S.R. Alcorn

Radiation dose to the floor of mouth muscles predicts swallowing complications following chemoradiation in oropharyngeal squamous cell carcinoma

OBJECTIVES While radiation dose to the larynx and pharyngeal constrictors has been the focus of swallowing complications, the suprahyoid muscles, or floor of mouth (FoM) muscles, are critical for hyoid and laryngeal elevation and effective bolus diversion, preventing penetration and aspiration. We hypothesize that radiation dose to these muscles may be important in the development of dysphagia. MATERIALS AND METHODS We studied 46 patients with OPSCC treated with CRT and who underwent baseline swallowing evaluations and post-treatment videofluoroscopic swallowing studies (VFSS) from 2007 to 2010. Patients with abnormal penetration aspiration scores (PAS>2) served as the study population and patients with normal PAS scores (≤ 2) served as the control cohort. Three suprahyoid muscles and two extrinsic tongue muscles were individually delineated and collectively referred to as the FoM muscles. Radiation dose-volume relationships for these muscles were calculated. Univariate logistic regression analysis was used to determine parameters of significance between patients with normal or abnormal PAS scores. A multivariate regression analysis was subsequently performed to isolate the most statistically critical structures associated with abnormal PAS. RESULTS Univariate analysis resulted in significance/borderline significance of multiple structures associated with abnormal PAS following irradiation. However, when a multivariate model was applied, only the mean dose to the floor of mouth and minimum dose to the geniohyoid were associated with post-radiation abnormal PAS. CONCLUSIONS The dose and volume delivered to the collective FoM muscles may be associated with an increased risk of laryngeal penetration/aspiration to a greater degree than previously recognized organs at risk.

Patterns of Care Among Patients Receiving Radiation Therapy for Bone Metastases at a Large Academic Institution

PURPOSE This study evaluates outcomes and patterns of care among patients receiving radiation therapy (RT) for bone metastases at a high-volume academic institution. METHODS AND MATERIALS Records of all patients whose final RT course was for bone metastases from April 2007 to July 2012 were identified from electronic medical records. Chart review yielded demographic and clinical data. Rates of complicated versus uncomplicated bone metastases were not analyzed. RESULTS We identified 339 patients whose final RT course was for bone metastases. Of these, 52.2% were male; median age was 65 years old. The most common primary was non-small-cell lung cancer (29%). Most patients (83%) were prescribed ≤10 fractions; 8% received single-fraction RT. Most patients (52%) had a documented goals of care (GOC) discussion with their radiation oncologist; hospice referral rates were higher when patients had such discussions (66% with vs 50% without GOC discussion, P=.004). Median life expectancy after RT was 96 days. Median survival after RT was shorter based on inpatient as opposed to outpatient status at the time of consultation (35 vs 136 days, respectively, P<.001). Hospice referrals occurred for 56% of patients, with a median interval between completion of RT and hospice referral of 29 days and a median hospice stay of 22 days. CONCLUSIONS These data document excellent adherence to American Society for Radiation Oncolology Choosing Wisely recommendation to avoid routinely using >10 fractions of palliative RT for bone metastasis. Nonetheless, single-fraction RT remains relatively uncommon. Participating in GOC discussions with a radiation oncologist is associated with higher rates of hospice referral. Inpatient status at consultation is associated with short survival.

Molecularly Targeted Agents as Radiosensitizers in Cancer Therapy—Focus on Prostate Cancer

As our understanding of the molecular pathways driving tumorigenesis improves and more druggable targets are identified, we have witnessed a concomitant increase in the development and production of novel molecularly targeted agents. Radiotherapy is commonly used in the treatment of various malignancies with a prominent role in the care of prostate cancer patients, and efforts to improve the therapeutic ratio of radiation by technologic and pharmacologic means have led to important advances in cancer care. One promising approach is to combine molecularly targeted systemic agents with radiotherapy to improve tumor response rates and likelihood of durable control. This review first explores the limitations of preclinical studies as well as barriers to successful implementation of clinical trials with radiosensitizers. Special considerations related to and recommendations for the design of preclinical studies and clinical trials involving molecularly targeted agents combined with radiotherapy are provided. We then apply these concepts by reviewing a representative set of targeted therapies that show promise as radiosensitizers in the treatment of prostate cancer.

