Survival outcomes after delayed cytoreduction surgery following neoadjuvant chemotherapy in advanced epithelial ovarian cancer.

OBJECTIVE: Interval cytoreduction following neoadjuvant chemotherapy is a well-recognized treatment alternative to primary debulking surgery in the treatment of advanced epithelial ovarian cancer where patient and/or disease factors prevent complete macroscopic disease resection to be achieved. More recently, the strain of the global COVID-19 pandemic on hospital resources has forced many units to alter the timing of interval surgery and extend the number of neoadjuvant chemotherapy cycles. In order to support this paradigm shift and provide more accurate counseling during these unprecedented times, we investigated the survival outcomes in advanced epithelial ovarian cancer patients with the intent of maximal cytoreduction following neoadjuvant chemotherapy with respect to timing of surgery and degree of cytoreduction. METHODS: A retrospective review of all patients aged 18 years and above with FIGO (2014) stage III/IV epithelial ovarian cancer treated with neoadjuvant chemotherapy and the intention of interval cytoreduction surgery between January 2008 and December 2017 was conducted. Overall and progression-free survival outcomes were analyzed and compared with patients who only received chemotherapy. Outcome measures were correlated with the number of neoadjuvant chemotherapy cycles and amount of residual disease following surgery. RESULTS: Six hundred and seventy-one patients (median age 67 (range 20-91) years) were included in the study with 572 patients treated with neoadjuvant chemotherapy and surgery and 99 patients with chemotherapy only. There was no difference in the proportion of patients in whom complete cytoreduction was achieved based on number of cycles of neoadjuvant chemotherapy (2-4 cycles: 67.7%, n=337/498); ≥5 cycles: 62.2%, n=46/74). Patients undergoing cytoreduction surgery after neoadjuvant chemotherapy had a median 5-year progression-free and overall survival of 24 and 38 months, respectively. No significant difference in overall survival between surgical groups was observed (interval cytoreduction: 41 months vs delayed cytoreduction: 43 months, p=0.52). Those who achieved complete cytoreduction to R0 (no macroscopic disease) had a significant median overall survival advantage compared with those with any macroscopic residual disease (R0: 49-51 months vs R<1: 22-39 months, p<0.001 vs R≥1: 23-26 months, p<0.001). CONCLUSIONS: Survival outcomes do not appear to be worse for patients treated with neoadjuvant chemotherapy if cytoreduction surgery is delayed beyond three cycles. In advanced epithelial ovarian cancer patients the imperative to achieve complete surgical cytoreduction remains gold standard, irrespective of surgical timing, for best survival benefit.

Prospective analysis of the utility of 18-FDG PET in Merkel cell carcinoma of the skin: A Trans Tasman Radiation Oncology Group Study, TROG 09:03.

INTRODUCTION: TROG 09.03 prospectively studied the utility of Fluorine-18 Fluorodeoxyglucose (18-FDG) PET in the management of Merkel cell carcinoma of skin. METHODS: Following consent and registration, a pre-treatment FDG-PET/CT was performed. Sites of avid disease were confirmed by cytology where practicable. Following surgery, patients with AJCCv7 Stages IIA-IIIB disease were treated with chemo-radiotherapy and reassessed with a post-treatment PET. RESULTS: Fifty-eight subjects (45 males and 13 females, median age 68 years) were enrolled between 2011 and 2015, 43 patients of whom went on to receive chemo-radiotherapy. An occult primary was present in 22 (37.9%), T1 in 22 (37.9%) and T2 disease in 14 (24.1%). Nodal disease was present in 69% of cases. Fifty per cent of subjects had gross residual disease at the primary site and/or nodal site at the time of registration. 18-FDG PET/CT had a sensitivity of 94.74% (95% CI 82-99.3%) and a specificity of 88.24% (95% CI 63.56-98.54). The positive predictive value was 94.74% (83.01-98.51) and the negative predictive value was 88.24% (95% CI 65.81-96.69). The pre-treatment PET influenced a treatment decision in 27.6% of cases. Upstaging occurred in 15 (25.9%), with no down staging. Other diseases were identified in 4 (6.9%) patients. Univariate analysis failed to demonstrate that pre-treatment SUV levels or a negative post-treatment PET had any impact on overall survival. PET staged patients had 89% 3-year in-field loco-regional control and 76% 3-year overall survival. CONCLUSION: Staging 18-FDG-PET significantly influenced treatment decisions in approximately one-third of cases of MCC and should be considered in the routine pre-treatment work-up. Post-treatment PET was not found to be prognostic. Funding through the Medicare Benefits Schedule needs to be considered for high risk MCC.

