Decrease In Tumor Markers Research Articles

Growing teratoma syndrome in an adolescent with a testicular germ cell tumor: a case report

Growing teratoma syndrome (GTS) is a condition characterized by a paradoxical increase in tumor size during or after chemotherapy and/or surgical treatment for germ cell tumors. Due to its relative rarity, GTS may be misinterpreted as disease progression. However, a decrease in tumor markers (alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG)) in the blood, a paradoxical increase in tumor size during chemotherapy, and a verified histological diagnosis of mature teratoma after the tumor removal confirm GTS. Here we report a clinical case of a patient in whom we observed a decrease in tumor markers (AFP and hCG) in the blood during treatment, a paradoxical increase in the tumor size and normal AFP and hCG levels 5 months after the end of chemotherapy and a histologically verified diagnosis. These clinical features are consistent with the diagnostic criteria of GTS. The patient's parents gave consent to the use of their child's data, including photographs, for research purposes and in publications.

Combination of Radiotherapy and Atezolizumab plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma: A Pilot Study

Following the results of the IMbrave150 study, Atezolizumab plus bevacizumab (Atezo/beva) became the first-line treatment in patients with advanced hepatocellular carcinoma (HCC). However, its real-world efficacy has been less satisfied. In this study, we investigated the efficacy of radiotherapy (RT) combined with Atezo/beva in patients with advanced HCC. Twenty patients received combination of RT and Atezo/beva between December 2021 and December 2022 at our institution. RT was administered in 10 fractions of 5 Gy between Atezo/beva cycles. Tumor response were evaluated on both imaging and tumor marker basis. The iRECIST guideline was used to assess treatment response after the combination treatment of RT and Atezo/beva. Primary endpoints were disease control rate (DCR) and overall response rate (ORR), and secondary endpoint was treatment related toxicity. All patients were BCLC C with advanced tumors associated with lymph node metastasis (7, 35%) or distant metastasis (8, 40%). Patients received RT between cycles of Atezo/beva, mostly (14, 70%) between 2nd and 3rd cycles. After a median follow-up of 3.2 months, DCR was 65% and ORR was 20%. Significant decrease in tumor marker of over 2-fold was shown in 10 patients (50%). Regarding treatment related toxicity, only 1 patient (5%) showed grade 3 neutropenic fever, and no grade 4 or 5 toxicity was seen. Combination of radiotherapy and Atezo/beva showed high response rate with tolerable treatment related toxicity in advanced HCC patients. Further prospective studies with larger patient cohort are warranted.

Clinical use of quality of life data for treatment and survivorship in oncology.

e24044 Background: Since cancer treatment and disease itself may cause chronic limitations, the challenge of reducing symptom burden during therapy and achieving good Quality of Life (QoL) for longevity with cancer becomes increasingly important. Research already shows that including QoL during treatment increases compliance, survivorship and outcome, but the transition of these concepts into regular care are mostly not implemented. Nevertheless, do regular measurements give a good insight to personal deviations and may enable a harmonious transition from clinical - to post treatment and into everyday life. Methods: For this research assessment of QoL was carried out within a registry study of gastrointestinal patients at the SLK Clinics Heilbronn (DRKS00018788). As a registry study, research is not bound to a fixed deadline, therefore we're still recruiting. First, we deployed a process for a continuous, digital measurement of QoL at clinical visits through the QLQ-C30. Parallel, a separate project implemented an app to measure QoL independently from home. Both ways, data is then structured to visualize the course of events for the identification of deviations or trends. Results: Up to now we included almost 100 patients with over 600 assessment points in our study. It could be shown that our process is applicable in the real world setting of clinical routine and accepted by patients. The study has been running for about 36 months and we were able to visualize QoL charts over several data collection points per patient. Trends within data indicate a relation of the clinical course to changes in QoL. Thus, a possible correlation of the decrease in tumor markers with an increase in QoL is shown. Also, progressions usually result in a significant decrease of QoL. Nevertheless, data also showed that one should be careful to relate the course exclusively to therapy or disease, since environmental influences such as injuries, infections or multimorbidity’s did also result in declines. Here, not only the interpretation of the overall QoL is important, but also the consideration of individual dimensions. Thereby specific limitations of how the patient experiences therapy or possible long-term consequences for survivors get more tangible. To better assess these factors, monitoring of QoL is necessary, not only at visits, but also at home. The developed app for assessing QoL independently was able to show that such a survey can be implemented and applied. Uniform data structure via HL7 FHIR ensures interoperability of the data for both systems. Conclusions: It could be shown that a standardized survey of QoL is possible both in clinical use and independently through patients at home. To close information gaps between clinical visits, both concepts should be merged next to enable an independent survey with a continuous measurement across all therapy stages. With that, adjustments or transitions in therapy could be tailored by limitations in a patients’ QoL.

