Independent predictive value of the overall number of metastatic N1 and N2 stations in lung cancer.

OBJECTIVE: The number of metastatic N2 stations is a known prognostic factor in patients with non-small-cell lung cancer (NSCLC). However, involvement of N1 stations as well as that of N2 stations seems to be important in the prognosis of these patients. We therefore attempt to clarify the significance of the total number of metastatic stations in pathologic N1 and N2 NSCLCs. METHODS: Patients with either pathologic N1 (n = 51) or N2 (n = 96) NSCLC who had undergone major pulmonary resection with complete mediastinal dissection were included in this retrospective study. All positive nodes were characterized by location according to the TNM classification system. The hilar station was included with the N2 stations. RESULTS: The total number of metastatic stations in patients with N2 disease ranged from 1 to 8 (average 2.5), whereas that in patients with N1 disease ranged from 1 to 3 (average 1.2). The incidence of multiple-station metastasis (> or = 3 metastatic stations) among N2 patients (35%) was significantly higher than that among N1 patients (2%) (p < 0.001). Multivariate analysis of survival showed pathologic N1 status (relative risk = 0.443, p = 0.013) and < or = 2 metastatic stations (relative risk = 0.515, p = 0.020) to be significant and independent prognostic factors. Age, sex, cell type, resected lobe, and pathological T status were statistically insignificant determinates of survival. CONCLUSIONS: The total number of metastatic stations (< or = 2 vs > or = 3) is an independent prognostic indicator in patients with completely resected pathologic N1 or N2 NSCLC. The number of metastatic stations will be useful as a stratification factor in prospective clinical trials of these patients.     

The impact on the prognosis of unsuspected N2 disease in non-small-cell lung cancer: indications for thorough mediastinal staging in the modern era

Purpose

Predicting the prognosis of advanced non-small-cell lung cancer (NSCLC) patients who present with clinically unsuspected N2 is very different due to the heterogeneity of this cohort. Thus, this study was undertaken to identify the clinicopathological features and survival of patients with clinical N0 or N1 and pathological N2, namely, unsuspected N2.

Methods

Among 239 patients with pathological N2 NSCLC, we reviewed the cases of 92 (38.5 %) patients who showed unsuspected N2. The prognosis was investigated using the Kaplan–Meier method and a Cox regression model.

Results

The 5-year overall survival (5yOS) of the patients with unsuspected N2 was 51.2 %. Based on a multivariate analysis, age and 18F-fluorodeoxyglucose (FDG) uptake in the lymph nodes were significant prognostic factors of unsuspected N2 (p = 0.0081, 0.0228, respectively). The 5yOS of PET-negative unsuspected N2 (n = 68) was 58.9 %, whereas that of PET-positive unsuspected N2 (n = 24) was 29.7 % (p = 0.0026). Furthermore, the 5yOS of PET-negative unsuspected N2 was significantly better than that of both clinical and pathological N2 s (i.e., suspected N2; n = 60; 5yOS, 42.1 %; p = 0.0051), while no significant difference was observed between PET-positive unsuspected N2 and suspected N2 (p = 0.6325).

Conclusions

A preoperative evaluation of the lymph nodes by PET/CT has a potential benefit in predicting the prognosis. A thorough evaluation of the lymph nodes is, therefore, needed if the lymph nodes show an FDG uptake, even in cases that show a clinical N0 status on thin section CT scans.

     

Survival Impact of Total Resected Lymph Nodes in Esophageal Cancer Patients With and Without Neoadjuvant Chemoradiation

Background

Current esophageal treatment guidelines suggest that, when more than 15 lymph nodes are detected, dissection should be done as the minimum requirement for staging in esophageal squamous cell carcinoma (ESCC) patients undergoing esophagectomy without induction chemoradiotherapy (CRT). However, for neoadjuvant CRT, there is limited information. We sought to clarify the role of lymphadenectomy in ESCC patients with and without neoadjuvant CRT.

