Lee Tripcony

High-Risk Merkel Cell Carcinoma of the Skin Treated With Synchronous Carboplatin/Etoposide and Radiation: A Trans-Tasman Radiation Oncology Group Study—TROG 96:07

PURPOSE The effectiveness of synchronous carboplatin, etoposide, and radiation therapy was prospectively assessed in a group of patients with high-risk Merkel cell carcinoma (MCC) of the skin. PATIENTS AND METHODS Patients were eligible if they had disease localized to the primary site and nodes, and were required to have at least one of the following high risk features: recurrence after initial therapy, involved nodes, primary tumor size greater than 1 cm, gross residual disease after surgery, or occult primary with nodes. Radiation was delivered to the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks and synchronous carboplatin (area under the curve, 4.5) and intravenous etoposide 80 mg/m2 days 1 to 3 was given in weeks 1, 4, 7, and 10. The median age of the group was 67 (range, 43-86) years, and there were 39 males and 14 females. Involved nodes (stage II) were present in 33 cases (62%). The sites involved were head and neck (22 patients), occult primary (13 patients), upper limb (eight patients), lower limb (eight patients), and trunk (two patients). RESULTS Fifty-three patients were entered between 1996 and 2001. The median potential follow-up was 48 months. There were no treatment related deaths. The 3-year overall survival, locoregional control, and distant control were 76%, 75%, and 76%, respectively. Tumor site and the presence of nodes were factors that were predictive for local control and survival. Multivariate analysis indicated that the major factor influencing survival was the presence of nodes; however, this was not a significant factor in locoregional control. CONCLUSION High levels of locoregional control and survival have been achieved with the addition of chemotherapy to radiation treatment for high-risk MCC of the skin. The role of chemoradiotherapy for high-risk MCC warrants further investigation.

A Phase III study on the efficacy of topical aloe vera gel on irradiated breast tissue.

The aim of the study was to see if topical aloe vera gel would be beneficial in reducing the identified skin side-effects of radiation therapy, including erythema, pain, itching, dry desquamation, and moist desquamation, when compared with aqueous cream. The secondary aim was to assess the effect of other factors known to predict severity of radiation skin reaction, ie, breast size, smoking habit, and one or more drainages of lymphocele after surgery, on other skin side effects. A Phase III study was conducted involving 225 patients with breast cancer after lumpectomy or partial mastectomy, who required a course of radiation therapy using tangential fields. Patients were randomized to either topical aloe vera gel or topical aqueous cream to be applied 3 times per day throughout and for 2 weeks after completion of radiation treatment. Weekly skin assessments were performed by nursing staff. Aqueous cream was significantly better than aloe vera gel in reducing dry desquamation and pain related to treatment. Subjects with D cup or larger size breasts experienced significantly more erythema, regardless of treatment arm. For subjects who had undergone lymphocele drainage, the aloe vera group experienced significantly more pain than the aqueous cream group. Within the aqueous cream arm, smokers were significantly more likely to experience itching within the treatment field than were nonsmokers. Within the aloe vera arm, subjects who had undergone one or more lymphocele drainages after surgery were significantly more likely to experience erythema and itching within the treatment field than those who did not have drainage. In this study, aloe vera gel did not significantly reduce radiation-induced skin side effects. Aqueous cream was useful in reducing dry desquamation and pain related to radiation therapy.

Do acute mucosal reactions lead to consequential late reactions in patients with head and neck cancer

BACKGROUND AND PURPOSE The relationship between acute and late mucosal reactions remains ill defined but is of considerable relevance to efforts to produce therapeutic gains through the use of altered fractionation schemes and concurrent chemotherapy. We therefore investigated whether acute mucosal reactions in patients treated with an accelerated and a conventionally fractionated radiotherapy regime predicted the severity of late mucosal reactions. PATIENTS AND METHODS The study population consisted of 191 patients randomised on a prospective trial comparing conventional fractionation at 2 Gy/fraction per day, 70 Gy over 47 days with an accelerated regimen of 59.4 Gy, 1.8 Gy b.i.d over 24 days for Stage III-IV carcinoma of the head and neck. Acute and late mucosal reactions were scored according to RTOG/EORTC criteria and analyzed using multiple regression techniques. RESULTS The duration of time spent by patients at the acute confluent mucositis grade 3 level was inversely related to the time to onset of the reaction for both fractionation schedules. Time to onset was more rapid for patients treated on the accelerated schedule but time spent at the reaction grade did not differ significantly between the schedules. After correction for treatment and patient related factors, anatomical site (oral cavity/oropharynx versus hypopharynx/larynx) and increasing duration of confluent mucositis emerged as independent predictors of the hazard of late mucosal reactions with the latter effect being more pronounced in the accelerated treatment arm. The expected reduction in late mucosal effects in the accelerated fractionation arm, predicted by the LQ model for late effects was identified only in patients whose acute confluent mucosal reactions lasted less than 20 days. CONCLUSIONS The presence of individual patient susceptibility factors that determine the severity of acute mucosal reactions is suggested. A link between severe and prolonged acute reactions and the risk of developing late mucosal reactions that is independent of biological dose, has also been found. Purpose designed prospective studies of these issues are necessary.

