Case Studies

May 22, 2018

Anaplastic thyroid cancer is almost uniformly fatal, with an average lifespan of about 5 months after diagnosis. And standard treatment for the condition includes 7 weeks of radiation, often along with chemotherapy.

“We put patients through toxic treatment for seven weeks when most will only live five months. I’m not sure that’s how I would want to spend my time,” says Sana Karam, MD, PhD, investigator at the University of Colorado Cancer Center and assistant professor in the CU School of Medicine Department of Radiation Oncology.

Now a paper published in the journal Thyroid suggests an alternative. Rather than conventional radiotherapy, the paper suggests that thyroid tumors may be more susceptible to treatment with precisely targeted radiation known as stereotactic body radiation therapy (SBRT), and possibly with fewer side effects.

The study was made possible by one of Karam’s patients.

“It was one of those journeys that reminds you why we are so fortunate to be physicians,” Karam says. The patient was only 50 years old at the time of diagnosis. “I treated him with six or seven weeks of radiation only to find that the cancer had already progressed elsewhere in his body. He had six kids, five of them adopted, and at the end of his life one of the only things he could enjoy eating was ice cream, and so they all enjoyed it together.”

After her patient passed, the family created a fundraiser called Cream Cancer that accepted small donations from ice cream parlors near where they lived. Eventually the family raised $10,000, which they donated to the Karam lab to fund research to improve treatments for future thyroid cancer patients.

“My biggest thing was seeing if we could replace seven weeks of radiation with a shorter regimen, say three sessions of targeted radiation instead of thirty of conventional radiation,” Karam says.

Because the laboratory of CU Cancer Center colleague, Bryan Haugen, MD, holds one of the largest existing batteries of thyroid cancer cell lines, Karam and first co-authors Andy Phan and Ayman Oweida, PhD, were able to show that anaplastic thyroid cancer cells are almost universally resistant to conventional radiotherapy.

Karam wondered if targeted radiation might succeed where conventional radiation failed. In collaboration with the lab of CU researchers Rebecca Schweppe, PhD, and Nikita Pozdeyev, MD, Karam tested these two radiation strategies in mouse models of the disease.

“What we found is that not only is this condensed regimen of targeted radiation equivalent to conventional radiation therapy, but it’s actually superior, not only in terms of local control but also distantly,” Karam says.

Karam’s last point is an important one. A common criticism of targeted radiation is the idea that while it may treat the deposits of cancer at which it is aimed, it may not treat invisible deposits of cancer elsewhere in the body – invisible deposits that might be irradiated as a byproduct of more system-wide, conventional radiation therapy. However, recent work in the Karam lab and elsewhere shows that focused radiation may have a systemic effect.

“It may be that SBRT eradicates the root of the cancer so that it can’t continue to send out cells that lead to metastases, or it may be that SBRT wakes up the immune system to the presence of cancer, which helps the immune system combat cancer elsewhere in the body,” Karam says.

Whatever the mechanism, mice treated with SBRT had less cancer and lived longer than mice treated with conventional radiation.

The work also found a genetic signature of cancers that resist radiotherapy, namely hyper-activation of the gene CXCR4, which is associated with inflammation and has been shown to aid tumor growth in models of other cancer types.

“Because of our patients who are willing to contribute their tumor tissue to create the cell lines we need for our experiments, and because of our expertise with animal models, Colorado is known to be one of the best places for thyroid cancer research,” Karam says.

And because of her patient’s motivated family who raised money for research through loose change from ice cream parlors, Karam is able to take another step on the path toward demonstrating more effective, less toxic strategies against anaplastic thyroid cancer.

Source:

http://www.coloradocancerblogs.org/ice-cream-funds-research-showing-new-strategy-against-thyroid-cancer/

In a follow­-up to a previous study on the safety and efficacy of stereotactic body radiotherapy for patients with small hepatocellular carcinomas, researchers found that incidence of grade 3 or higher adverse events did not increase after longer follow­ up times. 

“In several reports on the results of HCC treatment with [stereotactic body radiotherapy (SBRT)], the median follow­ up duration was close to 30 months and the authors assessed the outcomes at 3 years,” Katsumaro Kubo, MD, from the Hiroshima Prefectural Hospital, Japan, and colleagues wrote. “However, radiation therapy is not considered as an option for the treatment of HCC in the [Barcelona Clinic Liver Cancer (BCLC)] guidelines and the reason may be the uncertainty of the long­ term outcomes. To address this concern, we extended the follow­-up period and analyzed the long­ term outcomes at 5 years.” 

In the previous study, 77 patients with a total of 93 tumors underwent SBRT. Patients had either Child­ Pugh class A or B and had fewer than 3 HCC nodules no larger than 50 mm in diameter per lesion. Kubo and colleagues included 65 of the original patients in the new study. 

Sixty patients underwent transarterial chemoembolization (TACE) before SBRT and 13 patients underwent TACE within 1 month to 3 months after SBRT. 

Median follow­ up at the time of evaluation was 41 months (range, 3 79 months), while median follow­-up for the 26 survivors was 62 months (range, 24­79 months). 

In the original study, the 2­ year overall survival rate was 76% (95% CI, 65.4­86.7), progression­ free survival (PFS) was 40% (95% CI, 27.6­52.3) and local control (LC) was 100%. 

Comparatively, the 3­ year OS rate was 56.3% (95% CI, 44.1­68.5 and the 5­ year OS rate was 41.4% (95% CI, 28.7­54.1). 

Further, the 3 year PFS rate was 25.4% (95% CI, 14­36.8) and the 

5­ year PFS rate was 10.6% (95% CI, 1.5­19.8). 

Both the 3­ year and 5­ year LC rates were 100%. 

Fifteen patients experienced grade 3 or higher liver toxicities at 6 months follow­ up. 

After 1 year of follow­ up, 5 other patients experienced grade 3 or higher liver toxicities. No adverse events worsened in any patients and no patients developed gastrointestinal disorders or ulcers.

Multivariate analysis showed that tumor­node­metastasis stage at treatment was a significant prognostic factor for PFS at 3 years (P = .0008) and that grade 3 or higher adverse events were a prognostic factor for OS at 5 years (P = .0049). 

“Most patients in this study underwent resection and [radiofrequency ablation (RFA)] as initial therapies, which may have confused the results, including the OS and PFS rates,” the researchers wrote. “To compare with surgery or RFA, a prospective study of SBRT in HCC is necessary. If the efficacy and safety of SBRT are proved, it will be added as a treatment option that is comparable to resection or RFA for patients who were considered unfit or refused these other therapies.”  

To learn more talk to our cancer experts at the CyberKnife Center of Miami 305-279-2900

Abstract

Literature on the management of nonmetastatic pancreatic ductal adenocarcinoma in patients who are elderly or have poor performance status is sparse. The median survival of this unique cohort of patients is < 6 months, and most patients are only offered single-agent gemcitabine or supportive care. Recently, adding nanoparticle albumin-bound paclitaxel to gemcitabine was shown to improve survival of patients with metastatic disease with Eastern Cooperative Group performance status of 2. Although standard chemoradiotherapy provides long-term locoregional control in locally advanced pancreatic cancer, it is difficult for this group of patients to tolerate 6 weeks of therapy. Stereotactic body radiotherapy (SBRT) can be delivered in only 3 to 5 days, does not require concurrent chemotherapy, and has limited toxicity, and tumor control rates appear to be equivalent to or better than those achieved with standard chemoradiotherapy. Additionally, SBRT has been shown to improve cancer-related pain and patient-reported quality of life. Given the favorable toxicity profile, SBRT seems like an obvious choice for patients who are elderly, have multiple comorbidities, or have poor performance status. Herein, we review the literature on SBRT in this unique patient population and discuss future directions.

Read the full article here.

Stereotactic Ablative Radiotherapy (SABR) Achieves Better Overall Survival than Surgery for Early Lung Cancer

First randomized clinical trial comparing the two therapies suggests that the non-invasive SABR treatment should be considered an alternative to surgery, especially for elderly patients and those with comorbidities.

Patients with operable stage I non-small cell lung cancer (NSCLC) could achieve better overall survival rates if treated with stereotactic ablative radiotherapy (SABR) rather than the current standard of care – invasive surgery – according to research from a phase III randomized international study from the University of Texas MD Anderson Cancer Center.

The findings, published today in The Lancet Oncology, are from the first randomized clinical trials comparing SABR and surgery.

“For the first time, we can say that the two therapies are at least equally effective, and that SABR appears to be better tolerated and might lead to better survival outcomes for these patients,” said the first author and principal investigator Joe Y. Chang, M.D., Ph.D., professor, radiation oncology. “Stereotactic radiation treatment is a relatively new approach for operable early stage lung cancer, while surgery has been the standard for a century. This study can give physicians confidence to consider a non-invasive option.”

The researchers analyzed overall survival, recurrences, and toxicity in 58 patients. Estimated three-year survival rates were 79 percent in the surgery group and 95 percent in the SABR group, while recurrence-free survival rates at three years were 80 percent and 86 percent, respectively. Six patients in the surgery group died versus one death within the SABR group. None of the patients treated with SABR had high-grade toxicity.

