Neoantigen prediction and computational perspectives towards clinical benefit: recommendations from the ESMO Precision Medicine Working Group.

BACKGROUND: The use of next-generation sequencing technologies has enabled the rapid identification of non-synonymous somatic mutations in cancer cells. Neoantigens are mutated peptides derived from somatic mutations not present in normal tissues that may result in the presentation of tumour-specific peptides capable of eliciting antitumour T-cell responses. Personalised neoantigen-based cancer vaccines and adoptive T-cell therapies have been shown to prime host immunity against tumour cells and are under clinical trial development. However, the optimisation and standardisation of neoantigen identification, as well as its delivery as immunotherapy are needed to increase tumour-specific T-cell responses and, thus, the clinical efficacy of current cancer immunotherapies. METHODS: In this recommendation article, launched by the European Society for Medical Oncology (ESMO), we outline and discuss the available framework for neoantigen prediction and present a systematic review of the current scientific evidence. RESULTS: A number of computational pipelines for neoantigen prediction are available. Most of them provide peptide major histocompatibility complex (MHC) binding affinity predictions, but more recent approaches incorporate additional features like variant allele fraction, gene expression, and clonality of mutations. Neoantigens can be predicted in all cancer types with high and low tumour mutation burden, in part by exploiting tumour-specific aberrations derived from mutational frameshifts, splice variants, gene fusions, endogenous retroelements and other tumour-specific processes that could yield more potently immunogenic tumour neoantigens. Ongoing clinical trials will highlight those cancer types and combinations of immune therapies that would derive the most benefit from neoantigen-based immunotherapies. CONCLUSIONS: Improved identification, selection and prioritisation of tumour-specific neoantigens are needed to increase the scope of benefit from cancer vaccines and adoptive T-cell therapies. Novel pipelines are being developed to resolve the challenges posed by high-throughput sequencing and to predict immunogenic neoantigens.

Parenting Stress Undermines Mother-Child Brain-to-Brain Synchrony: A Hyperscanning Study.

Synchrony refers to the coordinated interplay of behavioural and physiological signals that reflect the bi-directional attunement of one partner to the other's psychophysiological, cognitive, emotional, and behavioral state. In mother-child relationships, a synchronous pattern of interaction indicates parental sensitivity. Parenting stress has been shown to undermine mother-child behavioural synchrony. However, it has yet to be discerned whether parenting stress affects brain-to-brain synchrony during everyday joint activities. Here, we show that greater parenting stress is associated with less brain-to-brain synchrony in the medial left cluster of the prefrontal cortex when mother and child engage in a typical dyadic task of watching animation videos together. This brain region overlaps with the inferior frontal gyrus, the frontal eye field, and the dorsolateral prefrontal cortex, which are implicated in inference of mental states and social cognition. Our result demonstrates the adverse effect of parenting stress on mother-child attunement that is evident at a brain-to-brain level. Mother-child brain-to-brain asynchrony may underlie the robust association between parenting stress and poor dyadic co-regulation. We anticipate our study to form the foundation for future investigations into mechanisms by which parenting stress impairs the mother-child relationship.

The influence of various reef sounds on coral-fish larvae behaviour.

The swimming behaviour of coral-reef fish larvae from 20 species of 10 different families was tested under natural and artificial sound conditions. Underwater sounds from reef habitats (barrier reef, fringing reef and mangrove) as well as a white noise were broadcasted in a choice chamber experiment. Sixteen of the 20 species tested significantly reacted to at least one of the habitat playback conditions, and a range of responses was observed: fishes were (1) attracted by a single sound but repelled by none (e.g. white-banded triggerfish Rhinecanthus aculeatus was attracted by the barrier-reef sound), (2) repelled by one or more sounds but attracted by none (e.g. bridled cardinalfish Pristiapogon fraenatus was repelled by the mangrove and the bay sounds), (3) attracted by all sounds (e.g. striated surgeonfish Ctenochaetus striatus), (4) attracted and repelled by several sounds (e.g. whitetail dascyllus Dascyllus aruanus was attracted by the barrier-reef sound and repelled by the mangrove sound) and (5) not influenced by any sound (e.g. convict surgeonfish Acanthurus triostegus). Overall, these results highlight two settlement strategies: a direct selection of habitats using sound (45% of the species), or a by-default selection by avoidance of certain sound habitats (35%). These results also clearly demonstrated the need to analyse the influence of sounds at the species-specific level since congeneric and confamilial species can express different behaviours when exposed to the same sounds.

