Combination Chemotherapy Regimens Research Articles

Synchronized Codelivery of Combination Chemotherapies Intratumorally Using a Lipidic Lyotropic Liquid Crystal System.

In this work, an injectable in situ depot-forming lipidic lyotropic liquid crystal (L3C) system is developed to codeliver a precisely synchronized combination of chemotherapeutics intratumorally. The developed L3C system is composed of amphiphilic lipids and surfactants, including monoolein, phosphatidylcholine, tocopherol acetate, and d-α-tocopherol polyethylene glycol 1000 succinate. Owing to its amphiphilic nature, the developed formulation can coaccommodate both hydrophobic and hydrophilic chemotherapeutic moieties simultaneously. The study presents a proof of concept by designing a combination chemotherapy regimen in vitro and demonstrating its in vivo translation using doxorubicin and paclitaxel as model hydrophilic and hydrophobic drug moieties, respectively. The synchronized combination of the two chemotherapeutics with maximum synergistic activity was identified, coloaded in the developed L3C system at predefined stoichiometric ratios, and evaluated for antitumor efficacy in the 4T1 breast tumor model in BALB/c mice. The drug-loaded L3C formulation is a low-viscosity injectable fluid with a lamellar phase that transforms into a hexagonal mesophase depot system upon intratumoral injection. The drug-loaded depot system locally provides sustained intratumoral delivery of the chemotherapeutics combination at their precisely synchronized ratio for over a period of one month. Results demonstrate that the exposure of the tumor to the precisely synchronized intratumoral chemotherapeutics combination via the developed L3C system resulted in significantly higher antitumor activity and reduced cardiotoxicity compared to the unsynchronized combination chemotherapy or the synchronized but uncoordinated drug delivery administered by a conventional intravenous route. These findings demonstrate the potential of the developed L3C system for achieving synchronized codelivery of the chemotherapeutics combination intratumorally and improving the efficacy of combination chemotherapy.

Plasmablastic lymphoma: 2024 update on diagnosis, risk stratification, and management.

Plasmablastic lymphoma (PBL) is a rare CD20-negative aggressive lymphoma with a poor prognosis under standard treatment options. Though PBL is associated with human immunodeficiency virus infection and other immunosuppressed states, it can also affect immunocompetent individuals. The diagnosis requires a high clinical suspicion and pathological confirmation. EBER expression and MYC gene rearrangements are frequently detected. The differential diagnosis includes EBV+ diffuse large B-cell lymphoma, extracavitary primary effusion lymphoma, ALK+ DLBCL, and HHV8+ large B-cell lymphoma, among others. Age ≥60 years, advanced clinical stage, and high intermediate and high International Prognostic Index scores are associated with worse survival. Combination chemotherapy regimens, such as EPOCH, are recommended. The addition of bortezomib, lenalidomide, or daratumumab might improve outcomes. Including PBL patients and their participation in prospective clinical trials is warranted.

Update on management of pancreatic cancer: a literature review.

Pancreatic cancer is an aggressive malignancy with high mortality. At the time of diagnosis, majority of patients (80-90%) present with either locally advanced unresectable disease or metastatic disease. Even after curative resection, the recurrence rate remains quite high. This article aimed at reviewing the updated management of pancreatic cancer. We identified literature by searching Medline and PubMed from January 2010 to June 2023 using the keywords. A multidisciplinary approach is essential to optimize the outcomes for both curable and advanced diseases. Management of pancreatic cancer divided into resectable, borderline resectable, locally advanced, and metastatic diseases. Surgery and adjuvant chemotherapy is a standard treatment approach for resectable pancreatic cancer. The recommended adjuvant chemotherapy regimen for patients with good functional status is modified FOLFIRINOX (5-fluorouracil, folinic acid, irinotecan, and oxaliplatin). The recommended adjuvant chemotherapy regimen for patients with suboptimal functional status is gemcitabine plus capecitabine or monotherapy gemcitabine. The optimal treatment strategy for borderline resectable pancreatic cancer is still uncertain. Traditionally, upfront surgery is the choice of treatment. There is increasing evidence showing benefits of neoadjuvant therapy in borderline resectable pancreatic cancer. However, the optimal neoadjuvant treatment regimen was not certain yet. Advancement of chemotherapy has a positive impact for the survival of advanced disease. For patients with good functional status, the recommended first-line systemic chemotherapy for unresectable locally advanced disease or metastatic disease is combination chemotherapy regimens such as FOLFIRINOX, gemcitabine plus nabpaclitaxel. For patients with suboptimal functional status, the recommended first-line systemic chemotherapy for unresectable locally advanced disease or metastatic disease is gemcitabine plus capecitabine or monotherapy gemcitabine. Recently, more researches showed promising results in the use of nanoliposomal irinotecan, targeted agents such as a poly [adenosine diphosphate (ADB)-ribose] polymerase inhibitor, tyrosine receptor kinase (TRK) inhibitors, and immune checkpoint-inhibitors. Pancreatic cancer is a challenging disease for management. Radical surgery itself is not enough for prolong survival. The improvement of chemotherapy, target agents and immunotherapy with multidisciplinary approach will be the only solution for improvement of survival outcome and quality of life for patients with pancreatic cancer.

