Undergoing Induction Chemotherapy Research Articles

Is pT0 a Reliable End Point for Biomarker Discovery for Preoperative Chemotherapy Response in Patients With Bladder Cancer?

Purpose: Traditional biomarker investigation schemas for chemotherapy response prediction in patients with bladder cancer relying on the pT0 status at radical surgery are confounded by the therapeutic effect of transurethral resection of bladder tumor (TURBT). Studying cN+ patients and assessing pN0 status presents a unique opportunity for overcoming this bias. Materials and Methods: We studied 26 patients with biopsy-proven cTanyN1-3M0 bladder cancer (2005-2016) who underwent induction chemotherapy and radical cystectomy with pelvic lymphadenectomy. Metastasis and overall survival (OS) outcomes were examined using Kaplan-Meier method and compared using log-rank test. Paired pretherapy primary bladder and nodal tissues were available for 10 patients. In these patients, whole-transcriptome RNA-seq analysis was performed on bladder tumor (for pT0 and pN0 prediction) and lymph-nodal metastasis (for pN0 prediction) tissues to identify differentially expressed genes (DEGs) with a false discovery rate < 0.1. Results: pN0 pathologic responders, but not pT0 responders, had significantly improved freedom from metastasis (5-year: pN0 88.9% vs pN+ 27.4%, log-rank P = .018) and OS (5-year: pN0 76.2% vs pN+ 12.2%, log-rank P = .024). Using RNA-seq data, we identified a significant discordance rate of 87.5% between DEG-based predictive signatures for pT0 and pN0 response to cisplatin-based chemotherapy. This datum, combined with the knowledge that ∼40% of patients who achieve pT0 status at radical surgery, achieve it simply through the therapeutic effect of TURBT (SWOG S8710), underscores a substantial bias in the current biomarker discovery initiatives that use pT0 as an end point. Conclusions: Our findings suggest a need for devising novel study designs to aid in the discovery of reliable biomarkers for preoperative chemo/immunotherapy response in bladder cancer. Clinical node-positive patients may be ideally situated but remain understudied.

Evaluation of Gemtuzumab Ozogamicin and Anthracycline Dosing for Favorable Risk Acute Myeloid Leukemia.

Gemtuzumab ozogamicin (GO) is a CD33-targeting antibody-drug conjugate approved for the treatment of CD33-positive de novo and relapsed and refractory acute myeloid leukemia (AML). Subset analyses have demonstrated improved clinical outcomes in patients with favorable-risk disease. It is unclear whether the addition of GO to cytarabine and anthracycline chemotherapy (7+3) improves clinical outcomes compared with other conventional regimens for AML. We evaluated the real-world experience with GO added to 7+3 chemotherapy for patients with favorable risk AML. This retrospective analysis included 174 patients with de novo favorable risk AML undergoing induction chemotherapy between 2010 and 2020. The primary outcome was overall survival (OS) and secondary outcomes included rates of remission, measurable residual disease (MRD), and toxicity. Eighteen patients received GO, 37 received a high-dose (HD) anthracycline, and 119 received an intermediate-dose anthracycline. Composite complete remission was achieved in 162 patients (93.1%). Among the 54 patients who were assessed for MRD at remission, 66.7% were undetectable. An improvement in OS was seen for patients who received GO and those treated with HD anthracycline, which was better explained by differences in patient performance status and comorbidities. Patients who received GO did not show increased toxicity.

Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer: Insights from the Western Australian Context.

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. This study aimed to evaluate the efficacy and safety outcomes of TNT for LARC in Western Australia. 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. 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. 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.

To study the efficacy of romiplostim in chemotherapy-induced thrombocytopenia in head and neck cancer patients

