In the summer of 2010, 20-year-old physical therapy student Hannah Komai saw an orthopedic surgeon after 2 months of right knee pain and difficulty ambulating. When plain x-rays revealed an unspecified mass, Hannah was admitted to City of Hope in Duarte, California. After additional x-rays, bone scanning, and computed tomography (CT), magnetic resonance imaging (MRI) revealed a 6.6 cm x 3.7 cm x 3.5 cm right distal femur mass, and Hannah was diagnosed with low-grade osteosarcoma after an incisional biopsy.

She then began eight rounds of chemotherapy with ifosfamide (1800 mg/m2/day), doxorubicin (37.5 mg/m

/day) along with occupational and physical therapy (PT). The hospital’s child life specialist and psychologist helped Hannah prepare for treatment and deal with the implications of her diagnosis.

After definitive resection and reconstruction with insertion of a metallic endoprosthesis the following October, pathology revealed negative margins but only 80% tumor necrosis (versus the optimal ≥90%), indicating the need for additional treatment. Resumption of chemotherapy was delayed by a reaction to suture material, requiring treatment of knee cellulitis with IV antibiotics, followed by two surgical wound revisions.

Hannah resumed chemotherapy later that autumn, undergoing 16 cycles with the agents administered preoperatively, with the addition of etoposide (100 mg/m2/day x 5 days) administered with ifosfamide (2800 mg/m

/day). She continued with outpatient PT until she was able to walk without intense pain. She was initially followed with blood work every 2 months, and chest CTs, bone scans, and whole-leg x-rays every 3 months. Now age 22, Hannah is learning to deal with the limitations and chronic daily pain she attributes to her reconstructive surgery and, in particular, her endoprosthesis. She has recently graduated to twice-yearly evaluations and is currently cancer-free.

Osteosarcoma is a highly aggressive neoplasm and the most common primary malignant bone tumor in children and adolescents. As recently as the 1970s, surgery alone or with radiotherapy typically produced 5-year overall survival rates of only 15% to 20%. Adding pre- and post-resection multi-agent chemotherapy has enabled long-term survival in approximately 60% to 70% of cases.

“In my experience, the presence or absence of metastasis is the most critical prognostic indicator in these patients,” notes pediatric oncology/ hematology/bone marrow transplant nurse II Molly Lambert, RN.

“Thankfully, the clear margins achieved during Hannah’s resection demonstrated an absence of metastasis, but the 80% tumor necrosis revealed a less-than-optimal response to preoperative chemotherapy, and guided the decisions related to Hannah’s postoperative chemotherapy regimen.”

The chemotherapy agents used to treat Hannah are those shown to be the most effective for osteosarcoma. Hannah was treated as an inpatient. She was discharged between rounds when symptoms, such as pain and nausea, were sufficiently controlled, and readmitted for each subsequent round of treatment when her blood counts had recovered sufficiently, sometimes needing 10 to 14 days between treatments due to immune suppression—related fever and infection. During the weeks Hannah received methotrexate, IV fluids and the rescue drug leucovorin were administered to ensure that the drug had cleared her system prior to discharge.

Lambert explains that adverse effects are common and numerous with these agents, and include nausea and vomiting from the ifosfamide and doxorubicin, often managed with ondansetron, diphenhydramine, lorazepam, and sometimes dexamethasone. Other adverse effects include constipation or diarrhea, infection-related neutropenia, and mucositis, which is prevented and managed with scrupulous oral care.

Hannah initially tolerated her chemotherapy well but recalls unrelenting constipation that was especially uncomfortable despite dietary changes and medications. As treatment progressed, her once-mild nausea became “unbearable” despite pharmacologic treatment. For 6 to 8 months after completing treatment, Hannah continued to experience severe nausea daily, and finally found relief with the oral antidopaminergic domperidone, which she continues to take along with esomeprazole.

Today, Hannah is working on her prerequisites for nursing school—a change inspired by her nurses. “I once had 27 visitors in a single day,” she says, “but it was the relationships with my nurses that really pushed me through.”

“Reinforcing the need for treatment compliance is especially critical in patients of Hannah’s age,” says Lambert. “We tried our best to establish trusting relationships that would motivate Hannah, especially during the difficult times. This involved giving her as much control and as many choices as possible, and also involved a great deal of education to ensure that Hannah could be an active and informed participant in her care while remaining as independent as possible.”

Hannah realizes that recurrence and late metastasis remain sources of concern for the first 12 to 35 months after diagnosis, but are rare after 5 years. “It’s been a rough road,” she says, adding that the loss of several fellow patients is what has been most difficult. “In the end, you learn who your true friends are, and what’s truly important in life.”

Laura Bruck is a freelance writer and editor based in Cleveland, Ohio. She has specialized in healthcare reporting since 1987.

	1. Sakamoto A, Iwamoto Y. Current status and perspectives regarding the treatment of osteosarcoma: chemotherapy. 

Articles

In the summer of 2010, 20-year-old physical therapy student Hannah Komai was diagnosed with low-grade osteosarcoma after an incisional biopsy.

A Life Redirected: Pursuing a Nursing Career After Osteosarcoma

In January 2007, Erik Kratky was 21 and pursuing his undergraduate degree when he experienced bilateral leg weakness. Magnetic resonance imaging (MRI) revealed multiple spinal cord lesions in the T10 region and, after surgical resection, Erik was diagnosed with low-grade (II) spinal cord ependymoma.

