NSCLC-IV, Adenocarcinoma - potential targeted therapy - 1242499

Sat, 03/03/2012 - 00:30

Dear Drs and fellow fighters,
My dad (67yrs) was diagnosed with NSCLC stage IV adenocarcinoma with Brain mets and Bone mets in L2 vertebra in May of 2010. We had the L2 lesion treated with Fractionated Stereotactic radiation therapy (14 cycles). Due to his history of non smoking and otherwise normal parameters he was eligible for a chemotherpy based clinical therapy for an experimental drug - YM155 at NCI/NIH. He underwent four sessions of chemo (Paclitaxel + carboplatin) with YM155. After four cycles the therapy was stopped because there was no change in the size of his primary tumor in the lung and there were no new mets. He was transfered on a double blind, vaccine therapy (Lucanix). This went on for another 6 months with a sub derma shot every month. After 6 months, the trial was stopped as she showed newer lesions in the brain. We treated these lesions with Gamma knife therapy. Since then he had been free of new mets till February. 2012. He is currently in India and during his recent MRI and CT scan, new lesion was detected in the D1 vertebra. We have treated it with cyberknife. A full body PET scan showed new bone met in the head of the femur. However this met associated with the femur is asymptomatic.
His oncologist team from NCI had suggested that we need to treat the femur lesion immdiately as it is a load bearing bone and hence there is a risk of fracture if left untreated. They also suggested him to go on a chemotherapy with either docetaxel or pemetrexed (Alimta). I conveyed these suggestions to the oncologists in India, who are currently treating him. They have advised to my dad that his body would be too weak to handle the chemo and so there is a possibility that he can come down crashing so he should make all arrangements and have his family with him. They also didn't think that it is necessary to treat the lesion on the femur with radiation adn that he should wait for another 2 months.
I find these suggestions from his oncologist in India disheartening. I am presenting my dad's case in this forum to seek better insight and options towards his treatment and help him make an informed decision. Please note that a biopsy sample from my dad was subjected to NexGen Exon sequencing for abotu 150 genes. There is a possible mutation and they are currently validating it before letting us know about the possibility of a targeted therapy trial for him.
Thanking you for all your time and kind assistance.

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Dr West


I can understand both sides of these discussions. First, the textbook answers to the leading choices for subsequent treatment after progression of advanced NSCLC in patients treated with chemo in the past are Taxotere (docetaxel), Alimta (pemetrexed) (for non-squamous NSCLC tumors only), or Tarceva (erlotinib). Other options may be reasonable to consider but aren't as well studied. On the other hand, patients who are quite debilitated, particularly if they are spending more than half of the day in bed or a chair rather than being up and able to care for themselves, may be too ill to benefit from more treatment. If someone is too weak for more anticancer treatment, it may shorten rather than prolong survival.

With regard to the femur lesion, that is actually a gray zone as well. While it's true that the femur is weight-bearing, there are lesions that are small enough or in a particular location where the risk of a fracture is not great. I have known knowledgeable radiation oncologists who have advised against radiating lesions that aren't associated with pain, since the pain is correlated with risk of fracture. I would consider this a somewhat debatable point and may ask a radiation oncologist colleague for input, but I would say that it isn't clear cut that every femur lesion requires immediate radiation.

Finally, I would just caution that the gene test his tissue has been sent for is not a standard or validated test. I have never sent a patient's tumor for a test like this and actually know no lung cancer expert who recommends this approach, since we really don't know how practically useful it is.

-Dr. West

dr loiselle

Arul -

With regard to the femoral head lesion detected by PET, whether this requires immediate treatment depends on the extent of the bone disease.

The anatomy bones is such that cancer involvement in the more central spongy aspect of the bone (medullary bone) poses less of a threat than involvement of the outer strength bearing aspect of the bone - the cortex. Lesions in load bearing bones with 50 to 70% cortical involvement are at significant immediate risk of fracture, and in these circumstances we typically favor surgical stabilization with hardware placement - usually a pin is tapped down the central aspect of the bone and secured with a few screws.

Less extensive cortical involvement can pose a risk for fracture with disease progression, and often we sometimse address the risk with radiation therapy to the bone. Whether the risk is significant enough for upfront treatment depends on assessment of the bone by the x-ray or catscan.

If the lesion has no significant cortical involvement and is not symptomatic, we often will follow the lesion carefully for progression on followup scans, and most importantly alert the patient to watch for any pain developing in the area.

I hope that helps.

Dr. Loiselle


Dear Drs. Loiselle and West,
Thank you for your insight into the possible treatment options for my dad. His oncologist from NCI had mentioned that the mutation that was identified with his primary tumor was found to be in the EGFR gene in exon 7, which is normally associated with gliomas. He said that the efficacy of Tarceva on this mutation is not known but based on the effect of the mutation on the gene's function, it is likely to function as a EGFR inhibitor. So, he had suggested that we should try putting my dad on Tarceva for 6 -9 weeks and then follow up with scans to check the effect on the tumors. If there is positive response, the treatment can be continued. If not we can stop it and go with pemetrexed or docetaxel.
Based on your (Dr. Loiselle) detailed explanation about the nature of bone met and the corresponding treatment, I had enquired about the nature of the lesion on my dad's femur. His radiation oncologist from India, had mentioned that the lesion is not present on the stress bearing part of the bone and hence it was prudent to wait and observe the lesion in a month before deciding on the next course of treatment.
The neurosurgeon who had performed the gammaknife treatment on my dad's brain in July had taken a look at his scans and mentioned that there are four new subcentimeter lesions in his brain. Also, he mentioned that what appeared like a tumor in the neck D1 vertebra was actually a result of degenerative spine disease. However, my dad had already undergone cyberknife radiation therapy to treat that tumor and I was wondering if the PET scan result would clear the discrepancy. Any advice and suggestion in this regard would be gratefully acknowledged.
Thank you for your time and assistance.