Objectives Scheduled delivery of adequate dose of chemotherapy is important to replicate the results expected from original trials. In head and neck malignancies, undue delay of chemotherapy is likely to be associated with poor control or progression. Chemotherapy-induced thrombocytopenia (CIT) is one of the reasons to delay chemotherapy. Thrombopoietin agonists (TPO-A) have been found to increase platelet counts by increasing production and mobilization of platelets. Romiplostim is a TPO agonist, studied widely and found to have good impact on prevention and treatment of CIT. The purpose of this study was to analyze the use and effect of romiplostim in CIT in locally advanced head and neck cancer patients. Material and Methods It is a retrospective study regarding practices of romiplostim use in controlling CIT, among patients of locally advanced head and neck carcinoma undergoing induction chemotherapy at a tertiary care cancer center. Data regarding delays in chemotherapy, response assessment, and modification of chemotherapy doses were also noted. Results Out of a total of 110 patients of head and neck malignancy enrolled during the study period, 18 patients received romiplostim support at least once in chemotherapy cycles and were analyzed. All patients were locally advanced and planned for induction chemotherapy. Median platelet counts before starting romiplostim was 76,000 per cumm. A median delay of ten days was noted among these cases where romiplostim was introduced after the first cycle of chemotherapy. Patient receiving romiplostim after the second cycle (n = 6) showed a median delay of 11.5 days (6–18 days) in the initiation of subsequent chemotherapy. None of them was shifted out of chemotherapy plan due to low platelet count. No dose reduction was noted in any of the cases. Conclusion This study provides a good insight about feasibility of using romiplostim in this subset of patients without delay, dose reduction, or discontinuation of chemotherapy.

Craniospinal irradiation and/or intraventricular radioimmunotherapy after high-dose chemotherapy and autologous stem cell rescue in patients with CNS retinoblastoma-Safety and outcomes.

The prognosis for patients with central nervous system (CNS) retinoblastoma (RB) (trilateral or stage 4b metastatic RB) treated with high-dose chemotherapy and autologous stem cell transplant (HDC-ASCT) remains poor. The impact of irradiation when administered as part of upfront therapy post HDC-ASCT on treatment outcomes and survival is unknown. We performed a retrospective review of all patients with CNS RB (seven stage 4b, eight trilateral, one pineal lesion belonging to methylation group RB) who underwent induction chemotherapy with an intent to proceed to HDC-ASCT at two institutions. Twelve of 16 patients (n=75%) achieved an objective response to induction chemotherapy, while four patients had progressive/refractory disease; two patients responded to subsequent therapy and proceeded to ASCT, and two patients did not. Seven of 14 patients who underwent HDC-ASCT, received radiotherapy as part of upfront therapy post HDC-ASCT in the form of craniospinal irradiation (CSI) (n=3), intraventricular radioimmunotherapy (n=3), or both CSI and intraventricular radioimmunotherapy (n=1). The Kaplan-Meier estimate of overall survival for these patients was 62.5% at 5years; no patients developed second malignant neoplasms within the radiation fields. For the seven patients who did not receive radiotherapy, the overall survival was 28.6% at 5years. CSI (23.4Gy) alone or in conjunction with intraventricular RIT may have clinical utility in eliminating persistent MRD post HDC-ASCT, contributing to improved disease-free survival in patients with CNS RB. This treatment strategy merits evaluation in a prospective, multicenter clinical trial for patients with CNS metastatic RB.

Assessment of measurable residual disease after induction chemotherapy in acute lymphoblastic leukemia patients in a tertiary care hospital

Background: Measurable residual disease (MRD) is a crucial prognostic factor in acute lymphoblastic leukemia (ALL), influencing treatment outcomes and long-term survival. This study investigates the prevalence of MRD post-induction chemotherapy and its association with clinical, demographic, and biochemical markers in ALL patients at a tertiary care hospital. Methods: This observational cross-sectional study was conducted at Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, from August 2021 to July 2022. A total of 22 newly diagnosed ALL patients underwent induction chemotherapy and MRD evaluation using flow cytometry. Clinical signs, demographic data, and laboratory findings, including serum creatinine, uric acid, and BCR-ABL1 status, were recorded. Statistical analyses assessed the relationships between MRD status and various predictors. Results: Of the 22 patients, 7 (31.82%) remained MRD positive after induction chemotherapy. Anaemia was prevalent, affecting 20 participants (90.91%). MRD positive patients had higher serum creatinine (mean 1.23±0.31 mg/dl) and uric acid levels (mean 7.09±1.62 mg/dl) compared to MRD negative patients. None of the MRD positive patients tested positive for BCR-ABL1. Six of the 7 MRD positive patients were male (85.71%). Bone marrow analysis showed 5 MRD positive patients (71.43%) achieved complete remission. Risk stratification did not significantly correlate with MRD status. Conclusions: MRD is a critical prognostic tool in ALL management, correlating with higher biochemical markers of tumor burden and a distinct clinical profile. These findings support integrating MRD assessment with detailed clinical and laboratory evaluations to refine treatment strategies and improve patient outcomes in ALL.

