Dustin Boothe

Transforming growth factor β-1 (TGF-β1) is a serum biomarker of radiation induced fibrosis in patients treated with intracavitary accelerated partial breast irradiation: preliminary results of a prospective study.

PURPOSE To examine a relationship between serum transforming growth factor β -1 (TGF-β1) values and radiation-induced fibrosis (RIF). METHODS AND MATERIALS We conducted a prospective analysis of the development of RIF in 39 women with American Joint Committee on Cancer stage 0-I breast cancer treated with lumpectomy and accelerated partial breast irradiation via intracavitary brachytherapy (IBAPBI). An enzyme-linked immunoassay (Quantikine, R&D, Minneapolis, MN) was used to measure serum TGF-β1 before surgery, before IBAPBI, and during IBAPBI. Blood samples for TGF-β1 were also collected from 15 healthy, nontreated women (controls). The previously validated tissue compliance meter (TCM) was used to objectively assess RIF. RESULTS The median time to follow-up for 39 patients was 44 months (range, 5-59 months). RIF was graded by the TCM scale as 0, 1, 2, and 3 in 5 of 20 patients (25%), 6 of 20 patients (30%), 5 of 20 patients (25%), and 4 of 20 patients (20%), respectively. The mean serum TGF-β1 values were significantly higher in patients before surgery than in disease-free controls, as follows: all cancer patients (30,201 ± 5889 pg/mL, P=.02); patients with any type of RIF (32,273 ± 5016 pg/mL, P<.0001); and women with moderate to severe RIF (34,462 ± 4713 pg/mL, P<0.0001). Patients with moderate to severe RIF had significantly elevated TGF-β1 levels when compared with those with none to mild RIF before surgery (P=.0014) during IBAPBI (P≤0001), and the elevation persisted at 6 months (P≤.001), 12 months (P≤.001), 18 months (P≤.001), and 24 months (P=.12). A receiver operating characteristic (ROC) curve of TGF-β1 values predicting moderate to severe RIF was generated with an area under the curve (AUC)ROC of 0.867 (95% confidence interval 0.700-1.000). The TGF-β1 threshold cutoff was determined to be 31,000 pg/mL, with associated sensitivity and specificity of 77.8% and 90.0%, respectively. CONCLUSIONS TGF-β1 levels correlate with the development of moderate to severe RIF. The pre-IBAPBI mean TGF-β1 levels can serve as an early biomarker for the development of moderate to severe RIF after IBAPBI.

Administration of concurrent vaginal brachytherapy during chemotherapy for treatment of endometrial cancer.

PURPOSE To evaluate the tolerability and toxicity of administering vaginal brachytherapy (VB) concurrently during chemotherapy compared with the sequential approach for patients with endometrial cancer. METHODS AND MATERIALS A retrospective analysis of 372 surgically staged patients with endometrial cancer American Joint Committee on Cancer 2009 stages I to IV treated with adjuvant postoperative radiation therapy (RT) at our institution from 2001 to 2012 was conducted. All patients received VB+external beam RT (EBRT)+6 cycles of adjuvant carboplatin- and paclitaxel-based chemotherapy. The VB mean dose was 15.08 Gy (range, 15-20 Gy), with 3 to 4 weekly applications, and the EBRT mean dose was 45 Gy delivered with 3-dimensional or intensity modulated RT techniques. Hematologic, gastrointestinal (GI), and genitourinary (GU) toxicities were assessed by Common Toxicity Criteria (CTC) and compared between sequential and concurrent chemotherapy and VB schedules. RESULTS Among patients who received RT and adjuvant chemotherapy, 180 of 372 patients (48%) received RT sandwiched between cycles 3 and 4 of chemotherapy. A separate group of 192 patients (52%) were treated with VB during the first 3 cycles of chemotherapy, with a weekly application on nonchemotherapy days, and received the EBRT portion in a sandwiched fashion. Patients treated with VB during chemotherapy had a decreased overall treatment time by 4 weeks (P<.001; 95% confidence interval: 3.99-4.02) and sustained no difference in CTC-graded acute hematologic, GI, or GU toxicities in comparison with the patients treated with VB and chemotherapy in a sequential manner (P>.05). CTC grade 3 or 4 hematologic, GI, and GU toxicities were zero. CONCLUSIONS VB during chemotherapy is well tolerated, decreases overall treatment time, and does not render more toxicity than the sequential regimen.

