Clinical Oncology - Articles in Press

Improving Target Definition for Head and Neck Radiotherapy: A Place for Magnetic Resonance Imaging and 18-Fluoride Fluorodeoxyglucose Positron Emission Tomography? - Corrected Proof

R.J.D. Prestwich, J. Sykes, B. Carey, M. Sen, K.E. Dyker, A.F. Scarsbrook — 2012-05-17

Abstract: Defining the target for head and neck radiotherapy is a critical issue with the introduction of steep dose gradients associated with intensity-modulated radiotherapy. Tumour delineation inaccuracies are a major source of error in radiotherapy planning. The integration of 18-fluoride fluorodeoxyglucose positron emission tomography (18FDG-PET) and magnetic resonance imaging directly into the radiotherapy planning process has the potential to greatly improve target identification/selection and delineation. This raises a range of new issues surrounding image co-registration, delineation methodology and the use of functional data and treatment adaptation. This overview will discuss the practical aspects of integrating 18FDG-PET and magnetic resonance imaging into head and neck radiotherapy planning.

Concurrent Chemoradiotherapy for Locally Advanced, Unresectable Non-small Cell Lung Cancer: A UK Survey of Current Practice - Corrected Proof

J. Helbrow, F. MacNicoll, N. Bayman, C. Faivre-Finn — 2012-05-14

Sir — Concurrent chemoradiotherapy (cCTRT) is the standard of care for locally advanced non-small cell lung cancer (LA-NSCLC) . However, most patients are not suitable for this treatment, and 5 year survival remains poor at 20–25% .

Effect of Anaemia Prevention on Survival and Local Control in Oesophageal Cancers Treated with Chemoradiotherapy - Corrected Proof

J. Tuan, T.C. Ha, W. Chen, M. Hawkins, D. Tait — 2012-05-10

Sir — In the UK, oesophageal cancer is the third most commonly diagnosed gastrointestinal cancer . Surgery is the treatment of choice for patients with operable cancer. For patients who are medically unfit or who refuse surgery, external beam radiotherapy with or without chemotherapy is a curative alternative .

Assessing Patient Outcomes after Palliative Radiotherapy using Image-guided Intensity-modulated Radiotherapy - Corrected Proof

Rajiv Samant, Michael Scopazzi, Kathy Carty — 2012-04-23

Sir — Radiotherapy is an effective tool for cancer palliation and can relieve symptoms in 50–80% of patients with minimal toxicity. Typically, palliative radiotherapy planning is simple and involves one or two beams. However, as radiotherapy technology evolves, it is important to investigate more sophisticated approaches for palliation.

Implementing Image-guided Prostate Radiotherapy: Use of the ACCULOC® System to Optimise the Planning Target Volume Margins and to Assess the Potential Clinical Benefit - Corrected Proof

A. Challapalli, R. McLauchlan, A. Robinson, A. Taylor, C. Harvey, S.A. Mangar — 2012-04-23

Sir — The use of fiducial markers for positional verification and image guidance is gaining impetus in the current era of prostate radiotherapy. They have been incorporated as part of the Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy (CHHiP) trial , and are a mandatory requirement for tracking the prostate when using Cyberknife . ACCULOC® is a commercially available software system to obtain patient set-up position accuracy and reproducibility, used in combination with implanted fiducial markers. However, the introduction of this new technique has resource implications for a busy radiotherapy department , and this needs to be balanced between clinically relevant optimal planning target volume (PTV) margins and the potential clinical benefit. Hence, we conducted this study, using ACCULOC® to optimise the PTV margins and to ascertain the magnitude of the clinical benefit in reducing the rectal dose.

Adjuvant Interferon Therapy for Patients at High Risk for Recurrent Melanoma: An Updated Systematic Review - Corrected Proof

J.M.G. Larkin, R.A. Fisher, M.E. Gore — 2012-04-20

The systematic review of studies published between July 2005 and July 2010 reported by Petrella and colleagues addresses an important and controversial area in melanoma therapy: adjuvant interferon for those at high risk of recurrent disease. There remains widespread variation in practice globally with regard to the administration of adjuvant interferon in melanoma, and in some countries, such as the USA, there is variation between academic centres. In the UK, adjuvant interferon is rarely given; observation is regarded as the standard of care and clinical trial participation is recommended wherever possible .

