Morbimortality after 1321 consecutive CRS+HIPEC procedures: seeking excellence in surgery for peritoneal surface malignancy

Purpose Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) treatment has classically presented a percentage of associated complications that have limited its expansion. The aim of this study is to describe the morbimortality results obtained from a referral center implemented with the support of a governmental health agency and directed by a surgical team experienced in CRS for Peritoneal Surface Malignancies (PSM). Methods Data from the Peritoneal Carcinomatosis Program of Catalonia (PCPC) prospective database, including patients who underwent CRS + HIPEC between September 2006 and January 2021, were analyzed. Results A total of 1151 consecutive patients underwent 1321 CRS + HIPEC procedures. Colonic origin of peritoneal metastasis was the most frequent (47.3%). Median PCI was 7 and most patients had CC0-1 (96.1%). Multivisceral resection was performed in 44% of all patients, 57% required digestive anastomosis. Median hospital stay was 11 days (range 6–144 days). High-grade complications occurred in 20% of all patient, most of them surgical complications. Anastomotic leak occurred in 0.6% of all cases. The overall in-stay and 30-day mortality rate was 0.4%. The low-rate of complications and the high rate of complete CRS were achieved from the beginning of the PCPC. Median overall survival was 54.7 months, with a 5-year survival rate of 47.5%. Conclusions Implementation of a CRS + HIPEC referral program for the treatment of PSM with preferably an experienced surgical team enables acceptable rates of severe morbidity (20%) and mortality (< 1%) (AU)

Terapia de privación de andrógenos en el cáncer de próstata localizado. Situación actual y tendencias futuras / Androgen deprivation therapy in localized prostate cancer. Current status and future trends

Introducción El cáncer de próstata (CaP) se ha reconocido como una enfermedad sensible a los andrógenos desde las investigaciones de Huggins y Hodges en 1941, quienes, gracias a estos hallazgos, recibieron el Premio Nobel en 1966. Aquí se originó el desarrollo de la terapia de privación de andrógenos (TPA) como tratamiento para los pacientes con CaP. Objetivo Resumir las indicaciones actuales de la TPA en el CaP localizado. Adquisición de la evidencia Hemos realizado una investigación bibliográfica exhaustiva en inglés y español, centrada en las principales indicaciones de la TPA en el CaP localizado. Síntesis de la evidencia En la actualidad, las indicaciones de la TPA como monoterapia en el CaP localizado se han limitado a situaciones específicas, a pacientes que no desean o no pueden recibir ninguna forma de tratamiento local y que tienen un PSA-DT<12 meses y un PSA>50 ng/mL, un tumor poco diferenciado o síntomas locales molestos relacionados con la enfermedad. La TPA puede utilizarse en combinación con tratamiento local en diferentes escenarios. Aunque el tratamiento neoadyuvante con TPA antes de la cirugía con intención curativa no tiene un impacto oncológico claro, el CaP es una enfermedad heterogénea y en el futuro podría haber un grupo de pacientes con enfermedad localizada de alto riesgo que se beneficiaran de este tratamiento. Conclusiones Necesitamos optimizar el tratamiento con TPA en el CaP localizado, seleccionando a los pacientes en función de las características de su enfermedad. Dado que el arsenal terapéutico evoluciona día a día, es necesario el desarrollo de nuevos ensayos clínicos, así como el estudio molecular en los pacientes, para identificar a aquellos que podrían beneficiarse de un tratamiento multimodal temprano (AU)