Practice patterns of photon and proton pediatric image guided radiation treatment: Results from an International Pediatric Research Consortium

PURPOSE Image guided radiation therapy (IGRT) has become common practice for both photon and proton radiation therapy, but there is little consensus regarding its application in the pediatric population. We evaluated clinical patterns of pediatric IGRT practice through an international pediatrics consortium comprised of institutions using either photon or proton radiation therapy. METHODS AND MATERIALS Seven international institutions with dedicated pediatric expertise completed a 53-item survey evaluating patterns of IGRT use in definitive radiation therapy for patients ≤21 years old. Two institutions use proton therapy for children and all others use IG photon therapy. Descriptive statistics including frequencies of IGRT use and means and standard deviations for planning target volume (PTV) margins by institution and treatment site were calculated. RESULTS Approximately 750 pediatric patients were treated annually across the 7 institutions. IGRT was used in tumors of the central nervous system (98%), abdomen or pelvis (73%), head and neck (100%), lung (83%), and liver (69%). Photon institutions used kV cone beam computed tomography and kV- and MV-based planar imaging for IGRT, and all proton institutions used kV-based planar imaging; 57% of photon institutions used a specialized pediatric protocol for IGRT that delivers lower dose than standard adult protocols. Immobilization techniques varied by treatment site and institution. IGRT was utilized daily in 45% and weekly in 35% of cases. The PTV margin with use of IGRT ranged from 2 cm to 1 cm across treatment sites and institution. CONCLUSIONS Use of IGRT in children was prevalent at all consortium institutions. There was treatment site-specific variability in IGRT use and technique across institutions, although practices varied less at proton facilities. Despite use of IGRT, there was no consensus of optimum PTV margin by treatment site. Given the desire to restrict any additional radiation exposure in children to instances where the exposure is associated with measureable benefit, prospective studies are warranted to optimize IGRT protocols by modality and treatment site.

