Neoadjuvant Chemoradiation for Rectal Cancer Reduces Lymph Node Harvest in Proctectomy Specimens

Purpose  The purpose of this study was to compare the number of lymph nodes retrieved following proctectomy for rectal cancer in patients either receiving no neoadjuvant therapy versus those treated with standard preoperative chemoradiation. Methods  A retrospective review was performed of all consecutive patients that underwent proctectomy for rectal cancer from 1997–2006. Specimens from patients that received neoadjuvant therapy were compared to patients that did not receive preoperative chemoradiation. Results  Of a total of 286 patients, 188 received neoadjuvant therapy and 88 did not. More patients with stage II or higher cancers received neoadjuvant therapy. Overall, fewer neoadjuvant patients underwent an anastomotic procedure than the no neoadjuvant group (17% vs. 7% APR). Significantly fewer total lymph nodes were retrieved in the neoadjuvant therapy patients compared to those who did not receive preoperatively therapy (Neo 14.6 ± 0.6 vs. No-Neo 17.2 ± 1.1, p < 0.029). Conclusions  Standard neoadjuvant therapy significantly decreases the number of lymph nodes retrieved following proctectomy for patients with rectal cancers. Quality initiatives or performance measures evaluating lymph node harvest following proctectomy should reflect the use of preoperative chemoradiation. Study presented at the 2007 Annual Meeting of the American Society of Colon and Rectal Surgeons in St. Louis, Missouri.     

Different Recurrence Pattern After Neoadjuvant Chemoradiotherapy Compared to Surgery Alone in Esophageal Cancer Patients

Purpose

To evaluate the rate and pattern of recurrences after neoadjuvant chemoradiotherapy (CRT) in esophageal cancer patients.

Methods

We described survival and differences in recurrences from a single center between neoadjuvant CRT (carboplatin/paclitaxel and 41.4 Gy) and surgery alone for the period 2000–2011. To reduce bias, we performed a propensity score matched analysis.

Results

A total of 204 patients were analyzed, 75 treated with neoadjuvant CRT and 129 with surgery alone. The pathologic response to neoadjuvant CRT was 69 % with a complete response rate of 25 %. After matching, baseline characteristics between the groups (both n = 75) were equally distributed. The 3- and 5-year disease-free survival was 53 and 42 % in the neoadjuvant CRT group compared with 24 and 18 % in the surgery-alone group (P = 0.011). After 3 and 5 years’ CRT, patients had an estimated locoregional recurrence-free survival of 83 and 73 % compared with 52 and 49 % in the surgery-alone group (P = 0.015). The distant recurrence-free survival was comparable in both groups. Locoregional recurrences were located less in the paraesophageal lymph nodes in the CRT group than in the surgery-alone group, 9 versus 21 %, respectively (P = 0.041). With respect to differences in distant recurrences, we observed more skeletal recurrences in the surgery-alone group compared to CRT, 12 versus 1 % (P = 0.009).

Conclusions

The neoadjuvant CRT regimen we used offers a significant improvement in outcome, with a different recurrence pattern compared with surgery alone. This effect is probably due to both the pathologic complete response and eradication of micrometastases in CRT group.     

Neoadjuvant Therapy for Rectal Cancer Down-Stages the Tumor but Reduces Lymph Node Harvest Significantly

