Some aggressive ovarian cancers start in the fallopian tubes, not the ovaries

The most aggressive type of ovarian cancer develops from cells that come from the fallopian tubes rather than the ovaries, according to a small study.

The findings confirms growing scientific suspicion around the origins of the disease, and could lead to news ways to prevent and treat it.
There are 5 types of ovarian cancer, of which high-grade serous ovarian carcinoma (HGSOC) accounts for the majority of cases and is also the most aggressive. It is normally diagnosed late,
Until recently it was thought that the disease developed from cells lining the surface of the ovary, but studies have suggested it might start in the fallopian tubes instead.
And for the first time scientists have traced specific genetic faults from the start of the disease through to it spreading.making it difficult to treat.

“The study confirms that faults in the p53 gene really are the initiating mutation in this disease."

More to read: http://www.cancerresearchuk.org/about-us/cancer-news/news-report/2017-10-24-some-aggressive-ovarian-cancers-start-in-the-fallopian-tubes-not-the-ovaries?utm_source=twitter_cr_uk&utm_medium=cruksocialmedia&utm_campaign=owntwitter_tweet



What are the top 5 breast cancer advancements of 2017?

Targeted therapies: PARP inhibitors

A highlight from American Society of Clinical Oncology (ASCO) this year (2–5 June 2017, IL, USA) was the OlympiAD trial Data. This Phase III clinical trial compared PARP inhibitor (olaparib) monotherapy with standard therapy in approximately 300 patients with a germline BRCA mutation and HER2–negative metastatic breast cancer. Data from the study demonstrated that olaparib provided a significant benefit over standard therapy, reduced the chance of progression of advanced BRCA-related breast cancer by 42%, and delayed progression by 2.8 months

Pre-pectoral implants

Pre-pectoral implant-based surgery, which works by placing the implant directly under the skin and over the muscle, has gained popularity due to its more minimal approach compared with traditional breast reconstruction methods. This transition to muscle-sparing reconstruction has demonstrated excellent short-term outcomes; the key advantages being that it avoids animation deformity, helps prevent shoulder dysfunction, and has a lower incidence of capsular contracture. While the initial short-term results are promising, long-term outcomes are yet to be reported and this is an area that will be one to watch over the coming year

Avoidance of further axillary surgery in sentinel node-positive patients

Another clinical highlight from this year was the results from the American College of Surgeons Oncology Group ACOSOG Z0011 trial, which questioned the belief that all breast cancer axillary nodes must be removed.
The multicentre, randomized Phase III trial demonstrated that 10-year overall survival for patients treated with sentinel lymph node dissection alone was noninferior to overall survival for those treated with axillary lymph node dissection (among women with T1 or T2 invasive primary breast cancer, no palpable axillary adenopathy and one or two sentinel lymph nodes containing metastases).
The findings demonstrated that avoidance of further axillary surgery in sentinel node-positive patients was feasible and did not support routine use of axillary lymph node dissection in this patient population, based on 10-year outcomes.
“Axillary lymph node dissection is an effective method of maintaining regional control but it is associated with a significant risk [for]complications such as lymphedema, numbness, axillary web syndrome and decreased upper-extremity range of motion”.

CDK4/6 inhibitors

At this year’s ASCO meeting, data were presented from the MONARCH 2 Phase iII trial, which demonstrated that adding abemaciclib to fulvestrant reduced the risk of disease progression or death by 45% versus fulvestrant alone in patients with HR+/HER2- advanced breast cancer who progressed on endocrine therapy.
Later in the year, the US FDA approved abemaciclib for use in combination with fulvestrant in women with HR+/HER2- advanced breast cancer with disease progression following endocrine therapy. This CDK4/6 inhibitor was approved as a monotherapy for patients with HR+/HER2- breast cancer with metastatic disease who have previously received endocrine therapy and chemotherapy.

