Meta-analysis of the prognostic and clinical value of serum 25-hydroxyvitamin D levels in previously untreated lymphoma.

Background: This meta-analysis explored the prognostic and clinical value of serum 25-hydroxyvitamin D, 25(OH)D, levels in previously untreated lymphoma. Materials & methods: PubMed, Web of Science, Embase and the Cochrane Central Register of Controlled Trials databases were searched for eligible studies. Summary effect estimates and 95% CIs were pooled using random-effects or fixed-effects models. Results: Twelve studies with 4139 patients were included. Low level of serum 25(OH)D was associated with inferior progression-free survival (hazard ratio [HR]: 2.06; 95% CI: 1.82-2.32) and overall survival (HR: 1.94; 95% CI: 1.71-2.19), advanced disease (odds ratio [OR]: 1.52; 95% CI: 1.09-2.13) and elevated lactate dehydrogenase (OR: 1.84; 95% CI: 1.08-3.15). Conclusions: Low level of serum 25(OH)D is a prognostic risk factor for newly diagnosed lymphoma.

Lay abstract Vitamin D is a nutrient. Vitamin D deficiency is common in lymphoma patients. Serum level of 25-hydroxyvitamin D, 25(OH)D, reflects vitamin D status. Aim: We studied whether low levels of 25(OH)D are related with poor survival for newly diagnosed lymphoma. Materials & methods: We researched four databases for eligible studies. We then extracted data from the studies. Finally, we pooled the effect sizes based on the data. Results: Twelve studies with 4139 patients were included in the study. Results showed that low levels of serum 25(OH)D were associated with greater lymphoma progression and death. Patients with low serum 25(OH)D were likely to have poor clinical features as well. Conclusions: Low serum 25(OH)D is a risk factor for lymphoma survival. Assessment of vitamin D status should be considered in clinical practice. Further research is needed to assess the effect of vitamin D supplementation therapy.

Clinical outcomes of newly diagnosed primary CNS lymphoma treated with ibrutinib-based combination therapy: A real-world experience of off-label ibrutinib use.

Ibrutinib-based combination therapy with high-dose methotrexate (HD-MTX) has recently shown clinical activity against relapse/refractory (R/R) primary central nervous system lymphoma (PCNSL). Herein, we report our real-world experience of treating 11 newly diagnosed PCNSL patients with the ibrutinib/MTX combination. HD-MTX was given at 3.5 g/m2 every 2-week for eight doses. Ibrutinib was held upon HD-MTX infusion until clearance and was administered daily post-induction until disease progression, intolerable toxicity, or death. Nine out of 11 patients completed the induction phase and received ibrutinib as maintenance therapy. An objective response rate (ORR) of 82% (9/11) was observed including complete response (64%) and partial response (18%). The median progression-free survival (PFS) was 7.4 months while the median overall survival (OS) was not reached. The ibrutinib/MTX combination was well tolerated in these treatment-naïve PCNSL patients with an acceptable safety profile. Moreover, the longitudinal analysis of cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) revealed that CSF ctDNA detection was closely associated with tumor response, and sustained tumor responses correlated with the clearance of ctDNA from the CSF. In sum, our data not only demonstrated the clinical benefit of the ibrutinib and HD-MTX combination regimen in treating newly diagnosed PCNSL patients in a real-world setting, but also highlighted the significance of liquid biopsy including CSF ctDNA in tracing tumor burden and assessing treatment response.

Priorities for Rural Lymphoma Survivors: A Qualitative Study.

BACKGROUND: We gathered rural patient perspectives on lymphoma care and unmet needs throughout the treatment course to better understand their attitudes toward treatment and their barriers to participating in clinical research studies. PATIENTS AND METHODS: We conducted 12 individual semi-structured telephone interviews in the spring of 2018 with lymphoma survivors from rural counties in Georgia. Patients were identified by a residential address in counties classified as rural according to the Rural-Urban Commuting Areas codes. Participants were recruited from regional patient education conferences and from current research participants at a university research hospital in Georgia. The interviews were recorded and transcribed verbatim. Thematic analysis and MAXQDA, version 18.0.8, were used to facilitate a constant comparative coding process during theme development. RESULTS: The greatest barrier to care was the travel distance. The participants described difficulty navigating between local clinics and larger cancer centers. The lack of communication between the local and specialized clinics complicated the process, and participants had difficulty contacting or seeking advice from the team at the larger cancer centers. Seeking treatment from specialized clinics farther away introduced additional barriers. Most participants agreed that the use of technology was important for improved communication. Participants described lymphoma etiology, subtype-specific studies, alternative therapies, and quality of life as key research priorities. CONCLUSION: These findings suggest that targeted research and interventions are necessary to address the specific needs of rural patients with and survivors of lymphoma. To address the disparity in health outcomes within rural populations, healthcare professionals and investigators can use these data to engage rural patients in treatment decision-making and research planning.

