Knowledge-Based Assessment of Focal Dose Escalation Treatment Plans in Prostate Cancer.

PURPOSE: In a randomized focal dose escalation radiation therapy trial for prostate cancer (FLAME), up to 95 Gy was prescribed to the tumor in the dose-escalated arm, with 77 Gy to the entire prostate in both arms. As dose constraints to organs at risk had priority over dose escalation and suboptimal planning could occur, we investigated how well the dose to the tumor was boosted. We developed an anatomy-based prediction model to identify plans with suboptimal tumor dose and performed replanning to validate our model. METHODS AND MATERIALS: We derived dose-volume parameters from planned dose distributions of 539 FLAME trial patients in 4 institutions and compared them between both arms. In the dose-escalated arm, we determined overlap volume histograms and derived features representing patient anatomy. We predicted tumor D98% with a linear regression on anatomic features and performed replanning on 21 plans. RESULTS: In the dose-escalated arm, the median tumor D50% and D98% were 93.0 and 84.7 Gy, and 99% of the tumors had a dose escalation greater than 82.4 Gy (107% of 77 Gy). In both arms organs at risk constraints were met. Five out of 73 anatomic features were found to be predictive for tumor D98%. Median predicted tumor D98% was 4.4 Gy higher than planned D98%. Upon replanning, median tumor D98% increased by 3.0 Gy. A strong correlation between predicted increase in D98% and realized increase upon replanning was found (ρ = 0.86). CONCLUSIONS: Focal dose escalation in prostate cancer was feasible with a dose escalation to 99% of the tumors. Replanning resulted in an increased tumor dose that correlated well with the prediction model. The model was able to identify tumors on which a higher boost dose could be planned. The model has potential as a quality assessment tool in focal dose escalated treatment plans.

ECCO essential requirements for quality cancer care: Oesophageal and gastric cancer.

BACKGROUND: ECCO essential requirements for quality cancer care (ERQCC) are checklists and explanations of organisation and actions that are necessary to give high-quality care to patients who have a specific type of cancer. They are written by European experts representing all disciplines involved in cancer care. ERQCC papers give oncology teams, patients, policymakers and managers an overview of the elements needed in any healthcare system to provide high quality of care throughout the patient journey. References are made to clinical guidelines and other resources where appropriate, and the focus is on care in Europe. OESOPHAGEAL AND GASTRIC: ESSENTIAL REQUIREMENTS FOR QUALITY CARE: CONCLUSION: Taken together, the information presented in this paper provides a comprehensive description of the essential requirements for establishing a high-quality OG cancer service. The ERQCC expert group is aware that it is not possible to propose a 'one size fits all' system for all countries, but urges that access to multidisciplinary units or centres must be guaranteed for all those with OG cancer.

Patient-specific bolus for range shifter air gap reduction in intensity-modulated proton therapy of head-and-neck cancer studied with Monte Carlo based plan optimization.

BACKGROUND & PURPOSE: Intensity-modulated proton therapy (IMPT) of superficial lesions requires pre-absorbing range shifter (RS) to deliver the more shallow spots. RS air gap minimization is important to avoid spot size degradation, but remains challenging in complex geometries such as in head-and-neck cancer (HNC). In this study, clinical endpoints were investigated for patient-specific bolus and for conventional RS solutions, making use of a Monte Carlo (MC) dose engine for IMPT optimization. METHODS AND MATERIALS: For 5 oropharyngeal cancer patients, IMPT spot maps were generated using beamlets calculated with MC. The plans were optimized for three different RS configurations: 3D printed on-skin bolus, snout- and nozzle-mounted RS. Organ-at-risk (OAR) doses and late toxicity probabilities were compared between all configuration-specific optimized plans. RESULTS: The use of bolus reduced the mean dose to all OARs compared to snout and nozzle-mounted RS. The contralateral parotid gland and supraglottic larynx received on average 2.9Gy and 4.2Gy less dose compared to the snout RS. Bolus reduced the average probability for xerostomia by 3.0%. For dysphagia, bolus reduced the probability by 2.7%. CONCLUSIONS: Quantification of the dosimetric advantage of patient-specific bolus shows significant reductions compared to conventional RS solutions for xerostomia and dysphagia probability. These results motivate the development of a patient-specific bolus solution in IMPT for HNC.

TOPGEAR: a randomised phase III trial of perioperative ECF chemotherapy versus preoperative chemoradiation plus perioperative ECF chemotherapy for resectable gastric cancer (an international, intergroup trial of the AGITG/TROG/EORTC/NCIC CTG).

