Alaska Oncology

Some Squamous Cell Skin Cancers Are Deadly

Wed, 19 Jun 2013 00:01:54 +0000

Cutaneous squamous cell carcinoma is usually easily treated with surgery; however, a subsection of patients with specific disease risk factors are more likely to develop metastases and die from the disease, according to the results of a study published in JAMA Dermatology.

Squamous cell carcinoma accounts for roughly 20% of all cases of non-melanoma skin cancer. Squamous cell carcinoma commonly involves the head or neck. The tumor may appear as a red bump or as a rough or scaly area on the skin. Squamous cell carcinoma is more likely than basal cell carcinoma to spread to lymph nodes or distant parts of the body, though this happens infrequently. Treatment of squamous cell carcinoma often involves surgery to remove the cancer.

The prognosis for cutaneous squamous cell carcinoma (CSCC) is usually good, but some patients have poor outcomes. To identify factors associated with poor outcomes, researchers conducted a 10-year retrospective cohort study that included 985 patients and 1,832 tumors. The majority of patients (73.3%) had one tumor, 21.2 percent of patients had two to four tumors, and a small percentage of patients had more than four tumors. Most (69.5%) were treated with standard excision and 20.2 percent were treated with Mohs surgery.

The data revealed that 4.6 percent of patients experienced local recurrence, 3.7 percent developed metastases, and 2.1 percent died from the disease. Upon analysis, one consistent predictor of poor outcome was tumor size of 2 cm or more. Multivariate risk analysis revealed that several specific disease factors were associated with metastasis and disease-specific death:

Risk Factors Associated with Metastasis	Risk Factors Predictive of Disease-Specific Death
Tumor diameter greater than 2 cm	Tumor diameter greater than 2 cm
Poor differentiation	Poor differentiation
Invasion beyond the subcutaneous fat	Invasion beyond the subcutaneous fat
Tumor location on the temple or ear	Perineural invasion
	Tumor location on the temple or ear
	Anogenital location of tumor

The researchers hope that identifying these risk factors will help with treatment decision-making. Prognosis worsens once local or distant metastasis occurs, so identifying patients who are at high risk would allow more aggressive treatment from the outset.

Reference:

Schmults CD, Karia PS, Carter JB, et al. Factors predictive of recurrence and death from cutaneous squamous cell carcinoma: A 10-year, single-institution cohort study. JAMA Dermatology. 2013;149(5):541-547.

Longer-Term Tamoxifen Improves Breast Cancer Outcomes

Wed, 19 Jun 2013 00:01:28 +0000

For women with early-stage, estrogen receptor-positive (ER-positive) breast cancer, ten years of adjuvant tamoxifen appears to be more effective than the standard five years. These results were presented at the 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO).

Tamoxifen is a hormonal therapy that interferes with the effects of estrogen. It is commonly used in the treatment of ER-positive breast cancer, and is also used to reduce the risk of breast cancer in women at high risk of the disease. For women with early-stage breast cancer, that standard duration of treatment with tamoxifen is five years.

To assess whether ten years of treatment with tamoxifen is more effective than five years of treatment, researchers in the UK conducted a Phase III clinical trial (the aTTom trial).[i] The study enrolled 6,953 women with ER-positive breast cancer. After five years of treatment with tamoxifen, women were randomly assigned to either stop taking tamoxifen or to continue it for another five years.

A majority of women have now been followed for more than 10 years, and some have been followed for up to 20 years.

10 years of tamoxifen reduced the risk of breast cancer recurrence. A recurrence occurred in 16.7% of women treated with 10 years of tamoxifen and 19.3% of women treated with 5 years of tamoxifen. Longer-term treatment also reduced the risk of dying of breast cancer. These benefits became apparent during the second decade after breast cancer diagnosis.
Longer-term treatment with tamoxifen did increase the risk of endometrial cancer (cancer of the lining of the uterus). Endometrial cancer can often be detected early. Furthermore, the researchers estimated that for every endometrial cancer death that occurred with longer-term tamoxifen, 30 breast cancer deaths would be prevented. The researchers concluded that the benefits of longer-term tamoxifen greatly outweigh the risks.

These results are consistent with another large clinical trial, the ATLAS study, which also found a benefit of longer-term tamoxifen.[ii] Together, these studies indicate that 10 years of tamoxifen is more effective than 5 years of tamoxifen for women with early-stage, ER-positive breast cancer.

