Thursday, May 15, 2014

Cancer Immunotherapy Method Could Be Effective Against a Wide Range of Cancers | DG News

May 14, 2014
BALTIMORE, Md -- May 14, 2014 -- A new method for using immunotherapy to specifically attack tumour cells that have mutations unique to a patient’s cancer has been developed by scientists at the National Cancer Institute (NCI), part of the National Institutes of Health (NIH).
The researchers demonstrated that the human immune system can mount a response against mutant proteins expressed by cancers that arise in epithelial cells which can line the internal and external surfaces (such as the skin) of the body. These cells give rise to many types of common cancers, such as those that develop in the digestive tract, lung, pancreas, bladder, and other areas of the body.
The research, published in the journal Science, provides evidence that this immune response can be harnessed for therapeutic benefit in patients.
“Our study deals with the central problem in human cancer immunotherapy, which is how to effectively attack common epithelial cancers,” said Steven A. Rosenberg, MD, NCI’s Center for Cancer Research, Rockville, Maryland. “The method we have developed provides a blueprint for using immunotherapy to specifically attack sporadic or driver mutations, unique to a patient’s individual cancer.”
All malignant tumours harbour genetic alterations, some of which may lead to the production of mutant proteins that are capable of triggering an antitumor immune response. Research led by Dr. Rosenberg had shown that human melanoma tumours often contain mutation-reactive immune cells called tumour-infiltrating lymphocytes (TILs). The presence of these cells may help explain the effectiveness of adoptive cell therapy (ACT) and other forms of immunotherapy in the treatment of melanoma.
In ACT, a patient’s own TILs are collected, and those with the best antitumor activity are grown in the laboratory to produce large populations that are infused into the patient. However, prior to this work it had not been clear whether the human immune system could mount an effective response against mutant proteins produced by epithelial cell cancers. These cells comprise more than 80% of all cancers. It was also not known whether such a response could be used to develop personalised immunotherapies for these cancers.
In the current study, Dr. Rosenberg and his team set out to determine whether TILs from patients with metastatic gastrointestinal cancers could recognise patient-specific mutations. They analysed TILs from a patient with bile duct cancer that had metastasised to the lung and liver and had not been responsive to standard chemotherapy. The patient, a 43-year-old woman, was enrolled in an NIH trial of ACT for patients with gastrointestinal cancers (Clinical trial number NCT01174121).
The researchers first did whole-exome sequencing, in which the protein-coding regions of DNA are analysed to identify mutations that the patient’s immune cells might recognise. Further testing showed that some of the patient’s TILs recognised a mutation in a protein called ERBB2-interacting protein (ERBB2IP). The patient then underwent adoptive cell transfer of 42.4 billion TILs, approximately 25% of which were ERBB2IP mutation-reactive T lymphocytes, which are primarily responsible for activating other cells to aid cellular immunity, followed by treatment with 4 doses of interleukin-2 to enhance T-cell proliferation and function.
Following transfer of the TILs, the patient’s metastatic lung and liver tumours stabilised. When the patient’s disease eventually progressed, after about 13 months, she was re-treated with ACT in which 95% of the transferred cells were mutation-reactive T cells, and she experienced tumour regression that was ongoing as of the last follow up (6 months after the second T-cell infusion). These results provide evidence that a T-cell response against a mutant protein can be harnessed to mediate regression of a metastatic epithelial cell cancer.
“Given that a major hurdle for the success of immunotherapies for gastrointestinal and other cancers is the apparent low frequency of tumour-reactive T cells, the strategies reported here could be used to generate a T-cell adoptive cell therapy for patients with common cancers,” said Dr. Rosenberg.
SOURCE: National Institutes of Health

Thursday, May 8, 2014

Vemurafenib Combination Effective in Advanced BRAF-Mutant Melanoma

ilas Inman
Published Online: Wednesday, May 7, 2014
Dr. Sandra Horning
Sandra Horning, MD
The combination of the BRAF inhibitor vemurafenib (Zelboraf) with the investigational MEK inhibitor cobimetinib (GDC-0973) demonstrated a 13.7-month median progression-free survival (PFS) and an overall response rate (ORR) of 87% in treatment-naïve patients with BRAFV600 mutation-positive metastatic melanoma, according to phase Ib results presented at the 10th European Association of Dermato Oncology Congress in Vilnius, Lithuania.

The large open-label phase Ib trial, known as BRIM7, enrolled 66 vemurafenib-refractory patients and 63 BRAF inhibitor-naïve patients with BRAFV600 mutation-positive metastatic melanoma. In the patients who progressed on vemurafenib, the median PFS was 2.8 months and the ORR was 15%. The median overall survival (OS) for the BRAF inhibitor-naïve patients had not been reached after a median 12.7-month follow-up. The 1-year survival estimate was 83%. Among vemurafenib-refractory patients, median OS was 8.3 months with an estimated 1-year survival of 32%.

The FDA approved single-agent vemurafenib in August 2011 for patients with unresectable or metastatic melanoma with the BRAFV600E mutation. This decision was based on an improvement in PFS and OS for vemurafenib compared with the chemotherapy dacarbazine. Median PFS with vemurafenib was 5.3 months compared with 1.6 months with dacarbazine. At the time of the approval, median OS was not reached for vemurafenib compared to a median of 7.9 months with dacarbazine. At 6 months, OS rate was 84% with vemurafenib compared with 64% with dacarbazine.

In 2012, Roche launched a phase III trial to compare cobimetinib in combination with vemurafenib to single-agent vemurafenib in previously untreated BRAFV600 mutation-positive patients with unresectable locally advanced or metastatic melanoma. Results from this study, labeled coBRIM, are expected later this year.

“These encouraging final data from the phase Ib BRIM7 study are an important step in understanding the potential role of combining the MEK inhibitor cobimetinib and the BRAF inhibitor Zelboraf to treat metastatic melanoma,” Sandra Horning, MD, the head of Global Product Development and chief medical officer at Roche, said in a press release. “In combining these molecules we aim to overcome resistance to BRAF inhibition and maximize potential patient benefit, and we look forward to the results of the ongoing phase III coBRIM trial.”

The primary endpoint of the BRIM7 study focused on safety, tolerability, and the identification of an optimal dose. The secondary outcome measures focused on efficacy. The study identified cobimetinib at 60 mg daily for 21 days followed by 7 days of rest with continuous vemurafenib twice daily at 960 mg as the optimal dose. This dose was used in the coBRIM study.

In the BRAF inhibitor-naïve arm of the BRIM7 study, 78% of patients experienced a partial response (PR), 10% achieved a complete response (CR), and 10% reached stable disease (disease control rate [DCR] = 97%). In patients refractory to vemurafenib, ORR was 15% and 42% of patients achieved stable disease (DCR = 57%).

Across all 129 treated patients, the most common all-grade adverse events were diarrhea (64%), non-acneiform rash (60%), fatigue (48%), nausea (45%), liver laboratory test abnormality (40%), and photosensitivity/sunburn (40%). The most frequently reported grade ≥3 adverse events were liver laboratory test abnormality (11%), cutaneous squamous cell carcinoma (9%), non-acneiform rash (8%), anemia (7%), joint pain (6%), fatigue (5%), and diarrhea (5%).

“Building on the previous data from the BRIM7 trial, these final results provide encouraging signs of clinical activity in BRAF inhibitor-naïve patients with the combination of cobimetinib and vemurafenib,” Michael M. Morrissey, PhD, president and chief executive officer of Exelixis, said in a release. “People with this disease still urgently need improved treatment options, and we look forward to the top-line data from coBRIM, the ongoing phase III pivotal trial, anticipated later this year.”

The dual inhibition of both MEK and BRAF is thought to circumvent treatment resistance that commonly occurs with single-agent therapy. Moreover, this combination is thought to reduce the incidence of secondary skin cancers associated with BRAF-targeted monotherapy.

In January 2014, the FDA approved the combination of the BRAF inhibitor dabrafenib (Tafinlar) and the MEK inhibitor trametinib (Mekinist) for patients with unresectable or metastatic melanoma who harbor a BRAF V600E or V600K mutation. This approval was based on an open-label phase I/II trial that demonstrated a 9.4-month PFS with the combination compared with 5.8 months for dabrafenib alone. This combination is being explored in phase III studies.
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BRAF V600E mutation did not independently predict thyroid cancer recurrence, persistence | Hematology Oncology

Russo M. Thyroid. 2014;doi:10.1089/thy.2013.0675.

  • May 7, 2014
Patients with BRAF V600E-mutated papillary thyroid cancer demonstrated more aggressive disease, but the mutation was not an independent prognostic factor for inferior outcomes, according to study results.
The analysis included 103 patients with classical variant papillary thyroid cancer who underwent total thyroidectomy between 2005 and 2008. Most patients were female (n=86), and the median age of patients at the time of diagnosis was 45 years (range, 15.2-78.2).
Mean follow-up was 55 months (range, 42-68).
Fifty-seven patients (55.3%) harbored aBRAF V600E mutation. Univariate analyses indicated these patients were more likely to have lymph node metastases at the time of diagnosis (P=.01), TNM stage III or IV (P=.03), and recurrent or persistent disease at follow-up (P=.03).
However, multivariate analyses indicated only lymph node metastases were significantly more common in BRAF V600E-mutated disease (OR=2.9; 95% CI, 1.1-7.3).
Patients with BRAF V600E mutations demonstrated a significantly increased risk for recurrence (OR=5.8; 95% CI, 1.2-27.9) and persistent disease at last visit (OR=3.5; 95% CI, 1.2-10.3). However, only lymph node metastases independently predicted persistent disease (OR=30.9; 95% CI, 6-159).
A Kaplan-Meier analysis also indicated BRAF V600E mutation status did not impact the risk for recurrence among patients with two or more risk factors (P=.2).
“The current evidence does not support the cost-effectiveness of the qualitative detection of BRAF V600E mutation in clinical practice,” the researchers wrote. “At present, the determination of the BRAF V600Emutation status should be considered among the many markers that indicate a high risk of more aggressive papillary thyroid cancer biology, although this is not true for all BRAF V600E-positive papillary thyroid cancers.”
Disclosure: The researchers report no relevant financial disclosures.

