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European Urology Oncology Jun 2024Oligometastatic castration-sensitive prostate cancer (omCSPC) represents an early state in the progression of metastatic disease for which patients experience better...
BACKGROUND AND OBJECTIVE
Oligometastatic castration-sensitive prostate cancer (omCSPC) represents an early state in the progression of metastatic disease for which patients experience better outcomes in comparison to those with higher disease burden. Despite the generally more indolent nature, there is still much heterogeneity, with some patients experiencing a more aggressive clinical course unexplained by clinical features alone. Our aim was to investigate correlation of tumor genomics with the mode of progression (MOP) and pattern of failure (POF) following first treatment (metastasis-directed and/or systemic therapy) for omCSPC.
METHODS
We performed an international multi-institutional retrospective study of men treated for metachronous omCSPC who underwent tumor next-generation sequencing with at least 1 yr of follow-up after their first treatment. Descriptive MOP and POF results are reported with respect to the presence of genomic alterations in pathways of interest. MOP was defined as class I, long-term control (LTC; no radiographic progression at last follow-up), class II, oligoprogression (1-3 lesions), or class III, polyprogression (≥4 lesions). POF included the location of lesions at first failure. Genomic pathways of interest included TP53, ATM, RB1, BRCA1/2, SPOP, and WNT (APC, CTNNB1, RNF43). Genomic associations with MOP/POF were compared using χ tests. Exploratory analyses revealed that the COSMIC mutational signature and differential gene expression were also correlated with MOP/POF. Overall survival (OS) was calculated via the Kaplan-Meier method from the time of first failure.
KEY FINDINGS AND CLINICAL IMPLICATIONS
We included 267 patients in our analysis; the majority had either one (47%) or two (30%) metastatic lesions at oligometastasis. The 3-yr OS rate was significantly associated with MOP (71% for polyprogression vs 91% for oligoprogression; p = 0.005). TP53 mutation was associated with a significantly lower LTC rate (27.6% vs 42.3%; p = 0.04) and RB1 mutation was associated with a high rate of polyprogression (50% vs 19.9%; p = 0.022). Regarding POF, bone failure was significantly more common with tumors harboring TP53 mutations (44.8% vs25.9%; p = 0.005) and less common with SPOP mutations (7.1% vs 31.4%; p = 0.007). Visceral failure was more common with tumors harboring either WNT pathway mutations (17.2% vs 6.8%, p = 0.05) or SPOP mutations (17.9% vs 6.3%; p = 0.04). Finally, visceral and bone failures were associated with distinct gene-expression profiles.
CONCLUSIONS AND CLINICAL IMPLICATIONS
Tumor genomics provides novel insight into MOP and POF following treatment for metachronous omCSPC. Patients with TP53 and RB1 mutations have a higher likelihood of progression, and TP53, SPOP, and WNT pathway mutations may have a role in metastatic organotropism.
PATIENT SUMMARY
We evaluated cancer progression after a first treatment for metastatic prostate cancer with up to five metastases. We found that mutations in certain genes were associated with the location and extent of further metastasis in these patients.
PubMed: 38862340
DOI: 10.1016/j.euo.2024.05.011 -
Radiotherapy and Oncology : Journal of... Jun 2024Current radiotherapy guidelines rely heavily on imaging-based monitoring. Liquid biopsy monitoring promises to complement imaging by providing frequent systemic...
BACKGROUND AND PURPOSE
Current radiotherapy guidelines rely heavily on imaging-based monitoring. Liquid biopsy monitoring promises to complement imaging by providing frequent systemic information about the tumor. In particular, cell-free DNA (cfDNA) sequencing offers a tumor-agnostic approach, which lends itself to monitoring heterogeneous cohorts of cancer patients.
METHODS
We collected plasma cfDNA from oligometastatic patients (OMD) and head-and-neck cancer patients (SCCHN) at six time points before, during, and after radiotherapy, and compared them to the plasma samples of healthy and polymetastatic volunteers. We performed low-pass (on average 7x) whole-genome sequencing on 93 plasma cfDNA samples and correlated copy number alterations and fragment length distributions to clinical and imaging findings.
RESULTS
We observed copy number alterations in 4/7 polymetastatic cancer patients, 1/7 OMD and 1/7 SCCHN patients, these patients' imaging showed progression following radiotherapy. Using unsupervised learning, we identified cancer-specific fragment length features that showed a strong correlation with copy number-based tumor fraction estimates. In 4/4 HPV-positive SCCHN patient samples, we detected viral DNA that enabled the monitoring of very low tumor fraction samples.
CONCLUSIONS
Our results indicate that an elevated tumor fraction is associated with tumor aggressiveness and systemic tumor spread. This information may be used to adapt treatment strategies. Further, we show that by detecting specific sequences such as viral DNA, the sensitivity of detecting cancer from cell-free DNA sequencing data can be greatly increased.
