Bladder preservation in older adults with muscle-invasive bladder cancer: A retrospective study with concurrent chemotherapy and twice-daily hypofractionated radiotherapy schedule.

INTRODUCTION: Bladder cancer occurs mainly in older adults and surgery is not always possible when there are geriatric conditions and comorbidities. Trimodal treatment (TMT) combining trans-urethral resection of bladder tumour (TURBT) followed by concurrent chemoradiation (CRT) would be a curative alternative in such patients. MATERIALS AND METHODS: All consecutive patients 75 years of age and older with non-metastatic muscle-invasive bladder cancer (MIBC) treated with TMT by Georges Pompidou European Hospital team were retrospectively analysed. Induction CRT combined hypofractionated twice-daily radiotherapy targeting bladder and pelvis to a total dose of 24 Gy (Gy) with concurrent platinum salt and 5-fluorouracil. Consolidation CRT to a total dose of 44 Gy was proposed to patients with biopsy-proven complete response after induction phase and those with persistent tumour underwent salvage cystectomy. We assessed using Kaplan-Meier method overall survival (OS), cancer specific survival (CSS), invasive recurrence-free survival (IRFS), metastasis-free survival (MFS), survival with bladder preserved (SBP), and toxicities. With a Cox model for OS and the Fine Gray method of competing risk for secondary endpoints, we analysed in univariate (u) and multivariate (m) analysis the impact of tumour characteristics and patient profiles: gender, age, age-adjusted Charlson comorbidity index, polypharmacy, and malnutrition. RESULTS: From 1988 to 2017, 85 patients were included. After induction, complete response rate was 83.5%. With a median follow-up of 63 months, 5 year-OS, CSS, IRFS, MFS and SBP were 61.0%, 77.6%, 71%, 82.9%, and 70.2% respectively. A persistent tumour after induction impacted SBP (SHRm 3.61; p = 0.004), CSS (SHRm 3.27; p = 0.023), and MFS (SHRm 3.68; p = 0.018). Late grade 3 urinary and gastrointestinal toxicities were 3.5% and 1.2%. DISCUSSION: We report here the largest series of bladder preservation over 75 years in a curative intent. Outcomes and tolerance in selected older adults compared favourably with surgical series and with CRT studies using classical fractionation.

Long-term outcomes after bladder-preserving tri-modality therapy for patients with muscle-invasive bladder cancer.

PURPOSE: To evaluate trimodal conservative treatment as an alternative to radical surgery for urothelial muscle-invasive bladder cancer (MIBC). PATIENTS AND METHODS: This retrospective study reported the carcinologic and functional results of patients (pts) presenting a cT2/T3 N0M0 operable MIBC and fit for surgery, treated by a conservative strategy. Treatment consisted of a transurethral resection (TURB) followed by concomitant bi-fractionated split-course radiochemotherapy (RCT) with 5FU-Cisplatine. A control cystoscopy was performed six weeks after the induction RCT (eq45Gy) with systematic biopsies. Patients with complete histologic response achieved RCT protocol. Salvage surgery was proposed to pts with persistent tumor. RESULTS: 313 pts (83% cT2 and 17% cT3) treated between 1988 and 2013 were included, with a median follow-up of 59 months and 67-year mean age. After the induction RCT, the histologic response rate was 83%. After five years, overall, disease-free, and functional bladder-intact survival rates were respectively 69%, 61%, and 69%, significantly better for pts in complete response after induction RCT. Late urinary and digestive toxicities were limited, with respective rates of 4% and 1.5% of grade 3 toxicity. CONCLUSION: Trimodal strategy with RCT after TURB showed interesting functional and oncologic results and should be considered as an alternative to surgery in well-selected pts.

Author Correction: Deep Learning and Radiomics predict complete response after neo-adjuvant chemoradiation for locally advanced rectal cancer.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Deep Learning and Radiomics predict complete response after neo-adjuvant chemoradiation for locally advanced rectal cancer.

Treatment of locally advanced rectal cancer involves chemoradiation, followed by total mesorectum excision. Complete response after chemoradiation is an accurate surrogate for long-term local control. Predicting complete response from pre-treatment features could represent a major step towards conservative treatment. Patients with a T2-4 N0-1 rectal adenocarcinoma treated between June 2010 and October 2016 with neo-adjuvant chemoradiation from three academic institutions were included. All clinical and treatment data was integrated in our clinical data warehouse, from which we extracted the features. Radiomics features were extracted from the tumor volume from the treatment planning CT Scan. A Deep Neural Network (DNN) was created to predict complete response, as a methodological proof-of-principle. The results were compared to a baseline Linear Regression model using only the TNM stage as a predictor and a second model created with Support Vector Machine on the same features used in the DNN. Ninety-five patients were included in the final analysis. There were 49 males (52%) and 46 females (48%). Median tumour size was 48 mm (15-130). Twenty-two patients (23%) had pathologic complete response after chemoradiation. One thousand six hundred eighty-three radiomics features were extracted. The DNN predicted complete response with an 80% accuracy, which was better than the Linear Regression model (69.5%) and the SVM model (71.58%). Our model correctly predicted complete response after neo-adjuvant rectal chemoradiotherapy in 80% of the patients of this multicenter cohort. Our results may help to identify patients who would benefit from a conservative treatment, rather than a radical resection.

Optimal post-operative radiation after soft-tissue sarcoma resection is achieved in less than two thirds of cases.

PURPOSE: Local control of soft tissue sarcomas frequently involves adjuvant radiation to the surgical resection. When opting for post-operative radiation, care should be taken that radiation is started within some reasonable time after the surgery. We were interested to the proportion of patients who did not recieve optimal post-operative radiation and the variables associated. METHODS: We retrospectively analyzed a series of 77 patients operated on for an extremity soft-tissue sarcoma and due for post-operative radiotherapy. Patients were considered to have received radiation optimally if radiation was started within 12 weeks of surgery. Variables associated with not receiving radiation optimally were looked for using univariable and multivariable regression models. RESULTS: Overall, 26 patients (34%; 95% CI: 23-45%) did not receive radiation optimally. Twenty (26%) did not start radiation within the 12-weeks mark and six (8%) could not have radiation at all. The main reason identified for not receiving radiation on time was the occurrence of a wound complication (14 (54%) patients). An increased body mass index (OR: 1.14; 95% CI: 1.02-1.26; p = 0.02) and an older age (OR: 1.55; 95% CI: 1.18-2.14; p = 0.04; of note, the OR are for a 10 year change) were significantly associated with not receiving radiation optimally. Patients with a social fragility (p = 0.04), metastatic spread at presentation (p = 0.04), and increased duration of surgery (p = 0.02) were more likely to develop a wound complication. CONCLUSIONS: About 34% of patients do not receive optimal post-operative radiation treatment. Older and obese patients have a higher risk of not receiving radiation optimally. The decision for pre- or post-operative radiation should account for these findings.

Prostate cancer characteristics and outcome in renal transplant recipients: results from a contemporary single center study.

BACKGROUND: Prostate cancer (PCa) incidence is expected to increase in renal transplant recipients (RTR) with no clear nor contemporary data on management and oncological outcome. METHODS: We conducted a retrospective single center study of RTR diagnosed with PCa after transplantation between 2000 and 2013. Demographics, PCa characteristics, and treatment were assessed. For each RTR in radical prostatectomy (RP) subset, we included 4 non-organ transplant patients who underwent RP by the same surgeons, and compared pre-operative and post-operative oncological features, and biochemical recurrence (BCR) rate. RESULTS: Twenty-four RTR were included (PCa incidence 1.5%). Mean follow-up was 47 months. PCa was mostly localized (n=21, 87.5%) with treatments including RP (n=16, 76.2%), brachytherapy (n=3, 14.3%), radiation therapy (n=1, 4.7%), and active surveillance (n=1, 4.7%). No graft loss due to PCa treatment was reported. Nineteen RTR with localized PCa (90.5%) were free from BCR. Considering RP subset, no difference in PCa characteristics at diagnosis and BCR rate was found between RTR (n=16) and control patients (n=64). CONCLUSIONS: Localized PCa following renal transplantation was not associated with adverse features as compared with non-transplant patients. Standard treatments could be proposed to RTR with satisfying results both on oncological outcome and graft function.

Induction therapy with cetuximab plus docetaxel, cisplatin, and 5-fluorouracil (ETPF) in patients with resectable nonmetastatic stage III or IV squamous cell carcinoma of the oropharynx. A GERCOR phase II ECHO-07 study.

Induction TPF regimen is a standard treatment option for squamous cell carcinoma (SCC) of the oropharynx. The efficacy and safety of adding cetuximab to induction TPF (ETPF) therapy was evaluated. Patients with nonmetastatic resectable stage III/IV SCC of the oropharynx were treated with weekly cetuximab followed the same day by docetaxel and cisplatin and by a continuous infusion of 5-fluorouracil on days 1-5 (every 3 weeks, 3 cycles). The primary endpoint was clinical and radiological complete response (crCR) of primary tumor at 3 onths. Secondary endpoints were crCR rates, overall response, pathological CR, progression-free survival, overall survival, and safety. Forty-two patients were enrolled, and 41 received ETPF. The all nine planned cetuximab doses and the full three doses of planned chemotherapy were completed in 31 (76%) and 36 (88%) patients, respectively. Twelve (29%) patients required dose reduction. The crCR of primary tumor at the completion of therapy was observed in nine (22%) patients. ETPF was associated with a tumor objective response rate (ORR) of 58%. The most frequent grade 3-4 toxicities were as follows: nonfebrile neutropenia (39%), febrile neutropenia (19%), diarrhea (10%), and stomatitis (12%). Eighteen (44%) patients experienced acne-like skin reactions of any grade. One toxic death occurred secondary to chemotherapy-induced colitis with colonic perforation. This phase II study reports an interesting response rate for ETPF in patients with moderately advanced SCC of the oropharynx. The schedule of ETPF evaluated in this study cannot be recommended at this dosage.

[Experimental program personalized care in patients with head and neck cancer]. / Expérimentation du parcours personnalisé des patients atteints d'un cancer des voies aéro-digestives supérieures.

OBJECTIVE: Describe the implementation and preliminary results of the "Experimental Program Personalized care" in patients with Head and Neck cancer. MATERIALS AND METHODS: After being selected a graduate nurse status, called coordination, participated in the development of forms of detection needs and concerns of patients, in collaboration with various health professionals. RESULTS: Between January 2011 and December 2012, 200 new patients with head and neck cancer were included: 62% with advanced cancer and 38% of early stage. No patient refused to participate in this experiment. At least one consultation with a psychiatrist was necessary for 82% of patients with advanced cancer. Social problems were the second axis of the needs of patients. CONCLUSION: By identifying the needs of patients and organizing their support, this evaluation optimizes not only the therapeutic care for the patient but also the management of human resources within the team.

Randomised Phase II study of oral lapatinib combined with chemoradiotherapy in patients with advanced squamous cell carcinoma of the head and neck: rationale for future randomised trials in human papilloma virus-negative disease.

BACKGROUND: This randomised Phase II study assessed the activity and safety of concurrent chemoradiotherapy (CRT) and lapatinib followed by maintenance treatment in locally advanced, unresected stage III/IVA/IVB head and neck cancer. PATIENTS AND METHODS: Patients were randomised 1:1 to concurrent CRT and placebo followed by placebo or concurrent CRT and lapatinib followed by lapatinib. Treatment continued until disease progression or study withdrawal. Primary end-point was complete response rate (CRR) by independent review 6 months post-CRT. RESULTS: Sixty-seven patients (median age 56 years; 97% Eastern Cooperative Oncology Group performance status ≤1; 82% stage IV) were recruited. CRT dose intensities were unaffected by lapatinib: median radiation dose 70 Gy (lapatinib, placebo), duration 49 (lapatinib) and 50 days (placebo); median cisplatin dose 260 mg/m(2) (lapatinib) and 280 mg/m(2) (placebo). Lapatinib combined with CRT was well-tolerated. Grade 3/4 toxicities during CRT were balanced between arms, with the exception of an excess of grade 3 diarrhoea (6% versus 0%) and rash (9% versus 3%) and two grade 4 cardiac events in the lapatinib arm. CRR at 6 months post-CRT was 53% with lapatinib versus 36% with placebo in the intent-to-treat population. The progression-free survival (PFS) and overall survival rates at 18 months were 55% versus 41% and 68% versus 57% for the lapatinib and placebo arms, respectively. The difference between study arms was greatest in p16-negative disease (median PFS >20.4 months [lapatinib] versus 10.9 [placebo]). CONCLUSION: Lapatinib combined with CRT is well-tolerated with numeric increases in CRR at 6 months post-CRT and median PFS in p16-negative disease.

