Updates in Management of Bone Metastatic Disease in Primary Solid Tumors with Systemic Therapies

2021 ◽  
Author(s):  
Virginia Falvello ◽  
Catherine Van Poznak
Keyword(s):  
Solid Tumors ◽  
Metastatic Disease ◽  
Systemic Therapies

scholarly journals 66. CLINICAL CHARACTERISTICS AND RESULTS OF PEDIATRIC SOLID TUMORS WITH BRAIN METASTASES: EXPERIENCE FROM A SINGLE REFERRAL CANCER CENTER

2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii14-ii14
Author(s):  
Clarissa Aguilar ◽  
Víctor Toro ◽  
Rina Medina
Keyword(s):  
Brain Metastases ◽  
Childhood Cancer ◽  
Solid Tumors ◽  
Metastatic Disease ◽  
Cancer Center ◽  
Middle Income ◽  
Middle Income Countries ◽  
Pediatric Solid Tumors ◽  
Low Middle Income Countries

Abstract BACKGROUND 80% of childhood cancer are located in low- and middle-income countries (LMIC). The most common form of presentation is disseminated or metastatic disease. The rate of survival has not been equitable across the world, since in these countries only 1 of 5 children are cured. OBJECTIVE To evaluate the clinical and histopathological features of patients with metastatic pediatric solid tumors, in a single referral cancer center in Honduras. METHODS We conducted a retrospective review of patients diagnosed with pediatric solid tumors from January 2010 to April 2020. Among the 260 patients through a collection form, we obtained: sociodemographic characteristics, clinical presentation at diagnosis, common histological subtypes, sites of metastasis, treatment and outcome at the time of follow-up. RESULTS During the last 10 years, 260 cases of childhood cancer were referred to our center for treatment. 127 patients (48.8%), have a solid tumor, patients ranged in age from 1 to 18 years and distribution for sex were 38% for males and 62% females. At the time of initial diagnosis 40/127 (31%) have advanced disease (stages III and IV). We found brain metastases in 22/40 cases (55%), the primary cancer was localized at CNS in 13/22 (59%) and the most common extracranial tumors causing brain metastases were neuroblastoma (4/22), rhabdomyosarcoma (3/22), retinoblastoma (2/22). Currently in the follow-up there were 18/22 (82%) died and 4/22 (18%) are in treatment with palliative intent. CONCLUSION There is a lack of information about the epidemiology of brain metastases among children with solid tumors in the low/middle income countries (LMIC) where the prognosis of metastatic disease is very poor, despite efforts, multimodal therapy and multidisciplinary management, in absence of other options like bone marrow transplantation, and reliable access to high-quality medicines. For our countries, timely diagnosis is still the main determining factor for cure.

Evaluation of the necessity of bilateral bone marrow aspirates and biopsies for the diagnosis of metastatic disease in pediatric patients with solid tumors.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 10054-10054
Author(s):  
Fernanda L. Abrantes ◽  
Lucas B. Vergamini ◽  
Carlos Rodriguez-Galindo ◽  
Inga Hofmann ◽  
Wendy B. London ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Solid Tumors ◽  
Bone Marrow Biopsy ◽  
Metastatic Disease ◽  
Diagnostic Yield ◽  
Kappa Statistics ◽  
Undifferentiated Sarcoma ◽  
Highly Correlated ◽  
Larger Sample ◽  
Positive Results

10054 Background: Standard practice for staging solid tumors has been to perform bilateral bone marrow aspirates (BMA) and biopsies (BMB). However, the diagnostic yield of performing all 4 tests has not been thoroughly evaluated. This study evaluated the concordance between test types (aspirate and biopsy) and sites (right and left) to evaluate whether one type or one side would be sufficient. Methods: All patients with solid tumors who underwent a diagnostic bilateral bone marrow biopsy and aspirate performed between 2006 and 2011 at Children’s Hospital Boston were identifed in a search of hematopathology records.. Kappa coeffcients were estimated. Results: A search of the hematopathology data records revealed a total of 112 patients who had had a diagnostic bilateral BMA and BMB including patients with neuroblastoma (n=70 ), Ewing’s Sarcoma (n=11), rhabdomyosarcoma (n=25), retinoblastoma (n=5), and undifferentiated sarcoma (n=1). 73% (n=82) of the patients were negative for all tests; 27% (n=30) had at least one positive test. The results between right and left and aspirate and biopsy were highly correlated.(Kappa statistics: BMA and BMB (0.85); BMA-left and BMB-left (0.82); BMA-right and BMB-right (0.84); BMA-left and BMA-right (0.77); BMB-left and BMB-right (0.95). All 4 tests were positive in 63%, 3 tests positive in 10%, 2 tests positive in 13% and one test positive in 13%. The distribution of positive results did not differ by disease. Among 11 patients with less than 4 positive tests, 10 would have been diagnosed correctly with bilateral aspirates; only one patient (neuroblastoma) had positive results on biopsy only. In this patient, neither aspirate had spicules and was therefore likely an inadequate specimen. Conclusions: Bone marrow biopsy may not be essential for accurate diagnosis of metastatic disease in pediatric solid tumor patients. Further confirmation of these findings in a larger sample is warranted.

