Patients Received Induction Chemotherapy Research Articles

Systemic induction therapy in patients with locally advanced or node-positive urothelial carcinoma: Evaluating treatment outcomes

Background The presence of lymph node metastases in patients with urothelial carcinoma (UC) plays a pivotal role in disease management and prognosis. Patients with locally advanced irresectable or clinically node-positive UC are often considered ineligible for surgery due to the extent of affected lymph nodes. Long term remission or even cure may be achieved in a subset of patients who experience response to systemic induction therapy and consolidative locoregional treatment. Objective To assess the pathological response to preoperative systemic induction therapy followed by radical surgery in patients with locally advanced irresectable or clinically node-positive UC. Methods Searches were performed until September 2023 in 5 databases (EMBASE, MEDLINE, Web-of-Science, Cochrane and Pubmed Publisher). Studies including patients with cT4bNxM0/cTxN1-3M0 UC, treated with induction chemotherapy or non-chemo induction therapy followed by radical surgery, were selected. The primary outcome was the pathological complete response (pCR) rate, i.e., the proportion of patients without residual disease in the surgical resection specimen (ypT0N0). Secondary outcomes included overall and cancer-specific survival (OS, CSS). Results Fourteen studies were included, representing 5715 patients. Two studies reported on non-chemo induction therapy. The reported pCR rate in patients receiving induction chemotherapy varied from 9% to 27% compared to 25% after induction immunotherapy. The 5-year OS and CSS after induction chemotherapy and radical surgery ranged from 25 to 34% and 30 to 49%. Conclusion Systemic induction therapy in patients with locally advanced irresectable or clinically node-positive UC resulted in modest pCR rates. Due to considerable heterogeneity between studies, no direct comparison on the efficacy of induction therapy regimens was possible.

Adaptive radiotherapy (up to 74 Gy) or standard radiotherapy (66 Gy) for patients with stage III non-small-cell lung cancer, according to [18F]FDG-PET tumour residual uptake at 42 Gy (RTEP7–IFCT-1402): a multicentre, randomised, controlled phase 2 trial

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.

The clinical impact of primary granulocyte-colony stimulating factor prophylaxis in children with acute lymphoblastic leukemia who underwent induction chemotherapy

BackgroundData describing the risk factors for the occurrence of severe infections in acute lymphoblastic leukemia (ALL) patients following induction chemotherapy and the role of prophylactic granulocyte-colony stimulating factor (G-CSF) in the era of antimicrobials prophylaxis are limited. MethodsThis study enrolled 188 children aged ≤18 years with newly diagnosed ALL who received Taiwan Pediatric Oncology Group ALL-2002 and 2013 treatments between January 1, 2010 and June 30, 2021. Prophylactic G-CSF was administered when a patient continues neutropenia after achieving the first bone marrow remission since June 1, 2015. Clinical factors were assessed for their association with severe infections. ResultsFrom January 2010 to May 2015, 80 children experienced a total of 11 (13.5%) episodes of severe infections; while 10 (9.2%) episodes were reported to occur in 108 patients who received prophylactic G-CSF. Reduction of severe infections occurrence did not achieve statistical significance during prophylactic G-CSF administration in ALL patients. Compared with ALL-high risk (HR) and very high risk patients with no G-CSF prophylaxis, the use of G-CSF prophylaxis significantly reduced episodes of febrile neutropenia. Occurrence of grade III-IV intestinal ileus, grade II-III oral mucositis, prolonged neutropenia, central venous catheter (CVC) placement, or the requirement insulin therapy for hyperglycemia were associated with higher risk of bloodstream infections. ConclusionsALL-HR patients with G-CSF prophylaxis were associated with reduction of febrile neutropenia episodes. Occurrence of severe ileus, oral mucositis, hyperglycemia, CVC placement, or prolonged neutropenia were associated with severe infections in ALL patients receiving induction chemotherapy.

Long-term Outcomes of Salvage Surgery Versus Induction Therapy Followed by Surgical Resection for Advanced NSCLC: A Propensity Score-matched Analysis.

The outcomes of lung cancer treatment have improved over time. However, in contrast to other treatments, the clinical outcomes of salvage surgery are seldom reported because the follow-up periods after salvage surgery are short. We conducted a comprehensive study involving consecutive patients who underwent salvage surgery at two different institutions. Our analysis encompassed the exploration of clinicopathological features, perioperative variables, and surgical outcomes. Additionally, we employed propensity score matching to compare the long-term survival of patients with non-small cell lung cancer (NSCLC) who underwent salvage surgery with those who received induction chemoradiotherapy prior to surgery. Twenty-five patients underwent salvage procedures, while 113 patients received induction chemotherapy followed by surgery during the same study period. When assessing the overall survival (OS) from the registration date to the initial treatment date, the five-year OS rates were 73.8% in the induction group and 70.5% in the salvage surgery group (p=0.674). No significant differences were identified between the two groups in a cohort of 48 patients with NSCLC who were matched using propensity scores. In patients who underwent salvage surgery, reasonable long-term survival was achieved with outcomes comparable to those of induction chemotherapy followed by surgical resection.

Impact of Chemotherapy Educational Videos for Patients with Acute Myeloid Leukemia.