Introduction Prostate cancer (PCa) has been recognized as an androgen-sensitive disease since the investigations from Huggins and Hodges in 1941. Thanks to these findings, they received the Nobel Prize in 1966. This was the beginning of the development of androgen deprivation therapy (ADT) as treatment for patients with PCa. Objective To summarize the current indications of ADT in localized PCa. Evidence acquisition We conducted a comprehensive English and Spanish language literature research, focused on the main indications for ADT in localized PCa. Evidence synthesis Nowadays, the indications for ADT as monotherapy in localized PCa have been limited to specific situations, to patients unwilling or unable to receive any form of local treatment if they have a PSA-DT<12 months, and either a PSA>50 ng/mL, a poorly differentiated tumor, or troublesome local disease-related symptoms. ADT can be used in combination with local treatment in different scenarios. Although neoadjuvant treatment with ADT prior to surgery with curative intent has no clear oncological impact, as a future sight, PCa is a heterogeneous disease, and there could be a group of patients with high-risk localized disease that could benefit. Conclusions We need to optimize the treatment with ADT in localized PCa, selecting the patients accordingly to their disease characteristics. Given that the therapeutic armamentarium evolves day by day, there is a need for the development of new clinical trials, as well as a molecular studies of patients to identify those who might benefit from an early multimodal treatment (AU)

Efficacy and safety of immune checkpoint inhibitors in Proficient Mismatch Repair (pMMR)/ Non-Microsatellite Instability-High (non-MSI-H) metastatic colorectal cancer: a study based on 39 cohorts incorporating 1723 patients.

PURPOSE: This study was designed to investigate the efficacy and safety of immune checkpoint inhibitors (ICIs)-based therapy in proficient mismatch repair (pMMR)/non-microsatellite instability-high (non-MSI-H) metastatic colorectal cancer (mCRC). METHODS: Electronic databases were screened to identify relevant trials. The primary endpoints were pooled objective response rate (ORR) and disease control rate (DCR). Stratified analysis was accomplished on ICIs-based regimens, treatment lines and RAS status. RESULTS: Totally, 1723 mCRC patients from 39 cohorts were included. The pooled ORR, DCR, 12-month overall survival (OS) rate and 6-month progression-free survival (PFS) rate of ICIs-based therapy in pMMR/non-MSI-H mCRC were 8.5% (95% CI: 4.4%-13.5%), 48.2% (95% CI: 37.8%-58.6%), 52.3% (95% CI: 46.4%-58.1%) and 32.8% (95% CI: 23.5%-42.7%) respectively. As a whole, no significantly differences were shown between ICIs-based and non-ICIs-based therapy for pMMR/non-MSI-H mCRC in terms of both PFS (HR = 1.0, 95% CI: 0.9-1.1, P = 0.91) and OS (HR = 1.0, 95% CI: 0.9-1.2, P = 0.51). It was worth noting that the addition of ICIs to anti-vascular endothelial growth factor (VEGF) agent plus chemotherapy displayed excellent efficacy in pMMR/non-MSI-H mCRC (ORR = 42.4%, 95% CI: 10.0%-78.6%; DCR = 92.0%, 95% CI: 68.3%-100.0%; 12-month OS rate = 71.4%, 95% CI: 50.0%-89.1%; 6-month PFS rate = 55.2%, 95% CI: 24.8%-83.8%; and PFS (compared with non-ICIs-based therapy): HR = 0.9, 95% CI: 0.8-1.0, P = 0.02), especially served as first-line therapy (ORR = 74.2%, 95% CI: 61.4%-85.4%; DCR = 98.7%, 95% CI: 92.0%-100.0%); and without additional treatment related adverse events (TRAEs) were observed. CONCLUSIONS: ICIs-based combination therapy, especially the addition of ICIs to first-line anti-VEGF agent plus chemotherapy, is promising in pMMR/non-MSI-H mCRC with good efficacy and controllable toxicity.

Effectiveness and safety of Pingxiao capsule as adjuvant therapy in treatment of breast cancer: a systematic review and Meta-analysis.

