Chemoherapy Of Bone Cancers
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Chemoherapy Of Bone Cancers

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    Chemoherapy Of Bone Cancers Chemoherapy Of Bone Cancers Presentation Transcript

    • CHEMOTHERAPY IN BONE CANCERS Prof. V. Vedhamoorthy. MD DM Professor and Head Department of Medical Oncology MMC, Chennai-3.
    • INTRODUCTION
      • CHEMOTHERAPY IN
        • Osteogenic sarcoma
        • Ewing’s sarcoma
        • Multiple myeloma
        • Bone lymphoma
        • Other bone primaries
    • OSTEOGENIC SARCOMA
      • Impact of chemo in osteogenic sarcoma
        • 5 years survival with surgery alone was less than 20%
        • Addition of chemotherapy as adjuvant increased the 5 year survival more than 80%
      • 2. Chemo as neo-adjuvant increased the percentage of limb conservative surgery
      • 3. Addition of chemo
        • Delayed the development of lung metastasis
        • Number of metastasis are fewer
        • Metastesectomy chances are improved
        • Increased the survival
      • Drugs effective in osteogenic sarcoma
        • Adriamycin
        • Methotrexate
        • Cisplatinum
        • Ifosfamide
      • Combination of drugs is the best
        • To increase the cell kill
        • To overcome drug resistance clones
      • Drug combination may be 3 or 4 drugs
      • Example
        • Adriamycin, Cisplatinum, Ifosfamide
        • Adriamycin, Methotrexate, Ifosfamide
      • SITUATION - 1
        • Osteogenic sarcoma
        • Limited to the bone of its origin
        • Smaller in size
        • Fit for immediate limb conservative surgery
      • 26 year male
      • Osteosarcoma of upper end of left tibia
      • X- ray chest
      • Normal
      • CT chest
      • Normal
    • PROTOCOL
      • Limb conservative surgery
      • Combination chemo administered as adjuvant
      • 6 courses
      • PRINCIPLE OF ADJUVANT CHEMO
        • To sterilize distant micro metastasis
        • To reduce distant relapse
        • To increase disease free interval
        • To improve overall survival
      • ADVANTAGES OF ADJUVANT CHEMO
        • Primary surgical treatment is executed immediately
        • Patient is mentally happy
        • Risk of progression and dissemination are avoided
        • Risk of development of drug resistance is avoided
      • DISADVANTAGES OF ADJUVANT CHEMO
        • Delay in care of distant micro metastasis
        • Risk of dissemination during surgical procedure is high
        • Clinical response of drug is not assessed
      • SITUATION - 2
        • Osteogenic sarcoma
        • Limited to the bone of its origin
        • Larger in size
        • Not fit for immediate limb conservative surgery
      • 25 year old male
      • Osteosarcoma of lower end of left femur
      • X-ray chest
      • Normal
      • CT chest
      • Normal
    • PROTOCOL
      • 3 courses of combination chemo as neo-adjuvant
      • Limb conservative surgery
      • 3 courses of adjuvant chemo
      • Pain and swelling reduced after 3courses of neo-adjuvant chemo
    • Underwent limb conservative surgery
    • X-ray after limb conservative surgery
    • Patient ambulant after limb conservative surgery
      • PRINCIPLES OF NEO-ADJUVANT CHEMO
        • To reduce the size of the primary tumor
        • Making the tumor amenable for limb conservative surgery
      • ADVANTAGES OF NEO-ADJUVANT CHEMO
        • Distant micrometastasis is taken care immediately
        • Size and vascularity of the tumor is reduced, hence dissemination risk is minimized during surgery
        • Clinical response is assessed
      • DISADVANTAGES OF NEO-ADJUVANT CHEMO
        • Delay in the primary surgical treatment
        • Patient is psychologically upset
        • Risk of progression and dissemination of the disease is high
        • Development of drug resistance is increased
      • ASSESSMENT OF RESPONSE OF NEO-ADJUVANT CHEMO
        • Symptoms
          • The size of the tumor is reduced
          • Pain is lessened
      • X-ray, CT, MRI
        • Size of the tumor is reduced
        • Margins become more clear and defined
        • Soft tissue infiltration recedes
        • Thickness of cortical involvement is not altered
      • Technetium 99 Bone scan
        • Size is reduced
        • Intensity of the hot spot decreased
      • Angiogram
        • In very good response
          • Arterial phase and capillary mess are reduced
        • In intermediate response
          • Arterial phase alone is reduced
        • In poor response
          • No change in arterial phase and capillary mess
      • Thallium bone scan and PET scan
        • Both give biological response directly
        • In good response – because of heavy necrosis, uptake is reduced
        • In poor response – because of no much change in viable cancer cell volume, uptake is not altered
      • Pathological response
        • Grade I
          • Volume of viable cancer cells is not altered
        • Grade II
          • Minimal reduction of viable cancer cells
        • Grade III
          • Good reduction of viable cancer cells
        • Grade IV
          • Complete disappearance of viable cancer cells, replaced by necrosis
      • SITUATION – 3
        • Osteogenic sarcoma
        • Limited to the bone of its origin
        • Presence of pathological fracture
        • (seen in less than 1%)
      • X-ray left femur
      • OS of lower end
      • Pathological fracture
    • PROTOCOL
      • Fractured segments are kept in alliance
      • Limb is immobilized by POP
      • 2 courses of combination chemo
