Non-cancer death causes after ovarian cancer diagnosis: A population-based cohort.

BACKGROUND: Research on non-cancer death causes in ovarian cancer (OC) patients remains limited. We aim to focus on and evaluate the non-cancer death causes after OC diagnosis. METHODS: We studied 82 590 OC patients diagnosed between 2000 and 2016, using the Surveillance, Epidemiology, and End Results (SEER) Program. Risks of death causes were calculated as standardized mortality ratios. RESULTS: Of included patients, 48 125 (58.3%) died during the follow-up period. The highest number of deaths, 21 722 (45.1%), occurred within 1-5 years after OC diagnosis. On the other hand, 19 992 (41.5%) of deaths occurred within a year from ovary cancer diagnosis, 5255 (10.9%) occurred within 5-10 years, and 1156 (2.4%) deaths occurred after more than 10 years following OC diagnosis. Non-cancer death causes comprise a significant percentage of deaths in OC patients, increasing with time after diagnosis. CONCLUSIONS: Cardiac diseases, cerebrovascular diseases, and COPD were among the most common non-cancer death causes after OC diagnosis. Other critical non-cancer death causes include septicemia and benign neoplasms. Mortality risk differences based on race and age were also highlighted. These findings provide critical insights into how OC survivors should be followed-up and counseled for relevant future health risks.

Circulating long non-coding RNAs HOTAIR, Linc-p21, GAS5 and XIST expression profiles in diffuse large B-cell lymphoma: association with R-CHOP responsiveness.

The reliable identification of diffuse large B-cell lymphoma (DLBCL)-specific targets owns huge implications for its diagnosis and treatment. Long non-coding RNAs (lncRNAs) are implicated in DLBCL pathogenesis; however, circulating DLBCL-related lncRNAs are barely investigated. We investigated plasma lncRNAs; HOTAIR, Linc-p21, GAS5 and XIST as biomarkers for DLBCL diagnosis and responsiveness to R-CHOP therapy. Eighty-four DLBCL patients and thirty-three healthy controls were included. Only plasma HOTAIR, XIST and GAS5 were differentially expressed in DLBCL patients compared to controls. Pretreatment plasma HOTAIR was higher, whereas GAS5 was lower in non-responders than responders to R-CHOP. Plasma GAS5 demonstrated superior diagnostic accuracy (AUC = 0.97) whereas a panel of HOTAIR + GAS5 superiorly discriminated responders from non-responders by ROC analysis. In multivariate analysis, HOTAIR was an independent predictor of non-response. Among patients, plasma HOTAIR, Linc-p21 and XIST were correlated. Plasma GAS5 negatively correlated with International Prognostic Index, whereas HOTAIR positively correlated with performance status, denoting their prognostic potential. We constructed the lncRNAs-related protein-protein interaction networks linked to drug response via bioinformatics analysis. In conclusion, we introduce plasma HOTAIR, GAS5 and XIST as potential non-invasive diagnostic tools for DLBCL, and pretreatment HOTAIR and GAS5 as candidates for evaluating therapy response, with HOTAIR as a predictor of R-CHOP failure. We provide novel surrogates for future predictive studies in personalized medicine.

The Emerging Treatment Options of Plasmablastic Lymphoma: Analysis of 173 Individual Patient Outcomes.

