Changes in New Patient Consultations During the COVID-19 Pandemic at a Canadian Comprehensive Cancer Center.

BACKGROUND: The impact of COVID-19 pandemic-related disruptions on cancer services is emerging. We evaluated the impact of the first 2 years of the pandemic on new patient consultations for all cancers at a comprehensive cancer center within a publicly funded health care system and assessed whether there was evidence of stage shift. METHODS: We performed a retrospective study using the Princess Margaret Cancer Registry. New consultations with medical, radiation, or surgical oncology were categorized by year and quarter. Logistic regression was used to assess the effect of period before and during the COVID-19 pandemic on cancer stage at consultation, adjusting for age, sex, and diagnosis location (our hospital network vs elsewhere). RESULTS: In all, 53,759 new patient consultations occurred from January 1, 2018, to June 30, 2022. After the pandemic was declared, there was a decrease in all types of consultations by 43.3% in the second quarter of 2020, and referral volumes did not recover during the first year. There was no evidence of stage shift for all cancer types during the later quarters of the pandemic for the overall population. CONCLUSIONS: New patient consultations decreased across cancer stages, referral type, and most disease sites at our tertiary cancer center. We did not observe evidence of stage shift in this population. Further research is needed to determine whether this reflects the resilience of our health care system in maintaining cancer services or a delay in the presentation of advanced cancer cases. These data are important for shaping future cancer care delivery and recovery strategies.

Telemedicine-enabled biofeedback electropalatography rehabilitation (TEBER): A pilot study for patients treated with surgery for oral cavity carcinoma.

BACKGROUND: To address the rehabilitative barriers to frequency and precision of care, we conducted a pilot study of a biofeedback electropalatography (EPG) device paired with telemedicine for patients who underwent primary surgery +/- adjuvant radiation for oral cavity carcinoma. We hypothesized that lingual optimization followed by telemedicine-enabled biofeedback electropalatography rehabilitation (TEBER) would further improve speech and swallowing outcomes after "standard-of-care" SOC rehabilitation. METHOD: Pilot prospective 8-week (TEBER) program following 8 weeks of (SOC) rehabilitation. RESULTS: Twenty-seven patients were included and 11 completed the protocol. When examining the benefit of TEBER independent of standard of care, "range-of-liquids" improved by +0.36 [95% CI, 0.02-0.70, p = 0.05] and "range-of-solids" improved by +0.73 [95% CI, 0.12-1.34, p = 0.03]. There was a positive trend toward better oral cavity obliteration; residual volume decreased by -1.2 [95% CI, -2.45 to 0.053, p = 0.06], and "nutritional-mode" increased by +0.55 [95% CI, -0.15 to 1.24, p = 0.08]. CONCLUSION: This pilot suggests that TEBER bolsters oral rehabilitation after 8 weeks of SOC lingual range of motion.

Multiple catechols in human plasma after drinking caffeinated or decaffeinated coffee.

BACKGROUND: Coffee is one of the most frequently consumed beverages worldwide. Research on effects of coffee drinking has focused on caffeine; however, coffee contains myriad biochemicals that are chemically unrelated to caffeine, including 3,4-dihydroxyphenyl compounds (catechols) such as caffeic acid and dihydrocaffeic acid (DHCA). OBJECTIVE: This prospective within-subjects study examined effects of drinking caffeinated or decaffeinated coffee on plasma free (unconjugated) catechols measured by liquid chromatography with series electrochemical detection (LCED) after batch alumina extraction. To confirm coffee-related chromatographic peaks represented catechols, plasma was incubated with catechol-O-methyltransferase and S-adenosylmethionine before the alumina extraction; reductions in peak heights would identify catechols. METHODS: Ten healthy volunteers drank 2 cups each of caffeinated and decaffeinated coffee on separate days after fasting overnight. With subjects supine, blood was drawn through an intravenous catheter up to 240 min after coffee ingestion and the plasma assayed by alumina extraction followed by LCED. RESULTS: Within 15 min of drinking coffee of either type, >20 additional peaks were noted in chromatographs from the alumina eluates. Most of the coffee-related peaks corresponded to free catechols. Plasma levels of the catecholamines epinephrine and dopamine increased with both caffeinated and decaffeinated coffee. Levels of other endogenous catechols were unaffected. Plasma DHCA increased bi-phasically, in contrast with other coffee-related free catechols. INTERPRETATION: Drinking coffee-whether caffeinated or decaffeinated-results in the rapid appearance of numerous free catechols in the plasma. These might affect the disposition of circulating catecholamines. The bi-phasic increase in plasma DHCA is consistent with production by gut bacteria.

