ORLANDO, June 2 — Oncologists may talk about preserving fertility but they don’t do much about it.

• Explain to interested patients that cancer therapy can impair fertility.
• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

That’s the bottom line of a national survey of doctors about their attitudes and knowledge of fertility preservation guidelines, as well as what they actually do, according to Gwendolyn Quinn, Ph.D., of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla.

The survey found that 70% of oncologists said they discuss the issue with newly diagnosed patients, but less than 25% refer patients to fertility specialists, Dr. Quinn said at the annual meeting of the American Society of Clinical Oncology.

She and her colleagues mailed the survey to a random sample of 1,979 oncologists, of whom 613 — or 33% — responded. The physicians were quizzed on their knowledge of the 2006 ASCO guidelines, as well as what they do about them.

Of the respondents, 38% said they had no knowledge of the guidelines, Dr. Quinn said, although, overall, seven out of 10 said they make a habit of discussing fertility with patients.

But the depth of that talk could vary considerably, she said. “It might be as simple as saying ‘you could become sterile as a result of your treatment’ to a lengthy discussion,” Dr. Quinn said.

Less than 25% of the doctors said they distributed educational materials on the subject to patients.

Dr. Quinn said about 450,000 people every year could be in need of fertility counseling after a diagnosis of cancer. It’s unlikely that an information campaign aimed at patients would give them the knowledge they need, she said.

“This is definitely a physician responsibility,” Dr. Quinn said.

One reason doctors give for not talking about the issue is that the nature of the patient’s disease is so pressing there’s no time for fertility preservation, Dr. Quinn said.

So they simply don’t discuss the option, she said.

Another issue is the cost of fertility preservation, which is not covered by any insurance plan in the U.S., she said.

The information gap is understandable, according to Jennifer Obel, M.D., of the NorthShore University HealthSystem in Evanston, Ill., who moderated a press conference at which the research was represented.

“Caring for a cancer patient is very complex at the moment of diagnosis,” Dr. Obel said. “Fertility preservation can run down to a less important priority.”

And patients are often “dumbstruck at the diagnosis,” she said. “They’re not thinking about it.”

But she said it’s important to “re-prioritize” the issue.

“Our patients lack the concrete information that may help them preserve their fertility,” she said.

Noting that the theme of this meeting is personalized care, Dr. Obel said, “we need to personalize care across the continuum of a patient’s life.”

The study was supported by the American Cancer Society. The researchers said they had no disclosures to report. Dr. Obel said she had financial links with Onyx Pharmaceuticals.

Primary source: Journal of Clinical Oncology

Source reference:

Quinn G, et al “National survey of physicians practice patterns: Fertility preservation and cancer patients” J Clin Oncol 2009; 27(15S): Abstract CRA9508.

ORLANDO, June 4 — Neoadjuvant chemotherapy demonstrated a small survival advantage over surgery alone for early-stage non-small cell lung cancer (NSCLC) and was better tolerated than adjuvant chemotherapy, researchers found.

• Explain to patients that giving chemotherapy before surgery led to a small improvement in disease-free survival in patients with non-small cell lung cancer.
• Note that preoperative and postoperative chemotherapy were not directly compared.
• Note, too, that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

But neither the 6.5% absolute difference in disease-free survival at three years nor the 4.2% difference at five years achieved statistical significance, Enriqueta Felip, M.D., of Valle d’Hebron Hospital in Barcelona, reported here.

“To better define the role of preoperative chemotherapy in patients with clinical stage I and II non-small cell lung cancer, studies addressing preoperative chemotherapy in early-stage disease should be analyzed in conjunction with each other and with our trial,” Dr. Felip told attendees at the American Society of Clinical Oncology meeting.

Stage I-II NSCLC has a five-year survival of 25% to 50%. Adjuvant chemotherapy is the standard of care for stage II-III but remains controversial for stage IB, said Dr. Felip.

Several studies have demonstrated a trend toward improved survival in patients treated with neoadjuvant chemotherapy, she said.

Collectively, the evidence provided a good rationale to examine adjuvant and preoperative chemotherapy in patients with early-stage disease, she continued.