Does Haemorrhage Associated with Brain Metastases in Lung Cancer Patients Predict Early Mortality after Cranial Irradiation? - Corrected Proof

F. Ampil, G. Caldito, P. Chittiboina, A. Nanda — 2012-04-20

Sir — Metastatic disease in the brain is a significant source of morbidity and mortality in people with cancer. Cranial irradiation is considered, for palliation, the standard of brain metastases (BRM) care because few effective therapeutic options exist. The incidence of haemorrhagic BRM (H-BRM) in non-small cell lung cancer patients was recently reported as 1% . The identification of factors that influence prognosis can be of value in clinical decision making. We hypothesised that people with lung cancer who were treated by cranial irradiation for H-BRM have a worse prognosis than those individuals with non-haemorrhagic BRM (NH-BRM).

Hyperbaric Oxygen Therapy for Late Rectal and Bladder Toxicity after Radiation in Prostate Cancer Patients. A Symptom Control and Quality-of-life Study - Corrected Proof

2012-04-20

Sir — Radiation therapy achieves a high level of disease control and cure rates for organ-confined prostate cancer , but a 5–20% incidence of late rectal/bladder toxicity can be expected . The aim of our study was to investigate the effects of hyperbaric oxygen therapy (HBOT) on symptom control and quality of life for late radiation proctitis and/or cystitis.

The Management of Lung Cancer: A UK Survey of Oncologists - Corrected Proof

S.L. Prewett, S. Aslam, M.V. Williams, D. Gilligan — 2012-04-19

Abstract: Aims: This report reviews current radiotherapy practice across the UK in the management of lung cancer, and the way new treatments and technologies are being introduced, where improvements have occurred, and where work is still required. We wanted to determine adherence to both National Radiotherapy Advisory Group and National Institute for Health and Clinical Excellence (NICE) guidance. This survey was conducted on behalf of the Department of Health Lung Cancer & Mesothelioma Advisory Group.Materials and methods: We sent a questionnaire to all UK radiotherapy departments. It covered radical radiotherapy dose fractionation, the use of concurrent or sequential chemotherapy for both non-small cell and small cell lung cancers, the use of continuous hyperfractionated accelerated radiotherapy, new radiotherapy techniques, the use of positron emission tomography/computed tomography for planning purposes and patient accrual into current National Cancer Research Network UK trials.Results: This UK-wide survey of radiotherapy practice for lung cancer showed broad compliance with NICE clinical guidance, but highlighted significant variation in fractionation schedules and the use of concomitant chemoradiotherapy. Clinical trial entry into lung cancer radiotherapy trials was variable and many centres are not fully participating in recruitment into these trials.Conclusions: This report has shown the variability of radiotherapy provision nationally. Current practice is largely consistent with current and updated NICE recommendations and best practice and should be recognised as such. It has also highlighted areas where improvements are still needed, particularly fractionation and new technologies. One particular aspect of concern is the poor recruitment to current UK-based clinical trials in lung cancer.

Whole Abdominal Radiation Using Helical Tomotherapy-based Intensity-modulated Radiotherapy: A Potential for Consolidation Therapy in Adequately Treated Locally Advanced Epithelial Ovarian Cancers - Corrected Proof

2012-04-16

Sir — Advanced epithelial ovarian cancers have generally been treated by maximal debulking surgery followed by chemotherapy. After adequate therapy, about 60–70% develop relapses confined to the abdominopelvic region . Therapies in the form of multiple surgeries and second- and third-line chemotherapy have been tried in these settings, but with limited success . Historically, whole abdominal radiation (WAR) has been effective but diminished due to the toxicities to the surrounding normal tissues, predominantly as a reason of lack of sophistication in the techniques . With the advent of newer radiation technology, WAR with intensity-modulated radiotherapy (IMRT) has the potential to curtail toxicities. WAR using rotational IMRT achieves excellent target coverage and optimal sparing of kidneys, partial liver and bone marrow . To assess clinical feasibility, we treated eight patients of relapsed epithelial ovarian cancer with WAR using helical tomotherapy-based IMRT and megavoltage computed tomography guidance. Of eight patients, six had a first relapse and had good response to second-line chemotherapy, whereas the other two patients had unresectable residual disease. All these patients had a component of residual disease in the pelvis. The planning details including definition of target volumes, dose prescription and constraints for various organs and dosimetric outcome has been previously reported .