Patients and Methods

Data on 3156 ESCC patients receiving esophagectomy with (group 1, n?=?1399) and without (group 2, n?=?1757) neoadjuvant CRT between 2008 and 2014 were collected from a national cancer registry in Taiwan. The impact of the resected lymph nodes on overall survival was assessed according to pathologic stages. A Cox regression model was used to identify prognostic factors for overall survival.

Results

Five-year overall survival rates were 35.6% for the entire group, 30.32% for group 1, and 39.55% for group 2 (p?<?0.0001 for group 1 vs group 2). The best cutoff value was 21 lymph nodes in both group 1 and group 2. In group 1, the independent prognostic factors included age?≥?54 years, clinical N status, y-pathologic T, y-pathologic N, y-pathologic stage, grade, location, margin status, esophagectomy (thoracoscopic vs open), and number of total resected lymph nodes (≤?21 vs?>?21). For group 2, the independent prognostic factors were gender, clinical stage, pathologic T, pathologic N, tumor length, grade, and margin status.

Conclusions

Extent of lymphadenectomy was associated with survival in patients with neoadjuvant CRT followed by esophagectomy. The optimum lymphadenectomy should be modulated by pathologic stage.

     

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.

     

Lymph node-positive prostate cancer after robotic prostatectomy and extended pelvic lymphadenectomy

Optimal management of node-positive prostate cancer patients after prostatectomy remains a challenge. We evaluated clinically localized patients who demonstrated node positivity and identified predictors for secondary treatment. From 2010 to 2015, clinically localized prostate cancer patients who underwent robot prostatectomy with extended lymphadenectomy and node-positive disease on pathologic analysis were identified. Clinical N1, M1 or salvage cases were excluded. Patients were stratified based on secondary treatments. Kaplan–Meier method was used to determine the time to biochemical and metastatic recurrence. Multivariate logistic regression was used to identify predictors for additional treatment. 145 patients (45 no additional therapy, 47 adjuvant, 53 salvage) had a median follow-up of 31.2 months. Salvage patients had higher median pre-operative prostate-specific antigen (10.8 vs. 9.7 vs. 8.2, p = 0.1), higher percentage of pathologic Gleason ≥8 (50.9 vs. 38.3% and 22.2%, p < 0.01), and higher median-positive nodes (3 vs. 1 and 1, p < 0.0001) compared to adjuvant and no treatment groups, respectively. Pathologic Gleason ≥8 (OR = 3.5, p = 0.007) and positive nodes ≥2 (OR = 3.3, p = 0.006) were associated with additional therapy. In the no treatment group, two-year estimated BCRFS was 74.3%. Two-year metastatic recurrence-free rates for no treatment, adjuvant and salvage groups were 100, 87.5, and 80.9%, respectively (p = 0.01). Observation is a viable alternative for low metastatic burden patients. In the largest series of node-positive patients from robotic prostatectomy and extended lymphadenectomy, those with pathologic Gleason ≥8 and positive lymph nodes ≥2 were more likely to receive additional treatment.     

Lymph Node Status in Breast Cancer Does Not Predict Tumor Biology

Background/Objective

The 21-gene Oncotype DX^® Breast Recurrence Score^® (RS) assay has been prospectively validated as prognostic and predictive in node-negative, estrogen receptor-positive (ER+)/HER2? breast cancer patients. Less is known about its prognostic role in node-positive breast cancer. We compared RS results among patients with lymph node-negative (N0), micrometastatic (N1mi), and macrometastatic (N+) breast cancer to determine if nodal metastases are associated with more aggressive biology, as determined by RS.

Methods

Overall, 610,350 tumor specimens examined by the Genomic Health laboratory from February 2004 to August 2017 were studied. Histology was classified centrally, while lymph node status was determined locally. RS distribution (low: <?18; intermediate: 18–30; high: ≥?31) was compared by nodal status.

