Systemic oncological therapy in breast cancer patients on dialysis

The advancement of renal replacement therapy has significantly enhanced the survival rates of patients with end-stage renal disease(ESRD)over time.How-ever,this prolonged survival has also been associated with a higher likelihood of cancer diagnoses among these patients including breast cancer.Breast cancer treatment typically involves surgery,radiation,and systemic therapies,with ap-proaches tailored to cancer type,stage,and patient preferences.However,renal replacement therapy complicates systemic therapy due to altered drug clearance and the necessity for dialysis sessions.This review emphasizes the need for opti-mized dosing and administration strategies for systemic breast cancer treatments in dialysis patients,aiming to ensure both efficacy and safety.Additionally,ch-allenges in breast cancer screening and diagnosis in this population,including soft-tissue calcifications,are highlighted.

Optimizing care for gastric cancer with overt bleeding:Is systemic therapy a valid option?

Gastric cancer(GC)and gastroesophageal junction cancer(GEJC)represent a significant burden globally,with complications such as overt bleeding(OB)further exacerbating patient outcomes.A recent study by Yao et al evaluated the effectiveness and safety of systematic treatment in GC/GEJC patients presenting with OB.Using propensity score matching,the study balanced the comparison groups to investigate overall survival and treatment-related adverse events.The study's findings emphasize that systematic therapy can be safe and effective and contribute to the ongoing debate about the management of advanced GC/GEJC with OB,highlighting the complexities of treatment decisions in these high-risk patients.

Re-evaluating the role of pelvic radiation in the age of modern precision medicine and systemic therapy

The efficacy of pelvic radiation in the management of locally advanced stage rectal cancer has come under scrutiny in the context of modern precision medicine and systemic therapy as evidenced by recent clinical trials such as FOWARC(J Clin Oncol 2019;37:3223-3233),NCT04165772(N Engl J Med 2022;386:2363-2376),and PROSPECT(N Engl J Med 2023;389:322-334).In this review,we comprehensively assess these pivotal trials and offer additional insights into the evolving role of pelvic radiation in contemporary oncology.

Systemic therapy in gastrointestinal stromal tumors

Gastrointestinal stromal tumors(GISTs)are the most common type of soft tissue sarcoma in the gastrointestinal tract.Most GISTs have been attributed to activated gain-of-function mutations in either KIT or platelet-derived growth factor receptorα,making these molecular features essential targets for therapeutic interventions.Although surgery is the standard treatment for localized GISTs,patients often experience relapse and disease progression even after surgery.In recent years,targeted therapy has significantly improved the prognosis of patients with advanced GISTs.Imatinib mesylate,a KIT inhibitor,is the first-line treatment for advanced GISTs and has revolutionized the treatment of this disease.However,drug resistance remains a major issue with imatinib treatment,as a significant majority of patients become resistant to imatinib either after initiation or after 2–3 years of treatment.Consequently,novel tyrosine kinase inhibitors such as sunitinib,regorafenib,ripretinib,and avapritinib have been introduced to address drug resistance.Immunotherapy has emerged as a potential approach for the treatment of advanced GISTs.This review comprehensively summarizes the pathogenesis of GISTs and the development of targeted therapies and immunotherapies,provides an overview of the emergence of drug resistance in advanced GISTs,and discusses the challenges and prospects associated with the treatment of GISTs.

Systematic sequential therapy for ex vivo liver resection and autotransplantation: A case report and review of literature

