Accumulating evidence suggests that characteristics of pre-treatment FDG-PET could be used as prognostic factors to predict outcomes in different cancer sites. Current risk analyses are limited to visual assessment or direct uptake value measurements. We are investigating intensity-volume histogram metrics and shape and texture features extracted from PET images to predict patient's response to treatment. These approaches were demonstrated using datasets from cervix and head and neck cancers, where AUC of 0.76 and 1.0 were achieved, respectively. The preliminary results suggest that the proposed approaches could potentially provide better tools and discriminant power for utilizing functional imaging in clinical prognosis.

Batch cultures of Lactococcus lactis NCDO 2118 and IL 1403 were performed in a Couette bioreactor operated in the modulated wavy vortex flow and the turbulent regimes. This study provides an overall analysis taking into account both mechanical stress and mixing in a Couette bioreactor. A unique phenotypic aspect has been proved to occur only in the modulated wavy vortex flow regime for the two studied strains, namely that the cells become entrapped in a filamentous form. No change in the metabolic behavior of the cells has been observed. The polymeric matrix has been microscopically observed through FISH and fluorescent lectin binding, showing cells entrapped in a glycoconjugate matrix. All hypotheses regarding insufficient mixing as a cause of this phenotype have been discarded, leading to the conclusion that this particular phenotypic feature is essentially due a combined effect of mechanical stress and flow structure. Particle size measurement during the fermentation course indicates that formation of filamentous form results from a continuous aggregation started in the early stages of the cultivation. According to our results a minimum shear is required to induce the ability for cells to aggregate. Then, it appears that both flow structure and mechanical stress (shear) are responsible for the appearance of such a filamentous form. As far as the authors know, this is the first experimental evidence of a bio polymerization induced by the flow structure. Biotechnol. Bioeng. 2011; 108:559–571. © 2010 Wiley Periodicals, Inc.

PURPOSE A previous retrospective study demonstrated that positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) was more sensitive than computed tomography for lymph node staging in patients with cervical cancer; the findings on FDG-PET were strongly associated with progression-free survival. Therefore, a prospective cohort study was initiated to evaluate FDG-PET lymph node staging in a larger patient population. PATIENTS AND METHODS The study was conducted between July 2000 and March 2009. All 560 patients with cervical cancer underwent pretreatment FDG-PET lymph node staging. Treatment included surgery alone, surgery and postoperative radiation therapy, and definitive radiation or combination radiation and chemotherapy. PET findings were correlated with the risk of disease progression and with survival. Results Overall, 47% of patients had lymph node involvement by FDG-PET at diagnosis. The frequency of lymph node metastasis increased with clinical stage and was similar to that in historical surgical series. Within a stage, patients with PET-positive lymph nodes had significantly worse disease-specific survival than those with PET-negative lymph nodes (P < .001). Disease-specific survival was stratified into distinct groups based on the most distant level of PET-detected nodal disease (none, pelvic, para-aortic, or supraclavicular; P < .001). The hazard ratios for disease recurrence increased incrementally based on the most distant level of nodal disease: pelvic 2.40 (95% CI, 1.63 to 3.52), para-aortic 5.88 (95% CI, 3.80 to 9.09), and supraclavicular 30.27 (95% CI 16.56 to 55.34). CONCLUSION Nodal involvement detected by FDG-PET in cervical cancer relates to clinical stage, is comparable to historical data, and stratifies patient recurrence and survival outcomes.

PurposeTo provide evidence-based, resource-stratified global recommendations to clinicians and policymakers on the management and palliative care of women diagnosed with invasive cervical cancer.MethodsASCO convened a multidisciplinary, multinational panel of cancer control, medical and radiation oncology, health economic, obstetric and gynecologic, and palliative care experts to produce recommendations reflecting resource-tiered settings. A systematic review of literature from 1966 to 2015 failed to yield sufficiently strong quality evidence to support basic- and limited-resource setting recommendations; a formal consensus-based process was used to develop recommendations. A modified ADAPTE process was also used to adapt recommendations from existing guidelines.ResultsFive existing sets of guidelines were identified and reviewed, and adapted recommendations form the evidence base. Eight systematic reviews, along with cost-effectiveness analyses, provided indirect evidence to inform the consensus process, which resulted in agreement of 75% or greater.RecommendationsClinicians and planners should strive to provide access to the most effective evidence-based antitumor and palliative care interventions. If a woman cannot access these within her own or neighboring country or region, she may need to be treated with lower-tier modalities, depending on capacity and resources for surgery, chemotherapy, radiation therapy, and supportive and palliative care. For women with early-stage cervical cancer in basic settings, cone biopsy or extrafascial hysterectomy may be performed. Fertility-sparing procedures or modified radical or radical hysterectomy may be additional options in nonbasic settings. Combinations of surgery, chemotherapy, and radiation therapy (including brachytherapy) should be used for women with stage IB to IVA disease, depending on available resources. Pain control is a vital component of palliative care. Additional information is available at www.asco.org/rs-cervical-cancer-treatment-guideline and www.asco.org/guidelineswiki. It is the view of ASCO that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.