PD-1 blockade with camrelizumab after chemoradiotherapy in nasopharyngeal carcinoma.

129 Background: Approximately 30% of locoregionally advanced nasopharyngeal carcinoma (NPC) experience disease relapse despite definitive chemoradiotherapy. The programmed death-1 (PD-1) blockade camrelizumab has demonstrated considerable value in recurrent/metastatic NPC, while its role in locoregionally advanced NPC is worth exploring. Methods: We conducted a randomized, open-label, phase 3 trial to evaluate adjuvant camrelizumab in locoregionally advanced NPC after definitive chemoradiotherapy. Patients with T4N1M0 or T1-4N2-3M0 NPC who have undergone induction chemotherapy and concurrent chemoradiotherapy were randomized in a 1:1 ratio to receive adjuvant camrelizumab (200mg intravenously once every 3 weeks for up to 12 cycles; Camrelizumab group) or observation ( Standard-therapy group). The primary endpoint was event-free survival (freedom from randomization to locoregional recurrence, distant metastasis, or death from any cause). The secondary endpoint included locoregional recurrence-free survival, distant metastasis-free survival, overall survival, safety, and quality of life. Results: A total of 226 patients were randomized to the Camrelizumab group and 224 to Standard-therapy group. At a median follow-up of 37 months, the 3-year event-free survival was 86.9% in the Camrelizumab group and 77.4% in the Standard-therapy groups (stratified hazard ratio, 0.61; 95% confidence interval [CI], 0.38 to 0.96; P = 0.03). Grade 3 or 4 adverse events were reported in 11.2% patients in the Camrelizumab group and 3.2% of those in the Standard-therapy group. The most common adverse event of grade 3 or 4 was leukopenia (4.9% and 1.4%, respectively). There was no meaningful deterioration in quality of life associated with the use of adjuvant camrelizumab. Conclusions: Adjuvant PD-1 blockade with camrelizumab significantly improved event-free survival, with mild toxicity, highlighting its compelling role in the management of locoregionally advanced NPC. (DIPPER,ClinicalTrials.gov numberNCT03427827). Clinical trial information: NCT03427827 . [Table: see text]

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.

Healthcare provider's perceptions of bleeding in patients with acute leukaemia undergoing induction chemotherapy: A qualitative study.

Bleeding is a primary outcome for many transfusion-related trials in acute leukaemia (AL) patients, typically graded using the World Health Organisation (WHO) bleeding scale (clinically significant bleed (CSB) is ≥grade 2). This composite outcome fails to differentiate minor bleeds that may not be significant, poorly represents the total burden of bleeding and lacks input from healthcare providers (HCPs) and patients. As part of a multi-step project to create a better bleeding tool for trials, our objective was to identify HCPs' perspectives on the components of CSB in AL patients. Using qualitative description, we interviewed 19 physicians and nurses who care for AL patients undergoing induction chemotherapy. Participants were recruited from professional organisations, networks and social media. An inductive approach to conventional content analysis was used. HCPs identified features of CSB as the anatomical site of bleeding, amount of bleeding, need for intervention and changes in vital signs. Using these characteristics, bleeding events were categorised into three groups: clinically significant, could evolve into a CSB and not clinically significant. HCPs considered the patient's condition, bleeding history and clinical intuitions when deciding whether a bleed could escalate into serious bleeding. Using data from HCPs, we categorised bleeds as clinically significant, could evolve into a CSB, and not significant. A study of patients' perspectives on the importance of different kinds of bleeding is the next step to creating a bleeding definition that is informed by evidence, clinicians and patients.

Early stoppage of empirical antibiotic therapy at clinical improvement in paediatric leukaemia patients with high-risk febrile neutropenia (ESAT-HR-FN study): Study protocol of a single centre investigator initiated randomised open label non-inferiority trial