Results

Eighty percent (n = 486,013) of patients were N0, 4% (n = 24,325) were N1mi, 9% (n = 56,100) were N+, and 7% (n = 43,912) had unknown nodal status. Mean RS result was 18, 16.7, 17.3 and 18.9 in the N0, N1mi, N+, and unknown groups, respectively. An RS?≥?31 was seen in 10% of N0 patients, 7% of N1mi patients, and 8.0% of N+ patients. The likelihood of an RS ≥ 31 in N1mi and N+ patients varied with tumor histology, with only 2% of patients with classic infiltrating lobular cancer having an RS?≥?31, versus 7–9% of those with ductal carcinoma.

Conclusions

RS distribution among N0, N1mi, and N+ patients is similar, suggesting a spectrum of biology and potential chemotherapy benefit exists among node-negative and node-positive ER+/HER2? breast cancer patients. If RxPONDER does not show a chemotherapy benefit in N+ patients with a low RS result, our findings indicate that substantial numbers of patients could be spared the burden of chemotherapy.

     

Utility and pitfalls of sentinel node identification using indocyanine green during segmentectomy for cT1N0M0 non-small cell lung cancer

Purposes

Sentinel node identification using indocyanine green (ICG) is not only simpler, but also more cost-effective, than using radioisotope tracers. We herein examined the utility and pitfalls of sentinel node (SN) identification using ICG during segmentectomy in patients with cT1N0M0 non-small cell lung cancer (NSCLC).

Methods

ICG was injected around the tumor after thoracotomy, followed by segmentectomy and lymph node dissection, in 135 patients with cT1N0M0 NSCLC. The dissected nodes were examined using an ICG fluorescence imaging system.

Results

SNs could be identified in 113 patients (84 %). The mean number of SNs was 2.3 ± 1.3. The percentages of being an SN were 57 % for both stations #12 and #13, which was significantly higher than the 18 % for #10 and 22 % for #11 (p < 0.001). Fourteen patients had N1 or N2 disease. Of these, the SNs were true positive (i.e., SNs contained metastasis) in 11 patients (79 %) and false negative (i.e., SNs did not contain metastasis, while non-SNs contained metastasis) in three patients (21 %). Of the three patients with false-negative results, all non-SNs containing metastases were at station #12 or #13.

Conclusion

While ICG makes it simple to identify SNs during segmentectomy for cT1N0M0 NSCLC, stations #12 and #13 should be submitted for frozen sections along with the identified SNs to avoid missing true SNs.

     

Cigarette Smoking and hOGG1 Ser326Cys Polymorphism are Associated with 8-OHdG Accumulation on Mitochondrial DNA in Thoracic Esophageal Squamous Cell Carcinoma

Background

We examined whether cigarette smoking affects the degrees of oxidative damage (8-hydroxyl-2′-deoxyguanosine [8-OHdG]) on mitochondrial DNA (mtDNA), whether the degree of 8-OHdG accumulation on mtDNA is related to the increased total mtDNA copy number, and whether human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys polymorphisms affect the degrees of 8-OHdG accumulation on mtDNA in thoracic esophageal squamous cell carcinoma (TESCC).

Methods

DNA extracted from microdissected tissues of paired noncancerous esophageal muscles, noncancerous esophageal mucosa, and cancerous TESCC nests (n = 74) along with metastatic lymph nodes (n = 38) of 74 TESCC patients was analyzed. Both the mtDNA copy number and mtDNA integrity were analyzed by quantitative real-time polymerase chain reaction (PCR). The hOGG1 Ser326Cys polymorphisms were identified by restriction fragment length polymorphism PCR and PCR-based direct sequencing.