PubMed: 38834154
DOI: 10.1016/j.radonc.2024.110364 -
Advances in Radiation Oncology Jul 2024Initial studies investigating the combination of local and systemic treatments in advanced esophageal cancer (EC) have conflicting conclusions regarding survival... (Review)
Review
PURPOSE
Initial studies investigating the combination of local and systemic treatments in advanced esophageal cancer (EC) have conflicting conclusions regarding survival benefits. The objective of this systematic review and meta-analysis is to assess the efficacy of the addition of local therapy to systemic treatments in patients with advanced EC.
METHODS AND MATERIALS
A systematic literature search was conducted in the PubMed, EMBASE, and CENTRAL databases. Key eligibility criteria included studies that enrolled patients with histologically confirmed EC or esophagogastric junction cancer with metastasis or recurrence and compared survival benefits between the combined local and systemic treatment group and the systemic treatment alone group. Survival outcomes, represented by hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS), were pooled using a random effects model. The MINORS score was adopted for quality assessment. Risk of bias was statistically examined by Begg's and Egger's tests.
RESULTS
A total of 1 randomized controlled trial (RCT) and 10 qualified retrospective studies including 14,489 patients were identified. Addition of local therapy to systemic treatment significantly improved PFS (HR, 0.52; 95% CI, 0.37-0.73; < .001) and OS (HR, 0.69; 95% CI, 0.58-0.81; < .0001) compared with systemic treatment alone. The subgroup analysis revealed that combined local and systemic treatment conferred a significant survival advantage in both patients with oligometastasis (PFS: HR, 0.45; 95% CI, 0.31-0.64; < .0001; OS: HR, 0.62; 95% CI, 0.48-0.79; < .0001) and recurrence (OS: HR, 0.55; 95% CI, 0.37-0.81; = .002).
CONCLUSIONS
In conclusion, addition of local treatment to systemic therapy can improve survival in patients with advanced EC, particularly in those with oligometastasis or recurrent diseases.
PubMed: 38826154
DOI: 10.1016/j.adro.2024.101522 -
Clinical and Translational Radiation... Jul 2024Stereotactic body radiotherapy (SBRT) is increasingly applied for pelvic lymph node recurrence. Thus far, knowledge on pelvic lymph node motion during CBCT-guided SBRT...
BACKGROUND AND PURPOSE
Stereotactic body radiotherapy (SBRT) is increasingly applied for pelvic lymph node recurrence. Thus far, knowledge on pelvic lymph node motion during CBCT-guided SBRT is lacking and the applied margins vary between institutions. This study evaluated pelvic lymph node motion during CBCT-guided SBRT and assessed the currently applied PTV margins of 3 and 5 mm.
MATERIAL AND METHODS
In total, 45 pelvic lymph node metastases were included. One observer delineated 45 GTVs on planning CT, 224 GTVs on pre-fraction and 216 on post-fraction CBCT. The GTV centroid coordinates were derived from all images for inter- and intrafraction motion analysis. Additionally, we assessed the influence of treatment time and lesion location on lesion motion. The expected coverage of a 3-mm and 5-mm PTV margin was assessed using the inclusiveness index for GTVs on pre- and post-fraction CBCT.
RESULTS
Lymph node interfraction motion was limited to 5 mm in 96-97 % of fractions for all translational directions and intrafraction lesion motion was limited to 3 mm in 97-100 % of fractions. Para-rectal lesions (11 %) were associated with significantly larger inter- and intrafraction motion compared to other pelvic locations and treatment duration showed no correlation with lesion motion. The mean (sd) lesion inclusiveness index was 99 % (5 %) for the 5-mm PTV margin and 96 % (9 %) for the 3-mm margin.
CONCLUSION
Pelvic lymph node motion during CBCT-guided stereotactic radiotherapy was within the widely applied PTV margin of 5 mm, providing an opportunity to reduce this margin for pelvic lymph node SBRT.
PubMed: 38798748
DOI: 10.1016/j.ctro.2024.100794 -
Journal of Mid-life Health 2024This case report describes a rare example of a solitary abdominal wall metastasis in a middle-aged endometrial cancer (EC) survivor 3 years following disease-free...
This case report describes a rare example of a solitary abdominal wall metastasis in a middle-aged endometrial cancer (EC) survivor 3 years following disease-free status. Following induction chemotherapy, she had a margin-negative surgical excision of the abdominal tumor. Surprisingly, the patient has been disease-free for more than 3 years after the operation. This emphasizes the necessity of addressing single metastasis amenable to surgical resection, as well as the need for diligent monitoring to discover recurrences sooner. Understanding rare locations of recurrence, such as the abdominal wall, is critical for optimum EC therapy and care. The data given in this article adds to the existing body of information on atypical presentations and recurrent EC therapy. Additional research is required to develop evidence-based guidance.