Background and rationaleFebrile neutropenia (FN) is one of the major causes of early mortality among children undergoing induction chemotherapy for haematological malignancies. FN occurs in up to 80 % of the children undergoing intensive chemotherapy and FN specific mortality is as high as 10 %. The management of high-risk FN (HR-FN) is by early initiation of broad-spectrum empirical antibiotic therapy (EAT) which is continued till blood count recovery. Adverse effects of prolonged EAT among children without proven infective focus have questioned the rationale behind the duration of EAT. The non inferiority of early stoppage of EAT in patients with low-risk FN (LR-FN) when afebrile for 48 h, irrespective of marrow recovery, is proven among adults and children. However, there is paucity of data regarding the same in children with HR-FN. This study aims to determine whether early discontinuation of EAT in children with HR-FN without proven infective focus who become afebrile and awaiting marrow recovery, would reduce antibiotic duration and their adverse effects without any negative consequences for patients. ObjectiveTo compare the rates of recurrent fever in paediatric patients (2–18 years) with HR-FN when EAT is continued till marrow recovery (control group) versus when stopped early at defervescence irrespective of marrow recovery (study group). MethodologyThis is the study protocol of a phase 3, single centre, randomized, open label, non-inferiority clinical trial. The primary outcome is the rate of fever recurrence among patients with HR-FN, when EAT is stopped early irrespective of marrow recovery (study group) and will be compared to the rate of fever recurrence on continuation of EAT till marrow recovery which is defined as an absolute neutrophil count (ANC) ≥ 500/mm3 (control group). Secondary outcomes include the comparison of duration of antibiotic use, mortality rates, hospital re-admission rates, requirement of multiple broad-spectrum antibiotics, therapeutic anti-fungal usage and need for organ support between the study and the control groups. A total of 280 children with acute leukaemia undergoing EAT for grade 3 or severe FN (ANC <500/μL) without clinico-laboratory evidence of infective foci are being randomized in the ratio of 1:1 between the study and the control group after defervescence for 48 h. The patients will be followed up for primary outcome (fever recurrence) till the end of induction period (day 35) or recovery of ANC ≥500/mm3 whichever is earlier. Expected outcomeESAT-HR FN study is the first large phase 3 randomised study to assess the impact of early stoppage of EAT irrespective of marrow recovery among a homogenous paediatric cohort of HR-FN in the setting of induction chemotherapy for acute leukaemia. This study will be seminal in addressing the duration of EAT in HR-FN among children without infective foci and if proven to be non-inferior this strategy will help to reduce the adverse effects from prolonged antibiotic use, the emergence of drug resistance, decrease hospital stay length and overall health care costs.

Is There any Benefit of Addition of Neo-Adjuvant Chemotherapy (FOLFOX4) to Standard Preoperative Treatment of Rectal Cancer? A Randomized Clinical Trial.

Total neoadjuvant therapy (TNT) before surgical intervention represents a unique therapeutic approach for the management of locally advanced rectal cancer (LARC) and has witnessed a notable rise in utilization within recent years. However, the efficacy and safety of this treatment remain subjects of ongoing debate and investigation. This randomized controlled trial aimed to evaluate the potential impact of administering induction chemotherapy (IC) before the conventional neoadjuvant concomitant chemoradiotherapy (nCRT) in LARC patients. patients with resectable stage II-III LARC were randomly allocated to receive either biweekly 6 cycles of FOLFOX4 regimen as IC followed by CRT and total mesorectal excision (TME) (experimental group) or nCRT followed by TME (control group). The primary endpoint was the rate of pathological complete response (pCR). The secondary endpoints encompassed the evaluation of treatment-related adverse events as well as the assessment of survival outcomes. 67 patients were enrolled in this study (32 in the experimental group and 35 in the control group). The median age of the patients was 45 years. Stage IIIB was observed in 46.3% of the patients. The patients who underwent induction chemotherapy demonstrated a notably higher rate of achieving pCR in comparison to the control group (28.1% vs 8.6%; P=0.001). There were no statistically significant differences observed in terms of their toxicity profile and survival outcomes. Implementation of induction chemotherapy utilizing the FOLFOX4 regimen has demonstrated a notable enhancement in the rate of pathological complete response. However, this improvement does not appear to translate into significant advancements in overall survival outcomes.

