SF-CORNER (splenic flexure colorectal cancer): an international survey of operative approaches and outcomes for cancers of the splenic flexure.

AIM: The optimum surgical approach to splenic flexure cancers (SFCs) remains uncertain. The aim of this survey was to explore the opinions of an international surgical community on the management and outcomes of SFC. METHOD: A questionnaire was constructed comprising five sections (information about respondents; definition and prognosis of SFC; operative approach; approach in specific scenarios; outcomes) and circulated through an international dissemination committee and social media. RESULTS: The survey received 576 responses over 4 weeks across 50 countries. There was no consensus regarding the definition of the splenic flexure, whilst the proportion of respondents who did and did not think that patients with SFC had a worse outcome was equal. The overall preferred operative approach was left hemicolectomy [203 (35.2%)], followed by segmental resection [167 (29%)], extended right hemicolectomy [126 (21.9%)] and subtotal colectomy [7 (12%)]. The stated pedicles for ligation varied between resection types and also within the same resection. One hundred and sixty-six (28.8%) respondents thought a segmental resection was associated with the worst survival and 190 (33%) thought it was associated with the best quality of life. CONCLUSION: This survey confirms a lack of consensus across all aspects SFC treatment. The differing approaches described are likely to represent different beliefs around the variable anatomy of this region and the associated lymphatic drainage. Future studies are required to address such inconsistencies and identify the optimum surgical strategy, whilst also incorporating quality-of-life metrics and patient-reported outcomes. A one-size-fits-all approach is probably not appropriate with SFC, and a more bespoke approach is required.

Accelerated discovery of two crystal structure types in a complex inorganic phase field.

The discovery of new materials is hampered by the lack of efficient approaches to the exploration of both the large number of possible elemental compositions for such materials, and of the candidate structures at each composition. For example, the discovery of inorganic extended solid structures has relied on knowledge of crystal chemistry coupled with time-consuming materials synthesis with systematically varied elemental ratios. Computational methods have been developed to guide synthesis by predicting structures at specific compositions and predicting compositions for known crystal structures, with notable successes. However, the challenge of finding qualitatively new, experimentally realizable compounds, with crystal structures where the unit cell and the atom positions within it differ from known structures, remains for compositionally complex systems. Many valuable properties arise from substitution into known crystal structures, but materials discovery using this approach alone risks both missing best-in-class performance and attempting design with incomplete knowledge. Here we report the experimental discovery of two structure types by computational identification of the region of a complex inorganic phase field that contains them. This is achieved by computing probe structures that capture the chemical and structural diversity of the system and whose energies can be ranked against combinations of currently known materials. Subsequent experimental exploration of the lowest-energy regions of the computed phase diagram affords two materials with previously unreported crystal structures featuring unusual structural motifs. This approach will accelerate the systematic discovery of new materials in complex compositional spaces by efficiently guiding synthesis and enhancing the predictive power of the computational tools through expansion of the knowledge base underpinning them.

Health-related quality of life analyses in nonfunctioning pituitary macroadenoma patients identifies at-risk populations.

PURPOSE: The quality of life (QoL) impact of multidisciplinary treatment for patients with nonfunctioning pituitary macroadenomas (NFPMA) is unclear. We sought to investigate associations between patient factors, clinical data, and patient-reported QoL in patients with NFPMA. METHODS: Patients with treated NFPMA and > 1 year of follow up after transsphenoidal surgery (TSS) and with no evidence of progressive disease were evaluated utilizing the following patient-reported outcome measures: RAND-36-Item Health Survey, Multidimensional Fatigue Inventory, Cognitive Failures Questionnaire. RESULTS: 229 eligible patients completed QoL questionnaires a median of 7.7 years after initial transsphenoidal surgery (TSS). 25% of participants received radiation therapy (RT) a median of 2.0 years (0.1-22.5) after initial TSS. Patients who received RT were younger (median age 46 v 58, p < 0.0001), had larger tumors (28 mm v 22 mm, p < 0.0001), were more likely to have visual symptoms (65% v 34%, p = 0.0002), and were more likely to have hypopituitarism (93% v 62%, p < 0.0001). Patients with hypopituitarism reported worse energy and fatigue and cognitive function (p < 0.03). Patients who received RT reported significantly worse general health, physical health, physical fatigue and cognitive functioning (p < 0.05). The largest QoL differences were in patients who experienced a financial stressor, independent of treatment type. CONCLUSION: Hypopituitarism, radiation therapy after TSS, and financial stressors are associated with more impaired QoL in patients with NFPMA. Awareness of these factors can better guide use and timing of radiation therapy in addition to identifying patients who can benefit from multidisciplinary surveillance.

