Purpose Fear of cancer recurrence (FCR) is prevalent, distressing, and long lasting. This study evaluated the impact of a theoretically/empirically based intervention (ConquerFear) on FCR. Methods ...Eligible survivors had curable breast or colorectal cancer or melanoma, had completed treatment (not including endocrine therapy) 2 months to 5 years previously, were age > 18 years, and had scores above the clinical cutoff on the FCR Inventory (FCRI) severity subscale at screening. Participants were randomly assigned at a one-to-one ratio to either five face-to-face sessions of ConquerFear (attention training, metacognitions, acceptance/mindfulness, screening behavior, and values-based goal setting) or an attention control (Taking-it-Easy relaxation therapy). Participants completed questionnaires at baseline (T0), immediately post-therapy (T1), and 3 (T2) and 6 months (T3) later. The primary outcome was FCRI total score. Results Of 704 potentially eligible survivors from 17 sites and two online databases, 533 were contactable, of whom 222 (42%) consented; 121 were randomly assigned to intervention and 101 to control. Study arms were equivalent at baseline on all measured characteristics. ConquerFear participants had clinically and statistically greater improvements than control participants from T0 to T1 on FCRI total ( P < .001) and severity subscale scores ( P = .001), which were maintained at T2 ( P = .017 and P = .023, respectively) and, for FCRI total only, at T3 ( P = .018), and from T0 to T1 on three FCRI subscales (coping, psychological distress, and triggers) as well as in general anxiety, cancer-specific distress (total), and mental quality of life and metacognitions (total). Differences in FCRI psychological distress and cancer-specific distress (total) remained significantly different at T3. Conclusion This randomized trial demonstrated efficacy of ConquerFear compared with attention control (Taking-it-Easy) in reduction of FCRI total scores immediately post-therapy and 3 and 6 months later and in many secondary outcomes immediately post-therapy. Cancer-specific distress (total) remained more improved at 3- and 6-month follow-up.
IMPORTANCE: Laparoscopic procedures are generally thought to have better outcomes than open procedures. Because of anatomical constraints, laparoscopic rectal resection may not be better because of ...limitations in performing an adequate cancer resection. OBJECTIVE: To determine whether laparoscopic resection is noninferior to open rectal cancer resection for adequacy of cancer clearance. DESIGN, SETTING, AND PARTICIPANTS: Randomized, noninferiority, phase 3 trial (Australasian Laparoscopic Cancer of the Rectum; ALaCaRT) conducted between March 2010 and November 2014. Twenty-six accredited surgeons from 24 sites in Australia and New Zealand randomized 475 patients with T1-T3 rectal adenocarcinoma less than 15 cm from the anal verge. INTERVENTIONS: Open laparotomy and rectal resection (n = 237) or laparoscopic rectal resection (n = 238). MAIN OUTCOMES AND MEASURES: The primary end point was a composite of oncological factors indicating an adequate surgical resection, with a noninferiority boundary of Δ = −8%. Successful resection was defined as meeting all the following criteria: (1) complete total mesorectal excision, (2) a clear circumferential margin (≥1 mm), and (3) a clear distal resection margin (≥1 mm). Pathologists used standardized reporting and were blinded to the method of surgery. RESULTS: A successful resection was achieved in 194 patients (82%) in the laparoscopic surgery group and 208 patients (89%) in the open surgery group (risk difference of −7.0% 95% CI, −12.4% to ∞; P = .38 for noninferiority). The circumferential resection margin was clear in 222 patients (93%) in the laparoscopic surgery group and in 228 patients (97%) in the open surgery group (risk difference of −3.7% 95% CI, −7.6% to 0.1%; P = .06), the distal margin was clear in 236 patients (99%) in the laparoscopic surgery group and in 234 patients (99%) in the open surgery group (risk difference of −0.4% 95% CI, −1.8% to 1.0%; P = .67), and total mesorectal excision was complete in 206 patients (87%) in the laparoscopic surgery group and 216 patients (92%) in the open surgery group (risk difference of −5.4% 95% CI, −10.9% to 0.2%; P = .06). The conversion rate from laparoscopic to open surgery was 9%. CONCLUSIONS AND RELEVANCE: Among patients with T1-T3 rectal tumors, noninferiority of laparoscopic surgery compared with open surgery for successful resection was not established. Although the overall quality of surgery was high, these findings do not provide sufficient evidence for the routine use of laparoscopic surgery. Longer follow-up of recurrence and survival is currently being acquired. TRIAL REGISTRATION: anzctr.org Identifier: ACTRN12609000663257
OBJECTIVE:The aim of the study was to determine the efficacy of laparoscopic rectal resection (Lap) versus open laparotomy and rectal resection (Open) for rectal cancer on locoregional recurrence ...(LRR) and disease-free survival (DFS) at 2 years.
