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The Lancet Oncology

Showing posts with label surgery. Show all posts
Showing posts with label surgery. Show all posts

Saturday, October 3, 2009

New Cancer Research Priorities Needed to Correct Imbalance that Leaves Important Questions Neglected

Cancer research is too focused on new drug development, while not enough money and effort is being devoted to pursuing important advances in knowledge likely to have the biggest impact on combating the disease in the next few decades, a leading research policy expert says, adding that a major shift in research priorities will be crucial to the ability to cope with the coming wave of cancer cases.

Professor Richard Sullivan of the King’s Health Partners Integrated Cancer Centre in London told Europe’s largest cancer congress, ECCO 15 – ESMO 34, the joint 15th European CanCer Organisation (ECCO) and 34th European Society for Medical Oncology (ESMO) Multidisciplinary Congress, September 20 – 24 in Berlin, Germany, that studies aiming to improve surgery, pathology and diagnostic and staging imaging, as well as a radical rethink of the approach to prevention research, must become the focus of public- and federally-funded cancer research now. The global public sector spend on cancer research was about €14 billion a year in 2004/05, the latest year for which figures are available. Non-commercial funders in Europe spent just over €3 billion on cancer research in 2004/05.

“An analysis we have just completed shows that, on average, European public funders are spending 74% of their money on fundamental biology and drug development research and that well over 70% of the cancer research initiatives at the European level are aimed at the same areas,” noted Prof Sullivan, who is also chairman of the European Cancer Research Managers Forum, which studies cancer research and funding in Europe.

“In the United States, the imbalance is even greater. There is no shortage of cancer drugs coming through pipeline and the whole area of drug research is quite healthy. What we need is a reapportioning of budgets from the charitable sector and public funders to carve out space for these other areas of cancer research that are largely invisible to a lot of policymakers."

“This is a deeply unfashionable view and the easy way out is to say that we must just ask for more money, but the reality is that we’ve got to prioritise,” Prof Sullivan said. “Most of the new medicines are having a small impact on the big picture of cancer burden at the moment, extending life by a few months. Research in this area is already heavily funded and that will continue regardless, as will the investments in fundamental cancer biology.”

The World Health Organization predicts that the number of people worldwide living with cancer will rise from about 28 million today to about 75 million in 2030. Detecting cancer early enough to treat it successfully and improving our understanding of how to make primary prevention strategies work hold the potential for the greatest gains, he said.

“This demands an overhaul of prevention research. You can take the quite reasonable view that we know the risk factors now. What we don’t understand is how to take that research on prevention and apply it in populations because we don’t understand the behaviour of those groups or how that might change over the next 20 or 30 years. For instance, how do we address the fact that many men across Europe will put up with rectal bleeding for a year before going to see a doctor? This is very important because cancer is not just about genes, it is predominantly about culture.”

"Cancer researchers must now be more imaginative and collaborate across unusual disciplinary boundaries to embrace behavioural engineering, population psychology, evolutionary biology, novel sociological methods and ideas such as cultural transmission theory – the study of how behaviours are learned and transmitted between generations," Sullivan explained

“Research in these novel areas addresses questions that can never be answered with classical epidemiological studies or standard social science questionnaires – we’ve reached the limits of enquiry with many standard approaches. There are people doing fantastic work that could be extremely useful not only to cancer research, but to medicine in general and most medics and researchers are completely ignorant about their existence and what they can do for medicine. It is a huge untapped area with massive potential to make a difference,” Prof Sullivan said.

The growing scale of cancer in developing countries also presents an imminent challenge for cancer research, he said. More than half of all cancer diagnoses occur in developing countries, which will bear a large majority of the global burden before long. Keeping the research focus as it is in developed countries will not address the problem in the developing and transitional countries because drug development is not going to be the answer. Surgery and radiotherapy are the most important approaches for reducing the global cancer burden and financial support for programmes that bring those treatments to developing countries is still very poor.

The argument is always made that there is enough to deal with in developing countries with the infectious disease challenges, but chronic disease is a major, often unrecognised problem and we can’t afford to wait any longer. Like it or not, developed countries have a responsibility to investigate which cancer control approaches are exportable and to support those institutions working in these areas,” he said.

Governments, research charities and European funders need to recognise the importance of shifting the focus to a new approach to prevention research and more investment in non-drug treatment research, but it will be largely up to cancer researchers to drive the change, Prof Sullivan said.

“There has already recently been a major shift in Europe toward hospital-university alliances driving the agenda. They need to start banging on the doors of the non-government organisations and the federal funders, lobbying hard and proving that it’s important to give attention to these neglected areas of cancer research.”

For more information:

Monday, September 28, 2009

Ultrasound can Predict Tumor Burden and Survival in Melanoma Patients, Sparing Unnecessary Surgery

Ultrasound can predict tumor burden and survival in melanoma patients. Researchers have shown for the first time that patterns of ultrasound signals can be used to identify whether or not cancer has started to spread in melanoma patients, and to what extent. The discovery enables doctors to decide on how much surgery, if any, is required and to predict the patient’s probable survival.

Dr Christiane Voit told Europe’s largest cancer congress, the joint 15th European CanCer Organisation (ECCO) and 34th European Society for Medical Oncology (ESMO) Multidisciplinary Congress, September 20 – 24 in Berlin, Germany: “We have identified two ultrasound patterns of lymph node metastasis in melanoma patients which can identify correctly any amount of tumor cells in the sentinel lymph nodes in 75-90% of cases before proceeding to surgery on the sentinel lymph nodes.”

Voit, who is a dermatologist and head of the diagnostic unit at the Skin Cancer Centre at Charité – Universitätsmedizin Berlin, the Medical University of Berlin, said that although her research needs to be confirmed in multi-centre, randomized clinical trials, it had the potential to spare patients unnecessary surgery, especially if it was combined with ultrasound-guided fine needle biopsy of lymph nodes rather than conventional surgery.

Since 2001 Dr Voit and her colleagues in Germany and The Netherlands have included 850 melanoma patients in a prospective study to investigate the use of ultrasound in diagnosis and treatment planning. They have already demonstrated that ultrasound-guided fine needle biopsy of sentinel nodes before conventional sentinel node surgery can identify up to 65% of patients in whom the cancer has started to spread. The study presented today shows how far ultrasound patterns correlate with disease progression, tumor burden, survival and prognosis in the first 400 of these patients with stage I/II melanoma and with the longest follow-up.

Before having sentinel node surgery the patients were investigated using ultrasound, and these results were checked against the results of the subsequent surgery. The researchers found that two ultrasound patterns together could correctly identify the amount of cancer cells in the lymph nodes in 80% of cases.

A balloon shape ultrasound pattern with or without loss of central echoes (where the lymph node has lost central echoes or still has some residual central echoes, but these are wandering toward the rim, giving an asymmetrical shape to the centre) was an indicator in up to 83% of cases of a large amount of cancer cells in the sentinel node. “This ultrasound pattern was a late sign, only occurring in cases of advanced metastasis,” said Voit.

A pattern of peripheral perfusion (where small blood vessels start to surround the lymph node) was an early sign of a small number of cancer cells present. “The early signs are signs of first disruption of the normal lymph node architecture by an early stage metastasis. The most important one is peripheral perfusion, which shows angiogenesis (the formation of new blood vessels) is occurring,” she explained.

The researchers found that these two ultrasound patterns could predict overall survival. Estimates for overall survival after five years for patients with stage I/II is between 50-90% depending on the state of the tumour. Dr Voit found that 93% of patients with neither of these ultrasound patterns, 87% of patients with peripheral perfusion, and 56% of patients with balloon shapes with or without loss of central echoes, survived for at least five years; survival without cancer spreading to other parts of the body was 74%, 60% and 26% respectively.

Dr Voit said: “For the first time we have established that ultrasound patterns can be used as criteria for diagnosing disease progression and tumor burden. Balloon shaped lymph nodes with or without loss of central echoes and peripheral perfusion are independent prognostic factors for survival.”

Discovering if cancer has spread to the lymph nodes is the most important factor influencing the prognosis and treatment of melanoma patients. Doctors usually cut out one or two key lymph nodes, called sentinel nodes, and use these as an indicator of whether or not the cancer has spread to the other lymph nodes. If the sentinel node is free of cancer, patients don’t need to have more extensive lymph node removal.

However, only 20% of patients who have a sentinel node biopsy have cancer that has spread there, and so the operation, which can be accompanied by side effects such as chronic swelling and seroma, is unnecessary for 80% of patients. Using ultrasound first to detect the presence or not of sentinel node metastases could be a non-invasive way of limiting the numbers of patients who require subsequent surgery or simply watchful follow-up care.