Precision genetic cellular models identify therapies protective against ER stress.

Rare monogenic disorders often share molecular etiologies involved in the pathogenesis of common diseases. Congenital disorders of glycosylation (CDG) and deglycosylation (CDDG) are rare pediatric disorders with symptoms that range from mild to life threatening. A biological mechanism shared among CDG and CDDG as well as more common neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral sclerosis, is endoplasmic reticulum (ER) stress. We developed isogenic human cellular models of two types of CDG and the only known CDDG to discover drugs that can alleviate ER stress. Systematic phenotyping confirmed ER stress and identified elevated autophagy among other phenotypes in each model. We screened 1049 compounds and scored their ability to correct aberrant morphology in each model using an agnostic cell-painting assay based on >300 cellular features. This primary screen identified multiple compounds able to correct morphological phenotypes. Independent validation shows they also correct cellular phenotypes and alleviate each of the ER stress markers identified in each model. Many of the active compounds are associated with microtubule dynamics, which points to new therapeutic opportunities for both rare and more common disorders presenting with ER stress, such as Alzheimer's disease and amyotrophic lateral sclerosis.

AGITG MASTERPLAN: a randomised phase II study of modified FOLFIRINOX alone or in combination with stereotactic body radiotherapy for patients with high-risk and locally advanced pancreatic cancer.

BACKGROUND: Among patients with non-metastatic pancreatic cancer, 80% have high-risk, borderline resectable or locally advanced cancer, with a 5-year overall survival of 12%. MASTERPLAN evaluates the safety and activity of stereotactic body radiotherapy (SBRT) in addition to chemotherapy in these patients. METHODS AND DESIGN: MASTERPLAN is a multi-centre randomised phase II trial of 120 patients with histologically confirmed potentially operable pancreatic cancer (POPC) or inoperable pancreatic cancer (IPC). POPC includes patients with borderline resectable or high-risk tumours; IPC is defined as locally advanced or medically inoperable pancreatic cancer. Randomisation is 2:1 to chemotherapy + SBRT (investigational arm) or chemotherapy alone (control arm) by minimisation and stratified by patient cohort (POPC v IPC), planned induction chemotherapy and institution. Chemotherapy can have been commenced ≤28 days prior to randomisation. Both arms receive 6 × 2 weekly cycles of modified FOLFIRINOX (oxaliplatin (85 mg/m2 IV), irinotecan (150 mg/m2), 5-fluorouracil (2400 mg/m2 CIV), leucovorin (50 mg IV bolus)) plus SBRT in the investigational arm. Gemcitabine+nab-paclitaxel is permitted for patients unsuitable for mFOLFIRINOX. SBRT is 40Gy in five fractions with planning quality assurance to occur in real time. Following initial chemotherapy ± SBRT, resectability will be evaluated. For resected patients, adjuvant chemotherapy is six cycles of mFOLFIRINOX. Where gemcitabine+nab-paclitaxel was used initially, the adjuvant treatment is 12 weeks of gemcitabine and capecitabine or mFOLFIRINOX. Unresectable or medically inoperable patients with stable/responding disease will continue with a further six cycles of mFOLFIRINOX or three cycles of gemcitabine+nab-paclitaxel, whatever was used initially. The primary endpoint is 12-month locoregional control. Secondary endpoints are safety, surgical morbidity and mortality, radiological response rates, progression-free survival, pathological response rates, surgical resection rates, R0 resection rate, quality of life, deterioration-free survival and overall survival. Tertiary/correlative objectives are radiological measures of nutrition and sarcopenia, and serial tissue, blood and microbiome samples to be assessed for associations between clinical endpoints and potential predictive/prognostic biomarkers. Interim analysis will review rates of locoregional recurrence, distant failure and death after 40 patients complete 12 months follow-up. Fifteen Australian and New Zealand sites will recruit over a 4-year period, with minimum follow-up period of 12 months. DISCUSSION: MASTERPLAN evaluates SBRT in both resectable and unresectable patients with pancreatic ductal adenocarcinoma. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ACTRN12619000409178 , 13/03/2019. Protocol version: 2.0, 19 May 2019.