[18-FDG PET-scan of intrathoracic gossypiboma during the monitoring of lung cancer]. / Fixation au TEP-FDG d'un gossypiboma intrathoracique au cours de la surveillance d'un cancer du poumon.

The 18-FDG PET-scan is today used to monitor patients operated for non small-cell lung cancer. The presence of an intrathoracic gossypiboma (or textiloma) can be responsible for intense enhancement in a PET-scan because of inflammatory phenomenon. The authors report the case of a patient who underwent surgery for lung cancer nine years ago, where a newly discovered intrathoracic mass with intensive enhancement on PET-scan, led to concern about a local recurrence in spite of the fine-needle transthoracic biopsy identifying textile fibers in the histological examination.

Correlation of visuospatial memory ability with right parietal EEG spindling during sleep.

Individual differences in human sleep EEG spindling were shown to be associated with psychometric measures of cognitive ability. Previous results revealed a frequency- and region specificity of this effect, suggesting that only fast, but not slow spindle-related oscillatory activity over the frontal region correlated with cognitive performance. Our aim is to test the hypothesis that region-specific spindle-type oscillatory activity is related to specific cognitive abilities reflecting the cortical localization of the corresponding cognitive function. The visuospatial abilities are the focus of the present report. Nineteen healthy volunteers were tested with the Rey-Osterrieth Complex Figure (ROCF) test and memory performances correlated with the spindle analysis of the second night's polysomnographic recordings. Correlations were age-corrected and subjected to descriptive data analysis. ROCF recall performances at 3 and 30 minutes delay, correlated positively and significantly with fast sleep spindle density measured over the right parietal area. No significant relationship between recognition performance and sleep EEG variables emerged. Slow spindle density did not correlate with test performances. Our findings converge with other data suggesting the involvement of right parietal functioning in visuospatial abilities. Moreover, these results support the hypothesis that region-specific differences in fast sleep spindling could be markers of specific neuropsychological performances.

Whole-body positron emission tomography using fluorodeoxyglucose in patients with metastases of unknown primary tumours (CUP syndrome).

The aim of this study was to evaluate the clinical performances of whole body 2-[18F]fluorodeoxyglucose positron emission tomography (FDG PET) imaging for the detection of the primary tumour in patients with metastases of unknown origin. Forty-one patients, without previous history of known cancer (18 women and 23 men; average age 64.1 years) with metastasis confirmed by histopathological analysis were included in a retrospective study. Results of PET were compared with those of techniques used in the current conventional diagnostic procedure. All known metastatic lesions were detected by PET. There were 26 true-positive and two false-negative results. Primary tumour remained undetermined in eight patients after conventional investigations and PET. PET was superior to conventional diagnostic procedure in 11 patients and led to modify treatment in 11 patients. Sensitivity of PET was superior than computed tomography in detecting abdominal primary tumours. FDG PET is useful in patients with unknown primary tumour because its sensitivity is good and it could modify the disease management. Otherwise, PET allows the evaluation of the extent of the disease and could be used to monitor treatment efficiency. Its contribution has to be evaluated particularly in patients with primary tumour with a specific treatment.

Early detection of relapse by whole-body positron emission tomography in the follow-up of patients with Hodgkin's disease.

