Combination Chemotherapy In Treatment Research Articles

Toxicity profile of camrelizumab-based immunotherapy in older adults with advanced cancer

Immune checkpoint inhibitors (ICIs) have become an important cornerstone of many tumour treatments. However, the toxicity profile of immune-chemotherapy combination treatment approaches among older adult cancer patients is still unclear. Patients with any cancer who received camrelizumab-based immunotherapy were eligible for inclusion. The primary endpoints were adverse events (AEs) and immune-related adverse events (irAEs), which were defined based on Naranjo's algorithm. Patients were stratified by age (≥ 70 years and < 70 years), and comparisons were made based on the type of camrelizumab-based therapy (monotherapy, combined chemotherapy, or combined anti-VEGF therapy). A total of 185 patients were administered camrelizumab-based immunotherapy, 55 (30%) of whom were ≥ 70 years old. A total of 146 (78.9%) patients received camrelizumab-based combination treatment. The incidence of all-grade AEs was 56.8% (105 patients), while that of irAEs was 36.8% (68 patients). There was no difference in the percentage of patients experiencing any grade or grade ≥ 3 AEs between age groups. However, the frequency of irAEs (both any grade and grade ≥ 3) significantly differed by age group (P = 0.001 and 0.009, respectively). The results of multivariable analysis revealed that age ≥ 70 years was the only independent risk factor for irAEs. The results of subgroup analysis revealed that the incidence of irAEs was higher in older patients treated with camrelizumab-chemotherapy, while the incidence rates were similar between age groups in the monotherapy and combination anti-VEGF treatment subgroups. Immune-related diabetes mellitus occurred more frequently among older adults. The spectrum of irAEs showed that combination immunotherapy had more widely effects on the organ system than monotherapy. In this study, older (≥ 70 years) patients had a higher risk of all-grade and high-grade irAEs when receiving camrelizumab chemotherapy combination treatment. Notably, long-term random glucose monitoring should be performed during ICI-based immunotherapy in older cancer patients.

Comprehensive assessment of pain characteristics, quality of life, and pain management in cancer patients: a multi-center cross-sectional study.

Pain is the most common complaint among cancer patients, significantly impairing their health-related quality of life (HRQOL). There is limited evidence on the characteristics of pain among cancer patients in Nepal with low-resource settings. The primary objective of this study was to evaluate the clinical characteristics of pain, factors influencing pain intensity, and the association of pain severity with quality of life (QoL) among cancer patients. Secondary objectives included investigating perceived barriers to pain management and medication adherence among these patients. This multi-center, cross-sectional study enrolled adult patients (over 18 years old) with reported cancer diagnoses experiencing pain. Socio-demographic characteristics (e.g., age, gender, educational status), clinical characteristics (e.g. cancer diagnosis, staging), and pain characteristics (e.g., duration, type, location, medicines used for pain management, etc.) were recorded. Outcomes were assessed using the Numeric rating scale (NRS), Pain management Index, European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire, Barriers Questionnaire II, Medication Adherence Rating Scale, and Hospital Anxiety and Depression Scale. Four hundred and eight patients participated in the study. The mean ± SD age was 54.87 ± 15.65, with226 patients (55.4%) being female. The most common cancer diagnoses were cervical (17.6%), lung (11.8%), and colon/rectum (12.0%) cancers. The most common pain locations were the head and neck (27.0%); a majority (55.6%) reported pain duration of more than 3 months. Nociceptive pain was reported by 42.4% of patients; the mean ± SD of NRS was 4.31 ± 2.69, with 32.4% of patients experiencing moderate pain. Patients with mixed pain type (B = 1.458, p < 0.001) or pain in multiple sites (B = 1.175, p < 0.001), lower Karnofsky Performance Status (KPS) (B = -1.308, p < 0.001), and specific cancer diagnoses such as prostate (B = -2.045, p = 0.002), pancreatic (B = 1.852, p = 0.004), oesophageal (B = 1.674, p = 0.012), and ovarian cancer (B = 1.967, p = 0.047), experienced varying degrees of increased NRS score. The combined chemotherapy and radiotherapy treatment modality was associated with a lower NRS score (B = -0.583, p = 0.017). A significant inverse relationship was observed between pain severity and global health status/QoL (B = -37.36, p < 0.001. Key barriers to pain management included moderate perceptions of physiological effects, communication issues between doctors and patients, and concerns about the harmful effects of pain medicine. The prevalence of non-adherence to pain medications was 13.97%. In conclusion, this study highlights the multi-faceted nature of pain management and QoL for cancer patients in Nepal with low-resource settings. These findings underscore the multifactorial nature of pain perception in cancer patients, with mixed pain types, pain in multiple sites, lower KPS, and specific cancer diagnoses, all contributing significantly to pain severity. Additionally, pain severity was associated with declining QoL. These findings contribute valuable insights into the complex aspects of cancer pain and its broader implications for the well-being of patients, offering a foundation for targeted interventions and improved pain management strategies in the context of cancer care in low-resource settings.

