High Risk Of Tumor Recurrence Research Articles

Circulating tumor cell phenotype detection based on epithelial-mesenchymal transition markers combined with clinicopathological risk has potential to better predict recurrence in stage III breast cancer treated with neoadjuvant chemotherapy: a pilot study.

The potential value of detecting epithelial-mesenchymal transition (EMT) CTCs in early breast cancer, especially during the neoadjuvant therapy period, requires further investigation. We analyzed dynamic CTC phenotype status, to improve recurrence risk stratification for patients with stage III breast cancers. We enrolled 45 patients with stage III breast cancers from 2 clinical trials undergoing neoadjuvant chemotherapy and utilized the CanPatrol CTC enrichment technique pre- and post-chemotherapy to identify CTC phenotypes, including epithelial CTCs, biphenotypic epithelial/mesenchymal CTCs, and mesenchymal CTCs, in peripheral blood samples. Kaplan-Meier analyses were conducted to explore the prognostic value of dynamic change of CTC count and the proportion of CTCs with different phenotypes. Then, redefine the risk stratification based on CTC status and clinicopathological risk in combination. Increased proportion of M + CTCs was a high-risk CTC status that was associated with decreased DFS (HR, 3.584; 95% CI, 1.057-12.15). In a combined analysis with clinicopathological risk, patients with high-risk tumors had an elevated risk of recurrence compared to patients with low-risk tumors (HR, 4.482; 95% CI, 1.246-16.12). The recurrence risk could be effectively stratified by newly defined risk stratification criteria, with 5-year DFS of 100.0%, 77.3%, and 50.0%, respectively, for low-risk, mid-risk, and high-risk patients (P = 0.0077). Finally, in the ROC analysis, the redefined risk stratification demonstrated higher predictive significance with an AUC of 0.7727, compared to CTC status alone (AUC of 0.6751) or clinicopathological risk alone (AUC of 0.6858). The proportion of M + CTCs increased after neoadjuvant chemotherapy indicating a higher risk of tumor recurrence. Combining CTC status with clinicopathological risk has potential to redefine the risk stratification of stage III breast cancers and provide improved predictions of relapse.

Efficacy and safety of donafenib as adjuvant therapy for patients with hepatocellular carcinoma undergoing curative resection: A retrospective, multicenter cohort study.

e16234 Background: A growing incidence of hepatocellular carcinoma and its high risk of recurrence after curative-intent treatment underscore the need for effective adjuvant treatment options. This study aimed to assess the efficacy of adjuvant donafenib in patients with hepatocellular carcinoma (HCC) following radical resection. Methods: This multicenter, real-world study retrospectively gathered clinical data of 82 patients who had undergone radical resection of HCC and received adjuvant therapy with donafenib. The primary endpoint was recurrence-free survival (RFS). The secondary endpoints included overall survival (OS) and safety. Kaplan-Meier analysis was performed to evaluate RFS and OS, while the Cox proportional-hazards model was used to estimate risk factors for tumor recurrence and death. Results: A total of 82 patients with HCC who received donafenib following surgical resection were included in the study, of which were classified as high risk for tumor recurrence (with multiple or large tumor, microvascular invasion, poor tumor differentiation). The median duration of donafenib adjuvant therapy was 10.6 months (range: 0.2–26.1 months). All patients completed follow-up as required, with a median follow-up time of 19.4 months (range: 2.8–57.6 months). During the follow-up period, a totally postoperative recurrence rate was 15.9% (13/82). 1-year recurrence rate and 2-year recurrence rate were 7.3% (6/82) and 12.2% (10/82), and 1-year survival rate and 2-year survival rate were 95.1% (78/82) and 93.9% (77/82). Kaplan-Meier analysis demonstrated that patients with higher preoperative AFP level (AFP > 400ng/mL), higher preoperative PIVKA-II level (PIVKA-II > 40mAU/mL), or poor tumor differentiation (Edmondson stage III-IV) exhibited higher rate of tumor recurrence after operation (all p value < 0.05). Multivariate analysis indicated that preoperative AFP level was an independent risk factor for tumor recurrence in patients with donafenib treatment. Treatment-related adverse events (TRAEs) occurred in 67.1% (55/82) of patients, of which the most frequent were hand-foot syndrome (25.6%, 21/82), diarrhea (20.7%, 17/82), and fatigue (17.1%, 14/82). Only 8.5% (7/82) of patients had a grade ≥3 TRAEs, with the most common being hand-foot syndrome (2.4%, 2/82) and hypertension (2.4%, 2/82). No treatment-related deaths were reported. Conclusions: This study represents the largest multicenter investigation of adjuvant therapy with donafenib to date, and the findings indicate that donafenib has the potential to be an effective treatment option for preventing postoperative recurrence in HCC. Furthermore, the preoperative AFP ≤400ng/mL can serve as an effective biomarker for postoperative administration of donafenib in HCC patients.

