Blandmcclain3952

Several studies reported improved outcomes with conventional treatments (CT, i.e., chemotherapy ± targeted therapy) administered after immune checkpoints inhibitors (ICI) in certain tumor types. No data are available concerning patients (pts) with metastatic colorectal cancer (mCRC) harboring mismatch repair deficiency/microsatellite instability (dMMR/MSI). We aimed to assess the outcomes of dMMR/MSI mCRC pts receiving CT after ICI failure.

We conducted a retrospective multicenter study investigating the outcomes of all dMMR/MSI mCRC pts who received post-ICI CT between 2015 and 2020.

31 pts (male 61%, median age 56 years) were included. ICI was an anti-PD(L)1 monotherapy in 71% of pts, and 61% received >2 lines before post-ICI CT. The overall response rate and disease control rate were 13% and 45%, with a median progression-free survival (PFS) and overall survival of 2.9 and 7.4 months, respectively. No association of the outcomes with either ICI efficacy or anti-angiogenic agents was observed. Prolonged PFS (range 16.1-21.3 months) was observed in 4 pts (13%).

Although conducted on a limited number of patients, our results do not support an association of previous ICI treatment with an enhanced efficacy of CT in dMMR/MSI mCRC. However, prolonged disease control was observed in several cases, suggesting that some pts might derive an unexpected benefit from post-ICI treatments.

Although conducted on a limited number of patients, our results do not support an association of previous ICI treatment with an enhanced efficacy of CT in dMMR/MSI mCRC. However, prolonged disease control was observed in several cases, suggesting that some pts might derive an unexpected benefit from post-ICI treatments.(1) Background The longitudinal relaxation time (T1), transverse relaxation time (T2), water proton chemical shift (CS), and apparent diffusion coefficient (ADC) are MR quantities that change with temperature. In this work, we investigate heat-induced intrinsic MR contrast types to add salient information to conventional MR imaging to improve tumor characterization. (2) Methods Imaging tests were performed in vivo using different rat tumor models. The rats were cooled/heated to steady-state temperatures from 26-36 °C and quantitative measurements of T1, T2, and ADC were obtained. Temperature maps were measured using the proton resonance frequency shift (PRFS) method during the heating and cooling cycles. (3) Results All tissue samples show repeatable relaxation parameter measurement over a range of 26-36 °C. Most notably, we observed a more than 3.3% change in T1/°C in breast adenocarcinoma tumors compared to a 1% change in benign breast fibroadenoma lesions. In addition, we note distinct values of T2/°C change for rat prostate carcinoma cells compared to benign tissue. (4) Conclusion These findings suggest the possibility of improving MR imaging visualization and characterization of tissue with heat-induced contrast types. Specifically, these results suggest that the temporal thermal responses of heat-sensitive MR imaging contrast mechanisms in different tissue types contain information for improved (i) characterization of tumor/tissue boundaries for diagnostic and therapy purposes, and (ii) characterization of salient behavior of tissues, e.g., malignant versus benign tumors.Ovarian cancer is the eighth global leading cause of cancer-related death among women. The most common form is the high-grade serous ovarian carcinoma (HGSOC). No further improvements in the 5-year overall survival have been seen over the last 40 years since the adoption of platinum- and taxane-based chemotherapy. Hence, a better understanding of the mechanisms governing this aggressive phenotype would help identify better therapeutic strategies. Recent research linked onset, progression, and response to treatment with dysregulated components of the tumor microenvironment (TME) in many types of cancer. In this study, using bioinformatic approaches, we identified a 19-gene TME-related HGSOC prognostic genetic panel (19 prognostic genes (PLXNB2, HMCN2, NDNF, NTN1, TGFBI, CHAD, CLEC5A, PLXNA1, CST9, LOXL4, MMP17, PI3, PRSS1, SERPINA10, TLL1, CBLN2, IL26, NRG4, and WNT9A) by assessing the RNA sequencing data of 342 tumors available in the TCGA database. Using machine learning, we found that specific patterns of infiltrating immune cells characterized each risk group. Furthermore, we demonstrated the predictive potential of our risk score across different platforms and its improved prognostic performance compared with other gene panels.Colorectal cancer (CRC) ranks second in the number of cancer deaths worldwide, mainly due to late diagnoses, which restrict treatment in the potentially curable stages and decrease patient survival. The treatment of CRC involves surgery to remove the tumor tissue, in addition to radiotherapy and systemic chemotherapy sessions. However, almost half of patients are resistant to these treatments, especially in metastatic cases, where the 5-year survival rate is only 12%. This factor may be related to the intratumoral heterogeneity, tumor microenvironment (TME), and the presence of cancer stem cells (CSCs), which is impossible to resolve with the standard approaches currently available in clinical practice. CSCs are APC-deficient, and the search for alternative therapeutic agents such as small molecules from natural sources is a promising strategy, as these substances have several antitumor properties. Many of those interfere with the regulation of signaling pathways at the central core of CRC development, such as the Wnt/β-catenin, which plays a crucial role in the cell proliferation and stemness in the tumor. This review will discuss the use of naturally occurring small molecules inhibiting the Wnt/β-catenin pathway in experimental CRC models over the past decade, highlighting the molecular targets in the Wnt/β-catenin pathway and the mechanisms through which these molecules perform their antitumor activities.Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) prognosis. LCL161 in vitro However, AFP is not useful in establishing a prognosis for patients with a tumor in the early stages. hPG80 (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers, including HCC. In this study, we evaluated the prognostic value of plasma hPG80 in patients with HCC, alone or in combination with AFP. A total of 168 HCC patients were tested prospectively for hPG80 and analyzed retrospectively. The prognostic impact of hPG80 and AFP levels on patient survival was assessed using Kaplan-Meier curves and log-rank tests. hPG80 was detected in 84% of HCC patients. There was no correlation between hPG80 and AFP levels in the training and validation cohorts. Both cohorts showed higher sensitivity of hPG80 compared to AFP, especially at early stages. Patients with high hPG80 (hPG80+) levels (optimal cutoff value 4.5 pM) had significantly lower median overall survival (OS) compared to patients with low hPG80 (hPG80-) levels (12.4 months versus not reached respectively, p less then 0.0001). Further stratification by combining hPG80 and AFP levels (cutoff 100 ng/mL) improved prognosis in particular for those patients with low AFP level (hPG80-/AFP+ and hPG80-/AFP-, 13.4 months versus not reached respectively, p less then 0.0001 and hPG80+/AFP+ and hPG80+/AFP-, 5.7 versus 26 months respectively, p less then 0.0001). This was corroborated when analyses were performed using the BCLC staging especially at early stages. Our findings show that hPG80 could serve as a new prognostic biomarker in HCC. Used in combination with AFP, it improves the stratification of the patients in good and poor prognosis, especially for those patients with negative AFP and early-stage HCC.