Metaplastic breast cancer with a unique presentation and complete response to chemotherapy: a case report

BackgroundMetaplastic breast carcinomas are a rare variant group of breast carcinomas. They are usually high-grade and triple-negative tumors. They often present with large primary tumor sizes. However, the involvement of axillary lymph nodes is infrequent at the time of diagnosis. Metaplastic breast carcinomas are associated with a worse prognosis and a poorer response to chemotherapy in comparison with other non-metaplastic triple-negative breast cancers. Up until this point, there are no specific treatment recommendations for metaplastic breast carcinomas beyond those intended for invasive breast cancer in general.Case presentationA 40-year-old woman complained of a palpable mass in her left axilla. On ultrasonography, the mass was solid, spindle-shaped, hypoechoic with regular borders, and exhibited decreased vascularity. At first, the mass appeared to be of a muscular origin. There was not any clinical nor ultrasonic evidence of a primary breast tumor. On magnetic resonance imaging, the axillary mass was a well-defined with regular borders, measuring 24 × 35 mm. Needle biopsy showed a spindle cell tumor with mild to moderate atypia. The subsequent surgical resection revealed a spindle cell neoplasm within a lymph node, favoring a metastatic origin of the tumor. The tumor cells lacked expression of estrogen, progesterone, and HER2 receptors. PET-CT scan indicated pathological uptake in the left breast. Accordingly, the patient was diagnosed with metaplastic breast cancer that had metastasized to the axillary lymph node. She commenced a combined chemotherapy regimen of doxorubicin and cyclophosphamide. After six treatment cycles, she underwent left modified radical mastectomy with axillary lymph node dissection. Pathological examination of the specimens revealed a total burn-out tumor in the breast due to excellent treatment response. There were no residual tumor cells. All dissected lymph nodes were free of tumor. At the one-year follow-up, the patient showed no signs of tumor recurrence.ConclusionThis report sheds light on a distinctive presentation of metaplastic breast carcinoma, emphasizing the need for vigilance in diagnosing this rare and aggressive breast cancer variant. In addition, the patient’s remarkable response to chemotherapy highlights potential treatment avenues for metaplastic breast cancer.

Management of urothelial cancer in patients with chronic kidney disease receiving platinum-based chemotherapy.

Despite recent advances in the management of urothelial cancer (UC), cisplatin-based combination chemotherapy regimens remain critical. However, their use can be complicated in patients with chronic kidney disease (CKD), which is not uncommon in UC patients. Based on the Galsky criteria for cisplatin ineligibility, most patients with CKD will be excluded from receiving cisplatin-based chemotherapy altogether. For patients with borderline kidney function, several strategies-such as the use of split-dose cisplatin, dose reductions,or extra hydration-may facilitate the use of cisplatin, but theseneedto be prospectively validated. This review highlights the critical need for a multidisciplinary team, including onco-nephrologists, to help manage renal complications and optimize delivery of cancer care in complex UC patients with CKD.

Abstract PO4-10-06: Cost-effectiveness analysis of ribociclib in the treatment for premenopausal or perimenopausal women with HR+/HER2− advanced breast cancer: a public health care system perspective in Mexico

