Decreasing Use of Axillary Dissection in Node-Positive Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

Background

Neoadjuvant chemotherapy (NAC) may downstage axillary disease in node-positive breast cancer. Several clinical trials have shown that sentinel lymph node (SLN) surgery after NAC is feasible for these patients. We sought to evaluate the use of SLN surgery and ALND in cN1 patients undergoing NAC.

Methods

We identified all patients with biopsy-proven cN1 breast cancer treated with NAC at our institution between January 2009 and December 2017. Approximated biologic subtype was determined by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status. Cochran–Armitage trend and Chi square tests were used for statistical analysis.

Results

Of 430 cN1 patients treated with NAC, 93 (22%) underwent SLN surgery only, 100 (23%) underwent SLN and ALND, and 237 (55%) underwent ALND only. The use of SLN surgery (±?ALND) increased from 28% in 2009 to 86% in 2017 (p?<?0.001), while the performance of ALND decreased from 100% in 2009 to 38% in 2017 (p?<?0.001). Among SLN+ patients who underwent ALND, disease was limited to the SLNs in 25/73 (34%) patients. The nodal pathologic complete response rate was 46% and varied by tumor subtype (p?<?0.001). Among patients undergoing SLN surgery, ALND was avoided in 48% of patients overall and varied by biologic subtype: 55% ER?/HER2+, 61% ER+/HER2+, 62% ER?/HER2?, and 31% ER+/HER2? (p?=?0.001). With short-term follow-up, no nodal recurrences have occurred in patients without ALND.

Conclusions

We observed a significant shift in axillary surgery for cN1 breast cancer patients treated with NAC, with increasing use of SLN surgery to assess nodal treatment response, and decreasing use of ALND.

     

Sentinel Lymph Node Biopsy Versus Axillary Dissection in Node-Negative Early-Stage Breast Cancer: 15-Year Follow-Up Update of a Randomized Clinical Trial

Background

Sentinel lymph node biopsy (SLNB) allows for staging of the axillary node status in early-stage breast cancer (BC) patients and avoiding complete axillary lymph node dissection (ALND) when the sentinel lymph node (SLN) is proven to be free of disease. In a previous randomized trial we compared SLNB followed by ALND (ALND arm) with SLNB followed by ALND only if the SLN presented metastasis (SLNB arm). At a mid-term of ≈ 6 years median follow-up, the two strategies appeared to ensure similar survival and locoregional control. We have revised these previous findings and update the results following a 15-year observation period.

Methods

Patients were randomly assigned to either the ALND or SLNB arm. The main endpoints were event-free survival (EFS), overall survival (OS), and axillary disease recurrence. EFS and OS were assessed using Kaplan–Meier analysis and the log-rank test.

Results

The ALND and SLNB arms included 115 and 110 patients, respectively. At 14.3 years median follow-up, 39 primary BC-related recurrences occurred, 22 (19 %) of which occurred in the ALND arm and 17 (16 %) occurred in the SLNB arm (p = 0.519). No axillary relapse developed in the SLNB arm, while two were observed in the ALND arm. OS (82.0 vs. 78.8 %) and EFS (72.8 vs. 72.9 %) were not statistically different between the ALND and SLNB arms (p = 0.502 and 0.953, respectively).

Conclusions

SLNB is a safe and efficacious component of the surgical treatment of early-stage BC patients. In the long-term, SLNB is equivalent to ALND in terms of locoregional nodal disease control and survival in this subset of patients.

     

Predicting Non-sentinel Lymph Node Metastases in Patients with a Positive Sentinel Lymph Node After Neoadjuvant Chemotherapy

Background

The standard of care for breast cancer patients treated with neoadjuvant chemotherapy (NAC) who have a positive sentinel lymph node (+SLN) after NAC is completion axillary lymph node dissection (ALND). This study aimed to develop a nomogram to predict additional nodal disease in patients with +SLN after NAC.

Methods

The study reviewed patients 18 years of age or older who had invasive breast cancer treated with NAC followed by SLN surgery with +SLN and ALND between 2006 and 2017 at the authors’ institution. Factors predictive of positive non-SLNs were analyzed using uni- and multivariable logistic regression.

