Kristin A. Bradley

Severe Late Toxicities Following Concomitant Chemoradiotherapy Compared to Radiotherapy Alone in Cervical Cancer: An Inter-era Analysis

PURPOSE To compare rates of severe late toxicities following concomitant chemoradiotherapy and radiotherapy alone for cervical cancer. METHODS AND MATERIALS Patients with cervical cancer were treated at a single institution with radiotherapy alone or concomitant chemoradiotherapy for curative intent. Severe late toxicity was defined as grade≥3 vaginal, urologic, or gastrointestinal toxicity or any pelvic fracture, using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE), occurring ≥6 months from treatment completion and predating any salvage therapy. Severe late toxicity rates were compared after adjusting for pertinent covariates. RESULTS At 3 years, probability of vaginal severe late toxicity was 20.2% for radiotherapy alone and 35.1% for concomitant chemoradiotherapy (P=.026). At 3 years, probability of skeletal severe late toxicity was 1.6% for radiotherapy alone and 7.5% for concomitant chemoradiotherapy (P=.010). After adjustment for case mix, concomitant chemoradiotherapy was associated with higher vaginal (hazard ratio [HR] 3.0, 95% confidence interval [CI], 1.7-5.2, P<.001), and skeletal (HR 7.0, 95% CI 1.4-34.1, P=.016) severe late toxicity. Compared to high dilator compliance, moderate (HR 3.6, 95% CI 2.0-6.5, P<.001) and poor (HR 8.5, 95% CI 4.3-16.9, P<.001) dilator compliance was associated with higher vaginal severe late toxicity. Age>50 was associated with higher vaginal (HR 1.8, 95% CI 1.1-3.0, P=.013) and skeletal (HR 5.7, 95% CI 1.2-27.0, P=.028) severe late toxicity. Concomitant chemoradiotherapy was not associated with higher gastrointestinal (P=.886) or urologic (unadjusted, P=.053; adjusted, P=.063) severe late toxicity. CONCLUSION Compared to radiotherapy alone, concomitant chemoradiotherapy is associated with higher rates of severe vaginal and skeletal late toxicities. Other predictive factors include dilator compliance for severe vaginal late toxicity and age for severe vaginal and skeletal late toxicities.

Motexafin gadolinium and involved field radiation therapy for intrinsic pontine glioma of childhood: A Children's Oncology Group phase I study

The purpose of this study was to determine the dose-limiting toxicities, maximum tolerated dose, pharmacokinetics, and intratumor and brain distribution of motexafin gadolinium (MGd) with involved field radiation therapy in children with newly diagnosed intrinsic pontine gliomas. MGd was administered as a 5-min intravenous bolus 2-5 h prior to standard radiation. The starting dose was 1.7 mg/kg. After first establishing that 5 doses/week for 6 weeks was tolerable, the dose of MGd was escalated until dose-limiting toxicity was reached. Radiation therapy was administered to 54 Gy in 30 once-daily fractions. Forty-four children received MGd at doses of 1.7 to 9.2 mg/kg daily prior to radiation therapy for 6 weeks. The maximum tolerated dose was 4.4 mg/kg. The primary dose-limiting toxicities were grade 3 and 4 hypertension and elevations in serum transaminases. Median elimination half-life and clearance values were 6.6 h and 25.4 ml/kg/h, respectively. The estimated median survival was 313 days (95% confidence interval, 248-389 days). The maximum tolerated dose of MGd and the recommended phase II dose was 4.4 mg/kg when administered as a daily intravenous bolus in conjunction with 6 weeks of involved field radiation therapy for pediatric intrinsic pontine gliomas.

Linear accelerator radiosurgery for trigeminal neuralgia.

OBJECTIVE: To report the clinical outcomes following treatment of trigeminal neuralgia with linear accelerator-based radiosurgery. METHODS: Twenty-eight patients with medication refractory idiopathic trigeminal neuralgia were treated with a single fraction of 80 Gy to the trigeminal nerve root. For treatment delivery, a 4-mm collimator and a 7-arc technique were delivered using a stereotactic floor stand system with an isocenter stability of 0.2 ± 0.1 mm to minimize dose to the brainstem. Treatment delivery time was approximately 55 minutes. RESULTS: With a median follow-up of 12 months (range, 1–40 mo), 57% of patients achieved complete pain relief and 75% (exact 95% confidence interval, 55 to 89%) had their pain reduced to 3 or less on a 10-point pain scale. Median time to pain relief was 1 month. Four patients did not respond to treatment. The actuarial mean time to pain recurrence in responders was 14 months, and the actuarial mean response duration in major to complete responders was 16 months. Women had significantly longer mean time to pain recurrence than men (16 versus 7 months; P = 0.05). Three patients reported new mild facial numbness after radiosurgery and one patient developed neurotrophic keratopathy. CONCLUSION: Linear accelerator-based radiosurgery for medication refractory trigeminal neuralgia provides effective pain relief with a low complication rate.

