eviQ Cancer Treatments Online: Providing evidence-based information to improve cancer patient outcomes.

AIM: To understand the current usage of eviQ Cancer Treatments Online (www.eviQ.org.au), an Australian, open-access website providing evidence-based and consensus-driven cancer treatment protocols and information, and the extent to which it is meeting its intended outcomes and providing value to its users. METHODS: A mixed-method evaluation was conducted in 2020-2022 which included a review of key program documentation and website usage data, and delivery of a focused online survey to its users. RESULTS: In 2022, 329 clinicians representing all Australian states and territories contributed to eviQ content development and review. eviQ content continues to grow with a 15.2% increase in total content from 2019 to 2022.  eviQ website users continue to grow with 90,000 total monthly users in 2022, representing a 166% increase from 2018. The proportion of international users compared to Australian users continues to grow with 57% of total users in Australia and 43% international in 2022. Of 466 survey responses, the most cited reason for eviQ use was for information on side effects/toxicity (67%). Ninety-three percent (93%) of respondents either agreed or strongly agreed that eviQ contributed to both health professionals providing the best evidence-based treatment and care and improving the standardization of treatment and care provided. CONCLUSION:  eviQ is embedded in Australian clinical practice, highly valued, and relied upon by users. Users agree that eviQ has a positive impact on patients by supporting the delivery of evidence-based treatment and that eviQ contributed to patients' improved health outcomes and quality of life. eviQ's increasing international usage should be explored.

Women's Preferences for Hypofractionated Radiation Therapy for Treatment of Early-Stage Breast Cancer: A Discrete Choice Experiment.

PURPOSE: The primary treatment recommended for early-stage breast cancer is breast conserving surgery followed by external beam radiation therapy of the whole breast. Previously, radiation therapy for early-stage breast cancer was given using more fractions over longer durations. Guidelines support treatments with fewer fractions over a shorter time (hypofractionated radiation therapy). This study aimed to understand women's preferences for different features of treatments for early-stage breast cancer. METHODS AND MATERIALS: A discrete choice experiment with 12 choice tasks was conducted, describing the treatments by extent of surgery, duration of radiation treatment, need to relocate for treatment, local side effects, changes in breast appearance, costs, and difficulty with daily activities during and after treatment. Participants were women with breast cancer and from the general population. Mixed logit analyses were conducted and trade-offs between attributes estimated. RESULTS: Four hundred twenty respondents completed the discrete choice experiment. The relative importance of attributes varied by respondent characteristics; the most influential attribute for younger women was type of surgery (breast conserving surgery). Type of surgery did not influence older women's preferences. Shorter treatment duration, avoiding relocation, fewer local side effects, and less difficulty with daily activities all positively influenced treatment preference. Younger women were willing to accept 32 to 40 days of radiation treatment before a treatment that included mastectomy was potentially acceptable. CONCLUSIONS: Attributes of treatment such as duration, need for relocation, side effects, and effects on normal daily activities during and after treatment significantly influenced women's preference for treatment, including surgery. Our findings have the potential for real impact for patients and services including supporting one-on-one clinical discussions, supporting program and patient resource development, and informing service funding, organization, and delivery.

Diagnostic value of 8.5 T magnetic resonance spectroscopy of benign and malignant skin lesion biopsies.

Proton magnetic resonance spectroscopy at 8.5 T ex vivo was used to investigate skin lesions for metabolic signatures to predict malignancy or indicate malignant potential. Magnetic resonance spectroscopy was performed on biopsy tissue obtained from 63 skin lesions and five melanoma metastases from 55 patients. Samples were grouped and compared according to five clinically significant distinctions: melanoma (n=38) or nonmelanoma (n=30), primary melanoma (n=33) or secondary melanoma (involved nodes and distant metastases, n=5), primary melanoma (n=33) or nevi (n=8), malignant (n=46) or nonmalignant (n=22), and melanocytic (n=46) or nonmelanocytic (n=22). In all comparisons, the average magnetic resonance spectrum of each class lay within 1 standard deviation of the average spectrum of the other class. There was a higher average choline metabolite signal intensity in melanoma-containing biopsies compared with nonmelanoma biopsies. Discriminant analysis based on the intensity of the choline resonance alone achieved 69% accuracy in separation of melanoma and nonmelanoma tissue. Inclusion of other metabolite resonances in the analysis did not increase discrimination accuracy. Tissue heterogeneity in conventionally collected full thickness skin biopsies and possible biochemical variance within individual tissue types limit classification accuracy using the methods and magnetic field strength that were earlier reported to provide accurate discrimination in other cancer types.

