Transcript of Live Chat, from June 14, 2000

Guest Host:

Dr. Stanley Order
Radiation Oncologist
Center For Molecular Medicine
Garden City, NY
516-222-2727

• Musella Welcome Dr. Order..

• Musella Can you tell us about your new treatment?
• Dr. Order: Thank you. Glad to be here.
• Dr. Order: Yes. The treatment uses compounds that make radiation retained in the tumor if the tumor is directly injected.
• Dr. Order: The doses achieved are beyond what any conventional dose can achieve.

• Musella Is it used after "regular" radiation, or instead of?
• Dr. Order: Previously irradiated patients can be treated since the method we use is restricted ONLY to tumor and not to normal brain.

• Musella Is there a size or shape limit on the tumor size?
• Dr. Order: Features include location of the tumor, tumor size - but not shape.

• Musella What are the results so far?
• Dr. Order: Shape is conformally treated by using macroaggregated albumin, heretofore referred to as MAA to distribute itself within the stroma of the cancer.
• Dr. Order: in the Phase I study, 11 patients have been treated with dose escalation of every 3 patients, and we are encouraged by the fact that there has been NO toxicity and clinical remission not as documented by subsequent scans.

• Musella Please clarify that last part:" no toxicity and clinical remission not as.."
• Dr. Order: not as YET, since more time must pass

• Musella steve asks: how much radiation can you give ? doesn`t it affect normal brain tissue ? how is it different from injecting radioactive antibodies into brain tumors like they do in Italy and at Duke ?
• Dr. Order: I will answer Steve's questions one at a time
• Dr. Order: This procedure has been used on other tumors where up to 1,800,000 rad has been given to pancreas cancers that then received 6,000 rad external radiation - without toxicity.
• Dr. Order: No radiation is deposited in the normal brain. The range of colloidal P32 is 8mm, and the dose on the periphery of the tumor is 50% of the center of the tumor. Therefore, with an isolated form of radiation we are only affecting the tumor.

• Musella steve adds:: I have a GBM that was treated by radiation and chemotherapy. Now it is growing. My doctor told me I cant get more radiation because glioblastoma is not sensitive to radiation. Is there any radiation treatment left for me ?
• Dr. Order: The radioactive anititenacin is based on the antibody recognizing the antigen still present in the malignancy that has been removed. The doses of radiation achieved are miniscule -even if effective. We are treating recurrent that already have dimesion of 3cm - 5cm.
• Dr. Order: The answer is you can be treated by this technique - as long as your tumor is not beyond 5cm. The previous irradiation does not matter, since this form of radiation is isolated to your tumor. You probably received external radiation which required the radiation to penetrate normal tissue to get at the tumor. By placing a needle directly into the tumor, stereotactically, and restricting the radiation to the tumor, we do not anticipate normal brain radi

• Musella Paul Asks: I have a five year old daughter with recurrent GBM. Whole head radiation has been recommended, but we`re very concerned about side effects at so young an age. She`s had Gamma Knife, and we`re considering another session for the new spot. Are there any other, newer modalities we should be on the lookout for? Would your treatment be appropriate for a child?
• Dr. Order: First of all, I do not believe, in this circumstance, that there many other options. Fractionated radiosurgery might be more attractive than single dose. Our technique, although very plausible for children, cannot be used until we determine the benefit for adults - and there no other facilities presently carrying out these studies.

• Musella dunenuthin@hamptons.com asks: I was told not to use any anti oxidents, such as green tea, while on radiation or chemo, do you think it would be a problem?
• Dr. Order: Radiation works by oxidation and creation of free radicles. Anti-oxidants, such as vitamins, would reduce the oxidation - and in some studies, vitamins have been shown to accelerate tumor growth. Green tea and vitamins are cancer preventitives, potentially, not cytotoxic agents.

• Musella Can you explain the side effects expected of whole brain radiation in a child?
• Dr. Order: There is an unqualified reduction in cortical function, which takes its expression differently in individual patients.