Plasmablastic lymphoma (PBL) is a newly recognized aggressive subtype of non-Hodgkin lymphoma. Its rarity hinders testing effective treatment options in clinical trials. We conducted a systematic review of PubMed and our internal records to retrieve patients with a PBL diagnosis with evaluable treatment outcomes. Aggressive chemotherapy was defined as more intense regimens than CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). We compiled a meta-dataset of 173 patients. The median age at diagnosis was 48.5 years, 75% of patients were male, and stages III/IV accounted for 47% of the cohort. Of 138 patients with known response status after first-line chemotherapy, 63 (45%) achieved a complete response with a 2-year relapse-free survival of 71.6%. Sixty-nine (50%) patients received first-line CHOP. There was no significant difference in the objective response rate among the 2 most commonly used regimens, CHOP and DA-EPOCH (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) (69% vs. 79%; P = .4). The median follow-up was 9 months, and the 2-year overall survival (OS) was 47.4%. A univariate analysis identified factors associated with worse OS, including stage III/IV (hazard ratio [HR], 2.82; P < .001), human herpes virus-8-positive (HR, 3.30; P = .01), bone marrow (HR, 1.07; P = .035), and cardiorespiratory involvement (HR, 2.26; P = .015). Meanwhile, Epstein-Varr virus-encoded small RNA-positivity (HR, 0.31; P < .001) and involvement of head and neck (HR, 0.44; P = .009) were associated with better OS. Multivariate analysis showed that aggressive chemotherapy was significantly associated with better OS (HR, 0.22; P = .016). Patients with PBL with high-risk features, such as advanced stage, human herpes virus-8-positivity, bone marrow, and cardiorespiratory involvement, require more aggressive chemotherapy. Bortezomib and lenalidomide are promising add-on agents.

Cimetidine a promising radio-protective agent through modulating Bax/Bcl2 ratio: An in vivo study in male rats.

Radiotherapy is one of the most effective modalities for treatment of neoplastic diseases. Radiation damage is to a large extent caused by overproduction of reactive oxygen species. To improve the therapeutic index, identifying effective substances for prevention or treatment of postirradiation intestinal and bone marrow injury should be prompted. This study was designed to evaluate the protective effects of cimetidine on the in rats exposed to γ-irradiation (5 Gy) and exploring the B-cell lymphoma 2 (Bcl2)/Bcl2 associated X (bax) pathway as a probable underlying mechanism. Eighteen adult male rats were randomly grouped into three: control, untreated irradiated rats, and irradiated rats pretreated with cimetidine. Seven days postirradiation the rats were culled, the bone marrow (BM) and jejunum tissue samples were collected for biochemical, histological, and immunohistological evaluation of BM cell count (BMCs), intestinal fibrosis, oxidative stress, tumor necrosis factor-α, Bcl2, and Bax. Cimetidine pretreatment significantly reversed the loss of BMCs, intestinal lining destruction, and fibrosis seen in the untreated irradiated rats and significantly decreased the underlying oxidative stress, inflammation, and Bax/Bcl2 ratio. There was a significant differential correlation between Bax/Bcl2 ratio, tissue oxidative stress level, and tissue injury. Cimetidine represents a very promising radioprotective agent with a potential differential beneficial effect on both cancer cells (inducing apoptosis) as previously proved through different studies and adjacent healthy cells (providing radioprotection via inhibiting apoptosis) as clearly demonstrated through this study, via its antioxidant effect and subsequent regulation of type 2 apoptotic pathway through modulation of Bax/Bcl2 ratio.

Evaluation of target volume margins for radiotherapy of prostate implanted with fiducial markers.

The planning target volume (PTV) depends on the method of radiotherapy guidance. This study aimed to measure the systemic and random errors using an online marker matching and offline bone structure matching to estimate PTVmarker, PTVbone, or PTVlaser for treatment verification and radiotherapy guidance, especially in centers lacking radiotherapy fiducial markers (FMs). Thirty patients with localized prostate cancer who were treated with FM-based dose escalation protocol were included. The initial set-up was done with laser marks and daily megavoltage images were acquired. The systematic and random errors were calculated. PTVmarker, defined as the sum of maximum marker migration, and PTV calculated to compensate for the difference between online marker matching and offline analysis of marker matching. PTVmarker was added to estimated PTV from online marker matching to obtain PTVlaser. PTVskin marks migration, was calculated and deducted from PTVlaser to acquire PTVbone. The mean maximum marker migration was 2 ± 1.2 mm. The resultant values of PTVmarker were 2.7 ± 0.6 mm, 3.3 ± 1.1 mm, and 4.4 ± 2.2 mm, in the lateral (lat.), longitudinal (long) & vertical (vert.) directions, respectively, whereas values of PTVlaser were 13 ± 0.6 mm, 17.7 ± 1.1 mm, and 15.8 ± 2.2 mm, and PTVbone were 5.9 ± 0.6 mm, 8.6 ± 1.1 mm, 7.2 ± 2.2 mm, respectively, in the lat., long., and vert. directions. Our results show that PTV needed with FM-based image guidance ranged between 3 and 4 mm in the three cardinal directions, was 10 mm smaller than that required with laser skin marks guidance, and narrower by 5 mm compared to that obtained by offline bone structure image matching.