OBJECTIVE: To systematically review the effectiveness and safety of Pingxiao capsule adjuvant chemotherapy in the treatment of breast cancer. METHODS: A total of 8 databases including the Cochrane Library, PubMed, EMBASE, Engineering Index, Chinese Biomedical Literature Database, Wanfang database, China National Knowledge Infrastructure Database, and China Science and Technology Journal Database were searched for the Randomized Controlled Trials (RCTs) of Pingxiao capsule combined with chemotherapy in the treatment of breast cancer published before June 2022. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias. R language was used for estimating risks of bias of included studies, data analysis, and plotting. RESULTS: A total of 15 RCTs involving 1272 patients were included in this study. Meta-analysis results indicated that compared with chemotherapy alone, Pingxiao capsule combined with chemotherapy could significantly improve breast cancer patients' objective response rate of breast cancer patients [rate ratio () = 1.35, 95% confidence interval () (1.12, 1.63), = 0.0017], the disease control rate [=1.16, 95% (1.08, 1.25), < 0.0001], the quality of life [ =1.42, 95% (1.16, 1.74), = 0.007], and the level of the immune cells [CD3+: standardized mean difference () =1.42, 95% (0.76, 2.09), < 0.001; CD4+: =1.18, 95% (0.70, 1.66), < 0.001]. In addition, Pingxiao capsule combined with chemotherapy can also significantly reduce CD8+ level ( < 0.0001) and reduce the symptoms of decreased white blood cell count [ = 0.62, 95% (0.39, 0.85), < 0.0001], and the occurrence of adverse reactions such as gastrointestinal adverse reactions and limb pain ( < 0.05). CONCLUSIONS: Pingxiao capsule can significantly improve the efficacy of chemotherapy, the quality of life and immune function of patients, and reduce the clinical side effects caused by chemotherapy. However, high-quality randomized clinical trials with large samples are required for further verification of these results.

[Exploration and prospect of the whole course management model of osteoporosis].

Osteoporosis is a chronic progressive bone disease whose prevalence has increased significantly in China. Fragility fractures caused by osteoporosis pose a heavy burden on patients and their families. Therefore, early and efficient whole course management of osteoporosis is imperative. However, there are great challenges currently in the whole course management of osteoporosis, including lack of disease awareness, low rates of diagnosis and treatment, as well as poor patient compliance. As there is no consensus on the whole course management path to follow in clinical practice, this review analyzes the key points of whole course management of osteoporosis, such as the risk identification of fragility fracture, diagnosis and differential diagnosis, selection of initial treatment drugs, sequential or combined treatment and evaluation of treatment response etc. Based on the current management modes, including fracture liaison service, this review explores the whole course management path of osteoporosis which is suitable for China, including the whole course management ideas and implementation steps, establishing a platform to connect hospitals, communities, and families by application of information technology, developing an innovative system and mechanism indicates that the general practitioner will be responsible for clinical management and follow-up under instruction of clinical osteoporosis specialists, providing the community liaison service, organizing patient education activities such as bone health clubs, ultimately achieving a closed-loop communication among osteoporosis specialist, general practitioner, and patient, so that patients can benefit from it.

Challenges and Future Trends in the Treatment of Psoriasis.

Psoriasis is a chronic inflammatory skin disorder, and current treatments include topical therapies, phototherapy, systemic immune modulators, and biologics, aiming to alleviate symptoms and improve quality of life. However, challenges persist, such as adverse effects, treatment resistance, high costs, and variability in response among individuals. The future of psoriasis treatment shows promising emerging trends. New biologic agents targeting novel pathways, such as interleukin 23 inhibitors like mirikizumab, offer enhanced efficacy. Small molecule inhibitors like RORγt inhibitors and ROCK2 inhibitors provide additional treatment options. Combination therapies, including biologics with methotrexate, may improve treatment response. Advancements in topical treatments utilizing microneedles and nanoparticle-based carriers can enhance drug delivery and improve therapeutic outcomes. Biomarkers and multi-omics technologies hold potential for personalized treatment approaches, thus aiding in diagnosis, predicting treatment response, and guiding therapeutic decisions. Collaboration among researchers, clinicians, and industry stakeholders is crucial to translating these scientific breakthroughs into clinical practice. By addressing current challenges and exploring these promising trends, we can optimize psoriasis management and improve the lives of those affected by this chronic condition.

A phase II study of bevacizumab and temsirolimus in advanced extra-pancreatic neuroendocrine tumors.

