Margin reduction from image guided radiation therapy for soft tissue sarcoma: Secondary analysis of Radiation Therapy Oncology Group 0630 results.

PURPOSE: Six imaging modalities were used in Radiation Therapy Oncology Group (RTOG) 0630, a study of image guided radiation therapy (IGRT) for primary soft tissue sarcomas of the extremity. We analyzed all daily patient-repositioning data collected in this trial to determine the impact of daily IGRT on clinical target volume-to-planning target volume (CTV-to-PTV) margin. METHODS AND MATERIALS: Daily repositioning data, including shifts in right-left (RL), superior-inferior (SI), and anterior-posterior (AP) directions and rotations for 98 patients enrolled in RTOG 0630 from 18 institutions were analyzed. Patients were repositioned daily on the basis of bone anatomy by using pretreatment images, including kilovoltage orthogonal images (KVorth), megavoltage orthogonal images (MVorth), KV fan-beam computed tomography (KVCT), KV cone beam CT (KVCB), MV fan-beam CT (MVCT), and MV cone beam CT (MVCB). Means and standard deviations (SDs) for each shift and rotation were calculated for each patient and for each IGRT modality. The Student's t tests and F-tests were performed to analyze the differences in the means and SDs. Necessary CTV-to-PTV margins were estimated. RESULTS: The repositioning shifts and day-to-day variations were large and generally similar for the 6 imaging modalities. Of the 2 most commonly used modalities, MVCT and KVorth, there were no statistically significant differences in the shifts and rotations (P = .15 and .59 for the RL and SI shifts, respectively; and P = .22 for rotation), except for shifts in AP direction (P = .002). The estimated CTV-to-PTV margins in the RL, SI, and AP directions would be 13.0, 10.4, and 11.7 mm from MVCT data, respectively, and 13.1, 8.6, and 10.8 mm from KVorth data, respectively, indicating that margins substantially larger than 5 mm used with daily IGRT would be required in the absence of IGRT. CONCLUSIONS: The observed large daily repositioning errors and the large variations among institutions imply that daily IGRT is necessary for this tumor site, particularly in multi-institutional trials. Otherwise, a CTV-to-PTV margin of 1.5 cm is required to account for daily setup variations.

Significant Reduction of Late Toxicities in Patients With Extremity Sarcoma Treated With Image-Guided Radiation Therapy to a Reduced Target Volume: Results of Radiation Therapy Oncology Group RTOG-0630 Trial.

PURPOSE: We performed a multi-institutional prospective phase II trial to assess late toxicities in patients with extremity soft tissue sarcoma (STS) treated with preoperative image-guided radiation therapy (IGRT) to a reduced target volume. PATIENTS AND METHODS: Patients with extremity STS received IGRT with (cohort A) or without (cohort B) chemotherapy followed by limb-sparing resection. Daily pretreatment images were coregistered with digitally reconstructed radiographs so that the patient position could be adjusted before each treatment. All patients received IGRT to reduced tumor volumes according to strict protocol guidelines. Late toxicities were assessed at 2 years. RESULTS: In all, 98 patients were accrued (cohort A, 12; cohort B, 86). Cohort A was closed prematurely because of poor accrual and is not reported. Seventy-nine eligible patients from cohort B form the basis of this report. At a median follow-up of 3.6 years, five patients did not have surgery because of disease progression. There were five local treatment failures, all of which were in field. Of the 57 patients assessed for late toxicities at 2 years, 10.5% experienced at least one grade ≥ 2 toxicity as compared with 37% of patients in the National Cancer Institute of Canada SR2 (CAN-NCIC-SR2: Phase III Randomized Study of Pre- vs Postoperative Radiotherapy in Curable Extremity Soft Tissue Sarcoma) trial receiving preoperative radiation therapy without IGRT (P < .001). CONCLUSION: The significant reduction of late toxicities in patients with extremity STS who were treated with preoperative IGRT and absence of marginal-field recurrences suggest that the target volumes used in the Radiation Therapy Oncology Group RTOG-0630 (A Phase II Trial of Image-Guided Preoperative Radiotherapy for Primary Soft Tissue Sarcomas of the Extremity) study are appropriate for preoperative IGRT for extremity STS.

Epithelioid malignant peripheral nerve sheath tumor arising in a schwannoma, in a patient with "neuroblastoma-like" schwannomatosis and a novel germline SMARCB1 mutation.

