Validation of the Prognostic Utility of ESTRO/EORTC Oligometastatic Disease Classification: A Secondary Analysis From the Population-Based Phase II SABR-5 Trial.

PURPOSE: The recently developed European Society for Radiotherapy and Oncology (ESTRO)/European Organization for Research and Treatment of Cancer (EORTC) oligometastatic disease (OMD) classification has not been validated in terms of its prognostic significance. This study stratified patients from the phase II SABR-5 trial based on ESTRO/EORTC criteria and compared progression-free survival (PFS) and overall survival (OS) to determine the prognostic significance of the classification scheme. METHODS AND MATERIALS: The SABR-5 trial was a single arm phase II study conducted at the 6 regional cancer centers across British Columbia (BC), Canada, where SABR for oligometastases was only offered on trial. Patients with up to 5 oligometastases (total or not controlled by prior treatment and including induced OMD) underwent SABR to all lesions. Patients were 18 years of age or older, Eastern Cooperative Oncology Group 0 to 2, and life expectancy ≥6 months. PFS and OS were calculated using the Kaplan-Meier method and differences between OMD groups were assessed with log-rank tests. Univariable and multivariable analyses were performed using Cox regression modeling. RESULTS: Between November 2016 and July 2020, 381 patients underwent SABR on trial. Median follow-up was 27 months (interquartile range, 18-36). The most frequent OMD group was de novo OMD (69%), followed by repeat (16%) and induced (13%). OMD groups differed significantly in PFS (P < .001) but not OS (P = .069). The OMD classification was an independent predictor of both PFS (P = .005) and OS (P = .002). Of the 5 classification factors, only chronicity (synchronous, hazard ratio, 0.52; P = .027) and oligoprogression (hazard ratio, 2.05; P = .004) were independently prognostic for OS. CONCLUSIONS: In this large prospective cohort, the ESTRO/EORTC classification was an independent predictor of PFS and OS and should be used to identify specific patient groups for clinical trials. In this trial population, the prognostic power is largely attributable to chronicity and oligoprogression. Simplification of the framework may be possible in the future and allow for greater ease of use; however, further data on underrepresented OMD groups and histologies will be required.

Prescribing practices of endocrine therapy for ductal carcinoma in situ in British Columbia.

Purpose: The mainstay of treatment for ductal carcinoma in situ (dcis) involves surgery in the form of mastectomy or lumpectomy. Inconsistency in the use of endocrine therapy (et) for dcis is evident worldwide. We sought to assess the variation in et prescribing for patients with dcis across a population-based radiotherapy (rt) program and to identify variables that predict its use. Methods: Data from a breast cancer database were obtained for women diagnosed with dcis in British Columbia from 2009 to 2014. Associations between et use and patient characteristics were assessed by chi-square test and multilevel multivariate logistic regression. The Kaplan-Meier method, with propensity score matching and Cox regression analysis, was used to assess the effects of et on overall survival (os) and relapse-free survival (rfs). Results: For the 2336 dcis patients included in the study, et use was 13% in dcis patients overall, and 17% in patients with estrogen receptor-positive (er+) tumours treated with breast-conserving surgery and rt. Significant variation in et use by treatment centre was observed (range: 8%-23%; p < 0.001), and prescription of et by individual oncologists varied in the range 0%-40%. After controlling for confounding factors, age less than 50 years [odds ratio (or): 1.72; p = 0.01], treatment centre, er+ status (or: 5.33; p < 0.001), and rt use (or: 1.77; p < 0.001) were significant predictors of et use. No difference in os or rfs with the use of et was observed. Conclusions: In this population-based analysis, 13% of patients with dcis in British Columbia received et, with variation by treatment centre (8%-23%) and individual oncologist (0%-40%). Age less than 50 years, er+ status, and rt use were most associated with et use.

Factors affecting radiotherapy prescribing patterns in the post-mastectomy setting.