Abstract BACKGROUND: Ribociclib (RIB) an inhibitor of cyclin-dependent kinase 4 and 6 for the treatment of advanced breast cancer (ABC), has demonstrated significant efficacy in prolonging progression-free survival and overall survival when added to endocrine therapy (ET). Because of the high-cost perception of this therapeutic class, it is crucial to assess their relative value compared to existing standards of care in the local setting. Chemotherapy is used as the first line of treatment in a conservative case in almost three-quarters of ABC patients with positive hormone receptors in the Public Health System in Mexico. Additionally, the high use of chemotherapy presents additional clinical and economic challenges for the Institute. Among the clinical challenges, the toxicity associated with chemotherapy regimens stands out. We evaluated the cost-effectiveness of the inclusion of RIB+ ET to usual care in the treatment of premenopausal or perimenopausal ABC from the perspective of the Public Health System in Mexico. Direct medical costs were considered. METHODS: We developed a partitioned survival model to simulate time to cancer progression and to compare lifetime clinical benefit and cost of standard alternative treatment strategies for patients with metastatic disease. Per approved indication, endocrine treatment-naive patients were assigned to RI plus ET or usual care (different chemotherapy schemes). Costs in Mexican Pesos (MXN) were estimated from the perspective of the Public Health System in Mexico. Costs and clinical benefits were discounted at 5% annually. The model assumptions were informed based on published clinical trial data from the randomized Phase III MONALEESA-7 trial and other peer-reviewed studies and indirect treatment comparisons. We carried out one-way and probabilistic sensitivity analyses to assess the robustness of our results to the changes in model assumptions. RESULTS: Ribociclib reduced monthly direct medical costs associated with the administration of breast cancer treatment and the management of adverse events. Direct drug acquisition costs per month of ribociclib were in the range of the cost of current available and used therapies. Indirect treatment comparisons did not show statistical significance of the benefit of ribociclib vs. standard of care, primarily due to heterogeneity leading to a mixed evaluation vs. two comparator groups according to the statistical significance of the survival improvement. Ribociclib is a 100% oral therapy with a manageable safety profile with dosage adjustments, so it does not require institutional resources for its administration or for managing adverse events. Its consolidated cost at 28 days of treatment is up to 40% less than combined chemotherapy regimens and up to 30% less than monotherapy schemes. Average cost-effectiveness for progression-free survival for ribociclib is among the lowest considering chemotherapy options even though generic versions are available for many of them. For the comparators with comparable efficacy, ribociclib was cost-saving at current public market prices. For the comparators where ribociclib showed a significant benefit, the incremental cost-effectiveness ratio of ribociclib vs. standard of care is also below the threshold of 3 GDPs per capita vs. most options, leading to cost-effectiveness. A longer treatment duration due to progression delay was a main driver of incremental cost. CONCLUSIONS: Ribociclib is cost-saving or cost-effective vs. standard of care in the Public Health System in Mexico. Other variables must be considered to inform clinical and funding decisions, such as disease burden and humanistic impact on this young, economically active population. Citation Format: Saúl Campos-Gomez, Christian Pichardo Piña. Cost-effectiveness analysis of ribociclib in the treatment for premenopausal or perimenopausal women with HR+/HER2− advanced breast cancer: a public health care system perspective in Mexico [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-10-06.

First-line Treatment Patterns and Outcomes in Advanced Non-Small Cell Lung Cancer in Sweden: A Population-based Real-world Study with Focus on Immunotherapy.

The treatment landscape for patients with advanced non-small cell lung cancer (NSCLC) has evolved significantly since the introduction of immunotherapies. We here describe PD-L1 testing rates, treatment patterns, and real-world outcomes for PD-(L)1 inhibitors in Sweden. Data were obtained from the Swedish National Lung Cancer Registry for patients with advanced NSCLC and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 who initiated first-line -systemic treatment from 01 April 2017 to 30 June 2020. PD-L1 testing was available in the registry from 01 January 2018. Kaplan-Meier was used for overall survival (OS) by type treatment and histology. A total of 2,204 patients with pathologically confirmed unresectable stage IIIB/C or IV NSCLC initiated first-line treatment, 1,807 (82%) with nonsquamous (NSQ) and 397 (18%) with SQ. Eighty-six per cent (NSQ) or 85% (SQ) had been tested for PD-L1 expression, a proportion that increased over time. The use of platinum-based therapy as first-line treatment decreased substantially over time while there was an upward trend for PD-(L)1-based therapy. Among patients with PS 0-1 initiating a first-line PD-(L)1 inhibitor monotherapy, the median OS was 18.6 and 13.3 months for NSQ and SQ NSCLC patients, respectively, while for the PD-(L)1 inhibitor and chemotherapy combination regimen, the median OS was 24.0 months for NSQ and not evaluable for SQ patients. The majority of advanced NSCLCs in Sweden were tested for PD-L1 expression. Real-world OS in patients with PS 0-1 receiving first-line PD-(L)1 inhibitor-based regimens was similar to what has been reported in pivotal clinical trials on PD-(L)1 inhibitors.

Cancer Cell-Mimicking Prussian Blue Nanoplatform for Synergistic Mild Photothermal/Chemotherapy via Heat Shock Protein Inhibition.

