Elsevier

The Lancet Oncology

Volume 10, Issue 9, September 2009, Pages 849-854
The Lancet Oncology

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Standard versus pH-adjusted and lidocaine supplemented radiocolloid for patients undergoing sentinel-lymph-node mapping and biopsy for early breast cancer (PASSION-P trial): a double-blind, randomised controlled trial

https://doi.org/10.1016/S1470-2045(09)70194-9Get rights and content

Summary

Background

Sentinel-lymph-node (SLN) mapping and biopsy maintains staging accuracy in early breast cancer and identifies patients for selective lymphadenectomy. SLN mapping requires injection of technetium-99m-sulfur colloid—an effective but sometimes painful method, for which better pain-management strategies are needed. In this randomised, double-blind trial, we compared degree of pain between standard radiocolloid injection and pH-adjusted and lidocaine-supplemented formulations for patients undergoing SLN mapping for breast cancer.

Methods

Between Jan 13, 2006, and April 30, 2009, 140 patients with early breast cancer were randomly assigned in a 1:1:1:1 fashion to receive the standard topical 4% lidocaine cream and injection of [99mTc]Tc-sulfur colloid (n=35), or to one of three other study groups: topical placebo cream and injection of Tc-sulfur colloid containing either sodium bicarbonate (n=35), 1% lidocaine (n=35), or sodium bicarbonate and 1% lidocaine (n=35). The randomisation sequence was computer generated, and all patients and investigators were masked to treatment allocation. The primary endpoint was patient-reported breast pain immediately after radioisotope injection, using the Wong-Baker FACES pain rating scale and McGill pain questionnaire, analysed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT00940199.

Findings

19 of the 140 patients enrolled were excluded from analysis: nine declined study participation or sought care elsewhere, nine did not undergo SLN mapping because of disease extent or a technical problem, and one had unreliable data. There were no adverse events. Mean pain scores on the Wong-Baker scale (0–10) were: 6·0 (SD 2·6) for those who received standard of practice, 4·7 (3·0) for those who received radiocolloid plus bicarbonate, 1·6 (1·4) for those who received radiocolloid plus 1% lidocaine, and 1·6 (1·3) for those who received radiocolloid plus bicarbonate and 1% lidocaine (p<0·0001). Mean pain rating, according to the McGill questionnaire (0–78), was 17·5 (SD 11·8) for the standard-of-care group, 15·4 (14·4) for the sodium bicarbonate group, 4·6 (4·5) for the 1% lidocaine group, and 3·4 (5·1) for the sodium bicarbonate plus 1% lidocaine group (p<0·0001). SLN identification rates for each group were: 96% for the standard of care, 97% for sodium bicarbonate, 90% for 1% lidocaine, and 90% for sodium bicarbonate plus 1% lidocaine group (p=0·56).

Interpretation

For centres that use radiocolloid injections for SLN mapping in patients with early breast cancer, the addition of 1% lidocaine to the radioisotope solution can improve patient comfort, without compromising SLN identification.

Funding

US Military Cancer Institute, the Clinical Breast Care Project, and the Army Regional Anesthesia and Pain Management Initiative.

Introduction

Sentinel-lymph-node (SLN) mapping and biopsy is the preferred axillary staging procedure for patients with early breast cancer. Staging accuracy is equivalent to axillary dissection, with lower rates of morbidity. Many studies have confirmed the accuracy of SLN mapping and biopsy using radiolabelled colloids or blue dye,1, 2, 3, 4, 5, 6, 7 but there has also been much controversy and technical variation with the technique. Many SLN injection techniques exist, including peritumoral or intraparenchymal, subdermal, dermal, and intratumoral (seldom used in the USA).8 Previously, we used peritumoral injection with technetium-99m-sulfur colloid and found an SLN identification of 93·2% and false-negative rate of 11·4%.9 We modified our approach to subareolar (subdermal) radioisotope injection after data showed improved SLN identification and false-negative rates with subdermal (96·3% and 6·4%, respectively) and dermal (98·0% and 6·5%) versus peritumoral (88·2% and 8·0%) radioactive colloid injection with or without blue dye.10 Subareolar[99mTc]Tc-sulfur colloid injection is a technically simple and practical approach; it allows for rapid axillary nodal uptake of radioisotope, avoids the overlap of radioactivity between peritumoral injection and SLN(s) for upper, outer quadrant, or multifocal lesions, and obviates the need for image-guided peritumoral injection for non-palpable breast cancers.

Surprisingly little has been published on pain related to radioisotope injection for lymphatic mapping in breast cancer. Krynyckyi and colleagues8, 11, 12 reported a reduction in cutaneous pain with the use of topical anaesthetics (EMLA cream [lidocaine 2·5% and prilocaine 2·5%], Astra Pharmaceuticals, Wayne, PA, USA) before intradermal radioisotope injection. The researchers reported adding lidocaine to the radioisotope preparation for shallow subareolar injections to improve patient comfort with the procedure, but they did not provide quantitative data or assess the effect of adding lidocaine on success of the nodal mapping technique. We have had success with subareolar injection as a technique; however, shallow subdermal sulfur colloid injections are more painful than intraparenchymal injections. To reduce pain, we included a topical anaesthetic (4% lidocaine cream), applied to the skin of the nipple-areolar complex 1 h before subareaolar injection of 4 mL [99mTc]Tc-sulfur colloid (1 mCi, 0·1 mL in 3·9 mL normal saline). We did not find this technique particularly effective for managing the pain associated with injection of low pH [99mTc]Tc-sulfur colloid, although others have reported effectiveness with topical anaesthetic creams, used in the same context, for control of local skin-surface pain.11, 12

In addition to a local anaesthetic, pH modification of the sulfur colloid has been suggested to improve patient comfort.8 We assessed whether pH adjustments or addition of 1% lidocaine to the radioisotope solution improves pain control, at time of injection, for patients undergoing SLN mapping for breast cancer.

Section snippets

Patients

140 patients were enrolled from January, 2006, to April, 2009, at the Walter Reed Army Medical Center in Washington, DC, USA. Eligible patients were those who presented with non-painful, biopsy-proven early stage (T1 or T2; node-negative) infiltrating breast cancer, without antecedent allergy to local anaesthetics, chronic pain syndromes (eg, fibromyalgia rheumatica), or active narcotic-based pharmacotherapy. Only patients who were not pregnant, older than 18 years of age, and capable of

Results

From Jan 13, 2006, to April 30, 2009, 140 patients were randomly assigned to one of the four study groups (figure 1). 28 patients in the control group, 31 patients in the sodium bicarbonate group, 32 patients in the 1% lidocaine group, and 30 patients in the sodium bicarbonate plus 1% lidocaine group completed the study protocol and were analysed for degree of pain at the time of subareolar injection of radioisotope (figure 1). Of the 19 patients who were excluded from the study, nine declined

Discussion

A significant degree of pain is associated with standard [99mTc]Tc-sulfur colloid injections for patients undergoing SLN mapping for breast cancer. Although modification of the pH of the radioisotope preparation, with sodium bicarbonate, provided no incremental benefit compared with the standard preparation, the addition of 1% lidocaine provided a significant reduction in pain associated with subareolar injection of sulfur colloid, according to both pain scales used in this study, and did not

References (13)

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