APHINITY trial

Data from the APHINITY Phase III trial,  presented at ASCO in June and published in the New England Journal of Medicine in July, demonstrated a very small benefit of chemotherapy plus trastuzumab plus placebo versus chemotherapy plus trastuzumab plus pertuzumab as adjuvant therapy alone on risk of recurrence of invasive disease in patients with HER2-positive early breast cancer.
“The addition of pertuzumab to trastuzumab-based chemotherapy improved disease-free survival in the adjuvant setting for patients with early-stage HER2-positive breast cancer. Double antibody therapy using trastuzumab and pertuzumab is commonly used in the neoadjuvant setting, but long-term outcomes data were lacking. Results from the APHINITY trial support the use of pertuzumab in the adjuvant setting, especially in women at high risk of distant metastases.
Following on from this, the FDA granted a priority review to a supplemental biologics license application for pertuzumab for use in combination with trastuzumab and chemotherapy for the adjuvant treatment of patients with HER2-positive early breast cancer.


More in the following link: https://www.oncology-central.com/2017/10/24/top-5-breast-cancer-advancements-2017/

New Drugs, PARP Inhibitors, Have Potential to Benefit Larger Patient Populations in Ovarian Cancer

The addition of 3 PARP inhibitors to the landscape of ovarian cancer—rucaparib (Rubraca), olaparib (Lynparza), and niraparib (Zejula)—have led to practice-changing, targeted treatment options for patients whose diseases progress on chemotherapy. The recent FDA approvals of olaparib and niraparib in the maintenance settings, specifically, have opened a new door where previously there were no such therapies available.

Now, clinical trials are testing PARP inhibitors in combination with immunotherapy to increase antitumor activity. Rucaparib is currently being explored in combination with atezolizumab (Tecentriq) in a phase Ib open-label study, with dose-finding and dose-expansion phases (NCT03101280). For the dose-expansion phase, patients must have a deleterious germline or somatic BRCA 1/2 mutation or tumors that are BRCA wild-type, but show high levels of loss of heterozygosity.

The ongoing confirmatory study for rucaparib’s approval, ARIEL4, is comparing rucaparib with chemotherapy in patients with BRCA-positive ovarian, fallopian tube, or primary peritoneal cancer, who have received at least 2 prior platinum-based chemotherapy regimens (NCT02855944).

More in the link below
http://www.onclive.com/printer?url=/web-exclusives/parp-inhibitors-have-potential-to-benefit-larger-patient-populations-in-ovarian-cancer

A closer look into US Senator McCain's cancer: video

http://www.oncologytube.com/video/a-closer-look-into-senator-mccain-s-glioblastoma/10001958

Survival of Patients With mRCC Continues to Improve in the Targeted Therapy Era

Using the SEER (Surveillance, Epidemiology, and End Results) registry (2001–2014) from the US NCI (National Cancer Institute) , 15,444 patients with mRCC were identified to evaluate the effect of diagnosis year on cancer-specific mortality. Of these patients, 41%, 28.7%, and 30.3% were diagnosed in the contemporary (2010–2014), intermediate (2006–2009), and historical (2001–2005) years, respectively. The 24-month cancer-specific mortality rates were 61%, 63.7%, and 67.3%, respectively. This study indicates "the introduction of new therapeutic agents led to decreased cancer-specific mortality over the study time; however, this effect was only seen in patients with clear-cell mRCC".
http://www.practiceupdate.com/content/survival-of-patients-with-mrcc-continues-to-improve-in-the-targeted-therapy-era/58697/37/10/1

Colorectal Cancer Screening: Which Test Is Best?

The 2016 US Preventive Services Task Force (USPSTF) recommendations list 7 different screening strategies including colonoscopy, fecal immunochemical testing (FIT) for occult blood, guaiac-based FOBT (gFOBT), sigmoidoscopy alone, sigmoidoscopy plus FIT, the FIT-DNA test (multitargeted stool DNA test), and computed tomography (CT) colonography.

Based on the development of more sensitive and specific tests to detect human hemoglobin in the stool, FIT largely replaces the gFOBT strategies previously endorsed. Although the majority of clinical trials that demonstrated reduction in colorectal cancer mortality used gFOBT, it is successfully argued that using a more accurate FIT will only improve the mortality benefit from FOBT screening while reducing harms due to unnecessary follow-up colonoscopy following false-positive results. However, there is variability in the test characteristics between different FITs, and although meta-analysis estimates an overall cancer sensitivity and specificity of 79% and 94%, respectively, these range from 73% to 92% and 87% to 95%, respectively.