Combined mild-temperature photothermal/chemotherapy has emerged as a highly promising modality for tumor therapy. However, its therapeutic efficacy is drastically compromised by the heat-induced overexpression of heat shock proteins (HSPs) by the cells, which resist heat stress and apoptosis. The purpose of this study was to downregulate HSPs and enhance the mild-temperature photothermal/chemotherapy effect. In detail, the colon cancer cell membrane (CT26M)-camouflaged HSP90 inhibitor ganetespib and the chemotherapeutic agent doxorubicin (DOX)-coloaded hollow mesoporous Prussian blue (HMPB) nanoplatform (named PGDM) were designed for synergistic mild photothermal/chemotherapy via HSP inhibition. In addition to being a photothermal agent with a high efficiency of photothermal conversion (24.13%), HMPB offers a hollow hole that can be filled with drugs. Concurrently, the cancer cell membrane camouflaging enhances tumor accumulation through a homologous targeting mechanism and gives the nanoplatform the potential to evade the immune system. When exposed to NIR radiation, HMPB's photothermal action (44 °C) not only causes tumor cells to undergo apoptosis but also causes ganetespib to be released on demand. This inhibits the formation of HSP90, which enhances the mild photothermal/chemotherapy effect. The results confirmed that the combined treatment regimen of mild photothermal therapy (PTT) and chemotherapy showed a better therapeutic efficacy than the individual treatment methods. Therefore, this multimodal nanoparticle can advance the development of drugs for the treatment of malignancies, such as colon cancer, and has prospects for clinical application.

Enhanced Therapeutic Efficacy of the Nanoscale Fluoropyrimidine Polymer CF10 in a Rat Colorectal Cancer Liver Metastasis Model.

Combination chemotherapy regimens that include fluoropyrimidine (FP) drugs, e.g., 5-fluorouracil (5-FU), are central to the treatment of colorectal cancer liver metastases (CRLMs), a major cause of cancer mortality. We tested a second-generation FP polymer, CF10, in a CC531/WAGRij syngeneic orthotopic rat model of liver metastasis to determine if CF10 improved response relative to 5-FU. CF10 displayed increased potency relative to 5-FU in CC531 rat colorectal cancer cells based on clonogenic assay results and caused increased apoptosis, as shown using a live/dead assay. The increased potency of CF10 to CC531 cells was associated with increased replication stress, as assessed by Western blot for biomarkers of ATR/Chk1 and ATM/Chk2 pathway activation. CF10 dosed to deliver equivalent FP content as an established dose of 5-FU in rats (50 mg/kg) did not cause weight loss in WAGRij rats even when combined with ethynyl uracil (EU), an inhibitor of dihydropyrimidine dehydrogenase, the enzyme primarily responsible for 5-FU degradation in the liver. In contrast, 5-FU caused significant weight loss that was exacerbated in combination with EU. Importantly, CF10 was significantly more effective than 5-FU at inhibiting tumor progression (~90% reduction) in the CC531/WAG/Rij CRLM model. Our results reveal strong potential for CF10 to be used for CRLM treatment.

Clinical analysis of 12 cases of ovarian yolk sac tumor

Objective: To investigate the diagnosis, treatment and prognosis of ovarian yolk sac tumor (OYST). Methods: The clinicopathological data and follow-up data of 12 patients with OYST admitted to the Affiliated Hospital of Qingdao University from January 2013 to December 2020 were retrospectively analyzed, and the diagnosis, treatment and prognosis of OYST patients were summarized. Results: (1) The age of 12 patients with OYST ranged from 11 to 37 years, with a median age of 20 years. At the first visit, all 12 patients had pelvic masses. Reasons for seeing a doctor: 6 cases of abdominal distension and abdominal pain, 4 cases of mass in the lower abdomen, 1 case of vaginal bleeding, and 1 case of appendicitis. International Federation of Obstetrics and Gynecology (FIGO) 2014 staging: 4 cases in stage Ⅰa, 2 cases in stage Ⅰc, 1 case in stage Ⅱc, 4 cases in stage Ⅲc, and 1 case in stage Ⅳb. (2) All 12 patients were examined by color Doppler ultrasound before operation, among which 10 cases showed unilateral adnexal masses and 2 cases bilateral adnexal masses. The median maximum diameter of tumor was 16.5 cm (range: 6.0-28.0 cm). The preoperative levels of alpha fetoprotein (AFP) in 12 patients (all >1 210 μg/L) were significantly higher than normal (<25 μg/L). Among the 11 patients with cancer antigen 125 (CA125) detection results, 9 patients showed elevated serum CA125 levels. (3) Among the 12 patients, 8 young infertile patients who needed to preserve their reproductive function underwent appendectomy, 3 infertile patients underwent staged surgery for ovarian malignant germ cell tumor, and only one bilateral lesion and infertile patient underwent unsatisfactory staged surgery for ovarian malignant germ cell tumor. Of the 12 patients, 11 patients were given combined chemotherapy regimen of bleomycin, cisplatin, and etoposide (BEP) after operation. One patient without chemotherapy developed metastasis 3 months after operation, and was given BEP chemotherapy, and her condition was controlled. (4) The deadline for follow-up was December 31st, 2022, and the median follow-up time was 60 months (range: 25-115 months). All the 12 patients survived without tumor during the follow-up period, and the median disease-free survival time was 84.5 months (range: 25-115 months). Conclusions: OYST mostly occurs in children and young women. Color Doppler ultrasound examination and serum AFP and CA125 detection have diagnostic value for OYST. Surgical treatment after diagnosis of OYST includes surgery to preserve reproductive function and timely and standardized chemotherapy after operation. The prognosis of patients is good regardless of stage.