Results

The study identified 120 patients with +SLN after NAC and ALND. Of these patients, 30.8% were clinically node-negative (cN?), and 69.2% were clinically node-positive (cN+) before NAC. Tumor biology was human epidermal growth factor receptor 2-positive (HER2+) for 20%, hormone receptor-positive (HR+)/HER2? for 66.7%, and triple-negative breast cancer (TNBC) for 13.3% of the patients. Additional nodal disease was found on ALND for 63.3% of the patients. In the univariate analysis, the factors predictive of positive non-SLNs were biologic subtype (TNBC and HR+/HER2? vs HER2+; p?<?0.001), higher grade (p?=?0.047), higher pT category (p?=?0.02), SLN extranodal extension (p?=?0.03), larger SLN metastasis size (p?<?0.001), and higher number of +SLNs (p?=?0.02). The factors significant in the multivariable analysis included number of +SLNs, grade 3 vs grade 1 or 2, HER2+ versus HER2?, cN+ versus cN?, and larger SLN metastasis size. The resulting model showed excellent discrimination (area under the curve, 0.82; 95% confidence interval, 0.74–0.90) and good calibration (p?=?0.54, Hosmer–Lemeshow).

Conclusion

A clinical prediction model incorporating biologic subtype, grade, clinical node status, size of the largest SLN metastasis, and number of +SLNs can help physicians and patients estimate the likelihood of additional nodal disease and may be useful for guiding decision making regarding axillary management.

     

Intraoperative Touch Imprint Cytology in Targeted Axillary Dissection After Neoadjuvant Chemotherapy for Breast Cancer Patients with Initial Axillary Metastasis

Background

For breast cancer patients, a false-negative rate lower than 10% can be achieved if targeted axillary dissection (TAD) is performed, which includes the excision of both biopsy-proven positive lymph nodes (BxLNs) and sentinel lymph nodes (SLNs). However, little evidence exists on the accuracy of intraoperative touch imprint cytology (ITPC) applied in TAD after neoadjuvant chemotherapy (NAC) for breast cancer patients with initial axillary metastasis. This study aimed to investigate the accuracy of ITPC in TAD after NAC.

Methods

Breast cancer patients with biopsy-confirmed nodal metastasis were prospectively enrolled in the study. After completion of NAC, all patients underwent TAD followed by axillary lymph node dissection (ALND). Then ITPC was performed to evaluate BxLNs and SLNs. The accuracy of TAD and ITPC was calculated in comparison with hematoxylin and eosin (H&E) staining of ALNs. The results of ITPC during 6 months at our center in the adjuvant setting were used for comparison.

Results

Overall, the false-negative rate of TAD was 10.8%. In a test with 92 patients, ITPC had an accuracy of 92.4%, a sensitivity of 87.9%, and a specificity of 94.9%. In the non-NAC group, ITPC showed similar accuracy (91.2%) and specificity (97.9%) but significantly lower sensitivity (68.9%; P?=?0.03).

Conclusions

The use of ITPC was feasible for TAD among breast cancer patients with biopsy-confirmed axillary metastasis who were treated with NAC. All the misses in the ITPC involved patients with micrometastases or isolated tumor cells. Use of ITPC can help decrease the number of second operations for patients with residual disease in ALNs after NAC.

     

Sentinel Lymph Node Biopsy is Precise After Primary Systemic Therapy in Stage II–III Breast Cancer Patients

Background

Sentinel lymph node biopsy (SLNB) without axillary lymph node dissection (ALND) in SLN negative patients is a standard of care for most breast cancer patients. SLNB for axillary staging after primary systemic therapy (PST) is still under discussion because of possibly reduced accuracy, while data are lacking. The purpose of this study was to evaluate the accuracy of SLNB after PST.

Materials and Methods

A total of 185 breast cancer patients were treated with PST; 160 patients received preoperative chemotherapy, and 25 patients received preoperative endocrine therapy. Thus, 143 of 160 patients with preoperative chemotherapy and 22 of 25 patients with preoperative endocrine therapy were eligible for evaluation. The combination of blue dye and radioactive tracer was used for identification of SLNs. All patients received SLNB and axillary lymph node dissection (ALND). Pathologic assessment of SLNs was performed and compared to non-SLN status.

Results

Pathologic complete response rates and breast conserving therapy rates were 15.4 and 78.3% in the preoperative chemotherapy group and 0 and 77.3% in the preoperative endocrine therapy group, respectively. Identification rate, sensitivity, overall accuracy, and false-negative rate were 81.1% (116 of 143), 91.7% (55 of 60), 95.7% (111 of 116), and 8.3% (5 of 60) in the preoperative chemotherapy group and 77.3% (17 of 22), 90.0% (9 of 10), 94.1% (16 of 17), and 10.0% (1 of 10) in the preoperative endocrine therapy group, respectively.

Discussion

SLNB after primary systemic therapy is accurate, and the results are comparable to those of primary SLNB. SLNB after PST could spare ALND in up to 40% of patients with primary positive axillary lymph nodes and should be considered as a standard for axillary staging in those patients.

