Browse Day: April 4, 2008

What about the bone sarcomas

What about the bone sarcomas? Even rarer than the soft tissue sarcomas, and the only one I’m going to talk about today is osteosarcoma. It’s about 35%. It’s usually a disease of the second decade, similar to Ewings sarcoma. Chondrosarcoma and malignant fibrocystic sarcoma are in older age group. It’s usually a tumor of the metaphyseal area of the bone, usually the distal femur as opposed to Ewings sarcoma which usually is a disease of the shaft or the diaphyseal portion of the bone. This is the most common primary bone tumor, excluding myeloma. There are about 1,000 new patients per year. Somewhat of an increased incidence in males versus females. There is a biphasic occurrence, mostly in adolescents with the growth spurt, but also in the elderly associated with Paget’s disease and previous radiation therapy. What you are looking for when you look at the pathology is malignant sarcomatous stroma, associated with the production of osteoid and immature bone. As I said, it involves the metaphyseal portion of bone and it usually either metastasizes to lung or other bone, again avoiding the liver. In about 15-20% of the time patients present with metastasis. So you want to see here abnormal-looking osteoblasts and osteocytes in a sea of osteoid. If you don’t see osteoid then you can’t call this an osteogenic sarcoma. There are multiple different types of osteogenic sarcomas. I don’t want you to memorize the slide. I just want you to be aware that of the conventional type, chondroblastic usually has somewhat of a worse prognosis, don’t respond as well to chemo. There are some clinical variants. Osteosarcoma of the jaw, mandible maxillary area where again you may not be able to achieve very wide margins, and here you may use radiation therapy. Postradiation osteosarcoma, which connotes somewhat of a worse prognosis. They are older patients as well as Paget’s disease being older patients as well. A variant, telangiectatic where when you cut through the bone of a telangiectatic sarcoma it’s markedly vascular. This used to have a much worse prognosis. With our newer forms of chemotherapy they respond very well.

A paraostial and periosteal sarcoma, which are the surface variants, which I’ll show you. And paraostial you want to be aware of because this really just occurs on the surface of the bone. It does not elevate the periosteum like periosteal. These are usually very low grade and although these can appear somewhat large, they are low grade and usually you can just treat them with surgery alone. The periosteal sort of have a mixed prognosis, and some of these are treated with chemotherapy.

What about prognostic factors for osteogenic sarcoma? I talked about the classification subtypes. Again, location; distal tumors do better than proximal. Extremities do better than axial or involvement of the pelvis or the vertebrae, and that’s because you can obtain better wide margins. Size becomes important, especially if it’s over 15 cm. Again, it’s going to be harder to achieve good margins and usually the tumor has been around for a longer time, possibility of metastasis. So they have a worse prognosis. Symptom duration; those patients who have a long symptom duration usually do better than short because it’s slower growing. Those very young patients or those patients older than 20 have a somewhat worse prognosis. Again, females do somewhat better than males, and there have been some studies to suggest that those patients who have very elevated alkaline phosphatases and LDH levels have a worse prognosis. But that’s probably more to connote what the tumor bulk is. If patients have skip lesions, they do worse. If they have a pathologic fracture they do worse. There is some evidence now to suggest that if those patients received induction neoadjuvant chemotherapy first that they can do well, and that not all these patients have to receive an amputation. Like soft tissue sarcoma, if you have lymph node involvement – which is extremely rare – it’s a very very poor prognosis. Or if there is extra-skeletal disease, there’s usually a worse prognosis. And those patients who have metastasis at presentation, specifically if there is metastasis to other bone, do much worse.

Histologic grade is important. We usually treat intermediate and high grade tumors. If it’s a low grade periosteal, as I mentioned, the patient usually just has surgery. The Italian group has shown that loss of heterozygosity of the retinal blastoma gene, also P-glycoprotein, connotes somewhat of a worse prognosis. Ploidy; the jury is still out, and recently reported at ASCO this year, approximately 30-40% of the patients are HER2/neu positive. Those patients that are HER2/neu positive have a worse prognosis, and when you give them neoadjuvant chemotherapy they have a worse response, in terms of histologic necrosis. Because of the availability now of Herceptin and because we know that there may be some synergy or added effect of Herceptin with cisplatin, you are going to see in the next few years, new studies looking at the use of cisplatin with Herceptin in osteogenic sarcoma in those patients who are HER2/neu positive.

Other special situations

Now what other special situations do you need to know about for the Boards, in terms of sarcomas? Well, desmoids which are mostly low grade, are mostly locally invasive. As I told you before, they are associated with the APC gene, Gardener’s syndrome. The treatment of choice is usually a wide excision with negative margins, if possible. But if you can’t achieve negative margins because there are vital structures in the area, then you ought to at least obtain the best margins you can and then the patient can either receive radiation therapy or, if the patient has a recurrence, they can then be re-resected and have radiation therapy. Then those who have further growth of tumor, you can treat them – there’s data for use with NSAID’s, with tamoxifen, low dose Velban with methotrexate or Adriamycin/DTIC. A recent article in your handout, for those patients who get into problems with neurotoxicity with Velban, you can substitute vinorelbine, Navelbine. That’s a recent article that came out in the American Journal of Clinical Oncology that’s in your handout.
Leiomyosarcomas, GI stromal, have an extremely poor response to chemo. I don’t know what to do for those. You need, if possible, to get them to a surgeon who does a lot of these the first time so that the tumor can be fully resected. Because if the tumor is not fully resected and the patient has positive margins, they are going to do extremely poorly. Those patients with uterine or extremity leiomyosarcomas, you may consider using Adriamycin/ifosfamide or specifically for the uterine sarcomas, continuous infusion DTIC at a dose of about 300 mg per meter squared over approximately seven days. Myxoid liposarcomas; you need to be aware that these have a very high incidence of extrapulmonary metastases and that for this specific sarcoma, soft tissue sarcoma, in addition to getting chest CT’s you need to get abdominal CT’s because they can have occurrences in the retroperitoneal area and other areas.

Clear cell sarcoma behaves more like a melanoma and is HB-45 positive, so they should be treated like a melanoma. Breast sarcomas; the treatment of choice is doing a total mastectomy, no axillary node dissection, because the incidence of lymph node metastasis is extremely rare.

So to review here, for soft tissue sarcomas, incisional or core biopsy. If you are at an institution that can do these, I would recommend core. To do a resection, wide if possible with at least 1-2 cm margins at minimum. Postoperative radiation therapy most of the time if the margins are not good, but there may be some patients now who don’t require postoperative radiation. That will depend on the location, grade, size, and margin status. Consider preoperative radiation for a very large tumor mass or possibly neoadjuvant chemo. Metastasectomy is beneficial in a select group of patients. In terms of chemotherapy, either the Adriamycin/ifosfamide regimen or MAID plus growth factors. There is an increased response rate but no survival advantage. If you are just palliating and it’s an elderly patient, just Adriamycin alone or Adriamycin plus DTIC, probably given as a continuous infusion where you are going to reduce cardiotoxicity and probably nausea and vomiting. Adjuvant therapy is unproven for soft tissue, except maybe for extremity, for large, deep, high grade extremity lesions. And neoadjuvant induction chemotherapy is now being looked at but certainly isn’t standard. We do it at our institution, but I would probably refer a patient into a center for that, if it’s a very large lesion that needs to be down-staged prior to surgery.