He did well for 2 years and went on to graduate college, but in November 2009, he experienced lower-extremity weakness requiring confinement to a wheelchair. Imaging revealed tumor recurrence at the original site, as well as new tumor growth at T5, T6, and the upper level of T7, along with cord compression. T5/T6/T7 and T9/T10/T11 laminectomy was performed with resection of intradural extramedullary tumor, and pathology again revealed grade II disease.

Erik failed to improve postoperatively, and imaging revealed another recurrence, continued cord compression, and new tumor growth in the lumbar region (L1 and L4), consistent with dropped metastasis. He underwent resection of tumor in T9 through T12, and the ependymoma was upgraded to III-IV, with pathology suggestive of highly aggressive disease.

The following month, Erik was referred to the Cleveland Clinic. He underwent 4 1/2 weeks of whole-brain and spine radiation (5 days/week; 20 treatments with a planned boost), along with a total of three infusions of bevacizumab (Avastin) administered once every other week to help manage spinal cord edema and reduce further loss of leg function.

Erik did well for about 1 year, completing his graduate studies, teaching college-level math, and, with the help of physical and occupational therapy, walking with a walker. An MRI in June 2011 revealed diffuse progression of tumor in the lumbar region, and Erik began one 28-day cycle of oral lapatinib (INN; daily) and oral temozolomide (Temodar; days 1-7, repeated on days 15-21).

During a July hospitalization for a pain crisis, scanning demonstrated tumor progression in the cauda equina with spinal cord nerve irritation. Erik was discharged after single-dose emergent radiation and treatment with dexamethasone (Decadron), but within 1 month, repeat imaging demonstrated continued interval progression, necessitating a rethinking of options.

Erik was put back on intravenous (IV) bevacizumab (every 2 weeks), and a carboplatin (Paraplatin) infusion was added every 4 weeks. The carboplatin was discontinued in May 2012 due to myelosuppression, and today Erik remains on twicemonthly infusions of bevacizumab, which he tolerates well. While recent imaging shows an absence of tumor growth, Erik has sustained significant injury to his spinal cord and is currently confined to a wheelchair.

Because ependymoma is not especially chemotherapy- sensitive, and residual malignant cells are likely after resection, tumor resection followed by radiotherapy is considered the most effective treatment for preventing recurrence. Tanya Tekautz, MD, oncologist at the Cleveland Clinic Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center and director of the Pediatric and Young Adult Brain Tumor Program, explains that despite the absence of brain metastasis, irradiation of Erik’s spine and brain was considered the standard of care in light of the likelihood of metastasis of small cancer cells not seen on imaging.

Burkhardt Center nurse clinician Mary Murphy, RN, BSN, notes that Erik tolerated the bevacizumab relatively well, and didn’t develop serious adverse effects (eg, brain hemorrhage, unilateral lower-extremity thrombi) despite his increased risk for clotting due to being nonambulatory. “We watch carefully for signs of brain hemorrhage, such as garbled speech and other cognitive deficits,” says Murphy, “and monitor the lower extremities for swelling, redness, and pain.” Because some of these symptoms can be insidious, Tekautz sees patients at every chemotherapy treatment, rather than every 2 months after scanning. Eric recalls the radiation-related esophagitis as the most difficult of the adverse effects he endured.

During Erik’s June 2011 disease progression, oral chemotherapy allowed him to be up and around to the extent possible. But with limited options after the 2012 progression, the change was made to IV bevacizumab and carboplatin, based primarily on data from small studies showing that the combination can help to control or slow tumor growth in ependymoma patients previously treated with surgery and radiation. “As was the case with Erik, carboplatin can cause severe myelosuppression. It also can cause renal toxicity, increased risk of infection, nausea, and fatigue, requiring frequent clinic assessment and monitoring with twice-monthly labs,” says Murphy.

It was at this time, at age 25, that Erik was transferred from pediatric to adult care.

“Aging out” of the pediatric population and transitioning to adult care can pose unique challenges. For Erik, who had developed strong attachments to his pediatric nurses, the change was a difficult one. “The adult care staff is great, but the pediatric environment was incredibly nurturing for me and my parents,” says Eric.

For Eric, the balance between the desire for independence and the need for compassionate care has been difficult to achieve, especially in light of his disability, which necessitated a return to his parents’ home just as his adult life had begun. “It’s the disability that’s hardest to deal with. I had to relearn how to do everything,” he says. Erik credits his family, Tekautz, Murphy, and all of his nurses for helping him to maintain a positive attitude.

Each time it progresses, Erik’s disease becomes more difficult to treat. While reluctant to make any long-term predictions, Murphy and Tekautz note that the current goal is to control any tumor growth for as long as possible in a patient they describe as “magic to everyone who knows him.”

In January 2007, Erik Kratky was 21 and pursuing his undergraduate degree when he experienced bilateral leg weakness, which was later diagnosed as low-grade spinal cord ependymoma. 

Spinal Cord Ependymoma in the Prime of Life

		Tiffany Keller-Fritz has been cancer-free for 2 years. She is a designer for a handbag company and is working with her employer on cancer-related bag designs and chemotherapy bag covers.

	In late 2008, 36-year-old Tiffany Keller-Fritz attributed intermittent diarrhea to stress related to an impending cross-country move. With the move completed, and pregnant with her third child, Tiffany’s diarrhea had persisted for 3 months and was now occurring several times daily, symptoms her OB-GYN dismissed as simply related to her pregnancy.

	By the end of October 2009, Tiffany was experiencing extreme fatigue, severe constipation, and progressively worsening rectal pain and pressure. With her physician once again dismissive, and now 29 weeks pregnant, Tiffany found a new OB-GYN practice, where a midwife nurse practitioner palpated a mass between the rectum and vagina. Two days later, on February 26, 2010, a sigmoidoscopy with biopsies revealed squamous cell carcinoma (SCC) of the anus.