SUMMARY BACKGROUND DATA:Although a Lap approach to colon cancer surgery may offer similar oncological outcomes to Open with potentially less morbidity, this remains to be clearly established for the treatment of rectal cancer.
METHODS:A randomized, multicenter noninferiority phase 3 trial of 475 patients with T1 to T3 rectal adenocarcinoma <15 cm from anal verge, given Lap or Open and followed for a minimum 2 years to assess LRR, DFS, and overall survival (OS).
RESULTS:Secondary endpoint analyses included 450 patients (95%) without metastases at baseline (mean age 64; 34% women) who received Lap (n = 225) or Open (n = 225). Median follow-up was 3.2 years (range0.1–5.4 yrs). LRR cumulative incidence at 2 yearsLap 5.4%; Open 3.1% difference, 2.3%; 95% confidence interval (CI), −1.5% to 6.1%; hazard ratio (HR) 1.7; 95% CI, 0.74–3.9. DFS at 2 yearsLap 80%; Open 82% (difference, 2.0%; 95% CI, −9.3% to 5.4%; HR for recurrence or death, 1.17; 95% CI, 0.81–1.68; P = 0.41). After adjustment for baseline factors HR = 1.07 (95% CI, 0.7–1.6). OS at 2 yearsLap 94%; Open 93% (difference 0.9%; 95% CI, −3.6% to 5.4%).
CONCLUSIONS:Laparoscopic surgery for rectal cancer did not differ significantly from open surgery in effects on 2-year recurrence or DFS and OS. Confidence intervals included potentially clinically important differences favoring open resection, so that the combination of primary and secondary study endpoints may not support laparoscopic resection of rectal cancer as a routine standard of care and further follow-up is required.
Summary Background & aims To examine the effect of supplementation with probiotics on respiratory and gastrointestinal illness in healthy active men and women. Methods A randomised double-blind ...placebo-controlled trial was conducted. Four hundred and sixty five participants (241 males; age 35 ± 12 y (mean ± SD) and 224 females; age 36 ± 12 y) were assigned to one of three groups: Group 1 – Bifidobacterium animalis subsp. lactis Bl-04 (Bl-04) 2.0 × 109 colony forming units per day, CFU per day, Group 2 – Lactobacillus acidophilus NCFM and Bifidobacterium animalis subsp. lactis Bi-07 (NCFM & Bi-07) 5 × 109 CFU each per day) or Group 3 – placebo mixed in a drink. Results The risk of an upper respiratory illness episode was significantly lower in the Bl-04 group (hazard ratio 0.73; 95% confidence interval 0.55–0.95; P = 0.022) compared to placebo. There was no significant difference in illness risk between the NCFM & Bi-07 group (hazard ratio 0.81; 0.62–1.08; P = 0.15) and the placebo group. There was a 0.7 and 0.9 month delay in the median time to an illness episode in the Bl-04 and NCFM & Bi-07 groups respectively compared to placebo (placebo 2.5 months; Bl-04 3.2 months; NCFM & Bi-07 3.4 months). There were insufficient GI illness episodes for analysis. The NCFM & Bi-07 group but not the Bl-04 group undertook significantly more physical activity (8.5%; 6.7%–10%; P < 0.003) than the placebo group. Conclusion The probiotic Bl-04 appears to be a useful nutritional supplement in reducing the risk of URTI in healthy physically-active adults. Trial registration Australia New Zealand Clinical Trials Registry: Number ACTRN12611000130965.
Purpose
To determine whether the benefits of sentinel-node-based management (SNBM) over routine axillary clearance (RAC) persisted to 5 years.
