scholarly journals Role of Resin Microsphere Y90 Dosimetry in Predicting Objective Tumor Response, Survival and Treatment Related Toxicity in Surgically Unresectable Colorectal Liver Metastasis: A Retrospective Single Institution Study

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4908
Author(s):  
Tina Sankhla ◽  
Bernard Cheng ◽  
Nariman Nezami ◽  
Minzhi Xing ◽  
Ila Sethi ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Liver Metastasis ◽  
Metastatic Disease ◽  
Colorectal Liver Metastasis ◽  
Roc Curve ◽  
Tumor Response ◽  
Liver Toxicity ◽  
Objective Tumor Response ◽  
Genomic Mutation ◽  
Grade 3

Purpose: To Evaluate the correlation between tumor dosimetric parameters with objective tumor response (OR) and overall survival (OS) in patients with surgically unresectable colorectal liver metastasis (CRLM) undergoing resin-based Ytrrium-90 selective internal radiation therapy (Y90 SIRT). Materials and Methods: 45 consecutive patients with CRLM underwent resin-based Y90 SIRT in one or both hepatic lobes (66 treated lobes total). Dose volume histograms were created with MIM Sureplan® v.6.9 using post-treatment SPECT/CT. Dosimetry analyses were based on the cumulative volume of the five largest tumors in each treatment session and non-tumoral liver (NTL) dose. Receiver operating characteristic (ROC) curve was used to evaluate tumor dosimetric factors in predicting OR by Response Evaluation Criteria for Solid Tumors at 3 months post-Y90. Additionally, ROC curve was used to evaluate non-tumoral liver dose as a predictor of grade ≥ 3 liver toxicity and radioembolization induced liver disease (REILD) 3 months post Y90. To minimize for potential confounding demographic and clinical factors, univariate and multivariate analysis of survival with mean tumor dose as one of the factors were also performed. Kaplan-Meier estimation was used for OS analysis from initial Y90 SIRT. Results: 26 out of 45 patients had OR with a median OS of 17.2 months versus 6.8 months for patients without OR (p < 0.001). Mean tumor dose (TD) of the five largest tumors was the strongest predictor of OR with an area under the curve of 0.73 (p < 0.001). Minimum TD, and TD to 30%, 50%, and 70% of tumor volume also predicted OR (p’s < 0.05). Mean TD ≥ 100 Gy predicted a significantly prolonged median OS of 19 vs. 11 months for those receiving TD < 100 Gy (p = 0.016). On univariate analysis, mean TD < 100 Gy, presence of any genomic mutation, presence of MAPK pathway mutation, bilobar hepatic metastases and diffuse metastatic disease (>10 lesions per liver lobe) were found to be predictors of shorter median OS. On multivariate analysis, mean TD < 100 Gy, presence of any genomic mutation, and diffuse hepatic metastatic disease were found to be independent predictors of shorter OS. Overall, six (13.3%) patients developed grade ≥ 3 liver toxicity post Y90 of whom two (4.4%) patients developed REILD. No dose threshold predicting grade ≥ 3 liver toxicity or REILD was identified. Conclusions: Mean TD ≥ 100 Gy in patients with unresectable CRLM undergoing resin-based Y90 SIRT predicts OR and prolonged OS.

Risk and determinants of developing severe liver toxicity during therapy with nevirapine-and efavirenz-containing regimens in HIV-infected patients

2003 ◽  
Vol 14 (11) ◽  
pp. 776-781 ◽  
Author(s):  
Javier Ena ◽  
Concepción Amador ◽  
Concepción Benito ◽  
Vicenta Fenoll ◽  
Francisco Pasquau
Keyword(s):  
Multivariate Analysis ◽  
Hepatitis C ◽  
Relative Risk ◽  
Antiretroviral Therapy ◽  
Alcohol Intake ◽  
Liver Toxicity ◽  
Severe Liver ◽  
Upper Limit ◽  
Median Period ◽  
Grade 3

