Craniofacial resection for malignant tumors involving the skull base in the elderly

BACKGROUND:

In this study by the International Collaborative Group, the authors examined a large cohort of patients accumulated from multiple institutions that had experience in craniofacial surgery with the objective of reporting outcomes and complications for craniofacial resection (CFR) in the elderly.

METHODS:

One hundred seventy patients aged ≥70 years were included in the study. The median age was 75 years (range, 70‐98 years). One hundred four patients (61%) had received previous single‐modality or combined treatment, which included surgery in 79 patients (46%), radiation in 47 patients (28%), and chemotherapy in 13 patients (8%). The most common histology was squamous cell carcinoma (67 patients; 39%). The margins of resection were close or microscopically positive in 56 patients (33%). Sixty‐eight patients received adjuvant radiotherapy (40%), and 3 patients received chemotherapy (2%). Complications were classified into overall, local, central nervous system (CNS), systemic, and orbital. Overall survival (OS), disease‐specific survival (DSS), and recurrence‐free survival (RFS) were determined by using the Kaplan‐Meier method. Outcomes were compared with patients aged <70 years. Statistical analyses for outcomes were performed in relation to patient characteristics, tumor characteristics (including histology and extent of disease), surgical resection margins, previous radiation, and previous chemotherapy to determine predictive factors.

RESULTS:

Postoperative mortality occurred in 16 patients (9%), and postoperative complications occurred in 72 patients (42%). Local wound complications occurred in 40 patients (24%), CNS complications occurred in 24 patients (14%), systemic complications occurred in 19 patients (11%), and orbital complications occurred in 4 patients (2%). Postoperative mortality and complications were significantly more frequent in elderly patients compared with patients aged <70 years (postoperative mortality: 9% vs 3%; P = .04; complications: 42% vs 32%; P = .0009). The 5‐year OS, DSS, and RFS rates were significantly poorer than those for patients aged <70 years (OS: 42% vs 56%; P < .0001; DSS: 53% vs 61%; P = .04; RFS: 46% vs 54%; P = .03). Surgical margin status and primary tumor histology were independent predictors of OS, DSS, and RFS in multivariate analysis.

CONCLUSIONS:

CFR for malignant skull base tumors in elderly patients (aged ≥70 years) was associated with increased mortality, complications, and poorer outcomes compared with patients aged <70 years. Cancer 2011. © 2010 American Cancer Society.     

Lymph node density is a significant predictor of outcome in patients with oral cancer

BACKGROUND:

The impact of lymph node metastases on prognosis in patients with oral cavity squamous cell carcinoma (OSCC) has been well recognized. However, accurate stratification of risk for recurrence among patients with lymph node metastases is difficult based on the existing staging systems. In the current study, the utility of lymph node density (LND) was evaluated as an alternative method for predicting survival.

METHODS:

Three hundred eighty‐six patients who underwent neck dissection were included. The median follow‐up was 67 months. Five‐year overall survival (OS), disease‐specific survival (DSS), and locoregional failure (LRF) rates were calculated using the Kaplan‐Meier method. LND (number of positive lymph nodes/total number of excised lymph nodes) and tumor‐node‐metastasis (TNM) staging variables were subjected to multivariate analysis.

RESULTS:

Using the median (LND = 0.06) as the cutoff point, LND was found to be significantly associated with outcome. For patients with LND ≤0.06, the OS was 58 percent versus 28 percent for patients with LND >0.06 (P < .001). Similarly, the DSS for patients with LND ≤0.06 was 65 percent and was 34 percent for those with LND >0.06 (P < .001). On univariate analysis, pathologic T and N classification, extracapsular spread, and LND were found to be significant predictors of outcome (P < .001). However, on multivariate analysis, LND remained the only independent predictor of OS (P = .02; hazards ratio, 2.0), DSS (P = .02; hazards ratio, 2.3), and LRF (P = .005; hazards ratio, 4.1). LND was also found to be the only significant predictor of outcome in patients receiving adjuvant radiotherapy (P < .05). Within individual subgroups of pN1 or pN2 patients, LND reliably stratified patients according to their risk of failure (P < .05).

CONCLUSIONS:

After surgery for OSCC, pathologic evaluation of the neck using LND was found to reliably stratify the risk of disease recurrence and survival. Cancer 2009. © 2009 American Cancer Society.     