Background: Radiation therapy (rt) after mastectomy for breast cancer can improve survival outcomes, but has been associated with inferior cosmesis after breast reconstruction. In the literature, rt dose and fractionation schedules are inconsistently reported. We sought to determine the pattern of rt prescribing practices in a provincial rt program for patients treated with mastectomy and reconstruction. Methods: Women diagnosed with stages 0-iii breast cancer between January 2012 and December 2013 and treated with curative-intent rt were identified from a clinicopathology database. Patient demographic, tumour, and treatment information were extracted. Of the identified patients, those undergoing mastectomy were the focus of the present analysis. Results: Of 4016 patients identified, 1143 (28%) underwent mastectomy. The patients treated with mastectomy had a median age of 57 years, and 37% of them underwent reconstruction. Treatment with more than 16 fractions of rt was associated with autologous reconstruction [odds ratio (or): 37.2; 95% confidence interval (ci): 11.2 to 123.7; p < 0.001], implant reconstruction (or: 93.3; 95% ci: 45.3 to 192.2; p < 0.001), and treating centre. Hypofractionated treatment was associated with older age (or: 0.94; 95% ci: 0.92 to 0.96; p < 0.001), and living more than 400 km from a treatment centre (or: 0.37; 95% ci: 0.16 to 0.86; p = 0.02). Conclusions: Prescribing practices in breast cancer patients undergoing mastectomy are influenced by reconstruction intent, age, nodal status, and distance from the treatment centre. Those factors should be considered when making treatment decisions.

Patient-reported outcome use in oncology: a systematic review of the impact on patient-clinician communication.

PURPOSE: Patient-reported outcomes (PROs) are an increasingly popular tool to optimize care and bridge the gap between patient experience and clinician understanding. The aim of this review was to identify mechanisms through which PROs facilitate patient-clinician communication in the adult oncology population. METHODS: We conducted a systematic review of the published literature using the following data sources: MEDLINE, EMBASE, CINAHL, PsycINFO, Cab Direct, and CDSR. Studies included in this review reported on the outcomes of PRO use, used PROs as an intervention and not as a study outcome measurement tool, included cancer patients or survivors as study participants, and analyzed patient-clinician communication. RESULTS: We identified 610 unique records, of which 43 publications met the inclusion and exclusion criteria. Synthesis of the reviewed studies provided evidence of the usefulness of PROs in facilitating patient-clinician communication on a variety of topics. We identified mechanisms though which PROs influenced patient-clinician communication to include increasing symptom awareness, prompting discussion, streamlining consultations, and facilitating inter-professional communication. Barriers to PRO use in communication improvement include technical problems impeding its administration and completion, compliance issues due to lack of incentive or forgetfulness, and use of PROs that do not appropriately assess issues relevant to the patient. Facilitators include increased education on PRO use, using PRO tools that patients find more acceptable, and providing patient data summaries in an easily accessible format for clinicians. CONCLUSIONS: Our review suggests that PROs facilitate patient-clinician communication through various mechanisms that could perhaps contribute to improvements in symptom management and survival. The impact of PROs on clinical outcomes, however, remains poorly studied.

Patient preferences for timing and access to radiation therapy.

PURPOSE: Patient preferences for radiation therapy (rt) access were investigated. METHODS: Patients completing a course of rt at 6 centres received a 17-item survey that rated preferences for time of day; day of week; actual, ideal, and reasonable travel times for rt; and actual, ideal, and reasonable times between referral and first oncologic consultation. Patients receiving single-fraction rt or brachytherapy alone were excluded. RESULTS: Of the respondents who returned surveys (n = 1053), 54% were women, and 74% had received more than 15 rt fractions. With respect to appointment times, 88% agreed or strongly agreed that rt between 08h00 and 16h30 was preferred; 14%-15% preferred 07h30-08h00 or 16h30-17h00; 10% preferred 17h00-18h00; and 6% or fewer preferred times before 07h30 or after 18h00. A preference not to receive rt before 07h30 or after 18h00 was expressed by 30% or more of the respondents. When days of the week were considered, 18% and 11% would have preferred to receive rt on a Saturday or Sunday respectively; 52% and 55% would have preferred not to receive rt on those days. A travel time of 1 hour or less for rt was reported by 82%, but 61% felt that a travel time of 1 hour or more was reasonable. A first consultation within 2 weeks of referral was felt to be ideal or reasonable by 88% and 73% of patients respectively. CONCLUSIONS: An rt service designed to meet patient preferences would make most capacity available between 08h00 and 16h30 on weekdays and provide 10%-20% of rt capacity on weekends and during 07h30-08h00 and 16h30-18h00 on weekdays. Approximately 80%, but not all, of the responding patients preferred a 2-week or shorter interval between referral and first oncologic consultation.

