Percentage grade 4 tumour predicts outcome for prostate adenocarcinoma in needle biopsies from patients with advanced disease: 10-year data from the TROG 03.04 RADAR trial.

Previous reports have shown that quantification of high tumour grade is of prognostic significance for patients with prostate cancer. In particular, percent Gleason pattern 4 (GP4) has been shown to predict outcome in several studies, although conflicting results have also been reported. A major issue with these studies is that they rely on surrogate markers of outcome rather than patient survival. We have investigated the prognostic predictive value of quantifying GP4 in a series of prostatic biopsies containing Gleason score 3+4=7 and 4+3=7 tumours. It was found that the length of GP4 tumour determined from the measurement of all biopsy cores from a single patient, percent GP4 present and absolute GP4 were all significantly associated with distant progression of tumour, all-cause mortality and cancer-specific mortality over a 10-year follow-up period. Assessment of the relative prognostic significance showed that these parameters outperformed division of cases according to Gleason score (3+4=7 versus 4+3=7). International Society of Urological Pathology (ISUP) Grade Groups currently divide these tumours, according to Gleason grading guidelines, into grade 2 (3+4=7) and grade 3 (4+3=7). Our results indicate that this simple classification results in the loss of important prognostic information. In view of this we would recommend that ISUP Grade Groups 2 and 3 be amalgamated as grade 2 tumour with the percentage of GP4 carcinoma being appended to the final grade, e.g., 3+4=7 carcinoma with 40% pattern 4 tumour would be classified as ISUP Grade Group 2 (40%).

Total depression and subtypes in prostate cancer survivors 10 years after treatment.

To describe the prevalence, severity and nature of depression in a sample of prostate cancer (PCa) survivors 10 years after diagnosis and treatment, 146 Australian patients from the RADAR trial who received their diagnosis 10 years previously completed the Zung Self-rating Depression Scale and a background questionnaire. Prevalence rates for clinically significant depression and severe depression were higher than those reported for the non-PCa men of the same age in Australia. The most common subtype of depression was Anhedonia, followed by Cognitive depression. Change in eating habits was the most powerful depression symptom predicting Anhedonia. By providing the first detailed documentation of major depression prevalence in PCa survivors, plus describing the nature of that depression, these data suggest that there is an ongoing need to provide treatments for these men and that those treatments should be focussed upon loss of previously available sources of enjoyment.

Validation of International Society of Urological Pathology (ISUP) grading for prostatic adenocarcinoma in thin core biopsies using TROG 03.04 'RADAR' trial clinical data.

In 2014 a consensus conference convened by the International Society of Urological Pathology (ISUP) adopted amendments to the criteria for Gleason grading and scoring (GS) for prostatic adenocarcinoma. The meeting defined a modified grading system based on 5 grading categories (grade 1, GS 3+3; grade 2, GS 3+4; grade 3, GS 4+3; grade 4, GS 8; grade 5, GS 9-10). In this study we have evaluated the prognostic significance of ISUP grading in 496 patients enrolled in the TROG 03.04 RADAR Trial. There were 19 grade 1, 118 grade 2, 193 grade 3, 88 grade 4 and 79 grade 5 tumours in the series, with follow-up for a minimum of 6.5 years. On follow-up 76 patients experienced distant progression of disease, 171 prostate specific antigen (PSA) progression and 39 prostate cancer deaths. In contrast to the 2005 modified Gleason system (MGS), the hazards of the distant and PSA progression endpoints, relative to grade 2, were significantly greater for grades 3, 4 and 5 of the 2014 ISUP grading scheme. Comparison of predictive ability utilising Harrell's concordance index, showed 2014 ISUP grading to significantly out-perform 2005 MGS grading for each of the three clinical endpoints.

Absence of adverse early quality of life outcomes of radiation therapy in breast conservation therapy for early breast cancer.

The New South Wales Breast Radiation Oncology Group has completed a prospective multicentre study of the impact of radiation therapy (RT) on acute toxicity and quality of life (QoL) in women with early breast cancer treated with breast conservation therapy. The patient group received adjuvant breast tangential RT after wide local excision of breast cancer. Acute toxicity and cosmesis was assessed quantitatively and qualitatively. European Organization of Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30) and Perceived Adjustment to Chronic Illness Scale (PACIS) were the QoL instruments used. Of 175 women, 34.3% described lethargy leading to a significant disruption to normal activity during RT. At week 6, this had reduced to 7.5% reporting significant lethargy. No negative effects on QoL were noted over the time period of RT; EORTC demonstrated no difference (P = 0.79). PACIS recorded a significant improvement in functioning (P < 0.001) from baseline to week 6. Univariate analysis on potential predictive patient, tumour and treatment factors demonstrated an association of baseline pre-RT breast discomfort with worse lethargy (P = 0.03), EORTC (P < 0.01) and PACIS (P < 0.01) measures. This study confirms the minimal impact of RT on patient functioning at 6 weeks post-treatment.

Impact of radiation therapy on acute toxicity in breast conservation therapy for early breast cancer.

AIMS: To document the acute toxicity experienced by women receiving radiation therapy as part of breast-conservation therapy (BCT) for early breast cancer. MATERIALS AND METHODS: A retrospective review was undertaken of the medical records of 234 consecutive women managed with radiation therapy for BCT over a 2-year period. A policy of formal acute toxicity documentation was present during this period with descriptive measures as well as the Radiation Therapy Oncology Group (RTOG) acute toxicity scoring system. Cutaneous moist desquamation, peak RTOG score, breast oedema and chemotherapy dose intensity were end points assessed. Patient and treatment characteristics were investigated for their association with study end points using Chi-squared and logistic regression analyses. RESULTS: A total of 223 (95%) of women had data available for analysis. All women were treated with tangential fields on megavoltage linear accelerators. Eighty-three (37.2%) women had systemic chemotherapy either delivered simultaneously in 58 and sequentially in 25. Moist desquamation occurred in 70 (31.4%) women; principally in the inframammary fold only in 43 (19.3%). Only 12 (5.4%) had a confluent moist reaction. Two hundred and ten (94%) women had a peak RTOG skin grade of 2 or less. Breast oedema was evident at treatment end in 46 (20.5%). On univariate analysis, physical factors, such as patient weight (P<0.001) and breast size (P<0.001), were significantly associated with moist desquamation, as were the volume of breast resected (P=0.02) and the use of chemotherapy (P=0.03). Only the physical factors remained significant on multivariate analysis. The presence of breast oedema was associated with surgical factors such as post-operative oedema (P<0.001) and infective complications (P<0.001). The use of concurrent chemoradiotherapy did not affect chemotherapy dose intensity, nor did the presence of moist desquamation increase the risk of febrile complications in chemotherapy-related neutropenia. CONCLUSION: This study confirms the relatively low incidence of significant acute toxicity experienced by women during radiation therapy as part of BCT. These study data should assist surgeons and women in the decision-making process for BCT.

Relapse patterns after chemo-radiation for carcinoma of the oesophagus.

AIM: The detailed review of patterns of failure in this report was undertaken to identify the continuing obstacles to the successful management of oesophageal cancer, and to establish whether there is a case to compare definitive chemo-radiation (Def-CR) and surgery for patients with squamous cancer in a randomized controlled trial. MATERIALS AND METHODS: First and subsequent sites of failure were reviewed in 274 patients treated with Def-CR using two cycles of cisplatin, infusional fluorouracil and 60 Gy; and 92 patients with limited chemo-radiation (CR), using one cycle and 35 Gy, followed by surgery (CR-Surg). All were treated on prospective non-randomized trials run by the Trans-Tasman Radiation Oncology Group between 1985 and 1999. Failure patterns were analysed using competing risks methodology, and pre-treatment variables predicting survival were identified by proportional hazards modelling. RESULTS: Site, stage, performance status and gender were independently predictive of survival following Def-CR. Local failure was evident in 42.3% of patients, but distant failure in isolation occurred in an additional 18.1%. Lowest rates of local and distant failure at 5 years (29.9% and 26%) occurred in patients with squamous cancer (SCC) located in the upper-third, whose 5-year survival was also the most favourable (49.2%). Survival was least favourable in patients with adenocarcinoma (AC) in the lower two-thirds (18.1%) due to higher rates of local (51.5%) and distant (36.1%) failure. Local failure occurred in 31.5% of patients undergoing CR-Surg but distant failure in isolation was observed in a further 34.7%. Outcomes were least favourable in patients with AC of the lower-third in whom 57.7% failed distantly and 5-year survival was 3.8%. Response to pre-operative chemo-radiation was also strongly predictive of outcome. Patients with no residual cancer in the resection specimen had the lowest rates of local (0%) and distant (16.7%) failure and the best survival (64.9%). Survival in patients with residual cancer in nodes, however, was extremely poor (3.5%) with distant failure occurring in 66.7%. CONCLUSION: The concurrent administration of chemotherapy with radiotherapy seems to have improved loco-regional control and has exposed distant failure as an obstacle to further improvements in outcome. Site, histological subtype, gender and response to chemo-radiation may predict biological differences in oesophageal cancer (OC) that influence outcome. A good case for a randomized comparison between Def-CR and CR-Surg in patients with SCC in the lower two-thirds exists.

A quality assurance audit: phase III trial of maximal androgen deprivation in prostate cancer (TROG 96.01).

In 1997 the Trans-Tasman Radiation Oncology Group (TROG) performed a quality assurance (QA) audit of its phase III randomized clinical trial investigating the effectiveness of different durations of maximal androgen deprivation prior to and during definitive radiation therapy for locally advanced carcinoma of the prostate (TROG 96.01). The audit reviewed a total of 60 cases from 15 centres across Australia and New Zealand. In addition to verification of technical adherence to the protocol, the audit also incorporated a survey of centre planning techniques and a QA time/cost analysis. The present report builds on TROG's first technical audit conducted in 1996 for the phase III accelerated head and neck trial (TROG 91.01) and highlights the significant progress TROG has made in the interim period. The audit provides a strong validation of the results of the 96.01 trial, as well as valuable budgeting and treatment planning information for future trials. Overall improvements were detected in data quality and quantity, and in protocol compliance, with a reduction in the rate of unacceptable protocol violations from 10 to 4%. Audit design, staff education and increased data management resources were identified as the main contributing factors to these improvements. In addition, a budget estimate of $100 per patient has been proposed for conducting similar technical audits. The next major QA project to be undertaken by TROG during the period 1998-1999 is an intercentre dosimetry study. Trial funding and staff education have been targeted as the key major issues essential to the continued success and expansion of TROG's QA programme.

Quality assurance audit in an Australasian phase III trial of accelerated radiotherapy for head and neck cancer (TROG 91.01). Trans-Tasman Radiation Oncology Group.

The Trans-Tasman Radiation Oncology Group (TROG) initiated a randomized trial, testing accelerated (twice daily) radiotherapy against conventional radiotherapy for stage III and stage IV squamous cell carcinoma of the head and neck in 1991. In 1996, the Trial Management Committee arranged for a technical audit of 76 cases from 11 institutions, conducted by investigators from interstate institutions. A 10% unacceptable protocol violation rate was detected, which compares favourably with initial Radiation Therapy Oncology Group (RTOG) experience in the late 1970s. Infrastructural deficits with poor quality of documentation, incomplete retrieval of films and document return have been demonstrated in some cases. The Trans-Tasman Radiation Oncology Group is actively pursuing procedural and resourcing issues in order to redress this and is actively expanding its Quality Assurance (QA) Programme with an intercentre dosimetry study. Ultimately, comprehensive clinical and technical QA site visits are planned.