Confirmation of sentinel lymph node identity by analysis of fine-needle biopsy samples using inductively coupled plasma-mass spectrometry.

BACKGROUND: The sentinel lymph node (SLN) biopsy technique is a reliable means of determining the tumor-harboring status of regional lymph nodes in melanoma patients. When technetium 99 m-labeled antimony trisulfide colloid (99 mTc-Sb2S3) particles are used to perform preoperative lymphoscintigraphy for SLN identification, they are retained in the SLN but are absent or present in only tiny amounts in non-SLNs. The present study investigated the potential for a novel means of assessing the accuracy of surgical identification of SLNs. This involved the use of inductively coupled plasma-mass spectrometry (ICP-MS) to analyze antimony concentrations in fine-needle biopsy (FNB) samples from surgically procured lymph nodes. METHODS: A total of 47 FNB samples from surgically excised lymph nodes (32 SLNs and 15 non-SLNs) were collected. The SLNs were localized by preoperative lymphoscintigraphy that used 99 mTc-Sb2S3, blue dye, and gamma probe techniques. The concentrations of antimony were measured in the FNB samples by ICP-MS. RESULTS: The mean and median antimony concentrations (in parts per billion) were .898 and .451 in the SLNs, and .015 and .068 in the non-SLNs, the differences being highly statistically significant (P < .00005). CONCLUSIONS: Our results show that ICP-MS analysis of antimony concentrations in FNB specimens from lymph nodes can accurately confirm the identity of SLNs. Used in conjunction with techniques such as proton magnetic resonance spectroscopy for the nonsurgical evaluation of SLNs, ICP-MS analysis of antimony concentrations in FNB samples could potentially serve as a minimally invasive alternative to surgery and histopathologic evaluation to objectively classify a given node as sentinel or nonsentinel and determine its tumor-harboring status.

Proton spectroscopy provides accurate pathology on biopsy and in vivo.

In the last 25 years, MR spectroscopy (MRS) has moved from being a basic research tool into routine clinical use. The spectroscopy method reports on those chemicals that are mobile on the MR time scale. Many of these chemicals reflect specific pathological processes but are complicated by the fact that many chemicals change at one time. There are currently two clinical applications for spectroscopy. The first is in the pathology laboratory, where it can be an adjunct to, and in some cases replacement, for difficult pathologies like Barrett's esophagus and follicular adenoma of the thyroid. The spectroscopy method on a breast biopsy can also report on prognostic indicators, including the potential for spread, from information present in the primary tumor alone. The second application for spectroscopy is in vivo to provide a preoperative diagnosis and this is now achievable for several organs including the prostate. The development of spectroscopy for clinical purposes has relied heavily on the serially-sectioned histopathology to confirm the high accuracy of the method. The combination of in vivo MRI, in vivo MRS, and ex vivo MRS on biopsy samples offers a modality of very high accuracy for preoperative diagnosis and provision of prognostic information for human cancers.

Magnetic resonance spectroscopy detects biochemical changes in the brain associated with chronic low back pain: a preliminary report.

Magnetic resonance (MR) spectroscopy is a noninvasive technique that can be used to detect and measure the concentration of metabolites and neurotransmitters in the brain and other organs. We used in vivo (1)H MR spectroscopy in subjects with low back pain compared with control subjects to detect alterations in biochemistry in three brain regions associated with pain processing. A pattern recognition approach was used to determine whether it was possible to discriminate accurately subjects with low back pain from control subjects based on MR spectroscopy. MR spectra were obtained from the prefrontal cortex, anterior cingulate cortex, and thalamus of 32 subjects with low back pain and 33 control subjects without pain. Spectra were analyzed and compared between groups using a pattern recognition method (Statistical Classification Strategy). Using this approach, it was possible to discriminate between subjects with low back pain and control subjects with accuracies of 100%, 99%, and 97% using spectra obtained from the anterior cingulate cortex, thalamus, and prefrontal cortex, respectively. These results demonstrate that MR spectroscopy, in combination with an appropriate pattern recognition approach, is able to detect brain biochemical changes associated with chronic pain with a high degree of accuracy.