	Magnetic resonance imaging (MRI) performed on March 7 depicted a 3.1-cm x 2.9-cm x 3.2-cm anal canal tumor involving 75% of the canal’s circumference. Now nearly 34 weeks pregnant, Tiffany was referred to Tampa’s H. Lee Moffitt Cancer Center, evaluated by a team of specialists, and scheduled for a March 22 C-section. Tiffany’s daughter Riley was delivered using a low vertical incision in an attempt to avoid the anticipated field of radiation. On April 15, a positron emission tomography (PET) scan showed locally advanced (stage III) anal cancer with involvement of the left inguinal and right iliac nodes.

	Needing time to heal before undergoing pelvic radiation, but also needing to begin treatment as soon as possible, Tiffany initially underwent one round of chemotherapy with a single dose of cisplatin and a 96-hour continuous infusion of 5-fluorouracil (5-FU) administered via a pump connected to an indwelling port. Two weeks later she began concurrent chemotherapy/radiation as follows:

		Radiotherapy (30 fractions) 5 days per week for 6 weeks (total dose, 5400 cGy)

		Chemotherapy during weeks 1 and 5 of radiotherapy, with a 96-hour continuous infusion of 5-FU plus mitomycin C administered via IV push on days 1 and 2

	On May 20, an interim PET scan demonstrated a significant response to treatment and helped to determine the final radiation dose. Treatment was completed on June 3, and a third PET scan, obtained on September 14, was completely normal. Two years post-treatment, Tiffany remains cancerand colostomy-free. She will be followed with twiceyearly physical exams, blood work, and annual chest, abdominal, and pelvic CT scans. After 5 years with no evidence of cancer, she will be referred to Moffitt’s survivorship program.

	As recently as the 1970s, SCC of the anus was considered a surgical disease necessitating permanent colostomy. Fortunately, combined chemotherapy and radiation became the standard of care; initially, it was used to shrink the tumor preoperatively but was ultimately deemed curative without surgery for stage I through III disease. Today, surgical resection is generally reserved for patients for whom chemotherapy/radiation fails. Also fortunate are the advent of improved radiotherapy techniques and equipment, along with the use of PET scanning to accurately shape the radiation dose, which have greatly reduced radiation-related toxicities that, in the past, often necessitated lengthy hospital stays.

	In Tiffany’s case, the safety of her unborn child, weighed against the urgent need to initiate treatment, required close collaboration between her oncologists and OB-GYN. If not pregnant, Tiffany would have immediately undergone concurrent chemotherapy/ radiation, but healing time was needed after the C-section before pelvic radiation could safely be started. With Moffitt’s associate professor of Radiation Oncology, Sarah Hoffe, MD, reluctant to delay treatment for what was a fast-growing malignancy, and Tiffany’s OB-GYN comfortable with performing the C-section at 34 weeks, the decision was made to administer a single chemotherapy dose shortly after delivery, and then commence combined therapy after 2 weeks of healing.

	Hoffe notes that this particular combination of mitomycin C and 5-FU delivered concurrently with radiotherapy has been shown to be the most effective in preventing the need for colostomy, as was the case with Tiffany.

	Tiffany did not develop the neutropenic fever and infection sometimes associated with this regimen. She did, however, develop oral lesions that made it difficult to eat during the first round of treatment. Despite some nausea (managed with oral prochlorperazine), extreme constipation, and feelings of panic during her initial chemotherapy, Tiffany recalls having had a strong sense that the cancer had stopped growing by day 5 of treatment.

	Radiotherapy in the anal region typically causes skin desquamation and, as in Tiffany’s case, can also cause urethritis. Two weeks after Tiffany began radiation, the topical moisturizer Aquaphor was used for anal and vaginal skin irritation. As the irritation worsened and she described feeling as if she were “urinating fire and glass,” Tiffany was taught to use a sitz bath. As skin breakdown progressed, she was taught to apply Radiocare, a hydrogel-type ointment containing lidocaine, and then Silvadene, which is often used toward the end of radiotherapy to provide pain relief, prevent infection, and hasten skin repair.

	Tiffany also developed vaginal stenosis, an often overlooked adverse effect of pelvic radiation. “If not dealt with proactively, vaginal stenosis can significantly impair sexual function,” says Moffitt Cancer Center radiation oncology nurse Gloria Wood, RN, BSN. “It can make intercourse and even vaginal exams extremely painful or even impossible, adversely affecting quality of life.”

For Tiffany Keller-Fritz, the safety of her unborn child, weighed against the urgent need to initiate treatment, required close collaboration between her oncologists and OB-GYN.

Squamous Cell Carcinoma of the Anus During Pregnancy

	In early August 2004, 44-year-old John Saltanovitz began to experience difficulty breathing, which he attributed to a sinus infection or allergies. The symptoms persisted despite John’s use of over-the-counter sinus medications, and on August 31, after he and his wife, Leah, noticed that his left eye seemed to be protruding, he saw his family physician.

	The doctor put John on a course of antibiotics for what appeared to be a sinus infection but, concerned about the eye, scheduled magnetic resonance imaging (MRI) for September 16. The MRI revealed a mass in the sinonasal area described as “likely malignant” and, the next day, a biopsy was performed by an ear, nose, and throat specialist, who recommended that John see an oncologist immediately.