Patient education in acute myeloid leukemia (AML) has become increasingly complex with the introduction of new treatments and chemotherapy regimens. Video education presents an opportunity to supplement traditional patient education and address some of the gaps associated with standard methods. This single-center study sought to assess the potential impact of supplemental video education on patients receiving induction chemotherapy for AML. Participants were consented to be randomized to receive their education with or without a supplemental video designed for their treatment regimen. We then provided a survey to each participant to assess knowledge retention, anxiety, and overall satisfaction with their care. Patients that received video education were found to have significantly improved knowledge retention compared to those that did not. There were no differences detected in anxiety or patient satisfaction. Video education appears to be an effective supplemental method for patient education in AML. Limitations include the single-center nature of the study at an urban academic medical center with a relatively well-educated, primarily Caucasian, younger population. Future research is warranted to assess the video in a diverse set of languages and to explore its broader benefits.

Medical complications among acute leukaemia patients receiving inward induction chemotherapy at haematooncology section of the National Cancer Institute, Sri Lanka

Introduction: Acute leukaemias are complicated with numerous disease and treatment related medical complications. Infection is one of the major complications and is related to chemotherapy associated-neutropaenia. This study aims to identify medical complications in acute leukaemia patients during the induction chemotherapy period. Results: Medical complications were observed in patients receiving induction chemotherapy N=50. Infections and electrolyte disturbances were the most frequently observed complications (74% each) followed by chemotherapy induced neutropaenia (38%), alteration of liver functions (32%), steroid induced hyperglycaemia (28%) and bleeding (16%). Thrombosis and tumour lysis were detected at lesser frequencies (4% each). Among infections, the majority showed evidence of blood stream infection (27%) followed by pulmonary infections (24.3%). Gram negative organisms were the most frequently identified pathogen. Among the electrolyte disturbances, hypokalaemia (48%), hyponatraemia (48%), and hypocalcaemia (44%) were more prevalent. Mean duration from initiation of chemotherapy to neutrophil nadir was 10.05 days.Conclusions: Patients with acute leukaemia encounter a multitude of disease and treatment related medical complications during induction chemotherapy. Infection is the most common complication with higher rates of bacteraemia and gram-negative sepsis. This is likely to be a result of treatment related neutropaenia. However, further focused studies on neutropaenic sepsis during induction chemotherapy are recommended. Clinical vigilance, strict and improved infection control strategies are necessary to improve the outcome of these patients.

Efficacy and Toxicity of (Chemo)Radiation Therapy in HIV+ Patients with Squamous Cell Anal Cancer, a Subgroup Analysis of the National Multicenter Cohort FFCD-ANABASE

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.

Role of induction chemotherapy in locally advanced oropharyngeal carcinoma in Indian population.

e18026 Background: Head and neck cancer is the third most frequent cancer in Indian men, it is a growing public health problem. Given the numerous disparities in head and neck cancer biology, etiologic and demography between the developing world and the developed world, management guidelines should be based on Indian literature rather than western data. This study aims to define role of Induction chemotherapy in locally advanced oropharyngeal cancer In Indian population by comparing the outcomes which are Overall response rate (O.R.R), Progression free survival (P.F.S), overall survival (O.S) between patients who received Induction chemotherapy followed by CTRT vs CTRT. Methods: Patients who were registered for treatment between jan-2018 to dec-2022 who met the selection criteria were included for the study. Selection criteria: Patients who were diagnosed with Stage III OR IV (a &amp; b, non-metastatic) oropharyngeal squamous cell carcinoma from age group of 20 to 70 who were HPV negative or unknown status were included for study. Total of 50 patients were chosen for the study after stringent selection criteria. Out of 50 ,23 patients received Induction chemotherapy and 27 patients received only CTRT. Results: Overall response rate was analysed using Interim PET CT after Induction chemotherapy and PET CT after 3 to 6 months of CTRT. Complete response and partial response is considered as ORR. It was observed that ORR in sequential therapy arm is 42% and only CTRT arm is 36%, however this is not statistically significant with p value of 0.54. Median PFS for CTRT arm is 8 months and median PFS for IC +CTRT arm is 12 months with p value = 0.97(&gt;0.05) (Log rank test) which is not statistically significant. Median OS for CTRT is 60 months and IC+ CTRT is 18 months. The log rank test has been used for comparing the overall survival outcomes of both the groups , and thus the p-value obtained is 0.56(&gt;0.05), which shows that there is no statistically significant difference in the survival outcome of the two groups. Conclusions: In conclusion, our study on induction chemotherapy in locally advanced head and neck cancer did not identify statistically significant differences in O.R.R, PFS and OS between the two treatment arms which is concordant with MACH- NC updated 2021 data. Several factors, including patient heterogeneity, sample size, treatment protocol, follow-up, duration, may have contributed to these results, it is essential to interpret these results in the context of the study's limitations. [Table: see text]

Induction immune checkpoint inhibitors and chemotherapy for patients with stage III non-small cell lung cancer: A real-world experience.