Flexible sigmoidoscopy was recommended in the prior recommendations at 5-year intervals, with FOBT every 3 years. Several randomized clinical trials confirm the mortality benefit of sigmoidoscopy screening, although Holme et al reported significant benefit only when FIT was added to sigmoidoscopy. The 2016 recommendations extend the sigmoidoscopy screening interval in the combined strategy to 10 years while increasing the frequency of FIT to annually. While it is difficult to exclude sigmoidoscopy from the list of recommended strategies based on the quality of evidence supporting benefit, sigmoidoscopy use in the United States has been declining—fewer than 1% of individuals reported cancer screening with sigmoidoscopy in 2012 compared with 10% who used FIT and 60% who underwent colonoscopy.

Colonoscopy screening at 10-year intervals remains the most prevalent strategy for colorectal cancer screening in the United States. There are no randomized clinical trials to demonstrate a reduction in colorectal cancer mortality with colonoscopy screening, but several are in progress that compare colonoscopy with FIT

The USPSTF recommendation statement also lists FIT-DNA, CT colonography, and a serological test. In 1 study, FIT-DNA was able to detect colorectal cancer with greater sensitivity than FOBT but with lower specificity however, there are no data to establish the morbidity, quality of life, cancer incidence, or mortality benefit of FIT-DNA in a screening population. Comparative effectiveness modeling estimates that other strategies can achieve similar benefits with fewer lifetime colonoscopies per life-year gained. Although the USPSTF report specifically does not address the economic effect of screening, the FIT-DNA test retails in the United States for $649 and is reimbursed by Medicare for $493, compared with the reimbursement for FIT ($22) or colonoscopy ($773). For these reasons FIT-DNA every 3 years is unlikely to represent a cost-effective alternative to screening with FIT or colonoscopy.

Similarly, CT colonography has not been subject to the rigor of a randomized clinical trial with clinically relevant outcomes including morbidity, quality of life, or cancer incidence and mortality. Additional concerns about CT colonography include extracolonic findings that require further evaluation accompanied by potential harms, the potential for radiation-induced cancers, and the lack of data to guide recommendations for the screening interval. A single blood test for circulating methylated septin 9 DNA has been approved by the US Food and Drug Administration for colorectal cancer screening. The sensitivity (48.2%) and specificity (91.5%) for detecting colorectal cancer are lower than for FIT, and no studies have been conducted to demonstrate mortality benefit.

The USPSTF used comparative effectiveness analysis to inform their updated colorectal cancer screening recommendations.

The absence of a USPSTF recommendation for any specific strategy leaves clinicians with a dilemma—the highest-quality data exist for gFOBT, which has been replaced by FIT, and sigmoidoscopy, which is largely unavailable. Colonoscopy is the most often used screening test, and observational studies report reductions in cancer incidence and mortality, yet validation from randomized clinical trials is lacking. The FIT-DNA should be at least as good as FIT, but there are no data to demonstrate greater reductions in cancer mortality beyond FIT. Radiographic and blood-based screening likewise have a paucity of clinical outcome data. It is in this context that the USPSTF has chosen to forgo specific test recommendations and instead highlight the advantages and disadvantages of the strategies presented in their statement. Perhaps the absence of data should not indicate the absence of benefit, and these recommendations should be viewed as a living document that is expected to change as more information become available.

Instead, the USPSTF recommendations highlight the great opportunity to reduce population mortality from colorectal cancer. National adherence to colorectal cancer screening ranges from 58% to 65% and has not increased over the past 5 years. The Affordable Care Act excluded cost sharing (deductible and copayment) for colorectal cancer screening; however, cost sharing is often imposed for colonoscopy either as a follow-up to positive FOBT findings or when a polypectomy is performed during a screening examination. These hidden costs represent a barrier to screening by any modality and should be removed to increase screening adherence.

In sum, we should focus on achieving our goal of screening “80% by 2018. While we may each have our own preference, this should be a patient-focused decision because the best test is not simply the one that gets done, but the one that gets done consistently.

