Accuracy of Ultrasonography-Guided Fine-Needle Aspiration in Detecting Persistent Nodal Disease After Chemoradiotherapy

IMPORTANCE: Few patients with persistent adenopathy following chemoradiotherapy (CRT) for head and neck squamous cell carcinoma harbor viable disease. Improved selectivity for surgical salvage is needed to prevent unnecessary salvage neck dissection. OBJECTIVE: To determine whether ultrasonography-guided fine-needle aspiration (FNA) can be used to identify viable cancer cells in the lymph nodes of patients with persistent radiographic adenopathy following CRT. DESIGN, SETTING, AND PARTICIPANTS: A pilot study included patients undergoing preoperative ultrasonography-guided FNA of lymph nodes considered suspicious on radiography prior to planned neck dissection at a quaternary care facility from February 28, 2011, to March 18, 2013. Data analysis was performed from April 28 to December 24, 2013. Patients treated for head and neck squamous cell carcinoma with CRT who were determined to have persistent neck disease on a 6-week posttreatment computed tomographic scan of the neck and scheduled for salvage neck dissection were considered candidates for this pilot study. All patients enrolled in the study underwent ultrasonography-guided FNA of the suspicious lymph nodes within 2 weeks of the planned neck dissection. The cytopathologist reading the samples was blinded to the patient's identity. EXPOSURES: Fine-needle aspiration with a 23- to 25-gauge needle following CRT. MAIN OUTCOMES AND MEASURES: The accuracy of ultrasonography-guided FNA cytologic results was compared with the standard of surgical pathologic examination of neck dissection specimens. RESULTS: Fourteen patients (11 [79%] men; mean [SD] age, 57.8 [11.2] years) were enrolled in this pilot study; data were collected on 17 lymph nodes. Among these 14 patients with incomplete radiographic clinical response, 17 lymph node aspirations were performed. Ultrasonography-guided FNA identified squamous cell carcinoma in the aspirates of 4 (80%) of the 5 nodes with squamous cell carcinoma identified on pathologic testing and confirmed the absence of disease in the remaining 12 (71%) lymph nodes. The statistical analysis of these results revealed a sensitivity of 80%; specificity, 100%; positive predictive value, 100%; and negative predictive value, 92.3%. The diagnostic accuracy of ultrasonography-guided FNA at detecting residual persistent cancer was 88%. CONCLUSIONS AND RELEVANCE: This pilot study suggests that ultrasonography-guided FNA may be a feasible ancillary diagnostic imaging tool to imaging to assess patients with radiographic persistent disease prior to consideration of salvage neck dissection

Antiproliferative and metabolic effects of metformin in a preoperative window clinical trial for endometrial cancer

We conducted a preoperative window study of metformin in endometrial cancer (EC) patients and evaluated its antiproliferative, molecular and metabolic effects. Twenty obese women with endometrioid EC were treated with metformin (850mg) daily for up to 4weeks prior to surgical staging. Expression of the proliferation marker Ki-67, estrogen receptor (ER), progesterone receptor (PR), adenosine monophosphate-activated protein kinase (AMPK), and downstream targets of the mammalian target of rapamycin (mTOR) pathway were measured by immunohistochemistry. Global, untargeted metabolomics analysis of serum pre- and postmetformin treatment, and matched tumor, was performed. Metformin reduced proliferation by 11.75% (P=0.008) based on the comparison of pre- and posttreatment endometrial tumors. A total of 65% of patients responded to metformin as defined by a decrease in Ki-67 staining in their endometrial tumors post-treatment. Metformin decreased expression of phosphorylated (p)-AMPK (P=0.00001), p-Akt (P=0.0002), p-S6 (51.2%, P=0.0002), p-4E-BP-1 (P=0.001), and ER (P=0.0002) but not PR expression. Metabolomic profiling of serum indicated that responders versus nonresponders to treatment were more sensitive to metformin's effects on induction of lipolysis, which correlated with increased fatty acid oxidation and glycogen metabolism in matched tumors. In conclusion, metformin reduced tumor proliferation in a pre-operative window study in obese EC patients, with dramatic effects on inhibition of the mTOR pathway. Metformin induced a shift in lipid and glycogen metabolism that was more pronounced in the serum and tumors of responders versus nonresponders to treatment.This study provides support for therapeutic clinical trials of metformin in obese patients with EC