	On September 28, John was seen at a world-renowned cancer center, where he was diagnosed with undifferentiated sinonasal carcinoma (T-4B) with invasion into the brain and into the eye, causing cranial nerve damage and ophthalmic extrusion. The tumor was deemed nonresectable, and no curative options were offered.

	John decided to seek a second opinion and was seen at the University of Chicago Comprehensive Cancer Center (UCCCC) in early October. The diagnosis was confirmed with a repeat MRI and panendoscopy, and distant metastasis was ruled out with computed tomography (CT).

	On October 12, John began three cycles of outpatient induction chemotherapy with cisplatin and paclitaxel. He tolerated the treatment well, and post-treatment MRI showed that his tumor had become appreciably smaller.

	On November 28, a port was inserted and John began five cycles of chemotherapy (paclitaxel, 5-FU, hydroxyurea) with concomitant radiation, administered in a 5-days-on, 9-days-off regimen.

	John recalls feeling fine until he was being prepared for discharge after the first week of treatment, and needed to be readmitted through the emergency department with a fever and severe mucositis. He also had apparent 5-FU-related hand/foot syndrome, causing the skin to peel off his hands and feet, for which he was treated with topical creams and instructed to wear gloves and socks, which he changed three to four times daily. Because of the mucositis, a g-tube was inserted during this hospital stay, and remained in place until the end of April.

	Roughly 1 month after completion of John’s chemotherapy, a repeat MRI showed that a complete response had been achieved, and a subsequent biopsy confirmed that John had no evidence of cancer. Scans performed during 5 years of follow-up continued to show no evidence of cancer.

	John describes residual treatment-related effects as episodic nose bleeds, a diminished sense of smell, increased nasal drainage, and dryness in the nasal passages requiring once-daily rinses with moisturizing drops. He also reports blocked tear ducts and excess watering.

	Allison Dekker, BSN, RN, OCN®, began educating and preparing John for treatment during his initial visit to UCCCC. She explained that the most common adverse effects seen with the selected induction chemotherapy are nausea and vomiting, as well as nephrotoxicity. Patients are typically pre-medicated with the NK1 receptor antagonist Emend (Merck) to prevent nausea, are given IV fluids to flush the kidneys, and are instructed to keep well-hydrated throughout treatment, she said.

	The mucositis and dermatitis John experienced after radiation and chemotherapy are typical side effects of that regimen, Dekker added. “We first attempt to manage the mucositis symptoms with a grade I mouth wash used four times daily but, as in John’s case, a feeding tube often needs to be inserted,” she said. She added that, due to skin breakdown, “we need to be especially vigilant about keeping the neck area clean and dry, and often use a triple-antibiotic ointment and a Vigilon dressing to manage pain and help prevent infection.”

	Dekker noted that “head and neck cancers can adversely impact a patient’s ability to speak, eat, and even swallow,” so many patients are referred to a speech and swallowing specialist. Due to nausea from treatment, she added, patients are encouraged to eat a diet high in fat, calories, and protein between rounds, and typically meet with a nutritional specialist before therapy begins.

	The Second Opinion: The Importance of Self-Advocacy

	“John’s case illustrates the importance of a patient’s willingness and ability to be his own advocate,” said UCCCC physician Ezra Cohen, MD, noting that John’s decision to seek out a second opinion was what saved his life. Even so, patients (and even clinicians) often don’t know which facilities are considered leaders in the treatment of various types of cancer, Cohen said, and a bit of detective work is generally required.

Patients (and even clinicians) often don’t know which facilities are considered leaders in the treatment of various types of cancer, and a bit of detective work is generally required.

	Not surprisingly, John is grateful not only to his physicians and nurses, but also to his wife and other family members and friends, all of whom refused to let him give up his fight.

	Initially, he said, “we were at one of the best cancer centers in the world, but it was on the suggestion of one of the physicians in that center, and with my wife’s research and persistence, that we ended up at a facility that has pioneered many of the treatments used for my type of cancer.”

Patients (and even clinicians) often don't know which facilities are considered leaders in the treatment of various types of cancer, and a bit of detective work is generally required.

A Patient Is His Own Best Advocate

	At age 40, Lisa Vance viewed her first mammogram more as a right of passage than a cause for concern. Even when she was told a biopsy would be needed, the mother of two was reassured by her physician’s assertion that he would be “very surprised if it turned out to be anything at all.”

	Despite this optimism, when Lisa had a biopsy following a suspicious finding on her mammogram, it revealed she had ductal carcinoma in situ. She was initially treated with lumpectomy, but subsequently had a right total mastectomy with immediate reconstruction.

	Lisa’s cancer was initially designated as stage I, but lymph node metastasis detected during her mastectomy necessitated four rounds of chemotherapy with dexamethasone, docetaxel (Taxotere), and cyclophosphamide (Cytoxan).

	During one of her chemotherapy treatments, Lisa had what she described as a “reaction,” feeling overheated and faint. The infusion was stopped, but Lisa was able to continue her treatment the same day, with the drugs infused at a slower pace. She also recalls feeling exhausted, especially after the later infusions; experiencing nausea and weight loss; and being extremely emotional.

	Lisa’s estrogen-sensitive malignancy also required treatment with tamoxifen (Nolvadex) and goserelin (Zoladex), initiated approximately one month after completion of her chemotherapy. In addition to feeling achy and experiencing bone pain, Lisa also experienced medically induced menopause as the result of her tamoxifen treatment.

	Lisa’s treatment was successful and she was declared “cancer-free” following a mammogram in July 2010. Subsequent mammograms, obtained twice annually, have continued to show no signs of cancer. Lisa’s goserelin was discontinued after two years; she will remain on tamoxifen indefinitely while being followed with semi-annual blood work.

	In March 2012, Lisa underwent endometrial biopsy after reporting to her OB-GYN with bleeding, despite having experienced menopause some two years prior. While her biopsy was negative for malignancies, Lisa will undergo robotic-assisted total hysterectomy with bilateral oophorectomy on June 26. According to her OB-GYN, the bleeding is most likely related to her tamoxifen treatment, and the procedure is being undertaken to prevent the development of endometrial and ovarian malignancies.

Whether surgically or medically induced, early menopause forces women to deal with a host of emotional, physical, and practical issues.

	As Lisa discovered, dealing with cancer is difficult enough without having to cope with the effects of treatment. And while most of those effects are temporary, menopause caused by medical or surgical interventions is a permanent reality.

	While natural menopause typically occurs at about age 51, and after a gradual transition, medically or surgically induced menopause can occur at any age and is much more abrupt. When surgically induced (bilateral oophorectomy), menopause occurs immediately and the abrupt decline in estrogen, progesterone, and androgen can cause symptoms (eg, hot flashes, vaginal dryness, difficulty sleeping, mood swings) that are significantly more severe than those experienced with natural menopause. When menopause is caused by medical interventions (various chemotherapy agents and pelvic radiation that damages both ovaries), there may be a brief transition while the ovaries gradually cease production of hormones.

	Indeed, women who experience induced menopause tend to require treatment for menopause-related symptoms more often—and sometimes for longer durations and at higher doses&mdash;than those who reach menopause spontaneously. Because cancer patients or surivors may be unable or unwilling to take hormonal medications, oncology clinicians need to be well-versed in the various nonhormonal treatments currently available for menopauserelated symptoms, or should consider referral to a practitioner with such expertise.

	Additionally, early or premature menopause (before age 40) puts women at increased risk for a number of conditions, such as osteoporosis, that were once kept at bay by normal production of estrogen. As with menopause-related symptoms, medical professionals need to be well-informed about a br oad range of pharmaceutical agents and lifestyle choices with the potential to help prevent and treat these conditions.

	Whether surgically or medically induced, early menopause forces women to deal with a host of emotional, physical, and practical issues—all in addition to the original diagnosis. While those who experience natural menopause often come to accept it as a new phase of life, the emotional consequences of early menopause can be quite different. Younger women like Lisa frequently express concerns about becoming “old before their time” or losing their femininity. For some of these women, the reality of being unable to bear children can be devastating.

	Ensuring that women fully understand the risk of early menopause both prepares women emotionally for the life transition and allows those concerned about reproduction to explore fertility preservation options. Furthermore, referral to a trusted source of information and support, such as The North American Menopause Society (

), a world leader in menopause information and education, can be invaluable in helping patients cope effectively, and as a resource for clinicians who want to learn more.

Breast Cancer and Early-Onset Menopause

	In summer 2008, Roman Catholic parish priest Father Arthur Humphrey presented with a hemorrhagic pigmented lesion on his back. Three months after the lesion was removed, he developed right arm lymphadenopathy and underwent surgical resection followed by interferon therapy (Kirkwood regimen) for one year.

	Two years after his initial diagnosis and six months after completion of his chemotherapy, Father Humphrey was referred to the John Theurer Cancer Center in Hackensack, New Jersey. When imaging studies revealed further metastasis, this time to the lung and brain, he underwent exploratory right thoracoscopy, right thoracotomy, and a superior segmentectomy. In March 2011 he began a combined regimen of oral thalidomide (Thalomid), oral temozolomide (Temodar), and IV docetaxel (Taxotere).

	After his first cycle of chemotherapy, Father Humphrey developed neutropenia. He was treated with filgrastim (Neupogen) and monitored closely, and continued with the regimen with no subsequent issues. However, in May 2011, computed tomography of the chest, abdomen, and pelvis revealed progressive disease, and the decision was made to switch him to the immunotherapeutic agent Yervoy (ipilimumab; IV infusion [3 mg/kg] every 21 days for 4 cycles), which had just been approved for the treatment of metastatic melanoma. He tolerated the treatment well despite experiencing an atypical immune response/reaction after his fourth infusion, and has subsequently been able to undergo two maintenance treatments with Yervoy.

	In June 2011, an MRI revealed multiple intercranial brain metastases, and Father Humphrey was started on whole-brain radiation. It was also during this regimen that Father Humphrey fell and fractured his right ankle. His ankle was casted and he was confined to a wheelchair until undergoing surgical repair with insertion of a plate and screws.

	As of spring 2012, Father Humphrey is showing a promising response to Yervoy. He is currently seen for blood work every two weeks, and will be followed with imaging studies every six months (more frequently if he becomes symptomatic) while continuing to receive Yervoy maintenance treatments every three months per patient tolerability and physician’s orders.

	Melinda S. Weber, RN, MS, APN, AONC, C-APN, manager, John Theurer Cancer Center, helped prepare, educate, and support Father Humphrey throughout his treatments.

	Weber recalled that Father Humphrey tolerated the thalidomide/ temozolomide/docetaxel combination well, despite the transient neutropenia, noting only that the treatment caused fatigue. “The oral medications are taken at bedtime because of their tendency to cause fatigue, and the temozolomide typically causes nausea,” said Weber. She also noted that some patients undergoing this regimen experience docetaxel infusion reactions, which can be quite overwhelming. To avert such reactions, patients are pretreated with oral dexamethasone (Decadron). The nursing staff also careful to prepare patients for the possibility of such reactions.

