Multiagent Chemotherapy Research Articles (Page 1)

Mesenchymal chondrosarcoma (MCS) is characterised by small round cell biology, frequent HEY1-NCOA2 fusion, and high vascularity. These features plausibly lessen extracellular matrix barriers and confer relative chemosensitivity. We synthesised peri-operative (preoperative/neoadjuvant; postoperative/adjuvant) and palliative chemotherapy outcomes separately across multiple cohorts and case reports as well as the summarised the guidelines (ESMO/NCCN) In localised disease, integrating multi-agent Ewing-type chemotherapy with complete resection is associated with improved disease control. Contemporary 5-year overall survival (OS) typically spans ~55–73% across studies, while event-free survival (EFS) gains are demonstrated more consistently than OS gains in pooled analyses. In advanced MCS, first-line polychemotherapy yields modest, non-curative activity, with objective response rates (ORRs) of ~25–35% in adults, median progression-free survival (PFS) of ~4.7–6.7 months, and median OS of ~18 months. Activity may be higher in younger patients and for platinum–anthracycline combinations. We also discussed emerging therapies. Trabectedin demonstrates low disease control rate in translocation-related sarcomas, including few MCS cases. Anti-angiogenic tyrosine kinase inhibitors, such as apatinib and pazopanib, demonstrate activity in chondrosarcoma, but MCS-specific data are lacking. IDH1 inhibition benefits conventional subtypes rather than MCS. Early immunotherapy experience is limited, but pathway-directed strategies targeting BCL2 and PI3K-mTOR warrant evaluation.

Toward a new standard: Sequential multi-agent neoadjuvant chemotherapy in resectable pancreatic cancer.

Bone metastases from osteosarcoma occur in only 10% of patients, and related preclinical models are lacking. A patient diagnosed with pelvic osteosarcoma developed a metachronous scapular metastasis and was treated with multi-agent chemotherapy and surgery. Patient-derived tissue fragments (PDTFs) were obtained from leftover material after diagnosis and biobanking. PDTFs were grown on chick chorioallantoic membrane, establishing an in vivo-like predictive model. Additionally, we obtained a patient-derived cell culture, OS-MET-R-092, which has been maintained in vitro for nearly one year. OS-MET-R-092 cells were authenticated based on short tandem repeats and on their morphology when grown on commercial 3D scaffolds. Using U-2 OS and SaOS-2 as controls, we characterized growth, clonogenic potential, ability to form spheroids, migration, osteogenic differentiation, and expression of related genes. OS-MET-R-092 cells showed a low proliferation rate, impaired differentiation potential, and migratory abilities comparable to SaOS-2, while expressing higher levels of some MMPs and CD44. Functionally, OS-MET-R-092 cells demonstrated a resistant phenotype to doxorubicin, cisplatin, gemcitabine, and docetaxel, corroborated by higher expression of chemo-resistance-related genes. Collectively, OS-MET-R-092 represents a valuable tool for studying bone metastasis from osteosarcoma across various experimental settings and serves as the foundational building block for composite and translatable 3D models.

The entity of Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) accounts for approximately 20-30% of newly diagnosed adults with B-cell ALL cases in the United States. Compared to other B-cell subtypes, Ph-like ALL is associated with overall poor prognosis and inferior outcomes with high measurable residual disease (MRD) rates following induction therapy, increased risk of treatment failure and relapse as well as short event-free and overall survival. Here we aim to highlight Ph-like ALL genetic subtypes and methods of genomic profiling for diagnosis and disease prognostication, and to summarize current management approaches for frontline treatment including multiagent chemotherapy, immunotherapy, tyrosine kinase and small molecule Inhibitors and the role for allogeneic stem cell transplantation. Despite the improvement in the treatment outcomes of adult patients with newly diagnosed B-cell ALL, patients with Ph-like ALL continue to do poorly with standard therapy. Thus, tailored therapeutic studies are indeed warranted to refine frontline treatment approaches and to improve outcomes for patients with Ph-like ALL.

The aim of this study was to describe renal ultrasonographic findings in cats with confirmed renal lymphoma receiving chemotherapy and correlate them with clinical and clinicopathological findings. For this multicenter retrospective study, cats were included if they had cyto/histological confirmation of renal lymphoma, received multi-agent chemotherapy, and ultrasonographic images of the kidneys before and after treatment were available. All images at T0 (diagnosis) and T1 (after chemotherapy) were reviewed. Oncology records were reviewed, and serum creatinine and BUN concentrations were recorded, when available. Twenty-four cats (20 males and 4 females, median age 8 years) who underwent COP-based chemotherapy were included. At T1 (median 33 days, range 20-60), 21 cats were considered to have experienced clinical benefit (20 with improved renal appearance on ultrasound, one with static appearance), two cats had stable clinical findings (one stable, one progressive ultrasound), and one cat clinically declined (progressive ultrasound). On ultrasonography, nephromegaly resolved in 12/20 cats, hypoechoic subcapsular rim disappeared in 6/17 and reduced in 7/17, nodules/masses disappeared in 8/14 and reduced in 5/14 cats.Six cats had normal creatinine and BUN concentrations both at T0 and T1 (5 improved and one stable US); in 11 cats, the azotemia detected at T0 resolved at T1; 4 cats were persistently azotemic (all with reduced creatinine and BUN concentrations) and one cat became azotemic on T1 (progressive US). After chemotherapy, kidneys affected by lymphoma commonly returned to normal size; subcapsular rim, nodules and masses markedly reduced or completely resolved. Ultrasonographic findings were often in agreement with clinical and clinicopathological findings.

Adult acute lymphoblastic leukemia (ALL) treatment protocols are evolving with frontline therapy now incorporates targeted immunotherapeutic agents. Targeted immune therapies like blinatumomab, inotuzumab ozogamicin (InO), rituximab, and nelarabine are being combined with traditional chemotherapy protocols to enhance remission rates and minimal residual disease (MRD) negativity while decreasing toxicities. The incorporation of blinatumomab into initial treatment protocols for both Philadelphia chromosome-negative (Ph -) and positive (Ph +) ALL patients results in notable early MRD elimination. The medical use of InO as an initial treatment has increased specifically for older or medically unfit patients. The addition of rituximab to chemotherapy treatment in CD20-positive B-ALL patients produces superior long-term results. Adding nelarabine to pediatric-inspired T-cell ALL treatment protocols in young adult and adolescent (AYA) patients resulted in decrease their risk of central nervous system (CNS) relapse. High-risk ALL subtypes including Ph + and Ph-like ALL now receive immunotherapeutic and molecularly targeted treatments. Ph + ALL patients receive standard treatment with multi-agent chemotherapy and TKIs dasatinib or ponatinib and blinatumomab as part of their frontline therapy to enhance molecular responses and minimize the requirement for allogeneic hematopoietic stem cell transplantation (allo-HCT). The combination of JAK inhibitors with ABL-class TKIs, chemotherapy, and immunotherapy represents current early-phase trial approaches for Ph-like ALL patients with kinase-activating alterations. The practice of testing MRD and genomic profiling at diagnosis revolutionized treatment approaches by allowing personalized curative strategies for all patients. Research on clinical trials aims to establish the best sequence of targeted therapies and CAR T-cell therapy for high-risk and MRD-positive patients to achieve longer survival rates with reduced toxicity and less dependence on allo-HCT in first remission.