Epithelioid malignant peripheral nerve sheath tumors arising in preexisting schwannomas are extremely rare. We report an unusual example occurring in a patient with multiple schwannomas (schwannomatosis), all but 1 of which showed "neuroblastoma-like" histology. By immunohistochemistry, both the epithelioid malignant peripheral nerve sheath tumor and the schwannomas showed a complete loss of the Smarcb1 protein. Subsequent genetic evaluation revealed the presence of a novel germline mutation in the SMARCB1/INI1 gene in the patient and in 3 of her children, 2 of whom were diagnosed with atypical teratoid/rhabdoid tumors of the brain.

2009 Canadian radiation oncology resident survey.

PURPOSE: Statistics from the Canadian post-MD education registry show that numbers of Canadian radiation oncology (RO) trainees have risen from 62 in 1999 to approximately 150 per year between 2003 and 2009, contributing to the current perceived downturn in employment opportunities for radiation oncologists in Canada. When last surveyed in 2003, Canadian RO residents identified job availability as their main concern. Our objective was to survey current Canadian RO residents on their training and career plans. METHODS AND MATERIALS: Trainees from the 13 Canadian residency programs using the national matching service were sought. Potential respondents were identified through individual program directors or chief resident and were e-mailed a secure link to an online survey. Descriptive statistics were used to report responses. RESULTS: The eligible response rate was 53% (83/156). Similar to the 2003 survey, respondents generally expressed high satisfaction with their programs and specialty. The most frequently expressed perceived weakness in their training differed from 2003, with 46.5% of current respondents feeling unprepared to enter the job market. 72% plan on pursuing a postresidency fellowship. Most respondents intend to practice in Canada. Fewer than 20% of respondents believe that there is a strong demand for radiation oncologists in Canada. CONCLUSIONS: Respondents to the current survey expressed significant satisfaction with their career choice and training program. However, differences exist compared with the 2003 survey, including the current perceived lack of demand for radiation oncologists in Canada.

Assessment of outcomes in surgically staged I/II endometrial adenocarcinoma patients treated with postoperative vaginal vault radiotherapy only.

OBJECTIVE: To examine the efficacy of vaginal vault radiotherapy as adjuvant treatment for patients with high-grade, stage I/II endometrial adenocarcinoma who have been surgically staged. METHODS: A retrospective chart review of 77 women between 1995 and 2006 with high-grade surgically staged I and II endometrial adenocarcinoma, who were treated with postoperative vaginal vault radiotherapy alone, was performed. The primary study end points were recurrence risk and sites of recurrence. The secondary end points were disease-free and overall survival. Kaplan-Meier estimates were calculated for overall and disease-free survival. RESULTS: Seventy-seven women were identified and met inclusion criteria. Sixty-seven (87%) had grade 3 histologic features on final pathologic report. Forty-two patients (55%) were classified as stage IB, having superficial myometrial invasion; 21 (27%) were stage IC, with deep invasion; and 6 (8%) were stage II, involving the cervix. The median follow-up was 80 months (6.6 years). There were 10 recurrences (13.0%), of which 3 were local: 1 involving the vaginal apex; 1, the lower vagina and pelvic sidewall; and 1, the lower vagina. The 5-year recurrence risk was 11.2% and the 5-year survival probability 88.9%. CONCLUSIONS: It seems that for this cohort of 77 patients with surgically staged I and II grade 3 endometrial adenocarcinoma, adjuvant vaginal vault radiotherapy alone leads to acceptable recurrence rates and survival while minimizing morbidity.

The management of inoperable Stage I endometrial cancer using intracavitary brachytherapy alone: a 20-year institutional review.

OBJECTIVE: To review our institution's results with primary low dose rate (LDR) intracavitary brachytherapy using Heyman's capsules for medically inoperable cancer of the endometrium. METHODS: The study was a retrospective review of inoperable early-stage endometrial cancer patients at the Cross Cancer Institute in Edmonton, Canada, treated with primary radiotherapy from January 10, 1986 to July 17, 2006. Forty-four patients with International Federation of Gynaecology and Obstetrics (FIGO) clinical Stage I disease were included in the study. Kaplan-Meier survival analysis was performed to obtain estimates of overall survival (OS), disease-free survival, and disease-specific survival (DSS). Tumor grade was assessed as a potential predictor of OS by comparing survival curves using a log-rank test. RESULTS: The median OS time was 75.5 months (95% confidence interval 55.6-95.3 months). For the entire group, the 5- and 10-year OS was 60.5% and 24.0%, respectively. The 5- and 10-year DSS was 87.7% and 79.7%, respectively. For a subset treated as planned, the 5- and 10-year OS was 54.5% and 34.5%, respectively. The 5- and 10-year DSS was 83.0% and 76.4%, respectively. When stratified by grade, trends in survival analysis are inversely related to grade. Both the trend analysis and the log-rank test were statistically significant at a p<0.05 level. CONCLUSIONS: Our experience with LDR brachytherapy for the treatment of Stage I endometrial cancer is comparable to surgical treatment and to results reported in the literature for high dose rate brachytherapy. Further study that would help define the indications for a primary radiotherapeutic approach in early-stage endometrial cancer may lower current thresholds for recommending primary radiotherapy versus surgery.

