Radiation recall dermatitis after treatment of stage IV breast cancer with nivolumab: a case report.

Radiation recall dermatitis (RRD) is an uncommon dermatologic reaction provoked notably by chemotherapy in an area of skin irradiated weeks to years prior. We report a case of RRD with nivolumab in a woman with breast cancer. The patient was diagnosed with invasive ductal carcinoma of the left breast with an isolated spinal metastasis approached in an oligometastatic fashion with neoadjuvant chemotherapy, modified radical mastectomy and adjuvant radiotherapy. Unfortunately, after progression of bony metastases treated with radiotherapy, the patient received nivolumab and subsequently developed a rash corresponding to the adjuvant radiation field. This case highlights the unpredictable nature and characteristic rash of RRD. It is an important differential diagnosis for multidisciplinary teams who also see chemotherapy-induced dermatitis and immune-related adverse events.

Predictors of urinary morbidity in Cs-131 prostate brachytherapy implants.

PURPOSE: Cesium-131 is a newer radioisotope being used in prostate brachytherapy (PB). This study was conducted to determine the predictors of urinary morbidity with Cs-131 PB. METHODS AND MATERIALS: A cohort of 159 patients underwent PB with Cs-131 at our institution and were followed by using Expanded Prostate Cancer Index Composite (EPIC) surveys to determine urinary morbidity over time. EPIC scores were obtained preoperatively and postoperatively at 2 and 4 weeks, and 3 and 6 months. Different factors were evaluated to determine their individual effect on urinary morbidity, including patient characteristics, disease characteristics, treatment, and dosimetry. Multivariate analysis of covariance was carried out to identify baseline determinants affecting urinary morbidity. Factors contributing to the need for postoperative catheterization were also studied and reported. RESULTS: At 2 weeks, patient age, dose to 90% of the organ (D90), bladder neck maximum dose (D(max)), and external beam radiation therapy (EBRT) predicted for worse function. At 4 weeks, age and EBRT continued to predict for worse function. At the 3-month mark, better preoperative urinary function, preoperative alpha blockers, bladder neck D(max), and EBRT predicted for worse urinary morbidity. At 6 months, better preoperative urinary function, preoperative alpha blockers, bladder neck D(max), and EBRT were predictive of increased urinary problems. High bladder neck D(max) and poor preoperative urinary function predicted for the need for catheterization. CONCLUSIONS: The use of EBRT plus Cs-131 PB predicts for worse urinary toxicity at all time points studied. Patients should be cautioned about this. Age was a consistent predictor of worsened morbidity immediately following Cs-131 PB, while bladder D(max) was the only consistent dosimetric predictor. Paradoxically, patients with better preoperative urinary function had worse urinary morbidity at 3 and 6 months, consistent with recently published literature.

Small molecule GS-nitroxide ameliorates ionizing irradiation-induced delay in bone wound healing in a novel murine model.

We studied radioprotection and mitigation by mitochondrial-targeted Tempol (GS-nitroxide, JP4-039), in a mouse injury/irradiation model of combined injury (fracture/irradiation). Right hind legs of control C57BL/6NHsd female mice, mice pretreated with MnSOD-PL, JP4-039, or with amifostine were irradiated with single and fractionated doses of 0 to 20 Gy. Twenty-four hours later, unicortical holes were drilled into the tibiae of both hind legs; at intervals, tibias were excised, radiographed, and processed for histology. Bone wounds irradiated to 20 or 30 Gy showed delayed healing at 21 to 28 days. Treatment with JP4-039 MnSOD-PL or amifostine, before or after single fraction 20 Gy or during fractionated irradiation followed by drilling accelerated wound healing at days 21 and 28. Orthotopic 3LL tumors were not protected by JP4-039 or amifostine. In nonirradiated mice, pretreatment with JP4-039 accelerated bone wound healing. This test system should be useful for the development of new small molecule radioprotectors.

Clinical and dosimetric factors associated with acute rectal toxicity in patients treated with (131)Cs brachytherapy for prostate cancer.