Abstract 1228: Selective FGFR4 inhibitor Irpagratinib (ABSK011) exhibits broad synergistic and combinatory anti-tumor effects with other therapeutic agents in preclinical HCC models

Abstract Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer, ranking as the sixth most prevalent cancer and the third leading cause of death worldwide. Approved therapeutic drugs, including chemotherapy, anti-angiogenesis agents and immunotherapy-based combination regimen (atezolizumab plus bevacizumab), have shown suboptimal clinical benefits for patients with HCC. There are critical unmet medical needs for additional therapeutic options to address this challenge. Deregulation of FGF19-FGFR4 signaling accounts for roughly 30% of HCC and plays a pivotal role in driving HCC tumorigenesis. To date, several FGFR4 inhibitors have advanced to the clinical stage for the treatment of HCC patients. Among them, a recently discovered novel and highly selective inhibitor, Irpagratinib (ABSK011), has demonstrated the potential to become a first-in-class or best-in-class FGFR4 inhibitor. It showed promising anti-tumor activity in an ongoing phase Ib clinical study, with an ORR of 40.7% observed in FGF19 overexpressed late line HCC patients in cohorts treated with BID regimens. To further expand the therapeutic potential of irpagratinib, we carried out an array of combination treatments and revealed its broad synergistic effects with various immune and targeted agents in treating HCC. Methods: We evaluated the combination effects of Irpagratinib with a variety of therapeutic agents, covering both targeted and immune-oncology agents, in preclinical HCC in vivo models. The tested agents, including lenvatinib, atezolizumab plus bevacizumab, anti-PD-(L)1, SHP2 inhibitors and EGFR antagonists, were assessed across a range of preclinical models, such as cell-derived or patient-derived xenografts, engineered syngeneic models and humanized models. Results: Synergistic anti-tumor effects of irpagratinib were observed in combination with the indicated agents, demonstrating more profound effects than either single agent alone in the selected preclinical in vivo models. This resulted in significant effects on inducing tumor regression or inhibiting tumor progression. Conclusions: In summary, these findings collectively illustrate very broad synergistic anti-tumor effects of irpagratinib when combined with various other therapeutic agents. These results may pave the road for potential novel combinatory therapeutic strategies that could expand the utility of irpagratinib and provide innovative and more effective therapies to HCC patients. Citation Format: Nannan Zhang, Bin Shen, Zhidong He, Cheng Dai, Jie Wang, Jie Zhang, Manqi Liu, Yongxian Zhang, Zhui Chen. Selective FGFR4 inhibitor Irpagratinib (ABSK011) exhibits broad synergistic and combinatory anti-tumor effects with other therapeutic agents in preclinical HCC models [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 1228.

Nimotuzumab-vinorelbine combination therapy versus other regimens in the treatment of pediatric diffuse intrinsic pontine glioma.

Pediatric diffuse intrinsic pontine glioma (DIPG) is a fatal disease associated with a median survival of < 1year despite aggressive treatments. This retrospective study analyzed the treatment outcomes of patients aged < 18years who were diagnosed with DIPG between 2012 and 2022 and who received different chemotherapy regimens. After radiotherapy, patients with DIPG received nimotuzumab-vinorelbine combination or temozolomide-containing therapy. When nimotuzumab was unavailable, it was replaced by vincristine, etoposide, and carboplatin/cyclophosphamide (VECC). Temozolomide was administered as a single agent or a part of the combination chemotherapy comprising temozolomide, irinotecan, and bevacizumab. Furthermore, 1- and 3-year overall survival (OS), progression-free survival (PFS), and median OS and PFS were analyzed. The median age of 40 patients with DIPG was 97 ± 46.93 (23-213) months; the median follow-up time was 12months. One and 3-year OS were 35.0% and 7.5%, respectively. Median OS was 12months in all patients (n = 40), and it was 16, 10, and 11months in those who received first-line nimotuzumab-vinorelbine combination (n = 13), temozolomide-based (n = 14), and VECC (n = 6) chemotherapy regimens, respectively (p = 0.360). One patient who received gefitinib survived for 16months. Conversely, patients who never received radiotherapy and any antineoplastic medicamentous therapy (n = 6) had a median OS of 4months. Nimotuzumab-vinorelbine combination therapy prolonged OS by 6months compared with temozolomide-containing chemotherapy, although the difference was not statistically significant.