Symptomatic spinal cord compression in spinal epidural metastasis of a testicular germ cell tumor: a case report with review of the literature

Metastatic germ cell tumors particularly in the bone are rare entities. They occur in young men and classified in the group of poor prognosis. Bone metastases are responsible for a significant functional handicap and a deep alteration in the quality of life of young patients. Metastatic germ cell tumors are rare entities with a high cure rate due to their extreme chemosensitivity. To our knowledge, epidural metastasis of this tumor has not yet been reported in the English medical literature. Tumors of the breast, lung and prostate are the most notorious for metastasizing in the epidural-spinal space. We report a clinical case of spinal cord compression secondary to metastasis in the spinal epidural space of a testicular germ cell tumor in a 23-year-old. Patient whose evolution was marked by a decrease in tumor markers and a clear clinical improvement with disappearance of lower back pain and horsetail syndrome after starting the treatment with decompressive radiotherapy and chemotherapy based on bleomycin cisplatin and etoposide. Through this, we want to emphasize that an epidural metastasis of this tumor is possible, and that it must be part of the diagnoses to be evoked in the face of metastatic spinal cord compression, which potentially allows to avoid a significant functional handicap and a profound alteration in the quality life of young patients.

Paclitaxel, ifosfamide, cisplatin (TIP) for the treatment of intermediateand poor-risk nonseminomatous germ cell tumors with an inadequate decrease in tumor markers: a phase II study

Purpose: To evaluate efficacy of TIP (paclitaxel, ifosfamid, cisplatin) in the 1st line treatment of germ cell tumors patients with unfavorable decline of serum tumor markers after 1 cycle of the standard regimen of chemotherapy. Patients and methods: In this phase II multicenter, nonrandomized trial, patients were enrolled from 4 centers of the Russian Federation. Patients were included if they were older than 18 years, had evidence of testicular, retroperitoneal, or mediastinal nonseminoma based on histologic findings or clinical evidence (high serum human chorionic gonadotropin or alpha-fetoprotein levels) that matched International Germ Cell Cancer Consensus Group (IGCCCG) intermediate and poor prognosis criteria. All patients got one cycle of BEP regimen (bleomycin 30 mg on days 1, 3, 5, etoposide 100 mg / m 2 on days 1–5, cisplatin 20 mg / m 2 on days 1–5). Patients with unfavorable serum tumor markers decline after the first cycle of chemotherapy at day 18–21 received four cycles of TIP regimen (paclitaxel 120 mg / m 2 on days 1–2, ifosfamide 1500 mg / m 2 on days 2–5, and cisplatin 25 mg / m 2 om days 2–5, granulocyte-colony stimulating factor 5 mg / kg on days 6–15). In the presence of a residual tumor larger than 1 cm and the technical possibility of its removal, surgical treatment was performed. The primary endpoint was 1-year progression-free survival. Results: Between 2017 and 2021, 28 patients were included in our study: seven patients with an intermediate prognosis according to IGCCCG classification and twenty-one with poor risk. Median follow-up was 15,5 months (range, 4,4–38,3 months). The 1-year progression-free survival and overall survival in intention-to-treat population were 76,6 % and 81,0 %, respectively. One-year progression-free survival and overall survival according IGCCCG classification were 100 % and 100 % for an intermediate risk patients and 68 % and 73,8 % for a poor risk, respectively. The favorable response rate (complete response + partial response with normalization STM) was observed in 19 (68 %) patients. During the follow-up period, disease progression was noted in 9 (32 %) patients, 7 (25 %) patients died, including one from an aggressive growing mature teratoma syndrome. Eleven (39 %) patients underwent surgical treatment: retroperitoneal lymph node dissection (55 %), mediastinal lymph node dissection (36 %), pulmonary resection (9 %). Pathological complete response was achieved in 6 (55 %) patients, mature teratoma — 2 (18 %), viable tumour — 3 (27 %). TIP showed acceptable safety profile and only in one case tumor lysis syndrome was observed. Conclusions: The TIP regimen may improve the results of treatment in the first line with unfavorable decrease of serum tumor markers after the first cycle of chemotherapy, which requires further study in a randomized trial.

Efficacy of active hexose correlated compound on survival of patients with resectable/borderline resectable pancreatic cancer: a study protocol for a double-blind randomized phase II study

BackgroundThe prognosis of pancreatic ductal adenocarcinoma remains very poor. One possible reason for the short survival of patients with this disease is malnutrition, which can be present at the initial diagnosis, and continue after pancreatectomy. Then, it is important to improve nutritional status and to decrease adverse events during neoadjuvant and adjuvant chemotherapy. Active hexose correlated compound (AHCC) is a standardized extract of cultured Lentinula edodes mycelia, and is considered a potent biological response modifier in the treatment of cancer. To evaluate the survival impact of AHCC on the patients with pancreatic ductal adenocarcinoma, we plan to perform this trial.MethodsThis is a prospective multicenter phase II trial in patients with resectable/borderline resectable pancreatic ductal adenocarcinoma to investigate the efficacy of AHCC regarding survival. Patients will begin taking AHCC or placebo on the first day of neoadjuvant therapy. AHCC or placebo will be continued until 2 years after surgery. The primary endpoint will be 2-year disease-free survival. The secondary endpoints are the completion rate, dose intensity, and adverse event profile of preoperative chemotherapy; response rate to preoperative chemotherapy; rate of decrease in tumor marker (carbohydrate antigen 19-9, carcinoembryonic antigen) concentrations during preoperative chemotherapy; entry rate, completion rate, dose intensity, and adverse event profile of adjuvant chemotherapy; safety of the protocol therapy (adverse effect of AHCC); 2-year overall survival rate; and nutrition score before and after preoperative chemotherapy, and before and after adjuvant chemotherapy. We will enroll 230 patients, and the study involves eight leading Japanese institutions that are all high-volume centers in pancreatic surgery.DiscussionAHCC is expected to function as a supportive food in patients with pancreatic ductal adenocarcinoma, to reduce the proportion of severe adverse events related to neoadjuvant chemotherapy, and to increase the completion proportion of multimodal treatments, resulting in improved survival.Trial registrationThe trial protocol has been registered in the protocol registration system at the Japan Registry of Clinical Trials (Trial ID: jRCTs051200029). At the time of the submission of this paper (October 2020), the protocol version is 2.0. The completion date is estimated to be November 2024.