	Father Humphrey’s ankle injury was a source of concern. “We needed to make sure that nothing about his ankle fracture, surgery, or the healing process would in any way interfere with the treatment. This was especially important as it related to the ipilimumab, which is such a new drug,” Weber said. She contacted medical experts and was assured that nothing with the injury or its treatment would pose any such problems.

	Father Humphrey described his Yervoy treatment as “very tiring,” recalling the difficulty breathing, swollen eyes, and abdominal rash that accompanied the immune reaction that occurred during his fourth infusion. Treatment with diphenhydramine (Benadryl) and hydrocortisone halted the reaction, but Father Humphrey was unable to continue with his final infusion. He was, however, able to undergo his planned maintenance treatments.

	This reaction notwithstanding, Weber noted that Father Humphrey has actually tolerated the Yervoy treatment quite well. He hasn’t experienced any of the serious immune-related effects associated with Yervoy, including immune-mediated enterocolitis, which can result in life-threatening diarrhea.

	Other potential adverse effects include immunemediated ocular manifestations, dermatitis, neuropathies, hepatitis, and endocrinopathy issues, all of which necessitate continual medical assessment and possible interventions, as well as a battery of blood work obtained prior to each infusion to assess for potential complications. Weber explained that symptoms—such as fatigue, headache, and changes in mental status&mdash;can sometimes be vague. “We grade all toxicities that occur and treat affected patients immediately as appropriate and continue to monitor them closely.”

	She noted that there is a “flip side” to these potentially dangerous toxicity profile. “When patients experience adverse effects from conventional chemotherapy, symptoms are treated but we essentially need to let them run their course until the nadir has passed and healing and resolution has occurred. On the other hand, Yervoy’s immune-related toxicities yield rapid resolution of symptoms because even the serious adverse effects of the drug can be reversed relatively quickly with the appropriate prednisone dosing and medical monitoring.”

	Father Humphrey said the Yervoy treatment appears to be working and has few complaints, other than some itching “underneath the skin” and some difficulty with the twice-monthly blood draws, which have been painful. He realizes that he’s fortunate to be receiving Yervoy “boosters,” which are not currently FDA-approved. Weber explained that Yervoy is currently approved for only four cycles of treatment, but that anecdotal evidence and scientific rationale has led some experts to believe that maintenance “boosters” given every 3 months will improve long-term survival.

After a long fight with melanoma, the Roman Catholic parish priest Father Arthur Humphrey was able to receive the immunotherapeutic agent Yervoy, which greatly improved his prognosis. 

Metastatic Melanoma: Timely Approval of Yervoy

		Right: Antonia Reyes with her husband, Billy, and her son, Anthony.

	Antonia Reyes was 39 years old and 18 weeks pregnant when, on July 24, 2006, she was admitted to Hackensack University Medical Center (HUMC) in New Jersey after a sudden-onset severe headache and apparent seizure followed by disorientation and left-sided weakness. Had she not been pregnant, Antonia would have undergone magnetic resonance imaging (MRI) with contrast and, depending upon the results, been treated with immediate surgical resection followed by chemotherapy and radiation.

	Instead, she had an MRI without contrast that revealed an apparent glioma (suspected to be an astrocytoma) in the right temporal-parietal lobe region. After 1 week, Antonia was discharged home on anti-seizure medication, returning for twice-monthly neurological evaluations and fetal monitoring until her November 15 C-section. Despite being moderately aggressive, astrocytomas are relatively slow-growing; the decision to postpone treatment was based on best evidence that such a delay would not place her at risk.

	The day after Antonia’s C-section, an MRI with contrast produced findings highly suspicious for a glioma, while more clearly delineating its right temporal-parietal location. Surgical resection was done on December 18. When postoperative MRI indicated that most, but not all, of the tumor had been resected, the decision was made to reoperate. Astrocytomas grow by infiltrating the brain, and residual astrocytoma cells remain even with a “clean” postoperative MRI; consequently, complete resection, as indicated by MRI, was Antonia’s best chance for survival and optimal quality of life.

	After her second surgery, a repeat MRI showed that all visible signs of the tumor were gone. She was discharged on Christmas Eve, after which she experienced mild pain, fatigue, and headaches. Two weeks later, pathology results confirmed the diagnosis of anaplastic (grade III) astrocytoma.

	On February 5, Antonia started the following combined temozolomide (Temodar)-radiation regimen:

		Low-dose (75 mg/m2), once-nightly oral temozolomide for 6 weeks in conjunction with daily radiation therapy, followed by a 4-week rest period, and

		Full-dose (150 mg/m2), followed by 200 mg/m2 once-nightly temozolomide, 5 days/week every 28 days for 19 weeks.

	Adverse effects included mild nausea, constipation, and stomach pain. Fatigue (primarily from the radiation) was sometimes extreme and, as is typical, worsened later in the day and during the latter portion of the radiotherapy regimen. Platelets and white blood cells were checked each week throughout treatment.

	The use of temozolomide for grade III astrocytomas was controversial in 2007 and remains so today, as all of the data on the drug are from studies of patients with grade IV tumors (glioblastomas). While some oncologists would opt to treat such patients with radiation alone, using temozolomide only in the event of a recurrence, gross resection followed by this relatively aggressive but well-tolerated combined modality is, today, considered prudent by most neuro-oncologists, especially since patients with anaplastic astrocytomas almost always relapse 2 to 5 years post-treatment.

	Antonia has now been in remission for over 5 years and her MRIs remain completely clean. Seizure-free since her first hospital admission, she is now off all medication and is doing her best to cope with hot flashes from medically induced menopause, which began shortly after treatment. Her occasional right-sided “ice cream headaches,” loss of balance, and minor episodes of forgetfulness are likely late post-radiation complications of vasculopathy, seen in a number of patients years after treatment, and may plateau or become slowly progressive. Most recently, Antonia was told that her MRIs, obtained every 3 months since surgery, will now be needed only twice yearly.

	Antonia’s pregnancy added layers of complexity to the already dire situation of a young woman with an infiltrative brain tumor. While in some cases, pregnant women can begin chemotherapy without risk to the fetus, it is unclear whether temozolomide adversely affects fetal brain development; therefore, Antonia’s preoperative nursing care consisted of close neurological monitoring along with developmental monitoring of the fetus.

	Antonia greatly appreciated the encouragement she received from her surgical intensive care unit (SICU) nursing team and, in particular, Jennifer Lee, RN. In an interview with 

, Lee said, “The unknown is frightening, and a nurse’s explanation of what’s happening and why puts patients at ease.” She added that Antonia’s steady stream of visitors—thanks to the SICU’s open visitation policy&mdash;undoubtedly had a positive impact on her recovery.

	Lee described her nursing duties as primarily standard-of-care neurologic monitoring (eg, pupil reaction, signs of weakness, orientation, ability to follow commands), initially performed every 2 hours, and then every 4. Antonia’s C-section 1 month prior did not alter her nursing care; adjustments in medications might have been needed had she been breast-feeding.

	While significant from Antonia’s perspective, Lee explains that it is not unusual for a patient to undergo a second surgical procedure so quickly, and that postoperative care tends to remain essentially unchanged. Once neurologically and clinically stable, patients like Antonia are typically transferred from the SICU, where the patient-to-nurse ratio is 2:1, to the immediate care unit, where this ratio more closely resembles that on a regular medical-surgical unit. At this point, patients are reassured and prepared for the change in their care routine.

Antonia Reyes was 39 years old and 18 weeks pregnant when an MRI revealed an apparent glioma in the right temporal-parietal lobe region.

Surviving Brain Cancer During Pregnancy

		Multiple myeloma patient Doug Rickert [right], with Ann McNeill, RN, MSN, APN, from the John Theurer Cancer Center multiple myeloma team.

	In 2001, Doug Rickert, a 46-year-old industrial management consultant and married father of 3, heard the life-altering words, “softball-sized tumor pressing against your spinal canal.”

	The tumor had been detected on an MRI, and, a subsequent biopsy at Hackensack University Medical Center (HUMC) revealed Doug had multiple myeloma. HUMC medical oncologist Andrew Jennis, MD, told Doug that while incurable, his cancer was manageable with a regimen that began with radiation, moved on to enrollment in a clinical trial of thalidomide (Thalomid), and also required treatment with several other drugs, including dexamethasone (Decadron), zoledronic acid (Zometa), and valacyclovir HCl (Valtrex). Ultimately, the goal was to prepare Doug for a stem cell transplant.

	Doug soon began a treatment course at HUMC (now the John Theurer Cancer Center) that would last 9 years. He knew that his family—his wife, 2-year-old son, and twin 5-year-old daughters&mdash;would be his inspiration during what would be a very literal fight for his life. What Doug didn’t yet know, but would soon realize, is that his nurses would be his lifeline.

		Multiple Myeloma: A Patient’s Treatment Journey

			January 2002: Enrollment in thalidomide (Thalomid) trial

			June 2002: Peripheral stem cell transplant

			July 2002: Beginning of 18-month remission

			December 2004: Thalidomide regimen reinitiated after relapse

			July 2006: Thalidomide replaced with lenalidomide (Revlimid); zolpidem (Ambien) added to aid with sleep

			October 2006: Temporary interruption of access to lenalidomide, necessitating return to thalidomide protocol before reinstatement of access to lenalidomide

			December 2006: Remission achieved and maintained for 25 months

			May 2009: Relapse and subsequent enrollment in carfilzomib trial; duloxetine HCl (Cymbalta) added to help control neuropathy

			August 2010: Remission achieved and maintained for 3 months

			December 2010-present: Entry into carfilzomib trial and subsequent maintenance regimen

	Only 7 days after his diagnosis, Doug began the regimen recommended by Dr. Jennis. This was only the first leg of Doug’s long treatment journey (see “Multiple Myeloma: A Patient’s Treatment Journey”), which would eventually lead to his enrollment in a clinical trial of carfilzomib (see 

), a selective, next-generation proteasome inhibitor that Doug is currently receiving in maintenance therapy.

	Without hesitation, Doug credits his nurses with seeing him through every twist and turn along the way, citing the compassion and take-charge attitude of those who cared for him during treatment, and the extraordinary knowledge and concern of those who prepared him for every eventuality of his drug regimens and trial protocols.

	A nurse named Anne Marie, who worked with Dr. Jennis, made a particularly strong impression on Doug early in the course of his treatment. “I really was astounded by the extent of her expertise and was truly touched by her compassion. In every way she was a true extension of my doctor, and was always there to answer questions, solve problems, and allay my concerns—something I’ve seen time and time again over the years.”

	It was, in fact, that combination of expertise and compassion that Doug needed and received during his first week-long hospitalization, when he got a taste of an unfamiliar and unpleasant feeling: helplessness. “Any movement was painful, and I was fighting the nurses who were trying to move me from the gurney to my bed,” he says. “Finally, one of the nurses looked me right in the eye and told me that I simply needed to stop. I still remember her saying, ‘This is what we need to do, and this is how we’re going to do it.’ At that moment I just let her take charge and do what needed to be done. It was actually a relief to give over that momentary control to someone who knew what she was doing.”

