Phase 1 in the development of a patient-reported measure to quantify perceived inconvenience of radiotherapy: generation of issues.

AIMS: Current patient-reported measures (PROMs) do not specifically address radiotherapy (RT) related inconvenience. We conducted, as per guidelines of the European Organization for Research and Treatment of Cancer (EORTC), the initial (issue generation) phase of development of a RT inconvenience PROM. Specifically, we aimed to develop a conceptual framework for RT inconvenience and generate a comprehensive list of issues pertaining to it. METHODS: We reviewed existing PROMs and literature and gathered qualitative and quantitative data from consumers and health professionals, in order to generate a comprehensive list of issues pertaining to RT inconvenience. A framework for the consideration of RT inconvenience was defined and used to ensure all possible issues were explored and to list the issues into conceptual domains. RESULTS: Qualitative data from 26 consumers and 30 health professionals, and quantitative data from 1191 consumers and 253 health professionals resulted in the identification of 38 issues grouped into five conceptual domains: (1) inconvenience of RT opportunity, (2) inconvenience of decision-making, (3) inconvenience of treatment, (4) inconvenience of side effects, and (5) inconvenience of follow-up. CONCLUSIONS: This list of RT inconvenience issues will, in future work, be operationalized into a set of items for pretesting and then large-scale field testing as per the EORTC guidelines.

Radiation therapy for people with cancer: what do written information materials tell them?

This study aimed to compare and contrast the contents of different types of written patient information about radiotherapy, namely (1) hospital radiotherapy departments vs. cancer control organisations and (2) generic vs. tumour-specific materials. A coding framework, informed by existing patients' information needs literature, was developed and applied to 54 radiotherapy information resources. The framework comprised 12 broad themes; cancer diagnosis, general information about radiotherapy, treatment planning, daily treatment, side effects, self-care management, external radiotherapy, internal radiotherapy, impact on daily activities, post-treatment, psychosocial health and other content, such as a glossary. Materials produced by cancer organisations contained significantly more information than hospital resources on diagnosis, general radiotherapy information, internal radiotherapy and psychosocial health. However, hospital materials provided more information about treatment planning, daily treatment and the impact on daily activities. Compared to generic materials, tumour-specific resources were superior in providing information about diagnosis, daily treatment, side effects, post-treatment and psychosocial health. Information about internal radiotherapy, prognosis and chronic side effects were poorly covered by most resources. Collectively, hospital and cancer organisation resources complement each other in meeting patients' information needs. Identifying ways to consolidate different information sources could help comprehensively address patients' medical and psychosocial information needs about radiotherapy.

Examining Determinants of Radiotherapy Access: Do Cost and Radiotherapy Inconvenience Affect Uptake of Breast-conserving Treatment for Early Breast Cancer?

AIMS: Radiotherapy utilisation is likely affected by multiple factors pertaining to radiotherapy access. Radiotherapy is an integral component of breast-conserving treatment (BCT) for early breast cancer. We aimed to determine if stepwise improvements in radiotherapy access in regional Australia affected the uptake of BCT and thus radiotherapy. MATERIALS AND METHODS: Breast cancer operations in the Central Coast of New South Wales between January 2010 and March 2014 for T1-2N0-1M0 invasive or in situ (≤5 cm) disease in female patients eligible for BCT were examined. BCT uptake was calculated for three 1 year periods: period 1 (local radiotherapy available at cost to user or out of area radiotherapy with travel cost and inconvenience); period 2 (as per period 1 + publicly funded transport and radiotherapy at out of area facilities at no cost to user); period 3 (as per period 1 + publicly funded local radiotherapy at no cost to user). RESULTS: In total, 574 cases met eligibility criteria. BCT declined with increasing distance to publicly funded radiotherapy (P = 0.035). BCT rates for periods 1, 2 and 3 were 63% (113/180), 61% (105/173) and 71% (156/221). There were no statistically significant differences in BCT between periods 1 and 2 in the whole cohort or within age, histology or tumour size subgroups. Overall, there was a 9% increase in BCT in the whole cohort in period 3 compared with periods 1 and 2 (P = 0.031). This increase was statistically significant for women over 70 years (19% increase, P = 0.034), for women with ductal carcinoma in situ (25% increase, P = 0.013) and for women with primary tumours that were ≤10 mm (21% increase, P = 0.016). CONCLUSIONS: Improving the affordability of radiotherapy through publicly funded transport and radiotherapy at out of area facilities did not improve BCT uptake in a region where radiotherapy was locally available, albeit at cost to the user. Improving both affordability and convenience through the provision of local publicly funded radiotherapy increased BCT uptake. Service availability and affordability have long been recognised as important determinants of radiotherapy access. Our findings suggest that inconvenience may also influence radiotherapy utilisation.