References:

[i] Gray RG, Rea D, Handley K et al. aTTom: Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 in 6,953 women with early breast cancer. Presented at the 49^th Annual Meeting of the American Society of Clinical Oncology. May 31-June 4, 2013; Chicago, IL. Abstract 5

[ii] Davies C, Pan H, Godwin J et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomized trial. Lancet. 2013;381:805-816.

ASTRO and AUA Issue Joint Guideline for Radiation After Prostate Surgery

Wed, 19 Jun 2013 00:01:20 +0000

The American Society for Radiation Oncology (ASTRO) and the American Urological Association (AUA) have issued a joint guideline regarding the use of radiation therapy after prostatectomy. It marks the first time the two medical organizations—most responsible for prostate treatment—have issued a joint guideline.

The 81-page document—a collaborative effort of many experts in the field—is a comprehensive review of 324 studies conducted between 1990 and 2012. The guideline is available online free as a PDF document and will be published in the August 1, 2013, print issue of the International Journal of Radiation Oncology • Biology • Physics (Red Journal), the official scientific journal of ASTRO, and in the August 2013 print issue of The Journal of Urology, the official journal of the AUA.

The purpose of the guideline is to provide a clinical framework for the use of radiation after prostatectomy in patients with and without evidence of prostate cancer recurrence. The guidelines offer nine major statements, which fall into four different categories:

Clinical principles (wide agreement by urologists)
Recommendations (grade C; low-quality and certainty evidence)
Standards (grade A or B; high/moderate-quality and certainty evidence)
Options (nondirectives)

Due to lack of compelling data, only one of the statements has an evidence strength of grade A (high quality, high certainty). In other words, the guideline’s statements are based mostly on less certain data or on expert opinion. Still, the panel hopes that the guidelines provide a practical approach to help guide clinicians in decision-making that will result in the best patient outcomes.

Reference:

Thompson IM, Valicenti R, Albertsen PC, et al. Adjuvant and Salvage Radiotherapy after Prostatectomy: ASTRO/AUA Guideline. Available at: http://www.auanet.org/education/guidelines/radiation-after-prostatectomy.cfm

Oncotype DX® Predicts Recurrence in Patients with DCIS

Tue, 18 Jun 2013 00:01:55 +0000

The Oncotype DX® DCIS Score predicts the 10-year risk of local recurrence, defined as recurrence of DCIS or invasive breast cancer in the same breast, and can help guide radiation treatment decision-making for women with DCIS who are treated with breast-conserving surgery, according to the results of a study published in the Journal of the National Cancer Institute.

Ductal carcinoma in situ refers to a condition in which abnormal cells are found within a breast duct but have not spread outside of the duct to other tissues in the breast. It is most commonly detected by screening mammography. If not treated, some cases of DCIS may progress to invasive breast cancer. More than 50,000 patients are diagnosed with DCIS each year.

Treatment for DCIS may involve breast-conserving surgery (lumpectomy) or mastectomy. For DCIS patients who choose breast-conserving surgery, additional treatment with radiation therapy has been shown to reduce the risk of recurrence, but may not be necessary for all women. If the characteristics of the DCIS suggest that it is unlikely to recur, surgery alone (without radiation therapy) may be an option.

The Oncotype DX breast cancer test was originally developed to provide information about recurrence risk and need for chemotherapy to certain groups of women with early-stage, invasive breast cancer. To determine whether the test can also predict recurrence risk in women with DCIS, researchers developed a DCIS Score that can be generated by the test. To evaluate whether the DCIS Score could predict recurrence risk, researchers analyzed 327 DCIS tumor samples from women with DCIS who had participated in an earlier clinical trial of DCIS treatment. The women had been treated with breast-conserving surgery but had not received radiation therapy.