Successful Spontaneous Pregnancy after Pelvic Chemoradiotherapy for Anal Cancer - Corrected Proof

P. Hürmüz, D. Sebag-Montefiore, P. Byrne, R. Cooper — 2012-04-09

Sir — Anal cancer is an uncommon cancer treated with pelvic chemoradiotherapy. A major late toxicity is sterility. A 25-year-old female presented with anal swelling. Investigations confirmed a T2N0M0 squamous cell carcinoma. She had one child and declined embryo cryopreservation or surgery. She received radiotherapy to the pelvis (30 Gy) () followed by involved field (20 Gy) with standard chemotherapy. At 4 months she was disease free, amenorrhoeic and gonadotrophin levels were raised. She started hormone replacement therapy (HRT) (Elleste duo 1 mg). Three months later withdrawal bleeds stopped and a pregnancy test was positive. She delivered a healthy baby by elective section at 39 weeks.

Dose-modified XELIRI Chemotherapy for Metastatic Colorectal Cancer — A Retrospective Study of 78 Patients - Corrected Proof

K. Tarver, J. Conibear, S. Raouf — 2012-04-03

Sir — The combination of capecitabine plus irinotecan (XELIRI) has proven problematic. Although studies have confirmed its efficacy in metastatic colorectal cancer (mCRC) , concerns remain regarding toxicity, particularly grade 3/4 diarrhoea. The European Organization for Research and Treatment of Cancer (EORTC) 40015 study found a 37% incidence of grade 3 diarrhoea with XELIRI compared with a 13% incidence with 5-fluorouracil and irinotecan (FOLFIRI).

Defining Target Volumes for Stereotactic Ablative Radiotherapy of Early-stage Lung Tumours: A Comparison of Three-dimensional 18F-fluorodeoxyglucose Positron Emission Tomography and Four-dimensional Computed Tomography - Corrected Proof

2012-03-27

Abstract: Aims: High local control rates are achieved in stage I lung cancer using stereotactic ablative radiotherapy. Target delineation is commonly based on four-dimensional computed tomography (CT) scans. Target volumes defined by positron emission tomography/computed tomography (PET/CT) are compared with those defined by four-dimensional CT and conventional (‘three-dimensional’) 18F-fluorodeoxyglucose (18F-FDG) PET/CT.Materials and methods: For 16 stage I non-small cell lung cancer tumours, six approaches for deriving PET target volumes were evaluated: manual contouring, standardised uptake value (SUV) absolute threshold of 2.5, 35% of maximum SUV (35%SUVMAX), 41% of SUVMAX (41%SUVMAX) and two different source to background ratio techniques (SBR-1 and SBR-2). PET-derived target volumes were compared with the internal target volume (ITV) from the modified maximum intensity projection (MIPMOD ITV). Volumetric and positional correlation was assessed using the Dice similarity coefficient (DSC).Results: PET-based target volumes did not correspond to four-dimensional CT-based target volumes. The mean DSC relative to MIPMOD ITV were: PET manual = 0.64, SUV2.5 = 0.64, 35%SUVMAX = 0.63, 41%SUVMAX = 0.57. SBR-1 = 0.52, SBR-2 = 0.49. PET-based target volumes were smaller than corresponding MIP ITVs.Conclusions: Conventional three-dimensional 18F-FDG PET-derived target volumes for lung stereotactic ablative radiotherapy did not correspond well with those derived from four-dimensional CT, including those in routine clinical use (MIPMOD ITV). Caution is required in using three-dimensional PET for motion encompassing target volume delineation.

A Population-Based Study of Factors Affecting the Use of Radiotherapy for Endometrial Cancer - Corrected Proof

T.P. Hanna, H. Richardson, Y. Peng, W. Kong, J. Zhang-Salomons, W.J. Mackillop — 2012-03-14

Abstract: Aims: To describe the use of adjuvant radiotherapy for endometrial cancer in Ontario, and identify factors associated with its use, and to determine whether variation in the use of radiation is associated with differences in survival.Materials and methods: This was a retrospective, population-based, cohort study of all patients who had a hysterectomy for endometrial cancer in Ontario between 1992 and 2003. We used multiple logistic regression to identify health system-related factors associated with the use of radiotherapy, while controlling for disease- and patient-related factors. Survival and cancer cause-specific survival were compared among regions of the province with higher and lower rates of use of radiotherapy.Results: The study population included a total of 9411 women with a median age of 63 years. Overall, 26.2% received adjuvant radiotherapy. Patients living further from regional cancer centres were slightly less likely to receive radiation (P = 0.02). Patients who had their surgery during longer prevailing waiting times for radiotherapy were less likely to receive radiation (P = 0.04). The use of radiotherapy varied widely from 18.0 to 34.3% among the catchment areas of provincial radiotherapy centres (P < 0.0001). In the overall population, there was no difference in survival among regions with higher and lower rates of use of radiotherapy. However, in the subgroup of cases with clear cell and serous carcinomas, both overall survival and cancer cause-specific survival were significantly lower in regions with lower rates of use of radiotherapy (P < 0.05). This difference remained significant after controlling for other factors (P < 0.05; hazard ratio 1.43; 95% confidence limits 1.06–1.93).Conclusions: Health system-related factors unrelated to patients’ needs affect the use of adjuvant radiotherapy in Ontario. Lower rates of use of adjuvant radiotherapy are associated with lower rates of survival in patients with serous and clear cell carcinomas.

Pemetrexed-induced Skin Sclerosis - Corrected Proof

2012-03-07

Sir — Pemetrexed is a new-generation antifolate that inhibits multiple folate-dependent enzymes, used in the treatment of non-small cell lung cancer and malignant pleural mesothelioma. We report three men who developed localised scleroderma-like induration of the legs while being treated with pemetrexed. The first patient was a 57-year-old man diagnosed with bronchioloalveolar carcinoma. After the 16th cycle of pemetrexed, we observed a rapid onset of oedema and redness in both legs, without fever. These oedematous areas became sclerotic with pigmentary changes (). The patient described a burning pain. Histological examination showed a dermal fibrosis. A complete recovery was observed after 18 months. The second patient was a 65-year-old man diagnosed with non-small cell lung cancer. Two weeks after the second cycle of pemetrexed we observed infiltrated erythemato-violaceous plaques of both legs () with fever, which gradually improved. For the next cycle, the dose was reduced to 75%. Nevertheless, we observed the recurrence of a well-limited erythematous, infiltrated and painful skin rash on the legs. After 2 years of follow-up, skin remained mildly sclerotic. The third patient was a 62-year-old man diagnosed with bronchioloalveolar carcinoma. After the seventh cycle of pemetrexed we noticed swollen ankles on both sides, which evolved into sclerotic plaques. Lipodermatosclerosis was suspected. Pemetrexed was stopped after the 12th cycle. The skin remained infiltrated with a brown pigmentation.

Stage for Stage Comparison of Recurrence Patterns after Definitive Chemoradiotherapy or Surgery for Oesophageal Carcinoma - Corrected Proof

T.D. Reid, I. Ll. Davies, J. Mason, S.A. Roberts, T.D.L. Crosby, W.G. Lewis — 2012-03-02

Abstract: Aims: Definitive chemoradiotherapy (dCRT) has been advocated as an alternative treatment for oesophageal carcinoma, but received criticism for perceived poorer locoregional disease control when compared with surgery. The aim of this study was to determine the relative incidence and pattern of oesophageal carcinoma recurrence after dCRT and surgery in patients receiving stage-directed therapy with curative intent.Materials and methods: In total, 623 consecutive patients with oesophageal carcinoma (207 squamous cell carcinoma, 416 adenocarcinoma) were studied. The primary outcome measure was disease-free survival, adjusted for baseline differences in gender, age and histological cell type.Results: Three hundred and eleven patients deemed unsuitable for surgery on the grounds of performance status (n = 137), bulky local disease (n = 121) or personal choice (n = 53) received dCRT and 312 surgery (200 received neoadjuvant chemotherapy). Oesophageal carcinoma recurrence was diagnosed in 44.1% of patients after dCRT compared with 40.7% after surgery (P = 0.222). Locoregional recurrence was more common after dCRT than after surgery (24.1% versus 9.3%, P < 0.0001). In contrast, distant metastases were more common after surgery than after dCRT (22.8% versus 12.9%, P = 0.001). The median time to recurrence in patients receiving dCRT and surgery were 15 and 17 months, respectively (P = 0.052). Stage-related disease-free 2 year survival for dCRT versus surgery was: stage I (68.6 versus 85.6%, P = 0.069), stage II (36.9 versus 47.4%, P = 0.011), stage III (31.0 versus 28.6, P = 0.878), stage IVa (21.4 versus 26.3%, P = 0.710).Conclusions: These findings provide further support for a randomised trial of dCRT versus surgery in both oesophageal squamous cell carcinoma and adenocarcinoma.

