Impact of being underweight on the long-term outcomes of patients with gastric cancer

Background

The aim of this study was to investigate the impact of being underweight on the long-term outcomes of gastric cancer patients.

Methods

This study reviewed the medical records of 638 patients with gastric cancer who underwent gastrectomy between January 2003 and December 2011. The patients were divided into three groups according to the WHO classification: underweight (BMI <18.5 kg/m²), normal weight (BMI ≥18.5 and <25 kg/m²), and overweight (BMI ≥25 kg/m²). A multivariate analysis was performed to identify prognostic factors.

Results

The mean BMI immediately before surgery was 22.5 kg/m² (standard deviation, 3.3 kg/m²). According to the BMI subgroup, 73 patients (11.4 %) were underweight, 431 patients (67.6 %) were of normal weight, and 134 patients (21 %) were overweight. The 5-year overall survival (OS) rate was 66.6 % in the underweight patients, 81.3 % in the normal weight patients, and 79.9 % in the overweight patients (P = 0.001). The OS rate was significantly lower in the underweight patients than in the normal weight and overweight patients among those with stage I disease, and it was also lower than in the normal weight patients among those with stage II and III disease. In the multivariate analysis, being underweight was found to be an independent predictor of OS, but it was not an independent predictor among patients with stage II and III disease.

Conclusions

Being underweight is a simple and reliable predictor of a worse long-term outcome among gastric cancer patients. Being underweight is considered to be associated with a higher risk of non-cancer death.

     

Obesity and mortality after locoregional breast cancer diagnosis

Purpose

Higher mortality after a breast cancer diagnosis has been observed among women who are obese. We investigated the relationships between body mass index (BMI) and all-cause or breast cancer-specific mortality after a diagnosis of locoregional breast cancer.

Methods

Women diagnosed in 2004 with AJCC Stage I, II, or III breast cancer (n?=?5394) were identified from a population-based National Program of Cancer Registries (NPCR) patterns of care study (POC-BP) drawing from registries in seven U.S. states. Differences in overall and breast cancer-specific mortality were investigated using Cox proportional hazards regression models adjusting for demographic and clinical covariates, including age- and stage-based subgroup analyses.

Results

In women 70 or older, higher BMI was associated with lower overall mortality (HR for a 5 kg/m² difference in BMI?=?0.85, 95% CI 0.75–0.95). There was no significant association between BMI and overall mortality for women under 70. BMI was not associated with breast cancer death in the full sample, but among women with Stage I disease; those in the highest BMI category had significantly higher breast cancer mortality (HR for BMI?≥?35 kg/m² vs. 18.5–24.9 kg/m²?=?4.74, 95% CI 1.78–12.59).

Conclusions

Contrary to our hypothesis, greater BMI was not associated with higher overall mortality. Among older women, BMI was inversely related to overall mortality, with a null association among younger women. Higher BMI was associated with breast cancer mortality among women with Stage I disease, but not among women with more advanced disease.

     

Radiation-related toxicities and outcomes in endometrial cancer: are obese women at a disadvantage?

Objective

To assess the impact of body mass index (BMI) on radiotherapy toxicities in endometrial cancer patients.

Methods

This was a retrospective cohort study of women diagnosed with endometrial cancer between January 2006 and December 2014 at the Royal Cornwall Hospital Trust. Women who received radiotherapy as part of their treatment, including external beam radiotherapy (EBRT) and/or vaginal brachytherapy were included. Radiation-related toxicities were graded according to the Radiation Therapy Oncology Group (RTOG) guidelines. Toxicity outcomes were compared across BMI groups—non-obese (BMI <30 kg/m²) and obese (BMI ≥30 kg/m²)—according to radiotherapy treatment received (EBRT, brachytherapy or a combination).

Results

Of a total of 159 women who received radiotherapy, 110 were eligible for inclusion in the study. Sixty-three women had a BMI <30 kg/m² and 47 women were obese. Obese women had poorer Eastern Cooperative Oncology Group performance status (P = 0.021) and more comorbidities (P < 0.001) compared to the non-obese group. Total (any) toxicity rates were 60.3, 72.7 and 52.0% for EBRT and brachytherapy (N = 63), single-mode EBRT (N = 22) and brachytherapy (N = 25), respectively. BMI was not associated with the incidence of acute and late radiation toxicities in the different radiotherapy groups, and there were no differences in individual complications between the BMI groups.