Racial disparities in non-recommendation of adjuvant chemotherapy in stage II-III ovarian cancer.

OBJECTIVES: To identify patient factors associated with not receiving a recommendation for adjuvant chemotherapy after primary surgery for ovarian cancer. METHODS: This retrospective cohort study used the National Cancer Database (NCDB) data from 2004 to 2015 to identify patients with stage II-III ovarian cancer who underwent primary surgery. Multivariate logistic regression analyses evaluated factors associated with notation in the NCDB that "chemotherapy was not recommended/administered because it was contraindicated due to patient risk factors (i.e., comorbid conditions, advanced age)." Survival data were assessed via Kaplan-Meier analyses. RESULTS: Of the 48,245 patients who met the inclusion criteria, 522 (1.08%) did not receive adjuvant chemotherapy because it was determined to be contraindicated. In multivariate analyses, independent predictors for not receiving a recommendation for adjuvant chemotherapy were age ≥ 70 years old (adjusted odds ratio, aOR = 2.43, p < 0.0001), non-zero Charlson-Deyo comorbidity scores (score 1, aOR = 1.41, p = 0.002; score ≥ 2, aOR = 2.57, p < 0.0001), and Black race (aOR = 2.12, p < 0.0001). For Black patients, recommendation against adjuvant chemotherapy occurred at a younger median age (64.5 years vs. 72 years) and was associated with lower 5-year survival (25.9% vs. 40.3%, p < 0.0001). CONCLUSIONS: Patients with ovarian cancer who underwent surgery but did not receive chemotherapy "because it was contraindicated due to patient risk factors" were older and had higher comorbidity scores. Even after controlling for these differences, Black patients were disproportionately not recommended for chemotherapy, which was associated with worse survival. Determining eligibility for adjuvant chemotherapy requires an individualized approach, and the possible influence of racial bias on risk estimation should be further investigated.

1D self-assembly of chemisorbed thymine on Cu(110) driven by dispersion forces.

Adsorption of thymine on a defined Cu(110) surface was studied using reflection-absorption infrared spectroscopy (RAIRS), temperature programmed desorption (TPD), and scanning tunnelling microscopy (STM). In addition, density functional theory (DFT) calculations were undertaken in order to further understand the energetics of adsorption and self-assembly. The combination of RAIRS, TPD, and DFT results indicates that an upright, three-point-bonded adsorption configuration is adopted by the deprotonated thymine at room temperature. DFT calculations show that the upright configuration adopted by individual molecules arises as a direct result of strong O-Cu and N-Cu bonds between the molecule and the surface. STM data reveal that this upright thymine motif self-assembles into 1D chains, which are surprisingly oriented along the open-packed [001] direction of the metal surface and orthogonal to the alignment of the functional groups that are normally implicated in H-bonding interactions. DFT modelling of this system reveals that the molecular organisation is actually driven by dispersion interactions, which cause a slight tilt of the molecule and provide the major driving force for assembly into dimers and 1D chains. The relative orientations and distances of neighbouring molecules are amenable for π-π stacking, suggesting that this is an important contributor in the self-assembly process.

Clustering of missense mutations in the ataxia-telangiectasia gene in a sporadic T-cell leukaemia.

Ataxia-telangiectasia (A-T) is a recessive multi-system disorder caused by mutations in the ATM gene at 11q22-q23 (ref. 3). The risk of cancer, especially lymphoid neoplasias, is substantially elevated in A-T patients and has long been associated with chromosomal instability. By analysing tumour DNA from patients with sporadic T-cell prolymphocytic leukaemia (T-PLL), a rare clonal malignancy with similarities to a mature T-cell leukaemia seen in A-T, we demonstrate a high frequency of ATM mutations in T-PLL. In marked contrast to the ATM mutation pattern in A-T, the most frequent nucleotide changes in this leukaemia were missense mutations. These clustered in the region corresponding to the kinase domain, which is highly conserved in ATM-related proteins in mouse, yeast and Drosophila. The resulting amino-acid substitutions are predicted to interfere with ATP binding or substrate recognition. Two of seventeen mutated T-PLL samples had a previously reported A-T allele. In contrast, no mutations were detected in the p53 gene, suggesting that this tumour suppressor is not frequently altered in this leukaemia. Occasional missense mutations in ATM were also found in tumour DNA from patients with B-cell non-Hodgkin's lymphomas (B-NHL) and a B-NHL cell line. The evidence of a significant proportion of loss-of-function mutations and a complete absence of the normal copy of ATM in the majority of mutated tumours establishes somatic inactivation of this gene in the pathogenesis of sporadic T-PLL and suggests that ATM acts as a tumour suppressor. As constitutional DNA was not available, a putative hereditary predisposition to T-PLL will require further investigation.