Melanoma metastases in regional lymph nodes are accurately detected by proton magnetic resonance spectroscopy of fine-needle aspirate biopsy samples.

BACKGROUND: Nonsurgical assessment of sentinel nodes (SNs) would offer advantages over surgical SN excision by reducing morbidity and costs. Proton magnetic resonance spectroscopy (MRS) of fine-needle aspirate biopsy (FNAB) specimens identifies melanoma lymph node metastases. This study was undertaken to determine the accuracy of the MRS method and thereby establish a basis for the future development of a nonsurgical technique for assessing SNs. METHODS: FNAB samples were obtained from 118 biopsy specimens from 77 patients during SN biopsy and regional lymphadenectomy. The specimens were histologically evaluated and correlated with MRS data. Histopathologic analysis established that 56 specimens contained metastatic melanoma and that 62 specimens were benign. A linear discriminant analysis-based classifier was developed for benign tissues and metastases. RESULTS: The presence of metastatic melanoma in lymph nodes was predicted with a sensitivity of 92.9%, a specificity of 90.3%, and an accuracy of 91.5% in a primary data set. In a second data set that used FNAB samples separate from the original tissue samples, melanoma metastases were predicted with a sensitivity of 87.5%, a specificity of 90.3%, and an accuracy of 89.1%, thus supporting the reproducibility of the method. CONCLUSIONS: Proton MRS of FNAB samples may provide a robust and accurate diagnosis of metastatic disease in the regional lymph nodes of melanoma patients. These data indicate the potential for SN staging of melanoma without surgical biopsy and histopathological evaluation.

In vivo and ex vivo proton MR spectroscopy of primary and secondary melanoma.

In vivo magnetic resonance (MR) spectroscopy at 1.5T was performed on a large polypoid cutaneous melanoma, and two enlarged lymph nodes containing metastatic melanoma, from three patients. Spectra were acquired in vivo from voxels wholly within the primary tumour or secondary lymph node and were thus uncontaminated by signals from adjacent tissue. Tissue biopsies taken after resection of primary tumours and secondary lymph nodes were examined by 8.5T magnetic resonance spectroscopy (MRS) and the results compared with the in vivo spectra, and with spectra from normal skin and a benign skin lesion. There was good agreement between the dominant features of 1.5T spectra acquired in vivo and 8.5T spectra acquired from resected tissue. However, less intense resonances observed at 8.5T in malignant biopsy tissue were not consistently observed at 1.5T in vivo. In vivo spectra from primary and metastatic melanoma showed high levels of choline metabolites. An intense lactate resonance was also present in the in vivo spectrum of primary melanoma. All 8.5T spectra of biopsies from primary and secondary melanoma showed high levels of choline metabolites and lactate, and additional resonances consistent with elevated levels of taurine, alanine, lysine, and glutamate/glutamine relative to normal and benign tissue. Elevated levels of choline, lactate, taurine, and amino acids appear to be clinically useful markers for identifying the pathology of primary and metastatic melanoma.

Specificity of choline metabolites for in vivo diagnosis of breast cancer using 1H MRS at 1.5 T.

The purpose was to determine if in vivo proton magnetic resonance spectroscopy ((1)H MRS) at 1.5 T can accurately provide the correct pathology of breast disease. Forty-three asymptomatic volunteers including three lactating mothers were examined and compared with 21 breast cancer patients. Examinations were undertaken at 1.5 T using a purpose-built transmit-receive single breast coil. Single voxel spectroscopy was undertaken using echo times of 135 and 350 ms. The broad composite resonance at 3.2 ppm, which includes contributions from choline, phosphocholine (PC), glycerophosphocholine (GPC), myo-inositol and taurine, was found not to be a unique marker for malignancy providing a diagnostic sensitivity and specificity of 80.0 and 86.0%, respectively. This was due to three of the asymptomatic volunteers and all of the lactating mothers also generating the broad composite resonance at 3.2 ppm. Optimised post-acquisitional processing of the spectra resolved a resonance at 3.22 ppm, consistent with PC, in patients with cancer. In contrast the spectra recorded for three false-positive volunteers, and the three lactating mothers had a resonance centred at 3.28 ppm (possibly taurine, myo-inositol or GPC). This improved the specificity of the test to 100%. Careful referencing of the spectra and post-acquisitional processing intended to optimise spectral resolution of in vivo MR proton spectra from human breast tissue resolves the composite choline resonance. This allows the distinction of patients with malignant disease from volunteers with a sensitivity of 80% and specificity of 100%. Therefore, resolution of the composite choline resonance into its constituent components improves the specificity of the in vivo (1)H MRS method, but does not overcome the problem of 20% false-negatives.

Determination of grade and receptor status from the primary breast lesion by magnetic resonance spectroscopy.

Magnetic resonance spectra (MRS) from fine needle aspiration biopsies (FNAB) from primary breast lesions were analysed using a pattern recognition method, Statistical Classification Strategy, to assess tumor grade and oestrogen receptor (ER) and progesterone receptor (PgR) status. Grade 1 and 2 breast cancers were separated from grade 3 cancers with a sensitivity and specificity of 96% and 95%, respectively. The ER status was predicted with a sensitivity of 91% and a specificity of 90%, and the PgR status with a sensitivity of 91% and a specificity of 86%. These classifiers provide rapid and reliable, computerized information and may offer an objective method for determining these prognostic indicators simultaneously with the diagnosis of primary pathology and lymph node involvement.

Pathologic characterization of human prostate tissue with proton MR spectroscopy.

PURPOSE: To assess the accuracy of magnetic resonance (MR) spectroscopy in documenting the chemical features of human prostate tissue and to ascertain if there are chemical criteria of diagnostic importance. MATERIALS AND METHODS: Seventy-seven prostate tissue specimens (peripheral zone, n = 61; transitional zone, n = 16) from 43 patients were analyzed with MR spectroscopy. Histologic features were compared with MR spectroscopic data. Statistical analysis was undertaken with analysis of variance and computer software. RESULTS: Histologically identified carcinomas were determined by using MR spectroscopy with a sensitivity of 100% and a specificity of 94%. Histologically benign tissue from patients without carcinoma of the prostate was distinguished from malignant tissue with a sensitivity of 100% and a specificity of 94%. When benign specimens from patients with cancer elsewhere in the prostate were included in the database, MR spectroscopy helped distinguish benign prostatic hyperplasia from adenocarcinoma with a sensitivity of 97% and specificity of 88%. Depleted citrate and elevated choline levels alone were not accurate markers of malignancy, since citrate levels remain high when a small amount of malignant disease is present. Carcinomas missed at routine histologic examination were identified with MR spectroscopy and confirmed with specialized, nonstandard histologic examination. CONCLUSION: By comparing the intensity of resonances assigned to choline, creatine, lipid, and lysine, MR spectroscopy can depict prostate carcinoma with a high degree of sensitivity and specificity. Citrate and choline resonances alone are not sufficiently accurate markers for distinguishing between various patterns of prostatic disease.

Rapid detection of metastatic melanoma in lymph nodes using proton magnetic resonance spectroscopy of fine needle aspiration biopsy specimens.

Accurate staging of patients with primary cutaneous melanoma includes assessment of regional lymph nodes for the presence of micrometastatic disease. Sentinel lymph node biopsy is highly accurate but is an invasive surgical procedure with a 5-10% complication rate, and requires labour-intensive and expensive histological examination to identify disease. A rapid, accurate and cost-effective non-surgical technique able to detect micrometastatic deposits of melanoma in regional lymph nodes would be of great benefit. Fine needle aspiration biopsies and tissue specimens were obtained from lymph nodes from 18 patients undergoing node resection for metastatic melanoma and five patients undergoing radical retropubic prostatectomy. One-dimensional proton magnetic resonance spectroscopy was undertaken at 360 MHz (8.5 T). Lymph nodes were cut into 3 mm thick slices and embedded. Four sequential 5 microm tissue sections were cut from each block and stained, with haematoxylin and eosin, for S100 protein, for HMB45, and again with haematoxylin and eosin, respectively. Proton magnetic resonance spectroscopy distinguished between benign and malignant lymph node tissue (P < 0.001, separate t-test) and benign and malignant lymph node fine needle aspiration biopsy (P < 0.012) based on the ratio of the integrals of resonances from lipid/other metabolites (1.8-2.5 p.p.m. region) and 'choline' (3.1-3.3 p.p.m. region). In conclusion, one-dimensional proton magnetic resonance spectroscopy on a simple fine needle aspiration biopsy can distinguish lymph nodes containing metastatic melanoma from uninvolved nodes, providing a rapid, accurate and cost-effective non-surgical technique to assess regional lymph nodes in patients with melanoma.

