A systematic review and meta-analysis of the impacts of germline pharmacogenomics on severe toxicity and symptom burden in adult patients with cancer.

The clinical application of Pharmacogenomics (PGx) has improved patient safety. However, comprehensive PGx testing has not been widely adopted in clinical practice, and significant opportunities exist to further optimize PGx in cancer care. This systematic review and meta-analysis aim to evaluate the safety outcomes of reported PGx-guided strategies (Analysis 1) and identify well-studied emerging pharmacogenomic variants that predict severe toxicity and symptom burden (Analysis 2) in patients with cancer. We searched MEDLINE, EMBASE, CENTRAL, clinicaltrials.gov, and International Clinical Trials Registry Platform from inception to January 2023 for clinical trials or comparative studies evaluating PGx strategies or unconfirmed pharmacogenomic variants. The primary outcomes were severe adverse events (SAE; ≥ grade 3) or symptom burden with pain and vomiting as defined by trial protocols and assessed by trial investigators. We calculated pooled overall relative risk (RR) and 95% confidence interval (95%CI) using random effects models. PROSPERO, registration number CRD42023421277. Of 6811 records screened, six studies were included for Analysis 1, 55 studies for Analysis 2. Meta-analysis 1 (five trials, 1892 participants) showed a lower absolute incidence of SAEs with PGx-guided strategies compared to usual therapy, 16.1% versus 34.0% (RR = 0.72, 95%CI 0.57-0.91, p = 0.006, I2 = 34%). Meta-analyses 2 identified nine medicine(class)-variant pairs of interest across the TYMS, ABCB1, UGT1A1, HLA-DRB1, and OPRM1 genes. Application of PGx significantly reduced rates of SAEs in patients with cancer. Emergent medicine-variant pairs herald further research into the expansion and optimization of PGx to improve systemic anti-cancer and supportive care medicine safety and efficacy.

What is the association of preoperative biopsy with recurrence and survival in retroperitoneal sarcoma? A systematic review by the Australia and New Zealand Sarcoma Association clinical practice guidelines working party.

Preoperative biopsy for retroperitoneal sarcoma (RPS) enables appropriate multidisciplinary treatment planning. A systematic review of literature from 1990 to June 2022 was conducted using the population, intervention, comparison and outcome model to evaluate the local recurrence and overall survival of preoperative biopsy compared to those that had not. Of 3192 studies screened, five retrospective cohort studies were identified. Three reported on biopsy needle tract seeding, with only one study reporting biopsy site recurrence of 2 %. Two found no significant difference in local recurrence and one found higher 5-year local recurrence rates in those who had not been biopsied. Three studies reported overall survival, including one with propensity matching, did not show a difference in overall survival. In conclusion, preoperative core needle biopsy of RPS is not associated with increased local recurrence or adverse survival outcomes.

A Scoping Review of Oncosexology Policy and Practice Tools Focused on Adolescents and Young Adults.

Background: Despite being considered a key component of quality-of-life, sexual health concerns in adolescents and young adults (AYA) patients with cancer (aged 15-39 years old) are often unmet due to barriers from both patients and health care professionals (HCPs). Investigation into policy and practice tools in this scope of practice is also limited. Aim: To review the literature on policy and practice tools in AYA oncosexology. Method: A scoping review was conducted using four databases: Medline, EMCARE, EMBASE, and PsycINFO, based on the Joanna Briggs Institute Scoping Review methodology. Retrieved articles were extracted into Covidence, followed by two screening rounds. Descriptive and basic content analyses were performed for evidence synthesis. Results: Seventy-four articles were included after screening rounds and citation searches. Overall, oncosexology policy and practice tools were categorized into screening tools (11 articles), guidelines (38 articles), training programs (15 articles), service delivery initiatives (5 articles), and the evaluation of their feasibility/challenges to implementation (5 articles). Among these, only ten articles were specifically about the AYA population. They helped identify and resolve sexual health concerns in AYA patients with cancer by providing strategies to overcome communication barriers, treatment options, and information resources for patients, and by advocating for more HCP education on this topic. Conclusion: The results warrant the need for more research, implementation and expansion of policy and practice tools for sexual health issues in AYA patients with cancer.