     

Multidisciplinary Management of the Axilla in Patients with cT1-T2 N0 Breast Cancer Undergoing Primary Mastectomy: Results from a Prospective Single-Institution Series

Background

The after mapping of the axilla: radiotherapy or surgery (AMAROS) trial concluded that for patients with cT1-2 N0 breast cancer and one or two positive sentinel lymph nodes (SLNs), axillary radiotherapy (AxRT) provides equivalent locoregional control and a lower incidence of lymphedema compared with axillary lymph node dissection (ALND). The study prospectively assessed how often ALND could be replaced by AxRT in a consecutive cohort of patients undergoing mastectomy for cT1-2 N0 breast cancer.

Methods

In November 2015, our multidisciplinary group agreed to omit routine intraoperative SLN evaluation for cT1-2 N0 patients undergoing upfront mastectomy and potentially eligible for postmastectomy radiation therapy (PMRT), including those 60 years of age or younger and those older than 60 years with high-risk features. Patients with one or two positive SLNs on final pathology were reviewed to determine whether PMRT including the full axilla was an appropriate alternative to ALND.

Results

From November 2015 to December 2016, 154 patients met the study criteria, and 114 (74%) formed the final study cohort. Intraoperative SLN evaluation was omitted for 76 patients (67%). Of these patients, 20 (26%) had one or two positive SLNs, and 14 of these patients received PMRT?+?AxRT as an alternative to ALND. Three patients returned for ALND, and three patients were observed. On univariate analysis, tumor size, LVI, number of positive lymph nodes, and receipt of chemotherapy were associated with receipt of PMRT.

Conclusions

For the majority of patients with one or two positive SLNs, ALND was avoided in favor of PMRT?+?AxRT. With appropriate multidisciplinary strategies, intraoperative evaluation of the SLN and immediate ALND can be avoided for patients meeting the AMAROS criteria and eligible for PMRT.

     

Is Low-Volume Disease in the Sentinel Node After Neoadjuvant Chemotherapy an Indication for Axillary Dissection?

Background/Objective

Intraoperative evaluation of sentinel lymph nodes (SLNs) after neoadjuvant chemotherapy (NAC) has a higher false-negative rate than in the primary surgical setting, particularly for small tumor deposits. Additional tumor burden seen with isolated tumor cells (ITCs) and micrometastases following primary surgery is low; however, it is unknown whether the same is true after NAC. We examined the false-negative rate of intraoperative frozen section (FS) after NAC, and the association between SLN metastasis size and residual disease at axillary lymph node dissection (ALND).

Methods

Patients undergoing SLN biopsy after NAC were identified. The association between SLN metastasis size and residual axillary disease was examined.

Results

From July 2008 to July 2017, 702 patients (711 cancers) had SLN biopsy after NAC. On FS, 181 had metastases, 530 were negative; 33 negative cases were positive on final pathology (false-negative rate 6.2%). Among patients with a positive FS, 3 (2%) had ITCs and no further disease on ALND; 41 (23%) had micrometastases and 125 (69%) had macrometastases. Fifty-nine percent of patients with micrometastases and 63% with macrometastases had one or more additional positive nodes at ALND. Among those with a false-negative result, 10 (30%) had ITCs, 15 (46%) had micrometastases, and 8 (24%) had macrometastases; 17 had ALND and 59% had one or more additional positive lymph nodes. Overall, 1/6 (17%) patients with ITCs and 28/44 (64%) patients with micrometastases had additional nodal metastases at ALND.

Conclusion

Low-volume SLN disease after NAC is not an indicator of a low risk of additional positive axillary nodes and remains an indication for ALND, even when not detected on intraoperative FS.

     

Micrometastatic Disease and Isolated Tumor Cells as a Predictor for Additional Breast Cancer Axillary Metastatic Burden

Background

Our study aims were to investigate breast cancer patients with micrometastases or isolated tumor cells (ITCs) in sentinel lymph nodes (SLNs) to determine the rate of non-SLN metastasis and axillary recurrences, and to compare actual non-SLN metastasis rates with those predicted by the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram.

Methods

We identified 116 stage I to III breast cancer patients who underwent sentinel lymph node biopsy and had micrometastases or ITCs (<2-mm deposits). Patients underwent completion axillary lymph node dissection (ALND) (group 1) or had no further axillary surgery (group 2). P < 0.05 was considered statistically significant.

