Patient-reported outcome (PRO) results from the AGITG DOCTOR trial: a randomised phase 2 trial of tailored neoadjuvant therapy for resectable oesophageal adenocarcinoma.

BACKGROUND: AGITG DOCTOR was a randomised phase 2 trial of pre-operative cisplatin, 5 fluorouracil (CF) followed by docetaxel (D) with or without radiotherapy (RT) based on poor early response to CF, detected via PET, for resectable oesophageal adenocarcinoma. This study describes PROs over 2 years. METHODS: Participants (N = 116) completed the EORTC QLQ-C30 and oesophageal module (QLQ-OES18) before chemotherapy (baseline), before surgery, six and 12 weeks post-surgery and three-monthly until 2 years. We plotted PROs over time and calculated the percentage of participants per treatment group whose post-surgery score was within 10 points (threshold for clinically relevant change) of their baseline score, for each PRO scale. We examined the relationship between Grade 3+ adverse events (AEs) and PROs. This analysis included four groups: CF responders, non-responders randomised to DCF, non-responders randomised to DCF + RT, and "others" who were not randomised. RESULTS: Global QOL was clinically similar between groups from 6 weeks post-surgery. All groups had poorer functional and higher symptom scores during active treatment and shortly after surgery, particularly the DCF and DCF + RT groups. DCF + RT reported a clinically significant difference (-13points) in mean overall health/QOL between baseline and pre-surgery. Similar proportions of patients across groups scored +/- 10 points of baseline scores within 2 years for most PRO domains. Instance of grade 3+ AEs were not related to PROs at baseline or 2 years. CONCLUSIONS: By 2 years, similar proportions of patients scored within 10 points of baseline for most PRO domains, with the exception of pain and insomnia for the DCF + RT group. Non-responders randomised to DCF or DCF + RT experienced additional short-term burden compared to CF responders, reflecting the longer duration of neoadjuvant treatment and additional toxicity. This should be weighed against clinical benefits reported in AGITG DOCTOR. This data will inform communication of the trajectory of treatment options for early CF non-responders. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry (ANZCTR), ACTRN12609000665235 . Registered 31 July 2009.

Short bowel syndrome and the impact on patients and their families: a qualitative study.

BACKGROUND: Short bowel syndrome (SBS) is a malabsorptive condition that can result in intestinal failure (SBS-IF). Many patients with SBS-IF require home parenteral nutrition (PN) for survival. However, PN has profound effects on patients and their family members. The present study aimed to understand the lived experience of SBS-IF for patients and their families. METHODS: In-depth semi-structured qualitative interviews were conducted with 15 patients with SBS-IF and five adult family members living with someone with SBS-IF. A patient-centric approach was taken, with a patient steering group providing input and guidance to develop the interview guide. Key concepts were identified using thematic analysis of interview transcripts. RESULTS: Patients' lives were dominated by having SBS-IF. They described physical impacts that included patient-reported signs and symptoms and physical restrictions comprising of restrictions on daily life, actives of daily living and physical functioning. In addition, they encountered emotional impacts with a plethora of negative feelings and social impacts, such as difficulties socialising and maintaining relationships. Patients coped by adapting their life around SBS-IF, having support and adopting an attitude of gratitude and acceptance. Family members were also affected and, along with patients, appreciated the respite of a night off from infusions. CONCLUSIONS: Patients and families face many difficulties with SBS-IF. Healthcare professionals can support patients by facilitating them explore what others have found beneficial; adapting their life around PN, viewing PN with acceptance and trying to cultivate gratitude. Further research into the support required for families may be beneficial.

Early-stage vaginal carcinoma--an analysis of 70 patients.

OBJECTIVES: The aims of this study were to assess outcomes and define prognostic factors for early-stage vaginal carcinoma. METHODS: A retrospective analysis was performed of women with FIGO stages I and II vaginal carcinoma identified from the database of the Queensland Centre for Gynaecological Cancer between January 1982 and December 1998. RESULTS: Seventy women were identified. The 5-year survivals for stages I and II carcinomas were 71 and 48%, respectively (P < 0.05). Sixty-one patients (87%) had squamous cell carcinomas with a 5-year survival of 68% versus 22% for adenocarcinomas (P < 0.01). Those women with grade 3 tumors had a 5-year survival of 40% versus 69% for grades 1 and 2 (P < 0.05). Tumor size and site were not significant prognostic factors. Patients treated by surgery alone or with combined surgery and radiotherapy had a significantly improved survival compared to the radiation alone group (P < 0.01). Eighty-five percent of recurrences were locoregional. The median time to relapse was 12 months after initiation of therapy. CONCLUSION: Tumor morphology, grade, and stage are important prognostic indicators. Measures aimed at improving local control of the disease, including surgery, are necessary.

