Author Correction: LSD1 activation promotes inducible EMT programs and modulates the tumour microenvironment in breast cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

LSD1 activation promotes inducible EMT programs and modulates the tumour microenvironment in breast cancer.

Complex regulatory networks control epithelial-to-mesenchymal transition (EMT) but the underlying epigenetic control is poorly understood. Lysine-specific demethylase 1 (LSD1) is a key histone demethylase that alters the epigenetic landscape. Here we explored the role of LSD1 in global epigenetic regulation of EMT, cancer stem cells (CSCs), the tumour microenvironment, and therapeutic resistance in breast cancer. LSD1 induced pan-genomic gene expression in networks implicated in EMT and selectively elicits gene expression programs in CSCs whilst repressing non-CSC programs. LSD1 phosphorylation at serine-111 (LSD1-s111p) by chromatin anchored protein kinase C-theta (PKC-θ), is critical for its demethylase and EMT promoting activity and LSD1-s111p is enriched in chemoresistant cells in vivo. LSD1 couples to PKC-θ on the mesenchymal gene epigenetic template promotes LSD1-mediated gene induction. In vivo, chemotherapy reduced tumour volume, and when combined with an LSD1 inhibitor, abrogated the mesenchymal signature and promoted an innate, M1 macrophage-like tumouricidal immune response. Circulating tumour cells (CTCs) from metastatic breast cancer (MBC) patients were enriched with LSD1 and pharmacological blockade of LSD1 suppressed the mesenchymal and stem-like signature in these patient-derived CTCs. Overall, LSD1 inhibition may serve as a promising epigenetic adjuvant therapy to subvert its pleiotropic roles in breast cancer progression and treatment resistance.

The Patterns of Practice and Outcomes of Penile Cancer in Ontario.

AIMS: Penile cancer is a rare malignancy in Western countries. The management guidelines are mainly derived from retrospective studies as there are no randomised trials. The primary objective of this study was to assess patterns of practice and outcomes of penile squamous cell carcinoma in Ontario. Secondary objectives included examining trends in incidence, pathological characteristics and prognostic factors. MATERIALS AND METHODS: All patients diagnosed with penile cancer between 2000 and 2010 were identified from the Ontario Cancer Registry and all available pathology reports related to penile cancer during this period were reviewed. RESULTS: Pathology reports of 419 new cases of penile squamous cell carcinoma were reviewed. There was a significant improvement in completeness of the pathology reports in recent years. The age-adjusted incidence was 0.9 per 100 000 person-years. Most patients presented with a pT1 lesion (63%). A partial penectomy (40%) was the most common surgical procedure. Over 38% of patients identified to be eligible for organ-sparing surgery had a total or partial penectomy. Only 23% of the eligible patients identified to require lymph node dissection underwent the procedure. The 5 year disease-specific survival for stage 0, I, II, III were 94%, 93%, 74% and 52%, respectively. CONCLUSIONS: There is a significant variation in the patterns of practice in Ontario. A large proportion of patients in this cohort were probably overtreated for the primary malignancy and undertreated for the regional nodes.

Benefit from cytoreductive nephrectomy and the prognostic role of neutrophil-to-lymphocyte ratio in patients with metastatic renal cell carcinoma.

BACKGROUND: The role of cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) in the era of targeted therapies is currently undefined. In recent years, neutrophil-to-lymphocyte ratio (NLR) has emerged as a prognostic marker in several cancers, including mRCC. In this multicentre retrospective study, we aim to assess the impact of CN in mRCC and the value of NLR in risk stratification and patient selection. METHODS: Retrospective data from patients with de novo mRCC from four large Australian hospitals were collected. Survival analyses were performed using the Kaplan-Meier method and compared using the log-rank test. Multivariate analyses were performed using the Cox proportional hazards method. RESULTS: Our study identified 91 de novo mRCC patients. Patients who underwent CN (n = 46, 51%) were more likely to be younger (59.0 years vs 64.6 years, P = 0.019) and to have received systemic therapy (91% vs 76%, P = 0.043). Median overall survival (mOS) was significantly improved in patients who underwent CN (23.0 months vs 10.9 months, hazard ratios (HR) 0.33, 95% confidence interval (CI) 0.20-0.55, P < 0.0001). Patients with NLR ≥ 5 also had inferior mOS (6.2 months vs 16.7 months, HR 1.94, 95% CI 1.14-3.29, P = 0.014). CN was associated with substantially improved survival in patients with both NLR < 5 (mOS 31.1 months vs 7.0 months, HR 0.41, 95% CI, 0.18-0.64, P = 0.0009) and NLR ≥ 5 (mOS 10.9 months vs 2.3 months, HR 0.33, 95% CI, 0.11-0.69, P = 0.009). Significant survival benefits associated with CN were maintained in multivariate analyses (HR 0.39, 95% CI 0.22-0.70, P = 0.0014). CONCLUSIONS: CN is associated with significantly improved overall survival in de novo mRCC. The incremental survival benefit associated with CN was seen irrespective of NLR.

