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The Journal of Urology Mar 2022The oncologic benefit of postchemotherapy (PC) residual tumor resection (RTR) in patients with germ cell tumors and elevated serum tumor markers (STMs) remains unclear....
PURPOSE
The oncologic benefit of postchemotherapy (PC) residual tumor resection (RTR) in patients with germ cell tumors and elevated serum tumor markers (STMs) remains unclear. This analysis was performed to better define patients who benefit from surgery in this setting.
MATERIALS AND METHODS
Of 575 PC-RTR procedures (July 2008-July 2019) 153 were performed in patients with elevated STMs (human chorionic gonadotropin [HCG] >2.0 mIU/ml, alpha-fetoprotein [AFP] >7.0 µg/l), including 55 after first line and 98 after second or later line chemotherapy.
RESULTS
Viable cancer in the resected specimen was significantly more common in the salvage group than in the first line group (48.98% vs 16.36%, p=0.0001988) and was a predictor of survival in both groups. A preoperative serum level of AFP ≥30 µg/l was a significant predictor of viable cancer in the first line and salvage groups (55.56% [p=0.0157] and 66.67% [p=0.0017], respectively). The overall relapse-free survival rate (22.7% and 50%, p=0.00032) and overall survival rate (37.8% and 65%, p=0.0059) were significantly worse in the salvage group than in the first line group. A preoperative serum level of AFP ≥30 µg/l and viable cancer/teratoma found in the histological examination of the RTR specimens were significant predictors of relapse after first line chemotherapy. Serum AFP ≥30 µg/l and HCG ≥20 mIU/ml were significant factors affecting survival in the first line group.
CONCLUSIONS
Patients with AFP serum levels >30 µg/l and HCG ≥20 mIU/ml after first line chemotherapy should receive salvage chemotherapy instead of surgery. After second or later line therapy, the prognosis of patients with elevated markers and surgery is poor regardless of the tumor marker levels. However, 38% of these patients are long-term survivors, which justifies PC-RTR in this setting.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chorionic Gonadotropin; Humans; Male; Middle Aged; Neoplasm, Residual; Neoplasms, Germ Cell and Embryonal; Prognosis; Salvage Therapy; Survival Rate; Testicular Neoplasms; alpha-Fetoproteins
PubMed: 34694152
DOI: 10.1097/JU.0000000000002270 -
BMC Medicine May 2023The sensitivity and specificity of minimal residual disease detected by circulating tumor DNA profiling (ctDNA MRD) in lung cancer, with particular attention to the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The sensitivity and specificity of minimal residual disease detected by circulating tumor DNA profiling (ctDNA MRD) in lung cancer, with particular attention to the distinction between landmark strategy and surveillance strategy, for predicting relapse in lung cancer patients after definitive therapy has yet to be determined.
METHODS
The prognostic value of ctDNA MRD by landmark strategy and surveillance strategy was evaluated in a large cohort of patients with lung cancer who received definitive therapy using a systemic literature review and meta-analysis. Recurrence status stratified by ctDNA MRD result (positive or negative) was extracted as the clinical endpoint. We calculated the area under the summary receiver operating characteristic curves, and pooled sensitivities and specificities. Subgroup analyses were conducted based on histological type and stage of lung cancer, types of definitive therapy, and ctDNA MRD detection methods (detection technology and strategy such as tumor-informed or tumor-agnostic).
RESULTS
This systematic review and meta-analysis of 16 unique studies includes 1251 patients with lung cancer treated with definitive therapy. The specificity of ctDNA MRD in predicting recurrence is high (0.86-0.95) with moderate sensitivity (0.41-0.76), whether shortly after treatment or during the surveillance. The landmark strategy appears to be more specific but less sensitive than the surveillance strategy.
CONCLUSIONS
Our study suggests that ctDNA MRD is a relatively promising biomarker for relapse prediction among lung cancer patients after definitive therapy, with a high specificity but suboptimal sensitivity, whether in landmark strategy or surveillance strategy. Although surveillance ctDNA MRD analysis decreases specificity compared with the landmark strategy, the decrease is minimal compared to the increase in sensitivity for relapse prediction of lung cancer.