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Purpose: Previous research has shown that the intertumoral maximum standardized uptake value (SUV Max ) of F-18 fluorodeoxyglucose (FDG)^positron emission tomography (PET) for cervical cancer predicts disease outcome. The purpose of this study was to evaluate the pretreatment intratumoral metabolic heterogeneity of FDG. Experimental Design: This is a prospective cohort study of 72 patients with International Federation of Gynecology and Obstetrics stages Ib1 to IVa cervical cancer treated with chemoradiation. Three-dimensional FDG-PET threshold tumor volumes were calculated using image segmentation and an adaptive thresholding method for the primary cervix tumor from the pretreatment FDG-PET/computerized tomography. Intratumor heterogeneity was obtained for each patient's cervical tumor by taking the derivative (dV/dT) of the volume-threshold function from 40% to 80%. The association between intratumoral heterogeneity and tumorspecific factors and patient outcomes were determined. Results: The mean cervix tumor SUV Max was 12.4 (range, 3.0-38.4). The mean differential tumor heterogeneity was -1.074 (range, -0.107 to -5.623).There was no association between dV/dTand SUV Max (R 2 = 0.069), but there was a relationship with dV/dT and tumor volume (R 2 = 0.881). There was no correlation of dV/dT with tumor histology (P = 0.4905). Heterogeneity was significantly associated with the risk of lymph node metastasis at diagnosis (P = 0.0009), tumor response to radiation as evaluated by FDG-PET obtained 3 months after completing treatment (P = 0.0207), risk of pelvic recurrence (P = 0.0017), and progression-free survival (P = 0.03). Conclusions: Cervical intratumoral FDG metabolic heterogeneity on the pretreatment FDG-PET predicts risk of lymph node involvement at diagnosis, response to therapy, and risk of pelvic recurrence.It is understood that, on a microscopic level, tumors are heterogeneous (1 -3). Evaluation of tumor microenvironments has shown heterogeneity relating to variation in tumor responsiveness to treatment (4, 5), degree of vascularity (6, 7), hypoxia (1, 7, 8), proliferation rates (7), energy metabolites, and gene expression (9 -11). Although tumor heterogeneity has been shown within these tumor microenvironments, intratumoral heterogeneity across the entire volume of primary tumors in humans has not been quantified or analyzed for its association with outcome measures. F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging allows intratumoral heterogeneity to be assessed using objective criteria.Cervical cancer is an example of a tumor that shows heterogeneity relating to hypoxia, variation in response to treatment, risk of metastatic spread, and gene expression (4, 5, 10, 12 -15). Additionally, the response of the primary cervical cancer to treatment has been shown to be a much more complex issue than simply relating outcome to clinical stage, tumor volume, or tumor hypoxia. Specifically, our previous research has shown that the primary cervix tumor maximal standardized uptake...

Purpose We previously found several individual FDG/PET-based prognostic factors for cervical cancer, specifically cervical tumor SUVmax, tumor volume, and highest level of lymph node (LN) involvement. For this study, we evaluate the combined use of these three prognostic factors assessed on pretreatment FDG-PET for predicting recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS). Patients and methods The study included 234 cervical cancer patients, FIGO stage Ib1–IVa, treated with definitive radiation or chemoradiation therapy. All patients underwent FDG-PET or FDG-PET/CT at diagnosis, from which cervical tumor volume, SUVmax, and LN status were recorded. Using these PET-based factors, prognostic nomograms were created for RFS, DSS, and OS, and their prediction accuracies were measured using the concordance index (c-statistic). Results Fifty-three percent of patients had FDG-avid LN on PET; the highest level of nodal involvement was pelvic in 84, para-aortic in 41, and supraclavicular in 10. The average cervix tumor SUVmax was 12.4 (range, 2.1–50.4) and PET tumor volume average was 66.4 cm3 (range, 3.0–535.7 cm3). The median follow-up was 40.7 months for patients alive at last follow-up. PET LN status had the greatest influence on outcome. The c-statistics for the 3 nomograms were 0.741 for RFS, 0.739 for DSS, and 0.658 for OS. The PET-based nomograms performed better than FIGO stage with c-statistics of 0.605, 0.600 and 0.559 for RFS, DSS and OS, respectively. Conclusions Pretreatment FDG-PET LN status, cervical tumor SUVmax, and tumor volume combined in a nomogram create good models for predicting cervical cancer RFS, DSS, and OS.

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. MethodsWe did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. FindingsIn the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo.Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases.