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  2. Therapeutic effect of neoadjuvant chemotherapy combined with : Medicine
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One thing that has improved significantly is imaging, so we know exactly where the tumor is. This enables us to successfully remove it while preserving as much normal tissue as possible. In many cases we can preserve the joint near the tumor, which makes reconstruction more effective. There also have been many advances in surgical techniques.

For many patients, after diseased bone is removed, we can combine bone grafts taken from donors with metal implants to reconstruct what has been taken out. We are indebted to the generosity of the organ donors who donate these grafts. It can be very hard to attach muscle to a metal implant, but bone grafts have natural muscle attachments.

Using a bone graft can work very well with joints, especially the rotator cuff, hip, and knee. These advances allow people to function much better with their reconstructed parts, for example enabling them to climb stairs and more easily get out of chairs. We cut off a piece of healthy bone about the size of a napkin ring and move it along the length of the limb, one millimeter each day.

When it gets to the other end, you have reconstituted a whole new bone. This technique was developed by Dan Prince , a member of our team, and can now be used in about one-quarter of patients who have sections of their long bones removed. But in some cases, amputation actually may help to preserve the way a limb functions. Sometimes amputation is the best option for younger kids because it helps them to avoid additional surgeries.

It gets them out of the hospital and back home much sooner, allowing them to grow up healthy instead of sick. Because these patients are young, quality of life is so important. In addition, because many of our patients are still small, we need to find the best methods to rebuild their bodies so that their reconstructed parts will be able to grow with them. It is particularly valuable for tumors around the pelvis, where the anatomy is complicated and reconstruction is a big challenge.

Nicola Fabbri performs very sophisticated, complex pelvic and joint reconstructions. Last but not least, Patrick Boland is a genius in handling the most difficult cases, for example removal of the sacrum. Dr Healey treated my dad, Anthony Guarneri, 32 years ago! Today my dad is Dr Healey has given him the chance to live life to the fullest!

Dear Corinne, we are glad to know that your father is doing well and felt well-cared for by Dr. Healey and his team. Thank you and your family for your generosity in donating to MSK and for sharing your kind words on our blog.

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Please wish your dad a very happy birthday from us! Hello, my father is dying of osteosarcoma in the base of his skull. The sarcoma has metastasized throughout his body. We are desperate for a treatment, are you offering any clinical trials? If you have any questions about any of these studies, or would like to make an appointment for a consultation, please call our Physician Referral Service at Thank you for reaching out to us.

BS Alert! It's time for oncologists to own the dismal survival rates of children with bone cancer so that the public can know the urgent need for more research. Dear Jeff, we sent your comment to Dr. Divers raises the critically important point that research is essential to improve survival in patients with metastatic and relapsed disease.

Funding for research remains critical to reduce the local and systemic toxicity of our current treatments and improve results for our patients. My son saurabh has died from osteosarcoma this year in January after 8 months of his diagnosis. Actually in my son case doctors perform wrong biopsy they done biopsy twice within three days and this wrong performed procedure made his Cancer metastatic to lungs and abdomen and Cancer became so aggressive and did not respond to chemo and despite of chemo his Cancer the tumor has increased and he died within eight months. It's a case of total medical negligence,.

I meet with Dr. Healy a few years back regarding PVNS in left knee.


  1. Osteosarcoma: Accelerating Progress Makes for a Hopeful Future.
  2. Molecular biology of B cells!
  3. SMALL ANIMAL CYTOLOGIC DIAGNOSIS;
  4. Introduction.
  5. Progress in the chemotherapeutic treatment of osteosarcoma (Review);

He was very compassionate and knowledgeable regarding this rare disease. Though I was operated closer to home I've had two surgeries but it is diffused and returns. Hearing of MSk's research advances if it reoccurs again I would be grateful if he would see me again. Dear Sue, we are sorry to hear about your recurring health issues. If the need arises and you would like to make an appointment in the future, please call our Physician Referral Service at Just let them know you have been seen by Dr. Healey in the past. Thanks for your comment.

My grandson has a tumor in the base of his skull, currently he is on chemotherapy. He was diagnosed with Langerhans cell Histiocytosis, can you please give me some insight on this disease and how long does it take to go into remission. Given that such devices are obviously still immature, one might look back to the bygone age of rotationplasties with never expected nostalgia.

