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Clinical Abstracts From Overseas

OBTN, June 2008, Volume 2, Issue 6

%u25BA India

Different HIV-Associated Cancers in India

In the United States, one of the most common cancers in patients with human immunodeficiency virus infection (HIV) is Kaposi’s sarcoma. However, a new study finds that in other countries, such as India, Kaposi’s sarcoma may not be common at all in patients with HIV infection.

Researchers from Tata Memorial Hospital, Mumbai, India, studied patients registered in the facility’s HIV Cancer Clinic. They recorded the site of any cancer occurring in these patients from 2002, and used this figure to estimate the site-specific incidence of cancer in patients with HIV infection over five years.

They found increased proportions of non-Hodgkin’s lymphoma, with a higher rate in males than females (proportional incidence ratio, 17.1 in males and 10.3 in females), and anal cancer (10.3 in men, 6.5 in females), and several other cancers (Table) that are not deemed to be “AIDS-defining.” The higher rate of cervical cancer (4.1 in women) and of vaginal cancer (7.7 in women) indicates an “urgent need for screening programs” among women with HIV infection. They did not observe any instance of Kaposi’s sarcoma, which they attribute to the low prevalence of HHV-8 virus in the Indian population.

Higher incidence of cancer found in Indian patients with HIV infection.

Non-Hodgkin’s Lymphoma

Anal Cancer

Testicular Cancer

Colon Cancer

Head and Neck Cancer

Cervical Cancer

Vaginal Cancer

Hodgkin’s Disease

The researchers concluded that the spectrum of HIV-related malignancies differs in India from that in other regions.

Dhir AA, Sawant S, Dikshit RP, et al: Spectrum of HIV/AIDS related cancers in India.

2008;19:147-153.

Cancer Causes Control

%u25BA United Kingdom

Does Surgery Have a Role In Improving Quality of Life In Patients With Spinal Metastases?

For patients whose cancer has spread to the spine, there is no consensus as to the value of spinal surgery to remove the tumors or the benefit of different surgical approaches. However, an article from London, England, explains that some benefit might be gained in these cases..

The surgeons from multiple centers included 223 patients (mean age, 61 yr) in the study who were confirmed to have metastasis to vertebral epithelial tissue. Breast, lung, renal, and prostate cancer accounted for twothirds of the primary tumors. In the majority of patients (60%), spinal tumors were characterized as widespread. Each of the patients underwent either debulking or excisional surgery (74%), or palliative decompression (26%) over a two-year period. Adjuvant therapy was administered in approximately half of the patients.

The surgery was deemed relatively safe, with a 30-day mortality of 6%. After the surgical intervention, 71% of patients who reported continual pain indicated lower pain levels. Urinary control improved in 39% of the 49 patients who had abnormal urinary sphincter function (few were incontinent before surgery).

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The surgeons noted a significantly longer median survival ( = .003) for patients undergoing excisional surgery compared with those who received palliative decompression. They cautioned that although the numbers of patients in this noncontrolled study were too small to make sweeping conclusions and the use of different surgeons may confound the results, based on these findings, active surgical treatment may show both quality of life and survival benefits for patients with spinal metastases.

Ibraham A, Crockard A, Antonietti P, et al: Does spinal surgery improve the quality of life for those with extradural (spinal) osseous metastases? An international multicenter perspective observational study of 223 patients.

2008;8:271-278.

J Neurosurg Spine

%u25BA Belgium / Italy

Pharmacogenomics Guides Treatment in Metastatic Colorectal Cancer Everyday, new molecular markers and genotypes are being identified that help define whether one pharmaceutical agent or another is best suited to specific therapy in individual patients. Unfortunately, the options for patients and clinicians in the presence of metastatic colorectal cancer are limited. Therapies are not associated with high response rates, but new findings from Belgian, Italian, and American researchers have pinpointed with greater accuracy which patients with metastatic colorectal cancer will benefit most from panitumumab treatment.