We aimed to describe the prevalence and spectrum of second primary cancer (SPC) in HIV-positive cancer survivors.

A multicenter retrospective study was performed using longitudinal data from the French Dat'AIDS cohort. Subjects who had developed at least two primary cancers were selected. The spectrum of SPCs was stratified by the first primary cancer type and by sex.

Among the 44,642 patients in the Dat'AIDS cohort, 4855 were diagnosed with cancer between 1 December 1983 and 31 December 2015, of whom 444 (9.1%) developed at least two primary cancers. The most common SPCs in men were non-Hodgkin lymphoma (NHL) (22.8%), skin carcinoma (10%) and Kaposi sarcoma (KS) (8.4%), and in women the most common SPCs were breast cancer (16%), skin carcinoma (9.3%) and NHL (8%). The pattern of SPCs differed according to first primary cancer and by sex in men, NHL was the most common SPC after primary KS and KS was the most common SPC after primary NHL; while in women, breast cancer was the most common SPC after primary NHL and primary breast cancer.

The frequency and pattern of subsequent cancers among HIV-positive cancer survivors differed according to the first primary cancer type and sex.

The frequency and pattern of subsequent cancers among HIV-positive cancer survivors differed according to the first primary cancer type and sex.

The purpose of this study was to evaluate the efficacy and toxicity of adding regional hyperthermia to intensity-modulated radiotherapy (IMRT) plus neoadjuvant androgen deprivation therapy (ADT) for high-risk localized prostate carcinoma.

Data from 121 consecutive patients with high-risk prostate carcinoma who were treated with IMRT were retrospectively analyzed. The total planned dose of IMRT was 76 Gy in 38 fractions for all patients; hyperthermia was used in 70 of 121 patients. Intra-rectal temperatures at the prostate level were measured to evaluate thermal dose.

Median number of heating sessions was five and the median total thermal dose of CEM43T90 was 7.5 min. Median follow-up duration was 64 months. Addition of hyperthermia to IMRT predicted better clinical relapse-free survival. Higher thermal dose with CEM43T90 (>7 min) predicted improved biochemical disease-free survival. The occurrence of acute and delayed toxicity ≥Grade 2 was not significantly different between patients with or without hyperthermia.

IMRT plus regional hyperthermia represents a promising approach with acceptable toxicity for high-risk localized prostate carcinoma. Further studies are needed to verify the efficacy of this combined treatment.

IMRT plus regional hyperthermia represents a promising approach with acceptable toxicity for high-risk localized prostate carcinoma. Further studies are needed to verify the efficacy of this combined treatment.

To elucidate whether previous cancer treatment affects graft recovery and follicle numbers, morphology, and development in grafts, cryopreserved ovarian biopsies obtained from 18 cancer patients aged 1-24 years with and without exposure to chemotherapy were xenografted as 1 mm

fragments to immunodeficient mice for 22 weeks with exogenous stimulation.

Graft recovery showed no association with chemotherapy exposure, pubertal stage, or leukemia contamination. Total follicle number per recovered graft varied between 0 and 1031 in the chemotherapy-exposed and between 0 and 502 in the non-chemotherapy-exposed group. Atretic follicles formed the largest proportion of the follicle pool in chemotherapy-exposed grafts. Increased atresia correlated with exposure to alkylating agents (mean ± SD 8866.2 ± 9316.3 mg/m

) but not with anthracyclines, pubertal stage, or leukemia contamination.

The observation confirms the harmful effects of alkylating agents on ovarian tissue. Therapy at the median cumulative dose of 8866 mg/m

leads to the decreased quality of cryopreserved ovarian follicles in children and young adults.