Availability of Informal Caregivers for Palliative Care Patients with Cancer: Is there a Difference between Higher- and Lower-Income Settings.

OBJECTIVE: Family caregivers are the default caring personnel for terminal cancer patients. The characteristics, demographics, distribution, psychological burden, and socioeconomic standards differ between high- and low-income countries. We aimed to assess those factors and their direct reflection on both the patient and the caregiver. PATIENTS AND METHODS: This is a comparative cross-sectional study for terminal cancer patients in the palliative care unit between the United Kingdom (UK) as a high-income community and Egypt as a low-income community. We assessed the different characteristics, demographics, living place, the degree of relevance, and the availability of caregivers. RESULTS: We have recruited 216 patients from the UK and 117 patients from Egypt. Informal caregivers were available in 74.5% and 92.3% for these patients with a mean age of 71.5 (standard deviation [SD] 16) years and 50.9 (SD 15.18) years, respectively. There has been a statistically significant difference between the two countries' caregivers in being married, family, and living in the same household (P < 0.0001). CONCLUSION: Low-income countries are more common to have an informal caregiver who is a family member of different degree of relevance. Caregivers in low-income settings tend to be younger, of the female gender, married, and living in the same household than in high-income ones.

Validity of a new immunochromatographic test in detection of Toxoplasma gondii in cancer patients.

Screening of toxoplasmosis in cancer patients is mandatory especially before starting treatment to guard against life-threatening disseminated disease. Diagnosis of toxoplasmosis rely mainly on serology. The most widely used method for detection of anti-Toxoplasma gondii (T. gondii) antibodies is the enzyme linked immunosorbent assay (ELISA), being available and reliable. Immunochromatographic tests (ICT) attracted a lot of attention recently being one of the high quality, rapid and easy to perform tests. Available data comparing the performance of ICT versus ELISA techniques have yielded inconsistent results and none compared their performance among the immunocompromised cancer patients. Therefore, we designed this study to compare the performance of a new ICT (the OnSite Toxo IgG/IgM Combo Rapid test) and ELISA techniques for the detection of anti-T. gondii antibody as a tool for screening for toxoplasmosis among cancer patients in Cairo-Egypt. Among 180 cancer patients, a total of 110 patients (61.1%) were positive for anti-T. gondii antibodies by one or both methods. Agreement between both methods was found in 78.8% of the samples. By using ELISA technique as a gold standard test for the detection of anti-T. gondii antibodies, our results showed 87.5% specificity and 74% sensitivity of ICT technique. Moreover, our results proved that ICT is more sensitive in detecting lower level of antibodies than ELISA, that makes it preferable as a screening test for the immunocompromised patients.

Safety issues with the ALK inhibitors in the treatment of NSCLC: A systematic review.

INTRODUCTION: Oral tyrosine kinase inhibitors targeting the chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) in non-small cell lung cancer (NSCLC) were associated with superior clinical outcome. Tyrosine Kinase inhibitors (TKIs) are known to have peculiar toxicity profile, hence, increasing awareness to the safety profile of ALK inhibitors is essential. METHODS: A comprehensive systematic review of literature has been conducted to include prospective trials that used the ALK inhibitors Crizotinib, Ceritinib, Alectinib, Brigatinib and Lorlatinib in patients with advanced NSCLC and have available efficacy and toxicity results. RESULTS: A total of 14 studies including 2793 patients were considered eligible for our review and included two phase IB, seven phase II and five phase III studies. The most common adverse events (AEs) observed with ALK inhibitors were gastrointestinal (GI) toxicities as nausea (up to 83%), vomiting (up to 67%) and diarrhea (up to 86%), elevation of liver enzymes occurred in up to 60% and fatigue (up to 43%). There were differences in the toxicity patterns between the different ALK inhibitors with more GI and hepatic toxicities with Ceritinib, more visual disorders with Crizotinib, more dysgeusia with crizotinib and Alectinib and possibly more respiratory complications with Brigatinib. Most of the AEs were low grade and treatment-related deaths were associated with ALK inhibitors in 0-1% of patients. CONCLUSION: Most of adverse effects of ALKi can be managed efficiently via dose modifications or interruptions. Timely identification of each ALKi pattern of toxicity can prevent treatment-related morbidity and mortality in this palliative setting.

