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Cancer Research and Treatment Oct 2023Despite numerous studies on the optimal treatments for oligometastatic disease (OMD), there is no established interdisciplinary consensus on its diagnosis or...
PURPOSE
Despite numerous studies on the optimal treatments for oligometastatic disease (OMD), there is no established interdisciplinary consensus on its diagnosis or classification. This survey-based study aimed to analyze the differential opinions of colorectal surgeons and radiation oncologists regarding the definition and treatment of OMD from the colorectal primary.
MATERIALS AND METHODS
A total of 141 participants were included in this study, consisting of 63 radiation oncologists (44.7%) and 78 colorectal surgeons (55.3%). The survey consisted of 19 questions related to OMD, and the responses were analyzed using the chi-square test to determine statistical differences between the specialties.
RESULTS
The radiation oncologists chose "bone" more frequently compared to the colorectal surgeons (19.2% vs. 36.5%, p=0.022), while colorectal surgeons favored "peritoneal seeding" (26.9% vs. 9.5%, p=0.009). Regarding the number of metastatic tumors, 48.3% of colorectal surgeons responded that "irrelevant, if all metastatic lesions are amendable to local therapy", while only 21.8% of radiation oncologist chose same answer. When asked about molecular diagnosis, most surgeons (74.8%) said it was important, but only 35.8% of radiation oncologists agreed.
CONCLUSION
This study demonstrates that although radiation oncologists and colorectal surgeons agreed on a majority of aspects such as diagnostic imaging, biomarker, systemic therapy, and optimal timing of OMD, they also had quite different perspectives on several aspects of OMD. Understanding these differences is crucial to achieving multidisciplinary consensus on the definition and optimal management of OMD.
Topics: Humans; Surveys and Questionnaires; Consensus; Biomarkers; Colorectal Neoplasms; Republic of Korea
PubMed: 37290481
DOI: 10.4143/crt.2023.479 -
European Urology Open Science Jun 2023We conducted and previously published a phase 2 trial of metastasis-directed therapy (MDT) in men with recurrence of prostate cancer at a low prostate-specific antigen...
UNLABELLED
We conducted and previously published a phase 2 trial of metastasis-directed therapy (MDT) in men with recurrence of prostate cancer at a low prostate-specific antigen level following radical prostatectomy and postoperative radiotherapy. All patients had negative conventional imaging and underwent prostate-specific membrane antigen (PSMA) positron emission tomography (PET). Patients without visible disease ( = 16) or with metastatic disease not amenable to MDT ( = 19) were excluded from the interventional study. The remaining patients with disease visible on PSMA-PET received MDT ( = 37). We analyzed all three groups to identify distinct phenotypes in the era of molecular imaging-based characterization of recurrent disease. Median follow up was 37 mo (interquartile range 27.5-43.0). There was no significant difference in time to the development of metastasis on conventional imaging among the groups; however, castrate-resistant prostate cancer-free survival was significantly shorter for patients with PSMA-avid disease not amenable to MDT ( = 0.047). Our findings suggest that PSMA-PET findings can help in discriminating diverging clinical phenotypes among men with disease recurrence and negative conventional imaging after local therapies with curative intent. There is a pressing need for better characterization of this rapidly growing population of patients with recurrent disease defined by PSMA-PET to derive robust selection criteria and outcome definitions for ongoing and future studies.
PATIENT SUMMARY
In men with prostate cancer with rising PSA levels following surgery and radiation, a newer type of scan called PSMA-PET (prostate-specific membrane antigen positron emission tomography) can be used to characterize and differentiate the patterns of recurrence, and inform future cancer outcomes.
PubMed: 37284049
DOI: 10.1016/j.euros.2023.03.016 -
Journal of Personalized Medicine May 2023To investigate the ability of radiotherapy (RT) to prolong progression-free survival (PFS) and to report treatment-related toxicities among oligoprogressive metastatic...