Clinical outcomes of radiation therapy for transgender and gender-expansive people with cancer.

Introduction: Approximately 1.6 million people in the US identify as transgender, many of whom undergo gender-affirming medical or surgical therapies. While transgender individuals are diagnosed with cancer at similar rates as those who are cisgender, the impacts of radiation therapy on outcomes of gender-affirming care in transgender, nonbinary, and gender-expansive people with cancer are understudied. We report on the experiences and outcomes of transgender and gender-expansive patients receiving radiation therapy for cancer treatment. Methods: This study is a multi-institutional retrospective review of patients evaluated from 2005-2019 identified as transgender or gender-expansive in the medical record and treated with radiation therapy. Results: We identified 23 patients who received radiation to 32 sites, including 12 (38%) to the brain, head, or neck, 8 (25%) to the thorax, and 7 (22%) to the pelvis. Seventeen patients (74%) received gender-affirming hormone therapy and 13 patients (57%) underwent gender-affirming surgery. Four patients had pelvic radiation before or after gender-affirming pelvic surgery, including two trans women who had pelvic radiation after vaginoplasty. Four patients had radiation to the chest or thorax and gender-affirming chest or breast surgery, including two trans men with breast cancer. Two pediatric patients developed hypopituitarism and hypogonadism secondary to radiation therapy and, as adults, changed their hormone replacement therapy to affirm their transgender identities. Discussion: Transgender people with cancer undergo radiation therapy for a wide range of cancers. Understanding their prior gender-affirming medical or surgical treatments and future gender affirmation goals may identify important considerations for their oncologic care.

Observer preference of artificial intelligence-generated versus clinical prostate contours for ultrasound-based high dose rate brachytherapy.

BACKGROUND: For trans-rectal ultrasound (TRUS)-based high dose rate (HDR) prostate brachytherapy, prostate contouring can be challenging due to artifacts from implanted needles, bleeding, and calcifications. PURPOSE: To evaluate the geometric accuracy and observer preference of an artificial intelligence (AI) algorithm for generating prostate contours on TRUS images with implanted needles. METHODS: We conducted a retrospective study of 150 patients, who underwent HDR brachytherapy. These patients were randomly divided into training (104), validation (26) and testing (20) sets. An AI algorithm was trained/validated utilizing the TRUS image and reference (clinical) contours. The algorithm then provided contours for the test set. For evaluation, we calculated the Dice coefficient between AI and reference prostate contours. We then presented AI and reference contours to eight clinician observers, and asked observers to select their preference. Observers were blinded to the source of contours. We calculated the percentage of cases in which observers preferred AI contours. Lastly, we evaluate whether the presence of AI contours improved the geometric accuracy of prostate contours provided by five resident observers for a 10-patient subset. RESULTS: The median Dice coefficient between AI and reference contours was 0.92 (IQR: 0.90-0.94). Observers preferred AI contours for a median of 57.5% (IQR: 47.5, 65.0) of the test cases. For resident observers, the presence of AI contours was associated with a 0.107 (95% CI: 0.086, 0.128; p < 0.001) improvement in Dice coefficient for the 10-patient subset. CONCLUSION: The AI algorithm provided high-quality prostate contours on TRUS with implanted needles. Further prospective study is needed to better understand how to incorporate AI prostate contours into the TRUS-based HDR brachytherapy workflow.

Gender-Affirming Surgery and Cancer: Considerations for Radiation Oncologists for Pelvic Radiation in Transfeminine Patients.

Access to gender-affirming surgery is increasing for many transgender and nonbinary people in the United States, and radiation oncologists must be equipped to care for patients who have undergone such surgery in the region of their planned radiation treatment field. There are no guidelines for radiation treatment planning after gender-affirming surgery, and most oncologists do not receive training in the unique needs of transgender people with cancer. We review common gender-affirming genitopelvic surgeries for transfeminine people, including vaginoplasty, labiaplasty, and orchiectomy, and summarize the existing literature on the treatment of cancers of the neovagina, anus, rectum, prostate, and bladder in these patients. We also describe our systematic treatment approach and rationale for pelvic radiation treatment planning.