Image-guided radiation therapy for muscle-invasive bladder cancer.

Organ preservation protocols that incorporate chemoradiotherapy have shown good efficacy in bladder cancer. Owing to changes in rectal filling, urinary inflow and subsequent bladder volume with bladder wall deformations, irradiation must take into account interfractional and intrafractional internal target motion. Growing evidence suggests that image guidance during irradiation is essential in order to appropriately treat bladder cancer in this way. We performed a literature search on the imaging techniques and margins used for radiation therapy planning in the context of whole-bladder and partial-bladder irradiation. The most common image-guided radiation therapy (IGRT) method was based on cone-beam CT using anisotropic margins. The role of cine-MRI for the prediction of intraindividual bladder changes, in association with cone-beam CT or ultrasonography, is promising. Drinking protocols, diet and laxatives were used in most cases to minimize large variations in bladder size and shape. IGRT is crucial for avoiding tumor undercoverage and undue toxicity during radiation therapy for bladder cancer. IGRT-based adaptive radiation therapy can be performed using cone-beam CT or ultrasonography: modeling of bladder changes with cine-MRI or other imaging techniques might also be useful for facilitating adaptive radiation therapy with personalized margins.

Neoadjuvant sorafenib combined with gemcitabine plus oxaliplatin in advanced hepatocellular carcinoma.

This paper reports the first case of a patient with hepatocellular carcinoma with lymph node metastasis treated by sorafenib combined with gemcitabine plus oxaliplatin, with a partial response and normalization of α fetoprotein, which allowed curative surgery. The potential synergy between these three drugs needs to be confirmed, and is currently being investigated in a randomized phase II trial.

Use of single MRI and 18F-FDG PET-CT scans in both diagnosis and radiotherapy treatment planning in patients with head and neck cancer: advantage on target volume and critical organ delineation.

BACKGROUND: The use of a single MRI and 18F-fluoro deoxyglucose positron emission tomography-CT (18F-FDG PET-CT) was evaluated, both in diagnostic procedure and radiotherapy planning, in patients with head and neck cancer. METHODS: Thirty-five patients with nasopharyngeal and oropharyngeal tumors were studied. The MRI and 18F-FDG PET-CT were used for both diagnostic work-up and gross tumor volume and critical structure delineation. The interobserver variation (IOV) of volumes determined on MRI and CT by a radiotherapist and by a radiologist were compared as well as their impact on dose distribution. RESULTS: The CT-MRI decreased the IOV of parotid glands in 12 of 35 and target volume in 15 of 35 patients. The use of 18F-FDG PET-CT changed the treatment design in 6 of 21 patients. CONCLUSIONS: Diagnostic imaging performed in the treatment position can improve the accuracy of radiotherapy planning in case of intracranial tumor extension, heavy dental work, or contraindication for contrast-enhanced CT, but not in the absence of these conditions.

[Modern methods for cancer external radiation therapies]. / Méthodes modernes d'irradiation externe des cancers.

Radiotherapy has been in constant progress for the past century. New technologies are based on modern imaging modalities, efficient 3D treatment planning systems, sophisticated immobilization systems and rigorous quality assurance and treatment verification. The central objective of conformal radiotherapy is to ensure a high dose distribution tailored to the limits of the target volume while reducing exposure of healthy tissues. These techniques would then allow a further tumor dose escalation. New systems like CyberKnife, tomotherapy and hadrontherapy represent major potential progress for the treatment of complex tumours that are very difficult to treat with conventional radiotherapy techniques.

Randomized clinical trial of post-operative radiotherapy versus concomitant carboplatin and radiotherapy for head and neck cancers with lymph node involvement.

BACKGROUND AND PURPOSE: Post-operative radiotherapy is indicated for the treatment of head and neck cancers. In vitro, chemotherapy potentiates the cytotoxic effects of radiation. We report the results of a randomized trial testing post-operative radiotherapy alone versus concomitant carboplatin and radiotherapy for head and neck cancers with lymph node involvement. MATERIALS AND METHODS: The study involved patients undergoing curative-intent surgery for head and neck cancers with histological evidence of lymph node involvement. Patients were randomly assigned to receive radiotherapy alone (54-72Gy, 30-40 fractions, 6-8 weeks) or identical treatment plus concomitant Carboplatin (50mg/m(2) administered by IV infusion twice weekly). RESULTS: Between February 1994 and June 2002, 144 patients were included. With a median follow-up of 106 months (95% confidence interval (CI) [92-119]), the 2-year rate of loco-regional control was 73% (95% CI: 0.61-0.84) in the combined treatment group and 68% (95% CI: 0.57-0.80) in the radiotherapy group (p=0.26). Overall survival did not differ significantly between groups (hazard ratio for death, 1.05; 95% CI: 0.69-1.60; p=0.81). CONCLUSIONS: Twice-weekly administration of carboplatin concomitant to post-operative radiotherapy did not improve local control or overall survival rates in this population of patients with node-positive head and neck cancers.

Aggressive adenoid cystic carcinoma with asymptomatic spinal cord compression revealed by a "curtain sign".

The authors present a case of unusually aggressive adenoid cystic carcinoma of the head and neck. The patient presented with sciatica one year after initial diagnosis. She was otherwise asymptomatic. Complete work-up for bone involvement, included bone scan and MRI. The patient had painful osteolytic sacral metastasis and asymptomatic thoracic (T5) vertebral metastasis revealed by a typical curtain sign on MRI. The curtain sign, originally described by Trolard, is due to the displacement of the Trolard's membrane with the median ligament attaching the dura to the bone while there is a dorsal displacement and loosening of the posterior longitudinal ligament. The patient benefited from radiotherapy and did not develop respiratory distress, paraplegia or pain but died of liver metastases.

UV-light induced radiation recall dermatitis after a chemoradiotherapy organ preservation protocol.

This case report documents a UV-light-induced recall phenomenon and reviews the medical literature. In this patient, we observed a severe recall phenomenon precipitated by an extensive sunlight exposure after a chemoradiotherapy organ preservation protocol. Radiation recall phenomenon is a rare but well-described phenomenon, without clear radiation or drug-specific characteristics. In the medical literature, radiation recall following UV-sunlight exposure seems to be an exceptional event. The etiology remains unknown but could involve local hypersensitivity through a non-immune activation of inflammatory pathways. Due to the increasing number of patients with head and neck malignancies managed with induction chemotherapy and/or chemoradiation organ preservation protocols, the otorhinolaryngologist--head and neck surgeons as well as the radiation therapist should become aware and familiar with this phenomenon.

Chemotherapy as initial treatment of locally advanced unresectable pancreatic cancer: a valid option?

INTRODUCTION: Radio-chemotherapy is the standard treatment for locally advanced unresectable pancreatic cancer (LAPC). Chemotherapy has been shown to be effective in the treatment of metastatic disease and we therefore evaluated its use as a first-line treatment for LAPC. PATIENTS AND METHODS: We carried out a retrospective analysis of all consecutive patients treated for LAPC (N=33) between July 1997 and April 2005, analysing the results of first-line chemotherapy (CT group) and radio-chemotherapy (RCT group) in this setting. RESULTS: The first-line treatment was RCT in six patients (18.3%) and CT in 26 patients (78.8%). Secondary treatment was administered to nine patients of CT group with well-controlled disease: "closure" radio-chemotherapy for seven patients (26.9%) and secondary resection for three (12%). After a median follow-up of 27 months, 23 patients died (69.7%). Overall survival was 13.8 months [95% CI: 10.1-19.4] for the whole population, 9.5 months [95% CI: 4.6-] for the RCT and 18.0 months [95% CI: 12.4-25.5] for the CT. Overall survival for the CT patients undergoing secondary surgery or "consolidation" radio-chemotherapy was 28.8 months [95% CI: 13.8-]. CONCLUSION: First-line chemotherapy is a valid option for LAPC treatment, making it possible to identify the patients who may benefit from secondary resection or radio-chemotherapy.

[External beam radiotherapy and brachytherapy in prostate cancer]. / Curiethérapie et radiothérapie des cancers de la prostate.