Strategies for targeted cancer therapy

Numerous therapeutic measures have been developed in oncology to combat various types of cancer, which is a leading cause of death worldwide. These therapies range from conventional approaches to high-end precision medicines, all aimed at ensuring therapeutic efficacy and the patient's survival. However, drug resistance and off-target side effects continue to hinder treatment efficacy. In the case of solid tumors that have hypoxic regions that cause treatment resistance and a high risk of tumor recurrence. To address this, advanced therapies have been designed or under pipeline to specifically target cancer cells by considering their unique features. This review article primarily focuses on different treatment methods developed using the peculiar properties of the tumor microenvironment.

Exploring Contribution of HMGA2 to the Aggressive Tumor Structure in Urothelial Carcinoma to Identify Prospective Clinical Applications

For patients with advanced upper tract urothelial carcinoma (UTUC), the five-year survival rate is approximately 20-40%. In previous real-world data analyses, we observed that UTUC patients with a sessile tumor architecture tend to exhibit more aggressive behavior and concurrently have poorer outcomes in terms of metastasis-free and cancer-specific survival. This suggests that tumor architecture may serve as a crucial prognostic factor for predicting outcomes. We utilized various tumor tissue specimens, categorizing them based on tumor architecture into papillary and sessile groups. RNA sequencing was used to analyze the two groups, and significant differences in the expression levels of high mobility group AT-hook 2 (HMGA2) were found. In the more aggressive sessile tumor architecture, HMGA2 exhibited higher expression levels. HMGA2 is currently known to participate in various biological processes, including the cell cycle, DNA damage repair, apoptosis, and epithelial-mesenchymal transition. Additionally, HMGA2 is abnormally regulated in several human cancers, such as lung, breast, ovarian, and bladder cancers. Elevated expression of HMGA2 is associated with a higher risk of tumor recurrence and cancer progression. Hence, we hypothesize that HMGA2 may regulate tumor cell epithelial-mesenchymal transition through the PI3K-Akt cell signaling pathway, influencing tumor architecture and cancer prognosis. Attempting to downregulate HMGA2 should theoretically enhance the effectiveness of chemotherapeutic drugs in achieving an anti-cancer effect. We discovered that inhibiting the expression of HMGA2 using siRNA in UTUC cells, such as BFTC909, significantly reduces cell proliferation and migration. Moreover, the addition of an HMGA2 inhibitor known as suramin enhances cytotoxic effects and decreases cell migration. Our preliminary findings provide evidence indicating a correlation between high levels of HMGA2 expression and aggressive tumor architecture in UTUC. We designed UTUC patient-derived organoids (PDO). The test results revealed that the organoids, as indicated by HE stain and Ki67 immunohistochemical (IHC) staining, closely resembled their corresponding parental tumors. Currently, it appears that the organoids have retained the original tumor structure and protein molecular expression characteristics. The PDO model is hoped to serve as a valuable tool in aiding the selection of suitable therapeutic strategies as clinical applications. This study was funded by the Chang Gung Medical Foundation, Taiwan (CMRPG8M0131, and CMRPG8M0132) and the Ministry of Science and Technology, Taiwan (MOST 111-2314-B-182A-140). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Immunologic aspects of colorectal cancer progression

