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Virtual Tumor Board: Multidisciplinary Management of Advanced Soft Tissue Sarcoma

i3 Health2023-08-10
CME#Oncology#Hematology#FREE CME#Continuing Medical Education#NCPD#Sarcoma#Sarcomas#Shreyaskumar R. Patel#Kathleen Polson#Brian Rubin#Dana-Farber Cancer Institute#MD Anderson Cancer Center#Cleveland Clinic Cancer Center#Robert J. Tomsich Pathology and Laboratory Medicine Institute#Tumor#Virtual Tumor Board
1K views|9 months ago
💫 Short Summary

The video showcases a multidisciplinary panel discussing the management and treatment of soft tissue sarcomas, highlighting challenges and advancements in therapeutic approaches. Various success stories, therapeutic options, and diagnostic markers are explored, emphasizing the importance of surgery, targeted therapies, and patient support. Case studies and patient outcomes are discussed, along with the significance of molecular testing and personalized treatment strategies. The segment concludes with a focus on the evolving landscape of cancer treatment, including kinase inhibitors and the potential for improved outcomes through targeted therapies and clinical trials.

✨ Highlights
📊 Transcript
Discussion on the multidisciplinary nature of soft tissue sarcomas and the importance of patient and tumor characteristics in diagnosis and treatment.
The panel highlights newer therapies available for soft tissue sarcomas and the challenges posed by the rarity and heterogeneity of over 50 subtypes.
Classifications based on tissue of origin and translocation status are examined, showcasing the diverse nature of these tumors and the need for personalized therapeutic approaches.
Challenges and Progress in Therapeutic Options for Translocation Fusions in Cancer.
Targeting chimeric transcription factors in translocation fusions poses complexity and difficulty.
Progress is being made in developing promising therapies expected within the next five to ten years.
Initial excitement around targeting gene fusions in tumors has not fully materialized.
Despite challenges, there is optimism for future breakthroughs in treating cancer through targeted therapies.
Success stories in cancer treatment are highlighted, including the use of ALK Inhibitors in inflammatory myofibroplastic tumors and mTOR inhibitors in TSC-12 mutations.
Challenges in developing effective therapies, such as with MDM2 and CDK4 inhibition in liposarcoma, are discussed.
The importance of identifying targets and achieving successful therapy outcomes is emphasized, despite only a few examples making it to the pharmacy shelf.
A case study of a 33-year-old female with synovial giant cell tumor is presented, demonstrating the challenges in diagnosis and treatment.
Pathology of synovial giant cell tumors.
The segment details the typical characteristics of synovial giant cell tumors including epithelioid cells, fibrous stroma, lymphocyte-like cells, and giant cells.
Staining techniques like Desmond and clustering are important in diagnosing synovial giant cell tumors.
The segment discusses the distinction between localized and diffuse types of tumors, their common locations, and the potential misdiagnosis as rhabdomyosarcoma.
Valuable insights into the histological features and diagnostic markers of synovial giant cell tumors are provided in the segment.
Treatment of the disease involves surgery as the primary option, with medical therapy only used in specific cases.
Inhibitors like csf1 are utilized to block the csf1 receptor, which is activated in the disease.
The disease is identified by cytogenic changes, particularly csf1 gene rearrangements.
While the neoplasm is locally aggressive, it has minimal metastatic potential.
Proper surgery from the beginning is essential, with emphasis on supportive care, pain management, and physical therapy for treatment.
Use of Pexidartinib in treating tumor symptoms showed positive results in a patient.
Patient initially on 400mg dose twice daily, but reduced to 200mg due to side effects.
Maximizing compliance on oral therapy is crucial, including communication on side effects and proactive measures.
Early intervention and dose adjustments can help patients stay on treatment.
Keeping a diary and regular follow-ups, along with a multi-disciplinary team approach, are recommended for patient care.
Changes to Hexadardnib Availability and Dosage
Hexadardnib is now only accessible through a Rems program due to liver function test concerns.
Providers and patients must enroll in the program and monitor liver function tests.
The dosing guidelines now recommend 250mg twice daily with a low-fat meal containing 11 to 14 grams of total fat.
Teaching materials and apps are available to help patients understand the new dietary requirements, and nutritionist referrals are an option for assistance with healthy food choices.
Importance of monitoring patients on oral therapy for potential side effects and treatment progress.
Side effects to watch for include hair depigmentation, edema, fatigue, rash, and taste alterations.
Monitoring liver values and other lab results is crucial for patient safety.
Delays in medication access due to insurance issues or prior authorizations can disrupt treatment progress.
Drug assistance programs and co-pay assistance can help mitigate delays and challenges in managing disease progression.
Patient presented with worsening symptoms and progressive disease, leading to supportive care and analgesic treatment.