PURPOSE: (131)Cs has been recently introduced for use in prostate brachytherapy. We wished to identify clinical and dosimetric factors associated with acute bowel/rectal toxicity in patients treated with (131)Cs. METHODS AND MATERIALS: Patients treated with (131)Cs prostate brachytherapy at the University of Pittsburgh were asked to complete expanded prostate cancer index composite surveys preoperatively and at 2-4 weeks and 3 months postimplant. We identified patients who experienced acute and persistent acute bowel toxicity to determine if any factors could correlate with either situation. RESULTS: One hundred six patients were treated with (131)Cs from September 2006 to May 2008. Thirty-eight percent of patients met our criteria for patient-appreciated acute bowel symptoms. On multivariate analysis, the volume of rectum receiving 50% of the prescribed dose (R-V(50); 4.1 vs. 2.6cc, p=0.01), R-V(75) (1.3 vs. 0.62cc, p=0.01), the percentage of the prescribed dose received by 1cc of the rectum (R-D-1cc; 75% vs. 64%, p=0.02), and R-D-2cc (63% vs. 54%, p=0.003) were found to be factors associated with a greater risk of severe acute bowel toxicity. At 3-month followup, 28% of patients had persistent acute bowel toxicity. On multivariate analysis, no factors were identified that correlated with persistent acute bowel toxicity. CONCLUSIONS: This study identifies R-V(50), R-V(75), R-D-1cc, and R-D-2cc as factors associated with patient-appreciated acute rectal toxicity. We are performing dosimetric analysis to determine the optimal distance for the posterior needles from the prostate-rectal interface to decrease rectal dose while still maintaining adequate coverage of prostate.

Management of patients treated with chemoradiotherapy for head and neck cancer without prophylactic feeding tubes: the University of Pittsburgh experience.

OBJECTIVES/HYPOTHESIS: Mucositis and dysphagia are common complications of chemoradiotherapy (CRT) for head and neck cancer that may necessitate nutritional support with a gastrostomy tube (G-tube). METHODS: We reviewed records of patients who underwent and completed CRT, which included at least one traditional chemotherapeutic, for previously untreated head and neck cancer. G-tubes were placed as needed. The timing and duration of G-tube placement and treatment-related complications and risk factors for long-term G-tube use were analyzed. RESULTS: A total of 91 consecutive patients who received CRT, 68 as primary and 23 as postoperative treatment, were studied. Radiation doses ranged from 59.4 to 74 Gy (median, 70 Gy). Seventy-nine percent of patients received platinum-based therapy during CRT. Severe mucositis occurred in 40% of patients. Forty percent of patients required G-tube placement (15 prior to CRT and 21 during CRT). Median duration of G-tube use was 5.8 months. Two patients who had a G-tube placed during CRT developed a G-tube-related complication. At 6 and 12 months, 15 (18%) and four (6%) patients who were disease free were using G-tubes, respectively. Patients with G-tubes placed prior to CRT or advanced T stage had longer G-tube dependence. CONCLUSIONS: With aggressive supportive care it is feasible to avoid G-tubes in the majority of patients undergoing CRT for head and neck cancer. G-tube placement prior to CRT due to pre-existing dysphagia and advanced T stage are associated with prolonged G-tube dependence.

Fractionated stereotactic body radiation therapy in the treatment of primary, recurrent, and metastatic lung tumors: the role of positron emission tomography/computed tomography-based treatment planning.

PURPOSE: The aim of this study was to assess the outcomes of patients treated with stereotactic body radiation therapy (SBRT) in patients with primary, recurrent, or metastatic lung lesions, with a focus on positron emission tomography (PET)/computed tomography (CT)-based management. PATIENTS AND METHODS: Fifty-one patients with primary stage I non-small-cell lung cancer (NSCLC; n = 26), recurrent lung cancer after definitive treatment (n = 12), or solitary lung metastases (n = 13) were treated with SBRT between 2005 and 2007. Patients were treated with the CyberKnife Robotic Radiosurgery System with Synchrony respiratory tracking. A dose of 60 Gy was delivered in 3 fractions. All patients had CT or PET/CT performed at approximately 3-month intervals after treatment. RESULTS: The median follow-up was 12 months. Local control at median follow-up was 85% in patients with stage I NSCLC, 92% in patients with recurrent lung cancer, and 62% in the patients with solitary lung metastasis. Analysis of the 28 patients with pre- and post-treatment PET/CT scans demonstrated that those with stable disease (n = 4) had a mean standardized uptake value (SUV) decrease of 28%, partial responders (n = 11) had a decrease of 48%, and patients with a complete response (n = 11) had a decrease of 94%. Patients with progressive disease (n = 2) had an SUV decrease of only 0.4%. Only 2 patients (7%) who had reduced fluorodeoxyglucose avidity later progressed locally. No correlations were found between pretreatment SUV and tumor response, disease progression, or survival. Overall 1-year survival rates were 81%, 67%, and 85% among the patients with primary NSCLC, recurrent lung cancer, and solitary lung metastases, respectively. CONCLUSION: Stereotactic body radiation therapy with CyberKnife is an effective treatment for patients with medically inoperable recurrent or metastatic lung cancer. Positron emission tomography/CT is valuable in staging, planning, and evaluating treatment response and might predict long-term outcome.