The collagen prolyl hydroxylases are novel transcriptionally silenced genes in lymphoma.

BACKGROUND: Prolyl hydroxylation is a post-translational modification that affects the structure, stability and function of proteins including collagen by catalysing hydroxylation of proline to hydroxyproline through action of collagen prolyl hydroxylases3 (C-P3H) and 4 (C-P4H). Three C-P3Hs (nomenclature was amended according to approval by the HGNC symbols and names at http://www.genenames.org/ and Entrez database at http://www.ncbi.nlm.nih.gov/gene) leucineproline-enriched proteoglycan (leprecan) 1 (Lepre1), leprecan-like 1 (Leprel1), leprecan-like 2 (Leprel2) and two paralogs Cartilage-Related Protein (CRTAP) and leprecan-like 4 (Leprel4) are found in humans. The C-P4Hs are tetrameric proteins comprising a variable α subunit, encoded by the P4HA1, P4HA2 and P4HA3 genes and a constant ß subunit encoded by P4HB. METHODS: We used RT-PCR, qPCR, pyrosequencing, methylation-specific PCR, western blotting and immunohistochemistry to investigate expression and regulation of the C-P3H and C-P4H genes in B lymphomas and normal bone marrow. RESULTS: C-P3H and C-P4H are downregulated in lymphoma. Down-regulation is associated with methylation in the CpG islands and is detected in almost all common types of B-cell lymphoma, but the CpG islands are unmethylated or methylated at lower levels in DNA isolated from normal bone marrow and lymphoblastoid cell lines. Methylation of multiple C-P3H and C-P4H genes is present in some lymphomas, particularly Burkitt's lymphoma. CONCLUSIONS: Methylation of C-P3H and C-P4H is common in B lymphomas and may have utility in differentiating disease subtypes.

Committed T lymphocyte stem cells of rats. Characterization by surface W3/13 antigen and radiosensitivity.

The existence of stem cells committed to the T lymphoid lineage was deduced from studying how rat T and B stem cells differ in their expression of membrane W3/13 antigen and in their susceptibility in vivo to gamma irradiation. Stem cell activity of rat bone marrow and fetal liver was measured in long-term radiation chimeras using B and T cell alloantigenic surface markers to identify the progeny of donor cells. Monoclonal mouse anti-rat thymocyte antibody W3/13 labeled approximately 40% of fetal liver cells and 60-70% of young rat bone marrow cells (40% brightly, 25% dimly). Bright, dim, and negative cells were separated on a fluorescence-activated cell sorter. All B and T lymphoid stem cells in fetal liver were W3/13 bright, as were B lymphoid stem cells in bone marrow. W3/13 dim bone marrow had over half the T cell repopulating activity of unseparated marrow but gave virtually no B cell repopulation. In further experiments, the radiosensitivity of endogenous B and T lymphoid stem cells was determined by exposing host rats to between 4.5 and 10 Gy of gamma irradiation before repopulation with genetically marked marrow. The results depended on whether chimerism was assayed before day 50 or after day 100. At early times, a radioresistant T stem cell was indicated, whose activity waned later. Thus committed T stem cells of rats carry moderate amounts of W3/13 antigen and are more radioresistant but less permanently chimeragenic than the stem cells that regenerate B lymphocytes.

Nonpegylated liposomal doxorubicin (MyocetTM) combination (R-COMP) chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL): results from the phase II EUR018 trial.

BACKGROUND: To evaluate the activity and safety of nonpegylated liposomal doxorubicin (Myocet) when substituted for doxorubicin in the R-CHOP regimen (R-COMP). PATIENTS AND METHODS: Seventy-five elderly patients with diffuse large B-cell lymphoma (DLBCL) were studied. Only patients with left ventricular ejection fraction (LVEF) > or =50% were allowed. R-COMP regimen was administered every 3 weeks for three cycles, followed by additional five cycles in case of complete response (CR) or partial response. RESULTS: From November 2002 to April 2005, 75 patients were registered, of which 72 were evaluated. Median age was 72 years (range 61-83); 56% of patients had high or high-intermediate International Prognostic Index score. Median LVEF at baseline was 61%. Thirty-eight patients had history of abnormal cardiovascular conditions. The overall response rate was 71%, with a CR rate of 57%. After a median follow-up of 33 months, the 3-year overall survival, failure-free survival, and progression-free survival rates were 72%, 39%, and 69%, respectively. Neutropenia (54%) was the most frequent grade 3-4 adverse event (AE); 21% of patients experienced cardiac AEs, graded as 3-4 in 4% of the cases. CONCLUSION: R-COMP is an effective regimen for the treatment of DLBCL in elderly patients, with an acceptable tolerability profile.