Comparison of First-Line Chemotherapeutics and Validation of the EORTC Prognostic Index in Malignant Pleural Mesothelioma: Retrospective Single-Centre Experience.

To evaluate the efficiency of pemetrexed cisplatin in comparison with gemcitabine cisplatin and to validate the EORTC (European Organisation for Research and Treatment of Cancer) prognostic score in combination chemotherapy treatment for malignant pleural mesothelioma. An observational study. Place and Duration of the Study:Department of Oncology, Dicle University Hospital, Diyarbakir, Turkiye, from October 2000 to November 2017. Malignant pleural mesothelioma (MPM) patients with EORTC score 0- were recruited. Factors affecting the prognosis of the disease and the effectiveness of first-line treatment were retrospectively analysed. EORTC prognostic score was calculated with a cut-off and survival analyses were used by the Kaplan-Meier method. Log-rank and univariable Cox regression tests were used to search for prognostic factors' impact on survival. Patients who received gemcitabine cisplatin treatment had a median progression-free survival (PFS) of 9 months, while those who received pemetrexed cisplatin therapy had a median PFS of 7 months. Median overall survival (OS) was 17 months in the gemcitabine cisplatin group and 18 months in the pemetrexed cisplatin group (p = 0.051). When the low-risk group was compared with the high-risk group, the median OS was found to be statistically significant (p = 0.009). The EORTC prognostic score, which is used for prognostic prediction in the period when pemetrexed is not utilised in the treatment of MPM, accurately predicts prognosis subsequent to the administration of pemetrexed in treatment. In the context of first-line treatment, cisplatin in combination with gemcitabine and cisplatin in combination with pemetrexed demonstrated comparable efficacy with respect to both overall survival and progression-free survival. Chemotherapy, Mesothelioma, Prognosis, Gemcitabine, Progression-free survival.

Advanced Ovarian Cancer Patients’ Experiences of Surgical Treatment: A Qualitative Analysis

ObjectivesRecommended treatment for advanced ovarian cancer involves a combination of debulking surgery and chemotherapy. Surgery places a significant burden on a patient's physical, social, sexual, and emotional wellbeing. Existing research exploring the impact of surgery is often limited to questionnaire administration with large gaps between data collection time points, missing key aspects of the perioperative period. Little is known of the experience of ovarian cancer surgical treatment from a patient perspective. This research aims to qualitatively explore advanced ovarian cancer patients’ experience of surgery and identify areas in which quality of life may be impacted. MethodsSemi-structured telephone or face-to-face interviews were conducted with patients who had undergone combined surgical and chemotherapy treatment. Interviews were audio-recorded and transcribed verbatim. Transcripts were analyzed using an inductive approach to thematic analysis. ResultsTwenty ovarian cancer patients who had undergone debulking surgery participated in interviews lasting between 33 and 68 minutes. Qualitative analysis generated five key themes: (1) care services; (2) experiences of a stoma; (3) preoperative experience; (4) impact of surgery; and (5) coping mechanisms. ConclusionsUnderstanding the patient experience of surgical treatment for advanced ovarian cancer can help inform and improve future care. This research explored the ways in which a patient's quality of life is impacted by surgery and highlights areas in which further support may be needed. Knowledge of the patient experience may also aid decision-making for both clinicians and patients when considering different treatment pathways. Implications for Nursing PracticeResults highlighted two crucial points in the surgical pathway where patients' need for emotional support was significant: during pre-op and recovering from surgery as an inpatient. Nursing staff are key to providing reassurance during this time. Specialized stoma nurses were also essential for supporting patients to adapt to their stomas both physically and psychologically.

Emulation and evaluation of tumor cell combined chemotherapy in isotropic/anisotropic collagen fiber microenvironments.

