Pseudocirrhosis in Gastric Cancer with Diffuse Liver Metastases after a Dramatic Response to Chemotherapy

We present the first reported case of pseudocirrhosis arising after a dramatic response to chemotherapy in metastatic gastric cancer. A 74-year-old man was diagnosed with gastric adenocarcinoma having multiple liver metastases. His general condition was poor, with an Eastern Cooperative Oncology Group performance status of 3, inadequate oral intake, and jaundice (total bilirubin 2.8 mg/dl). Chemotherapy with oxaliplatin, L-leucovorin, and 5-fluorouracil (modified FOLFOX-6) was initiated. After four treatment cycles, he experienced a marked regression of liver metastases; however, he developed massive ascites with a lobular liver surface and segmental atrophy, which were consistent with pseudocirrhosis. Chemotherapy was continued along with ascites management. Thereafter, ascites disappeared, and a complete response of the metastatic lesions was achieved at 11 months after initial treatment. He had no evidence of disease progression at 30 months after initial chemotherapy. This report suggests clinicians should recognize this entity, even in gastric cancer metastatic to the liver.

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CyBorD-DARA is potent initial induction for MM and enhances ADCP: initial results of the 16-BCNI-001/CTRIAL-IE 16-02 study

Blood Advances ◽

10.1182/bloodadvances.2019000010 ◽

2019 ◽

Vol 3 (12) ◽

pp. 1815-1825 ◽

Cited By ~ 4

Author(s):

M. O’Dwyer ◽

R. Henderson ◽

S. D. Naicker ◽

M. R. Cahill ◽

P. Murphy ◽

...

Keyword(s):

Partial Response ◽

Group Performance ◽

Residual Disease ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Staging System ◽

Complete Response ◽

Weekly Schedule ◽

Intention To Treat ◽

Good Partial Response

Abstract Daratumumab (DARA) has shown impressive activity in combination with other agents for the treatment of multiple myeloma (MM). We conducted a phase 1b study to assess the safety and preliminary efficacy, as well as potential mechanisms of action, of DARA (16 mg/kg) in combination with a weekly schedule of subcutaneous bortezomib (1.3-1.5 mg/m2), cyclophosphamide (150-300 mg/m2), and dexamethasone (40 mg) (CyBorD DARA) as initial induction before autologous stem cell transplantation (ASCT). Eligible patients were ≤70 years of age with untreated MM requiring treatment and who lacked significant comorbidities. A total of 18 patients were enrolled. Their median age was 56 years (range, 32-66 years), and all patients had Eastern Cooperative Oncology Group performance status ≤1. The International Staging System stages were I, II, and III in 78%, 17%, and 6% of patients, respectively; 28% of patients had high-risk genetic features. There was no dose-limiting toxicity, and the incidence of grade 3 or 4 infection or neutropenia was <10%. On an intention-to-treat basis, 94% achieved ≥very good partial response with ≥complete response in 44% of patients. Among 14 of 15 patients who underwent ASCT and were evaluable for response, all 14 achieved at least very good partial response, with 8 (57%) of 14 achieving complete response. After ASCT, 10 (83%) of 12 patients in whom minimal residual disease analysis was possible were negative at a sensitivity of 10−5 (56% on intention-to-treat/whole study population) according to next-generation sequencing. Flow cytometry analysis of patient samples indicated CyBorD DARA induced activation of macrophage-mediated antibody-dependent cellular phagocytosis. This trial was registered at www.clinicaltrials.gov as #NCT02955810.

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Prospective study of Burkitt lymphoma treatment in adolescents and adults in Malawi

Blood Advances ◽

10.1182/bloodadvances.2018029199 ◽

2019 ◽

Vol 3 (4) ◽

pp. 612-620 ◽

Cited By ~ 5

Author(s):

Matthew S. Painschab ◽

Kate D. Westmoreland ◽

Edwards Kasonkanji ◽

Takondwa Zuze ◽

Bongani Kaimila ◽

...

