Marker Of Tumor Response Research Articles

Significance of changes in tumor markers in patients treated with durvalumab plus tremelimumab combination therapy as a surrogate marker for tumor response to unresectable hepatocellular carcinoma.

When evaluating response to immune checkpoint inhibitor therapy, the tumor sometimes initially swells before shrinking and ultimately responding, also called pseudo-progression. In this study, we analyzed whether tumor markers were useful for reflecting the treatment response. Thirty-three patients who were treated with durvalumab plus tremelimumab combination therapy (Dur+Tre) were enrolled. Their functional reserve was Child-Pugh grade A. Their tumor markers α-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP), or AFP-Lectin 3 fraction (AFP-L3) were positive. Tumor markers were evaluated before treatment and at 1, 4, and 8weeks after the start of treatment. The first radiological evaluation was carried out at 4weeks and the second evaluation at 8-12weeks. The responders included those with complete response and partial response and the nonresponders included those with stable disease (SD) and progression disease at best response evaluated by Response Evaluation Criteria in Solid Tumors. In the responder group, the change ratio of AFP, DCP, and AFP-L3 specifically decreased at 8weeks. In the nonresponder group, the change ratio of DCP specifically increased at 4weeks. The optimal cut-off value to divide responders and nonresponders at 4weeks was approximately -40%. The ratio of responders was 72.7% in the patients whose AFP or DCP decreased over 40% at 4weeks. The change in tumor markers is a more useful predicter of tumor response to Dur+Tre than imaging evaluation alone.

NURS-21. EXPLORATION OF CORRELATIVE STUDIES IN EARLY PHASE TRIALS FOR PEDIATRIC AND YOUNG ADULT CENTRAL NERVOUS SYSTEM (CNS) TUMORS AND THE POTENTIAL TRANSLATION TO CLINICAL CARE

Abstract BACKGROUND Correlative studies are common in early phase clinical trials. In addition to primary aims establishing maximum tolerated dose or efficacy, supplementary information from biospecimens is frequently collected with patient consent. The Pediatric Neuro-Oncology Consortium (PNOC) has included several correlative studies with implications for understanding patterns in the development of tumors, response to treatment, and prognosis. A needs assessment survey of PNOC institutions by the Advanced Practice Provider and Investigational Nurse Committee (APPNIC) highlighted that nurses and advanced practice providers (APPs) desire further education regarding correlative studies. METHODS Blood, stool, cerebrospinal fluid (CSF) and hair strands are examples of correlative biospecimens incorporated in PNOC protocols. We will share a review of the literature and implications for practice. RESULTS Blood, drawn in conjunction with clinical labs, is commonly analyzed for circulating tumor DNA to conduct molecular profiling in blood compared to tissue, explore less invasive means of molecular evolution of tumor somatic mutations, and identify early markers of tumor response or resistance. Stool is collected to utilize the gut microbiome as a lens into treatment response in CNS tumors via the gut-brain axis. Stool samples are compared to normal controls and longitudinally within patients during treatment. CSF sampling provides less invasive disease monitoring, tumor molecular characterization, markers of tumor response or resistance, and drug pharmacokinetics. Hair sampling can be used to further quantify drug levels for pharmacokinetics and assess treatment compliance. The robustness of these correlative samples collected at various timepoints (diagnosis, pre-surgery and post-surgery, post-radiation and/or with recurrence) informs on prognosis, response to treatment; and ultimately, interventions to improve outcomes for pediatric and young adult CNS tumors. CONCLUSION Our assessment identified a need for APP and nursing-focused education on biospecimen collection to inform on emerging clinical and research advances while improving protocol compliance.

Prognostic Value of Postneoadjuvant Chemotherapy Neutrophil-to-Lymphocyte Ratio in Patients undergoing Radical Cystectomy.

Background: Neutrophil-to-lymphocyte ratio (NLR), a widely assessed biomarker in most common diseases, is typically evaluated before treatment initiation. However, data on NLR in the post-treatment setting is limited. Therefore, we assessed the NLR calculated after neoadjuvant chemotherapy (NAC) initiation in patients with bladder cancer (BC). We hypothesised that changes in blood cells after NAC could be a marker of tumour response and long-term survival. Materials and Methods: Our study included 214 patients who underwent NAC followed by radical cystectomy (RC) in two urological departments, wherein post-NAC NLR was used to categorize patients into the low (NLR ≤ 1.75) and high (NLR > 1.75) groups. Results: Logistic regression analysis indicated that a post-NAC NLR ≥ 1.75 is a good biomarker for pathologic response (odds ratio (OR), 0.045; p <0.001), emphasizing its ability to predict patient survival. The HRs for overall survival and cancer-specific survival were 2.387 (p = 0.048) and 2.342 (p < 0.001), respectively. Conclusions: We believe that post-NAC NLR can be used for patient stratification after NAC. Consequently, the post-NAC NLR may serve as a guide for the decision-making process regarding RC versus bladder-preserving strategies.

