other geriatric conditions in older outpatients with atrial fibrillation in a resource-limited setting in Lima, Peru. Methods: In this cross-sectional study, we included adults aged 60 years and older diagnosed with atrial fibrillation who were attending outpatient check-ups. Patients who were hospitalized, receiving chemotherapy induction, or presenting with acute infections or exacerbations were excluded. Standardized questionnaires were used to assess frailty, cognitive impairment, and functional dependence. Statistical analysis was performed using R Studio version 4.3.1, with a significance level set at p < 0.05. Results: Among the 200 patients who agreed to participate (mean age 74.76 ± 8.42 years, 41% females), 28.5% exhibited frailty, and 46.5% were classified as prefrail. Frailty and prefrailty were significantly associated with older age (p<0.01), female gender (p = 0.01), illiteracy (p<0.01), heart failure (p<0.01), falls (p<0.05), cognitive impairment (p<0.01), and functional dependence (p<0.01). Multivariate analysis revealed significant associations between frailty and cognitive impairment (p<0.05), frailty and functional dependence (p<0.05), and cognitive impairment and functional dependence (p<0.05). Conclusions: One-third of older outpatients with atrial fibrillation were identified as frail, while half were classified as prefrail. In this population, frailty frequently coexists with cognitive impairment and functional dependence, highlighting the need for timely screening and the implementation of evidence-based interventions for individuals with atrial fibrillation in resource-limited settings. [ABSTRACT FROM AUTHOR]

Background: Patients with locally advanced non-small cell lung cancer (LANSCLC) usually bear high tumor burden and are not tolerated well to concurrent chemoradiation therapy (CRT) followed by consolidation immunotherapy. We investigated the feasibility of chemoimmunotherapy as induction therapy before CRT for LA-NSCLC. Methods: We retrospectively analyzed data from 91 patients with unresectable stage III NSCLC treated with either induction chemoimmunotherapy or chemotherapy before CRT. Tumor responses, survival statistics, and toxic effects were compared. The dosimetric parameters of the RT protocol were evaluated. The primary endpoint was progression-free survival (PFS). The overall response (ORR), the depth of response (DpR) were accessed at the end of CRT (ORRinduc+CRT, DpRinduc+CRT) and induction therapy (ORRinduc, DpRinduc). Results: The median PFS (mPFS) were significantly longer in the chemoimmunotherapy induction group (13.5 months vs. 11.2 months; HR, 0.56; 95% CI, 0.32-0.97; p=0.036). The ORRinduc+CRT, median DpRinduc+CRT (mDpRinduc+CRT) and mDpRinduc were significantly higher in the chemoimmunotherapy induction group (ORRinduc+CRT, 84.0% vs. 65.9%, p=0.044; mDpRinduc+CRT, 49.5% vs. 39.0%, p = 0.012; mDpRinduc, 38.5% vs. 28.0%, p=0.044). Incidence of treatment-related adverse events (AE) was similar between groups, with myelosuppression being the most common grade = 3 AE. Regarding radiotherapy, adopting a mapping strategy with a 5-8 mm margin for clinical tumor volume resulted in decreased radiation doses to critical organs in the chemoimmunotherapy induction group. Conclusions: Chemoimmunotherapy induction therapy before CRT improves efficacy with comparable incidence of AEs compared to chemotherapy induction in LA-NSCLC patients. Further studies are warranted to validate these findings. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Locally advanced cervical cancer is treated with chemoradiotherapy (standard of care), but many patients still relapse and die from metastatic disease. We investigated chemoradiotherapy with or without induction chemotherapy to determine whether induction chemotherapy improves both progression-free survival and overall survival. The INTERLACE trial was a multicentre, randomised phase 3 trial done at 32 medical centres in Brazil, India, Italy, Mexico, and the UK. Adults (aged ≥18 years) with locally advanced cervical cancer (FIGO 2008 stage IB1 disease with nodal involvement, or stage IB2, IIA, IIB, IIIB, or IVA disease) were randomly assigned (1:1), by minimisation, using a central electronic system, to standard cisplatin-based chemoradiotherapy (once-a-week intravenous cisplatin 40 mg/m2 for 5 weeks with 45·0–50·4 Gy external beam radiotherapy delivered in 20–28 fractions plus brachytherapy to achieve a minimum total 2 Gy equivalent dose of 78–86 Gy) alone or induction chemotherapy (once-a-week intravenous carboplatin area under the receiver operator curve 2 and paclitaxel 80 mg/m2 for 6 weeks) followed by standard cisplatin-based chemoradiotherapy. Stratification factors were recruiting site, stage, nodal status, three-dimensional conformal radiotherapy or intensity modulated radiotherapy, age, tumour size, and histology (squamous vs non-squamous). Primary endpoints were progression-free survival and overall survival within the intention-to-treat population. This trial is registered with ClinicalTrials.gov , NCT01566240 , and EUDRACT, 2011-001300-35. Between Nov 8, 2012, and Nov 17, 2022, 500 eligible patients were enrolled and randomly assigned to the chemoradiotherapy alone group (n=250) or the induction chemotherapy with chemoradiotherapy group. Of 500 patients, 354 (70%) had stage IIB disease and 56 (11%) stage IIIB disease. Pelvic lymph nodes were positive in 215 (43%) patients. 230 (92%) patients who received induction chemotherapy had at least five cycles. Median interval between induction chemotherapy and chemoradiotherapy was 7 days. Four or more cycles of cisplatin were given to 212 (85%) participants in the induction chemotherapy with chemoradiotherapy group and to 224 (90%) of participants in the chemoradiotherapy alone group. 462 (92%) participants received external beam radiotherapy and brachytherapy with a median overall treatment time of 45 days. After a median follow-up of 67 months, 5-year progression-free survival rates were 72% in the induction chemotherapy with chemoradiotherapy group and 64% in the chemoradiotherapy alone group with a hazard ratio (HR) of 0·65 (95% CI 0·46–0·91, p=0·013). 5-year overall survival rates were 80% in the induction chemotherapy with chemoradiotherapy group and 72% in the chemoradiotherapy alone group, with an HR of 0·60 (95% CI 0·40–0·91, p=0·015). Grade 3 or greater adverse events were reported in 147 (59%) of 250 individuals in the induction chemotherapy with chemoradiotherapy group versus 120 (48%) of 250 individuals in the chemoradiotherapy alone group. Short-course induction chemotherapy followed by chemoradiotherapy significantly improves survival of patients with locally advanced cervical cancer. Cancer Research UK and University College London–University College London Hospitals Biomedical Research Centre. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