Conclusion

When comparing obese to non-obese women, obesity does not negatively impact the incidence of radiation toxicities in endometrial cancer. However, toxicities remain an important challenge as they are common and negatively influence the quality of life (QoL) of survivors. Future studies need to further explore the role of BMI and possible interventions to improve toxicities and QoL.

     

Does obesity modify the relationship between physical activity and breast cancer risk?

Purpose

With only 5–10% of breast cancer cases attributed to genetic inheritance, prevention efforts have focused on modifiable risk factors. Physical activity plays a role in reducing breast cancer risk; however, the interaction between physical activity and other modifiable risk factors, such as obesity, has received little attention.

Methods

A systematic review and meta-analysis was conducted of studies examining the relationship between physical activity and breast cancer and how it may be modified by body mass index (BMI).

Results

A total of 29 papers were included: 18 were cohort and 11 were case–control studies. Overall, a significant reduction in the relative risk of breast cancer was found in postmenopausal women with high versus low levels of physical activity for women with a BMI <25 kg/m² (RR 0.85, 95% CI 0.79, 0.92) and ≥25 kg/m² (RR 0.87, 95% CI 0.81, 0.93) but not ≥30 kg/m² (RR: 0.93, 95% CI 0.76, 1.13). Physical activity was not associated with a significant reduction in risk of breast cancer in premenopausal women in any BMI group.

Conclusion

The results of this meta-analysis suggest that physical activity is associated with a larger breast cancer risk reduction among women who are normal weight or overweight than among women who are obese. Since the included studies used diverse methods for assessment of physical activity and categories of BMI, results should be interpreted with caution and additional work is needed.

     

Multicenter randomized phase II clinical trial of oxaliplatin reintroduction as a third- or later-line therapy for metastatic colorectal cancer—biweekly versus standard triweekly XELOX (The ORION Study)

Background

The aim of this multicenter, open-label, randomized phase II trial was to evaluate the efficacy of a dose-dense capecitabine and oxaliplatin (XELOX) regimen in patients with metastatic colorectal cancer (mCRC) for whom reintroduction of oxaliplatin had been planned as a third- or later-line regimen.

Methods

The patients with mCRC who had received prior chemotherapy including oxaliplatin and were scheduled for reintroduction of oxaliplatin were randomized to capecitabine (1,000 mg/m²) twice daily on days 1–14 and oxaliplatin (130 mg/m²) on day 1 every 21 days (Q3W group) or capecitabine (2,000 mg/m²) twice daily on days 1–7 and oxaliplatin (85 mg/m²) on day 1 every 14 days (Q2W group). The primary endpoint was the time-to-treatment failure (TTF). Other endpoints included overall survival (OS), progression-free survival (PFS) and other adverse events (AEs).

Results

A total of 46 patients were enrolled in the trial—22 patients were randomly assigned to the Q3W group and 23 to the Q2W group. The median TTF was 3.4 months in both groups (hazard ratio [HR] 1.053; p = 0.880). The median PFS and OS were 3.3 and 9.2 months in the Q2W group and 4.3 and 12.1 months in the Q3W group, respectively (HR 1.15; p = 0.153 and 0.672; p = 0.836). The most common grade 3?4 AEs in the Q3W and Q2W groups were fatigue (27.3 vs 21.7), neuropathy (9.1 vs 0 %) and diarrhea (9.1 vs 0 %), respectively.

Conclusion

There was no significant inter-group difference in any of the efficacy and safety endpoints, including TTF, OS, RFS and AEs. The results of this clinical trial were convincingly negative.

     

A survival analysis using physique-adjusted tumor size of non-small cell lung cancer

Background

Differences in individual body sizes have not been well considered when analyzing the survival of patients with non-small cell lung cancer (NSCLC). We hypothesized that physique-adjusted tumor size is superior to actual tumor size in predicting the prognosis.

