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Clinical Abstracts from Overseas

OBTN, January 2008, Volume 2, Issue 1

Articles in this issue include:Sweden: What Do Genes Have to Do With Cancer Survival?

%u25BA SWEDEN

What Do Genes Have to Do With Cancer Survival?

It is well known that genetic phenotype has an effect on cancer incidence, such as breast cancer appearing in members of the same family. Does genetic phenotype also influence survival in cancer? According to researchers from the Karolinska Institute, Stockholm, Sweden, the answer is yes.

The investigators conducted a population-based study of a database of Swedish families, which covered approximately 3 million families. The database included specific information on cancer incidence, treatment, and survival. The database was examined to assess the association of parents and their grown children who were diagnosed with the same cancer. Using Kaplan-Meier survival modeling, offspring’s survival was compared with that of their parents.

The researchers found that grown children who experienced the same cancer as their parent and whose parent had died within 10 years of diagnosis demonstrated shorter survival for at least four common neoplasms compared with parents with longer survival. Specifically, the increased risk of shorter survival for offspring was 75% for breast cancer, 123% for cervical cancer, 107% for colorectal cancer, 107% for prostate cancer and 39% for lung cancer compared with children whose parents survived at least 10 years from diagnosis.

Increased risk of shorter survival in offspring with same cancer as parent who experienced short survival.

Cancer Type

Relative Risk

Lung

39%

Breast

75%

Prostate

107%

Colorectal

107%

Cervical

123%

The authors conclude that cancer-specific survival in parents may predict same cancer survival in their children. It is an interesting finding in that advances in treatment do not seem to affect these results, or compensate for what might be a less favorable genetic phenotype across many types of cancers. This finding may be of particular importance in choosing treatment approaches (e.g., watchful waiting vs. active treatment in patients with prostate cancer).

2007 Nov;8(11):1001-10016. E-pub 2007 Oct 24.

Lindström LS, Hall P, Hartman M, et al: Familial concordance in cancer survival: A Swedish population-based Study. Lancet Oncol

%u25BA UNITED KINDOM

New Renal Sarcoma Type Characterized

Researchers from Cardiff University, United Kingdom, have reported that they have isolated 20 cases of a previously unidentified kidney sarcoma type.

They sought out unusual anaplastic tumors with varying phenotypical features from a number of registries, including the National Wilms' Tumor Study Pathology Center, the U.K. Children’s Cancer Study Group Trial, and the International Society of Pediatric Oncology. From this evaluation, the investigators grouped 20 cases of a distinct class of renal sarcoma.

These tumors presented most commonly as a large mass (mean diameter, 12.7 cm; weight, 835 g). Cystic components were apparent in the majority of the tumors assessed. All of the tumors demonstrated spindle cells (either with multiple foci or diffuse), anaplastic changes and atypical mitotic figures.

They noted that most of the patients with this tumor type were young (mean age, 12 yr; median, 5 yr), although one patient was 41 years of age. Of these 20 cases, 13 were female patients. The tumors seemed to appear unilaterally, with the right kidney involved in 12 of the 17 evaluable cases.

Patients were usually diagnosed as having anaplastic Wilms' tumors and received treatment appropriate for the diagnosis. Roughly one-half of the patients were diagnosed in stages 1 and 2, and of the 13 patients with at least 2 years of follow-up, 3 died and 2 were lost to follow-up. Four patients experienced metastases to distant tissue (3 cases of lung, 2 cases of bone and liver) and 1 demonstrated a local recurrence. However, as the tumor has features that are different than that for Wilms' tumors, the researchers note that prognosis is difficult.

Vujanic GM, Kelsey A, Perlman EJ, et al: Anaplastic sarcoma of the kidney: A clinicopathologic study of 20 cases of a new entity with polyphenotypic features

. Am J Surg Pathol 2007;31(10):1459-1468.

Vinflunine for the Treatment of Malignant Pleural Mesothelioma

According to the Centers for Disease Control and Prevention, 2,500 Americans die each year as a result of malignant pleural mesothelioma, which is primarily a worksite-related carcinoma (caused by asbestos exposure). Globally, the incidence of this disease is rising, especially in countries where the use of asbestos is not largely regulated.