Case Report: Pathological Complete Response in a Lung Metastasis of Phyllodes Tumor Patient Following Treatment Containing Peptide Neoantigen Nano-Vaccine

Some of the mutant peptides produced by gene mutation transcription and translation have the ability to induce specific T cells, which are called new antigens. Neoantigen-based peptide, DNA, RNA, and dendritic cell vaccines have been used in the clinic. In this paper, we describe a lung metastasis of a phyllodes tumor patient demonstrating pathological complete response following treatment containing personalized multi-epitope peptide neoantigen nano-vaccine. Based on whole-exome sequencing (WES), RNA sequencing, and new antigen prediction, several mutated peptide fragments were predicted to bind to the patient’s human leukocyte antigen (HLA) allotypes, including ten peptides with high predicted binding affinity for six genes. The pulmonary metastases remained stable after the four cycles of anti-PD1 and anlotinib. After the addition of the multi-epitope peptide neoantigen nano-vaccine, the tumor began to collapse and contracture developed, accompanied by a decrease of tumor markers to normal, and complete pathological remission was achieved. With the use of the vaccination, recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was used every time, and low-dose cyclophosphamide was injected every 3 weeks to improve efficacy. Peripheral blood immune monitoring demonstrated immune reactivity against a series of peptides, with the most robust post-vaccine T-cell response detected against the HLA-DRB1*0901-restricted SLC44A5 V54F peptide.

Biochemical Evaluation of Antitumor Activity of Vitamin B17 Alone or in Combination with Platinum Based Drugs Against Ehrlich Ascites Carcinoma in Female Rats

Chemotherapeutic agents are associated with many side effects. Consequently, much research is interested in the discovery of natural phytochemical compounds that can be used in the prevention and/or treatment of cancer. Ehrlich ascites carcinoma (EAC) model was used to indicate the effectiveness of some chemotherapy and plant sources against cancer due to its similarity with human tumors. The present study was undertaken to investigate antitumor and antioxidant effects of vitamin B17 beside platinum-based drugs in EAC-bearing female rats. Animals were randomly distributed into seven groups (n=7) as follows: Group A, negative control. Group B, positive control that was injected by EAC cells as a cancer model. Group C, EAC-bearing rats were treated with cisplatin. Group D, rats with EAC and were treated by a single dose of oxaliplatin. Group E, rats with EAC and were treated with vitamin B17 (VB17). Group F, rats with EAC and were treated with cisplatin plus vitamin B17. Group G, EAC-bearing rats that were treated by single-dose oxaliplatin plus VB17. One week after the beginning of treatments, blood samples were collected and tumor markers (AFP, CEA, CA19-9, TPA, and LDH), as well as antioxidants biomarkers (SOD, CAT, GSH, and MDA), were measured. Liver and kidney functions were evaluated. Besides, histopathological examination was performed to evaluate antitumor activity and side effects of used drugs on hepatic and renal tissues. Results showed that administration of VB17 alone or in combination with cisplatin or oxaliplatin led to a decrease of tumor markers together with enhancement of antioxidant indicators compared with EAC-bearing rats. Statistical analysis showed a significant (P<0.05) increase in the activities of ALT, AST, ALP accompanied by an increase in the serum levels of creatinine, BUN, and total bilirubin in cisplatin and oxaliplatin treated groups, thus confirming their toxic effects on hepatocytes and renal cells. These findings were supported by histopathological alterations in these groups. VB17 treated groups showed improvement in the studied parameters. From the current study, it could be concluded that vitamin B17 possesses anticancer and antioxidant activities that justify its traditional use, and its potential hepatoprotective effect and kidney ameliorative role.

Early tumor marker decrease to predict the efficacy of combination therapy with lenvatinib plus anti-PD-1 antibodies in unresectable hepatocellular carcinoma (uHCC).