Colorectal cancer remains in the leading positions in the structures of morbidity and mortality among both sexes. A large number of studies are aimed to reveal new biomarkers targeted at both early diagnosis and improving the effectiveness of drug therapy. Colorectal carcinoma (CC) is heterogeneous in its morphological, molecular and immunological aspects and is a heterogeneous disease. The existing molecular genetic classifications and biomarkers capable of predicting the effectiveness of therapy aren’t optimal enough. New prognostic markers would make it possible to identify a subgroup of patients with a high risk of tumor recurrence, for whom enhanced monitoring and diagnostic monitoring should be established, as well as the selection of highly effective methods in the treatment of colorectal cancer. It has been established that some immune cells in the tumor microenvironment are able to stimulate the development of disease progression. Cytokines and chemokines in the tumor microenvironment stimulate the development of metastases, and their serum levels reflect the current inflammatory response in the tumor tissue. The identification and analysis of immune markers involved in the processes of metastasis and the mechanisms of progression remains an important task of modern medicine. The purpose of the study was to analyze modern ideas about the importance of the immunological microenvironment in the progression of colorectal cancer. The effect of molecular heterogeneity of the tumor on the development of metastases, as well as on resistance to ongoing antitumor therapy. The review reflects the immunological characteristics of CC, including in the context of molecular biological subtypes. It describes the involvement of cells of the immune system (lymphocytes, macrophages) and their products (cytokines, chemokines) in the progression of colorectal cancer, including in the processes of neoangiogenesis, as well as the relationship of the T- and B-cell composition of the tumor microenvironment on the course of the disease. The review also shows the immunogenomic stratification of CC, which can be used to predict the response to immunotherapy for colorectal cancer.

Multicentric Study on Oncological Outcomes and Prognostic Factors of Open Partial Horizontal Laryngectomies.

Objective: In recent years, the number of open preservation surgeries for the treatment of laryngeal Cancer has increased. This surgery aims to maintain laryngeal function and ensure oncological radicality, thereby avoiding a total laryngectomy (TL) that could significantly impact the patient's quality of life. The purpose of this study was to assess the oncologic results of OPHL I and II and to identify prognostic factors that could impact patient survival and local failure rates. Methods: This study was conducted on 182 patients with laryngeal squamous cell carcinoma treated with OPHLs between 2005 and 2015. The survival rates of a group of patients treated with TL between 2004 and 2014 were taken into consideration to compare survival outcomes. Results: The disease-specific survival in pT2 and pT3 tumors in relation to the type of surgery showed no statistically significant difference between OPHLs and TL (P = .54 and P = .63, respectively). The 5-year T-recurrence-free survival showed that pT4 tumors, perineural/vascular positive invasion, and OPHL IIb + ARY-treated tumors were associated with a higher risk of tumor recurrence (P < .0001, P = .0005 and P = .016 respectively). Conclusions: OPHLs represent an excellent alternative to TL considering the characteristics of the tumor and the general conditions of the patient.

Артериовенозная мальформация нижней носовой раковины у ребенка: клинический случай

Congenital arteriovenous malformations (AVMs) of the head and neck are not common in clinical practice. They may have various manifestations — from minor aesthetic changes to severe hemodynamic disorders. Diagnosis and treatment of AVM is a difficult task. Atypical structure of the vascular wall can provoke intense intraoperative bleeding, and incomplete removal of the neoplasm leads to a high risk of tumor recurrence. The clinical observation under review presents a rare case of AVM of the inferior nasal basin in a 5-year-old child who initially presented to the hospital with nasal bleeding. Surgical method is the only way of radical treatment of AVM. We chose the safest minimally invasive technique — endonasal endoscopic approach that allowed total removal of the AVM without hemorrhagic complications.

