Miller, Robert C.

Objectives: To evaluate outcomes among cancer patients with preexisting coronary artery disease and cardiac stenting who subsequently underwent thoracic radiotherapy (RT). Methods: From 1998 to 2012, 147 patients received percutaneous coronary intervention (PCI) and then curative external beam RT (>30 Gy, except for Hodgkin lymphoma patients) involving the heart and the lungs. Heart-specific and lung-specific dosimetric parameters were correlated to overall survival (OS) and cardiac-specific survival by Cox variate methods. Results: The mean interval between PCI and cancer diagnosis was 1.8 years (range, 0.1 to 14.2 y). Hypertension was present in 105 patients (71%), and hyperlipidemia in 82 (56%). At the time of analysis, 69 patients (47%) were alive, 3 (2%) died of cardiac causes, and 53 (36%) died of cancer. In multivariate analyses, OS since PCI was related to cancer type (P=0.004). Decreased OS since cancer diagnosis was related to older age (P<0.001) and increased percentage of targeted volume or organ receiving 20 Gy or more for lung (P<0.001), even after controlling for sex, cancer type, and stage. However, for non–cancer-specific survival and major adverse cardiac event-free survival, older age and underlying cardiopulmonary comorbidities dominated (rather than heart and lung dosimetric parameters) in predicting worse outcome for these patients with preexisting coronary artery disease who later underwent RT. Conclusions: Cancer type, older age, and preexisting cardiopulmonary comorbidities and risk factors most significantly predicted clinical outcome and survival for these patients with existing coronary stents who subsequently received thoracic RT. Dosimetric detrimental effects were not significant in our study.

Objectives: To determine long-term outcomes in patients with locally advanced esophageal carcinoma treated with trimodality therapy (chemoradiotherapy [CRT] and surgery, TMT) or definitive CRT. Methods: We retrospectively identified patients with advanced esophageal carcinoma treated with curative intent at our institution between 1998 and 2004. Identified patients were separated into 3 groups: patients who received TMT, patients who received CRT, and patients who began treatment with trimodality intent but did not undergo surgery (PTMT). Local control, overall survival (OS), and distant metastasis-free survival were compared using Kaplan-Meier statistics. Results: Among the 265 patients included, median follow-up was 6.4 years for surviving patients and 1.7 years for all patients. Type of esophageal cancer was adenocarcinoma in 213 patients (80%) and squamous cell carcinoma in 46 patients (17%). Treatment groups comprised 169 patients (64%) completing TMT, 46 patients medically unable to undergo surgery after neoadjuvant therapy (PTMT), and 50 (19%) who underwent CRT. Median OS was 20.5 months; actuarial 5- and 10-year OS were 27% and 12%, respectively. The TMT group had the highest 5- and 10-year OS (32% and 19%, respectively). Local control rates at 2, 5, and 10 years for all patients were 80%, 70%, and 69%, respectively. By treatment modality, 5-year local control was best (82%) for TMT, compared with 60% for CRT and 40% for PTMT groups (P<0.001). Conclusions: Patients who completed TMT had the best local control and long-term OS. In the context of TMT, surgery seemed more beneficial in patients with esophageal adenocarcinoma versus squamous cell carcinoma.

Purpose Painful oral mucositis (OM) is a significant toxicity during radiotherapy for head and neck cancers. The aim of this randomized, double-blind, placebo-controlled trial was to test the efficacy of doxepin hydrochloride in the reduction of radiotherapy-induced OM pain. Patients and Methods In all, 155 patients were randomly allocated to a doxepin oral rinse or a placebo for the treatment of radiotherapy-related OM pain. Patients received a single dose of doxepin or placebo on day 1 and then crossed over to receive the opposite agent on a subsequent day. Pain questionnaires were administered at baseline and at 5, 15, 30, 60, 120, and 240 minutes. Patients were then given the option to continue doxepin. The primary end point was pain reduction as measured by the area under the curve (AUC) of the pain scale using data from day 1. Results Primary end point analysis revealed that the AUC for mouth and throat pain reduction was greater for doxepin (−9.1) than for placebo (−4.7; P < .001). Crossover analysis of patients completing both phases confirmed that patients experienced greater mouth and throat pain reduction with doxepin (intrapatient changes of 4.1 for doxepin-placebo arm and −2.8 for placebo-doxepin arm; P < .001). Doxepin was associated with more stinging or burning, unpleasant taste, and greater drowsiness than the placebo rinse. More patients receiving doxepin expressed a desire to continue treatment than did patients with placebo after completion of each of the randomized phases of the study. Conclusion A doxepin rinse diminishes OM pain. Further studies are warranted to determine its role in the management of OM.