Methods

Eight hundred and forty-two patients who underwent R0 resection of NSCLC between 2005 and 2012 were retrospectively reviewed, and overall survival (OS) was evaluated. The physique-adjusted tumor size was defined as: x-adjusted tumor size = tumor size × mean value of x/individual value of x [x = height, weight, body surface area (BSA), or body mass index (BMI)]. Tumor size category was defined as ≤2, 2–3, 3–5, 5–7, and >7 cm. The separation index (SEP), which is the weighted mean of the absolute value of estimated regression coefficients over the subgroups with respect to a reference group, was used to measure the separation of subgroups.

Results

The mean values of height, weight, BSA, and BMI were 160.7 cm, 57.6 kg, 1.59 m², and 22.2 kg/m², respectively. The 5-year survival rates ranged from 88?59% in the non-adjusted tumor size model (SEP 1.937), from 90?57% in the height-adjusted model (SEP 2.236), from 91?52% in the weight-adjusted model (SEP 2.146), from 90?56% in the BSA-adjusted model (SEP 2.077), and from 91?51% in the BMI-adjusted model (SEP 2.169).

Conclusions

The physique-adjusted tumor size can separate the survival better than the actual tumor size.

     

Height,waist circumference,body mass index,and body somatotype across the life course and risk of glioma

Purpose

Recent studies have suggested height as a risk factor for glioma, but less is known regarding body mass index (BMI) or other anthropomorphic measures. We evaluated the association between body habitus and risk of glioma.

Methods

We evaluated the association of measures of height, BMI, waist circumference, and somatotypes with risk of glioma in two prospective cohorts, the Nurses’ Health Study and the Health Professionals Follow-Up Study.

Results

We documented 508 incident cases of glioma (321 glioblastoma [GBM]). In both cohorts, we found no significant association between adult BMI or waist circumference and risk of glioma, with pooled HR for BMI of 1.08 (95% CI 0.85–1.38 comparing?≥?30 to <?25 kg/m²) and for waist circumference of 1.05 (95% CI 0.80–1.37 highest vs. lowest quintile). Higher young adult BMI (at age 18 in NHS and 21 in HPFS) was associated with modestly increased risk of glioma in the pooled cohorts (pooled HR 1.35, 95% CI 1.06–1.72 comparing?≥?25 kg/m² vs. less; HR 1.34 for women and 1.37 for men). Analysis of body somatotypes suggested reduced risk of glioma among women with heavier body types at all ages this measure was assessed (HRs ranging from 0.52 to 0.65 comparing highest tertile to lowest tertile), but no significant association among men. Height was associated with increased risk of glioma among women (HR?1.09, 95% CI 1.04–1.14 per inch), but not significantly among men. Within the 8 years prior to diagnosis, cases had no material weight loss compared to non-cases. All results were similar when limited to GBM.

Conclusion

Adult BMI and waist circumference were not associated with glioma. Higher BMI at age 21 for men and at age 18 for women was modestly associated with risk in the pooled cohort. Based on body somatotypes, however, women with heavier body types during childhood and young adulthood may be at lower risk of glioma, although this association was not observed later in life with measurements of BMI. Greater height was associated with increased risk, and the trend was more pronounced in women.

     

Omega-3 fatty acid use for obese breast cancer patients with aromatase inhibitor-related arthralgia (SWOG S0927)

Purpose

Although aromatase inhibitors (AIs) prolong survival in post-menopausal breast cancer (BC) patients, AI-associated arthralgia can lead to discontinuation. Obese patients have higher rates of AI arthralgia than non-obese patients, but treatment options are limited. Omega-3 fatty acid (O3-FA) treatment for AI arthralgia has produced mixed results.

Methods

We performed an exploratory analysis of SWOG S0927, a multicenter randomized placebo-controlled trial of O3-FA use for AI arthralgia. Post-menopausal women with stage I–III BC taking an AI were randomized to 24 weeks of O3-FAs or placebo. Brief Pain Inventory (BPI) questionnaires and fasting serum were collected at baseline, 12, and 24 weeks. The BPI assessment included worst pain, average pain, and pain interference scores (range 0–10).