AbstractHypomethylating agents (HMA) and venetoclax (VEN) are commonly used in patients with IDH-mutated (IDHm) acute myeloid leukemia (AML) ineligible for induction chemotherapy. While prior studies demonstrated high response and survival rates with HMA/VEN in IDHm AML, the impact of treatment modifications in real-world settings is unclear. We retrospectively reviewed 89 IDHm AML patients treated with HMA/VEN from January 2018 to June 2023. CR/CRi rates were 76% in newly diagnosed (ND) and 55% in relapsed/refractory (R/R) patients, and median overall survival was 29.2 months (ND) and 17.1 months (R/R), respectively. Treatment modifications were common. Early VEN reductions were associated with lower response rates but not worse survival. Prolonged cycles were not associated with worse response rates or survival. Significant neutropenia and ED visits or unplanned hospitalizations were considerable before and after CR/CRi, though febrile neutropenia decreased afterward. HMA/VEN is efficacious, with treatment modifications not affecting survival, though long-term toxicities are notable. [ABSTRACT FROM AUTHOR]

Introduction: Olfactory carcinoma (OC) is a rare tumor that is often misdiagnosed as olfactory neuroblastoma (ONB). Due to its rarity, there is no established standard treatment for OC, and there have been no reports of successful long-term follow-up treatment yet. Case Presentation: Two male patients, aged 54 and 48 years, presented with similar symptoms of nasal obstruction, anosmia, facial swelling, and epistaxis. Imaging in both cases revealed large, locally advanced sinonasal neoplasms. Initial biopsies were concerning for ONB; however, final pathological analyses confirmed high-grade OC. Treatment comprised induction chemotherapy, extensive skull base tumor resection, adjuvant chemoradiotherapy, and reconstructive surgery in both cases. The 54-year-old remains disease-free at 7 years, while the 48-year-old demonstrates no evidence of disease at 8 months. Conclusion: Accurate diagnostic differentiation is imperative to optimize a treatment approach. Although outcomes with OC tend to be worse than those of ONB, effective control can be achieved with judicious concurrent use of neoadjuvant, surgery, and adjuvant treatments. Ongoing surveillance, biobanking, and genomic analysis are crucial to gain a better understanding of this complex disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Evaluation of Neoadjuvant Chemotherapy Followed by Concurrent Chemoradiation in Locally Advanced Head and Neck Squamous Cell Carcinoma This study investigated the effectiveness of adding neoadjuvant chemotherapy, a course of drugs given before radiotherapy, to standard chemoradiation treatment for patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) in a rural medical college in India. The researchers enrolled 252 patients with LAHNSCC who had not spread to other parts of the body. Half of the patients received neoadjuvant chemotherapy with paclitaxel and carboplatin followed by concurrent chemoradiation with cisplatin and radiation therapy. The other half received only concurrent chemoradiation. The analysis showed that a slightly higher percentage of patients achieved a complete response with neoadjuvant chemotherapy followed by chemoradiation compared to those who received only chemoradiation. However, the difference was not statistically significant, meaning it may have occurred by chance. Additionally, no significant difference was observed in terms of side effects between the two groups. In conclusion, the study did not find strong evidence that neoadjuvant chemotherapy improves response rates in patients with LAHNSCC when compared to standard chemoradiation treatment. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the efficacy and safety of using metronomic S-1 adjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma (LANPC). Materials and Methods: We retrospectively collected data on patients diagnosed with LANPC between January 2016 and December 2021. All patients were treated with induction chemotherapy and concurrent chemoradiotherapy with or without metronomic chemotherapy (MC). Toxicities during MC were recorded. The chi-square test, Kaplan-Meier methods, propensity score matching (PSM), and Cox proportional hazards model were used for statistical analyses. Results: A total of 474 patients were identified, including 64 (13.5%) and 410 (83.5%) patients with or without receiving MC, respectively. Patients who received metronomic S-1 had significantly better 3-year locoregional recurrence-free survival (LRFS) (100% vs. 90.9%, p=0.038), distant metastasis-free survival (DMFS) (98.5% vs. 84.1%, p=0.002), disease-free survival (DFS) (98.4% vs. 77.5%, p < 0.001), and overall survival (OS) (98.0% vs. 87.7%, p=0.008) compared to those without metronomic S-1. The multivariate prognostic analysis revealed that metronomic S-1 was identified as an independent prognostic factor associated with better DMFS (hazard ratio [HR], 0.074; p=0.010), DFS (HR, 0.103; p=0.002) and OS (HR, 0.127; p=0.042), but not in LRFS (p=0.071). Similar results were found using PSM. Common adverse events observed in the metronomic S-1 group included leukopenia, neutropenia, increased total bilirubin, anorexia, rash/desquamation, and hyperpigmentation. All patients with adverse events were grade 1-2. Conclusion: It is worth conducting a randomized controlled trial to assess the effect of metronomic S-1 on survival outcomes and toxicities of LANPC. [ABSTRACT FROM AUTHOR]

The document discusses the importance of antiviral prophylaxis to prevent herpes simplex virus (HSV) and varicella zoster virus (VZV) reactivation in adult patients with newly diagnosed acute leukemia. It highlights the efficacy of antiviral medications like acyclovir in reducing the incidence of symptomatic HSV reactivation during intensive chemotherapy. The study conducted in Italian centers belonging to SEIFEM group revealed a heterogeneous scenario in antiviral prophylaxis policies, with some centers not adhering to current international guidelines. The authors suggest the need for harmonization in applying antiviral prevention approaches and further prospective studies to optimize the schedule and duration of antiviral prophylaxis in different acute leukemia subgroups. [Extracted from the article]

The MEF2D rearrangement is a recurrent chromosomal abnormality detected in approximately 2.4–5.3% of patients with acute B-cell lymphoblastic leukemia (B-ALL). Currently, MEF2D-rearranged B-ALL is not classified as an independent subtype in the WHO classification. Consequently, the clinical significance of MEF2D rearrangement in B-ALL remains largely unexplored. In this study, we retrospectively screened 260 B-ALL patients with RNA sequencing data collected between November 2018 and December 2022. Among these, 10 patients were identified with MEF2D rearrangements (4 with MEF2D::HNRNPUL1, 3 with MEF2D::BCL9, 1 with MEF2D::ARID1B, 1 with MEF2D::DAZAP1 and 1 with MEF2D::HNRNPM). Notably, HNRNPM and ARID1B are reported as MEF2D fusion partners for the first time. The patient with the MEF2D::HNRNPM fusion was resistant to chemotherapy and chimeric antigen receptor T-cell therapy and relapsed early after allogenic stem cell transplantation. The patient with MEF2D::ARID1B experienced early extramedullary relapse after diagnosis. All 10 patients achieved complete remission after induction chemotherapy. However, 9/10 (90%) of whom experienced relapse. Three of the 9 patients relapsed with aberrant expression of myeloid antigens. The median overall survival of these patients was only 11 months. This small cohort showed a high incidence of early relapse and short survival in patients with MEF2D rearrangements. [ABSTRACT FROM AUTHOR]