Topics: Humans; Circulating Tumor DNA; Neoplasm, Residual; Lung Neoplasms; ROC Curve; Biomarkers, Tumor; Neoplasm Recurrence, Local
PubMed: 37173789
DOI: 10.1186/s12916-023-02849-z -
Journal of Gastrointestinal Cancer Dec 2021The goal of successful cancer treatment is targeting the eradication of cancer cells. Although surgical removal of the primary tumors and several rounds of chemo- and... (Review)
Review
The goal of successful cancer treatment is targeting the eradication of cancer cells. Although surgical removal of the primary tumors and several rounds of chemo- and radiotherapy reduce the disease burden, in some cases, asymptomatic dormant cancer cells may still exist in the body. Dormant cells arise from the disseminated tumor cells (DTCs) from the primary lesion. DTCs escape from immune system and cancer therapy and reside at the secondary organ without showing no sign of proliferation. However, under some conditions. dormant cells can be re-activated and enter a proliferative state even after decades. As a stress response mechanism, autophagy may help the adaptation of DTCs at this futile foreign microenvironment and may control the survival and re-activation of dormant cells. Studies indicate that hepatic microenvironment serves a favorable condition for cancer cell dormancy. Although, no direct study was pointing out the role of autophagy in liver-assisted dormancy, involvement of autophagy in both liver microenvironment, health, and disease conditions has been indicated. Therefore, in this review article, we will summarize cancer dormancy and discuss the role and importance of autophagy and hepatic microenvironment in this context.
Topics: Animals; Autophagy; Breast Neoplasms; Female; Humans; Liver Neoplasms; Male; Mice; Neoplasm Metastasis; Neoplasm, Residual; Tumor Microenvironment
PubMed: 34921672
DOI: 10.1007/s12029-021-00774-z -
Haematologica Jul 2024Multiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of plasma cells. MM is a heterogeneous disease, featured by various molecular... (Review)
Review
Multiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of plasma cells. MM is a heterogeneous disease, featured by various molecular subtypes with different outcomes. With the advent of very efficient therapies including monoclonal antibodies, bispecific T-cell engagers and chimeric antigen receptor T cells (CAR T cells), most MM patients now have a prolonged survival. However, the disease remains incurable, and a subgroup of high-risk patients continue to have early relapse and short survival. Novel and highly sensitive methods have been developed allowing the detection of minimal residual disease (MRD) during or after treatment. Achievement of MRD negativity is a strong and independent prognostic factor in both prospective randomized clinical trials and in the real-world setting. While MRD assessment is now a validated endpoint in clinical trials, its incorporation in clinical practice is not yet established and its potential impact on guiding therapy remains under in-depth evaluation. Here we discuss the different methods available for MRD assessment and the role of MRD evaluation in MM management.
Topics: Neoplasm, Residual; Multiple Myeloma; Humans; Prognosis; Disease Management; Biomarkers, Tumor
PubMed: 38328864
DOI: 10.3324/haematol.2023.284662 -
Jornal Brasileiro de Pneumologia :... Sep 2021
Topics: Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Neoplasm Recurrence, Local; Neoplasm, Residual; Neoplasms, Second Primary
PubMed: 34495181
DOI: 10.36416/1806-3756/e20210275 -
Annals of Oncology : Official Journal... Oct 2023We aimed to examine circulating tumor DNA (ctDNA) and its association with residual cancer burden (RCB) using an ultrasensitive assay in patients with triple-negative...
BACKGROUND
We aimed to examine circulating tumor DNA (ctDNA) and its association with residual cancer burden (RCB) using an ultrasensitive assay in patients with triple-negative breast cancer (TNBC) receiving neoadjuvant chemotherapy.
PATIENTS AND METHODS
We identified responders (RCB 0/1) and matched non-responders (RCB 2/3) from the phase II TBCRC 030 prospective study of neoadjuvant paclitaxel versus cisplatin in TNBC. We collected plasma samples at baseline, 3 weeks and 12 weeks (end of therapy). We created personalized ctDNA assays utilizing MAESTRO mutation enrichment sequencing. We explored associations between ctDNA and RCB status and disease recurrence.
RESULTS
Of 139 patients, 68 had complete samples and no additional neoadjuvant chemotherapy. Twenty-two were responders and 19 of those had sufficient tissue for whole-genome sequencing. We identified an additional 19 non-responders for a matched case-control analysis of 38 patients using a MAESTRO ctDNA assay tracking 319-1000 variants (median 1000 variants) to 114 plasma samples from 3 timepoints. Overall, ctDNA positivity was 100% at baseline, 79% at week 3 and 55% at week 12. Median tumor fraction (TFx) was 3.7 × 10 (range 7.9 × 10-4.9 × 10). TFx decreased 285-fold from baseline to week 3 in responders and 24-fold in non-responders. Week 12 ctDNA clearance correlated with RCB: clearance was observed in 10 of 11 patients with RCB 0, 3 of 8 with RCB 1, 4 of 15 with RCB 2 and 0 of 4 with RCB 3. Among six patients with known recurrence, five had persistent ctDNA at week 12.
