Reduced risk of CIN2+ recurrence in women immunized with a 9-valent HPV vaccine post-excision: Retrospective cohort study.

The main aim of our study was to investigate the specific contribution of a 9-valent human papillomavirus vaccine (9vHPV) to the recurrence risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women vaccinated post-excision. Therefore, we conducted a retrospective monocentric cohort study in women aged 22-49 years undergoing conization between 2014 and 2023. The 9vHPV-vaccinated women were matched to unvaccinated women for age and follow-up duration in a 1:2 ratio to eliminate allocation bias. The risk of CIN2+ recurrence was estimated by the incidence rate ratio using Poisson regression with adjustment for comorbidities, smoking status, nulliparity, CIN grade, positive cone margin, and HPV genotypes. The CIN2+ recurrence rates in 147 women enrolled in the analysis were 18 and 2 cases per 100,000 person-days for unvaccinated and vaccinated women, respectively, during a mean follow-up period of 30 months (±22 months). A reduction in CIN2+ recurrences by 90% (95% confidence interval: 12-99%) was documented in 9vHPV-vaccinated participants compared to women undergoing only surgical excision. Moreover, vaccinated women with a positive cone margin showed a 42% (though non-significant) reduction in relapse (p = .661). Full post-conization vaccination with the 9vHPV contributed to an additional reduction in the risk of CIN2+ recurrence. This finding is consistent with current knowledge and suggests a high adjuvant effect of the 9vHPV vaccine.

Hepatitis B relapse after entecavir or tenofovir alafenamide cessation under anti-viral prophylaxis for cancer chemotherapy.

BACKGROUND: No study has comparing hepatitis B virus (HBV) relapse rates among patients with both cancer and hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) who completed anti-viral prophylaxis for chemotherapy and then stopped taking entecavir or tenofovir alafenamide (TAF). METHODS: A total of 227 HBeAg-negative cancer patients without cirrhosis who previously took entecavir (n = 144) or TAF (n = 83) for antiviral prophylaxis were enrolled. RESULTS: The cumulative incidence of virological and clinical relapse at 2 years was 37% and 10.4%, respectively, in the entecavir group, and 46.7% and 19.5%, respectively, in the TAF group. The multivariate analysis revealed that the use of hematologic malignancy, TAF use, and high-viremia group at baseline were independent risk factors for virological relapse, and use of rituximab, TAF use, higher FIB-4 index and high-viremia group at baseline were independent risk factors for clinical relapse. After propensity score-matching, the patients who discontinued TAF therapy still exhibited higher virological (P = 0.031) and clinical relapse rates (P = 0.012) than did those who discontinued entecavir therapy. The patients were allocated to high- (> 2000 IU/mL), moderate- (between 20 and 2000 IU/mL) and low- (< 20 IU/mL) viremia groups. In the high-viremia group, those who had taken TAF for antiviral prophylaxis had higher rates of virological and clinical relapse than did those who had taken entecavir; in the moderate- and low-viremia groups, no significant difference in virological and clinical relapse rates was detected between the entecavir and TAF groups. Three patients experienced hepatic decompensation upon clinical relapse. All three patients were lymphoma and underwent rituximab therapy. One patient developed acute on chronic liver failure and died even though timely retreatment. CONCLUSIONS: In patients with both cancer and CHB who underwent antiviral prophylaxis, TAF use was associated with a higher chance of HBV relapse than entecavir use after nucleos(t)ide analogue cessation, particularly in the high-viremia group. Patients who are hematologic malignancy and undergo a rituximab-containing cytotoxic therapy should be monitored closely after withdrawal from prophylactic NA treatment.

Risk factors for lymph node metastasis in superficial esophageal squamous cell carcinoma.

