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Superficial melanoma conferred a risk of recurrent invasive melanoma similar to that of primary invasive melanoma, four to five times greater than the melanoma risk of the general population, Australian investigators reported. The study is one of several oncology-related news items summarized in OncoBriefs.

High Recurrence Risk With Invasive or In Situ Melanoma

Patients with invasive melanoma have an increased risk of invasive recurrence, but relatively few studies have examined the risk of invasive recurrence after primary in situ melanoma. Even fewer have studied recurrence after primary in situ melanoma by body site of the primary and recurrent lesions, , of Cancer Council Queensland, in Spring Hill, Australia, and colleagues reported online in .

The authors retrospectively analyzed population-based administrative data to identify new melanoma diagnoses documented by the Queensland Cancer Registry for 1982 to 2005. Follow-up continued through 2010. The final analysis comprised 39,668 cases of first primary invasive melanoma and 22,845 cases of first primary in situ melanoma.

Investigators calculated standardized incidence ratios (SIRs) for melanoma recurrences, excluding cases involving recurrence within 60 days of the primary diagnosis.

Subsequently, 5,358 patients had invasive melanoma recurrences, 3,520 among patients who initially had invasive melanoma and 1,838 patients who initially had melanoma in situ. Resulting SIRs were 5.42 for patients who had a first primary invasive melanoma and 4.59 for patients who had a first primary in situ melanoma.

The risk of invasive recurrence persisted throughout follow-up. In general, recurrent primary invasive melanoma arose more often on the body site of the initial melanoma. The highest risk of invasive first recurrence was observed in women who had initial primary invasive melanoma and recurrent primary invasive melanoma on the head (SIR 13.32).

"Clinical practice guidelines have recognized the importance of monitoring for people with invasive melanoma," the authors concluded. "The results of the present study highlight the need for similar levels of supervision for those with a diagnosis of in situ melanoma."

3-Drug Combo Active in Relapsed Myeloma

Almost two-thirds of patients with relapsed/refractory multiple myeloma had partial or better response to treatment with the combination of lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone, data from a phase II trial showed.

Three-fourths of the 64 patients remained alive and progression free for 6 months or longer. The regimen was associated with a median progression-free survival of 9.5 months and median overall survival of 30 months in a patient population with an extensive treatment history, Paul G. Richardson, MD, of Dana-Farber Cancer Institute in Boston, and co-authors reported in .

Phase I data had provided evidence of the combination's activity in heavily pretreated relapsed/refractory myeloma, including patients whose disease previously had proved refractory to one or more of the agents in the regimen.

To continue investigation of the three-drug combination, Richardson and colleagues enrolled patients who had relapsed or refractory myeloma and were exposed to as many as three prior regimens. Patients previously treated with bortezomib, thalidomide, or lenalidomide, with or without dexamethasone were eligible, but patients who had received bortezomib and lenalidomide in combination were not.

Median treatment duration was 8 months, and 18 of 64 patients continued treatment for more than 12 months. The median number of completed cycles of therapy was 11 and ranged as high as 64.

No unexpected toxicity was observed. The most frequent treatment-related toxicities (all grades) included sensory neuropathy (58%), fatigue (50%), and neutropenia (42%). The most common grade 3/4 toxicities were neutropenia (30%), thrombocytopenia (22%), and lymphopenia (11%).

The regimen had "substantial activity regardless of prior therapy or adverse prognostic characteristics" and warrants further investigation, including the potential benefits of adding a fourth drug, the authors concluded.

Durable Benefits of RT After Mastectomy

Adjuvant radiation therapy led to lasting benefits after mastectomy in women who had as many as three positive lymph nodes, irrespective of chemotherapy, an analysis of multiple clinical trials showed.

Women with limited nodal involvement had a 32% reduction in the risk of recurrence at 10 years and a 20% reduction in the risk of dying of breast cancer after 20 years. Women with four or more involved lymph nodes also benefited from adjuvant radiation therapy after mastectomy and nodal dissection, but patients with no nodal involvement did not.