Safety of Vinflunine in Patients with Advanced Urothelial Carcinoma Refractory to Platinum-based Chemotherapy: A Prospective Pilot Study.

BACKGROUND: Several single chemotherapeutic agents have been evaluated as the second-line treatment of advanced urothelial carcinoma. Despite encouraging efficacy outcomes, toxicity has often led to dose modifications or discontinuation. We aimed to assess the safety of vinflunine in a particular population of advanced transitional cell carcinoma of urothelium (TCCU), that were exposed to the previous toxicity of chemotherapy. METHODS: This is an open-label, prospective, single-center pilot study to evaluate the response rate and safety profile of vinflunine in patients with advanced TCCU. It was planned to enroll 25 evaluable patients. Eligible patients are those with progressive disease after first-line platinum-based regimen for advanced or metastatic disease. RESULTS: The study was prematurely closed due to two sudden deaths that were judged by the review board as treatment-related. Only ten patients were evaluated and received at least one cycle of vinflunine. All but one were male and seven underwent radical surgery. Eight had a distant metastasis (mainly lung and/or liver). Disease control rate was 40%, four patients had a partial response with median duration of response of 3.5 months. The median overall survival was 3.2 months (95% CI:1.67- 4.73). There were three serious adverse events namely two sudden deaths and one grade 4 thrombocytopenia. Nine grade 3/4 adverse events occurred. The most common all-grade adverse events were fatigue (50%), constipation (40%) and vomiting (40%). Moreover, grade 3 fatigue occurred in 30% of patients. Only one patient, who achieved PR for 5 months, was fit to receive further cytotoxic chemotherapy. CONCLUSION: The activity of vinflunine in advanced urothelial carcinoma came at the expense of its safety. The use of vinflunine has to be limited to the selected group of patients. However, this is a single institute experience in a limited number of patients.

Toxoplasmosis an Overlooked Disease: Seroprevalence in Cancer Patients

Background: Toxoplasmosis is one of the most important cosmopolitan life-threatening diseases in immune-compromised patients. It is caused by an intracellular protozoon: Toxoplasma gondii (T. gondii). The parasite can cause pneumonia, encephalitis or disseminated disease in immune-deficient patients and dangerous congenital anomalies in infants born to mothers infected during early pregnancies. The present study aims to evaluate the prevalence of toxoplasmosis in Egyptian cancer patients and to correlate the prevalence with type of malignancy and the different cancer treatment modalities. Materials and Methods: Blood samples from 150 cancer patients and 50 control subjects have been examined for presence of anti-toxoplasma antibodies using a lateral flow chromatographic immunoassay. Results: Among cancer patients included in this study, the prevalence of anti- T.gondii antibodies was 20% for IgG and 4% for IgM, while in the control group it was 8% and 2% in the same order. This difference was statistically significant for IgG (P =0.003) but not for IgM (P = 0.44). Patients with solid organ tumors treated with chemotherapy had the highest prevalence rate of toxoplasmosis (28%). It was also found higher in males (26%) than females (10%) and higher among urban (18%) than rural dwellers (16%). Conclusion: Cancer patients showed a significantly higher rate of infection with T. gondii than their cross-matched control. For that reason, we recommend the inclusion of a screening test for toxoplasmosis in their routine workup.

Transabdominal ultrasonographic features in the diagnosis of gastrointestinal lymphoma.