In this editorial, we comment on the article by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023. We focused on identifying risk factors for lymph node metastasis (LNM) in superficial esophageal squamous cell carcinoma (SESCC) patients and how to construct a simple and reliable clinical prediction model to assess the risk of LNM in SESCC patients, thereby helping to guide the selection of an appropriate treatment plan. The current standard treatment for SESCC is radical esophagectomy with lymph node dissection. However, esophagectomy is associated with considerable morbidity and mortality. Endoscopic resection (ER) offers a safer and less invasive alternative to surgical resection and can enable the patient's quality of life to be maintained while providing a satisfactory outcome. However, since ER is a localized treatment that does not allow for lymph node dissection, the risk of LNM in SESCC limits the effectiveness of ER. Understanding LNM status can aid in determining whether patients with SESCC can be cured by ER without the need for additional esophagectomy. Previous studies have shown that tumor size, macroscopic type of tumor, degree of differentiation, depth of tumor invasion, and lymphovascular invasion are factors associated with LNM in patients with SESCC. In addition, tumor budding is commonly associated with LNM, recurrence, and distant metastasis, but this topic has been less covered in previous studies. By comprehensively evaluating the above risk factors for LNM, useful evidence can be obtained for doctors to select appropriate treatments for SESCC patients.

Risk of recurrence after neoadjuvant chemotherapy and transoral robotic surgery in patients with oropharynx cancer that avoid adjuvant radiation.

BACKGROUND: De-escalation strategies for newly-diagnosed p16-positive oropharyngeal squamous cell carcinoma (p16+ OPSCC), aim to reduce treatment-related morbidity without compromising disease control. One strategy is neoadjuvant cisplatin and docetaxel chemotherapy (NAC + S) before transoral robotic surgery, with pathology-based risk-adapted adjuvant treatment. METHODS: We examined the recurrence-free survival (RFS) for patients who received NAC + S. RESULTS: Comparing outcomes in 103 patients between 2008 and 2023, 92% avoided adjuvant treatment and showed significantly higher 2-year recurrence-free survival (RFS) compared to those with adjuvant treatment (95.9% vs. 43.8%, p = 0.0049) CONCLUSION: Our findings suggest that pathology-based risk-adapted omission of adjuvant treatment following NAC + S does not appear to elevate recurrence risk and that NAC may identify patients with favorable tumor biology, yielding a 2-year RFS probability exceeding 95% without adjuvant treatment. Further, the study identifies a patient subset experiencing disease recurrence despite triple modality therapy. Despite limitations, including a retrospective design and modest sample size, the data advocate for controlled NAC + S studies.

Standard therapy or additionally radioactive iodine (131I) therapy; which will stop the recurrence of glioblastoma multiforme (GBM)?

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumour. The average survival time for a patient diagnosed with GBM, using standard treatment methods, is several months. Authors of the article pose a direct question: Is it possible to treat GBM solely with radioactive iodine (¹³¹I) therapy without employing the sodium iodide symporter (NIS) gene? After all, NIS has been detected not only in the thyroid but also in various tumours. The main author of this article (A.C.), with the assistance of her colleagues (physicians and pharmacologists), underwent ¹³¹I therapy after prior iodine inhibition, resulting in approximately 30% reduction in tumour size as revealed by magnetic resonance imaging (MRI). Classical therapy for GBM encompasses neurosurgery, conventional radiotherapy, and chemotherapy (e.g. temozolomide). Currently, tyrosine kinase inhibitors (imatinib, sunitinib, and sorafenib) are being used. Additionally, novel drugs such as crizotinib, entrectinib, or larotrectinib are being applied. Recently, personalised multimodal immunotherapy (IMI) based on anti-tumour vaccines derived from oncolytic viruses has been developed, concomitant with the advancement of cellular and molecular immunology. Thus, ¹³¹I therapy has been successfully employed for the first time in the case of GBM recurrence.

A photo-responsive self-healing hydrogel loaded with immunoadjuvants and MoS2 nanosheets for combating post-resection breast cancer recurrence.