304 Background: Combination therapy with anti-angiogenic agents plus anti-PD-1 antibodies has shown high anti-tumor activity in uHCC. However, predicting the efficacy of this combination therapy remains a challenge. Methods: This study included consecutive patients with uHCC who received lenvatinib (8 mg/d regardless of body weight) and an anti-PD-1 antibody as first-line systemic therapy between Sep 2018 and July 2020, and had at least one imaging evaluation. Tumor response was assessed every 2 months (± 2 week) by the investigators using modified RECIST criteria. Patients were evaluated as having a radiological response (complete or partial response) or non-radiological response (stable disease or progressive disease) at the best overall response evaluation. Serum tumor markers for HCC, including alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), were evaluated at baseline and 2-3 weeks after therapy was initiated and their association with radiological response were assessed. Patients with baseline AFP or PIVKA-II between the upper limit of normal and the maximum measuring range of the kit were evaluable for AFP decrease or PIVKA-II decrease. Results: A total of 76 patients were eligible for this study. Baseline AFP ≥400 ng/mL or PIVKA-II ≥400 mAU/mL was not associated with radiological response (P = 0.167 and P = 0.916, respectively). At 2-3 weeks after the initiation of therapy, 51 patients were evaluable for AFP decrease; 78.4% experienced a &gt; 20% AFP decrease and 51.0% experienced a &gt; 50% AFP decrease. Patients with a &gt; 50% AFP decrease had a higher rate of radiological response than those with AFP increase or a ≤50% AFP decrease (73.1% vs 32.0%, P = 0.003). In 57 patients evaluable for PIVKA-II decrease, 50.9% and 35.1% experienced a &gt; 20% and &gt; 50% PIVKA-II decrease, respectively. Patients with a &gt; 50% PIVKA-II decrease had a higher rate of radiological response than those with PIVKA-II increase or a ≤50% PIVKA-II decrease (85.0% vs 29.7%, P &lt; 0.001). Both AFP decrease &gt; 50% and PIVKA-II decrease &gt; 50% predicted radiological response, with an area under receiver operating characteristic curve of 0.706 (95% CI, 0.560-0.852, P = 0.012) and 0.752 (95% CI, 0.621-0.883, P = 0.001), respectively. Furthermore, patients with a &gt; 20% AFP or PIVKA-II increase from baseline had a lower rate of radiological response (0% vs 57.4%, P = 0.043; and 21.7% vs 69.7%, P &lt; 0.001, respectively). Conclusions: A tumor marker decrease was seen in most patients as early as 2-3 weeks after the initiation of the combination therapy. Early on-treatment AFP or PIVKA-II decrease may serve as a predictor for objective response for patients with uHCC receiving combination anti-angiogenic and immune therapy.

Complete Remission of the Severe Advanced Stage Cancer by miRNA-Mediated Transcriptional Control of Bcl-xL with Huaier Therapy Compared to the Conventional Chemotherapy with Platinum (II) Complex

Background: The severe advanced stage cancer has scarce choice of treatment except pain control. Conventional chemotherapy is commonly not applicable for these patients from severe adverse events and toxicity.

Conversion hepatectomy for advanced hepatocellular carcinoma after right portal vein transection and lenvatinib therapy

BackgroundLenvatinib is a novel tyrosine kinase inhibitor that exhibits an antitumor effect on hepatocellular carcinoma (HCC). An established strategy that involves surgery and usage of lenvatinib for advanced HCC remains elusive.Case presentationA 58-year-old male patient with advanced HCC and untreated hepatitis B was referred to our hospital. The tumor at the right lobe was 10 cm in diameter with right portal vein thrombus. Because of the possible lung metastasis and concern about the remaining hepatic function after extended right hepatectomy, lenvatinib was initiated before surgery. After the confirmation of a sharp decrease of tumor markers during the 3-week lenvatinib therapy, only a right portal vein transection was done leaving the enlargement of the left lobe for improved post-hepatectomy liver function while lenvatinib therapy was continued. The laparotomy revealed that the tumor was invading the right diaphragm. After 7 weeks of lenvatinib administration after right portal vein transection, an extended right hepatectomy with resection of the tumor-invaded diaphragm was successfully done. The lung nodules that were suspected as metastases had disappeared. The patient has been doing well without any sign of recurrence for 1 year.ConclusionThe strategy involving the induction of lenvatinib to conversion hepatectomy including the portal vein transection was effective for advanced HCC.

Predictive and prognostic factors of apatinib in metastatic colorectal cancer.

e16092 Background: It has been extremely challenging to identify suitable predictive or prognostic factors of anti-VEGF agents. Apatinib, a vascular endothelial growth factor receptor 2(VEGFR-2) inhibitor, showed promising efficacy in chemo-refractory metastatic colorectal cancer (mCRC) patients in a phase II trial. The aim of current study was to identify the potential predictive and prognostic factors of apatinib in this phase II trial. Methods: A total of 48 patients with mCRC who had failed from standard fluorouracil-containing chemotherapies were recruited in this prospective single-arm study. Apatinib at a 500mg dose was administered daily continuously. Clinical parameters, including patients background, biochemical parameters at baseline, tumor markers at baseline and day 28, and adverse events in initial 28 days were evaluated to identify predictive and prognostic factors. The median neutrophil/lymphocyte ratio (NLR) was adopted as a cutoff value to discriminate patients with low versus high NLR. Early tumor marker decrease was defined as an abnormal parameter with a decrease of &gt; 10% by day 28. This study is registered with the Chinese Clinical Trial Registry, number ChiCTR1900020503. Results: Patients characteristics were not associated with differences in PFS and OS. Seven (14.6%) and 11 (22.9%) patients had initial normal CEA and CA19-9, respectively, and were excluded from the analysis of tumor markers. The median NLR were 4.1. In univariate analysis, low baseline NLR, early CA19-9 decrease, and the hand-foot syndrome (HFS) were associated with good progression-free survival (PFS) [NLR, HR 0.38 (95% CI 0.16–0.89), P = 0.027; CA19-9, HR 0.37 (95% CI 0.16-0.83), P = 0.016; HFS HR 0.23 (95% CI 0.08-0.68, P = 0.007); respectively]. Low baseline NLR and early CA19-9 decrease were also associated with good overall survival (OS) [NLR, HR 0.34 (95% CI 0.17–0.67), P = 0.002; CA19-9, HR 0.46 (95% CI 0.23-0.95), P = 0.035; respectively]. NLR and HFS retained a significant association with PFS [NLR, HR 0.36 (95% CI 0.15–0.84), P = 0.019; HFS, HR 0.25 (95% CI 0.08–0.77), P = 0.016; respectively] while only NLR retained a significant association with OS [NLR, HR 0.35 (95% CI 0.17–0.70), P = 0.019] in the multivariate analysis using the aforementioned factors. Conclusions: Clinical parameters including low baseline NLR, early CA19-9 decrease and HFS could be positive predictive factors of the efficacy of apatinib in mCRC. NLR could be the independent prognostic factor of OS in mCRC. Additional studies are warranted for further validation.

