“Absolutely, yes. All of our therapies, surgery, radiation, chemotherapy, and targeted therapy for lung cancer come with risks and benefits,” says radiation oncologist Russell K. Hales, M.D. of the Johns Hopkins Kimmel Cancer Center on the Johns Hopkins Bayview campus. “We use those therapies only after careful evaluation of the risks of the therapy, versus the benefits of the therapy.”

Hales notes, “There are long term effects, or dangers, of radiation treatment, but in lung cancer, the benefits of radiation usually outweigh these risks. Individual risks would be really driven by an individual patient, and the lung cancer treatment that they're getting."

Specific side effects for lung cancer patients that undergo radiation treatment include:
• having pain or difficulty with swallowing, from irritation of the esophagus, during radiation therapy;
• inflammation of the lung, or pneumonitis, after radiation treatment, which usually goes away within a few months;
• long-term effects of radiation, such as scar tissue that forms in the lung, a rare chance of injury or damage to the heart, or other structures in the chest.

“These side effects sound scary, and treatment innovations can help reduce the likelihood of these side effects occurring,” Hales says, “but even in the most carefully delivered radiation treatment, there is a risk of side effects.”

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***With the end of summer, we bring you a three-part series about Camp Sunrise, a place of summer fun for pediatric oncology patients at the Johns Hopkins Kimmel Cancer Center. Part two features Amanda's story.

What began in 1986 with seven campers has grown into the Kimmel Cancer Center-managed and -operated Camp Sunrise. The camp is entirely volunteer run, with more than 120 campers, 80 trained volunteers and more than 50 medical staff members. Most of the volunteers, including camp directors Marilyn Scalf and Steve Mitchell, were former campers, and many of them have been associated with Camp Sunrise for more than 20 years.

Among them are Annapolis stained glass artist Bobbie Burnett, whoCamp Sunrise has made sun catchers with campers for the past 30 years, and Alex Johnston, who cooks meals for campers. Each year, volunteer Jaclyn Young helps campers make bracelets with special beads that commemorate the year. Some campers boast multiple bracelets, signifying their many visits to Camp Sunrise.

For one very special week each summer, campers and volunteers come together at Elks Camp Barrett in Crownsville, Maryland, for hiking, archery, swimming, rock wall climbing, dancing, crafts, games, sports, campfires and reunions with friends. “It really makes your heart warm. It’s the best feeling inside to see these kids so happy,” says Scalf.

A PLACE LIKE NO OTHER
Camp Sunrise may be the only place where cancer takes a backseat to childhood and teenage fun. For this one week, cancer is not their primary focus. “Our goal is to give campers the best week of their lives,” says Jordan May, a former camper turned volunteer. Beyond the fun, campers treasure the direct connection to other kids who understand and share their unique experience.

“I’ve been going to camp for nine years, and the reason I keep coming back is the relationships, the family I have with these people. I’ve known them almost my entire life. We’ve been through so much together. It just means so much to me. I have to come
back to see them,” says Billy.

Almost every year, there are a few campers who are in hospice care. Camp Sunrise is one of their last experiences, and that realization is not lost on the campers or volunteers. At the end of camp each year, the entire group gathers to plant a tree and decorate it with handmade ornaments that honor campers who lost their cancer battle. As campers return year after year, they see these trees and remember their friends.

SOMETHING FOR EVERYONE
At Camp Sunrise, there is something for everyone. Unlike other camps, no camper is too young, old or sick for Camp Sunrise. Younger campers, 4 and 5 years old, participate in a day camp, and campers 6 to 16 come for a traditional residential sleepover camp, complete with rustic cabins and plenty of outdoor adventures. The older 17 and 18-year-old campers take part in a leadership training program so, if they choose, they may join the ranks of the Camp Sunrise volunteers as camp counselors.

For patients who can’t leave the hospital to go to Camp Sunrise, there is “Camp at Hopkins.” Camp volunteers devote some time to go to the hospital and work with the Child Life teachers to make sure inpatients also have a camp experience with art projects and other activities. The highlight is a special robot that allows the campers at “Camp at Hopkins” to connect with campers at Camp Sunrise.