TRF2 as novel marker of tumor response to taxane-based therapy: from mechanistic insight to clinical implication

BackgroundBreast Cancer (BC) can be classified, due to its heterogeneity, into multiple subtypes that differ for prognosis and clinical management. Notably, triple negative breast cancer (TNBC) – the most aggressive BC form – is refractory to endocrine and most of the target therapies. In this view, taxane-based therapy still represents the elective strategy for the treatment of this tumor. However, due variability in patients’ response, management of TNBC still represents an unmet medical need.Telomeric Binding Factor 2 (TRF2), a key regulator of telomere integrity that is over-expressed in several tumors, including TNBC, has been recently found to plays a role in regulating autophagy, a degradative process that is involved in drug detoxification.Based on these considerations, we pointed, here, at investigating if TRF2, regulating autophagy, can affect tumor sensitivity to therapy.MethodsHuman TNBC cell lines, over-expressing or not TRF2, were subjected to treatment with different taxanes and drug efficacy was tested in terms of autophagic response and cell proliferation. Autophagy was evaluated first biochemically, by measuring the levels of LC3, and then by immunofluorescence analysis of LC3-puncta positive cells. Concerning the proliferation, cells were subjected to colony formation assays associated with western blot and FACS analyses. The obtained results were then confirmed also in mouse models. Finally, the clinical relevance of our findings was established by retrospective analysis on a cohort of TNBC patients subjected to taxane-based neoadjuvant chemotherapy.ResultsThis study demonstrated that TRF2, inhibiting autophagy, is able to increase the sensitivity of TNBC cells to taxanes. The data, first obtained in in vitro models, were then recapitulated in preclinical mouse models and in a cohort of TNBC patients, definitively demonstrating that TRF2 over-expression enhances the efficacy of taxane-based neoadjuvant therapy in reducing tumor growth and its recurrence upon surgical intervention.ConclusionsBased on our finding it is possible to conclude that TRF2, already known for its role in promoting tumor formation and progression, might represents an Achilles’ heel for cancer. In this view, TRF2 might be exploited as a putative biomarker to predict the response of TNBC patients to taxane-based neoadjuvant chemotherapy.

Role of CYFRA 21-1 and CEA as prognostic and predictive markers in locally advanced and metastatic gastric carcinoma.

Tumor-associated serum markers have demonstrated predictive and prognostic value in patients being treated for malignancies. However, the clinical importance of tumor markers in gastric cancers (GC) is poorly standardized. The objective is to assess the clinical utility of cytokeratin-19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA) as serum tumor markers in advanced GC. In this prospective study, CYFRA 21-1 and CEA levels were measured at baseline and after three cycles of chemotherapy in patients with advanced GC. The association of tumor marker levels with prognosis and decline of tumor markers with radiological overall response rates (ORR) and survival were analyzed. In the 105 patients, the proportion of patients with elevated baseline CYFRA 21-1 and CEA levels was 55% (N = 58) and 37% (N = 39) based on predefined cutoffs. Response assessment was done for 61 patients who received a minimum of three cycles of chemotherapy. A 15% and 13% reduction of serum levels from baseline for CYFRA 21-1 and CEA were selected for defining "CYFRA 21-1 response" and "CEA-response," respectively. Both responses were significant predictors of radiological ORR. The median overall survival (OS) was 9.6 months in the entire cohort and 13 months for patients who received at least three cycles of chemotherapy. In multivariate analysis, baseline CEA levels and ECOG status were significant predictors of OS. In a subset analysis of patients receiving palliative chemotherapy, any of the tumor marker responses predicted improved 1-year OS. In advanced GC, CYFRA 21-1 and CEA decline from baseline appeared to be reliable surrogate markers of chemotherapy efficacy and improved survival.

Three-Dimensional Ultrasound Imaging of Retinoblastoma and Its Correlation With Pathology.

Monitoring the response of retinoblastoma to globe-salvaging therapies is based on subjective assessments of changes determined by fundoscopy, ultrasound, and optical coherence tomography. Advances in organ-preserving therapies have increased the need for objective, quantitative estimates of tumor response to treatment. Primary tumor volume is a metric that can be objectively determined as a surrogate measure of treatment response. We evaluated the correlation of objective, quantitative estimates of tumor volume made with two-dimensional (2D) and three-dimensional (3D) ultrasound with gold standard pathological tumor volumes derived by analysis of enucleation specimens. Twelve eyes in 12 patients undergoing primary enucleation were evaluated by 2D and 3D ultrasound during ophthalmic examination under anesthesia prior to enucleation. 2D- and 3D-ultra-sound measurements of tumor volume were both strongly correlated with pathological estimates of tumor volume (r = 0.69, P = 0.018; and r = 0.66, P = 0.027, respectively). 2D- and 3D-ultrasound measurements of retinoblastoma primary tumor volume are highly correlated with pathological estimates. 3D measurements are easy to perform with volumetric probes and consider the irregular morphology of the tumor. Further study should be undertaken to evaluate the performance of these metrics as surrogate markers of tumor response to treatment. [Ophthalmic Surg Lasers Imaging Retina 2024;55:136-140.].

Early Tumor Marker Response Predicts Treatment Outcomes in Patients with Unresectable Hepatocellular Carcinoma Receiving Combined Lenvatinib, Immune Checkpoint Inhibitors, and Transcatheter Arterial Chemoembolization Therapy.

Few reliable biomarkers for predicting the efficacy of triple therapy (lenvatinib + immune checkpoint inhibitors + transarterial chemoembolization) exist for patients with unresectable hepatocellular carcinoma (uHCC). This study explored the prognostic role of alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) levels in patients with uHCC receiving triple therapy. This retrospective study included 93 patients with uHCC who received triple therapy at Fujian Provincial Hospital between August 2020 and November 2022. Depending on the respective baseline levels, the patients were divided into high-AFP and high-DCP groups. An early response was defined as an AFP or DCP concentration >50% less than the baseline concentration after 6 weeks of triple therapy. The primary endpoint was the objective response rate (ORR). The secondary endpoints were progression-free survival (PFS) and overall survival (OS). After 6 weeks of triple therapy, 75.3% (58/77) and 78.9% (60/76) of patients in the high-AFP and high-DCP groups achieved an objective response. Early AFP and DCP responses were positively associated with ORR (high-AFP group: odds ratio [OR]: 13.542; 95% confidence interval [CI]: 3.991-45.950, p<0.001; high-DCP group: OR: 17.853; 95% CI: 4.478-71.179, p<0.001). In the high-AFP group, the 6-month, 12-month, and 18-month PFS and OS rates were higher in the AFP responders than those in the non-responders (PFS: 66.4%, 59.6%, 48.2% vs 42.3%, 19.3%, 0%, p<0.001; OS: 94.5%, 90.4%, 77.3% vs 75.6%, 66.2%, 49.6%, p=0.006). In the high-DCP group, the 6-month, 12-month, and 18-month PFS and OS rates were higher in the DCP responders than those in the non-responders (PFS: 67.4%, 57.7%, 39.0% vs 38.9%, 8.1%, 0%, p<0.001; OS: 94.7%, 94.7%, 83.3% vs 77.0%, 53.9%, 36.0%, p<0.001). After 6 weeks of triple therapy, an AFP or DCP reduction of >50% predicts better treatment outcomes in uHCC patients.

Does gamma-glutamyltransferase correlate with liver tumor burden in neuroendocrine tumors?

PurposeIn patients with neuroendocrine tumors (NETs) and liver metastases, increased gamma-glutamyltransferase (GGT) is commonly assumed as an indicator for progressive disease. To date, however, empirical data are lacking. This study aimed to investigate associations between GGT and liver tumor burden. In longitudinal analyses, associations of GGT and radiographic responses of liver metastases under therapy were investigated.MethodsThe cross-sectional sample consisted of 104 patients who were treated at the University Medical Center Hamburg-Eppendorf from 2008 to 2021 (mean age 62.3 ± 12.6 years, 58.7% male). GGT and liver imaging were identified in a time range of 3 months. Radiologic reassessments were performed to estimate liver tumor burden. In a separate longitudinal sample (n = 15), the course of GGT levels under chemotherapy was analyzed. Data were retrospectively analyzed with a univariate ANOVA, linear regression analyses, and Wilcoxon tests.ResultsOf 104 cross-sectionally analyzed patients, 54 (51.9%) showed a GGT elevation. GGT levels and liver tumor burden were positively correlated (p < 0.001), independently from age, gender, primary tumor location, grading, and cholestasis. Notably, GGT increase was associated with a liver tumor burden of >50%. In the longitudinal sample, 10 of 11 patients with progressive disease showed increasing GGT, whereas 4 of 4 patients with regressive disease showed declining GGT.ConclusionOur findings indicate that GGT is associated with liver tumor burden. Over the course of therapy, GGT appears to change in line with radiographic responses. Further longitudinal studies with larger sample sizes are required to define GGT as a reliable marker for tumor response.

MRI Apparent Diffusion Coefficient (ADC) as a Biomarker of Tumour Response: Imaging-Pathology Correlation in Patients with Hepatic Metastases from Colorectal Cancer (EORTC 1423).

Background: Tumour apparent diffusion coefficient (ADC) from diffusion-weighted magnetic resonance imaging (MRI) is a putative pharmacodynamic/response biomarker but the relationship between drug-induced effects on the ADC and on the underlying pathology has not been adequately defined. Hypothesis: Changes in ADC during early chemotherapy reflect underlying histological markers of tumour response as measured by tumour regression grade (TRG). Methods: Twenty-six patients were enrolled in the study. Baseline, 14 days, and pre-surgery MRI were performed per study protocol. Surgical resection was performed in 23 of the enrolled patients; imaging-pathological correlation was obtained from 39 lesions from 21 patients. Results: There was no evidence of correlation between TRG and ADC changes at day 14 (study primary endpoint), and no significant correlation with other ADC metrics. In scans acquired one week prior to surgery, there was no significant correlation between ADC metrics and percentage of viable tumour, percentage necrosis, percentage fibrosis, or Ki67 index. Conclusions: Our hypothesis was not supported by the data. The lack of meaningful correlation between change in ADC and TRG is a robust finding which is not explained by variability or small sample size. Change in ADC is not a proxy for TRG in metastatic colorectal cancer.

Doxorubicin, paclitaxel, and cisplatin (ATP) for refractory germ cell tumors.

e17028 Background: Patients with refractory germ cell tumor (GCT) have limited treatment options and poor prognosis. We describe our institutional experience with doxorubicin, paclitaxel, and cisplatin (ATP) as an outpatient chemotherapy regimen for patients with refractory GCT. Methods: We performed a retrospective chart review of all patients who received ATP at our institution between August 2017 and August 2022. ATP consisted of doxorubicin 30 mg/m2, paclitaxel 100 mg/m2 over one hour, and cisplatin 30 mg/m2 every 2-3 weeks. We reviewed patient and disease characteristics including staging, histology, prior therapies, tumor marker and imaging responses. Progression free survival (PFS) and overall survival (OS) were respectively calculated from the first ATP dose date to disease progression/death and to death/last follow up. Results: A total of 39 patients with refractory GCT received ATP. Patients were 95% male, 54% white, with a mean age of 30 years (range 18-63). Prior to ATP administration, 92% of GCTs had elevated tumor markers, including 54% with elevated AFP, 56% with elevated HCG, and 18% with elevated both tumor markers. 8% of GCTs did not have elevated tumor markers at baseline. Further disease characteristics are described in table 1. Patients received a median of 2 lines of prior systemic therapies (range 1-6), including 97% with prior cisplatin-based regimens and 21% with prior high dose chemotherapy with stem cell rescue transplant. Patients received a median of 3 doses of ATP (range 1-8) with 31% for palliative intent and the rest as a bridge to transplant or other therapies. After ATP administration, 77% patients had decreased tumor markers, including 18% with tumor marker normalization. Of the 19 patients with imaging post-ATP, 53% had complete or partial response, 16% had stable disease, and 32% had disease progression. By December 2022, 79% patients had progression or death, with a median PFS of 3.8 months (95% CI: 1.94, 7.16) and median OS of 10.7 months (95% CI: 6.37, 32.69). 18% of patients experienced toxicities requiring admissions. Conclusions: Based on our retrospective single institution experience, ATP has clinical activity in refractory GCT and is associated with decreased tumor markers and imaging response in most patients. ATP is a convenient and feasible outpatient regimen and can be used in the salvage setting and as a bridge to other therapies. [Table: see text]

Comprehensive Profiling of Cancer-Associated Cells in the Blood of Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy to Predict Pathological Complete Response.

