Jennifer L. Harper

Skin toxicity during breast irradiation: pathophysiology and management.

Radiotherapy is a critical component in the treatment of breast cancer, a disease that is estimated to have affected 203,500 US women in 2002. According to the data from some series, an estimated 90% of patients treated with radiotherapy for breast cancer will develop a degree of radiation-induced dermatitis. This review describes the indications and techniques of radiotherapy for breast cancer. The pathophysiology, clinical presentation, and contributing factors of radiation-related skin injury are discussed. A review of recent clinical research addressing skin toxicity is provided.

Prospective randomized double-blind pilot study of site-specific consensus atlas implementation for rectal cancer target volume delineation in the cooperative group setting

PURPOSE Variations in target volume delineation represent a significant hurdle in clinical trials involving conformal radiotherapy. We sought to determine the effect of a consensus guideline-based visual atlas on contouring the target volumes. METHODS AND MATERIALS A representative case was contoured (Scan 1) by 14 physician observers and a reference expert with and without target volume delineation instructions derived from a proposed rectal cancer clinical trial involving conformal radiotherapy. The gross tumor volume (GTV), and two clinical target volumes (CTVA, including the internal iliac, presacral, and perirectal nodes, and CTVB, which included the external iliac nodes) were contoured. The observers were randomly assigned to receipt (Group A) or nonreceipt (Group B) of a consensus guideline and atlas for anorectal cancers and then instructed to recontour the same case/images (Scan 2). Observer variation was analyzed volumetrically using the conformation number (CN, where CN = 1 equals total agreement). RESULTS Of 14 evaluable contour sets (1 expert and 7 Group A and 6 Group B observers), greater agreement was found for the GTV (mean CN, 0.75) than for the CTVs (mean CN, 0.46-0.65). Atlas exposure for Group A led to significantly increased interobserver agreement for CTVA (mean initial CN, 0.68, after atlas use, 0.76; p = .03) and increased agreement with the expert reference (initial mean CN, 0.58; after atlas use, 0.69; p = .02). For the GTV and CTVB, neither the interobserver nor the expert agreement was altered after atlas exposure. CONCLUSION Consensus guideline atlas implementation resulted in a detectable difference in interobserver agreement and a greater approximation of expert volumes for the CTVA but not for the GTV or CTVB in the specified case. Visual atlas inclusion should be considered as a feature in future clinical trials incorporating conformal RT.

Outcomes in Women Treated With MammoSite Brachytherapy or Whole Breast Irradiation Stratified by ASTRO Accelerated Partial Breast Irradiation Consensus Statement Groups

PURPOSE The American Society for Radiation Oncology published a Consensus Statement for accelerated partial breast irradiation identifying three groups: Suitable, Cautionary, and Unsuitable. The objective of this study was to compare oncologic outcomes in women treated with MammoSite brachytherapy (MB) vs. whole breast irradiation (WBI) after stratification into Statement groups. METHODS Eligible women had invasive carcinoma or ductal carcinoma in situ (DCIS) ≤ 3 cm, and ≤ 3 lymph nodes positive. Women were stratified by radiation modality and Statement groups. Survival analysis methods including Kaplan-Meier estimation, Cox regression, and competing risks analysis were used to assess overall survival (OS), disease-free survival (DFS), time to local failure (TTLF), and tumor bed failure (TBF). RESULTS A total of 459 (183 MB and 276 WBI) patients were treated from 2002 to 2009. After a median follow-up of 45 months, we found no statistical differences by stratification group or radiation modality with regard to OS and DFS. At 4 years TTLF or TBF were not statistically different between the cohorts. Univariate analysis in the MB cohort revealed that nodal positivity (pN1 vs. pN0) was related to TTLF (hazard ratio 6.39, p = 0.02). There was a suggestion that DCIS histology had an increased risk of failure when compared with invasive ductal carcinoma (hazard ratio 3.57, p = 0.06). CONCLUSIONS MB and WBI patients stratified by Statement groups seem to combine women who will have similar outcomes regardless of radiation modality. Although outcomes were similar, we remain guarded in overinterpretation of these preliminary results until further analysis and long-term follow-up data become available. Caution should be used in treating women with DCIS or pN1 disease with MB.

Incidence and prognostic factors for seroma development after MammoSite breast brachytherapy.

PURPOSE Describe the incidence and identify risk factors for seroma development after MammoSite breast brachytherapy (MBT). METHODS AND MATERIALS MBT patient data were prospectively recorded into a quality assurance database. Departmental and electronic records were reviewed to extract patient-, treatment-, and outcome-specific data. Stepwise logistic regression analysis was performed to identify factors associated with development of any seroma including the subset of clinically significant seroma (CSS). CSS was defined as a symptomatic seroma requiring multiple aspirations, biopsy, and/or excision. Variables analyzed included age, weight, number of excisions, time from resection to catheter placement, placement technique, balloon volume, dosimetric factors, and postbrachytherapy infection. RESULTS MBT was performed in 109 patients, of whom 97 had minimum 6 months (median, 36) post-MBT follow-up or earlier development of seroma. All patients received 34 Gy to 1cm depth from balloon surface, delivered twice daily in 10 fractions. Seroma developed in 41% of patients at a median of 3 months (range, 0.1-25) post-MBT. One-third of seromas (13% of all patients) were CSS. The only factor identified as statistically significant for development of any seroma was catheter placement on day of resection vs. > or =1 day later (59% vs. 33%; p = 0.0066). Post-MBT infection was highly statistically significant for development of CSS (64% vs. 7%; p<0.0001). Prophylactic antibiotics reduced the risk of post-MBT infection from 37.5% to 6% (p = 0.011). CONCLUSIONS The incidence of CSS after MBT is low. Post-MBT infection is statistically significantly associated with CSS development, the incidence of which is reduced with prophylactic antibiotics.

Dose to level I and II axillary lymph nodes and lung by tangential field radiation in patients undergoing postmastectomy radiation with tissue expander reconstruction.

BackgroundTo define the dosimetric coverage of level I/II axillary volumes and the lung volume irradiated in postmastectomy radiotherapy (PMRT) following tissue expander placement.Methods and MaterialsTwenty-three patients were identified who had undergone postmastectomy radiotherapy with tangent only fields. All patients had pre-radiation tissue expander placement and expansion. Thirteen patients had bilateral expander reconstruction. The level I/II axillary volumes were contoured using the RTOG contouring atlas. The patient-specific variables of expander volume, superior-to-inferior location of expander, distance between expanders, expander angle and axillary volume were analyzed to determine their relationship to the axillary volume and lung volume dose.ResultsThe mean coverage of the level I/II axillary volume by the 95% isodose line (VD95%) was 23.9% (range 0.3 - 65.4%). The mean Ipsilateral Lung VD50% was 8.8% (2.2-20.9). Ipsilateral and contralateral expander volume correlated to Axillary VD95% in patients with bilateral reconstruction (p = 0.01 and 0.006, respectively) but not those with ipsilateral only reconstruction (p = 0.60). Ipsilateral Lung VD50% correlated with angle of the expander from midline (p = 0.05).ConclusionsIn patients undergoing PMRT with tissue expanders, incidental doses delivered by tangents to the axilla, as defined by the RTOG contouring atlas, do not provide adequate coverage. The posterior-superior region of level I and II is the region most commonly underdosed. Axillary volume coverage increased with increasing expander volumes in patients with bilateral reconstruction. Lung dose increased with increasing expander angle from midline. This information should be considered both when placing expanders and when designing PMRT tangent only treatment plans by contouring and targeting the axilla volume when axillary treatment is indicated.