The shift toward neo-adjuvant chemotherapy and interval debulking surgery for management of advanced ovarian and related cancers in a population-based setting: Impact on clinical outcomes.

OBJECTIVES: The aim of this study was to determine the proportion of patients with advanced ovarian and related cancers (EOC+RC), treated with neoadjuvant chemotherapy and interval debulking surgery (NACT - IDS), and to determine if there was any relationship with optimal cytoreduction rates and overall survival (OS) in a state-wide gynaecologic oncology service over time. METHODS: A retrospective review was undertaken using a population-based database of patients with stages 3 and 4 EOC+RC treated from 1982 till 2013 at the Queensland Centre for Gynaecological Cancer (QCGC). The proportion of patients treated with NACT - IDS compared with primary debulking surgery (PDS) was determined and compared with debulking rates and with the moving five-year OS probability. RESULTS: From 1982-2013, 2601 patients with advanced EOC+RC were managed at QCGC. No patients received NACT - IDS till 1995 when the first two patients received this treatment, rising to 55% of patients in 2013. Surgical cytoreduction rates to no macroscopic residual (R0) were achieved 32% of the time by 2006, rising to 48% in 2009, and 62% in 2013. Despite the increase in utilisation of NACT - IDS, our unit has noted a continued rise in the OS probability at five years to 45%. CONCLUSIONS: The increasing utilisation of NACT - IDS in the setting of a large centralised clinical service has been associated with increasing rates of optimal cytoreduction and survival rates have continued to rise in excess of those achieved in the trials reported to date.

Chemotherapy compliance in high-risk Merkel cell carcinoma treated with chemoradiotherapy.

OBJECTIVE: To evaluate chemotherapy (CT) compliance in patients treated with chemoradiotherapy (CRT) for high-risk Merkel cell cancer (MCC). METHODS: Data from three prospective clinical trials in high-risk MCC performed by the Trans-Tasman Radiation Oncology Group were included in this analysis. Patients were treated with one of two carboplatin-based CT schedules and standardised radiotherapy (RT) to the primary site and nodes to a dose of 50-60 Gy in 25-30 fractions. Patients' baseline characteristics were analysed using χ2 tests to determine compliance factors for completing CT. A Cox univariate analysis was performed to assess the impact of CT compliance on time to locoregional failure, time-to-distant failure, time-to-recurrence and time-to-death. RESULTS: A total of 88 patients were identified, with a median follow up of 38.5 months. Of these, 75 (85%) completed CT (median age 64.2 years, range 62.0-66.4), while 13 did not (median age 72 years, range 68.1-75.9), P = 0.006. Women comprised 18/75 patients who completed CT and 7/13 patients who did not complete it (P = 0.03). Performance status, site, stage, surgical margins, RT dose and toxicity did not impact on their CT compliance. At 5 years, 26% of patients had locoregional relapse, 26% had distant failure and 34% had died. CONCLUSIONS: In this small cohort of patients treated with CRT for high-risk MCC, older age and female sex were associated with failure to complete CT. Severe acute skin and haematological toxicity did not correlate with failure to complete CT.

Improving guideline sensitivity and specificity for the identification of proactive gastrostomy placement in patients with head and neck cancer.

BACKGROUND: Swallowing and nutrition guidelines for patients with head and neck cancer are available for identification of proactive gastrostomy placement in patients with high nutritional risk. The purpose of this study was to investigate improvements to the validity of these guidelines. METHODS: A multivariate analysis was fitted to the original dataset (n = 501) to examine the variables that may predict gastrostomy placement (eg, tumor site, treatment, sex, and age). Using these factors, the high risk category was modified and retrospectively validated in the same cohort to provide new measures of sensitivity and specificity. RESULTS: The following were positive predictors of gastrostomy placement: T3 (p = .01), T4 (p < .001), and chemoradiotherapy (p < .001). Laryngeal (p = .02) and skin cancer (p < .001) were negative predictors. Modification of the high risk definition improved sensitivity to 58% and maintained specificity at 92%. CONCLUSION: Minor modifications to the high risk definition in the guidelines have improved the guideline sensitivity for future use. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1163-E1171, 2016.