We examined the risk and determinants of developing severe liver toxicity in 108 HIV-infected patients showing adherence to nevirapine- and efavirenz-containing regimens. Between January 1997 and December 2000, 70 patients were treated with nevirapine- and 38 patients with efavirenz-containing regimens, for a median period of 127 days (interquartile range 65-240). Severe liver toxicity was defined as grade 3-4 elevations (>5×upper limit of normal) of aminotransferases AST or ALT. A total of 22 (20%) patients showed severe liver toxicity, 17 of them were treated with nevirapine- and five with efavirenz-containing regimens (relative risk [RR]: 1.85, 95% confidence intervals [CIs] 0.74-4.61; P=not significant). Multivariate analysis showed the association of severe liver toxicity with hepatitis C antibody positive (RR 7.64; 95% CI: 1.48-39.52; P=0.01), nevirapine- or efavirenz-containing regimens combined with a protease inhibitor (RR: 3.07, 95% CI: 1.01-9.32, P=0.04) and alcohol intake greater than 40 g per day (RR: 3.09, 95% CI: 1.27-7.54, P=0.01). These findings have potential implications for selecting and monitoring antiretroviral therapy in HIV-infected patients with hepatitis C virus coinfection and for avoiding alcohol intake during antiretroviral therapy.

scholarly journals Tumor response and outcome after reverse treatment for patients with synchronous colorectal liver metastasis: a cohort study

BMC Surgery ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Céline Du Pasquier ◽  
Didier Roulin ◽  
Pierre Bize ◽  
Christine Sempoux ◽  
Caterina Rebecchini ◽  
...  
Keyword(s):  
Cohort Study ◽  
Liver Metastasis ◽  
Colorectal Liver Metastasis ◽  
Tumor Response ◽  
Synchronous Colorectal Liver Metastasis

Initial results from a phase II trial of motesanib diphosphate (AMG 706) in patients with differentiated thyroid cancer (DTC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6017-6017 ◽  
Author(s):  
S. I. Sherman ◽  
M. J. Schlumberger ◽  
J. Droz ◽  
M. Hoffmann ◽  
L. Wirth ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Antitumor Activity ◽  
Tumor Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Open Label ◽  
Resistant Disease ◽  
Objective Tumor Response ◽  
Grade 5 ◽  
Grade 3

6017 Background: This phase 2 study evaluated the safety and efficacy of AMG 706, an oral, investigational multikinase (MKI) inhibitor with antiangiogenic and direct antitumor activity achieved by selectively targeting VEGF, PDGF, and Kit receptors and RET, in pts with advanced DTC or medullary thyroid cancer (MTC). Presented here are results from the DTC stratum. Methods: This was a multicenter, phase 2, open-label, single-arm study of pts with advanced thyroid cancer stratified by DTC or MTC (planned n=80 each). The primary endpoint was objective tumor response per modified RECIST by independent central review. Secondary DTC endpoints were duration of response and progression-free survival (PFS). Pts = 18 yrs with progressive, 131I-resistant disease, ECOG 0–2, and no prior treatment with VEGFr MKIs received AMG 706 125mg QD until disease progression or unacceptable toxicity. Assessments included tumor response (q8w), pharmacokinetics (PK), and safety. Results: 93 pts with DTC were enrolled and received at least 1 dose of AMG 706. DTC subtypes were: papillary, 58%; Hürthle cell, 18%; follicular, 16%; other, 8%. Median (range) age was 62 (36–81) yrs. 20% of pts had prior chemotherapy; 96% had prior 131I therapy. With median follow-up of 32 wks, objective tumor response (CR or PR) rate (95% CI) was 12% (6.1, 20.2); SD, n=64 (69%; durable SD =24 wks, 24%); PD, n=7 (8%). Median (95% CI) time to response was 103 (53, 161) days; median PFS was 276 (221, not estimable) days. 85% of pts were alive >8 months after starting therapy. All pts (100%) had some treatment- emergent adverse events (AE): grade 3, 55%; grade 4, 10%; grade 5, 5% (all grade 5 were deemed unrelated to AMG 706). Common AEs included diarrhea (70%; 11% grade 3), fatigue (58%; 5% grade 3), hypertension (49%; 22% grade 3), headache (43%; 4% grade 3), nausea (40%; 2% grade 3), and hypothyroidism and/or increased TSH (17%; no grade 3); none of these were grade 4 or 5. 6% of pts had cholecystitis. PK results showed that AMG 706 PK at 125mg QD was comparable to data obtained in other monotherapy studies at the same dose level. Conclusions: In this study of pts with advanced 131I-resistant DTC, AMG 706 showed encouraging antitumor activity and had tolerable and manageable toxicities. Further investigation is warranted. No significant financial relationships to disclose.

