C.A. Mantz

Reduction in Patient-reported Acute Morbidity in Prostate Cancer Patients Treated With 81-Gy Intensity-modulated Radiotherapy Using Reduced Planning Target Volume Margins and Electromagnetic Tracking: Assessing the Impact of Margin Reduction Study

OBJECTIVE To investigate whether patient-reported quality of life after high-dose external beam intensity-modulated radiotherapy for prostate cancer can be improved by decreasing planning target volume margins while using real-time tumor tracking. METHODS Study patients underwent radiotherapy with nominal 3-mm margins and electromagnetic real-time tracking. Morbidity was assessed before and at the end of radiotherapy using Expanded Prostate Cancer Index Composite (EPIC) questionnaires. Changes in scores were compared between the Assessing Impact of Margin Reduction (AIM) study cohort and the comparator Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment (PROST-QA) cohort, treated with conventional margins. RESULTS The 64 patients in the prospective AIM study had generally less favorable clinical characteristics than the 153 comparator patients. Study patients had similar or slightly poorer pretreatment EPIC scores than comparator patients in bowel, urinary, and sexual domains. AIM patients receiving radiotherapy had less bowel morbidity than the comparator group as measured by changes in mean bowel and/or rectal domain EPIC scores from pretreatment to 2 months after start of treatment (-1.5 vs -16.0, P = .001). Using a change in EPIC score >0.5 baseline standard deviation as the measure of clinical relevance, AIM study patients experienced meaningful decline in only 1 health-related quality of life domain (urinary) whereas decline in 3 health-related quality of life domains (urinary, sexual, and bowel/rectal) was observed in the PROST-QA comparator cohort. CONCLUSIONS Prostate cancer patients treated with reduced margins and tumor tracking had less radiotherapy-related morbidity than their counterparts treated with conventional margins. Highly contoured intensity-modulated radiotherapy shows promise as a successful strategy for reducing morbidity in prostate cancer treatment.

Sequential induction chemotherapy and concomitant chemoradiotherapy in the management of locoregionally advanced laryngeal cancer

PURPOSE To determine overall survival, progression-free survival, rate of voice preservation, and patterns of failure in locoregionally advanced laryngeal cancer treated with induction chemotherapy with or without surgery followed by concomitant chemoradiation. BACKGROUND Locoregionally advanced laryngeal cancer has been conventionally treated with either surgery and adjuvant radiotherapy or radiotherapy alone, and clinical and functional outcomes have been poor. Chemoradiotherapy has been demonstrated to improve functional outcome and disease control over conventional treatment in recent randomized head and neck trials. PATIENTS AND METHODS Advanced head and neck cancer patients were enrolled onto two consecutive phase II studies. Induction treatment consisted of three cycles of cisplatin, 5-fluorouracil (5-FU), leucovorin, and interferon-alpha 2b (PFL-IFN) followed by surgery for residual disease. Surgical intent was to spare the larynx when possible. All patients then proceeded to concomitant chemoradiation consisting of seven or eight cycles of 5-FU, hydroxyurea, and a planned total radiotherapy dose of 7000 cGy (FHX). RESULTS A subset of thirty-two laryngeal cancer patients with predominantly stage IV disease comprises the study group for this report. Clinical CR was observed in 59% of patients following induction therapy. The median follow-up was 63.0 months for surviving patients and 44.5 months for all patients. At five years, overall survival is 47%, progression-free survival is 78%, and locoregional control is 78%. No distant failures were observed. Voice preservation with disease control was 75% at five years. Only two total laryngectomies were performed during the course of treatment and follow-up. Treatment-related toxicity accounted for two deaths. CONCLUSIONS The addition of concomitant chemoradiotherapy to induction chemotherapy for locoregionally advanced laryngeal cancer appears to increase locoregional control and survival rates. PFL-IFN-FHX resulted in high rates of disease cure and voice preservation in a group of patients that has traditionally fared poorly in both clinical and functional outcome.

