Abhay S. Gokhale

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.

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

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).

Clinical and dosimetric factors associated with a prolonged feeding tube requirement in patients treated with chemoradiotherapy (CRT) for head and neck cancers

BACKGROUND Patients treated with chemoradiotherapy (CRT) for head and neck cancers often require feeding tubes (FTs) due to toxicity. We sought to identify factors associated with a prolonged FT requirement. PATIENTS AND METHODS We retrospectively reviewed 80 patients treated with CRT for head and neck cancers. The pharyngeal constrictors (PCs), supraglottic larynx (SGL), and glottic larynx (GL) were contoured and the mean radiation doses and the volumes of each receiving >40, 50, 60, and 70 Gy (V40, V50, V60, and V70) were determined. RESULTS A total of 33 of 80 patients required a FT either before or during the course of CRT. Fifteen patients required the FT for > or = 6 months. On univariate analysis, significant factors associated with a prolonged FT requirement were mean PC dose, PC-V60, PC-V70, SGL dose, SGL-V70, and advanced T3-T4 disease. Multivariate analyses found both PC-V70 and T3-T4 disease as significant factors .The proportions of patients requiring a FT > or = 6 months were 8% and 28% for treatment plans with PC-V70 <30% and > or = 30%, respectively. CONCLUSIONS Increased radiation dose to the PCs is associated with a higher risk of a prolonged FT need. Dose sparing of the PC muscles may reduce this risk.

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.

Clinical and dosimetric factors associated with acute rectal toxicity in patients treated with 131Cs 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.

Abstract 1404: Mitochondrial-targeted nitroxide JP4-039 ameliorates irradiation-induced delay in bone wound healing and inhibits orthotopic tumor growth

In the case of a nuclear explosion, combined injuries will result from radiation dispersal resulting in burns and cellular damage as well as a concussion wave resulting in traumatic bone fractures. Currently no available drugs are available to protect against both irradiation damage and traumatic bone damage. A new mitochondrial targeted small molecule hemigramicidin S nitroxide JP4-039 has been developed and shown to protect against total body irradiation. JP4-039 was tested to determine its effects on irradiation-induced delay of osseous wound healing. A model for osseous would healing was used where the right hind legs of C57BL/6NHsd female mice were irradiated to doses 0 to 30 Gy 24 hours prior to drilling tibial wounds. JP4-039 (10 mg/kg) was injected either 10 min before or after irradiation. Mice were sacrificed weekly after wounding; tibiae were removed and radiographed for measurement of hole diameter. The left non-irradiated leg served as a control for the irradiated right leg. To determine whether JP4-039 might enhance tumor growth while stimulating bone growth, we injected Lewis lung carcinoma cells subcutaneously above the knee in both legs. The tumor on the right leg was within the 10Gy irradiation field. Tumor growth was monitored daily with calipers. Tukey9s test was used to assess statistical significance between control and treated groups. Mice treated with JP4-039 before bone drilling showed significant improvement in osseous wound healing at 14 days and 21 days after drilling (0.55 ± 0.3 and 0.47 ± 0.04 mm, respectively), compared with 0.84 ± 0.05 and 0.64 ± 0.05 mm, respectively for control, untreated mice (p Thus, treatment with JP4-039 enhanced osseous bone healing when administered before wounding. Furthermore, JP4-039 enhanced healing when administered before or after irradiation. Finally, JP4-039 inhibited tumor growth and may have useful applications in cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1404.