Cristiane Takita

Phase III Trial of an Emulsion Containing Trolamine for the Prevention of Radiation Dermatitis in Patients With Advanced Squamous Cell Carcinoma of the Head and Neck: Results of Radiation Therapy Oncology Group Trial 99-13

PURPOSE This multicentered phase III trial was designed to compare an emulsion containing trolamine against the usual supportive care within each participating institution for patients with head and neck cancer undergoing radiation therapy. PATIENTS AND METHODS Patients with biopsy-proven squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx were randomly assigned to one of the following treatments: prophylactic trolamine emulsion, interventional trolamine emulsion, or declared institutional preference. The primary outcome was the reduction in grade 2 or higher skin toxicity, as per National Cancer Institute Common Toxicity Criteria version 2.0. Secondary outcomes included patient-reported quality of life (QOL). RESULTS From October 2000 to April 2002, 547 patients from 51 institutions were entered onto the trial. The average age was 59 years. Patients were predominately male (79%) and most continued to use tobacco products (52%). The rates of grade 2 or higher radiation dermatitis were 79%, 77%, and 79% in the prophylactic, interventional, and institutional preference arms of the study, respectively. No significant differences in QOL were found. CONCLUSION The results of this trial demonstrate no advantage for the use of trolamine in reducing the incidence of grade 2 or higher radiation dermatitis or improving patient-reported QOL. The use of 15 different local standards of care highlights the need to continue research that will result in evidence-based recommendations to reduce the burden of radiation dermatitis.

Small Cell Carcinoma of the Head and Neck: The University of Miami Experience

PURPOSE To describe the University of Miami experience in the treatment of small cell carcinoma of the head and neck. METHODS AND MATERIALS A total of 12 patients with nonmetastatic small cell carcinoma of the head and neck were treated between April 1987 and September 2007. Radiotherapy was the primary local treatment modality for 8 patients. RESULTS Of the 12 patients, 8 had died after a median follow-up of 13 months. The 4 patients who were alive were followed for a median of 14 months. The Kaplan-Meier estimate of the proportion of small cell head-and-neck cancer patients surviving to 1 and 2 years was 63% and 26%, respectively. The percentage of patients remaining disease free at 1 and 2 years was 71% and 44%, respectively. The patients with tonsil/parotid gland cancer had significantly greater disease-specific survival compared with the other patients. The median survival time was 30 months in the tonsil/parotid group compared with 15.2 months in the other group (patients with small cell carcinoma of the sinonasal cavity, nasopharynx, and larynx). A total of 4 patients developed recurrence, 3 of whom had a distant failure component. The treatment modality was not associated with a difference in disease-specific survival. The 1-year disease-specific survival rate was 73% in the radiotherapy or radiotherapy/chemotherapy group compared with 67% in the other group. CONCLUSION Radiotherapy with or without chemotherapy is a reasonable alternative to surgery for patients with small cell carcinoma of the head and neck. Patients with tonsillar or parotid small cell carcinomas did better than other sites. More aggressive treatment might be warranted for patients with sinonasal carcinoma. The outcome, however, continues to be suboptimal, and more effective therapy is needed because most patients had a component of local and distant failure.

Predictors of locoregional outcome in patients receiving neoadjuvant therapy and postmastectomy radiation

The objective of this study was to identify predictors of locoregional recurrence (LRR) after neoadjuvant therapy (NAT) and postmastectomy radiation (PMRT) in a cohort of patients with stage II through III breast cancer and to determine whether omission of the supraclavicular field had an impact on the risk of LRR.

Racial Variations in Radiation-Induced Skin Toxicity Severity: Data From a Prospective Cohort Receiving Postmastectomy Radiation