e20057 Background: Immune checkpoint inhibitors (ICIs) have become the standard consolidation therapy for stage III unresectable non-small cell lung cancer (NSCLC). Whether induction ICIs combined with chemotherapy can further improve efficacy is controversial. In this study, we used real-world data to explore the possibility of ICIs plus chemotherapy before definitive chemoradiation therapy (CRT). Methods: Patients with stage III NSCLC (including postoperative recurrence), who received definitive CRT from 2016 to 2022, was retrospective reviewed. Survival outcomes and the incidence of pneumonia were calculated and compared between patients with induction ICIs plus chemotherapy or not. Results: A total of 156 patients undergoing definitive RCT were analyzed. Among them, 103 patients received induction ICIs plus chemotherapy, and 53 patients received induction chemotherapy before RCT or concurrent chemoradiotherapy. The 5-year overall survival (OS) rates were 75.0% and 44.4%, respectively. The median OS was not reached (NR) and 36.5 months, indicating a significant improvement of survival with the addition of induction ICIs (P = 0.03). However, there were no significant differences between the two groups in median progression-free survival (PFS) (22.4 vs. 13.6 months; P = 0.09), locoregional recurrence-free survival (LRFS) (38.0 vs. 36.9 months; P = 0.73), and distant metastasis-free survival (DMFS) (37.8 vs. 25.5 months; P = 0.14). Multivariate analysis showed that induction ICIs plus chemotherapy was an independent favorable prognostic factor for OS (HR 2.89; 95% CI, 1.24-6.75; P = 0.01). The incidence of grade 2 or higher pneumonia in the two groups was 37.2% and 29.2%, respectively (P = 0.35). Additionally, we found that patients with consolidation ICIs after induction ICIs had a better OS, with a 4-year OS rate of 90.7% and 65.5% (P = 0.03). Patients undergoing 5-6 cycles of induction ICIs seemed to have a better outcome compared to those with 3-4 cycles or 1-2 cycles (93.8% vs. 77.4% vs. 60.5%). Conclusions: For patients with stage III NSCLC receiving definitive CRT, the combination of induction ICIs and chemotherapy improves OS without a significant increase of pneumonia in real-world practice. This treatment strategy warrants further research.

Acute myeloid leukemia with t(16;21)(q24;q22), CBFA2T3::RUNX1, in post-treatment setting, a case report

Abstract Introduction/Objective Acute myeloid leukemia (AML) with t(16;21)(q24;q22), CBFA2T3::RUNX1 is an uncommon entity that has been reported in both pediatric and adult patients as de novo AML or secondary to prior chemo/radiation therapy. CBFA2T3::RUNX1 AMLs share similar clinico-pathological features and gene expression profile with RUNX1::RUNX1T1 AML. Methods/Case Report We report a case of AML with CBFA2T3::RUNX1 in a 52 year old female who had history of small cell cervical cancer treated with chemotherapy (4 cycles of cisplatin and etoposide) and pelvic radiation therapy. About 17 months after completion of therapy, she presented with anemia and thrombocytopenia, normal WBC/neutrophil count, eosinophilia and increased blasts (up to 10%) in blood. Bone marrow biopsy shows AML with maturation (FAB-M2), erythropoiesis is present, whereas megakaryocytes are decreased. Flow cytometry analysis shows myeloblasts with aberrant CD19 and CD56 expression; in addition, increased CD117/tryptase positive cells are noted, mostly interstitial and more concentrated around bone trabeculae. By immunohistochemical stains, these cells are at least partially positive for CD25, negative CD2, CD30. Karyotype studies demonstrate t(16;21)(q24;q22) and trisomy 8 in all metaphases. FoundationOne heme NGS studies confirmed CBFA2T3::RUNX1 fusion, and no additional mutations were identified. Patient received induction chemotherapy with Idarubicin/Cytarabine plus GO (Gemtuzumab ozogamicin); day 14 bone marrow showed chemotherapeutic effect and she is now in morphologic remission 5 months after diagnosis. Results (if a Case Study enter NA) NA Conclusion Our case adds to the limited knowledge of CBFA2T3::RUNX1 AMLs. Our case shows morphological and immunophenotypic features similar to AML with RUNX1::RUNX1T1, with unusual presentation of peripheral eosinophilia, and increased CD117/tryptase positive cells in bone marrow, the latter has been reported occasionally in core binding factor AMLs. We emphasize the importance of comprehensive genetic studies in AML patients, lack of adverse genetic abnormalities in our patient indicates favorable risk category regardless of the post-treatment clinical setting.