Effect of metformin on survival outcomes in diabetic patients with triple receptor-negative breast cancer

BACKGROUND:

Recent observational studies have shown that metformin use in diabetic patients decreases both cancer incidence and mortality. Metformin use is also independently predictive of pathologic complete response. In the current study, the authors explored the association between metformin use and survival outcomes in patients with triple receptor‐negative breast cancer (TNBC) who were receiving adjuvant chemotherapy.

METHODS:

The Breast Cancer Management System database of The University of Texas MD Anderson Cancer Center identified 1448 women who received adjuvant chemotherapy for TNBC between 1995 and 2007. Patients were categorized by diabetes status and metformin use. The Kaplan‐Meier product‐limit method was used to calculate distant metastasis‐free survival (DMFS), recurrence‐free survival (RFS), and overall survival (OS). Cox proportional hazards models were fit to determine the association between metformin use and survival outcomes.

RESULTS:

The study cohort was comprised of 63 diabetic patients receiving treatment with metformin, 67 diabetic patients not receiving metformin, and 1318 nondiabetic patients. Patients in the diabetic groups tended to be older (P = .005); more diabetic patients were postmenopausal (P = .0007), black (P = .0001), and obese (P < .0001). At a median follow‐up of 62 months, there were no significant differences with regard to 5‐year DMFS (P = .23), RFS (P = .38), and OS (P = .58) between the 3 groups. Compared with the metformin group, patients who did not receive metformin (hazard ratio [HR], 1.63; 95% confidence interval [95% CI], 0.87‐3.06 [P = .13]) and nondiabetic patients (HR, 1.62; 95% CI, 0.97‐2.71 [P = .06]) tended to have a higher risk of distant metastases.

CONCLUSIONS:

The findings of the current study suggest that metformin use during adjuvant chemotherapy does not significantly impact survival outcomes in diabetic patients with TNBC. Cancer 2012;. © 2011 American Cancer Society.     

An analysis of human equilibrative nucleoside transporter‐1, ribonucleoside reductase subunit M1, ribonucleoside reductase subunit M2, and excision repair cross‐complementing gene‐1 expression in patients with resected pancreas adenocarcinoma

BACKGROUND:

Tumor overexpression of excision repair cross‐complementing gene‐1 (ERCC1) may be associated with decreased survival in patients with pancreas adenocarcinoma (PAC). Human equilibrative nucleoside transporter‐1 (hENT1) and ribonucleoside reductase subunits M1 and M2 (RRM1 and RRM2) are integral to cellular transport and DNA synthesis and are implicated as poor prognostic factors in other malignancies. To the authors's knowledge, their role in PAC is not defined.

METHODS:

A prospective database was used to randomly select 95 patients who underwent pancreaticoduodenectomy for PAC between January 2000 and October 2008. Immunohistochemical analysis was performed on tumor samples for hENT1, RRM1 and RRM2, and ERCC1. Main outcomes were recurrence‐free survival (RFS) and overall survival (OS).

RESULTS:

The median follow‐up, RFS, and OS were 49 months, 10.6 months, and 15.5 months, respectively. The median tumor size was 3 cm. Approximately 26% of patients had positive microscopic margins, 61% had lymph node involvement, and 88% and 45% had perineural and lymphovascular invasion, respectively. High tumor expression of hENT1, RRM1, RRM2, and ERCC1 was present in 85%, 40%, 17%, and 16%, respectively, of patients. High hENT1 expression was associated with reduced RFS (9.5 months vs 44.5 months; P = .029), but not with OS. RRM1 expression was not associated with survival. High RRM2 expression was associated with reduced RFS (6.9 months vs 16.0 months; P < .0001) and decreased OS (9.1 months vs 18.4 months; P < .0001). High ERCC1 expression was associated with reduced RFS (6.1 months vs 15 months; P = .04) and decreased OS (8.9 months vs 18.1 months; P = .03). After accounting for known adverse tumor factors, high expression of RRM2 and ERCC1 persisted as negative prognostic factors for RFS and OS. A subset analysis of patients who received adjuvant therapy (n = 74) revealed the same negative effect of high RRM2 and ERCC1 expression on RFS and OS.

CONCLUSIONS:

High tumor expression of RRM2 and ERCC1 are associated with reduced RFS and OS after resection of pancreas cancer. These biomarkers may help to personalize adjuvant therapy. Cancer 2013. © 2012 American Cancer Society.     