The study validated that the Oncotype DX DCIS Score predicted 10-year local recurrence (DCIS or invasive carcinoma) based on a patient’s individualized underlying tumor biology, regardless of whether adjuvant tamoxifen was given. Based on the DCIS Score, women were classified as low, intermediate, or high risk. The results indicated that 70 percent of patients had a low DCIS Score and may be able to forego radiation therapy. Compared with patients whose tumor had an intermediate or high DCIS Score, patients with a low DCIS Score had a significantly lower likelihood of a local recurrence at 10 years (about 11 percent vs. 26 percent, respectively). The table below shows specifics:

Table 1: DCIS Score and Risk of DCIS Recurrence or Invasive Carcinoma

	Low Risk	Intermediate Risk	High Risk
10-year risk of developing local recurrence of DCIS	10.6%	26.7%	25.9%
10-year risk of developing invasive carcinoma	3.7%	12.3%	19.2%

The researchers found that the DCIS Score was predictive of local recurrence across patient subgroups regardless of lesion size, grade, surgical margins, or menopausal status. They concluded that the DCIS Score quantifies the risk of local DCIS recurrence and invasive carcinoma. They note that the Oncotype DX DCIS Score provides a new tool that will help physicians and patients make more informed treatment decisions.

Reference:

Solin LJ, Gray R, Baehner FL, et al. A multigene expression assay to predict local recurrence risk for ductal carcinoma in situ of the breast. Journal of the National Cancer Institute. 2013; 105(10): 701-710.

Use of Radiation to Treat Axillary Lymph Nodes Reduces Lymphedema Risk in Early Breast Cancer

Tue, 18 Jun 2013 00:01:42 +0000

For women with early-stage breast cancer and a positive sentinel lymph node, use of radiation—rather than surgery—to treat the axillary lymph nodes appears to be effective and to have a lower risk of lymphedema. These results were presented at the 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO).

For women with early breast cancer, determining whether the cancer has spread to the axillary (under the arm) lymph nodes is an important part of cancer staging. Evaluation of the axillary nodes often involves a sentinel lymph node biopsy. The sentinel nodes are the first lymph nodes to which cancer is likely to spread. If the sentinel nodes contain cancer, women often undergo more extensive lymph node surgery (axillary lymph node dissection). A common side effect of axillary lymph node surgery is lymphedema of the arm—swelling of the arm due to an accumulation of lymph fluid.

To evaluate a different approach to treating the axillary lymph nodes, researchers in Europe conducted a Phase III clinical trial (the AMAROS trial). The study included 1,425 women with early-stage breast cancer and a positive sentinel lymph node (a sentinel lymph node that contained cancer). Women underwent additional lymph node treatment with either surgery or radiation therapy.

Five-year overall survival was 93.3% among women who underwent lymph node surgery and 92.5% among women who received radiation to the lymph nodes. Survival without a cancer recurrence was 86.9% with surgery and 82.7% with radiation. These differences between study groups did not meet the criteria for statistical significance, suggesting that they could have occurred by chance alone.
Lymphedema was less common among women in the radiation group. During the first year after treatment, lymphedema developed in 40% of the women who had lymph node surgery and 22% of women who had radiation to the lymph nodes. The frequency of lymphedema decreased during subsequent years, but continued to favor radiation: at five years, 28% of women in the surgery group and 14% of women in the radiation group had lymphedema.

This study suggests that radiation therapy to the lymph nodes may be an alternative to lymph node surgery for selected women with early-stage breast cancer. The two treatment approaches appear to have similar effectiveness, but radiation therapy may be less likely to cause lymphedema.

Reference: Rutgers EJ, Donker M, Straver ME et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer patients: final analysis of the EORTC AMAROS trial (10981/22023). Presented at the 49^th Annual Meeting of the American Society of Clinical Oncology. May 31-June 4, 2013; Chicago, IL. Abstract LBA1001.

Nexavar Shows Promise Against Aggressive Thyroid Cancers

Mon, 17 Jun 2013 00:01:45 +0000

The targeted drug Nexavar® (sorafenib) delays the growth of treatment-resistant, differentiated thyroid cancers. These results—from a Phase III clinical trial—were presented at the 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO).

Differentiated thyroid cancer is the most common type of thyroid cancer and can often be cured with surgery and radioactive iodine (RAI) treatment. In some cases, however, the cancer is resistant to RAI. RAI-resistant thyroid cancers have had few effective treatment options.

Nexavar is taken orally and targets certain proteins that contribute to cancer growth. It is used to treat advanced kidney cancer and inoperable liver cancer.

To evaluate Nexavar in the treatment of thyroid cancer, researchers conducted a Phase III trial (the DECISION trial). The study enrolled 417 patients with metastatic, RAI-resistant, differentiated thyroid cancer. Patients were treated with either Nexavar or a placebo.