Keyword(s):

Burkitt Lymphoma ◽

Group Performance ◽

Performance Status ◽

Intensive Therapy ◽

Eastern Cooperative Oncology Group ◽

Standard Of Care ◽

Complete Response ◽

Sub Saharan Africa ◽

High Dose ◽

Hiv Viral Load

Abstract Burkitt lymphoma (BL) is common in sub-Saharan Africa (SSA). In high-income countries, BL is highly curable with chemotherapy. However, there are few prospective studies from SSA describing nonpediatric BL and no regional standard of care. Thirty-five participants age 15 years or older with newly diagnosed BL were enrolled in Malawi from 2013 to 2018. Chemotherapy was administered according to institutional guidelines, with concurrent antiretroviral therapy if HIV infected. Median age was 21 years (range, 15-61) and 15 participants (43%) were HIV infected. Twenty-seven participants (77%) had stage III to IV disease, and 19 (54%) had Eastern Cooperative Oncology Group performance status >1. Among HIV-infected participants, median CD4 count was 130 (range, 29-605) and 10 (67%) had suppressed HIV viral load. Four participants (11%) died before receiving chemotherapy. First-line chemotherapy consisted of: cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (n = 22 [71%]); infusional etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin (n = 4 [13%]); high-dose methotrexate-based chemotherapy (n = 4 [13%]); and rituximab plus CHOP (n = 1 [3%]). Among 28 evaluable participants, 14 (50%) achieved a complete response. Median overall survival (OS) was 7 months; 1-year OS was 40% (95% confidence interval [CI], 24%-56%). Sixteen (73%) of 22 deaths were a result of disease progression. Compared with CHOP, more intensive chemotherapy was associated with decreased mortality (hazard ratio, 0.24; 95% CI, 0.05-1.02; P = .05). This is among the best characterized prospective cohorts of nonpediatric BL in SSA. Most deaths resulted from progressive BL. Patients who received more intensive therapy seemed to have better outcomes. Defining optimal approaches is an urgent priority in SSA.

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Use of circulating tumor cells to predict response to chemotherapy in patients with advanced gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.43 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 43-43

Author(s):

S. Matsusaka ◽

K. Chin ◽

N. Mizunuma ◽

M. Ogura ◽

M. Suenaga ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Cox Regression ◽

Performance Status ◽

Univariate Analysis ◽

Eastern Cooperative Oncology Group ◽

Cox Regression Analysis ◽

Response To Chemotherapy

43 Background: The purpose of this study was to quantify circulating tumor cells (CTCs) in advanced gastric cancer (AGC) patients, and to demonstrate the role of CTCs in cancer therapy. The purpose of this study was to identify CTC threshold proposal for determining response to chemotherapy in AGC. Methods: From November 2007 to June 2009, fifty-two patients with AGC were enrolled into a prospective study. All patients were enrolled using institutional review board-approved protocols at the Cancer Institute Hospital and provided informed consent. The study population consisted of patients of aged 18 years or older with histologically proven AGC. Other inclusion criteria were Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 2; adequate organ function. The subjects were five patients treated with S-1 (40 mg/m2, twice daily, days 1-28, repeated every 6 weeks), twenty-six patients treated with S-1 plus CDDP (S-1 40 mg/m2, twice daily, days 1-21, CDDP 60 mg/m2, day 8, repeated every 5 weeks), and twenty-one patients treated with paclitaxel (80 mg/m2, weekly). CTCs of whole blood at baseline, two weeks and four weeks after initiation of chemotherapy, were isolated and enumerated using immunomagnetics. Results: Patients with ≥4 CTCs at two-week points and four-week points had a shorter median PFS (1.4, 1.4 months, respectively), than those with the median PFS of <4 CTCs (4.9, 5.0 months, respectively) (p<0.001, p<0.001, respectively). Patients with ≥4 CTCs at two-week points and four-week points had shorter median OS (3.5, 4.0 months, respectively) than those with the median PFS of <4 CTCs (11.7, 11.4 months, respectively) (p<0.001, p=0.001, respectively). In univariate analysis, PS, treatment regimen, Line of chemotherapy, and CTC levels at 2 weeks and 4 weeks predicted PFS and OS. In order to evaluate the independent predictive effect of chemotherapy, multivariate Cox regression analysis was carried out. CTC levels at 2 weeks and 4 weeks were the strongest predictors. Conclusions: A threshold of lower than 4 CTC/7.5 ml at 2 weeks and 4 weeks was a significant predictor of the outcome for AGC patients treated with S-1 based regimen or paclitaxel regimen. No significant financial relationships to disclose.

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What care is appropriate and necessary for metastatic gastric cancer patients? Results of a RAND/UCLA expert panel.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.70 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 70-70

Author(s):

Alyson L. Mahar ◽

Lucy K. Helyer ◽

Carol Jane Swallow ◽

Calvin Law ◽

Lawrence Frank Paszat ◽

...