The use of adjuvant high-dose-rate breast brachytherapy in patients with collagen vascular disease: A collaborative experience

PURPOSE To analyze toxicity and cosmesis in patients with collagen vascular disease (CVD) treated with accelerated partial breast irradiation (APBI) via high-dose-rate (HDR) brachytherapy. METHODS AND MATERIALS This is a pooled analysis of patients with early stage and in situ breast cancer with CVD treated with adjuvant multicatheter or balloon brachytherapy. Physicians at multiple institutions were asked to review their experience and report data regarding toxicity and cosmesis in patients with CVD. All patients fit American Society of Breast Surgeons recommendations for APBI and were treated with HDR brachytherapy with ≥ 3 months followup. RESULTS Nine cases from five institutions are the subject of this analysis. The median patient age was 54 years and median followup was 31 months. All patients had documented history and active signs/symptoms of rheumatoid arthritis, systemic lupus erythematosis, psoriatic arthritis, or scleroderma. All patients had received medical therapy for CVD in the past, and 78% were under active treatment at the time of brachytherapy. All the patients were treated with multicatheter or balloon (MammoSite [Hologic, Inc., Marlboro, MA], MammoSite ML [Hologic, Inc., Marlboro, MA], or Contura [Senorx, Irvine, CA]) brachytherapy with a median volume of 45.5 cc and a median skin distance of 7.5mm. Acute toxicity included Grade 1 skin erythema (5) and catheter-site wound dehiscence (1). Late toxicity included seroma (5), induration (5), pain (2), telangectasia (2), and superficial infection (1). Cosmesis was excellent or good for all the patients. CONCLUSIONS Women with CVD have a toxicity and cosmesis profile consistent with other APBI series. Although confirmatory data is needed, it may not be necessary to exclude these patients from clinical trials of APBI.

Toxicity, Response Rates and Survival Outcomes of Induction Cisplatin and Irinotecan Followed by Concurrent Cisplatin, Irinotecan and Radiotherapy for Locally Advanced Esophageal Cancer

OBJECTIVE Cisplatin-based chemoradiotherapy is standard treatment for locally advanced esophageal and gastroesophageal cancers; however, the optimal chemotherapy regimen remains to be defined. METHODS Retrospective single institution analysis of toxicities, response rates and survival outcomes in patients with cT3-4 or N1/M1a esophageal squamous cell or adenocarcinoma treated with induction cisplatin and irinotecan followed by concurrent cisplatin, irinotecan and radiotherapy. Secondary analysis for association of disease control and outcomes with demographic, tumor and treatment factors (including histology). RESULTS Fifty-three patients were eligible for the present analysis. All patients underwent endoscopic ultrasonography and were either cT3-4 and/or cN1 disease. Fifty patients completed radiotherapy as planned (median dose 50.4 Gy, range 0-61.2), and 35 patients completed four cycles of chemotherapy as planned (range 1-4). Severe acute toxicities included Grade ≥ 3 neutropenia and esophagitis in 13 and 12 patients, respectively. There were no Grade 5 (fatal) toxicities noted. At mean survivor follow-up of 24.5 months (range 2.7-63), 17 patients were alive (8 without disease) and 36 deceased. Forty patients experienced disease recurrence, with initial loco-regional, distant or both failures in 28, 9 and 3 patients, respectively. Estimated 2-year overall survival and freedom from failure were 42 and 9%, respectively, without significant difference by histology. CONCLUSIONS Cisplatin/irinotecan chemoradiotherapy is tolerable, demonstrating similar efficacy for squamous cell and adenocarcinoma esophageal cancers.

A pilot randomized controlled trial testing a minimal intervention to prepare breast cancer survivors for recovery.

Background: Interventions addressing cancer survivors’ posttreatment concerns can be time-intensive and require specialized staff. Research is needed to identify feasible minimal intervention strategies to improve survivors’ quality of life after treatment. Objectives: The objective of this study was to evaluate the feasibility and short-term impact of a minimal clinic intervention on breast cancer survivors’ quality of life, unmet needs, distress, and cancer worry. Interventions/Methods: In this randomized controlled pilot trial, we enrolled breast cancer survivors at the end of treatment and administered baseline surveys. Participants were randomized to study arm (4-week video plus educational booklet intervention group and usual care group) and completed follow-up surveys at 10 weeks. Linear regression was used to examine intervention effects on quality of life outcomes controlling for clinical and demographic factors. Open-ended questions were used to examine program satisfaction and obtain feedback to improve the intervention. Results: We enrolled 92 survivors in the trial. Participants rated the intervention highly and reported feeling less isolated and having more realistic expectations about their recovery after completing the program. Despite positive qualitative findings, no significant intervention effects were observed for quality of life, unmet needs, distress, or cancer worry in unadjusted or adjusted analyses. Conclusions: Future research is needed to define optimal intervention elements to prepare breast cancer survivors for the posttreatment period. Implications for Practice: Effective survivorship interventions may require more intensive components such as clinical input and longer follow-up periods.

