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Purpose Prostate cancer survivors who receive androgen deprivation therapy (ADT) are at increased risk of cardiovascular disease. They require coordinated care between cancer specialists and primary care physicians to monitor for cancer control and manage cardiovascular risk factors. Methods and Materials We prospectively enrolled 103 men receiving ADT with radiation therapy (RT) from 7 institutions to assess cardiovascular risk factors and survivorship care. Medical records, fasting laboratory test values, and patient-reported outcomes using a validated instrument were assessed at baseline (pretreatment) and 1 year post-RT. Results Cardiovascular disease (39%) and risk factors (diabetes, 22%; hypertension, 63%; hyperlipidemia, 31%) were prevalent at baseline. During the first year after RT completion, 63% received cardiovascular monitoring concordant with American Heart Association guidelines. Fasting laboratory test values at 1 year showed 24% with inadequately controlled blood sugar and 22% elevated cholesterol. Patient perceptions about care coordination were relatively low. At 1 year, 57% reported that their primary care physicians “always know about the care I receive at other places,” 67% reported that their cancer physician “communicated with other providers I see,” and 65% reported that the cancer care physician “knows the results of my visits with other doctors.” Conclusions Patients with prostate cancer who receive ADT and RT are a vulnerable population with prevalent baseline cardiovascular disease and risk factors and suboptimal survivorship care specifically related to coordinated care and cardiovascular monitoring. Clinical trials examining ways to improve the care and outcomes of these survivors are needed.

Sorafenib, an inhibitor of multiple tyrosine kinases including vascular endothelial growth factor receptor and Raf/mitogen-activated protein kinase, increases progression-free survival in metastatic renal cell carcinoma (RCC) compared with placebo. The efficacy and toxicity of combined sorafenib and radiation therapy (RT) in the treatment of RCC are unknown. This is a retrospective report of 3 consecutive patients with metastatic or locally recurrent RCC treated with palliative RT while undergoing sorafenib therapy. All 3 patients experienced disease progression on sorafenib and remained on the drug without dose reduction during the RT plus sorafenib regimen. They were followed for toxicity and response by clinical history, physical examination, and contrast-enhanced computed tomography scans. Soon after completion of palliative RT, all 3 patients experienced complete pain relief without the need for narcotic pain medication. Posttreatment imaging revealed partial response with > 50% regression of tumor in all patients. None reported significant acute or late side effects at follow-up of 3, 6, and 8 months after RT and sorafenib. In the 3 patients with recurrent or metastatic RCC in this report, the combination of RT and sorafenib was well tolerated and resulted in excellent clinical and radiologic responses. This combination is promising and requires further study.

The aim of this retrospective review of patients with gynecologic malignancies treated with external beam radiotherapy (EBRT) and interstitial brachytherapy was to determine the rate of Gradeor =2 rectovaginal fistula and Gradeor =4 small bowel obstruction as defined by the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0.Thirty-six patients with primary and recurrent gynecologic cancers were treated with EBRT and interstitial brachytherapy. Median doses to tumor, bladder, and rectum were 75 Gy, 61 Gy, and 61 Gy, respectively. A univariate analysis was performed to identify variables that correlated with toxicity.At median follow-up of 19 months, the 3-year risk of small bowel obstruction was 6%. Those patients with prior abdomino-pelvic surgery who received EBRT with antero-posterior fields had higher rates of obstruction than patients without prior abdomino-pelvic surgery or those who received EBRT with four fields (50% vs. 0%, p0.0001). The 3-year risk of rectovaginal fistula was 18% and was significantly higher in patients who received76 Gy to the rectum compared with those who receivedor =76 Gy (100% vs. 7%, p = 0.009).Patients treated with EBRT and interstitial brachytherapy after abdomino-pelvic surgery should receive EBRT with four fields and the cumulative rectal dose should beor =76 Gy.

This review summarizes clinical studies in which glutathione was measured in tumor tissue from patients with brain, breast, gastrointestinal, gynecological, head and neck and lung cancer. Glutathione tends to be elevated in breast, ovarian, head and neck, and lung cancer and lower in brain and liver tumors compared to disease-free tissue. Cervical, colorectal, gastric, and esophageal cancers show both higher and lower levels of tumor glutathione. Some studies show an inverse relationship between patient survival and tumor glutathione. Based on this survey, we recommend approaches that may improve the clinical value of glutathione as a biomarker.