Disease-Free Survival According to the Use of Postmastectomy Radiation Therapy After Neoadjuvant Chemotherapy

INTRODUCTION The purpose of the study was to determine predictors of recurrence for patients treated with neoadjuvant chemotherapy (NAC) and mastectomy according to the use of postmastectomy radiation therapy (PMRT). PATIENTS AND METHODS An analysis of 161 clinically staged T1 to T3/N0 to N3 patients treated with NAC and mastectomy with and without PMRT at our institution from 2003 to 2010 was conducted. The Kaplan-Meier product limit method was used to estimate survival and time to recurrence rates and the log-rank test was used to compare groups. A Cox proportional hazard regression analysis was carried out for time to recurrence, radiation therapy, and their interaction in the model. RESULTS The median follow-up period was 48 months and 18 patients developed a recurrence. The 5-year recurrence rate and overall survival was 16.1% (95% confidence interval [CI], 9.6%-26.3%) and 93.6% (95% CI, 88.2%-97.0%), respectively. Patients who underwent PMRT had a decreased risk of recurrence compared with patients who did not (hazard ratio [HR], 0.25; 95% CI, 0.097-0.661; P < .005). The 5-year disease-free survival (DFS) rate for those who received PMRT was 91.3% (95% CI, 82.8%-95.7%) and 64.8% (95% CI, 37.8%-82.4%) for those who did not (P = .0126). Among all clinicopathologic factors examined, pathologic T stage (ypT) and pathological N stage (ypN) significantly correlated with the risk of recurrence (P < .05). Patients with any pathological nodal disease had an increased risk of recurrence compared with patients who were pathologically node-negative (HR, 7.196; 95% CI, 2.05-25.264; P < .002). CONCLUSION Patients treated with NAC and mastectomy, but without PMRT had a higher risk recurrence with increasing ypT and ypN stages. PMRT might increase DFS.

Comparing the rates of urinary tract infections among patients receiving adjuvant pelvic intensity modulated radiation therapy, 3-dimensional conformal radiation therapy, and brachytherapy for newly diagnosed endometrial cancer

PURPOSE The purpose of this study was to compare the rates of urinary tract infection (UTI) among patients with endometrial cancer receiving vaginal brachytherapy alone and brachytherapy plus 3-dimensional conformal radiation therapy (3DCRT) or intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS We retrospectively evaluated the rates of UTI among 581 patients diagnosed with endometrial cancer, treated between 2004 and 2012. A total of 37% (216/581) received brachytherapy alone, 28% (161/581) received brachytherapy plus 3DCRT, and 35% (204/581) received brachytherapy plus IMRT. UTI during the treatment was defined as evidence of pyuria detected by either urine dipstick or urinalysis. All specimens were collected as a clean catch, midstream void to avoid contamination and resultant false positives. The χ(2) and logistic regression analyses were subsequently employed for statistical analyses. RESULTS UTI was diagnosed in 14.6% (85/581) of all patients. Only 2.8% (6/216) of patients receiving brachytherapy were diagnosed with a UTI during treatment, whereas UTI was diagnosed in 37.3% (60/161) of patients receiving brachytherapy plus 3DCRT, and 9.3% (19/204) of patients receiving brachytherapy plus IMRT (P < .0005). Logistic regression analysis found a decreased association between UTI and stage III endometrial cancer (odds ratio [OR], 0.51, 95% confidence interval [CI], 0.26, 0.99; P = .048). When compared with brachytherapy, both types of external beam radiation therapy were associated with an increased risk of UTI, though adjuvant 3DCRT (OR, 47.52, 95% CI, 14.81, 152.47; P < .001) had a more dramatic risk increase than IMRT (7.89, 95% CI, 2.26, 27.62; P = .001). CONCLUSIONS When compared with IMRT, 3DCRT is associated with a significantly increased risk of UTI, supporting the use of IMRT as the less toxic external beam radiation therapy for endometrial cancer.