‘GAP’ in radiotherapy services in Australia and New Zealand in 2009

Aim: In this study we estimated (a) the number of linear accelerators required in Australia and New Zealand to achieve a 52.3% treatment rate; (b) the ‘GAP’ between the actual and required number of linear accelerators; c) the number of persons not treated (PNT), premature deaths (PD) and years of life lost (YLL) as a result of the ‘GAP’; and (d) to review the actions being taken by health jurisdictions in Australia and in New Zealand to address the ‘GAP’ and reach the 52.3% treatment rate. Material and Methods: The actual number of fully staffed and operating linear accelerators (A) in Australian and New Zealand was obtained from a survey of radiotherapy facilities in December 2009. The required number of linear accelerators (R) was calculated from the projected cancer incidence figures for 2009 and was based on 1.6 linear accelerators being required per 1000 new cancer patients. The ‘GAP’ in Radiotherapy services (G) was R minus A. The maximum treatment capacity (MTC) was the ratio of A over R multiplied by 52.3%, assuming that all linear accelerators were operating at 100% capacity. As each linear accelerator can treat 331 new patients each year, the number of new cancer PNT is G × 331. The estimated 5-year survival benefit from radiotherapy is 16%, and the average survival for all patients receiving radiotherapy (radical and palliative) is 0.76 year. Hence, the number of PD attributed to the ‘GAP’ is PNT × 16%, and the YLL to cancer is PNT × 0.76. A literature search and local knowledge of health department Radiotherapy Plans in all jurisdictions were used to determine the action being taken to achieve a 52.3% treatment rate. Results: In 2009, the ‘GAP’ was 50 linear accelerators in Australia and the MTC was 38%, the same as it was in 1999, but there has been an increase in PNT each year from 7419 in 1999 to 16 550 in 2009, and PD each year increased from 1187 in 1999 to 2649 in 2009, and YLL each year increased from 5638 in 1999 to 12 585 in 2009. In New Zealand in 2009, the ‘GAP’ was nine linear accelerators and the MTC was 38%. An estimated 3310 persons did not receive radiotherapy in 2009 in New Zealand, and as a result, there were 523 PD and 2266 YLL. The review showed that new and replacement machines were being installed in all jurisdictions in Australia and in New Zealand. Only Victoria and Queensland have a Radiotherapy Plan beyond 2010, but both have underestimated the projected cancer incidence. Conclusion: Urgent action is needed by health departments and governments on both sides of the Tasman to improve access and equity to this essential cancer treatment. There is merit in the Baume Report recommendation of establishing a national body to oversee radiotherapy services in all jurisdictions in Australia. A similar central body should also be considered for New Zealand.     

Bullatacin — in vivo and in vitro experience in an ovarian cancer model

The cytotoxicity and antitumor effects of the acetogenin Bullatacin were evaluated in vitro in multiple ovarian cancer cell lines and in vivo in a murine ovarian teratocarcinoma (MOT) model in C3HeB/FeJ mice. The in vitro cytotoxicity of Bullatacin against four human ovarian epithelial tumor cell lines (OC-194, OC-222, OVCAR-3, and A-2780) was assessed in 48- and 72-h tetrazolium-dye (MTT) cytotoxicity assays. The percentage of cytotoxicity was determined on the basis of the mean optical density of the respective untreated cells and the dose effective against 50% of the cells (ED₅₀) was calculated for each cell line. In vivo experiments were performed on adult female C3HeB/FeJ mice, which were injected i.p. with 10⁵ MOT cells and varying amounts of Bullatacin given either in a single dose or in 5 subsequent doses over 72 h. All mice were observed for survival relative to that of the control groups, which were injected either with 10⁵ MOT cells with or without serial injections of vehicle or with vehicle only. All four epithelial ovarian cancer cell lines displayed sensitivity to Bullatacin. The relative cytotoxic effects were very heterogeneous, with the ED₅₀ value ranging between 10^–7 g/ml for OC-194 and 4 g/ml for the cisplatin-resistant cell line OVCAR-3 in a 72-h MTT cytotoxicity assay. All mice that had been injected i.p. with 10⁵ MOT cells and 1.4 mg/kg or more of Bullatacin died within the first 24 h after injection, whereas all mice that had received 600 g/kg of Bullatacin or less survived equally as long as the controls that had been injected with MOT only (21.1±0.9 days). Mice that had received Bullatacin at a dose ranging from 600 g/kg to 1.4 mg/kg either died during the 1st day postinjection or survived, but not longer than the MOT control group. Serial i.p. injections of Bullatacin again either led to death of the mice within 24–48 h of the last dose of Bullatacin or did not have any effect on the survival of the mice as compared with the respective control groups, which had been injected with the tumor and serial injections of vehicle (22.5±2.2 days). In summary, Bullatacin showed no effect on MOT-caused animal death in C3HeB/FeJ mice at nonlethal dose ranges, whether it was given as a single i.p. dose or serially over 72 h. In vitro, however, it proved to be a very potent cytotoxic agent in a variety of ovarian cancer cell lines. As compared with other chemotherapeutic agents, which we accept as having clinically important antitumor efficacy against ovarian cancer, such as cisplatin or carboplatin, Bullatacin demonstrated a very favorable ED_{50 in vitro}/LD_{50 in vivo} (the dose lethal to 50% of the mice) ratio.This work was supported by the Bertha Warshaver Rubin Research Fund and was presented at the 21st annual meeting of the Western Association of Gynecologic Oncologists, May 19–23, 1993, Santa Monica, California     

What influences participation in clinical trials in palliative care in a cancer centre?

Like any other specialty, palliative care needs a scientific foundation on which to base its practice. Research in palliative care is particularly difficult because of the characteristics of the patient population under study (e.g. advanced disease, poor performance status and limited prognosis). The aim of this paper was to highlight the challenges of recruitment into clinical trials in palliative care. Information on all patients treated at a specialist cancer centre who were referred for consideration of entry into any one of 23 clinical trials in palliative care was collected prospectively over 4 years to determine factors that influence patients to accept or reject entry into a study. Of the 1206 patients referred, 558 (46%) met the entry criteria. Of these, 362 (30%) agreed to enter and 248 (21% of all those referred) completed the study. Thus, 65% of all eligible patients were entered into trials but only 44% of these completed the study. The relatively high percentage of patients entered probably reflects the site (a cancer centre with a high research profile) and is not typical of other palliative care centres or hospices. The most common reasons given for unwillingness to participate were a wish to defer to a later date, a deterioration in condition, distance from home to hospital, a lack of interest, transfer to another unit, inability to give consent and family objection. In order to maximise patient accrual into trials in palliative care, studies should be designed to suit the patient population under study (e.g. be of short duration with realistic entry criteria) and not necessarily mirror the trial methodology of therapeutic trials in oncology.     

Differential effects of tumor–platelet interaction in vitro and in vivo in glioblastoma

An elevated platelet count is considered an independent predictor of short survival in glioblastoma and various other tumor entities. Prothrombotic activity of the tumor microcirculation resulting in platelet activation and release of cytokines from activated platelets has been suggested to play a role. This study was designed to analyze the effects of platelet-released cytokines on glioblastoma and endothelial cell proliferation and migration in vitro, and the influence of platelet count on glioblastoma growth and angiogenesis in vivo. In cultured human glioblastoma, umbilical cord and cerebral microvascular endothelial cells platelet-released cytokines significantly stimulated proliferation and migration as well as sprouting and formation of capillary-like structures. In vivo, glioblastoma cells were implanted in mice followed by platelet depletion starting 1 or 8 days later. Tumor volume, proliferative index, and vessel density analyzed 14 days after engraftment did not differ between animals with a normal and a low platelet count. Likewise, no effect of platelet depletion over 20 days upon the volume of intracerebrally growing tumors was observed in mice. Additionally, proliferative activity and vessel density determined in tumor samples from patients operated upon glioblastoma did not show any correlation with the patients’ preoperative platelet count. Thus, we conclude that distinct proliferation- and chemotaxis-stimulating effects of platelet-derived cytokines can be achieved in vitro, while the platelet count does not exert a major influence on tumor growth and tumor angiogenesis in GBM in vivo.     

What is new in supportive care in cancer?

The Annual Symposium of the Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO) was held in Vancouver, Canada, June 24–26, 2010. The symposium brought together health care professionals from many countries and many fields of expertise for an excellent forum of ideas, lectures and collegial interactions, and discussed methods to minimize cancer-induced side effects, the symptoms and complications of its treatment, and psychosocial issues facing cancer patients and their families. Some ideas and studies selected from the presentations of different fields of supportive care in cancer presented in this symposium are introduced in this paper.     

Retention of paclitaxel in cancer cells for 1 week in vivo and in vitro

Purpose: Clinically, the administration of paclitaxel for ovarian cancer on a dose-dense weekly schedule, rather than the conventional every-3-week schedule, might demonstrate greater tumor-cell death. Here, we investigate the pharmacokinetics and the pharmacodynamics of weekly paclitaxel in cancer cells in vivo and in vitro. Experimental design: Paclitaxel concentrations were measured by HPLC, and apoptotic cells were detected by TUNEL assay in paclitaxel-pretreated cervical cancer cells treated with paclitaxel (10 ng/ml) and in the tissues of cervical cancer patients treated with weekly paclitaxel (60 mg/m²/week). Polymerized tubulin was detected with a tubulin polymerization assay, and the BrdU cell proliferation assay was used to assess the effect of paclitaxel. Results: Paclitaxel remained in the cancer tissues of six patients for 6 days after the last medication. In vitro, paclitaxel was retained in all cell lines for 24 h after its removal from the medium, and paclitaxel was still detectable in CaSki cells on day 7. Simultaneous treatment with depolymerizing drugs inhibited the retention of paclitaxel in cells and paclitaxel-induced polymerization of tubulin. After paclitaxel treatment, apoptotic cells were detected in cancer tissues and CaSki cells for 1 week. Under high magnification, apoptotic cells on day 7 after paclitaxel treatment showed multinucleation. Conclusions: Paclitaxel is unusual in that it accumulates especially in cancer cells and induces apoptosis for 1 week in vivo and in vitro. On the other hand, paclitaxel could not be detected in cancer tissues after 2 weeks. The administration of paclitaxel on a weekly schedule, rather than the standard every-3-week schedule, might produce greater tumor-cell death.     

Variation in the prevalence of gastric cancer in Perú

Most cases of gastric cancers occur in non-industrialized countries but there is scarce information about the epidemiology of this illness in these countries. Our study examined whether there was a variation in the prevalence of gastric cancer in Lima, Perú over the last 2 decades. Subjects older than 29 years of age were included. They underwent an esophagogastroduedonoscopy at 3 socioeconomically different health facilities in Lima: a county hospital (7,168 subjects), a Peruvian-Japanese Clinic (14,794 individuals) and a private hospital (4,893 individuals). Birth cohort prevalence of gastric cancer was used. Regression models were calculated to predict the future prevalence of gastric cancer. It was found that the birth cohort prevalence of gastric cancer decreased in Perú from 22.7 to 2% (p < 0.001), from 12 to 0.5% (p < 0.001), and from 6.5 to 0.1% (p < 0.001) in the low, middle and high socioeconomic group, respectively. The prevalence of intestinal metaplasia decreased from 44.3 to 12.5% (p < 0.001), from 28.4 to 5% (p < 0.001), and from 19.4 to 2.2% (p < 0.001) in the low, middle and high socioeconomic status, respectively. These trends will likely persist over the future decades. Nevertheless, the prevalence of gastric cancer remains high in subjects older than 59 years of age in the low socioeconomic status. It is concluded that the prevalence of gastric cancer is decreasing in Perú, similar to the current trend undergoing in industrialized nations. However, there are still specific groups with high prevalence that might benefit from screening for early detection and treatment.     

Tanshinone IIA induces growth inhibition and apoptosis in gastric cancer in vitro and in vivo

As a phytochemical derived from the roots of Salvia miltiorrhiza Bunge, Tanshinone?IIA has been reported to possess anti-inflammatory and antioxidant activity. Studies in breast, colon, prostate and lung cancer indicate that Tanshinone?IIA may exhibit a promising antitumor activity. However, systemic studies of the cytotoxic effects of Tanshinone?IIA on gastric cancer have not been described. The present study offers a comprehensive evaluation of the antitumor effects of Tanshinone?IIA in gastric cancer cells in?vitro and in a mouse xenograft model. Cell viability and apoptosis in?vitro were evaluated through the MTT assay and flow cytometry analysis. The results indicate that Tanshinone?IIA can induce gastric cancer cell growth inhibition and apoptosis in a time- and concentration-dependent manner. Furthermore, we investigated the mechanism of the apoptotic effects induced by Tanshinone?IIA. We found that Tanshinone?IIA can not only cause cell cycle arrest in the G2/M phase, but also trigger the intrinsic apoptotic signaling pathway. The results suggest that Tanshinone?IIA may serve as an effective adjunctive reagent in the treatment of gastric cancer.     

Was the drop in mammography rates in 2005 associated with the drop in hormone therapy use?

BACKGROUND:

In 2005, mammography rates in the United States dropped nationally for the first time among age‐eligible women. An increased risk of breast cancer related to hormone therapy (HT) use reported in 2002 led to a dramatic drop in its use by 2005. Because current users of HT also tend to have higher mammography rates, the authors examined whether concurrent drops in HT and mammography use were associated.

METHODS:

Multivariate logistic regression was used to test for an interaction between HT use and survey year, controlling for a range of measurable factors in data from the 2000 and 2005 National Health Interview Surveys (NHIS).

RESULTS:

Women ages 50 to 64 years were more likely to report a recent mammogram if they also reported more education, a usual source of care, private health insurance, any race except non‐Hispanic Asian, talking with an obstetrician/gynecologist or other physician in the past 12 months, or were currently taking HT. Women aged ≥65 years were more likely to report a recent mammogram if they also reported younger age (ages 65‐74 years), more education, a usual source of care, having Medicare Part B or other supplemental Medicare insurance, excellent health, any race except non‐Hispanic Asian, talking with an obstetrician/gynecologist or other physician in the past 12 months, or were currently taking HT.

CONCLUSIONS:

The change in HT use was associated with the drop in mammography use for women ages 50 to 64 years but not for women aged ≥65 years. NHIS data explained 70% to 80% of the change in mammography use. Cancer 2011;. © 2011 American Cancer Society.     

Epstein-Barr virus expression in Hodgkin’s lymphoma in Kuwait

The epidemiology of Hodgkin's lymphoma (HL) shows wide geographic variation in histological subtypes and in its association with the Epstein-Barr virus (EBV). The proportion of EBV positive HL is low in industrialized countries, high in non-industrialized countries and intermediate in early-industrialized countries. Reports from the Persian Gulf and Middle East are very limited. The aim of this study was to determine the epidemiology of HL in Kuwait, an early-industrialized country in the Persian Gulf, and to delineate the extent of its association with EBV. We reviewed 134 cases of HL for histological classification and demographic data. 107 cases were examined for the presence of EBV using immunohistochemistry (IHC) for the latent membrane protein I (LMPI) and in-situ hybridization (ISH) for EBVencoded RNA (EBER). 70.4% of the patients were males and 29.6% were females. The male: female ratio was 2.4:1. The mean age was 30.6 years (range, 4-71 years). Mixed cellularity HL (MCHL) was the most common subtype (45.5%), followed by nodular sclerosis (37.3%), nodular lymphocyte predominant (6.7%), lymphocyte rich (3%) and lymphocyte depletion (3%). 4.5% of cases were unclassifiable. EBV expression was seen in 56%, was significantly higher in MCHL, in children, and in males. Our findings suggest that the frequency of EBV expression in HL in Kuwait is similar to other early-industrialized countries. Further research from other countries in the Persian Gulf and the Middle East should shed more light on the epidemiology of HL and its relation to EBV in this region.     

Metastasis-suppressor genes in clinical practice: lost in translation?

Over the past 25 years, an expanding set of metastasis-suppressor genes (MSGs) has been identified that specifically regulate metastasis formation without affecting primary growth. MSGs are involved in diverse molecular processes in multiple tumor types. Given the wealth of metastasis biology that underlies their functions, treatment strategies based on MSGs have an unparalleled potential to improve patient care. Using NM23 as a prime example, we discuss how specific MSGs have been used as prognostic markers, tools for predicting response to treatment, and targets for the development of novel therapies. Barriers specific to the translation of MSG biology into clinical practice are reviewed and future research directions necessary for clinical advances are delineated. Although to date the impact of MSGs on patient care is limited, it is an expanding field with vast potential to help develop new treatments and identify patients who will most benefit from them.