bluuebunny/crossref_metadata_2025 huggingface dataset:
Between funder requirements and ‘jobbing scientists’: the evolution of patient and public involvement in a mental health biomedical research centre - a qualitative study
Authors: Evans Joanne , Papoulias Stan (Constantina)
Published: April 2020

Background

In the UK, there has been a strong drive towards patient and public involvement (PPI) in health research. Its benefits include improvements in the quality, relevance and acceptability of research, and empowerment, self-respect and value for service users. Organisational context can significantly influence the operationalisation of PPI. Research has highlighted power asymmetries between clinicians, researchers and service users. A resistance to power sharing, tokenism and assimilation into the existing culture suggest that a consultative, technocratic form of PPI is operating within health research settings. The aim of the study was to explore the development of PPI within a London based mental health biomedical research centre (BRC) over a period of 10 years from its inception.

Methods

This qualitative study compared data from 52 organisational documents and 16 semi-structured interviews with staff and service users associated with PPI within the Maudsley BRC. The data were analysed using inductive thematic analysis. Study design, data collection, analysis and write up were conducted by service user researchers.

Results

Our analysis showed a picture of increasing activity and acceptance of PPI, its alignment with the broader BRC research agenda, progressive involvement of service users in governance, and the development of a collaborative culture in research processes. The presence of salaried service user researchers in the organisation was key to this progress. However, PPI remained localised and under resourced and there was a reluctance to change working practices which resulted in perceptions of tokenism. Service users faced conflicting expectations and were expected to assimilate rather than challenge the organisation’s ‘biomedical agenda’.

Conclusions

Service user researchers may play a key role in establishing PPI in a scientific, hierarchical research environment. Adoption of a more democratic approach to involvement would build on the good work already being done and help to transform the culture and research processes. However, such an adoption requires considerable changes to the funding and policy environment orienting health research.
The metaphyseal sleeve: an unexplored option in the treatment of complex primary knee osteoarthritis
Authors: Wong W. K. , Chua H. S.
Published: April 2020

Background

In an ever-aging society that as a whole has become more affluent, significant emphasis has been accorded to an improved quality of life. Knee osteoarthritis is ever-increasingly treated with total knee arthroplasty. The benefits and satisfaction experienced by those who have undergone total knee replacements (TKR) are well documented in the literature. The issue arises when osteoarthritis of the affected knee is more complex than simple osteoarthritis, i.e. the patient has complex primary osteoarthritis. This collective term encompasses conditions such as massive bone loss, ligamentous laxity, coronal defects and those with contractures. There are various classifications to describe massive bone loss but we utilized the Anderson Orthopaedic Research Institute (AORI) classification. Numerous treatment options are available and we report the use of metaphyseal sleeves as a highly successful treatment option.

Methods

We retrospectively reviewed all the patients at our centre who underwent primary TKR using the metaphyseal sleeves. Patients were assessed on symptoms and functional status, and radiographs were also taken to assess for osseointegration. Only patients who completed 2 years of follow up were included in our study.

Results

The updated (2011) Knee Society Score (KSS) was used in conjunction with radiological assessments at each follow up. Mean KSS scores improved from 53.83 preoperatively to 193.39 postoperatively. All patients demonstrated increasing osseointegration throughout follow up.

Conclusion

The metaphyseal sleeve is an excellent treatment option for complex primary osteoarthritic knees with good results objectively, functionally and radiologically and would be a great choice for all orthopaedic surgeons to include in their armamentarium.
Identification of validated substitute for Asoka (Saraca asoca (Roxb.) Willd.) by phytochemical and pharmacological evaluations
Authors: C. T. Sulaiman , C. K. Jyothi , G. Jinu Krishnan Unnithan , K.M. Prabhukumar , Balachandran Indira
Published: April 2020

Background

Asokais an important drug used in many Ayurvedic formulations. The bark ofSaraca asoca(Roxb.) Willd. is the genuine source plant forAsoka. Due to diminishing availability and increasing requirement, the Ayurvedic industry is facing acute shortage of this crude drug. It is usual that traders try to deceive the consumers by tendering similar bark of other trees. The unscientific substitution may affect the quality of herbal preparations adversely. The aim of the present study is to identify a scientifically validated substitute forAsoka.

Results

Phytochemical and pharmacological evaluation has been carried out using plant parts of four medicinal plants viz,Saraca asoca(AB),Polyalthia longifolia(PB),Shorea robusta(SB), andTrema orientalis(TB). The results of the study showed that among the tested extracts, AB and SB showed significant dose-dependent protection against bilateral ovariectomy-induced changes in estrus cycle, uterus weights, and lipid profile. LC/MS analysis revealed the presence of active catechins in both AB and SB.Polyalthia longifolia, the common adulterant ofAsoka, showed entirely different chemical and biological properties.

Conclusion

This study concluded the possibility of usingS.robustabark as substitute forAsoka.

Graphical abstract
Scaling up mental health services in Sudan: Sudanese psychiatrists’ opinions
Authors: Osman Abdelgadir Hussein M. , Bakhiet Aisha , Elmusharaf Samia , Omer Abdelaziz , Abdelrahman Abdalla
Published: April 2020

We invited 108 psychiatrists of Sudanese origin, working in and outside Sudan, to take part in a study looking at the most appropriate method for scaling up mental health services in Sudan. Of those psychiatrists who were approached, 81 (75%) responded. Among the respondents, 30 (37%) resided and worked in Sudan, and 51 (63%) worked outside Sudan (mostly in the UK and Arab Gulf States). Most respondents preferred the lay counsellor model (43, 53.2%) to address the current shortage of human resources for scaling up mental health services.
Serial RT-PCR detection of circulating tumour cells as a marker of disease progression in patients with malignant melanoma
Authors: Ascierto P. A. , Budroni M. , Cossu A. , Scala S. , Simeone E. , Giuliano P. , Satriano S. M. , Caracò C. , Casula M. , Palmieri G.
Published: April 2020

18009

Background: Detection of circulating malignant cells (CMCs) through a reverse transcriptase-polymerase chain reaction (RT-PCR) assay seems to be a demonstration of systemic disease. We here evaluated the prognostic role of RT-PCR assays in serially-taken peripheral blood samples from patients with malignant melanoma (MM). Methods: One hundred forty-nine melanoma patients with disease stage ranging from I to III were consecutively collected in 1997. A multi-marker RT-PCR assay was used on peripheral blood samples obtained at time of diagnosis and every 6 months during the first two years of follow-up (total: 5 samples). Univariate and multivariate analyses were performed after 83 months of median follow-up. Results: Detection of at least one circulating mRNA marker was considered a signal of the presence of CMC (referred to as PCR-positive assay). A significant correlation was found between the rate of recurrences and the increasing number of PCR-positive assays (P = 0.007). Presence of CMC in a high number (≥2) of analysed blood samples was significantly correlated with a poor clinical outcome (disease-free survival: P = 0.019; overall survival: P = 0.034). Multivariate analysis revealed that presence of a PCR-positive status does play a role as independent prognostic factors for overall survival in melanoma patients, adding precision to the predictive power of the disease stage. Conclusions: Our findings indicated that serial RT-PCR assay may identify a high risk subset of melanoma patients with occult cancer cells constantly detected in blood circulation. Prolonged presence of CMCs seems to act as a surrogate marker of disease progression or a sign of more aggressive disease.

No significant financial relationships to disclose.
Correlation between hemodynamic parameters and response to high-dose interleukin-2 in metastatic melanoma
Authors: Dutcher J. P. , Dasanu C. , Codreanu I. , Yeddu M. , Muniswamy H. , Wiernik P. H. , Alexandrescu D. T.
Published: April 2020

18012

Background: A direct correlation between the levels of hypotension during IL-2 treatment and response in melanoma has not yet been demonstrated, although both have been correlated with higher IL-2 doses and production of nitric oxide. Methods: A retrospective study analyzed the association between response to IL-2 and systolic, diastolic, mean blood pressure (BP), and heart rate (HR) at baseline and during treatment, by using the t-test. Further, same comparison was performed after BP was corrected for the amount of neosynephrine (neo) utilized during IL-2 treatment (subtracting the raise in BP produced by neo using individual patient coefficients). 22 patients (13 females, 9 males) with a median age of 54 years (range 36–71) received a total of 26 courses of IL-2 (between 2001–2005). Median number of prior treatments was 2.5 (range 0–5). Outcomes were divided in (A) responders (1CR, 3PRs and 4SDs), and (B) non-responders (18PD). Results: When adjusting for the effects of neo, the corrected mean BP during treatment was significantly lower in (A) compared to (B) (52.17 vs 64.34 mmHg, P = 0.018; mean difference −12.17, 95% CI −22.06 to −2.27). Similarly, the decrease in corrected mean blood pressure from baseline was greater in (A) (−34.89 vs −20.67 mmHg, P = 0.003; mean difference −14.22, 95% CI −23.09 to −5.37). A trend towards statistical significance was recorded for the variation in uncorrected mean BP (17.86 vs. 23.22 mmHg, P = 0.085; mean difference −5.36, 95% CI −11.53 to 0.80). Separate analysis demonstrated a significant drop in both systolic (−17.85 mmHg, P = 0.009; 95% −30.77 to −4.91) and diastolic (−12.05 mmHg, P = 0.01; 95% CI −21.02 to −3.07) corrected BP in (A) vs. (B), but no significant difference for either uncorrected parameters. No correlation between response and the HR, number of IL-2 doses or total quantity of neo was observed. Conclusions: Uncorrected variation in mean BP shows a trend towards significance in predicting response to IL-2. However, corrected mean, systolic and diastolic BP correlate closely with response to treatment. Implications of this association may reside in better outcomes for an intensive IL-2 treatment, with aggressive pressor support. A common pathogenetic basis for response to IL-2 and induction of hypotension is possible.

No significant financial relationships to disclose.
A phase II trial of oxaliplatin in patients with advanced melanoma
Authors: Lutzky J. , Nunez Y. , Graham P.
Published: April 2020

18016

Background: Oxaliplatin is a platinum derivative without nephrotoxicity with in vitro activity against human melanoma cell lines. (Mohammed, MQ, 2000; Tashiro, T, 1989). A Phase I trial suggested activity in melanoma (Mathe, G, 1986) but Phase II data is lacking. A non-nephrotoxic platinum compound active in melanoma is of interest in the development of combination chemo-or chemoimmunotherapy. Methods: This was a Phase II prospective study of oxaliplatin in patients with previously treated or refractory advanced melanoma. The primary endpoint was to evaluate the response rate, survival, freedom from progression (FFP) and the tolerability of oxaliplatin in this patient population. Key inclusion criteria were: metastatic (stage IV) or unresectable malignant melanoma progressing following treatment with at least one and at most three chemotherapy regimens. ECOG PS 0–2, measurable disease and adequate organ and marrow function were required. Oxaliplatin 130 mg/m2 was given IV in 250–500 mL D5W over 120 minutes every 21 days for at least 2 cycles. Patients were evaluated for response every 2 cycles. Gehan’s two-stage design was utilized. Results: Ten patients were treated between March 2004 and March 2005. Three patients were female and 3 male with a median age of 62.5 years. All patients had PS 0–1. The median number of cycles was 2 (1–6). Three patients had disease stabilization (SD) for median of 3 months. No objective responses were seen; therefore, the study did not progress to the second stage.All patients have progressed and all have expired but one. Median survival from registration was 168 days (128–383). Toxicities included grade 2 fatigue (2 pts) and grade 2 neuropathy (3 pts); one patient had grade 3 diarrhea. Conclusions: Treatment with oxaliplatin in previously treated patients with melanoma is well tolerated at the dose and schedule studied but did not result in objective responses and further development in this population cannot be recommended. Incorporation into combination regimens in previously untreated patients may be of interest.

No significant financial relationships to disclose.
NAD(P)H:quinone oxidoreductase 1 expression in human primary melanotic melanomas of the skin
Authors: Zappa F. , Cavalli F.
Published: April 2020

18018

NAD(P)H:quinone oxidoreductase 1 (NQO1; DT-diaphorase; DTD) is a two-electron reducing enzyme which is often over-expressed in cancers and can activate quinones to form cytotoxic species. This over-expression is used as target in the design of novel anti-cancer drugs. DTD is also expressed in normal tissues, but little is known about its “body mapping”. Because of the dearth of information on the cell-specific expression of DTD in pigment-producing cells of the skin, we analysed its expression in normal and tumoral samples. Twenty skin biopsies of primary malignant melanotic melanomas (ten with vertical invasion, ten with superficial spreading) were analysed by immunohistochemistry. In normal skin DTD expression was weak in all epidermal layers, including normal melanocytes. Malignant melanomas showed a very strong DTD expression in tumoral cells of all samples and in endothelial lining of peri-tumoral vessels. These results suggest that DT-diaphorase may be a new marker that could be useful in determining the extent of a malignant melanocytic lesion, and also tend to support the potential of malignant melanomas as target for DTD-directed antitumour agents.

No significant financial relationships to disclose.
Do male partners of breast cancer patients perceive the quality of life of their mates?
Authors: Rabin E. G. , Ferreira Filho A. F. , Da Silva D. L. , De Almeida Fleck M. P.
Published: April 2020

18502

Background: Scant scientific data exists regarding the quality of life (QOL) of female breast cancer patients as perceived by their male partners. Methods: We evaluated the QOL of 73 breast cancer patients and their partners perception using the abbreviated and Portuguese (from Brazil) validated questionnaires forms of the World Health Organization Quality of life (WHOQOL-bref) and WHOQOL-bref adapted for the third person, respectively. The breast cancer patients were also evaluated by the Beck Depression Scale (BDS) and were considered depressed if they had a score equal or greater than 10. The inclusion criteria for this study were: female breast cancer patients with stage I to III, cohabitation with a male partner for at least one year, age from 18 to 65 years old, being able to understand the questionnaires and sign an informed consent term. In order to compare the the scores of the WHOQOL-bref of breast cancer patients and the scores of the adapted WHOQOL-bref of their partners, we used the Pearson correlation index, Student’s t test and variation analysis. All statistical tests were two-sided, and P < .05 was used to indicate statistical significance. Results: In the analysis of all 73 patients, we found no difference between the perceptions of QOL and its domains between the breast cancer patients and their partners (see table ). However, in the subgroups of patients who had a mastectomy (n = 32) or were depressed (n = 35) as measured by the BDS scale, we found differences as their partners rated them higher on the physical domain and psychological domain (P = 0.003 and P = 0.009), respectively. Conclusions: Male partners of breast cancer patients have an accurate perception of their mates’ QOL. The only exceptions we found were in subgroup analysis of women who had a mastectomy and/or were depressed. Our findings suggest that the male partners of breast cancer patients can be seen as reliable surrogates of their QOL.

[Table: see text]

No significant financial relationships to disclose.
Prednisone (P) prophylaxis decreases incidence and severity of lenalidomide (L) induced flare reaction (flr) in patients with relapse (rel) or refractory (ref) chronic lymphocytic leukemia
Authors: Musial L. , Miller K. , Depaolo D. , Swinnich D. , Chanan-Khan A. A.
Published: April 2020

18512

Background: Flare reaction (flr) is a new side effect unique to CLL pts treated with immunomodulating agents both thalidomide (T) and L. It is characterized by tender swelling of disease involved lymph nodes (LN), spleen, rash, low-grade fever and/or increase in absolute lymphocyte counts (ALC). Underlying biologic process remains unknown though it is postulated to be mediated through activation of immune effector cells and/or change in serum concentration of pro-inflammatory cytokines. In a phase II clinical trial of L in rel/ref CLL pts we noted a high incidence of flr. Here we report treatment schema for flr and a new preventive approach employed in this study. Methods: A total of 35 pts are enrolled. No prophylaxis given to initial cohort (A). Pts were treated at onset of symptoms with (1) ibuprofen (Ib) 600 mg po q6 hours (2) oxycodone (oxy) 5–10 mg po prn q 6 hours. In subsequent cohort (B) we are investigating prophylactic use of P 20 mg PO QD starting day −1 × 5 days followed by 10 mg QD × 5 days. Results: All pts had rel or ref disease. Median age 63 (range 48–76) year. In cohort A (n = 29) overall incidence of flr was 79% (n = 23). Of these the severity was graded as I, II and III in 48%, 24%, and 7% respectively. There was no grade IV flr. Symptoms initiated within hours of intake of the 1st dose of L lasting for a median of 14 days (cycle 1 only). Pts were adequately managed with symptom resolution using Ib/oxy. Recurrence in cycle 2 was noted in 1 pt. Pain in LN was the most common complaint. Increase ALC noted in 2 pts. Serum cytokine analysis (n = 5) pre and post 7-days of L treatment showed significant increase in TNF-α, IL-10 and MIG. In cohort B (n = 6) 2 pts had flr (grade I) lasting ≤ 10 days. Conclusions: Prophylactic use of P results in decrease incidence, severity and duration of flr. There was no correlation with clinical response. Elevation of ALC can be part of the flr, pts response should be interpreted cautiously for disease progression. Our findings suggest that use of P may be an effective prophylactic maneuver for prevention of L induced flr. Updated results of cohort B will be presented at this meeting.

[Table: see text]
Finding an effective dose of fentanyl effervescent buccal tablets: Combined results of open-label titration
Authors: Wertheim M. S. , Jhangiani H. , Niebler G. , Charu V.
Published: April 2020

18521

Background: Standard recommendations for short-acting oral opioid doses to manage breakthrough pain (BTP) assume some relation with the stable opioid dose used to treat persistent pain. Fentanyl effervescent buccal tablets (FEBT) are designed to enhance the efficiency of fentanyl absorption through the buccal mucosa. They may provide rapid-onset analgesia. This pooled analysis of data from 3 studies examined the relationship between effective FEBT dose and around-the-clock (ATC) dose in patients who completed open-label titration to an effective FEBT dose. Methods: Patients were 18–80 years of age with cancer, persistent pain, and BTP. Eligible patients experienced an average of 1–4 episodes of BTP per day and were receiving stable doses of opioids (≥60 mg/day of morphine or equivalent) for persistent pain. Titration guidelines were uniform across studies; the maximum allowed dose of FEBT was 800 μg. Results: Of 304 patients enrolled, 208 completed titration to an effective FEBT dose; of these, 100 μg was effective in 21 patients, 200 μg in 32, 400 μg in 45, 600 μg in 49, and 800 μg in 61. The effective dose of FEBT showed no relationship to the dose of either ATC or supplemental opioids. No correlation was found between the effective dose of FEBT and the average dose of prior supplemental opioids (r2 = .0322; Pearson’s coefficient = .1793), the effective dose of FEBT and the dose of ATC opioids in patients using oral ATC opioids (r2 = .0353; Pearson’s coefficient = .1878), or the effective dose of FEBT and the dose of ATC opioids in patients using transdermal fentanyl alone or in combination with other opioids as ATC medication (r2 = .0289; Pearson’s coefficient = .1701). Conclusions: No predictable relationship between the effective dose of FEBT and the dose of ATC opioids was observed. Titration will allow the identification of each patient’s effective dose of FEBT for relief of BTP.

[Table: see text]
Quality of life (QoL) measurement in breast cancer patients who were offered an evaluation at the hereditary cancer unit
Authors: Diz M. D. , Snitcovsky I. , Almeida G. F. , Maistro S. , Federico M. H.
Published: April 2020

18532

Background: An Hereditary Cancer Unity was recently established in our service and we aimed to determine how many of our pts with a history of breast cancer would fulfill the criteria for undergoing BRCA1/2 genetic counseling. In addition, we asked whether or not a routine referral for a consultation in this population should impact on QoL. Methods: From September to November 2005, 180 women being followed-up at our service with a history of breast cancer, not in chemotherapy, were invited to schedule a appointment for genetic counseling. 130 pts answered the invitation and were asked to complete QoL questionnaires EORTC QL30 and BR23 (QLQ) validated into Brazilian Portuguese, before and after genetic counseling. Data were analyzed by Wilcoxon test or regression analysis, whatever appropriate, p≤0.05 considered significant. Results: All 130 pts were evaluated and BRCA1/2 mutation risk assessed based on previously published criteria (Frank et al, JCO 20:1480,2002). We evaluated that, as a whole, 25 pts harbor at least 10% probability and 3 were identified that present at least 20% probability. Three additional pts had bilateral cancer. None of these pts had been previously referred to genetic counseling. Regarding EORTC QLQ pre- and post genetic counseling, we found no differences regarding global QoL (75 vs 66), functional scales physical (80 vs 86), role (100 vs 100), cognitive (83 vs 83, social (100 vs 100), sexual function (83 vs 83), sexual pleasure (50 vs 66) or future perspective (33 vs 66) (p > 0.05). Concerning the emotional scale, we found an improvement after counseling (58 vs 75, p = 0.034) which seems to be clinically meaningful. Emotional status and global QoL were positively correlated (p < 0.000, r = 0.473, Pearson correlation). Conclusions: Our impression is that genetic counseling benefit breast cancer pts in terms of QoL, perhaps decreasing emotional distress. Apart from that, we need to define which risk threshold should be adopted in our service. Acknowledgment: to Marcelo Lopes technical assistance.

No significant financial relationships to disclose.
Patients with stage IV lung cancer lose 25% of their valuable time in the office visits and hospital stay
Authors: Singh J. , Taylor S. , Huang C. , Malani A. K. , Gupta C. , Pabla M.
Published: April 2020

18533

Background: Patients with stage IV lung cancer have median survival of 4–6 months. Randomized trials have shown chemotherapy may have small but significant survival benefit. To achieve this small gain,patients may have to spend their last few days of life in the office visits and hospitalization. Last few days of person’s life need to be spent comfortably and most effective manner in accordance to their wishes, desires and priorties.We attempted to study the “Time Lost” in the stage IV lung cancer patients who either did not choose or were not offered the palliative care/Hospice. Methods: We retrospectively reviewed charts of patients diagnosed with stage IV lung cancer (at their initial presentation) from Jan 2002 to Dec 2005 at our institution. We calculated their inpatient and out patient visit hrs and hence “Time Lost” during the last few days of their life. Patients were divided into two groups—Group A (n = 12): Patients who opted to choose palliative/hospice care immediately after the diagnosis and GroupB (n = 46): Patients who either refused or were not offered palliative/hospice care. Results: The median age at diagnosis was similar in both groups (71 vs 69.5 yrs). The median survival was also similar in both groups (4 months vs 4 months). Patients in group B (non hospice) had 1 month “Lost Time” out of their median survival of 4 months. In comparison patients in group A (hospice) had median survival of 4 months with “No Lost Time”. Thus patients who were not offered hospice or refused hospice spent 25% of their precious time during last stages of their life in inpatient stays and outpatient visits. Conclusions: Patients with stage IV lung cancer should be actively offered palliative/Hospice care, though studies with large number of patients is further required.

[Table: see text]

No significant financial relationships to disclose.
A randomised crossover comparative study of e-diary (electronic diary) versus paper and pencil collection of quality of life data in patients with locally advanced and metastatic non small cell lung cancer
Authors: Ring A. E. , Burbridge S. , Cheong K. , Meddis D. , Underhill L. , Cella D. , Harper P.
Published: April 2020

18536

Background: Electronic diaries have been developed and facilitate collection of quality of life data. However there is concern that their use may alter the properties of the validated quality of life questionnaires which have traditionally been collated using a paper and pencil methodology. This study aimed to compare the results of e-diary and paper and pencil collection of FACT-L and EQ-5D quality of life data, and to ascertain patient preferences for the different modes of collection. Methods: Fifty patients with previously treated locally advanced or metastatic NSCLC were randomised in a 1:1 ratio to either complete a paper version of the questionnaires (FACT-L and EQ-5D) followed by the e-diary (Palm Tungsten W;CRF inc. Helsinki), or e-diary followed by paper questionnaire. Patient preference, ease of use and time for completion were recorded on a separate paper questionnaire. Results: The majority (88%) of the FACT-L and all (100%) of the EQ-5D individual question responses were within ± 1 point by the two methods, although for FACT-L 29% of patients had a total score greater than ± 6 points different by the two methods. There was no significant difference in FACT-L group mean total score for the two methods. The mean completion time was shorter for the paper and pencil than the e-diary (p < 0.0001). However, most patients stated that they preferred the e-diary to paper and pencil (60% vs. 12%). Conclusions: This study suggests that the mode of administration of the FACT-L and EQ-5D had a relatively small effect on the group mean responses given to the questionnaires. However data at the individual patient level looks quite variable between mode of administration. The group results obtained using the e-diary should therefore be comparable to the originally validated paper method, with the advantages of improved patient acceptability and ease of reliable interfacing with trial databases. However care need to be taken in interpreting data at the individual level.

No significant financial relationships to disclose.
Quality of life (QoL) in SAKK 19/03: A multicenter phase II study of first-line gefitinib followed by chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Swiss Group for Clinical Cancer Research (SAKK)
Authors: D’Addario G. , Strasser F. , Ribi K. , Rauch D. , Stupp R. , Pless M. , Stahel R. A. , Rufibach K. , Lerch S. , Betticher D.
Published: April 2020

18559

Background: 63 patients (pts) were accrued in this first study testing first-line tyrosine-kinase inhibitor treatment with gefitinib followed by chemotherapy at disease progression (gemcitabine-cisplatin q3w x6, 41 pts) in stage IIIB/IV NSCLC (ASCO 2005 # 7128). We investigated the longitudinal QoL patterns on both subsequent treatment modalities. Methods: FACT-L including TOI (Trial Outcome Index) and LCS (Lung Cancer Subscale) scores were assessed during both treatment phases (gefitinib: baseline, weeks 3,6,12,18 and every 12 weeks thereafter; chemotherapy: baseline and at d1 of cycle 3 and 5). QoL changes from baseline were descriptively analysed. Improvement was defined as a 6 point (FACT-L, TOI) and 2 point (LCS) increase. Results: QoL-scores are shown in the table below. On gefitinib, at week 6 31/18/32% of pts had improvements of FACT-L, TOI and LCS, respectively and 29/15/41% at week 12 (% based on pts with available data). During chemotherapy the respective improvement rates were 60/60/70% of pts at week 6 and 43/29/43% at week 12. At week 12 of gefitinib, 4 of the pts analysed had partial remission (PR, independently confirmed), 31 pts dropped out (none due to toxicity) and QoL submission rate was 84% based on expected forms. Chemotherapy week 12: 5 PR in analysed pts, 18 drop outs (5 due to toxicity), 43% submission rate. Conclusions: QoL was maintained in pts continuing treatment with gefitinib and decreased at disease progression. QoL and tumor symptoms improved in a considerable part of pts during gefitinib therapy despite low remission rates. Declining submission rate during treatment introduces a potential, unquantifiable bias in QoL.

[Table: see text]

[Table: see text]
Prevalence of written advance directives (AD) among cancer care providers at a community-based cancer center
Authors: Hammes B. A. , Lee J. A. , Mathiason M. A. , Ertz M. T. , Sheldon L. L. , Go R. S.
Published: April 2020

18563

Background: Cancer care providers frequently discuss AD with their patients. The providers’ own attitudes toward end-of-life planning likely influence the choices and actions of their patients. We investigated the prevalence of written AD among the care providers at our community-based cancer center. Methods: All cancer center employees who have face-to-face contacts with patients (N=170) were sent an email survey in October 2005. This included medical (physicians, 15), associate (physician assistants and nurse practitioners, 7), and support (nurses, radiation therapists, medical or nurse assistants, and patient liaisons; 148) staffs. We collected data on demographics, work history, and AD. Results: A reply was obtained from 136 (80%) individuals. There were more females (90.2%) and the median age was 43 years (range, 20–63). While 82.8% reported to have discussed their wishes regarding future life-sustaining medical care with those closest to them, only 35.1% had a written AD: medical (58.3%), associate (50%), and support staffs (32.2%). Among those with AD, only 66% had made their own care providers aware of this. The top 5 factors that influenced providers whether to have or not to have AD were: experience at work (36.6%), spouse/domestic partner (25.4%), time to complete written AD (23.9%), family members/friends (21.6%) and children (19.4%). Interestingly, no one considered medical condition or illness as a factor. Increased age was significantly associated with having AD (odds ratio: 1.068; 95% CI:1.029–1.108), while the sex, number of years working with cancer patients, provider role, and marital/living status were not. Among the medical and associate staffs, 55.6% reported routinely discussing AD with their patients. Although all medical/associate staffs rated themselves as knowledgeable about and comfortable with discussing AD, the group who had AD was more apt to rate themselves as very knowledgeable and very comfortable. Conclusions: Only about a third of all cancer care providers and about half of cancer physicians at our institution have a written AD. Despite work experience with a patient population having a high mortality rate, cancer care providers do not adequately communicate end-of-life planning to their own health care providers.

No significant financial relationships to disclose.
Is gabapentin effective for preventing delayed nausea and vomiting (NV) after moderately and highly emetogenic chemotherapy (CT)?
Authors: Menendez-Leal A. , Quijano C. , Menendez-Rivera A. G.
Published: April 2020

18575

Background: Following previous institutional observations,this protocol was designed to evaluate the efficacy of Gabapentin in the prophylaxis of delayed CT induced NV. Methods: The main elegibility criteria was moderate and severe NV on previous CT cycles.Gabapentin 300 mg caps. was given as follows: One capsule day -2, two capsules day -1 and one capsule tid from days 1 to 5. 24 pats. were evaluated; 22 (92%) female, 2 (8%) male.CT included Doxorubicin/Ciclofosfamide 15 (62.5%), Cis-Platin 5 (21%), Other regimens 4 (17%). Previous prophylaxis for all pats. included a 5-HT3 Antagonist plus Dexametasone. Pats. were instructed to complete a two-page Questionaire: On page 1 pats. indicated the intensity of nausea according a scale shown there. On page two they indicated the number of vomits they had.This was made three times daily for five days. The primary endpoint was reduction of NV aftyer CT. Results: The reduction observed in the number of vomits was as follows: Number of pats. that experienced 0 Vomits: day 1 (CT): 14 (58.3%); day 2: 18 (75%); day 3: 20 (83.3%); day 4: 18 (75%); day 5: 22 (91.7%). On the other hand, pats. that did not respond and had three or more vomits daily: day 1: 5 (20.8%); day 2: 2 (8.3%); day 3: 1 (4.2%); day 4: 3 (12.5%); day 5: 2 (8.3%).Most pats. experienced a decrease in the intensity of nausea as well. No significant side effects were seen. Conclusions: Gabapentin seems to have some efficacy preventing delayed NV after moderately and highly emetogenic CT. These results together with it’s possible effect on acute NV and good tolerability warrant further studies.

No significant financial relationships to disclose.
Quality of life intervention for men with biochemical recurrence of prostate cancer
Authors: Tan W. , Ames S. , Gretchen A. , Stone R. , Rizzo T. , Covil E. , Olmos J. , Clark M. M. , Rummans T.
Published: April 2020

18585

Background: The Quality of life (QOL) and psychosocial needs of the 30–40% of prostate cancer patients who experience biochemical recurrence are not known. The impact of having a rising PSA, anticipation of undergoing PSA testing, and living with prostate cancer may increase psychological distress and decrease QOL. Aim: to evaluate the psychosocial treatment needs of men with biochemical recurrence of prostate cancer (br-PCa) and to develop a treatment to address these needs. Methods: 28 men with br-PCa, 58–87 years, were enrolled. A qualitative research approach was used, consisting of six, 2 hour, semi-structured, focus groups containing 4–6 men per group. Data were content coded and grouped into categories following the structure of the focus group guide. The major conceptual themes were then summarized by 2 independent reviewers. Discrepancies were discussed with a third researcher until a consensus was reached. These results were used to guide development of a multi-disciplinary quality of life intervention. Results: Participants defined QOL as the ability to stay active both physically and mentally without limitation in the performance of usual activities. There was a consensus that prostate cancer led to substantial anxiety related to PSA testing, treatment side effects, and fear of recurrence. Participants were enthusiastic about receiving adjuvant multidisciplinary treatment for prostate cancer focusing on anxiety management, nutrition, exercise, management of treatment side effects, and medical education. Participants desired a male group leader and feedback was mixed regarding whether spouses should be involved. Conclusions: Men with br-PCa report experiencing substantial anxiety and were enthusiastic about receiving a structured intervention to these needs. Based on our findings an intervention has been developed and is currently being compared to usual care.

No significant financial relationships to disclose.
Piperacillin/tazobactam monotherapy versus combination ceftazidime plus amikacin for the treatment of febrile neutropenia in patients with cancer: A Hellenic Co-Operative Oncology Group Study
Authors: Pectasides D. , Fountzilas G. , Samonis G. , Panidis D. , Grimani I. , Bafaloukos D. , Pavlidis N. , Pectasides M. , Kyroudi-Markantoni S. , Aravantinos G.
Published: April 2020

18590

Background: Combinations of β-lactam antibiotics and aminoglycosides are considered standard therapy for febrile neutropenia. Monotherapies have been proposed as standard treatments, demonstrating equal efficacy and better safety. Methods: This is a prospective, multi-centre, randomized clinical trial. Cancer patients with absolute neutrophil count (ANC) <1,000/mm3 and fever >38oC for ≥ 2 hours were randomized to either piperacillin/tazobactam 4.5 g every 8 h i.v. (group A) or ceftazidime 2 g every 8 h plus amikacin 15 mg/kg i.v. per day (group B). In case of fever >38oC 48 h after initiation of the therapy, vancomycin 500 mg every 6 h i.v. was added. Minimal duration of treatment was 72 hours. Treatment was continued for 7 days in case of improvement, otherwise vancomycin was added or the study therapy was discontinued. Early efficacy was assessed on day 3 and overall response 4 days after the end of treatment. Complete success was defined the patient to become afebrile and no other antibiotics to be added. Treatment failures were classified in two categories, those in which vancomycin was added to the study regimen, and those in which other antibiotics were used. Categorical variables were compared between treatment groups with the use of Fisher’s exact test, while for continuous Wilcoxon’s rank sum test was used. Results: One hundred twenty-seven febrile episodes were treated (group A: 66, group B: 61). Patient characteristics were well balanced in terms of age, underlying malignancies, ANC, and granulocyte-colony stimulating factor (G-CSF) support. Both treatments were well tolerated. No significant differences were seen in terms of success to treatment. Complete success was achieved in 45 (68%) of patients in group A and 40 (66%) in group B, while another 8 patients in group A (12%) and 6 in group B (10%) required addition of pre-defined anti-staphyloccocci antibiotic. Conclusions: Empirical treatment of febrile neutropenic episodes with piperacillin/tazobactam monotherapy appears to be as effective as the “standard” ceftazidime/amikacin combination.

No significant financial relationships to disclose.
Oncologists practice with opioids in cancer pain
Authors: El-Foudeh M. , Alsirafy S. A. , Hassan A. , Hidayetullah M.
Published: April 2020

18602

Background: The majority of cancer patients are mostly under the care of their primary oncologists for both active and symptom management. Pain is the most feared symptom in cancer patients. In general, it is highly prevalent and under treated. Barriers to adequate pain management still exist even among specialized care givers. Improper opioid utilization is one of main factors within those impediments. The pattern of opioid prescription among oncologists in a specialized hospital was examined on referral to a palliative care unit within the same institution. Methods: Over a period of six months (between Dec. 2003 and June 2004) 290 cancer patients were referred to the section of palliative medicine from different medical specialties within the same institution. The medical records of 233 (80%) were analyzed, 116(50%) were referred from oncology specialists (radiation, medical & hematology oncology), 76 referred patients fulfilled the study criteria. On referral; all eligible patients had to be on opioids for pain. The pattern of opioid prescription by oncologists in this group of patients with reference to the currently available guidelines was examined. Results: The following results were found: Pain was inadequately controlled in 71% patients. Although, the majority of the patients 92% were able to utilize the oral route, it was only used in 36% of patients. The first strong regular opioid was the standard morphine in only 46% of patients. Breakthrough opioid was prescribed to most patients (91%). However, dose and interval were outside the general guidelines in 44% & 81% respectively. Laxatives were not prescribed in half of the patients Conclusions: Opioids are the principal effective, relatively simple and practical drugs in pain relief. Yet, within specialized care providers as shown in this study, opioid utilization was unsatisfactory. More understanding of pain assessment, better opioid utilization and more knowledge of opioid pharmacology still warranted.

No significant financial relationships to disclose.
Analysis of factors influencing outcome in patients with in transit malignant melanoma (MM) undergoing isolated limb perfusion (ILP) using standardized operative parameters with melphalan and biological agents
Authors: Soriano P. A. , Libutti S. K. , Pingpank J. F. , Beresenev T. , Steinberg S. M. , Bartlett D. L. , Fraker D. L. , Helsabeck C. , Alexander H. R.
Published: April 2020

8006

Background: In transit disease afflicts about 10% of MM patients and no single systemic or regional treatment has been widely accepted as most effective or appropriate. Previously, the impact of ILP on the natural history of MM patients has been difficult to gauge. We report long-term outcomes in MM patients undergoing hyperthermic ILP in an era of increasingly accurate staging, uniform operative and treatment conditions, and regular follow-up. Methods: Between 5/1992 to 2/2005, 90 patients (median age: 57 y [range: 24–84]; F: 49, M: 41) with Stage IIIA or IIIAB MM underwent a 90 min hyperthermic (mean calf T: 39.3° C) ILP (melphalan: 10–13 mg/L limb volume, TNF: 3–6 mg [n=44], or IFN: 200 μg [n=38]) using uniform operative technique including intra-operative leak monitoring. There was 1 operative mortality (1/91, 1.1%). Patients were prospectively followed for response, in-field progression free (PFS), and overall survival (OS). Parameters associated with in-field PFS and OS were analyzed by the Kaplan-Meier method with log rank tests, as well as by Cox proportional hazards models. Results: There were 61 complete responses (68%) and 23 partial responses (26%). At a median follow-up of 47 months, median in-field PFS was 12.4 months, and median OS was 47.4 months; 5 and 10-year actuarial OS were 43 and 34%, respectively. Female gender and low tumor burden (< 20 tumors) were associated with prolonged in-field PFS (M:F hazard ratio (HR): 2.07, CI:1.27–3.38; 21+ vs. ≤20 tumors HR: 2.29, CI: 1.21- 4.34; p<0.011 for both) in a Cox model, whereas TNF, IFN, perfusion pressure, and tumor stage were not. Female gender was associated with improved OS (p=0.027, M:F HR=1.82, 95% CI 1.07–3.09) and Stage IIIA marginally so, in univariate analysis, (p=0.065). Conclusions: ILP for MM patients is associated with noteworthy in-field PFS and prolonged OS. Neither use of TNF nor tumor stage were significantly associated with in-field PFS in Cox models, while female gender was associated with better outcomes. In appropriately selected patients using standardized technique, ILP has clinical benefit in this setting.

No significant financial relationships to disclose.
Estimating survival probability in stage III melanoma: A multivariable individualized patient risk assessment nomogram
Authors: Coit D. G. , Qin Zhou C. , Patel A. , Panageas K.
Published: April 2020

8020

Background: Recent revisions in the AJCC staging system have increased its complexity without comparable improvement in prognostic accuracy for patients with Stage III melanoma. Furthermore, there remains significant prognostic heterogeneity, even within Stages IIIA, IIIB, and IIIC. The current study was undertaken to develop a model for individual patient risk assessment, both to facilitate patient care, and to help define prognostically homogeneous patient populations for entry into clinical trials. Methods: Patients with AJCC Stage III melanoma were identified from a prospective single institution database. Overall survival was calculated from the date of Stage III to last followup. A multivariate Cox model of independent prognostic factors was developed, and a multivariable individualized patient risk assessment nomogram was built from that model. Results: Among 1,064 patients with Stage III melanoma, 535 have died, at a median followup of 44 months. Independent predictors of overall survival are shown in the table. Individual patient three and five year survival was predicted by incorporating all eight variables into a prognostic nomogram. The nomogram was superior to the AJCC Staging system in predicting outcome in Stage III melanoma patients. Conclusions: Individual patient risk assessment is more accurate than traditional AJCC staging in predicting outcome in Stage III melanoma. This approach, which can be easily incorporated into a handheld computing environment, offers potential advantages for both patient care and clinical research, and should be explored in the next iteration of the AJCC staging system.

[Table: see text]

No significant financial relationships to disclose.
Gene expression profiling of primary cutaneous melanoma: Expression of replication origins firing genes predicts clinical outcome
Authors: Spatz A. , Winnepenninckx V. , Lazar V. , Michiels S. , Dessen P. , Stas M. , Eggermont A. M. , Sarasin A. , Tursz T. , Van Den Oord J.
Published: April 2020

8024

Background: Gene-expression profiling in human cutaneous melanomas is impaired by the difficulty in getting access to a retrospective collection of frozen tumors. Thus, compared to other tumors, gene expression profiling data on human cutaneous melanomas are scarce, and data with prognostic implication are entirely lacking. In order to better understand the progression of this tumor and to identify key genes involved in melanoma prognosis, we correlated gene-expression profiles with clinical outcome in a cohort of 83 patients with primary melanoma. Methods: A class comparison and class prediction analysis was performed to identify genes able to predict 4-years. distant metastasis free-survival in 58 primary melanomas with at least 4-years follow-up or intercurrent distant metastasis or death. Results were also validated at the protein level in an independent population of 176 primary melanomas with a median clinical follow-up of 8.5 years. Results: We identified a set of sequences discriminating between primary melanomas associated with good and poor prognosis. Some of these sequences correspond to key-genes in the regulation of replication origins firing, such as mini-chromosome maintenance genes and geminin. The prognostic value of overexpression of replication origins firing genes is independent from thickness, ulceration, age and sex. Conclusions: This study has identified key-genes associated with in vivo metastatic dissemination of cutaneous melanomas. Some of our data provide new diagnostic tools for the accurate diagnosis of melanoma and shed new light on the molecular mechanisms underlying poor prognosis in melanoma patients. As some of these molecules are currently under study as targets for therapy, our data can have significant impact on the development of new melanoma therapies.

No significant financial relationships to disclose.