Tumor recurrence after surgical resection remains a significant challenge in breast cancer treatment. Immune checkpoint blockade therapy, as a promising alternative therapy, faces limitations in combating tumor recurrence due to the low immune response rate. In this study, we developed an implantable photo-responsive self-healing hydrogel loaded with MoS2 nanosheets and the immunoadjuvant R837 (PVA-MoS2-R837, PMR hydrogel) for in situ generation of tumor-associated antigens at the post-surgical site of the primary tumor, enabling sustained and effective activation of the immune response. This PMR hydrogel exhibited potential for near-infrared (NIR) light response, tissue adhesion, self-healing, and sustained adjuvant release. When implanted at the site after tumor resection, NIR irradiation triggered a photothermal effect, resulting in the ablation of residual cancer cells. The in situ-generated tumor-associated antigens promoted dendritic cell (DC) maturation. In a mouse model, PMR hydrogel-mediated photothermal therapy combined with immune checkpoint blockade effectively inhibited the recurrence of resected tumors, providing new insights for combating post-resection breast cancer recurrence.

[Prevention, diagnosis and management of osteoradionecrosis: Where do we stand?] / Prévention, diagnostic et prise en charge de l'ostéoradionécrose : où en est-on ?

Osteoradionecrosis (ORN) is a late secondary iatrogenic complication of external radiotherapy for cancers of the upper aero-digestive tract. Despite the systematization of intensity-modulated radiotherapy and its potential for preserving salivary secretion and limiting the dose delivered to the supporting bone, ORN remains a feared and frequent complication. The objective of this literature review was to provide an overview of the management of ORN and to determine the key points that would make it possible to improve patient care. The diagnosis of ORN requires to eliminate tumor recurrence then is based on clinical arguments and imaging by CT or Cone Beam evolving in a chronic mode (more than 3-6 months). The harmonization of its classifications aims to offer comprehensive and multidisciplinary care as early as possible. Primary prevention is based on pre-therapeutic oral and dental preparation, then associated with fluoroprophylaxis if salivary recovery is insufficient and requires supervision of invasive dental care and prosthetic rehabilitation. Semi-automatic contouring tools make it possible to identify doses delivered to dental sectors and guide dental care with personalized dosimetric mapping. Conservative medical treatment is offered at an early stage where innovative medical treatments, highlighted by early studies, could be of interest in the future. In the event of advanced ORN, a non-conservative treatment is then proposed and frequently consists of interruptive mandibulectomy associated with reconstruction by bony free flap, the conditions of implantation remaining to be defined with the support of prospective clinical trials.

Extremity and Truncal Soft Tissue Sarcoma: Risk Assessment and Multidisciplinary Management.

Extremity and truncal soft tissue sarcomas are a heterogeneous group of rare cancers that arise from mesenchymal tissues. Hence, the adoption of tailored risk assessment and prognostication tools plays a crucial role in optimizing the decision-making for which of the many possible treatment strategies to select. Management of these tumors requires a multidisciplinary strategy, which has seen significant development in recent decades. Surgery has emerged as the primary treatment approach, with the main goal of achieving microscopic negative tumor margins. To reduce the likelihood of local recurrence, loco-regional treatments such as radiation therapy and isolated limb perfusion are often added to the treatment regimen in combination with surgery. This approach also enables surgeons to perform limb-sparing surgery, particularly in cases where a positive tumor margin is expected. Chemotherapy may also provide a further benefit in decreasing the probability of local recurrence or reducing distant metastasis in selected patients. Selecting the optimal treatment strategy for these rare tumors is best accomplished by an experienced multi-disciplinary team.

Progress in Retroperitoneal Sarcoma Management: Surgical and Radiotherapy Approaches.

Surgical resection is the cornerstone of curative treatment for retroperitoneal sarcomas (RPS), aiming for complete excision, yet the complexity of RPS with its proximity to vital structures continues to lead to high local recurrence rates after surgery alone. Thus, the role of radiotherapy (RT) continues to be refined to improve local control, which remains an important goal to prevent RPS recurrence. The recently completed global randomized trial to evaluate the role of surgery with and without preoperative RT - STRASS1, did not demonstrate a significant overall benefit for neoadjuvant RT based on the pre-specified definition of abdominal recurrence-free survival, however, sensitivity analysis using a standard definition of local recurrence and analysis of outcomes by compliance to the RT protocol suggests histology-specific benefit in well- and some de-differentiated liposarcomas. Ultimately, multidisciplinary collaboration and personalized approaches that consider histological sarcoma types and patient-specific factors are imperative for optimizing the therapeutic strategy in the management of RPS.