Real World Outcomes in Patients with Ph-like ALL at the University of New Mexico

Introduction: Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a heterogenous subtype of ALL characterized by different translocations and molecular mutations, resulting in a gene expression profile similar to Philadelphia chromosome positive (Ph+) ALL without an identified BCR::ABL1 translocation. Unfortunately, Ph-like ALL is characterized by worse response rates to conventional therapies and poor overall survival compared to other ALL subtypes. It is reported that 20-30% of patients with newly diagnosed ALL in the United States have Ph-like ALL and the incidence appears to vary according to ethnicity. While many therapies are under investigation including the addition of a tyrosine kinase inhibitor or ruxolitinib to conventional chemotherapy, a standardized and molecularly-based approach to treating patients with Ph-like ALL is not yet defined. There also remain questions about the efficacy of integrating inotuzumab ozogamicin or blinatumomab into first-line therapy for these patients. In addition, recent retrospective data has demonstrated promising effects of using traditional salvage therapies for ALL such as Car T cells, inotuzumab, or blinatumomab in patients with Ph-like ALL. However, the optimal sequence of treatment as well the efficacy of combining salvage therapies with agents such as ruxolitinib remains unknown. Herein, we present our institutional experience with diagnosing and treating adult patients with Ph-like ALL at the University of New Mexico. Our goal was to characterize the demographics, molecular and cytogenetic landscape, and treatment outcomes at a medical center that serves a patient population enriched for this disease. Methods: After IRB approval, we performed a retrospective chart review of patients diagnosed and treated at the University of New Mexico between January 1, 2018 and April 1, 2023. We included patients who were 18 years or older at the time of diagnosis, received first-line therapy at the University of New Mexico, and had gene expression profiling or FISH testing that was consistent with Ph-like ALL. Statistical analysis was performed using SPSS Statistics v.27 (IBM, 2020). Results: We identified 9 patients who met inclusion criteria. All 9 patients self-identified as either ‘American Indian or Alaska Native’ or ‘Hispanic or Latino.‘ The median age at diagnosis was 34 and the mean BMI at diagnosis was 34.6. 5 patients were CD20 positive and 1 patient had a concurrent IKZF1 mutation. All patients received induction chemotherapy with either a BFM regimen or HyperCVAD. 5 (55%) patients were refractory to induction and 6 (66%) patients eventually underwent allogeneic stem cell transplant as part of their treatment. 1 patient received Car T cell therapy with Brexucabtagene autoleucel following relapse after allogeneic stem cell transplant. 1 patient died 124 days after diagnosis and 8 patients are alive currently. 4 patients had IGH:: CRLF2, 2 patients had P2RY8::CRLF2,1 patient had GTF2I::PDGFRB,1 patient had IGH::BCL2,and one patient had both a positive low-dose array and a positive gene expression profile without an identified molecular or cytogenetic abnormality consistent with Ph-like ALL. Discussion: We present our preliminary experience of patients with Ph-like ALL diagnosed and treated at the University of New Mexico. Our patients were young with a median age of 34. Consistent with published data describing patients with Ph-like ALL, our patients had poor responses to traditional ALL treatments and most commonly had an identified fusion with CLRF2. Our data supports the urgent need for the development of further treatment options for patients with Ph-like ALL as well as clinical trials aimed at standardizing management.

Long-Term Outcome of Multiple Myeloma Patients Receiving Autologous Stem Cell Transplantation (ASCT) - Impact of Therapeutic Strategy Following ASCT

Introduction Despite all the therapeutic progress made in multiple myeloma (MM), the standard of care for eligible patients remains an intensive induction therapy followed by high dose melphalan and autologous stem cell transplantation (ASCT). Material and methods This present retrospective study included MM patients treated in Lyon between 1997 and 2020. All patients received induction chemotherapy followed by intensive chemotherapy and ASCT, with or without consolidation and maintenance therapy. Number and type of therapeutic lines administered for relapse after ASCT were analyzed. All data were reported in the European blood and marrow transplantation (EBMT) PROMISE registry. Statistical analysis Descriptive analyses were used for demographic variables, biological parameters, and treatment characteristics. Overall survival (OS) and progression-free survival (PFS) were presented using the Kaplan-Meier method and log-rank tests were performed to compare survival curves. Univariate and multivariate analyses were computed using Cox regressions and the multivariate analyses considered the variables for which the univariate ANOVA p-value was≤ 10%. Statistical analyses and graphics were computed with R v4.1.2, with the help of ‘survival’ and ‘ggplot2‘ packages. Results Before ASCT A total of 342 patients were included in the study (median 60 years (range: 28-73), 58% were male, 89.4% were diagnosed with a type III myeloma according to the Salmon and Durie classification. No genetic analysis was performed at that time. Most patients (92.5%) had a performance status (PS) of 0 or 1. The type of myeloma was heavy chain and light chain myeloma for 75.7% patients (68.9% of IgG kappa) and light chain myeloma in 23.1%. The median delay between diagnosis and ASCT was 4.8 months. Before ASCT, patients received an induction therapy with VTD in 54.1% of cases, VD in 30.1%, and more recently VRD in 16.1%. Disease status before ASCT was complete remission (CR) for 17.5% of the patients, partial remission (PR) and very good partial remission (VGPR) for 79.2% of patients and progressive disease or relapse for 3.0% of them. After ASCT The median duration of aplasia was 11 days. At day 100, the response was CR in 166 patients (50.5%), 182 patients (54.7%) received a consolidation treatment and 71 patients (20.8%) a maintenance therapy (Revlimid® for 90% of them). Overall, 227 (66.4%) patients relapsed. The median delay between ASCT and relapse was 22.5 months (0.89-229.13) and the median follow-up duration was 46.7 months (0.33-287.97). Among the 227 patients who relapsed, 6 patients were not treated, 79 patients (23.1%) received one chemotherapy line, 32 patients (9.4%) received two lines, 38 (11.1%) received 3 and 72 (21.1%) received at least 4 lines and up to 8. Overall survival and progression free survival The median OS was 132 [95% CI 110.6; NR] months from diagnosis and 122.8 [100.9; NR] months from ASCT. The median PFS was 39.35 [36.25; 43.37] months from diagnosis and 31.07 [28.42; 35.91] months from ASCT (Figure 1 A, B). In multivariate analysis on OS, the shorter aplasia duration (p&amp;lt;0.001) and consolidation and maintenance (p&amp;lt;0.001) were significantly associated with a significant better OS. The median OS was not reached from ASCT for patients who have received both consolidation and maintenance treatments and no death was reported. (Figure 1 C). For patients receiving chemotherapy lines for relapses after ASCT (Figure 1D) regardless of the number of lines the median OS was102.4 months and the 10-year OS probability was 45.6%. The OS of patients who received 3 lines of treatment was identical to that of patients who received one or 2 lines after ASCT. The median OS after 1 to 2 lines of chemotherapy after ASCT was not reached and was 127.15 months [70.6-NR] for those receiving 3 lines (Figure 4B). The OS of patients who received more than 4 chemotherapy lines after ASCT was significantly lower compared to the OS (p=0.0096) with a median [95%CI] OS of 85.5 months [65.61-106.15]. In conclusion this study showed the significant positive impact on OS of the association consolidation and maintenance. We have also studied the impact of number of chemotherapy lines and the impact on OS and PFS of kind of treatment will be discussed.