Results

Among noncancerous esophageal mucosa, cancerous TESCC nests, and metastatic lymph nodes, the mtDNA integrity decreased (95.2 to 47.9 to 18.6 %; P < 0.001) and the mtDNA copy number disproportionally increased (0.163 to 0.204 to 0.207; P = 0.026). In TESCC, higher indexes of cigarette smoking (0, 0–20, 20–40, and >40 pack-years) were related to an advanced pathologic N category (P = 0.038), elevated mtDNA copy number (P = 0.013), higher mtDNA copy ratio (P = 0.028), and increased mtDNA integrity (P = 0.069). The TESCC mtDNA integrity in patients with Ser/Ser, Ser/Cys, and Cys/Cys hOGG1 variants decreased stepwise from 65.2 to 52.1 to 41.3 % (P = 0.051).

Conclusions

Elevated 8-OHdG accumulations on mtDNA in TESCC were observed. Such accumulations were associated with a compensatory increase in total mtDNA copy number, indexes of cigarette smoking, and hOGG1 Ser326Cys polymorphisms.

     

Positive Lymph Node Ratio as an Indicator of Prognosis and Local Tumor Clearance in N3 Gastric Cancer

Background

Nodal metastasis is an important clinical issue in gastric cancer patients. This study was designed to investigate the clinical usefulness of the positive lymph node ratio (PLNR), which reflects both metastatic and retrieved lymph node numbers, in patients with pN3 gastric cancer.

Methods

We retrospectively analyzed the records of 138 consecutive pN3 patients who underwent curative gastrectomy with lymphadenectomy from 2000 to 2012.

Results

A PLNR of 0.4 was proved to be the best cutoff value to stratify the prognosis of patients with pN3 gastric cancer (P?<?0.001). Univariate and multivariate analyses revealed that older age, larger tumor size (≥10 cm), and PLNR?≥?0.4 [P?<?0.001, HR 3.1 (95 % CI 1.7–5.4)] were independent prognostic factors in pN3 gastric cancer. Regarding the recurrence, patients with PLNR <0.4 had a significantly lower rate of lymph node recurrence than those with PLNR ≥0.4 (P?=?0.020). There was no significant difference in the lymph node recurrence rate between N3a and N3b patients in the PLNR <0.4 group [P?=?0.546, 11.6 % (7/60) vs. 12.5 (1/8)], indicating a better local control regardless of pN3 subgroups.

Conclusions

PLNR is useful to stratify the prognosis and evaluate the extent of local tumor clearance in pN3 gastric cancer.

     

Multifactorial Analysis of Prognostic Factors and Survival Rates Among 706 Mucosal Melanoma Patients

Background

The hypothesis that mucosal melanomas from different anatomic sites would have different prognostic features and survival outcome was tested in a multifactorial analysis.

Methods

Complete clinical and pathological information from 706 mucosal melanoma patients from different anatomical sites was compared for overall survival (OS) and prognostic factors.

Results

Mucosal melanomas arising from different anatomical sites did not have any significant differences in OS in a multivariate analysis (p?=?0.721). Among all 706 stage I–IV mucosal melanoma patients, depth of tumor invasion (p?<?0.001), number of lymph node metastases (p?<?0.001), and sites of distant metastases (p?<?0.001) were independent prognostic factors for OS; among 543 stage I–III patients, depth of tumor invasion (p?<?0.001) and number of lymph node metastases (p?<?0.001) were independent prognostic factors for OS; and among 547 stage IV patients, depth of tumor invasion (p?=?0.009), number of lymph node metastases (p?<?0.001), and combined distant metastases and elevation of serum lactate dehydrogenase (LDH; p?<?0.001) were independent prognostic factors for OS. The presence of c-KIT or BRAF mutations was not predictive of survival.

Conclusions

This is the first large-scale study comparing outcomes of mucosal melanomas from different anatomic sites in a multifactorial analysis. There were no significant survival differences among mucosal melanomas arising at different sites when matched for staging and prognostic and molecular factors, thus rejecting our hypothesis. We concluded that prognostic characteristics of mucosal melanomas can be staged as a single histological group, regardless of the anatomic site of the primary tumor.