Plasma levels of tumor M2-pyruvate kinase should not be used as a tumor marker for hematological malignancies and solid tumors

2006 ◽  
Vol 44 (1) ◽  
Author(s):  
Peter Staib ◽  
Melanie Hoffmann ◽  
Timo Schinköthe
Keyword(s):  
Tumor Marker ◽  
Solid Tumors ◽  
Pyruvate Kinase ◽  
Plasma Levels ◽  
Hematological Malignancies ◽  
Malignant Diseases ◽  
Healthy Individuals ◽  
The Mean ◽  
Circulating Levels ◽  
Systemic Therapies

AbstractIt has been reported that the dimeric isoform of the enzyme pyruvate kinase M2 was overexpressed in various solid tumor cells. Hence, it was suggested that circulating levels of the so-called tumor M2-pyruvate kinase (Tu M2-PK) could be used as a tumor marker for monitoring systemic therapies of various solid tumors. We analyzed its validity as a tumor marker by comparing plasma levels of Tu M2-PK in patients with different non-malignant diseases to levels in healthy individuals and in patients with hematological diseases. Plasma levels of Tu M2-PK were measured using an ELISA assay in a total of 284 patients. The mean Tu M2-PK concentration of 32 U/mL was significantly higher in the group of patients with hematological malignancies (n=121) (p<0.001). However, 37% of healthy individuals (n=63) and 44% of patients with non-malignant diseases (n=100), especially patients with an acute inflammatory reaction (67%), were found to have elevated levels of Tu M2-PK using a cutoff level of 15U/mL. The specificity was 59% and the sensitivity was 51%. There was no significant correlation between the prevalence of a hematological malignancy and positive Tu M2-PK result. Thus, our data imply that Tu M2-PK is not a useful tumor marker for hematological malignancies and solid tumors, as a significant number of false positive results were detected in healthy individuals and patients with non-malignant diseases.

Long-term survivorship in patients with metastatic renal cell cancer (mRCC) managed with metastasectomy: A retrospective study from the MD Anderson Cancer Center (MDACC).

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 504-504 ◽  
Author(s):  
Amishi Yogesh Shah ◽  
Matthew T. Campbell ◽  
Kirtan Das Nautiyal ◽  
Neda Hashemi ◽  
Surena F. Matin ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Metastatic Disease ◽  
Cell Cancer ◽  
Tumor Biology ◽  
Cancer Center ◽  
Md Anderson ◽  
Point Total ◽  
Long Term Survivors ◽  
Systemic Therapies

504 Background: Overall survival (OS) in mRCC has improved with targeted therapy; however, metastasectomy is still an important tool in select patients. This study evaluated outcomes of patients managed with metastasectomy ± systemic therapies. Methods: After IRB approval, we retrospectively reviewed records of mRCC patients who were treated at MDACC between 1/1/2001 and 12/31/2008 and report on those who survived >4 years with metastatic disease. OS was calculated from diagnosis of metastatic disease to death or last follow-up. Descriptive statistics were used. Results: 168 long-term survivors were identified; 101 patients were treated with metastasectomy at some point (total 205 resections). 42 patients had single metastasectomy; 59 had multiple resections (most common in lung and bone). 12 patients underwent serial metastasectomy alone (no systemic therapy), and 8 remain alive (range 4.6-12.9 years from met diagnosis). Conclusions: Patients with mRCC selected for metastasectomy had a significantly longer OS than those who received systemic therapies only. Whether this reflects tumor biology, therapeutic effect, or selection bias is unknown in this retrospective study. However, the prolonged survival in this group supports continued use of metastasectomy in carefully selected patients. [Table: see text] [Table: see text] [Table: see text]