Despite screen failure for a clinical trial, the patient underwent total hip arthroplasty for symptom management.
Follow-up showed no evidence of disease, but long-term effects remain uncertain.
Taxider nip and CSF1 receptor inhibitors were discussed as treatment options, with varying levels of benefit and tolerability.
Studies showed a response rate of 31% with magnib and 60% with hexaduct nib, indicating potential benefits for patients.
Liver toxicity monitoring is crucial in a rare tumor, with early detection in the first three months indicating severity.
Targeted therapy has proven successful in treating rare tumors, with ongoing clinical testing for safer and more effective molecules.
A case study on gastrointestinal stromal tumor is presented, detailing patient presentation, diagnosis, and treatment with surgical resection.
The histology of the tumor, particularly the spindle cell variant, is explained, highlighting low mitotic activity and key diagnostic markers.
Diagnosing gastrointestinal stromal tumors (GIST) has become more straightforward over the years.
Specific markers like kit and dog one aid in the diagnosis of GIST.
A sophisticated algorithm has been developed to differentiate between genetic subtypes of GIST.
Conducting an sdhb stain is important to detect rare cases caused by loss of succinate dehydrogenase.
Prognosis of GIST is assessed based on tumor size, location, and mitosis rate per five millimeter squared.
Importance of Molecular Testing in Determining Response to Adjuvant Imatinib for GIST.
Different genotypes such as kit exons and pdgfra exons are crucial in determining treatment options for GIST.
Identifying mutations like kit exon 9 duplication and pdgfra d842v is essential for guiding therapy decisions.
Additional mutations like B reputations and NF1 mutation are discussed for personalized treatment strategies.
Accurate genotyping is emphasized to ensure the effectiveness of targeted therapies for GIST patients.
Importance of Mitotic Index in Tumor Risk Assessment.
Mitotic index is a key factor in determining the risk of tumor recurrence and metastasis.
Molecular testing is crucial for identifying specific mutations like kit exon 11 557 to 559 deletion.
Treatments can be tailored based on specific mutations identified through molecular testing.
A patient is enrolled in the ecosox z9001 protocol for adjuvant therapy.
Treatment of spine and liver metastases with iMatnib.
Side effects of iMatnib include fatigue, fluid retention, muscle cramping, diarrhea, and rash.
Monitoring blood cell counts and organ function is crucial during treatment.
Kinase inhibitors like iMatnib can lead to extended survival and increased lifespan for patients with metastatic disease.
Adjusting medication dosage based on individual response is key for treatment efficacy.
Second-line therapy for chronic myeloid leukemia involves daily dosing of 37.5 milligrams of netanab.
Patients may experience side effects such as high blood pressure, fatigue, skin changes, hair thinning, diarrhea, nausea, and vomiting.
Monitoring for hypothyroidism is important due to its impact on thyroid function.
Patients should regularly assess their skin for calluses and use moisturizing creams to prevent skin issues.
Treatment options for calluses and strategies for management.
Patients are advised to seek help early for symptoms and may be referred to dermatology.
Effective strategies include Epsom salt soaks and retinoid-based creams.
Side effects like diarrhea can be managed with dietary changes, medications, and GI consults.
Referrals to nutrition and GI specialists may be necessary for fatigue management.
Side effects of sunitinib and FNB treatment in a patient with poor tolerance.
Patient experienced hand-foot syndrome, hypertension, fatigue, hoarse voice, hair loss, constipation, and joint pains.
Monitoring liver, kidney, and thyroid function is crucial during treatment.
Despite treatment breaks, side effects like fatigue and diarrhea limited drug use.
Disease progression led to liver-dominant issues, requiring embolizations for temporary control.
Kinase inhibitors can extend lifespan and transition metastatic disease to a chronic condition.
A case study showed symptom and disease progression control over 17 years with kinase inhibitors.
Active management and treatment efforts prolonged the patient's life despite eventual disease progression.
Kinase inhibitors have the potential to improve patient outcomes and turn metastatic disease into a manageable chronic condition for some individuals.
Study on regorafenib vs placebo for metastatic GIST patients after three prior lines of therapy.
Regorafenib showed longer median progression-free survival of over six months compared to placebo's one month.
Patients on regorafenib experienced disease stabilization and fewer side effects like diarrhea and fatigue.
Overall survival was significantly improved with a median of 18.2 months with regorafenib compared to six months with placebo.
Study results show no overall superiority in median PFS except for a specific molecular signature.
Drug demonstrates better tolerability compared to sunitinib, leading to updated guidelines for second-line treatment.
Patients intolerant to sunitinib may find the drug to be a suitable alternative.
Most patients tolerate the drug well with good quality of life, but some may experience side effects such as muscle and joint pains, hair thinning, weight loss, and nausea.