BACKGROUND: Relapse after treatment of Hodgkin's disease (HD) is usually identified as a result of the investigation of symptoms. We undertook this study to examine the value of whole-body positron emission tomography (PET) for the detection of preclinical relapse. PATIENTS AND METHODS: Thirty-six patients underwent 2-[fluorine-18]fluoro-2-deoxy-D-glucose ((18)F-FDG) PET at the end of treatment and than every 4-6 months for 2-3 years after the end of polychemotherapy and/or radiotherapy. In those cases of abnormal (18)F-FDG accumulation a confirmatory study was performed 4-6 weeks later. RESULTS: One patient had residual tumor and four patients relapsed during a follow-up of 5-24 months. All five events were correctly identified early by (18)F-FDG PET. Residual tumor or relapse was never first diagnosed based on clinical examination, laboratory findings or computed tomography (CT) studies. Two patients presented B symptoms and the three others were asymptomatic at the time of residual disease or relapse. Confirmation of residual disease or relapse was obtained by biopsy in four patients 1, 1, 5 and 9 months after PET and by unequivocal clinical symptoms and CT studies in one patient 3 months after PET. False-positive (18)F-FDG PET studies incorrectly suggested possible relapse in six other patients, but the confirmatory PET was always negative. Our study also provides important information about physiological (18)F-FDG uptake in the thymus. CONCLUSIONS: Our data suggest the potential of (18)F-FDG PET to detect preclinical relapse in patients with HD. This could help identify patients requiring salvage chemotherapy at the time of minimal disease rather than at the time of clinically overt relapse. Further studies are warranted to determine the impact of PET on treatment management and outcome. In fact, the aim of follow-up procedures is not only to detect preclinical relapse but mainly to obtain better results by starting salvage treatment earlier. A cost-benefit analysis will also be necessary before (18)F-FDG PET can be used routinely in the follow-up of patients with HD.

[Horton's disease and extra-temporal vessel locations: role of 18FDG PET scan. Report of 3 cases and review of the literature]. / Maladie de Horton et atteintes artérielles extratemporales: utilité de la tomographie par émission de positons au 18FDG. A propos de trois observations et d'une revue de la littérature.

PURPOSE: We report three cases of Horton's disease, in which F18-Fluorine-2-Deoxy-D-Glucose (18FDG) positron emission tomography (PET) demonstrated a clinically unsuspected extra-cranial vessels hypermetabolism. METHODS: Fully corrected whole-body PET was performed in three patients (two women, one man) for exploring a marked inflammatory syndrome. Scanning was acquired 60 min after i.v. injection of 222 MBq of 18FDG in average. RESULTS: In two patients with histologically proven Horton's disease, PET alone showed increased glucose metabolism involving the carotid and sub-clavian arteries as well as the ascending aorta, aortic arch, thoracic and abdominal aorta, and the iliac and femoral arteries. In the third patient, by detecting cervical, thoracic and abdominal vessel hypermetabolism, PET non-invasively contributed to the diagnosis of giant cell arteritis. All patients had complete clinical and biological response to corticoids. PET controls performed 3- to 6-months post-treatment, confirmed the disappearance of the metabolic stigma. CONCLUSION: 18FDG PET may show an increased glucose metabolism in asymptomatic extracranial vessels locations of Horton's arterities. If these observations are confirmed on controlled trials, PET could be particularly useful for non-invasive diagnosing, staging and monitoring atypical clinical forms of Horton's disease. The metabolic imaging could also contribute to a better understanding of the pathogenesis of GCA.

Fluorodeoxyglucose positron emission tomography and somatostatin receptor scintigraphy for diagnosing and staging carcinoid tumours: correlations with the pathological indexes p53 and Ki-67.

