Sunday, December 11, 2016

PET scans for prostate cancer

In the last few years there has been an explosion in the number of new PET scan indicators. I thought it a good idea to provide some background and an update.

Bone scans

PET scans may be understood as an improvement over bone scans. The traditional way of finding distant metastases is to use a technetium bone scan and CT. There are several problems with bone scans:
  • they show bone overgrowth, which may be bone metastases, but may just be arthritis or old injuries
  • only a bone biopsy can tell for sure, and it's not often feasible when the suspected mets are small or inaccessible
  • they reveal few mets when PSA is below 10-20 ng/ml or when PSA is stable
  • they only show bone mets, not soft tissue
The main advantage is that they are relatively inexpensive.

The principal uses are: 
  • to rule out bone mets in high risk patients prior to curative treatment
  • to diagnose metastases that may respond to chemo, Xofigo, or spot radiation
  • to track response to treatment among metastatic patients.

PET SCAN USES

Inherent limitations

The new PET scans are better than previous ones in terms of the size of the metastases they can detect, but they do not detect all metastases.

  • A cancer cell is many times smaller than the resolution of the CT or MRI. 
  • The activity of the cancer cell seems to influence whether it is detectable on any of the scans. 
  • There is "noise" in even the most specific tracer, with no sharp delineation between signal and background.

Salvage Radiation

The most important use of these new PET scans is to rule out salvage treatment when it would be futile. For men who have persistently elevated PSA after prostatectomy, or who have had a recurrence (nadir+2) after primary radiation treatment, a PET scan showing distant metastases can spare the man the ordeal and side effects of salvage treatment.

The FDA has approved Ga-68-PSMA-11 PET/CT for detection of recurrences after prostatectomy or radiation. They have also approved Axumin PET scans and C-11 Choline PET scans (at Mayo) for this purpose.

For salvage after primary radiation failure, it is necessary to locate areas within the prostate where the cancer may still be localized.  Memorial Sloan Kettering and the Mayo Clinic have effectively used PET scans to target areas within the prostate for salvage focal ablation or brachytherapy.

For salvage radiation after prostatectomy, it may be possible to identify areas of the prostate bed where spread is evident. While the entire prostate bed must be treated (most of the prostate cancer is below the limit of detection of even the most accurate PET/MRI scan), some radiation oncologists like to provide an extra boost of radiation to the detected cancer foci.

There has been accumulating evidence in the last few years (see this link) that very early salvage radiation treatment may improve salvage radiation outcomes over waiting until the PSA has risen above 0.2 ng/ml. Unfortunately, none of our PET indicators are any good at detecting metastases when PSA is below 0.2 ng/ml. It is unlikely that there are any distant metastases when PSA is that low, but there are some relatively rare forms of prostate cancer that metastasize without putting out much PSA. This leaves the patient without any assurance that salvage radiation will be successful. Perhaps the new PORTOS genetic test will be able to detect distant metastases biochemically, but this remains to be proven.

Pelvic Lymph Node (LN) Treatment

For men diagnosed with high risk prostate cancer, a difficult question is whether the pelvic lymph nodes ought to be treated, either with radiation or with pelvic lymph node dissection. Nomograms based on disease characteristics are used to determine whether the pelvic LNs merit treatment, but such nomograms are often inaccurate. A CT scan can sometimes identify lymph nodes enlarged (>1.2 cm) due to cancer. However, some LNs are only slightly enlarged (0.8-1.2 cm), and some cancerous LNs are not enlarged at all (<0.8 cm). LNs are usually enlarged by infection, so size alone is not a good indicator of cancer. An advanced PET scan can sometimes detect cancerous LNs. This may aid the decision on whether to have whole pelvic treatment for men with high risk cancer. Men who have already had radical prostate therapy that may have included radiation (primary or salvage) to other areas (i.e., the prostate or prostate bed) may face a similar decision as to whether to treat the pelvic LNs with radiation.

Just as it is necessary to irradiate the entire prostate bed and not just the detected foci when giving salvage radiation after prostatectomy, it is probably necessary to treat the entire pelvic LN area, and not just individual LNs, when cancer is detected anywhere in the pelvic LN area. Of course, such a decision must be balanced against the risk of side effects. There are ongoing clinical trials (RTOG 0534 for salvage therapy and RTOG 0924 for primary therapy) to determine whether such treatment provides any survival advantage when LN involvement is suspected. The STAMPEDE trial included an arm where patients were node positive (but negative for distant metastases) and were treated with radiation. Short term follow-up demonstrated an improvement in failure-free survival of 52% among those who had treatment.

Oligometastatic radiation of distant metastases

Although some have theorized that there is a stage in prostate cancer metastatic progression where the cancer is still curable, or where it can be delayed by removal of 1-3 detectable metastases, this theory has never been proven. In fact, a meta-analysis this year (see this link) showed that metastatic progression continues in almost all men despite such treatment. The possibility remains that progression may be slowed by spot treatment, although this remains uncertain as well. The natural history of metastatic progression is often very slow in early stages, with years between the first few metastases. The reason for this may be because the tissue in metastatic sites must first be biochemically transformed by signals from micrometastases in order to accommodate the growth of larger metastases. This preparation of fertile "soil" in which metastatic "seeds" can grow may take some time. PET scans for detection undoubtedly introduce lead-time bias into the calculation; i.e., the time between the first and second detected metastasis is certainly longer because a more sensitive PET scan was used, and not necessarily because the first detected metastasis was spot-treated.

In spite of the uncertainty concerning efficacy of spot treatment, patients often want to treat whatever can be detected. When such metastases are detected with sensitive PET scans and are in locations amenable to spot treatment with SBRT, and there is minimal risk of radiation damage to nearby organs, it is hard to argue against such use. However, the patient should understand that there is so far no evidence that such treatment will provide any benefit. He should also understand that detectable metastases in distant sites means that his cancer is systemic. There are thousands of circulating cancer cells and undetectable cancer cells already lodged in tissues. For this reason, it is never a good idea to delay systemic therapy (e.g., hormone therapy) in order to wait for PSA to increase to a point where metastases become detectable on a PET scan. The TOAD randomized clinical trial suggested that immediate hormone therapy at the first sign of recurrence after curative options were exhausted cut 5-year mortality in half compared to waiting for PSA to rise and metastases to become detectable.

Palliative treatment of metastases

Metastases can cause pain and interference with organ function. Bone scans can find larger bone metastases, and they are the ones most apt to cause pain, fracture, or spinal compression. Metastases in weight-bearing bones may be spot-radiated with SBRT to prevent such problems and to relieve pain. In the unusual event that a bone scan can't locate them accurately enough for SBRT treatment, a PET scan may be used.

Bone scans do not detect metastases in soft tissue, while most PET scans (other than the NAF18 PET) can. A PET scan may locate metastases in organs that may be biopsied or treated with radiation or other therapies, like embolization or ablation.

Multiple metastases

The CHAARTED study has taught us that prostate cancer with multiple distant metastases behaves in a different way and reacts to different therapies compared to prostate cancer with a low metastatic burden. Although the metastatic burden in the CHAARTED study was based on bone scan and CT, there may be a potential to identify patients who may respond to earlier systemic therapy if a PET scan were to be used. This use has yet to be explored.

Tracking success of treatments (radiographic progression)

PSA is not always the best measure of whether a treatment is successful and ought to be continued. Because they destroy cancer cells, some therapies may actually raise the PSA level for some time immediately following treatment. Chemotherapy does not always immediately reduce PSA, but the patient wants to know whether the potentially toxic treatment should be continued. Most of the time, serial bone scans can provide an adequate radiographic assessment. However, in patients with low PSA or low metastatic burden, serial PET scans may sometimes provide a more accurate assessment.

Initial detection, active surveillance, focal therapy, dose painting

Just as multiparametric MRIs can be used to detect significant prostate cancer when suspicion remains after a first negative biopsy, a PET scan can conceivably be used for such a purpose (as in this clinical trial). PET scans can also be used to track progression of prostatic foci in patients on active surveillance. It is hard to justify the cost for such purposes, and there is as yet no evidence that it is any better than a multiparametric MRI. In light of the recent evidence that multiparametric MRI may fail to delineate up to 80% of detected prostatic index tumors, they may find future use of PET/MRI in contouring treatment areas for focal ablation and for dose painting (see this link).

The FDA has approved Ga-68-PSMA-11 PET/CT at UCLA and UCSF for unfavorable risk prostate cancer.


How PET scans work

Positron Emission Tomography (PET) is a way of creating a 3D anatomical image. Instead of using X-rays, as a Computerized Tomography (CT) scan does, it detects positrons, which are positively charged electrons (which do not exist in nature). When a positron encounters a normal negatively-charged electron, they annihilate each other and release 2 gamma rays in opposite directions. When the machine detects such a pair of gamma rays, it extrapolates their source position, putting an image together. The PET scanner is combined with a CT scanner in the same device in order to provide anatomic detail.

As a cautionary note, PET scans do expose the patient to significant amounts of ionizing radiation from both the PET indicators and the simultaneous CT scan. It is not something one wants to do frequently.

PET emitters are short-lived radioisotopes that are created in a nearby cyclotron. Commonly used ones include carbon 11 (C11), fluorine 18 (F18), gallium 68 (Ga68), copper 64 (Cu64), zirconium 89 (Zr 89), and iodine 124 (I124). The choice of which one to use is based on cost, access, half-life, strength of signal, and ease of integration with the ligand. C11, for example, has an extremely short half life of only 21 minutes. This means it has to be manufactured very nearby where it will be incorporated into a ligand (like acetate or choline), and must be used immediately. F18 has a longer half-life (118 minutes) and has excellent detectability, but interferes somewhat with metabolism of acetate or choline. I124 has a long half-life (4.2 days) which may be too long for a patient who may have to remain isolated for the duration.

PET emitters are often chemically attached (chelated) to molecules, called ligands, that have particular affinity for prostate cancer cells. Some ligands are metabolically active, meaning they are food for the cancer cell, but not as much for healthy cells. Other ligands are created to attach to specific binding sites on the surface or inside prostate cancer cells. 

NaF(18) PET for bone metastases

Sodium fluoride (NaF18) replaces hydroxide with positronic fluoride when hydroxyapatite, the mineral that constitutes our bones, is actively accumulating in bone metastases. It is our most sensitive tool for detecting bone metastases. Fourquet et al. found that in the same patients, NaF18 detected 91% of bone metastases while DCFPyL detected only 46%.

Metabolic ligands

Because rapidly growing cancer cells metabolize a lot of glucose, fluoro-deoxy-glucose (FDG) has long been used in PET scans for cancer. Prostate cancer in its early stages does not metabolize glucose readily, so FDG can't be used until later stages.

Prostate cancer cells do metabolize fats, consuming choline and acetate. C-11 choline and acetate overcomes the interference problem of F-18 choline and acetate, but is very difficult to work with. Although the FDA has approved the C-11 Choline PET, only the Mayo Clinic offers it in the US. A few sites offer the C-11 Acetate PET, but it is expensive. It also requires a fairly high PSA, ideally ≥ 2.0 ng/ml, or fairly large metastases, to detect anything.

Fluciclovine has recently been FDA approved. It is incorporated into prostate cancer cells as part of amino acid metabolism. It can detect somewhat smaller metastases at lower PSAs.

PSMA ligands

95% of prostate cancers express a protein called Prostate-Specific Membrane Antigen (PSMA) on the surface of cells. There are a variety of ligands that are attracted to it. Some of the ligands are antibodies (like J591), some are shortened antibodies (called minibodies, like Df-IAb2M), and some are small molecules (peptides, like PSMA-HBED-CC or DCFPyL). PSMA-targeted ligands may accumulate in salivary glands, tear glands and kidneys, and urinary excretion may interfere with readings in the prostate area. PSMA has also been found on the cell surface of some other kinds of cancer. New PSMA ligands are still being developed and tried. So far, the one that seems to have the highest specific affinity for PSMA are the F18-based ligands (F18-DCFPyL, F18-PSMA-1007, and F18-rh-PSMA-7). They detect more metastases at lower PSA than the others. 

As prostate cancer progresses, PSMA expression reduces and the cancer metabolizes glucose to a greater extent. Then, it will be detected by FDG PET scans.



Other ligands

There are other prostate cancer-specific molecules for which ligands have been developed and to which positron emitters have been attached.  One of the most promising is the bombesin or RM2 ligand that attaches to the gastrin-releasing peptide receptor (GRPR) on the prostate cancer cell. In pre-clinical studies, it outperformed C-11 Choline. Clinical trials have started. Clinical trials have begun on several PET ligands that are designed for other receptor sites: human kallikrein-related peptidase 2 (hK2), FMAU, Ga-68-Citrate, I-124-Prostate-Stem-Cell-Antigen, Ga-68-DOTATATE (Somatostatin receptor), F18-DHT (androgen receptor), Cu-64-DOTA-AE105 (uPAR receptor), Cu-64-TP3805 (VPAC receptor). or multiple radiotracers.

The winner (so far) is...

Based on clinical trials, below are various PET indicators in approximate rank order of their sensitivity to detect recurrent prostate cancer, and their specificity for detecting it exclusively:
  1. F18-PSMA-1007
  2. F18-rhPSMA-7
  3. F18-DCFPyL
  4. F18-DCFBC
  5. Ga68-PSMA-HBED-CC (Ga68-PSMA-11)
  6. Fluciclovine (F18 - FACBC)/ Axumin
  7. C11-Choline/ C-11-Acetate
  8. F18-Choline
  • NaF18 (note: best for detecting bone metastases)
  • F18-FDG (note: better in late-stage PCa)
The following table shows the percent of patients who had metastases detected at various PSAs. F18-PSMA-1007 and F18-rhPSMA-7, are experimental PET indicators that are cleared quickly from the bladder, and are the best so far. F18-DCFPyL is much better than Ga68-PSMA at low PSA.  At PSAs between 0.5-3.5 ng/ml. it detected prostate cancer in 88% of recurrent patients, while Ga68-PSMA-11 only detected prostate cancer in 66% of the same patients - an improvement in sensitivity by a third. Next in line is fluciclovine, which was recently FDA approved. In 10 patients screened for recurrence at a median PSA of 1.0 with both Ga68-PSMA-11 and fluciclovine, the PSMA scan detected cancer in 5 of the 10 men that were negative on fluciclovine. In addition, positive lymph nodes were detected in 3 of the men using the PSMA scan that were undetected with fluciclovine (see this link). Most other PET indicators, like C-11 Choline or Acetate, or NaF18 are not at all reliable when PSA is less than 2.0.


Percent of patients in whom prostate cancer was detected by the PET indicator, broken down by the PSA of the patients


PSA range

Source

PET Indicator

<0.2 ng/ml

0.2- 0.5 ng/ml

0.5 -2.0 ng/ml

> 2.0 ng/ml


F18-DCFPyL



88% (0.5-3.5)



(1)

Ga68-PSMA-HBED-CC



66%  (0.5-3.5)


F18-rh-PSMA-7 (experimental)


71%

86% (0.5-1.0)

86% (1.0-2.0)

95%

(11)

F18-PSMA-1007 (experimental)


86%

89% (0.5-1.0)

100% (1.0-2.0)

100%

(12) (13)

F18-DCFPyL


48%

50% (0.5-1.0)

89% (1.0-2.0)

94%

(9)

F18-DCFPyL


38%

63% (0.5-1.0)

83% (≥ 1.0)


(14)

Ga68-PSMA-HBED-CC

31%

54%

88%

(2)

Ga68-PSMA-HBED-CC


58%

73% (0.5-1.0)

93% (1.0-2.0)

97%

(3)

Ga68-PSMA-HBED-CC


50%

69%

86%

(4)

F18-FluoromethylCholine


12.5%

31%

57%

Ga68-PSMA-HBED-CC



36% (PSA<1, PSADT>6 months)

95% 

(PSADT<6 months)

(5)

Ga68-PSMA-HBED-CC

11.3%

26.6%

53.3% (0.5-1.0)

71.4% (1.0-2.0)

95.5%

(6)

Ga68-PSMA-HBED-CC

33.3%

41.2%

69.2% (0.5-1.0)

86.7% (1.0-2.0)

94.4%(2.0-5.0)

100% (>5.0)

(7)

Ga68-PSMA-HBED-CC

43%

58%

72% (0.5-1.0)

84% (1.0-2.0)

90% (2.0-5.0)

(13)

Fluciclovine


37.5% (0.2-1.0)    77.8% (1.0-2.0)

88.6%

(8)

C-11 Choline


28%

46% (0.5-1.0)

62% (1.0-2.0)

81%

(10)


PET/MRI

PET scans are usually combined with simultaneous CT scans for image resolution. Siemens has a device that simultaneously provides a PET scan and an MRI. This enables  greater image resolution and the detection of smaller metastases than is possible with a PET/CT. (GE and Philips manufacture dual scanners rather than an integrated single scanner). The PET/MRI exposes the patient to a much lower dose of ionizing radiation than the PET/CT. These devices are expensive, and are only available at a few large tertiary care facilities. In one PET/CT vs. PET/MRI comparison using Ga-68-PSMA, the PET/MRI was able to detect 42% more metastases in recurrent patients, 10% more lymph node metastases, and 21% more bone metastases. In the US, PET/MRIs are in use at Mass General, Johns Hopkins, Stanford, UCSF, Washington University, Cleveland Clinic, and Memorial Sloan Kettering and several others.