25 year survival outcomes for squamous cell carcinomas of the head and neck: population-based outcomes from a Canadian province.

OBJECTIVES: Long term outcomes of patients with head and neck cancer (HNC) are rarely reported, but of potential benefit to clinicians and researchers. Squamous cell carcinomas (SCC) of the head and neck represent a heterogeneous group of cancers. The purpose of this population based study is to describe primary site specific, long term outcomes of HNC. METHODS: All patients from a Canadian province diagnosed between 1986 and 1990 with SCC of the oral cavity, pharynx, and larynx were identified. Chart review and patient data were abstracted through the provincial cancer registry database. Survival analysis was performed with Kaplan Meier methods, while differences in survival between groups were assessed with log-rank tests. Multivariable analysis was performed using Cox-regression. RESULTS: 1657 patients were analyzed during the study period. Almost half (50.9%) of the cases were advanced stage (stage III IV) at presentation. Two, 5, 15 & 25year overall survival (OS) and HNC specific survival for all the patients were 64%, 46%, 21%, 11% and 74%, 63%, 53% & 49%, respectively. OS and HNC-specific mortality were statistically inferior among men, older age at diagnosis, advanced stages of disease, and was primary cancer site specific, with worse survival in oropharyngeal & hypopharyngeal sites, p<0.001. CONCLUSIONS: Survival rates vary by primary HNC site, and the overall survival & HNC specific survival differ over this long follow up assessment. Head and neck cancer specific death is most common in the first five years, and is subsequently dominated by competing causes of mortality. These results are useful as a reference tool for clinicians, researchers, and trainees.

Prospective evaluation of unmet needs of rural and aboriginal cancer survivors in Northern British Columbia.

BACKGROUND: The unmet needs of cancer survivors in rural, remote, and aboriginal communities are largely unexplored. We explored potential differences between rural survivors (rss) in 4 general population (gp) and 4 First Nations (fn) communities. METHODS: We approached 4 gp and 4 fn rs communities to participate in a mixed-methods project. Participants completed the Hospital Anxiety and Depression Scale (hads) and the Survivor Unmet Needs Survey (suns) and provided demographic information. Each question on the suns can be scored from 0 to 4, with 0 representing "no unmet need" and 4 representing "very high unmet need." A directed approach to content analysis of focus group and interview data was used to triangulate the hads and suns results. RESULTS: We prospectively accrued 23 fn rss and 56 gp rss for this study. More fn rss had borderline or abnormal anxiety (5% vs. 21%, p = 0.02). Compared with gp rss, fn rss had higher unmet needs scores in all categories: Information (2.29 vs. 0.8, p < 0.001), Work and Financial (1.66 vs. 0.5, p < 0.001), Access and Continuity of Health Care (1.83 vs. 0.44, p < 0.001), Coping and Sharing (2.22 vs. 0.62, p < 0.001), and Emotional (2.12 vs. 0.63, p < 0.001). The qualitative findings provided examples and insight into the unmet needs experienced by rss. CONCLUSIONS: First Nations rss had significantly higher anxiety and unmet needs compared with their gp rs counterparts. In addition, different qualitative themes were identified in the groups. Our findings support the development of tailored approaches to survivorship for these populations.