Long‐term outcomes after hepatic resection for colorectal metastases in young patients

BACKGROUND:

Long‐term outcomes after hepatectomy for colorectal liver metastases in relatively young patients are still unknown. The aim of the current study was to evaluate long‐term outcomes in patients ≤40 years old, and to compare them with patients >40 years old.

METHODS:

All consecutive patients who underwent hepatectomy for colorectal liver metastases at the authors' hospital between 1990 and 2006 were included in the study. Patients ≤40 years old were compared with all other patients treated during the same period. Overall survival (OS), progression‐free survival (PFS), and disease‐free survival (DFS) rates were determined, and prognostic factors were identified.

RESULTS:

In total, 806 patients underwent hepatectomy for colorectal liver metastases, of whom 56 (7%) were aged ≤40 years. Among the young patients, more colorectal liver metastases were present at diagnosis, and they were more often diagnosed synchronous with the primary tumor. Five‐year OS was 33% in young patients, compared with 51% in older patients (P = .12). Five‐year PFS was 2% in young patients, compared with 16% in older patients (P < .001). DFS rates were comparable between the groups (17% vs 23%, P = .10). At multivariate analysis, age ≤40 years was identified as an independent predictor of poor PFS.

CONCLUSIONS:

In young patients, colorectal liver metastases seem to be more aggressive, with a trend toward lower OS, more disease recurrences, and a significantly shorter PFS after hepatectomy. However, DFS rates were comparable between young and older patients, owing to an aggressive multimodality treatment approach, consisting of chemotherapy and repeat surgery. Therefore, physicians should recognize the poor outcome of colorectal liver metastases in young patients and should consider an aggressive approach to diagnosis and early treatment. Cancer 2010. © 2009 American Cancer Society.     

Microsatellite instability and DNA ploidy in colorectal cancer

BACKGROUND:

Appropriate stratification tools for targeted surveillance after resection for colorectal cancer (CRC) are lacking. The objective of the current study was to investigate the effect of microsatellite instability (MSI) and DNA ploidy on surveillance after surgery.

METHODS:

The authors evaluated 186 consecutive, population‐based patients with stage I through III CRC who underwent surgery with curative intent and who entered a systematic surveillance program. MSI was analyzed with polymerase chain reaction for 5 known quasimonomorphic markers (BAT‐26, BAT‐25, NR‐21, NR‐24, and NR‐27), and DNA ploidy was analyzed with automated cytometry. Recurrence, recurrence‐free survival (RFS), and disease‐specific survival (DSS) were evaluated by univariate and multivariate statistical tests.

RESULTS:

Patients with MSI (20%) were significantly younger than patients without MSI (median age, 61 years vs 67 years; P = .016). Proximal location (adjusted odds ratio [AOR], 5.4; 95% confidence interval [95% CI], 2.1‐14.1 [P = .001]), large tumor size (≥5 cm: AOR, 3.5; 95% CI, 1.3–9.6 [P = .015]), and poor tumor differentiation (AOR, 6.6; 95% CI, 2–21.8 [P = .002]) were associated with MSI. MSI conveyed an increased risk for locoregional recurrence (OR, 2.9; 95% CI, 1.2–7 [P = .016]), with a trend toward a shorter time to recurrence (P = .060). Neither MSI status nor DNA ploidy predicted distant metastasis, RFS, or DSS. Lymph node status was the best predictor of distant spread (AOR, 3.9; 95% CI, 2–7.9 [P < .001]) and DSS (hazard ratio, 4.9; 95% CI, 2.6–9 [P < .001]).

CONCLUSIONS:

Patients who had microsatellite instable tumors were at increased risk for locoregional recurrence, whereas lymph node status was the best predictor of distant metastasis. Clinical surveillance and choice of modality (ie, endoscopy vs radiologic imaging) may be improved when patients are stratified according to these cancer features. Cancer 2009. © 2009 American Cancer Society.     

Impact of low estrogen/progesterone receptor expression on survival outcomes in breast cancers previously classified as triple negative breast cancers

PURPOSE:

To evaluate the impact of low estrogen/progesterone receptor (ER/PR) expression and effect of endocrine therapy on survival outcomes in human epidermal growth factor receptor 2 (HER2)‐negative tumors with ER/PR <10%, previously labeled as triple negative.

METHODS:

In a retrospective review, 1257 patients were categorized according their ER/PR percentages into 3 groups, ER/PR <1% (group A), ER/PR 1% to 5% (group B), and ER/PR 6% to 10% (group C). Kaplan‐Meier product limit method was used to estimate survival outcomes. Cox proportional hazards models was used to adjust for patient and tumor characteristics.