Preclinical Mechanisms of Topical PRN473, a Bruton Tyrosine Kinase Inhibitor, in Immune-Mediated Skin Disease Models.

The expression of Bruton tyrosine kinase (BTK) in B cells and innate immune cells provides essential downstream signaling for BCR, Fc receptors, and other innate immune cell pathways. The topical covalent BTK inhibitor PRN473 has shown durable, reversible BTK occupancy with rapid on-rate and slow off-rate binding kinetics and long residence time, resulting in prolonged, localized efficacy with low systemic exposure in vivo. Mechanisms of PRN473 include inhibition of IgE (FcεR)-mediated activation of mast cells and basophils, IgG (FcγR)-mediated activation of monocytes, and neutrophil migration. In vivo, oral PRN473 was efficacious and well tolerated in the treatment of canine pemphigus foliaceus. In this study, we evaluated in vitro selectivity and functionality, in vivo skin Ab inflammatory responses, and systemic pharmacology with topically administered PRN473. Significant dose-dependent inhibition of IgG-mediated passive Arthus reaction in rats was observed with topical PRN473 and was maintained when given 16 h prior to challenge, reinforcing extended activity with once-daily administration. Similarly, topical PRN473 resulted in significant dose-dependent inhibition of the mouse passive cutaneous anaphylaxis IgE-mediated reaction. Multiday treatment with topical PRN473 in rodents resulted in low-to-no systemic accumulation, suggesting that efficacy was mainly due to localized exposure. Reduced skin Ab inflammatory activity was also confirmed with oral PRN473. These preclinical studies provide a strong biologic basis for targeting innate immune cell responses locally in the skin, with rapid onset of action following once-daily topical PRN473 administration and minimal systemic exposure. Dose-dependent inhibition in these preclinical models of immune-mediated skin diseases support future clinical studies.

Patients' Preferences for 3 Months vs 6 Months of Adjuvant Chemotherapy for Colon Cancer.

Background: SCOT was an international, randomized phase 3 trial of 3 months vs 6 months of adjuvant chemotherapy with oxaliplatin and a fluoropyrimidine in patients with colorectal cancer. We sought patients' preferences for 3 months vs 6 months of adjuvant chemotherapy in the SCOT trial. Methods: SCOT participants from Australia and New Zealand completed a validated questionnaire (at 3 and 18 months) to elicit the minimum survival benefits judged necessary to make an extra 3 months of adjuvant chemotherapy worthwhile, based on their experience. Standardized hypothetical scenarios used the following baseline survivals (with 3 months of chemotherapy): life expectancies (LE) of 5 years and 15 years and 5-year survival rates (5YS) of 65% and 85%. Results: Of the 160 participants, 82 were assigned 3 months adjuvant chemotherapy, and 78 were assigned 6 months. Adjuvant chemotherapy was FOLFOX in 121 (75.6%) and XELOX in 39 (24.4%). Preferences varied substantially and did not differ according to treatment group. The median survival benefits judged necessary to make the extra 3 months of chemotherapy worthwhile were an extra 3 years beyond a LE of 5 years; 3 years beyond a LE of 15 years; 15% beyond a 5YS of 65%; and 5% beyond a 5YS of 85%. Preferences were similar at 3 months and 18 months. Preferences were not predicted by participants' baseline characteristics. Conclusion: Preferences varied substantially, and the benefits many required to warrant an extra 3 months of adjuvant chemotherapy were larger than the benefits of an extra 3 months of chemotherapy calculated in the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) meta-analysis.

Preclinical Efficacy and Anti-Inflammatory Mechanisms of Action of the Bruton Tyrosine Kinase Inhibitor Rilzabrutinib for Immune-Mediated Disease.