Chromothripsis refers to massive genomic rearrangements developed during a catastrophic event. In total acute myeloid leukemia (AML), the incidence of chromothripsis ranges from 0 to 6.6%, in cases of complex karyotype AML, the incidence of chromothripsis ranges from 27.3 to 100%, whereas in cases of AML with TP53 mutations, the incidence ranges from 11.1 to 90%. For other types of malignancies, the incidence of chromothripsis also varies, from 0 to 10.5% in myelodysplastic syndrome to up to 61.5% in cases of myelodysplastic syndrome with TP53 mutations. Chromothripsis is typically associated with complex karyotypes and TP53 mutations, and monosomal karyotypes are associated with the condition. ERG amplifications are frequently noted in cases of chromothripsis, whereas MYC amplifications are not. Moreover, FLT3 and NPM1 mutations are negatively associated with chromothripsis. Chromothripsis typically occurs in older patients with AML with low leukocyte counts and bone marrow blast counts. Rare cases of patients with chromothripsis who received intensive induction chemotherapy revealed low response rates and poor overall prognosis. Signal pathways in chromothripsis typically involve copy number gain and upregulation of oncogene gene sets that promote cancer growth and a concomitant copy number loss and downregulation of gene sets associated with tumor suppression functions. Patients with chromothripsis showed a trend of lower complete remission rate and worse overall survival in myeloid malignancy. Large-scale studies are required to further elucidate the causes and treatments of the condition. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Historically, multimodal therapeutic strategies involving preoperative chemoradiotherapy (CRT), surgery, and adjuvant chemotherapy (CT) have been employed to treat locally advanced rectal cancer (LARC). Total Neoadjuvant Therapy (TNT) is showing promise in improving outcomes. Despite its benefits, the optimal sequencing within TNT—whether induction chemotherapy should precede or follow chemoradiotherapy—remains a critical question. This study endeavors to explore the effects of different TNT sequencing strategies on patient outcomes, including tumor downstaging, pathological response, organ preservation, and the balance between efficacy and tolerability. Methods: Our methodology entailed a comprehensive literature review conducted on Medline, focusing on recent research, including retrospective studies, systematic reviews, and clinical trials. The review emphasized the comparison of induction chemotherapy versus consolidation chemotherapy within TNT regimens, assessing outcomes such as pathological response, organ preservation rates, and adverse effects. To ensure the selection of appropriate and high‐quality studies, specific inclusion and exclusion criteria were applied. Results: The analysis revealed that induction chemotherapy might lead to decreased adherence to subsequent chemoradiotherapy while offering an early intervention against micrometastasis and potentially improving overall chemotherapy compliance. Conversely, consolidation chemotherapy has been associated with higher pathological complete response (pCR) rates and improved tolerability, indicating its potential for patients requiring local symptom relief or those eligible for a nonoperative management approach. Comparative studies like CAO/ARO/AIO‐12 and the OPRA trials have significantly contributed to our understanding, suggesting that while both strategies have distinct advantages, the choice between induction and consolidation chemotherapy should be tailored based on individual patient profiles and tumor characteristics. Conclusion: This narrative review underscores the importance of a nuanced approach to TNT sequencing in locally advanced rectal cancer, highlighting the need for further research to refine treatment strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Daratumumab (DARA) plus bortezomib, thalidomide, and dexamethasone (D-VTd) represent the standard of induction care in Europe for autologous stem cell transplantation (auto-SCT)-eligible, newly diagnosed multiple myeloma (NDMM) patients. This study aimed to investigate the possible impact of D-VTd induction therapy on hematopoietic engraftment after auto-SCT. Our findings indicate that patients treated with D-VTd experienced longer neutrophil and platelet engraftment times than those treated with VTd. Additionally, D-VTd treatment was associated with a higher incidence of febrile neutropenia and grade 2 or higher diarrhea. However, no significant differences were observed in the median number of days to discharge. The conclusion we can draw from our real-life study is that a four-drug induction therapy containing DARA does not impact transplant safety outcomes. Background: This real-life study aimed to investigate the possible impact of D-VTd induction therapy on hematopoietic engraftment after autologous stem cell transplantation (auto-SCT). Methods: Sixty consecutive NDMM patients received four cycles of induction therapy with D-VTd. The conditioning regimen consisted of melphalan 200 mg/m2. These patients were compared with a historical control group of 80 patients who received four cycles of VTd as induction therapy. Results: The median days to reach neutrophil and platelet engraftment significantly differed between patients treated with D-VTd (11 and 13 days, respectively) and VTd (10 and 12 days). Univariate Cox analyses show that patients treated with D-VTd had a hazard ratio of neutrophil engraftment that was 42% significantly lower than those in the VTd arm (HR: 0.58, p = 0.002), and a multivariate model confirmed this result. Patients treated with D-VTd developed FN more frequently. Univariate and multivariate logistic regressions revealed an association between D-VTd and FN. Delayed engraftment did not correlate with more extended hospitalization. No patients died in the first six months after transplantation. Conclusions: Our real-life study showed that a four-drug induction therapy containing DARA does not impact transplant safety outcomes. [ABSTRACT FROM AUTHOR]

Sinonasal malignancies (SNMs) are rare heterogeneous malignancies that frequently present with locally advanced disease. The prognosis is poor when the disease is considered extensive and unresectable. In such cases, a high‐dose palliative radiotherapy regimen is often required, but the ideal dose and fractionation have not been established. We detail a 33‐year‐old male who initially presented with a progressively growing mass over the right cheek. A biopsy of the lesion revealed squamous cell carcinoma (SCC). Imaging revealed a very advanced and unresectable disease with the involvement of several head and neck subsites. He progressed further after receiving induction chemotherapy from an outside institution. The patient requested prompt tumor and symptom control to travel back to his home country. We offered him high‐dose split‐course palliative radiotherapy in the form of a quad Shot of 14.80 Gy in four fractions twice daily, followed by 30 Gy in five fractions every other day with a 2‐week interval. Treatment resulted in excellent clinical response with symptomatic relief in a short time, and the patient could travel back home safely. [ABSTRACT FROM AUTHOR]

The management of Langerhans cell histiocytosis (LCH) with accompanying liver dysfunction poses significant challenges, and this prompted the development of a modified low-dose cytarabine and prednisolone regimen. In this prospective observational study on children with LCH and liver dysfunction, four patients underwent induction and maintenance chemotherapy. The induction phase included 5 days of 100mg/m2 cytarabine and 4 weeks of 40mg/m2 daily prednisolone, with subsequent tapering. Maintenance included a regimen of 5 days of 100mg/m2 cytarabine, along with oral prednisolone, repeated every 3 weeks. Complete disease resolution occurred after varying chemotherapy cycles. Three patients had liver transplants, and the chemotherapy resumed for 52 weeks after the transplant. In one child, chemotherapy was continued after reaching remission. In conclusion, a modified, less toxic low-dose cytarabine-based chemotherapy effectively managed LCH with liver dysfunction, with liver transplantation as a postremission treatment option. [ABSTRACT FROM AUTHOR]