BACKGROUND: Gastrointestinal (GI) lymphoma is a challenging disease. We aimed to study and characterize the different endoscopic and transabdominal ultrasonography (TUS) features of gut lymphoma and to assess whether TUS has a complementary role to endoscopy in the diagnosis of GI lymphoma. METHODS: This study was conducted on 21 patients with GI lymphoma, attending the GI endoscopy and liver unit, Endemic Medicine Department and Oncology Department in Kasr El Aini Hospital, Cairo University. Patients were subjected to GI endoscopy (upper endoscopy & colonoscopy) and transabdominal ultrasonography. The diagnosis was finally based on histopathology of core biopsies (obtained either endoscopically or by ultrasonography) and immuno-histochemistry. RESULTS: In all 21 patients with GI lymphoma included in this study, TUS could accurately determine the site of disease affection compared to endoscopy which is considered the gold standard for site localization. The main TUS pathologic features detected were increased wall thickness of the affected bowel segment with a mean value of (15.6±5.9 mm) and loss of layering pattern in 16 patients (76%). While the most common endoscopic features were ulcers and mass lesions accounting for 38% of the patients for each. Diffuse large B-cell lymphoma was found in 19 patients (90%). Because of endoscopic biopsies were conclusive in 14 patients (67%), TUS guided biopsy was resorted to in 7 patients and was diagnostic in all of them. CONCLUSIONS: Transabdominal ultrasonography is a useful tool in the diagnosis of GI lymphoma that is complementary to conventional diagnostic endoscopic procedures.

Predicting Brain Metastasis in Breast Cancer Patients: Stage Versus Biology.

BACKGROUND: Brain metastasis (BM) is a life-threatening event in breast cancer patients. Identifying patients at a high risk for BM can help to adopt screening programs and test preventive interventions. We tried to identify the incidence of BM in different stages and subtypes of breast cancer. PATIENTS AND METHODS: We reviewed the clinical records of 2193 consecutive breast cancer patients who presented between January 1999 and December 2010. We explored the incidence of BM in relation to standard clinicopathological factors, and determined the cumulative risk of BM according to the disease stage and phenotype. RESULTS: Of the 2193 included women, 160 (7.3%) developed BM at a median follow-up of 5.8 years. Age younger than 60 years (P = .015), larger tumors (P = .004), lymph node (LN) positivity (P < .001), high tumor grade (P = .012), and HER2 positivity (P < .001) were associated with higher incidence of BM in the whole population. In patients who presented with locoregional disease, 3 factors independently predicted BM: large tumors (hazard ratio [HR], 3.60; 95% confidence interval [CI], 1.54-8.38; P = .003), axillary LN metastasis (HR, 4.03; 95% CI, 1.91-8.52; P < .001), and HER2 positivity (HR, 1.89; 95% CI, 1.0-3.41; P = .049). A Brain Relapse Index was formulated using those 3 factors, with 5-year cumulative incidence of BM of 19.2% in those having the 2 or 3 risk factors versus 2.5% in those with no or 1 risk factor (P < .001). In metastatic patients, 3 factors were associated with higher risk of BM: HER2 positivity (P = .007), shorter relapse-free interval (P < .001), and lung metastasis (P < .001). CONCLUSION: Disease stage and biological subtypes predict the risk for BM and subsequent treatment outcome.

Addition of 3-day aprepitant to ondansetron and dexamethasone for prophylaxis of chemotherapy-induced nausea and vomiting among patients with diffuse large B cell lymphoma receiving 5-day cisplatin-based chemotherapy.