Characteristics of sensorineural hearing loss in children with inner ear anomalies.

PURPOSE: To determine whether hearing loss in children with inner ear anomalies has some distinctive characteristics when compared to children with hearing loss but without inner ear anomalies. METHODS: Temporal bone computed tomography scans of 69 patients with sensorineural hearing loss were examined for inner ear abnormalities of which 17 were identified. The medical histories of these patients were reviewed for the characteristics of their hearing loss, including initial presentation, natural history, and nature of loss, as well as the family history of hearing loss and risk factors for hearing loss. These were compared to age-matched controls with hearing loss but without inner ear anomalies. RESULTS: Seventeen patients had inner ear anomalies. Records of 14 of these patients were compared to patients without inner ear anomalies. Regarding age of onset, 71.4% of patients with anomalies had onset of their hearing loss at less than 2 years old vs 78.6% without anomalies. Regarding unilateral vs bilateral, 42.9% of patients with anomalies were unilateral vs 28.6% of patients without anomalies. For patients with anomalies, 85.7% were stable and 14.3% were progressive; without anomalies, 71.4% were stable, 21.4% were progressive, and 7.1% were fluctuating. Regarding family history, only 14.3% of patients without anomalies had a positive family history vs 56% of patients with anomalies. CONCLUSIONS: Children with inner ear anomalies and sensorineural hearing loss have an increased incidence of unilateral hearing loss and stable hearing loss as compared to controls with sensorineural hearing loss without inner ear anomalies. In addition, children with inner ear anomalies and sensorineural hearing loss are less likely to have a family history of hearing loss.

Gamma camera scans and pretreatment tumor volumes as predictors of response and progression after Y-90 anti-CD20 radioimmunotherapy.

PURPOSE: To evaluate two potential approaches to predicting site-specific patterns of recurrence after yttrium-90 ibritumomab tiuxetan radioimmunotherapy (RIT) for CD20+ B-cell Non-Hodgkin's lymphoma. These predictive methods may be useful in evaluating the utility of local intensification of individual nodal or extranodal sites using external beam radiotherapy. METHODS AND MATERIALS: Records and images were evaluated for 20 patients previously treated with yttrium-90 ibritumomab RIT. Intensity of isotope uptake on the pretreatment two-dimensional antibody scans and maximal extent of tumor deposits found on computed tomography images of each anatomic site were correlated with response and subsequent patterns of recurrence or progression. RESULTS: Our data failed to suggest a significant correlation between the site-by-site two-dimensional image intensity on the pre-RIT scan and the likelihood of response at those sites. In contrast, an analysis of pretreatment target volumes did correlate significantly with progression. A collective analysis of disease sites from all 20 patients found that 83% (10/12) sites of "bulky" (maximal diameter > or = 5 cm) disease displayed evidence of progression vs. 28% (26/93) of "nonbulky" disease sites containing gross disease but no area measuring >5 cm (p < 0.001). All patients with at least one site of bulky disease had initial disease progression occur at a bulky site, with a bulky site being the sole first site of progression in approximately 50%. In patients with only nonbulky disease sites, approximately one third progressed initially at an entirely new site of disease. CONCLUSION: We conclude that we can use tumor bulk to establish a statistical hierarchy of likely tumor progression sites and use this pattern to direct the use of additional external beam radiotherapy to augment treatment.

Serum concentrations of interleukin-8, vascular endothelial growth factor, and epidermal growth factor receptor in patients with squamous cell cancer of the head and neck.

Squamous cell cancer of the head and neck (SCCHN) is associated with production of pro-inflammatory and pro-angiogenic cytokines. We hypothesized that cytokine serum levels will correlate with tumor volume and aggressiveness. We investigated interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), and epidermal growth factor receptor (EGFR) in SCCHN. The patient population consisted of normal and irradiated controls: patients with newly diagnosed SCCHN, and patients with recurrent or metastatic disease. Pretreatment sera were studied by ELISA. Serum IL-8 levels, as opposed to VEGF or EGFR, were consistently elevated in patients with recurrent or metastatic disease. The differences in mean serum IL-8, compared to controls, were significant (p=0.02). Serum levels of IL-8 are consistently elevated in patients with recurrent or metastatic SCCHN and elevated levels may correlate with advanced or aggressive disease. Further, more intensive, study of IL-8 as a biomarker in SCCHN is warranted.