To evaluate the relative impact of pre- and postoperative therapy compared with surgery alone, Dr. Felip and her colleagues studied 624 patients with clinical stage IA, IB, II, and T3N1 (stage IIIA) NSCLC. Patients with N2 disease, who typically have the worst prognosis, were not included in the study.

The patients were randomized to surgery alone, surgery followed by three cycles of postoperative paclitaxel-carboplatin chemotherapy, or to three cycles of preoperative chemotherapy followed by surgery.

The primary objective was to determine whether adjuvant or preoperative chemotherapy improves five-year disease-free survival compared with surgery alone.

Secondary objectives were chemotherapy-related toxicity, overall survival, and identification of predictive and prognostic molecular markers.

About three-fourths of the patients had clinical stage I (T1N0 or T2N0), and no more than 3% of patients in any treatment group had stage III disease.

About 90% of patients in each group had successful surgical resection. Substantially more patients received preoperative chemotherapy (97%) compared with adjuvant chemotherapy (66%).

Additionally, 90% of patients assigned to preoperative chemotherapy completed the planned three cycles, as did 93% of patients who received adjuvant chemotherapy.

Dr. Felip reported that 18 patients in the preoperative chemotherapy group had complete responses and 88 had partial responses, resulting in an overall response rate of 53%. An additional 63 patients (32%) had stable disease.

In the adjuvant therapy arm, toxicity was common but usually not severe. The most common toxicities (all grades) were anemia (42.4%), fatigue (34.4%), sensory neuropathy (32.4%), nausea/vomiting (31.9%), myalgia (28.7%), and neutropenia (27.2%). Only two patients had grade 4 toxicity.

Patients who received preoperative chemotherapy had a toxicity profile similar to that of the adjuvant therapy group, although more patients had grade 3-4 toxicity, including seven cases of grade 4 toxicity.

Comparing surgery alone with surgery plus adjuvant or preoperative chemotherapy revealed no significant differences in disease-free survival:

• Median: 25.1 months for surgery, 26.0 for adjuvant chemotherapy, 31.5 for preoperative chemotherapy
• Three-year disease-free survival: 41.9%, 44.9%, 48.4%
• Five-year disease-free survival: 34.1%, 36.6%, 38.3%

Comparison of disease-free survival by baseline disease stage revealed a trend favoring preoperative chemotherapy versus surgery alone at three years (39.4% versus 29%) and at five years (36.6% versus 25%, P=0.07).

The rate of disease-free survival was higher still in patients who had complete or partial responses to preoperative chemotherapy: 59% at three years and 51% at five years.

Overall survival did not differ significantly among the groups:

• Median: Surgery 48.8 months, adjuvant chemotherapy 50.3 months, preoperative chemotherapy 55.2 months
• Three-year: 58.6%, 58.4%, 59.2%
• Five-year: 44%, 45.5%, 46.6%

Dr. Felip and her co-investigators reported no disclosures.

Primary source: Journal of Clinical Oncology

Source reference:
Felip E, et al “Surgery alone, or surgery followed by adjuvant paclitaxel/carboplatin (PC) chemotherapy or preoperative PC followed by surgery, in early stage non-small cell lung cancer: results of the multicenter, randomized, phase III NATCH trial” J Clin Oncol 2009; 27(15 suppl): Abstract 7500.

ORLANDO, June 4 — The presence of micrometastases in sentinel lymph nodes mandates additional treatment for patients with early-stage breast cancer to reduce the risk of axillary recurrence, data from a Dutch study suggest.

• Explain to patients that the presence of small particles of tumor in a lymph node indicates a need for additional treatment to reduce the risk of breast cancer recurrence in the axilla.
• The findings are based on a retrospective review of a large database, not a prospective clinical trial, so the study can only show an association.
• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Micrometastases increased the five-year risk of axillary recurrence more than four-fold compared with no evidence of disease in sentinel nodes, Vivianne Tjan-Heijnen, M.D., Ph.D., of Maastricht University Medical Center in the Netherlands, reported at the American Society of Clinical Oncology meeting.