PubMed: 38764921
DOI: 10.4103/jmh.jmh_118_23 -
Cureus Apr 2024The present study aimed to evaluate proton beam therapy (PBT) for stage IV pancreatic adenocarcinoma and its metastases and define the criteria for eligibility....
BACKGROUND
The present study aimed to evaluate proton beam therapy (PBT) for stage IV pancreatic adenocarcinoma and its metastases and define the criteria for eligibility. Materials and methods: We retrospectively evaluated the patients who had a histopathological diagnosis of pancreatic adenocarcinoma, had progressed to stage IV, and underwent PBT for both the primary and some metastatic lesions between 2017 and 2022. PBT was performed using the passive scattering technique.
RESULTS
Sixteen patients (median age, 72 years; range, 55-85 years) were enrolled. All patients had stage IV pancreatic cancer at the initiation of PBT. The median duration from the date of stage IV diagnosis to the initiation of PBT was 5.8 (range, 0.4-13.5) months. Three patients had been diagnosed as having recurrent stage IV cancer at other institutions before their referral to our hospital because they had local recurrence and distant metastases after the resection of the primary tumor. Chemotherapy was as follows: pre-PBT, 0, 1, 2, and 3 lines in 4, 7, 4, and 1 patients, respectively; concurrent with PBT, 0 and 1 line in 11 and 5 patients, respectively; post-PBT, 0 and 1 line in 5 and 5 patients, respectively; and unknown, 6 patients. The median survival times (MSTs) from the date of stage IV diagnosis for the with or without non-irradiated active metastatic tumor were 11.4 and 20.1 months, respectively. Univariate analysis revealed that the performance status (PS) levels ( < 0.01), the carbohydrate antigen (CA) 19-9 tumor marker levels ( < 0.01), active tumors not treated with irradiation ( = 0.02), and with or without post-PBT chemotherapy ( < 0.01) were statistically significant factors. Multivariate analysis revealed that the CA 19-9 tumor marker levels (= 0.04), the number of metastatic lesions ( = 0.049), and with or without non-irradiated active metastatic tumors ( = 0.02) were significant factors.
CONCLUSION
PBT is indicated when the number of metastases is limited to ≤ 4 lesions and all tumors can be irradiated within the smallest possible number of irradiation fields that can be performed within the patient's tolerable time, which is a subjective duration that depends on the patient's reaction during each session. It may be a viable treatment option for patients with oligometastatic pancreatic cancer.
PubMed: 38716033
DOI: 10.7759/cureus.57771 -
Annals of Gastroenterological Surgery May 2024Whether surgical intervention for patients with oligometastatic recurrence can improve their post-recurrent prognosis is unclear. In this study, we introduce a novel...
PURPOSE
Whether surgical intervention for patients with oligometastatic recurrence can improve their post-recurrent prognosis is unclear. In this study, we introduce a novel concept of oligometastasis in post-surgical pancreatic ductal adenocarcinoma (PDAC) patients with hepatic recurrence, which we call "oligo-like liver metastasis (OLLM)." Patients with OLLM have better post-recurrence prognosis and could therefore be eligible for surgical intervention.
METHODS
A total of 121 PDAC patients who underwent radical resection, and who had an initial and single-organ metastasis to the liver, were analyzed. Independent prognostic factors for overall survival after recurrence (OSAR) were examined, and patients with all of these factors were defined as OLLM. The clinicopathological features and post-recurrent prognosis of OLLM patients were evaluated. In addition, a detailed analysis using the oligo-score, which was based on the prognostic factors, was performed.
RESULTS
The prognostic analysis revealed that short recurrence-free interval (RFI) (<6 months), short stable disease interval (SDI) (≤3 months), and four or more recurrent tumors were independent poor prognostic factors. OLLM patients were defined as those with all three conditions: long RFI (≥6 months), long SDI (>3 months), and three or less recurrent tumors. OLLM patients had a significantly better prognosis for OSAR than non-OLLM patients (HR = 0.272, < 0.001). Further analysis demonstrated that the OSAR of patients could be stratified using the oligo-score, which was calculated based on the prognostic factors.
CONCLUSION
We recommend that OLLM should be used to predict which patients are most likely to experience better post-recurrent prognosis after surgery with curative intent.
PubMed: 38707220
DOI: 10.1002/ags3.12753 -
European Journal of Cancer (Oxford,... Jun 2024The OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric...
INTRODUCTION
The OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric oligometastatic disease (OMD).
METHODS
Guidelines were developed according to AGREE II and GRADE principles. Guidelines were based on a systematic review (OMEC-1), clinical case discussions (OMEC-2), and a Delphi consensus study (OMEC-3) by 49 European expert centers for esophagogastric cancer. OMEC identified patients for whom the term OMD is considered or could be considered. Disease-free interval (DFI) was defined as the time between primary tumor treatment and detection of OMD.