     

Prognostic Value of Lymph Node Status and Extent of Lymphadenectomy in Pancreatic Neuroendocrine Tumors Confined To and Extending Beyond the Pancreas

Background

The impact of lymph node (LN) status and lymphadenectomy (LA) on survival in pancreatic neuroendocrine tumors (pNETs) remains controversial. We evaluated the impact of tumor extension and grade on nodal metastasis and survival.

Methods

Surgical pNET patients were queried in the Surveillance Epidemiology and End Results (SEER) database (1998–2012, N?=?981). Factors associated with LN status were analyzed by logistic regression and by Cox analyses.

Results

For T1–T2 tumors, N status was associated only with tumor size. N status (p?=?0.001), grade (p?<?0.001), age (p?=?0.001), and sex (p?=?0.007) predicted overall survival (OS). For T3–T4, grade (p?<?0.001), sex (p?=?0.004), size (p?=?0.013), and age (p?=?0.007) but not N status (p?=?0.789) predicted OS. For T1–T2, disease-specific survival (DSS; p?=?0.003) and OS (p?=?0.008) were longer for N0 vs N1, while N0 vs NX had similar OS (p?=?0.59) and DSS (p?=?0.80). While a difference was seen in DSS for NX vs N1 (p?=?0.04), no significant difference in OS was seen (p?=?0.08). For T3–T4, N status did not affect DSS (p?=?0.365) or OS (p?=?0.454). For all T groups and any N status, extended LA (≥10 nodes resected) was not associated with OS.

Conclusion

While in T1–T2 pNET N1 status is a predictor of negative OS, similar outcome between NX and N0 supports limited LN resection in selected patients. Extended LA is unlikely to be helpful in T3–T4.

     

Correlation Between Clinical and Pathologic Staging in Colon Cancer: Implications for Neoadjuvant Treatment

Background

Recent randomized trials suggest improved outcomes in patients with locally advanced colon cancer (LACC) treated with neoadjuvant chemotherapy (NAC). Optimal selection of patients for NAC depends on accurate clinical staging. The purpose of this study was to examine the degree of correlation between clinical and pathologic staging in patients with colon cancer (CC).

Methods

Adult patients with non-metastatic CC who underwent surgery were identified from the National Cancer Data Base between 2006 and 2014. Data on clinical and pathologic staging was obtained. Kappa index was used to determine the correlation between clinical and pathologic staging.

Results

One hundred five thousand five hundred sixty-nine patients were identified. The overall correlation rate between clinical and pathologic staging for T stage was 80% (kappa 0.7) and 83% for N stage (kappa 0.6). The correlation rate was 54% for T1, 76% for T2, 95% for T3, and 94% for T4 (P?<?0.001). This compared with 81% for N0, 82% for N1, and 97% for N2 (P?<?0.001). The sensitivity and specificity of clinical staging for identifying T3/T4 vs T1/T2 were 80 and 98%, respectively, compared to 60 and 98% for N1/N2 vs N0 (P?<?0.001).

Conclusions

Our findings suggest that current modalities used for clinical staging are accurate in predicting pathologic stage for advanced but not early T and N disease. Further optimization of clinical staging is essential for the accurate selection of patients who may benefit from neoadjuvant therapy and to avoid overtreatment of low-risk patients.

     

Prognostic significance of persistent mediastinal metastasis following induction therapy in large (&gt; or = 2cm) N2 or N3 non-small cell lung cancer

