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Thursday, August 25, 2016

​​Among patients with melanoma, those who received both ipilimumab (Yervoy) and local peripheral treatments such as radiotherapy or electrochemotherapy had significantly prolonged overall survival compared with those who received only ipilimumab, according to a retrospective clinical study published in Cancer Immunology Research (doi: 10.1158/2326-6066.CIR-15-0156).

"Ipilimumab is an immunotherapy that has revolutionized the treatment of malignant melanoma, a very aggressive type of skin cancer," said Sebastian Theurich, MD, Lecturer and Physician-Scientist in the Center of Integrated Oncology at the University Hospital of Cologne, Germany. "About 20 percent of patients who receive ipilimumab achieve durable responses, which is a major advance compared with historic outcomes, but physician-scientists are looking for ways to increase the percentage of patients who gain long-term benefit from this immunotherapy.

"We found that adding local peripheral treatments, including external radiotherapy, electrochemotherapy, or internal radiotherapy, to systemic ipilimumab treatment doubled survival chances in our patient cohort and did not increase immune-related side effects," Theurich continued. "Importantly, this survival advantage seemed to overcome even traditional risk factors of poor outcomes. This suggests that this combination could be an option for all patients with malignant melanoma, and this is being tested in ongoing prospective clinical trials."

Currently, local peripheral treatments are not used to try and cure patients with malignant melanoma; rather, they are used to provide relief from symptoms caused by the melanoma tumors, explained Theurich.

Theurich and his colleagues analyzed data from 127 patients with malignant melanoma who were treated consecutively at four cancer centers in Germany and Switzerland. Eighty-two patients received ipilimumab only and 45 received ipilimumab and local peripheral treatment to relieve tumor-related symptoms.

Median overall survival for patients receiving ipilimumab and local peripheral treatment was 93 weeks, compared with 42 weeks for those receiving only ipilimumab.

After excluding patients with brain metastases from the analysis, because these patients were not distributed equally among the two treatment groups, the median overall survival benefit for those receiving ipilimumab and local peripheral treatment remained—117 weeks compared with 46 weeks for those receiving only ipilimumab.

"Our results are concordant with those previously reported for 29 patients treated in the United States with ipilimumab and local radiotherapy," said Theurich. "Having data from different parts of the world improves the validity of the results, especially if you deal with retrospective analyses. Moreover, all our patients were treated with the same dose of ipilimumab, whereas those in the previous study received varying doses because they were being treated in a dose-escalation clinical trial.

"We were also able to begin to investigate the potential immunologic mechanism underlying the benefit of adding local peripheral treatment to ipilimumab," added Theurich. "It seems that local peripheral treatments activate immune cells, which are then able to attack tumors at sites away from the local treatment site. However, we are investigating this further in prospective studies."

According to Theurich, the main limitations of the study are that the data were not collected prospectively and in a randomized fashion, but the validity of the results is now being tested in prospective clinical trials.

Wednesday, August 24, 2016

​​A novel MRI method that detects low levels of zinc ion can help distinguish healthy prostate tissue from cancer, UT Southwestern (UTSW) Medical Center radiologists have determined.

Typical MRIs don't reliably distinguish between zinc levels in healthy, malignant, and benign hyperplastic prostate tissue, so discovery of the technique could eventually prove useful as a biomarker to track the progression of prostate cancer, according to researchers with the Advanced Imaging Research Center, part of UT Southwestern's Harold C. Simmons Comprehensive Cancer Center. The findings appear in the Proceedings of the National Academy of Sciences.

"This research provides the basis for differentiating healthy prostate from prostate cancer by use of a novel Zn(II) ion sensing molecule and MRI," said senior author A. Dean Sherry, PhD, Director of the Advanced Imaging Research Center and Professor of Radiology at UT Southwestern.

"The potential for translating this method to human clinical imaging is very good, and will be useful for diagnostic purposes. The method may prove useful for monitoring therapies used to treat prostate cancer," said Sherry, who is also Professor of Chemistry at UT Dallas, where he holds the Cecil and Ida Green Distinguished Chair in Systems Biology.

The majority of prostate cancers are classified as adenocarcinomas and originate in epithelial cells. The UTSW researchers initially determined that glucose stimulates release of the zinc ions from inside epithelial cells, which they could then track on MRIs. The prostate cancer tissue secreted lower levels of zinc ions, offering an opportunity to distinguish between malignant and healthy tissue. When they tested the technique on mouse models, they were able to successfully detect small malignant lesions as early as 11 weeks, making the non-invasive imaging procedure a potentially useful method for detecting the disease and its progression.