We performed this study in order to evaluate the diagnostic accuracy of whole-body fluorodeoxyglucose positron emission tomography (FDG PET) imaging and somatostatin receptor scintigraphy (SRS) for localizing primary carcinoid tumours and evaluating the extent of the disease. A secondary aim was to correlate those findings with the histological characteristics of the lesions. FDG PET was performed in 17 patients and SRS in 16. All patients had pathologically proven carcinoids. All lesions were verified by histopathological analysis or by follow-up. Ki-67 and p53 expression were assessed as an indicator of the tumours' aggressiveness. FDG PET correctly identified 4/7 primary tumours and 8/11 metastatic spreads, as compared to six and 10 respectively, for SRS. Most tumours were typical carcinoids with low Ki-67 expression. No correlation was found between the histological features and the tracer's uptake. We conclude that SRS remains the modality of choice for evaluating patients with carcinoid tumours, regardless of their proliferative activity. FDG PET should be reserved to patients with negative results on SRS.

Gamma-probe-directed lymphatic mapping and sentinel lymphadenectomy in primary cutaneous melanoma.

BACKGROUND: Radiotracer and blue-dye lymphatic mapping is a recommended combined method to guide sentinel lymphadenectomy and full regional lymph node dissection in selected patients with cutaneous melanoma. OBJECTIVE: To evaluate the diagnostic accuracy and the prognostic value of gamma-probe-directed lymphatic mapping in cutaneous melanomas. METHODS: Sixty-five stage I and II melanoma patients underwent gamma-probe-directed lymphatic mapping. Sentinel lymph nodes were studied by both conventional and immunohistochemical stainings. The median follow-up was 11 months. RESULTS: Sensitivities of preoperative and intraoperative sentinel lymph node detection were 100 and 98%, respectively. Only 1 failure of detection and 1 missed same-basin metastasis were experienced in the axillary and cervical areas, respectively. Eleven patients (16.9%) had sentinel node metastases leading to adjuvant therapy. CONCLUSION: Gamma-probe-directed lymphatic mapping is useful for staging melanoma. However, in the expectation of a more specific identification of the sentinel lymph node, the standard protocol remains recommended for exploring the axillary and cervical areas. The histological examination supported in some cases by immunohistochemistry remains mandatory in all cases.

Positron emission tomography (PET) evaluation of abdominal aortic aneurysm (AAA).

BACKGROUND: aneurysmal disease is associated with an inflammatory cell infiltrate and enzymatic degradation of the vessel wall. AIM OF THE STUDY: to detect increased metabolic activity in abdominal aortic aneurysms (AAA) by means of positron emission tomography (PET-imaging). STUDY DESIGN: twenty-six patients with AAA underwent PET-imaging. RESULTS: in ten patients, PET-imaging revealed increased fluoro-deoxy-glucose (18-FDG) uptake at the level of the aneurysm. Patients with positive PET-imaging had one or more of the following elements in their clinical history: history of recent non-aortic surgery (n = 4), a painful inflammatory aortic aneurysm (n = 2), moderate low back pain (n = 2), rapid (> 2;5 mm in 6 months) expansion (n = 4), discovery by PET-scan of a previously undiagnosed lung cancer (n = 3) or parotid tumour (n = 1). Five patients with a positive PET scan required urgent surgery within two to 30 days. Among the 16 patients with negative PET-imaging of their aneurysm, only one had recent non-aortic surgery, none of them required urgent surgery, only two had a rapidly expanding AAA, and in only one patient, PET-imaging revealed an unknown lung cancer. CONCLUSION: these data suggest a possible association between increased 18-FDG uptake and AAA expansion and rupture.

Positron emission tomography (PET) for staging low-grade non-Hodgkin's lymphomas (NHL).