Promoting a research culture among junior radiation oncologists: outcomes from the introduction of the Australian and New Zealand research requirement in training.

AIM: Since 2005, radiation oncology trainees in Australia and New Zealand have had to undertake a piece of original research during training, and submit a manuscript, as first author, for senior peer-review. Satisfactory completion of this requirement is one component of eligibility to sit the Royal Australian and New Zealand College of Radiologists Fellowship examinations. The purpose of this study was to examine the value of this curriculum requirement, including the publication rates and potential barriers to trainee research. MATERIALS AND METHODS: An online survey was sent to 116 radiation oncologists/trainees who trained since the mandatory research requirement was introduced (2005-2011). Questions concerned research topics, publications, subsequent research activity, perceptions on barriers to research and aids to conducting research during training. A web-based search of PubMed by author name was carried out to complete and verify publication statistics. RESULTS: In total, 108 (93.1%) of the 116 trainees across 20 centres who submitted their research papers to the Radiation Oncology Faculty Research Committee were successful in meeting the required standard first time. Half of these trainees ultimately published their paper in a peer-reviewed journal. Of trainees responding to the survey, 62% presented their research at a scientific meeting. Most of the studies were either retrospective (62.3%) or dosimetry/physics projects (10.1%). The main problems encountered in conducting projects were competing clinical commitments and lack of dedicated research time. Notably, long ethics approval processes, lack of supervision and statistical support for projects were not considered barriers. CONCLUSION: This mandatory research requirement ensures trainees initiate and complete at least one project during their training. Since the introduction of this curriculum component, half of the research projects have resulted in publication in a peer-reviewed journal. Increased 'protected time' and training in scientific writing and methods may improve publication rates and quality. This first review of the Australian and New Zealand radiation oncology trainee research requirement highlights areas that need to be addressed to further support and foster a research culture among junior radiation oncologists.

Are radiation oncologists aware of health literacy among people with cancer treated with radiotherapy?

Health literacy skills are important for people affected by cancer as they are exposed to complex treatment and follow-up care information. This study aimed to (1) explore radiation oncologists' understandings and awareness of health literacy among patients with a reasonable command of English; (2) gain insight into oncologists' views regarding health literacy; and (3) identify techniques oncologists employ to communicate to different literacy populations. We conducted semi-structured interviews with 26 radiation oncologists. Four key themes were identified: (1) identifying a patient's literacy level; (2) perceived impact of literacy; (3) challenges and strategies to communicating concepts and supporting decision-making; and (4) suggested improvements to the health system. Participants described subjectively assessing a person's literacy level by monitoring the types of questions asked; analysing the language used; examining non-verbal behaviour, and considering a person's socio-economic situation. Participants reported the challenges of discussing the subtleties of cancer treatments with lower literacy groups such as the benefits and risks of treatment options and clinical trials, and tended to provide the basic facts to facilitate understanding. Radiation oncologists acknowledged the importance of health literacy in oncology, and employed a number of techniques to tailor their communication to different literacy populations. Further research is needed to address the challenges faced by oncologists when interacting with different literacy groups.

Human papillomavirus modifies the prognostic significance of T stage and possibly N stage in tonsillar cancer.

BACKGROUND: Despite the association with more advanced nodal stage, patients with human papillomavirus (HPV) positive oropharyngeal cancers have better outcomes. We examined whether the HPV can modify the effect of known prognostic factors in tonsillar cancer. PATIENTS AND METHODS: A total of 489 patients from 10 centres were followed up for recurrence or death for a median of 3.2 years. Determinants of the rate of locoregional recurrence, death from tonsillar cancer and overall survival were modelled using Cox regression. RESULTS: The prognostic value of T and N stages were modified by HPV as indicated by statistically significant interaction terms. After adjusting for age, gender and treatment, T stage appeared relevant only for HPV-positive cancers (where a higher T stage was associated with worse outcomes). There was some evidence that N stage was a more relevant prognostic factor for HPV-negative than -positive cancers. There was no evidence that the HPV modifies the effect of age, gender or grade on outcomes. CONCLUSIONS: This study suggests that the prognostic significance of the conventional staging system in tonsillar cancer is modified by HPV.

Human papillomavirus predicts outcome in oropharyngeal cancer in patients treated primarily with surgery or radiation therapy.

OBJECTIVE: This study examines the prognostic significance of human papillomavirus (HPV) in patients with locally advanced oropharyngeal squamous cell carcinoma (SCC) treated primarily with surgery or definitive radiotherapy. METHODS: One hundred and ninety-eight patients with Stage 3/4 SCC were followed up for recurrence in any form or death from any cause for between 1 and 235 months after diagnosis. HPV status was determined using HPV E6-targeted multiplex real-time PCR/p16 immunohistochemistry. Determinants of recurrence and mortality hazards were modelled using Cox's regression with censoring at follow-up dates. RESULTS: Forty-two per cent of cancers were HPV-positive (87% type 16). HPV predicted loco-regional control, event-free survival and overall survival in multivariable analysis. Within the surgery with adjuvant radiotherapy (n=110), definitive radiotherapy-alone (n=24) and definitive radiotherapy with chemotherapy (n=47) groups, patients with HPV-positive cancers were one-third or less as likely to have loco-regional recurrence, an event or to die of any cause as those with HPV-negative cancers after adjusting for age, gender, tumour grade, AJCC stage and primary site. The 14 patients treated with surgery alone were considered too few for multivariable analysis. CONCLUSION: HPV status predicts better outcome in oropharyngeal cancer treated with surgery plus adjuvant radiotherapy as well as with definitive radiation therapy±chemotherapy.

Predicting regional control based on pretreatment nodal size in squamous cell carcinoma of the head and neck treated with chemoradiotherapy: a clinician's guide.

The aim of this study was to determine the regional control rate with concurrent chemoradiotherapy (CRT) based on pretreatment nodal size in mucosal head and neck squamous cell carcinoma (HNSCC) in patients who achieved a complete response (CR) at the primary site by 12 weeks post-treatment. Between December 1997 and November 2003, 117 patients with node-positive HNSCC were treated with concurrent CRT, with 108 (92%) achieving a CR at the primary site by 12 weeks. There were 93 males (86%), median age 55 (37-79) years and the most common primary site was the oropharynx (65%). Patients were divided into three subgroups: or=6.1 cm 8 (7%). All patients received concurrent platinum-based chemotherapy and the median radiation dose was 70 Gy (60-72 Gy). The 3-year regional control rate based on pretreatment nodal size was or=6.1 cm 50% (95%CI 15-77%) (P = 0.001). The 3-year regional control rate based on pre-treatment nodal size was or=6.1 cm 50% (95%CI 15-77%) (P = 0.001). These results provide a quantitative guide for the clinician as to the likelihood of regional control based on pretreatment nodal size following CRT in patients who achieve a CR at the primary site by 12 weeks post-treatment.

Hyperbaric oxygenation for tumour sensitisation to radiotherapy: a systematic review of randomised controlled trials.