Neoadjuvant chemotherapy (NAC) can affect pathological complete response (pCR) in breast cancers; the resection that follows identifies patients with residual disease who are then offered second-line therapies. Circulating tumor cells (CTCs) and cancer-associated macrophage-like cells (CAMLs) in the blood can be used as potential biomarkers for predicting pCR before resection. CTCs are of epithelial origin that undergo epithelial-to-mesenchymal transition to become more motile and invasive, thereby leading to invasive mesenchymal cells that seed in distant organs, causing metastasis. Additionally, CAMLs in the blood of cancer patients are reported to either engulf or aid the transport of cancer cells to distant organs. To study these rare cancer-associated cells, we conducted a preliminary study where we collected blood from patients treated with NAC after obtaining their written and informed consent. Blood was collected before, during, and after NAC, and Labyrinth microfluidic technology was used to isolate CTCs and CAMLs. Demographic, tumor marker, and treatment response data were collected. Non-parametric tests were used to compare pCR and non-pCR groups. Univariate and multivariate models were used where CTCs and CAMLs were analyzed for predicting pCR. Sixty-three samples from 21 patients were analyzed. The median(IQR) pre-NAC total and mesenchymal CTC count/5 mL was lower in the pCR vs. non-pCR group [1(3.5) vs. 5(5.75); p = 0.096], [0 vs. 2.5(7.5); p = 0.084], respectively. The median(IQR) post-NAC CAML count/5 mL was higher in the pCR vs. non-pCR group [15(6) vs. 6(4.5); p = 0.004]. The pCR group was more likely to have >10 CAMLs post-NAC vs. non-pCR group [7(100%) vs. 3(21.4%); p = 0.001]. In a multivariate logistic regression model predicting pCR, CAML count was positively associated with the log-odds of pCR [OR = 1.49(1.01, 2.18); p = 0.041], while CTCs showed a negative trend [Odds Ratio (OR) = 0.44(0.18, 1.06); p = 0.068]. In conclusion, increased CAMLs in circulation after treatment combined with lowered CTCs was associated with pCR.

Biomarker response to high-specific-activity I-131 meta-iodobenzylguanidine in pheochromocytoma/paraganglioma.

The objective of this study is to present the complete biomarker response dataset from a pivotal trial evaluating the efficacy and safety of high-specific-activity I-131 meta-iodobenzylguanidine in patients with advanced pheochromocytoma or paraganglioma. Biomarker status was assessed and post-treatment responses were analyzed for catecholamines, metanephrines, and serum chromogranin A. Complete biomarker response (normalization) or partial response, defined as at least 50% reduction from baseline if above the normal range, was evaluated at specified time points over a 12-month period. These results were correlated with two other study objectives: blood pressure control and objective tumor response as per RECIST 1.0. In this open-label, single-arm study, 68 patients received at least one therapeutic dose (~18.5 GBq (~500 mCi)) of high-specific-activity I-131 meta-iodobenzylguanidine. Of the patients, 79% and 72% had tumors associated with elevated total plasma free metanephrines and serum chromogranin A levels, respectively. Best overall biomarker responses (complete or partial response) for total plasma free metanephrines and chromogranin A were observed in 69% (37/54) and 80% (39/49) of patients, respectively. The best response for individual biomarkers was observed 6-12 months following the first administration of high-specific-activity I-131 meta-iodobenzylguanidine. Biochemical tumor marker response was significantly associated with both reduction in antihypertensive medication use (correlation coefficient 0.35; P = 0.006) as well as objective tumor response (correlation coefficient 0.36; P = 0.007). Treatment with high-specific-activity I-131 meta-iodobenzylguanidine resulted in long-lasting biomarker responses in patients with advanced pheochromocytoma or paraganglioma that correlated with blood pressure control and objective response rate. ClinicalTrials.gov number: NCT00874614.

