Quality of life in a real-world study of patients with metastatic colorectal cancer treated with trifluridine/tipiracil.

Background: Quality of life (qol) is important for oncology patients, especially for those with late-stage disease. The present study was initiated to address the lack of published prospective data about the qol benefits of trifluridine/tipiracil (ftd/tpi) compared with best supportive care (bsc) in patients with refractory metastatic colorectal cancer (mcrc). Methods: This prospective, cross-sectional, non-interventional study used multidimensional validated scales to evaluate patient-reported qol in two study cohorts of patients and also to measure differences in mcrc-related symptoms and pain in a real-world clinical setting. Results: Our findings demonstrate that patients with refractory mcrc report better overall qol when treated with ftd/tpi than with bsc alone. In that population, statistically significant differences in mean qol measures favoured ftd/tpi over bsc for physical symptom distress, psychological distress, activity impairment, overall valuation of life, and symptomatology. The overall better qol for patients receiving ftd/tpi implies that treatment was well tolerated and was associated with a lower symptom burden. No significant differences for pain were observed between the groups. Conclusions: This study suggests that ftd/tpi is a well-tolerated option for the treatment of patients with refractory mcrc, showcasing the value of capturing real-world qol data in routine clinical practice.

Adjuvant therapy for stages II and III colon cancer: risk stratification, treatment duration, and future directions.

Background: To date, the role of adjuvant systemic therapy in stages ii and iii colon cancer remains a topic of interest and debate. The objective of the present review was to assess the most recent data, specifically addressing methods of risk stratification, duration of therapy, and future directions. Methods: PubMed and medline were searched for literature pertinent to adjuvant chemotherapy in either stage ii or stage iii colorectal cancer. Summary: Locoregional disease, histopathology, age, laterality, and a number of other biologic and molecular markers appear to have a role in disease risk stratification. The duration of adjuvant therapy for stage iii disease can vary based on risk factors, but use of adjuvant therapy and duration of therapy in stage ii disease remain controversial. Future directions should include genomic assays and improved study design to provide concrete evidence about the duration of adjuvant folfox or capox and about other types of chemotherapy and immunotherapy.

What is a clinically meaningful survival benefit in refractory metastatic colorectal cancer?

Assessment of the clinical benefit of cancer treatments can be highly subjective, influenced by both perspective and context. Such assessments are required in regulatory and policy decision-making, but consistency between jurisdictions is often lacking. Clear and consistent standards for determining when a treatment offers a meaningful benefit, relative to the current standard of care, can help to address issues of equity and transparency in health technology assessment. For metastatic colorectal cancer (mcrc), no standardized Canadian definition of clinically meaningful benefit has yet been proposed. Colorectal Cancer Canada therefore convened a group of medical oncologists expert in colorectal cancer to review the literature about clinical significance. The resulting consensus is intended to apply to any therapeutic agent being considered in the setting of chemotherapy-refractory mcrc. It was agreed that overall survival is the appropriate measure of clinical efficacy in chemorefractory mcrc. As quantitative targets for efficacy, an improvement of 2 months or more in median overall survival or a hazard ratio for survival of 0.75 or lower (or both) are proposed as the threshold for clinically meaningful benefit. That threshold could be influenced by a treatment's effect on quality of life. Treatment toxicity is also relevant to the assessment of clinical benefit in this setting, specifically when significant differences in treatment tolerability are evident.

A retrospective observational study to estimate the attrition of patients across lines of systemic treatment for metastatic colorectal cancer in Canada.

Background: Selection and sequencing of treatment regimens for individual patients with metastatic colorectal cancer (mcrc) is driven by maintaining reasonable quality of life and extending survival, as well as by access to and cost of therapies. The objectives of the present study were to describe, for patients with mcrc, attrition across lines of systemic therapy, patterns of therapy and their timing, and KRAS status. Methods: A retrospective chart review at 6 Canadian academic centres included sequential patients who were diagnosed with mcrc from 1 January 2009 onward and who initiated first-line systemic treatment for mcrc between 1 January and 31 December 2009. Death was included as a competing risk in the analysis. Results: The analysis included 200 patients who started first-line therapy. The proportions of patients who started second-, third-, and fourth-line systemic therapy were 70%, 30%, and 15% respectively. Chemotherapy plus bevacizumab was the most common first-line combination (66%). The most common first-line regimen was folfiri plus bevacizumab. KRAS testing was performed in 103 patients (52%), and 38 of 68 patients (56%, 19% overall) with confirmed KRAS wild-type tumours received an epidermal growth factor receptor inhibitor (egfri), which was more common in later lines. Most KRAS testing occurred after initiation of second-line therapy. Conclusions: In the modern treatment era, a high proportion of patients receive at least two lines of therapy for mcrc, but only 19% receive egfri therapy. Earlier KRAS testing and therapy with an egfri might allow a greater proportion of patients to access all 5 active treatment agents.