The use of charged-particle radiation therapy (CPRT) is an increasingly important development in the treatment of cancer. One of the most pressing controversies about the use of this technology is whether randomised controlled trials are required before this form of treatment can be considered to be the treatment of choice for a wide range of indications. Equipoise is the key ethical concept in determining which research studies are justified. However, there is a good deal of disagreement about how this concept is best understood and applied in the specific case of CPRT. This report is a position statement on these controversies that arises out of a workshop held at Wolfson College, Oxford in August 2011. The workshop brought together international leaders in the relevant fields (radiation oncology, medical physics, radiobiology, research ethics and methodology), including proponents on both sides of the debate, in order to make significant progress on the ethical issues associated with CPRT research. This position statement provides an ethical platform for future research and should enable further work to be done in developing international coordinated programmes of research.

Kaposi's sarcoma (KS) most often affect the skin but occasionally affect the mucosa of different anatomic sites. The management of mucosal KS is seldom described in the literature. Data from 15 eligible patients with mucosal KS treated between 1994 and 2008 in five institutions within three countries of the Rare Cancer Network group were collected. The inclusion criteria were as follows: age >16 years, confirmed pathological diagnosis, mucosal stages I and II, and a minimum of 6 months’ follow-up after treatment. Head and neck sites were the most common (66%). Eleven cases were HIV-positive. CD4 counts correlated with disease stage. Twelve patients had biopsy only while three patients underwent local resection. Radiotherapy (RT) was delivered whatever their CD4 status was. Median total radiation dose was 16.2 Gy (0–45) delivered in median 17 days (0–40) with four patients receiving no RT. Six patients underwent chemotherapy and received from 1 to 11 cycles of various regimens namely vinblastin, caelyx, bleomycine, or interferon, whatever their CD4 counts was. Five-year disease free survival were 81.6% and 75.0% in patients undergoing RT or not, respectively. Median survival was 66.9 months. Radiation-induced toxicity was at worse grade 1–2 and was manageable whatever patients’ HIV status. This small series of mucosal KSs revealed that relatively low-dose RT is overall safe and efficient in HIV-positive and negative patients. Since there are distant relapses either in multicentric cutaneous or visceral forms in head and neck cases, the role of systemic treatments may be worth investigations in addition to RT of localized disease. Surgery may be used for symptomatic lesions, with caution given the risk of bleeding.

The Rare Cancer Network (RCN), founded in 1993, performs research involving rare tumors that are not common enough to be the focus of prospective study. Over 55 studies have either been completed or are in progress. The aim of the paper is to present an overview of the 30 studies done through the RCN to date, organized by disease site. Five studies focus on breast pathology, including sarcoma, lymphoma, phyllodes tumor, adenoid cystic carcinoma, and ductal carcinoma in situ in young women. Three studies on prostate cancer address prostatic small cell carcinoma and adenocarcinoma of young and elderly patients. Six studies on head and neck cancers include orbital and intraocular lymphoma, mucosal melanoma, pediatric nasopharyngeal carcinoma, olfactory neuroblastoma, and mucosa-associated lymphoid tissue lymphoma of the salivary glands. There were 4 central nervous system studies on patients with cerebellar glioblastoma multiforme, atypical and malignant meningioma, spinal epidural lymphoma and myxopapillary ependymoma. Outside of these disease sites, there is a wide variety of other studies on tumors ranging from uterine leiomyosarcoma to giant cell tumors of the bone. The studies done by the RCN represent a wide range of rare pathologies that were previously only studied in small series or case reports. With further growth of the RCN and collaboration between members our ability to analyze rare tumors will increase and result in better understanding of their behavior and ultimately help direct research that may improve patient outcomes.