RESULTS

Groups A, B, and C had 897 (71.4%), 241 (19.2%), and 119 (9.4%) patients, respectively. After a median follow‐up of 40 months there was no significant difference in 3‐year recurrence‐free survival (RFS): 64%, 67%, and 77% (P = .34) or overall survival (OS): 79%, 81%, and 88% (P = .33) for groups A, B, and C, respectively. ER/PR expression was not an independent predictor for RFS (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.86‐1.39; P = .46 for group B, and HR, 0.96; 95% CI, 0.66‐1.38; P = .81 for group C, compared with group A), or OS (HR, 1.11; 95% CI, 0.84‐1.46; P = .46 for group B, and HR, 0.94; 95% CI, 0.63‐1.42; P = .78 for group C, compared with group A). Endocrine therapy had no impact on survival outcomes (RFS: P = .10; OS: P = .45) among groups.

CONCLUSIONS:

In this cohort, a low ER/PR level (1%‐5%) does not appear to have any significant impact on survival outcomes. There was a tendency for survival advantages in the ER/PR 6% to 10% is seen. Benefit of endocrine therapy in these patients is unclear. Cancer 2011;. © 2011 American Cancer Society.     

Chromosome 9p deletions identify an aggressive phenotype of clear cell renal cell carcinoma

BACKGROUND:

The authors investigated whether deletion of chromosome 9p in clear cell renal cell carcinoma (ccRCC) predicted worse disease‐specific survival (DSS) and recurrence‐free survival (RFS) and whether it was associated with more aggressive behavior in small renal masses.

METHODS:

In total, 703 ccRCC tumors were analyzed using fluorescence in situ hybridization (316 tumors) and cytogenetics (388 tumors). Tumor grade, classification, and size; 9p status; Eastern Cooperative Oncology Group performance status (ECOG PS); lymph node involvement; and the presence of metastasis were recorded. Outcomes were stratified by 9p status, and a Cox proportional hazards models was constructed using TNM staging, ECOG PS, tumor size, tumor grade, and 9p status.

RESULTS:

Deletions of 9p were detected in 97 tumors (13.8%). At presentation, 9p‐deleted tumors were larger and were more likely to be high grade (grade 3 or 4), to have a high tumor (T) classification (T3‐T4), and to have lymph node or distant metastases (P < .01). The median DSS for patients with and without 9p deletions was 37 months and 82 months, respectively (P < .01). In patients with localized disease, the median RFS in those who had 9p deletions was 53 months and was not reached in those without 9p deletions (P < .01). In patients who had localized lesions that measured ≤4 cm in greatest dimension, 9p‐deleted tumors were more likely to recur (19% vs 2%; P = .01).

CONCLUSIONS:

Deletion of chromosome 9p in ccRCC occurred in 14% of patients and was associated with higher grade and T classification, and the presence of lymph node and distant metastases. In addition, 9p deletion independently conferred a worse prognosis for patients with localized ccRCC, and most noteworthy, in patients with localized, small renal masses. Preoperatively identifying patients with 9p deletions will improve risk stratification and will help to select appropriate patients for surveillance protocols or aggressive treatment. Cancer 2010. © 2010 American Cancer Society.     

Phase 2 trial of primary systemic therapy with doxorubicin and docetaxel followed by surgery,radiotherapy, and adjuvant chemotherapy with cyclophosphamide,methotrexate, and 5‐fluorouracil based on clinical and pathologic response in patients with stage IIB to III breast cancer

BACKGROUND:

This study was performed to evaluate the outcomes of patients with locally advanced breast cancer (LABC) who were treated with a multidisciplinary approach including primary systemic chemotherapy and noncross‐resistant adjuvant chemotherapy.

METHODS:

Patients with LABC received 4 or 6 cycles of doxorubicin and docetaxel (DT) as primary systemic chemotherapy (PST) every 21 days. Patients with adequate response underwent surgery followed by adjuvant chemotherapy according to pathologic response: complete (pCR), 2 more cycles of DT; partial (pPR), 2 more cycles of DT followed by 6 cycles of cyclophosphamide, methotrexate, and 5‐fluorouracil (5‐FU) (CMF); and minor (pMR), 6 cycles of CMF. Patients then received radiation and tamoxifen (hormone receptor‐positive patients only).

RESULTS:

Eighty‐eight patients were evaluable. Seventy‐four patients had an adequate response to DT and were considered operable, and 72 underwent surgery. Ten patients (13.9%) achieved a pCR, 22 (30.5%) achieved a pPR, and 40 achieved a pMR (55.5%). Fourteen patients were considered nonoperable after DT and underwent salvage CMF therapy. Five of these patients underwent surgery and 1 had achieved a pCR. The estimated 5‐year recurrence‐free survival (RFS) rates for patients with pCR, pPR, and pMR were 80%, 77%, and 59%, respectively, and the estimated 5‐year overall survival (OS) rates were 90%, 91%, and 74%, respectively. The 5‐year OS rates were 82% for initially operable and 21% for initially inoperable patients (P ≤ .001)

CONCLUSIONS:

Multidisciplinary therapy that includes PST with DT and adjuvant therapy with CMF administered according to the clinical and pathologic response is associated with high long‐term RFS and OS rates in patients with LABC. Clinical or pathologic PR or CR to DT predicts improved RFS and OS. Cancer 2010. Published 2010 by the American Cancer Society.     

Endoscopic ultrasound and computed tomography in restaging and predicting prognosis after neoadjuvant chemotherapy in patients with locally advanced gastric cancer

BACKGROUND.

The objective of the current study was to assess the staging accuracy and prognostic role of preoperative endoscopic ultrasound (EUS) and computed tomography (CT) in patients with locally advanced gastric cancer (LAGC) after neoadjuvant chemotherapy.

METHODS.

Presurgical LAGC patients underwent EUS and CT before and after 3 cycles of neoadjuvant chemotherapy. Chemotherapy was comprised of docetaxel (at a dose of 36 mg/m²) and cisplatin (at a dose of 40 mg/m²) on Days 1 and 8 of a 3‐week cycle.

RESULTS.

Forty patients were enrolled in the study. After chemotherapy, the accuracy of EUS and CT was found to be 47% and 57%, respectively for T classification (P = .22) and 39% and 37%, respectively for N classification (P > .99). The 3‐year overall survival (OS) rate for patients downstaged with EUS for T and/or N classification was greater than that for nondownstaged patients (69% vs 41%; P = .05). The 2‐year recurrence‐free survival (RFS) rate was also better for the EUS‐downstaged patients than for the nondownstaged patients (77% vs 47%; P = .04). On multivariate analysis, EUS downstaging was found to be correlated with OS (hazards ratio [HR] of 0.12; P = .04), and was correlated with RFS with borderline statistical significance (HR of 0.27; P = .07). The differences in OS and RFS between the patients downstaged with CT and those not downstaged were not found to be statistically significant.

CONCLUSIONS.

Restaging by EUS and CT after neoadjuvant chemotherapy in patients with LAGC was found to be inaccurate. However, T and/or N downstaging by EUS was found to be correlated with better OS and RFS. Thus, downstaging by EUS may be a useful clinical parameter with which to predict a better outcome for LAGC patients. Cancer 2008. © 2008 American Cancer Society.     

Osteosarcoma of the jaw/craniofacial region

BACKGROUND:

The current study was performed to evaluate outcomes in patients with osteosarcoma of the head and neck (OHN) who were treated with surgery with or without radiotherapy (RT).

METHODS:

Between 1960 and 2007, 119 patients with OHN underwent macroscopic total resection with or without RT. The median age of the patients was 33 years (range, 7‐77 years). Of these 119 patients 92 (77%) underwent surgery alone whereas 27 (23%) patients were treated with combined modality treatment (CMT) comprised of surgery and RT (median dose, 60 Gray [Gy]; range, 50‐66 Gy).

RESULTS:

The median follow‐up was 5.8 years. Overall survival (OS) rates at 5 years and 10 years were 63% and 55%, respectively. Corresponding disease?specific survival (DSS) rates were 67% and 61%, respectively. Stratified analysis by resection margin status demonstrated that CMT compared with surgery alone improved OS (80% vs 31%; P = .02) and DSS (80% vs 35%; P = .02) for patients with positive/uncertain resection margins. Multivariate analysis indicated that CMT for patients with positive/uncertain resection margins improved OS (P < .0001). A total of 44 (37%) patients experienced local disease recurrence (LR) and 25 (21%) developed distant metastases (DM). There was no difference noted with regard to DSS if disease recurrence was isolated (LR vs DM: 26% vs 29%, respectively, at 5 years; P = .48) The use of CMT versus surgery alone improved local control (LC) (75% vs 24%; P = .006) for patients with positive/uncertain resection margins. The rate of surgical complications was 28% at 5 years. The rates of RT‐associated complications were 40% and 47% at 5 years and 10 years, respectively.