Novel systemic therapies in hard to treat fibrolamellar hepatocellular carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16653-e16653
Author(s):  
Ariel Gliksberg ◽  
Claire O'Grady ◽  
Paul Kent
Keyword(s):  
High Risk ◽  
Metastatic Disease ◽  
Objective Response ◽  
Tumor Control ◽  
Primary Therapy ◽  
Early Results ◽  
Systemic Treatments ◽  
Multi Agent ◽  
Grade 3 ◽  
Systemic Therapies

e16653 Background: Fibrolamellar Carcinoma (FLC) is a very rare liver malignancy of young adults without underlying liver disease (0.02 per 100,000 in the US).. Complete resection is the primary therapy, but recurrence rates are still > 50%. Currently there are no established systemic treatments, especially for high-risk disease (unresectable, relapse, progression, or metastatic disease). At our institution triple therapy “TT” with Nivolumab/5FU/Interferon α-2b is our first line, followed by other novel combination therapies such as Gemcitabine/Oxaliplatin/Lenvantinib (GOL) or Nivolumb/Lenvantinib/Quecertin (NLQ). Objective: To evaluate the tolerability and early response of multi-agent systemic therapies in patients with high-risk FLC. Methods: Data from all patients with FLC who received systemic therapies from 5/2018 to 2/2020 was reviewed to assess tolerability, survival and toxicity. Results: Nineteen patients were treated with systemic therapies of which 16 (10F, 6M median age of 19) were evaluable based on follow up scans. Between our 16 patients they had relapsed 28 times, 12 had metastatic disease and 7 had tried 2+ systemic therapies. RECIST 1.1 objective response (CR+PR) and tumor control (CR+PR+SD) are 44% and 69%. Since starting multi-agent therapy, all 6 patients who had previously been treated with monotherapy, have already exceeded their previous longest time to progression. Thirteen patients were treated with “TT” [12.5 median cycles (6-38)]. Three patients were treated with NLQ including 2 who failed TT. Of these, the 1 evaluable patient achieved CR. Two patients were treated with GOL, 1 who failed TT and one who was post liver transplant, both had sustained PR of 6 and 9 months. Subsequently one died and one achieved CR. For the 6 patients who achieved remission before or during therapy, only 1 has relapsed. To date the period of response is already 68% longer than the previous best length of response. There was 1 withdrawal due to grade 3 colitis and 2 dose adjustments. All experienced mild adverse effects, most commonly fever, headache, and hypertension, with 3 patients with grade 3 toxicities. Conclusions: FLC is a devastating disease with patients often relapsing even after successful surgical remission. Currently there is a need for tolerable systemic therapies. Although at our institution, TT is our frontline therapy, there are other combinations of immunochemotherapies that we have used to treat FLC with preliminary success and minimal toxicities. Our early results show that multi-agent systemic therapy in hard-to-treat FLC is worthy of further study.

Association of systemic anticancer therapy with an increased risk of death in hospitalized COVID-19 positive oncology patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18594-e18594
Author(s):  
David Jacob Hermel ◽  
Samantha R. Spierling Bagsic ◽  
Munveer Singh Bhangoo ◽  
Kathryn Blount Bollin ◽  
James R. Mason ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Metastatic Disease ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Hematologic Malignancy ◽  
Anticancer Therapy ◽  
Cytotoxic Chemotherapy ◽  
Lung Involvement ◽  
Risk Of Death

e18594 Background: Malignancy is thought to be an independent risk factor for increased COVID-19 morbidity and mortality. However, neoplastic diseases encompass a heterogenous group of pathologic processes, and further stratification of those patients prone to severe disease is necessary. We sought to identify predictors of poor COVID-19 outcomes among hospitalized patients with malignancy. Methods: We retrospectively reviewed all patients with a diagnosis of hematologic and solid tumor malignancy within the regional Scripps Health hospital system in San Diego County from March 1, 2020 to January 5, 2021 with a PCR confirmed diagnosis of COVID-19. Cancer diagnoses were confirmed via manual chart review; in situ non-melanoma skin cancers were excluded. Only hospitalizations greater than one day were included in the analysis and readmissions were excluded. Outcomes of interest included admission to the ICU, intubation during hospitalization, and death. Associations between outcomes of interest and tumor types, metastatic disease (with or without lung involvement) and those receiving active systemic anticancer therapy (treatment within 3 months of admission) were determined using univariable logistic regression analyses. The study was approved by the Scripps Health Institutional Review Board. Systemic anticancer therapy included cytotoxic chemotherapy, immunomodulators, immune checkpoint inhibitors, and other targeted therapies. Results: Among a total of 2,771 hospitalized patients, 204 (7.36%) met inclusion criteria. The average age was 72.7 years, 48.5% were male, 33.3% were Hispanic and the average BMI was 27.5. The majority of patients (82.8%) had solid tumors, with the most prevalent being breast carcinoma (17.6%) and prostate carcinoma (17.2%). Overall, 21.9% had metastatic disease and 16% had lung involvement. 17.2% had been receiving active cancer systemic treatment. On univariate analysis, patients who were actively receiving treatment had an increased rate of death (37.1% vs 18.9%, OR: 2.5 (1.1-5.5) p= .021). Among patients receiving systemic anticancer therapy, 48.6% received cytotoxic chemotherapy, 5.7% immune checkpoint inhibitors, 22.9% immunomodulators, 17.1% molecularly targeted agents and 2.7% other agents. Moreover, there was a trend towards increased mortality in those with lung involvement (33.3% vs 17.6%, OR: 2.3 (0.9-5.7) p= .067) and those with hematologic malignancy (31.4% vs 20.1%, OR: 0.5 (0.2-1.3) p = 0.146). Conclusions: Among patients hospitalized with a diagnosis of cancer, systemic anticancer therapy was associated with a significantly increased odds of death. Other factors potentially increasing risk of death include hematologic malignancy and solid tumors with lung involvement. Further validation of these findings in a larger sample could impact therapeutic decision making during the COVID-19 pandemic.