Bruton tyrosine kinase (BTK) is expressed in B cells and innate immune cells, acting as an essential signaling element in multiple immune cell pathways. Selective BTK inhibition has the potential to target multiple immune-mediated disease pathways. Rilzabrutinib is an oral, reversible, covalent BTK inhibitor designed for immune-mediated diseases. We examined the pharmacodynamic profile of rilzabrutinib and its preclinical mechanisms of action. In addition to potent and selective BTK enzyme and cellular activity, rilzabrutinib inhibited activation and inflammatory activities of B cells and innate cells such as macrophages, basophils, mast cells, and neutrophils, without cell death (in human and rodent assay systems). Rilzabrutinib demonstrated dose-dependent improvement of clinical scores and joint pathology in a rat model of collagen-induced arthritis and demonstrated reductions in autoantibody-mediated FcγR signaling in vitro and in vivo, with blockade of rat Arthus reaction, kidney protection in mouse Ab-induced nephritis, and reduction in platelet loss in mouse immune thrombocytopenia. Additionally, rilzabrutinib inhibited IgE-mediated, FcεR-dependent immune mechanisms in human basophils and mast cell-dependent mouse models. In canines with naturally occurring pemphigus, rilzabrutinib treatment resulted in rapid clinical improvement demonstrated by anti-inflammatory effects visible within 2 wk and all animals proceeding to complete or substantial disease control. Rilzabrutinib is characterized by reversible covalent BTK binding, long BTK residence time with low systemic exposure, and multiple mechanistic and biological effects on immune cells. Rilzabrutinib's unique characteristics and promising efficacy and safety profile support clinical development of rilzabrutinib for a broad array of immune-mediated diseases.

Non-operative management for oral cavity carcinoma: Definitive radiation therapy as a potential alternative treatment approach.

PURPOSE: To determine the outcomes of oral cavity squamous cell cancer (OSCC) patients treated with non-surgical approach i.e. definitive intensity-modulated radiation therapy (IMRT). METHODS: All OSCC patients treated radically with IMRT (without primary surgery) between 2005-2014 were reviewed in a prospectively collected database. OSCC patients treated with definitive RT received concurrent chemotherapy except for early stage patients or those who declined or were unfit for chemotherapy. The 5-year local, and regional, distant control rates, disease-free, overall, and cancer-specific survival, and late toxicity were analyzed. RESULTS: Among 1316 OSCC patients treated with curative-intent; 108 patients (8%) received non-operative management due to: medical inoperability (n = 14, 13%), surgical unresectability (n = 8, 7%), patient declined surgery (n = 15, 14%), attempted preservation of oral structure/function in view of required extensive surgery (n = 53, 49%) or extensive oropharyngeal involvement (n = 18, 17%). Sixty-eight (63%) were cT3-4, 38 (35%) were cN2-3, and 38 (35%) received concurrent chemotherapy. With a median follow-up of 52 months, the 5-year local, regional, distant control rate, disease-free, overall, and cancer-specific survival were 78%, 92%, 90%, 42%, 50%, and 76% respectively. Patients with cN2-3 had higher rate of 5-year distant metastasis (24% vs 3%, p = 0.001), with detrimental impact on DFS (p = 0.03) and OS (p < 0.02) on multivariable analysis. Grade ≥ 3 late toxicity was reported in 9% of patients (most common: grade 3 osteoradionecrosis in 6%). CONCLUSIONS: Non-operative management of OSCC resulted in a meaningful rate of locoregional control, and could be an alternative curative approach when primary surgery would be declined, unsuitable or unacceptably delayed.

A Systematic Review and Meta-Analysis of the Diagnostic Performance of BRAF V600E Immunohistochemistry in Thyroid Histopathology.

Immunohistochemistry (IHC) in evaluating thyroid surgical specimens may facilitate diagnostic and prognostic evaluation, with potential therapeutic implications. We performed a systematic review and meta-analysis examining the analytic validity of IHC in detecting BRAFV600E mutations in thyroid cancer (primary or metastatic). We screened citations from three electronic databases (until December 20, 2018), supplemented by a hand search of authors' files and cross-references of reviews. Citations and full-text papers were independently reviewed in duplicate, and consensus was achieved on inclusion of papers. Two reviewers independently critically appraised and abstracted data from included papers. Random-effect meta-analyses were conducted for sensitivity and specificity estimates. We reviewed 1499 unique citations and 93 full-text articles. We included 1 systematic review and 30 original articles. The published review (from 2015) needed to be updated as there were multiple subsequent original studies. The pooled sensitivity of IHC in detecting a BRAFV600E mutation was 96.8% (95% confidence interval [CI] at 94.1%, 98.3%) (29 studies, including 2659 BRAFV600E mutant tumors). The IHC pooled specificity was 86.3% (95% CI 80.7%, 90.4%) (28 studies, including 1107 BRAFV600E wild-type specimens). These meta-analyses were subject to statistically significant heterogeneity, partly explained by antibody type (sensitivity and specificity) and tissue/tumor type (specificity). In conclusion, BRAF IHC is highly sensitive and reasonably specific in detecting the BRAFV600E mutation; however, there is some variability in analytic performance.