Routine screening of Indigenous cancer patients' unmet support needs: a qualitative study of patient and clinician attitudes.

BACKGROUND: Indigenous Australians have poorer cancer outcomes in terms of incidence mortality and survival compared with non-Indigenous Australians. The factors contributing to this disparity are complex. Identifying and addressing the psychosocial factors and support needs of Indigenous cancer patients may help reduce this disparity. The Supportive Care Needs Assessment Tool for Indigenous People (SCNAT-IP) is a validated 26-item questionnaire developed to assess their unmet supportive care needs. This qualitative study reports on patient and clinician attitudes towards feasibility and acceptability of SCNAT-IP in routine care. METHODS: Forty-four in-depth semi-structured interviews were conducted with 10 clinical staff and 34 Indigenous cancer patients with heterogeneous tumours. Participants were recruited from four geographically diverse Australian cancer clinics. Transcripts were imported into qualitative analysis software (NVivo 10 Software), coded and thematic analysis performed. RESULTS: Indigenous patients (mean age 54.4 years) found the SCNAT-IP beneficial and easy to understand and they felt valued and heard. Clinical staff reported multiple benefits of using the SCNAT-IP. They particularly appreciated its comprehensive and systematic nature as well as the associated opportunities for early intervention. Some staff described improvements in team communication, while both staff and patients reported that new referrals to support services were directly triggered by completion of the SCNAT-IP. There were also inter-cultural benefits, with a positive and bi-directional exchange of information and cultural knowledge reported when using the SCNAT-IP. Although staff identified some potential barriers to using the SCNAT-IP, including the time required, the response format and comprehension difficulties amongst some participants with low English fluency, these were outweighed by the benefits. Some areas for scaled improvement were also identified by staff. CONCLUSIONS: Staff and patients found the SCNAT-IP to be an acceptable tool and supported universal screening for Indigenous cancer patients. The SCNAT-IP has the potential to help reduce the inequalities in cancer care experienced by Indigenous Australians by identifying and subsequently addressing their unmet support needs. Further research is needed to explore the validity of the SCNAT-IP for Indigenous people from other nations.

Indigenous cancer patient and staff attitudes towards unmet needs screening using the SCNAT-IP.

INTRODUCTION: Indigenous Australians have a higher cancer incidence, worse mortality and are less likely to receive optimal cancer treatment compared with non-Indigenous Australians. Culturally appropriate supportive care helps ensure that Indigenous patients engage in and receive optimal care. However, many existing supportive care needs tools lack cultural relevance for Indigenous people, and their feasibility with Indigenous people has not been demonstrated. The Supportive Care Needs Assessment Tool for Indigenous People (SCNAT-IP) assesses the unmet supportive care needs of Indigenous cancer patients. PURPOSE: This descriptive study evaluates the clinical implementation of the SCNAT-IP in routine care. METHODS: Two large tertiary cancer treatment centres and two regional oncology clinics participated. Participants included 10 clinical staff and 36 adult Indigenous cancer patients (mean age 54 years). Patients and clinicians completed brief, purpose-designed questionnaires and interviews. RESULTS: Patients reported high ratings (means >8/10) for acceptability, helpfulness and timing items. The majority (≥80%) of staff agreed that the SCNAT-IP was useful to clinical practice, should be used in routine care and was acceptable to their patients. CONCLUSIONS: The study provides empirical support for the feasibility and acceptability of the SCNAT-IP in routine cancer care with Indigenous Australians. Routine screening with the SCNAT-IP has the potential to improve cancer care for Indigenous people with cancer.

Location of colon cancer (right-sided versus left-sided) as a prognostic factor and a predictor of benefit from cetuximab in NCIC CO.17.

BACKGROUND: Right- and left-sided colon cancers (RC, LC) differ with respect to biology, pathology and epidemiology. Previous data suggest a mortality difference between RC and LC. We examined if primary tumour side also predicts for outcome in chemotherapy refractory, metastatic colon cancer (MCC). We also compared RC versus LC as a predictor of efficacy of epidermal growth factor receptor (EGFR) inhibition with cetuximab. METHODS: Reanalyzing NCIC CO.17 trial (cetuximab versus best supportive care [BSC]), we coded the primary tumour side as RC (caecum to transverse colon) or LC (splenic flexure to rectosigmoid). The association between tumour side and baseline characteristics was assessed. Cox regression models determined factors affecting overall survival (OS) and progression free survival (PFS). RESULTS: Patients with RC (150/399) had more poorly differentiated, mutant KRAS, mutated PIK3CA and wild-type BRAF tumours, fewer liver and lung metastases, and shorter interval between diagnosis and study entry. Among BSC patients, tumour side was not prognostic for PFS (hazard ratios (HR) 1.07 [0.79-1.44], p = 0.67) or OS (HR 0.96 [0.70-1.31], p = 0.78). Among wild-type KRAS patients, those with LC had significantly improved PFS when treated with cetuximab compared to BSC (median 5.4 versus 1.8 months, HR 0.28 [0.18-0.45], p < 0.0001), whereas those with RC did not (median 1.9 versus 1.9 months, HR 0.73 [0.42-1.27], p = 0.26), [interaction p = 0.002]. CONCLUSION: In refractory MCC, tumour location within the colon is not prognostic, but is strongly predictive of PFS benefit from cetuximab therapy. Additional research is needed to understand the molecular differences between RC and LC and their interaction with EGFR inhibition.

Regorafenib-induced hyperammonemic encephalopathy.

WHAT IS KNOWN AND OBJECTIVE: Regorafenib improves progression-free survival as a late-line treatment for patients with metastatic gastrointestinal stromal tumour (GIST). As a multitargeted tyrosine kinase inhibitor (TKI), the expected adverse events of regorafenib are similar to those reported with imatinib, sunitinib or sorafenib. We report the first case of hyperammonemic encephalopathy related to regorafenib in a patient with metastatic GIST. CASE SUMMARY: A 61-year-old man maintained on regorafenib for metastatic GIST presented with acute confusion. Discontinuation of regorafenib led to complete resolution of confusion, which later recurred with hyperammonemia on recommencing regorafenib. Cessation of regorafenib and normalization of hyperammonemia then resulted in resolution of confusion. WHAT IS NEW AND CONCLUSIONS: Regorafenib withdrawal and recommencement had influenced the confusional state and hyperammonemia in this patient. There is a probable relationship between regorafenib and metabolic encephalopathy. There are case reports of similar encephalopathy thought to be induced by other multitargeted TKI, and, as such, a class effect could be postulated.

Treatment outcomes of rapid desensitisation protocols for chemotherapeutic agents and monoclonal antibodies following hypersensitivity reactions.

BACKGROUND: Hypersensitivity reactions (HSR) to chemotherapeutic agents and monoclonal antibodies are common and may limit further therapeutic options. Drug desensitisation aims to induce a temporary clinical unresponsiveness to drug antigens so the causative drugs of HSR can continue to be administered. Rapid desensitisation using standardised protocols has been conducted by the Department of Immunology at The Canberra Hospital for patients who developed HSR to chemotherapeutic agents and monoclonal antibodies. AIMS: This retrospective audit reviewed the safety and efficacy of the desensitisation protocols used for patients across the Capital Region Cancer Service (CRCS). METHODS: Patients across the CRCS who received rapid desensitisation were identified through a search of archived correspondence. Clinical files and pharmacy records were analysed to determine protocol safety and efficacy. RESULTS: From June 2006 to July 2013, 13 patients underwent rapid desensitisations to oxaliplatin, carboplatin, docetaxel or rituximab. A total of 25 desensitisations was conducted with 21 (84%) achieving full target dose without inducing recurrent HSR. As a result, nine patients were successfully desensitised and continued to receive treatment without any further HSR. Desensitisation was aborted in three patients because of recurrence of HSR, which was not of a greater severity than the initial HSR. After successful desensitisation, seven patients were able to resume the regular protocols without requiring additional supervision. CONCLUSION: Rapid desensitisation to various chemotherapeutic agents and monoclonal antibodies with standardised protocols used across CRCS is safe and effective; it provides a feasible treatment option enabling continuation of effective regimens in the setting of HSR.

Final results of Australasian Gastrointestinal Trials Group ARCTIC study: an audit of raltitrexed for patients with cardiac toxicity induced by fluoropyrimidines.

BACKGROUND: Cardiac toxicity an uncommon but serious side-effect of some fluoropyrimides. Cardiac toxicity from raltitrexed is rarely reported. With this background, we initiated this study to investigate the incidence of cardiac events in patients who had switched to raltitrexed following cardiac toxicity from fluoropyrimidines (5-fluorouracil or capecitabine). PATIENTS AND METHODS: Pharmacy records were used to identify patients receiving raltitrexed from January 2004 till March 2012. Medical records were then reviewed to confirm the use of raltitrexed after cardiac toxicity from 5-fluorouracil or capecitabine. The primary end point was the rate of further cardiac events after commencing raltitrexed. RESULTS: Forty-two patients were identified and the majority had colorectal cancer. Prior regimens included 5-fluorouracil ± leucovorin, capecitabine alone, FOLFOX, FOLFIRI, epirubicin/cisplatin/5-fluorouracil, and capecitabine/oxaliplatin. Seven patients (17%) had bolus 5-fluorouracil regimens, 26 patients (62%) had infusion 5-fluorouracil regimens, and 9 patients (21%) had capecitabine alone or in combination. Angina was the most common cardiac toxicity from 5-fluorouracil or capecitabine and usually occurred in the first or the second cycle. Four patients after their first cardiac event continued with the same 5-fluorouracil or capecitabine regimen with the addition of nitrates and calcium antagonists but still had further cardiac events. After changing to raltitrexed, either as a single agent or a continuing combination regimen, no patients experienced further cardiac toxicity. CONCLUSION: Raltitrexed is associated with no significant cardiac toxicity in patients who have experienced prior cardiac toxicity from 5-fluorouracil or capecitabine. Raltitrexed, alone or in combination with oxaliplatin or irinotecan, provides a safe option in terms of cardiac toxicity for such patients.

Developing a national database for metastatic colorectal cancer management: perspectives and challenges.

BACKGROUND: The changing treatment landscape for metastatic colorectal cancer creates multiple potential treatment strategies. An Australian-centric database capturing comprehensive information across a range of treatment locations would create a valuable resource enabling multiple important research questions to be addressed. AIMS: To establish a collection of a consensus dataset capturing treatment and outcomes at multiple public and private hospitals across Australia. METHODS: An electronic database was developed by a panel of clinicians, to capture an agreed dataset for patients with newly diagnosed metastatic colorectal cancer. Of particular interest were clinician decision-making, the impact of comorbidities and the frequency of major adverse events. RESULTS: Since July 2009, data collection has been established at six public and eight private hospitals across three Australian states and territories. Successful linkage and analysis, with support from BioGrid Australia, of selected data on the initial 864 patients demonstrates that data can be captured from diverse sites, including public and private practice, that multiple factors impact on treatment delivered and outcomes achieved and that comprehensive data on rare but important adverse events can be captured. As a clinical research tool, the project has been highly successful, generating multiple presentations at national and international conferences related to a diverse range of research questions. CONCLUSIONS: Multistate, project-specific data collection involving large numbers of patients is achievable. Providing invaluable insight into the routine clinical management of metastatic colorectal cancer in the era of targeted therapies, this also creates a significant resource for research, including many questions not being addressed by clinical trials.

Management of metastatic renal cell carcinoma in the era of targeted therapies.

BACKGROUND: Metastatic renal cell cancer is associated with poor prognosis and survival and is resistant to conventional chemotherapy. Therapeutic targeting of molecular pathways for tumour angiogenesis and other specific activation mechanisms offers improved tumour response and prolonged survival. AIMS: To conduct a retrospective audit of metastatic renal cell carcinoma patients treated with targeted therapies. METHODS: Data were extracted from clinical records of patients undergoing targeted treatment between 2005 and 2009 at two hospital sites. Data collected included pathology, systemic therapy class, toxicity and survival. Univariate and multivariate survival analyses were performed. RESULTS: Sixty-one patients were treated with 102 lines of therapy with a median overall survival (OS) of 23 months, median time to failure of first-line treatment (TTF1) of 10 months and median time to failure of second-line treatment (TTF2) of 5.2 months. Time from first diagnosis to treatment >12 months was significantly associated with improved OS, longer TTF1, TTF2 and response to first-line anti-vascular endothelial growth factor receptor tyrosine kinase inhibitors (anti-VEGF TKI) therapy. Variables associated with tumour biology, natural history and the systemic inflammatory response were associated with improved OS and TTF1. Development of hypertension was predictive of anti-VEGF TKI outcome. Toxicities were as expected for each drug class. CONCLUSIONS: Survival and toxicity outcomes from two Australian sites are comparable to published data. The adverse event profile differs to conventional chemotherapy. Clinicians caring for patients with metastatic renal cancer will need to become familiar with these toxicities and their management as these agents enter widespread use.