BACKGROUND: Neurokinin-1 receptor antagonists, such as aprepitant are currently emerging as powerful prophylactic agents for chemotherapy-induced nausea and vomiting (CINV). Therefore, it is important to adjust the anti-emetic regimens based on personal risk factors of the patient, duration of the chemotherapy regimen and cost-effectiveness. PURPOSE: To determine the efficacy of the 3-day aprepitant along with ondansetron and dexamethasone in controlling CINV in patients with large B cell lymphoma receiving multiday-cisplatin regimen chemotherapy. METHODS: This is a pilot prospective cross-over trial. Patients were allocated to either aprepitant 125mg on day 1 and 80mg on days 2 & 3 or placebo in the first 2 cycles, with crossover to the opposite treatment in the 3rd and 4th cycles. The primary end point was complete response (CR) of both acute (days 1-5) and delayed (days 6-8) CINV. CR means neither to develop emetic episodes nor to use rescue anti-emetics medication. RESULTS: Twelve of the 15 patients recruited for the study were fully evaluable and completed 4 cycles of ESHAP regimen with a total of 48 cycles given. In the cycles with aprepitant and those without the CR were 83.3% and 0% respectively (p<0.05). Patients receiving aprepitant in the first 2 cycles recorded less nausea in subsequent cycles that were given without aprepitant. This was not statistically significant. CONCLUSION: This triple anti-emetic regimen showed efficacy in controlling the multi-day cisplatin-induced nausea and vomiting. Further randomized controlled trials are needed to compare between 3-day and 7-day aprepitant for multi-day cisplatin regimens.

Efficacy and Safety of Cladribine: Subcutaneous versus Intravenous Administration in Hairy Cell Leukemia Patients.

Cladribine induces durable complete remission (CR) in approximately 85% of hairy cell leukemia (HCL) patients. In Egypt, cladribine is mainly used as IV continuous infusion at a dose of 0.1 mg/kg/day for 7 days and as SC bolus injection at a dose of 0.14 mg/kg/day for 5 days. We aimed to compare the outcome and toxicity between these two regimens. We retrospectively collected data from HCL patients treated at the National Cancer Institute and its affiliated center, Nasser Institute, Cairo, Egypt. Forty-nine patients were identified, 18 treated with the IV regimen (IV group) and 31 with the SC regimen (SC group). Forty-one patients were newly diagnosed. Patient characteristics were balanced across the two groups. The CR rates in the IV and the SC group were 94% and 97%, respectively. The main complications in the IV group and the SC were neutropenia G3-4 (67% vs. 87%), mucositis mainly G1-2 (67% vs 32%) and infections (mainly viral, 78% vs 34%). In the IV group, five patients died, three of progression and infection, one of unknown cause and one of late heart failure. In the SC group, one patient died of disease progression and one of second cancer. After 33.5 months, median follow-up, the 3-year event free survival was 60% and 96%, respectively (p=0.104). The 3-year overall survival was 81% and 100%, respectively (p=0.277). In conclusion, SC cladribine is an excellent alternative to the IV regimen for the treatment of HCL.

Impact of imatinib interruption and duration of prior hydroxyurea on the treatment outcome in patients with chronic myeloid leukemia: Single institution experience.

BACKGROUND: Optimal response requires that patients should be maintained on the drug continuously. OBJECTIVES: To evaluate the influence of imatinib interruption and prior hydroxyurea use on the outcome of patients with chronic myeloid leukemia. MATERIALS AND METHODS: Between January 2010 and November 2013, patients with chronic phase who received imatinib at the Kasr Al-ainy Center of Clinical Oncology were included. RESULTS: Sixty patients were included in this study, thirty three patients (55%) received imatinib upfront, while 27 (45%) received imatinib post hydroxyurea. Imatinib was not given regularly in 50% of patients. In terms of response, only major molecular response and complete molecular response were statistically significant in favor of patients who were receiving imatinib regularly compared to those who had interruption (p<0.001, p<0.001, respectively) , while there was no difference in patients stratified according to prior hydroxyurea. The median progression free survival was 30.3 months (95% CI 24.3-36.3). Among the group of patients who received imatinib regularly, progression free survival was longer (p=0.049), there was no difference between those who received prior hydroxyurea versus those who did not (p=0.67). CONCLUSION: Duration of prior hydroxyurea had no impact on response or progression free survival, while patients regular on imatinib had statistically significant difference with respect to major molecular response, complete molecular response and progression free survival compared to those who had periods of drug interruption, thus we need more governmental support to supply the drug without interruption to improve the outcome of therapy.