Significant disparities persist in timely, guideline-concordant breast cancer treatment across the United States, impacting cancer outcomes. The influence of both patient-level and facility-level socioeconomic status (SES) on adherence to Commission on Cancer (CoC) quality measures remains incompletely understood. We conducted a retrospective cohort study using the National Cancer Database (NCDB) to assess associations between patient and facility SES and concordance with timeliness of three CoC breast cancer quality measures: surgery, multi-agent chemotherapy, and radiotherapy, among patients diagnosed from 2018 to 2022. Multivariable logistic regression models were used to evaluate predictors of concordant care, including a composite measure of facility-level social risk. The analytic cohorts included 471,425 patients for surgery, 82,734 for chemotherapy, and 311,523 for radiotherapy. Black race, uninsured status, and low educational attainment were each independently associated with lower odds of guideline-concordant care across all measures. Patients treated at low-SES facilities had higher odds of timely surgery (adjusted OR, 1.27; 95% CI, 1.24-1.31) but lower odds of timely chemotherapy (OR, 0.85; 95% CI, 0.79-0.91) and radiotherapy (OR, 0.95; 95% CI, 0.92-0.97) compared to those at other institutions. Facility type, fragmented care, and comorbidities also contributed to variation in concordance. Significant disparities in guideline-concordant breast cancer care persist by race, insurance, education, and facility-level social risk, highlighting intervention opportunities to improve outcomes for these already vulnerable populations. These findings highlight the importance of policy and institutional strategies that address both patient- and facility-level barriers to ensure equitable access to high-quality multidisciplinary treatment.

Disseminated Lymphoma Cutis in a Patient with NK T Cell Lymphoma Managed with SMILE Multiagent Chemotherapy

Reproductive outcomes following chemotherapy for gestational trophoblastic neoplasia: experience from a tertiary care center.

Treatment patterns and survival outcomes for very elderly patients with acute myeloid leukemia: A National Cancer Database study.

Prognostic role of peritoneal lavage cytology: Proposal for staging laparoscopy criteria in biliary tract cancer.

ABSTRACTPurposeIntraoperative radiotherapy (IORT) is utilized as an adjunctive treatment in advanced rectal cancer, particularly in cases with threatened surgical margins. Although IORT has shown benefits in enhancing local tumor control, its impact on overall survival (OS) remains unclear. This study assesses the effect of IORT on survival outcomes using a large cohort from the National Cancer Database (NCDB) and examines factors influencing its application in clinical practice across the United States.MethodsThe National Cancer Database was retrospectively reviewed (2006–2019) to identify patients with pathological T3–T4, M0 rectal cancer who underwent surgery following neoadjuvant chemotherapy. Patients with microscopically residual margin‐positive were included and categorized into two groups: those who received neoadjuvant radiotherapy (RT) and those treated with intraoperative radiotherapy (IORT) combined with adjuvant/neoadjuvant RT. Groups were propensity score–matched (1:4) to balance baseline characteristics. The primary outcome was 5‐year overall survival (OS), assessed using Kaplan–Meier analysis and Cox proportional hazards modeling.ResultsAmong 1,788 patients with margin‐positive rectal cancer, IORT was administered to 119 patients (6.7%) while 1,669 patients (93.3%) received neoadjuvant RT. Patients receiving IORT were younger, more likely to have private insurance, more frequently treated at academic/research programs, and more commonly underwent pelvic exenteration and Multiagent chemotherapy. After propensity score matching, 119 IORT patients were compared with 476 neoadjuvant RT patients. IORT was associated with lower mortality in univariate analysis (HR: 0.63; p < 0.001); however, this benefit was attenuated after adjusting for confounders (HR: 0.84; p = 0.07). The 5‐year overall survival rates were 58.4% for IORT versus 54.9% for neoadjuvant RT alone (p = 0.18).ConclusionThis nationwide analysis suggests that adding IORT to treatment does not significantly improve overall survival in margin‐positive rectal cancer patients. However, due to heterogeneity in patient selection and dosing, further prospective trials are warranted to clarify its clinical role.