The authors suggest that the lower survival rate following surgery could be attributed to other simultaneous conditions that were worsened by the surgical reduction of lung function. As such, the findings support SABR as a non-invasive alternative, especially for elderly patients and for those with significant comorbidities.

According to the Centers for Disease Control and Prevention, lung cancer is the leading cancer killer in both men and women in the United States.

The American Cancer Society reports that over half of people with lung cancer die within one year of being diagnosed, and, according to the National Cancer Institute, an estimated 158,040 Americans are expected to die from the disease in 2015.

“The findings of our study provide strong support for a large clinical trial to investigate the potential superiority of SABR for patients with early-stage disease,” said senior author Jack A. Roth, M.D., Professor and Bud Johnson Clinical Distinguished Chair, Department of Thoracic & Cardiovascular Surgery. “While we wait for more data, physicians can consider SABR an effective treatment for these patients, especially for those whom surgery brings high risk.”

Over the last decade, SABR has been used to treat patients with inoperable NSCLC, showing outcomes that are better in some cases than traditional radiation.

However, there has been no data on SABR for patients with operable early-stage NSCLC because of concerns about the risk of recurrence after SABR. Surgery on the other hand, lobectomy (removal of half of a lung) with dissection of the lymph nodes, was thought to have less chance for cancer to recur.

However, lung cancer surgery is a major operation with a high complication rate and while recurrence rates are low, there is a 10-20 percent chance of the cancer coming back in the other lobes, regional lymph nodes and distant organs, noted Chang. In this study there was no difference between SABR and surgery for tumor recurrence.

He added that these findings should be interpreted with some caution, due to the small patient sample size and limited follow up time.

Two new randomized studies are in preparation and expected to be opened in 2015: VALOR (Veterans Affairs Lung cancer surgery Or stereotactic Radiotherapy trial) in the US, and, in the UK, SABRtooth, a multicenter pilot study of SABR versus surgery in patients with peripheral stage I NSCLC considered at higher risk of complications from surgical resection.

Other researchers contributing to this study include: Jack A. Roth, M.D.; Ritsuko Komaki, M.D.; Reza J. Mehran, M.D.; Peter Balter, Ph.D.; Stephen E. McRae, M.D.; Lei Feng, M.S.; Mark F. Munsell, M.S., Donald A. Berry, Ph.D. from MD Anderson; John J. Kresl, M.D. from the Phoenix CyberKnife and Radiation Oncology Center; Omar Dawood, M.D. from Kona Medical, Inc.; Larry S. Carpenter, M.D. from St. Luke’s Health Houston; Suresh Senan, F.R.C.R.; Alexander V. Louie, M.D.; Cornelis JA Haasbeek, M.D.; Ben J. Slotman, M.D.; Marinus A. Paul, M.D.; Egbert F. Smit, M.D. from VU University Medical Center in Amsterdam, The Netherlands; Harry JM Groen, M.D.; Joachim Widder, M.D. from University of Groningen and University Medical Center Groningen in Groningen, The Netherlands; Ben EEM van den Borne, M.D.; Katrien De Jaeger, M.D.; Coen Hurkmans, Ph.D. from Catharina Hospital in Eindhoven, The Netherlands; Erik van Werkhoven, M.S.c. from the Netherlands Cancer Institute in Amsterdam, The Netherlands and Anne-Marie Dingemans, M.D. from Maastricht University Medical Center, The Netherlands.

See more at: http://www.interventionaloncology360.com/content/stereotactic-ablative-radiotherapy-achieves-better-overall-survival-surgery-early-lung#sthash.9wltTc3G.dpuf

Patient History
G. M. is a 68-year-old with a history of adenocarcinoma of the left lower lobe of the lung, and a similar tumor in the right lower lobe of the lung, both treated surgically in 1999 and 2006, respectively. He also received postoperative chemotherapy. Later he presented with a PET positive 2.5 cm nodule in the right lower lobe. G.M. refused further surgery and contacted CyberKnife Miami for treatment alternatives.

CyberKnife Advantage
Scientific data suggests that stereotactic radiosurgery with devices such as the CyberKnife can deliver ablative doses of irradiation, potentially resulting in treatment outcomes similar to surgery. This approach is indicated for the medically inoperable or patient who refuses surgery for early stage carcinoma of the lung.

Treatment
The patient was treated on the CyberKnife. Stereotactic irradiation was delivered to the periphery of the tumor using three fractions.

Follow-up
At two weeks post treatment, the patient experienced moderate esophagitis, lasting two weeks. At three months post treatment, the PET scan showed no hypermetabolic activity within the treated field or elsewhere. Clinically, the patient is well with no complaints.

Patient History
This is a 68-year-old white female who presented with recurrent squamous cell carcinoma of the oral cavity with node recurrence, status post-modified neck dissection. She presented with a large recurrent mass in the parapharyngeal region treated with hyperfractionated radiotherapy and multiple surgical procedures. She had a large skull base parapharyngeal mass for plan boost radiosurgery.

CyberKnife Advantage
Because of both the prior history of multiple surgeries and the close proximity of this tumor to the skull base, major blood vessels and brain stem, surgical resection was not an option.

Treatment
The patient was treated on the frameless CyberKnife at Miami CyberKnife with 3 fraction of 7 Gy each with a total dose of 21 Gy plus the external radiation therapy.

Follow-Up
Four months post treatment patient was doing well and gaining weight.

Robotic Device Restores Man’s Voice

Stephen Wiley, a lifelong cowboy from Terrell, TX, has helped UT Southwestern Medical Center pioneer a new treatment for vocal cord cancer.

Mr. Wiley volunteered to be the world’s first known patient to be treated for vocal cord cancer with CyberKnife, a surgeon-controlled robotic device that destroys tumors with highly precise doses of radiation.

Mr. Wiley, a yard driver for a manufacturing company who also raises horses on his own time, said he started waking up in the morning with a hoarse voice and thought it was nothing more than aging. It got continually worse, until one day he was reduced to a whisper.

“We have to talk on the radio constantly and whenever my voice went away, it was a safety issue,” said Mr. Wiley, 59.

Doctors found tumors in both his vocal cords, and referred him to UT Southwestern, where he met with Dr. Larry Myers, Associate Professor of Otolaryngology.

“Dr. Myers said, ‘Well, we’ve been looking for someone like yourself for a research project that’s never been done before.’ I said, ‘Heck, if it works and it’s going to help other people, I’m willing to go for it,’” Mr. Wiley recalled. “It has worked out great. People here at work say, ‘Your voice is back to normal.’”

Six doctors had to unanimously agree that Mr. Wiley was a good candidate for the procedure, which he said gave him confidence that the CyberKnife trial was right for him.

The $7 million CyberKnife, built by the California-based company Accuray, has a small linear particle accelerator and a robotic arm that allows it to treat tumors on any part of the body with radiation, explained his surgeon, Dr. Baran Sumer, Associate Professor of Otolaryngology – Head and Neck Surgery. There are no records from the maker or in medical literature of the robotic device previously being used to treat vocal cord cancer.

UT Southwestern doctors’ success with treating Mr. Wiley yielded important information that UT Southwestern physicians are already using to make treatment shorter for other people with vocal cord tumors, said Dr. Sumer, also a member of the Harold C. Simmons Comprehensive Cancer Center, the only National Cancer Institute-designated cancer center in North Texas.

Only about 200 of these cutting-edge machines exist in the world, most of them in the United States.

Dr. Susie Chen, Assistant Professor of Radiation Oncology, oversaw Mr. Wiley’s treatments and said the unique resources, expertise, and collaborative atmosphere at UT Southwestern aligned perfectly to break new ground in cancer treatment and find the right solution for Mr. Wiley.

“We’re in a very unique situation at UT Southwestern where we have the tools to do it. It takes a lot of collaboration between the surgeons and the radiation doctors to actually get that done. The technology just hasn’t been there until recently,” she said.

Patients must be as still as possible for the CyberKnife treatment to be precise, but vocal cords move when people breathe and swallow, presenting a challenge in using the precision robot.

Dr. Sumer injected tiny bits of gold into Mr. Wiley’s neck for the CyberKnife to track so the robotic arm could adjust to even the slightest movements.

Mr. Wiley’s head also was covered with a mesh mask that held him snug and still.

“With the CyberKnife, it’s real time. When something moves, it’s actually moving. We adjust to the movement,” Dr. Chen said. “The whole time you’re getting treated, there are little X-rays that are being done that allow the machine to lock on to these little gold markers that are placed near the vocal cords. It’s just like you’re a fighter pilot, and you lock on to a target.”

Mr. Wiley completed his 15 treatments at St. Paul University Hospital.

“With the CyberKnife, I never lost my voice and never lost any weight. It’s great, and I feel great,” he said.

Three other UT Southwestern patients have since had CyberKnife treatment on vocal cord tumors, and Dr. Chen said they have been able to reduce the number of treatments each time as more is learned about the CyberKnife’s effectiveness on vocal cord tumors.