Results

Of 116 patients with micrometastases or ITCs in SLNs, 55 (47%) underwent completion ALND (group 1), and 61 (53%) had no further axillary surgery (group 2). The rate of non-SLN metastases in group 1 patients was 9 (16%) of 55, which was significantly less than that predicted by the MSKCC nomogram (median 30%, P < 0.001). Patient age, race, tumor histology, tumor grade, estrogen receptor/Her-2neu status, and lymphovascular invasion did not differ significantly between group 1 patients with positive non-SLNs and those with negative non-SLNs (P > 0.05 for each), but patients with positive non-SLNs had larger tumors (P < 0.001). No patient in group 1 experienced an axillary recurrence, while only one patient (1.6%) in group 2 experienced axillary recurrence.

Conclusions

The actual rate of positive non-SLNs for breast cancer patients with SLN micrometastases or ITCs who underwent completion ALND was significantly less than that predicted by the MSKCC nomogram. The rate of axillary recurrence is negligible, regardless of the extent of axillary staging.

     

The diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography and computed tomography in staging bladder cancer: a single-institution study and a systematic review with meta-analysis

Purpose

The purpose of this study was to assess the diagnostic accuracy of 18F-fluorodeoxyglucose with positron emission tomography and computed tomography (FDG–PET–CT) to predict nodal metastases in patients with bladder cancer (BC) scheduled to undergo radical cystectomy (RC).

Methods

We retrospectively reviewed records of patients diagnosed with BC and scheduled to undergo RC at our center from January 2011 through February 2015, who also underwent FDG–PET–CT at the time of diagnosis. All patients underwent RC and an extended pelvic lymph node dissection as the reference standard. The primary endpoints were the sensitivity, specificity and overall accuracy of FDG–PET–CT in detecting lymph node metastasis. We also examined its accuracy in identifying distant metastasis. In addition, we conducted a protocol-driven systematic review and meta-analysis of accuracy of FDG–PET–CT for preoperative staging of BC, as compared to CT alone, as reported in individual studies. To assess the methodological quality of eligible studies, we used the QUADAS-2 tool (a revised tool for the Quality Assessment of Diagnostic Accuracy Studies) and pooled diagnostic accuracy measures using Meta-DiSc statistical software.

Results

For detecting nodal metastases in 78 patients, the sensitivity of FDG–PET–CT was 0.56 (95 % CI 0.29–0.80) and the specificity, 0.98 (95 % CI 0.91–1.00). Pooled sensitivity and specificity for detecting lymph node metastasis were 0.57 and 0.95, respectively. Positive likelihood ratio was 9.02. All lesions that were suspicious for distant metastasis were found to be positive on biopsy.

Conclusion

FDG–PET–CT was more accurate than CT alone in staging BC in patients undergoing surgery. Standardization of FDG–PET–CT protocol and cost-effectiveness analysis are required before widespread implementation of this technology.

     

Reoperative Sentinel Lymph Node Biopsy: A New Frontier in the Management of Ipsilateral Breast Tumor Recurrence

Background

Breast conservation therapy (BCT) with sentinel lymph node (SLN) biopsy is a well-established standard of care for primary operable breast cancer; 5–10% of BCT patients will develop local recurrence (LR). The question then arises: How best to manage the axilla in the setting of LR after previous BCT and SLN biopsy or axillary dissection (ALND)?

Methods

Between 9/96 and 12/04, 117 reoperative SLN were performed for LR after BCT and either SLN biopsy or ALND more than 6 months previously. Because of wide variation in the number of nodes removed at the initial procedure, validation by backup ALND was not feasible in all cases.

Results

Reoperative SLN was successful in 64/117 (55%) patients. SLNs were identified by isotope and dye in 28/64 (44%); isotope only in 29/64 (45%); dye only in 4/64 (6%); 3/64 (5%) unknown. Positive reoperative SLN were found in 10/64 (16%) successful cases. Among 54/64 (84%) patients with negative reoperative SLNs, 23 (43%) had additional non-SLN removed concurrently: these were negative in 21/23 cases (91%). In 2/23 (9%), reoperative SLN were falsely negative: one with a positive intramammary node, and the other with a positive non-SLN palpated at surgery. Success of reoperative SLN was inversely related to number of nodes removed previously, and was more likely to be successful after a previous SLN biopsy than a previous ALND (74% vs. 38%, P = 0.0002). Non-axillary drainage was identified by lymphoscintigraphy significantly more often in reoperative SLN than in primary SLN biopsy (30% vs. 6%, P < 0.0001). There were no local or axillary recurrences at a mean follow up of 2.2 years; 6 patients developed systemic recurrence.