PURPOSE Radiation-induced skin toxicity is one of the most symptomatic side effects of postmastectomy radiation therapy (PMRT). We sought to determine whether the severity of acute skin toxicity was greater in black patients in a prospective cohort receiving PMRT and to identify other predictors of more severe skin toxicity. METHODS AND MATERIALS We evaluated the first 110 patients in an ongoing prospective study assessing radiation-induced skin toxicity in patients receiving PMRT. We recorded patient demographics, body mass index (BMI), and disease and treatment characteristics. Logistic regression analyses were conducted to evaluate the effect of potential predictors on the risk of skin toxicity. RESULTS A total of 23.6% respondents self-identified as black, 5.5% as non-Hispanic white, 69.1% as Hispanic white, and 1.8% as other; 57% were postmenopausal, and 70.9% had BMI of >25. Median chest wall dose was 50 Gy, and mastectomy scar dose was 60 Gy. Most patients, 95.5%, were treated with a 0.5-cm bolus throughout treatment. There were no significant differences in patient characteristics in black versus non-black patients. At RT completion, moist desquamation was more common in black patients (73.1% vs 47.6%, respectively, P=.023), in postmenopausal patients (63.5% vs 40.4%, respectively, P=.016), and in those with BMI of ≥25 (60.3% vs 37.5%, respectively, P=.030). On multivariate analysis, the effects of black race (odds ratio [OR] = 7.46, P=.031), BMI ≥25 (OR = 2.95, P=.043) and postmenopausal status (OR = 8.26, P=.004) remained significant risk factors for moist desquamation. CONCLUSIONS In this prospectively followed, racially diverse cohort of breast cancer patients receiving PMRT delivered in a uniform fashion, including the routine use of chest wall boost and bolus, black race, higher BMI, and postmenopausal status emerged as significant predictors of moist desquamation. There was a high frequency of moist desquamation, particularly in those patients with elevated risk. Continued study of patient selection for chest wall boost and bolus as well improved skin toxicity management strategies are needed.

Safety and Efficacy of Tiered Limited-Dose Gamma Knife Stereotactic Radiosurgery for Unilateral Acoustic Neuroma

Stereotactic radiosurgery has become a more widely employed modality of treatment for acoustic neuromas, but controversy still arises regarding the safety and efficacy of the technique. In general, radiation doses have been reduced over time. Since beginning treatments of acoustic neuromas with the Gamma Knife at the University of Miami/Jackson Memorial Medical Center in 1994, a dose regimen was adopted by the first author employing limited doses selected on the basis of tumor size with the anterior and medial regions of the prescription isodose surface kept just inside the gadolinium-enhanced limit of the tumor, in order to protect the facial nerve and brainstem. The records of patients treated for unilateral tumors were retrospectively reviewed. Fifty-two patients, aged 23–83 years, were treated with peripheral tumor doses of 10–14 Gy at the 45–70% isodoses. No patient developed new facial weakness or sensory loss; 3 patients had minor transient facial twitching within a few months of treatment. Of 34 patients followed more than 1 year (range 14–100 months, mean 43.4 months, median 37 months), 17 tumors reduced in size, 16 remained unchanged, and 1 increased in size. One patient, who had radiosurgery as planned postoperative adjuvant treatment after partial resection of a large tumor, developed an enlarging peritumoral arachnoid cyst that required surgical resection 79 months after radiosurgery. Patients with good pretreatment hearing retained approximately the same subjective level of hearing. Very good control of unilateral acoustic neuroma has been achieved by a limited-dose scheme that produces minimal complications, but due to the frequently indolent course of these tumors, continued long-term monitoring will be necessary.

Risk factors for locoregional failure in patients with inflammatory breast cancer treated with trimodality therapy

PURPOSE To compare patterns of local and regional failure between patients with inflammatory breast cancer (IBC) and non-IBC in patients treated with trimodality therapy. MATERIALS AND METHODS We reviewed records of 463 patients with stage II/III breast cancer, including IBC, who completed trimodality therapy from January 1999 to December 2009. RESULTS The median follow-up was 46.3 months (range, 4-152 months). Clinical stage was 29.4% (n = 136) II, 56.4% (n = 261) non-IBC III, 14.2% (n = 66) IBC, 30.5% (n = 141) cN0/Nx, and 69.5% (n = 322) N1-N3c. All the patients received neoadjuvant therapy and mastectomy (98%, n = 456 with axillary dissection), and all had postmastectomy radiation therapy to the chest wall with or without supraclavicular nodes (82.5%, n = 382) with or without axilla (6%, n = 28). The median chest wall dose was 60.4 Gy. Patients with IBC presented with larger tumors (P < .001) and exhibited a poorer response to neoadjuvant therapy: after surgery, fewer patients with IBC were ypN0 (P = .003) and more had ≥ 4 positive nodes (P < .001). Four-year cumulative incidence of locoregional recurrence was 5.9%, with 25 locoregional events, 9 of which had a regional component. On multivariate analysis, triple-negative disease (hazard ratio [HR] 7.75, P < .0001) and residual pathologic nodes (HR 7.10, P < .001) were associated with an increased risk of locoregional recurrence, but IBC was not. However, on multivariate analysis, the 4-year cumulative incidence of regional recurrence specifically was significantly higher in IBC (HR 9.87, P = .005). CONCLUSION In this cohort of patients who completed trimodality therapy, the patients with IBC were more likely to have residual disease in the axilla after neoadjuvant therapy and were at greater risk of regional recurrence. Future study should focus on optimizing regional nodal management in IBC.