Their function remains quite good even with long observation periods. A recent Italian series evaluated 25 patients living with rotationplasties for a mean of 15 years While arthritis of the tibiotalar, subtalar, and talonavicular joints was radiographically present in most, they showed improved gait parameters as adults compared with previously reported findings for children with rotationplasty Any osteosarcoma that can be operated on should be operated on to maximize the chance for local control and hence survival. However, not all osteosarcomas are operable. Several series have confirmed that selected patients may achieve permanent local control with radiotherapy, particularly if this is combined with effective chemotherapy and gross total resection 36 , Results of a meta-analysis suggest that debulking may no longer be required when radiation doses of 70 Gy or higher are administered.

Local control probabilities after radiotherapy were lower for craniofacial osteosarcomas than for those of other sites The high radiation doses required to sterilize osteosarcoma are difficult to achieve with conventional techniques, so that proton and heavy-ion radiotherapy have come into focus. In probably the largest series of 55 osteosarcomas treated with protons, the mean total radiation dose was Among 78 patients with inoperable osteosarcoma of the trunk irradiated with a median of Osteosarcomas were also included in an array of sarcomas of the spine 39 or extremities 40 treated with CIRT.

While the observed results were also encouraging, further research is required before such techniques can be considered standard. A systematic review of clinical outcome studies published between and concludes that there is insufficient evidence on the long-term effectiveness and harm of protons to either support or refute their use in children with osteosarcoma or basically any other pediatric cancer The MAP combination of HD-MTX, doxorubicin, and cisplatin 43 — 45 is frequently used, but similar results have been achieved with other protocols employing several of the mentioned agents 9 , A meta-analysis of published osteosarcoma trials concluded that using three of the drugs led to better results than using only two but that administering all four did not lead to further improvements Several prospective trials have attempted to introduce additional agents for either all patients or certain risk groups.

Some years ago, the prospective randomized INT trial addressed two potential additions to MAP using a randomized two-by-two factorial design: the cytotoxic agent ifosfamide and the macrophage activator liposomal muramyl tripeptide phosphatidylethanolamine L-MTP-PE, mifamurtide. A first publication 43 as well as a second 44 concluded that there was no benefit of adding ifosfamide.

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Therapeutic effect of neoadjuvant chemotherapy combined with : Medicine

The two papers differed in their conclusions regarding L-MTP-PE: while the first stated that analysis was prevented by an interaction between ifosfamide and L-MTP-PE 43 , the authors no longer detected a statistically significant interaction 3 years later and decided to examine each intervention separately, as originally planned. They called for additional clinical evaluations to define the role of the drug and to demonstrate whether any potential benefit requires concurrent use of ifosfamide We along with others have also argued for additional randomized comparative evaluation to substantiate the utility of the drug Since then, however, little new evidence concerning its potential efficacy has emerged.

Results from the metastatic cohort of INT pointed in the same direction as in non-metastatic patients but were not statistically significant Come , there is additional evidence that L-MTP-PE has a favorable safety profile: a patient access study of patients reported 3, infusion-related adverse events after 7, infusions, commonly chills, fever, headache, and fatigue, but only rarely severe However, there have been no further trials which shed more light upon the potential efficacy of the drug, so uncertainties remain regarding its potential role.

Another drug with immunological properties along with many other potential mechanisms of action 51 , interferon alpha-2b, was investigated in the largest prospectively randomized osteosarcoma study to date, the European and American Osteosarcoma Study Group EURAMOS -1 trial 45 , 52 , A total of patients whose resectable localized or primary metastatic osteosarcomas responded well to preoperative MAP were randomized after surgery to four additional cycles of MAP either with or without maintenance pegylated interferon alpha-2b Of patients randomized to receive the study drug, actually started, of whom stopped early.

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The hazard ratio from an adjusted Cox model was 0. Interpretation of the data is, of course, complicated to a certain extent by the relevant proportion of patients who never started or who prematurely stopped interferon alpha-2b. Nevertheless, the results do not argue for its inclusion in standard osteosarcoma treatment Encouraging results with the combination of high-dose ifosfamide and etoposide were reported from phase II trials of primary or relapsed metastatic osteosarcoma 54 , 55 , so that postoperative addition of the combination to MAP MAPIE was investigated in the poor responder cohort of EURAMOS-1 45 , MAPIE was more toxic and fewer patients received their intended chemotherapy doses.