Methods
A total of 1088 women with breast cancer less ...than 3 cm in diameter and clinically negative axillary nodes were randomized to SNBM with axillary clearance if the sentinel node was positive or RAC preceded by sentinel-node biopsy. The outcomes were: (1) objectively measured change in the volume of the operated and contralateral nonoperated arms; (2) the proportion with an increase in arm volume <15%; and (3) subjectively assessed arm morbidity for the domains swelling, symptoms, dysfunction, and disability. Assessments were performed at 1 and 6 months after surgery and then annually.
Results
Limb volume increased progressively in the operated and nonoperated arms for 2 years and persisted unchanged to year 5, accompanied by weight gain. Correction by change in the nonoperated arm showed a mean volume increase of 70 mL in the RAC group and 26 mL in the SNBM group (
P
< 0.001) at 5 years. Only 28 patients (3.3%) had a corrected increase >15% from baseline (RAC 5.0% vs. SNBM 1.7%). Significant predictors were surgery type (RAC vs. SNBM), obesity, diabetes, palpable tumor, and weight gain exceeding 10% of baseline value.
Conclusions
Subjective assessments revealed persisting patient concerns about swelling and symptoms but not overall disability at 5 years. Subjective scores were only moderately correlated with volume increase. SNAC1 has demonstrated that objective morbidity and subjective morbidity persist for 5 years after surgery and that SNBM significantly lowers the risk of both.
The aim of this study was to compare patient-reported urinary, bowel, and sexual functioning of ALaCaRT Trial participants randomized to open or laparoscopic surgery for rectal cancer.
The primary ...endpoint, noninferiority of laparoscopic surgical resection adequacy, was not established.
Participants completed QLQ-CR29 at baseline, 3, and 12 months post-surgery. Additionally, women completed Rosen's Female Sexual Functioning Index (FSFI). Men completed the International Index of Erectile Function (IIEF) and QLQ-PR25. We compared the proportions of participants in each group who experienced moderate/severe symptoms/dysfunction at each time-point and compared mean difference scores from baseline to 12 months between groups. All analyses were intention-to-treat. Sexual functioning analyses included only the participants who expressed sexual interest at baseline.
Baseline PRO compliance of 475 randomized participants was 88%. At 12 months, a lower proportion of open surgery participants experienced moderate-severe fecal incontinence and sore skin, compared to Laparoscopic participants, and a lower proportion of men randomized to open surgery experienced moderate-severe urinary symptoms. There were no differences at 3 months for bowel or urinary symptoms. Sexual functioning among sexually interested participants was similar between groups at 3 and 12 months; however, a lower proportion of women reported moderate to severe sexual dissatisfaction at 3 months in the open as compared to the laparoscopic group, (Rebecca.mercieca@sydney.edu.au., 95% CI 0.03-0.39).
Despite the slightly lower proportions of open surgery participants self-reporting moderate-severe symptoms for 3 of 16 urinary/bowel domains, and lack of differences in sexual domains, it remains difficult to recommend one surgical approach over another for rectal resection.
Low HDL cholesterol (HDL-C) and small HDL particle size may directly promote hyperglycemia. We evaluated associations of HDL-C, apolipoprotein A-I (apoA-I), and HDL-C/apoA-I with insulin secretion, ...insulin resistance, HbA1c, and long-term glycemic deterioration, reflected by initiation of pharmacologic glucose control.
The 5-year Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study followed 9,795 type 2 diabetic subjects. We calculated baseline associations of fasting HDL-C, apoA-I, and HDL-C/apoA-I with HbA1c and, in those not taking exogenous insulin (n = 8,271), with estimated β-cell function (homeostasis model assessment of β-cell function HOMA-B) and insulin resistance (HOMA-IR). Among the 2,608 subjects prescribed lifestyle only, Cox proportional hazards analysis evaluated associations of HDL-C, apoA-I, and HDL-C/apoA-I with subsequent initiation of oral hypoglycemic agents (OHAs) or insulin.