The Impact of Positive Resection Margins on Survival and Recurrence Following Resection and Adjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma.

OBJECTIVE AND BACKGROUND: Local and distant disease recurrence are frequently observed following pancreatic cancer resection, but an improved understanding of resection margin assessment is required to aid tailored therapies. METHODS: Analyses were carried out to assess the association between clinical characteristics and margin involvement as well as the effects of individual margin involvement on site of recurrence and overall and recurrence-free survival using individual patient data from the European Study Group for Pancreatic Cancer (ESPAC)-3 randomized controlled trial. RESULTS: There were 1151 patients, of whom 505 (43.9%) had an R1 resection. The median and 95% confidence interval (CI) overall survival was 24.9 (22.9-27.2) months for 646 (56.1%) patients with resection margin negative (R0 >1 mm) tumors, 25.4 (21.6-30.4) months for 146 (12.7%) patients with R1<1 mm positive resection margins, and 18.7 (17.2-21.1) months for 359 (31.2%) patients with R1-direct positive margins (P < 0.001). In multivariable analysis, overall R1-direct tumor margins, poor tumor differentiation, positive lymph node status, WHO performance status ≥1, maximum tumor size, and R1-direct posterior resection margin were all independently significantly associated with reduced overall and recurrence-free survival. Competing risks analysis showed that overall R1-direct positive resection margin status, positive lymph node status, WHO performance status 1, and R1-direct positive superior mesenteric/medial margin resection status were all significantly associated with local recurrence. CONCLUSIONS: R1-direct resections were associated with significantly reduced overall and recurrence-free survival following pancreatic cancer resection. Resection margin involvement was also associated with an increased risk for local recurrence.

A Systematic Review and Meta-Analysis of Subsequent Malignant Neoplasm Risk After Radioactive Iodine Treatment of Thyroid Cancer.

Background: The potential risk of subsequent malignant neoplasms (SMNs) after radioactive iodine (RAI) treatment of thyroid cancer (TC) is an important concern. Methods: A systematic review was updated comparing the risk of SMNs in TC patients treated with RAI to TC patients without RAI. Six electronic databases were searched (up to March, 2018), supplemented with a hand search. Two reviewers independently screened citations, reviewed full-text papers, and critically appraised/abstracted data. Random-effects meta-analyses were conducted using crude data and data statistically adjusted for confounders. The outcomes were any SMN and specific SMNs for which sufficient data were available. Results: In total, 3506 unique electronic search citations and 93 full-text papers were examined, including 17 studies (3 systematic reviews and 14 original studies). Published knowledge syntheses were limited by inclusion of small numbers of studies, with two systematic reviews suggesting an increased risk of any SMN and one meta-analysis suggesting a reduced risk of breast SMN after RAI treatment. In a meta-analysis of crude data, the risk ratio of any SMN in RAI-treated TC patients was 0.98 ([confidence interval (CI) 0.76-1.27]; n = 10 studies of 65,539 individuals, heterogeneity Q = 64.26, degrees of freedom [df] = 9, p < 0.001, I2 = 85.99). The pooled risk ratio for any SMN, adjusted for confounders, was 1.16 ([CI 0.97-1.39]; n = 6 studies, data from at least 11,241 TC patients, Q = 10.86, df = 5, p = 0.054, I2 = 53.96). In secondary analyses examining specific SMNs, although relatively rare, the risk of subsequent leukemia was increased, but the risk of multiple myeloma was reduced in RAI-treated TC patients. There was no significant increased relative risk of breast cancer, salivary cancer, or combined hematologic malignancies according to RAI treatment status. Conclusions: The body of evidence on whether 131I treatment of thyroid cancer is associated with the primary outcome of any SMN is highly heterogeneous and complex. More research examining the long-term risk of specific SMNs after 131I treatment is needed.

Cerebrospinal Fluid-Directed rAAV9-rsATP7A Plus Subcutaneous Copper Histidinate Advance Survival and Outcomes in a Menkes Disease Mouse Model.