Impact of lymphoma survivorship clinic visit on patient-centered outcomes.

PURPOSE: Cancer survivors may experience physical, social, and emotional effects of cancer and its treatments. National Comprehensive Cancer Network (NCCN) guidelines recommend the development of a survivorship care plan (SCP) for cancer patients following completion of treatment with curative intent. Our institution developed a lymphoma survivorship clinic (SC) to assess patient needs, provide education, and create and deliver SCPs. This study analyzed the impact of a SC visit on patient-centered outcomes. METHODS: Surveys were sent to lymphoma patients at Mayo Clinic Rochester within 4 weeks of their post-treatment visit to the SC that queried patient-reported outcomes, including experience of care, quality of life (QOL), and distress. We compared survey responses between those who attended the SC and those who were eligible but did not attend. RESULTS: From November 2013 to May 2015, 236 lymphoma patients were surveyed, 96 of whom had a SC visit and 140 of who were eligible but did not attend. Those who attended the SC were more likely to "definitely" recall discussion on improving health, preventing illness, and making changes in habits/lifestyle, diet, and exercise. There were no differences in QOL or distress. Adjusted analyses revealed that SC attendance was associated with better self-reported overall health among younger patients and better physical well-being in Hodgkin lymphoma patients compared to those with other subtypes of lymphoma. CONCLUSIONS: Participation in the lymphoma SC improved patient education on survivorship issues, particularly health behaviors. There may be a particular benefit in younger patients. However, there were no differences in QOL or distress. Further study is needed to determine if improved survivorship education and SCP delivery leads to long-term health benefits in cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Our study evaluates the clinical impact of a SC in patients treated for lymphoma. We demonstrate that a SC visit improves patient education regarding health behaviors.

Fotemustine, teniposide and dexamethasone versus high-dose methotrexate plus cytarabine in newly diagnosed primary CNS lymphoma: a randomised phase 2 trial.

OBJECTIVE: This prospective, randomized, controlled and open-label clinical trial sought to evaluate the tolerability and efficacy of the FTD regimen (fotemustine, teniposide and dexamethasone) compared to HD-MA therapy (high-dose methotrexate plus cytarabine) and to elucidate some biomarkers that influence outcomes in patients with newly diagnosed primary CNS lymphoma. METHODS: Participants were stratified by IELSG risk score (low versus intermediate versus high) and randomly assigned (1:1) to receive four cycles of FTD or HD-MA regimen. Both regimens were administered every 3 weeks and were followed by whole-brain radiotherapy. The primary endpoints were overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). RESULTS: Between June 2012, and June 2015, 52 patients were enrolled, of whom 49 patients were randomly assigned and analyzed. Of the 49 eligible patients, no significant difference was observed in terms of ORR between FTD (n = 24) and HD-MA (n = 25) groups (88% versus 84%, respectively, P = 0.628). Neither the 2-year PFS nor the 3-year OS rate differed significantly between FTD and HD-MA groups (37% versus 39% for 2-year PFS, P = 0.984; 51% versus 46% for 3-year OS, P = 0.509; respectively). The HD-MA group showed more serious neutropenia (P = 0.009) than the FTD group. High Bcl-6 expression correlated with longer OS (P = 0.038). CONCLUSIONS: FTD chemotherapy appeared to be safe and effective for PCNSL patients. High Bcl-6 expression correlated with longer survival.

More frequent use of health care services among distressed compared with nondistressed survivors of lymphoma and chronic lymphocytic leukemia: Results from the population-based PROFILES registry.