The standard of care for the treatment of locally advanced rectal cancer (LARC) results in an excellent local disease control but the metastasis rates remain high. PRODIGE 23 demonstrated improved disease-free survival (DFS) and metastasis-free survival (MFS) with total neoadjuvant therapy versus standard of care in this population. Long-term analysis of overall survival (OS) is reported here. The study design, participants, and primary endpoint DFS have been reported for this multicenter, randomized, open-label, phase III trial investigating the neoadjuvant chemotherapy with mFOLFIRINOX (6 cycles) followed by chemoradiotherapy, surgery, and adjuvant chemotherapy (6 cycles), versus chemoradiotherapy, surgery, and adjuvant chemotherapy (12 cycles) in patients with locally advanced rectal adenocarcinoma under peritoneal reflection on magnetic resonance imaging, and staged cT3/T4. Key secondary endpoints included OS, MFS, and local and metastatic recurrence rate. With a median follow-up of 82.2 months, the 7-year DFS was 67.6% [95% confidence interval (CI) 60.7% to 73.9%] and 62.5% (95% CI 55.6% to 68.6%) [restricted mean survival time (RMST) difference 5.73 months, 95% CI 0.05-11.41 months, P = 0.048] in the neoadjuvant chemotherapy and the standard-of-care groups, respectively. The 7-year MFS was 79.2% (95% CI 73.0% to 84.4%) in the neoadjuvant chemotherapy group and 72.3% (95% CI 65.8% to 77.8%) in the standard-of-care group (RMST difference 6.1 months, 95% CI 0.93-11.37 months, P = 0.021). The 7-year OS was 81.9% (95% CI 75.8% to 86.6%) in the neoadjuvant chemotherapy group and 76.1% (95% CI 69.7% to 81.2%) in the standard-of-care group (RMST difference 4.37 months, 95% CI 0.35-8.38 months, P = 0.033). The safety profile remained unchanged since the previous analysis. Neoadjuvant chemotherapy with mFOLFIRINOX followed by chemoradiotherapy improved OS, confirmed long-term DFS and MFS benefits in LARC patients, and should be considered as one of the best options of care for these patients. • With standard-of-care trimodality therapy for LARC, the 5-year metastasis rate is 25%-35%. • PRODIGE 23 investigated mFOLFIRINOX induction chemotherapy before standard of care, versus standard of care for LARC. • With 7 years of follow-up, induction chemotherapy significantly improved MFS. • DFS and OS were also significantly improved using mFOLFIRINOX induction chemotherapy. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to construct a radiomics-based model for prognosis and benefit prediction of concurrent chemoradiotherapy (CCRT) versus intensity-modulated radiotherapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (LANPC) following induction chemotherapy (IC). Materials and methods: A cohort of 718 LANPC patients treated with IC + IMRT or IC + CCRT were retrospectively enrolled and assigned to a training set (n = 503) and a validation set (n = 215). Radiomic features were extracted from pre-IC and post-IC MRI. After feature selection, a delta-radiomics signature was built with LASSO-Cox regression. A nomogram incorporating independent clinical indicators and the delta-radiomics signature was then developed and evaluated for calibration and discrimination. Risk stratification by the nomogram was evaluated with Kaplan–Meier methods. Results: The delta-radiomics signature, which comprised 19 selected features, was independently associated with prognosis. The nomogram, composed of the delta-radiomics signature, age, T category, N category, treatment, and pre-treatment EBV DNA, showed great calibration and discrimination with an area under the receiver operator characteristic curve of 0.80 (95% CI 0.75–0.85) and 0.75 (95% CI 0.64–0.85) in the training and validation sets. Risk stratification by the nomogram, excluding the treatment factor, resulted in two groups with distinct overall survival. Significantly better outcomes were observed in the high-risk patients with IC + CCRT compared to those with IC + IMRT, while comparable outcomes between IC + IMRT and IC + CCRT were shown for low-risk patients. Conclusion: The radiomics-based nomogram can predict prognosis and survival benefits from concurrent chemotherapy for LANPC following IC. Low-risk patients determined by the nomogram may be potential candidates for omitting concurrent chemotherapy during IMRT. Clinical relevance statement: The radiomics-based nomogram was constructed for risk stratification and patient selection. It can help guide clinical decision-making for patients with locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy, and avoid unnecessary toxicity caused by overtreatment. Key Points: • The benefits from concurrent chemotherapy remained controversial for locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy. • Radiomics-based nomogram achieved prognosis and benefits prediction of concurrent chemotherapy. • Low-risk patients defined by the nomogram were candidates for de-intensification. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the IRECAP study was to evaluate the rate of locally advanced pancreas cancer patients (LAPC) who could undergo R0 or R1 surgery after irreversible electroporation (IRE). Materials and methods: IRECAP study is a phase II, single-center, open-label, prospective, non-randomized trial registered at clinicaltrials.gov (NCT03105921). Patients with LAPC were first treated by 3-month neo-adjuvant chemotherapy in order to avoid inclusion of either patients with LAPC having become resectable after chemotherapy or patients with rapid disease progression. In cases of stable disease, IRE was performed percutaneously under CT guidance. Surgery was planned between 28 and 90 days after IRE. Tumor specimens were studied to evaluate the resection margins (R0/R1/R2). Results: Six men and 11 women were included (median age 61 years, range 37–77 years). No IRE-related death was observed. Ten patients (58%, 10/17) experienced 25 serious adverse events related to IRE. Four patients progressed between IRE and surgery and were excluded from surgery. Thirteen patients were finally operated, six withheld for pancreas resection, three for diffuse peritoneal carcinosis, two for massive vascular entrapment, and one for hepato-cellular carcinoma not diagnosed before surgery. Rate of R1-R0 was 35% (n = 6/17). Median overall survival was 31 months (95% CI; 4–undefined) for the six patients with R0/R1 resection and 21 months (95% CI; 4–25) for the 11 patients without resection or R2 resection (logrank p = 0.044). Conclusion: After neoadjuvant chemotherapy, IRE could provide R0 or R1 resection in 35% of LAPC, which seems to be associated with higher OS. Clinical relevance statement: After induction chemotherapy, stable locally advanced pancreatic cancers can be treated by irreversible electroporation, which could lead to a secondary 35% rate of R0 or R1 surgical resection which may be associated with a significantly higher overall survival. Key Points: • In cases of unresectable LAPC (locally advanced pancreatic cancer), percutaneous irreversible electroporation (pIRE) is feasible (100% success rate of the procedure), but is associated with a 58% rate of grade 3–4 adverse events. • In patients with unresectable LAPC, pIRE could lead 35% of patients to R0-R1 surgical resection. • From IRE, median overall survival was 31 months (95% CI; 4–undefined) for the patients with R0/R1 resection and 21 months (95% CI; 4–25) for the patients without resection or R2 resection (logrank p = 0.044). [ABSTRACT FROM AUTHOR]