A survey of children's acute, recurrent, and chronic pain: validation of the pain experience interview.

The ultimate objective of our epidemiological research is to complete a longitudinal population-based study to document the prevalence and impact of acute, recurrent, and chronic pain in children and adolescents. As the first phase of our epidemiological research, we developed a comprehensive screening instrument for identifying children with acute, recurrent, and chronic pain, the Pain Experience Interview. We designed this interview to provide information about the lifetime and point prevalence of various pains, and also to provide information about the intensity, affect, duration, and frequency of children's pain. The primary objective of this study was to validate the Pain Experience Interview using the discriminant validation procedure of group differences. The secondary objectives of our study were to obtain descriptive data on children's acute, recurrent, and chronic pain experiences and to conduct exploratory analyses on age- and gender-related differences in children's pain experiences. We interviewed 187 children from five different health groups (arthritis, cancer, enuresis, recurrent headaches, and healthy) to provide distinct subsets of children with respect to their acute, recurrent, and chronic pain experience, and from four different age groups (5-7, 8-10, 11-13, and 14-16 years) to provide distinct subgroups with respect to children's developmental level. To test the interview we determined a priori several study predictions about children's pain experiences. These included four predictions about the common response patterns that we would expect to observe for all children based on our understanding of acute pain caused by trauma/disease, and six predictions about the distinct response patterns that we would expect to observe based on the known differences among children in their experiences of headache, acute treatment-related pain, recurrent pain, and chronic pain. All study predictions were confirmed, demonstrating that the Pain Experience Interview is a valid screening instrument for differentiating children with different types of pain problems. The interview can provide estimates for the lifetime and point prevalence of various pains in children, and data on the intensity, affect, duration, and frequency of their pain experiences.

Thirty-four patients with carcinoma of the cervical esophagus treated with chemoradiation therapy.

OBJECTIVE: To review the experience of 2 institutions in the management of localized carcinoma of the cervical esophagus with chemoradiation therapy. DESIGN: A series of 34 patients received chemoradiation therapy for a 5-year period. All patients were treated with curative intent. Three different regimens were used, all involving concomitant chemotherapy and high-dose radiation therapy. Data relating to toxic effects, local control of disease, and disease-free and overall survival were prospectively collected. SETTING: Two combined clinics at separate major hospitals where multidisciplinary care is the standard practice for this disease. PATIENTS: Patients with biopsy-proved carcinoma of the cervical esophagus. INTERVENTIONS: Patients received 3 different chemotherapy regimens. Two of the regimens used a combination of cisplatin and fluorouracil. The high-dose cisplatin regimen was a large dose of cisplatin (80 mg/m2) given on days 1 and 22 followed by a 96-hour infusion of fluorouracil (800 mg/m2) from days 2 to 5 and from days 23 to 26. The low-dose cisplatin regimen was cisplatin, 20 mg/m2, from days 1 to 5 and from days 22 to 26 and the same 96-hour infusion of fluorouracil. The third regimen used fluorouracil alone. The mean radiation dose administered was 61.2 Gy in 29.6 fractions during 41.8 days using 4- or 6-mV photons and a shrinking field technique. RESULTS: The results of treatment have shown a high rate of local control, although some patients developed metastases. The local complete response rate following treatment was 91%, and the rate of local control of disease was 88%. The projected actuarial 5-year survival rate was 55%. Death from other causes was common. The acute toxic effects of the treatment were acceptable, with only 5 patients requiring nasogastric feeding or gavage. Two patients died of complications related to strictures. CONCLUSION: Concomitant chemoradiation therapy, should be the treatment of choice for carcinoma of the cervical esophagus.

Strontium and samarium therapy for bone metastases from prostate carcinoma.

A review was performed of all patients who received strontium-89 chloride or samarium-153 ethylenediamine-tetramethylenephosphonate for prostate cancer metastatic to bone at the Royal Brisbane Hospital between 1992 and 1997. There were 57 patients, 38 treated with strontium-89 and 19 with samarium-153. Forty patients had radionuclide therapy alone, and 28/40 (or 70%) responded in terms of experiencing a beneficial effect on pain. In the other 17 patients, the effect of the radionuclide on pain could not be assessed because they received external beam radiotherapy concomitant with a therapeutic radionuclide. There was no difference in response rates between the samarium and strontium groups as measured by the effect on pain or in the time to progression. The median time to progression for all patients was 2-3 months. The present study confirms that following administration of a therapeutic radionuclide, a high proportion of patients experienced improvement of pain, but the time to progression is not long, so that the overall degree of benefit is modest.

A full factorial analysis of nine factors influencing in vitro antagonistic screens for potential biocontrol agents.

The effect of nine factors on the outcome of classic in vitro screens testing the antagonistic action of endophytic bacterial isolates from grape vines against virulent Agrobacterium vitis has been examined. These factors were (i) the strain of A. vitis, (ii) the strain of endophyte, (iii) the growth medium of the pathogen, (iv) the growth medium of the endophyte, (v) the temperature of growth of the pathogen, (vi) the temperature of growth of the endophyte, (vii) the pH of growth of the pathogen, (viii) the pH of growth of the endophyte, and (ix) the medium of the assay plate. Analyses of variance of the full factorial design incorporating main effects and two- and three-way interactions accounted for 66% of the variance. All nine factors had a significant effect on the diameter of inhibition zones (p < 0.001). An examination of the three-way interactions revealed that generalizations were difficult to draw; each target agrobacterium had a specific response to a given antagonistic isolate. It was possible to determine that the growth history of bacterial strains, before they were administered to an assay plate to test for antagonism (especially the composition of the growth medium and the temperature of growth), had a profound effect on the outcome of the test. Generally the more chemically defined media produced less inhibition whereas the lower growth temperature of 15 degrees C produced more inhibition. These findings could be relevant to in situ inhibitory activity. The method used to conduct the inhibitory screen (order of strain application and the medium of the assay plate) had a profound influence on the results. These influences add to the caution necessary in the use of in vitro antagonistic screens for finding successful biocontrol agents.

Treatment decisions in T3N0M0 glottic carcinoma.

PURPOSE: To analyze the results of T3N0M0 glottic carcinoma treated with radiotherapy, surgery, or both. METHODS AND MATERIALS: The records were retrospectively reviewed of 97 patients with this tumor subsite and stage seen for treatment at the Queensland Radium Institute over a 29-year period. The results for radiotherapy with surgical salvage of failure (XRT/SS) were compared to those with surgery with or without radiotherapy (SURG/SURG+XRT). For those treated initially with radiotherapy alone, the results for different ranges of biologically equivalent doses were compared. These results were compared to those of other published studies. RESULTS: The 5-year disease-specific survival rats for the XRT/SS and SURG/SURG+XRT groups were 50% and 58%, respectively; this difference is not significant. For the XRT/SS group, there was a trend towards improved 5-year recurrence-free survival (73%) and 5-year disease-specific survival (86%) in those treated to a dose equivalent to 60-64 Gy in 2 Gy fractions, when compared with higher or lower dose equivalents. CONCLUSION: A group of patients with T3N0M0 glottic carcinoma is specified for which the option of radiotherapy offers a similar chance of survival to those treated surgically. More than 50% of the XRT/SS survivors will retain their larynx.

Self-assessed competence: before and after residency.

This study measures changes in clinical confidence experienced by 42 family practice residents as they progressed through a 2-year residency program. At the beginning, 20% or more of respondents reported they lacked confidence in 47 of the 177 topics. Self-assessed competence increased substantially in many areas. However, during the residency, new areas of concern emerged.

Changes in residents' self-assessed competences during a two-year family practice program.

PURPOSE: To compare changes in self-assessed clinical confidence over a two-year residency between two groups of family practice residents, one starting in a family practice center and the other starting in a hospital. METHOD: All 44 entering residents at the University of Western Ontario in either 1984 or 1985 were eligible. Forty-two participated at baseline, and 24 (57%) provided completed responses after two years. Confidence regarding 177 topics in 19 general topic areas was assessed using self-completed questionnaires administered at baseline and after six, 12, and 24 months. The residents rotated every six months between sites, with approximately half starting in each site. Nonrandom assignment to starting site included consideration of the residents' stated preferences; hence self-selection bias was possible. Mean differences were evaluated using t-tests, and trends over time were assessed using repeated-measures analysis of variance. RESULTS: There was no difference between the groups' grand means at any time. In the 19 areas, five statistically significant differences were seen, four at six months and one at 12 months; four involved greater confidence by the center-start group. No difference was seen after two years, and both groups displayed substantial increases in confidence over two years. CONCLUSIONS: The few significant differences in confidence between the two groups suggest that their training might have been deficient if it had omitted one of the settings. However, because these differences had disappeared after the groups had each experienced 12 months in each setting, the initial site of training appears not to affect learning.

Cancer of the cervix--old and young, now and then.

A study of two 5-year periods, 1960-1964 and 1982-1986, in Queensland is made. Changing patterns of preinvasive and invasive cervical carcinoma in the world literature are discussed. The age of presentation, stage, histology, and results in Queensland for cervical carcinoma are analyzed. There are over 500 patients in each quinquennium. While the total female population has increased 86%, the maximum increase is in patients under 35 years and over 65. There has been a 50% decrease in the incidence of cervical carcinoma, but a doubling under the age of 30. The stage at diagnosis has markedly improved with 88% stage Ib in the young as opposed to 50% formerly. Late-stage disease remains a problem of the aged. The mortality in both time spans increases with age. Histologic patterns show an increase in nonsquamous patterns and increased mortality in the rare patterns. We have no evidence of the emergence of a rapidly progressive carcinoma in the young. Papanicolaou smear and education programs appear to be preventing cervical carcinoma and allowing diagnosis of the disease at an earlier stage and age. This is reflected in a decrease in mortality from 9.6 per 100,000 (1960-1964) to 4 per 100,000 (1982-1986).

Prognostic significance of tumor ploidy in patients with advanced ovarian carcinoma.

Fresh tumor specimens obtained from 53 consecutive patients with FIGO Stage III ovarian carcinoma were analyzed by flow cytometry. All patients were treated by a standard protocol: maximal tumor excision and cisplatin/cyclophosphamide/adriamycin chemotherapy, and followed-up for at least 24 months. Thirty-two percent of tumors were diploid (DNA index = 1.00) and 68% aneuploid (DNA index greater than 1.00), with more aneuploid tumors being associated with larger residual tumor and poor cellular differentiation. Patients with diploid tumors were found to survive significantly better than those with aneuploid tumors, in terms of survival rate (65% versus 31%), median survival time (33 months versus 13 months), and mean disease-free interval (17.8 months versus 8.2 months). The influence of the amount of residual tumor after primary surgery on survival was only significant in patients with diploid tumors. Our results support previous findings that tumor ploidy is an important prognostic indicator in ovarian cancer. We found aneuploidy to be associated with a poorer clinical outcome in Stage III disease, regardless of the amount of residual tumor after primary surgery and the degree of cellular differentiation.

Analgesic efficacy and safety of single-dose oral and intramuscular ketorolac tromethamine for postoperative pain.

The efficacy and safety of the analgesic drug ketorolac tromethamine in the treatment of moderate to very severe postoperative pain was assessed in five dose-ranging studies with single-dose, double-blind, randomized, parallel-group designs. The drug was administered orally (2.5-200 mg, 352 patients in three trials) and intramuscularly (5-90 mg, 395 patients in two trials), and compared with placebo and reference drugs. Patients subjectively evaluated pain intensity and relief using verbal categoric and visual analog scales; efficacy values included pain intensity difference (PID), summed PID, and total pain relief. Oral ketorolac 10, 12.5, 100, and 200 mg were each statistically significantly superior to placebo in all efficacy measurements, and 10 mg was equivalent to intramuscular morphine 10 mg. Intramuscular ketorolac 90 mg was superior to and 10 and 30 mg were similar to intramuscular morphine 12 mg, and all of these ketorolac doses were superior to intramuscular morphine 6 mg. Intramuscular ketorolac 10 and 30 mg were superior to intramuscular meperidine 50 and 100 mg. Ketorolac was well tolerated, with rates of adverse events generally lower than those of the opiate comparators. Ketorolac doses of 2.5 and 5 mg were less effective than higher doses; 10 mg or more resulted in faster onset of action and greater peak efficacy; 90 mg or more gave more prolonged analgesic effects.