High-dose chemotherapy for Ewing sarcoma and Rhabdomyosarcoma: A systematic review by the Australia and New Zealand sarcoma association clinical practice guidelines working party.

INTRODUCTION: Patients with high-risk or metastatic Ewing sarcoma (ES) and rhabdomyosarcoma (RMS) have a guarded prognosis. High-dose chemotherapy (HDT) with autologous stem cell transplant (ASCT) has been evaluated as a treatment option to improve outcomes. However, survival benefits remain unclear, and treatment is associated with severe toxicities. METHODS: A systematic review was conducted, using the population, intervention, comparison outcome (PICO) model, to evaluate whether utilization of HDT/ASCT impacts the outcome of patients with ES and RMS compared to standard chemotherapy alone, as part of first line treatment or in the relapse setting. Medline, Embase and Cochrane Central were queried for publications from 1990 to October 2022 that evaluated event-free survival (EFS), overall survival (OS), and toxicities. Each study was screened by two independent reviewers for suitability. A qualitative synthesis of the results was performed. RESULTS: Of 1,172 unique studies screened, 41 studies were eligible for inclusion with 29 studies considering ES, 10 studies considering RMS and 2 studies considering both. In ES patients with high-risk localised disease who received HDT/ASCT after VIDE chemotherapy, consolidation with melphalan-based HDT/ASCT as first line therapy conveyed an EFS and OS benefit over standard chemotherapy consolidation. Efficacy of HDT/ASCT using a VDC/IE backbone, which is now standard care, has not been established. Survival benefits are not confirmed for ES patients with metastatic disease at initial diagnosis. For relapsed/refractory ES, four retrospective studies report improvement in outcomes with HDT/ASCT with the greatest evidence in patients who demonstrate a treatment response before HDT, and in patients under the age of 14. In RMS, there is no proven survival benefit of HDT/ASCT in primary localised, metastatic or relapsed disease. CONCLUSION: Prospective randomised trials are required to determine the utility of HDT/ASCT in ES and RMS. Selected patients with relapsed ES could be considered for HDT/ASCT.

Recommendation on the technical and dosimetric data to be included in stereotactic body radiation therapy clinical trial publications based on a systematic review.

The results of phase II and III trials on Stereotactic Body Radiation Therapy (SBRT) increased adoption of SBRT worldwide. The ability to replicate clinical trial outcomes in routine practice depends on the capability to reproduce technical and dosimetric procedures used in the clinical trial. In this systematic review, we evaluated if peer-reviewed publications of clinical trials in SBRT reported sufficient technical data to ensure safe and robust implementation in real world clinics. Twenty papers were selected for inclusion, and data was extracted by a working group of medical physicists created following the ESTRO 2021 physics workshop. A large variability in technical and dosimetric data were observed, with frequent lack of required information for reproducing trial procedures. None of the evaluated studies were judged completely reproducible from a technical perspective. A list of recommendations has been provided by the group, based on the analysis and consensus process, to ensure an adequate reproducibility of technical parameters in primary SBRT clinical trials. Future publications should consider these recommendations to assist transferability of the clinical trial in real world practice.

A systematic review of the role of chemotherapy in retroperitoneal sarcoma by the Australia and New Zealand sarcoma association clinical practice guidelines working party.