Obesity Is Associated With Worse Overall Survival in Women With Low-Grade Papillary Serous Epithelial Ovarian Cancer

To evaluate prognostic risk factors for survival in women with low grade serous epithelial ovarian cancer (LGSC)

Antiproliferative and metabolic effects of metformin in a preoperative window clinical trial for endometrial cancer

We conducted a preoperative window study of metformin in endometrial cancer (EC) patients and evaluated its antiproliferative, molecular and metabolic effects. Twenty obese women with endometrioid EC were treated with metformin (850 mg) daily for up to 4 weeks prior to surgical staging. Expression of the proliferation marker Ki-67, estrogen receptor (ER), progesterone receptor (PR), adenosine monophosphate-activated protein kinase (AMPK), and downstream targets of the mammalian target of rapamycin (mTOR) pathway were measured by immunohistochemistry. Global, untargeted metabolomics analysis of serum pre- and postmetformin treatment, and matched tumor, was performed. Metformin reduced proliferation by 11.75% (P = 0.008) based on the comparison of pre- and posttreatment endometrial tumors. A total of 65% of patients responded to metformin as defined by a decrease in Ki-67 staining in their endometrial tumors post-treatment. Metformin decreased expression of phosphorylated (p)-AMPK (P = 0.00001), p-Akt (P = 0.0002), p-S6 (51.2%, P = 0.0002), p-4E-BP-1 (P = 0.001), and ER (P = 0.0002) but not PR expression. Metabolomic profiling of serum indicated that responders versus nonresponders to treatment were more sensitive to metformin's effects on induction of lipolysis, which correlated with increased fatty acid oxidation and glycogen metabolism in matched tumors. In conclusion, metformin reduced tumor proliferation in a pre-operative window study in obese EC patients, with dramatic effects on inhibition of the mTOR pathway. Metformin induced a shift in lipid and glycogen metabolism that was more pronounced in the serum and tumors of responders versus nonresponders to treatment.This study provides support for therapeutic clinical trials of metformin in obese patients with EC

Obesity Is Associated With Worse Overall Survival in Women With Low-Grade Papillary Serous Epithelial Ovarian Cancer

OBJECTIVE: To evaluate prognostic risk factors for survival in women with low grade serous epithelial ovarian cancer (LGSC). METHODS: A multicenter retrospective analysis of patients with LGSC was conducted. Potential epidemiologic risk factors evaluated included obesity, age, parity, race, smoking, oral contraceptive pill and/or hormonal replacement therapy use, and previous hysterectomy or surgery on fallopian tubes and/or ovaries. Additional factors included stage, extent of debulking, residual disease, and disease status. RESULTS: Eighty-one patients were identified, and pathological diagnosis was independently confirmed. Median age of diagnosis was 56 years (range: 21 to 86). Thirty-four percent were obese, and 80% had optimally debulked disease. Forty-six percent were alive, 14% with disease; while 25% were dead of disease; 2% died of intercurrent disease; and 27% had an unknown status. In a univariate analysis, optimal surgical debulking was associated with improved PFS (p=0.01), DSS (p=0.03), and OS (p<0.001 and BMI with worse OS (p=0.05). On multivariate analysis, obesity (HR=2.8; 95% CI=1.05-7.3; p=0.04) and optimal tumor debulking (HR=0.05; 95% CI=0.008-0.29; p=0.001) were a significant predictor of OS. CONCLUSIONS: In a multivariate analysis, obesity and optimal tumor cytoreduction were significant predictors of OS. However, obesity was not associated with worse DSS, suggesting that mortality of obese patients with LGSC may result from other co-morbidities. Interventions addressing obesity may improve survival for women diagnosed with LGSC and further study is warranted to address the role of obesity in LGSC