Keyword(s):

Gastric Cancer ◽

Liver Metastases ◽

Surgical Resection ◽

Metastatic Disease ◽

Expert Panel ◽

Treatment Decision ◽

Metastatic Gastric Cancer ◽

Treatment Decision Making ◽

Gastric Cancer Patients ◽

Multiple Liver Metastases

70 Background: Most gastric cancer patients present with advanced stage disease precluding curative surgical treatment. The utility of surgical and non-surgical options for non-curative, advanced disease is debated and the appropriate treatment strategy unclear. Methods: A multi-disciplinary expert panel of 16 physicians from 6 countries, scored 47 scenarios using the RAND/UCLA Appropriateness Methodology. Appropriateness was scored from 1 (highly inappropriate) to 9 (highly appropriate). Median appropriateness scores (AS) from 1-3 were considered inappropriate, 4-6 uncertain, and 7-9, appropriate. Agreement was reached when 11 of 16 panelists scored the statement similarly. If a statement was agreed to be appropriate, it was then given a necessity score (NS) in the same manner. Results: Surgical resection and bypass were agreed to be inappropriate in patients with minor symptoms and visible carcinomatosis, liver metastases or more than one site of metastatic disease for cardia and distal lesions (AS 1.0-3.5). The expert panel disagreed on the role for surgical resection in patients who were cytology positive only (AS 4-6). The role of resection for patients with major symptoms if they had visible carcinomatosis, liver metastases or more than one site of metastatic disease (AS 2-5) was indeterminate. Patients with distal tumours and major symptoms and multiple liver metastases or more than one site of metastatic disease were considered indeterminate for surgical resection (AS 2). Best supportive care was agreed to be appropriate for patients with minor symptoms and multiple liver metastases or more than one site of metastatic disease (AS 8, NS 5-6). Conclusions: The role of surgery in metastatic gastric cancer treatment decision-making is not supported by experts for the majority of scenarios. Continued uncertainty in appropriate and necessary treatment decision-making for advanced patients with a minimal burden metastatic disease exists and underscores the need for randomized controlled trials.

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Phase II Trial of Biweekly Infusional Fluorouracil, Folinic Acid, and Oxaliplatin in Patients With Advanced Gastric Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2004.07.042 ◽

2004 ◽

Vol 22 (4) ◽

pp. 658-663 ◽

Cited By ~ 132

Author(s):

Salah-Eddin Al-Batran ◽

Akin Atmaca ◽

Susanna Hegewisch-Becker ◽

Dirk Jaeger ◽

Sabine Hahnfeld ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Folinic Acid ◽

Advanced Gastric Cancer ◽

Intravenous Infusion ◽

Group Performance ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Who Grade ◽

Grade 3

Purpose To evaluate the toxicity and activity of infusional fluorouracil (FU), folinic acid (FA), and oxaliplatin, administered every 2 weeks in patients with metastatic gastric cancer. Patients and Methods Forty-one previously untreated patients with measurable adenocarcinoma of the stomach were eligible for the study. Patients received FU 2.6 g/m2 (24-hour continuous infusion), FA 500 mg/m2 (2-hour intravenous infusion), and oxaliplatin 85 mg/m2 (2-hour intravenous infusion) every 2 weeks for 6 weeks. Treatment was continued until progression of disease was observed. Results All patients were assessable for toxicity and 37 of 41 patients were assessable for response. Patient characteristics were: sex (male, 28; female,13), median age 60 years (range, 20 to 77 years), and median Eastern Cooperative Oncology Group performance status of 1. Response was evaluated every 6 weeks. Of 37 assessable patients, one complete and 15 partial remissions were observed (overall response rate, 43%). Stable disease was observed in 12 patients (32%) and progressive disease in nine patients (24%). The median overall survival was 9.6 months. WHO grade 3 or 4 hematologic toxicities included neutropenia in two patients (4.9%) and thrombocytopenia in one patient (2.4%). Other WHO grade 3 or 4 toxicities included diarrhea in three patients (7.3%) and vomiting in two patients (4.9%). There were no cases of grade 3 peripheral neuropathy and no treatment-related deaths. Conclusion Biweekly fluorouracil, folinic acid, and oxaliplatin is active and well-tolerated in patients with advanced gastric cancer. Response rates, time to progression, and overall survival were comparable to those achieved with other combination chemotherapy regimens, including FOLFOX6, with significantly less toxicity.

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Efficacy of trastuzumab and potential risk factors on survival in patients with HER2-positive metastatic gastric cancer

Future Oncology ◽

10.2217/fon-2021-0398 ◽

2021 ◽

Author(s):

Atakan Topcu ◽

Muhammed Mustafa Atci ◽

Saban Secmeler ◽

Mehmet Besiroglu ◽

Murat Ayhan ◽

...