Conclusions

Reoperative SLN biopsy is feasible in the setting of LR after previous BCT/axillary surgery and deserves further study in this increasingly common clinical scenario. The added benefit of lymphoscintigraphy in identifying sites of non-axillary drainage may be greater in the setting of reoperative SLN than for the initial SLN procedure.

     

<Superscript>99m</Superscript>Tc-HDP bone scintigraphy and <Superscript>18</Superscript>F-sodiumfluoride PET/CT in primary staging of patients with prostate cancer

Introduction/Aim

Correct staging of patients with prostate cancer is important for treatment planning and prognosis. Although bone scintigraphy with ^99mTc-phosphonates (BS) is generally advised for staging by guidelines in high risk prostate cancer, this imaging technique is hampered by a high rate of inconclusive results and moderate accuracy. Potentially better imaging techniques for detection of bone metastases such as ¹⁸F-sodiumfluoride PET/CT (NaF PET/CT) are therefore being evaluated. In this observational cohort study we evaluate the performance and clinical impact of both BS and NaF PET/CT in primary staging of patients with prostate cancer.

Methods

The first of two cohorts consisted of patients who received a BS while the second included patients who received a NaF PET/CT for primary staging of prostate cancer. For both cohorts the number of positive, negative and equivocal findings, calculated diagnostic performance of the imaging modality in terms of sensitivity and specificity, as well as the impact on clinical management were studied. The ranges of the diagnostic performance were calculated both assuming that equivocal findings were positive and assuming that they were negative for bone metastases. For the NaF PET/CT cohort the number of patients with signs of lymph node metastases on low dose CT were also recorded, including the impact of these findings on clinical management.

Results

One-hundred-and-four patients underwent NaF PET/CT, whereas 122 patients underwent BS. Sensitivities of 97–100 and 84–95% and specificities of 98–100 and 72–100% were found on a patient basis for detection of bone metastases with NaF PET/CT and BS, respectively. Equivocal findings warranted further diagnostic procedures in 2% of the patients in the NaF cohort and in 16% in the BS cohort. In addition NaF PET/CT demonstrated lymph node metastases in 50% of the included patients, of which 25% showed evidence of lymph node metastases only.

Conclusion

Our data indicate better diagnostic performance of NaF PET/CT compared to BS for detection of bone metastases in primary staging of prostate cancer patients. Less equivocal findings are encountered with NaF PET/CT. Moreover, NaF PET/CT has additional value over BS since lymph node metastases are encountered frequently.

     

Glenohumeral and scapulohumeral kinematic analysis of patients with traumatic anterior instability wearing a shoulder brace: a prospective laboratory study

Study design

A retrospective case review of patients who underwent 18F sodium fluoride PET/CT imaging of the spine with postoperative pain following vertebral fusion.

Objective

To determine the benefit of 18F sodium fluoride PET/CT imaging in the diagnosis of persistent pain in the postoperative spine.

Summary of background data

The diagnosis of pain generators in the postoperative spine has proven to be a diagnostic challenge. The conventional radiologic evaluation of persistent pain after spine surgery with the use of plain radiographs, MRI, and CT can often fall short of diagnosis in the complex patient. 18F sodium fluoride PET/CT imaging is an alternative tool to accurately identify a patient’s source of pain in the difficult patient.

Methods

This retrospective study looked at 25 adult patients who had undergone 18F sodium fluoride PET/CT imaging. All patients had persistent or recurrent back pain over the course of a 15-month period after having undergone spinal fusion surgery. All patients had inconclusive dedicated MRI. The clinical accuracy of PET/CT in identifying the pain generator and contribution to altering the decision making process was compared to the use of CT scan alone.

Results

Of the 25 patients studied, 17 patients had increased uptake on the 18F sodium fluoride PET/CT fusion images. There was a high-level correlation of radiotracer uptake to the patients’ pain generator. Overall 88% of the studies were considered beneficial with either PET/CT altering the clinical diagnosis and treatment plan of the patient or confirming unnecessary surgery.

Conclusion

18F sodium fluoride PET/CT proves to be a useful tool in the diagnosis of complex spine pathology of the postoperative patients. In varied cases, a high correlation of metabolic activity to the source of the patient’s pain was observed.

     

Axillary Nodal Evaluation in Elderly Breast Cancer Patients: Potential Effects on Treatment Decisions and Survival

Background

Recent studies suggest that surgical lymph node (LN) evaluation may be omitted in select elderly breast cancer patients as it may not influence adjuvant therapy decisions. To evaluate differences in adjuvant therapy receipt and overall survival (OS), we compared clinically node-negative (cN0) elderly patients who did and did not undergo axillary surgery.