Background: We aimed to establish the most suitable threshold for objective response (OR) in the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in patients with nasopharyngeal carcinoma (NPC). Methods: According to RECIST 1.1, we retrospectively evaluated MR images of NPC lesions in patients before and after induction chemotherapy (IC). Restricted cubic spline and maximally selected rank statistics were used to determine the cut‐off value. Survival rates and differences between groups were compared with Kaplan–Meier curves and log‐rank tests. Results: Of 1126 patients, 365 cases who received IC treatment were suitable for RECIST 1.1 evaluation. The 20% cut‐off value maximized between‐group differences according to maximally selected rank statistics. No difference in distant metastasis‐free survival between OR and non‐response groups was shown using the primary threshold of OR (30%), while it differed when 20% was employed. Conclusions: With an optimal cut‐off value of 20%, RECIST may assist clinicians to accurately evaluate disease response in NPC patients. [ABSTRACT FROM AUTHOR]

Resistance to chemotherapy is a problem of major social and economic importance, when looking at factors like the decrease in life expectancy, the associated therapeutic costs, and a significant number of cancers that resist current chemotherapy. The development of chemotherapeutics for all theoretically possible tumor variants is an approach that requires unreasonable resources. We propose a theoretical model that serves the purpose of overcoming resistance to chemotherapeutic agents used in cancer therapy. The model describes a gene delivery system based on liposomes, which are optically guided to the tumor's location. The main aim of the gene delivery system is inhibiting the activity of enzymes involved in drug metabolism, hence offering the opportunity to use inexpensive chemotherapeutics that are already on the market. This model will reduce the costs of chemotherapy and will assure a positive outcome for patients. [ABSTRACT FROM AUTHOR]

Background: Recent studies have associated total neoadjuvant therapy (TNT) with better treatment adherence, decreased toxicity, improved complete clinical response and anal sphincter preservation rates in patients with locally advanced rectal cancer (LARC). However, real-world experience with TNT in the management of LARC remains limited. Aim: This study aimed to evaluate the efficacy and safety outcomes of TNT for LARC in Western Australia. Methods: Patients with LARC (cT2-4 and/or cN1-2) who underwent induction chemotherapy followed by neoadjuvant chemoradiotherapy or neoadjuvant chemoradiotherapy followed by consolidation chemotherapy, followed by surgery were recruited from two hospitals in Western Australia. Efficacy outcomes assessed included clinical response (complete, partial, no response), and pathologic complete response (pCR) rate, R0 resection rate, and R1 resection rate were evaluated. Those patients who achieved clinical complete response following TNT were given the option of active surveillance. The safety and tolerability of TNT were assessed. Results: 32 patients with LARC were treated with TNT. In total, 17 patients (53%) received chemoradiotherapy followed by consolidation chemotherapy and 15 patients (47%) received induction chemotherapy followed by chemoradiotherapy. Nine (28%) of the patients with LARC treated with TNT had a complete clinical response, twenty-one (66%) patients had a partial clinical response, and two (6%) patients had no response to TNT. Of the 32 patients, 27 (84%) underwent surgery. There was a 100% R0 resection rate. The pCR rate was 15%. pCR, clinical response, and the R0 resection rate were similar between the two TNT regimens. TNT was well tolerated, with the majority of patients (88%) completing the chemotherapy course with grade 1 and 2 adverse effects. Conclusions: In conclusion, TNT emerges as a promising approach for the management of LARC. However, further research is warranted to refine the optimal TNT protocols, determine its long-term outcomes, and identify patient populations who would benefit the most from this innovative therapeutic strategy. [ABSTRACT FROM AUTHOR]

Objective: The present study aims to provide outcome data in children with relapsed acute lymphoblastic leukemia (ALL) over two decades and variables that impact survival. Methods: This retrospective study included children who were diagnosed with ALL and treated at our center and relapsed between March 2002 and March 2021. Results: A total of 100 children (64 boys, 36 girls) were included; 80 had B-ALL, 20 had T-ALL. 50 children had a very early relapse, while 25 each had an early and late relapse. The site of relapse was bone marrow in 57, isolated central nervous system (CNS) in 10, isolated testicular in 1, and combined bone marrow and CNS relapse in 32 children. Thirty-six families opted for the best supportive care; 23 of these had very early relapse. Among the 35 who were in remission following induction chemotherapy, 32 (91%) underwent hematopoietic stem cell transplantation (HSCT); 17/32 (53%) were alive and disease-free. Overall survival (OS) was 19 (19%) with a median follow-up of 23.5 months with a significantly improved survival post-measurable risk of disease (MRD) based risk stratification (4% vs 35%, P = 0.02). The OS with very early, early, and late relapses were 8%, 28%, and 32% (P = 0.018), and 15%, 12.5%, and 50% with bone marrow, combined and isolated CNS relapses (P = 0.008). Conclusion: Relapsed ALL remains a challenge, with OS of 19% and 53% among those who underwent HSCT. Abandonment after relapse continues to be prevalent, and we need to integrate social support for providing care and optimal treatment. [ABSTRACT FROM AUTHOR]

Purpose: The duration of response to treatment is a significant prognostic indicator, with early recurrence (ER) often predicting poorer survival outcomes in nasopharyngeal carcinoma (NPC) survivors. This study seeks to elucidate the factors contributing to the onset of ER following radiotherapy in NPC survivors. Methods: This investigation encompassed 2,789 newly diagnosed NPC patients who underwent radical intensity-modulated radiotherapy. Ordinal logistic regression analysis was employed to evaluate the independent predictors of earlier recurrence. A machine learning-based prediction model of NPC recurrence patterns was developed. Tumorous RNA-sequencing (in-house cohort: N = 192) and biological tipping point analysis were utilized to infer potential molecular mechanisms associated with ER. Results: Our results demonstrated that ER within 24 months post-initial treatment was the optimal time frame for identifying early malignant progression in NPC survivors. The ER cohort (150 of 2,789, 5.38%) exhibited a notably short median overall survival of 48.6 months. Multivariate analyses revealed that male gender, T4 stage, local or regional residual disease, detectable pre- and post-radiotherapy EBV DNA, and the absence of induction chemotherapy were significant predictors of earlier recurrence. The machine learning-based predictive model further underscored the importance of tumor-related factors in NPC recurrence. Moreover, ER emerged as a pivotal stage in NPC progression, with 15 critical transition signals identified potentially associated with the negative modulation of the immune response. Conclusions: Our comprehensive analysis of NPC recurrence patterns has unveiled insights into the key factors driving ER and provided novel insights into potential early warning biomarkers and the mechanisms underlying NPC progression. [ABSTRACT FROM AUTHOR]

Background: It is accepted that tumor stage and size can influence response to neoadjuvant therapy in locally advanced rectal cancer (LARC). Studies on organ preservation to date have included a wide variety of size and TNM stage tumors. The aim of this study was to report tumor response based on each relevant TNM stage and tumor size. Methods: Patients treated with LARC from 2014 to 2021 with cT2–3NxM0 tumors who received neoadjuvant chemoradiotherapy with or without induction chemotherapy were included. Tumors were staged and tumor size calculated on pelvic MRI at the time of diagnosis (cTNM). Tumor size was based on the largest dimension taken on the longest axis of each tumor. Clinical response was defined on the basis of post-treatment pelvic MRI and pathological response following surgery, when performed. Statistical analysis was performed using IBM SPSS Statistics™, version 20. Data from 432 patients were analyzed as follows: cT2N0 (n = 51), cT2N+ (n = 36), cT3N0 (n = 76), cT3N+ (n = 270). Results: The rate of complete or near-complete response (cCR or nCR) varied from 77% in cT2N0 ≤ 3 cm to 20% in cT3N+ > 4 cm. Organ preservation without recurrence at 2 years was achieved in 86% of patients with cT2N0, 50% in cT2N+, 39% in cT3N0, and 12% in cT3N+. Conclusion: There is significant variation in tumor response according to tumor stage and size. Tumor response appears inversely proportional to increasing TNM stage and tumor size. This data can support both refinement of selective patient recruitment to organ preservation programs and shared decision-making. [ABSTRACT FROM AUTHOR]