Link: https://jamanetwork.com/journals/jamaoncology/fullarticle/2529562

Pictures of breast reconstruction after a diagnosis of breast cancer

http://www.breastcancer.org/treatment/surgery/reconstruction/pictures?utm_medium=OBWidget&utm_source=OB

Great results about advances for the cure of cancer

A new study shows that the number of women in the United States living with distant metastatic breast cancer (MBC), the most severe form of the disease, is growing. This is likely due to the aging of the U.S. population and improvements in treatment. See the picture below, which is self-explanatory.

CANCER HELP ONLINE: FDAApproves Inotuzumab for Adults with B-Cell Acut...

CANCER HELP ONLINE: FDAApproves Inotuzumab for Adults with B-Cell Acut...: FDA Approves Inotuzumab for Adults with B-Cell Acute Lymphoblastic Leukemia An electron micrograph of a human B cell. Most...

CANCER HELP ONLINE: FDAApproves Inotuzumab for Adults with B-Cell Acut...

CANCER HELP ONLINE: FDAApproves Inotuzumab for Adults with B-Cell Acut...: FDA Approves Inotuzumab for Adults with B-Cell Acute Lymphoblastic Leukemia An electron micrograph of a human B cell. Most...

FDA Approves Inotuzumab for Adults with B-Cell Acute Lymphoblastic Leukemia

An electron micrograph of a human B cell. Most forms of acute lymphoblastic leukemia arise in B cells.

Credit: National Institute of Allergy & Infectious Diseases

The Food and Drug Administration (FDA) has approved inotuzumab ozogamicin (Besponsa®) for some adults with B-cell acute lymphoblastic leukemia (ALL).
The approval, announced on August 17, is for the use of inotuzumab in patients with B-cell ALL whose disease has stopped responding to (relapsed) or never responded to (refractory) standard chemotherapy.
Patients with B-cell ALL whose cancer has a specific genetic alteration known as the Philadelphia chromosome can receive inotuzumab only if their cancer has progressed despite treatment with one of several targeted drugs approved for this cancer type.
In the randomized phase 3 clinical trial on which the approval was based, called INO-VATE ALL, substantially more patients treated with inotuzumab discaimer had a compltete remision compared with patients treated with chemotherapy. More patients in the inotuzumab group were also minimal residual disease (MRD) negative after treatment, meaning there was no evidence of leukemia cells present in the blood or bone marrow.
Patients in the trial treated with inotuzumab also had modest improvements in how long they lived without their disease progressing and in overall survival.

More Treatment Options for ALL

Although many patients with B-cell ALL respond well to chemotherapy, their cancer often returns. For patients with ALL whose cancer cells are positive for the Philadelphia chromosome—which occurs in 25% to 40% of cases—several targeted drugs, all part of a class of drugs known as tyrosine kinase inhibitors, have proven to be effective. But, as in patients treated with standard chemotherapy, the cancer develops resistance to the treatment and returns in many of these patients.
Inotuzumab is an antibody-drug conjugate, a type of drug in which an anticancer drug is chemically linked to another molecule that helps target the drug to cancer cells.
The targeting component of inotuzumab is a monoconal antibody that targets the CD22 protein, which is produced in excess on the surface of most ALL cells. The antibody is linked to a compound called calicheamicin that kills cancer cells. Once the antibody portion of inotuzumab binds to CD22 on cancer cells, the calicheamicin is released into the cell, where it damages the cell’s DNA and causes its death.
Inotuzumab is the third new therapy approved in recent months for people with advanced B-cell ALL.
Earlier this year, FDA granted full approval of blinatumomab (Blincyto®), a form of immunotherapy, for children and adults with relapsed or refractory B-cell ALL regardless of Philadelphia chromosome status. The approval was based on the results of a large clinical trial showing that patients treated with the drug had substantial improvement in how long they lived compared with patients treated with chemotherapy.
And approximately 2 weeks after inotuzumab was approved, the agency approved tisagenlecleucel (Kymriah™), the first-ever approved CAR T-cell therapy, for children and young adults with advanced ALL. That approval was based on findings from a small clinical trial in which 83% of patients achieved a complete remission 3 months after receiving the treatment.

High Remission Rates with Inotuzumab

The more than 300 patients in the INO-VATE ALL trial—funded by Pfizer, the drug’s manufacturer—had received at least one chemotherapy regimen and, for those with Philadelphia chromosome­–positive cancers, treatment with at least one FDA-approved tyrosine kinase inhibitor.

Of the first 218 patients in the trial (the group which served as the basis for the approval), approximately 36% of patients treated with inotuzumab had a complete remission, and nearly 90% of these patients were MRD negative. The complete remission and MRD-negative rates in patients treated with chemotherapy were approximately 17% and 32%, respectively.
Among patients who achieved a complete remission, the median length of the responses was 8 months in those who received inotuzumab and 4.9 months in those who received chemotherapy.
The median progression-free survival in the trial was 5 months in patients treated with inotuzumab and 1.9 months in patients treated with chemotherapy. Median overall survival was 7.7 months and 6.7 months, respectively.

Common side effects of inotuzumab included infections, anemia, hemorrhage, and nausea. A nearly identical number of patients in both groups experienced serious side effects, with febrile neutropenia being the most frequently reported serious event.
Link: https://www.cancer.gov/news-events/cancer-currents-blog/2017/fda-inotuzumab-

Development of breast cancer can be prevented with antibiotics?

In a newly published study, Cleveland Clinic researchers have uncovered differences in the bacterial composition of breast tissue of healthy women vs. women with breast cancer. The research team has discovered for the first time that healthy breast tissue contains more of the bacterial species Methylobacterium, a finding which could offer a new perspective in the battle against breast cancer.

Bacteria that live in the body, known as the microbiome, influence many diseases.
Most research has been done on the “gut” microbiome, or bacteria in the digestive tract. Researchers have long suspected that a “microbiome” exists within breast tissue and plays a role in breast cancer but it has not yet been characterized. The research team has taken the first step toward understanding the composition of the bacteria in breast cancer by uncovering distinct microbial differences in healthy and cancerous breast tissue.
“To my knowledge, this is the first study to examine both breast tissue and distant sites of the body for bacterial differences in breast cancer,” said co-senior author Charis Eng, M.D., Ph.D., chair of Cleveland Clinic’s Genomic Medicine Institute and director of the Center for Personalized Genetic Healthcare. “Our hope is to find a biomarker that would help us diagnose breast cancer quickly and easily.  In our wildest dreams, we hope we can use microbiomics right before breast cancer forms and then prevent cancer with probiotics or antibiotics.”
Link: https://www.biosciencetechnology.com/news/2017/10/researchers-find-link-between-bacterial-imbalances-and-breast-cancer

FDA Approves a New Treatment for Acute Myeloid Leukemia

The new treatment, Vyxeos, comprises a combination of two commonly used cytotoxic chemotherapeutics inside a nanosized particle.
The U.S. Food and Drug Administration (FDA) recently approved a new treatment called Vyxeos for treating certain patients with  acute myeloid leukemia (AML).
Vyxeos is intended for the treatment of adults with two types of AML that have particularly poor prognoses: newly diagnosed therapy-related AML and AML with myelodysplasia-related changes.
AML is the form of leukemia that carries the worst prognosis; according to the National Cancer Institute, the five-year relative survival rate is just 26.9 percent.
Vyxeos provides an alternative approach to delivering two of the cytotoxic chemotherapeutics commonly used to treat many patients with AML, daunorubicin and cytarabine. Until the approval of Vyxeos, these two agents were always given separately. In Vyxeos, a fixed combination of daunorubicin and cytarabine are enclosed together in a nanosized particle.
Nanotechnology refers to the manufacturing of objects with dimensions one million times smaller than a millimeter (the smallest width of a human hair is just 50 times smaller than a millimeter). Nanomedicine is the application of nanotechnology to the research and practice of medicine. Nanodrugs comprise an anticancer agent (or agents) and a nanosized carrier that selectively delivers the anticancer agent to the cancer and protects the anticancer agent from being destroyed by the body. Thus, nanodrugs allow the delivery of higher levels of anticancer agents to cancer cells than traditional systemic delivery methods, increasing effectiveness while reducing toxic side effects.
In the case of Vyxeos, the nanosized carriers are liposmes and the anticancer agents are daunorubicin and cytarabine. According to the FDA statement, Vyxeos was approved based on results from a randomized phase III clinical trial that showed that median overall survival for patients who received the new treatment was significantly improved compared with who received daunorubicin and cytarabine separately (9.56 months compared with 5.95 months).
The FDA approval was rendered on August 3, 2017.
https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm569883.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery

Brentuximab Vedotin Receives Breakthrough Therapy Designation for Frontline Hodgkin Lymphoma

The FDA has awarded brentuximab vedotin (Adcetris) on 02 October 2017 a breakthrough therapy designation for the first-line treatment of patients with classical Hodgkin lymphoma.

Brentuximab vedotin is an antibody-drug conjugate directed to CD30, a defining marker of the disease. The designation is based on phase III results from the ECHELON-1 clinical trial, which were released in June.
The 2-year rate of modified progression-free survival (PFS) for brentuximab vedotin plus AVD (adriamycin, vinblastine, dacarbazine) was 82.1% compared with 77.2% for patients receiving ABVD (adriamycin, bleomycin, vinblastine, dacarbazine). The experimental combination reduced the risk of disease progression or death by 23% (HR, 0.770; P = .035). An interim analysis of 2-year overall survival (OS) also showed a trend favoring the brentuximab arm.

Anti-cancer effects found in natural compound derived from onions

Research has found that a natural compound isolated from onions, onionin A (ONA), has several anti-ovarian cancer properties. This discovery is a result of research on the effects of ONA on a preclinical model of epithelial ovarian cancer (EOC) both in vivo and in vitro. 

www.sciencedaily.com/releases/2016/10/161020101051.htm

Seishu Hanaoka and his success in breast cancer surgery under general anesthesia two hundred years ago

Kan Aiya, a 60-year-old woman, had lost many loved ones to breast cancer. She had seen her sisters die of the cruel disease, so when a tumour formed in her left breast she was well aware of the likely outcome. For her, however, there was a chance of survival – an operation. It was 1804 and she was in the best possible place for surgery – feudal Japan.
Seishu Hanaoka (1760–1835) studied medicine in Kyoto and set up a practice in his hometown of Hirayama. He became interested in the idea of anaesthesia owing to stories that a third-century Chinese surgeon Houa T'o had developed a compound drug enabling patients to sleep through the pain. Hanaoka experimented with similar formulae and produced Tsusensan, a potent hot drink. Among other botanical ingredients it contained the plants Datura metel (aka Datura alba or ‘devil's trumpet’), monkshood and Angelica decursiva, all of which contain some potent physiologically active substances.
Tsusensan had quite a kick and if you glugged it down willy-nilly you would probably die, but in the correct dosage it rendered patients unconscious for between six and 24 hours, allowing ample time for surgery.
On 13 October 1804, Hanaoka excised Kan Aiya's tumour, the first successful surgical treatment of breast cancer under general anesthesia in the world. Sadly, Kan Aiya is thought to have died of her disease the following year.  Hanaoka performed operations for breast cancer in a total of 156 cases, and also for many other kinds of surgical procedures. He also eagerly contrived and modified many surgical instruments.

A new medication, lenvantinib, for patients with advanced hepatocarcinoma.

A supplemental new drug application for lenvatinib (Lenvima) as a frontline systemic treatment for patients with advanced hepatocellular carcinoma (HCC) has been accepted by the FDA, acccording to a statement from Eisai, the company developing the therapy.

Findings from the phase III REFLECT trial, on which the application for lenvatinib was based, showed overall survival (OS) was noninferior for lenvatinib versus sorafenib. Median OS with lenvatinib was 13.6 versus 12.3 months for sorafenib (HR, 0.92; 95% CI, 0.79-1.06). Lenvatinib was also associated with improvements in progression-free survival (PFS), time to progression (TTP) and objective response rate (ORR) compared with sorafenib.

More: http://www.targetedonc.com/news/lenvatinib-application-for-advanced-hcc-accepted-by-fda

Awesome! Propranolol, an anti-hypertensive drug, prevents the recurrence and death of the malignant melanoma

In a propective study, it was found that after 3 years of treatment with propranolol a big difference in the disease progression. It was observed a recurrence of 41.2% of the patients in the untreated cohort compared with only 15.8% in the propranolol cohort.

Find more information in the link

http://jamanetwork.com/journals/jamaoncology/fullarticle/2655005

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