THE FUNNY FARM
About one-quarter of patients who attend Camp Sunrise are actively being treated for cancer. They rely on the more than 50 Kimmel Cancer Center physicians, nurses and physician assistants who care for them in the medical room campers have dubbed the “Funny Farm.” The medical staff members leave the cancer center and volunteer their time to make sure caregivers are on hand 24 hours a day to administer chemotherapy, draw blood for lab work and provide any other care needed. Campers also come to the Funny Farm for care of camp-related bumps, scrapes, and bruises.

Donald Small, Director of Pediatric Oncology, is among the physicians providing care to campers. “When I see these kids in the Cancer Center, often they are sick, and we’re administering very complicated therapies,” says Small. “Then I see them at camp each year playing and having such a great time. It’s a wonderful thing for me and for all of the medical staff to see.”

CANCER DOESN’T CALL THE SHOTS
For most kids, a cancer diagnosis makes summer camp an impossibility. It becomes one more thing that makes them different from others their age. At Camp Sunrise, cancer doesn’t call the shots. Prostheses are hung behind doors on coat hooks, wigs and scarves are often put aside in favor of bald heads, and no explanations are necessary. Everyone fits in, and everyone there—campers, counselors and volunteers—understands.

Cancer, particularly in children and teens, is more than its physical manifestations. As it disrupts the normal, day-to-day activities and relationships, it also takes an emotional toll. The clinicians and scientists at the Kimmel Cancer Center provide the research, discovery and care that heal the body, and places like Camp Sunrise heal the soul.

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“Certainly, it’s never optimal to have deficiencies in vitamin levels,” says radiation oncologist Russell K. Hales, M.D. of the Johns Hopkins Kimmel Cancer Center on the Johns Hopkins Bayview campus. “We try to make sure that our patients are healthy, and taking a multivitamin every day.”

However, Hales warns against lung cancer patients taking high levels of multivitamins, because it can often counteract the effectiveness of chemotherapy, and radiation.

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Suzanne Topalian

Suzanne Topalian

Suzanne Topalian, M.D., associate director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy, is a pioneer in the search for biomarkers that predict responses to immunotherapy.

In April at the American Association for Cancer Research meeting in New Orleans, Topalian and her colleagues presented data linking a virus-associated cancer, called Merkel cell carcinoma - to response to one type of anti-PD-1 therapy.

In a new, preliminary study, Topalian takes a closer look at kidney cancer and immunotherapy. The kidneys are metabolic organs -- the filters of the body -- that control how nutrients are absorbed and waste is eliminated.

Up to 30 percent of patients with kidney cancer may respond to immunotherapy drugs that target the PD-1 and PD-L1 pathway, but scientists do not know why the majority of patients don't respond, says Topalian.

In the nine among 13 kidney cancers that did not respond to anti-PD-1 therapies, the expression of 110 genes involved in cell metabolism went into overdrive. One gene, called UGT1A6, had particularly high expression, found the researchers. It controls how some cells in the body get rid of toxins.

With these results, the researchers are asking: could tumors use this pathway to rid themselves of toxins, such as medicines and other chemical substances, thereby making the tumor cells more "fit" to keep up their hide-and-seek game with the immune system?

"This is a retrospective study in a limited number of patients, but we think it's a good start in exploring immunotherapy resistance," says Topalian.

In further research, Topalian and her colleagues will investigate the role of UGT1A6 and other metabolic genes in cancer cells and whether their results can be confirmed in larger groups of patients.

Read more: Topalian discusses advances in immunotherapy and the search for new biomarkers of response.

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Charles Drake

Charles Drake

So-called anti-PD-1 drugs, which block the interaction between proteins on cancer and immune cells, are currently approved by the Food and Drug Administration for certain patients with melanoma and non-small cell lung, kidney and bladder cancers. Now, a new study led by scientists at Oregon Health & Science University's Knight Cancer Institute and partially funded by the Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, has given clinicians hope that some prostate cancer patients may respond to the anti-PD-1 drugs.

In a preliminary report on a clinical trial, 10 patients with advanced prostate cancer that had become resistant to a common hormone therapy called enzalutamide were treated with the PD-1 blocking drug pembrolizumab.  Of these patients, three experienced substantial reductions in their levels of prostate specific antigen (PSA), a marker of treatment response, from 46, 71 and 2503 ng/ml to less than 0.1 ng/ml. Two of the three patients also experienced tumor shrinkage of at least 50 percent of their total tumor volume – i.e. “partial responses.”