Although positron emission tomography (PET) imaging is now recognized as a useful tool for staging intermediate and high-grade non-Hodgkin's lymphoma (NHL), few data are available regarding its accuracy in low grade NHL. We therefore studied 36 patients with histologically proven low-grade NHL. Whole-body 2-(fluorine-18) fluoro-2-deoxy-D-glucose (FDG) PET was performed at the time of initial diagnosis (n = 21) or for disease recurrence (n = 15) prior to any treatment. PET results were compared to those of physical examination and computed tomography (CT). PET studies were read without knowledge of any clinical data. Any focus of increased activity was described and given a probability of malignancy using a 5 point-scale (0: normal to 4: definitively malignant). An individual biopsy was available for a total of 31 lesions. The sensitivity and specificity were 87% and 100% for FDG-PET, 100% and 100% for physical examination and 90% and 100% for CT respectively. In addition, 42 of 97 peripheral lymph node lesions observed by FDG-PET were clinically undetected, whereas the physical examination detected 23 additional nodal lesions. PET and CT both indicated 12 extranodal lymphomatous localizations. FDG-PET showed 7 additional extranodal lesions while 5 additional unconfirmed lesions were observed on CT. Regarding bone marrow infiltration, PET and biopsy were concordant in 24 patients with 11 true positive (TP) and 13 true negative (TN). However PET was FN in 11 patients and no biopsy was performed in one patient. The combination PET/CT/physical examination seems to be more sensitive than the conventional approach for staging low grade NHL. Its sensitivity however is unacceptably low for diagnosing bone marrow infiltration.

Dobutamine stress echocardiography versus quantitative technetium-99m sestamibi SPECT for detecting residual stenosis and multivessel disease after myocardial infarction.

OBJECTIVE: To compare the relative accuracy of dobutamine stress echocardiography (DSE) and quantitative technetium-99m sestamibi single photon emission computed tomography (mibi SPECT) for detecting infarct related artery stenosis and multivessel disease early after acute myocardial infarction. DESIGN: Prospective study. SETTING: University hospital. METHODS: 75 patients underwent simultaneous DSE and mibi SPECT at (mean (SD)) 5 (2) days after a first acute myocardial infarct. Quantitative coronary angiography was performed in all patients after imaging studies. RESULTS: Significant stenosis (> 50%) of the infarct related artery was detected in 69 patients. Residual ischaemia was identified by DSE in 55 patients and by quantitative mibi SPECT in 49. The sensitivity of DSE and mibi SPECT for detecting significant infarct related artery stenosis was 78% and 70%, respectively, with a specificity of 83% for both tests. The combination of DSE and mibi SPECT did not change the specificity (83%) but increased the sensitivity to 94%. Mibi SPECT was more sensitive than DSE for detecting mild stenosis (73% v 9%; p = 0.008). The sensitivity of DSE for detecting moderate or severe stenosis was greater than mibi SPECT (97% v 74%; p = 0.007). Wall motion abnormalities with DSE and transient perfusion defects with mibi SPECT outside the infarction zone were sensitive (80% v 67%; NS) and highly specific (95% v 93%; NS) for multivessel disease. CONCLUSIONS: DSE and mibi SPECT have equivalent accuracy for detecting residual infarct related artery stenosis of >/= 50% and multivessel disease early after acute myocardial infarction. DSE is more predictive of moderate or severe infarct related artery stenosis. Combined imaging only improves the detection of mild stenosis.

Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) for the staging of low-grade non-Hodgkin's lymphoma (NHL).

BACKGROUND: Although PET has been shown to be highly sensitive in the primary staging of lymphoma, previous studies with small numbers of patients indicated that low-grade NHL may not always be adequately detected by PET. We undertook this study to determine factors influencing the detection of lesions by PET in low-grade NHL and to evaluate the utility of PET in this indication. PATIENTS AND METHODS: Forty-two patients underwent conventional staging procedures (clinical examination, oto-rhino-laryngologic examination, computed tomography of the chest, abdomen and pelvis, gastroscopy and bone marrow biopsy as well as whole-body non-attenuation corrected 18F-FDG-PET RESULTS: PET detected 40% more abnormal lymph node areas than conventional staging in follicular lymphoma but was inappropriate for the staging of small lymphocytic lymphoma where it detected less than 58% of abnormal lymph node areas. PET showed more lesions than conventional staging for peripheral (34% more lymph node areas detected) and thoracic lymph node (39% more) areas but not for abdominal or pelvic lymph nodes (26% fewer areas detected). The sensitivity to detect bone marrow infiltration was unacceptably low for PET. In contrast, PET was as effective as standard procedures for the detection of other extranodal localizations, although a few localizations were detected only by PET and a few others only by conventional procedures. CONCLUSIONS: PET may contribute to the management of patients with low-grade follicular NHL. For the other low-grade lymphoma subtypes, the role of PET is less evident. Further studies using PET to evaluate the results of treatment or to diagnose disease recurrence are warranted in low-grade follicular NHL.