Progression-free survival (survival without a worsening of the cancer) was 10.8 months in the Nexavar group and 5.8 months in the placebo group.
Tumor shrinkage of at least 30% occurred in 12% of patients in the Nexavar group and less than 1% of patients in the placebo group.
The disease control rate (tumor shrinkage or stable disease for at least six months) was 54% in the Nexavar group and 34% in the placebo group.

These results suggest that Nexavar almost doubles progression-free survival among patients with treatment-resistant, metastatic, differentiated thyroid cancer. If Nexavar is approved for this type of cancer, it would be the first new drug in decades to demonstrate effectiveness for this group of patients.

Reference: Brose MS, Nutting C, Jarzab B et al. Sorafenib in locally advanced or metastatic patients with radioactive iodine-refractory differentiated thyroid cancer: The phase III DECISION trial. Presented at the 49^th Annual Meeting of the American Society of Clinical Oncology. May 31-June 4, 2013; Chicago, IL. Abstract 4.

FDA Approves Xofigo for Advanced Prostate Cancer

Mon, 17 Jun 2013 00:01:17 +0000

The U.S. Food and Drug Administration (FDA) has approved Xofigo® (radium Ra 223 dichloride) to treat men with metastatic, hormone-refractory prostate cancer that has spread to bones but not to other organs. It is intended for men whose cancer has spread after receiving medical or surgical therapy to lower testosterone.

Prostate cancer is a hormonally sensitive disease that can often be controlled for long periods with androgen-deprivation therapy (ADT). When prostate cancer stops responding to this treatment, it is referred to as hormone-refractory prostate cancer. Metastatic hormone-refractory prostate cancer is a challenging form of the disease to treat because the cancer has spread to distant sites in the body and does not respond to treatment with standard hormonal therapy.

Xofigo is a radiopharmaceutical agent that binds with minerals in the bone to deliver radiation directly to bone tumors, thereby limiting the damage to the surrounding normal tissues.

The approval was based on the results of a clinical trial that included 809 men with symptomatic hormone-refractory prostate cancer that had spread to bones, but not other organs. Patients were randomly assigned to receive Xofigoor a placebo plus standard treatment. The results indicated that men who received Xofigo lived a median of 14 months, compared to a median of 11.2 months for the ment in the placebo group. An updated analysis has confirmed that Xofigo can extend overall survival.

The most common side effects associated with Xofigo were nausea, diarrhea, vomiting and swelling of the leg, ankle or foot. The most common abnormalities detected during blood testing included low levels of red blood cells (anemia), lymphocytes (lymphocytopenia), white blood cells (leukopenia), platelets (thrombocytopenia) and infection-fighting white blood cells (neutropenia).

Xofigo was approved as part of the FDA’s priority review program, which allows an expedited six-month review of drugs that may offer major advances in treatment. The drug was approved more than three months ahead of the goal date.

Reference:

FDA approves new drug for advanced prostate cancer. [FDA News Release]. U.S. Food and Drug Administration website. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm352363.htm

Genomic Testing May Reduce Medical Costs for Colon Cancer

Fri, 14 Jun 2013 00:01:28 +0000

Use of the Oncotype DX® colon cancer test to guide treatment decisions may reduce medical costs and improve patient well-being. These results were presented at the 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO).

The Oncotype DX colon cancer test evaluates 12 genes in a sample of tumor tissue and generates a Recurrence Score. The Recurrence Score provides information about the likelihood of cancer recurrence, and may help guide decisions about the need for adjuvant (post-surgery) chemotherapy.

Previous economic analyses reported that use of the test should both save money and improve patient well-being. To further evaluate these outcomes, researchers estimated costs and outcomes for patients with Stage II, T3 colon cancer before and after knowledge of the Oncotype DX test results. The analysis made use of information from 141 patients in the Mayo Clinic Cancer Research Consortium.

After the receiving the test results, physicians were less likely to recommend adjuvant chemotherapy.
Overall, average total direct medical costs decreased by $1,683
Patients experienced a modest improvement in quality of life

This study confirms that use of the Oncotype DX colon cancer test changes treatment decisions and reduces medical costs for patients with Stage II, T3 colon cancer.

Reference: Yu T, Alberts SR, Behrens RJ et al. Real-world comparative economics of a 12-gene assay for prognosis in stage II colon cancer. Presented at the 49^th Annual Meeting of the American Society of Clinical Oncology. May 31-June 4, 2013; Chicago, IL. Abstract 3640.

