Discrimination of normal and cancerous human skin tissues based on laser-induced spectral shift fluorescence microscopy.

A homemade spectral shift fluorescence microscope (SSFM) is coupled with a spectrometer to record the spectral images of specimens based on the emission wavelength. Here a reliable diagnosis of neoplasia is achieved according to the spectral fluorescence properties of ex-vivo skin tissues after rhodamine6G (Rd6G) staining. It is shown that certain spectral shifts occur for nonmelanoma/melanoma lesions against normal/benign nevus, leading to spectral micrographs. In fact, there is a strong correlation between the emission wavelength and the sort of skin lesions, mainly due to the Rd6G interaction with the mitochondria of cancerous cells. The normal tissues generally enjoy a significant red shift regarding the laser line (37 nm). Conversely, plenty of fluorophores are conjugated to unhealthy cells giving rise to a relative blue shift i.e., typically SCC (6 nm), BCC (14 nm), and melanoma (19 nm) against healthy tissues. In other words, the redshift takes place with respect to the excitation wavelength i.e., melanoma (18 nm), BCC (23 nm), and SCC (31 nm) with respect to the laser line. Consequently, three data sets are available in the form of micrographs, addressing pixel-by-pixel signal intensity, emission wavelength, and fluorophore concentration of specimens for prompt diagnosis.

Low-Dose Oral Cyclophosphamide and Methotrexate Maintenance for Hormone Receptor-Negative Early Breast Cancer: International Breast Cancer Study Group Trial 22-00.

PURPOSE: To evaluate the benefit of low-dose cyclophosphamide and methotrexate (CM) maintenance, which previously demonstrated antitumor activity and few adverse effects in advanced breast cancer, in early breast cancer. PATIENTS AND METHODS: International Breast Cancer Study Group (IBCSG) Trial 22-00, a randomized phase III clinical trial, enrolled 1,086 women (1,081 intent-to-treat) from November 2000 to December 2012. Women with estrogen receptor- and progesterone receptor-negative (< 10% positive cells by immunohistochemistry) early breast cancer any nodal and human epidermal growth factor receptor 2 status, were randomly assigned anytime between primary surgery and 56 days after the first day of last course of adjuvant chemotherapy to CM maintenance (cyclophosphamide 50 mg/day orally continuously and methotrexate 2.5 mg twice/day orally on days 1 and 2 of every week for 1 year) or to no CM. The primary end point was disease-free survival (DFS), which included invasive recurrences, second (breast and nonbreast) malignancies, and deaths. RESULTS: After a median of 6.9 years of follow-up, DFS was not significantly better for patients assigned to CM maintenance compared with patients assigned to no CM, both overall (hazard ratio [HR], 0.84; 95% CI, 0.66 to 1.06;P = .14) and in triple-negative (TN) disease (n = 814; HR, 0.80; 95% CI, 0.60 to 1.06). Patients with TN, node-positive disease had a nonstatistically significant reduced HR (n = 340; HR, 0.72; 95% CI, 0.49 to 1.05). Seventy-one (13%) of 542 patients assigned to CM maintenance did not start CM. Of 473 patients who received at least one CM maintenance dose (including two patients assigned to no CM), 64 (14%) experienced a grade 3 or 4 treatment-related adverse event; elevated serum transaminases was the most frequently reported (7%), followed by leukopenia (2%). CONCLUSION: CM maintenance did not produce a significant reduction in DFS events in hormone receptor-negative early breast cancer. The trend toward benefit observed in the TN, node-positive subgroup supports additional exploration of this strategy in the TN, higher-risk population.

Adjuvant ovarian function suppression and cognitive function in women with breast cancer.