Survival Analysis for Multimode Ablation Using Self-Adapted Deep Learning Network Based on Multisource Features.

Novel multimode thermal therapy by freezing before radio-frequency heating has achieved a desirable therapeutic effect in liver cancer. Compared with surgical resection, ablation treatment has a relatively high risk of tumor recurrence. To monitor tumor progression after ablation, we developed a novel survival analysis framework for survival prediction and efficacy assessment. We extracted preoperative and postoperative MRI radiomics features and vision transformer-based deep learning features. We also combined the immune features extracted from peripheral blood immune responses using flow cytometry and routine blood tests before and after treatment. We selected features using random survival forest and improved the deep Cox mixture (DCM) for survival analysis. To properly accommodate multitype input features, we proposed a self-adapted fully connected layer for locally and globally representing features. We evaluated the method using our clinical dataset. Of note, the immune features rank the highest feature importance and contribute significantly to the prediction accuracy. The results showed a promising C td-index of 0.885 ±0.040 and an integrated Brier score of 0.041 ±0.014, which outperformed state-of-the-art method combinations of survival prediction. For each patient, individual survival probability was accurately predicted over time, which provided clinicians with trustable prognosis suggestions.

Oral chemotherapy versus observation alone in nasopharyngeal carcinoma patients with persistently detected circulating cell-free Epstein-Barr virus DNA during follow-up

AimDespite the high risk of tumor recurrence, patients with nasopharyngeal carcinoma (NPC) with persistently (at least twice) detected circulating cell-free Epstein-Barr virus (EBV) DNA levels during follow-up are routinely recommended to keep observation. For these patients, whether administering more aggressive treatment could improve survival outcomes remains unknown. Materials and methodsWe retrospectively included 431 patients with nonmetastatic NPC with persistently detected EBV DNA during follow-up, who do not have clinical or imaging evidence of recurrence. Among these patients, 79 were administered oral chemotherapy, and the remaining 352 underwent observation alone. Baseline characteristics were balanced with propensity score matching (PSM) analysis. The primary endpoint was modified disease-free survival (mDFS), defined as time from detectable EBV DNA result to tumor recurrence or death. The secondary endpoints were disease-free survival (DFS) and overall survival (OS). ResultsOne-to-three PSM resulted in 251 eligible patients (oral chemotherapy group, 73; observation group, 178). In the matched cohort, the oral chemotherapy group had higher median mDFS (12.9 months [95 % confidence interval [CI] 9.6–16.3] vs. 6.8 months [95 % CI 5.8–7.8], p = 0.009) and DFS (24.1 months [95 % CI 18.5–29.7] vs. 16.7 months [95 % CI 14.4–19.1], p = 0.035) than the observation group. The median OS was numerically higher in the oral chemotherapy group than in the observation group (57.9 months [95 % CI 42.5–73.3] vs. 50.8 months [95 % CI 39.7–61.9], p = 0.71). A consistent benefit favoring oral chemotherapy was observed for mDFS in all subgroups analyses for male, <45 years, stage III-IVa disease, pretreatment EBV DNA load ≥ 4,000 copies/mL, no induction chemotherapy, or a detectable EBV DNA load ≥ 1,200 copies/mL. After adjusting for other confounders in the multivariate analysis, oral chemotherapy remained a significantly favorable factor for both mDFS (hazard ratio [HR] 0.67, 95 % CI 0.50–0.89; p = 0.006) and DFS (HR 0.68, 95 % CI 0.51–0.91; p = 0.01), but not a significant factor for OS (HR 0.89, 95 % CI 0.62–1.27; p = 0.52). ConclusionsIn patients with NPC having persistently detected EBV DNA levels but without clinical or imaging evidence of recurrence during follow-up, oral chemotherapy significantly prolongs mDFS and DFS. Employing oral chemotherapy as a more aggressive treatment option, as opposed to mere observation, could potentially benefit these patients, although further prospective validation is necessitated.

A Retrospective Multicenter Italian Analysis of Epidemiological, Clinical and Histopathological Features in a Sample of Patients with Acinic Cell Carcinoma of the Parotid Gland.

The acinic cell carcinoma (AciCC) of the parotid gland is a rare tumor with an indolent behavior; however, a subgroup of this tumor presents an aggressive behavior with a tendency to recur. The aim of this multicenter study was to identify and stratify those patients with AciCC at high risk of tumor recurrence. A retrospective study was carried out involving 77 patients treated with surgery between January 2000 and September 2022, in different Italian referral centers. Data about tumor characteristics and its recurrence were collected. The histological specimens and slides were independently reviewed by a senior pathologist coordinator (L.C.) and the institution's local head and neck pathologist. The patients' age average was 53.6 years, with a female prevalence in the group. The mean follow-up was 67.4 months (1-258, SD 59.39). The five-year overall survival (OS) was 83.2%. The 5-year disease-free survival (DFS) was 60% (95% CI 58.2-61.7). A high incidence of necrosis, extraglandular spread, lymphovascular invasion (LVI), atypical mitosis, and cellular pleomorphism was observed in the high-risk tumors compared to the low-risk ones. AciCC generally had an indolent behavior, optimal OS, DFS with few cervical node metastases, and rare distant relapses. This multicenter retrospective case series provides evidence of the need for clinical-epidemiological-histological stratification for patients at risk of poor outcomes. Our results suggest that the correct definition of high-risk AciCC should include tumor size, the presence of necrosis, extraglandular spread, LVI, atypical mitosis, and cellular pleomorphism.

Pheochromocytoma: Intricate Cardiovascular Manifestations

Abstract We present the case of a 60-year-old female patient, dyslipidemic, obese, diabetic and hypertensive, with a history of resected right adrenal pheochromocytoma (1999 - no subsequent surgical or endocrinological re-evaluation), presenting for increased blood pressure values and the recurrence of symptoms (headaches, palpitations, sweating), with progressive accentuation in the last months. The patient associates pain in the right costovertebral angle and weight loss. The clinical examination revealed facial erythrosis, excessive sweating, tachycardic heart sounds, increased blood pressure and orthostatic hypotension. Electrocardiography reveals sinus tachycardia, signs of left ventricular hypertrophy, with repolarization abnormalities, morphological aspect confirmed by the transthoracic echocardiography. An ultrasound of the abdomen and pelvis ultrasound objectified a large tumor formation at the level of the right adrenal gland and a liver nodule. In the context of the symptoms, the suspicion of recurrent pheochromocytoma was raised, confirmed biochemically by the increase in urinary normetanephrines and through imagistic methods (CT scan of the abdomen and pelvis), the patient having an indication for curative surgical treatment. After completing the preoperative assessment (ECG Holter monitor, ABPM), during the hospitalization period, the antihypertensive regimen was adjusted by combining 4 antihypertensive drugs, episodes of orthostatic hypotension being managed by administering glucocorticoids and colloidal solutions for volume repletion. The patient was referred to the general surgery clinic for resection of the tumor, following the antihypertensive preparation protocol. Although the post-procedural evolution was favorable, the patient presents a high risk of tumor recurrence, requiring annual evaluation for a period of 10 years. Also, due to the association of cardiovascular risk factors and target organ damage, the patient requires periodic cardiological evaluation.

Impact of Positive-Margin Resection of External Auditory Canal Squamous Cell Carcinoma.