Effects of Treatment Duration During Concomitant Chemoradiation Therapy for Cervical Cancer

PURPOSE To determine whether extended treatment duration (TD) impacts in-field relapse and survival in the setting of concomitant chemoradiation therapy (CRT) for cervical cancer. METHODS AND MATERIALS A total of 480 consecutive cervical cancer patients treated with radiation therapy (RT) alone or concomitant CRT for curative intent were retrospectively analyzed. Relapse was defined as in-field with respect to external beam radiation therapy fields. The effects of TD on in-field relapse, disease-free survival (DFS), and overall survival (OS) rates were assessed continuously and categorically within the separate RT and CRT cohorts. Covariates included age, histology, stage, and cumulative dose to point A. In-field relapse, DFS, and OS rates were estimated with Kaplan-Meier analysis; comparisons used log-rank statistic. Multivariate analysis used the Cox proportional hazards model. RESULTS A total of 372 patients (RT n=206, CRT n=166) were evaluable, with a median follow-up for relapse-free patients of 4.2 years (RT 4.4 years, CRT 4.2 years; P=.807). Treatment duration was longer in the RT cohort (median 55 days; range 35-99 days) versus the CRT cohort (median 51 days; range 35-92 days) (P=.001). In the RT cohort, TD ≥62 days trended to significance for predicting inferior DFS (hazard ratio 1.42, 95% confidence interval 0.86-1.98, P=.086). However, in the CRT cohort, TD assessed continuously or categorically across multiple cutoff thresholds did not predict for in-field relapse, DFS, or OS. CONCLUSION With RT alone, extended TD ≥62 days may adversely impact treatment efficacy. With the addition of concomitant chemotherapy to RT, however, extended TD has no effect on treatment efficacy.

The Impact of Hybrid PET-CT Scan on Overall Oncologic Management, with a Focus on Radiotherapy Planning: A Prospective, Blinded Study

Functional imaging using fluorodeoxyglucose positron-emission tomography (FDG-PET) has been increasing incorporated into radiotherapy planning in conjunction with computed tomography (CT). Hybrid FDG-PET/CT scanners allow these images to be obtained in very close temporal proximity without the need for repositioning patients, thereby minimizing imprecision when overlying these images. To prospectively examine the impact of hybrid PET/CT imaging on overall oncologic impact, with a focus on radiotherapy planning, we performed a prospective, blinded trial in 111 patients. Patients with lung cancer (n=38), head-and-neck squamous cell carcinoma (n=23), breast (n=8), cervix (n=15), esophageal (n=9), and lymphoma (n=18) underwent hybrid PET/CT imaging at the time of radiation therapy planning. A physician blinded to the PET dataset designed a treatment plan using all clinical information and the CT dataset. The treating physician subsequently designed a second treatment plan using the hybrid PET/CT dataset. The two treatment plans were compared to determine if a major alteration in overall oncologic management occured. In patients receiving potentially curative radiotherapy the concordance between CT-based and PET/CT-based GTVs was quantified using an index of conformality (CI). In 76/111 (68%) of patients, the PET/CT data resulted in a change in one or more of the following: GTV volume, regional/local extension, prescribed dose, or treatment modality selection. In 35 of these 76 cases (46%; 31.5% of the entire cohort) the change resulted in a major alteration in the oncologic management (dose, field design, or modality change). Thus, nearly a third of all cases had a major alteration in oncologic management as a result of the PET/CT data, and 29 of 105 patients (27.6%) who underwent potentially curative radiotherapy had major alterations in either dose or field design. Hybrid PET/CT imaging at the time of treatment planning may be highly informative and an economical manner in which to obtain PET imaging, with the dual goals of staging and treatment planning.

Motexafin-Gadolinium and Involved Field Radiation Therapy for Intrinsic Pontine Glioma of Childhood: A Children's Oncology Group Phase 2 Study

PURPOSE To evaluate the effects on 1-year event-free survival (EFS) and overall survival (OS) of combining motexafin and gadolinium (MGd), a potent radiosensitizer, with daily fractionated radiation therapy in children with newly diagnosed intrinsic pontine gliomas. METHODS AND MATERIALS Patients with newly diagnosed intrinsic pontine glioma were treated with MGd daily for 5 consecutive days each week, for a total of 30 doses. Patients received a 5- to 10-min intravenous bolus of MGd, 4.4 mg/kg/day, given 2 to 5 h prior to standard dose irradiation. Radiation therapy was administered at a daily dose of 1.8 Gy for 30 treatments over 6 weeks. The total dose was 54 Gy. RESULTS Sixty eligible children received MGd daily, concurrent with 6 weeks of radiation therapy. The estimated 1-year EFS was 18%±5%, and the estimated 1-year OS was 53%±6.5%. The most common grade 3 to 4 toxicities were lymphopenia, transient elevation of liver transaminases, and hypertension. CONCLUSIONS Compared to historical controls, the addition of MGd to a standard 6-week course of radiation did not improve the survival of pediatric patients with newly diagnosed intrinsic pontine gliomas.