Apixaban Is Effective and Safe in Reducing Venous Thromboembolism (VTE) in Obese Patients with Newly Diagnosed Pediatric Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma (ALL/LL) a Sub-Study Analysis of the Prevapix-ALL/Children's Oncology Group ACCL1333 Trial

Background: Pediatric patients with ALL/LL are at increased risk for VTE and obesity further increases VTE risk. Pediatric ALL/LL patients experiencing VTE have increased risk for mortality as compared to ALL/LL patients without VTE. Therefore, effective and safe pharmacologic VTE prevention options are urgently needed. The PREVAPIX-ALL trial was a multi-center, multinational, randomized, open-label, controlled trial assessing the safety and efficacy of primary prophylaxis using apixaban for the prevention of VTE in pediatric patients with ALL/LL. PREVAPIX-ALL was a collaboration between the Bristol Myers Squibb/Pfizer Alliance and the Children's Oncology Group. Patients with ALL/LL undergoing induction chemotherapy containing asparaginase therapy were randomized to either apixaban or standard of care (SOC - no anticoagulation). The objective of the current study was to separately analyze obese patients as a subgroup of the PREVAPIX-ALL trial. Aims: To assess the efficacy and safety of prophylactic apixaban vs. SOC for VTE prevention during induction chemotherapy in obese pediatric patients with ALL/LL. Methods: Obesity was defined as ≥ 95 th percentile for age and sex specific body mass index as per the Centers for Disease Control and Prevention childhood obesity definition. Patients newly diagnosed with ALL/LL, ages ≥ 1 to &amp;lt; 18 years, with a central venous line, and on induction chemotherapy with asparaginase were randomized to apixaban vs. SOC. Apixaban thromboprophylaxis was administered at a fixed dose per body weight until the end of induction when participants were screened for VTE. The primary efficacy outcome was a composite of symptomatic and asymptomatic VTE. The primary safety outcome was major bleeding, and the secondary safety outcome was a composite of major and clinically relevant non-major (CRNM) bleeding. Results: Out of 512 PREVAPIX-ALL participants, 498 (97.2%) were age 24 months or older with weight and height available. Of those, 82 were obese. Forty-two were randomized to apixaban and 40 were randomized to SOC (Table 1). For the primary efficacy outcome there was a statistically significant decrease in VTE events in the apixaban arm, 1/42 (2.4%) compared to the SOC arm 10/40 (25%) [RRR 91% (95% CI 3%, 99%) p 0.0067] (Table 2). No statistically significant difference was observed in bleeding between the two groups (Table 2). The mean apixaban exposure was similar among the obese and non-obese groups: obese apixaban mean exposure (SD) 23.4 days (5.55) and non-obese 23.5 days (6.44). No statistical difference was observed in the median steady-state area under the curve (AUC-TAU ng.h/mL) drug exposure between obese and non-obese categories stratified by age group on a linear scale: obese (n=38) 686.94 ng.h/mL (95% CI 397.8-1314.6) and non-obese (n=186) 663.50 ng.h/mL (95% CI 319.1-1090.9). Conclusion: Apixaban VTE prophylaxis in obese ALL/LL patients receiving asparaginase during induction chemotherapy resulted in a statistically significant 91% RRR in VTE compared to SOC. No statistical difference was observed in apixaban exposure days and AUC/TAU between obese and non-obese patients. Bleeding events were not increased in the apixaban arm as compared to SOC. Primary prophylaxis using apixaban safely reduces VTE in obese ALL/LL pediatric patients receiving induction chemotherapy containing asparaginase.

Survival Benefit of Induction Chemotherapy with Paclitaxel and Carboplatin Followed by Chemoradiation Versus Postoperative Treatment in Locally Advanced Gastric Cancer: A Retrospective Cohort Study.

