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Journal of Controlled Release :... Jun 2024Peritoneal carcinomatosis (PC) is characterized by a high recurrence rate and mortality following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy...
Peritoneal carcinomatosis (PC) is characterized by a high recurrence rate and mortality following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC), primarily due to incomplete cancer elimination. To enhance the standard of care for PC, we developed two cationic liposomal formulations aimed at localizing a toll-like receptor agonist, resiquimod (R848), in the peritoneal cavity to activate the immune system locally to specifically eradicate residual tumor cells. These formulations effectively extended R848 retention in the peritoneum by >10-fold, resulting in up to a 2-fold increase in interferon α (IFN-α) induction in the peritoneal fluid, without increasing the plasma levels. In a CT26 colon cancer model with peritoneal metastases, these liposomal R848 formulations, when combined with oxaliplatin (OXA)-an agent used in HIPEC that induces immunogenic cell death-increased tumor infiltration of effector immune cells, including DCs, CD4, and CD8 T cells. This led to the complete elimination of PC in 60-70% of the mice, while the control mice reached humane endpoints by 30 days. The cured mice developed specific antitumor immunity, as re-challenging them with the same tumor cells did not result in tumor establishment. However, inoculation with a different tumor line led to tumor development. Additionally, exposing CT26 tumor antigens to the splenocytes isolated from the cured mice induced the expansion of CD4 and CD8 T cells and the release of IFN-γ, demonstrating long-term immune memory to the specific tumor. The anti-tumor efficacy of these liposomal R848 formulations was mediated via CD8 T cells with different levels of involvement of CD4 and B cells, and the combination with an anti-PD-1 antibody achieved a cure rate of 90%.
PubMed: 38909698
DOI: 10.1016/j.jconrel.2024.06.041 -
Cancer Treatment Reviews Jun 2024In patients with resected non-metastatic melanoma, the liquid biopsy for the assessment of molecular residual disease (MRD) by circulating tumour DNA (ctDNA) represents... (Review)
Review
In patients with resected non-metastatic melanoma, the liquid biopsy for the assessment of molecular residual disease (MRD) by circulating tumour DNA (ctDNA) represents a promising tool to stratify the risk and to monitor tumour evolution. However, its validation requires the demonstration of analytical validity, clinical validity and utility. Indeed, the development of sensitive and specific assays can optimize prognostication and eventually help clinicians to modulate adjuvant treatments, in order to improve clinical outcomes. Data about ctDNA-guided prognosis stratification is emerging, but clinical trials assessing ctDNA-guided therapeutic decisions are still ongoing. This review aims to depict the role of ctDNA-based MRD assessment in patients with non-metastatic melanoma and to provide a roadmap to face challenges for its introduction into clinical practice.
PubMed: 38908229
DOI: 10.1016/j.ctrv.2024.102788 -
Clinical Nutrition (Edinburgh, Scotland) Jun 2024Malnutrition and sarcopenia are challenges for patients with metastatic breast cancer and have been proposed as independent prognostic factors. Very few studies have...
BACKGROUND
Malnutrition and sarcopenia are challenges for patients with metastatic breast cancer and have been proposed as independent prognostic factors. Very few studies have addressed the temporal evolution of these parameters and, notably, the separate and combined analysis of sarcopenia and malnutrition. This study aimed to i) determine the prevalence of malnutrition and sarcopenia, individually and combined, and their evolution over time, ii) identify risk factors for each condition, and iii) explore their impact on overall survival (OS).
METHODS
This retrospective study was conducted on 111 patients treated for at least a third-line metastatic breast cancer at the Institut Curie between January 1st and March 31st, 2018. Solitary malnutrition was defined from weight loss and body mass index values while solitary sarcopenia was defined solely based on low muscle mass. We analyzed solitary malnutrition, solitary sarcopenia, and then malnutrition with or without sarcopenia, at three key stages (T1: diagnosis of metastasis, T2: initiation of third-line treatment, and T3: 3-month re-evaluation). Univariate and multivariate logistic regression analyses were conducted to investigate the risk factors. We performed Cox proportional hazards analyses for each variable.
RESULTS
At T1, the prevalence of solitary malnutrition, solitary sarcopenia and malnutrition with or without sarcopenia was 18.6%, 36.1% and 48.9% respectively, increasing to 27.7%, 45.5% and 56.6% at T2. At T2, in multivariate logistic regression analyses, patients aged over 60 years were at an elevated risk of experiencing solitary malnutrition as well as malnutrition with or without sarcopenia, but not solitary sarcopenia. In multivariate analyses, solitary malnutrition was significantly associated with poorer OS (HR 2.2 [95% CI 1.1-4.1], p = 0.02), while solitary sarcopenia and malnutrition with or without sarcopenia showed no association.