CONCLUSIONS:

The results of the current study indicated that RT in addition to surgery improves OS, DSS, and LC for patients with OHN who have positive/uncertain resection margins. Cancer 2009. © 2009 American Cancer Society.     

Head and neck cancer-specific survival based on socioeconomic status in Asians and Pacific Islanders

BACKGROUND:

Lower socioeconomic status (SES) has been linked to higher incidence of head and neck cancer (HNC) and lower survival. However, little is known about the effect of SES on HNC survival in Asians and Pacific Islanders (APIs). This study's purpose was to examine the effect of SES on disease‐specific survival (DSS) and overall survival (OS) in APIs with HNC using population‐based data.

METHODS:

A total of 53,544 HNC patients (4,711 = APIs) were identified from the California Cancer Registry from 1988 to 2007. Neighborhood (block‐group‐level) SES, based on composite Census 1990 and 2000 data, was calculated for each patient based on address at diagnosis, categorized into statewide quintiles, and collapsed into 2 groups for comparison (low SES = quintiles 1‐3; high SES = quintiles 4‐5). DSS and OS were computed by the Kaplan‐Meier method. Adjusted hazards ratios (HR) were estimated using Cox proportional hazards regression models.

RESULTS:

Among APIs, lower neighborhood SES was significantly associated with poorer DSS (HR range for oral cavity, oropharynx, or larynx/hypopharynx cancer, 1.07‐1.34) and OS (HR, 1.13‐1.37) after adjusting for patient and tumor characteristics. Lower SES was significantly associated with poorer survival in API with all HNC sites combined: DSS HR: 1.26 (95% confidence interval [CI], 1.08‐1.48) and OS HR, 1.30 (95% CI, 1.16‐1.45).

CONCLUSIONS:

Neighborhood SES was associated with longer DSS and OS in API with HNC. The effect of SES on HNC survival should be considered in future studies, and particular attention should be paid to clinical care of lower‐SES HNC patients. Cancer 2011. © 2010 American Cancer Society.     

Efficacy of neoadjuvant therapy with trastuzumab concurrent with anthracycline- and nonanthracycline-based regimens for HER2-positive breast cancer

BACKGROUND:

The aim of this study was to evaluate the pathologic complete response (pCR) rates and relapse‐free survival (RFS) and overall survival (OS) of patients receiving neoadjuvant systemic therapy (NST) with trastuzumab in combination with an anthracycline‐ or nonanthracycline‐based regimen.

METHODS:

In this retrospective nonrandomized study, the authors reviewed records of 300 patients with HER2‐positive breast cancer treated with either sequential paclitaxel and trastuzumab and FEC75 in combination with trastuzumab (PH‐FECH) or docetaxel, carboplatin, and trastuzumab (TCH). The Kaplan‐Meier product‐limit method was used to estimate RFS and OS rates. Logistic regression models and Cox proportional hazards models were fit to determine the associations between NST, pCR, and survival.

RESULTS:

There was no significant difference in the decline in cardiac ejection fraction; however, patients who received PH‐FECH had fewer cardiac comorbidities at baseline (P = .002). pCR rates were 60.6% and 43.3% for patients who received PH‐FECH (n = 235) and TCH (n = 65), respectively (P = .016). Patients who received PH‐FECH were 1.45 times more likely to have a pCR (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.06‐1.98; P = .02). Three‐year RFS rates were 93% and 71% (P < .001), and 3‐year OS rates were 96% and 86% (P = .008) for patients who received PH‐FECH and TCH, respectively. Patients who received PH‐FECH had a lower risk of recurrence (hazard ratio [HR], 0.27; 95% CI, 0.12‐0.60; P = .001) and death (HR, 0.37; 95% CI, 0.12‐1.13; P = .08) than those treated with TCH.

CONCLUSIONS:

The type of NST in HER2‐positive breast cancer is predictive of pCR rate independent of disease and patient characteristics. Although TCH is active, PH‐FECH shows a higher pCR rate and RFS advantage. Cancer 2012. © 2011 American Cancer Society.     

A comparison of the outcomes of neoadjuvant and adjuvant chemotherapy for clinical T2-T4aN0-N2M0 bladder cancer

BACKGROUND:

Despite evidence supporting perioperative chemotherapy, few randomized studies compare neoadjuvant and adjuvant chemotherapy for bladder cancer. Consequently, the standard of care regarding the timing of chemotherapy for locally advanced bladder cancer remains controversial. We compared patient outcomes following neoadjuvant or adjuvant systemic chemotherapy for cT2‐T4aN0‐N2M0 bladder cancer.

METHODS:

In a retrospective review of a single institutional database from 1988 through 2009, we identified patients receiving neoadjuvant or adjuvant multiagent platinum‐based systemic chemotherapy for locally advanced bladder cancer. Survival analysis was performed comparing disease‐specific survival (DSS) and overall survival (OS).

RESULTS:

A total of 146 patients received systemic perioperative chemotherapy (73 neoadjuvant, 73 adjuvant). Of these, 84% (122/146) received cisplatin‐based chemotherapy compared with carboplatin‐based chemotherapy (24/146, 16.4%). Most patients receiving cisplatin‐based chemotherapy were treated with methotrexate/vinblastine/adriamycin/cisplatin (79/122, 64.8%), whereas the remaining patients received gemcitabine/cisplatin (GC) (43/122, 35.2%). In multivariable analysis, there was no significant difference in DSS (P = .46) or OS (P = .76) between neoadjuvant or adjuvant chemotherapy groups. There was statistically significant improvement in DSS when patients received neoadjuvant GC rather than adjuvant GC (P = .049, hazard ratio, 10.6; 95% confidence interval, 1.01‐112.2).

CONCLUSION:

In this study, there was no statistically significant difference in OS and DSS between patients receiving neoadjuvant versus adjuvant systemic platinum‐based chemotherapy for locally advanced bladder cancer. In addition, there was no significant difference between neoadjuvant and adjuvant cisplatin‐ or carboplatin‐based chemotherapy. Chemotherapy sequence relative to surgery appeared less important than whether or not a patient actually received perioperative chemotherapy. Cancer 2011;. © 2011 American Cancer Society.     

Early clearance of peripheral blood blasts predicts response to induction chemotherapy in acute myeloid leukemia

BACKGROUND:

Early marrow blast clearance 14 days after induction chemotherapy is an independent prognostic indicator of outcomes in acute myeloid leukemia (AML).

METHODS:

We evaluated the relationship between time to peripheral blood blast clearance after induction and disease status as assessed by day 14 and day 30 marrow biopsies in 162 patients with AML. Day 6 after induction was the optimal cutoff point determined by a receiver operating characteristic analysis and was selected to divide patients into early blast clearance (EBC; ≤6 days; n = 119) and delayed blast clearance (DBC; >6 days; n = 43) groups.

RESULTS:

DBC patients were older, but otherwise the 2 groups were comparable. Marrow blast clearance on day 14 after induction chemotherapy was observed in 84% of patients in the EBC group and 60% in the DBC group. With a median follow‐up of 1538 days, both relapse‐free survival (RFS) (442 vs 202 days, P = .0017) and overall survival (OS) (930 vs 429 days, P < .0001) were longer in the EBC group, and a multivariable analysis showed that EBC independently predicted clearance of marrow blasts at day 14 (P = .0018), remission (P = .0179), RFS (P = .0171), and OS (P = .0122).

CONCLUSIONS:

Early clearance of peripheral blood blasts after induction chemotherapy predicts for early marrow blast clearance, complete remission, RFS, and OS. Cancer 2012. © 2012 American Cancer Society.     

Pathologic complete response in breast cancer patients receiving anthracycline‐ and taxane‐based neoadjuvant chemotherapy

BACKGROUND:

The current study was conducted to evaluate the influence of race/ethnicity and tumor subtype in pathologic complete response (pCR) following treatment with neoadjuvant chemotherapy.

METHODS:

A total of 2074 patients diagnosed with breast cancer between 1994 and 2008 who were treated with neoadjuvant anthracycline‐ and taxane‐based chemotherapy were included. pCR was defined as no residual invasive cancer in the breast and axilla. The Kaplan‐Meier product‐limit was used to calculate survival outcomes. Cox proportional hazards models were fitted to determine the relationship of patient and tumor variables with outcome.

RESULTS:

The median patient age was 50 years; 14.6% of patients were black, were 15.2% Hispanic, 64.3% were white, and 5.9% were of other race. There were no differences in pCR rates among race/ethnicity (12.3% in black, 14.2% in Hispanics, 12.3% in whites, and 11.5% in others, P = .788). Lack of pCR, breast cancer subtype, grade 3 tumors, and lymphovascular invasion were associated with worse recurrence‐free survival (RFS) and overall survival (OS) (P ≤ .0001). Differences in RFS by race/ethnicity were noted in the patients with hormone receptor‐positive disease (P = .007). On multivariate analysis, Hispanics had improved RFS (hazard ratio [HR], 0.69; 95% confidence interval [95% CI], 0.49‐0.97) and OS (HR, 0.63; 95% CI, 0.41‐0.97); blacks had a trend toward worse outcomes (RFS: HR, 1.28 [95% CI, 0.97‐1.68] and OS: HR, 1.32 [95% CI, 0.97‐1.81]) when compared with whites.

CONCLUSIONS:

In this cohort of patients, race/ethnicity was not found to be significantly associated with pCR rates. On a multivariate analysis, improved outcomes were observed in Hispanics and a trend toward worse outcomes in black patients, when compared with white patients. Further research was needed to explore the potential differences in biology and outcomes. Cancer 2010. © 2010 American Cancer Society.     

Occult tumor burden contributes to racial disparities in stage-specific colorectal cancer outcomes

BACKGROUND:

There are differences in outcomes in blacks compared with whites with lymph node–negative (pN0) colorectal cancer. Recurrence in pN0 patients suggests the presence of occult metastases undetected by conventional approaches. This study explores the association of racial differences in outcomes with occult tumor burden in regional lymph nodes.

METHODS:

Lymph nodes (range, 2‐159) from 282 prospectively enrolled pN0 colorectal cancer patients followed for a median of 24 months (range, 2‐63 months) were subjected to molecular analysis. Occult tumor burden was estimated by quantifying the expression of GUCY2C, a biomarker for metastatic colorectal cancer cells. Risk categories defined using occult tumor burden was the primary outcome measure. Association of prognostic variables and risk were defined by multivariate polytomous logistic regression.

RESULTS:

Occult tumor burden stratified this cohort of 259 whites and 23 blacks into categories with low (60%; recurrence rate [RR] = 2.3%; 95% confidence interval [CI], 0.1%‐4.5%), intermediate (31%; RR = 33.3%; 95% CI, 23.7%‐44.1%), and high (9%; RR = 68.0%; 95% CI, 46.5%‐85.1%; P < .001) risk. Blacks compared with whites exhibited 4‐fold greater occult metastases in individual lymph nodes (P < .001). Multivariate analysis revealed that race (P = .02), T stage (P = .02), and number of lymph nodes collected (P = .003) were independent prognostic markers of risk category. Blacks compared with whites were more likely to harbor levels of occult tumor burden, associated with the highest recurrence risk (adjusted odds ratio = 5.08; 95% CI, 1.69‐21.39; P = .007).

CONCLUSIONS:

Racial disparities in stage‐specific outcomes in colorectal cancer are associated with differences in occult tumor burden in regional lymph nodes. Cancer 2012. © 2011 American Cancer Society.     

Number of metastatic sites is a strong predictor of survival in patients with nonsmall cell lung cancer with or without brain metastases

BACKGROUND:

The staging system for non–small cell lung cancer (NSCLC) does not consider tumor burden or number of metastatic sites, although oligometastases are more favorable.

METHODS:

Using log‐rank testing, the authors analyzed overall survival (OS) in 1284 patients newly presenting with metastatic NSCLC by number of metastatic organ sites and the presence of brain metastases.

RESULTS:

OS for patients without brain metastases was found to be correlated with the number of metastatic sites (P = .0009). Brain metastases conferred an inferior OS (median of 7 months vs 9 months; 95% confidence interval, 7‐8 months vs 8‐10 months [P = .00,002]). To evaluate the influence of tumor burden on OS, the authors considered subsets of patients in whom the brain (n = 135) or lung (n = 137) was the solitary metastatic organ site. In patients with brain metastases, OS was found to be correlated inversely with the volume of all metastases or the largest lesion (hazards ratio, 1.04 or 1.03, respectively; P = .01). For patients with lung metastases, OS was better for those with a maximum tumor size below the median of 40 mm (P = .0004).

CONCLUSIONS:

Staging of NSCLC and clinical trial patient stratification should include quantitation of tumor burden. The prognostic impact of brain metastases is small and partly dependent on tumor volume, which indicates the need for aggressive therapy for patients with NSCLC brain metastasis and their inclusion in clinical trials. Cancer 2009. © 2009 American Cancer Society.