Adjuvant Interferon Therapy for Patients at High Risk for Recurrent Melanoma: An Updated Systematic Review and Practice Guideline - Corrected Proof

2012-01-16

Abstract: After complete resection of melanoma, some patients remain at high risk for recurrence. The efficacy of adjuvant systemic therapy has been inconsistent in randomised trials and remains controversial. An updated systematic review was conducted to identify new evidence on the role of adjuvant interferon therapy in patients with high-risk resected primary melanoma. Outcomes of interest included overall survival, disease-free survival (DFS), adverse effects and quality of life. MEDLINE, EMBASE, Cochrane Library and the proceedings of the American Society of Clinical Oncology were systematically searched to identify new randomised controlled trials, systematic reviews or meta-analyses. An updated meta-analysis of trials comparing high-dose interferon alpha with observation alone was conducted. The new data are presented in this review. Seven randomised controlled trials met the inclusion criteria: six trials of interferon alone and two trials of interferon plus chemotherapy. Two meta-analyses of adjuvant interferon alpha were also identified. Overall survival was not significantly different between adjuvant high-dose interferon and observation alone (hazard ratio 0.93; 95% confidence interval 0.78–1.12; P = 0.45). A meta-analysis of DFS showed a significant benefit for high-dose interferon over control (hazard ratio 0.77; 95% confidence interval 0.65–0.92; P = 0.004). One trial reported a significant DFS benefit for pegylated interferon over observation alone. Our updated literature review indicates that adjuvant interferon therapy does not confer a significant long-term overall survival benefit in patients with high-risk resected primary melanoma; however, a significant DFS benefit for high-dose interferon or pegylated interferon treatment has been shown. An revised practice guideline was developed based on the systematic review.

Intra-fraction Motion during Extreme Hypofractionated Radiotherapy of the Prostate using Pre- and Post-treatment Imaging - Corrected Proof

2012-01-09

Abstract: Aims: To determine intra-fraction displacement of the prostate during extreme hypofractionated radiotherapy using pre- and post-treatment orthogonal images with three implanted gold seed fiducial markers.Materials and methods: In total, 265 image pairs were obtained from 53 patients who underwent extreme hypofractionated radiotherapy to a dose of 35 Gy in five fractions on standard linear accelerators. Position verification was obtained with orthogonal X-rays before and after treatment and were used to determine intra-fraction prostate displacement.Results: The mean intra-fraction prostate displacements were −0.03 ± 0.61 mm (one standard deviation), 0.21 ± 1.50 mm and −0.86 ± 1.73 mm in the left–right, superior–inferior and anterior–posterior directions, respectively. The mean intra-fraction displacement during the first two fractions was moderately correlated with the displacement in the remaining three fractions, with correlation coefficients of 0.63 (95% confidence interval 0.43–0.77) and 0.47 (95% confidence interval 0.22–0.65) in the superior–inferior and anterior–posterior directions, respectively. There was no significant correlation in the left–right direction with a coefficient of –0.04 (95% confidence interval −0.31–0.23).Conclusions: The mean intra-fraction prostate displacement during a course of extreme hypofractionated radiotherapy is small. A strategy using the first two fractions to predict future displacements >5 mm warrants further validation.

Long-term Outcomes and Prognostic Factors of Re-irradiation for Locally Recurrent Nasopharyngeal Carcinoma using Intensity-modulated Radiotherapy - Corrected Proof

2012-01-03

Abstract: Aims: To analyse the outcomes and to evaluate the prognostic factors involved in the re-irradiation of locally recurrent nasopharyngeal carcinoma (NPC) using intensity-modulated radiotherapy (IMRT).Materials and methods: A retrospective analysis of 239 NPC patients with local recurrence who were re-irradiated with IMRT between 2001 and 2008 was conducted. The distribution of disease re-staging was 5.4% for stage I, 18.4% for stage II, 29.7% for stage III and 46.4% for stage IV. Cisplatin-based chemotherapy was administered to 117 patients (49.0%) in addition to the IMRT.Results: The mean D95 and the V95 of the gross tumour volume (GTV) were 66.78Gy and 98.61%, respectively. The mean dose to the GTV was 70.04Gy (61.73–77.54Gy). The 5 year overall survival, local recurrence-free survival, distant metastasis-free survival and disease-free survival were 44.9, 85.8, 80.6 and 45.4%, respectively. In a univariate analysis, patient age, recurrent T (rT), recurrent N (rN), recurrent stage, tumour volume, mean dose and mean fractional dose of the GTV were significant prognostic factors for overall survival. In a multivariate analysis, only patient age, rN stage, recurrent stage, mean fractional dose and tumour volume remained significant for overall survival.Conclusions: Re-irradiation using IMRT is available to improve local tumour control and to prolong patients’ survival. A smaller tumour volume, higher fractional dose, younger patient ages, lower rN0 stage and early recurrent stage are all independent prognostic factors for overall survival of recurrent NPC. It is of clinical importance to select the appropriate recurrent NPC cases for salvage re-irradiation by IMRT.