BACKGROUND: In primary localised resectable retroperitoneal sarcoma (RPS), loco-regional and distant relapse occur frequently despite optimal surgical management. The role of chemotherapy in improving outcomes is unclear. METHODS: A systematic review was conducted, using the population, intervention, comparison outcome (PICO) model, to evaluate whether neoadjuvant or adjuvant chemotherapy improve outcomes in adults with primary localised resectable RPS. Medline, Embase and Cochrane Central were queried for publications from 1946 to June 2022 that evaluated recurrence free survival, overall survival, and post operative complications. Each study was screened by two independent reviewers for suitability. A qualitative synthesis of the results was performed. RESULTS: Twenty three studies were identified; one meta-analysis of retrospective studies and 22 retrospective studies including three with propensity matched cohorts. Most studies did not analyse outcomes by histology, detail treatment regimens, provide baseline characteristics or selection criteria for those receiving chemotherapy. Evidence of selection bias was illustrated in several studies. Newcastle-Ottawa quality of retrospective cohort studies was good for 12 studies and poor for 10 studies. All studies were assessed as Level III-2 evidence by the Australian NHMRC hierarchy. Overall, the addition of neoadjuvant or adjuvant chemotherapy to surgery was not associated with improvement in local recurrence, metastasis free survival, disease free survival or overall survival in primary localised resectable RPS. There is some evidence of an association of chemotherapy with worse overall survival. One single centre study showed that neoadjuvant chemotherapy was not associated with increased post operative complications compared to surgery alone in primary localised resectable RPS. CONCLUSIONS: There is currently no evidence that demonstrates the addition of chemotherapy to surgery improves outcomes in adult patients with primary localised resectable RPS. Available evidence is limited by its retrospective nature and high likelihood of selection bias with chemotherapy generally administered to patients at higher risk of recurrence and many patients not receiving care in high volume sarcoma centres. Randomised trials are required to conclusively determine the role of chemotherapy in primary localised resectable RPS.

Pain management for persistent pain post radiotherapy in head and neck cancers: systematic review.

OBJECTIVES: To systematically review the existing literature for evidence of efficacy around interventions in the management of persistent pain post radiotherapy for head and neck cancers. METHODS: A systematic review of the literature was conducted to assess the effectiveness and safety of interventions for the management of persistent post-radiotherapy pain in head and neck cancers. The primary outcome evaluated whether an intervention resulted in a reduction in pain which was determined using validated pain tools. RESULTS: Two randomised controlled trials involving 196 participants fulfilled the inclusion criteria, one evaluating the effect of hypnotherapy and the other evaluating the effect of pregabalin on radiotherapy related pain in head and neck cancer patients. In one study by Thuma et al. (2016) there was a decrease in pain scores in the hypnotherapy group (p<0.001). In the other study, by Jiang et al. (2018) patients treated with pregabalin had a greater reduction in pain intensity, pain severity and a reduction in pain functional interference (p<0.001). CONCLUSIONS: The findings of our review suggest that in chronic post-radiotherapy pain for head and neck cancers there is very-low level evidence for the use of hypnotherapy in reducing pain scores and for the use of pregabalin in reducing pain intensity, severity, functional interference and psychological distress with significant improvement in quality of life.

A systematic review of knowledge, attitude and practice of pharmacogenomics in pediatric oncology patients.

Pharmacogenomics remains underutilized in clinical practice, despite the existence of internationally recognized, evidence-based guidelines. This systematic review aims to understand enablers and barriers to pharmacogenomics implementation in pediatric oncology by assessing the knowledge, attitudes, and practice of healthcare professionals and consumers. Medline, Embase, Emcare, and PsycINFO database searches identified 146 relevant studies of which only three met the inclusion criteria. These studies reveal that consumers were concerned with pharmacogenomic test costs, insurance discrimination, data sharing, and privacy. Healthcare professionals possessed mostly positive attitudes toward pharmacogenomic testing yet identified lack of experience and training as barriers to implementation. Education emerged as the key enabler, reported in all three studies and both healthcare professionals and consumer groups. However, despite the need for education, no studies utilizing a pediatric oncology consumer or healthcare professional group have reported on the implementation or analysis of a pharmacogenomic education program in pediatric oncology. Increased access to guidelines, expert collaborations and additional guidance interpreting results were further enablers established by healthcare professionals. The themes identified mirror those reported in broader pediatric genetic testing literature. As only a small number of studies met inclusion criteria for this review, further research is warranted to elicit implementation determinants and advance pediatric pharmacogenomics.

Healthcare professionals' and consumers' knowledge, attitudes, perspectives, and education needs in oncology pharmacogenomics: A systematic review.

Clinical implementation of pharmacogenomic (PGx)-guided prescribing in oncology lags behind research evidence generation. We aimed to identify healthcare professionals' (HCPs) and consumers' knowledge, attitudes, perspectives, and education needs to inform strategies for implementation of scalable and sustainable oncology PGx programs. Systematic review of original articles indexed in EMBASE, EMCARE, MEDLINE, and PsycInfo from January 2012 until June 2022, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and using the Mixed Methods Appraisal Tool. PROSPERO registration number CRD42022352348. Of 1442 identified studies; 23 met inclusion criteria with 87% assessed high quality. Of these, 52% reported on HCPs, 35% on consumers, and 13% on both HCPs and consumers. Most were conducted in the United States (70%) and included multiple cancer types (74%). Across studies, HCPs and consumers mostly perceived value in PGx, however, both groups reported barriers to utilization, including cost, lack of consistent recommendations across guidelines, and limited knowledge among HCPs; test accuracy, clear testing benefits, and genomic information confidentiality among consumers. HCPs and consumers value and want to engage in PGx strategies in oncology care, however, are inhibited by unmet needs and practice and knowledge gaps. Implementation strategies aimed at addressing these issues may best support increased PGx uptake in oncology practice.

The role of radiation therapy in the management of primary retroperitoneal sarcoma: A systematic review and clinical practice guidelines from the Australia and New Zealand Sarcoma Association.

While surgery is the mainstay of treatment for localised retroperitoneal sarcoma, the use of radiotherapy (RT) remains controversial. This systematic review aimed to evaluate the role of RT for retroperitoneal sarcoma. A systematic review using the population, intervention, comparison, and outcome model from 1990 to 2022 identified 66 studies (a mixture of preoperative and postoperative RT); one randomised controlled trial (RCT) with two publications, 18 registry studies, and 46 retrospective studies. In the RCT of preoperative RT, there was no difference in local/abdominal recurrence. The pooled analysis of this RCT and a retrospective study showed a significant abdominal recurrence free survival benefit with preoperative RT in low grade liposarcoma. The RCT and the majority of retrospective series found RT did not improve recurrence free survival (11 of 16 no difference in combined local and distant RFS, 11 of 13 no difference in distant metastasis free survival), disease specific survival (9 of 12 studies) or overall survival (33 of 49 studies). The majority of studies found no association between RT and perioperative morbidity. In summary, preoperative RT may improve local control for low grade (well-differentiated or grades 1-2 dedifferentiated) liposarcoma, but not other histological subtypes. There is no strong evidence that perioperative RT provides an overall survival benefit. Patients with low grade retroperitoneal liposarcoma can be considered for preoperative RT to improve abdominal recurrence free survival. The rationale and level of evidence in this scenario should be carefully discussed by the multidisciplinary team with patients. RT should not be routinely recommended for other histological subtypes.

Surgery at specialised sarcoma centres improves patient outcomes - A systematic review by the Australia and New Zealand sarcoma association clinical practice guidelines working party.

BACKGROUND: Optimal management of sarcoma requires multidisciplinary team input throughout the process of diagnosis, treatment and follow up. This systematic review aimed to evaluate the impact of surgery performed at specialised sarcoma centres on outcomes. METHODS: A systematic review was conducted using the population, intervention, comparison and outcome (PICO) model. Medline, Embase, Cochrane Central databases were queried for publications that evaluated the local control, limb salvage rate, 30-day and 90-day surgical mortality, and overall survival in patients undergoing surgery in a specialist sarcoma centre compared with non-specialist centre. Each study was screened by two independent reviewers for suitability. A qualitative synthesis of the results was performed. RESULTS: Sixty-six studies were identified. The majority of studies were Level III-3 as assessed by the NHMRC Evidence Hierarchy, whilst just over half of the studies were of good quality. Definitive surgery performed at specialised sarcoma centres was associated with improved local control as defined by lower rate of local relapse, higher rate of negative surgical margins, improved local recurrence free survival and higher limb conservation rate. Available evidences show a favourable pattern of lower 30-day and 90-day mortality rates, and greater overall survival when surgery was performed in specialist sarcoma centres compared with non-specialised centres. CONCLUSIONS: Evidences support better oncological outcomes when surgery is performed at specialised sarcoma centre. Patients with suspected sarcoma should be referred early to a specialised sarcoma centre for multidisciplinary management, which includes planned biopsy and definitive surgery.

The benefit for radiotherapy at specialised sarcoma centres: A systematic review and clinical practice guidelines from the Australia and New Zealand Sarcoma Association.