Patient-reported quality of life after stereotactic body radiotherapy (SBRT), intensity modulated radiotherapy (IMRT), and brachytherapy

BACKGROUND AND PURPOSE Stereotactic body radiotherapy (SBRT) is being used for prostate cancer, but concerns persist about toxicity compared to other radiotherapy options. MATERIALS AND METHODS We conducted a multi-institutional pooled cohort analysis of patient-reported quality of life (QOL) [EPIC-26] before and after intensity-modulated radiotherapy (IMRT), brachytherapy, or SBRT for localized prostate cancer. Data were analyzed by mean domain score, minimal clinically detectable difference (MCD) in domain score, and multivariate analyses to determine factors associated with domain scores at 2-years. RESULTS Data were analyzed from 803 patients at baseline and 645 at 2-years. Mean declines at 2-years across all patients were -1.9, -4.8, -4.9, and -13.3 points for urinary obstructive, urinary incontinence, bowel, and sexual symptom domains, respectively, corresponding to MCD in 29%, 20%, and 28% of patients. On multivariate analysis (vs. IMRT), brachytherapy had worse urinary irritation at 2-years (-6.8 points, p<0.0001) but no differences in other domains (p>0.15). QOL after SBRT was similar for urinary (p>0.5) and sexual domains (p=0.57), but was associated with better bowel score (+6.7 points, p<0.0002). CONCLUSIONS QOL 2-years after brachytherapy, IMRT, or SBRT is very good and largely similar, with small differences in urinary and bowel QOL that are likely minimized by modern techniques.

Mortality in men with localized prostate cancer treated with brachytherapy with or without neoadjuvant hormone therapy

Discrepancies exist regarding the impact of neoadjuvant hormone therapy (NHT) on the risk of all‐cause mortality (ACM) in men who receive brachytherapy for localized prostate cancer. Therefore, the objective of the current study was to examine the effect of NHT on the risk of ACM in men with prostate cancer who receive with brachytherapy.

Combining Immunotherapy and Radiation for Prostate Cancer

Radiotherapy has conventionally been viewed as immunosuppressive, which has precluded its use in combination with immunotherapy for prostate and other cancers. However, the relationship between ionizing radiation and immune reactivity is now known to be more complex than was previously thought, and data on the use of radiotherapy and immunotherapy are accumulating. Herein, we review this topic in the light of recently available data in the prostate cancer setting. Recent research has shown no significant lymphopenia in patients undergoing radiotherapy for high-risk adenocarcinoma of the prostate. In addition, emerging evidence suggests that radiotherapy can have immunostimulatory effects, and that tumor cell death, coupled with related changes in antigen availability and inflammatory signals, can affect lymphocyte and dendritic cell activation. Initial studies have focused on combinations of tumor irradiation and immunotherapy, such as the autologous cellular immunotherapy sipuleucel-T and the monoclonal antibody ipilimumab, in metastatic castration-resistant prostate cancer. These combinations appear to have clinical promise, and further investigation of the potentially synergistic combination of radiotherapy and immunotherapy is continuing in clinical trials.

Building on sipuleucel-T for immunologic treatment of castration-resistant prostate cancer.

BACKGROUND Sipuleucel-T is an autologous cellular immunotherapy approved by the US Food and Drug Administration for the treatment of asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. Its mechanism of action is based on stimulation of the patients own immune system to target prostate cancer. Peripheral blood mononuclear cells, including antigen-presenting cells and T cells, are obtained from patients via leukapheresis and treated ex vivo with PA2024, a fusion protein consisting of prostatic acid phosphatase/granulocyte-macrophage colony-stimulating factor antigen. METHODS Data relating to the potential pharmacodynamic biomarkers associated with sipuleucel-T activity are reviewed, as well as considerations for patient selection and for sequencing sipuleucel-T with other prostate cancer treatments. Possible directions for future development are also discussed, including treatment of less advanced prostate cancer populations, combination treatment, and immune modulation. RESULTS Data from three randomized, double-blind, placebo-controlled phase III clinical trials of sipuleucel-T in patients with metastatic castration-rresistant prostate cancer have shown improvement in overall survival vs control. Here, we review its developing role in prostate cancer therapy and future directions for development. CONCLUSIONS There is potential to build on sipuleucel-T to further advance immunotherapy of prostate cancer.