Immunotherapeutic IL-6R and targeting the MCT-1/IL-6/CXCL7/PD-L1 circuit prevent relapse and metastasis of triple-negative breast cancer.

Rationale: Multiple copies in T-cell malignancy 1 (MCT-1) is a prognostic biomarker for aggressive breast cancers. Overexpressed MCT-1 stimulates the IL-6/IL-6R/gp130/STAT3 axis, which promotes epithelial-to-mesenchymal transition and cancer stemness. Because cancer stemness largely contributes to the tumor metastasis and recurrence, we aimed to identify whether the blockade of MCT-1 and IL-6R can render these effects and to understand the underlying mechanisms that govern the process. Methods: We assessed primary tumor invasion, postsurgical local recurrence and distant metastasis in orthotopic syngeneic mice given the indicated immunotherapy and MCT-1 silencing (shMCT-1). Results: We found that shMCT-1 suppresses the transcriptomes of the inflammatory response and metastatic signaling in TNBC cells and inhibits tumor recurrence, metastasis and mortality in xenograft mice. IL-6R immunotherapy and shMCT-1 combined further decreased intratumoral M2 macrophages and T regulatory cells (Tregs) and avoided postsurgical TNBC expansion. shMCT-1 also enhances IL-6R-based immunotherapy effectively in preventing postsurgical TNBC metastasis, recurrence and mortality. Anti-IL-6R improved helper T, cytotoxic T and natural killer (NK) cells in the lymphatic system and decreased Tregs in the recurrent and metastatic tumors. Combined IL-6R and PD-L1 immunotherapies abridged TNBC cell stemness and M2 macrophage activity to a greater extent than monotherapy. Sequential immunotherapy of PD-L1 and IL-6R demonstrated the best survival outcome and lowest postoperative recurrence and metastasis compared with synchronized therapy, particularly in the shMCT-1 context. Multiple positive feedforward loops of the MCT-1/IL-6/IL-6R/CXCL7/PD-L1 axis were identified in TNBC cells, which boosted metastatic niches and immunosuppressive microenvironments. Clinically, MCT-1high/PD-L1high/CXCL7high and CXCL7high/IL-6high/IL-6Rhigh expression patterns predict worse prognosis and poorer survival of breast cancer patients. Conclusion: Systemic targeting the MCT-1/IL-6/IL-6R/CXCL7/PD-L1 interconnections enhances immune surveillance that inhibits the aggressiveness of TNBC.

Treatment Options for Distal Rectal Cancer in the Era of Organ Preservation.

OPINION STATEMENT: The introduction of total mesorectal excision into the radical surgery of rectal cancer has significantly improved the oncological outcome with longer survival and lower local recurrence. Traditional treatment modalities of distal rectal cancer, relying on radical surgery, while effective, take their own set of risks, including surgical complications, potential damage to the anus, and surrounding structure owing to the pursuit of thorough resection. The progress of operating methods as well as the integration of systemic therapies and radiotherapy into the peri-operative period, particularly the exciting clinical complete response of patients after neoadjuvant treatment, have paved the way for organ preservation strategy. The non-inferiority oncological outcome of "watch and wait" compared with radical surgery underscores the potential of organ preservation not only to control local recurrence but also to reduce the need for treatments followed by structure destruction, hopefully improving the long-term quality of life. Radical radiotherapy provides another treatment option for patients unwilling or unable to undergo surgery. Organ preservation points out the direction of treatment for distal rectal cancer, while additional researches are needed to answer remaining questions about its optimal use.

Surgical margins and outcomes for eyelid melanoma: a systematic review and meta-analysis.