Results

Among the 249 participants, 139 had BMI?<?30 kg/m² (56%) and 110 had BMI?≥?30 kg/m² (44%). Among obese patients, O3-FA use was associated with significantly lower BPI worst pain scores at 24 weeks compared with placebo (4.36 vs. 5.70, p?=?0.02), whereas among non-obese patients, there was no significant difference in scores between treatment arms (5.27 vs. 4.58, p?=?0.28; interaction p?=?0.05). Similarly, O3-FA use was associated with lower BPI average pain and pain interference scores at 24 weeks compared with placebo among obese patients, but no significant difference between treatment arms in non-obese patients (interaction p?=?0.005 and p?=?0.01, respectively).

Conclusions

In obese BC patients, O3-FA use was associated with significantly reduced AI arthralgia compared to placebo.

     

The efficacy of lymphaticovenular anastomosis in breast cancer-related lymphedema

Background

U.S. Hispanic women have high rates of parity, breastfeeding, and obesity. It is unclear whether these reproductive factors are associated with breast cancer (BC) mortality. We examined the associations between breastfeeding, parity, adiposity and BC-specific and overall mortality in Hispanic and non-Hispanic white (NHW) BC cases.

Methods

The study population included 2921 parous women (1477 Hispanics, 1444 NHWs) from the Breast Cancer Health Disparities Study with invasive BC diagnosed between 1995 and 2004. Information on reproductive history and lifestyle factors was collected by in-person interview. Overall and stratified Cox proportional hazard regression models by ethnicity, parity, and body mass index (BMI) at age 30 years were used to calculate hazard ratios (HR) and 95% confidence intervals (CI).

Results

After a median follow-up time of 11.2 years, a total of 679 deaths occurred. Pre-diagnostic breastfeeding was associated with a 16% reduction in mortality (HR 0.84; 95% 0.72–0.99) irrespective of ethnicity. Parity significantly modified the association between breastfeeding duration and mortality (p interaction = 0.05), with longer breastfeeding duration associated with lower risk among women who had ≤2 births (p trend = 0.02). Breastfeeding duration was associated with reduced risk of both BC-specific and overall mortality among women with BMI <25 kg/m², while positive associations were observed among women with BMI ≥25 kg/m² (p interactions <0.01).

Conclusion

Pre-diagnostic breastfeeding was inversely associated with risk of mortality after BC, particularly in women of low parity or normal BMI. These results provide another reason to encourage breastfeeding and weight management among young women.

     

Investigating the prostate specific antigen,body mass index and age relationship: is an age–BMI-adjusted PSA model clinically useful?

Purpose

Previous studies indicate a possible inverse relationship between prostate-specific antigen (PSA) and body mass index (BMI), and a positive relationship between PSA and age. We investigated the associations between age, BMI, PSA, and screen-detected prostate cancer to determine whether an age–BMI-adjusted PSA model would be clinically useful for detecting prostate cancer.

Methods

Cross-sectional analysis nested within the UK ProtecT trial of treatments for localized cancer. Of 18,238 men aged 50–69 years, 9,457 men without screen-detected prostate cancer (controls) and 1,836 men with prostate cancer (cases) met inclusion criteria: no history of prostate cancer or diabetes; PSA < 10 ng/ml; BMI between 15 and 50 kg/m². Multivariable linear regression models were used to investigate the relationship between log-PSA, age, and BMI in all men, controlling for prostate cancer status.

Results

In the 11,293 included men, the median PSA was 1.2 ng/ml (IQR: 0.7–2.6); mean age 61.7 years (SD 4.9); and mean BMI 26.8 kg/m² (SD 3.7). There were a 5.1% decrease in PSA per 5 kg/m² increase in BMI (95% CI 3.4–6.8) and a 13.6% increase in PSA per 5-year increase in age (95% CI 12.0–15.1). Interaction tests showed no evidence for different associations between age, BMI, and PSA in men above and below 3.0 ng/ml (all p for interaction >0.2). The age–BMI-adjusted PSA model performed as well as an age-adjusted model based on National Institute for Health and Care Excellence (NICE) guidelines at detecting prostate cancer.

