Distinct patterns of stomatitis with concurrent cetuximab and radiotherapy for head and neck squamous cell carcinoma.

To describe the distinct patterns of severe anterior stomatitis seen with concurrent cetuximab and radiotherapy (RT) compared to chemoRT or altered fractionation RT (AFRT) and explore potential associations with clinical and dosimetric parameters. We reviewed acute toxicity data from 42 patients receiving cetuximab-RT and a matched cohort of 36 patients receiving chemoRT or AFRT. The occurrence of grade ≥3 oral toxicities was analysed with respect to clinical (age, gender, smoking/alcohol history, tumour subsite, grade of acneiform rash) and dosimetric parameters. Cetuximab-RT patients experienced higher rates of grade ≥3 cheilitis (26% vs 6%, p=0.01) and anterior stomatitis (38% vs 6%, p=0.002), despite these structures receiving low RT doses (median maximum dose to lips 9.3 Gy, anterior oral cavity 20 Gy). Multivariable analyses identified increasing severity of acneiform rash as the strongest predictor of grade ≥3 cheilitis whilst increasing RT dose was weakly correlated. A trend was observed for increasing pack years of smoking on univariate analysis only. The combination of cetuximab and low doses of RT to the anterior oral cavity has resulted in a distinctive pattern of cheilitis and anterior stomatitis in our patients. Further exploration of this phenomenon may yield additional insights into the interaction of cetuximab with RT in non-target tissues.

The sap from Euphorbia peplus is effective against human nonmelanoma skin cancers.

BACKGROUND: The sap from Euphorbia peplus, commonly known as petty spurge in the U.K. or radium weed in Australia, has been used as a traditional treatment for a number of cancers. OBJECTIVE: To determine the effectiveness of E. peplus sap in a phase I/II clinical study for the topical treatment of basal cell carcinomas (BCC), squamous cell carcinomas (SCC) and intraepidermal carcinomas (IEC). METHODS: Thirty-six patients, who had refused, failed or were unsuitable for conventional treatment, were enrolled in a phase I/II clinical study. A total of 48 skin cancer lesions were treated topically with 100-300 µL of E. peplus sap once daily for 3 days. RESULTS: The complete clinical response rates at 1 month were 82% (n = 28) for BCC, 94% (n = 16) for IEC and 75% (n = 4) for SCC. After a mean follow-up of 15 months these rates were 57%, 75% and 50%, respectively. For superficial lesions < 16 mm, the response rates after follow-up were 100% for IEC (n = 10) and 78% for BCC (n = 9). CONCLUSIONS: The clinical responses for these relatively unfavourable lesions (43% had failed previous treatments, 35% were situated in the head and neck region and 30% were > 2 cm in diameter), are comparable with existing nonsurgical treatments. An active ingredient of E. peplus sap has been identified as ingenol mebutate (PEP005). This clinical study affirms community experience with E. peplus sap, and supports further clinical development of PEP005 for the treatment of BCC, SCC and IEC.

Lung cancer patients in Queensland suffer delays in receiving radiation therapy--but not as a result of distance.

AIM: To determine whether lung cancer radiation therapy waiting times in Queensland public hospitals are associated with distance of residence from the nearest treatment facility. METHODS: Retrospective analysis of radiation therapy waiting times of 1535 Queensland residents who were diagnosed with lung cancer from 2000 to 2004 and received radiation therapy as initial treatment at a public hospital. The effect of distance of residence from treatment centre on median waiting time was analysed by quantile regression controlling for sex, age, lung cancer histology, stage and therapeutic intent. RESULTS: The median waiting time from diagnosis to start of radiation therapy was 33 days for all patients. There was no significant difference (P = 0.141) in median waiting times in relation to distance of residence from a treatment centre. However, in most patients, waiting times were significantly longer than recommended by the Royal Australian and New Zealand College of Radiologists. Curative patients waited longer than palliative patients, while patients with earlier stage cancer waited longer than those with more advanced disease. CONCLUSION: Waiting times for radiation therapy among lung cancer patients in Queensland was not associated with distance from place of residence to the nearest public treatment facility. However, delays overall are excessive and are likely to worsen unless radiation treatment capabilities are enhanced to keep pace with population growth in Queensland.

Biochemical markers for brain damage after carbon monoxide poisoning.

