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Impact of body fat distribution on neoadjuvant chemotherapy outcomes in advanced breast cancer patients.

ABSTRACT: Obesity is known to decrease the efficacy of neoadjuvant chemotherapy (NAC) against breast cancer; however, the relationship between actual body composition and NAC outcomes remains unknown. Therefore, we determined the effect of body composition on NAC outcomes. A total of 172 advanced breast cancer patients who underwent surgery after NAC were retrospectively analyzed. Body composition parameters including abdominal circumference (AC), subcutaneous fat area (SFA), visceral fat area (VFA), and skeletal muscle area (SMA) were calculated using computed tomography volume-analyzing software. VFA/SFA ratio was used to evaluate visceral obesity. The associations of body composition parameters with pathological complete remission (pCR) and survival were analyzed. AC, SFA, and VFA were significantly correlated with body mass index (BMI) (all P < 0.05; r = 0.82, r = 0.71, and r = 0.78, respectively). AC, SFA, and VFA increased significantly and SMA decreased significantly after menopause (all P < 0.05). VFA/SFA ratio increased significantly after menopause, even though BMI remained unchanged. Body composition parameters were not associated with pCR. Distant disease-free survival (DDFS) was significantly worse in the high VFA group than in the low VFA group (P < 0.05). Furthermore, in the high VFA group, postmenopausal patients had significantly shorter DDFS than premenopausal patients (P < 0.05). VFA was independently associated with DDFS in the multivariate analysis (P < 0.05). High visceral fat is associated with worse NAC outcomes in breast cancer patients, especially postmenopausal patients. Interventions targeting visceral fat accumulation will likely improve NAC outcomes.

SUBMITTER: Iwase T

PROVIDER: S-EPMC4708907 | biostudies-other | 2016 Jan

REPOSITORIES: biostudies-other

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Project description:The purpose of this study was to determine the association between body mass index (BMI) measurements (baseline BMI and changes in BMI during neoadjuvant systemic treatment [NST]) and clinical efficacy (pathologic complete response [pCR] rate and survival outcomes) in locally advanced breast cancer (LABC). We hypothesized that high baseline BMI and increases in BMI during NST are associated with lower pCR rates and poorer clinical outcomes in LABC. We retrospectively reviewed the medical records of 1002 patients, 204 with primary inflammatory breast cancer (IBC) and 798 with stage III non-IBC, who underwent standard NST and definitive surgery between November 1, 2006, and December 31, 2012. The median follow-up time for the survivors was 19.6 months (0.4 - 67.8 months). The pCR rates of patients whose BMI increased or decreased were 23.2% and 18.1%, respectively, (p=0.048). The unadjusted overall survival (OS) was significantly better in the group with increased BMI (p=0.006). However, increased BMI was not an independent predictor of pCR and clinical outcomes (recurrence-free survival and OS) after adjusting for other clinical variables. In subset analyses, increased BMI as a continuous variable was an independent predictor of higher pCR rates in the normal BMI/underweight group (odds ratio [OR]=1.35, 95% confidence interval [CI]: 1.06-0.71, p=0.015). Increased BMI (BMI change ≥0 vs. <0) was also an independent predictor of pCR (OR=1.65, 95% CI: 1.00-2.72, p=0.049) in the postmenopausal group. Our results show that increasing BMI shows improved clinical outcome in terms of better pCR rates in normal BMI/underweight group and in the postmenopausal group. These results contradict previously reported findings on the association between high BMI and poor clinical efficacy regarding pCR rate and survival outcomes in early-stage breast cancer. Thus, the role of BMI in breast cancer may depend on patients' clinical characteristics such as advanced stage.

Project description:BackgroundNeoadjuvant chemotherapy (NACT) treatment in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) can lead to considerable toxicity. Loss of skeletal muscle mass showed relevance with increased chemotherapy-related toxicity and poor survival in various cancer types, but its significance in NPC remains unclear. This study aimed to investigate the relationship between body composition parameters and the incidence of NACT toxicity in LA-NPC patients.MethodsNinety-six LA-NPC patients were retrospectively enrolled. All patients had pre-treatment abdominal computed tomography (CT) images to exclude distant metastasis. Lean body mass (LBM, kg) was estimated based on cross-sectional muscle area at the third lumbar vertebra (L3) level on CT, and skeletal muscle index (SMI, cm2/m2) was calculated. Doses of chemotherapeutics were normalized as dose/LBM (mg/kg). Grade 3-4 toxicity was defined as severe. The associations between body composition parameters and severe toxicities were assessed using univariate and multivariate logistic regression analyses. Optimal cutoff points were obtained with a receiver operating characteristic (ROC) curve.ResultsOf the 96 patients, 81.2% received the docetaxel + cisplatin (TP) regimen, and the rest received the gemcitabine + cisplatin (GP) regimen. Males had more LBM and a higher SMI at baseline, and females received a markedly higher dose of docetaxel and gemcitabine per kg LBM (P<0.001). With a cutoff value of 52.7 cm2/m2, patients with higher SMI showed lower risk of severe toxicity. For TP regimen group, those presented with grade 3-4 neutropenia had a higher dose per kg LBM. Univariate and multivariate analyses showed that the LBM-adjusted dose was significantly associated with severe neutropenia in the TP regimen group (P<0.001). The LBM-normalized docetaxel cutoff value of 2.64 mg/kg was a prominent predictor of ≥ grade 3 neutropenia (P=0.003), but a higher dose of docetaxel per kg LBM did not provide a better objective response rate.ConclusionsLA-NPC patients with lower SMI and higher dose of docetaxel per kg LBM are more likely to suffer from severe treatment-related toxicity. Higher docetaxel dose per kg LBM is a prominent predictor for severe neutropenia, but not for NACT response. LBM showed good potential in toxicity risk prediction and dose determination.

Project description:BackgroundThere is no agreed upon standard of care for borderline-resectable pancreatic cancer (BRPC) or locally-advanced pancreatic cancer (LAPC) patients regarding the benefit of chemotherapy or radiation alone or in combination.Patients and methodsWe completed a retrospective cohort analysis of BRPC and LAPC patients at a cancer center with expertise in multi-disciplinary pancreatic ductal adenocarcinoma (PDAC) treatment over a 5-year period from 03/01/2014 to 03/01/2019 (cut-off date). The total evaluable newly diagnosed, treatment naïve, BRPC, and LAPC patients with adequate organ function and ability to obtain treatment after multidisciplinary review was 52 patients. After analysis, patients were evaluated for rates of resection, extent of resection (R0 or R1), median progression-free survival (mPFS), and median overall survival (mOS).ResultsPatients were treated with chemotherapy alone (gemcitabine and nab-paclitaxel = 77% (20/26); FOLFIRINOX = 19% (5/26); single agent gemcitabine 3.8% (1/26)), or chemotherapy followed by chemoradiation (gemcitabine +5 Gy × 5 weeks), or chemoradiation alone prior to re-staging and potential resection. Of the 29% (15/52) of patients who went on to surgical resection, 73% (11/15) achieved R0 resection. An R0 resection was achieved in 35% (9/26) of patients treated with chemotherapy alone, 7.6% (1/13) in a patient treated with chemotherapy followed by radiation, and 7.6% (1/13) with concurrent chemoradiotherapy alone. Chemotherapy alone achieved a mPFS of 16.4 months (p < 0.0025) and mOS of 26.2 months (p < 0.0001), chemotherapy followed by chemoradiation was 13.0 months and 14.9 months respectively, while concurrent chemoradiotherapy was 6.9 months and 7.3 months.Conclusions and relevanceBRPC and LAPC patients capable of surgery after only receiving neoadjuvant treatment with chemotherapy had higher rates of R0 resection with prolonged median PFS and OS compared with any patient needing combination chemotherapy with radiotherapy.

Project description:BackgroundResidual microcalcifications after neoadjuvant chemotherapy (NAC) are challenging for deciding extent of surgery and questionable for impact on prognosis. We investigated changes in the extent and patterns of microcalcifications before and after NAC and correlated them with pathologic response. We also compared prognosis of patients depending on presence of residual microcalcifications after NAC.MethodsA total of 323 patients with invasive breast carcinoma treated with neoadjuvant chemotherapy at Kangbuk Samsung Hospital and Samsung Medical center from March 2015 to September 2018 were included. Patients were divided into four groups according to pathologic response and residual microcalcifications. Non-pCRw/mic group was defined as breast non-pCR with residual microcalcifications. Non-pCRw/o mic group was breast non-pCR without residual microcalcifications. pCRw/mic group was breast pCR with residual microcalcifications. pCRw/o mic group was breast pCR without residual microcalcifications. The first aim of this study is to investigate changes in the extent and patterns of microcalcifications before and after NAC and to correlate them with pathologic response. The second aim is to evaluate oncologic outcomes of residual microcalcifications according to pathologic response after NAC.ResultsThere were no statistical differences in the extent, morphology, and distribution of microcalcifications according to pathologic response and subtype after NAC (all p > 0.05). With a median follow-up time of 71 months, compared to pCRw/o mic group, the hazard ratios (95% confidence intervals) for regional recurrence were 5.190 (1.160-23.190) in non-pCRw/mic group and 5.970 (1.840-19.380) in non-pCRw/o mic group. Compared to pCRw/o mic group, the hazard ratios (95% CI) for distant metastasis were 8.520 (2.130-34.090) in non-pCRw/mic group, 9.120 (2.850-29.200) in non-pCRw/o mic group. Compared to pCRw/o mic, the hazard ratio (95% CI) for distant metastasis in pCRw/mic group was 2.240 (0.230-21.500) without statistical significance (p = 0.486).ConclusionsRegardless of residual microcalcifications, patients who achieved pCR showed favorable long term outcome compared to non-pCR group.

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Impact of body fat distribution on neoadjuvant chemotherapy outcomes in advanced breast cancer patients.

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