Tag Archives: Neoadjuvant Therapy

Sentinel lymph node surgery after neoadjuvant chemotherapy in node-positive breast cancer

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Cavalcante FP, Millen EC, Zerwes FP, Novita GG. Role of Axillary Surgery After Neoadjuvant Chemotherapy. JCO Glob Oncol. 2020 Feb;6:238-241.

“In a US study, associating selective localization and removal of clipped nodes with SLN dissection, known as targeted axillary dissection, reduced false-negative rates to approximately 2% compared with 4% with removal of the clipped lymph node alone. [20] However, patients are required to undergo two procedures: placement of the clip before systemic treatment and marking it to identify the lymph node during surgery. A retrospective analysis showed that in patients with clipped lymph nodes who were referred for preoperative marking, the clip failed to be identified in 20% of those patients, even when computed tomography was used, with the additional risk of the clip not being removed during surgery. [21] Therefore, the use of clips is controversial, because it is sometimes impossible to remove the clip alone. Despite the association between the number of lymph nodes and false-negative rates, there are still no convincing data regarding clinical outcome.”

Caudle AS, Yang WT, Krishnamurthy S, et al. Improved Axillary Evaluation Following Neoadjuvant Therapy for Patients With Node-Positive Breast Cancer Using Selective Evaluation of Clipped Nodes: Implementation of Targeted Axillary Dissection. J Clin Oncol. 2016 Apr 1;34(10):1072-8.

Results: Of 208 patients enrolled in this study, 191 underwent ALND, with residual disease identified in 120 (63%). The clipped node revealed metastases in 115 patients, resulting in an FNR of 4.2% (95% CI, 1.4 to 9.5) for the clipped node. In patients undergoing SLND and ALND (n = 118), the FNR was 10.1% (95% CI, 4.2 to 19.8), which included seven false-negative events in 69 patients with residual disease. Adding evaluation of the clipped node reduced the FNR to 1.4% (95% CI, 0.03 to 7.3; P = .03). The clipped node was not retrieved as an SLN in 23% (31 of 134) of patients, including six with negative SLNs but metastasis in the clipped node. TAD followed by ALND was performed in 85 patients, with an FNR of 2.0% (1 of 50; 95% CI, 0.05 to 10.7).

Conclusion: Marking nodes with biopsy-confirmed metastatic disease allows for selective removal and improves pathologic evaluation for residual nodal disease after chemotherapy.

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Total neoadjuvant therapy in rectal cancer

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Petrelli F, et al. Total Neoadjuvant Therapy in Rectal Cancer: A Systematic Review and Meta-analysis of Treatment Outcomes. Ann Surg. 2020 Mar;271(3):440-448.

Full-text for Emory users.

Results: A total of 28 studies (3 retrospective and 25 prospective for a total of 3579 patients) were included in the final analysis (n = 2688 treated with TNT and n = 891 with neoadjuvant chemoradiotherapy therapy). The pooled pCR rate was 22.4% (95% CI 19.4%-25.7%) in all patients treated with TNT (n = 27 studies with data available). In n = 10 comparative studies with data available, TNT was found to increase the odds of pCR by 39% (1.40, 95% CI 1.08-1.81, P = 0.01).

Conclusions: The addition of induction or consolidation chemotherapy to standard neoadjuvant chemoradiotherapy results in a higher pCR rate. Given that the comparative analysis was derived from few randomized publications, large confirmatory trials should be carried out before a strong recommendation is made in favor of TNT.

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The FOxTROT (Fluoropyrimidine, Oxaliplatin, and Targeted-Receptor pre-Operative Therapy [Panitumumab]) Trial

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Seymour MT, Morton D. FOxTROT: an international randomised controlled trial in 1052 patients (pts) evaluating neoadjuvant chemotherapy (NAC) for colon cancer. J Clin Oncol. 2019 May;37(15 Suppl):3504-3504.

Conclusions: NAC was well tolerated and safe, with no increase in perioperative morbidity and a trend toward fewer serious postoperative complications. Evidence of histological regression was seen in 59% pts after NAC, including some pCRs. This resulted in marked histological downstaging and a halving of the rate of incomplete resections. We observed an improvement in 2-yr failure rate (HR=0.77), but this fell short of statistical significance (p=0.11). NAC for colon cancer improves surgical outcomes and can now be considered as a treatment option; longer follow-up and further trials are required to confirm the long-term benefits, refine its use and optimise case selection. ClinicalTrials.gov Identifier: NCT00647530

Foxtrot Collaborative Group. Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomised controlled trial. Lancet Oncol. 2012 Nov;13(11):1152-60.

The FOxTrOT website (University of Birmingham)

The timing and accuracy of SLNB for nodal management after NAC

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One discussion this week included nodal management after neoadjuvant chemotherapy (NAC).

Reference: Pilewskie M and Morrow M. Axillary nodal management following neoadjuvant chemotherapy. JAMA Oncology. 2017 Apr 1;3(4):549-555.

Summary: The increasing use of NAC has raised questions about the optimal approach to the axilla, including accuracy and timing of sentinel lymph node biopsy (SLNB) in patients who are clinically node negative (cN0) at presentation, use of NAC to avoid axillary lymph node dissection (ALND) in patients presenting with node-positive disease, and the relative importance of pre-and post-NAC stage in predicting the risk of locoregional recurrence (LRR).

The decrease in nodal metastases in cN0 patients undergoing post-NAC axillary staging and the increasing rates of pCR in the breast in patients treated with current chemotherapy regimens led to the study of SLNB among patients presenting with cN+ disease. Table 3 (below) summarizes data from three prospective, multi-institutional trials assessing the accuracy of SLNB after NAC among node-positive patients.

SLNB

The authors conclude: NAC reduces the need for ALND, and SLNB is an accurate
method of determining nodal status post NAC. The demonstration that SLNB accurately stages the axilla after NAC regardless of the presenting nodal stage (cN0, cN1) provides an important rationale for the use of NAC for axillary downstaging in patients who are candidates for breast-conserving surgery at presentation or who desire mastectomy. SLN identification rates and FNRs in those who are cN0 are similar to those seen with initial SLN surgery, and nodal recurrence after a negative SLNB is uncommon.

 

Additional Reading: Boughey JC, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA. 2013 Oct 9;310(14):1455-1461. doi:10.1001/jama.2013.278932.

Neoadjuvant chemotherapy for initially unresectable intrahepatic cholangiocarcinoma

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One discussion this week included using chemotherapy to enable initially unresectable intrahepatic cholangiocarcinoma (ICC) to be resectable.

Reference: Le Roy B, et al. Neoadjuvant chemotherapy for initially unresectable intrahepatic cholangiocarcinoma. The British Journal of Surgery. 2018 Jun;105(7):839-847. doi: 10.1002/bjs.10641

Summary: Surgical resection is the standard treatment for ICC, with a 5-year survival rate of 25-35% for those presenting with potentially resectable disease. Those with initially unresectable ICC are treated with chemotherapy alone and have a poor prognosis (p.839). The strategy of conversion to secondary resectability through chemotherapy regimens has resulted in good long-term survival for other tumors (colorectal liver and neuroendocrine liver metastases).  The authors state there is no published data on the use of neoadjuvant chemotherapy to achieve secondary resectability in locally advanced ICC.

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