MAPIE was also associated with higher risk of secondary malignancy, predominantly leukemia, mostly with cytogenetic abnormalities associated with the administration of alkylating drugs monosomy-7 or chromosome-5 abnormalities or etoposide 11q23 abnormalities. When patients not receiving HDCT owing to disease progression were excluded, there were no differences in outcomes between patients who received HDCT or not A completely different drug, the bisphosphonate zoledronate, was investigated in the prospective, randomized French multi-center OS trial, which asked whether 10 courses of zoledronate added to chemotherapy and surgery might improve EFS Chemotherapy used in this trial varied by age.

Among patients, 55 with primary metastases, were randomized to zoledronate. While the use of different chemotherapy backbones for different patients might confound interpretation to a certain degree, these results argue against zoledronate's ability to improve oncologic outcomes in osteosarcoma. OS as well as EURAMOS-1 exemplify that prospective randomized trials are essential to adequately assess whether treatments which show promise in the lab or in early phase studies will truly increase cure rates. They also demonstrate that such trials are feasible, even in very rare cancers such as osteosarcoma.

In summary, there is currently no evidence whatsoever that altering postoperative treatment in patients whose osteosarcomas respond poorly to preoperative chemotherapy or that modifying standard systemic treatment for other reasons will lead to anything but additional side effects and risks. The use of such approaches should be limited to prospective trials and otherwise discouraged. While multi-modal treatment consisting of surgery and chemotherapy is the undisputed treatment standard for patients with high-grade central arising within the affected bone osteosarcoma of the extremities or axial skeleton, some osteosarcoma variants deserve special consideration.

As for all osteosarcomas, surgery should strive to achieve wide margins. The role of additional systemic treatment, however, varies: low-grade central osteosarcoma arises within bone, just like high-grade central osteosarcoma.


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  • These tumors may carry areas of de-differentiation, and the decision to employ chemotherapy is often made based on the most malignant component. An Italian series of low-grade central osteosarcomas included 33 in which high-grade grade 3 areas were detected in the resected specimen, and postoperative chemotherapy was given to 22 of these The only patient from this cohort treated by surgery only survived disease free These series suggest that low-grade osteosarcomas with small high-grade foci may still be treated by surgery only.

    The numbers are too small to draw conclusions for low-grade central osteosarcomas which contain larger high-grade areas. Parosteal osteosarcoma is a low-grade surface osteosarcoma which may also contain high-grade areas 8. The authors observed neither medullary involvement nor the use of chemotherapy to correlate with survival One may conclude that, similar to low-grade central osteosarcoma, adequate surgery is the treatment of choice for parosteal osteosarcoma, that it is imperative to avoid local failure, and that there is no proven role for chemotherapy.

    Periosteal osteosarcoma is a surface osteosarcoma of intermediate malignancy 8. While sometimes treated with chemotherapy in addition to surgery, the currently available retrospective evidence suggests that treatment should be surgery only. The authors did not find survival to be influenced by chemotherapy Craniofacial osteosarcomas carry a comparatively high local recurrence risk.

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    The benefit of adding systemic treatments to surgery is not as well defined as for other sites, and no prospective data on adjuvant therapy has recently emerged. Nevertheless, current guidelines suggest using the same multimodal approach as for other high-grade osteosarcomas Osteosarcoma recurrences may still be cured as long as they are operable 66 , The aim of tumor-directed follow-up is therefore to detect local recurrences or metastases while surgery is still feasible Surveillance usually includes chest X-rays or chest CTs in addition to history, physical, and imaging of the former primary tumor site.

    The wide variability of surveillance protocols actually employed is exemplified by a Musculoskeletal Tumor Society MSTS survey, where the number of first-year surveillance visits ranged from three to six, chest X-rays from zero to three, chest CT scans from one to four, and X-rays of the former primary site from three to six However, conventional chest CT is associated with considerable radiation exposure, which led to criticism of these guidelines Several recent studies have attempted to lend more of an evidence base to osteosarcoma-directed follow-up.

    Dr. David Thomas: Immunotherapy for Osteosarcoma

    A retrospective single-center analysis of patients with routine chest X-ray surveillance reported 34 recurrences. All eight local recurrences were noted clinically, and only two of all recurrences developed beyond 5 years.

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