Positive-margin resection of external auditory canal squamous cell carcinoma (EAC-SCC) is still a major cause of recurrence. The aim of this study is to examine the clinical impact of positive-margin resection of EAC-SCCs. We retrospectively reviewed 40 surgical cases with en bloc temporal bone resection of EAC-SCC at a tertiary referral center from October 2016 to March 2022. Two-year disease-specific, overall, and disease-free survival rates for all 40 cases reviewed were 85.2%, 88.85%, and 76.96%, respectively. En bloc resection with a negative margin significantly improved patient prognosis (p < 0.001). Positive-margin resection was observed in 9/40 cases (22.5%). Insufficient assessment of preoperative images was the cause in two of these cases. Postoperative lymph node metastasis and distant metastasis were observed in cases in which vascular, lymphatic duct or perineural invasion was found on postoperative pathological examination. In addition, three cases in which no vascular, lymphatic duct, or perineural invasion was found exhibited local recurrence during the follow-up period. Of the nine positive-margin resection cases, only two showed no postoperative recurrence. Once positive-margin resections are confirmed, cases might have a high risk of tumor recurrence, even with the addition of postoperative adjuvant chemoradiotherapy.

Homeobox Gene Expression Dysregulation as Potential Diagnostic and Prognostic Biomarkers in Bladder Cancer.

Homeobox genes serve as master regulatory transcription factors that regulate gene expression during embryogenesis. A homeobox gene may have either tumor-promoting or tumor-suppressive properties depending on the specific organ or cell lineage where it is expressed. The dysregulation of homeobox genes has been reported in various human cancers, including bladder cancer. The dysregulated expression of homeobox genes has been associated with bladder cancer clinical outcomes. Although bladder cancer has high risk of tumor recurrence and progression, it is highly challenging for clinicians to accurately predict the risk of tumor recurrence and progression at the initial point of diagnosis. Cystoscopy is the routine surveillance method used to detect tumor recurrence. However, the procedure causes significant discomfort and pain that results in poor surveillance follow-up amongst patients. Therefore, the development of reliable non-invasive biomarkers for the early detection and monitoring of bladder cancer is crucial. This review provides a comprehensive overview of the diagnostic and prognostic potential of homeobox gene expression dysregulation in bladder cancer.

A case of primary pulmonary follicular dendritic cell sarcoma

Here, we report a 66-year-old woman who presented with an irregular and lobulated pulmonary mass in the apical segment of the right superior lobe with an enlarged mediastinal lymph node. Abdominal computed tomography (CT), brain magnetic resonance imaging, and fluorine-18 fluorodeoxyglucose positron emission tomography/CT scans showed no extrapulmonary distant metastases. The patient underwent surgical sleeve resection of the right superior lobe with systematic hilar and mediastinal lymph node dissection. Post-operative histopathology, including hematoxylin and eosin staining, immunohistochemistry, and Epstein&amp;ndash;Barr virus in situ hybridization, suggested primary pulmonary follicular dendritic cell sarcoma (FDCS). A follow-up plain chest CT indicated recurrence with multiple metastases of the liver, ribs, and mediastinal lymph nodes 1 year after surgery. The patient declined further therapy and was lost follow-up. In this case, FDCS located in the lung was unusual and rare. Corresponding imaging and histopathological features have enhanced our understanding of this disease. Meanwhile, it is necessary to include this tumor as a differential diagnosis of lung tumors and pay particular attention to the possibility of post-operative recurrence and metastasis. Moreover, considering the heterogeneity of FDCS, it is essential to identify the biological or imaging features that can reflect or predict the high risk of tumor recurrence and metastasis. A corresponding post-operative examination is also necessary to determine if any lesions remain.

