Cisplatin-associated neuropathy characteristics compared with those associated with other neurotoxic chemotherapy agents (Alliance A151724).

PURPOSE: The current project was developed to obtain natural history information regarding cisplatin-induced peripheral neuropathy in males with testicular/germ cell cancers and to compare such neuropathy data with similarly obtained data in patients receiving other chemotherapy drugs in similarly conducted clinical trials. METHODS: Patients without baseline neuropathy symptoms, who were initiating cisplatin-based chemotherapy, completed the EORTC CIPN 20 patient-reported instrument to evaluate chemotherapy-induced peripheral neuropathy (CIPN). Results were compared with EORTC CIPN 20 data obtained from independent study sets regarding patients receiving (1) paclitaxel, (2) combined paclitaxel and carboplatin, (3) oxaliplatin, or (4) a combination of doxorubicin and cyclophosphamide (AC). The last study set of patients on AC was selected to evaluate the use of EORTC CIPN 20 data in patients receiving chemotherapy not known to cause CIPN. RESULTS: Cisplatin-induced neuropathy was more similar to neuropathy in patients receiving oxaliplatin than in those receiving paclitaxel. The cisplatin and oxaliplatin groups exhibited the coasting phenomenon and more prominent upper extremity symptoms than lower extremity symptoms during chemotherapy administration weeks. In contrast, paclitaxel-treated patients did not, on average, exhibit the coasting phenomenon; additionally, lower extremity symptoms were more prominent during the weeks when paclitaxel was administered. Cisplatin-induced neuropathy was less severe than was seen in patients in the other two groups, potentially because the cisplatin-receiving patients were younger. Patients receiving AC did not report substantial EORTC CIPN 20 changes. CONCLUSION: Understanding neuropathy similarities and differences with various chemotherapy agents may help elucidate CIPN processes and facilitate means to prevent and/or treat established CIPN. TRIAL REGISTRATION: NCT02677727.

Exploring Foods of the Pacific: Cultural Food Identity in the US Affiliated Pacific Region.

Indigenous peoples of the Pacific have seen major shifts in dietary patterns due to foreign colonization, which introduced an array of new foods. Today, foods considered traditional and acculturated are consumed in various extents. However, the definitions and identity of traditional versus acculturated foods has become unclear as many introduced foods have been incorporated into Pacific cultures. The purpose of this study was to capture culturally relevant definitions of traditional, acculturated, and locally grown foods among 10 jurisdictions of the US-Affiliated Pacific (USAP) region with a focus on fruits and vegetables. Questionnaires were used to capture definitions of these terms, and to identify a list of foods (n=121) as traditional, acculturated, and/or locally grown in addition to classify them into food groups (ie, fruit, vegetable, starch, and/or grain). For the most part, definitions of traditional, acculturated, and locally grown were agreed upon by participating USAP jurisdictions, with some supplementary caveats presented by different jurisdictions. More foods were identified as acculturated (n=75) than traditional (n=37). Fruits (n=55) were the most frequent designation and about a third were vegetables (n=44). The majority of the jurisdictions reported growing at least half of the food items. This is the first study to identify and classify foods of the Pacific from the perspective of those indigenous to the USAP region. Understanding these similarities and differences in how food is classified and identified, through the lens of those from the Pacific, is crucial for nutrition education, and understanding what foods are locally grown is important for future sustainability.

Consumption of Traditional Fruits and Vegetables among Children in the US-Affiliated Pacific Region.

Background: Traditional Pacific diets have many health benefits, including maintenance of a healthy weight and prevention of various diseases. Few studies have evaluated the frequency at which traditional diets are consumed in the Pacific, especially among children. Objectives: This study examined the frequency of traditional and acculturated fruit and vegetable (F&V) intake among children in the US-affiliated Pacific (USAP) region. Methods: Diet records of 3319 children ages 2 to 8 y old were analyzed for frequency of traditional or acculturated F&V intake within USAP jurisdictions of American Samoa, Commonwealth of the Northern Mariana Islands (CNMI), Federated States of Micronesia (FSM; FSM island states include Chuuk, Kosrae, Pohnpei, and Yap), Guam, Hawaii, Republic of the Marshall Islands (RMI), and Republic of Palau. Results: Of the 95,304 food items recorded among participating children in the USAP jurisdictions, 15.2% were F&Vs. Of the 10 jurisdictions, children in the islands of Chuuk, Kosrae, Yap, and Pohnpei recorded the highest frequencies of traditional F&V intake relative to their total F&V intake (67.8%, 64.8%, 56.7%, and 52.5%, respectively). American Samoa and RMI recorded moderate frequency of traditional F&V intake (38.9% and 46.4%, respectively), whereas children in Hawaii, Guam, and CNMI recorded the lowest frequencies of traditional F&V intake relative to their total F&V intake (10.4%, 12.4%, and 15.3%, respectively). Children in Hawaii, Guam, Palau, and CNMI recorded high frequencies of acculturated F&V intake (37.8%, 31.2%, 34.5%, and 27.9%, respectively). Conclusions: Overall, children in the USAP jurisdictions participating in this study recorded a low frequency of F&V intake. The differences in traditional F&V intake found between the USAP islands may be due to variation in economic income level and external influences on social and cultural norms among the island populations and variations of cost, accessibility, and convenience of each category of food to each island's population.