BACKGROUND: Follow-up care for a growing population of survivors of lymphoma and chronic lymphocytic leukemia (CLL) together with the adverse effects these survivors may experience as a result of their cancer and treatment have led to more pressure being placed on health care services. The objectives of the current study were to: 1) compare the use of medical care services by survivors with that of a normative population; 2) evaluate the use of medical and psychosocial care services among distressed and nondistressed survivors; and 3) identify associated sociodemographic and clinical factors. METHODS: Survivors of lymphoma and CLL diagnosed between 1999 and 2012 were selected via the population-based Netherlands Cancer Registry and completed the Hospital Anxiety and Depression Scale questionnaire and questions regarding health care. Outcomes were compared with an age-matched and sex-matched normative population. RESULTS: A total of 1444 survivors responded (69%). Survivors of lymphoma and CLL contacted their general practitioner (3.8 vs 2.3; P<.001) and medical specialist (5.7 vs 1.6; P<.001) more often within the last year compared with a normative population. In addition, psychologically distressed survivors had even more medical contacts and received psychosocial care more often compared with nondistressed survivors. In addition to psychological distress, comorbidity, female sex, and older age were found to be associated with a greater use of medical services, whereas younger age was associated with receiving psychosocial care. CONCLUSIONS: Survivors of lymphoma and CLL, especially those who are psychologically distressed, report an increased use of health care services compared with a normative population. Further studies are needed to explore whether the use of widely applicable psychosocial interventions could reduce the frequency of medical contacts. Cancer 2018;124:3016-24. © 2018 Netherlands Comprehensive Cancer Organisation. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

The clinical manifestation, survival outcome and predictive prognostic factors of 137 patients with primary gastrointestinal lymphoma (PGIL): Strobe compliant.

This retrospective study aimed to investigate clinical characteristics and prognostic factors in patients with primary gastrointestinal lymphoma (PGIL) of Chinese population.From January 2001 to December 2015, 137 patients diagnosed with PGIL were recruited. The clinical features, treatment, and follow-up information were analysed.The median patient age was 62.3 years. With 18.47 months follow-up, the 2-year progress-free survival and overall survival rate was 74.9% and 75.5%, respectively. The overall response rate was 33.6%. Age≥60 years, advanced Lugano staging (≥stage IIE), elevated lactate dehydrogenase (LDH) levels, ≥2 extra-nodal involved sites, National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI)≥4, Ki-67≥50% were associated with worse prognosis in univariate analysis (P < .05). By multivariate analyses, we determined that the involvement of extra-nodal involved sites was the only statistically significant poor prognostic factor in PGIL.Age, staging, LDH levels, NCCN-IPI, Ki-67 especially involvement of multiple extra-nodal sites were associated with poor overall survival of PGIL.

Malignancy Risk and Recurrence with Psoriasis and its Treatments: A Concise Update.

Psoriasis is a common inflammatory cutaneous disease that affects approximately 120 million people worldwide. Systemic treatments have significantly improved disease burden, but concerns persist regarding their association with increased risk of malignancy. Patients with psoriasis have a slightly elevated baseline risk of lymphoproliferative diseases. Studies on methotrexate and cyclosporine, as well as older biological agents such as tumor necrosis factor inhibitors, have found no increased risk of non-cutaneous solid tumors; however, positive associations between cutaneous squamous cell carcinomas and certain therapies have been found. There is conflicting evidence regarding the risk of lymphoma and melanoma. Further studies are needed to determine the long-term safety of newer psoriasis treatments (interleukin [IL]-12/23, IL-17, Janus kinase 1/3, and phosphodiesterase-4 inhibitors), specifically their safety in patients with a history of cancer. This review summarizes the most recent studies on malignancy risk from psoriasis, and its treatments in patients and cancer survivors, with the highest available level of evidence.

Incidence of hematologic malignancy and cause-specific mortality in the Women's Health Initiative randomized controlled trial of calcium and vitamin D supplementation.

