Aslam Sohaib

European Consensus Conference on Diagnosis and Treatment of Germ Cell Cancer: A Report of the Second Meeting of the European Germ Cell Cancer Consensus group (EGCCCG): Part I

OBJECTIVES The first consensus report presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in the year 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, Amsterdam, The Netherlands. METHODS Medical oncologists, urological surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference, and incorporated the new data into updated and revised guidelines. As for the first meeting, the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update. RESULTS The first part of the consensus paper describes the clinical presentation of the primary tumor, its treatment, the importance and treatment of testicular intraepithelial neoplasia (TIN), histological classification, staging and prognostic factors, and treatment of stage I seminoma and non-seminoma. CONCLUSIONS Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early- and advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. In addition, the particular needs of testicular cancer survivors have been acknowledged.

Maintaining success, reducing treatment burden, focusing on survivorship: highlights from the third European consensus conference on diagnosis and treatment of germ-cell cancer

In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377–1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478–496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497–513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues. The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, ∼50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements.

Scoring systems used for the interpretation and reporting of multiparametric MRI for prostate cancer detection, localization, and characterization: could standardization lead to improved utilization of imaging within the diagnostic pathway?

Multiparametric magnetic resonance imaging (mpMRI) is increasingly being used earlier in the prostate cancer diagnostic pathway in order to detect and localize disease. Its results can be used to help decide on the indication, type, and localization of a prostate biopsy for cancer diagnosis. In addition, mpMRI has the potential to contribute information on the characterization, or aggressiveness, of detected cancers including tumor progression over time. There is considerable variation in the way results of different MRI sequences are reported. We conducted a review of scoring systems that have been used in the detection and characterization of prostate cancer. This revealed that existing scoring and reporting systems differ in purpose, scale, and range. We evaluate these differences in this review. This first step in collating all methods of scoring and reporting mpMRI will ultimately lead to consensus approaches to develop a standardized reporting scheme that can be widely adopted and validated to ensure comparability of research outputs and optimal clinical practice. J. Magn. Reson. Imaging 2013;37:48–58.

AN EXPLORATORY STUDY INTO THE ROLE OF DYNAMIC CONTRAST-ENHANCED MAGNETIC RESONANCE IMAGING OR PERFUSION COMPUTED TOMOGRAPHY FOR DETECTION OF INTRATUMORAL HYPOXIA IN HEAD-AND-NECK CANCER

PURPOSE Hypoxia in patients with head-and-neck cancer (HNC) is well established and known to cause radiation resistance and treatment failure in the management of HNC. This study examines the role of parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and perfusion computed tomography (CT) as surrogate markers of intratumoral hypoxia, defined by using the exogenous marker of hypoxia pimonidazole and the endogenous marker carbonic anhydrase 9 (CA9). METHODS AND MATERIALS Patients with HNC underwent preoperative DCE-MRI, perfusion CT, and pimonidazole infusion. Imaging parameters were correlated with pimonidazole and CA9 staining. The strength of correlations was tested by using a two-tailed Spearmans rank correlation coefficient. RESULTS Twenty-three regions of interest were analyzed from the 7 patients who completed the DCE-MRI studies. A number of statistically significant correlations were seen between DCE-MRI parameters (volume transfer between blood plasma and extracellular extravascular space [EES], volume of EES, rate constant between EES and blood plasma, time at arrival of contrast inflow, time to peak, average gradient, and time to onset) and areas with a pimonidazole score of 4. In the case of CA9 staining, only a weak correlation was shown with wash-in rate. There were no significant correlations between perfusion CT parameters and pimonidazole staining or CA9 expression. CONCLUSION Intratumoral hypoxia in patients with HNC may be predicted by using DCE-MRI; however, perfusion CT requires further investigation.

Prostate MRI: Who, when, and how? Report from a UK consensus meeting

The current pathway for men suspected of having prostate cancer [transrectal biopsy, followed in some cases by magnetic resonance imaging (MRI) for staging] results in over-diagnosis of insignificant tumours, and systematically misses disease in the anterior prostate. Multiparametric MRI has the potential to change this pathway, and if performed before biopsy, might enable the exclusion of significant disease in some men without biopsy, targeted biopsy in others, and improvements in the performance of active surveillance. For the potential benefits to be realized, the setting of standards is vital. This article summarizes the outcome of a meeting of UK radiologists, at which a consensus was achieved on (1) the indications for MRI, (2) the conduct of the scan, (3) a method and template for reporting, and (4) minimum standards for radiologists.

The value of magnetic resonance imaging in target volume delineation of base of tongue tumours--a study using flexible surface coils.