The rapid emergence of anisotropic collagen fibers in the tissue microenvironment is a critical transition point in late-stage breast cancer. Specifically, the fiber orientation facilitates the likelihood of high-speed tumor cell invasion and metastasis, which pose lethal threats to patients. Thus, based on this transition point, one key issue is how to determine and evaluate efficient combination chemotherapy treatments in late-stage cancer. In this study, we designed a collagen microarray chip containing 241 high-throughput microchambers with embedded metastatic breast cancer cell MDA-MB-231-RFP. By utilizing collagen's unique structure and hydromechanical properties, the chip constructed three-dimensional isotropic and anisotropic collagen fiber structures to emulate the tumor cell microenvironment at early and late stages. We injected different chemotherapeutic drugs into its four channels and obtained composite biochemical concentration profiles. Our results demonstrate that anisotropic collagen fibers promote cell proliferation and migration more than isotropic collagen fibers, suggesting that the geometric arrangement of fibers plays an important role in regulating cell behavior. Moreover, the presence of anisotropic collagen fibers may be a potential factor leading to the poor efficacy of combined chemotherapy in late-stage breast cancer. We investigated the efficacy of various chemotherapy drugs using cell proliferation inhibitors paclitaxel and gemcitabine and tumor cell migration inhibitors 7rh and PP2. To ensure the validity of our findings, we followed a systematic approach that involved testing the inhibitory effects of these drugs. According to our results, the drug combinations' effectiveness could be ordered as follows: paclitaxel + gemcitabine > gemcitabine + 7rh > PP2 + paclitaxel > 7rh + PP2. This study shows that the biomimetic chip system not only facilitates the creation of a realistic in vitro model for examining the cell migration mechanism in late-stage breast cancer but also has the potential to function as an effective tool for future chemotherapy assessment and personalized medicine.

Evaluation of Helium Ion Radiotherapy in Combination with Gemcitabine in Pancreatic Cancer In Vitro.

Pancreatic cancer is one of the most aggressive and lethal cancers. New treatment strategies are highly warranted. Particle radiotherapy could offer a way to overcome the radioresistant nature of pancreatic cancer because of its biological and physical characteristics. Within particles, helium ions represent an attractive therapy option to achieve the highest possible conformity while at the same time protecting the surrounding normal tissue. The aim of this study was to evaluate the cytotoxic efficacy of helium ion irradiation in pancreatic cancer in vitro. Human pancreatic cancer cell lines AsPC-1, BxPC-3 and Panc-1 were irradiated with photons and helium ions at various doses and treated with gemcitabine. Photon irradiation was performed with a biological cabin X-ray irradiator, and helium ion irradiation was performed with a spread-out Bragg peak using the raster scanning technique at the Heidelberg Ion Beam Therapy Center (HIT). The cytotoxic effect on pancreatic cancer cells was measured with clonogenic survival. The survival curves were compared to the predicted curves that were calculated via the modified microdosimetric kinetic model (mMKM). The experimental relative biological effectiveness (RBE) of helium ion irradiation ranged from 1.0 to 1.7. The predicted survival curves obtained via mMKM calculations matched the experimental survival curves. Mainly additive cytotoxic effects were observed for the cell lines AsPC-1, BxPC-3 and Panc-1. Our results demonstrate the cytotoxic efficacy of helium ion radiotherapy in pancreatic cancer in vitro as well as the capability of mMKM calculation and its value for biological plan optimization in helium ion therapy for pancreatic cancer. A combined treatment of helium irradiation and chemotherapy with gemcitabine leads to mainly additive cytotoxic effects in pancreatic cancer cell lines. The data generated in this study may serve as the radiobiological basis for future experimental and clinical works using helium ion radiotherapy in pancreatic cancer treatment.

Development of tumor marker detection and tumor treatment based on silver nanozymes

Nanomaterials with intrinsic enzyme activity (nanozymes) have been widely used as artificial enzymes in biomedicine, especially in tumor diagnosis and treatment. Herein, a kind of water-soluble silver nanozyme (Ag@GQD) was developed with a simple method, which showed two enzymatic activities (peroxidase and oxidase-like activity). Based on the excellent catalytic performance of oxidase-like activity, a simple and highly sensitive colorimetric detection strategy for glutathione (GSH) was established. What’s more, after absorbing DOX, Ag/DOX@GQD could realize the combined treatment of reactive oxygen species and chemotherapy. In conclusion, this study provided evidences that Ag@GQD is effective in tumor diagnosis and treatment, which provided new ideas for exploring nanozymes based on the integration of diagnosis and treatment.

Abstract 1189: Modulation of the MSS and MSI colorectal cancer immune microenvironment with FOLFOX and FOLFIRI -/+ anti-PD-1 immunotherapy