Gastric cancer remains a prevalent worldwide illness that lacks a definitive cure. Recently, induction chemotherapy followed by concurrent chemoradiation has shown promising results in achieving a significant pathological response in locally advanced gastric cancer and improving survival rates. However, the optimal regimen for this approach continues to be a subject of discussion. This retrospective cohort study was conducted on treatment-naïve patients with locally advanced gastric cancer who were referred to Imam Hossain General Hospital in Tehran, Iran, between April 2016 and March 2019. Eligible patients met the criteria of clinical T3-4 or nodal-positive stage, or both, and had non-metastatic resectable tumors. The patients were categorized into two groups: (a) the neoadjuvant group, which received induction chemotherapy (carboplatin AUC 2 and paclitaxel 50mg/m2 weekly for 12 cycles) followed by concurrent neoadjuvant chemoradiation (radiotherapy 45-50Gy/1.8Gy per fraction concurrent with capecitabine 500mg/m2 BID and oxaliplatin 40mg/m2 weekly), and (b) the adjuvant group, which was treated with standard chemoradiation or chemotherapy regimens. The two groups were compared regarding the 3-year recurrence rate and 3-year overall survival. A total of 102 patients were included in the study (63.7% male, mean age ± standard deviation 56 ± 13 years). Among these, 45 patients received neoadjuvant treatment, and 57 received adjuvant treatment. The neoadjuvant group had a higher proportion of patients with advanced disease (stage III: 91.1% vs. 57.9%, P = 0.001). In the neoadjuvant group, 20 patients (44.4%) achieved a complete pathologic response, and all underwent curative surgery. The neoadjuvant group exhibited a lower 3-year recurrence rate (13 [28.9%] vs. 33 [57.9%], P = 0.003) and a higher 3-year overall survival rate (36 [80%] vs. 32 [56.1%], P = 0.003). Patients receiving induction chemotherapy with paclitaxel and carboplatin followed by chemoradiation demonstrated enhanced disease control and survival compared to standard adjuvant regimens. In addition, patients treated with the applied preoperative regimen in this study showed higher pathologic response and overall survival rates than in previous studies.

Radiomics Based Assessment of Tumor Infiltrating CD8 T-Cells Predicts Induction Systemic Therapy Response in HPV+ Oropharyngeal Cancer: Exploratory Analysis of Prospective Trials

The adaptive immune system is increasingly recognized to be important for tumor control in HPV+ oropharyngeal cancer (HPV+OPC), and pre-clinical models suggest tumor specific T-cell priming occurs in draining lymph nodes. De-escalation strategies incorporating T-cell infiltration present a novel prognostic biomarker. The purpose of this study was to examine the utility of a validated radiomics model of CD8 T-cell infiltration within the framework of 2 prospective HPV+OPC response-adaptive de-escalation trials. We hypothesized that nodal radiomics scores (RS) would be correlated with response to induction systemic therapy. Patients enrolled on 2 prospective phase II response adapted de-escalation trials for low- and high-risk HPV+OPC were included in the analysis. Patients received induction chemotherapy and chemoimmunotherapy in trials 1 and 2, respectively. Primary tumors and nodes were retrospectively delineated on diagnostic CT scans before and after induction therapy to ascertain volumetric tumor burden & response. RS were generated on pre-induction scans for both primary tumors and nodes. RS and tumor response were dichotomized using a 50% threshold (high vs low, responder vs non-responder, respectively). Linear regression was used to evaluate the correlation between % volume change in tumor burden and RS. Fisher's exact test was used to evaluate concordance between RS and tumor response. A total of 87 patients (N = 47 Trial 1, N = 40 Trial 2) were evaluable. The mean post-induction therapy reduction in primary and nodal volumetry was 80.7% and 67% respectively. Primary and nodal RS were not associated with primary (T1/T2 vs T3/T4) or nodal stage (N1-N2b vs N2c-N, p > 0.10 both). Both primary and nodal RS were correlated with % volume change, r = 0.24 (p = 0.034) and r = 0.37 (p = 0.002), respectively. The mean difference in % volume change in primary and node, using the RS, was 11.13% (p = 0.015) and 17. 69% (p = 0.004). There was no association between primary tumor RS and total lesion responder status (p = 0.312). However, there was an association between high vs low nodal RS and total lesion responder status (p = 0.005). This is the first report of a validated radiomics score of CD8-T cell infiltration in HPV+OPC to predict response to systemic therapy. While radiomics scores in both the primary and nodes were associated with percent volume response, this association was stronger in nodes. Higher nodal radiomics scores were associated with improved volume reduction in total lesion burden. This effect however was not observed in the primary tumor. CD8-T cell infiltration in nodes, but not in the primary tumor, was associated with overall tumor response after systemic induction therapy in HPV+ oropharyngeal cancer.

Evaluation of Metastatic Potential in Esophageal and Gastroesophageal Junction (GEJ) Cancer with Adherence to Elective Nodal Volume Guidelines: A Retrospective Analysis of Elective Nodal Irradiation