Adjusted for age and sex, baseline HDL-C, apoA-I, and HDL-C/apoA-I were inversely associated with HOMA-IR (r = -0.233, -0.134, and -0.230; all P < 0.001; n = 8,271) but not related to HbA1c (all P > 0.05; n = 9,795). ApoA-I was also inversely associated with HOMA-B (r = -0.063; P = 0.002; n = 8,271) adjusted for age, sex, and HOMA-IR. Prospectively, lower baseline HDL-C and HDL-C/apoA-I levels predicted greater uptake (per 1-SD lower: hazard ratio HR 1.13 CI 1.07-1.19, P < 0.001; and HR 1.16 CI 1.10-1.23, P < 0.001, respectively) and earlier uptake (median 12.9 and 24.0 months, respectively, for quartile 1 vs. quartile 4; both P < 0.01) of OHAs and insulin, with no difference in HbA1c thresholds for initiation (P = 0.87 and P = 0.81). Controlling for HOMA-IR and triglycerides lessened both associations, but HDL-C/apoA-I remained significant.
HDL-C, apoA-I, and HDL-C/apoA-I were associated with concurrent insulin resistance but not HbA1c. However, lower HDL-C and HDL-C/apoA-I predicted greater and earlier need for pharmacologic glucose control.
Background
Lymph node density (LND) has been described as a prognostic factor for survival in patients with head and neck squamous cell carcinoma, particularly of the oral cavity. The aim of this ...study was to determine the prognostic significance of LND in patients with node positive oral tongue squamous cell carcinoma (OTSCC).
Methods
Patients with pathological node positive OTSCC were identified in a retrospective review of prospectively collected data. The optimal cut‐point for LND was determined using the minimum P‐value method and the log‐rank test. The impact of this LND cut‐point on time to disease progression and overall survival was determined.
Results
In 72 patients with OTSCC, an LND of 14.3% was found to have the greatest separation using the log‐rank test (P < 0.001). LND ≤14.3% was predicted for longer time to disease progression with a median time of 73 months compared to 9.4 months in patients with an LND >14.3% (hazard ratio: 3.43; 95% confidence interval: 1.76–6.70; P < 0.001). LND was also a significant predictor of overall survival with a median overall survival with LND ≤14.3% of 82.3 months, compared with 14.7 months in patients with an LND >14.3% (hazard ratio: 3.28; 95% confidence interval: 1.61–6.68; P = 0.001). Patients with an LND >14.3% experienced a higher rate of regional recurrence.
Conclusion
Our findings confirm the prognostic significance of LND in patients with node positive OTSCC, with a similar LND cut‐point value to other published series. Improving regional control in these high‐risk patients may improve outcome.
RAS mutations predict lack of response to epidermal growth factor receptor monoclonal antibody therapy in patients with metastatic colorectal cancer (mCRC), but preclinical studies and retrospective ...clinical data suggest that patients with tumors harboring the exon 2 KRAS G13D mutation may benefit from cetuximab. We aimed to assess cetuximab monotherapy and cetuximab plus irinotecan in patients with molecularly selected (G13D mutation) chemotherapy-refractory mCRC in a randomized phase II trial of this rare molecular subtype.
Patients with chemotherapy-refractory KRAS G13D mutation-positive mCRC who had progressed within 6 months of irinotecan therapy were randomly assigned to cetuximab 400 mg/m(2) loading dose and then 250 mg/m(2) once per week with or without irinotecan 180 mg/m(2) once every 2 weeks. The primary end point was 6-month progression-free survival; secondary end points were response rate, overall survival, quality of life, and toxicity.
Fifty-one of 53 patients recruited over 2 years were eligible. The 6-month progression-free survival rate was 10% (95% CI, 2% to 26%) for cetuximab versus 23% (95% CI, 9% to 40%) for cetuximab plus irinotecan with a hazard ratio of 0.74 (95% CI, 0.42 to 1.32). Response and stable disease rates were 0% and 58% for monotherapy versus 9% and 70% for combination treatment, respectively. Overall survival and quality of life were similar; toxicities were higher with combination therapy.
In patients with G13D-mutated chemotherapy-refractory mCRC, there was no statistically significant improvement in disease control at 6 months with either cetuximab monotherapy or cetuximab plus irinotecan. No responses were seen with single-agent cetuximab. The responses observed with the combination of cetuximab and irinotecan may reflect true drug synergy or persistent irinotecan sensitivity. The ICECREAM (Irinotecan Cetuximab Evaluation and Cetuximab Response Evaluation Among Patients with a G13D Mutation) study demonstrates the need to prospectively evaluate hypotheses that were previously supported by retrospective analyses and exemplifies the value of international collaboration in trials of rare molecular subtypes.
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