CONCLUSIONS
Neoadjuvant chemotherapy for TNBC reduced ctDNA TFx by 285-fold in responders and 24-fold in non-responders. In 58% (22/38) of patients, ctDNA TFx dropped below the detection level of a commercially available test, emphasizing the need for sensitive tests. Additional studies will determine whether ctDNA-guided approaches can improve outcomes.
Topics: Humans; Female; Circulating Tumor DNA; Neoadjuvant Therapy; Triple Negative Breast Neoplasms; Neoplasm, Residual; Prospective Studies; Breast Neoplasms; Neoplasm Recurrence, Local
PubMed: 37597579
DOI: 10.1016/j.annonc.2023.08.004 -
Acta Obstetricia Et Gynecologica... Mar 2022It is debated whether women with FIGO (International Federation of Gynecology and Obstetrics) Stage IV epithelial ovarian cancer should be offered primary debulking...
INTRODUCTION
It is debated whether women with FIGO (International Federation of Gynecology and Obstetrics) Stage IV epithelial ovarian cancer should be offered primary debulking surgery (PDS) or interval debulking surgery (IDS). Furthermore, the impact of complete resection of intra-abdominal disease (R0) despite their extra-abdominal metastases is questioned. The objective of this study was to investigate the impact of intra-abdominal residual tumor, Stage IVA vs IVB, the localization and number of metastases defining Stage IV disease on overall survival (OS) comparing PDS and IDS in FIGO Stage IV epithelial ovarian cancer.
MATERIAL AND METHODS
We included 2091 women registered with Stage IIIC-IV ovarian cancer in the Danish Gynecological Cancer Database during 2009-2016. The impact of residual tumor was evaluated using univariate and multivariate analyses.
RESULTS
In total, 681 patients had stage IV disease, of whom 26% underwent PDS, 38% IDS, and 36% chemotherapy only. Overall survival for PDS and IDS were similar. Patients achieving R0 at PDS showed a tendency towards a higher OS than patients achieving R0 at IDS, though the difference was non-significant. In women with Stage IVA and IVB disease there was a survival benefit in achieving R0 both when treated with PDS and IDS. Women with Stage IVB disease treated with chemotherapy only had a significantly lower OS than patients achieving R0 at both PDS and IDS. Malignant pleural effusion and having five metastatic sites compared with having one was associated with a poorer OS.
CONCLUSIONS
Our study shows similar OS in patients with Stage IV disease treated with IDS compared with PDS. Complete intra-abdominal tumor resection improves the prognosis in both PDS and IDS in Stage IV ovarian cancer. Malignant pleural effusion seems to be a negative prognostic factor and should have more focus in future studies.
Topics: Carcinoma, Ovarian Epithelial; Cytoreduction Surgical Procedures; Female; Humans; Neoadjuvant Therapy; Neoplasm, Residual; Ovarian Neoplasms; Pleural Effusion, Malignant; Retrospective Studies
PubMed: 35187660
DOI: 10.1111/aogs.14319 -
Seminars in Radiation Oncology Jul 2023Recent breakthroughs in circulating tumor DNA (ctDNA) technologies present a compelling opportunity to combine this emerging liquid biopsy approach with the field of... (Review)
Review
Recent breakthroughs in circulating tumor DNA (ctDNA) technologies present a compelling opportunity to combine this emerging liquid biopsy approach with the field of radiogenomics, the study of how tumor genomics correlate with radiotherapy response and radiotoxicity. Canonically, ctDNA levels reflect metastatic tumor burden, although newer ultrasensitive technologies can be used after curative-intent radiotherapy of localized disease to assess ctDNA for minimal residual disease (MRD) detection or for post-treatment surveillance. Furthermore, several studies have demonstrated the potential utility of ctDNA analysis across various cancer types managed with radiotherapy or chemoradiotherapy, including sarcoma and cancers of the head and neck, lung, colon, rectum, bladder, and prostate . Additionally, because peripheral blood mononuclear cells are routinely collected alongside ctDNA to filter out mutations associated with clonal hematopoiesis, these cells are also available for single nucleotide polymorphism analysis and could potentially be used to detect patients at high risk for radiotoxicity. Lastly, future ctDNA assays will be utilized to better assess locoregional MRD in order to more precisely guide adjuvant radiotherapy after surgery in cases of localized disease, and guide ablative radiotherapy in cases of oligometastatic disease.