Objective: It is controversial whether or not surgery is beneficial for patients with non-small cell lung cancer accompanied by persistent lymph node metastasis in the mediastinum following induction therapy. We have therefore conducted a retrospective study to assess this issue Methods: Eligibility criteria were defined as follows: 1) the period of treatment was between January 1991 and April 1998, 2) the clinical stages were IIIA (N2) or IIIB (N3) with large lymph nodes (> or = 2 cm), 3) induction therapy had been administered, 4) tumor was resected completely, 5) at least one mediastinal lymph node had necrosis or scar if the pathological N status was p-N0 or p-N1 and 6) the p-stage was not IV. Dichotomous variables included the radiographic response of the tumor, the T status, and the N status. Results: Thirty-nine patients were eligible. There were 29 males and 10 females aged from 27 to 74 years, and involved 20 cases of adenocarcinoma. The pathological N status was as follows: p-N0 in 18 patients, p-N1 in 3, p-N2 in 16, and p-N3 in the other 2. In overall survival, the median survival time (MST) was 34 months and the actuarial 5-year-survival rate (5-YSR) was 28%. The group of patients with either N0 or N1 (n-21) had a 71-month MST and a 54% 5-YSR, and the group of patients with either N2 or N3 (n=18) had a 13-month MST and a 5-YSR of 0% (p<0.0001). On multivariate analysis, the pathological N factor was confirmed as an independently significant. Conclusions: Our retrospective study found that the survival rate of patients with persistent mediastinal nodal metastasis was very poor. A prospective study is needed to investigate whether or not surgery is beneficial for these patients.     

Prognostic value of post-treatment metabolic tumor volume from <Superscript>11</Superscript>C-methionine PET/CT in recurrent malignant glioma

We investigated the diagnostic and prognostic significance of metabolic parameters from ¹¹C-methionine (MET) positron emission tomography (PET) in patients with malignant glioma. The MET-PET was examined in 42 patients who had been previously treated with adjuvant treatment for malignant glioma. Both ratios of maximal MET uptake of the tumors to those of the contralateral normal gray matter (T/N ratio) and metabolic tumor volume (MTV) were estimated in each lesion. The diagnostic performance for recurrence was investigated in all enrolled patients. A definitive diagnosis was done with pathologic confirmation or clinical follow-up. Among recurrent patients, we evaluated the prognostic value of metabolic parameters (T/N ratio and MTV) as well as clinical factors. Among 42 patients, 35 patients were revealed with recurrence. Both T/N ratios (p?=?0.009) and MTV (p?=?0.001) exhibited statistical significance to differentiate between recurrence and post-treatment radiation effect. A T/N ratio of 1.43 provided the best sensitivity and specificity for recurrence (91.4 and 100 %, respectively), and a MTV of 6.72 cm³ provided the best sensitivity and specificity (77.1 % and 100 %, respectively). To evaluate the prognostic impact, different cutoffs of MTV were examined in patients with recurrent tumor and a threshold of 60 cm³ was determined as a best cutoff value to separate the patients in two prognostic groups. Univariate analysis revealed improved overall survival (OS) for patients with Karnofsky performance scale (KPS) score ≥70 (p?<?0.001) or MTV <60 cm³ (p?=?0.049). Multivariate analysis showed that patients with KPS score ≥70 (p?<?0.001; hazard ratio?=?0.104; 95 % CI, 0.029–0.371) or MTV?<?60 cm³ (p?=?0.031; hazard ratio?=?0.288; 95 % CI, 0.093–0.895) were significantly associated with a longer OS. However, T/N ratio was not correlated with patients’ outcome. Metabolic parameters had the diagnostic value to differentiate recurrence from post-treatment radiation effect. Compared with T/N ratio, MTV was an independent significant prognostic factor with KPS score in patients with recurrent tumor. Our study had a potential to manage these patients according to prognostic information using MET-PET.     

Ratio of C-reactive protein to albumin is a prognostic factor for operable non-small-cell lung cancer in elderly patients

Purpose

The aim of this retrospective study was to evaluate inflammation-based scoring as a prognostic factor for operable non-small-cell lung cancer (NSCLC) in elderly patients.

Methods

We collected preoperative data from 108 patients aged above 80 years with NSCLC. Inflammation-based scoring systems, including the C-reactive protein to albumin ratio (CAR) and the Glasgow prognostic score (GPS), as well as other clinicopathological factors, were evaluated as potential prognostic factors.