Multi-agent chemotherapy regimens have improved the survival of patients with pancreatic adenocarcinoma (PDAC). However, only a few studies have compared multi-regimen treatments with single-regimen followed by curative-intent resection. This study aimed to explore optimal treatment strategies and clarify the role of radiotherapy in borderline resectable PDAC (BRPC) and locally advanced PDAC (LAPC) treatment. Consecutive patients who underwent pancreatectomy for PDAC at our institution between January 2013 and December 2022, diagnosed with BRPC and LAPC, and subjected to radical resection following preoperative chemotherapy or chemoradiotherapy were included in this study. We divided the cohort into preoperative multiple regimen (MR) and single regimen (SR) groups to compare survival. Of the 527 patients with PDAC, 68 who responded favorably to neoadjuvant therapy and subsequently underwent curative-intent or conversion resection were included in the analysis. In terms of overall survival, the 5-year survival rate was significantly higher in the MR group (80.8%) than in the SR group (20.3%). Multivariate analysis identified R0 resection, preoperative carbohydrate antigen 19-9 levels <80 U/ml, and preoperative treatment with multiple regimens as factors associated with better prognosis. Treatment with multiple regimens may improve the prognosis of patients with LAPC or BRPC. The addition of chemoradiotherapy as a treatment modality may have a positive impact on prognosis.

Pancreatic metastasis of gestational trophoblastic neoplasia (GTN) is extremely rare, with only a few reported cases. A retrospective analysis was conducted on GTN patients with pancreatic metastasis at Peking Union Medical College Hospital (2000-2024) and a literature review was performed. A descriptive analysis was carried out on the clinical characteristics, treatment strategies, and outcomes of patients who met the inclusion criteria. Fisher's exact test was used to analyze differences in metastatic patterns and clinical outcomes among patients with different clinical characteristics. A total of 24 cases were identified (7 from our institute, 17 from literature): 18 choriocarcinomas, 5 placental-site trophoblastic tumors, and 1 epithelioid trophoblastic tumor. Pancreatic metastasis led to organ-specific symptoms. Treatments included chemotherapy (single/multi-agent), immunotherapy, and targeted therapy. Six patients underwent surgical or localized interventions. Outcomes varied: 9 (37.5%) achieved disease-free survival, 5 (20.8%) had partial remission, and 10 (41.7%) died. Surgical or invasive interventions were associated with significantly improved outcomes (P = 0.024). Pancreatic invasion in GTN is a high-risk condition often associated with poor outcomes. Advanced imaging techniques enhance diagnostic accuracy, while endoscopic ultrasound-guided fine-needle biopsy provides essential histopathological confirmation. Multi-agent chemotherapy remains the cornerstone of treatment, with surgical interventions carefully tailored to the individual patient's condition. For better management and prognosis, an initial treatment strategy integrating multi-agent chemotherapy, immunotherapy, and targeted therapies may offer benefits; however, further investigation is warranted.

BackgroundBurkitt lymphoma (BL) is a highly aggressive pediatric B-cell lymphoma with marked geographic heterogeneity. Up-to-date global estimates are needed to inform prevention and care.MethodsWe analyzed Global Burden of Disease (GBD) 2021 data to estimate incidence, mortality, and disability-adjusted life years (DALYs) for childhood BL (0–14 years) from 1990 to 2021 across 204 countries/territories, stratified by sex, age, region, and Sociodemographic Index (SDI). Trends were summarized using joinpoint annual percent change and estimated annual percentage change (EAPC). Bayesian age-period-cohort models projected the burden to 2035.FindingsIn 2021, there were 4,083 incident BL cases globally [95% uncertainty interval (UI) 2,688–5,171]. The global incidence rate was 0.20 per 100,000 (95% UI 0.13–0.26) versus 0.16 per 100,000 (95% UI 0.10–0.23) in 1990. Burden varied substantially by development level: the low-SDI region had the highest incidence rate (0.44 per 100,000, 95% UI 0.26–0.59), mortality rate (0.43 per 100,000, 95% UI 0.25–0.58), and DALY rate (36.19 per 100,000, 95% UI 21.00–48.64). High-SDI regions showed lower mortality rates and evidence of declines, consistent with broader access to timely diagnosis, multi-agent chemotherapy, and supportive care. By 2035, the incidence rate is expected to reach 0.15 (95% CI 0.11–0.19) per 100,000, the mortality rate to 0.10 (95% CI 0.07–0.13) per 100,000, and the DALY rate to 8.21 (95% CI 5.98–10.43) per 100,000.InterpretationGlobal BL rates appear broadly stable, with pronounced inequities concentrated in low-SDI settings. Apparent improvements are heterogeneous, not universal, and are most evident in high-SDI regions where treatment and supportive care are widely available. Projections to 2035 suggest modest declines in global rates, contingent on sustained malaria control and expanded access to diagnosis and curative therapy in high-burden regions. Targeted investments linking infection control with pediatric oncology capacity are required to reduce the global burden of childhood BL.