“What we’ve done is taken a treatment that takes 5 1/2 weeks, and we’re decreasing it,” Dr. Chen said. “The true goal of this study is to maintain excellent cure rates while decreasing the time of radiation and side effects. That’s the biggest thing – ease for the patient.”

Updated: ASTRO Model Policy Endorses Stereotactic Body Radiation Therapy (SBRT) for Prostate Cancer

SUNNYVALE, Calif., /PRNewswire/ — Accuray Incorporated (Nasdaq: ARAY), announced today the publication of study results involving hundreds of prostate cancer patients treated with the CyberKnife® Robotic Radiosurgery System, the most widely used form of prostate stereotactic body radiation therapy (SBRT).

The study followed 304 patients for a median of 5 years, and many to 6 years post-treatment and found that 97 percent of patients with low-risk and 90.7% of patients with intermediate-risk prostate cancer remained cancer-free throughout that time.

The CyberKnife treatment was also shown to be minimally harmful, producing low levels of toxicity that are similar to the level produced by other radiation treatment options including brachytherapy.

Preservation of sexual function was achieved for 75 percent of patients who were sexually potent prior to CyberKnife treatment. The positive quality of life outcomes, low side effects, and brief duration of CyberKnife treatment are especially encouraging for men weighing their many treatment options.

“Stereotactic Body Radiotherapy for Localized Prostate Cancer: Disease Control and Quality of life at 6 Years,” appears in the May 2013 edition of Radiation Oncology and was led by Dr. Alan Katz, a radiation oncologist with more than 30 years of experience who currently practices at Flushing Radiation Oncology in Queens, N.Y.

In related SBRT news, the American Society for Radiation Oncology (ASTRO) recently updated its position on the use of SBRT for prostate cancer.

According to its recently posted Model Policy, the Society believes that enough clinical evidence now exists to so that “SBRT could be considered an appropriate alternative for select patients with low to intermediate risk disease.”

“These latest long-term CyberKnife data coupled with ASTRO’s new position on SBRT for prostate cancer confirm what I have seen in my clinical practice,” said Dr. Alan Katz. “CyberKnife SBRT is a safe and effective treatment for prostate cancer that offers men the opportunity to complete a non-invasive treatment in five days and should be considered for patients with organ-confined prostate cancer.”

“Dr. Katz’s five-year CyberKnife prostate SBRT data show good disease-free survival, low toxicity, and preservation of sexual function. The data support prior findings that validate an approach to prostate SBRT that includes dynamic tracking and automatic correction for target motion,” said Fabienne Hirigoyenberry-Lanson, vice president of medical affairs at Accuray.

The first five-year outcomes on CyberKnife SBRT for prostate cancer patients were published in January 2011. For more information, please visit www.accuray.com.

Research finds that more than half of a group of men whose cancer was classified as slow growing turned out to be more dangerous then thought.

Men with prostate cancer are being given false hope by tests that underestimate the aggressiveness of their disease, according to a study.

Researchers found that more than half of a group of men whose cancers were initially classified as slow growing and confined later turned out to have more dangerous tumors.

The findings, published in the British Journal of Cancer, call into question the ability of experts to grade and stage prostate cancers on the basis of biopsy samples.

It also casts doubt on the “active surveillance” strategy of avoiding unnecessary radical treatment for patients with slow-growing prostate cancer.

Instead, these patients are closely monitored but left alone until tests suggest their condition has worsened.

Urological surgeon Greg Shaw, from the Cancer Research UK Cambridge Institute, said, “Our results show that the severity of up to half of men’s prostate cancers may be underestimated when relying on tests before they have surgery.”

Slow-growing prostate cancers, known as “pussycats”, are very different from the more aggressive “tiger” variety.

In some cases, especially when he is older when diagnosed, a patient can live to the end of his normal life span before a “pussycat” cancer becomes a threat.

An aggressive “tiger,” on the other hand, may quickly spread if it is not surgically removed or destroyed.

Biopsy samples examined under a microscope are used to rate prostate tumor aggressiveness with a score ranging from two to 10. A score of between two and six is a low-grade “pussycat.” A score of seven is intermediate, while scores of eight to 10 are high-grade “tigers.”

Tumors are also staged according to how far they have spread. A T2 tumor is contained completely inside the prostate gland, while a T3 tumor has started to break out, and one classified T4 has spread to other organs or sites in the pelvic cavity.

The Cambridge scientists compared the staging and grading of more than 800 men’s cancers before and after they had surgery to remove their prostate.

They found that of 415 patients whose cancer was classified as slow-growing and confined to the prostate, just over half (209) were found to have a more aggressive disease than originally thought when assessed after surgery.

Almost a third (131) had cancers that had spread beyond the prostate gland.

The prostate specific antigen (PSA) blood marker test used to identify men who might have prostate cancer has long been known to be unreliable and prone to giving false readings.

Professor Malcolm Mason, Cancer Research UK’s prostate cancer specialist, said, “At the moment the biopsy, MRI, and PSA tests that we use to assess the severity of prostate cancers are the best methods we have but, as this study shows, they don’t always get it right. Despite the limitations that this study shows, all evidence so far points to active surveillance being safe, provided that men are carefully selected. But we need better methods of assigning a grade and stage so that no man has to unnecessarily undergo treatment, while at the same time making sure we detect and treat the cancers that really need it.”

Each year around 41,700 men in the UK are diagnosed with prostate cancer and 10,800 die from the disease.

The scientists concluded in their paper, “In counseling patients for AS (active surveillance), the surgeon should be explicit regarding uncertainty in predicting stage/grade despite apparent short-term safety. There is an urgent need for development of a means by which to exclude aggressive PC (prostate cancer) in patients wishing to undergo conservative treatment.”

Dr. Iain Frame, director of research at the charity Prostate Cancer UK, said, “Accurate prostate cancer diagnosis continues to be one of the biggest challenges facing the disease today. The results of this study highlight yet again that existing tests cannot provide a precise picture of the aggressiveness of a man’s cancer, often leaving men and their doctors to make difficult decisions about treatment without all the facts.

Prostate Cancer UK is committed to finding a better diagnostic option for the 40,000 men diagnosed with the disease every year through research. In the meantime, until the accuracy of tests improves, it is important that men have the opportunity to discuss the pros and cons of every treatment option available with their clinician, so that they can decide what is best for them and their situation.”

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Widespread Adoption of CyberKnife Body Radiation Therapy (SBRT) has Improved Survival Rates for Elderly Patients With Early Stage Lung Cancer

SEER database study finds dramatic rise in overall and lung cancer-specific survival following SBRT for patients age 60 and older with stage I NSCLC

 BOSTON, September 26, 2016 — Survival rates for elderly patients who received stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) rose from roughly 40 to 60 percent over the past decade, concurrent with the increasing adoption of SBRT, according to research presented today at the 58th Annual Meeting of the American Society for Radiation Oncology (ASTRO).

In recent years, SBRT has become the standard of care for patients with inoperable early stage NSCLC. Compared to the conventional radiation therapy (RT) approach of small doses given daily over several weeks, SBRT delivers a highly targeted, escalated dose of radiation in a single session or as many as five of treatments, usually between one and five fractions.

For this study, researchers examined records from the nation’s largest cancer patient database to determine how rates of overall and disease-specific survival have changed as use of SBRT has increased, as well as to draw population-based comparisons between SBRT and surgery alone for elderly patients.

Records for the 62,213 patients age 60 and above who were diagnosed with stage I NSCLC between 2004 and 2012 were extracted from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database. Patients with squamous, adenocarcinoma and adenosquamous histologies and those with definite records defining local therapy were eligible for inclusion.

Overall survival (OS) and lung cancer-specific survival (CSS) rates were calculated for patients grouped into five-year subsets (i.e., 60-64, 65-69, 70-74, 75-79, 80-84, 85-89, and 90 and older). Researchers analyzed OS and CSS change over time based on type of therapy and age using Kaplan-Meier, logarithmic ranking and Cox multivariate hazard ratio (HR) methods as well as comparative analysis with Fisher test.

Over the study period, survival rates for SBRT rose dramatically among this large, nationally- representative population of elderly stage I NSCLC patients. From 2004 to 2012 — the years in which adoption of SBRT in community practice became widespread — the overall survival rate at 23 months following SBRT alone rose nearly 20 percentage points, from 39 to 58 percent (p < 0.001). OS rates for surgery alone rose five percentage points, from 79 to 84 percent (p < 0.001). There was no improvement for patients who received neither RT nor surgery (from 28 to 33 percent, p = 0.29).

In the same time period, CSS increased from 48 to 72 percent of patients who received SBRT alone (p < 0.001) and from 87 to 91 percent of patients receiving surgery alone (p < 0.001). CSS rates remained stable for patients who received neither surgery nor radiation, although the difference approached statistical significance (38 to 45 percent, p = 0.06).

“Our findings indicate that physicians should feel confident recommending radiation therapy to patients who are too sick to undergo surgery or who choose not to undergo surgery for other reasons,” said Andrew M. Farach, MD, a radiation oncologist at Houston Methodist Hospital and lead author on the study. “With continued adoption of SBRT in community cancer centers, it is our hope that more patients will receive curative SBRT and the number of patients left untreated based on age or medical comorbidity will continue to fall.”

