Here is a note I have prepared Sunday night 29 July for the ACT Hospice, to explain Margaret's situation.

Margaret Gray - notes by her husband, Dennis Argall.

Most recent developments:

Coping with a GBM diagnosed in April 2000, Margaret was doing very well to mid-May - socially, mentally and physically very well, KPS 75-80? She then encountered problems starting with a major seizure episode on 22 May, requiring eight days in hospital.

On 27 June, Margaret saw Dr Helen Wheeler, neuro-oncologist, in Sydney, with MRI scans taken as routine prior to anticipated round 7 of temozolomide. The scans showed new tumour in the top of the brain, infiltrating skull and scalp, and Margaret was immediately admitted to Royal North Shore Hospital for a third craniotomy, carried out by Dr Ray Cook on 2 July. (sorry, this image is huge, you can read on below while it loads)

The operation, precipitated particularly by the 'absolutely unacceptable' escape of the tumour from the brain, with some under the scalp, ready to burst, involved:
1. clean-out of moderate regrowth of first, left frontal, tumour site
2. removal of all visible (new) tumour from site at top of brain, closer to motor strip, including removing front half of superior sagittal sinus, installing 'huge' artificial dura,
3. removing a piece of tumour-infiltrated skull, 4cm or so, and replacing with acrylic,
4. clean out of tumour/fluid (egg-sized) under the scalp, uncertainty as to continued presence of tumour in the scalp.

Pathology samples from 1, 2 and 3 were glioblastoma, suspicion of sarcoma dismissed. A strip of skin-scalp, thought by the plastic surgeon to contain tumour, thought by neurosurgeons not to contain tumour, was found free of tumour. A major concern, for which plastic surgeons were brought in for possible further work, was the capacity of the scalp, in places only 1 to 2mm in depth, to heal. The neurosurgeon, Dr Cook, has been pleasantly surprised ("I'm amazed!") by the way the scalp and incision have recovered.

Margaret was responsive, verbally and with hand grip, promptly after the operation, but deteriorated over two weeks, with severe expressive dysphasia, loss of motor abilities on the right side, and some agnosia. Dr Wheeler and Dr Cook both returned from absences on 16 July:
· Dr Wheeler observed Margaret somnolent and in view of the pathology favoured no further treatment with temozolomide and thalidomide (the latter 100mg nocte 21 November - 27 June; Dr Wheeler carried out the Australian clinical trials of both and is the most experienced in Australia in using the combination; she reports 30% response to each, 'much much better' results with patients using both.) and a pursuit of comfort and palliation.
· Dr Cook saw Margaret at a better time of day and also worked from CT scans indicating increased swelling on the left side. He considered this most likely to be an 'angry' reaction to all the work done over 14 months (see below), expressed the view that 'You will recover, Margaret" and raised dex for several days to 8mgs tds, then 4mg qid for seven days, reduced Friday 27 July to 4mg bd (for say another seven days, before reducing to 4mg a day, depending on subjective indicators, hopefully continued improvement).
· Dr Cook favoured Margaret going to the more aggressive environment of rehab.
· When, later Dr Dunlop (Canberra Hospital) recommended Margaret go to Ryde Rehabilitation until a bed is available in Canberra Hospital rehab ward, Dr Wheeler and Dr Cook thought it best for Margaret to move to the ACT Hospice pending an opportunity to go to Canberra Hospital rehab.

Improvements in motor skills, end of agnosia, improved speech, have been steady and impressive since the dex was increased. However, on 25 July, an investigation of pain encountered in walking a few steps found a right leg DVT, 50% occluded, extending from below the knee to lower abdomen (top limit obscured by air but not affecting left leg). Neurosurgery team initiated Clexane-Warfarin transition, but Dr Wheeler ordered Warfarin excluded from treatment, just Clexane.

On 27 July Dr Wheeler put Margaret back on Thalidomide 100mg nocte, without great expectation of success, but on the basis that it has more chance of effect sooner rather than later, and will do no harm. Note that having resumed thalidomide Margaret is experiencing prompt, heavy but restorative sleep after the dose, which effect should wear off in a couple of weeks on past experience. Margaret is carrying a substantial supply of Thalidomide.

Dr Wheeler and Dr Cook have asked me to report by fax in three weeks on how Margaret is doing, with a view to planning an MRI to see whether she should resume temozolomide also. Dr Wheeler has in mind that Margaret could see Dr Craft (whom Margaret has seen alternate months between appointments with Dr Wheeler) but wishes herself to see the scans. While having somewhat different views on Margaret's prospects, Dr Wheeler and Dr Cook work closely as members of SNOG (the Sydney Neuro-Oncology Group). Dr Cook said to Margaret on Saturday 28 July: "You are better every time I see you; you will get better. [though not certain of restoration of full mobility] This is my practical opinion, not my optimistic opinion. I want you back on treatment."

So, we have to see just how rapidly there is tumour regrowth…

One note regarding medication. Margaret has not experienced much pain at any time, seldom needed analgesia, since diagnosis. In the last several weeks there has been pain arising from discomfort confined to bed with immobile right side and now with the DVT. But it has been very difficult to get medication right - not only has Margaret's aphasia made it hard for her to ask, but there is clearly something missing in frontal lobe perception of pain, though the impact of pain on the brain has been evident in distress, restlessness and irritability. Margaret now understands this, or professed so Saturday (memory still a bit gappy), and was happy for Tramadol dosage to be shifted from PRN to 100mg qid. There was earlier discretion in the dose, 50 or 100mg, but 50mg did not last more than a couple of hours of moderate effect, and the gap was filled to moderate extent with paracetamol. Given the moderately constipating effects of the thalidomide, tramadol has advantage over codeine.

Earlier treatment summary:

MRI of 27 April 2000 - symptoms of unresolving 'sinus' pain, becoming eye pain, weariness, moderate forgetfulness, otherwise 'no neurological signs at pre-admission clinic, Canberra Hospital 2 May. Craniotomy, Dr Chandran, 3 May, '80%' debulking.

Radiotherapy, Radiation Oncology of Sydney, June-July 2000 [Prof Phillip Yuile]; commenced seeing neuro-oncologist, Dr Helen Wheeler. Also commenced Chinese herbal remedies with which Shanghai University reported good survival for glioma patients (pathology??). (Dr Wheeler happy to observe.)

Visited Sun Yat Sen University of Medical Sciences Cancer Hospital, Guangzhou, China (a disease based cancer hospital being established on the model of M.D.Anderson) to pursue traditional medicine option further; also promptly given PET scan and gamma knife treatment 2 September - see details under 'China'.

Reported to Dr Wheeler 31 October 2000 with scan showing massive necrosis/regrowth and extensive oedema extending to the basal ganglia, impacting on speech and moderate Parkinsonian shuffle.

Dr Cook removed 'all visible tumour' 6 November.

There was in December 2000 scans a small tumour remnant, reducing slightly thereafter, over months of combined thalidomide-temozolomide treatment. Here is the February situation; note a continuing scalp collection of CFS, arising from a clean-out of the ventricles in November.

The 25 June scan shows developments clearly implicated in the seizure events of May and subsequent focal seizures and headache and right-side weakness dealt with with little 0.5mg doses of dex. Note that in the original incision the tumour still seems largely under control; the problem is in the area around the superior sagittal sinus and in the history-making infiltration of skull and scalp. ("As we have more survivors, we are learning more, we are seeing more things that are not supposed to happen. But I've never seen anything like this." - Ray Cook)