Microbial metagenomic shifts in children with acute lymphoblastic leukaemia during induction therapy and predictive biomarkers for infection

BackgroundEmerging evidence has indicated a link between the gut microbiota and acute lymphoblastic leukaemia (ALL). However, the acute changes in gut microbiota during chemotherapy and the predictive value of baseline gut microbiota in infectious complication remain largely unknown.MethodsFaecal samples (n = 126) from children with ALL (n = 49) undergoing induction chemotherapy were collected at three timepoints, i.e., initiation of chemotherapy (baseline, T0), 7 days (T1) and 33 days (T2) after initiation of chemotherapy. Gut microbiome profile was performed via metagenomic shotgun sequencing. The bioBakery3 pipeline (Kneaddata, Metaphlan 3 and HUMAnN) was performed to assign taxonomy and functional annotations. Gut microbiome at T0 were used to predict infection during chemotherapy.ResultsThe microbial diversities and composition changed significantly during chemotherapy, with Escherichia coli, Klebsiella pneumoniae and Bifidobacterium longum being the most prominent species. The microbial metabolic pathways were also significantly altered during chemotherapy, including the pathway of pyruvate fermentation to acetate and lactate, and assimilatory sulfate reduction pathway. The receiver operating characteristic (ROC) models based on Bifidobacterium longum at T0 could predict infectious complications during the first month of chemotherapy with the area under the curve (AUC) of 0.720.ConclusionsOur study provides new insights into the acute changes in microbial and functional characteristics in children with ALL during chemotherapy. The baseline gut microbiota could be potential biomarkers for infections during chemotherapy.Trial registrationThe study was approved by the Ethics Committee of Zhujiang Hospital, Southern Medical University (2021-KY-171-01) and registered on http://www.chictr.org.cn (ChiCTR2200065406, Registration Date: November 4, 2022).

Sarcopenia with decreased total psoas muscle area in children with high-risk neuroblastoma

BackgroundWe calculated psoas muscle area (PMA) z-scores in high-risk neuroblastoma patients undergoing treatment to examine the clinical significance of sarcopenia in this cohort. MethodsWe analyzed retrospective data from patients aged 0–18 who were diagnosed with abdominal neuroblastoma between 2005 and 2019 at Samsung Medical Center. Patients categorized as high-risk undergone induction chemotherapy, neuroblastoma excision, and tandem high-dose chemotherapy with autologous stem cell transplantation (HDCT/auto-SCT) were selected. L3-4 lumbar levels on axial CT images were identified and we measured the areas of the left and right psoas muscles to determine tPMA. Total PMA z-scores were calculated using an open online tool. ResultsThere were 45 boys and 25 girls with a mean age of 3.86 years. CT images taken at initial diagnosis and after tandem HDCT/auto-SCT were selected to calculate tPMA z-scores. Mean elapsed time between the two measurements was 12.91 ± 1.73 months. Mean tPMA z-score significantly decreased from −0.21 ± 1.29 to −0.66 ± 0.97 (p = 0.022). Length of hospital stay was significantly longer in the group of patients whose tPMA z-scores decreased by more than .45 (177.62 ± 28.82 days vs. 165.75 ± 21.34 days, p = 0.049). Presence of sarcopenia at initial diagnosis was a significant risk factor for bacterial infection during neuroblastoma treatment.Conclusion: tPMA z-scores in high-risk neuroblastoma patients decreased significantly following a treatment regimen that included induction chemotherapy, tumor resection surgery, and HDCT/auto-SCT. A greater decrease in tPMA z-score was associated with longer hospital stay during treatment.

Effectiveness and safety of irreversible electroporation when used for the ablation of stage 3 pancreatic adenocarcinoma: A registry study (DIRECT).