BACKGROUND: To examine the effect on cognitive function of adjuvant ovarian function suppression (OFS) for breast cancer. METHODS: The Suppression of Ovarian Function (SOFT) trial randomised premenopausal women with hormone receptor-positive breast cancer to 5 years adjuvant endocrine therapy with tamoxifen+OFS, exemestane+OFS or tamoxifen alone. The Co-SOFT substudy assessed objective cognitive function and patient reported outcomes at randomisation (T0), and 1 year later (T1); the primary endpoint was change in global cognitive function, measured by the composite objective cognitive function score. Data were compared for the pooled tamoxifen+OFS and exemestane+OFS groups vs the tamoxifen alone group using the Wilcoxon rank-sum test. RESULTS: Of 86 participants, 74 underwent both T0 and T1 cognitive testing; 54 randomised to OFS+ either tamoxifen (28) or exemestane (26) and 20 randomised to tamoxifen alone. There was no significant difference in the changes in the composite cognitive function scores between the OFS+ tamoxifen or exemestane groups and the tamoxifen group (mean±s.d., -0.21±0.92 vs -0.04±0.49, respectively, P=0.71, effect size=-0.20), regardless of prior chemotherapy status, and adjusting for baseline characteristics. CONCLUSIONS: The Co-SOFT study, although limited by small samples size, provides no evidence that adding OFS to adjuvant oral endocrine therapy substantially affects global cognitive function.

The median informs the message: accuracy of individualized scenarios for survival time based on oncologists' estimates.

PURPOSE: To determine the accuracy and usefulness of oncologists' estimates of survival time in individual patients with advanced cancer. PATIENTS AND METHODS: Twenty-one oncologists estimated the "median survival of a group of identical patients" for each of 114 patients with advanced cancer. Accuracy was defined by the proportions of patients with an observed survival time bounded by prespecified multiples of their estimated survival time. We expected 50% to live longer (or shorter) than their oncologist's estimate (calibration), 50% to live from half to double their estimate (typical scenario), 5% to 10% to live ≤ one quarter of their estimate (worst-case scenario), and 5% to 10% to live three or more times their estimate (best-case scenario). Estimates within 0.67 to 1.33 times observed survival were deemed precise. Discriminative value was assessed with Harrell's C-statistic and prognostic significance with proportional hazards regression. RESULTS: Median survival time was 11 months. Oncologists' estimates were relatively well-calibrated (61% shorter than observed), imprecise (29% from 0.67 to 1.33 times observed), and moderately discriminative (Harrell C-statistic 0.63; P = .001). The proportion of patients with an observed survival half to double their oncologist's estimate was 63%, ≤ one quarter of their oncologist's estimate was 6%, and three or more times their oncologist's estimate was 14%. Independent predictors of observed survival were oncologist's estimate (hazard ratio [HR] = 0.92; P = .004), dry mouth (HR = 5.1; P < .0001), alkaline phosphatase more than 101 U/L (HR = 2.8; P = .0002), Karnofsky performance status ≤ 70 (HR = 2.3; P = .007), prostate primary (HR = 0.23; P = .002), and steroid use (HR = 2.4; P = .02). CONCLUSION: Oncologists' estimates of survival time were relatively well-calibrated, moderately discriminative, independently associated with observed survival, and a reasonable basis for estimating worst-case, typical, and best-case scenarios for survival.

Effect of sertraline on symptoms and survival in patients with advanced cancer, but without major depression: a placebo-controlled double-blind randomised trial.

BACKGROUND: Depression, anxiety, fatigue, and impaired wellbeing are common, important, and closely related in advanced cancer. We aimed to identify the effects of an established antidepressant on these symptoms and survival in patients with advanced cancer who did not have major depression as assessed by clinicians. METHODS: Between July, 2001, and February, 2006, 189 patients with advanced cancer were randomly assigned sertraline 50 mg (n=95), or placebo (n=94), once per day. The primary outcome was depression as assessed by the Centre for Epidemiologic Studies Depression scale (CES-D); the main secondary outcomes were: anxiety as assessed by Hospital Anxiety and Depression Scales (HADS-A); overall quality of life and fatigue as assessed by Functional Assessment of Cancer Therapy General and Fatigue scales (FACT-G and FACT-F, respectively); and clinicians' ratings of quality of life by use of Spizter's Quality of Life Index (SQLI). Multiple measures were used for corroboration of the most important outcomes. Primary analyses were done by intention to treat and were based on scale scores at 4 weeks and 8 weeks. The benefits of sertraline compared with placebo are expressed on a range from +100 (ie, maximum benefit) to -100 (ie, maximum harm); a difference of 10 was deemed clinically significant. This clinical trial is registered at Current Controlled Trials website http://www.controlled-trials.com/ISRCTN72466475. FINDINGS: Sertraline had no significant effect (scale, benefit over placebo [95% CI]) on depression (CES-D 0.4 [-2.6 to 3.4]), anxiety (HADS-A 2.0 [-1.5 to 5.5]), fatigue (FACT-F 0.3 [-4.3 to 4.9]), overall quality of life (FACT-G 1.7 [-1.3 to 4.7]), or clinicians' ratings (SQLI 2.0 [-2.5 to 6.5]), and the 95% CI ruled out a clinically significant benefit for all main outcomes. Sertraline was discontinued more often and earlier than was placebo (hazard ratio 1.46 [1.03-2.06], p=0.03). Recruitment was stopped after the first planned interim analysis in February 2006 (n=150) showed that survival was longer in patients assigned placebo than in patients assigned sertraline (unadjusted hazard ratio 1.60 [95% CI 1.04-2.45], log-rank p=0.04; adjusted hazard ratio 1.62 [1.06-2.41], Cox model p=0.02). However, at the final analysis in July 2006 of all patients (n=189) and with longer follow-up, survival did not differ significantly between the treatment groups (unadjusted hazard ratio 1.35 [0.95-1.91], log-rank p=0.09; adjusted hazard ratio 1.27 [0.87-1.84], Cox model p=0.20). The trial was closed because it had ruled out a significant benefit of sertraline. INTERPRETATION: Sertraline did not improve symptoms, wellbeing, or survival in patients with advanced cancer who do not have major depression, and should be reserved for those with a proven indication.

XRCC1 codon 399 and ERCC2 codon 751 polymorphism, smoking, and drinking and risk of esophageal squamous cell carcinoma in a North Indian population.

XRCC1 (X-ray cross-complementing group 1) codon 399 and ERCC2 (excision repair cross-complementing group 2) codon 751 polymorphisms were studied in esophageal squamous cell carcinoma (ESQCC) in a North Indian population. Peripheral blood samples of 120 cases and 160 age-and-gender matching controls were collected from North India and the two polymorphisms were studied by means of polymerase chain reaction-restriction fragment length polymorphism techniques. The data were analyzed with a logistic regression model. The XRCC1 codon 399 Gln/Gln genotype was significantly associated with reduced risk of ESQCC (OR = 0.31, 95% CI = 0.12-0.78, P = 0.01). In smokers, the XRCC1 Arg/Gln genotype was marginally and statistically nonsignificantly (OR = 1.5) associated with increased risk of this cancer. In drinkers, the XRCC1 Gln/Gln genotype was significantly protective (OR = 0.06, 95% CI = 0.007-0.605, P = 0.03), whereas ERCC2 (Lys/Gln-Gln/Gln) was marginally associated with increased risk (OR = 2.1, 95% CI = 0.46-9.44). Upon analysis of gene-gene interaction, a relationship was observed, although statistically nonsignificant, between combined genotypes of XRCC1 (Arg/Gln-Gln/Gln)-ERCC2 Gln/Gln (OR = 0.33, 95% CI = 0.09-1.16) and XRCC1 (Gln/Gln)-ERCC2 (Lys/Gln) (OR = 0.36, 95% CI = 0.11-1.17) and reduced risk of ESQCC in the North Indian population. These observations suggest that the Gln/Gln genotype of XRCC1 might play an important role in DNA repair in ESQCC.