"Prostate cancer often has no early symptoms, so identifying potential new diagnostic methods that might catch the cancer at an earlier stage or allow us to track how it is progressing is an important opportunity," said co-author Neil Rofsky, MD, Chairman of Radiology, Director of Translational Research for the Advanced Imaging Research Center, and holder of the Effie and Wofford Cain Distinguished Chair in Diagnostic Imaging.

Prostate cancer is the most common cancer in men in the United States, after skin cancer, and is the second leading cause of death from cancer in men, according to the National Cancer Institute. Prostate cancer occurs more often in African-American men, who are more likely to die from the disease.

Tuesday, August 23, 2016

​Parents are more likely to support laws that would make the human papillomavirus vaccine mandatory for school entry if their state offers opt-out provisions, according to a study published in Cancer Epidemiology, Biomarkers & Prevention (doi:10.1158/1055-9965.EPI-15-1159​).

However, opt-out provisions may weaken the effectiveness of the vaccine requirements, cautioned the study's lead author, William A. Calo, PhD, JD, a Post-Doctoral Research Associate in the Department of Health Policy and Management at the University of North Carolina, Gillings School of Global Public Health.

The human papillomavirus (HPV) causes most cases of cervical cancer and a large proportion of vaginal, vulvar, anal, penile, and oropharyngeal cancers. The U.S. Centers for Disease Control and Prevention (CDC) recommend that boys and girls receive the three-dose HPV vaccination beginning at age 11 or 12. However, as of 2014, only 40 percent of girls and 22 percent of boys ages 13 to 17 had completed the HPV vaccine series, according to CDC statistics.

Calo said previous research has shown that school-entry requirements have contributed to high uptake rates for vaccinations such as Hepatitis B, Tdap, and MMR. Since 2006, half of U.S. state legislatures have introduced measures to add HPV to the list of required vaccines, however, most measures were rejected, often due to parental disapproval or ethical, political, or legal concerns, Calo said. Presently, only Virginia, Rhode Island, and the District of Columbia require the HPV vaccine for school enrollment, and all allow parents to opt out.

In order to evaluate parental support for making the HPV vaccine mandatory for school entry, Calo and colleagues, including Noel Brewer, PhD, the study's senior author, Professor of Health Behavior at the University of North Carolina, and a member of the UNC Lineberger Comprehensive Cancer Center, conducted a web-based survey of 1,501 parents between November 2014 and January 2015. To be eligible for the survey, parents had to have at least one 11- to 17-year-old child living primarily in their household. Noel Brewer

The survey stated, "Some states are trying to pass laws that would require all 11- and 12-year-olds to get HPV vaccine before they are allowed to start sixth grade." Parents were then asked whether they agreed with the statement, "I think these laws are a good idea." Overall, 21 percent of parents agreed that such laws are a good idea, and 54 percent disagreed. Twenty-five percent of respondents said they neither agreed nor disagreed with the statement; Calo said this group may benefit from public education about HPV vaccination and, as they learn about the benefits of vaccination, be more likely to support school-entry requirements.

Respondents who said they disagreed that the laws are a good idea then received this follow-up statement: "It is okay to have these laws only if parents can opt out when they want to." When the opt-out provision was added, 57 percent of respondents agreed that the school-entry requirements are a good idea, and 21 percent disagreed.

Calo cautioned that opt-out provisions could weaken the overall effectiveness of vaccination if large numbers of families opted out. "Any process for requesting an opt-out should have an educational component and encourage parents to carefully consider their decision," he said.

The study also identified several factors that influenced approval of HPV vaccine requirements. Nearly one-third (32%) of respondents felt that the vaccine was being promoted to make money for drug companies and only 40 percent felt that the vaccine was effective in preventing cervical cancer. Calo said changing some of those perceptions would be beneficial for improving HPV vaccination rates and for legislating school-entry requirements.

"HPV vaccination saves lives," Calo said. "We have an unprecedented opportunity to prevent thousands of HPV-associated cancers through vaccination and unfortunately, we are missing that opportunity."