Abstract Metastatic colorectal cancer (mCRC) is a deadly disease with a five-year survival rate of 14%. Most patients receive 5-FU (F) and folinic acid (FOL) combined with oxaliplatin (OX), irinotecan (IRI), or both (OXIRI). Immune checkpoint inhibitors (ICIs) are effective against microsatellite instable (MSI) tumors, but 95% of mCRC tumors are microsatellite stable (MSS) and ICI-resistant. Though the primary targets of 5-FU, irinotecan, and oxaliplatin are well-understood, their effects on the tumor microenvironment (TME) remain incompletely characterized. Chemotherapy-mediated immune stimulation in MSS CRC has been observed in preclinical models and clinical trials. We hypothesize that combination chemotherapy treatment modulates the immune microenvironment of CRC -/+ ICI, with differences across subtype and treatment regimen. Chemotherapy-dependent changes in cancer cell gene expression, PD-L1 levels, cytokine secretion, and T cell activation were measured using in vitro models of MSS and MSI CRC. A preliminary evaluation of spleen and tumor T cells and dendritic cells (DCs) in murine models of MSS and MSI CRC after immunotherapy -/+ chemotherapy was conducted. CD8+ T cells, DCs, PD-L1, CD69, and GM-CSF expression were measured in clinical specimens of chemotherapy-treated MSS mCRC patients. In MSS CRC, FOX increased GM-CSF and activated CD8+ T cells in vitro and activated splenic CD8+ and CD4+ T cells in vivo. FOX and FIRI suppressed an anti-PD-1-mediated enhancement of type 1 cDCs in the tumor in vivo. FOLFOX was associated with increased tumor CD8+ T cells and decreased GM-CSF in MSS mCRC biopsies. FIRI treatment increased PD-L1 in vitro. FOLFIRI was not associated with increased tumor CD8+ T cells in MSS mCRC biopsies. In MSI CRC, FOX increased tumor CD8+ T cells in vivo. Here, we elucidate novel effects of clinically relevant chemotherapy combinations on the TME in MSS and MSI CRC. These data point to a FOX-specific mechanism by which CD8+ T cell infiltration into MSS mCRC tumors is enhanced, but their activation is halted potentially by GM-CSF suppression and/or type 1 cDC depletion in the TME. These findings contribute to our understanding of the mechanisms of chemotherapy-dependent immune modulation and bring the field closer to harnessing these effects for therapeutic gain. Citation Format: Lindsey Carlsen, Maximilian Pinho-Schwermann, Leiqing Zhang, Andrew Elliott, Kelsey E. Huntington, William J. MacDonald, Brooke Verschleiser, Laura Jinxuan Wu, Wafik S. El-Deiry. Modulation of the MSS and MSI colorectal cancer immune microenvironment with FOLFOX and FOLFIRI -/+ anti-PD-1 immunotherapy [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 1189.

Antitumor efficiency and photostability of newly green synthesized silver/graphene oxide nanocomposite on different cancer cell lines

It is crucial to enhance new compounds for the treatment of most malignancies, and graphene oxide/silver nanocomposite (GO/Ag NC) has been paying attention to biomedical applications such as malignancies. In this work, green synthesized Ag@Cht NPs were successfully produced using chitosan for reduction and stabilization and added on GO sheet forming novel GO/Ag NC. Then, the produced anticancer nanomaterials GO, Ag@Cht NPs, and GO/Ag NC were assessed for their cytotoxicity against four distinct cancer cell lines: H460, HCT116, MDA-MB-468, and FaDu cells, at varying concentrations, using SRP assay after 48 h. The prepared nanomaterials were characterized by TEM, UV–Vis spectrophotometry, FTIRs, Raman spectroscopy and XRD. TEM images showed a regular spread of Ag@Cht NPs on the GO sheets with an average particle size of 15 nm. UV–Vis spectrophotometry shows two main characteristic peaks for GO/Ag NC, one close to 230 nm corresponds to GO, while the other peak at 425 nm due to Ag@Cht decorating the GO surface was blue shifted by few nanometers from 427 nm for Ag@Cht. Results of the laser irradiation by DPSS (diode-pumped solid state) confirm the photothermal stability of the prepared nanocomposite as there is no change in surface plasmon resonance (SPR) with varying exposure time. FTIRs measurements indicate that Ag ions interact with a hydroxyl group. This interaction shifts the O–H wavenumber and decreases the bond stretching intensity. In addition, Ag@Cht NPs and Ag/GO NC showed enhanced activity against cancerous cells. Results showed that GO, Ag@Cht NPs, and GO/Ag NC at (200, 400, and 600 µg/ml) had an impact on all evaluated cell lines. In MDA-MB-468, HCT116, H460, and FaDu cells, Ag@Cht NPs had the most effect across all employed cell lines, with IC50 values of 5.5, 9, 6, and 7.75 µg/ml, respectively. In conclusion, the produced novel nanocomposite may be an effective way to treat different cell lines, and future work is to use the prepared nanomaterials as anticancer drug delivery in photothermal chemotherapy combination treatment.