Friday, May 2, 2014

Cediranib Maleate With or Without Lenalidomide in Treating Patients With Thyroid Cancer - Full Text View -

This is my new Thyroid Cancer clinical trial, started April 9, 2014.  I am in the "Without Lenalidomide" arm of the study.

Cediranib Maleate With or Without Lenalidomide in Treating Patients With Thyroid Cancer - Full Text View - "Cediranib Maleate"

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Review Study Suggests an Overdiagnosis and Overtreatment in Thyroid Cancer

Review Study Suggests an Overdiagnosis and Overtreatment in Thyroid Cancer

Tony Berberabe, MPH
Published Online: Wednesday, April 30, 2014
ThyroidA review study of trends in patients diagnosed with thyroid cancer from 1975 to 2009 suggest the cancer has been overdiagnosed, and therefore overtreated, according to Louise Davies, MD, MS, and H. Gilbert Welch, MD, MPH, in their study published in JAMA Otolaryngology—Head & Neck Surgery.

The researchers had previously reported a doubling of thyroid cancer incidence—largely due to the detection of small papillary cancers. Because these tumors are commonly found in people who have died of other causes, and because thyroid cancer mortality had been stable according to data from the Surveillance, Epidemiology, and End Results (SEER) program, Davies and Welch argue that the increased incidence represented overdiagnosis. Thyroid cancer mortality rates were collected from the National Vital Statistics System.

The authors report that since 1975, the incidence of thyroid cancer has now nearly tripled, going from 4.9 to 14.3 per 100 000 individuals (absolute increase, 9.4 per 100 000; relative rate [RR], 2.9; 95% CI, 2.7-3.1). That increase was due to papillary thyroid cancer.

The absolute increase in thyroid cancer in women (from 6.5 to 21.4 = 14.9 per 100 000 women) was almost 4 times greater than that of men (from 3.1 to 6.9 = 3.8 per 100 000 men). The mortality rate from thyroid cancer was stable between 1975 and 2009 (approximately 0.5 deaths per 100 000).

The researchers conclude that the increased incidence is not due to an “epidemic of disease, but rather an epidemic of diagnosis.” They note that the problem is particularly acute for women, who have lower autopsy prevalence of thyroid cancer than men but higher cancer detection rates by a 3:1 ratio.

In a commentary that appeared in Clinical Oncology News, John H. Kim, MD, an associate professor of surgery at the City of Hope in California, says “overdiagnosis” is the wrong term to use. His argument is that data from the SEER database and the National Center for Vital Statistics have limitations. He writes that “one assumption pointing to overdiagnosis is made simply because there is a large increase in incidence of thyroid cancer while mortality remains stable. The implication made is that most of the new cancers identified are not killing patients. Notwithstanding the inability to identify which new cancers identified are killing the patients and which ones aren’t, this assumption simply has not been tested at all in this study.”
- See more at:

Sofia Vergara Wants to Educate You on Thyroid Cancer |

Some good pointers.

Sofia Vergara Wants to Educate You on Thyroid Cancer |

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ASCO Guidelines Address Key Symptoms Affecting Cancer Survivors | Cancer Network