KRAS, a G-protein that is related to the activity of epidermal growth factor receptor (EGFR), and mutated forms of KRAS seemed to be correlated with low efficacy of panitumumab monotherapy, an antibody against EGFR. The researchers have found in a phase III study of 427 patients with metastasized colorectal cancer that in the 39% of patients in whom mutated KRAS was found, treatment had virtually no effect compared with those receiving best supportive care. In the patients in whom “wild-type” or nonmutated KRAS was detected, treatment response was observed in 17%. Progression-free survival was significantly different between patients with the wild-type KRAS and those who received best supportive care (Figure).

As patients with wild-type KRAS receiving panitumumab for longer periods, they experienced more toxicity than patients in whom therapy did not work or patients receiving supportive care only.

The authors noted that in order for panitumumab therapy to have a chance of yielding objective responses, patients must have nonmutated KRAS protein. Therefore, all patients being considered for such therapy should be tested for mutated KRAS first.

Amado RG, Wolf M, Peeters M, et al: Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer.

2008;26:1626-1634.

J Clin Oncol

%u25BA France

A Cold Sock to the Jaw in Fight Against Food Toxicity

One of the most common side effects of docetaxel therapy is onycholysis, which is found in three of every 10 patients. There is evidence that cooling of the hands can help avoid skin and nail toxicity, and French oncologists tested the efficacy of a new device—essentially a frozen sock—in a case-control trial on the feet.

All 50 patients entering this prospective phase II trial were administered docetaxel 70—100 mg/m2 every three weeks and served as their own control: The right foot wore the frozen sock for 90 minutes and the left foot did not.

The oncologists revealed that none of the right feet adorned with the sock had evidence of grades 0 (mild) nail toxicity, compared with 79% of the left feet. In terms of grades 1 and 2 (moderate) nail toxicities, feet with the sock were protected (0% vs. 21%, respectively). The sock did not perform as well regarding skin toxicity, however: grade 0 toxicity (98% in protected feet vs. 94% in unprotected feet) and grades 1—2 toxicities (2% vs. 6%, respectively) comparisons revealed no significant differences.

The only negative effect of the frozen sock intervention was cold feet: One patient withdrew from the study because of this discomfort.

The oncologists concluded that frozen sock therapy was effective in preventing nail toxicity related to docetoxel treatment, but it did not protect against skin toxicity.

Scotté F, Banu E, Medioni J, et al: Matched case-control phase 2 study to evaluate the use of a frozen sock to prevent docetaxel-induced oncycholysis and cutaneous toxicity of the foot.

2008;112:1625-1631.

Cancer

%u25BA New Zealand

Is Ageism the Reason Why New Zealand Lags in Lung Cancer Outcomes?

Similar to many cancers, patients with non— small cell lung cancer (NSCLC) whose tumors are detected early have the best chance of survival. Survival in New Zealand patients with this type of cancer have previously been found to be below that for Western industrialized countries, and oncologists from Auckland decided to find out why.

The researchers reviewed the records of how 142 patients in two hospital centers (Auckland and Northland) were managed with stage I or II NSCLC, which was diagnosed in 2004. They found that 56% of patients were treated with an intent to cure, and the remainder received palliative treatment only.

In patients aggressively treated, surgical excision was performed in 87% (69 patients), and only 11% received radiation treatment. One patient received chemotherapy and radiation concurrently.

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Of the 61 patients receiving palliative treatment, 40 received supportive care only. The oncologists revealed that as patient age and comorbidity increased, the less likely they were to receive potentially curative treatment. Both trends were statistically significant and independent ( = .001 and = .004, respectively). Furthermore, the researchers found that treatment was delayed in half of the patients who began potentially curative surgery, which is against the recommendations of accepted guidelines.

The authors believe that emphasis of international guidelines is necessary to improve adherence to what is considered optimal curative practices in New Zealand. However, changing practitioners’ attitudes is imperative if the proportion of patients receiving aggressive intervention is to be increased.

Stevens W, Stevens G, Kolbe J, et al: Management of stages I and II non-small cell lung cancer in a New Zealand study: Divergence from International practice and recommendations.