Natural oil-based emulsion containing allantoin versus aqueous cream for managing radiation-induced skin reactions in patients with cancer: a phase 3, double-blind, randomized, controlled trial.

PURPOSE: To investigate the effects of a natural oil-based emulsion containing allantoin versus aqueous cream for preventing and managing radiation-induced skin reactions. METHODS AND MATERIALS: A total of 174 patients were randomized and participated in the study. Patients received either cream 1 (the natural oil-based emulsion containing allantoin) or cream 2 (aqueous cream). Skin toxicity, pain, itching, and skin-related quality of life scores were collected for up to 4 weeks after radiation treatment. RESULTS: Patients who received cream 1 had a significantly lower average level of Common Terminology Criteria for Adverse Events at week 3 (P<.05) but had statistically higher average levels of skin toxicity at weeks 7, 8, and 9 (all P<.001). Similar results were observed when skin toxicity was analyzed by grades. With regards to pain, patients in the cream 2 group had a significantly higher average level of worst pain (P<.05) and itching (P=.046) compared with the cream 1 group at week 3; however, these differences were not observed at other weeks. In addition, there was a strong trend for cream 2 to reduce the incidence of grade 2 or more skin toxicity in comparison with cream 1 (P=.056). Overall, more participants in the cream 1 group were required to use another topical treatment at weeks 8 (P=.049) and 9 (P=.01). CONCLUSION: The natural oil-based emulsion containing allantoin seems to have similar effects for managing skin toxicity compared with aqueous cream up to week 5; however, it becomes significantly less effective at later weeks into the radiation treatment and beyond treatment completion (week 6 and beyond). There were no major differences in pain, itching, and skin-related quality of life. In light of these results, clinicians and patients can base their decision on costs and preferences. Overall, aqueous cream seems to be a more preferred option.

Cutaneous carcinoma of the head and neck with clinical features of perineural infiltration treated with radiotherapy.

AIMS: To review the outcome of patients with non-melanomatous carcinoma of the skin of the head and neck with perineural infiltration (PNI) with clinical features treated with radiotherapy. MATERIALS AND METHODS: Between 1991 and 2004, 56 patients with non-melanomatous skin carcinoma with PNI with clinical features were identified from the institution's oncology database. All patients had radiotherapy as either definitive or adjuvant treatment. The factors that affected outcome were analysed. The primary end point was the 5 year relapse-free survival (RFS) from the time of diagnosis of PNI. RESULTS: The overall 5 year RFS for the whole group was 48%. Squamous histology had a more unfavourable outcome than basal cell histology (5 year RFS: 39% versus 80%; P = 0.07). Tumours located in the distribution of the cranial nerves V1 and V2 had a worse outcome than tumours at other sites (5 year RFS: 33% versus 72%, P = 0.056). Those with multiple cranial nerve involvement did worse than those with single nerve involvement (27% versus 62%, P = 0.1). The pattern of relapse was predominantly local (87%), with a low rate (15%) of successful salvage. CONCLUSION: Radiotherapy with or without surgery is curative in about half head and neck cutaneous non-melanomatous carcinomas with clinical PNI. The frequent local failure suggests that improvements in local treatment are required.

A retrospective analysis of survival outcomes for two different radiotherapy fractionation schedules given in the same overall time for limited stage small cell lung cancer.

PURPOSE: To compare survival outcomes for two fractionation schedules of thoracic radiotherapy, both given over 3 weeks, in patients with limited stage small cell lung cancer (LS-SCLC). METHODS AND MATERIALS: At Radiation Oncology Mater Centre (ROMC) and the Royal Brisbane & Women's Hospital (RBWH), patients with LS-SCLC treated with curative intent are given radiotherapy (with concurrent chemotherapy) to a dose of either 40 Gy in 15 fractions ('the 40 Gy/15# group') or 45 Gy in 30 fractions ('the 45 Gy/30# group'). The choice largely depends on institutional preference. Both these schedules are given over 3 weeks, using daily and twice-daily fractionation respectively. The records of all such patients treated from January 2000 to July 2009 were retrospectively reviewed and survival outcomes between the two groups compared. RESULTS: Of 118 eligible patients, there were 38 patients in the 40 Gy/15# group and 41 patients in the 45 Gy/30# group. The median relapse-free survival time was 12 months in both groups. Median overall survival was 21 months (95% CI 2-37 months) in the 40 Gy/15# group and 26 months (95% CI 1-48 months) in the 45 Gy/30# group. The 5-year overall survival rates were 20% and 25%, respectively (P = 0.24). On multivariate analysis, factors influencing overall survival were: whether prophylactic cranial irradiation (PCI) was given (P = 0.01) and whether salvage chemotherapy was given at the time of relapse (P = 0.057). CONCLUSIONS: Given the small sample size, the potential for selection bias and the retrospective nature of our study it is not possible to draw firm conclusions regarding the efficacy of hypofractionated thoracic radiotherapy compared with hyperfractionated accelerated thoracic radiotherapy however hypofractionated radiotherapy may result in equivalent relapse-free survival.