Patients with sarcoma are best managed at specialised sarcoma centres as supported by published literature. Optimal management requires multidisciplinary team input to formulate the diagnosis and treatment sequencing taking into consideration multiple clinical and pathologic factors. This systematic review aimed to evaluate the impact on outcomes of radiotherapy at specialised sarcoma centres. A systematic review was conducted using the population, intervention, comparison and outcome model. A literature search was performed using Medline, Embase, Cochrane Central databases for publications from 1990 to February 2022 that evaluated the local control, survival and toxicity of radiotherapy at specialised sarcoma centres. A total of 21 studies were included (17 cancer registry studies, four retrospective comparative studies). Four studies reported the local recurrence endpoint when radiotherapy was part of limb conservation treatment and showed better conformity to clinical practice guidelines and an improved local recurrence free rate when radiotherapy treatment is supported through, but may not be necessarily delivered at a specialised sarcoma centres. Only one retrospective study analysed toxicity specifically and demonstrated that patients who received preoperative radiotherapy at community centres compared to radiotherapy at a specialised sarcoma centre were more likely to develop a major wound complication. Fourteen studies reported overall survival, and 12 of these showed significantly better 5-year overall survival for patients managed at specialised sarcoma centres, however the specific impact of radiotherapy delivered at sarcoma centres could not be determined. In conclusion, patients with sarcoma should be managed through specialised sarcoma centres for better oncological outcomes. Radiotherapy in specialised sarcoma centre is associated with a lower rate of wound complications and may contribute to improved oncological outcomes as part of the limb conservation treatment at a specialised sarcoma centre.

A systematic review and meta-analysis of toxicity and treatment outcomes with pharmacogenetic-guided dosing compared to standard of care BSA-based fluoropyrimidine dosing.

BACKGROUND: Serious and potentially life-threatening toxicities can occur following 5-fluorouracil/capecitabine exposure. Patients carrying Dihydropyrimidine Dehydrogenase (DPYD) variant alleles associated with decreased enzymatic function are at a greater risk of early/severe 5-fluorouracil/capecitabine toxicity. The objective of this systematic review/meta-analysis was to evaluate treatment outcomes between Pharmacogenetics Guided Dosing (PGD) versus non-PGD and within PGD (DPYD variant allele carriers versus wild type). METHODS: A systematic review/meta-analysis of original publications indexed in Ovid Medline, Ovid Embase, and the Cochrane CENTRAL (Wiley) library from inception to 7-Dec-2020. Eligible studies evaluated at least one pre-defined treatment outcome measures (toxicity/hospitalisations/survival/overall response/quality of life). RESULTS: Of 1090 identified publications, 17 met predefined eligibility criteria. The meta-analysis observed reduced incidence of grade 3/4 overall toxicity (Risk Ratio [RR] 0.32 [95% Cl 0.27-0.39], p < 0.00001) and grade 3/4 diarrhoea (RR 0.38 [95% Cl 0.24-0.61], p < 0.0001) among PGD versus non-PGD cohorts. Within PGD cohorts, there was no statistical differences for overall response rates (complete/partial) (RR 1.31 [95% Cl 0.93-1.85], p = 0.12). Similar results were found with stable disease (RR 1.27 [95% Cl 0.66-2.44], p = 0.47). CONCLUSION: PGD improves patient outcomes in terms of grade 3/4 toxicity, in particular overall toxicity and diarrhoea, without impacting on treatment response. REGISTRATION NUMBER: The study is registered with PROSPERO, registration number CRD42020223768.

Immunogenicity of COVID-19 vaccines in patients with hematologic malignancies: a systematic review and meta-analysis.