Comparison of recurrence and survival rates after breast-conserving therapy and mastectomy in young women with breast cancer.

Multiple randomized trials have demonstrated that breast-conserving therapy with partial mastectomy and radiotherapy provides survival equivalent to that seen with mastectomy for patients with early-stage breast cancer. Breast-conserving therapy has been associated with better quality of life relative to mastectomy and has become the standard of care for patients with early-stage breast cancer. Young age has been identified as a risk factor for recurrence and death from breast cancer. Some studies have suggested that young women (less than 35 or 40 years of age) have inferior outcomes with breast-conserving therapy, implying that such women may be better served by mastectomy. On review of the available literature, there is no definitive evidence that mastectomy provides a consistent, unequivocal recurrence-free or overall survival benefit over breast-conserving therapy. However, available meta-analyses have not compared outcomes in young women specifically, and such analyses should be performed. In the interim, breast-conserving therapy is not contraindicated in young women (less than 40 years of age) and can be used cautiously; however, such women should be advised of the lack of unequivocal data proving that survival is equivalent to that with mastectomy in their age group.

A purified inactivated Japanese encephalitis virus vaccine made in Vero cells.

A second generation, purified, inactivated vaccine (PIV) against Japanese encephalitis (JE) virus was produced and tested in mice where it was found to be highly immunogenic and protective. The JE-PIV was made from an attenuated strain of JE virus propagated in certified Vero cells, purified, and inactivated with formalin. Its manufacture followed current GMP guidelines for the production of biologicals. The manufacturing process was efficient in generating a high yield of virus, essentially free of contaminating host cell proteins and nucleic acids. The PIV was formulated with aluminum hydroxide and administered to mice by subcutaneous inoculation. Vaccinated animals developed high-titered JE virus neutralizing antibodies in a dose dependent fashion after two injections. The vaccine protected mice against morbidity and mortality after challenge with live, virulent, JE virus. Compared with the existing licensed mouse brain-derived vaccine, JE-Vax, the Vero cell-derived JE-PIV was more immunogenic and as effective as preventing encephalitis in mice. The JE-PIV is currently being tested for safety and immunogenicity in volunteers.

Fish consumption advisories and outreach programs for Southeast Asian immigrants.

Southeast Asian immigrants and refugees, in particular the Hmong people of Laos, have settled in large numbers in metropolitan areas of Minnesota. These communities, accustomed to hunting and fishing for food in Laos, now fish in some of the most contaminated waters of Minnesota. Fishing and fish-preparation customs of their homeland emphasize using all fish caught and discarding very little waste. These practices result in a potentially high exposure to PCBs and mercury. Educational outreach efforts to inform this population of the potential health hazards from consuming the fish are hindered by language and cultural barriers. While most Hmong anglers welcome information about contaminants and fishing, the typical press releases and mailings that convey fish advisory information to the public do not reach this community. The Minnesota Department of Health and the Minnesota Department of Natural Resources collaborated to determine the health messages and communication methods that would best meet the needs of these communities. Using the results of interviews and a behavioral survey, the Minnesota Department of Health has tailored fish consumption advisories to meet the unique needs of Southeast Asian anglers. Over the past four years, educational programs involving specialized advisories, translations, signs, a Hmong language video, and workshops have been used to inform Hmong anglers and other Southeast Asians about fish contaminants.

Child and maternal adaptation to cystic fibrosis and insulin-dependent diabetes mellitus: differential patterns across disease states.

Investigated the relationship between maternal and child emotional adaptation both across and within samples of children with cystic fibrosis (CF) and insulin-dependent diabetes mellitus (IDDM). Higher levels of maternal depression were associated with increased depression in children with IDDM. In addition, increased illness severity and greater length of time since diagnosis were related to increased depression in children with IDDM. Whereas maternal depression was related to decreased trait anxiety for children in the CF group, neither maternal anxiety or depression were associated with child depression or state anxiety. Empirical and clinical implications of a disease-specific approach to studying chronic disease in children are discussed.