Activity of thalidomide and lenalidomide in mantle cell lymphoma.

Thalidomide and lenalidomide are immunomodulatory drugs that show promise in mantle cell lymphoma (MCL). In this study, their potential mechanisms of action against MCL cells were investigated, both alone and in combination with rituximab. Thalidomide, lenalidomide and rituximab have no direct effect on MCL cell viability. However, both immunomodulatory drugs indirectly affect viability by enhancing peripheral blood mononuclear cell-mediated cytotoxicity, with lenalidomide inducing significantly higher levels of toxicity than thalidomide. Rituximab induces both complement-dependent and antibody-dependent cellular cytotoxicity (ADCC) against MCL cells. Rituximab-induced ADCC is enhanced by lenalidomide and, to a lesser extent, thalidomide. Preliminary in vivo findings in MCL patients treated with thalidomide support a role for natural killer cells in the efficacy of these drugs. In conclusion, our data support a role for immunomodulatory drugs in the treatment of MCL.

Epothilone D alters normal growth, viability and microtubule dependent intracellular functions of cortical neurons in vitro.

Brain penetrant microtubule stabilising agents (MSAs) are being increasingly validated as potential therapeutic strategies for neurodegenerative diseases and traumatic injuries of the nervous system. MSAs are historically used to treat malignancies to great effect. However, this treatment strategy can also cause adverse off-target impacts, such as the generation of debilitating neuropathy and axonal loss. Understanding of the effects that individual MSAs have on neurons of the central nervous system is still incomplete. Previous research has revealed that aberrant microtubule stabilisation can perturb many neuronal functions, such as neuronal polarity, neurite outgrowth, microtubule dependant transport and overall neuronal viability. In the current study, we evaluate the dose dependant impact of epothilone D, a brain penetrant MSA, on both immature and relatively mature mouse cortical neurons in vitro. We show that epothilone D reduces the viability, growth and complexity of immature cortical neurons in a dose dependant manner. Furthermore, in relatively mature cortical neurons, we demonstrate that while cellularly lethal doses of epothilone D cause cellular demise, low sub lethal doses can also affect mitochondrial transport over time. Our results reveal an underappreciated mitochondrial disruption over a wide range of epothilone D doses and reiterate the importance of understanding the dosage, timing and intended outcome of MSAs, with particular emphasis on brain penetrant MSAs being considered to target neurons in disease and trauma.

A novel paradigm for rapid ABT-737-induced apoptosis involving outer mitochondrial membrane rupture in primary leukemia and lymphoma cells.

Primary chronic lymphocytic leukemia (CLL) cells are exquisitely sensitive to ABT-737, a small molecule BCL2-antagonist, which induces many of the classical biochemical and ultrastructural features of apoptosis, including BAX/BAK oligomerization, cytochrome c release, caspase activation and chromatin condensation. Surprisingly, ABT-737 also induces mitochondrial inner membrane permeabilization (MIMP) resulting in mitochondrial matrix swelling and rupture of the outer mitochondrial membrane (OMM), so permitting the rapid efflux of cytochrome c from mitochondrial cristae and facilitating rapid caspase activation and apoptosis. BAX and BAK appear to be involved in the OMM discontinuities as they localize to the OMM break points. Notably, ABT-737 induced mitochondrial matrix swelling and OMM discontinuities in other primary B-cell malignancies, including mantle cell, follicular and marginal zone lymphoma cells but not in several cell lines studied. Thus, we describe a new paradigm of apoptosis in primary B-cell malignancies, whereby targeting of BCL2 results in all the classical features of apoptosis together with OMM rupture independent of caspase activation. This mechanism may be far more prevalent than hitherto recognized due to the failure of most methods, used to measure apoptosis, to recognize such a mechanism.

MvirDB--a microbial database of protein toxins, virulence factors and antibiotic resistance genes for bio-defence applications.