Cost/Availability

So far, only Ga-68-PSMA-11, FDG, C11-Choline, and Fluciclovine are FDA approved for prostate cancer detection. NaF is approved for clinical trials and registries only. FDA approval opens the way for Medicare and private insurance to approve and pay for them. Sometimes, insurance plans will agree to pick up the cost. Otherwise, patients who want them must pay out of pocket, if they are available. Ga68-PSMA-11, while FDA-approved at UCLA and UCSF so far, costs $3,000  out of pocket. Hopefully, Medicare/insurance will reimburse soon.

Clinical trials

All of the newer PET tracers require validation with larger sample sizes. While there are some diagnostic tests that have a "gold standard" against which performance can be evaluated, this is problematic for detecting metastases. A positive finding can often be confirmed with a biopsy, so a PET scan's positive predictive value (true positives and false positives) can be ascertained. But there is no easy way to determine whether negatives were true or false in live patients.

F18-DCFPyL is available for free in a trial at NIH for free among any men who are (1) high risk or (2) recurrent (see this link). It is available as a PET/MRI for specific purposes at the  Northwestern University.

It is also available at Johns Hopkins, where it was first developed, for a wide range of indications if ordered by any of their physicians Contact details are available here, There are several studies in Canada: in BC.

Ga68-PSMA-11 is approved at UCLA and UCSF and is available in a clinical trial in the US, including one with a PET/MRI, at  Cleveland Clinic

Fluciclovine is available almost everywhere in the US, and is covered by Medicare for recurrent patients.

If you are interested in one of those PET scans for an indication outside of the clinical trial, call the contact anyway. Some are planning clinical trials for expanded indications shortly, and some may make the PET scan available for purchase outside of the clinical trial. Inquire about cost and get pre-authorization from your insurance company if you can. These can be very expensive.



Monday, December 5, 2016

SBRT vs. moderate hypofractionation: same or better quality of life

We have seen in several randomized clinical trials of external beam treatment of primary prostate cancer that moderately hypofractionated IMRT (HypoIMRT) treatment (accomplished in 12-26 treatments or fractions) is no worse than conventionally fractionated IMRT treatment (in 40-44 fractions).  We recently saw in a randomized clinical trial from Scandinavia that SBRT (in 5 fractions) is no worse than conventional IMRT (see this link) in long-term quality-of-life outcomes, even though they used inferior technology. The missing piece of the puzzle is to answer the question of whether SBRT is any worse than HypoIMRT.

We don’t yet have a definitive answer (which would require a randomized clinical trial), but an analysis of pooled data from 5 different clinical trials, suggests that SBRT is no worse and may be better than HypoIMRT in its urinary, rectal, and sexual outcomes. Johnson et al. pooled SBRT data from clinical trials among 534 men at 3 institutions (UCLA, Georgetown, and 21st Century Oncology) and HypoIMRT data from clinical trials among 378 men at Fox Chase Cancer Center and the University of Wisconsin. All patients were treated between 2002 and 2013 at those top institutions, with state-of-the-art equipment in the context of carefully controlled clinical trials. Because of this, all outcomes are probably better than those achieved in everyday community practice. The only significant difference in patient characteristics was that SBRT patients were about 5 years older (69 vs. 64 years of age for HypoIMRT). We expect older men to have more natural deterioration in urinary and sexual function.

The following table shows the percent of men receiving each treatment who suffered from at least the minimally detectable difference in patient-reported scores on validated quality-of-life questionnaires with respect to urinary, rectal, and sexual function. Numbers in bold typeface represent a statistically significant difference.