Clinical significance of serum tumor markers for advanced gastric cancer with the first-line chemotherapy.

BackgroundTumor markers play an important role in the diagnosis, monitoring and prognostic prediction of cancers. But the predictive value of serum tumor markers in gastric cancer is still unclear.MethodsIn this study, we detected serum levels of tumor markers to evaluate their relation to treatment response and prognosis in patients with unresectable advanced or metastatic gastric cancer.ResultsWe collected the clinical data of 109 patients with unresectable advanced or metastatic gastric cancer who had received the first-line chemotherapy in Peking University Cancer Hospital from July 2013 to May 2015, and collected the value of serum carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), carbohydrate antigen 72.4 (CA72.4) and carbohydrate antigen 125 (CA125) before and after chemotherapy. At diagnosis, the positive rates of CEA, CA199, CA72.4 and CA125 were 46.8%, 40.2%, 53.5% and 35.0%, respectively. And the positive rate of combined detection of the four markers was 87.2%. Although patients with prechemotherapy CA199 ≥80 U/mL (92.3% vs. 68.5%, P=0.016) or CA72.4 ≥20 U/mL (91.4% vs. 62.5%, P=0.003) had higher clinical benefit rate after chemotherapy, they showed poorer prognosis (P=0.023 and P=0.006, respectively). CA72.4 ≥20 U/mL was an independent unfavorable prognostic factor (Hazard Ratio 4.84; 95% confidence interval: 1.910–12.262; P=0.001). In patients with increased levels of tumor markers before treatment, the levels of tumor markers decreased after chemotherapy, especially in those with clinical benefit (CEA, CA72.4 reached statistical significance, P=0.013 and P=0.029, respectively). A decrease of CEA ≥35%, CA199 ≥30%, or CA72.4 ≥40% after chemotherapy had positive prediction value for the response to chemotherapy (P=0.016, P=0.029, and P=0.008, respectively).ConclusionsThe results showed that both high pre-chemotherapy serum levels of tumor markers (CA199 ≥80 U/mL or CA72.4 ≥20 U/mL) and a substantial decrease in tumor markers after chemotherapy (CEA ≥35%, CA199 ≥30%, or CA72.4 ≥40%) could predict a higher clinical benefit rate in patients with unresectable advanced or metastatic gastric cancer. However, this advantage in short-term response to chemotherapy failed to convert into prolonged survival benefits.

Helical tomotherapy for chemo-refractory multiple liver metastases.

BackgroundDespite advances in chemotherapy, curing multiple liver metastases is quite rare. Even when response is obtained, regrowth of the tumors is almost inevitable. We aimed to evaluate the efficacy and adverse events of helical tomotherapy for chemo‐refractory multiple liver metastases.MethodsForty‐five patients with chemo‐refractory multiple (3‐10) liver metastases after standard systemic chemotherapy entered the single‐institutional prospective study. Liver metastases were the major disease; however, 31 also had uncontrolled primary lesions and/or other metastases. The prescribed dose was 55 Gy in 25 fractions. The median planning target volume (PTV) and normal liver volume (NLV) of first treatment were 128 cm3 and 1175 cm3, respectively. The median of V15Gy, V30Gy, and mean dose to NLV were 45%, 23%, and 19.4 Gy, respectively.ResultsForty‐two patients (93%) completed the planned treatment. Median survival time (MST) for all patients was 8 months, and the 1‐year survival rate was 29%. The median local control (LC) period was 5 months and the 6‐month control rate of irradiated tumors was 33%. A ≥30% decrease in tumor markers was observed in 31%. The most common grade 3 toxicity was lymphocytopenia (40%), followed by fatigue (6%). Radiation‐induced liver disease (RILD) was not observed. Pancreatic cancer as the primary tumor, distant metastases outside the liver, low pretreatment neutrophil‐to‐lymphocyte ratio (NLR), and low pretreatment monocyte‐to‐lymphocyte ratio (MLR) were associated with poorer prognoses.ConclusionsHelical tomotherapy for chemo‐refractory multiple liver metastases is a feasible and potentially effective treatment. Incorporating tomotherapy into the first‐line treatment in combination with systemic chemotherapy should be considered.Trial registration numberCROG 12005.