The prognostic value of CD3+ tumor-infiltrating lymphocytes for stage II colon cancer according to use of adjuvant chemotherapy: A large single-institution cohort study.

BACKGROUND: High tumor infiltrating lymphocytes (TILs) density was previously shown to be associated with favorable prognosis for patients with colon cancer (CC). However, the impact of TILs on overall survival (OS) of stage II CC patients who received adjuvant chemotherapy (ADJ) or not (no-ADJ) is unknown. We assessed the prognostic value of CD3+ TILs in stage II CC patients according to whether they had ADJ or not. METHODS: Patients treated with curative surgery for stage II CC (2002-2013) were selected from the Santa Maria alle Scotte Hospital registry. TILs at the invasive front, center of tumor, and stroma were determined by immunohistochemistry and manually quantified as the rate of TILs/total tissue areas. High TILs (H-TILs) was defined as >20%. Patients were categorized as high or low TILs (L-TILs) and ADJ or no-ADJ. RESULTS: Of the 678 patients included, 137 (20%) received ADJ and 541 (80%) did not. The distribution of the 4 groups were: 16% (L-TIL/ADJ), 64% (L-TIL/no-ADJ), 5% (H-TIL/ADJ), 15% (H-TIL/no-ADJ). Compared to H-TILs/no-ADJ, ADJ patients showed a significantly increased OS (P<.01) regardless of the TILs rate whereas L-TILs/no-ADJ had significantly decreased OS and higher risk of death (HR=1.41; 95% CI, 1.06-1.88; P<.0001). On multivariable analysis, the unfavorable prognostic value of L-TILs (vs. H-TILs) for no-ADJ patients was confirmed (HR=1.36; 95% CI 1.02, 1.82; P=.0373). CONCLUSION: Low CD3+ TILs rate was associated with shorter OS in those with stage II colon cancer who did not receive adjuvant therapy. Low CD3+ TILs could be considered an additional risk factor for still ADJ-untreated stage II CC patients, which could facilitate clinical decision making.

Circulating Cell-Free DNA as Biomarker of Taxane Resistance in Metastatic Castration-Resistant Prostate Cancer.

There are no biomarkers predictive of resistance to docetaxel or cabazitaxel validated for patients with metastatic castration-resistant prostate cancer (mCRPC). We assessed the association between ABCB1 amplification and primary resistance to docetaxel or cabazitaxel for patients with mCRPC, using circulating cell-free DNA (cfDNA). Patients with ≥1 plasma sample drawn within 12 months before starting docetaxel (cohort A) or cabazitaxel (cohort B) for mCRPC were identified from the Dana-Farber Cancer Institute IRB approved database. Sparse whole genome sequencing was performed on the selected cfDNA samples and tumor fractions were estimated using the computational tool ichorCNA. We evaluated the association between ABCB1 amplification or other copy number alterations and primary resistance to docetaxel or cabazitaxel. Of the selected 176 patients, 45 samples in cohort A and 21 samples in cohort B had sufficient tumor content. No significant association was found between ABCB1 amplification and primary resistance to docetaxel (p = 0.58; odds ratio (OR) = 1.49) or cabazitaxel (p = 0.97; OR = 1.06). No significant association was found between exploratory biomarkers and primary resistance to docetaxel or cabazitaxel. In this study, ABCB1 amplification did not predict primary resistance to docetaxel or cabazitaxel for mCRPC. Future studies including ABCB1 amplification in a suite of putative biomarkers and a larger cohort may aid in drawing definitive conclusions.

Race, Income, and Survival in Stage III Colon Cancer: CALGB 89803 (Alliance).