Pathologic collision of urinary bladder urothelial carcinoma with small cell carcinoma: a case report

BackgroundUrothelial carcinoma is a major subtype of bladder cancer and small cell carcinoma (SCC) is a rare type of cancer in clinical practice. Pathologic collision of urinary bladder urothelial carcinoma with SCC is not common in clinical settings.Case presentationHere, we report a patient with high-grade papillary carcinoma which changed to collision tumor with SCC. The patient underwent radical cystectomy; however, neck and mediastinum lymph nodes metastases were detected 11 months after the operation. The lymph nodes were diagnosed pathologically as SCC. Chemoradiotherapy was subsequently prescribed. Unfortunately, this patient died of COVID-19 in early 2023.DiscussionWe hypothesized the mechanism underlying this pathological transformation. For patients with urothelial bladder cancer, pathological analysis should be conducted to allow standardized and persistent treatment. Moreover, drugs should be selected depending on the type of pathology, especially for patients who develop relapse, since collision tumor or other pathological tumors may be present.ConclusionsWe recommend that radical cystectomy be performed early enough for patients with non-muscle invasive bladder cancer, who are at a high risk of tumor recurrence. However, this conclusion needs to be validated in a larger number of patients.

Brachytherapy With 15- Versus 20-mm Ruthenium 106 Plaques Without Verification of Plaque Position Is Associated With Local Tumor Recurrence and Death in Posterior Uveal Melanoma

Brachytherapy with episcleral plaques is the most common primary tumor treatment for uveal melanoma. This study aims to compare the risk of tumor recurrence and metastatic death between two frequently used ruthenium-106 plaque designs: CCB (20.2 mm) and CCA (15.3 mm). Data were obtained from 1387 consecutive patients treated at XXX between 1981 and 2022 (439 with CCA and 948 with CCB plaques). During the period, scleral transillumination was performed to delineate tumor margins before plaque insertion, but no minimum scleral dose was used, and accurate plaque positioning was not verified after scleral attachment. Patients treated with CCA plaques had smaller tumors than those treated with CCB plaques (mean diameter 8.6 vs. 10.5 mm, P<0.001). There were no differences in patient sex, age, tumor distance to the optic disc, tumor apex dose, dose rate, or in rates of ciliary body involvement, eccentric plaque placement, or adjunct transpupillary thermotherapy. The average difference between plaque and tumor diameter was greater with the CCB plaque, and a smaller difference was an independent predictor of tumor recurrence. The 15-year incidence of tumor recurrence was 28% and 15% after treatment with CCA and CCB plaques, respectively (competing risk analysis, P<0.001). Multivariate Cox regression analysis revealed a lower risk for tumor recurrence with CCB plaques (HR 0.50). Similarly, patients treated with CCB plaques had a lower risk for uveal melanoma-related mortality (HR 0.77). Adjunct transpupillary thermotherapy did not reduce these risks. Uni- and multivariate time-dependent Cox regressions demonstrated that tumor recurrence was associated with uveal melanoma-related and all-cause mortality. Compared to 20 mm plaques, brachytherapy with 15 mm ruthenium plaques is associated with a higher risk for tumor recurrence and death. These adverse outcomes may be avoided by increasing safety margins and implementing effective methods to verify accurate plaque positioning.

A nanotherapeutic strategy that engages cytotoxic and immunosuppressive activities for the treatment of cancer recurrence following organ transplantation.

