Angel I. Blanco

Intensity-modulated radiation therapy in head and neck cancers: an update.

Intensity‐modulated radiation therapy (IMRT), an advent of three‐dimensional conformal radiotherapy (3D CRT), has excited the profession of radiation oncology more than any other new invention since the introduction of the linear accelerator. Approximately 1000 articles have been published on this topic to date, more than 200 of which focus on head and neck cancer. IMRT is based on computer‐optimized treatment planning and a computer‐controlled treatment delivery system. The computer‐driven technology generates dose distributions that sharply conform to the tumor target while minimizing the dose delivered to the surrounding normal tissues. The high dose volume that tailors to the 3D configuration of the tumor along with the ability to spare the nearby normal tissues allows the option of tumor dose escalation.

Renal-cell carcinoma.

Renal cell carcinoma (RCC) is traditionally considered to be a “radioresistant” malignancy. Surgery has been the mainstay of treatment in the management of primary RCC, from open to laparoscopic and more recently robotic radical nephrectomy. For selected patients, nephron-sparing partial nephrectomy is performed. Other local therapy options include radiofrequency ablation (RFA), cryoablation, and other ablative procedures. Adjuvant radiotherapy after nephrectomy in high-risk patients has been shown to improve local control but not overall survival. These patients have high propensity for developing distant metastases which may explain the lack of survival benefits with adjuvant radiotherapy. In addition, it is also very difficult to deliver high dose radiation with conventional technique because of the radiation tolerance of normal tissues, especially the small bowels. With the approved use of various effective targeted agents, patients with high risk and metastatic RCC are now surviving longer and the role of local therapy for both primary and metastatic RCC has also become more important. Stereotactic radiosurgery (SRS) has been shown to be very effective in the management of RCC brain metastases. Extracranially, conventional radiotherapy has played an important role in the palliation of metastatic RCC associated symptoms such as pain. Stereotactic body radiation therapy (SBRT), a continuum of technological advances in SRS from intracranial to extracranial application, has now evolved to show promise in the local management of primary RCC, local recurrence, and various metastatic sites.

A dose-response relationship for time to bone pain resolution after stereotactic body radiotherapy (SBRT) for renal cell carcinoma (RCC) bony metastases

Abstract Background. To investigate the utility of stereotactic body radiotherapy (SBRT) in the treatment of painful renal cell carcinoma (RCC) bone metastases, and for a possible dose effect on time to symptom relief. Material and methods. Eighteen patients with 24 painful osseous lesions from metastatic RCC were treated with SBRT. The most common treatment regimens were 24 Gy in 3 fractions and 40 Gy in 5 fractions. The times from treatment to first reported pain relief and time to symptom recurrence were evaluated. Median follow-up was 38 weeks (1–156 weeks). Results. Seventy-eight percent of all patients had pain relief. Patients treated with a BED > 85 Gy achieved faster and more durable pain relief compared to those treated with a BED < 85 Gy. There was decrease in time to pain relief after a change in treatment regimen to 8 Gy × 5 fractions (BED = 86). There was only one patient with grade 1 skin toxicity. No neurological or other toxicity was observed. Conclusions. SBRT can safely and effectively treat painful RCC bony metastases. There appears to be a relationship between radiation dose and time to stable pain relief.

Spontaneous Regression of Thoracic Metastases While Progression of Brain Metastases After Stereotactic Radiosurgery and Stereotactic Body Radiotherapy for Metastatic Renal Cell Carcinoma: Abscopal Effect Prevented by the Blood-Brain Barrier?

Department of Radiation Oncology, The Methodist Hospital, Research Institute, ouston, TX Department of Radiation Oncology, The Methodist Hospital, Houston, TX Department of Radiology and Radiation Oncology, Kitasato University School of edicine, Sagamihara, Kanagawa, Japan Department of Radiation Oncology, Cancer Hospital (Institute), Chinese Academy f Medical Sciences, Peking Union Medical College, Beijing, China Department of Radiology, The Methodist Hospital, Houston, TX Medical Branch, The University of Texas, Houston, TX Division of Oncology, The University of Texas, Health Science Center, Memorial ermann Cancer Center, Houston, TX

The effect of dental artifacts, contrast media, and experience on interobserver contouring variations in head and neck anatomy