In 2015, expert guidelines on esophageal/GEJ cancer contouring for intensity-modulated radiation therapy (IMRT) were published in IJROBP, which delineate recommended elective nodal basins (celiac, para-aortic, gastrohepatic ligament, supraclavicular) to be irradiated depending on the primary tumor location. We hypothesize that incomplete coverage of these areas increases the risk of the development of distant failures. Patients treated for non-metastatic esophageal or GEJ cancer with chemoradiotherapy pre-operatively or definitively from 2012 to 2021 were retrospectively identified from a single institution database. Radiation plans of eligible patients were then analyzed by tumor location. Plans were deemed guideline-compliant if radiation dose coverage, between 41.4 to 45 Gy, encompassed nodal basins recommended by the 2015 guidelines. The primary endpoint of this study was the overall rate of distant disease. Other endpoints included locoregional failures, defined as failures within the radiation field but outside of the primary tumor, and local failures within the gross tumor volume. Summary and descriptive statistics were used to define collected variables. Differences were measured using chi-square and Fisher's exact test for categorical variables and two-sided t-tests for continuous measures. Assessment of distant, locoregional, and local failures were assessed using univariate logistic regression with statistical significance at p < 0.05. With a median follow-up of 25.0 months, 37 patients, with a median age of 66, were included in the study. Most patients were male (94.6%) with cT3 (54.1%), cN0 (43.2%), moderately differentiated (47.1%) adenocarcinoma (75.7%) located at the GEJ (56.8%). The median radiation dose used was 50.4 Gy, with the majority of patients receiving concurrent carboplatin and paclitaxel (83.8%). Four patients received induction chemotherapy and 20 (55.6%) underwent esophagectomy. When examining guideline compliance, 17 (46.0%) radiation plans demonstrated adequate ENI. The most common improperly covered nodal basin was para-aortic (65.0%), followed by gastrohepatic (30.0%). No patients with sufficient ENI coverage (0/17) developed distant failure compared to 45.0% (9/20) with insufficient coverage (p = 0.001). There were inappreciable differences in locoregional or local failure rates between those with and without complete ENI. Patients with complete ENI were more likely to be of larger craniocaudal length (p = 0.007) or have N2 disease (p = 0.003). When examining other tumor characteristics (histologic subtype, location, HER2 status, esophagectomy rate) of patients with and without complete ENI, no further differences were noted. These results suggest that proper coverage of nodal basins, when indicated by expert guidelines, could improve distant metastasis. ENI analysis of previous prospective CRT studies for esophageal cancer could validate these findings.

Induction chemotherapy with nedaplatin, docetaxel and 5-fluorouracil followed by concurrent nedaplatin and radiotherapy in locoregionally advanced nasopharyngeal carcinoma: A single arm, open label, phase II clinical trial.

6067 Background: To evaluate the efficacy of induction chemotherapy with nedaplatin, docetaxel and 5-fluorouracil followed by concurrent nedaplatin combined with radical radiotherapy in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Methods: This is a prospective, single-arm, open-label, phase II trial. Patients with aged 18-65 years, newly diagnosed stage III-IVa (except T3-4N0) nasopharyngeal carcinoma were enrolled. Eligible patients received induction chemotherapy with docetaxel (60 mg/m² intravenously on days (D) 1, 22 and 43), Nedaplatin (60 mg/m² intravenously on D 1, 22 and 43) and fluorouracil (600 mg/m² per day as a continuous 120 hours (h) infusion on D 1-5, 22-26 and 43-47) every three weeks for three cycles, thereafter received intensity-modulated radiotherapy (IMRT) concurrently with nedaplatin (100mg/m2 intravenously on D 1, 22 and (or) 43) every three weeks for two or three cycles. The primary end point was objective response rate (ORR). The secondary end points included overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and local recurrence-free survival (LRFS). Results: Between March 2020 and June 2021, a total of 32 patients with LA-NPC were enrolled. With a median follow-up duration of 14.0 months (IQR 11.7-16.3), 32 patients (100%) achieved ORR at three months after treatment. The 12-month PFS was 95.7% (95% CI 87.3% to 100%) and the 12-month OS was 100%. The most common grade 3 or 4 adverse events during induction chemotherapy were neutropenia (3 [9.4%]), diarrhea (3 [9.4%]) and hepatoxicity (3 [9.4%]), followed by leucopenia (2 [6.3%]) and fatigue (1 [3.1%]). The most common grade 3 or 4 adverse events during concurrent chemotherapy were mucositis (3 [9.4%]), leucopenia (1 [3.1%]), neutropenia (1 [3.1%]) and thrombocytopenia (1 [3.1%]). All of these adverse events were manageable. Conclusions: Induction chemotherapy with nedaplatin, docetaxel and 5-fluorouracil followed by concurrent nedaplatin combined with radical radiotherapy showed promising antitumor activity and manageable toxicities in patients with LA-NPC. Further phase III randomized controlled trials are warranted to validate our findings. Clinical trial information: NCT04834206 .

Combined expression of WT1/PRAME genes and BIRC5/PRAME genes and their clinical significance in adult patients with acute myeloid leukemia