Methods

Patients aged ≥70 years in the National Cancer Database (2004–2014) with cT1-3, cN0 breast cancer were divided into two cohorts—those with surgical LN evaluation (one or more nodes removed) and those without (no nodes removed). Propensity scores were used to match patients based on age, year of diagnosis, tumor grade, cT stage, estrogen receptor status, and Charlson–Deyo comorbidity score. A Cox proportional hazards model was used to estimate the effect of LN surgery on OS.

Results

Overall, 133,778 patients were matched, of whom 102,247 patients (76.4%) underwent nodal surgery. Patients undergoing nodal surgery were more likely to receive chemotherapy (pN1-3: 22.2%; pN0: 5.8%; cN0-no nodal surgery: 2.8%; p < 0.001), radiation (pN1-3: 49.7%; pN0: 47.5%; cN0-no nodal surgery: 26%; p < 0.001), and endocrine therapy (pN1-3: 72%; pN0: 58.5%; cN0-no nodal surgery: 46.5%; p < 0.001). After adjustment for known covariates, patients who did not undergo nodal surgery had a worse OS (hazard ratio 1.66, 95% confidence interval 1.61–1.70).

Conclusions

For elderly cN0 breast cancer patients, axillary surgery was associated with higher rates of adjuvant therapy and improved OS. A selective approach to omitting nodal surgery should be considered in elderly patients with cN0 breast cancer as axillary staging may influence subsequent treatment decisions and long-term outcomes.

     

Risk Factor for Axillary Lymph Node Metastases in Microinvasive Breast Cancer

Background

Sentinel lymph node biopsy (SLNB) in patients with ductal carcinoma in situ (DCIS) was controversial. Usually we did not do a SLN biopsy when we performed conserving operations with small-sized DCIS. However, sometimes we find DCIS with microinvasive breast cancer (MIC) after the operation. Must reoperations be performed in all patients? The incidence of axillary metastases in microinvasive breast cancer (MIC) has not been extensively studied. We determined the incidence of positive axillary lymph node (ALN) in patients with MIC and the predictive factors of ALN metastases in these patients.

Methods

Between July 1989 and December 2008, 9635 patients had operation on invasive breast cancer in Asan Medical Center. Among these patients, 319 patients had MIC. The research conducted on the 293 patients (excluded were 26 who did not receive axillary lymph node dissection or SLN biopsy). We retrospectively checked clinical and pathologic variables.

Results

There were 22 cases of ALN metastases identified in this group of patients (7.5%). Lymphatic invasion (P < .001) and positive estrogen receptor status (P = 03) were independent significant predictors of axillary metastases.

Conclusions

Microinvasive breast cancer is associated with a low rate of lymph node metastases. Some breast cancer patients with MIC at low likelihood of lymph node metastases may be spared lymph node evaluation.

     

Ultrasound-Guided Restaging and Localization of Axillary Lymph Nodes After Neoadjuvant Chemotherapy for Guidance of Axillary Surgery in Breast Cancer Patients: Experience with Activated Charcoal

Objective

The aim of this study was to review our experience with ultrasound (US)-guided localization of axillary lymph nodes using activated charcoal for the guidance of axillary surgery after neoadjuvant chemotherapy (NAC) in clinically node-positive breast cancer patients.

Methods

Between April 2016 and April 2017, US-guided localization of the most suspicious axillary lymph nodes at restaging US using activated charcoal (Charcotrace?) was performed in 45 consecutive, clinically node-positive breast cancer patients who had less than two suspicious nodes after NAC and axillary surgery with sentinel node biopsy. Sentinel nodes were defined as radioactive nodes or nodes containing blue dye. The concordance between final pathological results for both the tattooed and sentinel nodes was analyzed.

Results

Sentinel node biopsy failed in five patients (11%) in whom axillary surgery was performed under the guidance of the tattooed node. The tattooed nodes were identified in the surgical field in 44 patients (98%). Of the 44 tattooed nodes, 25 (57%) were concordant with the sentinel nodes and 19 (43%) were non-sentinel nodes, including the five nodes with failed sentinel node biopsy. In the final pathological results, 18 patients (40%) had metastatic nodes. The sensitivities for detecting axillary metastasis of the sentinel node biopsy, tattooed node biopsy, and the sentinel and/or tattooed node biopsy were 61% (11/18), 67% (12/18), and 78% (14/18), respectively.

Conclusion

US-guided localization of axillary lymph nodes using activated charcoal at restaging after NAC in clinically node-positive breast cancer patients is a useful technique to guide axillary surgery, with a high identification rate.