Induction chemotherapy followed by autologous haematopoietic cell transplantation and post‐transplant therapy (including maintenance therapy with or without prior consolidation) is still considered as the standard of care for newly diagnosed young and fit multiple myeloma patients. Over the last years, superiority of quadruplet regimens for induction was established, with the addition of an anti‐CD38 monoclonal antibody to triplet regimen including a proteasome inhibitor, an IMiD (thalidomide or lenalidomide) or cyclophosphamide, and dexamethasone. Given quadruplet induction regimens are associated with deep response, including a high‐rate of sustained measurable residual disease negativity in a significant proportion of patients, they are now recommended for induction chemotherapy when available. [ABSTRACT FROM AUTHOR]

COVID-19 infection is still a mystery in terms of its long-term effect on health and its consequences on hematological disorders. Prior studies including ours have shown the abnormal changes in hematopoietic cells in COVID-19 patients. In this article, we are presenting 2 cases of pediatric B-lymphoblastic leukemia (B-ALL) with a previous history of COVID-19 infection. The first case describes a 22-month-old boy presenting with lymphadenopathy, neutropenia, and anemia with concurrent COVID-19 infection without any evidence of a hematolymphoid neoplasm as per bone marrow and lymph node biopsy. However, he presented after 2 months with bone marrow biopsy confirming B-ALL. The second case is that of a 4-year-old girl presenting with B-ALL who has had asymptomatic COVID-19 infection 5 months before this current presentation. Both the cases had complete resolution of COVID-19 infection during the time of presentation with acute leukemia. There were notably 2 rare findings along the course of the patients' illnesses. First, the unusual plasmacytosis in the marrow during active COVID-19 infection in the first patient and the second, is predilection of development of B-ALL following COVID-19. In both the cases the fluorescence in situ hybridization (FISH) studies showed pathologic alteration of the RUNX1 gene. Overall, there are no literature to support a causal association between acute B-ALL and COVID-19. The diagnosis of B-ALL in these patients after COVID-19 infection may be totally unrelated. However, if we consider Greaves proposed 2-hit model for childhood acute leukemia, that an infectious agent can precipitate development of B-ALL in a genetically susceptible individual. Alteration of the RUNX1 gene in both the patients, opens a door for further exploration of the "second-hit" hypothesis regarding an infectious agent precipitating development of B-ALL in a genetically susceptible individual. [ABSTRACT FROM AUTHOR]

The European Larynx Organ Preservation Study (ELOS; NCT06137378) is a prospective, randomized, open-label, two-armed parallel group controlled, phase II multicenter larynx organ preservation (LOP) trial in locoregionally advanced (LA) stage III, IVA/B head and neck squamous cell carcinoma of the larynx or hypopharynx (LHSCC) amenable for total laryngectomy (TL) with PD-L1 expression within tumor tissue biopsy, calculated as CPS = 1. Induction chemotherapy (IC) with docetaxel and cisplatin (TP) followed by radiation will be compared to TP plus PD-1 inhibition by pembrolizumab (MK-3475; 200 mg i.v. starting day 1 q3w for 17 cycles). After a short induction early response evaluation (ERE) 21 ± 3 days after the first cycle of IC (IC-1), responders achieving endoscopic estimated tumor surface shrinkage (ETSS) =30% will get an additional two cycles of IC followed by intensity-modulated radiotherapy 70-72 Gy (EQD2/a/b = 10) aiming at LOP. Nonresponders (ETSS < 30% or progressing disease) will receive TL and bilateral neck dissection followed by postoperative radiation or chemoradiation as recommended by the clinic's multidisciplinary tumor board. Pembrolizumab treatment will be continued in the intervention arm regardless of ETSS status after IC-1 in both responders and laryngectomized nonresponders, independent of subsequent decisions on adjuvant therapy after TL. [ABSTRACT FROM AUTHOR]

Oligometastatic (OMT) form of pancreatic adenocarcinoma (PDAC) is a particular entity of this tumor, the definition of which is being more precise: limited number of metastases which varies between 2 and 4 depending on the organs affected, most often liver and lung, and a low CA19-9 serum lever when contributory (classically < 1 000 IU/mL). This subgroup of patients, which represents 5%-10% of metastatic forms, has prolonged survival, particularly in case of pulmonary location. The incidence of OMT forms is increasing because patients are now better selected and have a longer survival since the improvement of surgical management and the advent of more effective adjuvant chemotherapies, such as modified FOLFIRINOX. Among the OMT forms, metachronous metastases occurring in a context of postoperative recurrence are the only ones AP that can be locally treated. Their management may consist of surgical excision, stereotactic radiotherapy or radiofrequency, which should only be discussed after prolonged induction chemotherapy between 6 and 12 months, at best lightened, in order to better select patients. For those not eligible for this type of approch despite a low tumor burden, a de-escalation of chemotherapy deserves to be better evaluated in order to preserve quality of life. This article focuses on the diagnosis, prognosis and therapeutic possibilities for OMT forms of PDAC diagnosed in a context of post-operative tumour relapse. [ABSTRACT FROM AUTHOR]

Approximately 30% of pancreatic adenocarcinoma are diagnosed in a locally advanced form (CPLA). This particular entity, intermediate between resectable and metastatic cancers, is defined by the importance of contact between the tumor and the main peripancreatic vessels. Due to this particularity, therapeutic approach is not well standardized. Until 2011, the treatment strategy remained limited to a first-line palliative metastatic chemotherapy, gemcitabine, with poor results, since a prompt progression to a metastatic form was observed in 30% of cases. Since the publication of the results of FOLFIRINOX study and gemcitabine-nab-paclitaxel combination as first-line therapy of metastatic form, the therapeutic possibilities of CPLA have been enriched. The use of these chemotherapies in CPLA, initially on the basis of non-comparative retrospective studies or phase 2 studies with small effectives, has been supported by the recent results of the phase 3 NEOPAN study, demonstrating the superiority of FOLFIRINOX on gemcitabine. For the majority of patients whose tumor remains unresectable but non-progressive after induction chemotherapy, closure chemoradiotherapy is sometimes proposed, which remains controversial. To better understand the chemoresistance mechanisms of these tumors, intensify chemotherapy or use more efficient techniques of radiation therapy in order to increase the dose received by the tumor tissue, evolve imaging techniques towards functional imaging, identify prognostic factors and predictive are challenges that remain to be addressed. The inclusion of patients with CPLA in therapeutic trials asking clinical and translational questions is an essential condition to hope to meet this challenge. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 nearcomplete 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. [ABSTRACT FROM AUTHOR]