Menkes disease is a lethal neurodegenerative disorder of copper metabolism caused by mutations in an evolutionarily conserved copper transporter, ATP7A. Based on our prior clinical and animal studies, we seek to develop a therapeutic approach suitable for application in affected human subjects, using the mottled-brindled (mo-br) mouse model that closely mimics the Menkes disease biochemical and clinical phenotypes. Here, we evaluate the efficacy of low-, intermediate-, and high-dose recombinant adeno-associated virus serotype 9 (rAAV9)-ATP7A delivered to the cerebrospinal fluid (CSF), in combination with subcutaneous administration of clinical-grade copper histidinate (sc CuHis, IND #34,166). Mutant mice that received high-dose (1.6 × 1010 vg) cerebrospinal fluid-directed rAAV9-rsATP7A plus sc copper histidinate showed 53.3% long-term (≥300-day) survival compared to 0% without treatment or with either treatment alone. The high-dose rAAV9-rsATP7A plus sc copper histidinate-treated mutant mice showed increased brain copper levels, normalized brain neurochemical levels, improvement of brain mitochondrial abnormalities, and normal growth and neurobehavioral outcomes. This synergistic treatment effect represents the most successful rescue to date of the mo-br mouse model. Based on these findings, and the absence of a large animal model, we propose cerebrospinal fluid-directed rAAV9-rsATP7A gene therapy plus subcutaneous copper histidinate as a potential therapeutic approach to cure or ameliorate Menkes disease.

A Systematic Review of Unmet Information and Psychosocial Support Needs of Adults Diagnosed with Thyroid Cancer.

BACKGROUND: Patient education and psychosocial support to patients are important elements of comprehensive cancer care, but the needs of thyroid cancer survivors are not well understood. METHODS: The published English-language quantitative literature on (i) unmet medical information and (ii) psychosocial support needs of thyroid cancer survivors was systematically reviewed. A librarian information specialist searched seven electronic databases and a hand search was conducted. Two reviewers independently screened citations from the electronic search and reviewed relevant full-text papers. There was consensus between reviewers on the included papers, and duplicate independent abstraction was performed. The results were summarized descriptively. RESULTS: A total of 1984 unique electronic citations were screened, and 51 full-text studies were reviewed (three from the hand search). Seven cross-sectional, single-arm, survey studies were included, containing data from 6215 thyroid cancer survivor respondents. The respective study sizes ranged from 57 to 2398 subjects. All of the studies had some methodological limitations. Unmet information needs were variable relating to the disease, diagnostic tests, treatments, and co-ordination of medical care. There were relatively high unmet information needs related to aftercare (especially long-term effects of the disease or its treatment and its management) and psychosocial concerns (including practical and financial matters). Psychosocial support needs were incompletely met. Patient information on complementary and alternative medicine was very limited. CONCLUSIONS: In conclusion, thyroid cancer survivors perceive many unmet information needs, and these needs extend to aftercare. Psychosocial information and supportive care needs may be insufficiently met in this population. More work is needed to improve knowledge translation and psychosocial support for thyroid cancer survivors.

The Impact of Mismatch Repair Status in Colorectal Cancer on the Decision to Treat With Adjuvant Chemotherapy: An Australian Population-Based Multicenter Study.

BACKGROUND: Testing for mismatch repair (MMR) status in colorectal cancer (CRC) may provide useful prognostic and predictive information. We evaluated the impact of such testing on real-world practice regarding adjuvant chemotherapy for patients with resected CRC. PATIENTS AND METHODS: A total of 175 patients with stage II and III mismatch repair-deficient (MMRD) CRC were identified from an Australian population-based study of incident CRCs. Their treatment decisions were compared with those for a cohort of 773 stage-matched patients with mismatch repair-proficient (MMRP) CRCs. The effect of MMR status, age, and pathologic characteristics on treatment decisions was determined using multiple regression analysis. RESULTS: Overall, 32% of patients in stage II and 71% of patients in stage III received adjuvant chemotherapy. Among the stage II patients, those with MMRD cancer were less likely to receive chemotherapy than were MMRP cases (15% vs. 38%; p < .0001). In this group, the treatment decision was influenced by age, tumor location, and T stage. MMR status influenced the treatment decision such that its impact diminished with increasing patient age. Among patients with stage III tumors, no difference was found in the chemotherapy rates between the MMRD and MMRP cases. In this group, age was the only significant predictor of the treatment decision. CONCLUSION: The findings of this study suggest that knowledge of the MMR status of sporadic CRC influences treatment decisions for stage II patients, in an era when clear recommendations as to how these findings should influence practice are lacking. IMPLICATIONS FOR PRACTICE: Microsatellite instability (MSI) is a molecular marker of defective DNA mismatch repair found in 15% of sporadic colorectal cancers. Until recently, expert guidelines on the role of MSI as a valid biomarker in the selection of stage II patients for adjuvant chemotherapy were lacking. Conducted at a time when the clinical utility of routine MSI testing was unclear, this study found that clinicians were influenced by MSI status in selecting stage II patients for chemotherapy. Furthermore, the impact of MSI on treatment decisions was greatest in younger patients and declined progressively until age 80 years, when no effect was found.