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 (Pa 0:323) and the hazard ratio was 0.87 in favour of ART (95% CI, 0.66‐1.15). The 5-year diseasespecific survival rates were 40% for CRT and 46% for ART (Pa 0:398) and the loco-regional control was 47% for CRT vs. 52% for ART (Pa 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. q 2001 Elsevier Science Ireland Ltd. All rights reserved.

Pituitary adenomas: Long-term results for radiotherapy alone and post-operative radiotherapy

PURPOSE Analysis of prognostic factors and long-term results of treatment of pituitary adenomas. METHODS AND MATERIALS The study involved a retrospective review of outcome in a series of 268 patients with pituitary adenomas, treated at the Queensland Radium Institute from January 1962 to December 1986. The study population included 108 patients treated with radiotherapy alone and 160 patients treated by surgery and post-operative radiotherapy. In each group, univariate and multivariate analyses were conducted of possible prognostic factors including age, sex, performance status, tumor type, tumor extent, visual disturbance, radiotherapy dose, and field size. RESULTS For radiotherapy alone, the 10-year progression-free survival rate was 60%, and overall tumor control was obtained in 77%. Univariate analysis suggested that tumor type and radiotherapy field size were of prognostic significance. Multivariate analysis confirmed that Prolactinoma subtype and increasing radiotherapy field size were independently predictive of reduced progression-free survival. Long-term visual complications occurred in 1% of patients treated by radiotherapy alone. In patients treated by surgery and post-operative radiotherapy, the 10-year progression-free survival rate was 77%, and overall tumor control was achieved in 83%. Univariate analysis suggested that tumor type, completeness of surgical excision, and radiotherapy dose were predictive of outcome. However, on multivariate analysis, only the extent of surgical excision predicted prognosis independently. Long-term visual sequelae were noted in 3% of patients treated by surgery and post-operative radiotherapy. CONCLUSION Both radiotherapy alone and post-operative radiotherapy are effective in long-term control of pituitary adenomas, and produce acceptably low complication rates.

Prognostic Importance of Preoperative CA-125 in International Federation of Gynecology and Obstetrics Stage I Epithelial Ovarian Cancer: An Australian Multicenter Study

PURPOSE To evaluate the prognostic significance of preoperative CA-125 levels on overall survival of patients with International Federation of Gynecology and Obstetrics (FIGO) stage I epithelial ovarian cancer (EOC). PATIENTS AND METHODS Data from 518 patients with FIGO stage I EOC treated in seven gynecologic oncology centers throughout Australia between 1990 and 2002 were analyzed. Patients with borderline tumors and nonepithelial ovarian carcinomas were excluded, as were women in whom CA-125 had not been determined preoperatively. Preoperative CA-125 levels were studied in surgically staged and incompletely staged patients and compared with prognostic factors, such as substage, grade, and histologic type. Multivariate Cox models were calculated. RESULTS CA-125 levels more than 30 U/mL were associated with higher grade, substage 1B and 1C, nonmucinous histologic type, and older age. In univariate analysis, higher histologic grade, the absence of surgical staging, and preoperative CA-125 levels more than 30 U/mL were associated with impaired survival. Multivariate analysis identified histologic grade, preoperative CA-125, and surgical staging as independent predictors for survival. In the subgroup of completely surgically staged patients, the 5-year overall survival rate was 82% (95% CI, 76% to 88%) for patients with CA-125 levels more than 30 U/mL and 95% (95% CI, 90% to 99%) for patients with CA-125 levels of 30 U/mL or less (P = .028). In the group of incompletely staged patients, the 5-year survival rates were similar for patients with elevated and normal serum CA-125 levels. CONCLUSION Complete surgical staging, histologic grade, and preoperative serum CA-125 levels are independent prognostic factors and should be included in the decision making for chemotherapy.