No randomized trials exist to inform the peripheral surgical margins or depth of wide excision for eyelid melanoma. We performed a meta-analysis examining surgical margins and Breslow depth for eyelid melanomas. A systematic review was performed in August 2022 using PubMed, Cochrane, and Medline databases (1/1/1990 to 8/1/2022). Inclusion criteria included studies reporting surgical treatment of primary cutaneous melanomas of the eyelid with reported surgical margins. Ten articles were included. The studies were examined by surgical margin size (group 1: ≤ 0.5 cm; group 2 > 0.5 cm and ≤ 1.5 cm) and Breslow depth (group 1: ≤ 1 mm; group 2: > 1 mm). The odds ratio (OR) for local recurrence was 2.55 [95% CI 0.36-18.12], p = 0.18; regional metastasis was 0.70 [95% CI 0.00-23671.71], p = 0.48; and distant metastasis was 2.47 [95% CI 0.00-1687.43], p = 0.66. When examining by Breslow depth, the OR for local recurrence was 0.53 [95% CI 0.14-1.94], p = 0.34; regional metastasis was 0.14 [0.00-176.12], p = 0.54; and the OR for distant metastasis was 0.24 [95% CI 0.01-8.73], p = 0.46. There was a trend toward higher likelihood of recurrence and metastasis in the ≤ 0.5 cm group. Similarly, there is a trend toward higher likelihood of recurrence and metastasis with Breslow depth > 1 mm. A surgical margin of at least 0.5 cm and achievement of negative margins via permanent sections or MMS are likely needed to prevent adverse outcomes. En face sectioning may be a superior method of histological processing for eyelid melanoma.

mTOR inhibitor reduces nontumour-related death in liver transplantation for hepatocellular carcinoma.

Sirolimus is a regularly applied immunosuppressant for patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC). Sirolimus not only significantly inhibits HCC recurrence but also protects renal function. However, the improvement effect of sirolimus on nontumour-related death in patients is still unknown. The aim of our study was to investigate the therapeutic effect of sirolimus on nontumour-related deaths. In this study, we retrospectively enrolled 403 LT patients with HCC from January 1, 2015, to December 31, 2018. The median follow-up time was 47.1 months. The patients were divided into the sirolimus group (N = 184) and the sirolimus-free group (N = 219). There were no significant differences between the sirolimus group and the sirolimus-free group in survival (P = 0.054). In transplant patients who exceeded the Milan or Hangzhou criteria, the sirolimus group achieved higher survival than the sirolimus-free group (P = 0.005; P = 0.02). Moreover, multivariate analysis showed that sirolimus strongly reduced the hazard ratio (HR) for nontumour-related death in LT patients who exceeded the Milan (HR: 0.42; 95% CI: 0.18-1; P = 0.05) or Hangzhou criteria (HR: 0.26; 95% CI: 0.08-0.89; P = 0.032). HCC recurrence increased the risk of nontumour-related death. In conclusion, sirolimus-based immunosuppression can significantly reduce nontumour-related death in LT patients who exceed the criteria for transplantation. In addition, this finding will further promote the application of sirolimus after liver transplantation for hepatocellular carcinoma.

Tertiary prevention strategies for micrometastatic lymph node cervical cancer: A systematic review and a prototype of an adapted model of care.

PURPOSE: We found a need for balancing the application of clinical guidelines and tailored approaches to follow-up of cervical cancer (CC) patients in the lymph node micrometastatic (MICs) setting. This review aimed to determine the current knowledge of management of MIC-positive CC cases. METHODOLOGY: We addressed prognostic and risk of recurrence monitoring impacts associated with MIC+ cases. The electronic databases for literature and relevant articles were analysed. RESULTS: Fifteen studies, (4882 patients), were included in our systematic review. While the results show that MICs significantly worsen prognosis in early CC. A tertiary prevention algorithm for low volume lymph node disease may stratify follow-up according to the burden of nodal disease and provide data that helps improve follow-up performance. CONCLUSION: MICs worsen prognosis and should be managed as suggested by the algorithm. However, this algorithm must be externally validated. The clinical impact of isolated tumor cells (ITC) remains unclear.