‘Elderly’ patients with newly diagnosed glioblastoma deserve optimal care

The treatment of ‘elderly’ patients with newly diagnosed glioblastoma (GBM) has received considerable attention following the recently published results of two randomized, prospective, multicenter trials designed to establish optimal therapy in this patient population [1, 2]. The first trial, NOA-08, randomized 373 patients over the age of 65 years with anaplastic astrocytoma or GBM to either standard radiation (60 Gy in 30 fractions) or dose dense temozolomide (100 mg/m2 1 week on, 1 week off) [1]. The second trial, named the Nordic trial, randomized 342 patients over the age of 60 to three arms: (1) hypofractionated radiation (34 Gy in 10 fractions), (2) standard radiation, and (3) single-agent temozolomide (200 mg/m2 for five consecutive days every month) [2]. Both of these studies conclude that temozolomide alone was ‘not inferior’ to radiation, implying that single-agent chemotherapy should be considered as a standard of care in this patient population. However, the standard of care for patients with newly diagnosed GBM consists of 6 weeks of radiation to 60 Gy with daily concomitant temozolomide, followed by 6 months of adjuvant temozolomide, based on the landmark EORTC/NCIC study published in 2005 [3]. The 5-year follow-up data of this trial demonstrated that radiation with temozolomide provided superior outcomes compared to radiation alone in each accrued age group, including patients age 61–70 (hazard ratio of 0.7 {0.5–0.97}) [4]. Median survival (months) 2 year survival 3 year survival 4 year survival 5 year survival Radiation 11.8 5.7 % 2.3 % 2.3 % 0% Radiation and temozolomide 10.9 21.8 % 12.3 % 8.8 % 6.5 % View it in a separate window From: Stupp et al. Lancet Oncol 2009. Patients over the age of 60 It should be noted that neither the NOA-08 nor the Nordic trial contained a comparison arm of standard radiation and temozolomide. In the Nordic trial, the 60–70 year old patients had a median survival of only 8.3 months if they received hypofractionated radiation and 7.8 months if they received temozolomide alone. These results are inferior to the age-matched results from the EORTC/NCIC trial [3, 4]. In the N0A-08 trial, the definitions for non-inferiority were so broad that radiation alone would have been considered ‘not inferior’ to radiation combined with temozolomide in the pivotal EORTC/NCIC study, based on treatment-specific median survivals reported in the latter study. Furthermore, using a non-inferiority design when predictable treatment crossovers will occur is likely to yield ‘‘non-inferior’’ survival results, which ultimately have little or no impact on medical practice. Institutional and national bodies that establish clinical practice treatment guidelines will review these two prospective randomized trials. Extreme caution should be used in concluding that temozolomide alone is an acceptable standard in this patient population, since approximately 45 % of all patients with GBM are over the age of 65 [5]. Chronologic age alone is simply insufficient to determine if an individual patient will tolerate combination therapy [6]. Prescribing single agent temozolomide to an older patient with an excellent performance status after a gross total resection of an MGMT promoter-methylated glioblastoma was entirely possible within the context of these research studies and could be viewed as acceptable practice using the conclusions of these studies. However, this approach is unlikely to provide optimal therapy for such a patient. One ongoing trial (EORTC 22061-26062) randomizes elderly patients with glioblastoma to radiation and chemotherapy versus radiation (www.clinicaltrials.gov). Unfortunately, this study will not resolve the outstanding question as it employs a non-standard short-course of radiation in both arms without a standard treatment arm. As a result, until proven otherwise, older patients with newly diagnosed GBM who are clinically fit should be offered the best available therapy, which as of 2013 remains radiation and temozolomide as defined by the EORTC/NCIC study [3, 4].

Practice patterns of palliative radiation therapy in pediatric oncology patients in an international pediatric research consortium

The practice of palliative radiation therapy (RT) is based on extrapolation from adult literature. We evaluated patterns of pediatric palliative RT to describe regimens used to identify opportunity for future pediatric‐specific clinical trials.

Solitary Plasmacytoma of the Penile Urethra Treated With Primary Radiotherapy

Introduction Solitary plasmacytomas are localized, potentially curable collections of monoclonal plasma cells, accounting for less than 5% of plasma cell neoplasms. Approximately 80% of solitary extramedullary plasmacytomas (SEPs) are found in the upper aerodigestive tract, with uncommon involvement of other sites including the GI tract, urogenital region, and epidermis. SEPs of the urethra are rare, with up to eight published cases reported to date (Table 1). Here we describe a patient with SEP of the penile urethra managed with primary radiotherapy.

Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma (NHL) is a heterogeneous group of B-cell, T-cell, and natural killer (NK)-cell neoplasms that lack the pathologic characteristics seen in Hodgkin disease (HD).

Image Guidance in Pediatric Brain Radiotherapy

Image guided radiotherapy (IGRT) in pediatrics provides a means for reduction of treatment volumes by permitting for the use of highly conformal plans with smaller treatment margins. IGRT may additionally allow for dose escalation and adaptive radiotherapy strategies. Current practice patterns and clinical protocols support the use of weekly or daily IGRT as standard practice in pediatric brain-directed IGRT. However, the benefits of IGRT must be weighed against its costs including potentially significant additional radiation dose, supporting the need to study lower dose IGRT protocols in this population. This chapter reviews common modalities of IGRT and the literature regarding its use specific to pediatric brain radiotherapy.

Radiotherapy for Primary and Metastatic Soft Tissue Sarcomas: Altered Fraction Regimens with External Beam and Brachytherapy

This chapter describes altered fraction regimens used in the management of localized and metastatic soft tissue sarcomas. Rationale, disease outcomes, toxicity, and planning and delivery methodology are provided for stereotactic radiotherapy, interdigitated chemoradiation, intraoperative radiation therapy, and postoperative interstitial brachytherapy techniques.