BACKGROUND: Radiotherapy is a well-established treatment for some solid tumours. Hyperbaric oxygenation (HBO) may improve radiotherapeutic killing of hypoxic cancer cells, so the simultaneous administration of radiotherapy and HBO may reduce mortality and tumour recurrence. METHODS: We performed a systematic search of the literature in September 2007 for randomised controlled trials, and made pooled analyses of pre-determined clinical outcomes. RESULTS: Nineteen trials contributed to this review (2286 patients). There was a reduction in mortality for head and neck cancers at one and five years after therapy (at five years RR 0.82, P=0.03, NNT=5), and improved local tumour control at three months (RR 0.58, P=0.006, NNT=7). Any advantage is achieved at the cost of an increased rate of both severe radiation tissue injury (RR 2.35, P<0.0001, NNH=8) and the chance of seizures during therapy (RR 6.76, P=0.03, NNH=22). CONCLUSIONS: There is some evidence that HBO improves local tumour control and mortality for cancers of the head and neck, and local tumour recurrence in cancers of the uterine cervix. These benefits may only occur with unusual fractionation schemes. HBO is associated with significant adverse effects including oxygen toxic seizures and severe radiation tissue injury. The methodological and reporting inadequacies of the studies included in this review demand a cautious interpretation. More research is needed for head, neck and uterine cervical cancer, but is probably not justified for bladder cancer. There is little evidence available concerning malignancies at other sites.

A pilot randomised comparison of dexamethasone 96 mg vs 16 mg per day for malignant spinal-cord compression treated by radiotherapy: TROG 01.05 Superdex study.

AIM: To test the viability of a full-scale randomised comparison of two steroid doses given with radiotherapy for malignant spinal-cord compression (MSCC), to test Internet randomisation and to compare different functional outcome measures. MATERIALS AND METHODS: A log of screened patients at eight recruiting centres was maintained. Patients were randomised via the Superdex website to either 96 mg or 16 mg daily of dexamethasone. Radiotherapy treatment was 30 Gy in 10 fractions. Outcomes assessed used ambulation, Barthel Index ambulation, Functional Independence Measure (FIM) ambulation and Functional Improvement Score (FIS) at 1 month. RESULTS: One hundred and thirty-one patients were screened. Ninety-three (71%) were ineligible, 65% of these were because duration of prior steroid use was greater than 12 h, failure to meet strict definition of magnetic resonance imaging, defined MSCC, multi-level disease or previous spinal-cord compression treatment. Twenty of the 38 eligible patients were randomised, including seven outside standard office hours. There was a high rate of serious adverse events (n = 9), but only one was considered likely to be related to study medication. At baseline, 75% were ambulant, 70% had FIM ambulation scores greater than 5 and 50% had Barthel Index ambulation scores greater than 2. At day 28, including all randomised patients (by scoring four dead patients as non-ambulant), ambulation scores by the various definitions were 60%, 45% and 40%, respectively. For the 16 patients evaluable at day 28, the mean FIS was -1.4. Median survival was 69 days and 1-year survival 13%. CONCLUSION: Web randomisation was successful; however, the high ineligibility rate precludes a full-scale dexamethasone dose trial in Australia. Choice of measure of ambulation has potentially significant effects on outcomes and implications for the design of any future MSCC trials. Referral delays are of concern.

Hyperbaric oxygenation for tumour sensitisation to radiotherapy.

BACKGROUND: Cancer is common and radiotherapy is one well-established treatment for some solid tumours. HBO may improve the ability of radiotherapy to kill hypoxic cancer cells, so the administration of radiotherapy while breathing HBO may result in a reduction in mortality and tumour recurrence. OBJECTIVES: To assess the benefits and harms of radiotherapy while breathing HBO. SEARCH STRATEGY: In November 2004 we searched The Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library Issue 3), MEDLINE, EMBASE , CINAHL, DORCTHIM and reference lists of articles. Relevant journals were handsearched. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing the outcome of malignant tumours following radiation therapy while breathing HBO versus air (with or without sham therapy). DATA COLLECTION AND ANALYSIS: Three reviewers independently evaluated the quality of the relevant trials using the method of Schulz (Schulz 1995) and extracted the data from the included trials. MAIN RESULTS: Nineteen trials contributed to this review (2286 patients: 1103 allocated to HBO and 1153 control). With HBO, there was a reduction in mortality for head and neck cancers at both one year and five years after therapy (Relative risk (RR) 0.83, P = 0.03, number needed to treat (NNT) = 11 and RR 0.82, P = 0.03, NNT = 5 respectively), as well as improved local tumour control at three months (RR with HBOT 0.58, P = 0.006, NNT = 7). The effect of HBO varied with different fractionation schemes. Local tumour recurrence was less likely with HBO at one year (head and neck, RR 0.66, P < 0.0001, NNT = 5), two years (uterine cervix RR 0.60, P = 0.04, NNT = 5) and five years (head and neck (RR 0.77, P = 0.01). Any advantage is achieved at the cost of some adverse effects. There was a significant increase in the rate of both severe radiation tissue injury (RR 2.35, P < 0.0001, (number needed to harm (NNH) = 8) and the chance of seizures during therapy (RR 6.76, P = 0.03, NNH 22) with HBO. AUTHORS' CONCLUSIONS: There is some evidence that HBO improves local tumour control and mortality for cancers of the head and neck, and local tumour recurrence in cancers of the head and neck, and uterine cervix. These benefits may only occur with unusual fractionation schemes. HBO is associated with significant adverse effects including oxygen toxic seizures and severe tissue radiation injury. The methodological and reporting inadequacies of the primary studies included in this review demand a cautious interpretation. More research is needed for head and neck cancer, but is probably not justified for bladder cancer. There is little evidence available concerning malignancies at other anatomical sites on which to base a recommendation.

Hyperbaric oxygen therapy for late radiation tissue injury.

BACKGROUND: Cancer is a significant global health problem. Radiotherapy is a treatment for many cancers and about 50% of patients having radiotherapy with be long-term survivors. Some will experience LRTI developing months or years later. HBOT has been suggested for LRTI based upon the ability to improve the blood supply to these tissues. It is postulated that HBOT may result in both healing of tissues and the prevention of problems following surgery. OBJECTIVES: To assess the benefits and harms of HBOT for treating or preventing LRTI. SEARCH STRATEGY: We searched The Cochrane Central Register of Controlled Trials (CENTRAL) Issue 3, 2004, MEDLINE, EMBASE, CINAHL and DORCTHIM (hyperbaric RCT register) in September 2004. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI prevention or healing. DATA COLLECTION AND ANALYSIS: Three reviewers independently evaluated the quality of the relevant trials using the guidelines of the Cochrane Handbook Clarke 2003) and extracted the data from the included trials. MAIN RESULTS: Six trials contributed to this review (447 participants). For pooled analyses, investigation of heterogeneity suggested important variability between trials. From single studies there was a significantly improved chance of healing following HBOT for radiation proctitis (relative risk (RR) 2.7, 95% confidence Interval (CI) 1.2 to 6.0, P = 0.02, numbers needed to treat (NNT) = 3), and following both surgical flaps (RR 8.7, 95% CI 2.7 to 27.5, P = 0.0002, NNT = 4) and hemimandibulectomy (RR 1.4, 95% CI 1.1 to 1.8, P = 0.001, NNT = 5). There was also a significantly improved probability of healing irradiated tooth sockets following dental extraction (RR 1.4, 95% CI 1.1 to 1.7, P = 0.009, NNT = 4). There was no evidence of benefit in clinical outcomes with established radiation injury to neural tissue, and no data reported on the use of HBOT to treat other manifestations of LRTI. These trials did not report adverse effects. AUTHORS' CONCLUSIONS: These small trials suggest that for people with LRTI affecting tissues of the head, neck, anus and rectum, HBOT is associated with improved outcome. HBOT also appears to reduce the chance of osteoradionecrosis following tooth extraction in an irradiated field. There was no such evidence of any important clinical effect on neurological tissues. The application of HBOT to selected patients and tissues may be justified. Further research is required to establish the optimum patient selection and timing of any therapy. An economic evaluation should be also be undertaken. There is no useful information from this review regarding the efficacy or effectiveness of HBOT for other tissues.

Prolonged ex vivo culture of cord blood CD34(+) cells facilitates myeloid and megakaryocytic engraftment in the non-obese diabetic severe combined immunodeficient mouse model.

A clinical goal for ex vivo expansion of cord blood (CB) CD34(+) cells is to shorten the period of neutropenia and thrombocytopenia following myeloablative therapy and transplantation. Prolongation of cytokine expansion leads to the production of greater numbers of cells, and should have an impact on neutrophil and platelet recovery. Furthermore, expansion of CD34(+) cells should support the continued production of neutrophils and platelets in the 6-week period following transplantation. We tested these hypotheses by characterization of the kinetics (human CD45(+) cells in the blood) and phenotype (CD45, CD34, CD61, CD33, CD19 and CD3) of human engraftment in the non-obese diabetic severe combined immunodeficient mouse (NOD-SCID) following 7 or 14 d of ex vivo expansion of CB CD34(+) cells. Mice transplanted with 14 d cells showed greater percentages of human CD45(+) cells in the blood, bone marrow and spleen than mice transplanted with unexpanded cells or 7 d cells. Prolonging cytokine exposure of CD34(+) cells and transplantation with increasing numbers of input cells facilitated the production of absolute numbers of CD34(+), CD33(+), CD61(+) and CD19(+) cells in vivo. Furthermore, analysis of SCID engrafting potential showed that prolongation of culture duration facilitates in vivo expansion of CD45(+), CD34(+) and CD19(+) cells after transplantation. It is anticipated that prolonged (2 weeks) ex vivo culture of CB will have a beneficial clinical effect.

Australian high-dose-rate brachytherapy protocols for gynaecological malignancy.

There is no consensus over the optimal dose fractionation schedules for high-dose-rate (HDR) brachytherapy used for gynaecological malignancy. In Australian public hospital departments of radiation oncology, HDR brachytherapy for gynaecological cancer is being more commonly used. A survey of public departments that are using this technology, or that plan to introduce this technology, was performed. Their current protocols are presented. In general, protocols are similar biologically; however, the practical aspects such as the number of fractions given do vary and may reflect resource restrictions or, alternatively, differences in interpretations of the literature and of the best protocols by clinicians.

Prior cryopreservation of ex vivo-expanded cord blood cells is not detrimental to engraftment as measured in the NOD-SCID mouse model.

Cytokine-mediated expansion has been proposed and successfully used to facilitate engraftment post transplantation. This study examined whether cryopreservation following expansion has a detrimental effect on the ability of cells to engraft, using the NOD-SCID mouse model. Cord blood (CB) CD34(+) cells were incubated for 7 days with stem cell factor (SCF), flt-3 ligand (FL), and megakaryocyte growth and development factor (MGDF). Expanded CD34(+) cells were transplanted into NOD-SCID mice either fresh or following cryopreservation and thawing. After thawing, recovery of nucleated cells was 94%, of CD34 cells was 63%, and of day-14 progenitors was 17%. The loss of day-14 progenitor cells among the thawed expanded cells did not influence the kinetics of human engraftment in the mouse. Bone marrow (BM) of mice transplanted with thawed expanded CD34(+) cells (14 +/- 3.9%) showed significantly higher levels of human engraftment than mice transplanted with fresh expanded CD34(+) cells (1.5 +/- 0.5%, p = 0.0064). Thawed expanded CD34(+) cells had significantly higher SCID Engrafting Potential (SEP) than freshly expanded CD34(+) cells (p < 0.001). Results suggest that prior cryopreservation does not prevent expanded cells engrafting in NOD-SCID mice.

Laparoscopic port-site recurrence following surgery for a stage IB squamous cell carcinoma of the cervix with negative lymph nodes.

BACKGROUND: Port-site metastases are commonly reported after laparoscopic surgery for ovarian cancer, but have also been reported in patients with cervical or endometrial cancer with positive lymph nodes. Recently, a case of port-site recurrence after laparoscopic surgery for a patient with node-negative early-stage adenocarcinoma of the cervix was reported. We report the first case of port-site metastasis in a patient with stage IB squamous cell carcinoma of the cervix with negative lymph nodes. CASE: A 31-year-old woman had a laparoscopy for pelvic pain. Under anesthesia, she was noted to have a grossly abnormal-looking cervix and a biopsy revealed squamous cell carcinoma. She was referred to a gynecological oncologist and underwent radical hysterectomy and pelvic lymph node dissection through a transverse lower abdominal incision 6 weeks later. Nineteen months postoperatively, she presented with a soft tissue mass in a suprapubic laparoscopic trocar site. CONCLUSION: It is postulated that cells dislodged at the time of cervical manipulation and biopsy may have passed through the fallopian tubes and implanted in the laparoscopic port site due to the "chimney effect" caused by the pneumoperitoneum.