Conclusions

Age and BMI were associated with small changes in PSA. An age–BMI-adjusted PSA model is no more clinically useful for detecting prostate cancer than current NICE guidelines. Future studies looking at the effect of different variables on PSA, independent of their effect on prostate cancer, may improve the discrimination of PSA for prostate cancer.

     

The effect of dose escalation for large squamous cell carcinomas of the anal canal

Purpose

Chemoradiation allows for organ preservation in patients with anal cancer, but patients with large tumors (>?5 cm) have elevated rates of locoregional recurrence. With conformal radiation techniques, there is interest in dose escalation to decrease local recurrence in patients with large tumor size.

Methods/patients

The National Cancer Database (NCDB) was used to identify patients with anal cancer from 2004 to 2013 with tumors?>?5 cm. Adult patients who received definitive chemoradiation were included. Patients with prior resection were excluded. High dose was defined as greater than or equal to 5940 cGy. Statistical analyses were performed using logistic regression, Kaplan–Meier, and Cox proportional hazards for overall survival (OS).

Results

In total, 1349 patients were analyzed with 412 (30.5%) receiving high-dose radiation therapy (RT). 5-year OS was 58 and 60% for high and standard dose RT, respectively (p?=?0.9887). On univariate analysis, high-dose RT was not associated with improved OS (HR?=?0.998, CI 0.805–1.239, p?=?0.9887). On multivariate analysis, high-dose RT (HR?=?0.948, CI 0.757–1.187, p?=?0.6420) was not associated with improved OS but older age (HR?=?1.535, CI 1.233–1.911, p?=?0.0001), male sex (HR?=?1.695, CI 1.382–2.080, p?<?0.0001), comorbidities (HR?=?1.389, CI 1.097–1.759, p?=?0.0064), and long RT (HR?=?1.299, CI 1.047–1.611, p?=?0.0173) were significantly associated with decreased OS.

Conclusions

There was no observed difference in OS for dose escalation of anal cancers?>?5 cm in this population-based analysis. Differences in local control and salvage therapy cannot be assessed through the NCDB. Whether dose escalation of large tumors may improve local control and colostomy-free survival remains an important question and is the subject of ongoing trials.

     

Concurrent chemoradiation for locally advanced stage III non-small cell lung cancer with cisplatin,vinorelbine, and thoracic radiotherapy: a phase II study from the Galician Lung Cancer Group

Purpose

The aim of this phase II study was to evaluate the activity and safety of the combination of cisplatin and vinorelbine with thoracic radiotherapy in unresectable locally advanced stage III non-small cell lung cancer (NSCLC). The primary endpoint was the objective response rate (ORR). Secondary objectives included toxicity profile, progression-free survival (PFS), and overall survival (OS).

Materials and methods

A total of 48 NSCLC patients were enrolled (median age 60 years, 52% stage IIIA and 48% stage IIIB, 52% adenocarcinoma). Patients received three cycles of chemotherapy every 21 days [intravenous cisplatin 80 mg/m² and intravenous vinorelbine 25 mg/m² on day 1 and oral vinorelbine on day 8 (60 mg/m²)] concurrent with radiotherapy (66 Gy, administered at 1.8 Gy per day, five consecutive days per week).

Results

ORR was 79.2% (72.9% showing partial response and 6.3% showing complete response). With a median follow-up of 20.7 months, median PFS was 12 months and median OS was 36 months. Grade 3/4 toxicities were: neutropenia (14.5%), anaemia (6.2%), vomiting (2%), and oesophagitis (4.2%). No toxic deaths were reported.

Conclusion

This combined regimen shows efficacy and a manageable safety profile. PFS and OS outcomes are encouraging and warrant further research.

     

Ramucirumab as Second-Line Therapy in Metastatic Gastric Cancer: Real-World Data from the RAMoss Study

Background

Ramucirumab—alone or combined with paclitaxel—represents one of the main options for patients failing first-line treatment for advanced gastric cancer.

Objective

The RAMoss study aimed to evaluate the safety and efficacy profile of ramucirumab in the “real-life setting”.