INTRODUCTION Magnetic resonance imaging (MRI) provides superior diagnostic accuracy over computed tomography (CT) in oropharyngeal tumours. Precise delineation of the gross tumour volume (GTV) is mandatory in radiotherapy planning when a GTV boost is required. CT volume definition in this regard is poor. We studied the feasibility of using flexible surface (flex-L) coils to obtain MR images for MR-CT fusion to assess the benefit of MRI over CT alone in planning base of tongue tumours. METHODS Eight patients underwent CT and MRI radiotherapy planning scans with an immobilisation device. Distortion-corrected T1-weighted post-contrast MR scans were fused to contrast-enhanced planning CT scans. GTV, clinical target and planning target volumes (CTV, PTV) and organs at risk (OAR) were delineated on CT, then on MRI with blinding to the CT images. The volumetric and spatial differences between MRI and CT volumes for GTV, CTV, PTV and OAR were compared. MR image distortions due to field inhomogeneity and non-linear gradients were corrected and the need for such correction was evaluated. RESULTS The mean primary GTV was larger on MRI (22.2 vs. 9.5 cm(3), p=0.05) than CT. The mean primary and nodal GTV (i.e. BOT and macroscopic nodes) was significantly larger on MRI (27.2 vs. 14.4 cm(3), p=0.05). The volume overlap index (VOI) between MRI and CT for the primary was 0.34 suggesting that MRI depicts parts of the primary tumour not detected by CT. There was no significant difference in volume delineation between MR and CT for CTV, PTV, nodal CTV and nodal PTV. MRI volumes for brainstem and spinal cord were significantly smaller due to improved organ definition (p=0.002). Susceptibility and gradient-related distortions were not found to be clinically significant. CONCLUSION MRI improves the definition of tongue base tumours and neurological structures. The use of MRI is recommended for GTV dose-escalation techniques to provide precise depiction of GTV and improved sparing of spinal cord and brainstem.

Consensus Guidelines and Contouring Atlas for Pelvic Node Delineation in Prostate and Pelvic Node Intensity Modulated Radiation Therapy.

PURPOSE The purpose of this study was to establish reproducible guidelines for delineating the clinical target volume (CTV) of the pelvic lymph nodes (LN) by combining the freehand Royal Marsden Hospital (RMH) and Radiation Therapy Oncology Group (RTOG) vascular expansion techniques. METHODS AND MATERIALS Seven patients with prostate cancer underwent standard planning computed tomography scanning. Four different CTVs (RMH, RTOG, modified RTOG, and Prostate and pelvIs Versus prOsTate Alone treatment for Locally advanced prostate cancer [PIVOTAL] trial) were created for each patient, and 6 different bowel expansion margins (BEM) were created to assess bowel avoidance by the CTV. The resulting CTVs were compared visually and by using Jaccard conformity indices. The volume of overlap between bowel and planning target volume (PTV) was measured to aid selection of an appropriate BEM to enable maximal LN yet minimal normal tissue coverage. RESULTS In total, 84 nodal contours were evaluated. LN coverage was similar in all groups, with all of the vascular-expansion techniques (RTOG, modified RTOG, and PIVOTAL), resulting in larger CTVs than that of the RMH technique (mean volumes: 287.3 cm(3), 326.7 cm(3), 310.3 cm(3), and 256.7 cm(3), respectively). Mean volumes of bowel within the modified RTOG PTV were 19.5 cm(3) (with 0 mm BEM), 17.4 cm(3) (1-mm BEM), 10.8 cm(3) (2-mm BEM), 6.9 cm(3) (3-mm BEM), 5.0 cm(3) (4-mm BEM), and 1.4 cm(3) (5-mm BEM) in comparison with an overlap of 9.2 cm(3) seen using the RMH technique. Evaluation of conformity between LN-CTVs from each technique revealed similar volumes and coverage. CONCLUSIONS Vascular expansion techniques result in larger LN-CTVs than the freehand RMH technique. Because the RMH technique is supported by phase 1 and 2 trial safety data, we proposed modifications to the RTOG technique, including the addition of a 3-mm BEM, which resulted in LN-CTV coverage similar to that of the RMH technique, with reduction in bowel and planning target volume overlap. On the basis of these findings, recommended guidelines including a detailed pelvic LN contouring atlas have been produced and implemented in the PIVOTAL trial.