Serum Tumor Marker Response Predicts Survival and Intracranial Control after Radiation Therapy for Germ Cell Tumor Brain Metastases

<h3>Purpose/Objective(s)</h3> Patients with brain metastases (BM) from germ cell tumors (GCT) demonstrate poor overall survival (OS). However, multimodality treatment enables durable disease control in some patients. Serum tumor markers including beta-human chorionic gonadotropin (β-HCG) and alpha-fetoprotein (AFP) are used to evaluate response to systemic therapy. However, their utility in assessing the efficacy of intracranial radiation therapy (RT) is unclear. We evaluated whether changes in β-HCG and AFP after RT for GCT BM predict OS and freedom from intracranial progression (iPFS). <h3>Materials/Methods</h3> Patients with GCT BM who received intracranial RT at our institution were identified retrospectively. At least one β-HCG or AFP value before and after RT was required for inclusion. Serum tumor marker values were obtained prior to RT and 1 month after RT. Univariate and multivariate Cox regression analyses evaluated changes in β-HCG and AFP as predictors of OS and iPFS. Patients with normal tumor markers prior to RT were excluded from analyses. <h3>Results</h3> Sixty-two male patients who received RT between 2002 and 2021 were included. Median age was 30 years (range, 2 to 61). The primary tumor was testicular in 81% and mediastinal in 15%. Histology was seminoma in 10%. At diagnosis, the median number of BM was 2, and the median largest diameter was 1.8 cm. Initial RT included whole brain radiation therapy in 55%, stereotactic radiosurgery in 34%, and both in 10%. 31% had resection preceding RT. Most patients had extracranial disease (79%) and received chemotherapy within a month of RT (66%). During RT, radiographic progression of extracranial disease occurred in 34% of patients. Median OS and iPFS were 20.6 and 27.7 months, respectively. Among 41 patients with baseline β-HCG above the normal range, β-HCG decreased at 1 month after RT in 51%. Patients with decreased β-HCG, versus those with increased β-HCG, had significantly better OS (median not reached versus 5.4 months) and iPFS (median not reached versus 4.7 months). These correlations remained significant on multivariate analysis, controlling for largest BM diameter and RT modality (OS: HR = 13, 95% CI = [4.6, 37], p = 1 × 10⁻⁶; iPFS: HR = 6.4, 95% CI = [2.2, 19], p = 6 × 10⁻⁴). These correlations also remained significant whether or not patients had extracranial disease progression during RT (p < 0.05). Among 20 patients with baseline AFP above the normal range, AFP decreased at 1 month after RT in 75%. Likewise, decreased AFP was correlated with better OS on univariate regression (p = 0.04). <h3>Conclusion</h3> To our knowledge, this is the first study to evaluate changes in serum tumor markers as predictors of outcomes after RT for GCT BM. Decrease in β-HCG one month after RT was associated with better OS and iPFS on multivariate analysis, and likewise, decrease in AFP was associated with better OS on univariate analysis. These data indicate that post-RT β-HCG and AFP levels are useful predictors of outcomes in patients with GCT BM.

Tumor marker response to SARS-CoV-2 infection among patients with cancer.

BackgroundInflammatory responses from benign conditions can cause non‐cancer‐related elevations in tumor markers. The severe acute respiratory coronavirus 2 (SARS‐CoV‐2) induces a distinct viral inflammatory response, resulting in coronavirus disease 2019 (COVID‐19). Clinical data suggest carcinoembryonic antigen (CEA), carbohydrate antigen 19–9 (CA 19–9), and cancer antigen 125 (CA 125) levels might rise in patients with COVID‐19. However, available data excludes cancer patients, so little is known about the effect of COVID‐19 on tumor markers among cancer patients.MethodsWe conducted a case series and identified patients with a positive SARS‐CoV‐2 PCR test, diagnosis of a solid tumor malignancy, and a CEA, CA 19–9, CA 125, or CA 27–29 laboratory test. Cancer patients with documented COVID‐19 infection and at least one pre‐ and two post‐infection tumor marker measurements were included. We abstracted the electronic health record for demographics, cancer diagnosis, treatment, evidence of cancer progression, date and severity of COVID‐19 infection, and tumor marker values.ResultsSeven patients were identified with a temporary elevation of tumor marker values during the post‐COVID‐19 period. Elevation in tumor marker occurred within 56 days of COVID‐19 infection for all patients. Tumor markers subsequently decreased at the second time point in the post‐infectious period among all patients.ConclusionWe report temporary elevations of cancer tumor markers in the period surrounding COVID‐19 infection. To our knowledge this is the first report of this phenomenon in cancer patients and has implications for clinical management and future research.