• Musella GBM asks: Do you ever use a radiation sensitizer when giving "standard radiation" for a glioblastoma
• Dr. Order: Since the normal brain continues to expand to 18 years of age, it would be preferable to avoid whole brain irradiation - since it has not shown a greater benefit than radiation with a several cm border around the tumor.
• Dr. Order: No. Radiation sensitizers have not been proven to accelerate the results - in almost all tumors studied. A publication many years ago in the New England Journal indicated a benefit from sensitizers, only when a larger study was done was this demonstrated not to be effecacious.

• Musella GBM adds: Can you discuss the difference between gamma knife and linac stereotactic radiosurgery and fractionated stereotactic radiosurgery?, Which is better for a gbm?
• Dr. Order: The gamma knife consists of multiple cobalt sources in a huge lead chamber with a block in front of each source. The blocks are removed in the right location thus exposing the tumor to a high fractionated dose.
• Dr. Order: Linac stereo-radiosurgery uses the linear accelerator which rotates 360 degress and can create the same pattern of radiation -with higher radiation energy. Cobalt 60 1.2MEV linear accel. 15MEM or higher.
• Dr. Order: Fractionated radiosurgery uses the system at a modified dose over a period of time - even though the dose is higher, it requires multiple setups and is more sparing to normal tissue because the extreme high dose is not given.

• Musella neal asks: What would your best treatment plan be for a newly diagnosed glioblastoma?
• Dr. Order: Surgery -if possible, dependent on location; conformal radiotherapy to the tumor with a margin of 3-4cm; monthly CT scans for recurrance, P32 infusion and temodar or other chemotherapy in combination.

• Musella We had 2 folow-up questions on the topic of radiation sensitizers: Do you have any experiance or know the early results of the new trials using RSR13, Xcytrin and angiostatin with radiation?
• Dr. Order: It is too premature to evaluate the compounds. The WR2721 developed by Walter Reed has been shown to be protective to normal tissues, and probably, at this time, is the most interesting compound.

• Musella neal asks follow-up: What is p32?
• Dr. Order: It colloidal radioactive phosphorus, produced commercially for pleural effusions and peritoneal ascites. It is a beta irradiating produces, thereby not requiring hospitalization due to radioactivity. And not dangerous to the public.

• Musella Div33 asks: Could you expand on the radiation side effects of pediatric whole brain radiation? Son, at 9 months of age, in 1980 received 2350 rads whole head over a 20 day period pre-op. Thyroid was in field of radiation.
• Dr. Order: The dose response curve was partially established by the use of radiation whole brain in Israel, when they treated children for fungal growth in the hair and subsequently reported reduced mentation in these children. The doses of radiation for this reduction are not firmly established. The thyroid being in the field of radiation runs a risk long term for Thyroid CA. Frequent tri-monthly examinations and if a nodule is detected, technititium scans are

• Musella We had a few people just ask: Why CT scans and not MRI scans for follow up? Also - what is the best test to determine tumor regrowth vs. radiation necrosis?
• Dr. Order: Unfortunately in this day and age, the expense of CT scans and MRI are disequivalent. We must have a lesion that is measurable, and therefore if a CT scan shows a lesion, we would then obtain an MRI. The best test to determine tumor regrowth vs. radiation necrosis is unfortunately a needle biopsy. PET scans can not differentiate - with accuracy - these two phenomena.

• Musella Betsey Asks: I have an anaplastic oligo with a size of 8cm x 4cm (after surgery took approximately 50%). Would I be eligable for your treatment? Have you ever done a patient with an oligo before? And do you have any other ideas for treatment?
• Dr. Order: With a poorly differentiate oligo, you would be a candidate for our procedure- if the tumor were not bigger than 5cm and not located in a critical site, such as the mid-brain. You are also a candidate for temador in combination with other drugs.

• Musella pigface asks: What treatment is available for residual 1% of a pilocytic astrocytoma in cerebrum of child
• Dr. Order: Pilocytic astrocytoma has a better prognosis than standard GBM. Why can the tumor not be removed? Is the threat too much loss of function or not?

• Musella pj asks: Doctor, if a gbm patient had gliadel wafers implanted, can they also do your treatment?
• Dr. Order: The answer is yes - the complicating factor would be the location of the wafer in terms of introducing the needle required in the tumor.