Purpose The impact of neoadjuvant therapy (NAT) for rectal cancer on lymph node yield is not well known. This study evaluates the impact of NAT on tumor regression and lymph node harvest.Methods The subjects were 40 patients with rectal cancer; 20 receiving high-dose, long-course neoadjuvant therapy, and 20 age- and sex-matched controls who did not receive neoadjuvant therapy. Tumor regression (TRG) was graded from 1 to 5 as: TRG1, no residual tumor cells; TRG2, occasional residual tumor cells with marked fibrosis; TRG3, marked fibrosis with scattered tumor cells or groups; TRG4, abundant cancer cells with little fibrosis; TRG5, no tumor regression. We also evaluated the number of lymph nodes retrieved from excised specimens, the size of the largest node, and the extent of lymph node involvement by the tumor.Result Tumor regression was seen in all patients; as TRG1 in 6 (30%), TRG2 in 2 (10%), TRG3 in 3 (15%), and TRG4 in 9 (45%). The median nodal harvest was 4 (range (0–12) in the NAT group vs 9 (range 1–19) in the control (P = 0.001). The median size of the largest lymph node was 5mm (range 2–12mm) in the NAT group vs 9mm (range 4–15mm) in the control group (P = 0.004). Tumor-positive nodes were identified in 4 of 17 of the NAT group patients and in 9 of the 20 controls (P = 0.308).Conclusion Although NAT down-stages rectal cancer, it results in a significantly low yield of lymph nodes, which are also significantly smaller than those in nonirradiated controls. Therefore, surgeons and histopathologists must ensure adequate sampling and accurate staging is done for patients with irradiated rectal cancer.This paper was presented at the British Society of Gastroenterology Meeting held in Glasgow in 2001, and published as an abstract in Gut 2001;(suppl)48:A57     

Lymph Node Retrieval after Preoperative Chemoradiotherapy for Rectal Cancer

Background

Current guidelines recommend the assessment of at least 12 lymph nodes for rectal cancer staging. Preoperative chemoradiotherapy may affect lymph node yield in this malignancy. This study investigated the impact of neoadjuvant chemoradiotherapy on the number of lymph nodes retrieved from rectal cancer patients.

Methods

An analysis of 162 rectal cancer patients who underwent curative surgery between 2005 and 2010. Seventy-one patients with stage II or III tumors received preoperative chemoradiotherapy. Using multivariate analysis, we assessed the correlation between clinicopathologic variables and number of retrieved lymph nodes. We also evaluated the association between survival and number of lymph nodes obtained.

Results

On multivariate analysis, preoperative chemoradiotherapy was the only variable to independently affect the number of lymph nodes obtained. The mean number of lymph nodes was 14.2 in patients treated with preoperative chemoradiotherapy and 19.4 in those not treated (P?P?=?0.003). After chemoradiation, the number of retrieved lymph nodes was inversely correlated with tumor regression grade. Results showed that 5-year overall and disease-free survival were similar whether the patient had 12 or more nodes retrieved or not.

Conclusions

Preoperative chemoradiotherapy reduces the lymph node yield in rectal cancer. The number of retrieved lymph nodes is affected by degree of histopathologic response of the tumor to chemoradiation. Thus, number of lymph nodes should not be used as a surrogate for oncologic adequacy of resection after neoadjuvant chemoradiotherapy for rectal cancer.     

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.

     

Sentinel Node Lymph Node Surgery After Neoadjuvant Therapy: Principles and Techniques

Annals of Surgical Oncology - Surgical management of the axilla in breast cancer has been a topic of great interest. While sentinel lymph node biopsy (SLNB) is an established approach for patients...     

Identifying Residual Nodal Disease in Sentinel Lymph Node Surgery After Neoadjuvant Chemotherapy for Breast Cancer

Annals of Surgical Oncology -     

Neoadjuvant Chemoradiotherapy for Esophageal Cancer: A Review of Meta-Analyses

Background  

Most randomized controlled trials (RCTs) that have compared neoadjuvant chemoradiation followed by surgery with surgery alone for locally advanced esophageal cancer have shown no difference in survival between the two treatments. Meta-analyses on neoadjuvant chemoradiation in esophageal cancer, however, are discordant.     

Salvage Lymphadenectomy for Recurrent Esophageal Cancer After Chemoradiotherapy

Although salvage esophagectomies are widely performed, reports on salvage lymphadenectomy (SL) are few. We review our SL cases to clarify the indications. Fifty-five patients with esophageal cancer underwent chemoradiotherapy or radiotherapy, including 3 patients with single lymph node (LN) recurrences and one with allochronic double cervical node recurrence. Our department removed 5 recurrent LNs from these 4 patients. In Case 1, right supraclavicular LN was judged to be metastatic and R0 resection was carried out; he is alive without recurrence. In Case 2, we found, allochronically, metastases in his left cervical paraesophageal LN and left supraclavicular LN; residual tumors were R1 in both lesions. He is alive despite esophageal recurrence. In Case 3, a lymphadenectomy was performed on his thoracic para-aortic LN; however, tumor was removed incompletely, and he died 4 months after SL from disease progression. In Case 4, a subcarinal LN was thought to be metastatic, and was removed but no malignant tissues detected. He died 17 months after SL from pneumonia. Our experiences suggest that some patients survive relatively long with SL. Moreover, molecular examination of resected lesions could guide subsequent therapies. SL might be more widely used for these patients if not otherwise contraindicated.Key words: Esophageal cancer, salvage lymphadenectomy, Salvage surgery, Esophagectomy, ChemoradiotherapyEsophageal cancer is the eighth most common form of cancer worldwide, and is one of the most difficult malignancies to cure.¹ Excluding cases with severe concomitant diseases, surgery is the best modality to cure esophageal cancer.² However, many patients with esophageal cancer have concomitant diseases that are associated with alcohol and tobacco consumption, such as chronic obstructive pulmonary disease, liver cirrhosis, and synchronous cancers of the lung or head and neck region.³ For patients with such concomitant diseases, chemoradiotherapy (CRT) is usually performed to cure esophageal cancer. For unresectable advanced-stage tumors, CRT is also used, and sometimes has favorable results. The Radiation Therapy Oncology Group trial (RTOG 85-01) has established CRT without surgery as one standard for definitive treatment.⁴ Many patients and oncologists have accepted the nonsurgical approach with CRT as definitive therapy for esophageal carcinoma. Although complete response (CR) rates are high and short-term survival is favorable after definitive CRT, locoregional disease persists or recurs in 40–60% of patients.⁵ From Japan, a phase II study of CRT for Stage II–III esophageal squamous cell carcinoma (JCOG9906)⁶ found a CR rate of 62.2%, with 34.2% patients having residual or locoregional recurrence without distant metastasis after CRT.For resectable residual or recurrent lesions after definitive CRT, surgical excision is the only curative modality. Therefore, such operations are called salvage surgery. In Japan, salvage surgery is defined as a procedure for recurrent or residual cancer after definitive CRT (RT > 50 Gy)⁷ and thought to be the only curative method. Conversely, salvage surgery is widely considered elsewhere to be a type of palliative surgery—the excision of tissue to reduce the risk of death due to physiologic derangement. Although salvage esophagectomy is performed in many institutions in Japan,^8–13 reports on salvage lymphadenectomy (SL) are still few.^14,15 In this article, we review our SL cases, and examine indications for this kind of surgery.     

Clinicopathological Factors and Nomograms Predicting Nonsentinel Lymph Node Metastases After Neoadjuvant Chemotherapy in Breast Cancer Patients

Background  Studies have demonstrated the feasibility and accuracy of sentinel lymph node (SLN) biopsy after neoadjuvant chemotherapy (NAC) in breast cancer. Some SLN-positive patients have low risk of nonsentinel lymph node (non-SLN) involvement. Our goal was to determine clinicopathological factors correlating with the presence of non-SLN metastases in patients after NAC and to assess the validity of nomograms predicting additional axillary metastases. Methods  Patients with infiltrating breast carcinoma (n = 132) were studied prospectively. All patients received NAC. At surgery, SLN biopsy followed by axillary lymph node dissection was performed. Lymphatic mapping was done using the isotope method. Fifty-one patients were SLN positive. Results  In univariate analysis, tumor size (P = 0.016) and the size of SLN metastases (P = 0.0055) were significantly correlated with the presence of non-SLN metastases. In multivariate analysis, SLN macrometastases (P = 0.047) conferred significantly increased risk of non-SLN metastases. The Memorial Sloan-Kettering Cancer Center nomogram was not reliably predictive for non-SLN metastases (area under the receiver operating characteristic curve, AUC, of 0.542), whereas the MD Anderson (AUC 0.716) and Tenon scoring systems (AUC 0.778) were validated. Conclusion  Our results suggest that clinicopathological factors predicting non-SLN involvement in SLN-positive patients with and without NAC are essentially the same. The risk of involvement may be assessed using existing nomograms, but additional large prospective studies are needed to determine their accuracy in patients after NAC.     

Accuracy of Lymph Node Staging in Pancreatic Cancer after Neoadjuvant Therapy

World Journal of Surgery -     

Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Patients with Cytologically Proven Node-positive Breast Cancer at Diagnosis

Background

The performance of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NCT) was investigated in patients with locally advanced breast cancer (LABC).

Methods

After NCT of 178 patients with cytology-proven axillary/supraclavicular nodes metastasis at the time of diagnosis, SLNB using radioisotope was performed including completion node dissection between 2008 and 2011. The detection rate, sensitivity, false negative rate (FNR), negative predictive value (NPV) and accuracy of SLNB were analyzed.

Results

SLNB was successfully performed in 169 (94.9 %) patients. Tumor nonresponse and extensive residual nodal disease were found to be significantly associated with detection failure of sentinel nodes. Sensitivity, FNR, NPV, and accuracy of SLNB were 78.0, 22.0, 75.8, and 87.0 %, respectively, and a greater number of retrieved SLNs increased all four of these performance measures. Conversion to node-negative disease was achieved in 69 (40.8 %) patients: 24 % of patients with the luminal A subtype, 51.6 % of patients with the luminal B, 51.7 % of patients with the HER2-enriched, and 58.5 % of patients with the triple-negative breast cancer (TNBC) subtype. Luminal B, HER2-enriched, and TNBC subtypes showed comparable responses to NCT; however, the TNBC subtype had a significantly better FNR and accuracy.

Conclusions

SLNB was found to be technically feasible, but its routine use was not recommended for LABCs after NCT. However, acceptable performance was noted for locally advanced TNBCs, and thus SLNB might be safely considered in these selected patients.     

Size of Residual Lymph Node Metastasis After Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients Is Prognostic

Background The prognostic significance of micrometastasis after neoadjuvant chemotherapy for locally advanced breast cancer is unknown. We examined the residual lymph node metastasis size in patients after treatment with neoadjuvant chemotherapy to determine the relevance of metastasis size on outcome. Methods Stage II/III breast cancer patients treated with neoadjuvant chemotherapy at our institution from 1991 to 2002 were included. We examined the relationship of postneoadjuvant chemotherapy lymph node metastasis size and number with distant disease-free survival (DDFS) and overall survival (OS). Results In 122 patients with a median follow-up of 5.4 years, we found not only that patients with an increasing number of residual positive nodes had progressively worse DDFS and OS (P < .0001 for both) compared with patients with negative nodes, but also that the size of the largest lymph node metastasis was associated with worse DDFS and OS (P < .0001 for both) in both univariate and multivariate analysis. Compared with negative nodes, even lymph node micrometastasis (<2 mm) was associated with worsened DDFS and OS (adjusted P = .02 and P = .005, respectively). Conclusions Residual micrometastatic disease in the axillary lymph nodes after neoadjuvant chemotherapy is predictive of worse prognosis than negative nodes. In this study, the lymph node metastasis size and the number of involved lymph nodes were independent powerful predictors of DDFS and OS.     