Background: Disparities in colon cancer outcomes have been reported across race and socioeconomic status, which may reflect, in part, access to care. We sought to assess the influences of race and median household income (MHI) on outcomes among colon cancer patients with similar access to care. Methods: We conducted a prospective, observational study of 1206 stage III colon cancer patients enrolled in the CALGB 89803 randomized adjuvant chemotherapy trial. Race was self-reported by 1116 White and 90 Black patients at study enrollment; MHI was determined by matching 973 patients' home zip codes with publicly available US Census 2000 data. Multivariate analyses were adjusted for baseline sociodemographic, clinical, dietary, and lifestyle factors. All statistical tests were 2-sided. Results: Over a median follow-up of 7.7 years, the adjusted hazard ratios for Blacks (compared with Whites) were 0.94 (95% confidence interval [CI] = 0.66 to 1.35, P = .75) for disease-free survival, 0.91 (95% CI = 0.62 to 1.35, P = .65) for recurrence-free survival, and 1.07 (95% CI = 0.73 to 1.57, P = .73) for overall survival. Relative to patients in the highest MHI quartile, the adjusted hazard ratios for patients in the lowest quartile were 0.90 (95% CI = 0.67 to 1.19, P trend = .18) for disease-free survival, 0.89 (95% CI = 0.66 to 1.22, P trend = .14) for recurrence-free survival, and 0.87 (95% CI = 0.63 to 1.19, P trend = .23) for overall survival. Conclusions: In this study of patients with similar health-care access, no statistically significant differences in outcomes were found by race or MHI. The substantial gaps in outcomes previously observed by race and MHI may not be rooted in differences in tumor biology but rather in access to quality care.

Weight loss over time and survival: a landmark analysis of 1000+ prospectively treated and monitored lung cancer patients.

BACKGROUND: Eligibility criteria and endpoints for cancer cachexia trials-and whether weight loss should be included-remain controversial. Although most cachexia trials enrol patients after initial cancer diagnosis, few studies have addressed whether weight loss well after a cancer diagnosis is prognostic. METHODS: We pooled data from non-small cell lung cancer patients from prospectively conducted trials within the Alliance for Clinical Trials in Oncology (1998-2008), a nationally funded infrastructure. We examined (i) weight data availability and weight changes and (ii) survival. RESULTS: A total of 822 patients were examined. Of these, 659 (80%) were on treatment at the beginning of Cycle 2 of chemotherapy; weight was available for 656 (80%). By Cycles 3 and 4, weight was available for 448 (55%) and 384 (47%), respectively. From baseline to immediately prior to Cycle 2, 208 (32%) gained weight; 225 (34%) lost <2% of baseline weight; and 223 (34% of 656) lost 2% or more. Median survival from the beginning of Cycle 2 was 13.0, 10.9, and 6.9 months for patients with weight gain, weight loss of <2%, and weight loss of 2% or more, respectively. In multivariate analyses, adjusted for age, sex, performance score, type of treatment, and body mass index, weight loss of 2% or more was associated with poor overall survival compared with weight gain [hazard ratio (HR) = 1.66; 95% confidence interval (CI): 1.33-2.07; P < 0.001] and compared with weight loss of <2% (HR = 1.57; 95% CI: 1.27-1.95; P < 0.001). Although weight loss of <2% was not associated with poorer overall survival compared with weight gain, it was associated with poorer progression-free survival (HR = 1.24; 95% CI: 1.01-1.51; P = 0.036). Similar findings were observed in a separate 255-patient validation cohort. CONCLUSIONS: Weight should be integrated into cancer cachexia trials because of its ease of frequent measurement and sustained prognostic association.

Oxybutynin vs Placebo for Hot Flashes in Women With or Without Breast Cancer: A Randomized, Double-Blind Clinical Trial (ACCRU SC-1603).

BACKGROUND: Hot flashes (HFs) negatively affect quality of life among perimenopausal and postmenopausal women. This study investigated the efficacy of oxybutynin vs placebo in decreasing HFs. METHODS: In this randomized, multicenter, double-blind study, women with and without breast cancer with 28 or more HFs per week, lasting longer than 30 days, who were not candidates for estrogen-based therapy, were assigned to oral oxybutynin (2.5 mg twice a day or 5 mg twice a day) or placebo for 6 weeks. The primary endpoint was the intrapatient change from baseline in weekly HF score between each oxybutynin dose and placebo using a repeated-measures mixed model. Secondary endpoints included changes in weekly HF frequency, HF-related daily interference scale questionnaires, and self-reported symptoms. RESULTS: We enrolled 150 women. Baseline characteristics were well balanced. Mean (SD) age was 57 (8.2) years. Two-thirds (65%) were taking tamoxifen or an aromatase inhibitor. Patients on both oxybutynin doses reported greater reductions in the weekly HF score (5 mg twice a day: -16.9 [SD 15.6], 2.5 mg twice a day: -10.6 [SD 7.7]), placebo -5.7 (SD 10.2); P < .005 for both oxybutynin doses vs placebo), HF frequency (5 mg twice a day: -7.5 [SD 6.6], 2.5 mg twice a day: -4.8 [SD 3.2], placebo: -2.6 [SD 4.3]; P < .003 for both oxybutynin doses vs placebo), and improvement in most HF-related daily interference scale measures and in overall quality of life. Patients on both oxybutynin arms reported more side effects than patients on placebo, particularly dry mouth, difficulty urinating, and abdominal pain. Most side effects were grade 1 or 2. There were no differences in study discontinuation because of adverse effects. CONCLUSION: Oxybutynin is an effective and relatively well-tolerated treatment option for women with HFs.

