Oligometastases in prostate cancer:Ablative treatment

Technological advances in radiotherapy have led to the introduction of techniques such as stereotactic body radiation therapy(SBRT), allowing the administration of ablative doses. The hypothesis that oligometastatic disease may be cured through local eradication therapies has led to the increasing use of SBRT in patients with this type of disease. At the same time, scientific advances are being made to allow the confirmation of clinically suspected oligometastatic status at molecular level. There is growing interest in identifying patients with oligometastatic prostate cancer(PCa) who may benefit from curative intent metastasis-directed therapy, including SBRT. The aim is to complement, replace or delay the introduction of hormone therapy or other systemic therapies. The present review aims to compile the evidence from the main ongoing studies and results on SBRT in relation to oligometastatic PCa; examine aspects where gaps in knowledge or a lack of consensus persist(e.g., optimum schemes, response assessment, identification and diagnosis of oligometastatic patients); and document the lack of first-level evidence supporting the use of such techniques.

Successful Surgical Treatment of Metachronous Oligometastases from Non-B, Non-C Hepatocellular Carcinoma

Hepatocellular Carcinoma (HCC) rarely metastasizes to bone or mediastinum. In some patients, surgical treatment of oligometastatic lesions from colorectal cancer, breast cancer, or non-small cell lung cancer results in satisfactory survival. However, data concerning oligometastatic lesions from HCC are scarce. We report the case of a patient with long-term survival after resection of metachronous oligometastases of HCC. A 54-year-old woman underwent hepatic resection for non-B, non-C HCC. A solitary left tenth rib tumor was detected 20 months after initial surgery and was surgically resected. A solitary mediastinal tumor was detected 6 months after the second operation and the patient again underwent surgical resection. Histopathological examination of both lesions confirmed metastasis of HCC. The patient has had no further recurrence 7 years after initial surgery without chemotherapy or radiotherapy.

Is there a survival benefit from adjuvant chemotherapy for patients with liver oligometastases from colorectal cancer after curative resection?

Background:Although colorectal oligometastases to the liver can potentially be cured with aggressive local abla-tion,the efficacy of adjuvant chemotherapy(ACT)for such metastasis remains unclear.The present study explored the effects of ACT on patients with colorectal liver oligometastases(CLO)after curative resections and aimed to iden-tify patients who could benefit from ACT.Methods:We retrospectively analyzed 264 eligible patients with CLO who underwent curative resection between September 1999 and June 2015.Recurrence-free survival(RFS)and overall survival(OS)were analyzed using the Kaplan-Meier method and log-rank test;prognostic factors were a by Cox regression modeling.Results:Among 264 patients,200(75.8%)patients received ACT and 64(24.2%)did not receive ACT.These two groups did not significantly differ in clinicopathologic characteristics,and had comparable 3-year OS and RFS rates(RFS:42.1%vs.45.7%,P=0.588;OS:69.7%vs.62.7%,P=0.446)over a median follow-up duration of 35.5 months,irrespective of preoperative chemotherapy.ACT markedly improved 3-year OS in high-risk patients with Memorial Sloan-Kettering Cancer Center clinical risk scores(MSKCC-CRS)of 3-5(68.2%vs.33.8%,P=0.015),but presented no additional benefit in patients with MSKCC-CRS of 0-2(72.2%vs.78.6%,P=0.834).In multivariate analysis,ACT was independently associated with improved OS in patients with MSKCC-CRS of 3-5.Conclusions:ACT might offer a prognostic benefit in high-risk patients with CLOs after curative liver resection,but not in low-risk patients.Therefore,patients’risk status should be determined before ACT administration to optimize postoperative therapeutic strategies.

Therapeutic strategy for postoperative recurrence in patients with non-small cell lung cancer

Postoperative recurrence occurs in approximately half of patients with non-small cell lung cancer(NSCLC), even after complete resection. Disease recurrence after surgical resection reduces the patient's life expectancy sharply. The prognosis after postoperative recurrence is considered to largely depend on both the mode of first recurrence(distant, locoregional or combined) and the treatment modality:(1) The majority of cases of postoperative recurrence involve distant metastasis with or without locoregional recurrence. Platinum-based systemic chemotherapy is practically accepted as the treatment for these diseases on the basis of evidence for original stage Ⅳ disease. The advent of both pemetrexed and molecular-targeted drugs has improved the survival of nonsquamous NSCLC and changed the chemotherapeutic algorithm for NSCLC;(2) Among patients with distant metastatic recurrence without locoregional recurrence at the primary tumor site, the metastasis is often limited in both organ and number. Such metastases are referred to as oligometastases. Local therapy, such as surgical resection and radiotherapy, has been suggested to be the first-line treatment of choice foroligometastatic recurrence; and(3) While locoregional recurrence is likely to cause troublesome symptoms, it is a potentially limited disease. Therefore, providing local control is important, and radiation is usually beneficial for treating local recurrence. In order to obtain better control of the disease and provide treatment with curative intent in patients with limited disease, the administration of concurrent platinum-based chemoradiotherapy is recommended according to the results of originally nonresectable stage ⅢA and ⅢB disease.

Management of oligometastatic non-small cell lung cancer patients:Current controversies and future directions

Oligometastatic non-small cell lung cancer(NSCLC)describes an intermediate stage of NSCLC between localized and widely-disseminated disease.This stage of NSCLC is characterized by a limited number of metastases and a more indolent tumor biology.Currently,the management of oligometastatic NSCLC involves radical treatment(radiotherapy or surgery)that targets the metastatic lesions and the primary tumor to achieve disease control.This approach offers the potential to achieve prolonged survival in patients who,in the past,would have only received palliative measures.The optimal therapeutic strategies for the different scenarios of oligometastatic disease(intracranial vs extracranial disease,synchronous vs metachronous)remain undefined.Given the lack of head-to-head studies comparing radiotherapy to surgery in these patients,the decision to apply surgery or radiotherapy(with or without systemic treatment)must be based on prognostic factors that allow us to classify patients.This classification will allow us to select the most appropriate therapeutic strategy on an individualized basis.In the future,the molecular or microRNA profiles will likely improve the treatment selection process.The objective of the present article is to review the most relevant scientific evidence on the management of patients with oligometastatic NSCLC,focusing on the role of radiotherapy and surgery.We also discuss areas of controversy and future directions.

Oligometastatic disease, the curative challenge in radiation oncology

The concept of oligometastatic disease was first described by Hellman and Weichselbaum in 1995. The mere insight of this concept led to the hypothesis that this disease may be cured using local ablative weapons. Surgery has already demonstrated this hypothesis. Surgery limitations, either technical or due to refusalor associated comorbidity, have led to implement alternative ablative options such as stereotactic body radiation therapy(SBRT). SBRT evolved from(stereotactic radiosurgery) because of the need to irradiate extracranial lesions and has been shown to be safe and effective. SBRT achieves local control rates ranging from 70%-90%, but highly variable survival rates depending on the group analyzed. Series with heterogeneous metastatic sites and tumor origin have reported 20% survival rates at 2-3 years, similar to those achieved with surgery. Despite its excellent results, SBRT still faces significant clinical challenges. Its optimal integration with systemic treatment is unknown, and response assessment is very difficult. However, the greatest challenge lies in selection of patients most likely to remain oligometastatic, those who will most benefit from the technique. Biomarkers, molecular signatures, that accurately predict the biological behavior of malignancy are needed. The expression profile of specific mi RNAs has been shown to have a potential in this regard.

Management of single pulmonary metastases from colorectal cancer:State of the art

Colorectal cancer(CRC)is one of the most common causes of death from cancer.Lung seeding occurs in approximately 10%of patients surgically treated for primary CRC with radical intent:the lung is the most common site of metastases after the liver.While surgical treatment of liver metastases is widely accepted to affect long-term outcomes,more controversial and not standardized is the therapy for CRC patients developing lung metastases.Experience suggests the potential curative role of pulmonary metastasectomy,especially in oligometastatic disease.However,the optimal strategy of care and the definition of prognostic factors after treatment still need to be defined.This review focused on the uncommon scenario of single pulmonary metastases from CRC.We explored pertinent literature and provide an overview of the epidemiology,clinical characteristics and imaging of single pulmonary metastases from CRC.Additionally,we identified the best available evidence for overall management.In particular,we analyzed the role and results of locoregional approaches(surgery,radiotherapy or ablative procedures)and their integration with systemic therapy.

Stereotactic body radiotherapy for oligo-recurrence within the nodal area from colorectal cancer

Recurrence of colorectal cancer(CRC)often presents as solitary metastases,oligometastases or oligo-recurrence.Surgical resection became the preferred treatment for patients with CRC lung and hepatic metastases.However,surgical treatment for oligo-recurrence within nodal area is not a widely accepted treatment due to due to their relative rarity and high postoperative morbidity.Stereotactic body radiotherapy(SBRT)is one of the emerging radiation treatment techniques in which a high radiation dose can be delivered to the tumor.High-dose SBRT can ablate the tumor with an efficacy similar to that achieved with surgery,especially for small tumors.However,there have been very few studies on SBRT for oligo-recurrence within nodal area,although several studies have evaluated the role of SBRT in the treatment of liver and lung metastases from CRC.This article reviews the current clinical status of and treatment methods for oligo-recurrence within nodal area from CRC,with particular emphasis on SBRT.

Oesophageal cancer metastases:An observational study of a more aggressive approach

BACKGROUND The prognosis for oesophageal carcinoma is poor,but once distant metastases emerge the prognosis is considered hopeless.There is no consistent protocol for the early identification and aggressive management of metastases.AIM To examine the outcome of a policy of active postoperative surveillance with aggressive treatment of confirmed metastases.METHODS A prospectively maintained database of 205 patients diagnosed with oesophageal carcinoma between 1998 and 2019 and treated with curative intent was interrogated for patients with metastases,either at diagnosis or on follow-up surveillance and treated for cure.This cohort was compared with incomplete clinical responders to neoadjuvant chemoradiotherapy(nCRT)who subsequently underwent surgery on their primary tumour.Overall survival was estimated using the Kaplan-Meier method,and the log-rank test was used to compare survival differences between groups.RESULTS Of 205 patients,11(5.4%)had metastases treated for cure(82%male;median age 60 years;9 adenocarcinoma and 2 squamous cell carcinomas).All had undergone neoadjuvant chemotherapy or chemoradiotherapy,followed by surgery in all but 1 case.Of the 11 patients,4 had metastatic disease at diagnosis,of whom 3 were successfully downstaged with nCRT before definitive surgery;2 of these 4 also developed oligometastatic recurrence and were treated with curative intent.Following definitive treatment,7 had treatment for metachronous oligometastatic disease;5 of whom underwent metastasectomy(adrenal×2;lung×2;liver×1).The median overall survival was 10.9 years[95%confidence interval(CI):0.7-21.0 years],which was statistically significantly longer than incomplete clinical responders undergoing surgery on the primary tumour without metastatic intervention[n=62;median overall survival=1.9(95%CI:1.1-2.7;P=0.012].The cumulative proportion surviving 1,3,and 5 years was 100%,91%,and 61%,respectively compared to 71%,36%,and 25%for incomplete clinical responders undergoing surgery on the primary tumour who did not undergo treatment for metastatic disease.CONCLUSION Metastatic oesophageal cancer represents a unique challenge,but aggressive treatment can be rewarded with impressive survival data.In view of recent advances in targeted therapies,intensive follow-up may yield a greater number of patients with curative potential and thus improved long-term survival.

Observation on the Clinical Effect of Stereotactic Body Radiotherapy in Patients with Oligometastatic Tumors

Objective:To observe the efficacy and safety of stereotactic body radiotherapy(SBRT)in the treatment of extracranial oligometastases.Method:A retrospective analysis of 70 patients with extracranial oligometastasis of malignant tumors who underwent SBRT in our hospital(Shaanxi Provincial People’s Hospital)from January 2019 to December 2021 with≤5 metastases,≤3 metastatic organs,and metastases with diameters of≤5 cm.According to the clinical data of patients,the dose-fractionation mode of SBRT is mainly determined according to the pathology of the primary tumor,the location of the metastatic tumor,and the important structures around the tumor.The local control,survival and adverse reactions were observed.Results:A total of 219 oligometastatic lesions in 70 patients were treated with SBRT.The median follow-up time was 24 months(12-40 months).The local control rate(LCR)of all target lesions assessed 3 months after radiotherapy was 94.1%;the 1-,2-,and 3-year LCRs were 88.6%,74.6%,and 64.9%,respectively.The median progression-free survival(PFS)was 11.8 months(95%CI,8.9-14.7 months),and the 1-and 2-year PFS rates were 48.6%and 32.6%,respectively;the median overall survival(OS)was 31.9 month(95%CI 26.0-37.8 months),the 1-year OS rate was 84.3%.The local control time,PFS,and OS of patients with metastases≤3 cm were significantly better than those with metastases>3 cm,and the differences were statistically significant(P<0.05).Acute adverse reactions after SBRT treatment in oligometastatic patients were mainly bone marrow suppression and gastrointestinal reactions,with incidence rates of 48.98%and 30.61%,respectively;chronic adverse reactions were mainly pain(bone,muscle),radiation enteritis,and radiation pneumonitis,with incidence rates of 38.57%,30.00%,and 24.29%,respectively.The treatment-related adverse reactions were mainly grade 1,which were all improved after symptomatic treatment,except for one patient with bone metastases from lung cancer who had grade 4 myelosuppression.No grade 4 or 5 adverse events occurred in the other patients.Conclusion:The application of SBRT in the treatment of extracranial oligometastases is safe,effective,and has high tolerability.

程序性细胞死亡配体1在结直肠癌肝脏寡转移灶的表达及其预后价值

背景:程序性细胞死亡配体1(PD-L1)在结直肠癌肝脏寡转移灶(CLO)表达的临床价值尚不明确。本研究旨在检测CLO微环境中PDL1的表达,并分析其与患者预后的关系。方法:收集1999年6月至2016年12月之间126例行根治性肝切除术的CLO患者的肝转移瘤标本。免疫组织化学法检测PD-L1在石蜡包埋标本中的表达水平。采用Kaplan-Meier法和Log-rank检验分析总体生存(OS)和无复发生存(RFS)。结果:PD-L1主要在肝转移灶的间质中表达。PD-L1高表达患者的临床风险更高(临床风险评分2–4分者比例:67.7%vs 40.4%,P=0.004)。中位随访58个月,PD-L1高表达患者3年OS(65.5%vs 92.7%,P=0.001)和3年RFS(34.7%vs 83.8%,P<0.001)均显著低于PD-L1低表达者。多因素Cox分析显示,PD-L1高表达(HR=3.581;95%CI 2.301–9.972,P=0.015),CRS 2–4分(HR=6.960,95%CI 1.135–42.689,P=0.036)及术前CA19-9增高(HR=2.843,95%CI 1.229–6.576,P=0.015)是OS的独立危险因素。PD-L1高表达(HR=4.815,95%CI 2.139–10.837,P<0.001)和原发灶淋巴结转移(HR=2.115,95%CI 1.041–4.297,P=0.038)是RFS的独立危险因素。结论:本研究发现PD-L1在CLO患者的肝转移灶间质中普遍表达,其高表达提示预后不良。