Regular skin assessments and monitoring for potential heart issues are recommended for patient safety.
The benefits of diuretics, molecular genotyping, and kinase inhibitors in managing blood pressure and fluid retention in patients.
Molecular genotyping is essential for selecting the most suitable therapy for individuals.
Multiple kinase inhibitors are effective in managing side effects and improving patient survival rates.
Progress in personalized cancer medicine has led to the development of four lines of effective therapy for certain patients.
Liquid biopsies may be utilized in the future for managing patient genotypes and treatment, showcasing the continuous success of targeted therapy and personalized cancer medicine in treating various types of cancer.
Summary of the patient's treatment for a spindle cell tumor and subsequent development of metastatic sarcoma.
The patient received radiation therapy and systemic therapy for the spindle cell tumor, which initially reduced the mass.
However, the tumor reappeared as metastatic sarcoma in the lung and pelvis, leading to unsuccessful treatment regimens.
A re-biopsy revealed a TRK fusion, indicating a new area of mesenchymal tumor pathology.
The case highlights the complexity and challenges in effectively treating the disease.
Overview of n-track rearranged spindle cell neoplasms.
Tumors usually found in young patients and exhibit S100 and cd34 co-expression.
Diagnosis requires genetic confirmation due to antibody specificity issues.
Tumors can be mistaken for peripheral nerve sheath tumors and have specific gene fusions.
Treatment options include participating in trials with track inhibitors.
Discussion on decrease and disappearance of soft tissue mass in sarcomas patient undergoing therapy.
Impressive response to targeted therapy, regardless of tumor type or age, showcasing potential for future treatments.
Ongoing clinical trials with second and third-generation track inhibitors offering hope for improved outcomes and resistance studies.
Importance of considering NGS early on in cases of certain sarcoma entities for evolving and promising developments in sarcoma research.
Debate on the necessity of next-generation sequencing (NGS) in medical oncology.
NGS can identify actionable targets like gene fusions that respond effectively to treatment.
Concerns exist about the cost and feasibility of NGS for all patients, especially those with advanced sarcomas.
Research efforts are underway to find more cost-effective methods for NGS, potentially resolving the debate on its widespread use in cancer treatment.
Discussion on the differences between two drugs in terms of cognitive impairment and side effects for a patient case of epithelioid sarcoma in a 26-year-old male from Emirates.
Details on the presentation, mass size, lymph nodes involvement, and pathology confirmation of an epithelioid sarcoma proximal variant are provided.
Emphasis on the recognition of two types of epithelioid sarcoma - classic and proximal.
The proximal type is highlighted for its occurrence on the limb girdle and distinct characteristics compared to the classic type.
Discussion of histological features and characteristics of breast cancer.
Epithelioid sarcomas stain positively for keratin and cd34, leading to potential misdiagnosis.
Coverage of the two subtypes of UI sarcoma, their aggressive nature, poor prognosis, and potential metastasis.
Patient progression with primary tumor and lymphadenopathy, treatment with gemcitabine and endocytaxel, partial response, and pre-operative radiation therapy.
Treatment for epithelioid sarcomas involves a combination of chemo and radiation therapy.
The patient underwent radical resection of the perineal mass with clear margins.
As of January 2022, the patient was free of any gross evidence of disease.
Different chemotherapy regimens showed varying response rates, with Jim starting Windows to taxol having a 25% response rate.
The choice of therapy depends on the patient's objectives and disease presentation, with attention to achieving the desired outcome in cases of primary tumors and regional disease.
Loss of INI1 in synovial sarcoma leads to chromatin remodeling and transcriptional changes.
Targeted treatment towards INI1 loss activates the EZH2 pathway, showing potential benefits.
Trials with EZH2 inhibitor tazematostat had low response rates in epithelial sarcoma patients but good tolerability.
Tazematostat is now approved for metastatic epithelioid sarcoma to stabilize tumors and improve quality of life.
Spider plot data shows most patients experience tumor stabilization, leading to the drug's approval based on its efficacy and tolerability in a disease with limited treatment options.
Importance of a multidisciplinary approach in patient care.
Collaboration among diagnostic, surgical, medical, and radiation oncology teams is crucial for optimal care.
Key takeaways include prolongation of survival, management of side effects, and future precise targeting based on molecular profiles.
Progress made in identifying effective treatments for resistant clones in soft tissue tumors.
Continued research is needed to make advancements in treating complex diseases.
Importance of patient and tumor characteristics in personalized therapeutic approaches.
Continued research and clinical trial enrollment are necessary for progress in disease treatment.
Collaboration and teamwork are essential in treating complex cases like sarcomas.
Constant learning and progress are key in the field of oncology.
Gratitude is expressed for the educational experience and anticipation for future presentations discussing advancements in the field.