Impact of “poorly differentiated clusters” in primary lesion as a novel prognostic indicator in colorectal liver metastasis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3625-3625
Author(s):  
Tsuyoshi Konishi ◽  
Hideki Ueno ◽  
Yuichi Ishikawa ◽  
Masashi Ueno ◽  
Akio Saiura ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Liver Metastasis ◽  
Colorectal Liver Metastasis ◽  
Prognostic Indicator ◽  
Primary Lesion ◽  
Clinicopathological Parameters ◽  
Perioperative Chemotherapy ◽  
Poorly Differentiated Clusters ◽  
Poorly Differentiated ◽  
The Impact

3625 Background: Preoperative predictors for survival are needed in colorectal liver metastasis in order to select poor-risk group that truly requires perioperative chemotherapy. This study aimed to elucidate survival predictors in patients undergoing curative hepatectomy for colorectal liver metastasis, particularly focusing on the impact of poorly differentiated clusters (PDC); a novel histologic grading system in primary lesion. Methods: A total of 424 consecutive patients undergoing curative resection of both primary colorectal cancers and metastatic liver lesions at two referral centers were enrolled in the study. Determinants of overall survival (OS) and recurrence free survival (RFS) after hepatectomy were investigated by univariate and multivariate analysis, using detailed clinicopathological parameters in primary and metastatic lesions. Cancer clusters of ≥5 cancer cells and lacking a gland-like structure were counted under a x20 objective lens in a field containing the highest number of clusters at invasive front of primary lesions, and tumors with <5, 5 to 9, and ≥10 clusters were classified as PDC grade (G)1, G2 and G3, respectively (n=65, 132, and 227 tumors, respectively). Results: OS and RFS at 3 years were 59% and 27%, respectively, with average follow up period of 43 months. PDC grade in primary lesion was strongly associated with both 3-year-OS (83%, 62%, and 51%, respectively, p<0.0001) and 3-year-RFS (55%, 30%, and 17%, respectively, p<0.0001). Multivariate analysis revealed that PDC grade in primary lesion was the most potent prognostic factor after hepatectomy independent of T and N of primary lesion and size of liver metastasis. Conclusions: PDC grade in primary lesion is a novel potent prognostic indicator in colorectal liver metastasis, which is independent of T and N. It is noteworthy that PDC grade can bias the survival in clinical studies targeting perioperative chemotherapy in colorectal liver metastasis.

scholarly journals Randomized Phase II Trial of Gemcitabine Plus TH-302 Versus Gemcitabine in Patients With Advanced Pancreatic Cancer

2015 ◽  
Vol 33 (13) ◽  
pp. 1475-1481 ◽  
Author(s):  
Mitesh J. Borad ◽  
Shantan G. Reddy ◽  
Nathan Bahary ◽  
Hope E. Uronis ◽  
Darren Sigal ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Metastatic Disease ◽  
Tumor Response ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Randomized Phase Ii ◽  
Grade 3