Twenty-year review of radiotherapy for vaginal cancer: an institutional experience.

OBJECTIVE: To evaluate clinical outcome, prognostic factors and chronic morbidity with radiotherapy for vaginal cancer treatment. MATERIALS AND METHODS: 68 patients with vaginal cancer treated by radical or adjuvant radiotherapy (RT) were selected. Five with rare subtypes of histopathology and 8 with adenocarcinoma were excluded from this study. 76.4% of the remainder had early-stage diseases (stage I: 14, II: 28, III: 9, and IV: 4). The patients in the years from which they were treated were almost evenly distributed (1st 5 years: 13, 2nd: 14, 3rd: 16, and 4th: 12). There were four treatment groups: external beam radiotherapy (EBRT) alone (n=18), brachytherapy (BT) alone (n=4), EBRT and BT (n=30), and surgery plus RT (n=3). RESULTS: Median follow-up was 50.3 months ranging from 3 to 213 months. 5-year overall survival (OS) was 55.6%, disease-specific survival (DSS) was 77.3%, disease-free survival was 74.2%, and local control was 87.7%. Independent prognostic factors for DSS and OS were tumor stage, site and size (p<0.05). Late radiation toxicity was minimal in the bladder (4.6%) and bowel (4.6%). Vaginal morbidity was observed in 35 patients (63.6%). It was lowest in the BT alone (0%), and highest in the EBRT and BT group (82.1%), especially for those received more than 70 Gy (p=0.05, Odds ratio=4.64, 95% confidence interval: 1.01-21.65). CONCLUSION: This retrospective review suggested that tumor stage, site, and size were important prognostic factors in patients with vaginal cancer. Higher radiation dose was associated with more frequent vaginal toxicity.

Assessment of extended-field radiotherapy for stage IIIC endometrial cancer using three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and helical tomotherapy.

PURPOSE: To perform a dosimetric comparison of three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and helical tomotherapy (HT) plans for pelvic and para-aortic RT in postoperative endometrial cancer patients; and to evaluate the integral dose (ID) received by critical structures within the radiation fields. METHODS AND MATERIALS: We selected 10 patients with Stage IIIC endometrial cancer. For each patient, three plans were created with 3D-CRT, IMRT, and HT. The IMRT and HT plans were both optimized to keep the mean dose to the planning target volume (PTV) the same as that with 3D-CRT. The dosimetry and ID for the critical structures were compared. A paired two-tailed Student t test was used for data analysis. RESULTS: Compared with the 3D-CRT plans, the IMRT plans resulted in lower IDs in the organs at risk (OARs), ranging from -3.49% to -17.59%. The HT plans showed a similar result except that the ID for the bowel increased 0.27%. The IMRT and HT plans both increased the IDs to normal tissue (see Table 1 and text for definition), pelvic bone, and spine (range, 3.31-19.7%). The IMRT and HT dosimetry showed superior PTV coverage and better OAR sparing than the 3D-CRT dosimetry. Compared directly with IMRT, HT showed similar PTV coverage, lower Ids, and a decreased dose to most OARs. CONCLUSION: Intensity-modulated RT and HT appear to achieve excellent PTV coverage and better sparing of OARs, but at the expense of increased IDs to normal tissue and skeleton. HT allows for additional improvement in dosimetry and sparing of most OARs.

Can serum markers be used to predict acute and late toxicity in patients with lung cancer? Analysis of RTOG 91-03.

PURPOSE: To identify factors that are predictive of satisfactory acute and long-term pulmonary tolerance of definitive irradiation and, conversely, factors that are predictive of excessive impairment of pulmonary functions. To determine if there is any correlation between early elevation of biochemical markers obtained in blood of irradiated patients and subsequent pulmonary abnormalities as detected by clinical findings, pulmonary function tests, and/or radiographic findings of pneumonitis/fibrosis. MATERIALS AND METHODS: This was a multi-institutional prospective trial sponsored by the Radiation Therapy Oncology Group. Eligible patients had surgically unresectable or medically inoperable stage II or III non-small cell lung cancer. Pretreatment evaluation included baseline dyspnea index (BDI) and pulmonary function tests (PFT). Radiation therapy consisted of once-daily treatment with 2 Gy to a total of 60 to 66 Gy. A quantitative nuclear medicine perfusion study was correlated to the radiation therapy portals to assess the proportion of lung irradiated. Blood for serum markers (surfactant apoprotein, procollagen type III, interleukin [IL]-1, interleukin-6, and tumor necrosis factor-alpha) was drawn prior to the beginning of radiation therapy and then weekly during treatment (at 10, 20, 30, 40, 50, and 60 Gy). Post-treatment follow-up included PFT every 3 months for 1 year and then annually. The BDI was reevaluated at the same intervals. RESULTS: There were 127 analyzable patients. Squamous cell carcinoma was the predominant histology and 93% of the patients had AJCC stage III disease. The median survival time is 10.9 months with 43% of patients living 1 year and 10% living 3 years. Grade >or=2 acute lung toxicity was seen in 18% of patients; patients least likely to develop lung toxicity are those with undetectable levels of IL-6 at 10 Gy and diffusing capacity of the lung for carbon monoxide percent (DLCO%) >54. Patients most likely to develop acute toxicity are those with elevated IL-6 and age >60 years. Grade >or=2 late lung toxicity was seen in 30% of patients. Karnofsky performance status was the only pretreatment factor predictive of late lung toxicity. The proportion of lung within the irradiated field, BDI indices, physician-assessed baseline dyspnea, and baseline PFT were not predictive of pulmonary toxicity. Using grade >or=2 toxicity as an event, age >60 years, gender, and a surfactant level <797 at 20 Gy were predictive of late lung toxicity. CONCLUSIONS: Elevated levels of serum IL-6 after 10 Gy of lung irradiation appear to predict grade >or=2 acute lung toxicity, and high serum levels of surfactant apoproteins at 20 Gy correlated with grade >or=2 late pulmonary toxicity. These findings need to be confirmed but could be useful in a model to predict risk of pulmonary injury with high doses of radiation. For future studies, it is necessary to evaluate serum markers at multiple time-points during treatment, and quality control is critical during the collection, storage, and analysis of these serum markers.

Correlates of exercise motivation and behavior in a population-based sample of endometrial cancer survivors: an application of the Theory of Planned Behavior.

BACKGROUND: Despite evidence of the benefits of exercise in cancer survivors, exercise participation rates tend to decline after treatments. Few studies have examined the determinants of exercise in less common cancer sites. In this study, we examined medical, demographic, and social cognitive correlates of exercise in endometrial cancer survivors using the Theory of Planned Behavior (TPB). METHODS: A mailed survey was completed by 354 endometrial cancer survivors (1 to 10 years postdiagnosis) residing in Alberta, Canada. The study was cross-sectional. Exercise behavior was assessed using the Godin Leisure Time Exercise Questionnaire and the TPB constructs were assessed with standard self-report scales. Multiple regression analyses were used to determine the independent associations of the TPB constructs with intention and behavior. RESULTS: Chi-square analyses indicated that marital status (p = .003), income level (p = .013), and body mass index (BMI) (p = .020) were associated with exercise. The TPB explained 34.1% of the variance in exercise behavior with intention (beta = .38, p < .001) and self-efficacy (beta = .18, p = .029) being independent correlates. For intention, 38.3% of the variance was explained by the TPB with self-efficacy (beta = .34, p < .001) and affective attitude (beta = .30, p < .001) being the independent correlates. The TPB mediated the associations of marital status and BMI with exercise but not income level. Age and BMI moderated the associations of the TPB with intention and behavior. CONCLUSION: The TPB may be a useful framework for understanding exercise in endometrial cancer survivors. Exercise behavior change interventions based on the TPB should be tested in this growing population.

Exercise preferences of endometrial cancer survivors: a population-based study.