Efficacy and safety of compound Kushen injection combined with chemotherapy on postoperative Patients with breast cancer: A meta-analysis of randomized controlled trials.

Background:This meta-analysis aimed to assess efficacy and safety of combination of Kushen and chemotherapy or chemotherapy alone among postoperative patients with breast cancer receiving.Methods:A systematic literature search was conducted for relevant randomized controlled trials from 2000 to July 2017. Primary outcomes were clinical response rate (CRR) and performance status improvement by Karnofsky performance scale score (KPSS); secondary outcomes were adverse drug reactions (ADRs) rate and tumor marker decrease rate. Quality assessment and data analysis were performed with Review Manager 5.3.Results:A total of 16 studies with 1315 participants were included in the analysis. Compared with chemotherapy alone, compound Kushen injection (CKI or KI) combined with chemotherapy did not significant increase CRR. However, performance status improvement rate was significantly higher among patients given Kushen injection combined with chemotherapy (relative risk 1.25, 95% confidence interval 1.09–1.42, P = .001). In the analysis of ADRs, combination of Kushen and chemotherapy was indicated to significantly reduce the rate liver dysfunction, kidney dysfunction, nausea and vomiting, diarrhea, hair loss, platelet decrease, and oral mucositis.Conclusion:Using CKI on the basis of chemotherapy might improve performance status and reduce ADRs among postoperative patients with breast cancer.

Abstract A52: Cell free DNA (cfDNA) to monitor clonal evolution in patients (pts) with KRAS wild-type (WT) metastatic colorectal cancer (mCRC): Preliminary results of a phase I/II clinical trial of the anti-MET multi-kinase inhibitor cabozantinib (C) plus the anti-EGFR monoclonal antibody panitumumab (P)

Abstract Background: Several molecular alterations drive acquired resistance to anti-EGFR therapies in pts with KRAS WT mCRC. We designed a clinical trial to identify and treat MET amplification (amp), a well described driver of acquired EGFR resistance. Methods: Pts with KRAS WT mCRC were enrolled in 3 cohorts: 1) C+P Dose Finding (Dose Find): 3+3 design to determine the maximum tolerated dose (MTD) and recommended phase II dose (RPTD) of C+P; 2) C+P Expansion (Exp): to define the safety, tolerability and activity of C+P; and 3) MET amplified monotherapy (MET Mono): to determine the response rate of C alone in pts with prospectively identified MET amp/ EGFR refractory mCRC. Response assessment occurred every 2 months with computed tomography (CT) using RECIST criteria, version 1.1. cfDNA was collected at baseline and each restaging until progression. In the C+P Dose Find and Exp cohorts, peripheral blood was retrospectively sequenced for 54 gene mutations (mut) and focal amplifications, including MET (Guardant Health, Inc.). MET expressing circulating tumor cells (CTCs) were captured utilizing nanomagnetic particles conjugated to an antibody targeting extracellular MET (Janssen R&amp;D, LLC). Genomic amp was tested in tumor tissue using next generation sequencing (NGS) or FISH. These data allowed subgroup and individual pt profiling. Results: There were no dose limiting toxicity (DLT) events at the RPTD (C 60mg PO daily and P 6 mg/kg IV Q2 weeks) in the Dose Find cohort (n = 6). Assessment of treatment response in C+P cohorts: As of 7/21/2015, 13 pts were treated at the RPTD. 3 pts had not yet received response assessment; 10 pts (6 Dose Find; 4 Exp) were evaluable for response. 8/10 evaluable pts had failed prior anti-EGFR therapy. 6/10 had reduction in RECIST lesions (2/2 EGFR naïve; 4/8 EGFR refractory). Median change was -10% (range -40% to +18%). 2/2 evaluable pts with MET amp cfDNA had a reduction in target lesions (both EGFR refractory). 7/10 had a decrease in tumor marker (CEA). Median CEA change was -39% (range -86% to +103%). Baseline cfDNA profiling in C+P and MET Mono cohorts: 13 pts with EGFR refractory mCRC (6 Dose Find; 3 Exp; 4 MET mono) had baseline cfDNA profiling. 4/13 BRAF mut (2/4 subclonal), 3/13 KRAS mut (2/3 subclonal), 1/13 NRAS mut (0/1 subclonal), 3/13 HER2 amp (3/3 confirmed in tissue), 4/13 MET amp (0/2 in tissue; 2 not tested). Pt examples: One subject (EGFR refractory) had a lymph node biopsy 3 months prior to C+P that revealed no MET amp by NGS (Foundation Medicine). Pre-treatment cfDNA revealed MET amp. Treatment with C+P resulted in a partial response (-40% in RECIST lesions). MET amp was no longer detected in cfDNA at first restaging. A second subject had MET amp in pre-treatment cfDNA. MET-expressing CTCs were captured from peripheral blood. Single cell FISH on CTCs-but not archival tissue-confirmed MET amp. Conclusions: This ongoing phase I/II study demonstrates the feasibility of: 1) using cfDNA to detect MET amp in pts with EGFR refractory mCRC, even when archival tissue is negative; and 2) capturing MET-expressing CTCs to confirm MET amp. Preliminary clinical results support prospective cfDNA screening to identify and treat pts with EGFR refractory/ MET amp mCRC. Citation Format: John H. Strickler, Tian Zhang, Andrew J. Armstrong, Donna Niedzwiecki, Hope E. Uronis, Michael A. Morse, S. Yousuf Zafar, Shiao-Wen D. Hsu, Christy C. Arrowood, Rebecca Nagy, AmirAli Talasaz, Richard Lanman, Sherri Haley, Herbert I. Hurwitz. Cell free DNA (cfDNA) to monitor clonal evolution in patients (pts) with KRAS wild-type (WT) metastatic colorectal cancer (mCRC): Preliminary results of a phase I/II clinical trial of the anti-MET multi-kinase inhibitor cabozantinib (C) plus the anti-EGFR monoclonal antibody panitumumab (P). [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A52.