• Musella Pigface said 99% of the tumor was removed. they couldn't get that last 1%
• Dr. Order: If the tumor that is remaining can be encompassed by radiosurgery, the sparing of normal brain would be a great advantage over conventional radiation. Again size and location would dominate a treatment decision.

• Musella JChou asks: My daughter Emily is 7 years old now and was diagnosed with Medulloblastoma last July. After surgery, there is a 2cm tumor left in pineal region. This tumor shrink to 2mm after two run of Vincristine and Cytoxin. We will have 6 more chemo in next 6 months. It seems that tumor is staying in the same area and did not spread to other area after 11 months. My question is it necessary to have whole brain and spine radiation. That is what our doctor rec
• Dr. Order: Medulloblastoma often spreads through the spinal fluid. In order to know whether such radiation would be advantageous cytospins of spinal fluid are carried out to see if there free tumor cells in the fluid. The sequellae of whole brain radiation and spinal irradiation are not attractive nor is recurrence in the spinal canal. The recommendation being made to you is the present conventional approach.

• Musella neal asks: Can you explain in more detail how your treatment gets to the tumor only and not normal brain? Is it a 1 shot deal? Does it make you feel sick?
• Dr. Order: The treatment is carried out in a hospital with a stereotaxic frame for localization, along with anasthetics and the placement of the needle by a neurosurgeon. In a dose escalation study, every 3 patients get a higher dose and we are allowed to up to 3 infusions, 5 weeks apart. There has been no illness nor acute side-effects from the treatments. The radioactivity is isolated to the tumor only by the pre-use of 10 million particles of MAA. Therefore,

• Musella ConnieBee : Getting back to your response on gamma knife vs. linac: Which is better for a gbm? The gamma knife people say bad things about the linac, and the linac people say gamma knife is old technology and just has better public relations. .
• Dr. Order: This is a commercial question. The intellectual answer is that the higher energy of the linac offers greater sparing of normal brain, HOWEVER, both techniques on the expertise of the physician - which is equally important. In most facilities, neurosurgeons have found great appeal to the gamma knife and some restrictions in understanding the linac method of accomplishing better dose distribution.

• Musella Nancy asks: Do you see your treatment as being a possible "cure" for a gbm or just to buy time? Can other treatments be done at the same time as yours - for example temodar?
• Dr. Order: One normally enters studies with the hope of superior results. To describe results in a Phase I study would be premature. If other treatments can be added to the present methods this could not be accomplished in the present approach. Ultimately, one would hope to be able to use combination therapies in this setting, but this is not presently available.

• Musella Pete asks: How do you feel about delaying (or avoiding alltogether) radiation and trying chemo first (after surgery) for a gbm?
• Dr. Order: Location, size and residual disease would all play a role in such a decision. The adult brain does not have the cortical risk of the maturing pediatric brain.

• Musella Deborah asks: what tumor types do you accept now?
• Dr. Order: All highly aggressive primary brain tumors, such as GBM, poorly differentiated oligo - that have recurred, following surgery and radiation.

• Musella We are runnin glow on time.. this is our last question:

• Musella A few people ask: How do you feel about radiation vs. surgery for meningioma,s and for acoustic neuromas.
• Dr. Order: Radiation for meningioma has been associated with excellent results. Always location is critical. The same can be said for acoustic neuromas, since now conformal radiation restricting it to the tumor can be accomplished. In some acoustic neuromas, surgery would be preferred when the lesions are small, but not preferable when they are large due to loss of normal function due to surgery. Please see a Review of Radiaiton Therapy of Benign Diseases, by O
• Dr. Order: I hope this has been a constructive analysis who have forwarded their questions.

• Musella Thank You Dr. Order!
• Dr. Order: Your Welcome. Thank you for the privilege and opportunity.

• Musella May we ask you back in a few months?
• Dr. Order: Sure.

• Musella Good luck with your trial. it sounds interesting..
• joyce It seems that Dr. Order's treatment is available after surgery, chemo, and conventional radiatiation has failed. Am I correct?
• Dr. Order: Yes!
• PatBeaver At what facility are you running your trial?
• Dr. Order: The Center for Molecular Medicine, Garden City, NY in conjunction with Long Beach Medical Center, Long Beach, NY