We assessed the efficacy and safety of combining bevacizumab with temsirolimus in patients with advanced extra-pancreatic neuroendocrine tumors. This NCI-sponsored multicenter, open-label, phase II study (NCT01010126) enrolled patients with advanced, recurrent, or metastatic extra-pancreatic neuroendocrine tumors. All patients were treated with temsirolimus and bevacizumab until disease progression or unacceptable toxicity. Temsirolimus 25 mg was administered i.v. on days 1, 8, 15, and 22 and bevacizumab 10 mg/kg i.v. on days 1 and 15 of a 4-week cycle. Discontinuation of temsirolimus or bevacizumab did not require discontinuation of the other agent. The primary endpoints were objective response rate and 6-month progression-free survival rate. Fifty-nine patients were enrolled in this study, and 54 were evaluated for efficacy and adverse events. While median progression-free survival was 7.1 months, the median duration of treatment with temsirolimus was 3.9 months and that with bevacizumab was 3.5 months. The objective response rate of combination therapy was 2%, and 6-month progression-free survival was 48%. The most frequently reported grade 3-4 adverse events included fatigue (13%), hypertension (13%), and bleeding (13%). Close to 54% of the patients discontinued treatment due to adverse events, refusal of further treatment, or treatment delays. Three deaths occurred in the study, of which two were due to treatment-related bowel perforations. Given the minimal efficacy and increased toxicity seen with the combination of bevacizumab and temsirolimus, we do not recommend the use of this regimen in patients with advanced extra-pancreatic neuroendocrine tumors.

[Progress in the application of artificial intelligence in gastric cancer imaging].

Gastric cancer is a common malignant tumor of digestive tract, and its prognosis varies greatly with different stages of the tumor. In recent years, more and more evidence shows that artificial intelligence (AI) technology has excellent performance in imaging diagnostic applications, with remarkable diagnostic effects and broad prospects. AI not only improves the accuracy of diagnosis and staging of gastric cancer, but also has great application value in pathological assessment, adjuvant therapy and prognosis prediction. This article systematically reviews domestic and foreign literature to explore the application progress of AI in gastric cancer imaging.

Long-course chemoradiation plus concurrent/sequential PD-1 blockade as neoadjuvant treatment for MMR-status-unscreened locally advanced rectal cancer: protocol of a multicentre, phase 2, randomised controlled trial (the POLAR-STAR trial).

INTRODUCTION: Recent preclinical studies have discovered unique synergism between radiotherapy and immune checkpoint inhibitors, which has already brought significant survival benefit in lung cancer. In locally advanced rectal cancer (LARC), neoadjuvant radiotherapy plus immune checkpoint inhibitors have also achieved surprisingly high pathological complete response (pCR) rates even in proficient mismatch-repair patients. As existing researches are all phase 2, single-cohort trials, we aim to conduct a randomised, controlled trial to further clarify the efficacy and safety of this novel combination therapy. METHODS AND ANALYSIS: Eligible patients with LARC are randomised to three arms (two experiment arms, one control arm). Patients in all arms receive long-course radiotherapy plus concurrent capecitabine as neoadjuvant therapy, as well as radical surgery. Distinguishingly, patients in arm 1 also receive anti-PD-1 (Programmed Death 1) treatment starting at Day 8 of radiation (concurrent plan), and patients in arm 2 receive anti-PD-1 treatment starting 2 weeks after completion of radiation (sequential plan). Tislelizumab (anti-PD-1) is scheduled to be administered at 200 mg each time for three consecutive times, with 3-week intervals. Randomisation is stratified by different participating centres, with a block size of 6. The primary endpoint is pCR rate, and secondary endpoints include neoadjuvant-treatment-related adverse event rate, as well as disease-free and overall survival rates at 2, 3 and 5 years postoperation. Data will be analysed with an intention-to-treat approach. ETHICS AND DISSEMINATION: This protocol has been approved by the institutional ethical committee of Beijing Friendship Hospital (the primary centre) with an identifying serial number of 2022-P2-050-01. Before publication to peer-reviewed journals, data of this research will be stored in a specially developed clinical trial database. TRIAL REGISTRATION NUMBER: NCT05245474.