Clinical value of in vitro drug sensitivity testing based on short-term effects on DNA and RNA metabolism in ovarian cancer.

The hypothesis that in vitro chemosensitivity testing could predict clinical outcome was tested in women with ovarian cancer. Short-term drug effects on DNA and RNA metabolism (by inhibition of 3H-thymidine and 3H-uridine incorporation) were measured in primary cultures of tumor cells. In vitro inhibitory effects were found with the four drugs tested: cisplatin, adriamycin, melphalan, and methotrexate. From data based on impaired RNA and/or DNA metabolism (greater than or equal to 20% inhibition), correct prediction of "sensitivity" was 79% and that of "resistance" was 84%. An analysis of the predictive value of both assays, used singly or together, revealed a high specificity but moderate sensitivity; the best positive predictive value (94%) was obtained when both RNA and DNA metabolisms were impaired. Our results support the idea that two subsets of patients who are being considered for cytotoxic chemotherapy can be selected; those who may benefit from treatment and those who may not, regardless of the drugs tested in vitro or used in vivo.

Does memory of childhood determine parenting? Correlation in family practice.

The authors studied 46 eldest or only children under school age and their parents to determine the relationship between parents' recollections of their own childhoods and the way they use their family physician for care of their children. The parents completed a questionnaire that measured the caring and overprotection dimensions of the parenting they themselves remember. Positive correlations were found between perceptions of maternal overprotection and the frequency of children's visits. Negative correlations were found between perceptions of parental affection and children's visits and non-routine diagnoses. Neuroticism was found to be a confounding variable that slightly weakened the relationship between maternal caring and children's visits.

Cisplatin chemotherapy of ovarian cancer: is short-term in vitro chemosensitivity predictive of long-term patient survival?

The in vitro response to cis-diamminodichloroplatinum (cisplatin) in primary culture of tumour samples obtained at surgery was studied in 61 patients with Stage III ovarian cancer who were also treated with cisplatin. The drug-induced inhibitory effect on cell proliferation (measured by 3H-thymidine incorporation) and metabolism (by 3H-uridine incorporation) was assessed over a 3-hour incubation. At greater than or equal to 20% level of inhibition, the true prediction rate of survival by the proliferative assay was 72% among those with 'sensitive' tumours and of mortality was 66% among those with 'resistant' tumours; at greater than or equal to 50% level of inhibition, the prediction rate of survival by the proliferative assay increased to 88% but that of mortality decreased to 58%. The results with the metabolic assay were comparatively lower at all levels. When the amount of residual disease was taken into the determination of mortality rate, significant differences were found between 'sensitive' and 'resistant' tumours as defined by the proliferative assay in patients with no/minimal disease. The pattern of survival differed significantly between 3 subgroups of tumours, as defined by their responses to cisplatin in the proliferative and metabolic assays -- the best survival was obtained in patients whose tumours were 'sensitive' in both assays.

Measurement of tumor cell activity in short-term primary culture. Clinical significance in women with ovarian cancer.

In vitro activity was determined by primary culture of tumor samples obtained at surgery from 63 patients with Stage III ovarian cancer. These patients had completed at least 24 months of follow-up. Proliferative activity was measured after 3-hour culture by 3H-thymidine incorporation and metabolic activity by 3H-uridine incorporation. A large range of individual tumor activity was found; no correlation was present between proliferative and metabolic activity in the same tumor, the distribution of tumors with high and low activity was similar between histologic types, and the activity was not higher in undifferentiated tumors. There was a strong association between in vitro activity of the tumor and patient outcome (both clinical status and survival). On the basis of in vitro activity, a subset of patients was identified within subgroups with known amount of residual tumor; proliferative activity was a better predictor of good outcome in patients with no residual disease, whereas metabolic activity was better in those with more extensive disease. In these patients, a tumor showing high proliferative and/or metabolic activity (greater than 5000 cpm) was associated with poor survival.