A tsunami of unmet needs: pancreatic and ampullary cancer patients' supportive care needs and use of community and allied health services.

OBJECTIVE: People diagnosed with pancreatic cancer have the worst survival prognosis of any cancer. No previous research has documented the supportive care needs of this population. Our objective was to describe people's needs and use of support services and to examine whether these differed according to whether or not patients had undergone surgical resection. METHODS: Queensland pancreatic or ampullary cancer patients (n = 136, 54% of those eligible) completed a survey, which assessed 34 needs across five domains (Supportive Care Needs Survey-Short Form) and use of health services. Differences by resection were compared with Chi-squared tests. RESULTS: Overall, 96% of participants reported having some needs. More than half reported moderate-to-high unmet physical (54%) or psychological (52%) needs, whereas health system/information (32%), patient care (21%) and sexuality needs (16%) were described less frequently. The three most frequently reported moderate-to-high needs included 'not being able to do things they used to do' (41%), 'concerns about the worries of those close' (37%) and 'uncertainty about the future' (30%). Patients with non-resectable disease reported greater individual information needs, but their needs were otherwise similar to patients with resectable disease. Self-reported use of support was low; only 35% accessed information, 28%, 18% and 15% consulted a dietician, complementary medicine practitioner or mental health practitioner, respectively. Palliative care access was greater (59% vs 27%) among those with non-resectable disease. CONCLUSION: Very high levels of needs were reported by people with pancreatic or ampullary cancer. Future work needs to elucidate why uptake of appropriate supportive care is low and which services are required.

Time to Definitive Failure to the First Tyrosine Kinase Inhibitor in Localized GI Stromal Tumors Treated With Imatinib As an Adjuvant: A European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Intergroup Randomized Trial in Collaboration With the Australasian Gastro-Intestinal Trials Group, UNICANCER, French Sarcoma Group, Italian Sarcoma Group, and Spanish Group for Research on Sarcomas.

PURPOSE: In 2004, we started an intergroup randomized trial of adjuvant imatinib versus no further therapy after R0-R1 surgery patients with localized, high- or intermediate-risk GI stromal tumor (GIST). PATIENTS AND METHODS: Patients were randomly assigned to 2 years of imatinib 400 mg daily or no further therapy after surgery. The primary end point was overall survival; relapse-free survival (RFS), relapse-free interval, and toxicity were secondary end points. In 2009, given the concurrent improvement in prognosis of patients with advanced GIST, we changed the primary end point to imatinib failure-free survival (IFFS), with agreement of the independent data monitoring committee. We report on a planned interim analysis. RESULTS: A total of 908 patients were randomly assigned between December 2004 and October 2008: 454 to imatinib and 454 to observation. Of these, 835 patients were eligible. With a median follow-up of 4.7 years, 5-year IFFS was 87% in the imatinib arm versus 84% in the control arm (hazard ratio, 0.79; 98.5% CI, 0.50 to 1.25; P = .21); RFS was 84% versus 66% at 3 years and 69% versus 63% at 5 years (log-rank P < .001); and 5-year overall survival was 100% versus 99%, respectively. Among 528 patients with high-risk GIST by local pathologist, 5-year IFFS was 79% versus 73%; among 336 centrally reviewed high-risk patients, it was 77% versus 73%, respectively. CONCLUSION: This study confirms that adjuvant imatinib has an overt impact on RFS. No significant difference in IFFS was observed, although in the high-risk subgroup there was a trend in favor of the adjuvant arm. IFFS was conceived as a potential end point in the adjuvant setting because it is sensitive to secondary resistance, which is the main adverse prognostic factor in patients with advanced GIST.