P1-11-05: Investigation of Epidemiological Factors as Barriers to Indicated Radiation Therapy in Post-Mastectomy Breast Cancer Patients in South Carolina.

Purpose: Post-mastectomy radiation therapy (PMRT) has been shown to provide improved locoregional control and overall survival in intermediate and high-risk breast cancer patients 1,2 . To investigate the frequency of utilization and potential barriers to receipt of adjuvant PMRT in South Carolina, an analysis of the S.C. Cancer Registry (SCCR) database was undertaken. Methods: Epidemiological factors such as age, race, and geographic distance from a radiation therapy facility were analyzed as potential predictors of whether patients received the indicated radiotherapy. Post-mastectomy breast cancer patients (n=1080) recorded in the SCCR from 2006–2008 were stratified as low (Tis/T1, N0) (43%), intermediate (T1/T2, N1) (27%), or high (T3/T4, N2/N3) (30%) risk. Logistic regression models were used to predict receipt of adjuvant radiotherapy based on factors such as race, age, and geographical distance from radiation treatment facility. Results: Adjuvant PMRT was received in 4% (19/469) of low risk patients, 23% (67/288) of intermediate risk patients, and 44% (141/323) of high risk patients. In both intermediate and high risk groups, older patients were less likely to receive PMRT. The odds of receiving PMRT decreased by 3% (OR= 1.03; 95% CI: 1.01−1.05; p=0.01) and 2% (OR=1.02; 95% CI: 1.002−1.035; p=0.03) per year in the intermediate and high risk groups, respectively. Race and distance from treatment facility were not predictive of receipt of PMRT in high risk patients. Conclusion: Utilization of adjuvant PMRT in intermediate and high risk breast cancer patients in South Carolina is low, despite the evidence that it confers a survival benefit in both premenopausal and postmenopausal women. Of the patient-related factors analyzed, only age predicted lower odds of receiving radiotherapy in both the intermediate and high risk group. In high risk patients of advanced age (>70), breast cancer continues to be a major cause of mortality which can be improved by radiotherapy 3 . Future educational efforts should focus on addressing patient and physician bias against radiotherapy based on patient age. Further study is needed to identify socio-economic-, physician- and health system- related factors that maybe impacting the underutilization of PMRT in South Carolina. References : 1. Overgaard, M, PS Hansen, et al. 1997. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. NEJM, 337:14, pg 949–955. 2. Overgaard M, Jensen M-J, Overgaard J, et al. 1999. Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet. 353: 1641–1648. 3. Smith, BD, BG Haffty, A Hurria, DH Galusha, and CP Gross. 2006. Postmastectomy radiation and survival in older women with breast cancer. JCO, 24:30, pg 4901–4907. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-11-05.

Imaging applications in multicatheter brachytherapy for soft tissue sarcomas

Abstract Multicatheter brachytherapy can be applied as a monotherapy or in combination with external beam radiotherapy as an adjuvant treatment for soft tissue sarcoma. Successful application of brachytherapy in the treatment of soft tissue sarcoma requires implementation of multiple imaging modalities during preoperative and postoperative planning. Preoperative imaging is essential in planning local therapy for soft tissue sarcoma in that it defines the proximity of the tumor to adjacent critical structures, predicts the likelihood of close or positive surgical margins, and aids in defining the target volume for a brachytherapy implant. In the postoperative setting, imaging is utilized to assess the accuracy of target volume coverage and integrity of the implant, as well as in three-dimensional treatment planning.