The use of surgery to treat stage I NSCLC declined with age (p < 0.001). While 81 percent of patients age 60-64 underwent surgery, only 47 percent of patients age 80 or older were able to undergo surgery. The use of RT, conversely, rose with increasing age, ranging from 11 percent of patients age 60-64 to 39 percent of patients age 90 or above (p < 0.001). The number of patient receiving no treatment also increased from 7 to 40 percent for the youngest and oldest elderly patient cohorts in the study.

Despite improvements in OS and CSS, survival rates following RT remained lower than those for elderly patients who received surgery. Researchers explained that this difference may be due, in part, to a selection bias where healthier patients were treated with surgery, and they underscored the need for a controlled clinical trial with matched patients receiving each treatment first-line to compare the efficacy of these therapies. Instances of palliative SBRT or conventional RT also may have skewed results in favor of surgical outcomes.

“While survival rates remain highest for surgical candidates, this study demonstrates both clear benefits from SBRT for nonsurgical NSCLC patients and that outcomes following radiation therapy have improved at a more accelerated pace over the past decade than those for any other therapeutic approach,” said Dr. Farach. “With increased access to this potentially life-saving treatment, we can continue to improve outcomes for the growing population of elderly patients fighting early stage cancer.”

Purpose/Objective(s): Stereotactic body radiation therapy (SBRT) is now considered the standard of care for patients with inoperable stage I non-small cell lung cancer (NSCLC). For elderly patients, competing comorbidities limit operability. With widespread adoption of SBRT in community practice, an increasing number of elderly patients are receiving definitive SBRT. The purpose of this study is to review population-based outcomes based on treatment modality using the Surveillance, Epidemiology, and End Result (SEER) database for stage I NSCLC patients treated between 2004-2012 in the SBRT era.

Materials/Methods: The national SEER database was used to draw NSCLC patients age 60 and above between 2004 and 2012 with squamous, adenocarcinoma, and adenosquamous histologies. Only patients with definite records defining local therapy were included. Survival analysis included Kaplan-Meier, log-rank, cox-multivariate hazard ratio (HR), and comparative analysis with Fisher test. Patients were grouped in 5-year bins: 60-64, 65-69, 70-74, 75-79, 80-84, 85-89, and 90 and older for survival based on local therapy. Temporal trends in survival based on local therapy and age were also analyzed.

Results: For the 62,213 patients meeting criteria for analysis, the distribution by histology was comparable across all age groups. The use of surgery declined with age as patients aged 60 to 64 had surgical rates of 81% compared to 21% for ages 90 and over (p < 0.001). Radiation use increased from 11 to 39% (p < 0.001), as did the percentage of patients receiving neither surgery or radiation treatment from 7 to 40% (p < 0.001) for the same age groups. Multivariate analysis demonstrated HR of treatment types compared to surgery at baseline as radiation only = 3.1, surgery and radiation = 2.3, and neither surgery or radiation = 5.9 (all p < 0.01). From 2004 to 2011, overall survival (OS) at 23 months improved dramatically for patients treated with radiation only (39 to 58%, p < 0.001) and more subtly for those receiving surgery only (79 to 84%, p < 0.001), while it was stable for those having neither surgery nor radiation (28 to 33%, p = 0.29). Similarly, lung cancer specific survival (CSS) at 23 months improved significantly for patients treated with radiation only (48 to 72%, p < 0.001), and less so for those receiving surgery only (87 to 91%, p < 0.001), while it was stable for those having neither surgery nor radiation (38 to 45%, p = 0.06).

Conclusion: With advancing age, radiation replaces surgery as the most appropriate modality for early stage NSCLC. Concurrent with the adoption of SBRT as a community standard, both OS and CSS have improved significantly for elderly stage I NSCLC patients treated with radiation alone.

Here is a link to the original study:

Study Concludes CyberKnife Therapy is Safe & Effective for Most Patients With Previously Irradiated Head & Neck Cancer

Biology – Radiation Effects on Normal Tissue
Risk of severe toxicity based on site of recurrence in patients treated with stereotactic body radiation therapy for recurrent head and neck cancer

DC Ling, J Vargo, RL Ferris, J Ohr, DA Clump II, WYW Yau, U Duvvuri, S Kim, JT Johnson, JE Bauman, BF Branstetter, DE Heron

Summary: Researchers assessed the risk of severe toxicity based on site of recurrence in patients treated with stereotactic body radiation therapy (SBRT) for recurrent head and neck cancer because recently, SBRT ± cetuximab has emerged as a viable re-irradiation strategy for patients with locally-recurrent, previously-irradiated head and neck cancers, with potentially lower rates of acute and late toxicity compared to conventional treatment options.

They concluded that salvage SBRT is a safe and effective option for most patients with previously-irradiated head and neck cancer. They did find, however, that patients treated to the larynx or hypopharynx experienced significantly more late toxicity compared and should be carefully selected.

Methods:
    •    Researchers conducted this retrospective review in 291 patients treated with SBRT± cetuximab or recurrent, previously-irradiated head and neck cancer between April 2002 and March 2013.
    •    They included patients treated in both of their previously-reported institutional phase I dose-escalation study UPCI 04-144 and phase II study of SBRT + concurrent cetuximab UPCI 06-093.
    •    The primary endpoints were incidence of severe acute and late toxicity, defined as ≥ Grade 3 above baseline according to Common Terminology Criteria for Adverse Events v4.
    •    They performed both univariate and multivariate logistic regression analysis to identify predictors of severe acute and late toxicity.
    •    Patients with < 3 months of follow-up (n=43) or who died within 3 months of treatment (n=21) were excluded from late toxicity analysis.

Results:
    •    Among surviving patients, median time to death or last clinical follow-up was 9.8 (interquartile range: 5.3-21.7) months among the entire cohort and 53.1 (interquartile range: 35.4-72.5) months.
    •    The 1-year, 3-year, 5-year, and 10-year actuarial overall survival rates were 41.4%, 16.6%, 10.8%, and 3.6%, respectively.
    •    Overall, 33 (11.3%) patients experienced ≥ Grade 3 acute toxicity, and 43 (18.9%) experienced ≥ Grade 3 late toxicity.
    •    Fifty percent of patients with a larynx/hypopharynx recurrence experienced severe late toxicity, compared to 6-20% for other sites.
    •    Upon univariate analysis, researchers observed that, compared to larynx/hypopharynx, treatment of nodal recurrence was associated with a lower risk of severe acute toxicity (P=0.03), with no significant differences in severe acute toxicity among other sites.
    •    On both univariate and multivariate analysis, patients treated for a recurrence in the larynx/hypopharynx experienced significantly more severe late toxicity than all other recurrence sites (P < 0.05 for each) except for nasopharynx.

Here’s a link to the original study:

Here is a link to the original article and study:

Hypofractionated Radiation Therapy Can Reduce Treatment Time by One-third With Comparable Quality of Life for Prostate Cancer Patients

NRG Oncology/RTOG 0415 trial shows similar side effects following conventional and accelerated Radiation Therapy for early stage, low-risk disease

BOSTON, September 26, 2016 — For men with early stage, low-risk prostate cancer, treatment with hypofractionated radiation therapy (RT) offers comparable health-related quality of life outcomes in one- third less treatment time than conventional RT, according to research presented today at the 58th Annual Meeting of the American Society for Radiation Oncology (ASTRO).

While efficacy results from NRG Oncology/RTOG 0415 were reported previously, this study is the first to report patient-reported outcomes from the trial, which included patients from across the U.S. and Canada.

This trial assessed the differences in health-related quality of life (HRQoL), including bowel, urinary, sexual and hormonal side effects, following a conventional or fractionated RT schedule. Compared to conventional (C) RT, hypofractionated (H) RT is delivered in larger doses over a shorter period of time.

“Studies have suggested that higher amounts of radiation over shorter periods of time might be more effective in destroying cancer cells, but the concern has been that stronger doses might also cause quality of life issues such as more diarrhea or decrease in sexual function,” said lead study author Deborah Watkins Bruner, PhD, a professor at the Nell Hodgson Woodruff School of Nursing and a professor of radiation oncology at Emory University School of Medicine in Atlanta.

Patients in the study were randomly assigned to receive either conventional RT, consisting of 73.8 Gy in 41 daily treatments delivered over 8.2 weeks, or hypofractionated RT, consisting of 70 Gy in 28 daily treatments delivered over 5.6 weeks. A total of 962 patients reported HRQoL data, including 478 men from the C group and 448 men from the H group. The median patient age was 67 years, and baseline characteristics were similar between the treatment groups.

HRQoL was assessed with the Expanded Prostate Index Composite (EPIC),a comprehensive instrument designed to evaluate patient-reported side effects after prostate cancer treatment.

The questionnaire measured side effects in each of EPIC’s four domains – bowel, urinary, sexual and hormonal.

EPIC assesses prostate cancer-specific HRQoL on a Likert scale with responses transformed to 0-100, where higher scores indicate a better HRQoL. Participant feedback was collected at baseline, six months after treatment began and one year post-treatment, with change scores compared between the C and H groups. A Wilcoxon test was used to assess differences.

At baseline, there were no statistically significant differences between treatment groups in any of the HRQoL domains. Results indicated that, compared to men without prostate cancer, most patients in both groups reported poor baseline EPIC sexual domain scores, with the C group’s score averaging 47.5 and the H group’s score averaging 44.2. At baseline, the groups reported only slightly lower than average bowel and urinary scores.

Following treatment, patients who received higher doses of RT in fewer sessions (the H group) reported similar HRQoL as the patients who received conventional RT (the C group).

There were no differences in change scores for either group on any EPIC domain at six months follow-up. At 12 months follow-up, hypofractionation patients reported a larger decline in the bowel domain compared to those who received conventional RT, with an average from baseline of -3.6 vs. -1.8, respectively, (p = 0.0037), but the change was not deemed clinically significant to patients.

“This research shows that hypofractionated radiation therapy offers patients value-based care for their disease. If patients with low-risk prostate cancer choose radiation therapy, they can live equally long and have the same quality of life outcomes with 28 daily treatments, compared to what has been the standard care of 41 daily treatments,” said Dr. Bruner. “This reduction of treatment time by almost a third translates into other types of value for patients, such as decreased drive time, lower transportation costs and fewer days off of work.”

Purpose/Objective(s): To assess differences in health related quality of life (HRQoL) between hypofractionated (H) and conventional (C) schedule radiation therapy (RT) in men with low-risk prostate cancer.

Materials/Methods: Eligibility included: stage T1-2a, Gleason ≤6, PSA <10, randomized to a C schedule (3D/IMRT 73.8 Gy in 41 fractions [fx] over 8.2 wks) or a H schedule (3D/IMRT 70 Gy in 28 fxs over 5.6 wks). HRQoL was assessed with the Expanded Prostate Index Composite (EPIC) at baseline, 6 and 12 mos. EPIC assesses prostate cancer-specific HRQoL on a Likert scale with responses transformed to 0-100 (higher scores indicating better HRQoL; 0.5 SD change indicating clinical significance). EPIC has 4 domains: bowel, urinary, sexual, and hormonal.

Each domain requires at least 80% of items to be completed. Change scores, calculated as follow-up – baseline, at 6 and 12 mos were compared between arms. Wilcoxon test was used to assess differences. A significance level of 0.0125 to adjust for multiple comparisons with respect to the 4 domain scores was used for an overall two-sided type I error of 0.05.

Results: Of 1092 pts analyzable for the primary endpoint, 962 consented to HRQoL (478 on 73.8 Gy arm; 448 on 70 Gy arm). Baseline characteristics were similar between treatment arms. Median age = 67 yrs; HRQoL compliance was 89.4% at baseline, 72.7% at 6 mos, and 65.9% at 1 yr. Compared to men without cancer1, most pts reported poor baseline EPIC sexual domain scores in both H and C arms, median 44.2 and 47.5, and only slightly lower than average bowel and urinary scores.

No statistically significant differences with regard to any of the HRQoL baseline domains were measured between treatment arms. There were no differences in change score between arms of any domain scores at 6 mos. At 12 mos, those on the 70 Gy arm experienced a larger decline as compared to those on the 73.8 Gy arm in the bowel domain (median 12 mo. scores 91.1 vs 94.6; median change scores from baseline -3.6 vs. -1.8, respectively, p=0.0037), but not clinically significant.

Conclusion: Compared to a study of EPIC norms1 in men without cancer, baseline scores for bowel and urinary domains were about 5-6 points lower and sexual function was 15 points lower than norms. Men receiving either H or C fractionation schedules demonstrated 12 mo. bowel, urinary, and better sexual HRQoL comparable to the recent large European H study.2 EPIC scores exhibited only a small magnitude of decline at 1 yr follow-up from baseline. As compared with C fx, pts treated with H demonstrated a small statistically, but not clinically significant, larger decline in bowel HRQoL at 1 yr, thus late toxicity is comparable between arms, supporting value based care with H.

Acknowledgements: This project was supported by grants U10CA21661 (RTOG-Ops-Stat), U10CA37422 (RTOG- CCOP), U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC) from the National Cancer Institute (NCI).

Here is a link to the original study:

CyberKnife for Liver Cancer Shows Long-term Safety! 

In a follow­-up to a previous study on the safety and efficacy of stereotactic body radiotherapy for patients with small hepatocellular carcinomas, researchers found that incidence of grade 3 or higher adverse events did not increase after longer follow­ up times. 

“In several reports on the results of HCC treatment with [stereotactic body radiotherapy (SBRT)], the median follow­ up duration was close to 30 months and the authors assessed the outcomes at 3 years,” Katsumaro Kubo, MD, from the Hiroshima Prefectural Hospital, Japan, and colleagues wrote. “However, radiation therapy is not considered as an option for the treatment of HCC in the [Barcelona Clinic Liver Cancer (BCLC)] guidelines and the reason may be the uncertainty of the long­ term outcomes. To address this concern, we extended the follow­-up period and analyzed the long­ term outcomes at 5 years.” 

In the previous study, 77 patients with a total of 93 tumors underwent SBRT. Patients had either Child­ Pugh class A or B and had fewer than 3 HCC nodules no larger than 50 mm in diameter per lesion. Kubo and colleagues included 65 of the original patients in the new study. 

Sixty patients underwent transarterial chemoembolization (TACE) before SBRT and 13 patients underwent TACE within 1 month to 3 months after SBRT. 

Median follow­ up at the time of evaluation was 41 months (range, 3 79 months), while median follow­-up for the 26 survivors was 62 months (range, 24­79 months). 

In the original study, the 2­ year overall survival rate was 76% (95% CI, 65.4­86.7), progression­ free survival (PFS) was 40% (95% CI, 27.6­52.3) and local control (LC) was 100%. 

Comparatively, the 3­ year OS rate was 56.3% (95% CI, 44.1­68.5 and the 5­ year OS rate was 41.4% (95% CI, 28.7­54.1). 

Further, the 3 year PFS rate was 25.4% (95% CI, 14­36.8) and the 

5­ year PFS rate was 10.6% (95% CI, 1.5­19.8). 

Both the 3­ year and 5­ year LC rates were 100%. 

Fifteen patients experienced grade 3 or higher liver toxicities at 6 months follow­ up. 

After 1 year of follow­ up, 5 other patients experienced grade 3 or higher liver toxicities. No adverse events worsened in any patients and no patients developed gastrointestinal disorders or ulcers.

Multivariate analysis showed that tumor­node­metastasis stage at treatment was a significant prognostic factor for PFS at 3 years (P = .0008) and that grade 3 or higher adverse events were a prognostic factor for OS at 5 years (P = .0049). 

“Most patients in this study underwent resection and [radiofrequency ablation (RFA)] as initial therapies, which may have confused the results, including the OS and PFS rates,” the researchers wrote. “To compare with surgery or RFA, a prospective study of SBRT in HCC is necessary. If the efficacy and safety of SBRT are proved, it will be added as a treatment option that is comparable to resection or RFA for patients who were considered unfit or refused these other therapies.”  

To learn more talk to our cancer experts at the CyberKnife Center of Miami 305-279-2900

#CancerTreatmentCenterMiami

The latest research evaluates the use of CyberKnife Radiation Therapy for recurrent Trigeminal Neuralgia. 

This Non-Invasive Radiosurgery technique often eliminates the pain with just one treatment but is also highly effective if it returns. 

Click the link below to see the full study & talk to our Trigeminal Neuralgia experts at the CyberKnife Center of Miami who were part of this vital research involving multi medical centers 305-279-2900.

Latest Study on CyberKnife for Treating Recurrent Trigeminal Neuralgia:

Definitive radiotherapy for prostate cancer (PCa), even high-risk cases, is effective long-term, Australian researchers concluded.

After a median follow-up of 92 months (maximum 163.8 months), the 8-year overall survival rates and biochemical relapse-free survival rates among 1121 patients who underwent PCa radiotherapy were 78.4% and 68.1%, respectively, a team led by Jeremiah F. de Leon, MBBS, of the Illawarra Cancer Care Centre in Wollongong, New South Wales, reported online ahead of print in the Journal of Medical Imaging and Radiation Oncology. 

The median survival time for the entire cohort was 157.1 months. The median time to biochemical failure was 76 months.

The 8-year OS rates were 84.5%, 78.4%, and 68% among patients with low-, intermediate-, and high-risk disease, respectively. The biochemical relapse-free survival rates were 80.3%, 65.7%, and 53.7%, respectively.

“To our knowledge, this is the largest prospective cohort of Australian prostate cancer patients treated with radiotherapy,” the authors wrote, noting that their overall findings are consistent with those reported in the international literature.

Patients had a median age of 69.6 years (range 45 to 87 years). All patients were treated to a dose of 70 to 74 Gy. Patients were classified as having low-, intermediate-, and high-risk disease based on PSA level, clinical staging, and Gleason score. Intermediate-risk patients were treated with up to 6 months of androgen-deprivation therapy (ADT); high-risk patients were offered neoadjuvant and adjuvant ADT.

Overall, 61.6% of patients received either adjuvant or neoadjuvant ADT and the proportion varied by risk category, with 8.3%, 50.3%, and 96.2% of patients with low-, intermediate-, and high-risk disease receiving any hormonal therapy.

Reference

De Leon JF, Kneebone A, Gebski V, et al. Long-term outcomes in 1121 Australian prostate cancer patients treated with definitive radiotherapy. J Med Imaging Radiat Oncol. 2018; published online ahead of print.

To determine if you are a candidate for CyberKnife Radiation Therapy talk to our Prostate Cancer Experts 305-279-2900 and visit our prostate cancer website www.prostatecancertreatmentmiami.com 

#ProstateCancerTreatmentMiami

#CancerTreatmentCenterMiami

CyberKnife: An emerging treatment option for patients with liver metastasis unsuitable for surgery. This study reports on a large, multi-institutional series of patients with liver metastasis treated with CyberKnife resulting in reasonable overall survival and local control were observed. 

Abstract

BACKGROUND:

Stereotactic body radiotherapy (SBRT) is an emerging treatment option for liver metastases in patients unsuitable for surgery. We investigated factors associated with clinical outcomes for liver metastases treated with SBRT from a multi-center, international patient registry.

METHODS:

Patients with liver metastases treated with SBRT were identified in the RSSearch® Patient Registry. Patient, tumor and treatment characteristics associated with treatment outcomes were assessed. Dose fractionations were normalized to BED10. Overall survival (OS) and local control (LC) were evaluated using Kaplan Meier analysis and log-rank test.

RESULTS:

The study included 427 patients with 568 liver metastases from 25 academic and community-based centers. Median age was 67 years (31-91 years). Colorectal adenocarcinoma (CRC) was the most common primary cancer. 73% of patients received prior chemotherapy. Median tumor volume was 40 cm3 (1.6-877 cm3), median SBRT dose was 45 Gy (12-60 Gy) delivered in a median of 3 fractions [1-5]. At a median follow-up of 14 months (1-91 months) the median overall survival (OS) was 22 months. Median OS was greater for patients with CRC (27 mo), breast (21 mo) and gynecological (25 mo) metastases compared to lung (10 mo), other gastro-intestinal (GI) (18 mo) and pancreatic (6 mo) primaries (p < 0.0001). Smaller tumor volumes (< 40 cm3) correlated with improved OS (25 months vs 15 months p = 0.0014). BED10 ≥ 100 Gy was also associated with improved OS (27 months vs 15 months p < 0.0001). Local control (LC) was evaluable in 430 liver metastases from 324 patients. Two-year LC rates was better for BED10 ≥ 100 Gy (77.2% vs 59.6%) and the median LC was better for tumors < 40 cm3 (52 vs 39 months). There was no difference in LC based on histology of the primary tumor.

CONCLUSIONS:

In a large, multi-institutional series of patients with liver metastasis treated with SBRT, reasonable LC and OS was observed. OS and LC depended on dose and tumor volume, while OS varied by primary tumor. Future prospective trials on the role of SBRT for liver metastasis from different primaries in the setting of multidisciplinary management including systemic therapy, is warranted.

Here’s a link to the study:

https://www.ncbi.nlm.nih.gov/pubmed/29439707

To learn more and find out if you’re a candidate for CyberKnife Radiation Therapy, talk to our cancer experts at the CyberKnife Center of Miami. 305-279-2900

#CancerTreatmentCenterMiami

#SBRT #Liver Metastasis

Melanoma Brain Metastases: CyberKnife Also Known as Radiosurgery Appears to Enhance Immunotherapy Effects

Combination particularly effective for patients receiving PD-1 inhibitors

By: Mark L. Fuerst, MedPage Today

Radiosurgery was effective for melanoma patients with brain metastases receiving immune checkpoint inhibitors, with acceptable toxicities, according to new research.

Clinicians often treat melanoma with checkpoint inhibitors and patients who develop brain metastases commonly receive precisely targeted stereotactic radiosurgery for local control, the authors noted. Prolonged survival is observed for melanoma patients with brain metastases treated with combinations of therapies, and the reason may be an underlying synergy between these therapies.

“Our study supports that it is safe to use radiosurgery in patients receiving immune checkpoint inhibitors, and importantly we also describe excellent outcomes for patients with this combination of therapies, especially those who were treated with PD-1 inhibitors,” Tyler Robin, MD, PhD, of the University of Colorado Cancer Center Anschutz Medical Campus, told the Reading Room.

“It is important to point out that all patients in our study received radiosurgery and immune checkpoint inhibitors. Our study did not compare the outcomes for patients treated with immune checkpoint inhibitors with or without radiosurgery or vice versa, and so it remains possible that our findings are not the result of a synergy between these two therapies. However, the promising outcomes seen in our study, especially in patients receiving PD-1 inhibitors, lead to the hypothesis that while PD-1 inhibitors alone are active against brain metastases, radiosurgery might enhance their efficacy.”

For the study, Robin and colleagues retrospectively identified all consecutive cases of newly diagnosed melanoma brain metastases treated with Gamma Knife radiosurgery at their institution between 2012 and 2017. Included were 38 patients who had initiated checkpoint inhibitor immunotherapy within 8 weeks before or after radiosurgery.

After a median follow-up of 31.6 months, the 2-year local control rate was 92%. The median time to out-of-field central nervous system (CNS) progression was 8.4 months and 7.9 months to extra-CNS progression. Median progression-free survival (PFS) was 3.4 months, and median overall survival (OS) was not reached.

Two-thirds of patients (n=25) received anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4) and one-third (13 patients) received anti-PD-1 with or without anti-CTLA4. Patients who received anti-PD-1 therapy had significant improvements in time to out-of-field CNS progression, extra-CNS progression, and PFS as compared with those who receive anti-CTLA4 therapy.

While the study did not report on the mechanisms underlying a potential advantage to anti-PD-1 and radiosurgery compared with anti-CTLA4 and radiosurgery, preclinical data from other groups have demonstrated that radiation can upregulate PD-L1, synergizing with therapies targeting this pathway, he said.

“Our study was limited to patients with melanoma, which commonly metastasizes to the brain, and immune checkpoint inhibitors have comparatively good efficacy in this disease. We are interested in studying this paradigm in other cancer types that respond well to immune checkpoint inhibitors and metastasize to the brain.”

Looking forward, the researchers said, they plan to focus on developing prospective studies aimed at defining the optimal timing and sequencing to combine radiosurgery with immune checkpoint inhibition.

Ipilimumab + Radiosurgery

Another research team noted that the anti-CTLA4 agent ipilimumab was the first checkpoint inhibitor to demonstrate a survival benefit in patients with metastatic melanoma, with an estimated medial survival of 6 months after initiation of ipilimumab alone for brain metastasis. The group’s recent open-label, multicenter, phase II study evaluated the efficacy of one administration of ipilimumab at 10 mg/kg followed by stereotactic radiosurgery and maintenance ipilimumab in a cohort of 57 melanoma patients, median age of 54, with brain metastases.

Median survival time was 13.2 months — longer than the median survival time of 5.6 months in the reference population. The disease control rate was 49%.

The most serious treatment-related adverse events were colitis (10.5%), hepatitis (10.5%), hypophisitis (8.8%), and headache (8.8%); one patient developed radionecrosis.

“High-dose ipilimumab combined with stereotactic radiosurgery provides a rather good OS in melanoma patients with brain metastases, with the usual manageable safety profile of ipilimumab,” wrote Laurent Mortier, MD of the University of Lille in France, and colleagues. “Whether this result is simply due to the addition of local control of the immediate neurological risk of stereotactic radiosurgery and the systemic effect of ipilimumab or to a real synergistic effect of radio-immunotherapy remains unclear.”

Treatment-related Injury

Immunotherapy-treated melanoma patients with brain metastases who receive stereotactic radiosurgery may have higher rates of treatment-related injury, including radiation necrosis, which can be difficult to differentiate from disease progression.

In another study, a cohort of 104 melanoma patients with brain metastases who received stereotactic radiosurgery or stereotactic body radiation therapy and immunotherapy was compared with a group of 29 patients who had not received radiosurgery to examine characteristic radiographic findings to guide decision-making.

Among the immunotherapy group, the treatment appeared to be effective in 16 patients (15.4%). Of the 29 who did not receive immunotherapy, only one had a pathologically confirmed treatment effect.

“MRI findings were consistent with existing data on radiation necrosis in glioblastoma multiforme, which could help guide decision making in melanoma brain metastases, although perfusion data for clear tumor progression was limited,” stated the researchers, led by Justin L. Sovich, MD, of the University of Texas MD Anderson Cancer Center.

Here is the link to the study:

To learn more talk to our cancer experts at the CyberKnife Center of Miami 305-279-2900

A high dose of precision radiation could drastically increase the survival rates of patients with metastatic cancer, and double the time patients live without cancer growth, according to study results presented at the 60th Annual Meeting of the American Society for Radiation Oncology.