Abstract CT216: Phase I/IIa non-randomized open-label trials with mouse renal adenocarcinoma (RENCA) cell containing agarose-agarose macrobeads in patients with treatment-resistant metastatic colorectal carcinoma

Abstract Background: The purpose of phase I/IIa trials of RENCA tumor cells encapsulated in two concentric agarose layers is to evaluate safety and efficacy of agarose-agarose MB in various cancers, particularly advanced colorectal cancer (CRC) as reported in this abstract. MB release signals that inhibit tumor growth at primary or metastatic tumor locations. This novel approach has been substantiated in in vitro and in vivo models as reported in Cancer Research 71(3), 716-735, 2011. We report results of phase I/IIa studies in advanced metastatic CRC patients. Methods: CRC patients who have progressive disease after all available treatment modalities with ECOG PS of 0-2 were enrolled to the trial after informed consents were obtained. Patients underwent laparoscopic intraperitoneal implantations up to 4 times with 8 (43/46 patients- established dose) or 16 (3/46 patients) RENCA MB/kg. Serial clinical examinations, blood tests, and imaging were obtained before and 3 months (mo.) after implantations to assess safety and efficacy. Endpoints of safety as measured by description of adverse events, and efficacy as measured by tumor marker response, were noted. Results: 46 pts were implanted with RENCA MB (12 pts phase I; 34 pts phase II); of which 18 were males and 28 were females. Mean age was 58.2 years. 29/46 pts had a total of 1 implant (14 had a total of 2 implants; 1 had a total of 3 implants; 2 had a total of 4 implants). Response to MB is marked by a prominent initial rise in CRP, ESR, and IL-6, indicating a systemic inflammatory response (SIR) (100% of pts) and a parallel decrease in CEA and/or CA 19-9 in approximately 72%. SIR including its accompanying fatigue and anorexia lasts days to 3 wks. Overall, there was a significant difference in OS between the 72% of pts showing a decrease in tumor markers by at least 20% during the first 30 days post-implant (mean OS; 10.76 mo.) and those who did not (mean OS; 4.9 mo.). On PET-CT imaging, an important feature of response, most often seen in patients with the longest survival, was tumor necrosis. MB were well-tolerated. No Grade ≥3 adverse events were determined to be treatment-related. Conclusions: In reported phase I/IIa trials in advanced, metastatic, treatment-resistant CRC patients, response to RENCA MB after implantation was characterized by decrease in tumor markers in association with SIR. This response was correlated with a significant increase in OS. RENCA MB represent a possible new therapeutic option for advanced, metastatic CRC. Citation Format: Allyson J. Ocean, Nathaniel Berman, Tapan Parikh, Zoe P. Andrada, Angelica Nazarian, Joanne Thomas, Eugene Akahoho, George Stoms, Alex Yaroshinsky, Thomas J. Fahey, David J. Wolf, Lawrence S. Gazda, Barry H. Smith. Phase I/IIa non-randomized open-label trials with mouse renal adenocarcinoma (RENCA) cell containing agarose-agarose macrobeads in patients with treatment-resistant metastatic colorectal carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT216. doi:10.1158/1538-7445.AM2015-CT216

Abstract CT315: Phase I study of BPM 31510 (ubidecarenone) in patients with advanced solid tumors