BACKGROUND: Prior evidence of a possible link between vitamin D status and hematologic malignancy (HM) in humans comes from observational studies, leaving unresolved the question of whether a true causal relationship exists. METHODS: The authors performed a secondary analysis of data from the Women's Health Initiative Calcium/Vitamin D (CaD) trial, a large randomized controlled trial of CaD supplementation compared with placebo in older women. Kaplan-Meier and Cox proportional hazards survival analysis methods were used to evaluate the relationship between treatment assignment and 1) incident HM and 2) HM-specific mortality over 10 years following randomization. HMs were classified by cell type (lymphoid, myeloid, or plasma cell) and analyzed as distinct endpoints in secondary analyses. RESULTS: A total of 34,763 Women's Health Initiative CaD trial participants (median age, 63 years) had complete baseline covariate data and were eligible for analysis. Women assigned to CaD supplementation had a significantly lower risk of incident HM (hazard ratio [HR], 0.80; 95% confidence interval [95% CI], 0.65-0.99) but not HM-specific mortality (HR, 0.77 [95% CI, 0.53-1.11] for the entire cohort; and HR, 1.03 [95% CI, 0.70-1.51] among incident HM cases after diagnosis). In secondary analyses, protective associations were found to be most robust for lymphoid malignancies, with HRs of 0.77 (95% CI, 0.59-1.01) and 0.46 (95% CI, 0.24-0.89), respectively, for cancer incidence and mortality in those assigned to CaD supplementation. CONCLUSIONS: The current post hoc analysis of data from a large and well-executed randomized controlled trial demonstrates a protective association between modest CaD supplementation and HM risk in older women. Additional research concerning the relationship between vitamin D and HM is warranted. Cancer 2017;123:4168-4177. © 2017 American Cancer Society.

Comparative toxicities of 3 platinum-containing chemotherapy regimens in relapsed/refractory lymphoma patients.

Optimal salvage chemotherapy regimen for patients with relapsed or refractory Hodgkin and non-Hodgkin lymphoma remains unclear but often based on platinum regimens. This retrospective study assesses in real life the toxicities profiles of patients with relapsed or refractory lymphoma treated with DHA (dexamethasone, high dose aracytine cytarabine) plus platinum salt (dexamethasone-High dose aracytine (cis)platin (DHAP), dexamethasone-High dose aracytine carboplatin (DHAC), or dexamethasone-High dose aracytine Oxaliplatin (DHAOX)), from February 2007 to May 2013 in 2 French hospitals. Toxicities were recorded from medical files and assessed according to the National Cancer Institute Common Toxicity Criteria version 3.0. Potential risk factors of renal insufficiency were tested by univariate analyses. A total of 276 patients were treated: 168 with DHAP (60.9%), 79 with DHAOX (28.6%), and 29 with DHAC (10.5%). Rituximab was associated in 80.1% of patients (n = 221). Renal failure was reported in 97 patients, mainly with cisplatin regimen (86.6%) leading to 8.9% grade III to IV renal failure (P = .001). Renal insufficiency was reversible in most patients but remained persistent in 24, with all of them being treated with DHAP except 1. Cisplatin-based regimen (50.0% versus 12.0%, P < .05) and female (44.6% versus 29.7%, P < .05) appeared to be at higher risks of renal failure. Platinum cumulative dose is a significant risk factor of nephrotoxicity. Hematologic toxicity was more frequent with carboplatin and cisplatin with at least 1 event (all toxicity grade) respectively in 79.3% and 71.4% of patients treated (P < .005). Auditory toxicity was mainly reported with cisplatin (n = 19; 4 grade I-II and 15 grade III-IV). Oxaliplatin was implicated in 77.6% of neurotoxicity (n = 59), mainly moderate (grade I-II). In conclusion, DHAOX and DHAC regimens have more favorable toxicity profile than DHAP regimen. Their lack of renal toxicity makes them attractive regimens, which may be interesting for patients eligible for autologous stem cell transplantation. Nevertheless, these results have to be confirmed by the therapeutic efficacy of these 3 regimens.

Richter's syndrome: Novel and promising therapeutic alternatives.