Immunotherapy or Chemoimmunotherapy in Older Adults With Advanced Non–Small Cell Lung Cancer

Immune checkpoint inhibitor (ICI) plus chemotherapy combination treatment (ICI-chemotherapy) is now a standard treatment for non-small cell lung cancer (NSCLC) without targetable oncogene alterations, but there are few data on ICI-chemotherapy for patients 75 years and older. To inform the choice of first-line drugs in clinical practice and assess the safety and efficacy of ICI-chemotherapy combination treatment in older adult patients with previously untreated advanced NSCLC. This retrospective cohort study included 58 centers in Japan. The cohort consisted of patients 75 years and older with clinical stage IIIB, IIIC, IV, postoperative or radiotherapy recurrent NSCLC. Patients started first-line systemic therapy between December 2018 and March 2021. Those receiving first-line molecular targeted drugs were excluded. The data were analyzed from February 2022 to October 2022. Systemic therapy. The main outcomes were overall survival (OS), progression-free survival (PFS), and safety. A total of 1245 patients (median [range] age, 78 [75-95] years; 967 [78%] male) with NSCLC were included in the cohort. Programmed death ligand-1 (PD-L1) expression of less than 1% occurred in 268 tumors (22%); 1% to 49% in 387 tumors (31%); 50% and higher in 410 tumors (33%), and unknown expression in 180 tumors (14%). Median OS was 20.0 (95% CI, 17.1-23.6) months for the 354 patients receiving ICI-chemotherapy (28%); 19.8 (95% CI, 16.5-23.8) months for the 425 patients receiving ICI alone (34%); 12.8 (95% CI, 10.7-15.6) months for the 311 patients receiving platinum-doublet chemotherapy (25%); and 9.5 (95% CI, 7.4-13.4) months for the 155 patients receiving single-agent chemotherapy (12%). After propensity score matching, no differences in OS and PFS were found between the patients receiving ICI-chemotherapy vs ICI alone. Each group consisted of 118 patients. For PD-L1 expression of 1% and higher the OS hazard ratio (HR) was 0.98 (95% CI, 0.67-1.42; P = .90), and the PFS HR was 0.92 (95% CI, 0.67-1.25; P = .59). Significance was also not reached when separately analyzed for lower or higher PD-L1 expression (1%-49% or ≥50%). However, grade 3 or higher immune-related adverse events occurred in 86 patients (24.3%) treated with ICI-chemotherapy and 76 (17.9%) with ICI alone (P = .03). In this study, ICI-chemotherapy combination treatment did not improve survival and increased the incidence of grade 3 and higher immune-related adverse events compared with ICI alone in patients 75 years and older. Based on these results, ICI alone may be recommended for older adult patients with PD-L1-positive NSCLC.

Tyrosine kinase inhibitor resistance in de novo BCR::ABL1–positive BCP-ALL beyond kinase domain mutations

AbstractA better understanding of ABL1 kinase domain mutation–independent causes of tyrosine kinase inhibitor (TKI) resistance is needed for BCR::ABL1–positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Although TKIs have dramatically improved outcomes, a subset of patients still experiences relapsed or refractory disease. We aimed to identify potential biomarkers of intrinsic TKI resistance at diagnosis in samples from 32 pediatric and 19 adult patients with BCR::ABL1–positive BCP-ALL. Reduced ex vivo imatinib sensitivity was observed in cells derived from newly diagnosed patients who relapsed after combined TKI and chemotherapy treatment compared with cells derived from patients who remained in continuous complete remission. We observed that ex vivo imatinib resistance was inversely correlated with the amount of (phosphorylated) BCR::ABL1/ABL1 protein present in samples that were taken at diagnosis without prior TKI exposure. This suggests an intrinsic cause of TKI resistance that is independent of functional BCR::ABL1 signaling. Simultaneous deletions of IKZF1 and CDKN2A/B and/or PAX5 (IKZF1plus), as well as deletions of PAX5 alone, were related to ex vivo imatinib resistance. In addition, somatic lesions involving ZEB2, SETD2, SH2B3, and CRLF2 were associated with reduced ex vivo imatinib sensitivity. Our data suggest that the poor prognostic value of IKZF1(plus) deletions is linked to intrinsic mechanisms of TKI resistance other than ABL1 kinase domain mutations in newly diagnosed pediatric and adult BCR::ABL1–positive BCP-ALL.

Synergistic and Additive Effects of Herbal Medicines in Combination with Chemotherapeutics: A Scoping Review.

Natural products are increasingly gaining interest as potential new drug candidates for cancer treatment. Herbal formula, which are combinations of several herbs, are primarily used in East Asia and have a long history of use that continues today. Recently, research exploring the combination of herbal formulas and chemotherapy for cancer treatment has been on the rise. This study reviewed research on the co-administration of herbal formulas and chemotherapy for cancer treatment. The databases PubMed, Embase, and Cochrane Library were used for article searches. The following keywords were employed: "Antineoplastic agents," "Chemotherapy," "Phytotherapy," "Herbal medicine," "Drug synergism," and "Synergistic effect." The selection process focused on studies that investigated the synergistic interaction between herbal formulas and chemotherapeutic agents. Among the 30 studies included, 25 herbal formulas and 7 chemotherapies were used. The chemotherapy agents co-administered included cisplatin, 5-fluorouracil, docetaxel, doxorubicin, oxaliplatin, irinotecan, and gemcitabine. The types of cancer most frequently studied were lung, breast, and colon cancers. Most studies evaluating the anticancer efficacy of combined herbal formula and chemotherapy treatment were conducted in vitro or in vivo. Most studies reported synergistic effects on cytotoxicity, apoptosis, and tumor growth inhibition. These effects were found to be associated with cell cycle arrest, anti-angiogenesis, and gene expression regulation. Further studies leading to clinical trials are required. Clinical experiences in East Asian countries could provide insights for future research.