The impact of preradiation residual disease volume on time to locoregional failure in cutaneous Merkel cell carcinoma--a TROG substudy.

PURPOSE: This study evaluated the impact of margin status and gross residual disease in patients treated with chemoradiation therapy for high-risk stage I and II Merkel cell cancer (MCC). METHODS AND MATERIALS: Data were pooled from 3 prospective trials in which patients were treated with 50 Gy in 25 fractions to the primary lesion and draining lymph nodes and 2 schedules of carboplatin based chemotherapy. Time to locoregional failure was analyzed according to the burden of disease at the time of radiation therapy, comparing patients with negative margins, involved margins, or macroscopic disease. RESULTS: Analysis was performed on 88 patients, of whom 9 had microscopically positive resection margins and 26 had macroscopic residual disease. The majority of gross disease was confined to nodal regions. The 5-year time to locoregional failure, time to distant failure, time to progression, and disease-specific survival rates for the whole group were 73%, 69%, 62%, and 66% respectively. The hazard ratio for macroscopic disease at the primary site or the nodes was 1.25 (95% confidence interval 0.57-2.77), P=.58. CONCLUSIONS: No statistically significant differences in time to locoregional failure were identified between patients with negative margins and those with microscopic or gross residual disease. These results must, however, be interpreted with caution because of the limited sample size.

Validated swallowing and nutrition guidelines for patients with head and neck cancer: identification of high-risk patients for proactive gastrostomy.

BACKGROUND: The "Swallowing and Nutrition Guidelines for Patients with Head and Neck Cancer" were developed to guide early identification and management of dysphagia and nutritional risk before, during, and after cancer treatment. The purpose of this study was to validate these guidelines. METHODS: Patients attending a Combined Head and Neck Clinic at a major tertiary hospital in 2007 to 2008 were assessed using the guidelines, with high-risk category patients recommended for proactive gastrostomy. Data were collected on guideline adherence, gastrostomy tube insertion, and weight. Sensitivity, specificity, and positive predictive value were calculated for validation. RESULTS: Proactive gastrostomy tubes were inserted in 173 of 501 patients (25%). Overall guideline adherence was 87%. High-risk category adherence was 75%. Validation outcomes were sensitivity 54%, specificity 93%, and positive predictive value 82%. CONCLUSION: The risk categories in the guidelines are valid to assist early identification of swallowing and nutritional risk and guide decision-making on proactive gastrostomy tube insertion.

Decreased hospital stay and significant cost savings after routine use of prophylactic gastrostomy for high-risk patients with head and neck cancer receiving chemoradiotherapy at a tertiary cancer institution.

BACKGROUND: Evidence-based nutritional and swallowing guidelines were developed to identify patients at high risk of developing malnutrition during chemoradiation for head and neck cancer. These guidelines recommended a prophylactic gastrostomy and were actively implemented at our institution in January 2007. This study assesses the effect of this policy change on patient outcomes. METHODS: This retrospective cohort study was carried out for the years before (2005) and after (2007) implementation of these guidelines. RESULTS: In all, 165 patients were treated with radical chemoradiation for head and neck cancer at our institution in the years 2005 and 2007. Gastrostomy tube complications were low. Patients in 2007 had significantly fewer hospital admissions, unexpected admissions, and a shorter mean duration of hospital stay in comparison with those in 2005. CONCLUSIONS: Prophylactic gastrostomy tubes in patients with high-risk head and neck cancer resulted in a significant decrease in hospital admissions and length of stay, and led to increased bed availability.

A double-blind randomised controlled trial of a natural oil-based emulsion (Moogoo Udder Cream®) containing allantoin versus aqueous cream for managing radiation-induced skin reactions in patients with cancer.