Richter's syndrome (RS) is the development of an aggressive lymphoma in patients with a previous or concomitant diagnosis of chronic lymphocytic leukemia (CLL). The incidence rate for RS is ∼0.5% per year of observation. In the presence of clinical suspicious of RS, diagnosis of transformation and choice of the site of biopsy may take advantage of 18FDG PET/CT. Molecular lesions of tumor suppression regulators (TP53), cell cycle (CDKN2A) and cell proliferation (NOTCH1, MYC) overall account for ∼90% of RS and may be responsible for its aggressive clinical phenotype. The prognosis of RS is generally highly unfavorable. However, the pattern of survival is not homogeneous and the clonal relationship between the CLL and the aggressive lymphoma clones is the most important prognostic factor. Rituximab-containing polychemotherapy represents the back-bone for induction treatment in RS. Younger patients who respond to induction therapy should be offered stem cell transplant to prolong survival.

Lymphomatoid papulosis: Treatment response and associated lymphomas in a study of 180 patients.

BACKGROUND: Lymphomatoid papulosis (LyP) is a CD30(+) lymphoproliferative disorder, with a self-regressing clinical course and malignant histopathology. OBJECTIVE: The aim of this study was to evaluate characteristics, risk factors, associated malignancies, long-term outcome, and treatment of LyP in a large cohort representing the experience of the MD Anderson Cancer Center. METHODS: Patient charts and clinical and histopathologic data of 180 patients with LyP were retrospectively assessed. RESULTS: A total of 56.7% of patients was men. Histologic subtype A was found in 47.2%, type B in 17.2%, type C in 22.8%, type D in 7.8%, type E in 0.6%, and mixed subtype in 4.4% of the patients. One hundred fourteen lymphomas were observed in 93 patients, with mycosis fungoides (61.4%) and anaplastic large cell lymphoma (26.3%) being the most common forms. Risk factors for development of lymphoma included sex and histologic subtype. Number of lesions and symptom severity were not associated with lymphoma development. Patients with type D were less likely to have lymphomas. Treatment provided symptomatic relief but did not prevent progression to lymphoma. LIMITATIONS: The limitation of this study is the retrospective study design. CONCLUSION: Patients with LyP are at increased risk of associated lymphomas. Thorough patient counseling is needed and long follow-up periods are required to detect and treat secondary lymphomas.

Treatment of Primary Central Nervous System Lymphoma with High-dose Methotrexate and Radiotherapy in HIV-negative Patients.

BACKGROUND: We assessed the outcome of high-dose methotrexate (HD-MTX) chemotherapy with or without radiotherapy (RT) in primary central nervous system lymphoma (PCNSL) patients. METHODS: Fifty-one HIV-negative patients with an average age of 50.3 years were treated with chemotherapy regimen included 2500 mg/m(2) MTX with Leucovorin rescue and 1.4 mg/m(2) vincristine (day two), which was administered every other week for 6 weeks. Only the patients who were younger than 60 years received RT. All patients received two cycles of 3000 mg/m(2) cytarabine at the end of the treatment for two successive days. RESULTS: Diffuse large B-cell lymphoma was the most common histologic subtype (90.2%), and twenty-six (51.0%)patients had multiple brain lesions. The median survival of patients who were younger than 60 years was 37 months. For patients who were older than 60 years, the median survival was 20 months. The median survival of men and women were 30 and 34 months, respectively. There was no significant difference in survival of patients in terms of age and sex. Overall, sixteen patients (31%) out of fifty-one patients died, five of them were older than 60 years and eleven were younger than 60 years. Twenty-five (49%) of all patients experienced relapse, and 10 (40%) of them died after rechemotherapy. CONCLUSIONS: The base of our chemotherapy regimen was HD-MTX as the regular doses of MTX cannot penetrate the blood brain barrier (BBB). Our results indicated that the combination of HD-MTX with RT may not influence the outcome of PCNSL; thus, RT cannot be the first line therapy.

Models of survivorship care provision in adult patients with haematological cancer: an integrative literature review.

PURPOSE: Increasing numbers of haematology cancer survivors warrants identification of the most effective model of survivorship care to survivors from a diverse range of haematological cancers with aggressive treatment regimens. This review aimed to identify models of survivorship care to support the needs of haematology cancer survivors. METHOD: An integrative literature review method utilised a search of electronic databases (CINAHL, Medline, PsycInfo, PubMed, EMBASE, PsycArticles, and Cochrane Library) for eligible articles (up to July 2014). Articles were included if they proposed or reported the use of a model of care for haematology cancer survivors. RESULTS: Fourteen articles were included in this review. Eight articles proposed and described models of care, and six reported the use of a range of survivorship models of care in haematology cancer survivors. No randomised controlled trials or literature reviews were found to have been undertaken specifically with this cohort of cancer survivors. There was variation in the models described and who provided the survivorship care. CONCLUSION: Due to the lack of studies evaluating the effectiveness of models of care, it is difficult to determine the best model of care for haematology cancer survivors. Many different models of care are being put into practice before robust research is conducted. Therefore, well-designed high-quality pragmatic randomised controlled trials are required to inform clinical practice.