Design, synthesis and antitumor study of novel NO-type porphyrin–ferulic acid derivatives for chemotherapy and photodynamic therapy

NO-type porphyrin-ferulic acid derivatives were obtained by combining NO donor, ferulic acid, and porphyrin. It can realize the combined treatment of phototherapy and chemotherapy and effectively kill cancer cells.

CB[8]- and triarylboron-based supramolecular organic framework for microRNA detection, tumor-targeted drug delivery, and photodynamic therapy.

Supramolecular organic frameworks (SOFs) are widely used for biological detection and drug delivery. In this study, a SOF system was fabricated through the self-assembly of photosensitive triarylboron (TAB), TAB-6-methyl, and CB[8]. The maximum fluorescence emission of TAB-6-methyl was greatly enhanced and red-shifted from 560 nm to 610 nm after SOF formation. The SOF can specifically respond to a microRNA by dissembling and then combining with microRNA, which is accompanied by a fluorescence shift from 610 nm to 560 nm, thus providing a ratiometric readout for microRNA detection. The photosensitivity of TAB-6-methyl can be further improved by forming a SOF, which can be used in photodynamic therapy. By constructing another guest molecule, TAB-5-1-cRGD, we successfully embedded cRGD in the SOF system to improve its tumor-targeting ability. Moreover, we used this SOF system as a fluorescence imaging probe for targeted tumor imaging and as a drug carrier system for loading DOX to achieve combined photodynamic and chemotherapy treatment of tumors.

Assessment of Risk Factors for Dental Developmental Disorders in Pediatric Cancer Survivors

This study was to examine the developmental dental abnormalities in childhood cancer survivors. Risk factors were assessed for 125 children with radiographic data through a retrospective analysis of medical records and panoramic images. 68.0% of childhood cancer survivors exhibited at least one dental abnormality. The types of abnormalities varied depending on the age at cancer diagnosis and treatment intensity, ranging from microdontia (43.2%), to abnormal root development (39.2%) and tooth agenesis (33.6%). Logistic regression analysis demonstrated that a young age at diagnosis (under 3 years), the use of heavy metal agents, a history of hematopoietic stem cell transplantation (HSCT), and combination treatment of chemotherapy, radiation therapy, and HSCT were associated with a significantly higher risk for overall dental abnormalities. The increased risk ratios were 6.00, 3.06, 3.22, and 7.87, respectively (p &lt; 0.05). The results of this study will predict dental abnormality in permanent dentition according to the diagnosis age and treatment method of childhood cancer.

Acute Non-Lymphoblastic Leukemias Presenting with Gingival Hyperplasia: Diagnosis and Management Updates