Metabolic Adaptations in an Endocrine-Related Breast Cancer Mouse Model Unveil Potential Markers of Tumor Response to Hormonal Therapy.

Breast cancer (BC) is the most common type of cancer in women and, in most cases, it is hormone-dependent (HD), thus relying on ovarian hormone activation of intracellular receptors to stimulate tumor growth. Endocrine therapy (ET) aimed at preventing hormone receptor activation is the primary treatment strategy, however, about half of the patients, develop resistance in time. This involves the development of hormone independent tumors that initially are ET-responsive (HI), which may subsequently become resistant (HIR). The mechanisms that promote the conversion of HI to HIR tumors are varied and not completely understood. The aim of this work was to characterize the metabolic adaptations accompanying this conversion through the analysis of the polar metabolomes of tumor tissue and non-compromised mammary gland from mice implanted subcutaneously with HD, HI and HIR tumors from a medroxyprogesterone acetate (MPA)-induced BC mouse model. This was carried out by nuclear magnetic resonance (NMR) spectroscopy of tissue polar extracts and data mining through multivariate and univariate statistical analysis. Initial results unveiled marked changes between global tumor profiles and non-compromised mammary gland tissues, as expected. More importantly, specific metabolic signatures were found to accompany progression from HD, through HI and to HIR tumors, impacting on amino acids, nucleotides, membrane percursors and metabolites related to oxidative stress protection mechanisms. For each transition, sets of polar metabolites are advanced as potential markers of progression, including acquisition of resistance to ET. Putative biochemical interpretation of such signatures are proposed and discussed.

Circulating tumour DNA: a challenging innovation to develop "precision onco-surgery" in pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the third leading cause of cancer-related mortality within the next decade. Management of PDAC remains challenging with limited effective treatment options and a dismal long-term prognosis. Liquid biopsy and circulating biomarkers seem to be promising to improve the multidisciplinary approach in PDAC treatment. Circulating tumour DNA (ctDNA) is the most studied blood liquid biopsy analyte and can provide insight into the molecular profile and individual characteristics of the tumour in real-time and in advance of standard imaging modalities. This could pave the way for identifying new therapeutic targets and markers of tumour response to supplement diagnostic and provide enhanced stratified treatment. Although its specificity seems excellent, the current sensitivity of ctDNA remains a limitation for clinical use, especially in patients with a low tumour burden. Increasing evidence suggests that ctDNA is a pertinent candidate biomarker to assess minimal residual disease after surgery but also a strong independent prognostic biomarker. This review explores the current knowledge and recent developments in ctDNA as a screening, diagnostic, prognostic and predictive biomarker in the management of resectable PDAC but also technical and analytical challenges that must be overcome to move toward "precision onco-surgery."

Nivolumab-DTPA-Based PD-1 Imaging Reveals Structural and Pathological Changes in Colorectal Carcinoma.

Programmed cell death protein 1 (PD-1) expression is considered a prognostic marker of tumor response to the immuno-blocking therapy. In this study, nivolumab was conjugated with diethylenetriamine pentaacetate (DTPA) via condensation reaction between amidogen and p-SCN-Bn-DTPA, which provided labeling sites for 99mTc4+ or Gd3+ ions. SPECT and magnetic resonance T1 weighted imaging (T1WI) analyses were performed on mouse models of colorectal carcinoma expressing humanized PD-1 antigen. Furthermore, PD-1 expression in intestinal tracks was assessed by immunohistochemistry, and then compared with the imageological findings. Nivolumab-DTPA was synthesized with varying molar ratios and was labeled with Gd or 99mTc with a chemical purity of 96.28 ± 1.16% and good stability. In SPECT images, lesions with high 99mTc-DTPA-nivolumab uptake and relatively clear background were shown at 6 h. Thereafter, the suspected intestinal thickening in Gd-free T1WI was observed at 2 h after the addition of Gd-DTPA-nivolumab. Notably, the results of both SPECT and T1WI analyses were consistent with the postmortem examination and immunohistochemistry results (for linear correlation with target to non-target ratios, R 2 = 0.8038, p < 0.05). In conclusion, nivolumab-DTPA could act as a probe precursor for identifying PD-1-positive lesions, not only through integrating the advantages of immunohistochemistry and molecular imaging but also by providing a noninvasive method for monitoring systemic changes.