The latest approved therapy specific for mesothelioma, pemetrexed and cisplatin chemotherapy, has been found to increase survival by only 3 months. Oncologists are desperately seeking additional options. In Oxford, United Kingdom, a group of oncology researchers found that monotherapy with a novel investigational therapy can help improve tumor response.

In this multicenter trial, 62 evaluable patients with malignant pleural mesothelioma were given vinflunine, a microtubule inhibitor, if they had not not received previous chemotherapy or radiotherapy. Vinflunine 320 mg/m2 was administered intravenously on day 1 of multiple 21-day cycles.

Of the 62 patients with assessable data, median tumor response rate was 13.8% and survival was 10.8 months. Neutropenia (45%) and constipation (9%) were the most common grade 3 and 4 toxicities associated with the agent.

Although the data do not demonstrate a major therapeutic advance, these data “are encouraging for a single agent” say the authors, and offer clinicians another option in treating patients with malignant pleural mesothelioma.

Talbot DC, Margery J, Dabouis G, et al: Phase II study of vinflunine in malignant pleural mesothelioma.

2007;25(3):4751-4756.

J Clin Oncol

%u25BA SOUTH KOREA

Do-not-Resuscitate Orders in South Korea

Attitudes in Another Country

Journal of Palliative Medicine

For terminal patients, U.S. hospitals, hospices, and other facilities actively seek and catalogue do-not-resuscitate (DNR) orders. Do-not-resuscitate orders are also used in other nations, but little is known here about DNR practices around the world. Oncologists from Gyeonggi, South Korea, described in the how DNR orders are used in teaching cancer centers in their country.

They examined records of 387 cancer deaths at four cancer centers over a 12-month period in 2005, assessing how the DNR was obtained, population demographics, and the period of time between DNR order consent and death.

They found that 76% of the cases examined had DNR orders. Each of the DNR orders were approved by the family; none of the patients signed the orders. The DNR consent forms were preprinted in 57% of the cases. The other DNR consents were provided verbally (43%). Of the patients without DNR orders, the physician decided, without family consultation, to withhold resuscitation in 16% (62 patients). Despite the presence of DNR orders, it was provided anyway in 7% of the patients. Interestingly, two of the hospitals interpreted the DNR orders differently than the other two centers, which forbade resuscitation: For them, it implied “limited care.”

The DNR discussion took place within one week of death for 77% of the 296 for whom consent was obtained. The investigators concluded that there is much need for improvement in the use of DNR orders in Korean cancer centers, including the need to involve the patient in the decision by having the discussion earlier, and better documentation of the orders themselves.

Kim DY, Lee KE, Nam EM, et al: Do-not-resuscitate orders for terminal patients with cancer in teaching hospitals of Korea

2007;10(5):1153-1158.

. J Palliative Med

%u25BAFRANCE

Attempting to Account for Cancers not Related to Lifestyle or Genetics

Assuming that lifestyle-related factors, increased screening, and the aging of the population cannot fully explain the overall growing incidence of cancer, French investigators sought to determine the role played by environmental factors. It is expected that environmental factors play a greater role than previously thought.

The researchers, from the European Hospital Georges Pompidou and the Association for Research and Treatments Against Cancer, analyzed data from environmental factors that are rated as definitely carcinogenic and potentially carcinogenic. The list included microbial factors, radiation, and chemicals. They found that chemicals related to environmental pollution play an important role, particularly because of their relation to occupational cancers.

The list of major concern included outdoor air pollution (associated with polycyclic aromatic hydrocarbons), indoor air pollution (secondhand tobacco smoke, formaldehyde, benzene and 1,3-butadiene exposure), and food pollution (food additives and carcinogenic contamination with pesticides, nitrates, dioxins). The investigators also point to a possible role played by pharmaceutical medicines and cosmetic products.

They believe that the number of carcinogens and mutagenic factors found in the environment must play a major role in idiopathic tumor development, but studies have not yet been conceived to adequately attribute what proportion of cancers may be related to our surroundings.

Belpomme D, Irigaray P, Hardell L, et al: The multitude and diversity of environmental carcinogens

.

2007;105(3):414-429.