Background: Leukemias represent a heterogeneous group of hematological malignancies, which are characterized by the disordered proliferation of neoplastic hematopoietic cells, with the diffuse bone marrow involvement. Most frequent oral findings in leukemias are cyanotic or erythematous gingival hyperplasia with or without necrosis, petechiae, ecchymoses, mucosal ulcers and hemorrhage. Gingival hyperplasia is reported as a consistent symptom, which forwards patients for a dentistry consultation, that may lead to an early diagnosis of acute leukemias. The recognition of gingival enlargement as an initial oral manifestation of leukemic involvement assumes major practical significance, especially for the early diagnosis of non-lymphoblastic leukemias. Objectives: The aims of researches were the evaluation of diagnosis and management of hyperplastic gingivitis in acute leukemias. Material and Methods: The patients' follow-up and treatment were realized at the comprehensive cancer center. Our observational, analytical and descriptive study enrolled 8 patients with acute leukemias, who were treated at the Institute of Oncology from Moldova between 2012-2023. The diagnosis was asserted by the bone marrow aspiration with cytochemical reactions, tissue biopsy, buccal swab, or fine needle aspiration cytology. The immunophenotyping was performed in selected cases. The types of acute leukemias were assessed and distinguished according to the 2017 Revision of WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues. This prospective study was related to the hospitalized and outpatient care. Results: Hyperplastic gingivitis developed in cases with myelomonocytic and monocytic acute leukemias. The leukemia patients were admitted to the Institute of Oncology with a history of fatigue, fever, bone pain, gingival bleeding and enlargement detected by dentistry and family doctors from the consulting centers. ECOG-WHO performance score was 2-3. The intra-oral examination revealed generalized gingival hyperplasia. There were the amounts of plaque and calculus, which did not justify the enlargement degree. The gingiva was spongy and painless on palpation, with solitary sectors of necrosis and mucosal bleeding. Multiple soft and tender lymph nodes ranging from 0.8-1.5 cm in diameter were palpable bilaterally in the cervical and axillary regions. Splenomegaly of various degree was revealed by ultrasound scan in all patients. Complete blood count values ranged between: Hb 66-104 g/l, RBC 2.3-3.7 x 10 12/l, WBC 11.3-47.2 x 10 9/l, PLT 17.0-115.0 x 10 9/l, blast cells 17-65%. The bone marrow aspiration detected hypercellularity, myeloid and monocytic blast cells (31.0-58.0%), as well as monocytes (9.0-14.0%). The studied cases were not suggestive of presence of FLT3 mutations. Hyperplastic gingivitis regressed in 5 (62.5%) cases after the achievement of complete (4 patients) and partial (1 patient) hematological responses under the first-line combined chemotherapy with conventional doses of cytarabine, anthracyclines and etoposide (2 patients). Local treatment included daily administration of oral steroids, antiseptic and hemostatic drugs. The narrative review of the recent references revealed that 37-53% of patients with monocytic and myelomonocytic leukemias were reported to develop gingival hyperplasia. Conclusions: Hyperplastic gingivitis emerges in acute leukemias mostly due to the gingival infiltration with neoplastic blast cells. Gingival hyperplasia may regress under the combined chemotherapy and local treatment in patients with complete or partial hematological responses. Early diagnosis and treatment, thus, can increase the leukemia patients' prospects for complete hematological and local responses.

Single-cell RNA-seq reveals characteristics in tumor microenvironment of PDAC with MSI-H following neoadjuvant chemotherapy with anti-PD-1 therapy

Accumulating evidence suggests the minority of patients with advanced pancreatic ductal adenocarcinoma (PDAC) that have microsatellite instability high (MSI-H) can benefit from immune checkpoint inhibitors (ICIs). However, the effects of ICIs on the tumor microenvironment (TME) of PDAC remain elusive. We conducted single-cell RNA-seq (scRNA-seq) analysis on a residual lesion from a MSI-H PDAC patient who received a radical operation after eight cycles of neoadjuvant treatment (nab-paclitaxel/gemcitabine plus pembrolizumab). Multiple tumor subclusters were identified in residual lesion after neoadjuvant treatment, one of which was mainly composed of cells in the S and G2M phases. This subcluster also had enriched expression of MKI67 and PCNA and cell cycle-related signatures and was thus defined as a proliferating tumor subcluster. This subcluster had higher S_score, Fatty acid_score, UPR_score, and Glycolysis_score than others. We also identified characteristics of the TME after neoadjuvant treatment by comparing the excised primary tumors form nontreated PDAC and the residual lesion. The residual lesion was characterized with activated pancreatic stellate cells (PSCs) and exhausted T cells (Tex). We compared the receptor-ligand interactions between the two groups, and found that no checkpoint receptor-ligand pairs between T cells and tumor cells were identified in the residual lesion, while there were many checkpoint receptor-ligand pairs in the nontreated primary PDAC. In conclusion, our findings revealed the characteristics of residual lesion of advanced PDAC with MSI-H upon combination treatment of chemotherapy and immunotherapy, which might provide some valuable clues for solving the puzzle of ICI in PDAC.

Correlation of Lung Immune Prognostic Index With Efficacy of PD-1/PD-L1 Inhibitor Combined With Chemotherapy and Prognosis in Patients With Advanced Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is a devastating but universal class of lung carcinoma with an unfavorable prognosis. This paper mainly investigated the correlation between lung immune prognostic index (LIPI) score and combined treatment of immune checkpoint inhibitor and chemotherapy (CHT) in patients with advanced NSCLC. Totally, 301 advanced NSCLC patients with programmed death-ligand 1 (PD-L1) expression ≥1% were assigned into good LIPI group (N=113), intermediate LIPI group (N=101), and poor LIPI group (N=87) based on LIPI scoring system, followed by treatment of CHT plus programmed cell death-1 (PD-1)/PD-L1 inhibitor. The differences in clinical parameters between subgroups of NSCLC patients were analyzed by χ 2 test, 1-way analysis of variance, and Kruskal-Wallis H test. All patients were followed up until June 30, 2022, and objective response rate, disease control rate, progression-free survival (PFS), and overall survival (OS) were recorded. The independent associations of LIPI score with PFS and OS were assessed via the Cox regression model. There were evident differences in clinical stage and lymphocyte among the 3 subgroups of NSCLC patients. The efficacy of PD-1/PD-L1 inhibitor combined with CHT was better in patients with good LIPI score, manifested by higher objective response rate and disease control rate. Moreover, LIPI score was an independent factor influencing PFS and OS in patients with advanced NSCLC, with longer PFS and OS in patients with good LIPI score. LIPI score has a predictive value for combination therapy of PD-1/PD-L1 blockade and CHT in advanced NSCLC patients.