Patients and Methods

Patients from 25 Italian hospitals started therapy consisting of ramucirumab 8 mg/kg i.v. d1,15q28 with or without paclitaxel 80 mg/m² i.v. d1,8,15q28. The primary endpoint was safety, and secondary endpoints were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Results

One hundred sixty-seven patients with disease progression on first-line therapy received ramucirumab as monotherapy (10%) or combined with paclitaxel (90%). Median treatment duration was 4 months (1–17 months). Global incidence of grade (G) 3–4 toxicity was 9.6%, and for neutropenia 5.4%; treatment was discontinued due to toxicity in 3% of patients. The most frequent adverse events (AE) were G1–2 fatigue (27.5%), G1–2 neuropathy (26.3%), and G1–2 neutropenia (14.9%). ORR was 20.2%. Stable disease was observed in 39.2% of patients, with a disease control rate of 59.4%. With a median follow-up of 11 months, median PFS was 4.3 months (95% confidence interval [CI] 4.1–4.7), whereas median OS was 8.0 months (95% CI: 7.09–8.9). In a multivariate analysis, ECOG performance status <1 or ≥1 (HR 1.13, 95% CI 1.0–1.27, p?=?0.04) and the presence versus absence of peritoneal metastases (HR 1.57, 95% CI 1.63–2.39, p?=?0.03) were independent poor prognostic factors.

Conclusions

These “real-life” efficacy data on ramucirumab treatment are in line with previous randomized trials. Ramucirumab is well tolerated in daily clinical practice.

     

Screening status,tumour subtype,and breast cancer survival: a national population-based analysis

Purpose

Nearly half of the 3.5 million female breast cancer survivors in the US are aged 65 years or older at diagnosis, yet little is known about associations of obesity and physical activity with breast cancer-specific mortality (BCSM) among older survivors.

Methods

Between 1992 and 2013, 5254 women in the Cancer Prevention Study-II Nutrition Cohort were diagnosed with local or regional breast cancer among whom 1771 deaths (505 breast cancer deaths) occurred. Multivariable Cox proportional hazards regression models were used to examine associations of pre- and post-diagnosis body mass index (BMI) and moderate–vigorous physical activity (MET-hours/week) with mortality outcomes stratified by age at diagnosis (<65, ≥65 years).

Results

Among women ≥65 years of age at diagnosis (n = 4226), pre- and post-diagnosis BMI (per 5 kg/m²) were associated with a higher risk of BCSM (pre-diagnosis, HR 1.27, 95% CI 1.14–1.41; post-diagnosis, HR 1.19, 95% CI 1.04, 1.36); neither pre- nor post-diagnosis physical activity was associated with BCSM. Among women <65 years of age at diagnosis (n = 1028), BMI at both time points were not significantly associated with BCSM; however, there was a significant inverse trend of post-diagnosis physical activity with BCSM (P-trend = 0.01). Among both age groups, BMI and physical activity, regardless of when assessed, were significantly associated with all-cause mortality.

Conclusions

Higher BMI, pre- or post-diagnosis, was associated with a higher risk of BCSM in older patients, independent of comorbidities and stage at diagnosis. Weight management should be discussed even with women aged 65 years or older to lower rates of BCSM.

     

The impact of body mass index on oncological outcomes in colorectal cancer patients with curative intent

Background

Excess body weight is associated with a risk of several malignancies, including colon cancer. However, the oncological significance of evaluating body mass index (BMI) preoperatively in colorectal cancer (CRC) patients undergoing curative surgery has not been fully evaluated.

Methods

Clinicopathological findings including BMI and laboratory data [carcinoembryonic antigen (CEA) and neutrophil/lymphocyte ratio (NLR)] from 358 curative CRC patients (open surgery group: n = 157; laparoscopic surgery group: n = 201) were assessed as indicators of survival outcome. BMI <20 was defined as underweight in both groups.