Environ ResDoes Split-Course Radiation Produce Better Results in Esophageal Cancer?

For patients with locally advanced esophageal cancer, resection of the carcinoma is often preferred. However, combination chemotherapy and radiotherapy has been found to be a promising alternative. Researchers from Dijon, France, tested whether combination chemoradiotherapy may provide similar long-term results when administered as a split regimen, compared with continuous, protracted therapy, which is often used.

The investigators followed the outcomes of 446 patients treated between 1993 and 2000, stratifying patient groups according to the type of radiation therapy applied. For the patients receiving protracted radiotherapy, a dose of 46 Gy was scheduled to be administered for 4.5 weeks. For patients receiving split-course radiotherapy, 15-Gy doses of radiation were administered in two 1-week cycles. In both patient groups, two cycles of cisplatin and fluorouracil were delivered concomitantly.

In case of exclusive CRT, a further course of 20 Gy over 2 weeks in the P-RT group and one 1-week course of 15 Gy in the SC-RT group were delivered with three courses of chemotherapy.

Of the 285 patients receiving split-course induction radiation therapy, 68% had a response. This result was not significantly different from the response rate in the 161 patients receiving protracted radiation therapy (67%). The investigators noted a 2-year local relapse-free survival of 57% for those receiving receiving split-course radiochemotherapy compared with 77% in those receiving protracted treatment (P = .002). Overall 2-year survival favored protracted treatment versus the split-course treatment, although this difference was not significantly different.

Two-Year Local Relapse-Free Survivals

Radiation Therapy Regimen

Relapse-Free Survival

Split-Course

57%

Protracted Course

77%

The authors, radiation oncologists, concluded that protracted, continued chemoradiotherapy leads to better local esophageal tumor control.

Crehange G, Maingon P, Peignaux K, et al: Phase III trial of protracted compared with split-course chemoradiation for esophageal carcinoma: Federation Francophone de Cancerologie Digestive 9102

.

2007;25(31):4895-4901.

J Clin Oncol

%u25BA SWEDEN, FINLAND, JAPAN

Does High Fiber Intake Prevent Postmenopausal Breast Cancer?

Much investigation has been undertaken into whether increasing dietary fiber intake can ward off colorectal cancer, but researchers from Sweden, Finland, and Japan examined a new question related to dietary fiber: Do patients who eat a high amount of fiber have reduced risk of breast cancer, and does it affect the risk of tumors of different hormone-receptor types?

Using a Swedish mammography screening database of nearly 52,000 women, the researchers assessed estrogen receptor (ER) and progesterone receptor (PR)—stratified breast cancer incidence and a number of lifestyle and hereditary factors. They evaluated each woman’s fiber intake using a food-frequency questionnaire that was completed 10 years apart (in 1987 and 1997). The women were classified according to fiber-intake quintile.

The study cohort was followed for an average of 8.3 years. During follow-up, 1,188 breast cancer cases were registered in which the tumor’s receptor status was identified. When examining breast cancer rates for the highest to the lowest quintile of fiber intake, the investigators found inverse correlations between total fiber intake and the risk of all tumor-receptor subtypes. These correlations were not statistically significant (Table).

Relative Risk of Breast Cancer by Hormone Receptor and Fiber Intake

Highest vs. Lowest Quintile for Overall Fiber Intake

ER /PR Tumor

0.85*

ER /PR- Tumor

0.83*

ER-/PR- Tumor

0.94*

*Not statistically significant.

When further evaluating the cohort’s ingestion of high amounts of a specific fiber type (e.g., fruit fiber), a 38% relative risk of ER and PR tumors was revealed, compared with the lowest quintile of fiber intake.

If the women had used hormone replacement therapy postmenopausally, total fiber intake (particularly for cereal fiber) was associated with nearly a 50% reduced risk for overall breast cancer and for ER and PR tumors when comparing the highest to the lowest quartile. This relationship did not exist for women who never used postmenopausal hormone therapy.

Suzuki R, Rylander-Rudqvist T, Ye W, et al: Dietary fiber intake and risk of postmenopausal breast cancer defined by estrogen and progesterone receptor status: A prospective cohort study among Swedish women

.

2007;122:403-412.

Int J Cancer