Whole-body positron emission tomography using 18F-fluorodeoxyglucose compared to standard procedures for staging patients with Hodgkin's disease.

BACKGROUND AND OBJECTIVES: Accurate staging is essential in order to determine appropriate treatment in Hodgkin's disease (HD). (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) offers the advantage of metabolic imaging that is largely independent of morphologic criteria. In the present study we evaluated the role of (18)F-FDG PET compared to routine procedures for the staging of patients with HD. DESIGN AND METHODS: Thirty-three patients with HD underwent standard staging procedures (clinical examination, laboratory screening, chest X-ray, computed tomography (CT) of the chest and abdomen and bilateral bone marrow biopsies) and a whole-body (18)F-FDG PET study. In clinical examination, an isolated lymph node > 1 cm or multiple lymph nodes > or = 1 cm in size were considered abnormal. Positive findings at both clinical examination or CT and (18)F-FDG PET were regarded as actual locations of disease. Negative findings with both methods were regarded as true negative (no involvement by HD). In cases of discrepancy, response to treatment and follow-up data were used to assess the overall accuracy of the patient's original evaluation. RESULTS: Completely concordant results in lymph node staging were observed in 20 patients. The two staging procedures indicated complementary information in 1 patient. Conventional staging indicated more pathologic lymph node areas in 6 patients (at least 1 false positive). (18)F-FDG PET showed more sites in 6 patients. The sensitivity of (18)F-FDG PET in detecting all known pathologic lymph nodes was 83% for peripheral lymph nodes, 91% for thoracic lymph nodes and 75% for abdominal and pelvic lymph nodes. Conventional staging procedures and (18)F-FDG PET indicated the same tumor stage in 26 patients. Based on (18)F-FDG PET, downstaging was suggested in 4 patients, including a biopsy-proven case. However in 1 of these cases this was incorrect. (18)F-FDG PET suggested upstaging in 3 patients. Based on conventional staging or (18)F-FDG PET the same treatment strategy was defined in 32 patients. In one patient (18)F-FDG PET downstaged disease extension (stage IIIA-->IIA) that would have suggested radiotherapy as a possible treatment option. INTERPRETATION AND CONCLUSIONS: (18)F-FDG PET provides an easy and efficient whole-body method for the evaluation of patients with HD. (18)F-FDG PET never missed tumor masses >1 cm. (18)F-FDG PET detected additional sites of disease not seen by conventional procedures and identified absence of disease in some sites suspected to be involved. However, in our patients this did not translate into changes in treatment strategy.

Combined corrections for attenuation, depth-dependent blur, and motion in cardiac SPECT: a multicenter trial.

BACKGROUND: The diagnostic accuracy of cardiac single photon emission computed tomography (SPECT) is limited by image-degrading factors, such as heart or subject motion, depth-dependent blurring caused by the collimator, and photon scatter and attenuation. We developed correction approaches for motion, depth-dependent blur, and attenuation and performed a multicenter validation. METHODS AND RESULTS: Motion was corrected both transversely and axially with a cross-correlation technique. Depth-dependent blurring was corrected by first back-projecting each projection and then applying a depth-dependent Wiener filter row by row. Attenuation was corrected with an iterative, nonuniform Chang algorithm, based on a transmission scan-generated attenuation map. We validated these approaches in 112 subjects, including 36 women (20 healthy volunteers, 8 angiographically normal patients, and 8 patients with coronary artery disease [CAD] found by means of angiography) and 76 men (23 healthy volunteers, 10 angiographically normal patients, and 43 patients with CAD found by means of angiography). Either technetium 99m or thallium 201 was used for emission; either gadolinium 153 or Tc-99m was used for transmission. Images were reconstructed and blindly interpreted with a 5-point scale for receiver operating characteristic analysis in 2 ways: motion correction plus a Butterworth filter, and combined motion and blur and attenuation corrections. The interpretation by means of consensus was for the overall presence of CAD and vascular territory. The receiver operating characteristic curves for overall presence and each of the 3 main coronary arteries were all shifted upward and to the left and had larger areas under the curve, for combined corrections compared with motion correction and Butterworth. Sensitivity/specificity for motion correction and Butterworth were 84/69, 64/71, 32/94, and 71/81 overall for the left anterior descending, the right coronary artery, and circumflex territories, respectively, compared with 88/92, 77/93, 50/97, and 74/95, respectively, for the combined corrections. CONCLUSIONS: The proposed combined corrections for motion, depth-dependent blur, and attenuation significantly improve diagnostic accuracy, when compared with motion correction alone.