The objectives of this study were to assess the immunogenicity and safety of COVID-19 vaccines in patients with hematologic malignancies. A systematic review and meta-analysis of clinical studies of immune responses to COVID-19 vaccination stratified by underlying malignancy and published from January 1, 2021, to August 31, 2021, was conducted using MEDLINE, EMBASE, and Cochrane CENTRAL. Primary outcome was the rate of seropositivity after 2 doses of COVID-19 vaccine with rates of seropositivity after 1 dose, rates of positive neutralizing antibodies, cellular responses, and adverse events as secondary outcomes. Rates were pooled from single-arm studies while rates of seropositivity were compared against the rate in healthy controls for comparator studies using a random effects model and expressed as a pooled odds ratios with 95% confidence intervals. Forty-four studies (16 mixed group, 28 disease specific) with 7064 patients were included in the analysis (2331 after first dose, 4733 after second dose). Overall seropositivity rates were 62% to 66% after 2 doses of COVID-19 vaccine and 37% to 51% after 1 dose. The lowest seropositivity rate was 51% in patients with chronic lymphocytic leukemia and was highest in patients with acute leukemia (93%). After 2 doses, neutralizing antibody response rates were 57% to 60%, and cellular response rates were 40% to 75%. Active treatment, ongoing or recent treatment with targeted and CD-20 monoclonal antibody therapies within 12 months were associated with poor immune responses to COVID-19 vaccine. New approaches to prevention are urgently required to reduce COVID-19 infection morbidity and mortality in high-risk patient groups that respond poorly to COVID-19 vaccination.

Do antispasmodics or rectal enemas improve image quality on multiparametric prostate MRI? An 'Evidence-Based Practice' review of the literature.

Multiparametric magnetic resonance imaging (mpMRI) of the prostate is increasingly used for the preoperative detection and staging of prostate cancer. Image quality of prostate mpMRI can be significantly degraded by motion related artefact due to bowel peristalsis and susceptibility related artefact, which reduces cancer detection sensitivity. The use of several different methods including anstispasmodic medications and rectal enemas were proposed as potential methods to reduce mpMRI artefacts, but current recommendations in the scientific literature are conflicting and inconsistent. This article seeks to identify the best available evidence to determine which patient preparation method is most effective in improving prostate mpMRI, and provides recommendations for further areas of research. We used the five-step 'Evidence-Based Practice' systematic approach of 'Ask, Search, Appraise, Apply and Evaluate' described by the McMaster University and National Health Service for critical appraisal of topics. We developed a focused clinical question using a PICO format, and performed a primary and secondary literature search through Ovid Medline, Ovid Embase and Cochrane CENTRAL (Wiley). All identified articles were appraised for strength and validity. Seven articles were retrieved which demonstrated conflicting sensitivities and specificities for intravenous hyoscine butylbromide and rectal enema in improving image susceptibility artefact, motion artefact, and anatomic distortion on the T2 or diffusion weighted imaging sequences. Intravenous hysoscine butylbromide is the optimum patient preparation method for improving T2W and DWI image quality in prostate mpMRI. The use of a preparatory rectal enema is not currently recommended, but better quality studies are required.

A systematic review and meta-analysis of the prognostic value of radiomics based models in non-small cell lung cancer treated with curative radiotherapy.

BACKGROUND AND PURPOSE: Radiomics allows extraction of quantifiable features from imaging. This study performs a systematic review and meta-analysis of the performance of radiomics based prognostic models in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: A literature review was performed following PRISMA guidelines. Medline, EMBASE and Cochrane databases were searched for articles investigating radiomics features predictive of overall survival (OS) in NSCLC treated with curative intent radiotherapy. A random-effects meta-analysis of Harrell's Concordance Index (C-index) was performed on the performance of radiomics models. RESULTS: Of the 2746 articles retrieved, 40 studies of 55 datasets and 6223 patients were eligible for inclusion in the systematic review. There was significant heterogeneity in the methodology for feature selection and model development. Twelve datasets reported the C-index of radiomics based models in predicting OS and were included in the meta-analysis. The C-index random effects estimate was 0.57 (95% CI 0.53-0.62). There was significant heterogeneity (I2 = 70.3%). CONCLUSIONS: Based on this review, radiomics based models for lung cancer have to date demonstrated modest prognostic capabilities. Future research should consider using standardised radiomics features, robust feature selection and model development, and deep learning techniques, absolving the need for pre-defined features, to improve imaging-based models.

Understanding and information needs of cancer patients regarding treatment-focused genomic testing: A systematic review.