CONCLUSION
Solitary malnutrition and sarcopenia were highly prevalent in patients with metastatic breast cancer, affecting around a quarter and half of patients respectively at third-line treatment initiation. Notably, solitary malnutrition emerged as a prognostic factor for overall survival, whereas no significant association was observed for solitary sarcopenia or malnutrition with or without sarcopenia. This highlights the critical need for early identification of patients at risk of malnutrition and the importance of timely intervention.
PubMed: 38908032
DOI: 10.1016/j.clnu.2024.06.014 -
Medicina 2024Ewing sarcoma (ES) and primitive neuroectodermal tumor (PNET) belong to the group of neoplasms called small round cell tumors. PNETs have been divided into central and...
Ewing sarcoma (ES) and primitive neuroectodermal tumor (PNET) belong to the group of neoplasms called small round cell tumors. PNETs have been divided into central and peripheral. ES and peripheral PNETs arise from bones, soft tissues, or peripheral nerves. We present a case of hepatic ES/PNET in a healthy man that began four months before consultation with abdominal symptoms and weight loss. Upper gastrointestinal endoscopy and laboratory tests revealed no notable findings. The abdominal tomography revealed an enlarged liver due to a solid lesion that involved all its segments with intravenous contrast enhancement and large areas of necrosis. It compressed and displaced neighboring structures. Core needle biopsy of the liver lesion was performed: small round cell neoplasm. Immunohistochemistry revealed negativity for CD45, CKA1/A3, chromogranin, synaptophysin, and cytokeratins CK7 and CK20. Dim CD56 expression and CD99, FLI-1, and NKX2 positivity. He underwent chemotherapy treatment with carboplatin and etoposide for 6 cycles with clinical improvement and tolerance. Control images showed reduction of the mass with involvement of the right hepatic lobe, involvement of the inferior vena cava, infiltration of the right adrenal gland and upper pole of the right kidney. He was referred to hepatobiliary surgery for surgical resection of the residual lesion. The patient rejected the proposed surgical procedure. Our objective is to highlight the clinical and histological diagnostic challenge of this entity that requires ruling out other clinical entities.
Topics: Humans; Male; Liver Neoplasms; Sarcoma, Ewing; Tomography, X-Ray Computed; Immunohistochemistry; Adult; Neuroectodermal Tumors, Primitive, Peripheral
PubMed: 38907976
DOI: No ID Found -
Cancer Control : Journal of the Moffitt... 2024For patients with stage III epithelial ovarian cancer, there are limited studies on the effects of postoperative adjuvant radiotherapy (RT). Here we assessed the...
BACKGROUND
For patients with stage III epithelial ovarian cancer, there are limited studies on the effects of postoperative adjuvant radiotherapy (RT). Here we assessed the therapeutic efficacy and toxicity of postoperative radiotherapy to the abdominal and pelvic lymphatic drainage area for stage III epithelial ovarian cancer patients, who had all received surgery and chemotherapy (CT).
METHODS
We retrospectively collected patients with stage III epithelial ovarian cancer after cytoreductive surgery (CRS) and full-course adjuvant CT. The chemoradiotherapy (CRT) group patients were treated with intensity modulated radiotherapy (IMRT) to the abdominal and pelvic lymphatic drainage area in our hospital between 2010 and 2020. A propensity score matching analysis was conducted to compare the results between the CRT and CT groups. Kaplan-Meier analysis estimated overall survival (OS), disease-free survival (DFS), and local control (LC) rates. The log-rank test determined the significance of prognostic factors.
RESULTS
A total of 132 patients with median follow-up of 73.9 months (9.1-137.7 months) were included (44 and 88 for the CRT and RT groups, retrospectively). The baseline characteristics of age, histology, level of CA12-5, surgical staging, residual tumour, courses of adjuvant CT, and courses to reduce CA12-5 to normal were all balanced. The median DFS time, 5-year OS, and local recurrence free survival (LRFS) were 100.0 months vs 25.9 months ( = .020), 69.2% vs 49.9% ( = .002), and 85.9% vs 50.5% ( = .020), respectively. The CRT group mainly presented with acute haematological toxicities, with no statistically significant difference compared with grade III intestinal adverse effects (3/44 vs 6/88, = .480).