Potent Graft-Versus-Renal Cell Carcinoma (RCC) Effects in a Murine Minor Histocompatibility Antigen (mHa)-Mismatched Allogeneic Transplant Model.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4982-4982
Author(s):  
Andreas Lundqvist ◽  
Ramaprasad Srinivasan ◽  
Dante Suffredini ◽  
Yoshiyuki Takahashi ◽  
Jason Wynberg ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Metastatic Disease ◽  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Bone Marrow Cells ◽  
Host Disease ◽  
Minor Histocompatibility Antigens ◽  
Graft Versus Host ◽  
Total Body ◽  
Improvement In Survival

Abstract Donor immune-mediated anti-neoplastic effects make the greatest contribution to the durable disease remissions obtained in hematological malignancies following allogeneic hematopoietic cell transplantation (a-HCT). Recent studies have demonstrated that clinically meaningful graft-versus-tumor (GVT) effects can also be induced against select solid tumors following a-HCT. GVT effects have been most extensively documented in RCC, where response rates in the range of 20%–50% have been reported. Unfortunately, death from eventual disease progression and morbidity from graft-versus-host disease (GVHD) limit a broader application of a-HCT to manage this tumor. In order to explore mechanisms underlying GVT effects against RCC, and to optimize outcome following transplantation, we sought to establish a murine MHC-compatible, but mHA-disparate a-HCT model in mice with metastatic RCC. Recipient Balb/C (H-2d) mice were conditioned with a myeloablative regimen consisting of 950cGy total body irradiation and transplanted with bone marrow cells and splenocytes from either syngeneic (Balb/C) or allogeneic, mHA mismatched B10.d2 (H-2d) mice. Murine RCC cells (RENCA, 1x105 cells/mouse) were injected into the tail veins of both Balb/C recipient groups 3 days after transplantation and were followed for survival and the establishment of metastatic pulmonary lesions. Recipients of allo-HCT had improved survival (mean 54±2 days) compared to those receiving syngeneic transplants (mean 31±0 days: p<0.001). At death, 4/4 mice receiving syngeneic transplants demonstrated widespread pulmonary metastatic disease while none of the allo-HCT recipients (n=4) developed metastatic disease (Figure 1A). A slight improvement in survival for allo-HCT recipients was also noted when Balb/C mice were injected subcutaneously with RENCA (1x105 cells) three days following transplantation (31±0 for syngeneic and 40±7 for allogeneic recipients; p=0.04). Serial measurements of subcutaneous tumor nodules (Figure 1B) revealed significantly slower tumor growth in allo-HCT recipients (mean volume = 272mm3, day 31) compared to recipients of syngeneic grafts (mean volume = 11mm3, day 31). Graft-versus-host disease (GVHD) characterized by alopecia, weight loss and diarrhea occurred at a median 28±3 days after transplantation and was the primary cause of death in a-HCT recipients. Unlike previously reported murine a-HCT models for solid tumors, pre-transplant priming of donor mice with recipient splenocytes or tumor cells was not required for the generation of GVT effects. These data suggest donor immune responses against minor histocompatibility antigens can mediate potent GVT effects against RCC following allo-HCT. This murine model will serve as a platform for the development of tumor- targeted a-HCT strategies aimed at refining and enhancing GVT effects while mitigating GVHD. Figure Figure

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