[Stratified endocrine therapy for advanced breast cancer: stratification guided, combination preferred].

The endocrine therapy of hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancer has stepped into an era of targeted combination therapy. Many targeted agents, led by cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), have provided abundant treatment options for patients with HR-positive HER2-negative advanced breast cancer. To meet the needs of clinical practice in China and standardize the administration of targeted agents, the stratified endocrine strategy for advanced breast cancer has been proposed by Chinese Society of Clinical Oncology (CSCO) Breast Cancer guidelines based on medicine evidence and drug accessibility, offering scientific and organized decision-making guidance for clinical oncologists.

Head and neck cancer treatment in the era of molecular medicine.

Head and neck cancers are a heterogeneous group of highly aggressive tumors and collectively represent the sixth most common cancer worldwide. Most head and neck cancers are squamous cell carcinomas (HNSCCs). Current multimodal treatment concepts combine surgery, chemotherapy, irradiation, immunotherapy, and targeted therapeutics. Recent scientific advancements have enabled a more precise molecular characterization of HNSCC and revealed novel therapeutic targets and prognostic/predictive biomarkers. Notably, HNSCC is characterized by complex relations between stromal, epithelial, and immune cells within the tumor microenvironment (TME). The TME consists of different subsets of immune cells that infiltrate the tumors and interact with the tumor cells or with each other. Understanding multiple pivotal factors in HNSCC tumorigenesis and tumor progression may help define novel targets and develop more effective therapies for patients. This review provides a comprehensive overview of the latest advances in the molecular biology of HNSCC and their effects on clinical oncology; it is meant for a broad readership in the head and neck cancers field.

Is Axillary Staging Obsolete in Early Breast Cancer?

This article reviews the incidence of nodal metastases in early-stage breast cancer and the need for axillary staging to maintain local control in the axilla or to determine the need for adjuvant systemic therapy across the spectrum of patients with breast cancer, and reviews clinical trials addressing this question. At present, sentinel lymph node biopsy should be omitted in women age ≥70 years with cT1-2 N0, HR+/HER2- cancers. The importance of nodal status in selecting patients for radiotherapy remains the main reason for axillary staging in younger postmenopausal women with cT1-2N0, HR+/HER2- cancers.

How to Navigate the Treatment Spectrum from Multimodality Therapy to Observation Alone for ductal carcinoma in situ.

DCIS detection has increased dramatically since the introduction of screening mammography. Current guidance concordant care recommends surgical intervention for all patients with DCIS, followed by radiation and/or endocrine therapy for some. Adjuvant therapies after surgical excision have reduced recurrence rates but not breast cancer mortality. Given the lack of evidence of current treatment regimens and the morbidity associated with these treatments, there is concern that DCIS is over-treated. Active surveillance may be a favorable alternative for selected patients and is currently being investigated through four international clinical trials.

Real-world analysis of survival benefit of surgery and adjuvant therapy in elderly patients with colorectal cancer.

Treatment guidelines for colorectal cancer (CRC) in elderly patients remain unclear. This study aimed to investigate whether elderly patients (≥ 70 years) with CRC benefit from surgery and adjuvant therapy. A total of 90,347 eligible CRC patients older than 70 years were collected from the Surveillance, Epidemiology, and End Results (SEER) database and divided into a surgery group and a no-surgery group. After being matched by propensity score matching at a 1:1 ratio, 23,930 patients were included in our analysis. The Kaplan‒Meier method and log-rank test were applied to compare overall survival (OS) and cancer-specific survival (CSS). Univariate and multivariate Cox regression analyses were utilized to confirm independent prognostic factors for OS and CSS. In age-stratified analysis (70-74; 75-79; 80-84; ≥ 85), the OS and CSS rates of patients in the surgery group were significantly higher than those of patients in the no-surgery group (all P < 0.001). Adjuvant therapy was an independent prognostic factor for OS and CSS in elderly patients with CRC (all P < 0.001). Further analysis showed that elderly colon cancer patients with stage III and stage IV disease gained a survival benefit from adjuvant chemotherapy. Adjuvant chemoradiotherapy can significantly improve OS and CSS in elderly rectal cancer patients with stage II, III, and IV disease. In conclusion, among CRC patients aged ≥ 70 years reported in the SEER database, treatment with surgical resection is significantly associated with improved OS and CSS. Moreover, adjuvant therapy led to a significant prognostic advantage for elderly advanced CRC patients who underwent surgery.