Rare NUP98::PRRX1 fusion transcript in a therapy-related acute myeloid leukemia associated with del(7q) following chemotherapy for diffuse large B-cell lymphoma

BackgroundTherapy-related acute myeloid leukemia (t-AML) is increasingly recognized as a treatment complication in patients receiving chemotherapy, radiotherapy, or immunosuppressive agents for primary neoplasms. NUP98::PRRX1 fusion gene, caused by t(1;11)(q23;p15), is a rare recurrent cytogenetic alteration in leukemia, and only seven cases with NUP98::PRRX1 were reported so far. MethodsA 53-year-old female patient was diagnosed with t-AML after 20 months of complete remission (CR) from diffuse large B-cell lymphoma (DLBCL). Conventional karyotype, fluorescence in situ hybridization (FISH), and DNA/RNA next-generation sequence (NGS) were used to detect genetic abnormalities. ResultsAbnormal karyotype of 46, XX, t(1;11)(q25;p15), del(7)(q22) was revealed. NUP98 gene rearrangement and del(7)(q22) were verified by FISH. Further, RNA NGS detected NUP98::PRRX1 fusion transcript, and DNA NGS detected KRAS gene mutation. The patient achieved CR after a combined chemotherapy regimen containing BCL-2 inhibitor and underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), but she died of leukemia recurrence 14 months later. ConclusionsNovel targeted drugs may provide opportunities for patients with NUP98::PRRX1 to undergo allo-HSCT. However, since the cases of carrying the NUP98::PRRX1 are limited, more patients with this genetic change need to be investigated to elucidate the prognostic significance.

Tumour response following preoperative chemotherapy is affected by body mass index in patients with colorectal liver metastases.

Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality, with the liver being the primary organ of metastasis. Preoperative chemotherapy is widely recommended for initially or potentially resectable colorectal liver metastases (CRLMs). Tumour pathological response serves as the most important and intuitive indicator for assessing the efficacy of chemotherapy. However, the postoperative pathological results reveal that a considerable number of patients exhibit a poor response to preoperative chemotherapy. Body mass index (BMI) is one of the factors affecting the tumorigenesis and progression of colorectal cancer as well as prognosis after various antitumour therapies. Several studies have indicated that overweight and obese patients with metastatic colorectal cancer experience worse prognoses than those with normal weight, particularly when receiving first-line chemotherapy regimens in combination with bevacizumab. To explore the predictive value of BMI regarding the pathologic response following preoperative chemotherapy for CRLMs. A retrospective analysis was performed in 126 consecutive patients with CRLM who underwent hepatectomy following preoperative chemotherapy at four different hospitals from October 2019 to July 2023. Univariate and multivariate logistic regression models were applied to analyse potential predictors of tumour pathological response. The Kaplan-Meier method with log rank test was used to compare progression-free survival (PFS) between patients with high and low BMI. BMI < 24.0 kg/m2 was defined as low BMI, and tumour regression grade 1-2 was defined as complete tumour response. Low BMI was observed in 74 (58.7%) patients and complete tumour response was found in 27 (21.4%) patients. The rate of complete tumour response was significantly higher in patients with low BMI (29.7% vs 9.6%, P = 0.007). Multivariate analysis revealed that low BMI [odds ratio (OR) = 4.56, 95% confidence interval (CI): 1.42-14.63, P = 0.011], targeted therapy with bevacizumab (OR = 3.02, 95%CI: 1.10-8.33, P = 0.033), preoperative carcinoembryonic antigen level < 10 ng/mL (OR = 3.84, 95%CI: 1.19-12.44, P = 0.025) and severe sinusoidal dilatation (OR = 0.17, 95%CI: 0.03-0.90, P = 0.037) were independent predictive factors for complete tumour response. The low BMI group exhibited a significantly longer median PFS than the high BMI group (10.7 mo vs 4.7 mo, P = 0.011). In CRLM patients receiving preoperative chemotherapy, a low BMI may be associated with better tumour response and longer PFS.

Progress in the study of reproductive toxicity of platinum-based antitumor drugs and their means of prevention.

Platinum-based antitumor drugs are broad-spectrum agents with unique mechanisms of action. Combination chemotherapy regimens based on platinum drugs are commonly used in cancer treatment. However, these drugs can cause various adverse reactions in the human body through different routes of administration, including reproductive toxicity, genetic toxicity, and embryonic developmental toxicity. Preventing adverse effects is crucial to enhance patients' quality of life and reduce healthcare costs. This article discusses the types and developmental history of antitumor active platinum compounds, their mechanisms of action, routes of administration, and their potential reproductive, genetic, and embryonic developmental toxicity. This text explores preventive measures based on animal experimental results. Its aim is to provide references for personalized treatment and occupational protection when using platinum drugs. The continuous progress of science and technology, along with the deepening of medical research, suggests that the application of platinum drugs will broaden. Therefore, the development of new platinum drugs will be an important direction for future research.