Pediatric liver transplantation in Georgia: a paradigm for the health care crisis in the United States?

The United States health care system, felt by many to be the most technologically advanced program in the world, has many critics. Two indisputable facts that drive such criticism are 1) inequitable access and 2) rising costs out of proportion to other countries. Although Georgia is a poor state and ranks nationally near the bottom in most measures of child and adolescent care, we decided to start a pediatric liver transplant program at Egleston Children's Hospital at Emory, Atlanta. Over the past 2 1/2 years, 18 transplants have been performed in 14 patients; 10 children are presently surviving. Looking carefully at the expenses of the first 10 patients, the average cost of orthotopic liver transplantation for the eight survivors was $206,375. The hospital costs for providing care to these 10 children were over $2 million. In a state that ranks 49th out of 50 states in infant mortality and with nearly one-third of its pre-school children not immunized against preventable diseases, is this a fair and equitable distribution of our resources?

Carbon dioxide embolization and laparoscopic cholecystectomy.

The risk of venous air or CO2 embolization during laparoscopic biliary procedures is unknown. Sixty-one consecutive patients undergoing laparoscopic cholecystectomy at La Crosse Lutheran Hospital/Gundersen Clinic were monitored by precordial Doppler ultrasound and end-tidal capnography to determine the risk of gas embolization. Patients ranged in age from 19 to 77 years (mean, 47 years). No venous embolization was detected by Doppler ultrasound or capnography. The highest end-tidal CO2 ranged from 34 to 53 mm Hg (mean, 41 mm Hg). No patient demonstrated an abrupt change in end-tidal CO2. No significant intraoperative hemodynamic changes occurred, and no postoperative neurologic defects developed. We caution the surgical community to remain alert concerning the possibility of venous gas embolization as newer laparoscopic procedures are developed that may have increased risks of embolization.

Changing trends with mandibular fractures: a review of 1,067 cases.

To evaluate current trends in facial trauma, records from 1,067 patients sustaining 1,515 mandibular fractures from 1979 to 1989 were reviewed. The greatest number of fractures occurred between the ages of 20 to 29 years. Sex distribution was approximately three males to one female. Altercations were found to have caused about half of the fractures, and motor vehicle accidents accounted for nearly one-third. Angle fractures were most common, constituting 26.7% of the total. The most common site of mandibular fracture resulting from altercation was the angle (39.1%); condylar, symphysis, and alveolar fractures less commonly resulted from altercations than from motorcycle and automobile accidents.

Comparison of 26- and 27-G needles for spinal anesthesia for ambulatory surgery patients.

Seven hundred thirty ambulatory surgery patients, randomly assigned to receive spinal anesthesia with a 26- or 27-G needle, were studied for the incidence of post-dural puncture headache (PDPH), postoperative back pain, and patient acceptance. The incidence of PDPH following the use of 26- and 27-G needles was 9.6% and 1.5%, respectively (P less than 0.05). The incidence of PDPH was 5.7% among men and 13.4% among women following the use of 26-G needles (P less than 0.05), whereas no difference between men and women was noted after the use of 27-G needles. Of the patients who were 40 yr of age or younger, the overall incidence of PDPH was 11.9%, with a 7.5% incidence among men and a 16.4% among women following the use of 26-G needles (P less than 0.05) and a 1.8% incidence of PDPH following the use of 27-G needles, with no statistical difference between genders. Postoperative back pain was experienced in 18.3% of the patients in the 26-G group and 20.2% in the 27-G group (difference not significant). Favorable acceptance of spinal anesthesia was reported in 89.4% of patients in the 26-G group and 98.2% in the 27-G group (P less than 0.01). Results from this study demonstrate that, in patients who received spinal anesthesia for ambulatory surgery, the use of 27-G needles resulted in a significantly lower incidence of PDPH and greater patient acceptance compared with the use of 26-G needles. The incidence of postoperative back pain was not significantly different between the two groups.

