Stereotactic Body Radiation Therapy (SBRT) for NSCLC

One emerging alternative to standard radiation therapy for medically inoperable patients with early stage NSCLC is stereotactic body radiation therapy (SBRT). This technique requires fixation and very precise treatment planning for a brief course of radiation that targets a more limited radiation field. One key issue with SBRT is that it presumes you don’t need to do extensive radiation to lymph node areas around the primary tumor — this is a big topic, but the evidence generally suggests this to be true, that we really need to focus more on treating the disease we see with stronger and more precise radiation, rather than get too distracted by the potential presence of microscopic regional disease in lymph nodes that appear normal on scans (abstract here, for example).

Our standard radiation dose of 60-66 Gray (the unit of radiation administration) for NSCLC is based on remarkably little evidence and goes back several decades. In fact, we know that similar or lower doses of RT are very effective in eradicating microscopic disease and laryngeal cancers that measure just a few millimeters, but radiation that is routinely administered in the 70 Gray and higher range are fair to good at treating smaller tumors like prostate and cervical cancers, both of which generally falling in the range of a few cm. In contrast, radiation for NSCLC lung lesions are often in the 5-10 cm range, and radiation in the 60 Gy range just isn’t that effective for such large and not especially radiosensitive tumors.

Newer techniques allow us to potentially deliver one or just a few fractions of very high dose radiation to a precisely limited area, thus reducing the risk of damage to surrounding areas and the need to administer radiation over many fractions over several weeks (radiation at low doses over many weeks takes advantages of the fact that normal non-cancer cells can recover better from radiation-induced DNA damage, leading to our routines of small doses accumulating over many weeks). By giving very high doses to a very defined area, stereotactic radiation becomes similar to a non-invasive form of surgery, leading to it being marketed as “gamma knife” or “cyber knife” (if you actually see any knives during these procedures, you should be concerned). This line of study was pioneered in the field of treating brain lesions, where the skull can serve as a reference system and the entire area can be immobilized with a fixed frame screwed into the skull (temporarily). These strategies are now very widely used for primary brain tumors or metastases to the brain from other sites.

But there are new techniques that allow introduction of the previously brain-based approach to body lesions as well. One of the less technical ones is to have a device that compresses the abdomen to minimize the ability of the diaphragm to move up and down and change the shape of the lungs:

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That white arc is where a patient’s abdomen is, and the vertical screw clamps down on the abdomen to limit motion. You may also note the presence of a metal frame on either side of the chest to hold it in place as well. It may seem medieval, but this is a potential step forward in treating cancer. Read the rest of this entry »

Radiation Therapy for “Medically Inoperable” Patients with Early Stage NSCLC

Many patients with early stage NSCLC but marginal or just plain poor pulmonary function tests and/or significant comorbidities pursue non-surgical therapy options rather than resection of the cancer. This primarily entails definitive radiation therapy (RT), stereotactic body radiation therapy (SBRT), or radiofrequency ablation (RFA) of these lung tumors. There is far more experience with definitive RT than with the other options, but I’ve never covered it. I’ve really only covered the newcomer RFA (prior post here), which was recently the subject of an FDA announcement of a number of patient deaths following RFA to lung tumors (post here). So now I need to rectify that. The most common primary treatment modality for “medically unresectable” patients with early stage NSCLC has been definitive RT alone. There has been a wide range in the reasons for patients to be ineligible for surgery, and many of these patients have other serious medical problems. A meta-analysis of multiple trials that enrolled medically inoperable patients with stage I or II NSCLC who received definitive RT (abstract here) reviewed results of a total of approximately 2000 patients in 26 non-randomized trials. This analysis demonstrated that overall survival at two, three, and five years ranged from 22-72%, 17-55%, and 0-42%, respectively. Cancer-specific survival was 54-93%, 22-56%, and 13-39% for those time intervals, respectively. Notably, 11-43% of the patients enrolled died from non-cancer-related causes, highlighting the real competing risks of these patients. Results with surgically treated patients are clearly better, but it’s not possible to separate how much of this is from the benefit of surgery over RT vs. how much is due to the difference in general level of health in the surgical vs. non-surgical early stage NSCLC populations. Another central problem with interpreting non-surgical data is the fact that the latter are derived from clinical staging, which consistently understages patients compared with pathologic staging in surgical trials. Approximately 40% of patients with clinical stage I NSCLC are subsequently found to have higher stage disease on surgical staging (abstract here), so surgical series reflect a higher stage, while non-surgical studies report an inferior survival at a lower clinical stage.

In addition to RFA as an alternative local therapy, stereotactic body radiation therapy (SBRT) has emerged as a novel technique, and one that hasn’t been the subject of a recent FDA warning. I’ll cover that work soon.

Stereotactic Radiosurgery for Brain Metastases

We’ve previously discussed whole brain radiation therapy (WBRT) has been the historical cornerstone of treatment for brain metastases, and how surgery is sometimes employed in certain cases, but stereotactic radiosurgery (SRS) has dramatically changed the treatment of brain metastases. SRS involves using a high dose of extremely focused radiation to a small area, most commonly in the brain tissue. Several machines can be used for this approach, most commonly Gamma Knife, potentially Cyber Knife, but sometimes other machines.

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It has been best studied in the setting of just 1-3 brain metastases, but it’s being used increasingly in patients with many brain metastases, a setting in which we have no real data, and there’s a good deal of controversy around whether patients are better served by whole brain radiation in that setting. Read the rest of this entry »

Whole Brain Radiation Therapy (WBRT) for Brain Metastases

Up to a few years ago, whole brain radiation therapy (WBRT) was the clear standard intervention for patients with lung cancer and brain metastases. Although median survival after WBR has been typically measured as a several months, that clearly exceeded the survival without treatment (typically in the range of weeks). There are several schedules, but the most common one has been 30 Gray (Gy) delivered in 10 three-Gy fractions over a two week period (Mon-Fri x 2 weeks) (abstract here). In addition to improving survival, WBRT also has a good likelihood of improving symptoms. Generally, about 60% of patients experience a complete or partial response to WBRT in terms of tumor shrinkage and/or improvement in neurologic symptoms. The dose is not likely to be enough to definitely control disease in the brain long-term, but the dose and schedule evolved as a compromise of trying to reduce the duration, minimize side effects, and control lung cancer in the brain for reasonably well. All too often, disease outside of the brain is progressing as well, so pushing the brain metastases onto the back burner has been the main achievement. It has remained the cornerstone of treatment for multiple brain mets, and particularly so for SCLC, where patients are particularly likely to have multiple lesions in the brain.

The other setting where WBRT is commonly recommended is after either surgery or radiosurgery (”gamma knife”) for one or a few lesions, in order to reduce the risk for further brain metastases. Studies have shown that on MRI patients with a brain metastasis have an 80% likelihood of an additional lesion, 50% have more than three, and over 70% of patients will develop recurrence in the brain if WBRT is not included after resection or radiosurgery (reference here).

The downside is that there is a real risk of developing significant symptoms from WBRT itself, including dementia or even, rarely, death (abstract here). It has actually been quite hard to assess the degree of neurocognitive decline in patients who receive WBRT, because detailed cognitive testing has often demonstrated a subtle deficits before starting WBRT, presumably as a function of their brain metastases. One study shows that memory (delayed recall) initially declines by three months after WBRT but then improves, even beyond pre-WBRT baseline (abstract here):

(click to enlarge) Read the rest of this entry »

Radiopharmaceuticals for Bone Metastases

As a follow-up to my discussion of the role of radiation in treating bone mets, I also wanted to cover another option that is rarely used for lung cancer but may be an attractive consideration for particular patients with extensive bone involvement. In addition to external beam radiation, or XRT, for focal treatment of 1-2 bony metastatic foci at a time, it is also possible for radiation oncologists to treat multiple metastatic sites at one time by infusing a radioisotope like strontium or samarium. These are minerals that include a radioactive isotope that is infused through an IV, like chemotherapy. From there, it goes through the bloodstream and hones to bone, particularly to metastatic regions. It’s similar to a bone scan, except that it’s not just showing where metastases are, but delivering radiation to the sites that would light up on the scan. This can kill tumor cells in the bone and lead to improvement in pain from bone metastases. In fact, pain has been reported to be relieved in more than 80% of patients treated with radiopharmaceuticals (another term for radioisotope therapy for bone metastases) (summary article abstract here); however, the trials of these agents have generally included very few patients with lung cancer, so it’s hard to interpret whether these numbers apply readily to lung cancer patients.

In real practice, however, I have only very rarely had patients for whom infused radioisotope treatment has been considered. This is because most of my patients have not had widely diffuse bone metastases, but rather a few areas causing pain, spread out over time. In contrast, the radioisotope approach is most well suited for patients with a large number of painful bone metastases all at the same time, which is most commonly seen in prostate cancer, quite a bit less common in lung cancer. The other concern is that the primary side effect of radioisotope therapy is a risk of prolonged low blood counts, which can make it more challenging and even sometimes unsafe/infeasible to administer further chemotherapy afterward.

For a patient with a wide range of bone metastases all at the same time, especially one who may not planning to receive more standard chemo later, an approach like a radiopharmaceutical injection may be a good choice to know about. Next well cover some surgical interventions and when they might be most appropriate.

Radiation Pneumonitis in Lung Cancer

Radiation pneumonitis is defined as inflammation in the lungs following radiation, and it is a common problem we see in patients who have received recent radiation therapy for lung cancer. It typically occurs several weeks or even a few months after radiation has been completed, with symptoms of shortness of breath, cough, and sometimes a fever. Chest x-rays or CT scans show an infiltrate, which is a cloudy area in the lung tissue that looks like pneumonia. It is very hard to determine how commonly it occurs, because 1) the symptoms are often presumed to be due to lung cancer or pneumonia and therefore may not be recognized as being from pneumonitis, 2) people who have the radiologic findings but minimal or no symptoms will not be recognized as having it, and, 3) patients who develop progressive or recurrent cancer may actually decline too quickly to develop it. Overall, the estimates of moderate to severe pneumonitis are in the 5-20% range in most recent studies with full dose radiation alone or radiation with chemotherapy. Although it often resolves, with or without any treatment, severe cases can be fatal. Read the rest of this entry »

Prophylactic Cranial Irradiation in Locally Advanced NSCLC?

While PCI is a recommended component of aggressive multimodality treatment for LD-SCLC, PCI does not at this time have any clear role in the treatment of NSCLC. To be potentially valuable, the risk of brain metastases needs to be high enough to justify to potential side effects, time, and expense of PCI, and is likely to be of value only if the risk of cancer recurrence elsewhere is low enough to make risk of brain recurrence a limiting factor in survival. With stage I and II disease, the risk of brain recurrence is not especially high compared with the risk of disease in the rest of the body, and in stage IV disease, control outside of the brain is usually a more pressing issue. But in stage III, or locally advanced NSCLC, as we have gotten better at controlling cancer in the chest, dealing with the potential for cancer in the brain has become enough of a problem that PCI for stage III disease is now a very timely question. Read the rest of this entry »