Clinical Correlations and Prognostic Relevance of Tissue Angiogenic Factors in Patients with Gastric Cancer - Corrected Proof

Y. Mohri, C. Miki, K. Tanaka, A. Kawamoto, M. Ohi, T. Yokoe, M. Kusunoki — 2011-11-30

Abstract: Aims: To evaluate the relationship between vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) levels in gastric cancer tissue and clinicopathological features and to determine whether these factors were correlated with survival.Materials and methods: We analysed tissue samples from 58 patients with gastric cancer and used 24 normal gastric mucosae as controls. Tissue levels of VEGF and HGF were measured in tissue extracts by enzyme-linked immunosorbent assay.Results: HGF and VEGF levels were significantly higher in gastric cancer tissue than in matched normal gastric mucosa. VEGF levels were significantly increased in cancer tissue from cases involving lymphatic invasion. HGF levels were significantly increased according to the disease stage. Patients with high levels of VEGF or HGF showed significantly worse survival rates than patients with low levels. Using multivariate analysis, a high level of VEGF or HGF was an independent factor predicting poor survival.Conclusions: Intratumoral levels of HGF and VEGF are an important prognostic determinant in gastric cancer. The current findings suggest that high concentrations of HGF and VEGF may induce aggressive tumour growth and metastasis.

Concurrent Chemotherapy and Intensity-modulated Radiation Therapy for Anal Carcinoma — Clinical Outcomes in a Large National Cancer Institute-designated Integrated Cancer Centre Network - Corrected Proof

2011-11-10

Abstract: Aims: To report the clinical outcomes of patients with anal carcinoma treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy in a large integrated academic-community cancer centre network.Materials and methods: Seventy-eight patients were treated with IMRT for anal carcinoma at 13 community cancer centres. IMRT planning for all centres was carried out at one central location. Sixty-five patients (83%) were T1–T2, 64% were N0, 9% were M1; five patients were HIV positive. All but one patient received concurrent chemotherapy. The median dose to the pelvis including inguinal nodes was 45Gy. The primary site and involved nodes were boosted to a median dose of 55.8Gy. All acute and late toxicities were scored according to the Common Terminology Criteria for Adverse Events, version 3.0.Results: The median follow-up for the entire cohort was 16 months (range 0–72 months). Acute grade ≥3 toxicity included 27.7% gastrointestinal and 29.0% dermatological. Acute grade 4 haematological toxicity occurred in 12.9% of patients. Sixty-four (88.9%) patients experienced a complete response. The 2 year colostomy-free survival, overall survival, freedom from local failure and freedom from distant failure rates were 81.2, 86.9, 83.6 and 81.8%, respectively.Conclusions: Early results seem to confirm that IMRT used concurrently with chemotherapy for treatment of anal carcinoma is effective and well tolerated. This complex treatment can be safely and effectively carried out in a large integrated healthcare network.