Acacia ferruginea inhibits tumor progression by regulating inflammatory mediators-(TNF-a, iNOS, COX-2, IL-1ß, IL-6, IFN-γ, IL-2, GM-CSF) and pro-angiogenic growth factor- VEGF.

The aim of the present investigation was to evaluate the effect of A ferruginea extract on Dalton's lymphoma ascites (DLA) induced tumours in BALB/c mice. Experimental animals received A ferruginea extract (10 mg/ kg.b.wt) intraperitoneally for 14 consecutive days after DLA tumor challenge. Treatment with extract significantly increased the life span, total white blood cell (WBC) count and haemoglobin (Hb) content and decreased the level of serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (γ-GT) and nitric oxide (NO) in DLA bearing ascites tumor models. In addition, administration of extract significantly decreased the tumour volume and body weight in a DLA bearing solid tumor model. The levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and granulocyte monocyte-colony stimulating factor (GM-CSF), as well as pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) were elevated in solid tumour controls, but significantly reduced by A ferruginea administration. On the other hand, the extract stimulated the production of interleukin-2 (IL-2) and interferon-gamma (IFN-γ) in animals with DLA induced solid tumours. Increase in CD4+ T-cell population suggested strong immunostimulant activity for this extract. GC/MS and LC/MS analysis showed quinone, quinoline, imidazolidine, pyrrolidine, cyclopentenone, thiazole, pyrazole, catechin and coumarin derivatives as major compounds present in the A ferruginea methanolic extract. Thus, the outcome of the present study suggests that A ferruginea extract has immunomodulatory and tumor inhibitory activities and has the potential to be developed as a natural anticancer agent.

Developing a nurse-led survivorship service for patients with lymphoma.

PURPOSE: There are two million people in the UK living with cancer and this figure is rising each year. The consequences of cancer and its treatment are devastating and many patients suffer long-term effects for years after completion of treatment. National UK policy recognises that current follow-up fails to meet patients' survivorship needs and new methods of service-delivery are required. An analysis of local service provision in a London teaching hospital demonstrated that the needs of patients with lymphoma were not being met. The aim of this project was to develop a nurse-led service that would provide comprehensive survivorship care for patients with lymphoma. METHOD: A nurse-led survivorship service was implemented using a comprehensive service development framework and was evaluated through a variety of methods such as a patient satisfaction questionnaire, note audit, waiting time audit and an analysis of patients comment and suggestions. RESULTS: The project was successfully implemented with risk management and advanced practice requirements addressed. It was demonstrated that patients were satisfied with the new service, the quality of documentation had improved and waiting times were reduced. CONCLUSION: This work adds to the current survivorship knowledge-base and provides evidence that nurses can provide safe and effective survivorship care for patients with lymphoma.

Orbital lymphoma: diagnostic approach and treatment outcome.