Purpose: For tonsillar cancer with multiple ipsilateral neck lymph nodes, the safety and efficacy of unilateral radiotherapy (RT) have long been a topic of debate. We performed retrospective analyses of patients having ipsilateral neck lymph nodes treated with unilateral RT in two tertiary referral hospitals. Materials and Methods: This study accrued 29 patients who were diagnosed as well-lateralized tonsillar cancer with multiple ipsilateral neck lymph nodes and underwent unilateral RT from March 2000 to March 2020. Patients underwent treatment with one of the following options or a combination of them: induction chemotherapy, surgery, RT, and concurrent chemoradiotherapy. We analyzed the recurrence pattern and survival with special attention to contralateral neck failure. Also, treatment- related toxicities were compared with a 1:1 matched cohort of those who received bilateral RT, using propensity score matching analysis. Results: At a median follow-up of 68 months, no contralateral neck failure was observed. Five-year actuarial locoregional recurrence-free survival, distant metastasis-free survival, and overall survival were 85.6%, 91.8%, and 92.7%, respectively. Both the acute and chronic grade 2 xerostomia occurred in 10.3% of the patients. When the toxicity for unilateral RT was compared to that of bilateral RT using a propensity score-matched cohort, a significantly lower rate of acute xerostomia was observed in unilateral RT group (55.1% vs. 82.7%, p=0.002), primarily at grade 2 level (10.3% vs. 51.7%, respectively) Conclusion: The results of our study suggest that unilateral RT can be safely performed in well-lateralized tonsillar cancer patients with multiple ipsilateral neck lymph nodes. [ABSTRACT FROM AUTHOR]

Background: Autologous hematopoietic cell transplantation (HCT) among Multiple myeloma (MM) cases has resulted in greater response rates, higher overall survival (OS) and event-free survival (EFS) over the last two decades compared with the outcome of comparable individuals given conventional treatment. We aimed at this study to determine the prognostic value of the time interval between end of induction chemotherapy and autologous stem cell transplantation among multiple myeloma patients. Methods: This observational retrospective cohort study was held at Nasser Institute, Dar El-Salam Hospital and El-Sheikh Zayed Hospital on 211 cases with an initial diagnosis of MM during the study period (2017-2022). We evaluated the influence of the time interval between the end of induction of chemotherapy and Autologous Stem Cell Transplantation on free survival, relapse-free survival and overall survival. Results: There was a statistically significant relation between relapse-free survival and interval from last chemotherapy date to stem cell infusion among studied patients (significantly lower 26.0 ± 1.67 months in patients with interval>60 days vs. 56.32 ± 2.22 months in patients with interval≤60 days and with increasing interval quartile (with p<0.001 for each). Similarly, there was a statistically significant relation between overall survival and interval from last chemotherapy date to stem cell infusion among studied patients (significantly lower 58.28 ± 3.97 months in patients with interval>60 days vs. 67.48 ± 1.45 months in patients with interval≤60 days with P value =0.004). Conclusions: The present study demonstrated the prognostic value of the time interval between the end of induction of the chemotherapy and autologous stem cell transplantation in multiple myeloma cases, as the overall survival rate was substantially lower in patients whose intervals were greater than 60 days and with increasing interval quartiles. [ABSTRACT FROM AUTHOR]

Simple Summary: Induction regimens using 4-drugs for patients with newly diagnosed multiple myeloma have shown impressive results in multiple trials. However, trials of 4-drug regimens typically use a 3-drug regimen as their comparator, which limits our ability to determine whether the benefit is from the specific combination of drugs or just the addition of more agents. We performed a meta-analysis to compare all trials that compared 4-drug to 3-drug regimens and found that the addition of an anti-CD38 antibody (daratumumab or isatuximab) resulted in improved responses, while 4-drug regimens without an anti-CD38 antibody performed similarly to 3-drug regimens. While the addition of an anti-CD38 antibody led to increased adverse effects, these were predominantly mild and easily managed. These data suggest that an anti-CD38 antibody should be part of all 4-drug induction regimens for newly diagnosed myeloma patients. The use of 4-drug induction regimens for treatment naïve newly diagnosed multiple myeloma (NDMM) is associated with improved depth of response and progression-free survival (PFS). However, head-to-head trials of 4-drug combinations are lacking, and instead, these regimens are typically compared to 3-drug backbones; limiting the ability to discern whether any additional benefit (or toxicity) is simply additive or represents a synergy (or interaction). We conducted a meta-analysis of phase 2 and phase 3 clinical trials that randomized treatment naïve NDMM patients to either a 4-drug or 3-drug induction regimen. We included 11 trials which represented 6509 unique patients. PFS for all trials in the meta-analysis was 54 months with a 4-drug induction and 8.9 months with a 3-drug induction (HR: 0.49; 95% CI: 0.45; 0.54), but there was no benefit to using a 4-drug induction that did not include an anti-CD38 antibody (PFS 4-drug 8.1 months, PFS 3-drug 8.0 months; HR 0.95; 95% CI 0.86; 1.06). Adverse events were more frequent with the quadruplet regimens but were predominately mild. High-grade (≥3) adverse events (AEs) that were more common with 4-drug regimens were infections (RR: 1.34; 95% CI 1.17; 1.54) and thrombocytopenia (RR: 1.39; 95% CI 1.12; 1.74). This study suggests that 4-drug induction regimens which include an anti-CD38 antibody improve efficacy although with additional toxicity in NDMM patients. [ABSTRACT FROM AUTHOR]

Introduction: Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ALL) is treated as standard of care (SoC) by imatinib-based treatment combined with induction and consolidation chemotherapy followed by allogeneic stem cell transplantation (SCT) in first remission. The German Multicenter ALL Study Group for Adult ALL (GMALL) reports about a trial to evaluate the impact of ponatinib-based therapy, blinatumomab treatment for suboptimal responders, and the possibility of omission of SoC Allo SCT in optimal responders entitled GMALL-EVOLVE. Methods: Herein, imatinib is randomized versus ponatinib as frontline treatment combined with chemotherapy, optimal responders also get randomized between SCT and chemo-immunotherapy, and suboptimal responders receive immunotherapy before SCT. The trial is registered under the EudraCT number 2022-000760-21. Conclusion: This trial will answer several major questions in the treatment of Ph+ALL. [ABSTRACT FROM AUTHOR]