SBRT
HypoIMRT
Odds Ratio (adjusted)
Urinary
14%
33%
0.24
Rectal
25%
37%
0.66
Sexual
33%
39%
0.73

The data support the following conclusions:
  • Urinary and rectal problems at 2 years were experienced by fewer of the men who had SBRT.
  • Urinary and rectal problems improved after 2 years compared to 1 year post-treatment. For SBRT, they approached baseline values.
  • Sexual issues did not improve at 2 years.
  • While we expected the SBRT patients to experience greater deterioration owing to their age, the opposite occurred.
(update: 4/11/2020) Kwan et al. reported on 78 patients randomized to SBRT (36.25 Gy in 5 weekly treatments) or moderate hypofractionation (70 Gy in 28 treatments). After at least 6 months of follow-up:
  • there were no statistically significant differences in grade 2+ or grade 3 toxicities
  • there were no minimally important differences in patient-reported quality of life on incontinence, irritative/obstructive urinary issues or bowel issues.


Why were the SBRT outcomes better?

SBRT is not just a high-dose-per-fraction version of IMRT, although it is that too. When the linear accelerator is delivering only 2 Gy per fraction, missing the beam target by a little bit is not likely to make much difference – it will average out in the long run. Because a geographic “miss” of the beam target has much greater consequence for SBRT, where the dose per fraction can be 8 Gy, much more care is taken to achieve pinpoint accuracy. This includes such steps as:
  • Fiducials/transponders aligned within each treatment and not just between treatments.
  • Fast linear accelerators that minimize the time during which the prostate can move.
  • No treatment if the bowel is distended or the bladder is not full.
  • Tighter margins: as low as 0 mm on the rectal side and 2 mm on the front side. This compares to margins of 0.5-1 cm for IMRT.
  • Narrower dose constraints for organs at risk, including the bladder, rectum, urethra, femurs and penile bulb.
  • More care taken to find a plan that optimizes prostate dose relative to organs at risk.


It is entirely possible that IMRT outcomes might be equivalent to SBRT outcomes if the same factors were incorporated into IMRT planning and delivery. But fractionation probably has an effect as well. To understand why, we must look at the radiobiology of prostate cancer. Prostate cancer has been found to respond remarkably well to fewer yet higher doses of radiation. This is reflected in a characteristic called the “alpha/beta ratio (α/β).” The α/β of prostate cancer is very low, at about 1.5. It is lower, in fact, than that of surrounding healthy tissues. Many of those healthy tissues have an early response, which is responsible for acute toxicity, typically within 3 months of treatment (α/β = 10.0). Rectal mucosal tissue is an example. This means that a hypofractionated dosing schedule will kill relatively more cancer cells, while preserving more of the cells in the nearby organs.

There are fewer types of tissue in the pelvic area that have a delayed response to radiation, and those tissues, like nerve cells, tend to be radio-resistant. This is why late-term toxicity is relatively low. Some of the late-term effects we do see are due to cumulative responses to radiation, like the buildup of scar tissue and other reactive responses in vasculature, along the urethra, and in the rectum. Late responding tissue has an α/β of about 3.5

We can compare the biologically effective dose (BED) of the various dosing schedules to see the effect that hypofractionation would theoretically have in killing cancer cells and preserving healthy tissue.



BED for cancer control
Relative BED for cancer control
BED for acute side effects
Relative BED for acute side effects
BED for late side effects
Relative BED for late side effects
80 Gy in 40 fractions
187 Gy
1.00
96 Gy
1.00
126 Gy
1.00
60 Gy in 20 fractions
180 Gy
0.96
78 Gy
0.81
111 Gy
0.89
40 Gy in 5 fractions
253 Gy
1.35
72 Gy
0.75
131 Gy
1.05

So the kind of fractionation used in SBRT theoretically has about 35% more effective cancer-killing power than conventional fractionation, while its ability to generate acute toxic side effects is reduced by 25%, and its late-term side effects would be similar.

Why isn’t everyone who elects to have primary treatment with external beam radiation treated with SBRT?

It’s one thing to make predictions based on theory, but it’s quite another to determine whether it works as well in clinical practice. So far, non-randomized trials like the ones examined in this study have shown excellent oncological and quality-of-life outcomes for SBRT with up to 9 years of follow-up. We await the oncological results of randomized trials comparing SBRT to IMRT. The oncological outcomes from the randomized Scandinavian trial are expected any time now. There are several others that are ongoing.

With SBRT, the patient enjoys the obvious benefits of appreciably lower cost and a more convenient therapy regimen. Medicare and most (but far from all) insurance companies now cover SBRT. There is considerable resistance from radiation oncologists in private practice who would get reduced revenues, and would have to learn the new techniques and gain adequate experience in using them.