Knowledge of toxins, virulence factors and antibiotic resistance genes is essential for bio-defense applications aimed at identifying 'functional' signatures for characterizing emerging or engineered pathogens. Whereas genetic signatures identify a pathogen, functional signatures identify what a pathogen is capable of. To facilitate rapid identification of sequences and characterization of genes for signature discovery, we have collected all publicly available (as of this writing), organized sequences representing known toxins, virulence factors, and antibiotic resistance genes in one convenient database, which we believe will be of use to the bio-defense research community. MvirDB integrates DNA and protein sequence information from Tox-Prot, SCORPION, the PRINTS virulence factors, VFDB, TVFac, Islander, ARGO and a subset of VIDA. Entries in MvirDB are hyperlinked back to their original sources. A blast tool allows the user to blast against all DNA or protein sequences in MvirDB, and a browser tool allows the user to search the database to retrieve virulence factor descriptions, sequences, and classifications, and to download sequences of interest. MvirDB has an automated weekly update mechanism. Each protein sequence in MvirDB is annotated using our fully automated protein annotation system and is linked to that system's browser tool. MvirDB can be accessed at http://mvirdb.llnl.gov/.

Cost analysis of an integrated care model in the management of acute exacerbations of chronic obstructive pulmonary disease.

Home treatment models for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) proved to be a safe alternative to hospitalization. These models have the potential to free up resources; however, in the United Kingdom, it remains unclear to whether they provide cost savings compared with hospital treatment. Over a 12-month period from August 2003, 130 patients were selected for the integrated care group (total admissions with AECOPD = 546). These patients were compared with 95 retrospective controls in the hospital treatment group. Controls were selected from admissions during the previous 12 months (total of 662 admissions) to match the integrated care group in age, sex, and postal code. Resource use data were collected for both groups and compared using National Health Service (NHS) perspective for cost minimization analysis. In the integrated care group (130 patients), 107 (82%) patients received home support with average length of stay 3.3 (SD 3.9) days compared with 10.4 (SD 7.7) in the hospital group (95 patients). Average number of visits per patients in the integrated care group was 3.08 (SD = 0.95; 95% CI = 2.9-3.2). Cost per patient in the integrated care group was pound1653 (95% CI, pound1521-1802) compared with pound2256 (95% CI, pound2126- 2407) in the hospital group. The integrated care group resulted in cost saving of approximately pound600 (P < 0.001) per patient. This integrated care model for the management of patients with AECOPD offered cost savings of pound600 per patient over the conventional hospital treatment model using the new NHS tariff from an acute trust provider perspective.

Weyl-like points from band inversions of spin-polarised surface states in NbGeSb.

Band inversions are key to stabilising a variety of novel electronic states in solids, from topological surface states to the formation of symmetry-protected three-dimensional Dirac and Weyl points and nodal-line semimetals. Here, we create a band inversion not of bulk states, but rather between manifolds of surface states. We realise this by aliovalent substitution of Nb for Zr and Sb for S in the ZrSiS family of nonsymmorphic semimetals. Using angle-resolved photoemission and density-functional theory, we show how two pairs of surface states, known from ZrSiS, are driven to intersect each other near the Fermi level in NbGeSb, and to develop pronounced spin splittings. We demonstrate how mirror symmetry leads to protected crossing points in the resulting spin-orbital entangled surface band structure, thereby stabilising surface state analogues of three-dimensional Weyl points. More generally, our observations suggest new opportunities for engineering topologically and symmetry-protected states via band inversions of surface states.

The impact of follicular lymphoma on health-related quality of life.

BACKGROUND: The purpose of this study was to determine whether there was a relationship between disease activity and health functioning, as measured by a range of patient-reported outcome (PRO) measures in patients with follicular lymphoma (FL). PATIENTS AND METHODS: A total of 222 patients with FL were recruited from eight sites across the UK and they completed a number of PRO measures. The participants were analyzed across five disease states: 'active disease-newly diagnosed', 'active disease-relapsed', 'partial response', 'complete response' and 'disease free'. The relationship between these disease states and their level of health functioning was assessed as well as the relationship between being 'on' or 'off' chemotherapy and disease state. RESULTS: In terms of health-related quality of life (HRQoL), participants in the relapsed category had the lowest mean physical well-being, emotional well-being, functional well-being and social well-being score. In a regression analysis, the 'active disease-relapsed' group acted as a significant predictor for each PRO variable. In addition, the remission group acted as a significant predictor of high anxiety scores as measured by the Hospital Anxiety and Depression Scale. CONCLUSION: The results of this study demonstrate that various aspects of patient-reported health outcomes differ according to disease state in patients with FL. For those patients who have relapsed, they are more likely to experience worse HRQoL and other patient-reported health outcomes than patients newly diagnosed, in partial or complete remission or when completely disease free.