     

Outcomes of initial surgery in patients with clinical N2 non-small cell lung cancer who met 4 specific criteria

Purpose

The role of surgery for patients with non-small cell lung cancer (NSCLC) with clinical mediastinal lymph node metastasis (N2) remains controversial. We specified 4 criteria for performing initial surgery in these patients (single-station N2, non-bulky N2, N2 with regional mode of spread, and N2 without N1) and examined the outcomes to validate the treatment options.

Methods

Between September 2002 and December 2010, of 1290 patients who underwent complete resection for NSCLC, 808 patients underwent initial standard resection, including 779 patients with cN0–1 and 29 with cN2. We compared the outcomes, and evaluated patients with cN2–pN2.

Results

The median follow-up was 45.5 months (3–119 months). Seventy (9.0 %) and 24 (82.8 %) patients had p-N2 in the cN0–1 and cN2 groups, respectively (p < 0.0001). The 5-year disease-free survival (DFS) rates in the cN0–1 and cN2 groups were 73.3 and 50.6 %, respectively (p = 0.0053), and the 5-year overall survival (OS) rates were 81.3 and 71.1 %, respectively (p = 0.051). The 5-year DFS and OS of patients with cN2–pN2 were 52.5 and 72.6 %, respectively.

Conclusions

Patients with clinical N2 disease based on our criteria represent a highly specific group with a favorable prognosis. Resection should therefore be the initial treatment for these patients.

     

Lymphadenopathies in patients with renal cell carcinoma: clinical and pathological predictors of pathologically confirmed lymph node invasion

Introduction

In renal cell carcinoma (RCC), lymph node status at preoperative imaging is affected by a non-negligible false-positive rate. We aimed to investigate which factors are related to a concordance between clinical suspicion and pathological confirmation of lymph node invasion (LNI).

Methods

At a single tertiary care institution, 2954 RCC patients underwent either partial or radical nephrectomy. For the aim of the study, only clinically positive lymph node cases were included (cN1). Statistical analyses assessed the concordance between preoperative and pathological nodal status.

Results

Preoperative axial CT scans revealed 424 (14.4 %) patients showing at least one enlarged lymph node suspected for LNI (cN1). All lymphadenopathies were removed at surgery, and LNI was pathologically confirmed (pN1) in 122 patients (28.8 %). When focusing the analyses on clinical characteristics (variables known before surgery), metastases at diagnosis [OR 3.0 (95 %1.9–4.8), p < 0.001] and tumor size [OR 1.1 (95 % 1.1–1.2), p < 0.001] were the two most informative predictors of concordance between clinical and pathological nodal status. Concordance was also more likely in patients with papillary type II tumors (55.6 %) relative to papillary type I (38.1 %), clear cell (27.7 %) and chromophobe (8.3 %) tumors. At multivariable analyses, none of the considered blood markers resulted to be independently associated with LNI.

Conclusions

Roughly 70 % of patients showing a suspected lymph node preoperatively do not show LNI at the final pathological report. Among patients with clinically positive nodes, clinical tumor size and metastases at diagnosis represent the most informative and independent predictors of confirmed LNI at final pathology.

     

Response to Treatment is Highly Predictable in cN0 Patients with Papillary Thyroid Carcinoma

Background

While involvement of macrometastatic lymph nodes is a recognized independent predictor of an adverse course in papillary thyroid cancer (PTC) patients, the clinicopathological variables associated with disease persistence/recurrence in clinically node-negative (cN0) disease are not well defined. The indications for prophylactic central neck dissection (pCND) in this patient group remain unclear as well. We aim to investigate the risk factors associated with short- and long-term persistence/recurrence of PTC in patients with cN0 disease at presentation compared to patients with PTC and cervical lymph node involvement (N1) and the response to initial treatment in these subgroups of patients.

Methods

Data were collected retrospectively for 392 consecutive patients with PTC, 223 with cN0 disease and 169 with N1 disease, who were treated and followed at a single tertiary medical center in which pCND is not routinely performed for PTC.

Results

Compared to patients with N1 disease, patients with cN0 disease had significantly smaller tumors, lower rates of multifocality, and less extrathyroidal extension. Persistency rates at 1 year were 6.7 % in the cN0 group and 47 % in the N1 group, and at last follow-up, 3.6 and 33.5 %, respectively (p = 0.001 for both time points). Within the cN0 group, those with persistent disease at 1 year (n = 15) had significantly larger tumors and higher stimulated thyroglobulin. Only six had structural residual disease, four of them lymph node metastases. All patients with persistent disease were initially treated with total thyroidectomy and radioiodine. Recurrence occurred in only three patients. After 8.3 ± 3.8 years of follow-up, eight patients with cN0 had persistent disease, three of them biochemical. Higher American Joint Committee of Cancer stage and extrathyroidal extension were the only factors that predicted disease persistence at the last follow-up in this group.