Abstract Background Several tumor-associated antigens have been recently recognized that qualify to monitor tumor burden of acute myeloid leukemia (AML) or are used as antigen-specific approach for anticancer immunotherapy. Aim The current study was designed to assess the intracellular expression levels of the immunogenic tumor antigens ( WT1 , BIRC5, and PRAME genes) and clarify the prognostic effect of their combined overexpression, that is, WT1 /PRAME and BIRC5 / PRAME , on the clinical course, the outcome, and the response to treatment in patients with AML. Settings and design A total of 61 patients with AML were included in the study. All patients received induction chemotherapy. Detection of intracellular WT1, BIRC5, and PRAME genes in myeloid blast cells was done by real-time PCR on bone marrow samples. Their levels were correlated with the demographic data, the clinical and pathological data, the defined subgroups, the overall survival, and the response to treatment in patients with AML. Results WT1, BIRC5, and PRAME overexpression was detected in 73.8, 28, and 38.6% of patients, respectively. Nearly half of the patients (51.7%) were WT1+/PRAME− and significantly associated with absence of both favorable cytogenetic prognosis and complete remission. In addition, it expression was correlated with female sex, higher count of blasts in peripheral blood, positive CD34 expression, and higher FAB classification (M4) but with no statistically significant difference. Most patients were double negative BIRC5−/PRAME− (45.6%). A significant relation was found between BIRC5+/PRAME− and older age patients (P=0.003) and a lower overall survival (P=0.005) and also associated with higher count of blast cells but not statistically significant. Most BIRC5−/PRAME+ (72.7%) achieved complete remission at 28 days, followed by double negative BIRC5−/PRAME− (56.6%) at 28 days, most of BIRC5+/PRAME− patients died (77.8%). Conclusion In patients with AML, the expression levels of genes WT1, BIRC5, and PRAME were high, and these genes had a substantial correlation with poor prognostic factors, including a poor cytogenetic prognosis, incomplete remission, and a reduced survival rate. Therefore, they could be considered as targets for anticancer immunotherapy as well as possible markers for monitoring AML.

Allogeneic hematopoietic stem cell transplantation in acute leukemia patients with the SET-NUP214 fusion gene: Efficacy and survival analysis

Objective: To investigate the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute leukemia who are positive for the SET-NUP214 fusion gene (SET-NUP214+AL). Methods: This was a retrospective case series study. Clinical data of 18 patients with SET-NUP214+AL who received allo-HSCT in the First Affiliated Hospital of Soochow University and Soochow Hongci Hematology Hospital from December 2014 to October 2021 were retrospectively analyzed to investigate treatment efficacy and prognosis. The Kaplan-Meier method was used for survival analysis. Results: Of the 18 patients, 12 were male and 6 were female, and the median age was 29 years (range, 13-55 years). There were six cases of mixed phenotype acute leukemia (three cases of myeloid/T, two cases of B/T, one case of myeloid/B/T), nine cases of acute lymphoblastic leukemia (ALL) (one case of B-ALL and eight cases of T-ALL), and three cases of acute myeloid leukemia. All patients received induction chemotherapy after diagnosis, and 17 patients achieved complete remission (CR) after chemotherapy. All patients subsequently received allo-HSCT. Pre-transplantation status: 15 patients were in the first CR, 1 patient was in the second CR, 1 was in partial remission, and 1 patient did not reach CR. All patients were successfully implanted with stem cells. The median time of granulocyte and platelet reconstitution was +12 and +13 days, respectively. With a median follow-up of 23 (4-80) months, 15 patients survived, while 3 patients died. The cause of death was recurrence of SET-NUP214+AL after transplantation. After allo-HSCT, 5 patients relapsed. The estimated 3-year overall survival (OS) and relapse-free survival (RFS) rates were 83.3%±15.2% and 55.4%±20.7%, respectively. Among the 15 patients who achieved CR before transplantation, there was no significant difference in OS and RFS between haploidentical HSCT and matched sibling donor HSCT (all P>0.05). Conclusions: Allo-HSCT can improve the prognosis and long-term survival rate of patients with SET-NUP214+AL. Disease recurrence is the most important factor affecting long-term survival.

Clinical study of induction chemotherapy followed by allogeneic hematopoietic stem cell transplantation in the treatment of FLT3-ITD(+) acute myeloid leukemia with normal karyotype

Objective: To assess the efficacy of induction chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of FLT3-ITD(+) acute myeloid leukemia (AML) with normal karyotype. Methods: The clinical data of FLT3-ITD(+) AML patients with normal karyotype in the First Affiliated Hospital of Nanjing Medical University from Jan 2018 to March 2021 were retrospectively analyzed. Results: The study included 49 patients with FLT3-ITD(+)AML, 31 males, and 18 females, with a median age of 46 (16-59) years old. All patients received induction chemotherapy, and 24 patients received sequential allo-HSCT (transplantation group) . The median follow-up time was 465 days, the one-year overall survival (OS) from diagnosis was (70.0 ± 7.4) %, and one-year disease-free survival (DFS) was (70.3±7.4) %. The one-year OS was significantly different between the transplantation group and the non-transplantation group [ (85.2 ± 7.9) % vs (52.6 ± 12.3) %, P=0.049]. but one-year DFS [ (84.7 ± 8.1) % vs (55.2 ± 11.9) %, P=0.061] was not. No significance was found in one-year OS between patients with low-frequency and high-frequency FLT3-ITD(+) (P>0.05) . There were 12 patients with high-frequency FLT3-ITD(+) in the transplantation and the non-transplantation groups, respectively. The one-year OS [ (68.8 ± 15.7) % in the transplantation group vs (26.2 ± 15.3) % in the non-transplantation group, P=0.027] and one-year DFS [ (45.5 ± 21.3) % in the transplantation group vs (27.8±15.8) % in the non-transplantation group, P=0.032] were significantly different between the two groups. Conclusion: Induction chemotherapy followed by allo-HSCT can enhance the prognosis of FLT3-ITD(+) patients, particularly those with FLT3-ITD high-frequency mutation.