Association of Diet Quality With Survival Among People With Metastatic Colorectal Cancer in the Cancer and Leukemia B and Southwest Oncology Group 80405 Trial.

Importance: Diet has been associated with survival in patients with stage I to III colorectal cancer, but data on patients with metastatic colorectal cancer are limited. Objective: To examine the association between diet quality and overall survival among individuals with metastatic colorectal cancer. Design, Setting, and Participants: This was a prospective cohort study of patients with metastatic colorectal cancer who were enrolled in the Cancer and Leukemia Group B (Alliance) and Southwest Oncology Group 80405 trial between October 27, 2005, and February 29, 2012, and followed up through January 2018. Exposures: Participants completed a validated food frequency questionnaire within 4 weeks after initiation of first-line treatment for metastatic colorectal cancer. Diets were categorized according to the Alternative Healthy Eating Index (AHEI), Alternate Mediterranean Diet (AMED) score, Dietary Approaches to Stop Hypertension (DASH) score, and Western and prudent dietary patterns derived using principal component analysis. Participants were categorized into sex-specific quintiles. Main Outcomes and Measures: Multivariable hazard ratios (HRs) and 95% CIs for overall survival. Results: In this cohort study of 1284 individuals with metastatic colorectal cancer, the median age was 59 (interquartile range [IQR]: 51-68) years, median body mass index was 27.2 (IQR, 24.1-31.4), 521 (41%) were female, and 1102 (86%) were White. There were 1100 deaths during a median follow-up of 73 months (IQR, 64-87 months). We observed an inverse association between the AMED score and risk of death (HR quintile 5 vs quintile 1, 0.83; 95% CI, 0.67-1.04; P = .04 for trend), but the point estimates were not statistically significant. None of the other diet scores or patterns were associated with overall survival. Conclusions and Relevance: In this prospective analysis of patients with metastatic colorectal cancer, diet quality assessed at initiation of first-line treatment for metastatic disease was not associated with overall survival.

Processing fine stainless-steel slag using spiral concentration.

In this study, the effectiveness of spiral concentration to process a fine (-1 mm) stainless-steel slag was evaluated. Specifically, testing was conducted to determine the feasibility of producing a high metal content stainless steel product and a low metal content aggregate product. This involved investigating a key operating variable for both five-and seven-turn spiral concentrators. The raw slag and spiral products were characterized to determine their respective size and metal distributions. Separation testing was carried out using the two full-scale spiral concentrators to evaluate the effects of feed solids concentration on spiral performance at solids feed rates ranging from 15 to 30 kg/min. The results indicated that under certain conditions, a high-quality metal fraction could be produced. For example, using the five-turn spiral, a product containing 95% metal was obtained at a low metal recovery. Both spirals were ineffective at concentrating the aggregate fraction. Overall, the feed solids concentration did not significantly affect the quality or recoveries of the products, particularly for feed solids concentrations less than 35% by weight. In order to improve the metal recoveries and to produce a low-metal aggregate material, reprocessing of the product streams and/or additional liberation of the raw slag would be required.

An investigation of wide-angle dense-medium cycloning for the recovery of metal and aggregate from fine slag.

An investigation was carried out to evaluate the feasibility of using wide-angle dense-medium cycloning to process a fine (-600 microm) stainless-steel slag. The slag was characterized by size and density using a combination of sieving and pycnometer measurements. Separation testing was carried out using a laboratory dense-medium cyclone to concentrate the stainless-steel fraction and produce a low-metal aggregate material. The effects of cyclone geometry (cone angle, underflow diameter, overflow diameter, cylinder length, and vortex finder length) and medium density on cyclone performance were evaluated. A Plackett-Burman statistical design was used to determine the significant variables as related to recovery and purity of the metal and aggregate products. Based on these results, full-factorial designs were performed at two different medium densities. Regression models relating the significant variables to product recovery and purity were developed for both the metal and aggregate fractions.