OBJECTIVE: To systematically review literature exploring experiences of cancer patients regarding their understanding of treatment-focused genomic testing as well as their information needs and related themes. METHODS: Six databases were searched for the original studies published in English language that explored patients' understanding of the information related to the genomic testing and its implications for treatment of cancer. The Mixed-Method Assessement Tool was used to examine the methodological quality of selected articles. RESULTS: There were 14 studies (5 qualitative and 9 quantitative) that met inclusion and exclusion criteria. The majority of studies revealed that a considerable proportion of cancer patients lacked good undertstanding of treatment-focused genomic testing and wanted to be better informed. Some of the factors associated with poor knowledge about genomic testing were low education, older age, low income, and unemployment. The majority of people with cancer preferred face-to-face communication with their oncologists to discuss and ask questions about genomic testing and treatment. Most also wanted to receive simple, easy to understand written information about treatment-focused genomic testing. CONCLUSIONS: Genomic testing and its implications for treatment emerge as an important aspect of health care across different types of cancer. The evidence indicates that cancer patients want to understand and be well informed about treatment-focused genomic testing in order to be part of decision-making process. Further studies addressing ways to improve cancer patients' understanding and knowledge of genomic testing are needed.

Systematic Review of Clinical Outcomes Following Various Treatment Options for Patients with Extraabdominal Desmoid Tumors.

BACKGROUND: Desmoid tumors (DT) are rare clonal proliferations that arise from mesenchymal cells. These tumors do not metastasize but are locally aggressive, and their growth may lead to significant morbidity. Their clinical course is both variable and unpredictable; tumors may rapidly progress but in other instances remain stable or regress without intervention. AIMS: To examine current treatment of DT and assist with decision-making at time of presentation. METHODS: A literature search was conducted of MEDLINE and Cochrane databases for published studies (1995-July 2015) using the search terms fibromatosis aggressive, desmoid with drug therapy, radiation therapy, prevention and control, radiotherapy, surgery, and therapy. Articles were categorized as surgery, radiation, surgery + radiation, systemic therapy, and front-line observation. Articles were included if they reported a retrospective or prospective comparative or observational study with an analyzed sample size of 10 patients or more with confirmed diagnosis of desmoid tumor and described one of the following clinical outcomes: relapse- or progression-free survival, local control rate, response rate. RESULTS: 258 articles were reviewed; following screening for eligibility, 54 were identified; following full-text screen, 31 were included in final evaluation. The control rate for patients treated with a "wait and see" observational approach compared favorably with management with surgery and resulted in disease control rates of between 60 and 92%. CONCLUSIONS: Decision-making in this rare tumor is complicated by the range of treatment options available. Our evidence supports use of an upfront observational approach.

Sentinel Lymph Node Biopsy in T4 Melanoma: An Important Risk-Stratification Tool.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a sensitive test for detecting subclinical nodal metastatic disease in patients with melanoma without evidence of lymph node involvement. The prognostic significance of SLN positivity in patients with melanoma >4 mm thick (T4) is unclear. The survival curves in the current AJCC staging system suggest that the status of the SLN is not predictive of outcome for patients with T4 melanoma. METHODS: Patients with primary T4 melanoma without clinical nodal involvement who underwent SLNB between 2002 and 2012 at Peter MacCallum Cancer Centre were included in the analysis with chart review performed to collect clinical, pathological, and outcome data. A meta-analysis was performed including similar studies of SLNB in T4 melanoma, which reported overall survival (OS) data. RESULTS: Of 217 patients who underwent SLNB, 78 patients had a positive SLN (36 %). The 5-year OS for SLNB negative and positive patients was 68 and 45 %, respectively [hazard ratio (HR) 2.82; 95 % CI 1.76-4.51; P = .001]. On multivariate analysis, the only predictors of OS were the status of the SLN (HR 2.88; 95 % CI 1.75­4.73) and the presence of satellitosis (HR 2.59; 95 % CI 1.30-5.76). The meta-analysis identified 10 studies that met the inclusion criteria. All reported similar findings, demonstrating a significant difference in OS according to sentinel lymph node status; the pooled analysis of 2104 patients demonstrated an overall HR for OS according to SLNB status of 2.3 (95 % CI 1.95-2.71). CONCLUSIONS: SLNB provides important prognostic information for patients with T4 melanoma. This information is important when stratifying patients for clinical trials.