[How I explore ... value of isotopic techniques in the detection of sepsis in valvular prostheses]. / Comment j'explore ... apport des techniques isotopiques dans la recherche de sepsis sur prothèse vasculaire.

Vascular graft infection is a rare but serious complication of vascular surgery. The diagnosis is frequently difficult. White blood cell imaging (111In or 99mTc-HMPAO) is an adequate technique for detecting vascular graft infection. This is a sensitive and specific method and has some advantages in the detection of perioperative or low grade infection in comparison to conventional imaging. The usefulness of other techniques like the 18FDG-PET scan is studied, but not yet evaluated. We compare the different methods actually used by illustrating three case reports of vascular graft infection for whom the diagnosis was formally made by isotopic imaging.

Persistent tumor 18F-FDG uptake after a few cycles of polychemotherapy is predictive of treatment failure in non-Hodgkin's lymphoma.

BACKGROUND AND OBJECTIVE: Early recognition of the ineffectiveness of chemotherapy could result in lower cumulative drug toxicity and tumor burden at the start of salvage therapy, which might improve clinical outcome. Therefore, we studied the value of (18)F-FDG PET for early evaluation of response in patients with non-Hodgkin's lymphoma (NHL). DESIGN AND METHODS: We studied 28 patients by (18)F-FDG PET after a median of 3 cycles of polychemotherapy. The presence or absence of abnormal (18)F-FDG uptake was correlated to clinical outcome (median follow-up: 17.5 months, range 4-47 months). RESULTS: Five of 28 patients still had increased (18)F-FDG uptake in one or more sites previously shown to be involved by lymphoma at baseline evaluation. Only one of these five patients entered complete remission (CR), whereas among the 23 patients with negative (18)F-FDG PET studies, two died of toxicity during chemotherapy and all the others entered clinical CR (p<0.00001). All five patients with and 7/21 patients without residual abnormal (18)F-FDG uptake relapsed or reprogressed (positive predictive value for relapse: 100%, negative predictive value: 67%). By Kaplan-Meier analysis, progression-free survival (PFS) at 1 and 2 years was respectively 20+/-18% and 0% for (18)F-FDG PET positive patients and 81+/-9% and 62+/-12% for (18)F-FDG PET negative patients (p=0.0001). Overall survival (OS) at 1 and 2 years was respectively 20+/-18% and 0% for (18)F-FDG PET positive and 87+/-7% and 68+/-11% for (18)F-FDG PET negative patients (p<0.0001). INTERPRETATION AND CONCLUSIONS: Persistent tumoral (18)F-FDG uptake after a few cycles of polychemotherapy is predictive of CR, PFS and OS in NHL. Further studies are warranted to determine whether (18)F-FDG PET has a predictive value independent from conventional prognostic factors. However, the sensitivity of qualitative (18)F-FDG PET imaging in identifying patients with a poor outcome was insufficient. Earlier evaluation after only one cycle of chemotherapy and quantitative analysis might increase the sensitivity of 18F-FDG PET is predicting treatment failure.