Usually, metastatic disease is considered incurable, but one theory suggests otherwise. “There’s a theory — called the oligometastatic theory — that if a patient only has a few spots of cancer returning, those spots could be killed with radiation or surgery to improve their survival,” lead author David Palma, M.D., Ph.D., from Lawson Health Research Institute, explained in a statement.

The phase 2, open-label multi-center SABR-COMET study was created to challenge this theory by examining the effects of highly precise radiation therapy in 99 patients from four countries (Canada, Scotland, the Netherlands and Australia).

All patients had previously treated cancer that returned in new sites. The most common malignancies were breast (18 patients), lung (18 patients), colon or rectum (18 patients) and prostate (16 patients) cancers.

Between February 2012 and August 2016, participants were randomly placed into one of two treatment arms: a control arm that received palliative standard of care and an arm that received the standard of care plus stereotactic ablative radiotherapy (SABR), a high-precision therapy that delivers substantially higher doses of radiation to the tumor in fewer treatment sessions – usually one or just a few. The median follow-up time was 27 months.

In addition to living longer without cancer growth, researchers ultimately found that patients who received stereotactic radiation also lived considerably longer than those who did not.

Patients in the radiation arm saw a median progression-free survival of 12 months compared to six months in those who received standard of care. Median overall survival in those who received radiation was 41 months, versus 28 months in the control group.

“We were surprised and quite pleased,” said Palma. “We didn’t expect the survival benefit to be quite so long for patients with metastatic disease.”

“Now, we’ve been able to show, for the first time in a randomized trial, that high-dose radiation can effectively treat these limited recurrences, and we’ve been able to increase survival by a median of 13 months.”

There were no differences in quality of life between the two treatment arms; however, the researchers noted that radiation therapy does have drawbacks such as more negative side effects. The most common side effects noted in this study included fatigue, difficulty breathing and muscle and joint pain. Nine percent of patients in the standard of care arm and 30 percent of those who received radiation reported serious side effects.

While three patients in the radiation arm died due to side effects – one from a pulmonary abscess, one from subdural hemorrhage after surgery to repair a stereotactic ablative radiotherapy-related perforated gastric ulcer and one from radiation pneumonitis. However, the researchers noted that such events can occur with standard radiation therapy and are rare.

“Stereotactic radiation therapy needs to be delivered carefully and by an experienced team, and there is a small risk of very serious side effects, as well as mortality,” explained Palma. “But overall, for patients whose cancers have spread, and who are not expected to survive otherwise, the overall survival benefit of SABR appear to outweigh these risks.”

Because 46 percent of the patients who received stereotactic radiation were still alive after five years – compared to 24 percent of patients in the control group — this kind of treatment is worth consideration and could offer hope for some, Palma said.

“Stereotactic radiation therapy can increase how long these patients live and how long they live without their cancer coming back,” he added. “and it doesn’t seem to have a detrimental impact on their quality of life.”

To learn more talk to our team of cancer experts at the CyberKnife Center of Miami 305-279-2900

Here’s a link to the published article:

High-dose radiation therapy, like CyberKnife safe for kidney cancer patients with a single kidney

Using high-dose, high-precision radiation therapy to treat renal cell carcinoma (RCR) is safe for patients with one kidney, according to findings presented at the American Society for Radiation Oncology (ASTRO) annual meeting in San Antonio, Texas.

RCR is a common form of kidney cancer among adults, responsible for nearly 15,000 deaths in the United States each year. Surgery is the most common treatment, followed by tumor ablation, but stereotactic ablative radiotherapy (SABR) represents a potential alternative. Previous research published in Cancer found SABR was save for RCR patients who still have two kidneys; these new findings confirm it is safe for patients with one kidney as well.

“Although RCC historically has been considered resistant to conventional radiation therapy, the high doses and high precision achievable with SABR overcome this resistance,” lead author Rohann J.M. Correa, MD, PhD, of London Health Sciences Center in London, Canada, said in a prepared statement.

“Kidney SABR is thus emerging as a versatile, non-invasive outpatient treatment requiring one visit or a few visits. Our analysis demonstrates SABR to be highly effective with minimal side effects for RCC patients with a single kidney.”

Researchers analyzed data from 81 patients with a single kidney who underwent SABR. The average age at the time of treatment was 67.5 years old, 69 percent of the patients were male and the median radiation therapy dose was 87.5 Gray (gy). Median follow-up was 2.6 years.

Overall, 98 percent of patients with a single kidney who underwent SABR had two-year local control. Ninety-eight percent also had a two-year cancer-specific survival rate of 98 percent. Rates were “not significantly different” from patients with two kidneys who underwent SABR, according to the authors.

Renal function was “modestly” impacted by SABR, though none of the patients with a single kidney required dialysis.

“We were somewhat surprised that SABR could achieve such a high local control rate without more significantly impacting renal function in the solitary kidney setting,” Correa said in the same statement.

The ASTRO Annual Meeting is Oct. 21-24 at the Henry B. Gonzalez Convention Center in San Antonio. 

Here is a link to the article:

Talk to our Kidney Cancer experts at CyberKnife Miami to learn more 

305-279-2900

“Our prime purpose in this life is to help others. And if you can’t help them, at least don’t hurt them.”
~ Dalai Lama

A new study by researchers at UT Southwestern Medical Center found no major long-term differences in the effectiveness of radiation therapy versus surgery in treating an increasingly diagnosed head and neck cancer.

Given these results, investigators suggest quality-of-life factors should help inform a treatment decision between the two therapies.

The findings comparing the effectiveness of definitive radiotherapy with primary surgery were published in JAMA Otolaryngology-Head & Neck Surgery.1

The investigators performed a comparative effectiveness analysis in patients with oropharyngeal squamous cell carcinoma (OPSCC), focusing on survival, side effects and costs. 

The study merged the HealthCore Integrated Research Database with state cancer registry data to identify 884 patients diagnosed with OPSCC from 2007 to 2014. 

The authors found no statistical differences between radiotherapy vs. surgery in overall survival, long-term gastrostomy dependence (stomach tube use), esophageal dilation or restriction, and bone toxicity effects. There was, however, an increase in acute gastrostomy use among radiotherapy patients who also received chemotherapy.

“While historical treatment outcomes for oropharyngeal cancer were quite poor, the combination of treatment innovations and more favorable tumor biology have resulted in three-year survival for over 75 percent of patients in this analysis,” said David Sher, M.D., associate professor of radiation oncology and of clinical sciences at UT Southwestern, and first author of this JAMA Otolaryngology study.

Sher believes that future research in this area should focus not just on oncologic results but also on patient quality of life and functional outcomes. 

“Both local therapy paradigms for HPV-associated oropharyngeal cancer are expected to change significantly over the next five years, so it is crucial to prospectively study the impact of novel treatment approaches on patient-centered outcomes.”

The study was funded by the Radiation Oncology Institute and co-authored by HealthCore, the outcomes research subsidiary for Anthem Inc.

It further showed that, for both treatments, costs were about $100,000 for payers and $5,000 for patients. Sher observed, “The absence of any significant cost differences further emphasizes how central patient-reported outcomes will be on the comparative value of the two therapies.”

Abiy Agiro, Ph.D., director of translational research at HealthCore concurred: “Our findings suggest that patient preference can be the main driver of local therapy selection as both surgery and radiation therapy were equally viable choices in terms of clinical outcomes with no cost difference.”

For more information: www.jamanetwork.com/journals/jamaotolaryngology

CyberKnife Radiation Therapy is highly effective at treating head and neck cancer. Talk to our cancer experts at CyberKnife Miami to see if CyberKnife is your best treatment option. 305-279-2900

New Research confirms CyberKnife, also known as Stereotactic Body Radiation Therapy (SBRT) should always be considered as an option to treat Lung Cancer. 

Stereotactic body radiation therapy (SBRT) improved overall survival and local disease control over standard radiotherapy (RT) for stage I lung cancer patients with inoperable disease, the phase III CHISEL trial showed. 

In the randomized study of 101 non-small cell lung cancer (NSCLC) patients, median overall survival was 5 years in the SBRT arm compared with 3 years in the conventional RT arm (HR 0.53, 95% CI 0.30-0.94, P=0.027), reported David Ball, MD, of Peter MacCallum Cancer Centre in Melbourne, Australia, and colleagues. 

At 2 years, 77% of patients treated with SBRT were still alive, compared with 59% of those treated with standard RT, as shown in the Lancet Oncology. 

And there was a 68% reduction in the study’s primary endpoint of local treatment failure for the SBRT group (HR 0.32, 95% CI, 0.13-0.77, P=0.008). At 2 years, the cumulative incidence of local treatment failure was 26% with standard RT versus 10% with SBRT. 

“To the best of our knowledge, this study is the first to make a direct comparison that indicates that SBRT is associated with improved survival,” Ball’s team wrote, noting that this finding, plus the observed improvement of local control, provides evidence supporting SBRT as the “standard of care for the treatment of inoperable peripherally located stage I NSCLC.” 