Untousling the Role of Tousled-like Kinase 1 in DNA Damage Repair.

DNA damage repair lies at the core of all cells' survival strategy, including the survival strategy of cancerous cells. Therefore, targeting such repair mechanisms forms the major goal of cancer therapeutics. The mechanism of DNA repair has been tousled with the discovery of multiple kinases. Recent studies on tousled-like kinases have brought significant clarity on the effectors of these kinases which stand to regulate DSB repair. In addition to their well-established role in DDR and cell cycle checkpoint mediation after DNA damage or inhibitors of replication, evidence of their suspected involvement in the actual DSB repair process has more recently been strengthened by the important finding that TLK1 phosphorylates RAD54 and regulates some of its activities in HRR and localization in the cell. Earlier findings of its regulation of RAD9 during checkpoint deactivation, as well as defined steps during NHEJ end processing, were earlier hints of its broadly important involvement in DSB repair. All this has opened up new avenues to target cancer cells in combination therapy with genotoxins and TLK inhibitors.

Treatment approaches for FGFR-altered urothelial carcinoma: targeted therapies and immunotherapy.

The treatment of metastatic urothelial carcinoma has dramatically changed over the past decade with the approval of several therapies from multiple drug classes including immune checkpoint inhibitors, targeted therapies, and antibody drug conjugates. Although next generation sequencing of urothelial carcinoma has revealed multiple recurring mutations, only one targeted therapy has been developed and approved to date. Erdafitinib, a pan-fibroblast growth factor receptor (FGFR) inhibitor, has been approved for treating patients with select FGFR2 and FGFR3 alterations and fusions since 2019. Since then, emerging data has demonstrated efficacy of combining erdafitinib with immunotherapy in treating FGFR-altered urothelial carcinoma. Ongoing trials are evaluating the use of erdafitinib in non-muscle invasive urothelial carcinoma as well as in combination with enfortumab vedotin in the metastatic setting, while other FGFR targeted agents such as infigratinib, AZD4547, rogaratinib and pemigatinib continue to be in development. Future challenges will include strategies to overcome FGFR acquired resistance and efficacy and safety of combination therapies with erdafitinib and other FGFR targeted agents.

Long-term survival benefit of anti-PD-1 therapy in patients with relapsed or refractory classical Hodgkin lymphoma.

Anti-programmed cell death-1 (anti-PD-1) therapies have shown a favorable efficacy and good tolerance for relapsed or refractory (r/r) classical Hodgkin lymphoma (cHL). However, there are limited data on long-term outcomes among patients with r/r cHL who achieve an objective response to anti-PD-1 therapies. A total of 260 responders from four, phase 2 clinical trials were included in this study. The median age was 32 years with a male/female ratio of 1.3:1. After a median follow-up period of 31.1 months, 116 (44.6%) responders experienced disease progression and 18 (6.9%) died. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 55.1% and 89.7% overall. Patients with partial remission (PR) had inferior outcomes compared with those who achieved complete remission (3-year PFS, 29.5% vs. 72.3%, P < 0.001; 3-year OS, 81.5% vs. 94.4%, P = 0.017). Moreover, the survival outcome was inferior for patients with refractory disease compared with those with relapsed disease. Multivariate Cox regression analysis showed PR and refractory disease were independent risk factors for PFS. In conclusion, PR and refractory disease have a negative impact on the survival benefit of anti-PD-1 therapeutics in patients with r/r cHL, which highlights the need for multimodal treatment strategies.