Purpose TH-302 is an investigational hypoxia-activated prodrug that releases the DNA alkylator bromo-isophosphoramide mustard in hypoxic settings. This phase II study (NCT01144455) evaluated gemcitabine plus TH-302 in patients with previously untreated, locally advanced or metastatic pancreatic cancer. Patients and Methods Patients were randomly assigned 1:1:1 to gemcitabine (1,000 mg/m2), gemcitabine plus TH-302 240 mg/m2 (G+T240), or gemcitabine plus TH-302 340 mg/m2 (G+T340). Randomized crossover after progression on gemcitabine was allowed. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), tumor response, CA 19-9 response, and safety. Results Two hundred fourteen patients (77% with metastatic disease) were enrolled between June 2010 and July 2011. PFS was significantly longer with gemcitabine plus TH-302 (pooled combination arms) compared with gemcitabine alone (median PFS, 5.6 v 3.6 months, respectively; hazard ratio, 0.61; 95% CI, 0.43 to 0.87; P = .005; median PFS for metastatic disease, 5.1 v 3.4 months, respectively). Median PFS times for G+T240 and G+T340 were 5.6 and 6.0 months, respectively. Tumor response was 12%, 17%, and 26% in the gemcitabine, G+T240, and G+T340 arms, respectively (G+T340 v gemcitabine, P = .04). CA 19-9 decrease was greater with G+T340 versus gemcitabine (−5,398 v −549 U/mL, respectively; P = .008). Median OS times for gemcitabine, G+T240, and G+T340 were 6.9, 8.7, and 9.2 months, respectively (P = not significant). The most common adverse events (AEs) were fatigue, nausea, and peripheral edema (frequencies similar across arms). Skin and mucosal toxicities (2% grade 3) and myelosuppression (55% grade 3 or 4) were the most common TH-302–related AEs but were not associated with treatment discontinuation. Conclusion PFS, tumor response, and CA 19-9 response were significantly improved with G+TH-302. G+T340 is being investigated further in the phase III MAESTRO study (NCT01746979).

scholarly journals Enterocolitis in Patients With Cancer After Antibody Blockade of Cytotoxic T-Lymphocyte–Associated Antigen 4

2006 ◽  
Vol 24 (15) ◽  
pp. 2283-2289 ◽  
Author(s):  
Kimberly E. Beck ◽  
Joseph A. Blansfield ◽  
Khoi Q. Tran ◽  
Andrew L. Feldman ◽  
Marybeth S. Hughes ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Tumor Response ◽  
Cytotoxic T Lymphocyte ◽  
High Dose ◽  
Necrosis Factor Alpha ◽  
Objective Tumor Response ◽  
Systemic Corticosteroids ◽  
Immune Mediated ◽  
Alpha Blockade ◽  
Grade 3

Purpose Cytotoxic T-lymphocyte–associated antigen 4 (CTLA4) is an inhibitory receptor on T cells. Knocking out CTLA4 in mice causes lethal lymphoproliferation, and polymorphisms in human CTLA4 are associated with autoimmune disease. Trials of the anti-CTLA4 antibody ipilimumab (MDX-010) have resulted in durable cancer regression and immune-mediated toxicities. A report on the diagnosis, pathology, treatment, clinical outcome, and significance of the immune-mediated enterocolitis seen with ipilimumab is presented. Patients and Methods We treated 198 patients with metastatic melanoma (MM) or renal cell carcinoma (RCC) with ipilimumab. Results The overall objective tumor response rate was 14%. We observed several immune mediated toxicities including dermatitis, enterocolitis, hypophysitis, uveitis, hepatitis, and nephritis. Enterocolitis, defined by grade 3/4 clinical presentation and/or biopsy documentation, was the most common major toxicity (21% of patients). It presented with diarrhea, and biopsies showed both neutrophilic and lymphocytic inflammation. Most patients who developed enterocolitis responded to high-dose systemic corticosteroids. There was no evidence that steroid administration affected tumor responses. Five patients developed perforation or required colectomy. Four other patients with steroid-refractory enterocolitis appeared to respond promptly to tumor necrosis factor alpha blockade with infliximab. Objective tumor response rates in patients with enterocolitis were 36% for MM and 35% for RCC, compared with 11% and 2% in patients without enterocolitis, respectively (P = .0065 for MM and P = .0016 for RCC). Conclusion CTLA4 seems to be a significant component of tolerance to tumor and in protection against immune mediated enterocolitis and these phenomena are significantly associated in cancer patients.

scholarly journals Efficacy of upfront hepatectomy without neoadjuvant chemotherapy for resectable colorectal liver metastasis

2020 ◽  
Author(s):  
Kosuke Ono ◽  
Tomoyuki Abe ◽  
Akihiko Ohshita ◽  
Yusuke Sumi ◽  
Takuya Yano ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Liver Metastasis ◽  
Neoadjuvant Chemotherapy ◽  
Propensity Score ◽  
Colorectal Liver Metastasis ◽  
Vascular Invasion ◽  
Propensity Score Analysis ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Score Analysis