Pathology of Barrett's esophagus by proton magnetic resonance spectroscopy and a statistical classification strategy.

BACKGROUND: Barrett's esophagus is thought to be a precursor of adenocarcinoma. The incidence of adenocarcinoma of the lower esophagus in the Western world is rising and accounts for more than 40% of esophageal carcinomas in males. It is not possible to identify which Barrett's patients are at high risk of developing malignancy. Here we applied a statistical classification strategy to the analysis of magnetic resonance spectroscopy and histopathological data from esophageal biopsies to ascertain whether this risk could be identified in Barrett's patients. METHODS: Tissue specimens from 72 patients (29 noncancer-bearing and 43 cancer-bearing) were analyzed by one-dimensional proton magnetic resonance spectroscopy at 8.5 Tesla. Diagnostic correlation was performed between the magnetic resonance spectra and histopathology. The magnetic resonance magnitude spectra were preprocessed, followed by identification of optimal spectral regions, and were then classified by cross-validated linear discriminant analysis of rank orders of the first derivative of magnetic resonance spectra. RESULTS: Magnetic resonance spectroscopy combined with a statistical classification strategy analysis distinguished normal esophagus from adenocarcinoma and Barrett's epithelium with an accuracy of 100%. Barrett's epithelium and adenocarcinoma were distinguished with an accuracy of 98.6% but only when 4 of the Barrett's specimens and 7 of the carcinoma specimens, determined to be "fuzzy" (ie, unable to be accurately assigned to either class) were withdrawn. The 7 cancer and 4 Barrett's specimens, determined to be "fuzzy" using the Barrett's versus cancer (B versus C) classifier, were submitted to the other two classifiers (Barrett's versus normal [B versus N] and normal versus cancer [N versus C], respectively). The 4 Barrett's specimens were assigned to Barrett's by the N versus B classifier and to normal (n = 2) or cancer (n = 2) classes by the N versus C classifier. The 7 cancer specimens were crisply assigned to the cancer class (N versus C), or for the B versus N classifier, to the Barrett's class (ie, more similar to Barrett's than to normal tissue). Visual inspection of the spectra from histologically identified Barrett's epithelium showed a gradation from normal to carcinoma. CONCLUSIONS: Proton magnetic resonance spectroscopy of esophageal biopsies combined with a statistical classification strategy data analysis provides a robust diagnosis with a high degree of accuracy for discriminating normal epithelium from esophageal adenocarcinoma and Barrett's esophagus. Different spectral categories of Barrett's epithelium were identified both by visual inspection and by statistical classification strategy, possibly reflecting the risk of future malignant transformation.

Pathology of hepatocellular carcinoma and its precursors using proton magnetic resonance spectroscopy and a statistical classification strategy.

AIM: Apply the statistical classification strategy (SCS) to magnetic resonance spectroscopy (MRS) data from liver biopsies and test its potential to discriminate between normal liver, cirrhotic nodules and nodules of hepatocellular carcinoma with a high degree of accuracy. METHODS: Liver tissue specimens from 54 patients undergoing either partial (hemi) or total hepatectomy were analysed by one-dimensional proton MRS at 8.5 Tesla. Histologically, these specimens were confirmed as normal (n=31), cirrhotic (n=59), and hepatocellular carcinoma (HCC, n=32). Diagnostic correlation was performed between the MR spectra and histopathology. An SCS was applied consisting of pre-processing MR magnitude spectra to identify spectral regions of maximal discriminatory value, and cross-validated linear discriminant analysis. RESULTS: SCS applied to MRS data distinguished normal liver tissue from HCC with an accuracy of 100%. Normal liver tissue was distinguished from cirrhotic liver with an accuracy of 92% and cirrhotic liver was distinguished from HCC with an accuracy of 98%. CONCLUSIONS: SCS applied to proton MRS of liver biopsies provides a robust method to distinguish, with a high degree of accuracy, HCC from both cirrhotic and normal liver.