Pathological complete response following neoadjuvant chemotherapy for locally advanced intrahepatic cholangiocarcinoma

BackgroundIntrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer. Cases when found are often advanced with vascular invasion, and radical resection is often difficult. Despite curative resection, the postoperative recurrence rate of patients with histological lymph node metastasis is high, and their prognosis is poor. Therefore, there is an urgent need to establish multidisciplinary treatment that combines chemotherapy and surgical resection. The efficacy of neoadjuvant chemotherapy (NAC) for locally advanced ICC is unclear. In this report, a case of locally advanced ICC in which pathological complete response (pCR) was achieved after NAC is described.Case presentationA 79-year-old woman was admitted to a local hospital with appetite loss. Computed tomography showed a 100 × 90 mm low-contrast tumor in the left hepatic lobe and segment 1 with invasion to the inferior vena cava (IVC), and several lymph nodes along the left gastric artery and lesser curvature were enlarged. Therefore, she was treated with a combined chemotherapy regimen of gemcitabine and cisplatin. After four courses, the tumor size decreased to 30 × 60 mm without invasion to the IVC. Left hepatectomy extending to segment 1 with bile duct resection combined with middle hepatic vein resection (H1234-B-MHV), dissection of regional lymph nodes and pyloroplasty were performed. After radical resection, pCR was achieved. She is alive with no evidence of disease, 2 years after surgery.ConclusionsIn this case, a patient with locally advanced ICC achieved pCR to NAC. NAC may be effective for ICC. Patients who achieve pCR may have a better prognosis.

A phase II trial of cemiplimab alone or in combination with standard of care chemotherapy in locally advanced or metastatic penile carcinoma (EPIC trial).

TPS14 Background: Penile cancer is rare, &lt;1% of male malignancies diagnosed each year, but its incidence is increasing with an 18% increase over the last decade projected to rise a further 9% in the next 10 years. Patients with locally advanced/metastatic penile cancer (la/mPC) have very few treatment options and there is a lack of clinical trial data to guide management. Cisplatin containing combination chemotherapy regimens are regarded as the standard of care (SOC) in this setting. However, with response rates of 50% or less there is a need to further improve treatment outcomes. PDL1 is upregulated in 40–60% of PC cases and is correlated with poor prognosis making a case for immunotherapy as a treatment for la/mPC. The PD-1 inhibitor cemiplimab is approved for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (SCC) suggesting efficacy against penile SCC. The EPIC trial was set up to evaluate the benefit and safety of cemiplimab alone, or, in combination with SOC chemotherapy in patients with la/mPC. Methods: This is a non-randomised, 2 arm, phase II multi-centre trial. Arm 1 cemiplimab + SOC chemotherapy (local site choice of cisplatin/5FU, TPF or TIP regimes); Arm 2 single agent cemiplimab. The choice of arm decided by the investigator site based on chemotherapy eligibility. 47 patients will be recruited from 10 UK centres: 29 patients into ARM 1 who will receive 4 cycles of cemiplimab 350mg IV q3 weekly + SOC chemotherapy, followed by single agent cemiplimab x 30 cycles (24 months total). 18 patients into ARM 2 who will receive single agent cemiplimab 350mg IV q3 weekly x 34 cycles (24 months total). The primary endpoint is clinical benefit rate (CBR) of cemiplimab: objective response rate (ORR) plus stable disease as assessed radiologically (RECIST 1.1) at 12 weeks from first dose in patients with la/mPC. Secondary end-points include safety, tolerability, CBR at 1, 2 and 3 years, ORR, progression-free survival, overall survival and assessment of patient health status and quality of life using the patient reported outcome measures EQ-5D-5L and EORTC QLQ-C30. Each arm will be analysed separately as a Fleming A’Hern study α=0.05 + power (1-β)=0.8. Arm 1 assumes 25% meeting the clinical end point is a poor treatment (p0=0.25) and 50% is a good treatment (p1=0.5). Arm 2 assumes 5% meeting the clinical end point is a poor treatment (p0=0.05) and 25% is a good treatment (p1=0.25). Progress: By February 2023 10 UK sites had been opened to recruitment. The first patient entered the trial in November 2021 and to date 25 patients have been recruited into Arm 1 and 10 into Arm 2. Opening sites was slower than anticipated following emergence from the COVID pandemic. However, a recruitment rate of 1-2 patients per month has shown the feasibility of running a trial for this rare patient population. Clinical trial information: ISRCTN95561634 .

Study on the efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy regimen for III–IVA esophageal squamous cell carcinoma post-surgery

Background and aimsThe treatment of esophageal squamous cell carcinoma is still controversial, and neoadjuvant chemotherapy combined with immunotherapy is a hot topic of current research. We investigated the recent efficacy and surgical safety of patients with III–IVA esophageal squamous cell carcinoma after neoadjuvant regimen of paclitaxel + cisplatin/nedaplatin/carboplatin + sindilizumab, to provide a theoretical basis for evaluating the feasibility of surgery after neoadjuvant therapy.MethodsThe clinical data of patients with stage III–IVA esophageal squamous cell carcinoma admitted from January 2022 to April 2023 at our hospital were collected for retrospective analysis. The patients were divided into the neoadjuvant combination surgery group (34 patients with the regimen of paclitaxel + cisplatin/nedaplatin/carboplatin + sintilimab two/three cycles of preoperative neoadjuvant therapy) and surgery-only group (36 patients). Statistical analysis was performed to compare the differences between both groups particularly for intraoperative bleeding, operative time, incidence of postoperative pulmonary complications, laryngeal recurrent nerve injury, thoracic duct injury, anastomotic fistula, and postoperative hospital days. Additionally, the pCR/MPR rates of the neoadjuvant group were analysed.ResultsSignificant differences were present in the clinical and pathological staging before and after neoadjuvant treatment (P ≤ 0.001). The neoadjuvant group had a pCR rate of 26.47% and an ORR rate of 88.23%. No significant differences were discovered in R0 resection rate between both groups, as well as intraoperative bleeding, operative time, intraoperative laryngeal recurrent nerve injury rate, thoracic duct injury rate, postoperative anastomosis incidence, postoperative hospital days, and postoperative lung infection incidence (P > 0.05).ConclusionsThe neoadjuvant immune combination chemotherapy regimen had considerable tumor regression and pathological remission benefits, without reducing the safety of surgery, possibly presenting as a new treatment plan.

Perioperative and palliative systemic treatments for biliary tract cancer.

Due to the fact biliary tract cancer (BTC) is often diagnosed at an advanced stage, thus, not eligible for resection, and due to the aggressive tumor biology, it is considered as one of the cancer types with the worst prognosis. Advances in diagnosis, surgical techniques, and molecular characterization have led to an improvement of the prognosis of BTC patients, recently. Although neoadjuvant therapy is expected to improve surgical outcomes by reducing tumor size, its routine is not well established. The application of neoadjuvant therapy in locally advanced disease may be indicated, the routine use of systemic therapy prior to surgery for cholangiocarcinoma patients with an upfront resectable disease is less well established, but discussed and performed in selected cases. In advanced disease, only combination chemotherapy regimens have been demonstrated to achieve disease control in untreated patients. Molecular profiling of the tumor has demonstrated that many BTC might bear actionable targets, which might be addressed by biological treatments, thus improving the prognosis of the patients. Furthermore, the addition of the immunotherapy to standard chemotherapy might improve the prognosis in a subset of patients. This review seeks to give a comprehensive overview about the role of neoadjuvant as well as palliative systemic treatment approaches and an outlook about novel systemic treatment concept in BTC.

Engineering lauric acid-based nanodrug delivery systems for restoring chemosensitivity and improving biocompatibility of 5-FU and OxPt against Fn-associated colorectal tumor.

Colorectal cancer (CRC) occurs in the colorectum and ranks second in the global incidence of all cancers, accounting for one of the highest mortalities. Although the combination chemotherapy regimen of 5-fluorouracil (5-FU) and platinum(IV) oxaliplatin prodrug (OxPt) is an effective strategy for CRC treatment in clinical practice, chemotherapy resistance caused by tumor-resided Fusobacterium nucleatum (Fn) could result in treatment failure. To enhance the efficacy and improve the biocompatibility of combination chemotherapy, we developed an antibacterial-based nanodrug delivery system for Fn-associated CRC treatment. A tumor microenvironment-activated nanomedicine 5-FU-LA@PPL was constructed by the self-assembly of chemotherapeutic drug derivatives 5-FU-LA and polymeric drug carrier PPL. PPL is prepared by conjugating lauric acid (LA) and OxPt to hyperbranched polyglycidyl ether. In principle, LA is used to selectively combat Fn, inhibit autophagy in CRC cells, restore chemosensitivity of 5-FU as well as OxPt, and consequently enhance the combination chemotherapy effects for Fn-associated drug-resistant colorectal tumor. Both in vitro and in vivo studies exhibited that the tailored nanomedicine possessed efficient antibacterial and anti-tumor activities with improved biocompatibility and reduced non-specific toxicity. Hence, this novel anti-tumor strategy has great potential in the combination chemotherapy of CRC, which suggests a clinically relevant valuable option for bacteria-associated drug-resistant cancers.