Prospective Study of Adjuvant Radiotherapy on Preventing Lymph Node Metastasis After Ivor-Lewis Esophagectomy in Esophageal Cancer

Purpose

To investigate whether Ivor-Lewis esophagectomy combined with adjuvant radiotherapy prevents lymphatic metastatic recurrence in esophageal cancer patients.

Methods

A total of 113 stage IIA esophageal squamous cell carcinoma patients after Ivor-Lewis esophagectomy were accepted mRNA expression of Mucoid 1 (MUC1) gene detection. Positive patients were enrolled onto the adjuvant radiotherapy group (with postoperative adjuvant radiotherapy). Negative patients were enrolled onto the control group (without postoperative adjuvant radiotherapy or chemotherapy). The radiotherapy area consisted of the neck, supraclavicular region, and superior mediastinum (including paraesophageal and paratracheal region). Survival difference was compared by the χ² test, and the Kaplan–Meier method was performed to calculate the survival rate and recurrence rate. Logistic regression analysis was performed to determined independent risk factors.

Results

The radiotherapy area lymphatic metastatic recurrence rate in adjuvant radiotherapy group (16.7 %, 5 of 30) was lower than patients without postoperative adjuvant radiotherapy (45.8 %, 38 of 83) (P < 0.05). Only compared to positive patients without postoperative adjuvant radiotherapy (60.0 %, 6 of 10) was the rate (16.7 %, 5 of 30) significantly lower (P < 0.01). Cancer recurrence was recognized in 48.6 % (55 of 113) patients within 3 years after surgery, including 38.1 % (43 of 113) patients with radiotherapy area recurrence. Logistic analysis revealed that T status (P < 0.01) and adjuvant radiotherapy (P < 0.05) were independent risk factors of lymph node metastasis in the first 3 years after surgery.

Conclusions

In MUC1 mRNA-positive esophageal squamous cell carcinoma patients, adjuvant radiotherapy could significantly reduce the lymph node metastasis rate in the radiotherapy area after Ivor-Lewis esophagectomy. Compared with traditional therapeutic methods, Ivor-Lewis esophagectomy combined with adjuvant radiotherapy can achieve similar curative effects in MUC1 mRNA-positive patients.     

Laparoscopic Sentinel Node Procedure for Cervical Cancer: Impact of Neoadjuvant Chemoradiotherapy

Background: SN detection based on combined blue dye and radiocolloid labeling can reliably show lymph node status in cervical cancer, but the influence of prior neoadjuvant chemoradiotherapy has not yet been reported. The aim of this study was to evaluate the effect of neoadjuvant chemoradiotherapy on the accuracy of a dual-labeling laparoscopic sentinel node (SN) procedure in patients with cervical cancer.Methods: Between July 2001 and June 2003, 26 patients (mean age, 50.3 years) with cervical cancer underwent a laparoscopic SN procedure based on dual labeling with patent blue and radiocolloid. After the SN procedure, all the patients underwent complete laparoscopic pelvic lymphadenectomy and laparoscopic radical hysterectomy (n = 19), the Schauta-Amreich operation (n = 5), or trachelectomy (n = 2). The results of the SN procedure were compared between 11 patients who received neoadjuvant chemoradiotherapy and 15 patients who did not receive neoadjuvant treatment.Results: The SN identification rates were 100% in the 11 patients who underwent neoadjuvant chemoradiotherapy and 93.3% in the 15 patients who did not receive adjuvant therapy. A total of 59 SNs were removed. Eight SNs (13.6%) from five patients (19.2%) were found to be metastatic at the final histological assessment. Three SN involvements were detected by hematoxylin and eosin staining of the SN. Immunohistochemical studies identified five metastatic SNs in three patients. There were no false-negative SN results.Conclusions: This study suggests that SN detection with a combination of radiocolloid and patent blue is feasible and accurate in patients with cervical cancer undergoing neoadjuvant chemoradiotherapy or primary surgery. The combination of laparoscopy and the SN procedure permits minimally invasive management of cervical cancer.