Results

Not all categories of pathological findings were associated with BMI in both groups. Patients with BMI <20 showed significant poorer overall survival (OS) in the open surgery group. In addition, patients with BMI <20 in the laparoscopic surgery group were also significantly worse in OS and disease-free survival (DFS). Furthermore, multivariate analysis demonstrated that BMI was validated as independent predictors for OS and DFS in both groups. BMI had a significant negative correlation with NLR, which reflects host immune response in both groups.

Conclusions

Lower BMI is a promising predictor of recurrence and prognosis in curative CRC patients.

     

Whither surgical quality assurance of breast cancer surgery (surgical margins and local recurrence) after paterson

Purpose

The randomized phase III JO21095 trial compared the efficacy and safety of low-dose capecitabine plus docetaxel combination therapy (XT) versus single-agent administration of docetaxel in anthracycline-pretreated HER2-negative metastatic breast cancer.

Methods

Patients were randomized to either low-dose XT (capecitabine 825 mg/m² twice daily, days 1–14; docetaxel 60 mg/m², day 1 every 3 weeks) or docetaxel (70 mg/m², day 1 every 3 weeks). The primary objective was to demonstrate superior progression-free survival (PFS) with low-dose XT versus single-agent docetaxel. Overall survival (OS) and safety were secondary endpoints.

Results

In total, 162 patients were treated. Median PFS was 10.5 months with low-dose XT and 9.8 months with single-agent docetaxel (hazard ratio [HR] 0.62 [95% confidence interval (CI) 0.40–0.97]; p = 0.03). The OS HR was 0.89 (95% CI 0.52–1.53; p = 0.68). Grade ≥3 treatment-related toxicities occurred in 74% of XT-treated patients and 76% of docetaxel-treated patients. The main differences in grade ≥3 treatment-related toxicities were hand-foot syndrome (7.3% of XT-treated patients vs 0% receiving docetaxel), fatigue/malaise (2.4 vs 10.0%), and peripheral edema (1.2 vs 7.5%). Dose modifications were required in 100% of low-dose XT and 49% of docetaxel patients. Toxicity-related treatment discontinuations occurred in 18 and 33%, respectively.

Conclusion

The improved PFS with low-dose XT versus docetaxel alone is consistent with higher-dose XT phase III experience, but the safety profile was more favorable and manageable.

     

The impact of obesity on outcomes for patients undergoing mastectomy using the ACS-NSQIP data set

Purpose

According to the World Health Organization (WHO), 34.7% of females in the United States are obese (BMI ≥ 30) in 2014, compared to 32.5% in 2010. The previous research has demonstrated high BMI as an independent risk factor for surgical complications after breast surgery. As more patients become obese, we sought to examine whether increasing obesity had an effect on outcomes of women who underwent a unilateral mastectomy without breast reconstruction.

Methods

The study reviewed the 2007–2012 ACS-NSQIP database and identified all patients who underwent a unilateral mastectomy without reconstruction. Patients were then categorized and compared according to the World Health Organization obesity classification. Data were analyzed for minor complications (e.g., UTI and SSI) and major complications (e.g., renal failure, sepsis, deep vein thrombosis, return to operating room [RTOR], and cardiac arrest).

Results

A total of 7207 women were identified. Median BMI was 27.3 kg/m². From the cohort, 453 patients (6.29%) had a major complication and 173 patients (2.40%) had a minor complication. 53 (0.74%) had bleeding complications, 148 (2.05%) had a surgical site infection (SSI), 352 (4.88%) RTOR, and 7 (0.01%) died within 30 days. Major complications (p = 0.005) and minor complications (p < 0.001) significantly increased as BMI increased. SSI and RTOR had increasing trends, but were not statistically significant.

Conclusions

This study characterizes the risk of complications in women undergoing unilateral mastectomies and shows that increasing obesity is associated with major and minor postoperative complications. Our finding highlights the need for personalized preoperative risk assessment and counseling of obese patients.

     

Calcium as a chemopreventive agent against colorectal neoplasm: does obesity play a role?

Background

Concerning the chemopreventive potential of calcium against colorectal neoplasms, strong evidence from initial randomized controlled trials (RCTs) of colorectal adenoma has not been confirmed from the most recent large RCT. To explain the conflicting results, a new hypothesis was proposed that the benefit of calcium may be confined to lean individuals.

Methods

To test this hypothesis, we examined heterogeneity of the associations of calcium intake with adenoma and CRC, using data from the most recent meta-analyses of observational studies and conducting subgroup analysis by average body mass index (BMI) of study population.

Results

An inverse association of calcium intake with adenoma and CRC did not vary by population average BMI. By anatomical subsites of CRC, while there was no significant evidence of heterogeneity by population average BMI (P _{heterogeneity} > 0.05), the benefit of calcium was confined to studies with population average BMI of ≥25 kg/m² for both colon cancer and rectal cancer, contradicting the hypothesis.

Conclusions

In our study-level meta-analysis, we found no evidence to support that the chemopreventive potential of calcium, if real, may be stronger in leaner individuals.

     

A large prospective study of risk factors for adenocarcinomas and malignant carcinoid tumors of the small intestine

Purpose

Small intestinal cancer is increasing in the U.S.A, yet little is known about its etiology. Our aim was to prospectively evaluate risk factors for this malignancy by the two main histologic subtypes (adenocarcinomas and carcinoids).

Methods

Hazard ratios and 95 % confidence intervals (CI) were estimated for all incident small intestinal cancers (n = 237), adenocarcinomas (n = 84), and malignant carcinoids (n = 124), by demographic and lifestyle factors among 498,376 men and women.

Results

Age was the only risk factor for adenocarcinomas (HR for ≥65 vs. 50–55 years = 3.12, 95 % CI 1.33, 7.31). Age (HR for ≥65 vs. 50–55 years = 3.31, 95 % CI 1.51, 7.28), male sex (HR = 1.44, 95 % CI 1.01, 2.05), body mass index (BMI, HR for ≥35 vs. 18.5–<25 kg/m² = 1.95, 95 % CI 1.06, 3.58), and current menopausal hormone therapy use (HR = 1.94, 95 % CI 1.07, 3.50) were positively associated with malignant carcinoids. A family history of any cancer or colorectal cancer (HR = 1.42, 95 % CI 0.99, 2.03; 1.61, 0.97, 2.65, respectively), or a personal history of colorectal polyps (HR = 1.51, 95 % CI 0.92, 2.46) produced elevated, but not statistically significant, risks for malignant carcinoids. Race, education, diabetes, smoking, physical activity, and alcohol intake were not associated with either histologic subtype.

Conclusions

Risk factors differed according to cancer subtype; only age was associated with adenocarcinomas, whereas age, male sex, BMI, and menopausal hormone therapy use were positively associated with malignant carcinoids.

     

Ovarian suppression in combination endocrine adjuvant therapy in premenopausal women with early breast cancer

Purpose

The benefits of adding ovarian suppression to either tamoxifen or aromatase inhibitors as adjuvant breast cancer therapy in premenopausal women are controversial. Therefore, we performed a systematic literature review and meta-analysis of relevant randomized trials.

Methods

We identified and combined four qualifying trials reporting disease-free survival (DFS) and overall survival (OS) using meta-analysis.

Results

Combining ABCSG-12, SOFT, and TEXT studies, there were 65 fewer DFS events (HR 0.89, 95% CI 0.57–1.39) but 30 more deaths for ovarian suppression plus aromatase inhibitor compared to ovarian suppression plus tamoxifen (HR 1.31, 95% CI 0.93–1.84, P = 0.12, τ = 0.03, heterogeneity, P = 0.18). DFS and OS were more concordant for combined SOFT and E-3193 findings; for ovarian suppression plus tamoxifen compared to tamoxifen alone, there were 24 fewer DFS events (HR 0.83, 95% CI 0.67–1.07, P = 0.09, τ ² = 0) and 14 fewer deaths (HR 0.76, 95% CI 0.53–1.07). The SOFT Estrogen Substudy demonstrated inconsistent estrogen suppression with combined ovarian suppression and aromatase inhibitor.

Conclusion

Given the discordance between DFS and OS and inconsistent estrogen suppression with ovarian suppression plus aromatase inhibitor, adding aromatase inhibitor to ovarian suppression as adjuvant therapy in premenopausal women is premature.