Introducing Radiotherapy in Metastatic Merkel Cell Carcinoma Patients with Limited Progression on Avelumab: An Effective Step against Primary and Secondary Immune Resistance?
PURPOSE
To investigate the ability of radiotherapy (RT) to prolong progression-free survival (PFS) and to report treatment-related toxicities among oligoprogressive metastatic Merkel cell carcinoma (mMCC) patients on avelumab.
METHODS
We retrospectively collected clinical data on mMCC patients who underwent radiotherapy for limited progression on avelumab. Patients were categorized as primary or secondary immune refractory depending on the time of onset of resistance to immunotherapy (at the first or subsequent follow-up visits after avelumab initiation). Pre- and post-RT PFS were calculated. Overall survival (OS) from the first progression treated with RT was also reported. Radiological responses and toxicities were evaluated according to the irRECIST criteria and RTOG scoring system, respectively.
RESULTS
Eight patients, including five females, with a median age of 75 years, met our inclusion criteria. The median gross tumor and clinical target volumes at first progression on avelumab were 29.85 cc and 236.7 cc, respectively. The treatment sites included lymph node, skin, brain, and spine metastases. Four patients received more than one course of RT. Most patients were treated with palliative radiation doses (mainly 30 Gy in 3 Gy/day fractions). Two patients were treated with stereotactic RT. Five/eight patients were primary immune refractory. The objective response rate at the first post-RT assessment was 75%, whereas no local failure was reported. The median pre-RT PFS was 3 months. The pre-RT PFS was 37.5% at 6 months and 12.5% at 1 year. The median post-RT PFS was not reached. The post-RT PFS was 60% at 6 months and 1 year. The post-RT OS was 85.7% at 1 year and 64.3% at 2 years. No relevant treatment-related toxicity was observed. After a median follow-up of 18.5 months, 6/8 patients are still alive and continuing on avelumab therapy.
CONCLUSIONS
Adding radiotherapy to mMCC patients with limited progression on avelumab seems to be safe and effective in prolonging the successful use of immunotherapy, regardless of the type of immune refractoriness.
PubMed: 37241012
DOI: 10.3390/jpm13050841 -
Clinical and Translational Radiation... Jul 2023Stereotactic ablative radiotherapy (SABR) is popularly used to treat bone metastasis. Despite its efficacy, adverse events, including vertebral compression fracture...
BACKGROUND AND PURPOSE
Stereotactic ablative radiotherapy (SABR) is popularly used to treat bone metastasis. Despite its efficacy, adverse events, including vertebral compression fracture (VCF), are frequently observed. Here, we investigated VCF risk after SABR for oligometastatic vertebral bone metastasis from hepatocellular carcinoma.
MATERIALS AND METHODS
A total of 84 patients with 144 metastatic bone lesions treated at three institutions between 2009 and 2019 were retrospectively reviewed. The primary endpoint was VCF development, either new or progression of a pre-existing VCF. VCFs were assessed using the spinal instability neoplastic score (SINS).
RESULTS
Among 144 spinal segments, 26 (18%) had pre-existing VCF and 90 (63%) had soft tissue extension. The median biologically effective dose (BED) was 76.8 Gy. VCF developed in 14 (12%) of 118 VCF-naïve patients and progressed in 20 of the 26 with pre-existing VCF. The median time to VCF development was 6 months (range, 1-12 months). The cumulative incidence of VCF at 12 months with SINS class I, II and III was 0%, 26% and 83%, respectively (p < 0.001). Significant factors for VCF development were pre-existing VCF, soft tissue extension, high BED, and SINS class in univariate analysis, and pre-existing VCF in multivariate analysis. Of the six components of SINS, pain, type of bone lesion, spine alignment, vertebral body collapse, and posterolateral involvement were identified as predictors of VCF development.
CONCLUSION
SABR for oligometastatic vertebral bone lesions from HCC resulted in a substantial rate of new VCF development and pre-existing VCF progression. Pre-existing VCF was significant risk factor for VCF development, which require special attention in patient care. Patients with SINS class III should be considered surgical treatment rather than upfront SABR.