Keyword(s):

Risk Factors ◽

Gastric Cancer ◽

Overall Survival ◽

Clinical Response ◽

Potential Risk ◽

Group Performance ◽

Eastern Cooperative Oncology Group ◽

Metastatic Gastric Cancer ◽

Her2 Positive ◽

Potential Risk Factors

Aim: To evaluate the efficacy of trastuzumab and potential risk factors on survival in patients with HER2-positive metastatic gastric cancer. Methods: We retrospectively included 138 patients who were given trastuzumab-based chemotherapy as first-line treatment and analyzed the relationship between clinical response rates and maintenance treatment status and survival outcomes. Results: In the whole group, the median progression-free survival and overall survival were 10.2 and 16 months, respectively. Clinical response was obtained in 79% of patients. The median overall survival was 16.9 months in follow-up group and 19.0 months in the maintenance group in patients with clinical response. Continuation of maintenance trastuzumab created a significant survival advantage (p = 0.021). Eastern Cooperative Oncology Group performance status 2 (hazard ratio [HR]: 2.02), grade 3 (HR: 1.78) and more than four metastatic lesions (HR: 1.67) were determined as risk factors for death. Conclusion: We recommend the continuation of maintenance trastuzumab in patients with clinical response, but those with identified risk factors may not benefit from treatment because life expectancy may be low.

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Effects of baseline lactate dehydrogenase (LDH), interferon gamma (IFN-g) expression, and tumor mutational burden (TMB) on treatment response to first-line atezolizumab (A) + vemurafenib (V) and cobimetinib (C) in BRAFV600 mutation–positive advanced melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.9523 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 9523-9523

Author(s):

Caroline Robert ◽

Karl D. Lewis ◽

Paolo Antonio Ascierto ◽

Rodrigo Ramella Munhoz ◽

Gabriella Liszkay ◽

...

Keyword(s):

Group Performance ◽

Performance Status ◽

Recursive Partitioning ◽

Objective Response ◽

Eastern Cooperative Oncology Group ◽

Complete Response ◽

Advanced Melanoma ◽

First Line ◽

L1 Data ◽

Metastatic Sites

9523 Background: The phase 3 IMspire150 study showed that first-line A+V+C improved investigator-assessed PFS vs placebo (P)+V+C in BRAFV600E/K mutation–positive advanced melanoma (hazard ratio 0.78; P=.0249). Prior biomarker analyses showed that IFN-g or TMB > 10 mut/Mb were associated with greater PFS benefits with A+V+C (Lewis et al. J ImmunoTher Cancer 2020;8:A188-A189). We further evaluated the association of these biomarkers with outcomes. Methods: Exploratory recursive partitioning analysis (RPA) was used to model associations between PFS and age ( < 65 vs ≥65 y), Eastern Cooperative Oncology Group performance status (0 vs 1), liver metastases (yes vs no), metastatic sites (≤3 vs > 3), sum of longest tumor diameters ( < 44 mm vs ≥44 mm), baseline LDH (normal [n] vs elevated [e]), TMB ( < 10 vs ≥10 mut/Mb), PD-L1 (negative vs positive), and IFN-g (high [h; > Quartile 3; Q3] vs intermediate [ > Q1 and ≤Q3] vs low [≤Q1]). Time-to-event analyses were summarized using Kaplan-Meier estimates. Results: The RPA analysis included 208/256 (81.3%) patients (pts) from the A+V+C arm of IMspire150 for whom LDH, TMB, IFN-g, and PD-L1 data were available. RPA showed that LDH was associated with PFS. In pts treated with A+V+C and n-LDH, h-IFN-g signature was associated with longer PFS and higher rates of objective response (OR) and complete response (CR) vs low/intermediate (l/i) IFN-g (2-y PFS: 59% vs 38%; ORR: 77% vs 69%; CR: 38% vs 15%, respectively); TMB ≥10 mut/Mb was associated with more favorable outcomes in pts with e-LDH (Table). In contrast, neither IFN-g nor TMB discriminated PFS outcomes in n-LDH or e-LDH pt subgroups receiving P+V+C. Pts with e-LDH and TMB < 10 mut/Mb had poor PFS outcomes, with 2-y PFS rates of 9% and 3% and lower rates of OR (51% and 62%) and CR (5% and 9%) in the A+V+C and P+V+C arms, respectively. Similar trends were observed for duration of response (DOR), and for the subset of pts with BRAFV600E mutation–positive melanoma. A+V+C improved PFS vs P+V+C across all subgroups with the exception of e-LDH and TMB < 10. Conclusions: IFN-g and TMB discriminated PFS benefit in pts receiving A+V+C but not for those receiving P+V+C. Durable responses were observed for pts treated with A+V+C in the n-LDH + h-IFNg subgroups.[Table: see text]