The study also showed that about 10% of physicians do not treat micrometastases, presumably because of concern about overtreatment, she added.

“For patients with completely negative nodes, omission of axillary therapy is safe and standard policy,” Dr. Tjan-Heijnen concluded. “For patients with isolated tumor cells, omission of axillary therapy may only be safe in the presence of otherwise favorable tumor characteristics.”

Dr. Tjan-Heijnen said she and her colleagues recommend complete axillary treatment in patients with micrometastases to reduce the risk of axillary recurrence.

Studies conducted before the sentinel node era yielded conflicting results about the prognostic implications of small nodal metastases, said Dr. Tjan-Heijnen.

The Dutch investigators recently extended the examination of prognostic significance to sentinel node biopsies in the MIRROR study (Micrometastases and Isolated Tumor Cells: Relevant and Robust Or Rubbish?).

As reported last year, MIRROR showed that both isolated tumor cells and micrometastases significantly increased the hazard for disease-free survival. Moreover, the patients benefited from adjuvant systemic therapy. (See SABCS: Nodal Micrometastases Raise Breast Recurrence Risk)

The first analysis of MIRROR data showed that almost half of 795 patients with isolated tumor cells and 15% of 1,028 with micrometastases did not receive additional therapy targeted to the axilla. Another 8% of patients received only axillary radiotherapy, said Dr. Tjan-Heijnen.

The current analysis focused on the clinical implications of not treating microscopic residual tumor or treating only with axillary radiation.

MIRROR included 2,680 patients who had sentinel node biopsies from 1997 to 2005 and a final nodal status of pN0, pN0(i+) [isolated cells], or pN1mi (micrometastases).

All patients had favorable characteristics by 2002 Dutch guidelines, defined as tumor size ?1 cm irrespective of grade or tumor size 1 to 3 cm and grades 1 to 2.

Dr. Tjan-Heijnen reported that 1,218 patients had only sentinel node procedures, 1,314 had complete axillary node dissection, and 148 received axillary radiation therapy.

Only 13% of the sentinel-node group received adjuvant systemic therapy, compared with a majority of patients in the other two categories (P<0.0001).

The entire study population had a five-year axillary recurrence rate of 1.7%.

For patients with negative sentinel nodes (pN0), the recurrence rate did not differ significantly between patients who had complete axillary dissection and those who had sentinel node evaluation only (1.6% versus 2.3%).

The presence of isolated tumor cells (pN0[i+]) increased the hazard ratio for recurrence in patients who had only a sentinel node biopsy and those who had complete axillary dissection. However, the difference was not statistically significant (2.0% versus 0.9%, HR 2.39, 95% CI 0.67 to 8.48).

Patients with micrometastases (pN1mi) did have a significantly greater risk of recurrence compared with patients who had complete axillary dissection or irradiation of the axilla (5% versus 1%, HR 4.39, 95% CI 1.46 to 13.24).

None of the patients who had axillary radiotherapy after a positive sentinel node procedure had an axillary recurrence, regardless of whether the sentinel node contained isolated tumor cells or micrometastases.

The number of patients was too small (148) for meaningful comparisons with the other groups, but the findings are “provocative, challenging the current recommendation of complete axillary node dissection,” said Dr. Tjan-Heijnen.

In multivariate analysis, other factors that influenced the risk of axillary recurrence in patients with micrometastases included tumor size (HR 8.62, P=0.021), histologic grade (HR 25.05, P=0.035), and negative hormone-receptor status (HR 4.96, P=0.010).

Omission of systemic therapy or breast radiotherapy did not increase the risk of axillary recurrence, the researchers noted.

Dr. Tjan-Heijnen reported no disclosures.

Primary source: Journal of Clinical Oncology

Source reference:
Tjan-Heijnen V, et al “Impact of omission of completion axillary lymph node dissection or axillary radiotherapy in breast cancer patients with micrometastases or isolated tumor cells in the sentinel lymph node: Results from the MIRROR study.” J Clin Oncol 2009; 27(15 suppl): Abstract CRA596.

Related Article(s):

• SABCS: Nodal Micrometastases Raise Breast Cancer Recurrence Risk