Immunotherapy Combination Promising for Metastatic Melanoma

Fri, 14 Jun 2013 00:01:20 +0000

For people with metastatic melanoma, treatment with a combination of Yervoy® (ipilimumab) and Leukine® (sargramostim; GM-CSF) may result in better overall survival than treatment with Yervoy alone. These results, from a Phase II clinical trial, were presented at the 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO).

Of the more than one million new diagnoses of skin cancer each year, roughly 68,000 involve melanoma. More than 8,000 people die of melanoma each year in the United States. Melanoma is dangerous because it is more likely than other types of skin cancer to spread (metastasize) to other parts of the body.

Immunotherapy refers to treatments that activate the immune system to attack cancer cells. Yervoy, a drug approved in 2011 for the treatment of advanced melanoma, targets a molecule known as CTLA4. CTLA4 is found on the surface of T cells and is thought to inhibit immune responses. Leukine is a growth factor that is used to increase white blood cells counts after chemotherapy or stem cell transplantation.

To evaluate the effect of adding Leukine to Yervoy, researchers conducted a Phase II clinical trial among 245 patients with metastatic melanoma [i]. Study participants were treated with either Yervoy alone or Yervoy in combination with Leukine.

Tumor shrinkage rates were similar in the two study groups.
Overall survival was better among patients who received combination treatment: 69% of patients treated with both Yervoy and Leukine survived for at least a year, compared with 53% of patients treated with Yervoy alone.
Combination treatment also resulted in fewer serious side effects.

These results suggest that that adding Leukine to Yervoy may improve both the efficacy and the safety of treatment for patients with metastatic melanoma.

Reference:

Hodi FS, Lee SJ, MCDermott DF et al. Multicenter, randomized phase II trial of GM-CSF (GM) plus ipilimumab (Ipi) versus ipi alone in metastatic melanoma: E1608. Presented at the 49^th Annual Meeting of the American Society of Clinical Oncology. May 31-June 4, 2013; Chicago, IL. Abstract CRA9007.

[i] Hodi FS, Lee SJ, MCDermott DF et al. Multicenter, randomized phase II trial of GM-CSF (GM) plus ipilimumab (Ipi) versus ipi alone in metastatic melanoma: E1608. Presented at the 49^th Annual Meeting of the American Society of Clinical Oncology. May 31-June 4, 2013; Chicago, IL. Abstract CRA9007.

Maintenance Therapy with Votrient Provides Benefit in Advanced Ovarian Cancer

Thu, 13 Jun 2013 00:01:34 +0000

In a Phase III clinical trial, treatment with Votrient® (pazopanib) after initial chemotherapy improved outcomes among women with advanced ovarian cancer. These results were presented at the 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO).

Ovarian cancer is often diagnosed at an advanced stage, highlighting the importance of finding new and more effective ways of treating this stage of the disease.

Votrient is an oral drug that blocks several biological pathways involved in the growth of tumors and new blood vessels. It is used for the treatment of advanced kidney cancer and advanced soft-tissue sarcoma.

To evaluate Votrient for the treatment of ovarian cancer, researchers conducted a Phase III clinical trial among 940 women with Stage III or Stage IV ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. All of the study participants had undergone surgery and initial chemotherapy. Women were only included in the study if chemotherapy had successfully prevented their cancer from worsening.

After completion of chemotherapy, study participants received either Votrient or a placebo daily for up to two years. Treatment that is given after a patient responds to initial treatment, but before cancer progression, is called maintenance treatment.

Maintenance treatment with Votrient improved progression-free survival (survival without the cancer worsening). Progression-free survival was 17.9 months among women treated with Votrient and 12.3 months among women treated with placebo. Side effects of Votrient included high blood pressure, diarrhea, nausea, headache, and fatigue.

These results suggest that maintenance treatment with Votrient delays cancer progression among women with advanced ovarian cancer. Longer-term follow-up will provide information about the effect of Votrient on overall survival.

Reference: Du Bois A, Floquet A, Kim JW et al. Randomized, double-blind, phase III trial of pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (AEOC): results of an international Intergroup trial (AGO-OVAR16). Presented at the 49^th Annual Meeting of the American Society of Clinical Oncology. May 31-June 4, 2013; Chicago, IL. Abstract LBA5503.