e16301 Background: Outcomes for patients with Stage 3 pancreatic ductal adenocarcinoma (PDAC) remain poor with a mean overall survival (OS) of 11 months. Irreversible electroporation (IRE) is a method of local tumor ablation that causes cell death by disrupting homeostasis in the cell membrane. Previous research suggests IRE can be useful in the multi-disciplinary treatment of Stage 3 PDAC. The present study was designed to assess the effectiveness and safety of IRE for Stage 3 PDAC in a real-world setting after induction chemotherapy. Methods: Patients with Stage 3 PDAC treated with IRE were prospectively enrolled in a multicenter registry study. Enrollment required 3 months of active multi-agent chemotherapy, with no progression before IRE treatment. Endpoints were 30- and 90-day mortality from enrollment and the new onset of an adverse event (AE). Results: 87 patients were enrolled in the registry between May 2019 and May 2023. Mean age was 64.0 ± 8.4 years, 57.5% were female and mean tumor diameter was 2.2 ± 0.7 cm. Mean time from diagnosis to IRE treatment was 8.9 ± 4.9 months. All subjects underwent induction chemotherapy with the most common being FOLFIRINOX alone, gemcitabine with albumin-bound paclitaxel, or a combination of both in 47 (54.0%) patients. Thirty-seven (42.5%) patients had prior radiation therapy. All procedures were performed using an open approach with 50 (57.5%) for in-situ tumor ablation and 37 (42.5%) with the intent of margin accentuation in combination with resection. Major adjunctive procedures were performed for 70 (80.5%) patients. Common adjunctive surgeries were cholecystectomy (33.3%), Whipple procedure (28.7%) and either distal or subtotal pancreatectomy (11.4%). Mean IRE delivery time was 55.7 ± 54.5 minutes with an average of 3.1 probes (range 2 to 6) used per procedure. There was a mean of 1031.1 ± 882.1 pulses delivered per procedure. The 30- and 90-day mortality was 3/87 (3.4%) and 4/82 (4.9%) respectively. There were 21 (24.1%) patients who developed AEs related to IRE treatment during the 90-day post-procedure period (9 patients had AEs that were definitely related to IRE, 5 probably and 7 possibly). Of these related events, only three were Grade 4 or higher (arterial hemorrhage, cardiac arrest, and septic shock). Overall, gastrointestinal related AEs were the most common representing 16 of the 28 (57.1%) of all AEs associated with the IRE procedure. One patient died within 30 days of the procedure due to an intraperitoneal arterial hemorrhage that was deemed to be definitely related to the IRE treatment. Conclusions: The use of IRE for curative intent tumor ablation alone or in combination with resection following induction chemotherapy in patients with locally advanced Stage 3 PDAC has acceptable safety and is associated with acceptable morbidity and mortality rates in appropriately selected patients. Clinical trial information: NCT03899649 .

Stereotactic Magnetic Resonance-Guided Daily Adaptive SABR (SMART) for Localised Non-Metastatic Pancreatic Cancer: First Reported Clinical Outcomes From the UK

AimsPrognosis of locally advanced pancreatic cancer (LAPC) remains poor with limited therapeutic options. Radiation therapy in pancreatic cancer has been restricted by the disease's proximity to radiosensitive organs at risk (OAR). However, stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) has demonstrated promise in delivering ablative doses safely. We sought to report clinical outcomes from a UK-based Compassionate Access Programme that provided access to SMART to patients with LAPC. Materials and methodsThis was a registry retrospective study conducted at a single centre with access to SMART. Patients with LAPC were treated with prescription dose of 40 Gy in 5 fractions. The planning objective was that 98% of PTV received ≥95% of the prescribed dose, prioritising duodenal, stomach and bowel UK SABR consortium constraints. Daily online adaptation was performed using magnetic resonance guidance and on-table re-optimisation. 0–3 months and > 3-month post-treatment-related toxicities, local progression-free survival, metastatic-free survival and overall survival were evaluated. Results55 patients were treated with SMART at our institution from 2020 to 2022. Median follow-up from date of diagnosis was 17 months (range 5–37 months). Median age was 69.87% of patients underwent induction chemotherapy. 71% of patients reported 0–1 grade acute toxicity only. No grade >3 acute toxicity was reported. 5 patients (9%) reported a grade 3 toxicity (fatigue, nausea, abdominal pain, duodenal stricture). No grade >3 toxicity after 3 months was reported. 6 (10%) of patients had grade 3 toxicity (fatigue, nausea, abdominal pain, duodenal haemorrhage). Median local PFS post diagnosis was 17 months (95% CI 15.3–18.7). Median OS post diagnosis was 19 months (95% CI 15.9–22.1). One-year local control post SMART was 65%. ConclusionThis is the first UK-reported experience of MR-guided daily adaptive pancreatic SABR. SMART shows promise in delivering ablative doses with acceptable toxicity rates and good clinical outcomes.

Impact of magnetic resonance imaging-derived skeletal muscle index in locoregionally advanced nasopharyngeal carcinoma.