Higher Chest Wall Dose Results in Improved Locoregional Outcome in Patients Receiving Postmastectomy Radiation

PURPOSE Randomized trials demonstrating decreased locoregional recurrence (LRR) and improved overall survival (OS) in women receiving postmastectomy radiation therapy (PMRT) used up to 50 Gy to the chest wall (CW), but in practice, many centers boost the CW dose to ≥60 Gy, despite lack of data supporting this approach. We evaluated the relationship between CW dose and clinical outcome. METHODS AND MATERIALS We retrospectively reviewed medical records of 582 consecutively treated patients who received PMRT between January 1999 and December 2009. We collected data on patient, disease, treatment characteristics, and outcomes of LRR, progression-free survival (PFS) and OS. RESULTS Median follow-up from the date of diagnosis was 44.7 months. The cumulative 5-year incidence of LRR as first site of failure was 6.2%. CW dose for 7% (43 patients) was ≤50.4 Gy (range, 41.4-50.4 Gy) and 93% received >50.4 Gy (range, 52.4-74.4 Gy). A CW dose of >50.4 Gy vs. ≤50.4 Gy was associated with lower incidence of LRR, a 60-month rate of 5.7% (95% confidence interval [CI], 3.7-8.2) vs. 12.7% (95% CI, 4.5-25.3; p = 0.054). Multivariate hazard ratio (HR) for LRR controlling for race, receptor status, and stage was 2.62 (95% CI, 1.02-7.13; p = 0.042). All LRR in the low-dose group occurred in patients receiving 50 to 50.4 Gy. Lower CW dose was associated with worse PFS (multivariate HR, 2.73; 95% CI, 1.64-4.56; p < 0.001) and OS (multivariate HR, 3.88; 95% CI, 2.16-6.99; p < 0.001). CONCLUSIONS The addition of a CW boost above 50.4 Gy resulted in improved locoregional control and survival in this cohort patients treated with PMRT for stage II-III breast cancer. The addition of a CW boost to standard-dose PMRT is likely to benefit selected high-risk patients. The optimal technique, target volume, and patient selection criteria are unknown. The use of a CW boost should be studied prospectively, as has been done in the setting of breast conservation.

Racial disparity in estrogen receptor positive breast cancer patients receiving trimodality therapy

INTRODUCTION We assessed racial differences in progression-free survival (PFS) and overall survival (OS) in relation to subtype in uniformly treated stage II-III breast cancer patients. METHODS We reviewed records of 582 patients receiving post-mastectomy radiation (PMRT) between 1/1999 and 12/2009 and evaluated the effect of demographic, tumor, and treatment characteristics on PFS and OS. RESULTS Median follow up was 44.7 months. 24% of patients were black and 76% white. All had mastectomy and PMRT; 98% had chemotherapy; Estrogen receptor (ER)+ patients received endocrine therapy. Black patients were more likely to have ER- (56% vs. 38%, p=0.0001), progesterone receptor (PR)- (69% vs. 54%, p = 0.002), and triple negative (TN) (46% vs. 24%, p < 0.0001) tumors. Overall, black patients had worse PFS (60.6% vs. 78.3%, p = 0.001) and OS (72.8% vs. 87.7%, p < 0.0001). There was no racial difference in PFS (p = 0.229 and 0.273 respectively) or OS (p = 0.113 and 0.097 respectively) among ER- or TN. Among ER+, black patients had worse PFS (55% vs. 81%, p < 0.001) and OS (73% vs. 91%, p < 0.0001). The difference in PFS was seen in the ER+/PR+/HER2- subgroup (p = 0.002) but not ER+/PR-/HER2- (p = 0.129), and in the post-menopausal ER+/HER2- subgroup (p = 0.004) but not pre/peri-menopausal ER+/HER2- (p = 0.150). CONCLUSIONS Black women had worse survival outcomes in this cohort. This disparity was driven by (1) a higher proportion of ER- and TN tumors in black women and (2) worse outcome of similarly treated black women with ER+ breast cancer. The underlying causes of racial disparity within hormone receptor categories must be further examined.