BACKGROUND: Carbon monoxide poisoning is associated with high mortality and a substantial risk for brain damage in survivors. Evidence for acute brain dysfunction may be obtained by measuring concentrations of suitable biochemical markers. We hypothesized that increased serum concentrations of Neuron-specific enolase (NSE) and S-100beta protein could be detected after carbon monoxide poisoning and that the concentration would correlate with the severity of intoxication. METHODS: Prospective non-interventional study in the university hospital. We included 20 patients admitted for hyperbaric treatment due to carbon monoxide poisoning. Serum levels of NSE and S-100beta protein were measured in all patients on admission and after 12, 24, 36 and 48 h. As a control group, we included 20 patients who underwent elective hyperbaric treatment. RESULTS: Serum concentrations of NSE and S-100beta protein were not significantly different from the controls, with median values at admission being 10.6 vs. 9.7 microg l(-1) and 0.15 vs. 0.13 microg l(-1), respectively (P = 0.82 and P = 0.38). The concentrations did not change significantly during the sampling period. We were unable to show any significant relation to level of consciousness. CONCLUSION: Blood concentrations of NSE and S-100beta protein were not significantly increased after carbon monoxide poisoning and do not seem to be related to a history of unconsciousness.

A randomised trial of accelerated and conventional radiotherapy for stage III and IV squamous carcinoma of the head and neck: a Trans-Tasman Radiation Oncology Group Study.

PURPOSE: The aims of this randomized controlled trial were to determine whether there were differences in the disease-free survival (DFS) and toxicity between conventional radiotherapy (CRT) and a continuous 3 week accelerated radiotherapy regimen (ART) in stage III and IV squamous cell carcinoma of the oral cavity, oropharynx, larynx and hypopharynx. PATIENTS AND METHODS: Patients from 14 centres throughout Australia and New Zealand were randomly assigned to either CRT, using a single 2 Gy/day to a dose of 70 Gy in 35 fractions in 49 days or to ART, using 1.8 Gy twice a day to a dose of 59.4 Gy in 33 fractions in 24 days. Treatment allocation was stratified for site and stage. The accrual began in 1991 and the trial was closed in 1998 when the target of 350 patients was reached. RESULTS: The median potential follow-up time was 53 months (range, 14-101). The DFS at 5 years was 41% (95% CI, 33-50%) for ART and 35% (95% CI, 27-43%) for CRT (P=0.323) and the hazard ratio was 0.87 in favour of ART (95% CI, 0.66-1.15). The 5-year disease-specific survival rates were 40% for CRT and 46% for ART (P=0.398) and the loco-regional control was 47% for CRT vs. 52% for ART (P=0.300). The respective hazard ratios were 0.88 (95% CI, 0.65-1.2) and 0.85 (0.62-1.16), favouring the accelerated arm. In the ART arm, confluent mucositis was more severe (94 vs. 71%; P<0.001) and peaked about 3 weeks earlier than in the CRT arm, but healing appeared complete in all cases. There were statistically significant reductions in the probability of grade 2 or greater late soft tissue effects over time in the ART arm (P<0.05), except for the mucous membrane where late effects were similar in both arms. CONCLUSIONS: Differences in DFS, disease-specific survival and loco-regional control have not been demonstrated. ART resulted in more acute mucosal toxicity, but this did not result in greater prolongation of the treatment time compared with the CRT arm. There were less late effects in the ART arm, with the exception of late mucosal effects. This trial has confirmed that tumour cell repopulation occurs during conventionally fractionated radiotherapy for head and neck cancer. However, it has also provided additional evidence that overall improvements in the therapeutic ratio using accelerated fractionation strategies are seriously constrained by the need to limit total doses to levels that do not exceed acute mucosal tolerance. The accelerated schedule tested has been shown in this trial to be an acceptable alternative to conventionally fractionated irradiation to 70 Gy.

Is routine follow-up useful after combined-modality therapy for advanced head and neck cancer?

OBJECTIVE: To evaluate the usefulness of routine follow-up in a selected group of patients with head and neck cancer. DESIGN: Retrospective cohort study with follow-up of 5 years for all patients. PATIENTS: Three hundred two patients with advanced (stage II or IV) squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx were treated with curative intent with surgery and postoperative radiation therapy between January 1, 1970, and December 31, 1990. MAIN OUTCOME MEASURE: Survival after recurrence of the index tumor or the development of a second head and neck primary tumor. RESULTS: Overall actuarial 5-year survival was 56%. Relapse occurred in 119 patients, and salvage therapy was attempted in 49 patients. Only 2 patients survived to 5 years after relapse. CONCLUSION: In patients with advanced head and neck squamous cell carcinoma, routine follow-up is more important for evaluation of treatment results and emotional support than of benefit in improving patient survival.