Objectives:To investigate interobserver variability in the delineation of head-and-neck (H&N) anatomic structures on CT images, including the effects of image artifacts and observer experience. Methods:Nine observers (7 radiation oncologists, 1 surgeon, and 1 physician assistant) with varying levels of H&N delineation experience independently contoured H&N gross tumor volumes and critical structures on radiation therapy treatment planning CT images alongside reference diagnostic CT images for 4 patients with oropharynx cancer. Image artifacts from dental fillings partially obstructed 3 images. Differences in the structure volumes, center-of-volume positions, and boundary positions (1 SD) were measured. In-house software created three-dimensional overlap distributions, including all observers. The effects of dental artifacts and observer experience on contouring precision were investigated, and the need for contrast media was assessed. Results:In the absence of artifacts, all 9 participants achieved reasonable precision (1 SD ≤3 mm all boundaries). The structures obscured by dental image artifacts had larger variations when measured by the 3 metrics (1 SD = 8 mm cranial/caudal boundary). Experience improved the interobserver consistency of contouring for structures obscured by artifacts (1 SD = 2 mm cranial/caudal boundary). Conclusions:Interobserver contouring variability for anatomic H&N structures, specifically oropharyngeal gross tumor volumes and parotid glands, was acceptable in the absence of artifacts. Dental artifacts increased the contouring variability, but experienced participants achieved reasonable precision even with artifacts present. With a staging contrast CT image as a reference, delineation on a noncontrast treatment planning CT image can achieve acceptable precision.

Role of Radiation Therapy in the Management of Renal Cell Cancer

Renal cell carcinoma (RCC) is traditionally considered to be radioresistant; therefore, conventional radiotherapy (RT) fraction sizes of 1.8 to 2 Gy are thought to have little role in the management of primary RCC, especially for curative disease. In the setting of metastatic RCC, conventionally fractionated RT has been an effective palliative treatment in 50% of patients. Recent technological advances in radiation oncology have led to the clinical implementation of image-guided radiotherapy, allowing biologically potent doses to the tumors intra- and extra-cranially. As predicted by radiobiologic modeling, favorable outcomes have been observed with highly hypofractionated schemes modeled after the experience with intracranial stereotactic radiosurgery (SRS) for RCC brain metastases with reported local control rates averaging 85%. At present, both primary and metastatic RCC tumors may be successfully treated using stereotactic approaches, which utilize steep dose gradients to maximally preserve function and avoid toxicity of adjacent organs including liver, uninvolved kidney, bowel, and spinal cord regions. Future endeavors will combine stereotactic body radiation therapy (SBRT) with novel targeted therapies, such as tyrosine kinase inhibitors and targeted rapamycin (mTOR) inhibitors, to maximize both local and systemic control.

A conceptual model integrating spatial information to assess target volume coverage for IMRT treatment planning.

PURPOSE We propose a model that integrates the spatial location of each voxel within a clinical target volume (CTV) to differentiate the merit of intensity-modulated radiation therapy (IMRT) plans with similar dose-volume histogram (DVH). This conceptual model is based on the hypothesis that various subregions within a given CTV that may carry different degree of risk in containing microscopic disease. METHODS AND MATERIALS We hypothesize that a correlation between the probability of microscopic tumor extension and the risk of lymph node metastasis of a particular voxel point within CTV can be inferred based on its distance from the surface of radiographically evident gross disease. A preliminary observation was gathered from existing clinicopathologic data, and, based on these observations, a conceptual model for exponential-decay microscopic-extension probability function around primary tumor and linear function parameters relating the likelihood of lymph node metastasis to the distance from primary tumor was proposed. This model was generated to provide scoring functions to examine the merit of IMRT plans. To test the feasibility of this model, we generated two IMRT plans with similar and clinically acceptable DVH-based CTV coverage. Planning data were transferred to a data analysis software package (Matlab, The Mathworks Inc.). A 3D scoring function was calculated for each voxel inside the CTV. The adequacy of target coverage was evaluated by several novel approaches: 2D dose-volume scoring-function histograms (DVSH), the integral probability of relative residual tumor burden (RRTB), and tumor control probabilities (TCP) employing the scoring function as a pseudo-clonogen density distribution. RESULTS Incorporating parameters for the risk of containing microscopic disease in each voxel into the scoring function algorithm, 2D DVSHs, RRTBs, integral RRTBs, and TCPs were computed. On each axial image, an RRTB map could locate the regions at greatest risk. These scoring functions were able to differentiate the merit of CTV coverage of clinically different IMRT plans but having very similar DVHs; one with cold spots centrally located over the gross tumor, and the other with more acceptable cold spots on the periphery of the CTV further away from the gross tumor volume. CONCLUSIONS We demonstrated the feasibility and potential utility of an IMRT scoring method derived from this conceptual modeling approach. These methods are capable of ranking treatment plans with similar DVH profiles but different underdosed regions within the target. We will examine the accuracy of model parameters by performing tumor-specific image-pathologic correlation studies. Upon validation of these parameters, incorporating this scoring function model into plan optimization may have the potential to avoid underdosing subvolumes within CTV that harbor a higher likelihood of microscopic disease.