To evaluate the clinical implication of magnetic resonance imaging (MRI)-derived skeletal muscle index (SMI) in locoregionally advanced nasopharyngeal carcinoma (LANPC) patients undergoing induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) and further to develop a nomogram for predicting survival prognosis. SMI was determined through baseline MRI at the third cervical level. The nomogram was based on a training cohort involving 409 LANPC patients. We validated the prognostic accuracy of this prognostic model in an internal validation cohort (n = 204) and an external independent cohort (n = 272). SMI was an independent risk factor for OS. A prognostic model comprising age, TNM stage and SMI for individual survival prediction was developed and graphically represented as a nomogram. The model showed favorable discrimination (C-index: 0.686), predictive accuracy [time dependent area under the curve (tAUC) at 5years: 0.70], and calibration, and was further validated in the internal and external validation datasets. A risk stratification derived from the model stratified these patients into three prognostic subgroups with significantly different survival. Low SMI accessed by MRI was significantly associated with poor overall survival in LANPC patients undergoing IC + CCRT. Moreover, we established and validated a novel nomogram involving age, TNM stage and SMI that could provide accurate prognostic stratification among this population.

Abstract 3626: Day 21 early bone marrow response does not offer high concordance with response bone marrow in the induction chemotherapy setting of FLT3 mutant acute myeloid leukemia

Abstract Purpose: Day 14 early bone marrow biopsies are routinely initiated to determine need for reinduction chemotherapy, but poorly predict true response and risk overtreatment. Day 21 (D21) bone marrow biopsies have been performed in the context of trials utilizing FLT3-targeted therapies in combination with induction chemotherapy (Stone et al. NEJM 2017). However, the utility of D21 bone marrow responses is not well defined. Methods: We retrospectively identified 26 newly diagnosed FLT3 mutant AML patients who underwent induction chemotherapy with midostaurin and Next Generation Sequencing (NGS) of bone marrow aspirate within a week of diagnosis. Results: 19/26 (73%) of patients had both D21 and response bone marrow biopsy. Of the remaining 7 patients, 4 patients did not have D21 bone marrow, 2 died of unrelated complications prior to response bone marrow, and 1 did not have recovery marrow available for assessment. Our cohort included 13 (50%) men with a median age of 57 years (range, 21 - 73 years). All patients had ECOG of 0 - 1. 96% of cases were de novo AML and 81% had normal cytogenetics. FLT3 ITD mutations were detected in 17 (65%) patients with a median FLT3 ITD ratio of 0.305 (range, 0.03 - 1) and median FLT3 VAF of 23.8% (range, 3.2 - 80.6%). 7 patients (26.9%) underwent additional allogeneic stem cell transplant. In the 19 patients evaluable for analysis, 13/13 (100%) patients with blast % ≤ 5 at D21 achieved a complete response (CR) based on recovery marrow. 4/6 (67%) patients with blast % &amp;gt; 5 at D21 which were considered to have residual disease based on pathology review (median blast % 11 (range, 6 - 17%) ultimately achieved a CR. The 2 patients that did not achieve a CR has a blast % of 29% and 9% on D21 marrow. Thus, the positive predictive value of D21 early bone marrow response corresponding with the response bone marrow was only 33% in our patient cohort. Of the 4 patients that did not have D21 marrow but had recovery marrows available for review, the CR rate was 100%. No other significant differences in initial disease characteristics were seen. There were no differences proportion of co-mutations in NPM1, DNMT3A, TP53, IDH2, and IDH1, and higher FLT3 ITD ratio nor FLT3 VAF corresponded with ability to clear D21 bone marrow. Additionally, there were no differences in minimal residual disease (MRD) and overall survival (OS) between the groups. Conclusions: Our study suggests early bone marrow response in the context of FLT3-mutant disease is not dependent on inherent disease characteristics and does not correspond to overall response to targeted induction chemotherapy. The utility of these marrows in is this population needs to be studied further in a larger cohort to better understand the clinical necessity to avoid unnecessary cost/procedures to patients and even more importantly unnecessary reinductions. Citation Format: Vincent Lok, Su Bin Hahn, Nikesh N. Shah, Daniel A. Kerr, Ivan M. Borrello, Eduardo M. Sotomayor, David M. Swoboda. Day 21 early bone marrow response does not offer high concordance with response bone marrow in the induction chemotherapy setting of FLT3 mutant acute myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3626.