Peritoneal cytology: impact on disease-free survival in clinical stage I endometrioid adenocarcinoma of the uterus

The prognostic significance of positive peritoneal cytology in endometrial carcinoma has led to the incorporation of peritoneal cytology into the current FIGO staging system. While cytology was shown to be prognostically relevant in patients with stage II and III disease, conflicting data exists about its significance in patients who would have been stage I but were classified as stage III solely and exclusively on the basis of positive peritoneal cytology (clinical stage I). Analysis was based on the data of 369 consecutive patients with clinical stage I endometrioid adenocarcinoma of the endometrium. Standard treatment consisted of an abdominal total hysterectomy, bilateral salpingo-oophorectomy with or without pelvic lymph node dissection. Peritoneal cytology was obtained at laparotomy by peritoneal washing of the pouch of Douglas and was considered positive if malignant cells could be detected regardless of the number of malignant cells present. Disease-free survival (DFS) was considered the primary statistical endpoint. In 13/369 (3.5%) patients, positive peritoneal cytology was found. The median follow-up was 29 months and 15 recurrences occurred. Peritoneal cytology was independent of the depth of myometrial invasion and the grade of tumour differentiation. Patients with negative washings had a DFS of 96% at 36 months compared with 67% for patients with positive washings (log-rank P<0.001). The presence of positive peritoneal cytology in patients with clinically stage I endometrioid adenocarcinoma of the endometrium is considered an adverse prognostic factor.

Conservative therapy of breast cancer in Queensland

PURPOSE Primary radiation therapy following breast-conserving surgery has been an accepted alternative to mastectomy in Europe and North America for many years. In Australia, however, the history of breast conservation for early invasive breast cancer is much shorter. The purpose of this study was to evaluate the results of breast conservation in a state-wide Australian radiotherapy service. METHODS AND MATERIALS Between January 1982 and December 1989, 512 patients were treated with primary radiation therapy after breast conserving surgery. This analysis is based on a review of these patients, all of whom had Stage I or II breast cancer. RESULTS With a median follow-up of 50 months, the 5-year actuarial rate of overall survival was 84% and disease-free survival was 80%. There have been 22 isolated local recurrences in the breast. The time to an isolated breast recurrence ranged from 12 to 83 months (median, 26 months). The 5-year actuarial rate of an isolated breast recurrence was 4%. The recurrence rate was higher for patients with involved margins (15% vs. 2%, p < 0.01). Local recurrence was also more likely in the presence of extensive ductal carcinoma in situ (DCIS), as opposed to no extensive DCIS (10% vs. 2%, p < 0.01). CONCLUSION These results affirm that primary radiation therapy after breast conserving surgery in Queensland, has been given with a low rate of local recurrence, comparable to that obtained in other centers.

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.

Predictors of acute grade 4 swallowing toxicity in patients with stages III and IV squamous carcinoma of the head and neck treated with radiotherapy alone

PURPOSE The purpose of the study was to investigate the predictive factors for acute grade 4 swallowing toxicity in an attempt to identify which patients may benefit from early intervention with enteral feeding during curative radiation treatment for localised Stages 3-4 squamous cell carcinoma of the head and neck. It was hypothesised that craniocaudal length of the treatment field to the upper neck and pharynx would correlate with grade 4 swallowing toxicity due to the increased volume of pharynx irradiated. PATIENTS AND METHODS Toxicity data were collected prospectively as part of a phase III randomised trial (TROG 91:01) that assigned patients to either conventional (CRT) or accelerated radiotherapy (ART). Patients were randomly assigned to either CRT, using a single 2 Gy per 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. Accrual commenced in 1991 and the trial was closed in 1998 when the target of 350 patients was reached. Potential factors were analysed that predicted for Grade IV swallowing toxicity. RESULTS The treatment field lengths >82mm for the second phase increased the probability of requiring intervention with percutaneous endoscopic gastrostomy (PEG) or Nasogastric tube (NGT). The probability of grade 4 swallowing was 36% if the phase 2 treatment length was >82mm vs 16% for less < or = 82mm(p=0.0001). A predictive enteral grading score (PEG score) was derived using the Cox regression coefficients: Field length of the boost volume >82mm scored 3 points, Stage grouping greater than 1 scored 1 point, altered fractionation scored 2 points, ECOG greater than 1 scored 1 point. The PEG score was 45% if the score was 6 and 19% if the score was <6 (p=0.0). CONCLUSIONS More attention needs to be focused on developing robust dose and volume constraints for the pharyngeal mucosa and the musculature in order to reduce the need for enteral feeding. Patients with PEG score of 6 or greater are at high risk of requiring enteral feeding during radiation treatment and should be considered for prophylactic PEG or NG feeding.