BACKGROUND: Lymphomas of the orbit and orbital adnexae are rare tumors, comprising only 1% of all non-Hodgkin's lymphoma. The majority of non-Hodgkin's lymphomas of the orbit are extranodal marginal-zone B-cell lymphomas of mucosa-associated lymphoid tissue type. Because of nonspecific clinical signs and symptoms, some diagnostic delay may occur. The purpose of the study was to evaluate the diagnostic approach in orbital lymphomas and to analyze their treatment outcome. METHODS: In the period from 2005 to 2012, from a group of 135 patients with tumors of the orbit, we identified 11 patients diagnosed with orbital lymphoma. This patient cohort was reviewed retrospectively. RESULTS: The patient group consisted of 11 patients (seven females, male males) with a median age of 57.7 years (range 42 to 88 years). Orbital swelling, pain and motility impairment were the leading clinical symptoms. Diagnosis was confirmed by surgical biopsy. Depending on the anatomic location of the tumor, a surgical biopsy was taken using a blepharoplasty incision, a lateral orbitotomy or a navigation-guided biopsy. The predominant histology was extranodal non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue type (82%). All patients underwent complete clinical staging. These were clinical stage IEA in seven patients, and stages IIEA (n = 2) and IIIEA (n = 2) in four patients . Patients in stage IEA were treated with radiation therapy alone, with radiation doses between 25 and 40 Gy, and patients with stage IIEA received systemic chemotherapy with bendamustin/rituximab. Those two patients diagnosed with diffuse large B-cell lymphoma and mantle cell lymphoma received systemic chemotherapy according to the R-CHOP protocol. CONCLUSIONS: Owing to unspecific clinical symptoms, some diagnostic delay may occur in orbital lymphoma. If unspecific orbital symptoms are present, adequate imaging studies followed by early surgical biopsy will contribute to early diagnosis. Once diagnosis is established and staging is complete, radiation therapy is the recommended treatment for stage IEA patients. Systemic chemotherapy is indicated in selected stage IIEA patients and in patients with stage IIIEA disease.

Cytotoxic podophyllotoxin type-lignans from the steam bark of Bursera fagaroides var. fagaroides.

The hydroalcoholic extract of the steam bark of B. fagaroides var. fagaroides displayed potent cytotoxic activity against four cancer cell lines, namely KB (ED50 = 9.6 × 10(-2) µg/mL), PC-3 (ED50 = 2.5 × 10(-1) µg/mL), MCF-7 (ED50 = 6.6 µg/mL), and HF-6 (ED50 = 7.1 × 10(-3) µg/mL). This extract also showed anti-tumour activity when assayed on mice inoculated with L5178Y lymphoma cells. Bioactivity-directed isolation of this extract, afforded seven podophyllotoxin-type lignans identified as podophyllotoxin (1), ß-peltatin-A-methylether (2), 5'-desmethoxy-ß-peltatin-A-methylether (3), desmethoxy-yatein (4), desoxypodophyllotoxin (5), burseranin (6), and acetyl podophyllotoxin (7) by 1D and 2DNMR and FAB-MS analyses, and comparison with reported values. All the isolated compounds showed potent cytotoxic activity in the cell lines tested, especially compound 3, which exhibited greater activity than camptothecin and podophyllotoxin against PC-3 (ED50= 1.0 × 10(-5) µg/mL), and KB (ED50 = 1.0 × 10(-5) µg/mL). This is the first report of the isolation of podophyllotoxin and its acetate in a Bursera species.

The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 55 cases of lymphomas.

OBJECTIVES: Lymphomas are the main form of haematological neoplasms, representing 55.6% of all tumours of the blood. Overall, they account for 5.3% of all malignant tumours (excluding basal and squamous cell skin cancer) in Italy with a prevalence constantly increasing at a rate of 3% per year. From a histological point of view, they represent a vast heterogeneous group of haematological diseases, their staging being based on defined cyto-morphological and anatomo-pathological criteria. Although the combined use of standard approaches can provide good response rates, recurrence is particularly frequent in patients undergoing traditional treatment, with critical and often irreversible side effects such as myelosuppression and a high frequency of opportunistic infections and sterility. Numerous epidemiological studies and preclinical data have for some time now reported the anticancer effects of molecules such as Melatonin, Retinoids, Vitamins E, D3, and C, Somatostatin and prolactin inhibitors in neoplastic diseases. There are, however, very few publications on the combined effects of these substances in vivo. METHODS: We report an observational study carried out on 55 patients affected by various forms of lymphoma, treated with the biological therapy known as the Di Bella Method (DBM). The 1, 3 and 5-year survival rates are reported, together with any signs of toxicity. RESULTS: The DBM treatment achieved partial or complete objective responses in a shorter time and in greater percentages if administered as first-line therapy. The adjuvant treatment increased survival time and improved quality of life with respect to the data reported in the literature for the same types and stages of lymphoma. CONCLUSION: Overall, the treatment was well tolerated, with minor and transient side effects. The patients were able to continue the treatment at home, carrying out their normal activities without problems.