Revised Choi Imaging Criteria Correlate with Clinical Outcomes in Patients with Metastatic Renal Cell Carcinoma Treated with Sunitinib

PURPOSE To compare revised Choi criteria that incorporate concurrent size and attenuation changes at early follow-up imaging with Response Evaluation Criteria in Solid Tumors ( RECIST Response Evaluation Criteria in Solid Tumors ) 1.1 and original Choi criteria in stratification of clinical outcomes in patients with metastatic renal cell carcinoma ( mRCC metastatic renal cell carcinoma ) treated with sunitinib. MATERIALS AND METHODS Institutional review board approved this retrospective study and waived informed consent. Baseline and first follow-up computed tomographic scans in 69 patients (50 men, 19 women; mean age, 60.3 years; range, 19-83 years) with mRCC metastatic renal cell carcinoma treated with sunitinib from October 1, 2008, to March 1, 2013, were evaluated for tumor response by using RECIST Response Evaluation Criteria in Solid Tumors 1.1, original Choi criteria, and revised Choi criteria. Correlations with overall survival ( OS overall survival ) and progression-free survival ( PFS progression-free survival ) were compared and stratified according to each radiologic criteria with Kaplan-Meier and multivariate Cox regression analysis. RESULTS Median follow-up time was 29.7 months (95% confidence interval [ CI confidence interval ]: 18.9, 45.9). Response according to revised Choi criteria was independently correlated with OS overall survival (hazard ratio, 0.47 [95% CI confidence interval : 0.23, 0.99]; P = .046) and PFS progression-free survival (hazard ratio, 0.53 [95% CI confidence interval : 0.29, 0.99]; P = .047). Response according to RECIST Response Evaluation Criteria in Solid Tumors was not significantly correlated with OS overall survival (hazard ratio, 0.65 [95% CI confidence interval : 0.27, 1.58]; P = .344) or PFS progression-free survival (hazard ratio, 0.89 [95% CI confidence interval : 0.42, 1.91]; P = .768). Response according to original Choi criteria was not significantly correlated with OS overall survival (hazard ratio, 0.60 [95% CI confidence interval : 0.32, 1.11]; P = .106) or PFS progression-free survival (hazard ratio, 0.59 [95% CI confidence interval : 0.34, 1.02]; P = .060). Median OS overall survival and PFS progression-free survival in responders according to revised Choi criteria was 39.4 months (95% CI confidence interval : 9.1, upper limit not estimated) and 13.7 months (95% CI confidence interval : 6.4, 24.6), respectively, compared with 12.8 months (95% CI confidence interval : 8.7, 18.0) and 5.3 months (95% CI confidence interval : 3.9, 8.4), respectively, in nonresponders. CONCLUSION Contemporaneous reduction in tumor size and attenuation were correlated with favorable clinical outcomes. Response according to revised Choi criteria showed better correlation with clinical outcomes compared with that according to RECIST Response Evaluation Criteria in Solid Tumors or original Choi criteria in patients with mRCC metastatic renal cell carcinoma treated with sunitinib.

Neoadjuvant carboplatin before radiotherapy in stage IIA and IIB seminoma

BACKGROUND Extended field radiotherapy is a standard of care for low volume stage II testicular seminoma. We hypothesized that neoadjuvant carboplatin might reduce the recurrence risk. PATIENTS AND METHODS In a single-arm study, 51 patients were treated between May 1996 and November 2011 with a single cycle of carboplatin followed by radiotherapy. The radiation field was reduced from an extended abdomino-pelvic field to just the para-aortic region, and the radiation dose from 35 Gy to 30 Gy in 39 patients. RESULTS After a median follow-up of 55 months (range 8-151 months) with 38 (74%) of the patients having been followed for >2 years, there have been no relapses (95% confidence limits of 5-year relapse-free survival of 93%-100%). Toxicity has been low with grade 3 toxicity limited to four patients with grade 3 haematological toxicity (with no clinical sequelae) and one patient with grade 3 nausea (during radiotherapy). No patients experienced grade 4 toxicity. CONCLUSIONS The results of this pilot study suggest that a single cycle of neoadjuvant carboplatin before radiotherapy may reduce recurrence risk compared with radiotherapy alone and permit a smaller radiation field, and this approach is proposed for further investigation.

Diffusion-Weighted Imaging of the Male Pelvis

Diffusion-weighted magnetic resonance (MR) imaging (DWI) is now widely incorporated as a standard MR imaging sequence for the assessment of the male pelvis. DWI can improve the detection, characterization, and staging of pelvic malignancies, such as prostate, bladder, and rectal cancers. There is growing interest in applying quantitative DWI for the assessment of tumor treatment response. In addition, the technique seems promising for the evaluation of metastatic nodal and bone disease in the pelvis.