Two cases of acrometastasis to the hands and review of the literature.

This paper reports two cases of acrometastasis to the hands. The first case involved a 78-year-old woman with a permeative osteolytic lesion in her proximal second metacarpal. A biopsy of this lesion suggested a diagnosis of non-small-cell lung carcinoma with secondary osseous metastasis. This was the first presentation of the woman's primary diagnosis. A single 8-Gy fraction of palliative radiotherapy was delivered to the patient's left hand. The treatment proved successful: the woman soon experienced pain relief and regained the use of her hand. The second case involved a 69-year-old woman with extensive lytic destruction involving the proximal two thirds of her third metacarpal. This patient had been diagnosed with carcinoma of the breast in 1990. She also received a single 8-Gy fraction of radiation, which improved both her pain and her hand mobility.An extensive review of the literature uncovered 257 previously reported cases of acrometastasis. Articles were analyzed based on age and sex of the patient, site of the primary carcinoma, metastatic locations within the hand and affected appendage or appendages, the treatment given, and the patient's length of survival. Men were almost twice as likely to experience acrometastasis as women, and the median age of the patients overall was 58 years (range: 18 months-91 years). Lung, kidney, and breast carcinoma were the three most prevalent primary diagnoses reported in the literature. Cancers of the colon, stomach, liver, prostate, and rectum affected the remainder of the population.Overall, the right hand was more often host to the metastatic lesions. In addition, almost 10% of the patients experienced lesions in both hands. The third finger was the digit most affected by osseous metastases reported in the literature. Lesions of the thumb, fourth finger, second finger, and fifth finger were less commonly reported. The region of the digit most often affected within the patient population was the distal phalanx. The metacarpal bones, proximal phalanges, and middle phalanges comprised the remainder of the four most frequent acrometastatic sites. In the literature, single lesions were more prevalent than multiple bony lesions.Based on the reported cases, amputation appeared to be the preferred method of treatment. Radiation, excision, and systemic therapy were the next most frequently used treatments. Patient survival was not well documented within the literature. However, the median survival of patients in the reported cases was 6 months. Thus, our review suggested that a diagnosis of hand metastasis is an indication of poor prognosis.This report serves to emphasize the importance of properly diagnosing acrometastases. Identifying and effectively treating these metastases in a timely manner can lead to a dramatic improvement in a patient's quality of life.

After radiotherapy, do bone metastases from gastrointestinal cancers show response rates similar to those of bone metastases from other primary cancers?

PURPOSE: Reports investigating whether the response rates to palliative radiation therapy (RT) for painful bone metastases from gastrointestinal (GI) cancers are similar to rates for bone metastases from other primary cancer sites have been limited. The present study evaluated response rates for symptomatic bone metastases from gi cancers after palliative outpatient rt in the Rapid Response Radiotherapy Program (RRRP). PATIENTS AND METHODS: We identified 69 patients with bone metastases from gi primaries who received palliative rt in the RRRP clinic during 1999-2006. We extracted records for 31 of these patients during 1999-2003 from an RRRP database that used the Edmonton Symptom Assessment Scale (ESAS). Record for the remaining 38 patients during 2003-2006 were extracted from an RRRP database that used the Brief Pain Inventory (BPI). Eligibility criteria for encryption in the two RRRP databases and for collection of patient demographic information (age, sex, primary cancer site, and Karnofsky performance status) were identical. Response rates for this cohort of metastatic gi patients were then compared to rates for 479 patients receiving palliative RT for bone metastases from other primary cancer sites. Pain scores from the ESAS and BPI and data on analgesic consumption were collected at baseline and by telephone follow-up at 4, 8, and 12 weeks after RT for all patients. Complete (CR), partial (PR), and overall (CR+PR) responses were evaluated according to International Consensus Endpoints. RESULTS: Assessment of the 69 patients with metastatic GI cancers revealed CR, PR, and CR+PR rates of 18%, 42%, and 61% at 4 weeks; 22%, 35%, and 57% at 8 weeks; and 50%, 21%, and 71% at 12 weeks for evaluable patients. The 479 evaluable patients with metastatic cancer from other primary cancer sites had CR, PR, and CR+PR rates of 25%, 27%, and 51% at 4 weeks; 26%, 22%, and 48% at 8 weeks; and 22%, 29%, and 51% at 12 weeks. No statistically significant differences were observed in RT response rates for bone metastases from GI cancers than from other primary cancer sites. CONCLUSIONS: After palliative RT, bone metastases from gi cancers demonstrate response rates that are similar to rates for metastases from other primary cancer sites. Patients with symptomatic bone metastases from GI malignancies should be referred for palliative RT as readily as patients with osseous metastases from other primary cancer sites.

Bilateral knee lipoma arborescens: a case report.

A 45-year-old Chinese man presented with recurrent bilateral knee swelling and pain. He was initially diagnosed with gouty arthritis, but later found to have lipoma arborescens. Magnetic resonance imaging demonstrated frond-like proliferations of fatty synovium. Arthroscopic synovectomy was performed. Histological examination of the specimen revealed villiform fatty tissue covered by slightly thickened synovium characteristic of lipoma arborescens. Magnetic resonance imaging is useful in differentiating lipoma arborescens from other intra-articular lesions in patients with recurrent knee pain and swelling.

Chemotherapy and radiotherapy for inoperable advanced pancreatic cancer.

BACKGROUND: Pancreatic cancer has a poor prognosis. The benefit of chemotherapy, radiotherapy or both as a palliative treatment of advanced or relapsed disease is uncertain. OBJECTIVES: To assess the effects of chemotherapy and/or radiotherapy in the management of pancreatic adenocarcinoma in people with inoperable advanced disease. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which includes the Cochrane Upper Gastrointestinal and Pancreatic Diseases (UGPD) Group Trials Register (The Cochrane Library 2005, Issue 1); CANCERLIT (1975-2002); MEDLINE (1966 to January 2005); and EMBASE (1980 to January 2005). We handsearched reference lists from trials revealed by electronic searches to identify further relevant trials. We searched published abstracts from relevant conference proceedings. We contacted colleagues and experts in the field, and asked them to provide details of outstanding clinical trials and any relevant unpublished materials. SELECTION CRITERIA: Randomised controlled trials (single- or double-blind) in patients with advanced inoperable pancreatic cancer, in which one of the intervention types (chemotherapy or radiotherapy) was contrasted with either placebo or another type of intervention. Studies comparing non-chemotherapy agents such as biological agents, hormones, immunostimulants, vaccines and cytokines were excluded. DATA COLLECTION AND ANALYSIS: Studies were assessed for eligibility and quality. Data were extracted by groups of two independent reviewers, with conflicts resolved by a third reviewer. Study authors were contacted for more information. MAIN RESULTS: Fifty trials (7043 participants) were included. Chemotherapy significantly reduced the one-year mortality (odds ratio (OR) 0.37, 95% confidence interval (CI) 0.25 to 0.57, P value < 0.00001) when compared to best supportive care. Also, chemoradiation improved one year survival (0% versus 58%, P value 0.001) when compared to best supportive care. There was no significant difference in one-year mortality for 5FU alone versus 5FU combinations (OR 0.90, 95% CI 0.62 to 1.30); single-agent chemotherapy versus gemcitabine (OR 1.34, 95% CI 0.88 to 2.02, P value 0.17); or gemcitabine alone versus gemcitabine combinations (OR 0.88, 95% CI 0.74 to 1.05). However, subgroup analysis showed that platinum-gemcitabine combinations reduced six-month mortality compared to gemcitabine alone (OR 0.59, 95% CI 0.43 to 0.81, P value 0.001). A qualitative overview suggested that chemoradiation produced better survivals than either best supportive care or radiotherapy. Chemoradiation treatment was associated with more toxicity. AUTHORS' CONCLUSIONS: Chemotherapy appears to prolong survival in people with advanced pancreatic cancer and can confer clinical benefits and improve quality of life. Combination chemotherapy did not improve overall survival compared to single-agent chemotherapy. Gemcitabine is an acceptable control arm for future trials investigating scheduling and combinations with novel agents. There is insufficient evidence to recommend chemoradiation in patients with locally advanced inoperable pancreatic cancer as a superior alternative to chemotherapy alone.