BACKGROUND Perihilar cholangiocarcinoma(pCCA)is a highly malignant tumor arising from the biliary tree.Radical surgery is the only treatment offering a chance of long-term survival.However,limited by the tumor’s anatomic location and peri-vascular invasion,most patients lose the chance for curative treatment.Therefore,more methods to increase the resectability of tumors as well as to improve outcomes are needed.CASE SUMMARY A 68-year-old female patient had a hepatic hilar mass without obvious symptoms.Laboratory results showed hepatitis B positivity.Magnetic resonance imaging indicated that the mass(maximum diameter:41 mm)invaded the left and right branches of the main portal vein,as well as the middle,left and right hepatic veins;enlarged lymph nodes were also detected in the hilum.The patient was diagnosed with pCCA,and the clinical stage was determined to be T4N1M0(stage IIIC).Considering the tumor’s anatomic location and vascular invasion,systematic conversion therapy followed by ex vivo liver resection and autotrans-plantation(ELRA)was determined as personalized treatment for this patient.Our original systemic sequential therapeutic strategy(lenvatinib and tislelizumab in combination with gemcitabine and cisplatin)was successfully adopted as conversion therapy because she achieved partial response after three cycles of treatment,without severe toxicity.ELRA,anastomotic reconstruction of the middle hepatic vein,right hepatic vein,root of portal vein,inferior vena cava and right hepatic artery,and lymph node dissection were performed at one month after systemic therapy.Pathological and immunohistochemical examination confirmed the diagnosis of pCCA with lymph node metastasis.Although the middle hepatic vein was partially obstructed four months later,hepatic vein stent implantation successfully addressed this problem.The patient has survived for 22 mo after the diagnosis,with no evidence of recurrence or metastasis.CONCLUSION An effective therapeutic strategy for conversion therapy greatly increases the feasibility and efficiency of ELRA.

Combining local regional therapy and systemic therapy:Expected changes in the treatment landscape of recurrent hepatocellular carcinoma

Improvements in early screening,new diagnostic techniques,and surgical treatment have led to continuous downward trends in hepatocellular carcinoma(HCC)morbidity and mortality rates.However,high recurrence and refractory cancer after hepatectomy remain important factors affecting the long-term prognosis of HCC.The clinical characteristics and prognosis of recurrent HCC are heterogeneous,and guidelines on treatment strategies for recurrent HCC are lacking.Therapies such as surgical resection,radiofrequency ablation,and transhepatic arterial chemoembolization are effective for tumors confined to the liver,and targeted therapy is a very important treatment for unresectable recurrent HCC with systemic metastasis.With the deepening of the understanding of the immune microenvironment of HCC,blocking immune checkpoints to enhance the antitumor immune response has become a new direction for the treatment of HCC.In addition,improvements in the tumor immune microenvironment caused by local treatment may provide an opportunity to improve the therapeutic effect of HCC treatment.Ongoing and future clinical trial data of combined therapy may develop the new treatment scheme for recurrent HCC.This paper reviews the pattern of recurrent HCC and the characteristics of the immune microenvironment,demonstrates the basis for combining local treatment and systemic treatment,and reports current evidence to better understand current progress and future approaches in the treatment of recurrent HCC.

Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

Systemic treatment of hepatocellular carcinoma secondary to nonalcoholic fatty liver disease

Hepatocellular carcinoma(HCC)is the third leading cause of cancer death globally,with 15%of cases arising on a background of non-alcoholic fatty liver disease(NAFLD).NAFLD is a heterogenous condition ranging from fatty liver to cirrhosis and is itself a growing global problem,with estimated worldwide prevalence of 50%in 2040.Pathophysiology of NAFLD-HCC is not well understood,there are no dedicated screening programs,and there have been no clinical studies of anticancer treatments in this population specifically.However,the NAFLD-HCC population appears different than other aetiologies-patients tend to be older,diagnosed at more advanced stages,have more comorbidities,and overall worse prognosis.Understanding of best treatment options for this group of patients is an urgent unmet clinical need.This narrative review discusses NAFLD-HCC pathophysiology and systemic treatment,and offers suggestions for future directions in this therapy area.