Predictors of locoregional outcome in HER2-Overexpressing breast cancer treated with neoadjuvant chemotherapy

Objectives:We identified prognostic factors for locoregional recurrence (LRR) in a cohort of patients with HER2-overexpressing breast cancer treated with neoadjuvant chemotherapy (NACT). Methods:We reviewed records of 157 patients with HER-overexpressing tumors who received NACT between May 1999 and December 2009 and collected demographics, disease/treatment characteristics, and clinical outcome. We estimated rate of LRR by the method of cumulative incidence. Results:Presentation was 33% stage II and 67% stage III; 29.9% were clinically node positive. All patients received NACT, 94% trastuzumab containing. 90.4% had mastectomy and 6.4% breast-conserving surgery; 3.2% had no surgery. Among surgical patients, 48% were pathologically N0, 28.8% had 1 to 3 positive nodes, and 23.7% had ≥4 positive nodes. 79.6% received radiation therapy (RT) to the breast/chest wall±supraclavicular field. Median follow-up was 43 months. Three-year cumulative incidence of LRR was 8.2%; 50% of LRR had a regional component. Predictors for LRR included use of RT (HR=4.70, P=0.006), lymph node positivity (≥4 vs. 0 HR=19.99, P=0.008; 1 to 3 vs. 0 HR=10.8, P=0.031), and ER status (negative vs. positive HR=6.02, P=0.006). The only risk factor for regional failure specifically was residual nodal disease (≥4 HR=6.5, 1 to 3 HR=5.1, P=0.031). Conclusions:In a cohort with stage II to III HER2-overexpressing breast cancer treated predominantly with trastuzumab-containing NACT followed by mastectomy±RT, we identified omission of RT, negative ER status, and residual positive lymph nodes as significant predictors of LRR, with 50% of LRR having a regional component.

Inflammatory Biomarker C-Reactive Protein and Radiotherapy-Induced Early Adverse Skin Reactions in Patients with Breast Cancer

Background: Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in American women. Postsurgery adjuvant radiotherapy (RT) significantly reduced the local recurrence rate. However, many patients develop early adverse skin reactions (EASR) that impact quality of life and treatment outcomes. Methods: We evaluated an inflammatory biomarker, C-reactive protein (CRP), in predicting RT-induced EASRs in 159 patients with breast cancer undergoing RT. In each patient, we measured pre- and post-RT plasma CRP levels using a highly sensitive ELISA CRP assay. RT-induced EASRs were assessed at weeks 3 and 6 using the National Cancer Institute Common Toxicity Criteria (v3.0). Associations between EASRs and CRP levels were assessed using logistic regression models after adjusting for potential confounders. Results: RT-induced grade 2+ EASRs were observed in 8 (5%) and 80 (50%) patients at weeks 3 and 6 (end of RT), respectively. At the end of RT, a significantly higher proportion of African Americans developed grade 3 EASRs (13.8% vs. 2.3% in others); grade 2+ EASRs were significantly associated with: change of CRP > 1 mg/L [odds ratio (OR), 2.51; 95% confidence interval (CI), 1.06–5.95; P = 0.04], obesity (OR, 2.08; 95% CI, 1.03–4.21; P = 0.04), or combined both factors (OR, 5.21; 95% CI, 1.77–15.38; P = 0.003). Conclusion: This is the first study to demonstrate that an inflammatory biomarker CRP is associated with RT-induced EASRs, particularly combined with obesity. Impact: Future larger studies are warranted to validate our findings and facilitate the discovery and development of anti-inflammatory agents to protect normal tissue from RT-induced adverse effects and improve quality of life in patients with breast cancer undergoing RT. Cancer Epidemiol Biomarkers Prev; 23(9); 1873–83. ©2014 AACR.