Magnetic resonance spectroscopic imaging has been used to follow glutathione metabolism and evaluate glutathione heterogeneity in intact tumor tissue. Stable isotope-labeled glutathione was detected in s.c. implanted fibrosarcoma tumors in anesthetized rats following infusion of [2-13C]glycine. Using 1H-decoupled 13C magnetic resonance spectroscopy, the appearance of [2-13C]glycine at 42.4 ppm and the subsequent incorporation of this isotope label into the glycyl residue of glutathione at 44.2 ppm can be detected. The identity and relative concentrations of labeled metabolites observed in the in vivo spectrum were confirmed in studies of tissue extracts. The high level of isotopic enrichment and the concentration of glutathione in tumor tissue allow for collection of spatially localized spectra using 13C chemical shift imaging methods. These data provide the first direct images of glutathione in intact tumor tissue and show metabolic heterogeneity. This method may lead to the ability to monitor changes in tumor tissue redox state that may ultimately affect diagnosis, monitoring, and treatment.

The purpose of this paper to identify the optimal therapy after radical prostatectomy (RP) for patients with adenocarcinoma of the prostate invading the seminal vesicles (pT3bN0M0 or SVI). A PubMed search using the keywords 'prostate', 'seminal vesicle', 'prostatectomy', 'radiotherapy', 'androgen blockade' was performed to identify literature regarding rates of disease failure in patients with SVI who are observed or treated with androgen blockade (AB), radiotherapy (RT) or RT + AB after RP. The outcome of 68 patients treated at Duke University with post-operative AB, RT or RT + AB for pT3bN0M0 is also presented. More than 70% of patients with SVI develop disease recurrence after surgery. For many, recurrence occurs within 2 y after RP. These patients have poor control rates with postoperative RT alone. While experience with AB and RT+AB is limited, control rates are generally superior to RT alone. At Duke University, after a median follow-up of nearly 4 y, patients treated with RT + AB or AB alone for pT3bN0M0 achieved better 5-y progression-free survival (PFS) compared with those who received RT alone (78 and 68 vs 30%, P = 0.03 and 0.046, respectively). There was no PFS difference between those who received AB alone or RT + AB (68 vs 78%, P=0.5). Seminal vesicle invasion confers a poor prognosis after RP. SVI is a consistent predictor of poor outcome after RT. The limited data available examining AB and RT + AB in pT3bN0M0 disease, including data from Duke University, are encouraging. Nonetheless, postoperative AB, RT and RT + AB for pT3bN0M0 disease require prospective evaluation, as RP alone is rarely curative.

Is androgen suppression therapy associated with early onset of fatal myocardial infarction?

14056 Background: Epidermal growth factor receptor (EGFR) is over expressed in pancreatic cancer. Cetuximab is an EGFR-antagonist which has synergy with gemcitabine (gem) and radiation. Gem is a potent radiosensitizer. We are conducting a Phase II trial of cetuximab with IMRT and twice-weekly gem. Eligibility includes stage I-III adenocarcinoma, with EGFR staining by immunohistochemistry. Pretreatment evaluation includes chest/abdomen CT scan and laparoscopy. Methods: Cetuximab 400 mg/m2 IV load was given over two hours. One week later, treatment continued with weekly cetuximab 250mg/m2 IV over one hour, and gem 50mg/m2 IV twice-weekly for twelve doses, concurrent with IMRT given in 28 daily fractions to 54Gy. Cetuximab/gem was given prior to that day’s IMRT. GI prophylaxis was with a proton pump inhibitor. Patients were considered for resection 4–8 weeks following therapy. Results: Ten patients enrolled to date, median age 70 years (range 54–83). Ninety percent of tumors were EGFR positive (range 1+ to 3+). At presentation, three tumors were unresectable, three borderline resectable and four resectable. One patient was removed from study following cetuximab anaphylaxis. Eight patients experienced grade III-IV hematotoxicity. Two patients had ischemic stroke in the backdrop of infection, one from stent obstruction/cholangitis, the other during neutropenic fever. One of these patients (age 81) died. Autopsy revealed severe atherosclerotic disease and evidence of prior strokes. Eight patients were evaluable for response. No patient had local progression. One patient had liver metastases post treatment. Two patients (25%) exhibited partial response. All others had stable disease. EGFR over expression did not predict response. Six patients went on to margin (−) resection, including one patient each with borderline resectable and unresectable disease prior to therapy. At median follow up of 8.5 months, there were no recurrences. Conclusions: Therapy yields modest efficacy and high resectability rates in patients with pancreatic cancer. Downstaging of tumor can occur in some patients. Toxicity may in part reflect the elderly patient demographic. Planned accrual is 48 patients. [Table: see text]