PubMed: 37216046
DOI: 10.1016/j.ctro.2023.100636 -
European Urology Dec 2023In metastatic castration-sensitive prostate cancer (mCSPC), disease volume plays an integral role in guiding treatment recommendations, including selection of docetaxel...
Clinical and Genomic Differences Between Advanced Molecular Imaging-detected and Conventional Imaging-detected Metachronous Oligometastatic Castration-sensitive Prostate Cancer.
In metastatic castration-sensitive prostate cancer (mCSPC), disease volume plays an integral role in guiding treatment recommendations, including selection of docetaxel therapy, metastasis-directed therapy, and radiation to the prostate. Although there are multiple definitions of disease volume, they have commonly been studied in the context of metastases detected via conventional imaging (CIM). One such numeric definition of disease volume, termed oligometastasis, is heavily dependent on the sensitivity of the imaging modality. We performed an international multi-institutional retrospective review of men with metachronous oligometastatic CSPC (omCSPC), detected via either advanced molecular imaging alone (AMIM) or CIM. Patients were compared with respect to clinical and genomic features using the Mann-Whitney U test, Pearson's χ test, and Kaplan-Meier overall survival (OS) analyses with a log-rank test. A total of 295 patients were included for analysis. Patients with CIM-omCSPC had significantly higher Gleason grade group (p = 0.032), higher prostate-specific antigen at omCSPC diagnosis (8.0 vs 1.7 ng/ml; p < 0.001), more frequent pathogenic TP53 mutations (28% vs 17%; p = 0.030), and worse 10-yr OS (85% vs 100%; p < 0.001). This is the first report of clinical and biological differences between AMIM-detected and CIM-detected omCSPC. Our findings are particularly important for ongoing and planned clinical trials in omCSPC. PATIENT SUMMARY: Metastatic prostate cancer with just a few metastases only detected via newer scanning methods (called molecular imaging) is associated with fewer high-risk DNA mutations and better survival in comparison to metastatic cancer detected via conventional scan methods.
Topics: Male; Humans; Prostatic Neoplasms; Docetaxel; Molecular Imaging; Genomics; Castration
PubMed: 37173210
DOI: 10.1016/j.eururo.2023.04.025 -
Annals of Gastroenterological Surgery May 2023Oligometastatic disease has been proposed as an intermediate state between localized and polymetastatic disease that can benefit from multimodal treatment, including... (Review)
Review
Oligometastatic disease has been proposed as an intermediate state between localized and polymetastatic disease that can benefit from multimodal treatment, including surgery. There is a growing concern about performing surgery for oligometastatic pancreatic ductal adenocarcinoma, although there is still little evidence. We reviewed articles published between 2021 and 2022, focusing mainly on surgical outcomes. Furthermore, we summarized the current status of surgery in the multidisciplinary treatment of oligometastatic pancreatic cancer and discuss future perspectives. In liver oligometastasis, multimodal treatment including surgery achieved favorable long-term survival, especially in patients with good responses to preoperative chemotherapy, with a median survival time from 25.5 to 54.6 months. In addition, the data from the National Cancer Database in the United States showed that patients who underwent surgery for oligometastatic liver metastases had a significantly longer overall survival than those who received chemotherapy alone. Prognostic biomarkers were identified, including carbohydrate antigen 19-9 (CA19-9) levels at diagnosis and preoperative chemotherapy with normalization of CA19-9 levels or favorable radiological response. Patients with lung oligometastasis had a more favorable long-term prognosis than those with other recurrence sites, and the updated literature further confirmed the previous studies. Overall survival was favorable, with 84 months after initial surgery and 29.2 months after metastasectomy, and a 5-year survival rate of 60.6% was also reported. In peritoneal oligometastasis, the results of conversion surgery after good responses to preoperative treatment with intraperitoneal therapy or systematic chemotherapy were reported, and the conversion rate and long-term prognosis were favorable. There is a growing concern about performing surgery for oligometastatic pancreatic ductal adenocarcinoma. We reviewed articles published between 2021 and 2022, focusing mainly on surgical outcomes. Furthermore, we summarize the current status of surgery in multidisciplinary treatment of oligometastatic pancreatic cancer and discuss future perspectives.