Treatment algorithm in cancer-associated thrombosis: Canadian expert consensus.

Management of anticoagulant therapy for the treatment of venous thromboembolism (vte) in cancer patients is complex because of an increased risk of recurrent vte and major bleeding complications in those patients relative to the general population. Subgroups of patients with cancer also show variation in their risk for recurrent vte and adverse bleeding events. Accordingly, a committee of 10 Canadian clinical experts developed the consensus risk- stratification treatment algorithm presented here to provide guidance on tailoring anticoagulant treatment choices for the acute and extended treatment of symptomatic and incidental vte, to prevent recurrent vte, and to minimize the bleeding risk in patients with cancer. During a 1-day live meeting, a systematic review of the literature was performed, and a draft treatment algorithm was developed. The treatment algorithm was refined through the use of a Web-based platform and a series of online teleconferences. Clinicians using this treatment algorithm should consider the bleeding risk, the type of cancer, and the potential for drug-drug interactions in addition to informed patient preference in determining the most appropriate treatment for patients with cancer-associated thrombosis. Anticoagulant therapy should be regularly reassessed as the patient's cancer status and management change over time.

Eastern Canadian Colorectal Cancer Consensus Conference 2017.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2017 was held in St. John's, Newfoundland and Labrador, 28-30 September. Experts in radiation oncology, medical oncology, surgical oncology, and cancer genetics who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of gastric, rectal, and colon cancer, including ■ identification and management of hereditary gastric and colorectal cancer (crc);■ palliative systemic therapy for metastatic gastric cancer;■ optimum duration of preoperative radiation in rectal cancer-that is, short- compared with long-course radiation;■ management options for peritoneal carcinomatosis in crc;■ implications of tumour location for treatment and prognosis in crc; and■ new molecular markers in crc.

Functional Neuroanatomy of Secondary Self-Injurious Behavior.

BACKGROUND: Secondary self-injurious behavior (SSIB) is underreported and predominantly not associated with suicide. In both adults and children, SSIB can cause intractable self-harm and is associated with a variety of clinical disorders, particularly those involving dysfunctional motor control. METHODS: We performed a literature review evaluating the clinical efficacy of deep-brain stimulation (DBS) as modulating SSIB observations and review current progress in preclinical SSIB animal studies. RESULTS: Neuromodulation is an effective therapeutic option for several movement disorders. Interestingly, this approach is emerging as a potentially effective treatment for movement disorder-associated SSIB (secondary); however, it is important to understand the neuroanatomy, clinical appraisal, and outcome data when considering surgical therapy for SSIB. CONCLUSION: The current review examines the literature encompassing animal models and human case studies while identifying existing hypotheses from cytoarchitectonic-based targeting to neurotransmitter-based pathways. This review also highlights the need for awareness of an underrecognized pathology that may be amenable to DBS.

Progression pattern and adverse events with bevacizumab in glioblastoma.

BACKGROUND: The use of bevacizumab in the management of glioblastoma multiforme (gbm) remains controversial. In Canada, bevacizumab is approved for the treatment of recurrent gbm. We describe a pattern of progression across treatment lines in gbm. METHODS: During 2008-2014, 64 patients diagnosed with gbm were treated with bevacizumab at McGill University hospitals. Of those patients, 30 (46.9%) received bevacizumab in the first line (B1L), and 34 (53.1%) received it in the second line and beyond (B2L+). The average length of treatment with bevacizumab was 24.4 weeks (range: 0-232.7 weeks). The patterns of progression were categorized as local, distant, diffuse, multifocal, or multi-pattern. RESULTS: Local progression was seen in 46.7% of B1L patients and 26.5% of B2L+ patients, distant in 3.3% and 2.9%, diffuse in 20% and 47%, multifocal in 10% and 8.8%, and multi-pattern in 3.3% and 11.8%. No differences between the groups were observed for the distant (p = 0.3) or diffuse (p = 0.4) patterns. Grades 3 and 4 adverse events in the B1L and B2L+ groups were fatigue (33.3% vs. 17.6% respectively), hypertension (26.7% vs. 5.9%), thrombocytopenia (26.7% vs. 11.8%), neutropenia (26.7% vs. 11.8%), anemia (23.3% vs. 11.8%), leucopenia (20% vs. 8.8%), deep vein thrombosis (23.3% vs. 5.9%), seizure (16.7% vs. 8.8%), brain hemorrhage (6.7% vs. <1%), and delayed wound healing (6.7% vs. 2.9%). More total grades 3 and 4 adverse events occurred in the B1L group (p = 0.000519). CONCLUSIONS: In our cohort, patterns of progression were not different in B1L and B2L+ patients. Moreover, both groups experienced similar adverse events, although more grades 3 and 4 events occurred in the B1L group, implying that severe adverse events in B1L patients could negatively affect survival outcomes.