Chemotherapy for hepatocellular carcinoma:The present and the future

Hepatocellular carcinoma(HCC) is the most common primary tumor of the liver. Its relationship to chronic liver diseases, in particular cirrhosis, develops on a background of viral hepatitis, excessive alcohol intake or metabolic steatohepatitis, leads to a high incidence and prevalence of this neoplasia worldwide. Despite the spread of HCC, its treatment it's still a hard challenge, due to high rate of late diagnosis and to lack of therapeutic options for advanced disease. In fact radical surgery and liver transplantation, the most radical therapeutic approaches, are indicated only in case of early diagnosis. Even local therapies, such as transarterial chemoembolization, find limited indications, leading to an important problem regarding treatment of advanced disease. In this situation, until terminal HCC occurs, systemic therapy is the only possible approach, with sorafenib as the only standard treatment available. Anyway, the efficacy of this drug is limited and many efforts are necessary to understand who could benefit more with this treatment. Therefore, other molecules for a targeted therapy were evaluated, but only regorafenib showed promising results. Beside molecular target therapy, also cytotoxic drugs, in particular oxaliplatinand gemcitabine-based regimens, and immune-checkpoint inhibitors were tested with interesting results. The future of the treatment of this neoplasia is linked to our ability to understand its mechanisms of resistance and to find novel therapeutic targets, with the objective to purpose individualized approaches to patients affected by advanced HCC.

Clinical and pathological portraits of axillary presentation breast cancer and effects of preoperative systemic therapy

There is a lack of investigation into the biological characteristics and preoperative systemic therapy （PST） for occult breast cancer （OBC）. For this study, departmental records in Breast Disease Center of Peking University First Hospital from January 2008 to December 2015 were retrospectively reviewed to identify cases of OBC. Eleven cases were included, and all patients were female, with a median age of 56 （range： 29-75） years. The sensitivity of magnetic resonance imaging （MRD was I00%, and the false positive rate was 33.3%. Based on histologic analysis of the axillary node, 9 （81.8%） cases were grade 3, and 2 （18.2%） cases were grade 2; 4 （36.4%） cases were 〉10% estrogen receptor （ER） positive and 6 （54.5%） human epidermal growth receptor 2 （HER2） positive. Nine cases （81.8%） exhibited over 30% Ki67 expression. PST was performed in 5 of the 11 cases. The lymph node response rate was 100% （5/5）, but no complete remission was achieved. In conclusion, aggressive subtypes were predominant among the included cases, and PST should be considered for OBC treatment options.

Human Systems Therapy:Use of Interpersonal Relations in Promoting Therapeutic Change

The aim of this work is to present the central role of interpersonal relations in Human Systems Therapy(HST).Psychotherapies can be classified as(a)down-top therapies,such as individual therapies following reductionism,namely influencing the whole(behavior)through the intra-psychic parts,(b)top-down or holistic therapies,such as family therapies influencing the parts(individuals)through the whole family,and(c)the combination of down-top and top-down.Emotionally Focused Therapy(EFT)and Multisystemic Therapy(MST)act on two levels that influence each other,namely the individuals and their relations.This is also applied,more or less,on relational and interpersonal therapies.When there is an intervention in two interacting parts or levels,then the result of the intervention is more than additive and more effective.When the levels are more than two,then the effectiveness is expected to be even higher.This is the case of Human Systems Therapy(HST),which is applied intrapsychically,on interpersonal relations and on family and/or larger systems,with interpersonal relations having a central role.HST is based on general systems principles and it constitutes a multilevel approach:(a)a definition of a human system,(b)epistemology,(c)a model of human systems personality/intelligence,(d)an increase in order and variety.Besides,HST includes a large number of techniques.Empirical support of HST effectiveness shows that(a)after seven sessions with schizophrenics,39%of psychotic symptoms are reduced,(b)after eight sessions with hashish adolescent users,all users stop the use completely,and(c)9 out of 11 psychiatric non-psychotic cases(81%),after four sessions,become non-psychiatric ones(treated).

Analogous Systems Principles and Concepts of Traditional Chinese Medicine and Congruence Couple Therapy

This article explicates the analogous principles and concepts between traditional Chinese medicine(TCM)and congruence couple therapy(CCT).Although originating out of vastly different times and places,TCM and CCT share a view of health based on systems understanding to facilitate the interconnections of the parts of an organism rather than focusing on eliminating symptoms.Both approaches aim to release Qi(气)and vitality by removing blockages through adjusting the interactions,adaptation,and balance of multiple elements and Yin‑Yang energies.The goal is to liberate the Qi or life force through improved holistic balance and cooperation.While TCM focuses on interventions at the level of the body,CCT focuses on the attention,awareness,acknowledgement,and alignment of the four human dimensions consisting of the intrapsychic,interpersonal,intergenerational,and universal‑spiritual.In light of the current trend toward increasing mental,substance use,and neurological disorders,in particular among countries of middle and low income,dialogue to explore these compatibilities between TCM and CCT is conducive to the continuous evolution of TCM and Western therapies to address not only physical health but also the exigencies of contemporary addiction and mental health care within a mind–body relationship matrix.

Lenvatinib as first-line therapy for recurrent hepatocellular carcinoma after liver transplantation:Is the current evidence applicable to these patients?

Liver transplantation(LT)is one of the leading curative therapies for hepatocellular carcinoma(HCC).Despite recent optimization of transplant selection criteria,including alpha-feto protein,HCC recurrence after LT is still the leading cause of death in these patients.During the last decades,effective systemic treatments for HCC,including tyrosine kinase inhibitors and immunotherapy,have been approved.We describe the clinical scenario of a patient with recurrence of HCC five years after LT,who received lenvatinib as first-line systemic therapy to introduce systemic treatment options in this clinical setting.In this opinion review,we detail first and second-line systemic treatment options,focusing on those feasible for patients with recurrent HCC after LT.Several trials have evaluated new drugs to treat HCC patients in first and secondline therapy,but patients with recurrent HCC after LT have been excluded from these trials.Consequently,most of the evidence comes from observational retrospective studies.Whether tyrosine kinase inhibitors will remain the primary therapeutic approach in these patients,due to a relative contraindication for immunotherapy,may be clarified in the near future.

Treatment Patterns and Economic Assessment of Systemic Therapy for Metastatic Colorectal Cancer

Introduction: Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the third leading cause of cancer deaths in the United States. The goal of this study was to understand treatment patterns, biomarker testing practices, treatment adherence, and the clinical and economic outcomes associated with chemotherapy for metastatic disease. Methods and Materials: We retrospectively examined electronic health records of patients with metastatic CRC who initiated chemotherapy between 01 January 2007 and 30 June 2011, with follow-up to 30 June 2012. Parameters analyzed included demographics and clinical characteristics, treatment patterns, clinical outcomes, and health care resource utilization. Results: In the analysis, 756 patients were included;median age was 61 years (55% male) at start of first line therapy. The most commonly used regimens in the first, second, and third line were FOLFOX + bevacizumab (46%), FOLFIRI + bevacizumab (23%), and irinotecan + cetuximab (23%) respectively. Adherence to guidelines decreased with increasing line of therapy. When assessed by treatment backbone categories in the third line, outcome measures including overall survival (OS), and time to treatment discontinuation (TTD) were not statistically different between groups. In the multivariable model, body mass index (BMI), performance status, and KRAS were significant predictors of survival. Conclusions: This study provides insight into patterns of care and outcomes of mCRC patients for the aforementioned time period. As treatment options for mCRC evolve, it is valuable to understand the continuum of care to help inform future treatment among candidates for continued therapy.

Current and novel approaches in the pharmacological treatment of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is one of the most lethal malignant tumours worldwide.The mortality-to-incidence ratio is up to 91.6%in many countries,representing the third leading cause of cancer-related deaths.Systemic drugs,including the multikinase inhibitors sorafenib and lenvatinib,are first-line drugs used in HCC treatment.Unfortunately,these therapies are ineffective in most cases due to late diagnosis and the development of tumour resistance.Thus,novel pharmacological alternatives are urgently needed.For instance,immune checkpoint inhibitors have provided new approaches targeting cells of the immune system.Furthermore,monoclonal antibodies against programmed cell death-1 have shown benefits in HCC patients.In addition,drug combinations,including first-line treatment and immunotherapy,as well as drug repurposing,are promising novel therapeutic alternatives.Here,we review the current and novel pharmacological approaches to fight HCC.Preclinical studies,as well as approved and ongoing clinical trials for liver cancer treatment,are discussed.The pharmacological opportunities analysed here should lead to significant improvement in HCC therapy.

Cohort study to assess geographical variation in cholangiocarcinoma treatment in England

BACKGROUND Outcomes for cholangiocarcinoma(CCA)are extremely poor owing to the complexities in diagnosing and managing a rare disease with heterogenous sub-types.Beyond curative surgery,which is only an option for a minority of patients diagnosed at an early stage,few systemic therapy options are currently recommended to relieve symptoms and prolong life.Stent insertion to manage disease complications requires highly specialised expertise.Evidence is lacking as to how CCA patients are managed in a real-world setting and whether there is any variation in treatments received by CCA patients.AIM To assess geographic variation in treatments received amongst CCA patients in England.METHODS Data used in this cohort study were drawn from the National Cancer Registration Dataset(NCRD),Hospital Episode Statistics and the Systemic Anti-Cancer Therapy Dataset.A cohort of 8853 CCA patients diagnosed between 2014-2017 in the National Health Service in England was identified from the NCRD.Potentially curative surgery for all patients and systemic therapy and stent insertion for 7751 individuals who did not receive surgery were identified as three end-points of interest.Linear probability models assessed variation in each of the three treatment modalities according to Cancer Alliance of residence at diagnosis,and for socio-demographic and clinical characteristics at diagnosis.RESULTS Of 8853 CCA patients,1102(12.4%)received potentially curative surgery.The mean[95%confidence interval(CI)]percentage-point difference from the population average ranged from-3.96(-6.34 to-1.59)%to 3.77(0.54 to 6.99)%across Cancer Alliances in England after adjustment for patient sociodemographic and clinical characteristics,showing statistically significant variation.Amongst 7751 who did not receive surgery,1542(19.9%)received systemic therapy,with mean[95%CI]percentage-point difference from the population average between-3.84(-8.04 to 0.35)%to 9.28(1.76 to 16.80)%across Cancer Alliances after adjustment,again showing the presence of statistically significant variation for some regions.Stent insertion was received by 2156(27.8%),with mean[95%CI]percentage-point difference from the population average between-10.54(-12.88 to-8.20)%to 13.64(9.22 to 18.06)%across Cancer Alliances after adjustment,showing wide and statistically significant variation from the population average.Half of 8853 patients(n=4468)received no treatment with either surgery,systemic therapy or stent insertion.CONCLUSION Substantial regional variation in treatments received by CCA patients was observed in England.Such variation could be due to differences in case-mix,clinical practice or access to specialist expertise.

Acute respiratory distress syndrome and severe pneumonitis after atezolizumab plus bevacizumab for hepatocellular carcinoma treatment:A case report

BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common cancers worldwide and has a high mortality.However,the treatment options for advanced HCC are limited to tyrosine kinase inhibitors,such as sorafenib and lenvatinib.Since previous regimens have an insufficient efficacy,the combination therapy of atezolizumab and bevacizumab(Ate/Bev)has been investigated,which showed an improvement in progression-free and overall survival.However,the adverse events of this combination therapy in advanced HCC have not been established.Herein,we report a novel case of an unresectable HCC and acute respiratory distress syndrome(ARDS)after a combination therapy of Ate/Bev.CASE SUMMARY An 82-year-old male visited our outpatient clinic for an incidentally detected liver mass.Liver magnetic resonance imaging and enhanced chest computed tomography(CT)were performed,which showed arterial hyperenhancement with washout in delayed phase suggesting HCC,and a well-defined metastatic solid nodule,respectively.F-18 fluorodeoxyglucose positron emission tomography(PET)-CT exhibited multiple hypermetabolic lesions in the iliac bone,lumbar vertebrae,and femur.Because of the high burden of the intrahepatic tumor,transarterial radioembolization was initially performed;after 37 d,a combination therapy of Ate/Bev was administered.The patient visited the emergency department three days after Ate/Bev treatment complaining of dyspnea.He was diagnosed with severe pneumonitis based on CT.Despite administering oxygen via a high-flow nasal cannula,the P/F ratio was only 74;therefore,the patient was diagnosed with ARDS based on the overall examination results.Low tidal volume with high positive end-expiratory pressure,sedative agents combined with a neuromuscular blocker,and a systemic steroid were promptly applied to manage the ARDS.However,the patient did not recover from the hypoxia and expired 31 h after being admitted.CONCLUSION Clinicians should be aware of severe pneumonitis due to the immune-related adverse events of this combination therapy,and patients should be closely monitored after therapy.