The three patients remain progression-free at 30, 55 and 16 weeks of follow up. The rest of the patients had stable disease or did not benefit from the treatment. One patient died of his prostate cancer. Adverse events included hypothyroidism in two patients and muscle inflammation in one subject.

Although it remains to be seen whether anti-PD-therapy has an effect on survival in prostate cancer, immunology expert Charles Drake, M.D., Ph.D., an associate director of the Bloomberg-Kimmel Institute, says that this type of treatment response is not the norm for prostate cancer patients whose disease has progressed after hormone therapy.

“Prior to these data, there was consensus that PD-1 blockade was ineffective for these patients, but this may change the way we think about immunotherapy and prostate cancer,” says Drake. Going forward, additional prostate cancer patients will be enrolled in the ongoing study, and several related studies are being planned.

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Stefanie Joho

Stefanie Joho

Stefanie Joho, 25, had been given a death sentence. Diagnosed with advanced colon cancer, she traveled to cancer centers around the U.S. in search of a therapy that could buy her time. She found it at the Johns Hopkins Kimmel Cancer Center -- the result of a combination of recent scientific advances in immunotherapy and a genetic discovery from 30 years earlier. Today, she received her last treatment, known as anti-PD-1 therapy, which breaks down barriers to the immune system's ability to recognize cancer cells. Johns Hopkins investigators at the Bloomberg-Kimmel Institute for Cancer Immunotherapy played a leading role in the clinical development of PD-1 blockade/anti-PD-1 therapy and the scientific studies to develop biomarkers for response to the therapy. Hopkins scientists also have led pioneering work in understanding the PD-1 pathway and how the therapy works. There is still plenty of ongoing research on these therapies, particularly on why they don't work for everyone, and much of the research is initiated and led by Johns Hopkins investigators. But Joho, who was days from dying from what would be considered an incurable colon cancer, is now in complete remission.

**Note: Stefanie participated in a clinical trial funded by the Swim Across America. In September, she'll join other Baltimore swimmers in the Swim Across America event to benefit cancer research at the Johns Hopkins Kimmel Cancer Center. Learn more about the event and the research.

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Radiation oncologist Russell K. Hales, M.D. of the Johns Hopkins Kimmel Cancer Center on the Johns Hopkins Bayview campus notes that clinical trials are treatments that are usually done at cancer centers with researchers, like Hopkins. “Clinical trials take an existing therapy, and add to it an investigational therapy, or give an investigational therapy altogether,” he says.

What are the advantages in each choice?
• The standard of care is the standard treatment that you should receive, anywhere across the world that you're treated.
• Clinical trials take discovery that's been found in the lab, or in smaller clinical trials, and apply it to a group of patients. Often, clinical trials can give a patient an opportunity to have a therapy that they otherwise wouldn’t be able to get, that may one day become the clinical standard of care.

Clinical trials also benefit the field at large, by helping the patient to-to be a participant in innovation, in lung cancer care. Hales notes that “We are at the heart of innovation in cancer treatment, because of patients that have gone before, and have been a part of clinical trials. This is the way that we transform cancer care. If you are choosing between the standard of care, versus the clinical trial, it really comes down to the individual clinical trial. I want to reassure you that no clinical trial is done without much data gathering beforehand, to show that there's promise in the therapy that's being tried. Clinical trials are always a good option, but they need to be taken on a case by case basis.”

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An antibody drug that targets part of the bone growth pathway can slow the growth of human osteosarcoma implanted in mice and prevent the tumor from spreading to other parts of the body, according to a study led by Johns Hopkins Kimmel Cancer Center scientists.

David Loeb

David Loeb

Osteosarcoma is one of the most common bone tumors affecting children and adolescents. It is usually treated with surgery and chemotherapy, but the disease spreads in between 25 and 40 percent of patients, and 75 percent of those patients will die of their disease.

These survival rates remain “mostly unchanged” since the 1980s, making it important to uncover new therapeutic options, says David M. Loeb, M.D., Ph.D., an associate professor of oncology and pediatrics and director of the Musculoskeletal Tumor Program at the Kimmel Cancer Center.