CONCLUSION
This report demonstrates that long-term DFS could be achieved in stage III epithelial ovarian cancer patients treated with IMRT preventive radiation to the abdominal and pelvic lymphatic area. Compared with the CT group, DFS and OS were significantly prolonged and adverse effects were acceptable.
Topics: Humans; Female; Middle Aged; Retrospective Studies; Neoplasm Staging; Ovarian Neoplasms; Adult; Aged; Carcinoma, Ovarian Epithelial; Cytoreduction Surgical Procedures; Radiotherapy, Intensity-Modulated; Radiotherapy, Adjuvant
PubMed: 38907367
DOI: 10.1177/10732748241263703 -
World Journal of Surgical Oncology Jun 2024Additional resection for invasive cancer at perihilar cholangiocarcinoma (pCCA) resection margins has become a consensus. However, controversy still exists regarding...
Residual biliary intraepithelial neoplasia without malignant transformation at resection margin for perihilar cholangiocarcinoma does not require expanded resection: a dual center retrospective study.
BACKGROUND
Additional resection for invasive cancer at perihilar cholangiocarcinoma (pCCA) resection margins has become a consensus. However, controversy still exists regarding whether additional resection is necessary for residual biliary intraepithelial neoplasia (BilIN).
METHOD
Consecutive patients with pCCA from two hospitals were enrolled. The incidence and pattern of resection margin BilIN were summarized. Prognosis between patients with negative margins (R0) and BilIN margins were analyzed. Cox regression with a forest plot was used to identify independent risk factors associated with overall survival (OS) and recurrence-free survival (RFS). Subgroup analysis was performed based on BilIN features and tumor characteristics.
RESULTS
306 pCCA patients receiving curative resection were included. 255 had R0 margins and 51 had BilIN margins. There was no significant difference in OS (P = 0.264) or RFS (P = 0.149) between the two group. Specifically, 19 patients with BilIN at distal bile ducts and 32 at proximal bile ducts. 42 patients showed low-grade BilIN, and 9 showed high-grade. Further analysis revealed no significant difference in long-term survival between different locations (P = 0.354), or between different grades (P = 0.772). Portal vein invasion, poor differentiation and lymph node metastasis were considered independent risk factors for OS and RFS, while BilIN was not. Subgroup analysis showed no significant difference in long-term survival between the lymph node metastasis subgroup, or between the portal vein invasion subgroup.
CONCLUSION
For pCCA patients underwent curative resection, residual BilIN at resection margin is acceptable. Additional resection is not necessary for such patients to achieve absolute R0 margin.
Topics: Humans; Male; Female; Bile Duct Neoplasms; Margins of Excision; Retrospective Studies; Klatskin Tumor; Middle Aged; Aged; Prognosis; Follow-Up Studies; Survival Rate; Carcinoma in Situ; Neoplasm, Residual; Adult; Cell Transformation, Neoplastic; Neoplasm Recurrence, Local; Hepatectomy; Aged, 80 and over
PubMed: 38907218
DOI: 10.1186/s12957-024-03395-5 -
World Neurosurgery Jun 2024Enucleation is a surgical technique to resect peripheral nerve schwannomas. The procedure has a low risk for postoperative deficit, but a small chance for recurrence,...
BACKGROUND
Enucleation is a surgical technique to resect peripheral nerve schwannomas. The procedure has a low risk for postoperative deficit, but a small chance for recurrence, because tumor cells may remain inside the pseudocapsule that is left after resection. MRI scans are frequently performed after surgery to investigate potential residual tumor, but currently there is little information in the literature on the value of follow-up with MRI.
MATERIAL AND METHODS
All patients that underwent enucleation of a peripheral nerve schwannoma between October 2013 and June 2022 were included. Postoperative MRI scans (Gadolinium enhanced) made at different time-points after the surgery were re-examined for residual enhancement. Patients with residual enhancement were contacted to inform whether symptoms had recurred.
RESULTS
A total of 75 schwannoma enucleations in 74 patients were included. The first postoperative MRI scan, performed three months after the surgery, showed no residual enhancement in 50 patients. In the remaining 24 patients, another MRI scan was made one year after the surgery, which still showed a possible remnant in 11 patients. On the third MRI scan, performed two years after enucleation, there were seven suspected cases (9%). None of these patients had clinical symptoms at a mean postoperative follow-up of five years.
CONCLUSIONS
Our data shows that the value of postoperative MRI scans after enucleation of peripheral nerve schwannomas is limited, because residual enhancement in the beginning can be non-specific and the small percentage of patients, that persistently had a potential remnant, were all asymptomatic.
