Graeme Dickie

Effect of Radiotherapy Dose and Volume on Relapse in Merkel Cell Cancer of the Skin

PURPOSE To assess the effect of radiotherapy (RT) dose and volume on relapse patterns in patients with Stage I-III Merkel cell carcinoma (MCC). PATIENTS AND METHODS This was a retrospective analysis of 112 patients diagnosed with MCC between January 2000 and December 2005 and treated with curative-intent RT. RESULTS Of the 112 evaluable patients, 88% had RT to the site of primary disease for gross (11%) or subclinical (78%) disease. Eighty-nine percent of patients had RT to the regional lymph nodes; in most cases (71%) this was for subclinical disease in the adjuvant or elective setting, whereas 21 patients (19%) were treated with RT to gross nodal disease. With a median follow-up of 3.7 years, the 2-year and 5-year overall survival rates were 72% and 53%, respectively, and the 2-year locoregional control rate was 75%. The in-field relapse rate was 3% for primary disease, and relapse was significantly lower for patients receiving >or=50 Gy (hazard ratio [HR] = 0.22; 95% confidence interval [CI], 0.06-0.86). Surgical margins did not affect the local relapse rate. The in-field relapse rate was 11% for RT to the nodes, with dose being significant for nodal gross disease (HR = 0.24; 95% CI, 0.07-0.87). Patients who did not receive elective nodal RT had a much higher rate of nodal relapse compared with those who did (HR = 6.03; 95% CI, 1.34-27.10). CONCLUSION This study indicates a dose-response for subclinical and gross MCC. Doses of >or=50 Gy for subclinical disease and >or=55 Gy for gross disease should be considered. The draining nodal basin should be treated in all patients.

Lymphoproliferative Disease of the Ocular Adnexa: A Clinical and Pathologic Study With Statistical Analysis of 69 Patients

Purpose: To evaluate the clinical features, treatment, and outcomes of a cohort of patients with ocular adnexal lymphoproliferative disease classified according to the World Health Organization modification of the Revised European-American Classification of Lymphoid neoplasms and to perform a robust statistical analysis of these data. Methods: Sixty-nine cases of ocular adnexal lymphoproliferative disease, seen in a tertiary referral center from 1992 to 2003, were included in the study. Lesions were classified by using the World Health Organization modification of the Revised European-American Classification of Lymphoid neoplasms classification. Outcome variables included disease-specific survival, relapse-free survival, local control, and distant control. Results: Stage IV disease at presentation, aggressive lymphoma histology, the presence of prior or concurrent systemic lymphoma at presentation, and bilateral adnexal disease were significant predictors for reduced disease-specific survival, local control, and distant control. Multivariate analysis found that aggressive histology and bilateral adnexal disease had significantly reduced disease-specific survival. Conclusions: The typical presentation of adnexal lymphoproliferative disease is with a painless mass, swelling, or proptosis; however, pain and inflammation occurred in 20% and 30% of patients, respectively. Stage at presentation, tumor histology, primary or secondary status, and whether the process was unilateral or bilateral were significant variables for disease outcome. In this study, distant spread of lymphoma was lower in patients who received greater than 20 Gy of orbital radiotherapy.

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

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.

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.

Weekly Carboplatin Reduces Toxicity During Synchronous Chemoradiotherapy for Merkel Cell Carcinoma of Skin

PURPOSE The toxicity of radiotherapy (RT) combined with weekly carboplatin and adjuvant carboplatin and etoposide was prospectively assessed in a group of patients with high-risk Stage I and II Merkel cell carcinoma of the skin. This regimen was compared with the Trans-Tasman Radiation Oncology Group 96:07 study, which used identical eligibility criteria but carboplatin and etoposide every 3 weeks during RT. PATIENTS AND METHODS Patients were eligible if they had disease localized to the primary site and lymph nodes, with high-risk features. RT was delivered to the primary site and lymph nodes to a dose of 50 Gy and weekly carboplatin (area under the curve of 2) was given during RT. This was followed by three cycles of carboplatin and etoposide. A total of 18 patients were entered into the study, and their data were compared with the data from 53 patients entered into the Trans-Tasman Radiation Oncology Group 96:07 study. RESULTS Involved lymph nodes (Stage II) were present in 14 patients (77%). Treatment was completed as planned in 16 patients. The weekly carboplatin dose was delivered in 17 patients, and 15 were able to complete all three cycles of adjuvant carboplatin and etoposide. Grade 3 and 4 neutrophil toxicity occurred in 7 patients, but no cases of febrile neutropenia developed. Compared with the Trans-Tasman Radiation Oncology Group 96:07 protocol (19 of 53 cases of febrile neutropenia), the reduction in the febrile neutropenia rate (p = 0.003) and decrease in Grade 3 skin toxicity (p = 0.006) were highly statistically significant. CONCLUSION The results of our study have shown that weekly carboplatin at this dosage is a safe way to deliver synchronous chemotherapy during RT for MCC and results in a marked reduction of febrile neutropenia and Grade 3 skin toxicity compared with the three weekly regimen.

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.

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.

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 & Womens 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.

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 institutions 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.

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

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.