They noted that the rapid and widespread adoption of SBRT has been largely driven by “convenience, tolerability, and high primary tumor control.” 

But level 1 evidence supporting its use in this setting had been lacking, said Faiez AlShafa, MD, and David Palma, MD, both of the London Health Sciences Centre in Ontario, Canada, in an accompanying editorial. They noted that new technologies and approaches are often adopted into radiological clinical practice without any firm evidence that the advances are actually beneficial. 

“Premature adoption of a technology that is later proven to be unhelpful leads to unnecessary cost and possibly harm,” they wrote. “We should recognize that although we ourselves might believe that our new technologies are beneficial, if we do not complete randomized controlled trials, other important stakeholders might not believe in these benefits.” 

This in itself is what makes the completed phase III CHISEL trial “a major step forward,” said AlShafa and Palma, and the findings establish SBRT as the “standard radiotherapy approach in patients with stage I NSCLC who are not undergoing surgery.” 

CHISEL recruited a total of 101 patients at 11 hospitals in Australia and three in New Zealand with peripherally localized stage I NSCLC who were either ineligible for or refused surgery, and randomized them 2:1 to either SBRT or conventional RT. 

For tumors <2 cm from the chest wall, SBRT patients received four 12 Gy fractions for a total of 48 Gy. Otherwise, SBRT patients received three 18 Gy fractions for a total of 54 Gy. For those in the conventional RT arm, treatment consisted of daily 2 Gy fractions for a total of 66 Gy or daily 2.5 Gy fractions for a total of 50 Gy, depending on institutional 

preference. 

A total of 61 patients randomized to SBRT were treated according to protocol, as were 33 patients in the standard RT group. At a slightly longer median follow-up for the SBRT group (2.6 vs 2.1 years), fewer patients (14%) had progressed locally compared with 31% of those in the conventional RT arm. At the same follow-up point, 39% of patients treated with SBRT had died compared with 62% of patients treated with conventional RT. 

Treatment was generally well tolerated in both groups, the researchers reported, with only one grade 4 adverse event (AE) and seven grade 3 AEs in SBRT-treated patients. Only two grade 3 AEs were documented in the standard RT arm. 

One study limitation, according to Ball’s group, was the choice of time to local treatment failure as the primary endpoint. “Initially, we planned to use the widely accepted RECIST criteria to record local treatment failure, with confirmation by biopsy or FDG-PET imaging,” the authors explained. However, they found that by following SBRT treatment, “many patients developed dense fibrosis within the irradiated volume that would erroneously satisfy the criteria for progressive disease using the RECIST criteria.” 

This obstacle was overcome by providing a list of radiological features associated with a higher risk of recurrence to the panel of independent radiology reviewers so that they could compensate for this limitation. 

The study was funded by the Radiation and Optometry Section of the Australian Government Department of Health with the assistance of Cancer Australia, the Cancer Society of New Zealand, and the Cancer Research Trust New Zealand. 

Ball reported grant funding from Cancer Australia for the conduct of the study and personal fees from Pfizer; other co-authors reported relationships with the Cancer Society of New Zealand, the Cancer Research Trust New Zealand, Pfizer, Novartis, Roche/Genentech, AstraZeneca, Merck, Bristol-Myers Squibb, and Loxo Oncology. 

Alshafa and Palma reported having no competing interests. 

Primary Source 

The Lancet Oncology 

Source Reference: Ball D, et al “Stereotactic ablative radiotherapy versus standard radiotherapy in stage 1 non-small-cell lung cancer (TROG 09.02 CHISEL): A phase 3, open-label, randomised controlled trial” Lancet Oncol 2019; DOI: 10.1016/S1470- 2045(18)30896-9. 

Secondary Source 

The Lancet Oncology 

Source Reference: AlShafa F, Palma D “CHISELing a path forward in the treatment of early-age non-small-cell lung cancer” Lancet Oncol 2019; DOI: 10.1016/S1470- 2045(18)30953-7. 

Here’s the link to the Lung Cancer study:

A new UCLA-led study shows that men with low- or intermediate-risk prostate cancer can safely undergo higher doses of radiation over a significantly shorter period of time and still have the same, successful outcomes as from a much longer course of treatment.

1 dose of CyberKnife (SBRT) is more effective at controlling & eliminating pain from metastatic bone cancer than 10 conventional multi fraction radiotherapy sessions (MFRT) according to a new study published in JAMA.

In this prospective randomized phase 2 trial, 160 patients with mostly non-spine bone lesions were randomly assigned to receive single-fraction SBRT (12 Gy for ≥4-cm lesions or 16 Gy for 4-cm lesions) or MFRT to 30 Gy in 10 fractions. Single-fraction radiation led to more patients experiencing complete or partial pain response at 2 weeks, 3 months, and 9 months compared with standard MFRT.

Pain response rates were higher for high-dose, single-fraction SBRT, which should be considered for patients with bone metastases and long estimated survival times.

Here is the published study:

Single-Fraction Stereotactic vs Conventional Multifraction Radiotherapy for Pain Relief in Patients With Predominantly Nonspine Bone Metastases

A Randomized Phase 2 Trial

Quynh-Nhu Nguyen, MD¹; Stephen G. Chun, MD¹; Edward Chow, MBBS, PhD³; et al

Ritsuko Komaki, MD¹; Zhongxing Liao, MD¹; Rensi Zacharia, MD¹; Bill K. Szeto, BA¹; James W. Welsh, MD¹; Stephen M. Hahn, MD¹; C. David Fuller, MD¹; Bryan S. Moon, MD²; Justin E. Bird, MD²; Robert Satcher, MD²; Patrick P. Lin, MD²; Melenda Jeter, MD¹; Michael S. O’Reilly, MD¹; Valerae O. Lewis, MD²

Author Affiliations

JAMA Oncol. Published online April 25, 2019. doi:10.1001/jamaoncol.2019.0192

Audio Interview (11:46)

Single-Fraction Stereotactic vs Multifraction Radiotherapy for Pain Relief in Patients With Nonspine Bone Metastases

Key Points

Question  Does single-fraction stereotactic body radiotherapy (SBRT) for bone metastases lead to better pain response rates than standard multifraction radiotherapy (MFRT)?

Findings  In this prospective randomized phase 2 noninferiority trial, 160 patients with mostly nonspine bone lesions were randomly assigned to receive single-fraction SBRT (12 Gy for ≥4-cm lesions or 16 Gy for <4-cm lesions) or MFRT to 30 Gy in 10 fractions. Single-fraction radiation led to more patients experiencing complete or partial pain response at 2 weeks, 3 months, and 9 months compared with standard MFRT.

Meaning  Pain response rates were higher for high-dose, single-fraction SBRT, which should be considered for patients with bone metastases and long estimated survival times.

Abstract

Importance  Consensus is lacking as to the optimal radiotherapy dose and fractionation schedule for treating bone metastases.

Objective  To assess the relative efficacy of high-dose, single-fraction stereotactic body radiotherapy (SBRT) vs standard multifraction radiotherapy (MFRT) for alleviation of pain in patients with mostly nonspine bone metastases.

Design, Setting, and Participants  This prospective, randomized, single-institution phase 2 noninferiority trial conducted at a tertiary cancer care center enrolled 160 patients with radiologically confirmed painful bone metastases from September 19, 2014, through June 19, 2018. Patients were randomly assigned in a 1:1 ratio to receive either single-fraction SBRT (12 Gy for ≥4-cm lesions or 16 Gy for <4-cm lesions) or MFRT to 30 Gy in 10 fractions.

Main Outcomes and Measures  The primary end point was pain response, defined by international consensus criteria as a combination of pain score and analgesic use (daily morphine-equivalent dose). Pain failure (ie, lack of response) was defined as worsening pain score (≥2 points on a 0-to-10 scale), an increase in morphine-equivalent opioid dose of 50% or more, reirradiation, or pathologic fracture. We hypothesized that SBRT was noninferior to MFRT.

Results  In this phase 2 noninferiority trial of 96 men and 64 women (mean [SD] age, 62.4 [10.4] years), 81 patients received SBRT and 79 received MFRT. Among evaluable patients who received treatment per protocol, the single-fraction group had more pain responders than the MFRT group (complete response + partial response) at 2 weeks (34 of 55 [62%] vs 19 of 52 [36%]) (P = .01), 3 months (31 of 43 [72%] vs 17 of 35 [49%]) (P = .03), and 9 months (17 of 22 [77%] vs 12 of 26 [46%]) (P = .03). No differences were found in treatment-related toxic effects or quality-of-life scores after SBRT vs MFRT; local control rates at 1 and 2 years were higher in patients receiving single-fraction SBRT.

Conclusions and Relevance  Delivering high-dose, single-fraction SBRT seems to be an effective treatment option for patients with painful bone metastases. Among evaluable patients, SBRT had higher rates of pain response (complete response + partial response) than did MFRT and thus should be considered for patients expected to have relatively long survival.

Trial Registration  ClinicalTrials.gov identifier: NCT02163226