Exercise has gained recognition as an effective supportive care intervention for cancer survivors, yet participation rates are low. Knowledge of the specific exercise counseling and programming preferences of cancer survivors may be useful for designing effective interventions. In this study, we examined the exercise preferences of 386 endometrial cancer survivors. Participants completed a questionnaire that included measures of past exercise behavior, exercise preferences, and medical and demographic information. Some key findings were as follows: (a) 76.9% of participants said they were interested or might be interested in doing an exercise program and (b) 81.7% felt they were able or likely able to actually do an exercise program. Participants also indicated that walking was their preferred activity (68.6%) and moderate exercise was their preferred intensity (61.1%). Logistic regression analyses showed that meeting public health guidelines for exercise, being overweight or obese, receiving adjuvant treatment, months since diagnosis, income, marital status, and level of education all influenced exercise preferences. These results suggest that endometrial cancer survivors have unique exercise preferences that are moderated by a number of demographic and medical variables. These findings may have implications for the design and implementation of clinical and population-based exercise interventions for endometrial cancer survivors.

Associations among exercise, body weight, and quality of life in a population-based sample of endometrial cancer survivors.

OBJECTIVES: Lack of exercise and excess body weight may exacerbate treatment-related declines in quality of life (QoL) in endometrial cancer survivors. The primary purpose of this study was to examine the associations among exercise, body weight, and QoL in a population-based sample of endometrial cancer survivors. METHODS: Participants were 386 endometrial cancer survivors residing in Alberta, Canada who completed a mailed survey that assessed self-reported exercise, height, and weight to calculate body mass index (BMI) and QoL using the Functional Assessment of Cancer Therapy-Anemia (FACT-An) scale. RESULTS: Descriptive data indicated that 70% of the sample were not meeting public health exercise guidelines and 72% were overweight or obese. Multivariate analyses of variance demonstrated that endometrial cancer survivors meeting public health guidelines for exercise and body weight reported significantly better QoL than survivors not meeting guidelines. The differences in QoL between the groups were clinically meaningful and were not altered when controlling for important demographic and medical variables. There were no interactions between exercise, BMI, age, or time since diagnosis. Lastly, multiple regression analysis identified that both exercise (beta = .21; P < .001) and BMI (beta = -.17; P < .001) were independently associated with QoL. CONCLUSIONS: These results suggest that exercise and body weight are important independent correlates of QoL in endometrial cancer survivors. Randomized controlled trials designed to test the causal effects of exercise and/or weight loss on QoL in endometrial cancer survivors are warranted.

2003 survey of Canadian radiation oncology residents.

PURPOSE: Radiation oncology's popularity as a career in Canada has surged in the past 5 years. Consequently, resident numbers in Canadian radiation oncology residencies are at all-time highs. This study aimed to survey Canadian radiation oncology residents about their opinions of their specialty and training experiences. METHODS AND MATERIALS: Residents of Canadian radiation oncology residencies that enroll trainees through the Canadian Resident Matching Service were identified from a national database. Residents were mailed an anonymous survey. RESULTS: Eight of 101 (7.9%) potential respondents were foreign funded. Fifty-two of 101 (51.5%) residents responded. A strong record of graduating its residents was the most important factor residents considered when choosing programs. Satisfaction with their program was expressed by 92.3% of respondents, and 94.3% expressed satisfaction with their specialty. Respondents planning to practice in Canada totaled 80.8%, and 76.9% plan to have academic careers. Respondents identified job availability and receiving adequate teaching from preceptors during residency as their most important concerns. CONCLUSIONS: Though most respondents are satisfied with their programs and specialty, job availability and adequate teaching are concerns. In the future, limited time and resources and the continued popularity of radiation oncology as a career will magnify the challenge of training competent radiation oncologists in Canada.

radiotherapy-induced ID reaction.

To the authors' knowledge, there is a paucity of published accounts of radiotherapy-induced ID reaction. We report a case of generalized dermatitis pathologically defined as an ID reaction after a course of local radiotherapy.

Cutaneous angiosarcoma of the scalp: a case report of sustained complete response following liposomal Doxorubicin and radiation therapy.

Cutaneous angiosarcomas of the head and neck are aggressive cancers with a mean overall survival of 30 months. We add to the literature a case report of a 65-year-old man with a large, >10 cm, unresectable, angiosarcoma of the scalp who was treated with two cycles of liposomal doxorubicin (Caelyx(R)) followed by electron beam radiation therapy (30 Gy in 10 fractions over 2 weeks) who has sustained a complete response with a 4-year follow-up. The dose and fractionation of the radiation therapy in this case was palliative and was not expected to give lasting local control of this lesion. It is therefore possible that either the genetic profile of the tumour conferred radiosensitivity or that the radiation therapy induced a recall phenomenon of the liposomal doxorubicin.