Impact of increased plasma levels of calreticulin on prognosis of patients with advanced lung cancer undergoing combination treatment of chemotherapy and immune checkpoint inhibitors

BackgroundDamage-associated molecular pattern (DAMP)-related immunogenic cell death triggers secondary adaptive immune responses. The relationship between DAMP levels and prognosis in patients with non-small cell lung cancer (NSCLC) who undergo a combination therapy of immune checkpoint inhibitors (ICI) and chemotherapy remains unclear. MethodsSerial plasma samples were prospectively collected from 45 patients treated with ICI combination therapy for advanced NSCLC. Plasma concentrations of high-mobility group box 1 (HMGB1), calreticulin (CRT), annexin A1, and heat shock protein 70 were measured. Associations between increases in plasma DAMP levels and the efficacy of the ICI combination therapy were evaluated. ResultsThe maximum fold changes in plasma levels differed across individuals but demonstrated a marked increase, especially for CRT (mean ± SEM, 11.61 ± 46.15). Increased plasma DAMP levels were not clearly associated with clinical responses. There was a significant correlation between the maximum fold change in CRT levels and progression-free survival (PFS; r = 0.49, P < 0.001). Median PFS and overall survival (OS) rates were higher in patients with a ≥ 2-fold increase in plasma CRT levels than in those with a < 2-fold increase (PFS, 14.9 versus 6.0 months, hazard ratio (HR), 0.58; P = 0.17; OS, not reached versus 21.6 months, HR, 0.31, P = 0.02). ConclusionsPlasma CRT level monitoring has the potential to predict the efficacy of ICI combination therapy and shed light on the mechanisms underlying DAMP-related immunogenic cell death.

Clinical research of the value of high-risk CTV setting on intensity-modulated radiotherapy for stage IIB-IVA cervical cancer

BackgroundThis study aims to evaluate the clinical efficacy and side effects of setting up a high-risk clinical target volume (CTV-hr) alongside simultaneous integrated boost intensity-modulated radiotherapy (IMRT-SIB) in patients diagnosed with stage IIB-IVA cervical cancer.MethodsThis study retrospectively analysed patients with stage IIB-IVA cervical cancer who received radical radiotherapy at the Affiliated Hospital of Qingdao University between November 2014 and September 2019. The patients were divided into experimental and control groups based on whether CTV-hr was set. All patients received a combined treatment of radiotherapy and chemotherapy. The dosage for paclitaxel was 135 mg/m2, while for cisplatin it was 75 mg/m2 or for carboplatin it was AUC 4–6, given in a cycle of 21 days. Radiotherapy (RT) included external beam radiation therapy (EBRT) and intracavitary brachytherapy (ICBT). In the control group, positive lymph nodes (GTV-n) were treated at a dose of 58–62 Gy/26–28 fractions(f), while clinical target volumes (CTV) were treated with a dose of 46–48 Gy/26-28f. The experimental group received a simultaneous integrated boost (SIB) to CTV-hr at a dose of 54–56 Gy/26-28f, with the same CTV and GTV-n as the control group. Both groups were combined with brachytherapy with a total dose (EQD2, the equivalent dose in 2 Gy/f) of 80-90 Gy. The study measured objective remission rate (ORR), 3-year progression-free survival (PFS) rate, 3-year overall survival (OS) rate, recurrence rate, and side effects as endpoints.ResultsThe study enrolled 217 patients, with 119 in the experimental group and 98 in the control group. Results showed that the experimental group had a higher 3-year OS rate (87.4% vs. 71.4%, p = 0.001) and 3-year PFS rate (72.3% vs. 51.0%, p = 0.000) compared to the control group. Additionally, the experimental group had significantly lower rates of overall recurrence (26.1% vs. 50.0%, p = 0.003), in-field recurrence (15.1% vs. 36.7%, p = 0.000), and out-field recurrence(13.4% vs. 35.7%, p = 0.000) compared to the control group. All observed differences were found to be statistically significant. However, the experimental and control groups had no statistically significant difference in ORR and radiological side effects, such as radiation cystitis and enteritis (p > 0.05).ConclusionsSetting CTV-hr and performing IMRT-SIB on patients with stage IIB-IVA cervical cancer effectively increased the 3-year OS rate, 3-year PFS rate and reduced recurrence rate, with no significant differences in side effects.