Patient-reported quality of life after stereotactic body radiation therapy versus moderate hypofractionation for clinically localized prostate cancer

BACKGROUND AND PURPOSE Evaluate changes in bowel, urinary and sexual patient-reported quality of life following treatment with moderately hypofractionated radiotherapy (<5Gray/fraction) or stereotactic body radiation therapy (SBRT;5-10Gray/fraction) for prostate cancer. MATERIALS AND METHODS In a pooled multi-institutional analysis of men treated with moderate hypofractionation or SBRT, we compared minimally detectable difference in bowel, urinary and sexual quality of life at 1 and 2years using chi-squared analysis and logistic regression. RESULTS 378 men received moderate hypofractionation compared to 534 men who received SBRT. After 1year, patients receiving moderate hypofractionation were more likely to experience worsening in bowel symptoms (39.5%) compared to SBRT (32.5%; p=.06), with a larger difference at 2years (37.4% versus 25.3%, p=.002). Similarly, patients receiving moderate fractionation had worsening urinary symptom score compared to patients who underwent SBRT at 1 and 2years (34.7% versus 23.1%, p<.001; and 32.8% versus 14.0%, p<.001). There was no difference in sexual symptom score at 1 or 2years. After adjusting for age and cancer characteristics, patients receiving SBRT were less likely to experience worsening urinary symptom scores at 2years (odds ratio: 0.24[95%CI: 0.07-0.79]). CONCLUSIONS Patients who received SBRT or moderate hypofractionation have similar patient-reported change in bowel and sexual symptoms, although there was worse change in urinary symptoms for patients receiving moderate hypofractionation.

The promise of combining radiation therapy and immunotherapy: morbidity and toxicity

Radiation therapy and immunotherapy in partnership may have the capability of delivering a therapeutic effect exceeding the sum of its parts. The possible relationship has been demonstrated in murine models and has been extended to a variety of clinical trials. Though the standard notion of whole body radiation therapy is immunosuppressive, there is growing evidence toward the contrary for focal radiation therapy. Furthermore, if immunotherapeutic techniques can retune the immune system against cancerous cells, they should have obvious benefits for advanced treatments moving forward. Herein, we explore the promise in combining radiation therapy and immunotherapy with distinct focus on potential morbidities and toxicities through analysis of completed clinical trials.

Treatment-Related Sexual Dysfunction in Male Nonprostate Pelvic Malignancies

Treatment of testicular, penile, and bladder cancer with surgery, radiation therapy, and chemotherapy may result in significant sexual morbidity. The pathophysiology of erectile dysfunction is reviewed. The incidence of posttreatment erectile dysfunction, infertility, loss of libido, retrograde ejaculation, loss of orgasm, and sexual dissatisfaction is estimated from the published literature. Morbidity resulting from different treatment options are compared and innovative approaches which hold promise for reducing sexual dysfunction in this patient population are highlighted.

Best of the Radiosurgery Society® Scientific Meeting 2014: stereotactic radiosurgery/stereotactic body radiotherapy treatment of extracranial and intracranial lesions.

The SRS/SBRT Scientific Meeting 2014, Minneapolis, MN, USA, 7-10 May 2014. The Radiosurgery Society(®), a professional medical society dedicated to advancing the field of stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT), held the international Radiosurgery Society Scientific Meeting, from 7-10 May 2014 in Minneapolis (MN, USA). This years conference attracted over 400 attendants from around the world and featured over 100 presentations (46 oral) describing the role of SRS/SBRT for the treatment of intracranial and extracranial malignant and nonmalignant lesions. This article summarizes the meeting highlights for SRS/SBRT treatments, both intracranial and extracranial, in a concise review.