      • If good callus formation occurs – suggests chemo clears tumor tissue in between fractured fragments
      • Proceed with limb conservative surgery
      • Followed by 4 more courses of adjuvant chemo
      • If no callus formation occurs
      • Suggests tumor tissue is not sterilized by chemo
      • Proceed with amputation
      • 6 courses of tailored adjuvant chemo
      • SITUATION – 4
        • Osteogenic sarcoma
        • Presence of resectable pulmonary secondary
      • X-ray chest shows solitary coin shadow at right lower zone
      • CT chest
      • Solitary lung secondary
    • PROTOCOL
      • Manage the primary tumor by LCS / amputation
      • 2 courses of combination chemo
      • CT chest confirms no progression of pulmonary secondary
      • Metastesectomy
      • 4 courses of combination chemo
      • SITUATION – 5
        • Osteogenic sarcoma
        • Unresectable, multiple, bilateral pulmonary secondaries
      • X-ray chest
      • Multiple, bilateral, subpleural and basal lung secondaries
      • CT chest
      • Multiple bilateral lung secondaries
      • Cavitating secondary left lower lobe
    • PROTOCOL
      • Palliative combination chemo
      • If chemo has not given good response to primary tumor
      • Proceed with palliative surgical resection
      • SITUATION – 6
        • Osteogenic sarcoma
        • Limited to the bone of its origin
        • Underwent surgery and chemo
        • While on follow up develops resectable pulmonary secondary
    • PROTOCOL
      • Resect the pulmonary secondary
      • Observation
      • or
      • Second line chemo
      • SITUATION – 7
        • Osteogenic sarcoma
        • Limited to the bone of its origin
        • Underwent surgery and chemo
        • While on follow up develops unresectable pulmonary secondary
      • Option 1
        • Symptomatic treatment
      • Option 2
        • Second line combination chemo
      • Option 3
        • High dose chemo with autologous peripheral stem cell transplant
      • Newer experimental drugs
        • Muramyl Triphosphate (Macrophage stimulant)
        • Aerosol GM-colony stimulating factor
        • Herceptin – If Her 2 over expression present
    • EWING’S SARCOMA
    • INTRODUCTION
      • Second common bone primary in the paediatric age group
      • Highly radio and chemo sensitive
      • SITUATION - 1
        • Ewing’s sarcoma
        • Limited to the bone of its origin
        • Size is less than 8cm
        • Cured by surgery or radiotherapy
    • PROTOCOL
      • ADJUVANT CHEMOTHERAPY
      • EVOLUTION
        • 1960s
          • Vincristine, Actinomycin-D, Cyclophosphamide
        • 1970s
          • Intergroup Ewing’s sarcoma study -1
            • Vincristine, Actinomycin-D, Cyclophosphamide, Adriamycin and pulmonary irradiation
          • Intergroup Ewing’s sarcoma study -2
            • Vincristine, Actinomycin-D, Cyclophosphamide, Adriamycin in escalated dose
      • 1980s onwards
        • Pediatric Oncology Group
        • Vincristine, Adriamycin, Cyclophosphamide, alternated with Etoposide, Ifosfamide
        • Every 3 weeks
        • 8 courses each
        • Covering 48 weeks
        • Gives longest disease free interval and overall survival
      • SITUATION - 2
        • Ewing’s sarcoma
        • Limited to the bone of its origin
        • Size is more than 8cm
        • Planed for limb conservative surgery
        • (No role for curative radiotherapy)
      • 26 year old male
      • Ewing’s sarcoma of right forearm
    • PROTOCOL
      • Neo-adjuvant 3 courses of VAC / IE
      • Tumor size is reduced
      • Limb conservative surgery is done
      • 5 more courses of adjuvant VAC / IE
      • SITUATION – 3
        • Ewing’s sarcoma as disseminated disease with
        • Pulmonary / bone / marrow metastasis
      • 16 year old boy
      • Ewing’s sarcoma of left tibia
    •  
    •  
      • Principle
        • Palliative
      • Plan
        • Combination chemo
      • Schedule
        • 3 drugs regimen – V Act C
        • 4 drugs regimen – V Act C + Adriamycin
        • 5 drugs regimen – VAC / IE
      • Results
        • All the regimens give equal results of survival
      • Newer approaches
        • High dose chemo with autologous peripheral stem cell transplant
        • Indicated in
          • High risk limited stage Ewing’s sarcoma
          • Post chemo relapse
          • Disseminated stage
      • Newer drugs
        • Topoisomerase – I inhibitor
          • Topotecan
          • Irinotecan
        • Taxanes
          • Paclitaxel
          • Docitaxel
      • Chondrosarcoma
      • Malignant giant cell tumor
      • Protocol as osteogenic sarcoma
      • Fibrosarcoma of bone
      • Malignat fobrous histiocytoma of bone
      • Angiosarcoma of bone
      • Chemo protocol is MAID schedule
        • Messna
        • Adriamycin
        • Ifosfamide
        • D-actinomycin
      • Bone lymphoma
        • CHOP schedule
          • Cyclophosphamide
          • Hydroxyl doxorubicin
          • Oncovin
          • Predinisolone
        • R-CHOP
          • Rituximab with CHOP
      • Multiple myeloma
        • VAD (Vincristine, Adriamycin, Dexamethasone)
        • Thalidomide with dexamethasone
        • High dose melphalan with ABMT / APSCT
    • CONCLUSION
      • Bone lymphoma and multiple myeloma
        • Primary modality of treatment is chemo
      • Ewing’s sarcoma
        • Radiotherapy and surgery are equal options
      • Osteogenic sarcoma, chondrosarcoma
        • Surgery is the primary modality
      • Role of chemo in osteogenic sarcoma as
        • Neo-adjuvant
        • Adjuvant
        • Palliative role
        • has been clearly established
    • Thank you