Abstract Background This study evaluated the impact of neoadjuvant chemotherapy on the prognosis of patients with resectable colorectal liver metastasis and assessed the usefulness of Beppu’s nomogram for predicting prognosis. Methods This retrospective study identified 88 consecutive inpatients who underwent primary hepatic resection for colorectal liver metastasis; 58 received neoadjuvant chemotherapy and 30 underwent upfront surgery. Factors associated with recurrence-free survival were identified via univariate and multivariate analysis. Propensity score analysis using inverse probability of treatment weighting was also performed. Results On univariate analysis, poor recurrence-free survival was associated with multiple tumors, advanced primary tumor stage, vascular invasion by the primary tumor, a Beppu score ≥ 6, and neoadjuvant chemotherapy. On multivariate analysis, a Beppu score ≥ 6 and neoadjuvant chemotherapy were independent risk factors for recurrence. Neoadjuvant chemotherapy recipients had a higher incidence of lymph node metastasis and vascular invasion than non-recipients. Propensity score analysis revealed no significant difference in the recurrence-free survival rate between these groups. Conclusions Our results show the usefulness of Beppu scores for predicting the prognosis of patients with colorectal liver metastasis, but do not support the use of neoadjuvant chemotherapy in these patients.

Successful treatment of conversion chemotherapy for initially unresectable synchronous colorectal liver metastasis

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Liver Metastasis ◽  
Colorectal Liver Metastasis ◽  
Surgical Intervention ◽  
Liver Volume ◽  
Sigmoid Colon Cancer ◽  
Remnant Liver ◽  
Future Remnant Liver ◽  
The Right ◽  
Synchronous Colorectal Liver Metastasis ◽  
Right Hepatic Vein

A 72-year-old woman with a sigmoid colon cancer anda synchronous colorectal liver metastasis (CRLM), whichinvolved the right hepatic vein (RHV) and the inferiorvena cava (IVC), was referred to our hospital. Themetastatic lesion was diagnosed as initially unresectablebecause of its invasion into the confluence of theRHV and IVC. After she had undergone laparoscopicsigmoidectomy for the original tumor, she consequentlyhad 3 courses of modified 5-fluorouracil, leucovorin,and oxaliplatin (mFOLFOX6) plus cetuximab. Computedtomography revealed a partial response, and theconfluence of the RHV and IVC got free from cancerinvasion. After 3 additional courses of mFOLFOX6 pluscetuximab, preoperative percutaneous transhepaticportal vein embolization (PTPE) was performed tosecure the future remnant liver volume. Finally, a righthemihepatectomy was performed. The postoperativecourse was uneventful. The patient was dischargedfrom the hospital on postoperative day 13. She hadneither local recurrence nor distant metastasis 18 moafter the last surgical intervention. This multidisciplinarystrategy, consisting of conversion chemotherapy usingFOLFOX plus cetuximab and PTPE, could contributein facilitating curative hepatic resection for initiallyunresectable CRLM.Key words: Initially unresectable; Colorectal liver metastasis;Conversion chemotherapy; Cetuximab; Percutaneoustranshepatic portal vein embolization

scholarly journals Presepsin values and prognostic nutritional index predict mortality in intensive care unit patients with sepsis: a pilot study

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yuichiro Shimoyama ◽  
Osamu Umegaki ◽  
Noriko Kadono ◽  
Toshiaki Minami
Keyword(s):  
Multivariate Analysis ◽  
Roc Curve ◽  
Operating Characteristic ◽  
Prognostic Nutritional Index ◽  
Early Mortality ◽  
Curve Analysis ◽  
Rank Test ◽  
Roc Curve Analysis ◽  
Log Rank Test ◽  
Nutritional Index

Abstract Objective Sepsis is a major cause of mortality for critically ill patients. This study aimed to determine whether presepsin values can predict mortality in patients with sepsis. Results Receiver operating characteristic (ROC) curve analysis, Log-rank test, and multivariate analysis identified presepsin values and Prognostic Nutritional Index as predictors of mortality in sepsis patients. Presepsin value on Day 1 was a predictor of early mortality, i.e., death within 7 days of ICU admission; ROC curve analysis revealed an AUC of 0.84, sensitivity of 89%, and specificity of 77%; and multivariate analysis showed an OR of 1.0007, with a 95%CI of 1.0001–1.0013 (p = 0.0320).

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