Long-term treatment with immunosuppressants is necessary to attenuate allograft rejection following organ transplantation (OT). Consequently, the overall survival of OT recipients with malignancies has been substantially compromised by tumour recurrence. Rapamycin (RAPA) is a clinically approved immunosuppressive agent with antitumour activity that is considered beneficial in preventing posttransplant tumour recurrence. However, the clinical outcome of RAPA is impeded by acquired drug resistance and its poor oral bioavailability. A nanotherapeutic strategy was developed by supramolecular assembly of RAPA into a polymer cytotoxic 7-ethyl-10-hydroxycamptothecin (SN38) prodrug nanoparticle (termed SRNP) for simultaneous codelivery of cytotoxic/immunosuppressive agents. Cell-based experiments were used to evaluate the cytotoxicity of SRNPs against hepatocellular carcinoma (HCC). The therapeutic efficacy of SRNPs was evaluated in multiple preclinical models including an orthotopic HCC mouse model, an orthotopic liver transplantation (OLT) rat model and a clinically relevant cancer-transplant model to examine its antitumour and immunosuppressive activity. The combination of SN38 with RAPA resulted in synergetic effects against HCC cells and alleviated RAPA resistance by abrogating Akt/mTOR signalling activation. SRNPs exhibited potent antitumour efficiency in the orthotopic HCC model while substantially prolonging the survival of allografts in the OLT model. In the cancer-transplant model that simultaneously bears tumour xenografts and skin allografts, SRNPs not only effectively inhibited tumour growth but also attenuated allograft damage. The nanotherapy presented here had enhanced efficacy against tumours and maintained satisfactory immunosuppressive activity and thus has great potential to improve the survival outcomes of patients with a high risk of tumour recurrence following OT. This work was supported by the National Natural Science Foundation of China (32171368 and 31671019), the Zhejiang Provincial Natural Science Foundation of China (LZ21H180001), the Zhejiang Province Preeminence Youth Fund (LR19H160002), and the Jinan Provincial Laboratory Research Project of Microecological Biomedicine (JNL-2022039c).

Nanotherapeutics for solid organ transplantation: new kid onthe block.

Nanotherapeutics for solid organ transplantation: new kid onthe block.

The case for adjuvant BRAF-targeted therapy versus adjuvant anti-PD-1 therapy for patients with resected, high-risk melanoma.

The development of highly effective BRAF-targeted therapy and immune checkpoint inhibition for patients with advanced metastatic melanoma has transformed the treatment of this disease. More recently, these advances have moved into the resected, high-risk stage II and III settings. For patients with resected, BRAF-mutant stage III melanoma, there are no head-to-head data to support the use of BRAF-targeted therapy (specifically the combination of dabrafenib and trametinib) with either single-agent nivolumab or pembrolizumab. Because the relapse-free and distant metastasis-free survivals are similar in a cross-trial comparison, it is not clear what the best option for these patients is. In this piece, the authors argue on behalf of and against both approaches. PLAIN LANGUAGE SUMMARY: Two types of therapy exist for patients diagnosed with melanoma who have completed surgery and remain at high risk for tumor recurrence: (1) drugs that target the BRAF mutation (found in ∼50% of patients) and (2) immunotherapy. There are no data showing that either approach is better than the other, so the choice of which therapy is best for an individual patient can be challenging. In this article, we make arguments for and against each option.

Impact of smoking on urologic cancers: a snapshot of current evidence

PurposeThe purpose of this paper is to present evidence regarding the associations between smoking and the following urologic cancers: prostate, bladder, renal, and upper tract urothelial cancer (UTUC).MethodsThis is a narrative review. PubMed was queried for evidence-based analyses and trials regarding the associations between smoking and prostate, bladder, renal, and UTUC tumors from inception to September 1, 2022. Emphasis was placed on articles referenced in national guidelines and protocols.ResultsProstate—multiple studies associate smoking with higher Gleason score, higher tumor stage, and extracapsular invasion. Though smoking has not yet been linked to tumorigenesis, there is evidence that it plays a role in biochemical recurrence and cancer-specific mortality. Bladder—smoking is strongly associated with bladder cancer, likely due to DNA damage from the release of carcinogenic compounds. Additionally, smoking has been linked to increased cancer-specific mortality and higher risk of tumor recurrence. Renal—smoking tobacco has been associated with tumorigenesis, higher tumor grade and stage, poorer mortality rates, and a greater risk of tumor recurrence. UTUC—tumorigenesis has been associated with smoking tobacco. Additionally, more advanced disease, higher stage, lymph node metastases, poorer survival outcomes, and tumor recurrence have been linked to smoking.ConclusionSmoking has been shown to significantly affect most urologic cancers and has been associated with more aggressive disease, poorer outcomes, and tumor recurrence. The role of smoking cessation is still unclear, but appears to provide some protective effect. Urologists have an opportunity to engage in primary prevention by encouraging cessation practices.