BACKGROUND: Radiation-induced skin reaction (RISR) is one of the most common and distressing side effects of radiotherapy in patients with cancer. It is featured with swelling, redness, itching, pain, breaks in skin, discomfort, and a burning sensation. There is a lack of convincing evidence supporting any single practice in the prevention or management of RISR. METHODS/DESIGNS: This double-blinded randomised controlled trial aims to investigate the effects of a natural oil-based emulsion containing allantoin (as known as Moogoo Udder Cream®) versus aqueous cream in reducing RISR, improving pain, itching and quality of life in this patient group. One group will receive Moogoo Udder Cream®. Another group will receive aqueous cream. Outcome measures will be collected using patient self-administered questionnaire, interviewer administered questionnaire and clinician assessment at commencement of radiotherapy, weekly during radiotherapy, and four weeks after the completion of radiotherapy. DISCUSSION: Despite advances of radiologic advances and supportive care, RISR are still not well managed. There is a lack of efficacious interventions in managing RISR. While anecdotal evidence suggests that Moogoo Udder Cream® may be effective in managing RISR, research is needed to substantiate this claim. This paper presents the design of a double blind randomised controlled trial that will evaluate the effects of Moogoo Udder Cream® versus aqueous cream for managing in RISR in patients with cancer. TRIAL REGISTRATION: ACTRN 12612000568819.

Primary chemoradiotherapy for oral cavity squamous cell carcinoma.

OBJECTIVES: To evaluate the survival of patients with oral cavity squamous cell carcinoma (SCC) treated with chemoradiotherapy (CRT) or radiotherapy (RT). To record the rate of osteoradionecrosis (ORN) and need for alternative feeding of patients with oral cavity cancer treated with CRT or RT. MATERIALS AND METHODS: All patients with first presentation of oral cavity SCC treated with CRT or RT only at the Royal Brisbane & Women's Hospital (RBWH) between 2000 and 2007 were included. Patient Demographics (age, sex), ACE-27 Co-morbidity index, Staging (TNM staging system), Type of Chemotherapy and Dose of RT, Overall Survival (OS) and Disease-Specific Survival (DSS), Attempt at Salvage, development of distant metastases, development of ORN and success of treatment for ORN and requirement for alternative feeding (PEG/NGT) were recorded. RESULTS: Fifty-four patients met the inclusion criteria. One patient died due to toxicity of treatment. The 5-year OS was 29%. The 5-year DSS was 30%. The rate of ORN amongst survivors was 36%. CONCLUSIONS: CRT is successful in a small number of patients with oral cavity SCC. When compared to the published literature, surgery with or without post-operative RT has better survival rates. Salvage surgery does not appear to be a viable option for management of recurrence post CRT. The consequences of treatment, namely ORN and need for alternative feeding, are high.

Tubular breast carcinoma: an argument against treatment de-escalation.

PURPOSE: To evaluate the role of adjuvant radiotherapy in management of patients with tubular carcinoma of the breast. METHODS: One hundred seventy-eight patients treated for tubular carcinoma were identified from the Queensland Radium Institute database. A retrospective review of medical records identified 115 patients meeting eligibility criteria: breast-conserving surgery for a histological diagnosis of tubular carcinoma, minimum follow up of 12 months and adequate medical records. RESULTS: Median follow up was 64 months. There were no significant differences between patient characteristics treated with and without radiotherapy. Median age at diagnosis was 54 (36-78) years. Ninety-five percent tumours were T1 and four patients had positive axillary lymph nodes. Of 94 patients treated with adjuvant radiotherapy, one developed local relapse. Five of 21 patients who did not have adjuvant radiotherapy failed locally. Five-year relapse-free survival with and without radiotherapy was 100 and 89%, respectively (hazard ratio for radiotherapy: 0.06; 95% confidence interval 0.01-0.32, P = 0.001). CONCLUSION: Radiotherapy has a significant impact on relapse-free survival in patients treated with breast-conserving surgery for tubular carcinoma.

Analysis of prognostic variables, development of predictive models, and stratification of risk groups in surgically treated FIGO early-stage (IA-IIA) carcinoma cervix.