Brewer noted the findings suggest that states should consider school-entry requirements for HPV vaccination once states have implemented other approaches that have proven successful in raising vaccination rates, such as centralizing vaccination reminders in state health departments, focusing quality-improvement visits to providers on HPV vaccination, and training physicians to use announcements to introduce vaccination.

The authors noted that a limitation of this study is that it asked about hypothetical school-entry requirements, rather than actual laws, and did not describe the scope of opt-out provisions. The researchers said parents' opinions could differ if they were discussing actual legislation, and may vary depending on whether the opt-out provisions were based on medical, religious, or philosophical reasons. ​

Thursday, August 18, 2016

​​New research out of Roswell Park Cancer Institute shows that expression of the vitamin D receptor protein may help protect against aggressive forms of breast cancer but has not yet been linked to improved patient survival. The study has been published online ahead of print in Clinical Cancer Research (doi: 10.1158/1078-0432.CCR-16-0075).

"A complex interplay exists among vitamin D, hormone receptors and the development and progression of breast cancer cells," said the study's senior author, Song Yao, PhD, Associate Professor of Oncology in the Department of Cancer Prevention and Control at Roswell Park. "This study offers new and valuable insights into the mechanisms of vitamin D and the influence this important micronutrient has on aggressive breast cancer subtypes."

Vitamin D receptor is a protein that regulates numerous genes involved in a myriad of cell functions and has been implicated in cancer. In this study, a team that included Jamila Al-Azhri, MD, a Surgical Oncologist from King Fahad Specialist Hospital, Dammam, Saudi Arabia, who at the time was a visiting physician at Roswell Park, analyzed breast tumor tissues from 1,114 female patients. They evaluated vitamin D receptor status along with tumor characteristics and hormone receptor status.

Low levels of vitamin D receptor expression were associated with more aggressive disease. "Our findings imply that vitamin D might have preventive benefits against triple-negative cancers, an aggressive breast cancer subtype," noted Yao.

The scientists also examined overall survival, progression-free survival and breast-cancer-specific survival. Despite the strong associations of low levels of vitamin D receptor with tumor characteristics, there appeared to be no association between low levels of vitamin D receptor with patient survival outcomes after a median follow-up of six years. These findings suggest that although vitamin D receptor protein levels are correlated with many characteristics of aggressive breast tumors, the associations might not be strong enough to impact patient survival.

"We speculate that the tumor vitamin D receptor levels might change throughout the course of the disease, are modified by circulating vitamin D levels, or are subject to molecular controls by vitamin D, genetic variations and other factors. Further studies are needed to elucidate the mechanisms impacting the regulation of vitamin D receptor expression in breast tumors," added Yao.

Wednesday, August 17, 2016

A first-time study published in PLOS ONE (http://dx.doi.org/10.1371/journal.pone.0157692) shows that a combined assessment of multiple types of protein biomarkers in the blood offers an important advancement for detecting early breast cancer. The study compared the ability of Serum Protein Biomarkers (SPBs) and Tumor-Associated Autoantibodies (TAAbs), either alone or in combination, to detect breast cancer.

The retrospective study evaluated 210 samples, collected prior to biopsy. Samples from a single site (Mercy Women's Center, which was renamed Mercy Breast Center in June 2016) were used including specimens from 18 participants with no evidence of breast disease, 92 participants diagnosed with benign breast disease and 100 participants diagnosed with breast cancer (both invasive breast cancer and ductal carcinoma in situ).

Study results show that when SPB data were used independently, clinical sensitivity and specificity for detection of breast cancer were 74.7 percent and 77.0 percent respectively. When TAAb data were independently used, clinical sensitivity and specificity for detection of breast cancer were 72.2 percent and 70.8 percent respectively. However, when TAAb and SPB data were used together, clinical sensitivity and specificity for detection of breast cancer improved to 81.0 percent and 78.8 percent respectively, demonstrating that a combined proteomic biomarker assay is an important avenue for developing new approaches for detecting breast cancer.

The new data affirms the role of protein biomarkers in addressing the diagnostic challenges associated with imaging, particularly for women whose imaging results fall into Category 3 (probably benign finding), Category 4 (suspicious finding) on the American College of Radiology's BI-RADS (Breast Imaging – Reporting and Data System) scale. When women present with abnormal mammography results and/or have dense breasts, clinicians and patients often face a difficult decision whether to proceed with additional imaging or biopsy.

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