For the last 10 years, along with surgery, radiotherapy has become a major issue in the curative treatment of prostate cancer. Several radiotherapy techniques can be used. In good prognosis cancers, when the prostate is small, brachytherapy is one of the therapeutic options. By implanting radioactive seeds within the prostate, this technique permits strictly limited intraprostatic irradiation. Conformal external beam (3D) radiotherapy adapts to individual morphology according to dosimetric CT scan data. This is particularly useful to deliver a high dose in the target volume while limiting the dose in surrounding organs. It is indicated either for localised tumours as an alternative solution to surgery, or for tumours with more aggressive patterns or locally advanced that will in both cases require adjuvant hormotherapy; conventional (2D) radiotherapy can be used in case of isolated clinical or biological relapse after prostatectomy. These last two techniques induce two main types of late toxicity: radio-induced rectitis and sexual impotence. Last but not least, radiotherapy as well as nuclear medicine can be used with palliation intent and may be of great help to relieve pain in case of bone metastases.

[Anal canal squamous-cell carcinomas in HIV positive patients: clinical features, treatments and prognosis]. / Caractéristiques cliniques, thérapeutiques et pronostiques des carcinomes épidermoïdes du canal anal chez les malades VIH positifs.

UNLABELLED: The prevalence of squamous-cell carcinoma of the anus seems to be increasing in HIV positive patients. Clinical features and prognosis in this population have not been well evaluated. AIMS: To assess the prognosis of anal squamous-cell carcinoma in HIV positive patients as well as clinical features and treatment procedures. METHODS: A series of 20 HIV positive patients presenting with invasive anal squamous-cell carcinoma was retrospectively analyzed. Data have been compared to those obtained from 24 randomly selected HIV negative patients who were followed during the same periods in the same centers for anal carcinoma with similar histopathological features. RESULTS: The follow-up ranged from 10 to 172 months. No difference was observed between the two groups concerning the clinical features leading to anal cancer diagnosis, although HIV positive patients were younger. Anal cancer was more frequently associated with lymph node metastasis in HIV positive (60%) than in HIV negative (17%) patients, although its size was similar in both groups. Radiotherapy was similarly performed in both groups, while chemotherapy was administered less frequently in HIV positive than in HIV negative patients (54% vs 25%). Immediate side effects and mortality at 1 year follow-up were similar in both groups, whereas the objective initial response to therapy (50% versus 88%), the remission rate with anal conservation at 1 year follow-up (45% versus 88%), and the mortality at 3 years were better in HIV negative patients. CONCLUSION: The prognosis of anal squamous-cell carcinoma is poor in HIV positive patients. This correlates with a more advanced tumor stage and an alteration of systemic immunity status at the time of diagnosis and less response rate to treatment. Detection of precancerous lesions and treatment procedures should be evaluated in HIV infected patients.

Conformal radiotherapy for lung cancer: different delineation of the gross tumor volume (GTV) by radiologists and radiation oncologists.

PURPOSE: Delineation of the gross tumor volume (GTV) and organs at risk constitutes one of the most important phases of conformal radiotherapy (CRT) procedures. In the absence of a clear redefinition of the GTV, for a given pathology, complemented by detailed contouring procedures, the GTV are likely to be estimated rather arbitrarily with the risk of tumor underdosage or detriment to the surrounding healthy tissues. The objective of this study was to compare the delineation of the GTV of intrathoracic tumors by radiologists and radiation oncologists with experience in the field in various centers. MATERIALS AND METHODS: The computed tomography images of ten patients with nonoperated non-small cell lung cancer (NSCLC) eligible for CRT were reviewed. Nine radiologists and eight radiation oncologists working in five different centers, classified as either 'junior' or 'senior' according to their professional experience, had to delineate the GTV (primary tumor and involved lymph nodes) with predefined visualization parameters. A dedicated software was used to compare the delineated volumes in terms of intersection and union volumes and to calculate the 'concordance index' for each patient and each subgroup of physicians. RESULTS: Significant differences between physicians and between centers were observed. Compared to radiation oncologists, radiologists tended to delineate smaller volumes and encountered fewer difficulties to delineate 'difficult' cases. Junior physicians, regardless of their specialty, also tended to delineate smaller and more homogeneous volumes than senior physicians, especially for 'difficult' cases. CONCLUSIONS: Major discordances were observed between the radiation oncologists' and the radiologists' delineations, indicating that this step needs to be improved. A better training of radiation oncologists in thoracic imaging and collaboration between radiation oncologists and radiologists should decrease this variability. New imaging techniques (image fusion, positron emission tomography, magnetic resonance imaging spectroscopy, etc.) may also provide a useful contribution to this difficult delineation.