BACKGROUND: The optimal management of patients with resectable gastric cancer continues to evolve in Western countries. Following publication of the US Intergroup 0116 and UK Medical Research Council MAGIC trials, there are now two standards of care for adjuvant therapy in resectable gastric cancer, at least in the Western world: postoperative chemoradiotherapy and perioperative epirubicin/cisplatin/fluorouracil (ECF) chemotherapy. We hypothesize that adding chemoradiation to standard perioperative ECF chemotherapy will achieve further survival gains. We also believe there are advantages to administering chemoradiation in the preoperative rather than postoperative setting. In this article, we describe the TOPGEAR trial, which is a randomised phase III trial comparing control arm therapy of perioperative ECF chemotherapy with experimental arm therapy of preoperative chemoradiation plus perioperative ECF chemotherapy. METHODS/DESIGN: Eligible patients with resectable adenocarcinoma of the stomach or gastroesophageal junction will be randomized to receive either perioperative chemotherapy alone (3 preoperative and 3 postoperative cycles of ECF) or perioperative chemotherapy plus preoperative chemoradiation. In the chemoradiation arm, patients receive 2 cycles of ECF plus chemoradiation prior to surgery, and then following surgery 3 further cycles of ECF are given. The trial is being conducted in two Parts; Part 1 (phase II component) has recruited 120 patients with the aim of assessing feasibility, safety and preliminary efficacy of preoperative chemoradiation. Part 2 (phase III component) will recruit a further 632 patients to provide a total sample size of 752 patients. The primary endpoint of the phase III trial is overall survival. The trial includes quality of life and biological substudies, as well as a health economic evaluation. In addition, the trial incorporates a rigorous quality assurance program that includes real time central review of radiotherapy plans and central review of surgical technique. DISCUSSION: TOPGEAR is an international, intergroup collaboration led by the Australasian Gastro-Intestinal Trials Group (AGITG), in collaboration with the Trans-Tasman Radiation Oncology Group (TROG), European Organisation for Research and Treatment of Cancer (EORTC) and the NCIC Clinical Trials Group. It addresses a globally significant question that will help inform future international standards for clinical practice in resectable gastric cancer. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12609000035224 . Registered 30 May 2009.

Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials).

BACKGROUND: Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. METHODS: Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9). RESULTS: For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items. CONCLUSION: The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer.

Value of diffusion-weighted magnetic resonance imaging for prediction and early assessment of response to neoadjuvant radiochemotherapy in rectal cancer: preliminary results.

PURPOSE: To evaluate diffusion-weighted magnetic resonance imaging (DWI) for response prediction before and response assessment during and early after preoperative radiochemotherapy (RCT) for locally advanced rectal cancer (LARC). METHODS AND MATERIALS: Twenty patients receiving RCT for LARC underwent MRI including DWI before RCT, after 10-15 fractions and 1 to 2 weeks before surgery. Tumor volume and apparent diffusion coefficient (ADC; b-values: 0-1000 s/mm(2)) were determined at all time points. Pretreatment tumor ADC and volume, tumor ADC change (∆ADC), and volume change (∆V) between pretreatment and follow-up examinations were compared with histopathologic findings after total mesorectal excision (pathologic complete response [pCR] vs. no pCR, ypT0-2 vs. ypT3-4, T-downstaging or not). The discriminatory capability of pretreatment tumor ADC and volume, ∆ADC, and ∆V for the detection of pCR was compared with receiver operating characteristics analysis. RESULTS: Pretreatment ADC was significantly lower in patients with pCR compared with patients without (in mm(2)/s: 0.94 ± 0.12 × 10(-3) vs. 1.19 ± 0.22 × 10(-3), p = 0.003), yielding a sensitivity of 100% and specificity of 86% for detection of pCR. The volume reduction during and after RCT was significantly higher in patients with pCR compared with patients without (in %: ΔV(during): -62 ± 16 vs. -33 ± 16, respectively, p = 0.015; and ΔV(post): -86 ± 12 vs. -60 ± 21, p = 0.012), yielding a sensitivity of 83% and specificity of 71% for the ΔV(during) and, respectively, 83% and 86% for the ΔV(post). The ∆ADC during (ΔADC(during)) and after RCT (ΔADC(post)) showed a significantly higher value in patients with pCR compared with patients without (in %: ΔADC(during): 72 ± 14 vs. 16 ± 12, p = 0.0006; and ΔADC(post): 88 ± 35 vs. 26 ± 19, p = 0.0011), yielding a sensitivity and specificity of 100% for the ΔADC(during) and, respectively, 100% and 93% for the ΔADC(post). CONCLUSIONS: These initial findings indicate that DWI, using pretreatment ADC, ΔADC(during), and ΔADC(post) may be useful for prediction and early assessment of pathologic response to preoperative RCT of LARC, with higher accuracy than volumetric measurements.

Multidisciplinary Rectal Cancer Management: 2nd European Rectal Cancer Consensus Conference (EURECA-CC2).

BACKGROUND AND PURPOSE: During the first decade of the 21st century a number of important European randomized studies were published. In order to help shape clinical practice based on best scientific evidence from the literature, the International Conference on 'Multidisciplinary Rectal Cancer Treatment: Looking for an European Consensus' (EURECA-CC2) was organized in Italy under the endorsement of European Society of Medical Oncology (ESMO), European Society of Surgical Oncology (ESSO), and European Society of Therapeutic Radiation Oncology (ESTRO). METHODS: Consensus was achieved using the Delphi method. The document was available to all Committee members as a web-based document customized for the consensus process. Eight chapters were identified: epidemiology, diagnostics, pathology, surgery, radiotherapy and chemotherapy, treatment toxicity and quality of life, follow-up, and research questions. Each chapter was subdivided by a topic, and a series of statements were developed. Each member commented and voted, sentence by sentence thrice. Sentences upon which an agreement was not reached after voting round # 2 were openly debated during a Consensus Conference in Perugia (Italy) from 11 December to 13 December 2008. A hand-held televoting system collected the opinions of both the Committee members and the audience after each debate. The Executive Committee scored percentage consensus based on three categories: "large consensus", "moderate consensus", and "minimum consensus". RESULTS: The total number of the voted sentences was 207. Of the 207, 86% achieved large consensus, 13% achieved moderate consensus, and only 3 (1%) resulted in minimum consensus. No statement was disagreed by more than 50% of the members. All chapters were voted on by at least 75% of the members, and the majority was voted on by >85%. CONCLUSIONS: This Consensus Conference represents an expertise opinion process that may help shape future programs, investigational protocols, and guidelines for staging and treatment of rectal cancer throughout Europe.