OBJECTIVES: The objectives of the study were to evaluate clinicopathologic prognostic variables in surgically treated International Federation of Obstetrics and Gynecology early-stage (IA-IIA) cervical cancer, develop prognostic models, and note the role of adjuvant treatment, patterns of failure, and salvage survival (SS) in each group. METHODS: Records of 542 patients who received primary surgical treatment for International Federation of Obstetrics and Gynecology (IA-IIA) cervical cancer were reviewed. Ninety-eight patients who relapsed after primary treatment were identified and matched for stage and age with a control group. Clinicopathologic prognostic variables were identified and used to develop a prognostic model with 3 risk groups for overall survival (OS) and relapse-free survival (RFS). The roles of adjuvant treatment, relapse sites, and SS were also noted in the groups. RESULTS: The 5-year OS was 70% for the whole group, 97% in the control group, and 44% in the relapse group. There was a statistically significant decrease in survival in patients 70 years or older, those with positive lymphovascular space invasion (LVSI), and in patients with positive LVSI and increasing depth of invasion in both univariate and multivariate analyses (P < 0.001). Positive lymph node status and tumor size of 31 mm or greater showed only a trend toward lower OS and RFS, respectively, in multivariate analysis. An additive model using regression coefficients from multivariate Cox model stratified patients into low-, medium-, and high-risk groups. Relapse-free survival and OS were significantly different in all 3 groups (P < 0.001). Salvage survival was better in low-risk group relative to medium- and high-risk groups, (P = 0.05) as well as between the medium- and high-risk groups (P = 0.03). More distant and locoregional relapses were noted in the medium- and high-risk groups, and SS was better with a local versus locoregional or distant recurrence (P < 0.001). CONCLUSIONS: In this study, age 70 years or older and positive LVSI were found to be statistically significant prognostic factors for both OS and RFS. Positive lymph nodes status showed only a trend toward lower OS. Positive LVSI status had significant adverse prognostic effects on RFS and OS in tumors with increasing depth of invasion. Additive prognostic model helps identify predictors and stratify patients into low-, medium-, and high-risk groups for survival. Many of these factors can be identified preoperatively and may assist in decision to offer primary surgery or alternative therapies in patients with potentially operable cervix cancer. Prognostic model can be used as a tool to design clinical trials and select the group of patients who are the appropriate target for a trial.

Perineural infiltration of cutaneous squamous cell carcinoma and basal cell carcinoma without clinical features.

PURPOSE: To review the factors that influence outcome and patterns of relapse in patients with cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with perineural infiltration (PNI) without clinical or radiologic features, treated with surgery and radiotherapy. METHODS AND MATERIALS: Between 1991 and 2004, 222 patients with SCC or BCC with PNI on pathologic examination but without clinical or radiologic PNI features were identified. Charts were reviewed retrospectively and relevant data collected. All patients were treated with curative intent; all had radiotherapy, and most had surgery. The primary endpoint was 5-year relapse-free survival from the time of diagnosis. RESULTS: Patients with SCC did significantly worse than those with BCC (5-year relapse-free survival, 78% vs. 91%; p < 0.01). Squamous cell carcinoma with PNI at recurrence did significantly worse than de novo in terms of 5-year local failure (40% vs. 19%; p < 0.01) and regional relapse (29% vs. 5%; p < 0.01). Depth of invasion was also a significant factor. Of the PNI-specific factors for SCC, focal PNI did significantly better than more-extensive PNI, but involved nerve diameter or presence of PNI at the periphery of the tumor were not significant factors. CONCLUSIONS: Radiotherapy in conjunction with surgery offers an acceptable outcome for cutaneous SCC and BCC with PNI. This study suggests that focal PNI is not an adverse feature.

Persistence and malignant sequelae of gestational trophoblastic disease: Clinical presentation, diagnosis, treatment and outcome.

BACKGROUND: The major concern in gestational trophoblastic disease is management of persistent disease and malignant sequelae. However, prediction of response to treatment is difficult and methods used controversial. AIM AND METHODS: To evaluate the usefulness of clinical presentation, methods of diagnosis and categorisation of risk in determining clinical outcomes, by analysis of a database of 705 registered patients collected over 30 years. RESULTS: From the database, there were 97 patients who developed persistent disease and malignant sequelae on the basis of defined criteria - 80.4% had molar pregnancy and 19.6% non-molar pregnancy. Vaginal bleeding was not a common presentation; 59.8% had no clinical symptoms. According to protocol, monitoring by serial human chorion gonadotrophin (HCG) levels followed by imaging screen was used in all patients; histology was also available in 41.2% from hysterectomy and curettage specimens. There were 16 of 76 patients with persisting disease who had metastases (21.1%), and 2 of 20 patients with choriocarcinoma who had an antecedent molar pregnancy (10.0%). Based on five risk factors, 25 patients were categorised as 'high risk' and assigned to receive multi-drug chemotherapy. There were two deaths (2.1% for all malignant sequelae); both were from molar pregnancies. One patient failed to respond and the other suffered a complication of intensive chemotherapy. CONCLUSION: Serial HCG levels remain the best monitor to determine therapeutic response. Categorisation of 'high risk' by five factors is useful in treatment. Albeit a small series, clinical outcome is favourable with a five-year survival of 89.7%.