New First-line Immunotherapy-based Therapies for Unresectable Hepatocellular Carcinoma: A Living Network Meta-analysis

Background and Aims:Several first-line immune checkpoint inhibitor(ICI)-based combination therapies have been identified for unresectable hepatocellular carcinoma(uHCC).This network meta-analysis(NMA)aimed to provide the most updated evidence about the preferred first-line ICI-based regimens for uHCC.Methods:A comprehensive literature search was performed in various databases from database inception to May 2022.The phase 3 trials evaluating first-line single-agent ICIs,molecular-target agents(MTAs),or their combinations in uHCC were included.The main endpoints were overall survival(OS)and progression-free survival(PFS).Pooled effect estimates were calculated using a random effects model within the frequentist framework.Subgroup analyses based on etiology were also conducted.Results:Twelve trials at low risk of bias with 8,275 patients comparing 13 treatments were included.OS with atezolizumab plus bevacizumab was comparable to sintilimab plus IBI305[hazard ratio(HR):1.16;95%confidence interval(CI):0.80–1.68]and camrelizumab plus apatinib(HR:1.06;95%CI:0.75–1.51).The combination therapies,apart from atezolizumab plus cabozantinib in OS and durvalumab plus tremelimumab in PFS,had higher P-score than single-agent MTAs or ICIs.The survival benefits were associated with a high risk of adverse events leading to treatment discontinuation.The proportion of patients with hepatitis B virus-related HCC receiving ICIs combinations might positively correlate with survival advantages(R2=0.8039,p=0.0155).Conclusion:This NMA demonstrated that atezolizumab plus bevacizumab remains the stand of care and confers comparable survival benefits to sintilimab plus IBI305 and camrelizumab plus apatinib in first-line therapy for uHCC.The optimal treatment algorithms should consider efficacy,safety,and etiology.

Progress in surgical and nonsurgical approaches for hepatocellular carcinoma treatment

BACKGROUND： Hepatocellular carcinoma （HCC） is a com- plex and heterogeneous malignancy, frequently occurs in the setting of a chronically diseased organ, with multiple con- founding factors making its management challenging. HCC represents one of the leading causes of cancer-related mortal- ity globally with a rising trend of incidence in some of the de- veloped countries, which indicates the need for better surgical and nonsurgical management strategies.

Rectal neuroendocrine tumors:Current advances in management,treatment,and surveillance

Rectal neuroendocrine neoplasms(r-NENs)are considered among the most frequent digestive NENs,together with small bowel NENs.Their incidence has increased over the past few years,and this is probably due to the widespread use of endoscopic screening for colorectal cancer and the advanced endoscopic procedures available nowadays.According to the current European Neuroendocrine Tumor Society(ENETS)guidelines,well-differentiated r-NENs smaller than 10 mm should be endoscopically removed in view of their low risk of local and distant invasion.R-NENs larger than 20 mm are candidates for surgical resection because of their high risk of distant spreading and the involvement of the muscularis propria.There is an area of uncertainty regarding tumors between 10 and 20 mm,in which the metastatic risk is intermediate and the endoscopic treatment can be challenging.Once removed,the indications for surveillance are scarce and poorly codified by international guidelines,therefore in this paper,a possible algorithm is proposed.