PubMed: 38906466
DOI: 10.1016/j.wneu.2024.06.081 -
Die Ophthalmologie Jun 2024
PubMed: 38904721
DOI: 10.1007/s00347-024-02060-2 -
Journal of Advanced Pharmaceutical... 2024Small molecules are considered a source of novel medicines targeting carcinogenic intracellular pathways including epidermal growth factor receptor (EGFR) signaling. The...
Small molecules are considered a source of novel medicines targeting carcinogenic intracellular pathways including epidermal growth factor receptor (EGFR) signaling. The main goal of the study is to assess whether LHT-17-19 could be considered an effective target molecule against EGFR-expressing tumor cells , and . This was an , and experimental study. LHT-17-19 affinity to EGFR's kinase domain was assessed by the ligand's molecular docking. EGFR-expressing Hs746T human gastric cancer cell culture and patient-derived organoid (PDO) model of EGFR-positive breast cancer (BC) were used for assessment of the molecule anticancer property. IC and GI indexes were estimated using MTT- and MTS-based tests, respectively. Anticancer activity of LHT-17-19 against EGFR-expressing mutant lung carcinoma was studied on patient-derived xenograft (PDX) model established in 10 humanized BALB/c male mice. Continuous variables were presented as a mean ± standard deviation. Intergroup differences were assessed by two-way -test. Kaplan-Meier's curves were used for survival analysis. High affinity of LHT-17-19 for the EGFR kinase domain with dG score -7.9 kcal/mol, EDoc-5.45 kcal/mol, and Ki 101.24 uM was due to intermolecular π-σ bonds formation and the ligand intramolecular transformation. LHT-17-19 induced anti-EGFR-expressing gastric cancer cells cytotoxicity with IC 0.32 µM (95% confidence interval [CI] 0.11-0.54 µM). The derivative inhibited growth of EGFR-expressing BC PDO with GI 16.25 µM (95% CI 4.44-28.04 µM). 2 mg/kg LHT-17-19 intravenously daily during 7 days inhibited PDX tumor growth and metastatic activity, prolonged animals' survival, and eliminated EGFR-mutant lung cancer cells from residual tumor's node. LHT-17-19 may be considered a molecular platform for further search of promising molecules, EGFR-expressing cancer cell inhibitors.
PubMed: 38903549
DOI: 10.4103/JAPTR.JAPTR_392_23 -
Journal of Nanobiotechnology Jun 2024Cancer recurrence following surgical resection is a major cause of treatment failure. Finding effective methods to prevent postoperative recurrence and wound infection...
BACKGROUND
Cancer recurrence following surgical resection is a major cause of treatment failure. Finding effective methods to prevent postoperative recurrence and wound infection is an important component of successful surgery. With the development of new nanotechnology, more treatment options have been provided for postoperative adjuvant therapy. This study presents an innovative hydrogel system that stimulates tumoricidal immunity after surgical resection of non-small cell lung cancer (NSCLC) and prevents cancer relapse.
RESULTS
The hydrogel system is based on the excellent photothermal conversion performance of single-atom platinum (CN-Pt) along with the delivery and release of the chemotherapy drug, gemcitabine (GEM). The system is coated onto the wound surface after tumor removal with subsequent near-infrared (NIR) photothermal therapy, which efficiently induces necroptosis of residual cancer cells, amplifies the levels of damage-associated molecular patterns (DAMPs), and increases the number of M1 macrophages. The significantly higher levels of phagocytic macrophages enhance tumor immunogenicity and sensitize cancer cells to CD8 + T-cell immunity to control postoperative recurrence, which has been verified using an animal model of postoperative lung cancer recurrence. The CN-Pt-GEM-hydrogel with NIR can also inhibit postoperative wound infection.
CONCLUSIONS
These findings introduce an alternative strategy for supplementing antitumor immunity in patients undergoing resection of NSCLC tumors. The CN-Pt-GEM-hydrogel with the NIR system also exhibits good biosafety and may be adaptable for clinical application in relation to tumor resection surgery, wound tissue filling, infection prevention, and recurrence prevention.
Topics: Animals; Lung Neoplasms; Mice; Deoxycytidine; Hydrogels; Gemcitabine; Humans; Carcinoma, Non-Small-Cell Lung; Necroptosis; Neoplasm Recurrence, Local; Cell Line, Tumor; Immunotherapy; Photothermal Therapy; Wound Infection; Macrophages; Mice, Inbred C57BL; CD8-Positive T-Lymphocytes
PubMed: 38902678
DOI: 10.1186/s12951-024-02568-4