CXCL10-induced chemotaxis of ex vivo-expanded natural killer cells combined with NKTR-255 enhances anti-tumor efficacy in osteosarcoma

IntroductionThe treatment of B-cell acute lymphoblastic leukemia (ALL) in India involves multi-agent chemotherapy and central nervous system (CNS) prophylaxis, but relapsed/refractory (R/R) B-cell ALL presents with high mortality and limited salvage options. Inotuzumab ozogamicin (InO), a monoclonal antibody targeting cluster of differentiation-22 (CD22) conjugated to calicheamicin, has improved outcomes for R/R B-cell ALL. A phase 3 multicenter trial (INO-VATE) in adult patients with CD22+ B-cell ALL has shown that InO significantly increases response rates and overall survival (OS) compared to standard treatments, with ongoing studies assessing its real-world effectiveness in India.MethodologyA multicentric, retrospective, observational study was conducted across five oncology centers in India to evaluate the effectiveness of InO in adult patients with R/R B-cell ALL. The study aimed to assess clinical outcomes, including the rate of complete remission (CR)/CR with incomplete hematologic recovery (CRi), minimal residual disease (MRD) negativity, duration of remission (DOR), OS, and the safety and tolerability of InO in real-world settings.ResultsThe medical records of adult patients (n = 32) aged >18 years with R/R B-cell ALL treated with InO between February 2017 and October 2022 were assessed. Among the total study participants, 59.4% (n = 19) achieved CR/CRi. Of these responders, MRD negativity was achieved in 94.7% (n = 18/19), and 68.4% (n = 13/19) achieved deep responses (MRD negative CR/CRi) after a median of two cycles of InO. The median DOR for those achieving CR/CRi was 6 months. Of the entire cohort, 34.4% (11/32) of the participants proceeded to hematopoietic stem cell transplantation (HSCT). The OS rates at 6 and 12 months in the entire cohort were 46.9% and 28.1%, respectively. The median relapse-free survival (RFS) among the responders was 7 months. Grade 3/4 treatment-related liver toxicity following InO initiation was reported in 37.5% of the participants. Myelosuppression-related adverse events were observed in 87.5% of the recipients.ConclusionThe real-world study (RWS) highlights the effectiveness of InO in achieving remission and MRD negativity in R/R B-cell ALL, although treatment-related toxicities remain a concern.

Adjuvant chemotherapy in older patients with stage II and III colon cancers: Is less more?

2247P Growth differentiation factor 15 (GDF-15) in localized, non-metastatic pancreatic cancer treated with multiagent induction chemotherapy: A biomarker analysis from the randomized phase II NEOLAP-1 trial (AIO-PAK-0113)

Bloom syndrome is an autosomal recessive condition of genomic instability caused by increased sister-chromatid exchange, which results in a predisposition to a variety of cancers at a young age. The molecular alterations in Bloom Syndrome predisposing to chromosomal instability alter the expected response to and toxicities of chemotherapy in patients with this condition. We report a 16-year-old patient with previously undiagnosed Bloom syndrome who presented with metastatic mucinous adenocarcinoma and tolerated palliative chemotherapy, initially with modified FOLFOX and subsequently with FOLFIRI, both at 50% dose reduction, without significant toxicity. Dose modified multiagent chemotherapy was well tolerated in an adolescent patient with Bloom Syndrome and metastatic colorectal cancer.