Development of a CCD array imaging system for measurement of dose distributions in doped agarose gels.

An imaging system for agarose gel sections has been investigated for applications in rapid two-dimensional radiation dosimetry. The imaging system, with white light illumination and CCD camera detection, was designed for measurement of the radiation-induced optical density changes in iron- and xylenol orange dye-doped agarose gels. The performance of the imaging system was compared with that of a laser scanning system for the gels and with the accepted dosimetry standard, the ionization chamber. In measurement of beam profiles of two therapeutic radiation fields, relative dose values from the CCD camera imaging system were on average within 3% ranging from 0.005% to 7.5%) of values recorded with a parallel plate ionization chamber. In comparison with the laser scanner, the CCD camera imaging system provided comparable spatial resolution and an increased rate of data acquisition, although a consistently reduced signal to noise ratio was observed. Suggestions for improving the camera imaging technique include noise reduction through camera cooling and further frame averaging.

Preliminary results of combined chemotherapy and radiotherapy for non-AIDS primary central nervous system lymphoma. Trans-Tasman Radiation Oncology Group (TROG).

OBJECTIVES: To assess the results and toxicity of a regimen of combined chemotherapy and radiotherapy for patients with non-AIDS-related primary central nervous system lymphoma. DESIGN: Prospective assessment of patients treated with intravenous methotrexate followed by cranial irradiation between 1 January 1991 and 31 July 1995. PATIENTS AND SETTING: Patients attending nine Australian and New Zealand centres who were eligible and gave informed consent. MAIN OUTCOME MEASURES: Probability of survival at two years, and acute toxicity. RESULTS: Twenty-four patients were treated. Their probability of survival at two years was 70% (95% confidence interval [CI], 45%-95%). The acute toxicity of the regimen was minimal in most cases, but one patient died of treatment-related neutropenia and subsequent sepsis. Two patients showed progression of pre-existing short term memory disturbance, without evidence of recurrent lymphoma. CONCLUSIONS: Combined-modality therapy improves survival in patients with non-AIDS-related primary central nervous system lymphoma, at least in the short term, relative to radiotherapy alone. The combined regimen resulted in only moderate treatment-related morbidity. Longer follow-up is required for a more accurate estimate of late effects and long-term survival prospects.

Treatment decisions in T3N0M0 glottic carcinoma.

PURPOSE: To analyze the results of T3N0M0 glottic carcinoma treated with radiotherapy, surgery, or both. METHODS AND MATERIALS: The records were retrospectively reviewed of 97 patients with this tumor subsite and stage seen for treatment at the Queensland Radium Institute over a 29-year period. The results for radiotherapy with surgical salvage of failure (XRT/SS) were compared to those with surgery with or without radiotherapy (SURG/SURG+XRT). For those treated initially with radiotherapy alone, the results for different ranges of biologically equivalent doses were compared. These results were compared to those of other published studies. RESULTS: The 5-year disease-specific survival rats for the XRT/SS and SURG/SURG+XRT groups were 50% and 58%, respectively; this difference is not significant. For the XRT/SS group, there was a trend towards improved 5-year recurrence-free survival (73%) and 5-year disease-specific survival (86%) in those treated to a dose equivalent to 60-64 Gy in 2 Gy fractions, when compared with higher or lower dose equivalents. CONCLUSION: A group of patients with T3N0M0 glottic carcinoma is specified for which the option of radiotherapy offers a similar chance of survival to those treated surgically. More than 50% of the XRT/SS survivors will retain their larynx.

New concepts in radiotherapy for advanced squamous cell carcinoma of the head and neck.

This paper reviews two of the newer concepts - multiple daily fractions of radiotherapy - in improving the treatment of squamous cell carcinoma of the head and neck.

Prognostic variables in malignant epithelial tumors of the parotid.

A retrospective analysis was performed on 209 patients with carcinoma of the parotid who were treated with curative intent using surgery and post-operative irradiation. The five and ten-year actuarial survival were 71% and 65%. Failure at the primary site occurred in 24%, at nodal sites in 14%, and distantly in 23%. Multivariate analysis of prognostic variables identified age greater than 60 years, involved nodes, post-surgical residual disease, and poor differentiation to be bad prognostic variables.