The results might underestimate the true benefits of adjuvant radiation therapy after mastectomy, investigators in the (EBCTCG) reported online in .

"The proportional gains from radiotherapy might, however, be greater for women irradiated today than suggested by this example, because radiotherapy planning has changed substantially and women today receive better coverage of target areas," the authors noted. "Furthermore, doses to normal tissues are lower today, so the risks of radiotherapy are also likely to be lower."

Randomized clinical trials conducted by the EBCTCG have demonstrated that post-mastectomy radiation therapy improves outcomes after mastectomy for early breast cancer with nodal spread. Clinical guidelines have incorporated the findings by recommending adjuvant radiation therapy for women with four or more positive lymph nodes.

However, previous reports provided limited data regarding outcomes in women with one to three positive lymph nodes. To address the issue, members of the EBCTCG analyzed data from long-term follow-up in 22 clinical trials conducted during 1964 to 1986. The authors analyzed recurrence during 10 years of follow-up, as well as 20-year mortality.

The analysis included 3,786 women whose treatment included axillary lymph node dissection at least to level II, which revealed zero positive nodes, one to three positive nodes, or four or more involved nodes. Adjuvant radiation therapy did not significantly reduce recurrence or mortality in 700 women with no nodal involvement.

For the subgroup of 1,314 women who had one to three positive nodes, adjuvant radiation therapy was associated with a significant reduction in the 10-year risk of recurrence (P=0.00006) and in 20-year mortality (P=0.01). The remaining 1,772 women who had four or more involved lymph nodes had a 21% reduction in the 10-year risk of recurrence (P=0.0003) and a 13% lower 20-year mortality (P=0.04).

Colonoscopy Good but Not Perfect

A study of 2,600 patients who developed colorectal cancer showed that 6% of the cancers occurred within 5 years of a negative colonoscopy evaluation.

Analysis of factors associated with the interval cancers (referring to the interval between colonoscopy procedures) showed associations with location in the proximal colon, earlier-stage disease, a lower risk of proving fatal, a higher rate of adenomas, and a family history of colorectal cancer.

"These findings indicate that interval colorectal tumors may arise as the result of distinct biologic features and/or suboptimal management of polyps at colonoscopy," N. Jewel Samadder, MD, of the University of Utah in Salt Lake City, and colleagues concluded in an article published in the April issue of .

Oncologists have long recognized that a small number of colorectal cancers are diagnosed within a few years after a negative colonoscopy procedure. Whether the tumors represent a lesion missed by colonoscopy or a new cancer has remained unclear. To inform the issue, Samadder and colleagues analyzed records for 126,851 patients who underwent colonoscopy at two healthcare systems from 1995 through 2009.

During follow-up, 2,659 patients subsequently developed colorectal cancer, including 159 that were diagnosed within 60 months of a negative colonoscopy procedure. Neither sex nor age was associated with interval cancers. The authors found that adenomas were seen during colonoscopy in 57% of the patients with interval cancers compared with 36% of patients who had cancer identified at colonoscopy and 26% of patients who did not develop colorectal cancer (P<0.001).

Interval cancers were more than twice as likely to be proximally located (OR 2.24, P<0.001), and the patients were more than twice as likely to have a family history of colorectal cancer (OR 2.27, P=0.008). The tumors tended to be earlier stage as compared with tumors detected at colonoscopy, and patients were almost 40% less likely to die of an interval cancer (HR 0.63, P<0.001).

"The association of proximal tumor location, earlier stage at diagnosis, and survival advantage compared with detected colorectal cancers suggest that tumor biology may play an important role in the pathogenesis of these lesions," the authors said.

"There are at least three predominant pathways for sporadic colorectal cancer development: the chromosomal instability pathway, the mismatch repair pathway, and the serrated pathway. These pathways have been associated with different clinicopathologic associations and prognostic potential."