Results Of PET/CT Scans May Predict Survival In Multiple Myeloma Patients
According to a recent Italian study, the results of PET/CT scans conducted at diagnosis, after induction therapy, and after stem cell transplantation may predict survival in multiple myeloma patients.
Specifically, the study authors found that patients with PET/CT scans negative for cancer cells, bone lesions, or other signs of active cancer had longer progression-free and overall survival times than patients with positive PET/CT scans.
“[Our study shows] a clear identification of the prognostic relevance of PET/CT [along with] other more known prognostic factors such as chromosomal abnormalities,” said Dr. Elena Zamagni of the Bologna University School of Medicine in Italy and lead author of the study.
“These factors are predictive for a more aggressive disease which could require more intensive treatments,” she added.
Based on their findings, Dr. Zamagni and her colleagues suggested that disease management could be improved by the incorporation of PET/CT scans into myeloma treatment plans. Moreover, they added that if their results were confirmed in larger clinical trials, the use of PET/CT scans after both induction therapy and stem cell transplantation could contribute to the development of individualized therapies for myeloma patients.
A positron emission tomography (PET) scan is a type of imaging test that detects the level of cell activity throughout the body. Patients undergoing a PET scan typically receive an injection of a radioactive sugar molecule called FDG, which accumulates in cancer cells more than in healthy cells. The PET scan then reveals the activity and locations of cancer cells in different parts of the body based on detected radioactivity levels.
PET scans provide more detailed results when combined with a computerized tomography (CT) scan, an X-ray imaging technique that gives clear images of the human anatomy. A PET scan plus a CT scan is called a PET/CT scan.
In their study, researchers inItalysought to determine whether the results of PET/CT scans could predict survival outcomes of multiple myeloma patients.
The study included 192 newly diagnosed myeloma patients with a median age of 56 years.
All patients received thalidomide (Thalomid) plus dexamethasone (Decadron) as induction therapy, followed by high-dose melphalan (Alkeran) and autologous stem cell transplantation. Of the 192 patients included in the study, 40 percent received one transplant and 60 percent received two back-to-back stem cell transplants. All patients then received 160 mg/month of dexamethasone as maintenance therapy until their disease progressed.
All patients received a PET/CT scan at diagnosis and another after stem cell transplantation. Forty-four percent of patients received an additional PET/CT scan within 10 days of completing induction therapy.
The majority of patients (88 percent) were also screened for chromosomal abnormalities. Forty-three percent of these patients had del(13q), 23 percent had t(4;14), and 15 percent had del(17p) abnormalities, which are all associated with a poor prognosis.
At diagnosis, 24 percent of patients had a negative and 76 percent had a positive PET/CT scan, which the researchers defined by the presence of bone lesions, a high level of myeloma activity (measured by a standard uptake value, or SUV level, above 2.5), or the presence of extramedullary disease (the presence of myeloma cells outside the bone marrow).
After induction therapy, 37 percent of patients had a negative PET/CT scan, and that number increased to 65 percent after stem cell transplantation.
At a median follow-up time of 42 months, 80 percent of patients achieved at least a very good partial response as best response after transplantation, with 52 percent of patients showing a complete response. The median progression-free survival time was 56 months, and the four-year overall survival rate was 88 percent.
The researchers found that patients with negative PET/CT scans at diagnosis had significantly better survival outcomes than patients with positive PET/CT scans.
Specifically, patients who had fewer than three lesions had a higher progression-free survival rate after four years than patients who had more than three lesions (69 percent versus 50 percent). Patients who had lower myeloma activity also had higher progression-free (66 percent versus 42 percent) and overall survival (92 percent versus 76 percent) rates after four years than patients with high myeloma activity. Similarly, progression-free survival (63 percent versus 22 percent) and overall survival (92 percent versus 76 percent) rates were higher after four years for patients without extramedullary disease than those with the disease.
After induction therapy, patients whose PET/CT scans showed low myeloma activity also had higher progression-free survival (69 percent versus 44 percent) and overall survival (88 percent versus 75 percent) rates after four years than patients who had higher myeloma activity after induction therapy.
Moreover, patients who had negative PET/CT scans three months after receiving autologous stem cell transplantation had higher progression-free survival (47 percent versus 32 percent) and overall survival (79 percent versus 66 percent) rates than patients who had negative PET/CT scans three months after the transplant.
The chromosomal abnormalities t(4;14), and del(17p) were also associated with shorter progression-free survival in myeloma patients.
Dr. Zamagni acknowledged, however, that while the results of this study may not have immediate practice-changing implications, they could lead to better individualized therapies in the future.
“It is not yet time to tailor treatment based on the PET/CT data, as there is not by now a real tailored treatment based on chromosomal abnormalities. But in the future, [we may expect] prospective protocols based on these prognostic factors,” Dr. Zamagni told The Myeloma Beacon.
For more information, please see the article in the journal Blood (abstract).
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- Revlimid, Velcade, and Dexamethasone, Followed By Stem Cell Transplantation, Yields Deep Responses And Considerable Overall Survival In Newly Diagnosed Multiple Myeloma
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I have no idea how Dr. Zamagni will use PET/CT scans to "contribute to the development of individualized therapies for myeloma patients" beyond the current high risk versus low risk classification.