Metastatic Extra-Adrenal Pheochromocytoma with Single Kidney and Renal Compromise: A Case Report of Excellent Response, Tolerability, and Outcome to a Modified Regimen of 131I-mIBG, and Decision-Making between 131I-mIBG Therapy and PRRT

AbstractDetermining the choice and the goal is key element for decision-making of a systemic radionuclide therapy. They should be clearly defined in deciding and individualizing the dose and regimen. For iodine-131 metaiodobenzylguanidine (131I-mIBG) therapy, the important considerations during dose fractionation include disease burden, tumor biology, functional symptoms, and associated comorbidities, all of which are important determinants for the intent and course of treatment. Herein, we present the case of a 67-year-old elderly female with highly functional metastatic recurrent extra-adrenal pheochromocytoma (presenting 42 years after the primary surgery and 32 years following excision of pararenal recurrence) with multiple comorbidities including single kidney and borderline renal compromise, treated successfully with a relatively lower dose of 131I-mIBG (cumulative dose of 22.2 GBq in four cycles with a mean dose of 5.7 GBq per therapy cycle). The excellent tumor burden reduction, hormonal tumor marker response, and most importantly asymptomatic status could be achieved with the administered dose. On follow-up, none of the pretherapeutic parameters (including renal function) showed any further derangement compared with the baseline during next 24 months following the treatment. All cycles were well tolerated with only reversible hematological toxicity that normalized without any active intervention. The report is intended to provide some guidance for future therapeutic regimens.

Evaluation and Predictive Factors of Complete Response in Rectal Cancer after Neoadjuvant Chemoradiation Therapy.

The response to neoadjuvant chemoradiation therapy is an important prognostic factor for locally advanced rectal cancer. Although the majority of the patients after neoadjuvant therapy are referred to following surgery, the clinical data show that complete clinical or pathological response is found in a significant proportion of the patients. Diagnostic accuracy of confirming the complete response has a crucial role in further management of a rectal cancer patient. As the rate of clinical complete response, unfortunately, is not always consistent with pathological complete response, accurate diagnostic parameters and predictive markers of tumor response may help to guide more personalized treatment strategies and identify potential candidates for nonoperative management more safely. The management of complete response demands interdisciplinary collaboration including oncologists, radiotherapists, radiologists, pathologists, endoscopists and surgeons, because the absence of a multidisciplinary approach may compromise the oncological outcome. Prediction and improvement of rectal cancer response to neoadjuvant therapy is still an active and challenging field of further research. This literature review is summarizing the main, currently known clinical information about the complete response that could be useful in case if encountering such condition in rectal cancer patients after neoadjuvant chemoradiation therapy, using as a source PubMed publications from 2010–2021 matching the search terms “rectal cancer”, “neoadjuvant therapy” and “response”.

Outcome of Postchemotherapy Residual Disease in Extracranial Germ Cell Tumor in Children: Experience of a Tertiary Care Center.

The aim was to review outcome with residual disease at the end of first line chemotherapy in patients with extracranial germ cell tumor (GCT) in our resource limited setting. A retrospective analysis of 196 patients with GCT recruited at Shaukat Khanum Memorial Cancer Hospital (SKMCH) from January 2008 to December 2016. Data fields included site, histopathology, stage, risk groups, baseline alpha fetoprotein, beta human chorionic gonadotropin levels, residuum after primary treatment, completeness of surgical excision and outcomes. Data analysis involved quantitative analysis, mean and median calculations, event free survival (EFS) and overall survival (OS) calculations using Kaplan-Meier curves. In 196 included patients, M:F ratio was 1. There were 81 (41.3%) adolescents. Alpha fetoprotein was >10,000 IU/L in 56 (28.6%) patients. Sixty-two (31.6%) patients had extragonadal disease. Most patients (n=137, 69.9%) presented with advanced stage (III/IV). Seventy-six patients had postchemotherapy residual disease (n=59 [78%] with partial response (PR) and 17 [22%] with no response [NR]). Five-year OS was 83% and EFS was 67%. Five-year EFS of patients with complete remission after primary chemotherapy was 85% versus 70% in patients with PR and 6% in those with NR (P=0.001). OS in patients with complete remission, PR and NR was 94%, 87%, and 46%, respectively. All patients with NR progressed or relapsed and 8/17 died. Four patients with normalized tumor marker response were found to have active tumor on resection of postchemotherapy residuum. Patients with postchemotherapy residual disease in pediatric extracranial GCTs, fare better if their residuum is resected compared with those who do not undergo resection.