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Moving beyond Karnofsky and ECOG Performance Status Assessments with New Technologies

Journal of Oncology ◽

10.1155/2016/6186543 ◽

2016 ◽

Vol 2016 ◽

pp. 1-13 ◽

Cited By ~ 63

Author(s):

Ciara M. Kelly ◽

Armin Shahrokni

Keyword(s):

New Technologies ◽

Group Performance ◽

Functional Performance ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Activity Monitoring ◽

Assessment Tools ◽

Routine Practice ◽

Response To Chemotherapy ◽

Electronic Activity

Progress in cancer research is coupled with increased treatment complexity reliant upon accurate patient selection. Oncologists rely upon measurement instruments of functional performance such as the Karnofsky or Eastern Cooperative Oncology Group Performance Status scales that were developed over fifty years ago to determine a patient’s suitability for systemic treatment. These standard assessment tools have been shown to correlate with response to chemotherapy, chemotherapy tolerability, survival, and quality of life of cancer patients. However, these scales are subjective, subject to bias and high interobserver variability. Despite these limitations important clinical decisions are based on PS including eligibility for clinical trials, the “optimal” therapeutic approach in routine practice, and the allocation of healthcare resources. This paper reviews the past, present, and potential future of functional performance status assessment in an oncology setting. The potential ability of electronic activity monitoring systems to provide an objective, accurate measurement of patient functional performance is explored. Electronic activity monitoring devices have the potential to offer positive health-related opportunities to patients; however their introduction to the healthcare setting is not without difficulty. The potential role of this technology in healthcare and the challenges that these new innovations pose to the healthcare industry are also examined.

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Importance of HER2 Work-Up and Treatment Even in Patients with Poor Performance Status: A Case Report

Case Reports in Oncological Medicine ◽

10.1155/2014/731581 ◽

2014 ◽

Vol 2014 ◽

pp. 1-4

Author(s):

Ali Suner ◽

Hakan Buyukhatipoglu ◽

Ozan Balakan ◽

Mehmet Emin Kalender ◽

Turgay Ulas ◽

...

Keyword(s):

Gastric Cancer ◽

Performance Status ◽

Poor Performance ◽

Complete Response ◽

Metastatic Gastric Cancer ◽

Poor Performance Status ◽

Her2 Overexpression ◽

First Line ◽

Work Up

Gastric cancer is one of most common types of cancers. Metastatic gastric cancer has a poor prognosis and is accepted as incurable at this stage. Treatment of metastatic gastric cancer did not progress substantially until new targeted agents have come out. Recently published ToGA trial showed promising results in HER2 overexpressing metastatic gastric cancer. In this case we present a case with an excellent complete response with anti-HER2 treatment. Most importantly, we wanted to emphasize (1) the importance of early determination of HER2 overexpression, and (2) to draw attention of anti-HER2 agents in the first line treatment even in patients with a poor performance status.

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Ramucirumab combined with paclitaxel as the second-line chemotherapy for elderly patients with disseminated gastric cancer

Medical Council ◽

10.21518/2079-701x-2018-10-169-171 ◽

2018 ◽

pp. 169-171

Author(s):

T. A. Titova ◽

N. S. Besova ◽

V. A. Gorbunova ◽

R. N. Nasyrova ◽

A. A. Fedenko

Keyword(s):

Gastric Cancer ◽

Liver Metastases ◽

Advanced Gastric Cancer ◽

Metastatic Gastric Cancer ◽

Phase Iii ◽

Second Line ◽

Her2 Positive ◽

Second Line Chemotherapy ◽

Multiple Liver Metastases ◽

Line Chemotherapy

Gastric cancer is the third leading cause of cancer-related deaths worldwide. The prognosis of advanced gastric cancer remains poor despite therapeutic advances in recent decades. Several recent positive phase III trials established the efficacy of second-line chemotherapy for metastatic gastric cancer in prolonging overall survival. Many targeted-therapies failed to show a significant survival benefit in GC, only 2 of them are approved FDA: trastuzumab in the 1-st line treatment of HER2-positive gastric cancer and ramucirumab with or without paclitaxel as second line chemotherapy. The article presents the case of effective treatment of patient with Her2-negative advanced gastric cancer. A 76-year-old man had a moderately differentiated adenocarcinoma of gastric with synchronous multiple liver metastases. He received ramucirumab with paclitaxel as second -line chemotherapy. The size of the liver metastases was reduced and he maintained a partial response for one year. This clinical case report demonstrates that new option in the treatment of advanced gastric cancer can to allow our patients to live longer without losing the quality of life.

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