Uterine Neoplasms, Version 1.2018: Clinical practice guidelines in oncology

Endometrial carcinoma is a malignant epithelial tumor that forms in the inner lining, or endometrium, of the uterus. Endometrial carcinoma is the most common gynecologic malignancy. Approximately two-thirds of endometrial carcinoma cases are diagnosed with disease confined to the uterus. The complete NCCN Guidelines for Uterine Neoplasms provide recommendations for the diagnosis, evaluation, and treatment of endometrial cancer and uterine sarcoma. This manuscript discusses guiding principles for the diagnosis, staging, and treatment of early-stage endometrial carcinoma as well as evidence for these recommendations.

Predictive factors of recurrence following adjuvant vaginal cuff brachytherapy alone for stage I endometrial cancer

PURPOSE The purpose of this study is to identify risk factors for recurrence in a cohort of stage I endometrial cancer patients treated with vaginal cuff brachytherapy at a single academic institution. METHODS AND MATERIALS From 1989 to 2011, 424 patients with stage I endometrial cancer underwent total hysterectomy and bilateral salpingo-oophorectomy, with or without lymphadenectomy (LND), followed by high-dose-rate vaginal cuff brachytherapy (VCB) to patients felt to be high or intermediate risk FIGO stage IA and IB disease. Covariates included: 2009 FIGO stage, age, grade, histology, presence of lymphovascular space invasion, LND, and receipt of chemotherapy. RESULTS With a median follow-up of 3.7years, the 5 and 10-year disease free survival were 98.4% and 95.9%, respectively. A total of 30 patients developed recurrence, with the predominant pattern of isolated distant recurrence (57.0%). On multivariate analysis, grade 3 (p=0.039) and LND (p=0.048) independently predicted of increased recurrence risk. χ(2) analysis suggested that higher-risk patients were selected for LND, with significant differences in age, stage, and grade noted between cohorts. Distant metastatic rate was significantly higher for patients who qualified for GOG 0249 at 23.1% (95% CI 10.7-35.5%) compared to those who did not at 6.8% (95% CI 1.8-11.8%, p<0.001). CONCLUSION Overall disease-free survival for this cohort of patients was >95% at 10years. Univariate analysis confirmed previously identified risk factors as predictors for recurrence. Multivariate analysis found that grade 3 and LND correlated with risk for recurrence. Of those that did recur, the initial site of relapse included distant metastasis in most cases.

Radiation therapy for leptomeningeal cancer.

Radiotherapy has multiple roles in the treatment of leptomeningeal cancer. While it is uncommon for patients to experience regression of neurologic deficits due to leptomeningeal cancer, focal radiotherapy often provides significant palliation of pain, increased intracranial pressure and other focal symptoms. Focal radiotherapy may also be used to eliminate blockages of cerebrospinal fluid (CSF) and allow for safe administration of intrathecal chemotherapy. Craniospinal irradiation (CSI) is most often used as prophylaxis for patients at high risk of leptomeningeal tumor dissemination, but may result in symptom palliation and prolonged disease control for patients with active leptomeningeal tumor.

Radiation Oncology Residency Selection: A Targeted Assessment of Factor Importance Among Fourth-Year Medical Students

Fourth-year medical students (MS4s) have limited meaningful exposure to radiation oncology training programs and thus base their decision largely on a limited number of factors. The assessment of variables utilized by MS4s during the selection process has never formally been investigated. We sought to better understand the importance of factors assessed by MS4s during the process of residency selection to gain perspective, which might be useful to training programs and future applicants. An anonymous survey was developed to assess factor importance during the radiation oncology training program selection process (1-3). The survey was a multiple-item Likert scale (1 Z not at all important to 5 Z extremely important, critical) and was distributed to current MS4s and to those in postgraduate year 1 (PGY1s) (4). The data were analyzed by use of mean and median Likert values, with interquartile range for median values (5). Responses were obtained from 70 MS4/PGY1s. The respondents were 59 MD and 11 MD/PhD candidates/graduates. Of the respondents, 56 were male (80%) and 14 were female (20%). The data from all survey participants were analyzed as a group and by subgroups of MD versus MD/PhD. Program factors were arranged in order of decreasing relative importance for the entire group (Table 1). The factors of highest importance overall were “perceived happiness of residents” (mean 4.43), “geographic location” (mean 3.71), and “clinical research