Risk and resistance factors in the adaptation of mothers of children with cystic fibrosis.

Examined 35 mothers of children with cystic fibrosis (CF) to assess the relationship of risk and resistance factors to level of psychological adjustment. Dimensions of maternal adaptation, disease severity, family adaptability and cohesion, family life stress, and intrapersonal coping style were assessed. As a group, mothers evidenced significant levels of general psychological distress, and appear to constitute an at-risk population. Multiple regression analyses indicated higher levels of maternal distress were associated with increased levels of stressful family life events and an escape-avoidance coping style. Disease severity, family financial resources, and family adaptability and cohesion did not significantly contribute to the regression model.

Diagnosis of pancreatic transplant dysfunction: value of gadopentetate dimeglumine-enhanced MR imaging.

Sixteen MR studies performed in four patients who had undergone combined pancreatic and renal transplantation were reviewed retrospectively to determine if dynamic gadopentetate dimeglumine-enhanced gradient-echo imaging is useful in the early diagnosis of pancreatic transplant rejection. The MR studies were performed between 3 days and 6 months after transplantation and consisted of T1- and T2-weighted spin-echo images as well as a gradient-echo image prior to administration of an IV bolus of gadopentetate dimeglumine (0.1 mmol/kg). After injection of gadopentetate dimeglumine, a static dynamic gradient-echo scan was obtained. Signal-intensity measurements were determined for each of the gradient-echo images and used to generate an enhancement curve. Because T2 values have previously been used as an objective indicator of rejection, the mean T2 of each pancreatic transplant was calculated also. The MR results were compared with clinical and laboratory data and/or percutaneous biopsy results. In six studies of normally functioning pancreatic allografts, the percent enhancement during the first minute of the enhancement curve was 98 +/- 23% (1 SD). In six episodes of acute dysfunction (rejection or infarction), the first-minute enhancement was 42 +/- 20%. In four cases of dysfunction, the finding of an abnormal enhancement curve preceded a significant drop in urinary amylase by 1-4 days. The calculated T2 value was prolonged in only two cases in which biopsy-proved pancreatic infarction had occurred. No prolongation of T2 was evident in four cases of rejection alone. These results suggest that mean T2 calculation at 1.5 T may not be a reliable indicator of pancreatic transplant rejection, but that gadopentetate dimeglumine-enhanced gradient-echo MR imaging of the pancreatic transplant may be a reliable early indicator of pancreatic transplant dysfunction.

Atrial natriuretic factor does not improve the outcome of cadaveric renal transplantation.

Atrial natriuretic factor (ANF) ameliorates renal damage in animal models of acute ischemic renal failure. Consequently, ANF could blunt acute tubular necrosis related to ischemia that occurs frequently in cadaveric renal transplants. Ten pairs of cadaveric kidneys were transplanted into 20 recipients. Paired recipients received either alpha-human ANF (hANF) or vehicle alone in a prospective, double-blind protocol. Upon revascularization of the allograft, either hANF or vehicle was administered intravenously as a 50-micrograms bolus, followed by a 4-h infusion (0.1 microgram/kg/min). Glomerular filtration rate ([125I]iothalamate clearance) was measured between 4 and 7 days posttransplant and again between 14 and 21 days posttransplant. Serum creatinine was measured daily when patients were in the hospital, then twice weekly as patients were examined in the outpatient clinic. Between the groups, there was no significant difference in age of the recipients or donors, cold ischemia time, or histocompatibility leukocyte antigen match. Infusion of hANF had no adverse effects. When subjects receiving hANF were compared with those treated with vehicle alone, there were no significant differences in serum creatinine or glomerular filtration rate. Three hANF and four vehicle recipients required dialysis postoperatively. At 1 month posttransplant, 19 of 20 patients had functioning allografts; an allograft from one hANF recipient never functioned. It was concluded that hANF, when given by the protocol of this study, had no beneficial effect on the outcome of cadaveric renal transplantation in humans.