2008 Feb 20 [E-pub ahead of print].

Intern Med J

%u25BA Germany / Sweden

Higher Risk of Solid Tumors After Non-Hodgkin’s Lymphoma Diagnosis

Reporting in the Journal of Clinical Oncology, German and Swedish clinicians and molecular geneticists found that the risk of subsequent tumors in patients with non-Hodgkin’s lymphoma (NHL) was increased even 30 years after the diagnosis.

They evaluated the records of the 11.5 million patients in the Swedish Family—Cancer Database, and calculated standardized incidence ratios for new malignancies in the 28,131 patients who had a diagnosis of NHL.

A total of 2,290 patients had a subsequent solid tumor, for an overall incidence ratio of 1.65. The incidence ratio for new malignancies of the lymph or blood systems was 5.36, based on 369 patients. The investigators reported that the highest incidence ratio for a solid tumor was for spinal meningioma (40.8), and the incidence for new solid tumors seemed to be relatively high for most sites (except for 9).

However, they pointed out that the standardized incidence ratio for new solid tumors increased with time, up to 30 years beyond the initial NHL diagnosis in survivors. They found that the greatest probability of new solid tumors occurred between 21 and 30 years after NHL diagnosis. Not surprisingly, advancing age at the time of initial NHL diagnosis was associated with lower incident rates of new tumors.

The authors believe that the greater incidence of solid tumors with time signifies that the risk associated with the damage caused by initial therapy does not diminish up to 30 years later.

Hemminki K, Lenner P, Sundquist J, et al: Risk of subsequent solid tumors after non- Hodgkin’s lymphoma: Effect of diagnostic age and time since diagnosis.

2008;26:1850-1857.

J Clin Oncol

%u25BA China

Can Chemoembolization and Radioblation Increase Survival in Patients With Large Liver Tumors?

As the incidence of hepatitis infection rises globally, so does the incidence of hepatocellular cancer. Only 30% of patients may receive benefit from aggressive therapy, such as resection, percutaneous ablation, or liver transplant. The use of chemoembolization, in which targeted chemotherapy is combined with induced ischemic necrosis using transcatheter embolization, and collectively referred to as TACE has been used to some effect in patients with multinodular liver cancer. The use of radiofrequency thermal ablation (RFA) has been proposed as an adjuvant therapy in some cases and as a primary therapy for uninodular hepatocellular cancer. Researchers from Linan, China, have attempted to evaluate the benefits of these technologies in combination treatment, or in individual treatment.

In this randomized trial of patients with tumors of at least 3 cm in diameter, 96 patients were assigned to receive TACE before receiving RFA, 95 to receive TACE alone, and 100 to receive RFA alone. The investigators evaluated both the survival and response rate to each intervention.

They found that the likelihood for overall survival was increased for patients in the combined therapy group (hazard ratio, 2.50 for uninodular carcinoma and 1.87 for all carcinomas). The survivals in patients with uninodular tumors at one, three, and five years were 87%, 50%, and 15% in the RFA group and 93%, 79%, and 53%, respectively in the combined therapy group. The one- and five-year survivals in patients with multinodular tumors were also increased in the combined therapy group: 75% and 13% in the combined therapy group compared with 56% and 0% in the TACE-only group, respectively.

The authors also found lower recurrence rates in the combined therapy group (59% vs. 80% in TACE only and 81% in the RFA only group.

Effect of Therapies in Patients With Large Liver Tumors

Treatment

Median Survival*

Complete Response Rate

At Least Partial Response Rate

TACE and RFA

36 mo

55%

79%

TACE

24 mo

5%

59%

RFA

22 mo

37%

69%

*Based on 28.5 months median follow-up.

Based on these results, the investigators believe that performing TACE before RFA in patients with large hepatocellular tumors is a more effective intervention than either therapy alone, and it is effective in patients with uninodular and multinodular carcinomas.

Cheng BQ, Jia CQ, Liu CT, et al: Chemoembolization combined with radiofrequency ablation for patients with hepatocellular carcinoma larger than 3 cm: A randomized controlled trial.

2008;299:1669-1677.

JAMA