Olfactory neuroblastoma--management of a rare tumour at the Queensland Radium Institute and literature review.

Olfactory neuroblastoma (esthesioneuroblastoma) is an extremely rare tumour arising from the olfactory epithelium of the nasal cavity close to the cribriform plate. Most institutions will have little experience in recognising the clinical and histological features, or management of this tumour and reliance is placed on researching the literature when the individual patient presents. This study reviews seven patients with olfactory neuroblastoma treated at the Queensland Radium Institute from 1971 to January 1990. The overall local control rate in this series is 57% (four of seven patients) and 43% of patients (three of seven) remain alive. Conservative surgery and post-operative radiotherapy is recommended for early disease and more radical surgery with post-operative radiotherapy for advanced disease.

Testicular lymphoma--the need for a new approach.

Thirteen cases of malignant lymphoma of the testis were referred to the Queensland Radium Institute between 1975 and 1989. The age varied from 43 years to 84 years and the histology was intermediate to high grade in all cases. Seven patients had Stage I/II and 6 had Stage III/IV. The 4 year survival was only 16%. Half of the relapses were systemic, 1 was in the para-aortic nodes (unirradiated) and 2 were in the opposite testicle. Adjuvant radiotherapy to para-aortic nodes and mild chemotherapy have produced disappointing results. A new approach using aggressive combination chemotherapy and adjuvant scrotal irradiation is proposed for early stage disease.

Nodal recurrence in primary malignant epithelial tumours of the parotid gland.

An analysis has been made of the incidence of nodal recurrence in 237 patients with primary carcinoma of the parotid gland. Fifty eight patients (24.4%) developed nodal metastases; mostly in the cervical region. Eighteen of these metastases were within the radiation field and 13 were outside the radiation field. Factors which were predictive for nodal relapse were: Age greater than 60 years, T3 and T4 tumours, node metastases at initial presentation, and macroscopic disease at either the primary site or the nodal site. The complete response rate for treatment of nodal relapse was 19% and the partial response rate was 17.2%. The 5 year actuarial survival from the time of first presentation was 58%. The pattern of nodal recurrence in this study indicates that radiation portals should cover more than the first eschalon (upper deep cervical) nodes. Our current policy is to recommend elective irradiation of the lower cervical nodes in patients with primary parotid malignancies.

The salvage of recurrent endometrial carcinoma in the vagina and pelvis.

A retrospective analysis was performed on 93 patients who developed recurrent endometrial carcinoma in the pelvis, vaginal vault, and lower 1/3 vagina. There were 12 lower 1/3 vaginal recurrences, 24 vault recurrences and 57 pelvic recurrences from the 1005 patients treated between 1960 and 1976. Median time to recurrence was 30 months. Twenty-six patients had distant metastases also present at the time of recurrence in the sites mentioned above. Thirty-three percent of lower 1/3 vaginal recurrences, 12.5% of vault recurrences, and 5.3% of pelvic recurrences were salvaged with further treatment. The 10-year actuarial survival rates of isolated lower 1/3 vaginal, vaginal vault, and pelvic recurrences were 50%, 45%, and 24% respectively.

Arteriovenous malformations--a summary of 6 cases treated with radiation therapy.

Six cases of inoperable arteriovenous malformations (AVM) treated with conventional megavoltage radiation therapy are reviewed. One of the six cases had complete angiographic clearance of the AVM. None of the cases have had recurrent bleeding. One has had uncontrolled epilepsy. There were no treatment complications.

Prognostic variables in endometrial carcinoma.

Data were obtained retrospectively on 1005 patients with histologically proven endometrial carcinoma from January 1960 to December 1976 inclusive. The 5- and 10-year actuarial survivals for all stages were 83 and 80% respectively. Recurrent disease developed in 14% of patients. The site of first recurrence was vaginal vault in 2.5%, lower vagina in 1.1%, pelvis in 5.7%, and lungs in 1.9%. Thirty-eight patients (27%) had multiple sites of metastatic disease at the time of first relapse. The only significant independent prognostic variables for clinical Stage I adenocarcinoma treated with surgery and radiation were no myometrial penetration and poorly differentiated tumors.