Retrospective analysis of the effect of CAPOX and mFOLFOX6 dose intensity on survival in colorectal patients in the adjuvant setting.

BACKGROUND: Despite lack of a true comparative study, the folfox (5-fluorouracil-leucovorin-oxaliplatin) and capox (capecitabine-oxaliplatin) regimens are believed to be similar in their efficacy and tolerability in the treatment of stage iii colorectal cancer. However, that belief has been disputed, because real-life data suggest that the capox regimen is more toxic, leading to more frequent reductions in the delivered dose intensity-thus raising questions about the effect of dose intensity on clinical outcomes. METHODS: A retrospective data review for two Canadian institutions, the Segal Cancer Centre and the Tom Baker Cancer Centre, considered patients diagnosed with stage iii colorectal cancer during 2006-2013. Primary endpoints were dose intensity and toxicity, with a secondary endpoint of disease-free survival. RESULTS: The study enrolled 180 eligible patients (80 at the Segal Cancer Centre, 100 at the Tom Baker Cancer Centre). Of those 180 patients, 75 received capox, and 105 received mfolfox6. In the capox group, a significant dose reduction was identified for capecitabine compared with 5-fluorouracil in mfolfox6 group (p = 0.0014). Similarly, a significant dose reduction was observed for oxaliplatin in mfolfox6 compared with oxaliplatin in capox (p = 0.0001). Compared with the patients receiving capox, those receiving mfolfox6 were twice as likely to experience a treatment delay of more than 1 cycle-length (p = 0.03855). Toxicity was more frequent in patients receiving mfolfox6 (nausea: 30% vs. 18%; diarrhea: 47% vs. 24%; peripheral sensory neuropathy: 32% vs. 3%). At a median follow-up of 40 months, preliminary data showed no difference in disease-free survival (p = 0.598). Pooled data from both institutions were also separately analyzed, and no significant differences were found. CONCLUSIONS: Our results support the use of capox despite a lack of head-to-head randomized trial data.

Eastern Canadian Colorectal Cancer Consensus Conference 2013: emerging therapies in the treatment of pancreatic, rectal, and colorectal cancers.

The annual Eastern Canadian Colorectal Cancer Consensus Conference held in Montreal, Quebec, 17-19 October 2013, marked the 10-year anniversary of this meeting that is attended by leaders in medical, radiation, and surgical oncology. The goal of the attendees is to improve the care of patients affected by gastrointestinal malignancies. Topics discussed during the conference included pancreatic cancer, rectal cancer, and metastatic colorectal cancer.

Comparative net cost impact of the utilization of panitumumab versus cetuximab for the treatment of patients with metastatic colorectal cancer in Canada.

OBJECTIVE: Clinical practice guidelines support the use of the epidermal growth factor receptor (EGFR) inhibitors panitumumab and cetuximab for the treatment of metastatic colorectal cancer (mCRC) after failure of other chemotherapy regimens, based on significant clinical benefits in patients with wild-type KRAS. The purpose of the analysis was to compare provincial hospital costs when using panitumumab vs cetuximab with or without irinotecan in this patient population using a Net Impact Analysis (NIA) approach. METHODS: The NIA determined the total per patient cost of the reimbursed regimens of panitumumab vs cetuximab in British Columbia, Alberta, Manitoba, Ontario, and Québec. Utilization of healthcare resources related to EGFR inhibitor infusions, follow-up monitoring, and treatment of adverse events (AEs) were also included. Healthcare resource use including drugs, medical supplies, laboratory testing, oncology infusion time, and healthcare professionals' time was obtained through expert consultation and the use was then multiplied by the province-specific cost of each resource. Numerous sensitivity analyses were conducted. RESULTS: Based on the dosing regimens in place in each province, the total annual per patient cost of panitumumab ranged from $22,203-$32,600, while the total annual per patient cost of cetuximab treatment varied from $30,321-$40,908. Treatment with panitumumab resulted in lower costs in all cost categories including drug acquisition, infusion preparation/administration, patient monitoring, and AE management. Per patient savings with panitumumab ranged from a low of $3815 in British Columbia to a high of $10,603 in Ontario. In sensitivity analyses, panitumumab remained cost saving in all scenarios where the savings ranged from $150-$16,006 per patient. CONCLUSIONS: Treating chemorefractory mCRC patients with panitumumab rather than cetuximab reduced healthcare resource costs. Provincial healthcare savings achieved with the use of panitumumab could potentially be re-allocated to other cancer treatments, although further study would be needed to validate this assumption.

Quantifying treatment delays in adolescents and young adults with cancer at McGill University.

BACKGROUND: Since the end of the 1980s, the magnitude of survival prolongation or mortality reduction has not been the same for adolescents and young adults (ayas) with cancer as for their older and younger counterparts. Precise reasons for those observations are unknown, but the differences have been attributed in part to delays in diagnosis and treatment. In 2003 at the Jewish General Hospital, we developed the first Canadian multidisciplinary aya oncology clinic to better serve this unique patient population. The aim of the present study was to develop an approach to quantify diagnosis delays in our aya patients and to study survival in relation to the observed delay. METHODS: In a retrospective chart review, we collected information about delays, treatment efficacy, and obstacles to treatment for patients seen at our aya clinic. RESULTS: From symptom onset, median time to first health care contact was longer for girls and young women (62 days) than for boys and young men (6 days). Median time from symptom onset to treatment was 173 days; time from first health care contact to diagnosis was the largest contributor to that duration. Delays in diagnosis were shorter for patients who initially presented to the emergency room, but compared with patients whose first health contact was of another type, patients presenting to the emergency room were 3 times more likely to die from their disease. CONCLUSIONS: Delays in diagnosis are frequently reported in ayas with cancer, but the duration of the delay was unrelated to survival in our sample. Application of this approach to larger prospective samples is warranted to better understand the relation between treatment delay and survival in ayas-and in other cancer patient groups.

Establishing a clinic-based pancreatic cancer and periampullary tumour research registry in Quebec.

BACKGROUND: Enrolling patients in studies of pancreatic ductal adenocarcinoma (pdac) is challenging because of the high fatality of the disease. We hypothesized that a prospective clinic-based study with rapid ascertainment would result in high participation rates. Using that strategy, we established the Quebec Pancreas Cancer Study (qpcs) to investigate the genetics and causes of pdac and other periampullary tumours (pats) that are also rare and underrepresented in research studies. METHODS: Patients diagnosed with pdac or pat were introduced to the study at their initial clinical encounter, with a strategy to enrol participants within 2 weeks of diagnosis. Patient self-referrals and referrals of unaffected individuals with an increased risk of pdac were also accepted. Family histories, epidemiologic and clinical data, and biospecimens were collected. Additional relatives were enrolled in families at increased genetic risk. RESULTS: The first 346 completed referrals led to 306 probands being enrolled, including 190 probands affected with pdac, who represent the population focus of the qpcs. Participation rates were 88.4% for all referrals and 89.2% for pdac referrals. Family history, epidemiologic and clinical data, and biospecimens were ascertained from 91.9%, 54.6%, and 97.5% respectively of patients with pdac. Although demographics and trends in risk factors in our patients were consistent with published statistics for patients with pdac, the qpcs is enriched for families with French-Canadian ancestry (37.4%), a population with recurrent germ-line mutations in hereditary diseases. CONCLUSIONS: Using rapid ascertainment, a pdac and pat research registry with high participation rates can be established. The qpcs is a valuable research resource and its enrichment with patients of French-Canadian ancestry provides a unique opportunity for studies of heredity in these diseases.

Canadian consensus recommendations on the management of venous thromboembolism in patients with cancer. Part 1: prophylaxis.

Patients with cancer are at increased risk of venous thromboembolism (vte). Anticoagulation therapy has been shown to prevent vte; however, unique clinical circumstances in patients with cancer can often complicate the decisions surrounding the administration of prophylactic anticoagulation. No national Canadian guidelines on the prevention of cancer-associated thrombosis have been published. We therefore aimed to develop a consensus-based, evidence-informed guideline on the topic. PubMed was searched for clinical trials and meta-analyses published between 2002 and 2013. Reference lists of key articles were hand-searched for additional publications. Content experts from across Canada were assembled to review the evidence and make recommendations. Low molecular weight heparin can be used prophylactically in cancer patients at high risk of developing vte. Direct oral anticoagulants are not recommended for vte prophylaxis at this time. Specific clinical scenarios, including renal insufficiency, thrombocytopenia, liver disease, and obesity can warrant modifications in the administration of prophylactic anticoagulant therapy. There is no evidence to support the monitoring of anti-factor Xa levels in clinically stable cancer patients receiving prophylactic anticoagulation; however, factor Xa levels could be checked at baseline and periodically in patients with renal insufficiency. The use of anticoagulation therapy to prolong survival in cancer patients without the presence of risk factors for vte is not recommended.

Canadian consensus recommendations on the management of venous thromboembolism in patients with cancer. Part 2: treatment.

Patients with cancer are at increased risk of venous thromboembolism (vte). Anticoagulation therapy is used to treat vte; however, patients with cancer have unique clinical circumstances that can often make decisions surrounding the administration of therapeutic anticoagulation complicated. No national Canadian guidelines on the management of established cancer-associated thrombosis have been published. We therefore aimed to develop a consensus-based, evidence-informed guideline on the topic. PubMed was searched for clinical trials and meta-analyses published between 2002 and 2013. Reference lists of key articles were hand-searched for additional publications. Content experts from across Canada were assembled to review the evidence and make recommendations. Low molecular weight heparin is the treatment of choice for cancer patients with established vte. Direct oral anticoagulants are not recommended for the treatment of vte at this time. Specific clinical scenarios, including the presence of an indwelling venous catheter, renal insufficiency, and thrombocytopenia, warrant modifications in the therapeutic administration of anticoagulation therapy. Patients with recurrent vte should receive extended (>3 months) anticoagulant therapy. Incidental vte should generally be treated in the same manner as symptomatic vte. There is no evidence to support the monitoring of anti-factor Xa levels in clinically stable cancer patients receiving prophylactic anticoagulation; however, levels of anti-factor Xa could be checked at baseline and periodically thereafter in patients with renal insufficiency. Follow-up and education about the signs and symptoms of vte are important components of ongoing patient care.

Real-Life Report on Chemoembolization Using DEBIRI for Liver Metastases from Colorectal Cancer.

Background. Transarterial chemoembolization (TACE) has been investigated in patients with liver metastases from colorectal cancer (LMCRC). Limited experience and available data suggest that TACE can achieve disease stabilization or improvement, even in heavily pretreated patients. Methods. Patients with LMCRC, ECOG 0-2, who failed at least 1 line of systemic chemotherapy, received embolizations with 2 mL of microspheres preloaded with 100 mg of irinotecan. Beads were delivered selectively into hepatic arteries. Primary endpoint was overall survival (OS), analyzed using the Kaplan-Meier method. Secondary endpoint was safety, assessed using CTCAE version 4.0. Results. 27 patients were treated using DEBIRI. Patient median age was 57 years (range was 45-82 years). The median number of total embolizations was 1.3 (range 1-3). The median OS was 5.4 months (95% CI; 1.1-22.7 months). The most reported postembolization events were nausea (8/27), vomiting (6/27), right upper quadrant pain (16/27), fatigue (9/27), and the development of ascites (6/27). 5/26 patients required hospitalization after TACE for severe pain. Hospitalization was also required for 1 case of allergic reaction and 1 case of infection. Conclusion. Our data suggest that TACE with DEBIRI could be efficacious in a palliative setting for patients with LMCRC, but they do not necessarily support routine use in clinical practice.

Bevacizumab-based therapy for colorectal cancer: experience from a large Canadian cohort at the Jewish General Hospital between 2004 and 2009.

BACKGROUND: Before its regulatory approval in Canada, bevacizumab to treat patients with colorectal cancer (crc) was accessed through the Bevacizumab Expanded Access Trial and a special-access program at the Jewish General Hospital. We retrospectively evaluated patient outcomes in that large cohort. METHODS: All patients (n = 196) had metastatic crc, were bevacizumab-naïve, and received bevacizumab in combination with chemotherapy at the Jewish General Hospital between 2004 and 2009. We collected patient demographics and clinical characteristics; relevant medical history, disease stage and tumour pathology at diagnosis; type, duration, and line of therapy; grades 3 and 4 adverse events (aes), time to disease progression (ttp), and overall survival (os) from diagnosis. RESULTS: Median follow-up was 36.0 months. Median ttp was 8.0 months [95% confidence interval (ci): 7.0 to 9.0 months). Median os was 41.0 months (95% ci: 36.0 to 47.0 months). Of the 40 grades 3 and 4 bevacizumab-related aes experienced by 38 patients (19.4%), the most common were thrombocytopenia (n = 17), deep-vein thrombosis (n = 6), pulmonary embolism (n = 4), and hypertension (n = 3). CONCLUSIONS: In an expanded access setting, our data reflect the efficacy and safety of bevacizumab-based therapy in the controlled post-registration clinical trial setting.

A real-life experience using panitumumab in chemo-refractory metastatic colorectal cancer patients: a retrospective analysis at the Jewish General Hospital, 2009-2012.

BACKGROUND: Panitumumab is a fully human monoclonal antibody, directed against the epidermal growth factor receptor, that was shown to be effective in third-line metastatic colorectal cancer. We performed a retrospective analysis of patients with chemo-refractory non-KRAS-mutated metastatic colorectal cancer, who received panitumumab at the Jewish General Hospital in Montreal, Canada, between 2009 and 2012. METHODS: This chart review included 44 patients (median age: 60 years; performance status: 0-3), of whom 50% had already received three lines of treatment. The primary endpoint was progression-free survival (pfs). Secondary endpoints were overall survival and safety. Tumour progression was determined by radiologic assessments performed once every 3 months per clinical guidelines or by clinical deterioration as determined by the clinician-investigator. RESULTS: In our sample, median pfs was 21.86 ± 5.23 weeks (95% confidence interval: 12.9 to 36.9 weeks) and overall survival was 35.14 ± 7.75 weeks (95% confidence interval: 25.6 to 73.4 weeks) with a median of 5 cycles of panitumumab treatment. The most frequently reported toxicities with panitumumab were skin toxicity (16.2% grade 3) and hypomagnesemia (10.8% grade 3). No infusion reactions were reported. CONCLUSIONS: Despite a small sample size from a single institution, our survival and efficacy data are encouraging and comparable to results obtained from the registration panitumumab trial. Our findings suggest that panitumumab can be effective and tolerable in a real-world setting.

Clinical significance of molecular biomarkers in glioblastoma.

AIM: To review the impact of molecular biomarkers on response to therapy and survival in patients with primary glioblastoma (GBM). MATERIALS & METHODS: Tissue specimens were analyzed for p53 mutations, EGFR amplification, loss of PTEN and p16, and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Demographic and clinical data were gathered from medical records. RESULTS: Clinical and pathological data of 125 patients were collected and analysed. MGMT promoter methylation was associated with improved median overall survival (OS) (61 vs. 42 weeks, p = 0.01) and was an important prognosticator independent of age at diagnosis, extent of resection and post-operative ECOG performance status (HR 2.04, 95% CI 1.11-3.75). Among patients with MGMT promoter methylation, survival was significantly improved with chemoradiotherapy (CRT) over radiotherapy (RT) alone (71 vs. 14 weeks, p < 0.01). Furthermore, amongst those treated with temozolomide (TMZ) based CRT, the presence of EGFR amplification, maintenance of PTEN and wild-type p53 and p16 were each associated with trends towards improved survival. CONCLUSION: MGMT promoter methylation is a strong, independent prognostic factor for OS in GBM. EGFR amplification, maintenance of PTEN, wild-type p53 and p16 all appear to be associated with improved survival in patients treated with CRT. However, the prognostic value of these biomarkers could not be ascertained and larger prospective studies are warranted.

Complete response of hepatocellular carcinoma with sorafenib and Y radioembolization.

Advanced hepatocellular carcinoma has a dismal prognosis, with a median overall survival of 7.9 months if untreated and of 10.7 months if treated with sorafenib. We present a case of advanced previously unresectable hepatocellular carcinoma in a 49-year-old man that achieved a pathologic complete response and was made amenable to surgery with sorafenib in combination with (90)Y radioembolization. The patient's survival was more than double the median for patients treated with sorafenib alone.