PubMed: 37152775
DOI: 10.1002/ags3.12655 -
Clinical Cancer Research : An Official... Aug 2023The "oligometastasis" hypothesis proposes that metastases exist as a spectrum and are not always disseminated. According to this theory, a subset of patients with... (Review)
Review
The "oligometastasis" hypothesis proposes that metastases exist as a spectrum and are not always disseminated. According to this theory, a subset of patients with metastatic disease could benefit from aggressive local therapies. However, the identification of patients most likely to exhibit an oligometastatic phenotype remains challenging. Recent literature focusing on basic and translational studies has identified novel epigenetic regulators of epithelial-mesenchymal transition (EMT) and the emergence of a spectrum of metastatic behavior. Herein, we review these scientific advances and suggest that the spectrum of metastatic virulence produced by these epigenetic mechanisms broadly contributes to the emergence of clinically evident "oligometastases." Epigenetic regulation of EMT programs can result in a spectrum of cell trajectories (e.g., quasi-mesenchymal and highly mesenchymal states) with differential propensity to develop metastases. We propose that quasi-mesenchymal cell states may be associated with a polymetastatic phenotype, whereas highly mesenchymal cell states may be associated with a more oligometastatic phenotype. The mechanisms governing epigenetic regulation of EMT and its array of intermediate states are multifaceted and may contribute to the development of the metastatic spectrum observed clinically. Within this context, translational studies that support the role of EMT and its epigenetic regulation are discussed. Continued translation of these mechanistic discoveries into novel biomarkers may help optimally select patients most likely to exhibit an oligometastatic phenotype and benefit from aggressive local therapies, such as surgery, radiotherapy, and other ablative procedures.
Topics: Humans; Epigenesis, Genetic; Epithelial-Mesenchymal Transition; Neoplasms
PubMed: 37115507
DOI: 10.1158/1078-0432.CCR-23-0376 -
In Vivo (Athens, Greece) 2023Radiotherapy is a salvage therapy type for postoperative recurrence of esophageal cancer. Compared to conventional photon-based radiotherapy, proton beam therapy can...
BACKGROUND/AIM
Radiotherapy is a salvage therapy type for postoperative recurrence of esophageal cancer. Compared to conventional photon-based radiotherapy, proton beam therapy can reduce the irradiated dose to the surrounding organs, facilitating the management of patients who are unfit for radiotherapy. In this study, the outcomes and toxicity of proton beam therapy for postoperative lymph node oligorecurrence of esophageal cancer were investigated.
PATIENTS AND METHODS
We retrospectively evaluated the clinical outcomes and toxicity of 13 sites in 11 patients treated with proton beam therapy for postoperative lymph node oligorecurrence of esophageal cancer. In total, eight men and three women with a median age of 68 years (range=46-83 years) were included.
RESULTS
The median follow-up period was 20.2 months. During the follow-up period, four patients died of esophageal cancer. Eight of the 11 patients developed recurrence; of these, seven patients had recurrence outside the irradiated field, and one had recurrence inside and outside the irradiated field. The 2-year overall survival, progression-free survival, and local control rates were 48.0%, 27.3%, and 84.6%, respectively. The median survival time was 22.4 months. There were no severe acute or late adverse events.
CONCLUSION
Proton beam therapy could be a safe and effective treatment method for postoperative lymph node oligorecurrence of esophageal cancer. It may be beneficial even in cases where conventional photon-based radiotherapy is difficult to administer in combination with increased doses or with chemotherapy.
Topics: Male; Humans; Female; Middle Aged; Aged; Aged, 80 and over; Proton Therapy; Retrospective Studies; Esophageal Neoplasms; Treatment Outcome; Lymph Nodes; Neoplasm Recurrence, Local
PubMed: 37103111
DOI: 10.21873/invivo.13202 -
Cirugia Y Cirujanos 2023Pancreatic cancer is the seventh leading cause of death worldwide, with ductal adenocarcinoma as the most frequent neoplasm. Half of the patients who are diagnosed have... (Review)
Review
BACKGROUND
Pancreatic cancer is the seventh leading cause of death worldwide, with ductal adenocarcinoma as the most frequent neoplasm. Half of the patients who are diagnosed have metastases at the time of diagnosis.
OBJECTIVE
A review of the treatment of resectable pancreatic adenocarcinoma with oligometastatic disease was carried out in order to present an overview of the existing evidence.
METHOD
A bibliographic search was carried in PubMed/Medline, Clinical Key and Index Medicus vhith MESH terms, from the year 1993 to 2022.
RESULTS
Patients with liver or lung metastases due to pancreatic ductal adenocarcinoma who undergo surgery and chemotherapy have a longer survival in carefully selected patients.
CONCLUSIONS
The evidence regarding surgery in patients with pancreatic ductal adenocarcinoma and oligometastasis is limited and further randomized controlled trials are needed for both scenarios. As well as established criteria that help the selection of patients who can receive this type of treatment.
Topics: Humans; Pancreatic Neoplasms; Adenocarcinoma; Carcinoma, Pancreatic Ductal; Lung Neoplasms
PubMed: 37084317
DOI: 10.24875/CIRU.22000364 -
International Journal of General... 2023To investigate the clinical efficacy of intensity-modulated radiotherapy (IMRT) combined with transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma...
Evaluation of the Clinical Efficacy of Intensity-Modulated Radiotherapy Combined with Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma with Extrahepatic Oligometastasis and Prognostic Factors for Patient Survival.
OBJECTIVE
To investigate the clinical efficacy of intensity-modulated radiotherapy (IMRT) combined with transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients with extrahepatic oligometastasis and the prognosis of patients receiving this treatment.
PATIENTS AND METHODS
Twenty-one HCC patients with extrahepatic oligometastasis were retrospectively analyzed; seven patients received IMRT only, and 14 received IMRT plus TACE. TACE treatment was administered before IMRT (50 mg epirubicin, oxaliplatin 100 mg, and mitomycin 10 mg). The short-term efficacy of this treatment and patient prognosis were evaluated.
RESULTS
Complete response (CR) and partial response (PR) in the intrahepatic region were achieved in three and 14 patients, respectively. The objective response rate (ORR) approached 81%. CR and PR were achieved in six and 10 patients with extrahepatic metastases, respectively, for an ORR of 100%. Pain was completely relieved in all patients with bone metastases. The median overall survival (OS) and progression-free survival (PFS) were 21 months and 9.1 months, respectively. The 1-year PFS rate was 43%, and the 1-, 2-, 3-, and 4-year OS rates were 83%, 35%, 9%, and 4%, respectively. Univariate analysis showed that the prognostic factors for patient survival included Child-Pugh class, vascular thrombus, Karnofsky performance status (KPS), radiotherapy dose, ascites, combination therapy, and pattern of progression. Multivariate analysis showed that vascular thrombus, combination therapy, and pattern of failure were prognostic factors for PFS, and the KPS was the only prognostic factor for OS. No grade 3-4 adverse reactions were observed.
CONCLUSION
IMRT combined with TACE is safe and feasible without major toxicities for the treatment of advanced HCC patients with extrahepatic oligometastasis and results in excellent objective efficacy and a potential survival benefit. The KPS is the only predictive factor for OS. This approach is expected to be a useful palliative option for selected HCC patients with extrahepatic metastases.
PubMed: 37077764
DOI: 10.2147/IJGM.S403316