ASCO Guidelines Address Key Symptoms Affecting Cancer Survivors

GuidelinesNew guidelines from ASCO address key symptoms affecting survivors of c...
The American Society of Clinical Oncology (ASCO) has released its first ever guidelines for prevention and management of symptoms that affect many cancer survivors. In three separate publications based on available medical literature and other guideline sources, ASCO members have published clinical practice guides for anxiety and depression, fatigue, and chemotherapy-induced neuropathy.
These guides are part of a planned ASCO series that addresses cancer survivorship issues.
A cancer survivor is a broad term defined by the American Cancer Society (ACS) as any person diagnosed with cancer starting from the time of their diagnosis through the course of his or her life, but is mainly focused on the period of time after active cancer therapy ends. ACS estimates that a total of 13.7 million Americans who have had a history of cancer were alive as of January 1, 2012. This population is projected to increase to 18 million (9.2 million women and 8.8 million men) by 2022.
Among male survivors, the most common cancers are prostate (43%), colon and rectal (9%), and melanoma (7%). For female survivors, the most common cancers are breast (41%), uterine (8%), and colon and rectal (8%).
This survivor population has physical and mental health challenges as a result of the effects of the specific cancer and treatment, as well as psychological effects from the diagnosis and treatment process. Studies and evidence from real-world clinical care show that the transition from active treatment to post-treatment is important, including addressing unique health issues and health risks for these patients. How patients care for themselves and whether their concerns are addressed clinically affect their long-term health outcomes.
The anxiety and depression guideline was adapted from the Pan-Canadian Practice Guideline on Screening, Assessment, and Care of Psychosocial Distress (Depression, Anxiety) in Adults With Cancer. The guidelines on cancer survivors’ fatigue combined a pan-Canadian guideline on cancer-related fatigue and two National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines on cancer-related fatigue and general cancer survivorship. The ASCO guideline on chemotherapy-induced neuropathy is novel, developed by a group of experts from different disciplines and based on a review of 48 randomized controlled trials for neuropathy treatment, as well as outcome and quality of life reports.

Key Guideline Recommendations

• All patients should be periodically evaluated for depression and anxiety symptoms using validated protocols.
• Treatment of patients with depression or anxiety should be tailored based on severity of symptoms and history of depression. Follow-up of patients is crucial, as many symptomatic patients are less likely to comply with referrals and treatments.
• Health care providers should be aware of their institutions’ resources for treatment of depression and anxiety and should have patients make use of supportive care services, including those that facilitate prevention and mitigation of symptoms.
For fatigue:
• Regular screening is highly recommended, starting at the time of diagnosis and continuing after completion of primary treatments, at least annually and using semi-quantitative or quantitative measures.
• Patients should be offered education and advice about managing fatigue following treatment. Maintaining adequate levels of physical activity are encouraged, particularly walking.
• Other non-drug treatments such as psychosocial interventions and mind-body interventions (yoga, acupuncture) are encouraged.
• Pharmacological interventions for post-treatment patients are not encouraged, as there is limited evidence that drugs are effective in reducing fatigue in those who have completed therapy and are currently disease-free.
• Duloxetine is recommended for treatment of chemotherapy-induced peripheral neuropathy (CIPN).
• No agents are recommended for prevention of CIPN during active chemotherapy treatment.
• No strong clinical evidence for benefits from other agents such as tricyclic antidepressants, gabapentin, and topical gels containing baclofen, amitriptyline HCL, and ketamine are seen, but they may be tried in certain patients.
- See more at:

Thursday, May 1, 2014

Laughter May Work Like Meditation in the Brain

Laughter May Work Like Meditation in the Brain

health day
Study monitored brain waves of people watching different types of videosSUNDAY, April 27, 2014 (HealthDay News) -- Laughter triggers brain waves similar to those associated with meditation, according to a small new study.
It also found that other forms of stimulation produce different types of brain waves.
The study included 31 people whose brain waves were monitored while they watched humorous, spiritual or distressing video clips. While watching the humorous videos, the volunteers' brains had high levels of gamma waves, which are the same ones produced during meditation, researchers found.
During the spiritual videos, the participants' brains showed higher levels of alpha brain waves, similar to when a person is at rest. The distressing videos caused flat brain wave bands, similar to when a person feels detached, nonresponsive or doesn't want to be in a certain situation.
Researchers were led by Lee Berk, an associate professor in the School of Allied Health Professions, and an associate research professor of pathology and human anatomy in the School of Medicine, at Loma Linda University, in California.
The study was scheduled to be presented Sunday at the Experimental Biology meeting held in San Diego. The data and conclusions should be viewed as preliminary until published in a peer-reviewed journal.
"What we have found in our study is that humor associated with mirthful laughter sustains high-amplitude gamma-band oscillations. Gamma is the only frequency found in every part of the brain," Berk said in a university news release.
"What this means is that humor actually engages the entire brain -- it is a whole brain experience with the gamma wave band frequency and humor, similar to meditation, holds it there; we call this being 'in the zone,'" Berk explained.
He said that with laughter, "it's as if the brain gets a workout." This effect is important because it "allows for the subjective feeling states of being able to think more clearly and have more integrative thoughts," Berk said. "This is of great value to individuals who need or want to revisit, reorganize or rearrange various aspects of their lives or experiences, to make them feel whole or more focused."
More information
The U.S. National Center for Complementary and Alternative Medicine has more about meditation.
SOURCE: Loma Linda University, news release, April 27, 2014
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