Hybrid Ginseng-derived Extracellular Vesicles-Like Particles with Autologous Tumor Cell Membrane for Personalized Vaccination to Inhibit Tumor Recurrence and Metastasis.

Personalized cancer vaccines based on resected tumors from patients is promising to address tumor heterogeneity to inhibit tumor recurrence or metastasis. However, it remains challenge to elicit immune activation due to the weak immunogenicity of autologous tumor antigens. Here, a hybrid membrane cancer vaccine is successfully constructed by membrane fusion to enhance adaptive immune response and amplify personalized immunotherapy, which formed a codelivery system for autologous tumor antigens and immune adjuvants. Briefly, the functional hybrid vesicles (HM-NPs) are formed by hybridizing ginseng-derived extracellular vesicles-like particles (G-EVLPs) with the membrane originated from the resected autologous tumors. The introduction of G-EVLPs can enhance the phagocytosis of autologous tumor antigens by dendritic cells (DCs) and facilitate DCs maturation through TLR4, ultimately activating tumor-specific cytotoxic T lymphocytes (CTLs). HM-NPs can indeed strengthen specific immune responses to suppress tumors recurrence and metastasis including subcutaneous tumors and orthotopic tumors. Furthermore, a long-term immune protection can be obtained after vaccinating with HM-NPs, and prolonging the survival of animals. Overall, this personalized hybrid autologous tumor vaccine based on G-EVLPs provides the possibility of mitigating tumor recurrence and metastasis after surgery while maintaining good biocompatibility.

Preventing viral relapse with prophylactic tenofovir in hepatitis B carriers receiving chemotherapy: a phase IV randomized study in Taiwan.

BACKGROUND AND AIMS: This study aimed to compare the efficacy of shorter vs. longer tenofovir disoproxil fumarate (TDF) prophylaxis in preventing hepatitis B virus (HBV) relapse in cancer patients with chronic hepatitis B (CHB) undergoing chemotherapy. METHODS: This phase IV, prospective randomized trial enrolled cancer patients with CHB from 2014 to 2019 in Taiwan. Included patients were randomized to receive either 24- (Arm A) or 48-week (Arm B) post-chemotherapy TDF and compared for cumulative incidence of virological and clinical relapse. Logistic regressions were conducted to determine the factors associated with HBV relapse. RESULTS: One hundred patients were randomized, and 41 patients in Arm A and 46 in Arm B completed the TDF treatment. No significant difference was found in cumulative incidence of virological relapse (Arm A: 94.4%, Arm B: 93.1%, p = 0.110) or clinical relapse among patients with baseline HBV DNA > 2000 IU/mL (Arm A: 38.9%, Arm B: 26.7%, p = 0.420) between the two arms. High baseline HBV DNA ≥ 10,000 IU/mL (OR = 51.22) and HBsAg ≥ 1000 IU/mL (OR = 8.64) were independently associated with an increased virological relapse. Alanine aminotransferase (ALT), serum phosphorus, vitamin D, and estimated glomerular filtration rate (eGFR) remained stable throughout the study. CONCLUSIONS: The 24-week preventative TDF has comparable efficacy to the 48-week treatment in virologic and clinical relapse. High baseline HBsAg or HBV DNA is associated with a higher risk of HBV relapse. These findings imply a 24-week duration of TDF treatment with a close monitor for patients with a high baseline viral load. Hepatitis B virus infection is a prominent cause of liver cancer and chronic liver disease and affected millions of people worldwide. When HBV-infected people are exposed to immunosuppressive medication or chemotherapy for cancer, the chance of HBV reactivation rises considerably. This trial showed 24-week tenofovir disoproxil fumarate (TDF) may be sufficient for preventing HBV relapse in cancer patients receiving chemotherapy. CLINICAL TRIAL REGISTRATION NUMBER: NCT02081469.