Significance of sarcopenia as a prognostic factor for metastatic urothelial carcinoma patients treated with systemic chemotherapy

Abstract

Background

Recently, numerous studies have reported an association between sarcopenia and poor outcomes in various kinds of malignancies. We investigated whether sarcopenia predicts the survival of patients with metastatic urothelial carcinoma who underwent systemic chemotherapy.

Methods

We reviewed 87 metastatic urothelial carcinoma patients who underwent chemotherapy (gemcitabine plus cisplatin or gemcitabine plus carboplatin for cisplatin-unfit patients) between 2007 and 2015. A computed tomography scan prior to chemotherapy was used for evaluating sarcopenia, and we measured three cross-sectional areas of skeletal muscle at the third lumbar vertebra and calculated the skeletal muscle index (SMI), the paraspinal muscle index (PSMI), and the total psoas area (TPA) of each patient. Predictive values of survival were assessed using Cox regression analysis.

Results

The median overall survival (OS) was 16 months (95% CI 13.5–18). Although SMI alone was not a significant predictor of shorter OS (P = 0.117) in univariate analysis, SMI stratified by the value of the body mass index (BMI) was a significant predictor of shorter OS in univariate analysis (P = 0.037) and was also an independent predictor of shorter OS in multivariate analysis (P = 0.026). PSMI and TPA were not significant prognostic factors even when stratified by BMI (P = 0.294 and 0.448), respectively.

Conclusion

Neither PSMI nor TPA could substitute SMI as a predictor for poor outcomes in metastatic urothelial carcinoma patients treated with systemic chemotherapy in our study. SMI stratified by BMI is a useful predictor of prognosis in these patients.

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The detection of sentinel lymph nodes in laparoscopic surgery can eliminate systemic lymphadenectomy for patients with early stage endometrial cancer

Abstract

Background

The examination of a sentinel lymph node (SLN), where lymph node metastasis first occurs, may be advocated as an alternative staging technique. The aim of this study was to evaluate the feasibility and detection rates of an SLN biopsy in patients with endometrial cancer.

Study design

Two hundred and eleven patients with endometrial cancer underwent an SLN biopsy at hysterectomy using three kinds of tracers including 99m-technetium-labeled tin colloid (^99mTc), indigo carmine and indocyanine green. Factors related to the side-specific detection rate, sensitivity and false negative rate were analyzed.

Results

The detection rates of the SLN biopsy using ^99mTc, indigo carmine and indocyanine green were 77.9, 17.0 and 73.4%, respectively. The detection rate was lower in elderly patients (≥60 years) (67.9 vs 89.2%, p < 0.01), patients with >50% myometrial invasion (68.3 vs 85.2%, p < 0.01), patients with high-grade tumors (69.5 vs 84.9%, p < 0.01) and patients who underwent laparotomy (71.2 vs 84.9%, p < 0.01). There were no significant differences in body mass index. The sensitivity was not significantly different in any factor. However, the false negative rate was higher in patients with > 50% myometrial invasion (11.5 vs 1.2%, p < 0.01), high-grade tumors (13.3 vs 0.8%, p < 0.01) and who underwent laparotomy (12.2 vs 0.4%, p < 0.01).

Conclusion

Patients who underwent laparoscopy with < 50% myometrial invasion and low-grade tumors not only have higher detection rates, but also have lower false negative rates. These patients may avoid systemic lymphadenectomy according to the status of the SLN biopsy.

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Randomized Phase III Trial of Low Molecular Weight Heparin Enoxaparin in Addition to Standard Treatment in Small Cell Lung Cancer: the RASTEN Trial

Abstract

Background

Coagulation activation and venous thromboembolism (VTE) are hallmarks of malignant disease and represent a major cause of morbidity and mortality in cancer. Coagulation inhibition with low molecular weight heparin (LMWH) may improve survival specifically in small cell lung cancer (SCLC) patients by preventing VTE and tumor progression; however, randomized trials with well-defined patient populations are needed to obtain conclusive data. The aim of RASTEN was to investigate the survival effect of LMWH enoxaparin in a homogenous population of SCLC patients.