Abstract Background: BPM 31510 is a novel small molecule that targets the metabolic machinery of the cancer microenvironment to create a hallmark shift from lactate dependency towards mitochondrial oxidative phosphorylation, reversing the Warburg effect. Preclinical data indicates Ubidecarenone causes this shift resulting in tumor regression and enhances the antitumor activity in combination with chemotherapy agents in a priming schedule. This is the first clinical study to evaluate the BPM 31510 at a 4-days continuous infusion in four arms; as a single agent, and in combination with Gemcitabine, 5-FU or Docetaxel. Methods: Eligible patients (pts) (aged ≥18 y) had previously treated relapsed/refractory solid tumors. Pts in the monotherapy arm received IV BPM 31510 for 4 days in continuous infusion in 28-d cycles. Patients in the combination arms were primed for 3 weeks with BPM 31510 and then started in a weekly dosing (either gemcitabine, 5-FU or docetaxel) after the BPM 31510 infusion in a 6-week cycle. Doses were escalated in a 3+3 schema. Phase I endpoints were safety, pharmacokinetics (PK) and Multi-Omics based pharmacodynamics (PD). Dose limiting toxicities (DLTs) are determined using Cycle 1 safety data. Tumor response is evaluated at week 2 and every 4 -6 weeks. Results: As of 01 Dec 2014, 56 pts with advanced solid tumors have been enrolled. Pts have been treated at 3 dose levels up to 137 mg/kg of BPM 31510. No DLTs or study treatment-related SAEs have been reported. The MTD has not yet been established. The most frequently reported related AEs in all 4 arms were grade 1-2 INR prolongation that was resolved after Vitamin K administration. Pre-load of pts with Vitamin K have resolved these events. No bleeding reported. Grade 1-2 thrombocytopenia has been seen in the Gemcitabine arm requiring dose modification. Preliminary PK data indicated linear distribution. Tmax and Cmax are associated with the end of the infusion. Twelve out of twenty five patients (48%) that are evaluable for efficacy after cycle 2 showed various responses including: tumor reductions, decrease FDG, arrested tumor progression, stable disease, decrease in tumor markers, clinical improvements reflected on QOL. Conclusions: Emerging data from this study suggest that BPM 31510 is well tolerated in monotherapy or in combination with chemotherapy agents. Early anti-tumor activity is seen. Dose-escalation on a 6-day infusion schedule is ongoing to determine the recommended phase II dose. Citation Format: Manish A. Shah, Peter Yu, Niven Narain, Rangaprasad Sarangarajan, Michael Kiebish, Vivek Vishnudas, Yezhou Sun, Leonardo Rodrigues, Viatcheslav R. Akmaev, Susan Brouwer, Janice Stevens, Ely Benaim, Ralph Zinner. Phase I study of BPM 31510 (ubidecarenone) in patients with advanced solid tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT315. doi:10.1158/1538-7445.AM2015-CT315

Endometriosis peritoneal masiva asociada a gran elevación de CA-125: discrepancia entre hallazgos y clínica

SUMMARY Background: Frequently, patients with endometriosis present elevated tumor marker Ca 125 and Ca 19.9. However, there is no clear correlation with the clinical expression or the degree of involvement. In some cases, differential diagnosis is necessary with malignancies. Case report: A 29 year old woman with moderate dysmenorrhea and finding of bilateral ovarian masses with intense elevation of tumor markers, CA125: 7,716 U/mL and Ca-19.9: 995 U/mL. Laparoscopic surgery is decided evidenced massive ovarian endometriosis and peritoneal extension with involvement of abdominal peritoneum, uterine surface, Douglas, parametrium, bladder, right hemidiaphragm, liver and intestinal serosa. Careful liberation of adherences, ovarian cystectomy and removal of multiple endometriosic implants. A decrease of tumor markers was observed at 48 hours (Ca-125: 253 U/mL and Ca-19.9: 4.9 U/mL), and negative one month after surgery. Conclusion: An intense elevated tumor markers accurate differential diagnosis in the context of endometriosis. There is a large discrepancy between the values of tumor markers with clinical and severity of endometriosis.

Radium-223 dichloride bone-targeted alpha particle therapy for hormone-refractory breast cancer metastatic to bone.

BackgroundHormone-refractory breast cancer metastatic to bone is a clinically challenging disease associated with high morbidity, poor prognosis, and impaired quality of life owing to pain and skeletal-related events. In a preclinical study using a mouse model of breast cancer and bone metastases, Ra-223 dichloride was incorporated into bone matrix and inhibited proliferation of breast cancer cells and differentiation of osteoblasts and osteoclasts (all P values < .001) in vitro. Ra-223 dichloride also induced double-strand DNA breaks in cancer cells in vivo.MethodsThe US Food and Drug Administration recently approved radium-223 (Ra-223) dichloride (Ra-223; Xofigo injection) alpha-particle therapy for the treatment of symptomatic bone metastases in patients with castration-resistant prostate cancer. On the basis of a strong preclinical rationale, we used Ra-223 dichloride to treat bone metastases in a patient with breast cancer.ResultsA 44-year-old white woman with metastatic breast cancer who was estrogen receptor–positive, BRCA1-negative, BRCA2-negative, PIK3CA mutation (p.His1047Arg) positive presented with diffuse bony metastases and bone pain. She had hormone refractory and chemotherapy refractory breast cancer. After Ra-223 therapy initiation her bone pain improved, with corresponding decrease in tumor markers and mixed response in 18F-FDG PET/CT and 18F-NaF bone PET/CT. The patient derived clinical benefit from therapy.ConclusionWe have shown that Ra-223 dichloride can be safely administered in a patient with hormone-refractory bone metastasis from breast cancer at the US FDA–approved dose for prostate cancer. Furthermore, because the treatment did not cause any drop in hematologic parameters, it has the potential to be combined with other radiosensitizing therapies, which may include chemotherapy or targeted therapies. Given that Ra-223 dichloride is already commercially available, this case report may help future patients and provide a rationale for initiating clinical research in the use of Ra-223 dichloride to treat bone metastasis from breast cancer. A randomized clinical trial is needed to provide evidence of efficacy, safety, and good outcomes.