Topics: Male; Humans; Circulating Tumor DNA; Radiation Oncology; Leukocytes, Mononuclear; Neoplasms; Liquid Biopsy; Biomarkers, Tumor; Neoplasm, Residual
PubMed: 37331781
DOI: 10.1016/j.semradonc.2023.03.004 -
Cancer Metastasis Reviews Mar 2023Cancer is one of the three leading causes of death worldwide. Even after successful therapy and achieving remission, the risk of relapse often remains. In this context,... (Review)
Review
Cancer is one of the three leading causes of death worldwide. Even after successful therapy and achieving remission, the risk of relapse often remains. In this context, dormant residual cancer cells in secondary organs such as the bone marrow constitute the cellular reservoir from which late tumor recurrences arise. This dilemma leads the term of minimal residual disease, which reflects the presence of tumor cells disseminated from the primary lesion to distant organs in patients who lack any clinical or radiological signs of metastasis or residual tumor cells left behind after therapy that eventually lead to local recurrence. Disseminated tumor cells have the ability to survive in a dormant state following treatment and linger unrecognized for more than a decade before emerging as recurrent disease. They are able to breakup their dormant state and to readopt their proliferation under certain circumstances, which can finally lead to distant relapse and cancer-associated death. In recent years, extensive molecular and genetic characterization of disseminated tumor cells and blood-based biomarker has contributed significantly to our understanding of the frequency and prevalence of tumor dormancy. In this article, we describe the clinical relevance of disseminated tumor cells and highlight how latest advances in different liquid biopsy approaches can be used to detect, characterize, and monitor minimal residual disease in breast cancer, prostate cancer, and melanoma patients.
Topics: Male; Humans; Neoplasm, Residual; Early Detection of Cancer; Breast Neoplasms; Liquid Biopsy; Recurrence
PubMed: 36607507
DOI: 10.1007/s10555-022-10075-x -
Breast (Edinburgh, Scotland) Jun 2023Residual tumor cellularity (RTC) and pathologic complete response (pCR) after neo-adjuvant chemotherapy (NAC) are prognostic factors associated with improved outcomes in...
INTRODUCTION
Residual tumor cellularity (RTC) and pathologic complete response (pCR) after neo-adjuvant chemotherapy (NAC) are prognostic factors associated with improved outcomes in breast cancer (BC). However, the majority of patients achieve partial pathologic response (pPR) and no clear correlation between RTC patterns and outcomes was described. Our aims were to define predictive factors for pCR and compare different outcomes of patients with pCR or pPR and with different RTC patterns.
MATERIALS AND METHODS
Baseline and post-NAC demographics, clinicopathological characteristics, post-operative data, survival and recurrence status were recorded from our institutional database. A multivariable analysis was performed using a logistic regression model to identify independent predictors of pCR. Disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) analyses were performed using the Kaplan-Meier method.
RESULTS
Overall, of the 495 patients analyzed, 148 (29.9%) achieved pCR, 347 (70.1%) had pPR, and the median RTC was 40%. Multivariable analysis identified 3 independent factors predictive of pCR: tumor stage before NAC (cT1-2 84.5% versus cT3-4 15.5%), BC sub-type (HER2-positive 54.7% versus triple-negative 29.8% versus luminal-like 15.5%), and vascular invasion (absence 98.0% versus presence 2.0%). We found statistically significant longer DFS, DDFS, and OS in patients with pCR and with RTC <40%; no difference was observed in terms of OS between RTC <40% and RTC ≥40% groups.
CONCLUSIONS
Tumor stage before NAC, BC sub-type, and vascular invasion are significant and independent factors associated with pCR. Patients with pCR and with RTC <40% have longer DFS, DDFS, and OS compared with patients with pPR.
Topics: Humans; Female; Breast Neoplasms; Neoplasm, Residual; Neoadjuvant Therapy; Prognosis; Disease-Free Survival; Chemotherapy, Adjuvant; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37001289
DOI: 10.1016/j.breast.2023.03.016