Effect of lifestyle factors and hormone therapy on heart function by serial echocardiography in postmenopausal women.

BACKGROUND: There is conflicting information on the effects of oestrogen on the heart in women, especially those using postmenopausal hormone therapy. Whilst some studies reported a beneficial effect, others showed adverse outcomes. The interplay of lifestyle factors and type/timing of therapy remains to be clarified. AIM: The aim of this study was to determine the effects of lifestyle and hormone therapy on heart function and structure in postmenopausal women. METHOD: As part of a large longitudinal study of women randomly recruited from an urban population, the study assessed 410 suitable women by echocardiography in Year 1 and Year 5 of the study by two independent cardiologists. RESULTS: In lifestyle characteristics, the difference in age and body mass (as markers of cardiovascular risk) was in favour of never-users versus hormone therapy-users. Using an arbitrary cut-off > or =15% change for an effect, we found lifestyle factors had minimal effect on the two measured parameters - ejection fraction, left ventricular mass. Effects of hormone therapy were variable and mixed; greatest effect was found for an 'early start' of hormone therapy with oestrogen-only preparation - the risk of reduced ejection fraction was decreased [hazard ratio (HR) 0.42, confidence interval = 0.17-1.03, P = 0.06] and risk of increased left ventricular mass was increased (HR 2.21, 1.09-4.49, P = 0.03). CONCLUSION: Our findings add to the evidence that oestrogen given to postmenopausal women has a mixed effect on the heart, with effect best shown when started early.

Factors influencing relapse-free survival in Merkel cell carcinoma of the lower limb--a review of 60 cases.

PURPOSE: Factors affecting relapse-free survival (RFS) in patients with Merkel cell carcinoma (MCC) of the lower limb were reviewed. METHODS AND MATERIALS: The records of 60 patients from 1986 to 2005 with a diagnosis of MCC of the lower limb or buttock were retrospectively reviewed. The patients were treated with curative intent with surgery, radiation, or chemotherapy. RESULTS: The 5-year overall survival, disease-specific survival, and RFS were 53%, 61%, and 20%, respectively. Factors influencing RFS were analyzed using univariate analysis. It appeared that recurrent disease worsened RFS (p = 0.03) and the addition of any radiotherapy improved RFS (p <0.001), as did radiotherapy to the inguinal nodes (p = 0.01) or primary site and inguinal nodes (p = 0.003). Age, surgical margins, and stage were not statistically significant. On multivariate analysis, the only significant factor was the addition of radiotherapy (hazard ratio = 0.51 p = 0.03). CONCLUSION: The addition of radiotherapy improves RFS compared with surgery alone. Elective treatment should be given to the inguinal nodes to reduce the risk of relapse.

Radiotherapy for perineural invasion in cutaneous head and neck carcinomas: toward a risk-adapted treatment approach.

BACKGROUND: We retrospectively reviewed outcomes in patients treated with radiotherapy (RT) for cutaneous head and neck carcinoma with perineural invasion (PNI), with the aim of developing risk-adapted treatment guidelines. METHODS: A total of 118 patients were treated with RT between April 1992 and July 2000. Ninety-seven patients had PNI discovered through histology (pPNI) and 21 patients had symptoms/signs of PNI (cPNI). All received RT (median dose, 55 Gy; range, 17-74): 114 postoperatively and 4 definitively. Median follow-up was 84 months (range, 4-201). RESULTS: The 5-year local control (LC) rates were 90% with pPNI and 57% with cPNI (p < .0001). The pPNI and cPNI groups also differed in relapse-free survival (76% vs 46%, p = .003), disease-specific survival (90% vs 76%, p = .002), and overall survival (69% vs 57%, p = .03). pPNI patients with BCC histology (n = 42) had better LC (97% vs 84%, p = .02) than pPNI SCC (n = 55). CONCLUSION: Surgery plus RT provides a high rate of LC in patients with pPNI, particularly those with BCC. Therapeutic improvements are needed for patients with cPNI.