RESULTS
Moderate to high quality of evidence was found (i.e. 1 randomized and 4 non-randomized phase II trials) resulting in moderate recommendations. OMD is considered in esophagogastric cancer patients with 1 organ with ≤ 3 metastases or 1 involved extra-regional lymph node station. In addition, OMD continues to be considered in patients with OMD without progression in number of metastases after systemic therapy. F-FDG PET/CT imaging is recommended for baseline staging and for restaging after systemic therapy when local treatment is considered. For patients with synchronous OMD or metachronous OMD and a DFI ≤ 2 years, recommended treatment consists of systemic therapy followed by restaging to assess suitability for local treatment. For patients with metachronous OMD and DFI > 2 years, upfront local treatment is additionally recommended.
DISCUSSION
These multidisciplinary European clinical practice guidelines for the uniform definition, diagnosis and treatment of esophagogastric OMD can be used to standardize inclusion criteria in future clinical trials and to reduce variation in treatment.
Topics: Humans; Esophageal Neoplasms; Stomach Neoplasms; Europe; Consensus; Neoplasm Metastasis; Delphi Technique
PubMed: 38678762
DOI: 10.1016/j.ejca.2024.114062 -
Current Oncology Reports Jun 2024We examine the potential for curative approaches among metastatic breast cancer (MBC) patients by exploring the recent literature on local ablative therapies like... (Review)
Review
PURPOSE
We examine the potential for curative approaches among metastatic breast cancer (MBC) patients by exploring the recent literature on local ablative therapies like surgery and stereotactic body radiation therapy (SBRT) in patients with oligometastatic (OM) breast cancer. We also cover therapies for MBC patients with oligoprogressive (OP) disease.
KEY FINDINGS
Surgery and SBRT have been studied for OM and OP breast cancer, mainly in retrospective or non-randomized trials. While many studies demonstrated favorable results, a cooperative study and single-institution trial found no support for surgery/SBRT in OM and OP cases, respectively.
CONCLUSION
While there is interest in applying local therapies to OM and OP breast cancer, the current randomized data does not back the routine use of surgery or SBRT, particularly when considering the potential for treatment-related toxicities. Future research should refine patient selection through advanced imaging and possibly explore these therapies specifically in patients with hormone receptor-positive or HER2-positive disease.
Topics: Humans; Breast Neoplasms; Female; Radiosurgery; Disease Progression; Neoplasm Metastasis
PubMed: 38652425
DOI: 10.1007/s11912-024-01529-2 -
BMC Cancer Apr 2024The treatment for lung oligometastasis from colorectal cancer (CRC) remains challenging. This retrospective study aimed to compare the local tumor control, survival and...
BACKGROUND
The treatment for lung oligometastasis from colorectal cancer (CRC) remains challenging. This retrospective study aimed to compare the local tumor control, survival and procedure-related complications in CRC patients undergoing low-dose rate stereotactic ablative brachytherapy (L-SABT) versus percutaneous microwave ablation (MWA) for lung oligometastasis.
METHODS
Patients between November 2017 and December 2020 were retrospectively analyzed. Local tumor progression-free survival (LTPFS) and overall survival (OS) were analyzed in the entire cohort as well as by stratified analysis based on the minimal ablation margin (MAM) around the tumor.
RESULTS
The final analysis included 122 patients: 74 and 48 in the brachytherapy and MWA groups, respectively, with a median follow-up of 30.5 and 35.3 months. The 1- and 3-year LTPFS rate was 54.1% and 40.5% in the brachytherapy group versus 58.3% and 41.7% in the MWA group (P = 0.524 and 0.889, respectively). The 1- and 3-year OS rate was 75.7% and 48.6% versus 75.0% and 50.0% (P = 0.775 and 0.918, respectively). Neither LTPFS nor OS differed significantly between the patients with MAM of 5-10 mm versus > 10 mm. Pulmonary complication rate did not differ in the overall analysis, but was significantly higher in the MWA group in the subgroup analysis that only included patients with lesion within 10 mm from the key structures (P = 0.005). The increased complications was primarily bronchopleural fistula.
CONCLUSIONS
Considering the caveats associated with radioisotope use in L-SABT, MWA is generally preferable. In patients with lesion within 10 mm from the key pulmonary structures, however, L-SABT could be considered as an alternative due to lower risk of bronchopleural fistula.
Topics: Humans; Lung Neoplasms; Retrospective Studies; Salvage Therapy; Microwaves; Brachytherapy; Treatment Outcome; Lung; Colorectal Neoplasms; Fistula; Liver Neoplasms; Catheter Ablation
PubMed: 38627695
DOI: 10.1186/s12885-024-12163-3