		Multiple myeloma patient Doug Rickert celebrates Father’s Day 2002 with his son and twin daughters after undergoing peripheral stem cell transplantation. He carries this photo in his briefcase to this day.

	Doug credits a number of nurses with helping him to navigate the clinical trial process, but is especially grateful to Multiple Myeloma Division Oncology Research Nurse Coordinator Laura McBride, RN, BSN, OCN®, CCRP, who he says took great pains to make sure he knew what to expect. “We do all we can to inform our clinical trial patients about known treatment effects,” she says, “but equally important is our ability to make patients understand that we don’t always know all the short- and long-term adverse effects associated with a particular drug in an early-phase trial; hence, the reason the drug is being studied.” It is because of this uncertainty, says McBride, that the research team makes every effort to forge a true partnership with clinical trial patients, and to give each patient a go-to person for questions and concerns. “There’s no doubt that Doug’s optimism and upbeat attitude helped him through the process,” she says.

	Doug’s memories of his clinic visits during preparation for his stem cell transplant are just as vivid. “Back then the process was sterile and lonely, with virtually no visitors allowed,” he says. He recalls the tedium of the daily trips between his HUMC patient apartment and the clinic, where he spent 8 hours each day, and also recalls the attentiveness of his nurses and the way they walked him through each step of the process and made certain he knew what to expect. “I was lucky that I tolerated almost all of my treatments very well and didn’t experience most of the side effects I was told about,” he says. “But knowing what might happen gave me a sense of control.”

		Carfilzomib, a selective, next-generation proteasome inhibitor that has demonstrated encouraging response rates and tolerability in patients with advanced multiple myeloma, was granted orphan drug status by the FDA in 2008. In December 2010, positive results from a phase IIb 003-A1 study of single-agent carfilzomib for patients with relapsed and refractory multiple myeloma were announced. Only a month later, in January 2011, the drug was granted fast-track designation by the FDA, giving hope to the more than 50,000 US residents currently living with this second most common hematologic cancer, as well as to the 20,000 diagnosed with the disease each year.

		Through the fasttrack designation, Onyx Pharmaceuticals has initiated a rolling submission of a new drug application (NDA) for possible accelerated approval. With the nonclinical section of the NDA already submitted, Onyx hopes to complete submission as soon as possible.

		Currently, the “Carfilzomib Development Program” includes a large, international, randomized phase III trial (ASPIRE), in which investigators are studying the combination of lenalidomide (Revlimid) and low-dose dexamethasone (Decadron) with and without carfilzomib in patients with relapsed multiple myeloma. A second phase III trial (FOCUS) is being conducted in Europe, and involves analysis of carfilzomib in patients with relapsed and refractory disease. An investigator-sponsored program is also evaluating the drug as a first-line multiple myeloma treatment, in combination studies, and to treat lymphoma and other malignancies.

David S. Siegel, MD, PhD, chief, Multiple Myeloma at John Theurer Cancer Center discusses the FDA approval process for Carfilzomib

	Throughout it all, Doug kept a promise to himself to never “play the cancer card” or use his illness as an excuse. “That would have gotten me nowhere,” he says.

	Indeed, it’s Doug’s optimism and positive attitude that John Theurer multiple myeloma team member Ann McNeill, RN, MSN, APN, admires most about the patient she first met in 2005. “I’m a firm believer in the role that emotions and attitude play in coping with a cancer diagnosis,” she says. “Doug’s attitude has always been positive, and there’s no doubt that his optimistic outlook has been an asset.”

	McNeill goes on to note that frequent office visits, scheduling of diagnostic tests, undergoing treatment, and dealing with adverse effects can all be extremely challenging, adding that patients and family members often seek out nurses to answer their questions and allay their concerns. “Supporting our patients by clearly outlining treatment plans, providing calendars that delineate those plans, and providing assistance in making follow-up appointments will likely help to reduce anxiety,” she says.

	Doug, who is especially grateful to McNeill for an unrivaled level of compassion and accessibility, says he was able to essentially carry on with his life and work because he knew what to expect throughout the course of his treatments. “When patients are educated about their medications and their potential adverse effects, they’re more likely to comply with the treatment regimen,” says McNeill. “Open communication is the key.”

	Today, Doug isn’t always sure whether his aches and pains are due to his myeloma or to the fact that he’s now nearly a decade older than when he began his journey. He has neuropathy but overall “feels great” and has hope for the future. He does his best to encourage others just beginning the struggle that he now knows so well, and also attends multiple myeloma fundraisers and volunteers his services at a local blood bank.

	At home, Doug’s cancer is rarely a topic of discussion. “My hospital bracelet is the only clue that I’ve been at the clinic for treatment,” he says. “I don’t want anyone to make a fuss. It’s just a fact of life, a necessary evil.”

	Even so, Doug allows himself a small indulgence in the form of a now-wrinkled photo he keeps in his briefcase. “It was Father’s Day 2002 and just about a week after my transplant when the kids were given special permission to visit. Their smiling faces, along with my sunglasses and headphones, remind me that life went on even then, and certainly goes on now. It’s all about attitude, and it’s all about hope.”

In 2001, Doug Rickert, a 46-year-old industrial management consultant and married father of 3, heard the life-altering words, "softball-sized tumor pressing against your spinal canal." 

Laura Bruck