Results

The median patient age was 82 (range 80–93) years and the 5-year overall and disease-specific survival rates were 49.7 and 73.9%, respectively. The cut-off value for CAR was calculated using a receiver operator characteristics analysis and patients were dichotomized accordingly. Patients with a low CAR had significantly higher overall survival than those with a high CAR (<0.028; 65.2% vs. ≥0.028; 31.0%, respectively; p < 0.01). In univariate analysis, female gender, a low Charlson comorbidity index of 0 or 1 and a low CAR were significantly identified in overall survival. On multivariate analysis, a low CAR (p = 0.03, hazard ratio: 2.13, 95% confidence interval 1.074–4.295) was identified as a significant prognostic factor.

Conclusions

The preoperative CAR is a useful predictor of overall survival and could be a simple prognostic tool to help identify resectable NSCLC in elderly patients.

     

Reconstruction in the Metastatic Breast Cancer Patient: Results from the National Cancer Database

Purpose

Modern treatments are prolonging life for metastatic breast cancer patients. Reconstruction in these patients is controversial. The purpose of this study was to characterize de novo metastatic breast cancer patients who undergo mastectomy and reconstruction and to report complication and survival rates.

Methods

We queried the National Cancer Database for de novo metastatic breast cancer patients, who underwent systemic therapy and mastectomy with reconstruction (R) or without reconstruction (NR) between 2004 and 2013. Patient-tumor characteristics, mortality, and readmissions were compared. Propensity score matched analysis was performed, and survival was calculated using the Kaplan–Meier method.

Results

A total of 8554 patients fulfilled study criteria (n?=?980/11.5% R vs. n?=?7574/88.5% NR). There was a significant increase in reconstruction rates by year: 5.2% in 2004, 14.3% in 2013 (p?<?0.0001). Compared with the NR patients, R patients were younger (mean age 49 vs. 58 years, p?<?0.0001), more hormone receptor-positive (76.1% vs. 70.5%, p?=?0.0004), had lower grade disease (p?=?0.0082), and fewer sites of metastases (85.7% had 1 metastasis; 14.3% had?≥?2 R vs. 79% had 1; 21% had?≥?2 NR, p?=?0.0002). R patients received more hormonal and chemotherapy than NR but equally received radiation. Median overall survival of the total cohort was 45 months, and median overall survivals of R and NR groups by matched analysis were 56.7 and 55.3 months respectively (p?=?0.86). Thirty-day mortality (0.2%-R, 0.3%-NR, p?=?0.56) and readmissions (5.9%-R, 5.8%-NR, p?=?0.81) were similar; 90-day mortality also was similar (1.1%-R vs. 1.6%-NR, p?=?0.796).

Conclusions

There is an increasing trend to reconstruct metastatic breast cancer patients with low complication rates, without survival compromise. Impact on quality of life warrants further assessment.

     

Prognostic value of urinary cytology and other biomarkers for recurrence and progression in bladder cancer: a prospective study

Purpose

Urinary cytology (C) and cystoscopy remain the gold standard for the detection and screening of bladder cancer (BC). In this prospective study, we analyzed whether baseline C, ImmunoCyt (I), BTA Stat (B), hemoglobin dipstick (H), and NMP22 BladderChek (N) can predict recurrence and progression.

Methods

Urinary samples from 91 patients with BC were prospectively collected over an 18-month period. Baseline characteristics of the population included patient demographics, various clinicopathological variables and use of intravesical therapy. Progression and recurrence were then assessed after a median follow-up of 48 months (IQR 23.7–59.5). Univariate and multivariate analyses were performed using COX proportional hazards models.