As Loeb and colleagues reported earlier this year in Oncotarget, the antibody targets a molecule called DKK-1, which may promote tumor growth in osteosarcoma. DKK-1 blocks part of the Wnt molecular signaling pathway that is key to normal bone development.

Loeb and colleagues implanted tumors grown from human osteosarcoma cells into mice and were able to detect human DKK-1 circulating in the blood shortly afterward. The higher the levels of DKK-1, the faster the tumors grew in the mice, the researchers found. When DKK-1 levels in the mice were high, during the first six weeks of tumor growth, tumors increased in volume at a rate of almost 1 percent every three days, while the rate later slowed to .35 percent when DKK-1 levels were low.

When the mice were treated with a DKK-1 antibody, their human DKK-1 levels became undetectable, and they experienced a substantial slowdown in tumor growth — a .47 percent volume increase every three days, compared to a .95 percent increase in untreated mice.

The researchers then studied the antibody’s effects on metastasis using a mouse model that Loeb and his colleagues developed to more closely mimic osteosarcoma treatment in young patients. They implanted the tumor in a leg bone in the mice, waited for the tumor to grow before doing surgery or amputation to remove the tumor, and then watched to see if the cancer would metastasize.

Only one of 24 mice treated with the DKK-1 antibody developed metastatic disease, compared to six of 18 mice that did not receive the antibody. The one mouse that developed a metastasis appeared to have a local recurrence of its cancer, suggesting that the original surgery to remove the tumor was not completely successful.

“The major limitation to treating patients with osteosarcoma is prevention of metastasis, and I think our major finding is that in the mice who had a good surgery — meaning no local relapse — none of the [antibody]-treated animals developed metastasis,” says Loeb. “I would want to give this to patients early on in their treatment but continue throughout treatment and even up to a year after chemotherapy ended to maximize our chance of preventing metastasis.”

The antibody drug used in the study, called BHQ880 and manufactured by Novartis, also has been tested in clinical trials for the treatment of multiple myeloma. Novartis has discontinued the drug, but Loeb says that comparable antibody drugs could be developed.

It is also possible, Loeb says, that there may be other therapeutic targets to be discovered within the Wnt signaling pathway. “I think we’ve only scratched the surface in terms of understanding how Wnt signaling affects osteosarcoma,” he says.

Other scientists who contributed to the research include Johns Hopkins researchers Seth D. Goldstein, Wendy Bautista Guzman and Masanori Hayashi and Matteo Trucco of the University of Miami Sylvester Cancer Center.

Funding for the study was provided by the National Cancer Institute (1R01CA138212-01, 2P30CA006973), the Pablove Foundation and the Giant Food Children’s Cancer Research Fund.

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“Many lung cancers are not treated with one therapy alone,” says Russell K. Hales, M.D. “Sometimes it takes all three treatments—surgery, radiation, and chemotherapy-- to fully treat the lung cancer. And patients may be anxious after a surgery, about waiting in recovery for other treatments like chemotherapy and radiation.”

Hales, who is a radiation oncologist at the Johns Hopkins Kimmel Cancer Center on the Johns Hopkins Bayview campus, says, “Our goal is to start therapy as quickly as we can, but starting the therapy too quickly after surgery will just result in an unnecessary delay. If a patient starts therapy too quickly after surgery, they may not have fully recovered or healed. Then we may find a month into the next therapy that we need to put it on hold, so that they can recover. There's a balance that has to be maintained between recovering from surgery, and trying to start that therapy as quickly as possible,” he notes.

“At Hopkins, the window we usually use for that time of recovery is somewhere between three and seven weeks, after surgery. But that's going to be individualized, based on how well a patient recovers from surgery,” Hales says.

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The two main categories of lung cancer are small-cell lung cancer, and non-small-cell lung cancer, says Russell K. Hales, M.D. “Non-small cell lung cancer is further divided into adenocarcinoma, and squamous cell carcinoma.

“All lung cancer is aggressive, but all cancer in its early stages can be treated, and patients can have long term control of their disease,” says Hales, a radiation oncologist at the Johns Hopkins Kimmel Cancer Center on the Johns Hopkins Bayview campus. He notes that patients with small cell lung cancer are more likely to have disease that spreads outside of the lung, and although their tumors respond better to therapy, they're more likely to grow back.

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