Terapia de conversión en cáncer gástrico: experiencia del Instituto Nacional de Cancerología de Colombia

Background: Gastric cancer (GC) represents a public health problem in Colombia and worldwide. Since most patients are at advanced stages at the time of diagnosis, it is necessary to develop management strategies as conversion therapy (CT). Objective: The aim of this study was to estimate the results of CT for treating patients with advanced and GC at Instituto Nacional de Cancerología de Colombia (INC). Material and methods: We included patients with incurable gastric cancer who underwent induction chemotherapy and intended curative surgery between 2010 and 2021. The clinical and pathological data and survival of the patients included were retrospectively reviewed. Overall survival (OS) was calculated from the time of initiation of chemotherapy until the date of death. Survival functions were estimated using the life table and Kaplan-Meier methods, and survival curves at 3 and 5 years were constructed. Results: 23 patients were analyzed; mean age was 56 years, and 17 (74%) were men. The most common criterion indicating unresectability was a T4b tumor in 13 cases (56.5%). All the patients underwent CT. Median follow-up was 28 months. Eleven patients developed disease recurrence (52%). Median survival was 41.2 months, and 3- and 5-year OS was 57.7% and 38.5%, respectively. Conclusions: CT provided an acceptable OS rate for selected patients with incurable advanced GC. This strategy requires a

Timing of Surgery and Social Determinants of Health Related to Pathologic Complete Response after Total Neoadjuvant Therapy for Rectal Adenocarcinoma: Retrospective Study of National Cancer Database.

Total neoadjuvant therapy (TNT) for rectal adenocarcinoma (RAC) involves multi-agent chemotherapy and radiation before definitive surgery. Previous studies of the rest period (time between radiation and surgery) and pathologic complete response (pCR) have produced mixed results. The objective of this study was to evaluate the relationship between the rest period and pCR. This study utilized the National Cancer Database (NCDB) to retrospectively analyze 5997 stage-appropriate RAC cases treated with TNT from 2016 to 2020. The overall pCR rate was 18.6%, with most patients undergoing induction chemotherapy followed by long-course chemoradiation (81.5%). Multivariable logistic regression models revealed a significant non-linear relationship between the rest period and pCR (p = 0.033), with optimal odds at 14.7-15.9 weeks post radiation (odds ratio: 1.49, 95% confidence interval: 1.13-1.98) when compared to 4.0 weeks. Medicaid, distance to the treatment facility, and community education were associated with decreased odds of pCR. Findings highlight the importance of a 15-16-week post-radiation surgery window for achieving pCR in RAC treated with TNT and socioeconomic factors influencing pCR rates. Findings also emphasize the need for clinical trials to incorporate detailed analyses of the rest period and social determinant of health to better guide clinical practice.

Survivorship Struggles: Navigating Etiologies and Clinical Parameters of Febrile Neutropenia During Induction Chemotherapy in Acute Leukemia Patients.

Background Acute leukemia, characterized by the uncontrolled proliferation of immature white blood cell precursors, poses significant challenges during induction chemotherapy, including the elevated risk of febrile neutropenia and its associated complications. Our study aims to explain the clinical and etiological parameters of these patients in a resource-limited setting. Methods This retrospective study focused on a total of 102 adult patients with acute leukemia who developed febrile neutropenia during the induction chemotherapy phase. Patients with disease relapse, prior bone marrow transplantation, and cases of acute promyelocytic leukemia were excluded from the study. Demographical characteristics, symptoms at presentation, diagnoses, infectious causes, and outcomes were systematically reported. Infectious etiologies and detailed culture reports were meticulously tabulated, and subsequent data were analyzed. Results Of the 102 patients, 43 (42.2%) were males, with a mean age of 31.9 ± 6.5 years. During the induction chemotherapy, a total of 31 patients died of complicated febrile neutropenia. Severe vomiting was the most common symptom present in 37 (36.2%), followed by cough in 35 (34.3%) and loose stools in 28 (27.5%). Community-acquired pneumonia, neutropenic sepsis, and neutropenic colitis were among the most common etiologies of febrile neutropenia. A total of 72 (70.6%) patients had culture-proven multidrug-resistant Gram-negative bacteremia that contributed to poor outcomes. Conclusions Acute leukemia patients undergoing induction chemotherapy face high infection-associated mortality due to their immunocompromised state. Inadequate infection control measures and antimicrobial resistancecontribute to the emergence of multidrug-resistant organisms. Enhanced infection prevention strategies and evidence-based antibiotic prescription guidelines are need of time in resource-limited settings such as Pakistan to address febrile neutropenia complications and bridge the existing care gap in its management.