Results

On univariate analysis, C (HR 1.36; p = 0.26), I (HR 0.89; p = 0.66), B (HR 0.80; p = 0.42), H (HR 0.75; p = 0.30), and N (HR 0.82; p = 0.48) were not associated with recurrence-free survival (RFS). With regard to progression-free survival (PFS), C was significantly prognostic (HR 2.67; p = 0.017), whereas I, B, H, and N were not. On multivariable analysis, NMP22 was the only marker to be independently associated with RFS (HR 0.41, p < 0.01) and PFS (HR 0.32, p = 0.02).

Conclusion

Based on the results of this study, baseline C, B, I, and H were not independently prognostic. Prognostic impact of NMP22 requires further validation in a multicenter larger study.

     

Overall Survival of Papillary Thyroid Carcinoma Patients: A Single-Institution Long-Term Follow-Up of 5897 Patients

Introduction

Papillary thyroid carcinoma (PTC) generally shows an excellent prognosis except in cases with aggressive backgrounds or clinicopathological features. Although the cause-specific survival (CSS) of PTC patients has been extensively investigated, the overall survival (OS) of these patients is unclear. We herein investigated both the OS and CSS of a large PTC patient series.

Materials and methods

We enrolled 5897 PTC patients who underwent initial surgery between 1987 and 2005 (658 males and 5339 females; median age 51 years). Their median postoperative follow-up period was 177 months. Univariate and multivariate analyses for OS and CSS assessed the effects of gender, older age (≥55 years), distant metastasis at diagnosis (M1), significant extrathyroid extension, tumor size (cutoffs 2 and 4 cm), large node metastasis (N ≥ 3 cm), and extranodal tumor extension.

Results

To date, 387 patients (7%) in this series have died from various causes, including 117 (2%) due to PTC. The 10-, 15-, and 20-year OS rates are 97, 95, and 90%, respectively. Older age and M1 were important prognostic factors for OS and CSS. Older age was a more significant factor than M1 for OS and vice versa for CSS. In the older patients, M1 was a prominent prognostic factor for both OS and CSS. In the young patients, M1 had less prognostic impact than in the older patients, and the prognostic values of M1 and N ≥ 3 cm for OS and CSS were identical and similar, respectively.

Conclusions

The most important prognostic value for OS was patient age, indicating that PTC is generally indolent. However, the control of distant metastasis in older patients remains a future challenge in order to further improve their OS and CSS. PTC of ≥3 cm in young patients should be carefully followed, even in the absence of metastases, and these patients should undergo aggressive therapies for recurrent lesions and metastases.

     

Assessment of the Lymph Node Status in Patients Undergoing Liver Resection for Intrahepatic Cholangiocarcinoma: the New Eighth Edition AJCC Staging System

Introduction

The role of routine lymphadenectomy for intrahepatic cholangiocarcinoma (ICC) is still controversial. The AJCC eighth edition recommends a minimum of six harvested lymph nodes (HLNs) for adequate nodal staging. We sought to define outcome and risk of death among patients who were staged with ≥6 HLNs versus <6 HLNs.

Materials and Methods

Patients undergoing hepatectomy for ICC between 1990 and 2015 at 1 of the 14 major hepatobiliary centers were identified.

Results

Among 1154 patients undergoing hepatectomy for ICC, 515 (44.6%) had lymphadenectomy. On final pathology, 200 (17.3%) patients had metastatic lymph node (MLN), while 315 (27.3%) had negative lymph node (NLN). Among NLN patients, HLN was associated with 5-year OS (p = 0.098). While HLN did not impact 5-year OS among MLN patients (p = 0.71), the number of MLN was associated with 5-year OS (p = 0.02). Among the 317 (27.5%) patients staged according the AJCC eighth edition staging system, N1 patients had a 3-fold increased risk of death compared with N0 patients (hazard ratio 3.03; p < 0.001).

Conclusion

Only one fourth of patients undergoing hepatectomy for ICC had adequate nodal staging according to the AJCC eighth edition. While the six HLN cutoff value impacted prognosis of N0 patients, the number of MLN rather than HLN was associated with long-term survival of N1 patients.