Conclusions

Patients with cN0 PTC and no distant metastases are usually disease free after thyroidectomy with/without radioactive iodine and do not need further interventions. The initial staging in these patients is a valid prognostic factor for disease outcomes.

     

Impact of Neoadjuvant Chemotherapy on Nodal Disease and Nodal Surgery by Tumor Subtype

Background

Neoadjuvant chemotherapy (NAC) is known to downstage disease in the breast and increase breast conservation. It can also decrease nodal disease extent. We evaluated the impact of NAC on nodal positivity, nodal burden, and nodal surgery by tumor subtype.

Methods

All cT1–4c breast cancers from 2010 to 2014 in the National Cancer Database were evaluated, comparing patients receiving NAC with those undergoing primary surgery (PS). Rates of pathologic node-negative status (pN0) and sentinel lymph node (SLN) surgery (1–5 nodes) were compared using chi-square tests, and adjusted odds ratios (OR) were estimated.

Results

Of 461,549 patients, 36,715 (8.0%) received NAC and 424,834 (92.0%) had PS. In cN0 patients, pN0 rates were higher in NAC compared with PS patients in ER?/HER2+ [93.2 vs. 79.0%, odds ratio (OR) 3.64, p < 0.001], ER?/HER2? (89.9 vs. 85.2%, OR 1.55, p < 0.001), and ER+/HER2+ (84.7 vs. 78.3%, OR 1.54, p < 0.001). Patients with cT2–3, N0 tumors had significantly higher rate of SLN surgery for NAC versus PS for each biologic subtype except for ER+/HER2? tumors, amongst which this was true only for T3 tumors. In cN1–3 patients, pN0 rates after NAC were 61.3% in ER?/HER2+, 47.7% in ER+/HER2+, 47.3% in ER?/HER2?, and 20.2% in ER+/HER2? and SLN surgery was highest in ER?/HER2+ (28.9%, p < 0.05 versus other subtypes).

Conclusion

NAC increases rates of pN0 among cN0 patients compared with PS. Among cN+ patients, 20–61% undergoing NAC convert to pN0 depending on tumor type, with lowest nodal response in ER+/HER2? disease. Use of NAC results in less extensive axillary surgery than in patients treated with PS in both cN0 and cN+ disease.

     

The Added Diagnostic Value of <Superscript>18</Superscript>F-Fluorodihydroxyphenylalanine PET/CT in the Preoperative Work-Up of Small Bowel Neuroendocrine Tumors

Background

The precise localization of the primary tumor and/or the identification of multiple primary tumors improves the preoperative work-up in patients with small bowel (SB) neuroendocrine tumor (NET). The present study assesses the diagnostic value of ¹⁸F-fluorodihydroxyphenylalanine (¹⁸F-FDOPA) positron emission tomography/computed tomography (PET/CT) during the preoperative wok-up of SB NETs.

Methods

Between January 2010 and June 2017, all consecutive patients with SB NETs undergoing preoperative ¹⁸F-FDOPA PET/CT and successive resection were analyzed. Preoperative work-up included computed tomography (CT), somatostatin receptor scintigraphy (SRS), and ¹⁸F-FDOPA PET/CT. Sensitivity and accuracy ratio for primary and multiple tumor detection were compared with data from surgery and pathology.

Results

There were 17 consecutive patients with SB NETs undergoing surgery. Nine patients (53%) had multiple tumors, 15 (88%) metastatic lymph nodes, 3 (18%) peritoneal carcinomatosis, and 9 patients (53%) liver metastases. A total of 70 SB NETs were found by pathology. Surgery identified the primary in 17/17 (100%) patients and recognized seven of 9 patients (78%) with multiple synchronous SB. Preoperatively, ¹⁸F-FDOPA PET/CT displayed a statistically significant higher sensitivity for primary tumor localization (100 vs. 23.5 vs. 29.5%) and multiple tumor detection (78 vs. 22 vs. 11%) over SRS and CT. Compared with pathology, ¹⁸F-FDOPA PET/CT displayed the highest accuracy ratio for number of tumor detected over CT and SRS (2.0?±?2.2 vs. 0.4?±?0.7 vs. 0.6?±?1.5, p?=?0.0003).

Conclusion

¹⁸F-FDOPA PET/CT significantly increased the sensitivity and accuracy for primary and multiple SB NET identification. ¹⁸F-FDOPA PET/CT should be included systematically in the preoperative work-up of SB NET.