Purpose: Patients with acute myeloid leukemia (AML) experience significant distress. Expressive writing is an intervention designed to improve well-being by encouraging expression of emotions related to traumatic experiences. Expressive writing has been shown to be generally feasible and effective at improving the cancer experience but has not been examined in patients with recently diagnosed hematologic malignancies. We examined the feasibility of an expressive writing intervention for hospitalized patients with AML receiving induction chemotherapy. Methods: Fifteen hospitalized AML patients were randomized to complete expressive writing or neutral prompts. Feasibility was defined as 80% of enrolled subjects completing the study. Participants completed validated questionnaires measuring depression, anxiety, resilience, rumination, and quality of life at baseline, completion of the second and fourth writing exercises, and 3 months after enrollment. Participants also completed post-writing surveys following the writing exercise to reflect on the experience. Findings: We enrolled 15 participants and 8 of 15 subjects (53%) completed the study. Due to low enrollment, we examined the pre-to-post intervention changes, rather than comparing results across intervention arms. Pre-to-post intervention changes in the expected direction were seen at the second assessment for depression and resilience, at the fourth assessment for rumination, emotional well-being, and social well-being, and at the 3-month follow-up for anxiety and emotional well-being. Similar changes in patient-reported outcomes were also seen in the control condition. Participants who completed the intervention reported the experience was meaningful and were able to express their deepest thoughts and feelings, more so than participants in the control arm. Conclusion: In our work, the expressive writing intervention was not found to be feasible. The trial was interrupted by the COVID-19 pandemic which likely impacted the feasibility. Future studies should aim to identify ways to make the intervention more accessible, such as developing an electronic application for expressive writing. [ABSTRACT FROM AUTHOR]

Thoracic radiation intensification is debated in patients with stage III non-small-cell lung cancer (NSCLC). We aimed to assess the activity and safety of a boost radiotherapy dose up to 74 Gy in a functional sub-volume given according to on-treatment [18F]fluorodeoxyglucose ([18F]FDG)-PET results. In this multicentre, randomised, controlled non-comparative phase 2 trial, we recruited patients aged 18 years or older with inoperable stage III NSCLC without EGFR mutation or ALK rearrangement with an Eastern Cooperative Oncology Group performance status of 0–1, and who were affiliated with or a beneficiary of a social benefit system, with evaluable tumour or node lesions, preserved lung function, and who were amenable to curative-intent radiochemotherapy. Patients were randomly allocated using a central interactive web-response system in a non-masked method (1:1; minimisation method used [random factor of 0·8]; stratified by radiotherapy technique [intensity-modulated radiotherapy vs three-dimensional conformal radiotherapy] and by centre at which patients were treated) either to the experimental adaptive radiotherapy group A, in which only patients with positive residual metabolism on [18F]FDG-PET at 42 Gy received a boost radiotherapy (up to 74 Gy in 33 fractions), with all other patients receiving standard radiotherapy dosing (66 Gy in 33 fractions over 6·5 weeks), or to the standard radiotherapy group B (66 Gy in 33 fractions) over 6·5 weeks. All patients received two cycles of induction platinum-based chemotherapy cycles (paclitaxel 175 mg/m2 intravenously once every 3 weeks and carboplatin area under the curve [AUC]=6 once every 3 weeks, or cisplatin 80 mg/m2 intravenously once every 3 weeks and vinorelbine 30 mg/m2 intravenously on day 1 and 60 mg/m2 orally [or 30 mg/m2 intravenously] on day 8 once every 3 weeks). Then they concomitantly received radiochemotherapy with platinum-based chemotherapy (three cycles for 8 weeks, with once per week paclitaxel 40 mg/m2 intravenously and carboplatin AUC=2 or cisplatin 80 mg/m2 intravenously and vinorelbine 20 mg/m2 intravenously on day 1 and 40 mg/m2 orally (or 20 mg/m2 intravenously) on day 8 in 21-day cycles). The primary endpoint was the 15-month local control rate in the eligible patients who received at least one dose of concomitant radiochemotherapy. This RTEP7–IFCT-1402 trial is registered with ClinicalTrials.gov (NCT02473133), and is ongoing. From Nov 12, 2015, to July 7, 2021, we randomly assigned 158 patients (47 [30%] women and 111 [70%] men) to either the boosted radiotherapy group A (81 [51%]) or to the standard radiotherapy group B (77 [49%)]. In group A, 80 (99%) patients received induction chemotherapy and 68 (84%) received radiochemotherapy, of whom 48 (71%) with residual uptake on [18F]FDG-PET after 42 Gy received a radiotherapy boost. In group B, all 77 patients received induction chemotherapy and 73 (95%) received radiochemotherapy. At the final analysis, the median follow-up for eligible patients who received radiochemotherapy (n=140) was 45·1 months (95% CI 39·3–48·3). The 15-month local control rate was 77·6% (95% CI 67·6–87·6%) in group A and 71·2% (95% CI 60·8–81·6%) in group B. Acute (within 90 days from radiochemotherapy initiation) grade 3–4 adverse events were observed in 20 (29%) of 68 patients in group A and 33 (45%) of 73 patients in group B, including serious adverse events in five (7%) patients in group A and ten (14%) patients in group B. The most common grade 3–4 adverse events were febrile neutropenia (seven [10%] of 68 in group A vs 16 [22%] of 73 in group B), and anaemia (five [7%] vs nine [12%]). In the acute phase, two deaths (3%) occurred in group B (one due to a septic shock related to chemotherapy, and the other due to haemotypsia not related to study treatment), and no deaths occurred in group A. After 90 days, one additional treatment-unrelated death occurred in group A and two deaths events occurred in group B (one radiation pneumonitis and one pneumonia unrelated to treatment). A thoracic radiotherapy boost, based on interim [18F]FDG-PET, led to a meaningful local control rate with no difference in adverse events between the two groups in organs at risk, in contrast with previous attempts at thoracic radiation intensification, warranting a randomised phase 3 evaluation of such [18F]FDG-PET-guided radiotherapy dose adaptation in patients with stage III NSCLC. Programme Hospitalier de Recherche Clinique National 2014. [ABSTRACT FROM AUTHOR]

Introduction: Limited data exist on interphase fluorescent in situ hybridization (iFISH)-based survival outcomes in newly diagnosed multiple myeloma (NDMM) from India. Objectives: To study the demographics and iFISH-based survival outcomes in NDMM patients treated with proteasome inhibitors from a community-based cancer setup. Materials and Methods: We reviewed the records of 25 patients treated with proteasome inhibitors between June 2017 and April 2023 using five high-risk (HR) iFISH markers based on mSMART 3.0. Results: The median age was 60 years (range 34–87). HR iFISH was detected in 12 (48%) patients. With a median follow-up of 27 months, the overall response at the last follow-up was 80% (very good partial response - 52%, complete remission - 20%, and partial response - 8%), with 8 (32%) relapses. Twenty (80%) patients remain alive, with five deaths in HR (sepsis [ n = 3]). The 2.5-year overall survival in HR and standard risk was 55.6% ± 15.2% and 100% (P = 0.01), and event-free survival was 32.4% ± 16.5% and 77.8% ± 13.8% (P = 0.02), respectively. Conclusions: Using limited iFISH HR markers helps in the early and effective stratification of NDMM in the real world. Sepsis remains an important cause of mortality in an Indian setup. [ABSTRACT FROM AUTHOR]