For more information:

  • Abstract no: 9303. Melanoma session, Wednesday 14.45-17.00 hrs CEST (Hall 7)

Also read these PubMed abstracts:

Images courtesy American Society of Clinical oncology (ASCO).

Saturday, May 30, 2009

Surgical Removal of the Primary Tumor Not Immediately Needed in Patients with Metastatic Colorectal Cancer

New research shows that patients who are newly diagnosed with metastatic, surgically incurable, colorectal cancer (mCRC) do not need immediate surgery to remove their primary tumor unless the tumor is causing complications.

Surgical removal of the primary tumor at the time of diagnosis was once standard practice and is still common in patients with metastatic colorectal cancer. Because cancer has already spread to other parts of the body by this stage, the purpose of this surgery is not to extend survival, but to prevent future complications, such as intestinal blockage, perforation of the bowel, and severe bleeding. However, over the past decade several new effective chemotherapy drugs for colorectal cancer have been introduced and until now there has been little data to assess whether this pre-emptive surgery is still warranted.

The research will be presented on Monday, June 1, by Philip B. Paty, MD, Memorial Sloan-Kettering Cancer Center, New York, NY, during the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO) being held from May 27 – June 2, 2009 in Orlando, Florida.

Incidence of metastatic Colorectal Cancer (mCRC)
According to GLOBOCAN 2002, a cancer incidence database produced by the International Agency for Research on Cancer (IARC) of the World Health Organization (WHO), the worldwide incidence of colorectal cancer is approximately one million cases per year. The National Cancer Institute (NCI) reports that approximately 50 percent of patients diagnosed with colorectal cancer will suffer from advanced disease that has metastasized to other parts of the body, most commonly to the liver.

Uncertain benefit
The researchers rationale is that in the absence of symptoms (bleeding, perforation, obstruction) or resectable metastatic disease, primary tumor resection in patients who present with synchronous metastatic colorectal cancer (mCRC) is of uncertain benefit.

The purpose of their study was to describe the frequency of intervention necessary to palliate the intact primary tumor in patients who present with synchronous stage IV CRC and receive up-front modern combination chemotherapy without prophylactic surgery.

“In this era of modern chemotherapy, routine surgery to remove the primary tumor in patients with unresectable metastases is no longer supported by the data,” explained Philip Paty, MD, an attending surgeon and vice chairman of clinical research at Memorial Sloan-Kettering Cancer Center (MSKCC) and the study’s senior author. “In addition to being an unnecessary procedure that carries its own risks of morbidity and mortality, surgery delays the start of chemotherapy for several weeks, and in some cases may make the patient less fit for and less tolerant of chemotherapy. Unless there is an immediate need for surgery, patients should begin chemotherapy first.”

FOLFOX, IFL and FOLFIRI
This retrospective study identified 233 consecutive patients who presented with metastatic colorectal cancer between 2000 and 2006, and were treated with chemotherapy at MSKCC, but had no serious symptoms to prompt immediate surgery. The patients received one of three triple-drug chemotherapy combinations as their initial treatment (the regimens known as FOLFOX, IFL, and FOLFIRI).

Some were also treated with the targeted therapy bevacizumab (Avastin, Roche).

Investigators determined that 217 (93%) patients never developed complications that required removal of their tumor. For the 16 patients (7%) who did eventually need surgery, the vast majority (14/16) had successful operations.

10 patients (4%) required nonoperative intervention (stent or radiotherapy), whereas 213 (89%) never required any direct symptomatic management for their intact primary. Of those, 47 (20%) ultimately underwent elective colon resection at the time of metastasectomy and 8 (3%) during laparotomy for hepatic artery infusion pump placement. Neither use of bevacizumab, location of the primary tumor in the rectum, or metastatic disease burden was associated with increased intervention rate. In addition, when included as a time-varying covariate in a Cox regression model, the need for emergent intervention did not correlate with overall survival.

Most patients with synchronous stage IV CRC who receive up-front modern combination chemotherapy never required palliative surgery for their intact primary. The data support the use of chemotherapy, without routine prophylactic resection, as the appropriate standard practice for patients with neither obstructed nor hemorrhaging primary colorectal tumors in the setting of metastatic disease.

Overall, the researchers concluded that the mortality attributable to surgery was very low (0.8 percent), suggesting that this approach, by avoiding unnecessary surgery, improves the overall safety of treatment.

For more information:


PubMed abstracts:

Other ASCO 2009 abstracts:

Illustration courtesy of the American Society of Clinical Oncology.