Cancer of unknown primary site.

BACKGROUND: Cancer of unknown primary (CUP) is the diagnosis given to patients with metastatic cancer with no known site of origin. OBJECTIVE: This review summarises the current knowledge regarding the epidemiology, diagnosis, treatment and care of CUP. DISCUSSION: The incidence and mortality rates of CUP are declining in Australia. CUP was the twelfth most common cancer and fifth most common cause of cancer death in 2011. Smoking is the only identified risk factor. Incidence patterns implicate reduced access to healthcare and many registered cases have only a clinical diagnosis. Favourable prognosis subtypes with specific clinical and histopathological criteria must be recognised and treated on the basis of the presumed primary site. Emerging data reveal high rates of emergency department admission, hospitalisations and psychological distress, and low rates of specialist consultations for patients with CUP. General practitioners (GPs) have a key role in earlier identification, integrated care and preventing patients with CUP from falling through the cracks.

Decision aid on radioactive iodine treatment for early stage papillary thyroid cancer: update to study protocol with follow-up extension.

BACKGROUND: Patient decision aids (P-DAs) are used to inform patients about healthcare choices, but there is limited knowledge about their longer term effects, beyond the time period of decision-making. METHODS/DESIGN: We developed a computerized P-DA that explains the choice of radioactive iodine (RAI) adjuvant treatment or no RAI, for patients with low risk papillary thyroid cancer after total thyroidectomy. The original protocol for a randomized controlled trial, comparing the use of the P-DA (with usual care) to usual care alone, has been published in Trials http://www.trialsjournal.com/content/11/1/81. We found that P-DA (with usual care) significantly improved patients' medical knowledge at the time of decision-making (primary outcome) compared to usual care alone (control). In this update, we present the protocol for an extended follow-up study (15 to 23 months post-randomization), including qualitative and quantitative methods. The patient outcomes evaluated using quantitative questionnaires include: the degree to which patients feel well-informed about their RAI treatment choice, decision satisfaction, decision regret, cancer-related worry, mood, and trust in the treating physician. The qualitative component explores the experiences of RAI treatment decision-making, treatment satisfaction, and trial participation in a representative subgroup of patients. Extended follow-up study results will be described for the entire study population, and data will be compared between the P-DA and control groups. RESULT AND CONCLUSION: This mixed methods extended follow-up study will provide data on long term outcomes, relating to the use of a computerized P-DA in decision-making about adjuvant RAI treatment in early stage papillary thyroid cancer. DISCUSSION: Our results are intended to inform future research in this area, particularly relating to long term effects of the use of P-DAs in making healthcare choices. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01083550, registered 24 February 2010 and last updated 5 January 2015.

Exploring the relationship between patients' information preference style and knowledge acquisition process in a computerized patient decision aid randomized controlled trial.

BACKGROUND: We have shown in a randomized controlled trial that a computerized patient decision aid (P-DA) improves medical knowledge and reduces decisional conflict, in early stage papillary thyroid cancer patients considering adjuvant radioactive iodine treatment. Our objectives were to examine the relationship between participants' baseline information preference style and the following: 1) quantity of detailed information obtained within the P-DA, and 2) medical knowledge. METHODS: We randomized participants to exposure to a one-time viewing of a computerized P-DA (with usual care) or usual care alone. In pre-planned secondary analyses, we examined the relationship between information preference style (Miller Behavioural Style Scale, including respective monitoring [information seeking preference] and blunting [information avoidance preference] subscale scores) and the following: 1) the quantity of detailed information obtained from the P-DA (number of supplemental information clicks), and 2) medical knowledge. Spearman correlation values were calculated to quantify relationships, in the entire study population and respective study arms. RESULTS: In the 37 P-DA users, high monitoring information preference was moderately positively correlated with higher frequency of detailed information acquisition in the P-DA (r = 0.414, p = 0.011). The monitoring subscale score weakly correlated with increased medical knowledge in the entire study population (r = 0.268, p = 0.021, N = 74), but not in the respective study arms. There were no significant associations with the blunting subscale score. CONCLUSIONS: Individual variability in information preferences may affect the process of information acquisition from computerized P-DA's. More research is needed to understand how individual information preferences may impact medical knowledge acquisition and decision-making.