Patients and Methods

We performed a randomized, multicenter, open-label trial to investigate the addition of enoxaparin at a supraprophylactic dose (1 mg/kg) to standard treatment in patients with newly diagnosed SCLC. The primary outcome was overall survival (OS), and secondary outcomes were progression-free survival (PFS), incidence of VTE and hemorrhagic events.

Results

In RASTEN, 390 patients were randomized over an 8-year period (2008-2016), of which 186 and 191 were included in the final analysis in the LMWH and control arm, respectively. We found no evidence of a difference in OS or PFS by the addition of enoxaparin (HR 1.11; 95% CI: 0.89-1.38, P=0.36 and HR 1.18; 95% CI: 0.95-1.46, P=0.14, respectively). Subgroup analysis of patients with limited and extensive disease did not show reduced mortality by enoxaparin. The incidence of VTE was significantly reduced in the LMWH arm (HR 0.31; 95% CI: 0.11-0.84, P=0.02). Hemorrhagic events were more frequent in the LMWH-treated group but fatal bleedings occurred in both arms.

Conclusion

LMWH enoxaparin in addition to standard therapy did not improve OS in SCLC patients, despite being administered at a supraprophylactic dose and despite resulting in a significant reduction in VTE incidence. Addition of LMWH cannot be generally recommended in the management of SCLC patients, and predictive biomarkers of VTE and LMWH-associated bleeding in cancer patients are warranted.ClinicalTrials.gov: NCT00717938

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Programmed death-1 inhibition and atherosclerosis: can nivolumab vanish complicated atheromatous plaques?

anti-programmed death 1 inhibitionatherosclerosiscomplicated plaquesnivolumab

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Medical Oncologists’ Perception of Anti-Estrogen Therapy Benefit in Premenopausal Women with Hormone Receptor-Positive Early Breast Cancer

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Novel tools to assist neoepitope targeting in personalized cancer immunotherapy

Abstract

Current cancer immunotherapy approaches utilize the remarkable surveillance capacity of the human immune system, which is capable of recognizing and eliminating cancer cells based on identification of tumor-associated antigens arising as a consequence of the transformation process. Among these, mutational-derived neoepitopes have proved to be powerful targets for tumor elimination and mutational load has been shown to correlate with the clinical response to treatment with checkpoint inhibitors in many different tumor types. This suggests a crucial role for neoepitope recognition in T-cell-mediated tumor eradication. Consequently, strategies to further boost neoepitope recognition, through vaccination or adoptive cell transfer, has received substantial interest. Although such strategies have enormous potential, there are also considerable challenges associated with these approaches. In the present review, we will focus on how novel technological developments can facilitate and improve feasibility and efficacy in neoepitope targeting.

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Thirty-five years of single surgeon experience in the reconstruction of esophagus and voice with free ileocolon flap following total pharyngolaryngectomy

Background

Several surgical options exist for the reconstruction of total pharyngolaryngectomy defect. The purpose of this report is to present our experience with ileocolon flap for simultaneous reconstruction of both esophagus and voice.

Methods

Demographic data, clinical information, and outcomes of 205 patients who underwent the ileocolon flap procedure over the last 35 years were examined. Preoperative evaluation, intraoperative details, and postoperative management were analyzed. The types of additional procedures performed to improve outcomes were explored.

Results

Of the 205 patients, 191 had a free ileocolon flap and the remaining 14 a pedicled flap. Ninety-seven percent of the flaps were successful with a fistula rate of 5.4%. Seven patients required reexploration and six flaps failed. Seventy-eight percent of the patients reported their swallowing function to be very good to excellent. Speech function was rated as good in 64% of patients and moderate in 21%. Three patients develop bowel obstruction, two of which required enterolysis. Five patients had postoperative diarrhea that responded to conservative measures.

Conclusion

Reconstruction of pharyngoesophageal defects with ileocolon flap permits resumption of swallowing and production of speech without the need for voice prosthesis and with minimal complications.

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