The role of radiotherapy for local control of marginally resected, unresectable, and recurrent giant cell tumors of bone (GCToB) has not been well defined. The number of patients affected by this rare disease is low. We present a series of 58 patients with biopsy proven GCToB who were treated with radiation therapy. A retrospective review of the role of radiotherapy in the treatment of GCToB was conducted in participating institutions of the Rare Cancer Network. Eligibility criteria consisted of the use of radiotherapy for marginally resected, unresectable, and recurrent GCToB. Fifty-eight patients with biopsy proven GCToB were analyzed from 9 participating North American and European institutions. Forty-five patients had a primary tumor and 13 patients had a recurrent tumor. Median radiation dose was 50 Gy in a median of 25 fractions. Indication for radiation therapy was marginal resection in 33 patients, unresectable tumor in 13 patients, recurrence in 9 patients and palliation in 2 patients. Median tumor size was 7.0 cm. A significant proportion of the tumors involved critical structures. Median follow-up was 8.0 years. Five year local control was 85%. Of the 7 local failures, 3 were treated successfully with salvage surgery. All patients who received palliation achieved symptom relief. Five year overall survival was 94%. None of the patients experienced grade 3 or higher acute toxicity. This study reports a large published experience in the treatment of GCToB with radiotherapy. Radiotherapy can provide excellent local control for incompletely resected, unresectable or recurrent GCToB with acceptable morbidity.

Primary pancreatic small cell carcinoma (SCC) is rare, with just over 30 cases reported in the literature. Only 7 of these patients underwent surgical resection with a median survival of 6 months. Prognosis of SCC is therefore considered to be poor, and the role of adjuvant therapy is uncertain. Here we report two institutions’ experience with resectable pancreatic SCC. Six patients with pancreatic SCC treated at the Johns Hopkins Hospital (4 patients) and the Mayo Clinic (2 patients) were identified from prospectively collected pancreatic cancer databases and re-reviewed by pathology. All six patients underwent a pancreaticoduodenectomy. Clinicopathologic data were analyzed, and the literature on pancreatic SCC was reviewed. Median age at diagnosis was 50 years (range 27–60). All six tumors arose in the head of the pancreas. Median tumor size was 3 cm, and all cases had positive lymph nodes except for one patient who only had five nodes sampled. There were no perioperative deaths and three patients had at least one postoperative complication. All six patients received adjuvant therapy, five of whom were given combined modality treatment with radiation, cisplatin, and etoposide. Median survival was 20 months with a range of 9–173 months. The patient who lived for 9 months received chemotherapy only, while the patient who lived for 173 months was given chemoradiation with cisplatin and etoposide and represents the longest reported survival time from pancreatic SCC to date. Pancreatic SCC is an extremely rare form of cancer with a poor prognosis. Patients in this surgical series showed favorable survival rates when compared to prior reports of both resected and unresectable SCC. Cisplatin and etoposide appears to be the preferred chemotherapy regimen, although its efficacy remains uncertain, as does the role of combined modality treatment with radiation.

Survival in patients with unresectable pancreatic carcinoma is poor. Studies by Mayo Clinic and the Gastrointestinal Tumor Study Group (GITSG) have established combined modality treatment with chemotherapy and radiation as the standard of care. Use of gemcitabine-based chemotherapy alone has also been shown to provide a benefit, but 5‑year overall survival still remains less than 5%. Conventional radiotherapy is traditionally delivered over a six week period and high toxicity is seen with the concomitant use of chemotherapy. In contrast, SBRT can be delivered in 3–5 days and, when used as a component of combined modality therapy with gemcitabine, disruption to the timely delivery of chemotherapy is minimal. Early single-institution reports of SBRT for unresectable pancreatic carcinoma demonstrate excellent local control with acceptable toxicity. Use of SBRT in unresectable pancreatic carcinoma warrants further investigation in order to improve the survival of patients with historically poor outcomes.