Management of Radiation-Induced Head and Neck Injury

Toxicity from H&N cancer irradiation is complex and multifactorial. The nature and severity of the side effect profile for a given patient result from the interplay of patient-related, tumor-related, and treatment-factors. Among the side effects studied, skin toxicity and mucositis represent the most common acute effects of irradiation. Supportive care is essential to prevent superimposed infection and other complications that might lead to treatment breaks or, in extreme cases, discontinuation of therapy. Technological advances with conformal radiotherapy techniques have allowed for increasing salivary gland sparing. Further protection may be achieved with existing and future medical therapies. Swallowing dysfunction following chemoradiation for laryngeal cancer is significant and may persist for 1-2 years. Efforts should be made to ensure proper patient education and reassurance in this regard.

Dose escalation in locally advanced carcinoma of the prostate

Radiotherapeutic management of advanced prostate cancer is challenging. Several retrospective analyses showed a dose response for local tumor control before the availability of conformal radiation therapy. Attempts to escalate dose without the benefit of modern treatment planning was commonly fraught with high rates of bowel or bladder complications. The advent of image-guided or computed tomography-based treatment planning has allowed safe delivery of high-dose radiation therapy in men with prostate cancer with an acceptable rate of side effects and complications. Several prospective clinical trials have been conducted both at single institutions and in the cooperative group setting. Early evidence suggests that patients with high-risk factors such as advanced clinical stage, high initial prostate-specific antigen, or poorly differentiated tumors may benefit from high-dose 3-dimensional conformal radiation therapy with improved biochemical and local tumor control. A published randomized trial with conformal radiation therapy shows that a modest escalation of radiation dose leads to improved biochemical disease-free survival for a select group of patients. A confirmatory trial within the Radiation Therapy Oncology Group is underway to determine if dose escalation will improve overall survival in men without compromising quality of life.

Head and neck squamous cell carcinoma: Optimizing the therapeutic index

The four recent noteworthy strategies aimed at improving therapeutic outcomes for the curative treatment of head and neck squamous cancers include the development of altered fractionation regimens, integration of chemotherapy, incorporation of intensity-modulated radiation therapy and introduction of targeted biologic therapy. Clinical investigations during the last 30 years have demonstrated the benefits of biologically sound altered fractionation and concurrent chemoradiation regimens in improving locoregional control and overall survival. These results have contributed to redefining the standard of care, with the caveat that proper patient selection for those who will benefit from potentially toxic combined modality treatment regimens remains controversial. These benefits have come at the expense of increased acute toxicity (i.e., mucositis) and sometimes at the expense of late toxicity (i.e., fibrosis and dysphagia). There are two additional developments that may help to further widen the therapeutic ratio. Intensity-modulated radiation therapy allows for the delivery of a highly conformal 3D radiation dose distribution around intended targets, thereby limiting the volumes of mucosa receiving a high dose per fraction and high total doses. The technical basis for intensity-modulated radiation therapy delivery reopens many fractionation questions that are still being addressed and challenges us to determine which of these is optimal for use with intensity-modulated radiation therapy alone or in combination with concurrent sensitizers. Finally, combined radiation therapy and biologic therapies directed at targets expressed predominately or exclusively by tumor cells have the promise to help increase tumor cell kill, while at least not substantially increasing normal tissue toxicity. These strategies are reviewed in a clinical context.