But at least he stated individualized therapy as a goal and that's great.
All of which validates the cancer stem cell theory!!
Gary,
Here's are thoughts this article makes me ponder..
Is this a double edged sword when it comes to eligibility for clinical trials?
After all the mfgr wants patients who have the least disease and therefore most likely to have the greatest efficacy, and typically those would also be healthier patients less likely to have toxicities. We already see this in terms of the median age in many trials being 52-57, despite MM supposedly being a disease of old age.
Even more unsettling is that PET/CT are also being used it to determine the patients with best prognosis following stem cell transplants.
Which will then provide insurers, based on PET/CT, with clinical evidence to deny coverage. After all cancer is a million dollar disease for insurers and billion dollar industry for mfgrs...so I suppose, the good part of this could possibly pit big pharma up against big insurance.
But for us average cancer patients out here, we may get bad news of poor prognosis followed by worse news that the insurers will not cover it based on PET/CT outcomes and then the subsequent terrible news that we are not even eligible for any clinical trial nor a SCT.
The possibly good news,in terms of individualizing therapy, is that PET/CT can determine how aggressive the initial therapy needs to be. Where it is dose density not intensity..IOW's successful combinations of sequential treatment.
Suzierose: YTou read a lot more into this article than I did. Thee results of this study have been known for quite some time.
"The National Oncologic PET Registry, a large prospective program, enrolled 22 975 cancer patients, including more than 1300 patients with myeloma, and revealed that 36.5% of the time, treating physicians changed the intended management on the basis of PET/CT results.6 But is this justified for myeloma patients? The study by Bartel et al gives us important information for the use of FDG-PET/CT in myeloma patients treated with both novel agents and high-dose therapy. In 239 patients who underwent total therapy 3 (TT3), the authors performed standard skeletal survey, MRI, and FDG-PET/CT at baseline and then at specified points in their multiphased treatment. The presence of more than 3 focal lesions (FLs) in the PET/CT (PET-FL) independently predicted for inferior overall survival (OS) and event-free survival (EFS). Furthermore, complete FDG suppression in PET-FL before transplantation conferred superior OS and EFS. As in other studies, the presence of FLs in MRI and of lytic lesions in plain radiography (MBS-osteolytic lesions [OLs]) also predicted for shorter survival in the univariate analysis. However, the logistic regression analysis showed that although PET-FL was independently positively linked to both MRI-FLs and MBS-OL, only PET-FL retained its independent predictive value for survival, identifying a subset of patients with otherwise low-risk myeloma who had inferior survival. In addition, CR based on PET/CT criteria (absence of PET-FL and extramedullary disease) occurred more rapidly than the clinical CR or near CR and especially than the MRI-CR status among patients presenting with MRI-FL. Do these data indicate that PET/CT is superior to MRI in patients with myeloma? All reported studies to date have confirmed the superiority of PET/CT over conventional radiography However, these studies have also revealed that if PET/CT was the sole imaging procedure, it would have missed additional small lytic skeletal lesions and diffuse spine involvement, which is readily detected by MRI.3,7 Another disadvantage of PET/CT is the false positive results especially in areas of inflammation or infection, deposits of brown fat, postsurgical changes, vertebroplasty changes, and occasionally other benign or malignant processes.8 In a prospective comparison among FDG-PET/CT, MRI, and conventional radiography, PET-CT was superior to plain radiographs, but, in 30% of patients, PET-CT scans of the spine and pelvis failed to show abnormal findings in areas in which MRI revealed an abnormal pattern of bone marrow involvement, more frequently of diffuse type. In contrast, in 35% of patients, PET-CT enabled the detection of myelomatous lesions in areas that were outside the field of MRI. By combining MRI of the spine-pelvis and PET-CT, the ability to detect sites of active multiple myeloma (MM), both medullary and extramedullary, was as high as 92%."
In other words you need to do MRI along with PET/CT. I have had two three PET/CT looking for focal lesion. All my results were negative but in one instance they overlayed the MRI and PET/CT and found what they thought was a tumor on one of my vertebrae. It wasn't.
I had to pay for one of these tests myself and it wasn't cheap but I was newly diagnosed at the time and didn't know any better. I would seriously question the value of PET/CT.
I suspect the Italians who initiated this work were trying to get their patients PET scans and they used clinical trials to gain experience with them since the European Health are system would not cover them. The results of this study suggest to me that have not made a convincing case for PET/CT.
The question of cost has not yet been addressed in the US. It definitely will be and I really appreciate your vigilance on the topic. Rather than a battle between drug companies and insurance providers it will probably be a battle between the forces within the government over who gets/deserves coverage and who doesn't.
Gary,
I think the article is about a subsequent study validating the initial large prospective study from the National Oncology PET Registry you cite, whose results have been known for awhile.
Perhaps, you are right that the Italians were simply looking for more evidence to use in the European Health System.
Unfortunately, I pondered/extrapolated how that same evidence can be potentially used in the US health care system as well.
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