The Role of Autophagy in Clinical Practice - Corrected Proof

A.L. Swampillai, P. Salomoni, S.C. Short — 2011-10-28

Abstract: Resisting cell death is one of the six hallmarks of cancer. Autophagy is a highly adaptable metabolic process that plays an important role in stressful conditions, such as nutrient deprivation and hypoxia. In these conditions, it is becoming evident that autophagy protects cells, by providing an alternative energy source and by eliminating dysfunctional organelles or proteins. In tumourigenesis, autophagy plays a dual role, which may be related to the different stages in cancer development. The autophagy-mediated removal of damaged proteins and organelles may prevent cancer initiation by limiting tissue inflammation. In contrast, autophagy has been shown to allow established tumours to survive in nutrient-deprived or hypoxic conditions during cancer progression. Key regulators of the autophagy pathway are modulated or aberrantly expressed in cancer and modulating autophagy is an attractive concept for cancer therapy. The difficulties, however, lie in the complexity of the crosstalk between apoptosis and autophagy and the lack of robust tissue biomarkers and in vivo assessment of autophagic flux. Currently there are 19 clinical trials in both solid and haematogenous cancers investigating the efficacy and toxicity of adding an autophagy inhibitor to standard treatment. Hydroxychloroquine, a drug routinely used in the treatment of malaria and autoimmune disorders, is the most common autophagy inhibitor under investigation due to its more favourable toxicity profile. This overview summarises the role of autophagy in cancer initiation, progression and resistance to treatment and thereby the therapeutic benefit that may be gained by modulating its effects.

Gefitinib Compared with Systemic Chemotherapy as First-line Treatment for Chemotherapy-naive Patients with Advanced Non-small Cell Lung Cancer: A Meta-analysis of Randomised Controlled Trials - Corrected Proof

F. Wang, L.D. Wang, B. Li, Z.X. Sheng — 2011-10-24

Abstract: To define the efficacy of gefitinib in chemotherapy-naive patients with advanced non-small cell lung cancer, we carried out a meta-analysis of randomised controlled trials. Medline, Embase, the Cochrane controlled trials register and the Science Citation Index were searched. Seven trials were identified, covering a total of 4656 subjects. As compared with chemotherapy, gefitinib was effective in the selected patients: the corresponding summary hazard ratios (gefitinib versus chemotherapy) for progression-free survival were 0.43 (0.32, 0.58) (P < 0.001) for the subgroup of patients with epidermal growth factor receptor (EGFR) mutant treated with gefitinib monotherapy, 0.71 (0.60, 0.83) (P < 0.001) for the subgroup of patients with lung adenocarcinoma; but was detrimental for the patients without EGFR mutant treated by gefitinib monotherapy [hazard ratio = 2.16 (1.17, 3.99), P = 0.01]. Significantly improved survival was found in the gefitinib group compared with the control in the subgroup of patients with lung adenocarcinoma [hazard ratio = 0.89 (0.81, 0.99); P = 0.03], but not found in the subgroup of patients with EGFR mutant [hazard ratio = 0.87 (0.68, 1.12); P = 0.28]. In conclusion, first-line treatment with gefitinib conferred prolonged progression-free survival than treatment with systemic chemotherapy in a molecularly or histologically defined population of patients with non-small cell lung cancer, and improved survival in the subgroup of patients with lung adenocarcinoma.

Single Agent Weekly Paclitaxel as Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer: A Feasibility Study - Corrected Proof

2011-10-20

Abstract: Aim: To study the toxicity profile and response rates of weekly paclitaxel given as neoadjuvant chemotherapy (NACT) in patients with locally advanced breast cancer.Materials and methods: The study was planned as a single arm, prospective phase II study. Twenty-six patients with locally advanced breast cancer were enrolled in the study from December 2006 to October 2007. These patients underwent NACT with weekly paclitaxel at 100 mg/m2 for 8 consecutive weeks followed by surgery. This was followed by anthracycline-based chemotherapy for three to four cycles followed by radiation. The patients received standard adjuvant hormonal therapy. The patients were carefully monitored for side-effects using common toxicity criteria. The clinical and pathological response rates were documented. The response rates were descriptively stated.Results: The median age of the patients was 52 years (30–67 years) and the median tumour size was 7 cm (2.5–15 cm). Of the 208 planned weekly cycles, 207 could be given. The rates of grade 3–4 neutropenia, thrombocytopenia and neuropathy were 4, 12 and 4%, respectively. A complete clinical response was observed in 10 patients (38.5%) and a completed pathological response, defined as the absence of invasive cancer from the breast and axillary nodes, was seen in 11.5% of patients. Breast-conserving surgery was possible in 23% of patients.Conclusion: The regimen of weekly single agent paclitaxel is feasible in patients with locally advanced breast cancer with acceptable toxicity. It resulted in a pathological response rate that was comparable with other regimens in this group of advanced stage patients. Considering the efficacy and low toxicity of this regimen, it is worth exploring in larger studies.

WITHDRAWN: Recent Advances in Angiopoietin Biology in Cancer — A Review - Corrected Proof

Suhasini Joshi, Ashish Tiwari — 2011-02-09

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause.The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy